FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patent Rules, 2003
COMPLETE SPECIFICATION (See section 10 and rule 13)
QUINOLINE DERIVATIVES AS RENIN INHIBITORS
SUN PHARMA ADVANCED RESEARCH COMPANY LIMITED
A company incorporated under the laws of India having their office at 17/B, Mahal Industrial Estate, Mahakali Caves Road, Andheri (E), Mumbai-400093. Maharashtra,
India
The following specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performed

QUINOLINE DERIVATIVES AS RENIN INHIBITORS
The present invention relates to novel quinoline derivatives as renin inhibitors, process of preparation thereof, and to the use of the compounds in the preparation of pharmaceutical compositions for the therapeutic treatment of cardiovascular disorders related to hypertension, in warm-blooded animals. Further the present invention also provides a method for treatment of disorders like congestive heart failure, cardiac hypertrophy, cardiac fibrosis, coronary artery disease, vasculopathy, neuropathy, intraocular hypertension, glaucoma, diabetic nephropathy, abnormal vascular growth, hyperaldosteronism etc.
BACKGROUND OF THE INVENTION
Hypertension is one of the major risk factor for cardiovascular diseases such as stroke, myocardial infarction, and heart failure, the leading causes of death worldwide. Inhibitors of the renin-angiotensin systems (RAS) are known to be successful treatments for hypertension. As renin specifically catalyses the rate-limiting step of the RAS, it represents the optimal target for RAS inhibition.
Several peptide-like renin inhibitors have been reported earlier but due to their poor pharmacokinetic properties (poor absorption and rapid elimination) these compounds were not clinically useful. The development of oral renin inhibitors thus met with several challenges. The clinical development of aliskiren was a significant breakthrough for this class of compounds. However, there still exist a need to develop renin inhibitors with improved oral bioavailability, specificity for human renin, efficacy and good pharmacokinetic properties.
The first non-peptide renin inhibitors with high in vitro activity have been reported in PCT application WO 1997/009311. Amine based non-peptidic renin inhibitors have been disclosed in WO2007/099509. The quinoline derivatives disclosed in JP2010-

163361 (WO2008/136457) and JP2010-208947 are not considered to be the part of the present invention.
The present invention relates novel quinoline derivatives as renin inhibitors. SUMMARY OF THE INVENTION
The present invention relates to compounds of formula (I),

or pharmaceutically acceptable salt thereof,
wherein;
X is selected from O or S;
Y is bond or a group selected from O or NH, with the proviso that Y is NH when X is S;
Z is a group selected from -CO, -CH2,-CH2CO -C=NH;
R is selected from the group consisting of substituted or unsubstituted -C1-5-linear or branched alkyl, -C3-8-cycloalkyl and cycloalkylalkyl; wherein cycloalkyl group may be optionally substituted with C1-3 -linear or branched alkyl group;
R! is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-,2-cycloalkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -SO2C1-8-alkyl, -SO2-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical, and may

contain one or more heteroatom selected from O, S and N in the cycloalkyi or heterocyclic ring system, and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C1-12-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, '-(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, - (CH2)qCO-heteroaryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyi or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6, with proviso that R2 is -C7-12-linear or branched alkyl when Z is -CO;
R3 is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted -C1-8-alkyl, -C3-12-cycloalkyl;
or OR2 and R3 together with the carbon atom to which they are attached form a 3 to 6-
membered cyclic ring system, ring 'c' of the formula , with optional
one or more double bond, R" is a substitutent selected from -C1-8-alkyl or -C3.12-cycloalkyl and 'p' is an integer selected from 0, 1 or 2;
'n' is an integer selected from 0, 1 and 2;
'm1', 'm2' and 'm3' are integers independently selected from 0, 1, 2, 3 and 4;
( * ) at the ring carbon, indicate (R) or (5) configuration or a racemate (RS). One aspect of the present invention relates to compounds of formula (la),


or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkyialkyl, -(CH2)qO-C1-8-alkyl, --(CH2)qCO -C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 4q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-Iinear or branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, - (CH2)qCO-heteroaryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryi and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2;

( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS). Another aspect of the present invention relates to compounds of formula (lb),

or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3_12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, - -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -(CH2)q-C3-2-cycloalkyl -, -(CH2)qO-C1-8-alkyI, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C!_8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;

'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS). Another aspect of the present invention relates to compounds of formula (Ic),

or pharmaceutically acceptable salt thereof,
wherein;
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloaIkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -(CH2)q-C3.i2-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;

'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (5) configuration or racemate (RS). Another aspect of the present invention relates to compounds of formula (Id),

or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -Ci.gCi.g-linear or branched alkyl, -C3-12-cycloalkyI, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, --(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -SO2-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
ring 'c' of the formula , contains optionally one or more double bond;
R" is a substitutent selected from -C1-8-alkyl or -C3-12-cycIoalkyl and 'p' is an integer selected from 0, 1 or 2;

V is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS). Another aspect of the present invention relates to compounds of formula (Ie),

or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, --(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-aIkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3_12-cycloalkyI, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7_12-linear or branched alkyl, - -(CH2)q-C3-12-cycloalkyl --(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12 cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-aIkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-aIkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may

contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2;
'm1, 'm2' and 'm3' are integers independently selected from 0, 1, 2, 3 and 4;
( * ) at the ring carbon indicate (R) or (S) configuration or racemate (RS). Another aspect of the present invention relates to compounds of formula (If),

or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R is selected from the group consisting of substituted or unsubstituted -C1-5-linear or branched alkyl, -C3-8-cycloalkyl and cycloalkylalkyl; wherein cycloalkyl group may be optionally substituted with C1-3-linear or branched alkyl group;
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -SO2-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more

heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0,1,2, 3,4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2; ( * ) at the piperidin-3-yl carbon, indicate (R) or (5) configuration or racemate (RS).
The invention also provides the use of compound of formula (Ia-If) or salt or TV-oxides thereof for the preparation of pharmaceutical composition comprising compound of formula (Ia-If) or N-oxidc thereof and a pharmaceutically acceptable carrier, diluent or excipient thereof
Further the present invention also provides a method for treatment of disorders like hypertension as well as congestive heart failure, cardiac hypertrophy, cardiac fibrosis coronary artery disease, vasculopathy, neuropathy, intraocular hypertension, glaucoma, diabetic nephropathy, abnormal vascular growth, hyperaldosteronism comprising administering to a mammal in need of such treatment an effective amount of compound of formula (Ia-If) or salt orN-oxides thereof.
DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to compounds of formula (I),

or pharmaceutically acceptable salt thereof,
wherein;
X is selected from O or S;
Y is bond or a group selected from O or NH, with the proviso that Y is NH when X is S;
Z is a group selected from -CO, -CH2,-CH2CO , -C=NH;
R is selected from the group consisting of substituted or unsubstituted -C1-5-linear or branched alkyl, -C3-8-cycloalkyl and cycloalkylalkyl; wherein cycloalkyl group may be optionally substituted with C1-3 -linear or branched alkyl group;
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3. 12-cycloalkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical, and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C1-12-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyl, ~(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-

cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, - (CH2)qCO-heteroaryl, -COC1-8-aIkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyI, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6, with proviso that R2 is -C7-12-alkyl when Z is -CO,;
R is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted -C1-8-alkyl, -C3-12-cycloaIkyl;
or OR2 and R3 together with the carbon atom to which they are attached form a 3 to 6-
membered cyclic ring system, ring 'c' of the formula , with optional
one or more double bond, R" is a substitutent selected from -C1-8-alkyl or -C3-12-cycloalkyl and 'p' is an integer selected from 0, 1 or 2;
sn' is an integer selected from 0, 1 and 2;
'm1', 'm2' and 'm3' are integers independently selected from 0, 1, 2, 3 and 4;
( * ) at the ring carbon, indicate (R) or (5) configuration or a racemate (RS).
According to one embodiment, specifically provided are compounds of the formula (Ia),


formula (la)
or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycIoalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, --(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloaIkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S2C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, - (CH2)qCO-heteroaryl, -COC1-8-alkyl, -COC3_i2-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3,4, 5 or 6;
'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS).
According to one embodiment, specifically provided are compounds of the formula (la) in which Y is O.
According to another embodiment, specifically provided are compounds of the formula (la) in which 'n' is 1.

According to yet another embodiment, specifically provided are compounds of the formula (la) in which 'n' is 2.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R1 is -C1-8-linear or branched alkyl group selected from methyl, ethyl, w-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (f-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R1 is -COOC1-8-alkyl, wherein -C1-8-alkyl group selected from methyl, ethyl, n-propyl, isopropyl, w-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R1 is cycloalkylalkyl, selected from cyclopropylmethyl, cyclobutylethyl and cyclopentylethyl.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R1 is -CH2O-C1-8-alkyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (/-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (Ia) in which, 'n' is 0, Y is absent and R1 is substituted aryl selected from phenyl substituted with alkoxy, halogen, or haloalkyl group.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which, R2 is substituted or unsubstituted -C7-12-Hnear or branched alkyl group selected from heptyl, octyl, nonyl, decyl etc.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which, R2 is -(CH2)q-C3-12-cycloalkyl ring selected from cycloheptyl, cyclooctyl, cyclohexyl methyl, cyclopentylethyl, cyclohexylethyl, cyclopentylpropyl, cyclohexylpropyl etc. and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which, R2 is -(CH2)q-C4-12-heterocyclic ring containing heteroatom

oxygen or nitrogen, selected from tetrahydrofuran-2-ylmethyl, tetrahydropyran-4-ylmethyl, tetrahydrofuran-3-yl, oxetan, piperidine, pyrrolidine etc. and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which, R is aralkyl, selected from benzyl or phenethyl optionally substituted, with one or more substituent selected from -C1-8-alkyl, halogen, trifluormethyl and -C3-12-cycloalkyI etc.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which, R2 is aryl or heteroaryl group selected from pyridine-2-ylmethyl, pyridine-3-ylmethyl and indan-2-yl.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R is -CH20-C1-8-alkyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, w-butyl, isobutyl, and 1,1-dimethylethyl (/-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is -CH2CO-C1-8-alkyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (r-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is -CH2CO-C3-12-cycloalkyl, wherein the -C3-12-cycloalkyl group is selected from cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and adamantan-1-yl.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is -CH2CO-aryl, wherein the aryl group is phenyl optionally substituted with one or more substituent selected from -Cj.g-alkyl, halogen, trifluormethyl and -C3-12-cycloalkyl.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is - (CH2)qCO-heteroaryl„ wherein the heteroaryl group

oxazolyl, isoxazolyl, imidazolyl, furyl, indolyl, isoindolyl, pyrrolyl, triazolyl, triazinyl, tetrazoyl, thienyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzofuranyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzopyranyl, carbazolyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, naphthyridinyl, pteridinyl, purinyl, quinoxalinyl, quinolinyl, isoquinolinyl, thiadiazolyl, indolizinyl, acridinyl, phenazinyl, imidazo[l,2-a]pyridyl, imidazo[l,2-a]pyridine and phthalazinyl and and 'q' is an integer selected from 0, 1, 2, 3,4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is -COCi.s-aikyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is -COC3-12-cycloalkyl, wherein the -C3-12-cycloalkyl group is selected from cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and adamantan-1-yl.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is -CO-aryl, wherein the aryl group is phenyl optionally substituted with one or more substituent selected from -C1-8-alkyl, halogen, trifluormethyl and -C3-12-cycloalkyl.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which R2 is -COOC1-8-aIkyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (f-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (la) in which the configuration at the chiral centre ( * ) is R.
According to yet another embodiment, specifically provided are compounds of the formula (la) in which the configuration at the chiral centre ( * ) is S.
According to one embodiment, specifically provided are compounds of formula (lb),


or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, - -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
R is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyI, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-2-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2; ( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS).

According to another embodiment, specifically provided are compounds of the formula (lb) in which Y is O.
According to yet another embodiment, specifically provided are compounds of the formula (lb) in which 'n' is 1.
According to yet another embodiment, specifically provided are compounds of the formula (lb) in which 'n' is 2.
According to yet another embodiment, specifically provided are compounds of the formula (lb) in which R1 is -C1-8-linear or branched alkyl group selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (lb) in which, R2 is -(CH2)q-C3-12-cycloalkyl ring which may contain one or more heteroatom selected from oxygen, nitrogen and sulphur and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (lb) in which the configuration at the chiral centre ( * ) is R.

or pharmaceutically acceptable salt thereof,
According to another embodiment, specifically provided are compounds of the formula (Ic),

wherein;
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -SO2-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS).
According to one another embodiment, specifically provided are compounds of the formula (Ic) in which 'n' is 1.
According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which 'n' is 2.
According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which R1 is -COC1-8-alkyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).

According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which R1 is -SO2C1-8-alkyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (f-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which R1 is -CO-aryl, wherein the aryl group is phenyl optionally substituted with one or more substituent selected from -C1-8-alkyl, halogen, trifluormethyl and -C3-1i2-cycloalkyl.
According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which, R2 is substituted or unsubstituted -C1-8-alkyl, selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (/t-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which, R2 is -(CH2)q-C3-12-cycloalkyl ring which may contain one or more heteroatom selected from oxygen, nitrogen and sulphur and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which, R2 is aralkyl, selected from benzyl or phenethyl optionally substituted with one or more substituent selected from -C1-8-alkyl, halogen, trifluormethyl and -C3-12-cycloalkyl etc.
According to yet another embodiment, specifically provided are compounds of the formula (Ic) in which the configuration at the chiral centre ( * ) is R.
According to one embodiment, specifically provided are compounds of the formula (Id),


or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, --(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3_12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3,4, 5 or 6;
ring 'c' of the formula , contains optionally one or more double bond;
R" is a substitutent selected from -C1-8-alkyl or -C3-12-cycloalkyl and 'p' is an integer selected from 0, 1 or 2;
'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (5) configuration or racemate (RS).

According to another embodiment, specifically provided are compounds of the formula (Id) in which Y is O.
According to yet another embodiment, specifically provided are compounds of the formula (Id) in which 'n' is 1.
According to yet another embodiment, specifically provided are compounds of the formula (Id) in which 'n' is 2.
According to yet another embodiment, specifically provided are compounds of the formula (Id) in which R1 is -C1-8-linear or branched alkyl group selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).
According to yet another embodiment, specifically provided are compounds of the
formula (Id) in which ring 'c'of the formula is 5-membered furan
ring.
According to yet another embodiment, specifically provided are compounds of the formula (Id) in which ring 'c' is 5-membered furan ring optionally containing a double bond.
According to yet another embodiment, specifically provided are compounds of the formula (Id) in which ring 'c' is 5-membered furan ring is substituted with one or more methyl group i.e. R" is a methyl group and 'p' is 1 or 2.
According to yet another embodiment, specifically provided are compounds of the formula (Id) in which the configuration at the chiral centre ( * ) is R.
According to another embodiment, specifically provided are compounds of the formula (Ie),


or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (0);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-aIkyI, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COCi-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyl ring --(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2;
'm1', 'm2' and 'm3' are integers independently selected from 0, 1, 2, 3 and 4;

( * ) at the ring carbon indicate (R) or (S) configuration or racemate (RS).
According to another embodiment, specifically provided are compounds of the formula (Ie) in which 'n' is 1.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which 'n' is 2.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which R1 is -C1-8-linear or branched alkyl group, selected from methyl, ethyl, n-propyl, isopropyl, w-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which, R2 is -(CH2)q-C3-12-cycloalkyl ring selected from cycloheptyl, cyclooctyl, cyclohexyl methyl, cyclopentylethyl, cyclohexylethyl, cyclopentylpropyl, cyclohexylpropyl etc. and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which, R2 is -(CH2)q-C4-12-heterocyclic ring containing heteroatom oxygen or nitrogen, selected from tetrahydrofuran-2-ylmethyl, tetrahydropyran-4-ylmethyl, tetrahydrofuran-3-yl, oxetan, piperidine, pyrrolidine etc. and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which R2 is -CH2CO-C1-8-alkyl, wherein -C1-8-alkyl selected from methyl, ethyl, ^-propyl, isopropyl, w-butyl, isobutyl, and 1,1-dimethylethyl (r-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which, 'm1' is 0 or 1.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which, 'm2' is an integer selected from 1, 2, 3 or 4.

According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which, '1113' is an integer selected from 0 or 1.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which the configuration at the chiral centre (*)isR.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which the configuration at the chiral centre ( * ) is S.
According to yet another embodiment, specifically provided are compounds of the formula (Ie) in which the configuration at the chiral centre ( * ) is RS.
According to another embodiment, specifically provided are compounds of the formula (If),

or pharrriaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R is selected from the group consisting of substituted or unsubstituted -C1-5-linear or branched alkyl, -C3-8-cycloalkyl and cycloalkylalkyl; wherein cycloalkyl group may be optionally substituted with C1-3-Hnear or branched alkyl group;
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qCO-

C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyI, -COC3_12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-linear or branched alkyl, -(CH2)q-C3.12-cycloalkyl -, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyI, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, *q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS),
According to another embodiment, specifically provided are compounds of the formula (If) in which 'Y' is O.
According to yet another embodiment, specifically provided are compounds of the formula (If) in which R is -C1-8-linear or branched alkyl group, selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (/-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (If) in which R is -C3-8-cycloalkyl, selected from cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
According to yet another embodiment, specifically provided are compounds of the formula (If) in which 'n' is 1.

According to yet another embodiment, specifically provided are compounds of the formula (If) in which 'n' is 2.
According to yet another embodiment, specifically provided are compounds of the formula (If) in which R1 is -C1-8-alkyl group selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (If) in which, R2 is -(CH2)q-C3-12-cycloalkyl ring with the total number of carbon atom is more than six, selected from cycloheptyl, cyclooctyl, cyclohexyl methyl, cyclopentylethyl, cyclohexylethyl, cyclopentylpropyl, cyclohexylpropyl etc. and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6.
According to yet another embodiment, specifically provided are compounds of the formula (If) in which R2 is -CH2CO-C1-8-alkyl, wherein -C1-8-alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and 1,1-dimethylethyl (t-butyl).
According to yet another embodiment, specifically provided are compounds of the formula (If) in which the configuration at the chiral centre ( * ) is R.
The following are definitions of the terms used in this specification. The initial definition provided for a group or term herein applies to that group or term throughout the present specification, individually or as part of another group, unless otherwise indicated.
The general terms used hereinbefore and hereinafter preferably have within the context of this disclosure the following meanings, unless otherwise indicated.
The term "alkyl" refers to a hydrocarbon chain radical that includes solely carbon and hydrogen atoms in the backbone, either linear or branched, having from one to eight carbon atoms, both inclusive, and which is attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl,

and 1,1-dimethylethyl (t-butyl). The term "C1-8 alkyl" refers to an alkyl chain, linear or branched having 1 to 8 carbon atoms, both inclusive. Unless set forth or recited to the contrary, all alkyl groups described or claimed herein may be, substituted or unsubstituted.
The term "cycloalkyl" denotes a non-aromatic mono-, or multicyclic ring system of 3 to about 12 carbon atoms. Monocyclic rings include include, but are not limited to cylcopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Examples of simple multicyclic cycloalkyl groups include perhydronapththyl, perhydroindenyl etc; bridged multicyclic groups include adamantyl and norbornyl etc, and spriromulticyclic groups for e.g., spiro(4,4)non-2-yl. Unless set forth or recited to the contrary, all cycloalkyl groups described or claimed herein may be substituted or unsubstituted and may optionally contain one or more heteroatom selected from O, S and N.
The term "cycloalkylalkyl" refers to a cyclic ring-containing radical having 3 to about 8 carbon atoms directly attached to an alkyl group. The cycloalkylalkyl group may be attached to the main structure at any carbon atom in the alkyl group that results in the creation of a stable structure. Non-limiting examples of such groups include cyclopropylmethyl, cyclobutylethyl and cyclopentylethyl. Unless set forth or recited to the contrary, all cycloalkylalkyl groups described or claimed herein may be substituted or unsubstituted and may optionally contain one or more heteroatom selected from O, S and N.
The term "alkoxy" denotes an alkyl group attached via an oxygen linkage to the rest of the molecule. Representative examples of such groups are -OCH3 and -OC2H5. Unless set forth or recited to the contrary, all alkoxy groups described or claimed herein may be straight chain or branched, substituted or unsubstituted.
The terms "halogen" or "halo" means fluorine, chlorine, bromine or iodine.

Similarly, "haloalkyl" or "haloalkoxy" refers to an alkyl or alkoxy group substituted with one or more halogen atoms.
The term "aryl" refers to an aromatic radical having 6 to 14 carbon atoms, including monocyclic, bicyclic and tricyclic aromatic systems such as phenyl, naphthyl, tetrahydronapthyl, indanyl and biphenyl. Unless set forth or recited to the contrary, all aryl groups described or claimed herein may be substituted or unsubstituted.
The term "arylalkyl" refers to an aryl group as defined above directly bonded to an alkyl group as defined above, e.g., -CH2C6H5 and -C2H4C6H5. Unless set forth or recited to the contrary, all arylalkyl groups described or claimed herein may be substituted or unsubstituted.
The term "heteroaryl" unless otherwise specified refers to substituted or unsubstituted 5 to 14 membered aromatic heterocyclic ring radicals with one or more heteroatom(s) independently selected from N, O or S. The heteroaryl may be a mono-, bi- or tricyclic ring system. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. Examples of such heteroaryl ring radicals include, but are not limited to oxazolyl, isoxazolyl, imidazolyl, furyl, indolyl, isoindolyl, pyrrolyl, triazolyl, triazinyl, tetrazoyl, thienyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzofuranyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzopyranyl, carbazolyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, naphthyridinyl, pteridinyl, purinyl, quinoxalinyl, quinolinyl, isoquinolinyl, thiadiazolyl, indolizinyl, acridinyl, phenazinyl, imidazo[l,2-cr]pyridyl, imidazo[l,2-a]pyridine and phthalazinyl. Unless set forth or recited to the contrary, all heteroaryl groups described or claimed herein may be substituted or unsubstituted.
Unless otherwise specified, the term "substituted" as used herein refers to a group or moiety having one or more of the substituents attached to the structural skeleton of the group or moiety, including, but not limited to such substituents as hydroxy,

halogen, carboxyl, cyano, nitro, oxo (=0), thio (=S), alkyl, haloalkoxy, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, amino, alkylamino, dialkylamino, heteroaryl, heterocyclylalkyl ring, heteroarylalkyl, heterocyclic ring, guanidine, alkylguanidine, -COORX) -C(0)Rx, -C(S)RX, -C(0)NRxRy, -(O)ONRxRy, -NRxCONRyRz, -N(Rx)SORy, -N(Rx)S02Ry, -(=N-N(Rx)Ry), -NRxC(0)ORy, -NRxRy, -NRxC(0)Ry, -NRxC(S)Ry, -NRxC(S)NRyRz, -SONRxRy, -S02NRxRy, -0RX, -ORxC(0)NRyRz, -ORxC(0)ORy, -OC(0)RX, -OC(0)NRxRy, -RxNRyC(0)Rz, -RxORy, -RxC(0)ORy, -RxC(0)NRyRz, -RxC(0)Ry, -RxOC(0)Ry, -SRx, -SORx, -S02Rx, and -0N02, wherein Rx, Ry and Rz are independently selected from hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkenyl, amino, alkylamino, dialkylamino, aryl, heteroaryl, heterocyclylalkyl ring, heteroarylalkyl, or substituted or unsubstituted heterocyclic ring.
As mentioned above the term "heterocyclic ring" or "heterocyclic radical" unless otherwise specified refers to substituted or unsubstituted non-aromatic 3 to 15 membered ring radical which consists of carbon atoms and from one to five heteroatoms selected from nitrogen, phosphorus, oxygen and sulfur. The heterocyclic ring radical may be a mono-, bi- or tricyclic ring system, which may include fused, bridged or spiro ring systems, and the nitrogen, phosphorus, carbon, oxygen or sulfur atoms in the heterocyclic ring radical may be optionally oxidized to various oxidation states. In addition, the nitrogen atom may be optionally quarternized; also, unless otherwise constrained by the definition the heterocyclic ring or heterocyclyl may optionally contain one or more olefinic bond(s). Examples of such heterocyclic ring radicals include, but are not limited to azepinyl, azetidinyl, benzodioxolyl, benzodioxanyl, chromanyl, dioxolanyl, dioxaphospholanyl, decahydroisoquinolyl, indanyl, indolinyl, isoindolinyl, isochromanyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, oxazolinyl, oxazolidinyl, oxadiazolyl, 2-oxopiperazinyl, 2-

oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, octahydroindolyl,
octahydroisoindolyl, perhydroazepinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, piperidinyl, phenothiazinyl, phenoxazinyl, quinuclidinyl, tetrahydroisquinolyl, tetrahydrofutyl, tetrahydropyranyl, thiazolinyl, thiazolidinyl, thiamorpholinyl, thiamorpholinyl sulfoxide and thiamorpholinyl sulfone. The heterocyclic ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. Unless set forth or recited to the contrary, all heterocyclyl groups described or claimed herein may be substituted or unsubstituted.
The term "heterocyclylalkyl" refers to a heterocyclic ring radical directly bonded to an alkyl group. The heterocyclylalkyl radical may be attached to the main structure at any carbon atom in the alkyl group that results in the creation of a stable structure. Unless set forth or recited to the contrary, all heterocyclylalkyl groups described or claimed herein may be substituted or unsubstituted.
With the groups of preferred compounds of formula (la), (lb), (Ic), (Id), (Ie), (If) and N-oxides thereof mentioned hereinafter, definitions of substituents from the general definitions mentioned hereinbefore may reasonably be used, e.g. to replace more general definitions with more specific definitions or especially with definitions characterized as being preferred.
Any asymmetric carbon atom may be present in the (R)-, (S)- or (i?,iS)-configuration. The compounds may thus be present as mixtures of stereoisomers or as pure stereoisomers. The invention relates also to possible tautomers of the compounds of formula (la), (lb), (Ic), (Id), (Ie) and (If).
Where the plural form is used for compounds, salts and the like, this is taken to mean also a single compound, salt or the like.
Salts of compounds of formula (la), (lb), (Ic), (Id), (Ie) and (If) are the physiologically acceptable salts. Physiologically acceptable salts are particularly suitable for medical

applications, due to their greater solubility in water compared with the starting or base compounds. Suitable physiologically acceptable acid addition salts of the compounds of the invention may be salts of inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, and the like or of organic acids such as, for example, acetic acid, benzenesulfonic acid, methanesulfonic acid, benzoic acid, citric acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, suberic acid, azelaic acid, malic acid, tartartic acid, amino acids, such as glutamic acid or aspartic acid, and the like. Examples of suitable physiologically acceptable basic salts are ammonium salts, or suitable organic amines, such as tertiary monoamines, e.g. triethylamine or tris(2-hydroxyethyl)amine etc., alkali metal salts such as sodium salts and potassium salts and alkaline earth metal salts such as magnesium salts and calcium salts. When a basic group and an acid group are present in the same molecule, a compound of formula (la), (lb), (Ic), (Id), (Ie), (If) may also form internal salts.
Below are the representative compounds of the present invention, which are illustrative in nature only and are not intended to limit to the scope of the invention.
8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-[(R)-(tetrahydrofuran-3-yl)oxy]quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8~Benzyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(tetrahydrofuran-2-ylmethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

8-(4-Fluorobenzyloxy)-4-(2-methoxy ethoxy)quinoline-2-carboxyIic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-[(S)-l-(tetrahydrofuran-2-yl)methoxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(tetrahydropyran-4-ylmethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(3-Cyciopentylpropoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-phenethyloxyquinoline-2-carboxyl ic acid isopropyl-(R)-piperidin-3-yl amide;
8-(4-Isopropyl cycIohexyimethoxy)-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-[4-(4-Chlorophenyl)cyclohexylmethoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(2-propylpentyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(Indan-2-yloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl piperidin-3-yl amide;
8-(2-Cyclohexylethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

8-(4-Isobutylbenzyloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(4-Isopropylbenzyloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(4-trifluoromethylbenzyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(4-Cyclohexylbenzyloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Heptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yI amide;
8-[2-(4-Fluorophenyl)ethoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(5-oxohexyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclooctyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(pyridin-2-ylmethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(pyridin-3-ylmethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-[2-(2-oxopyrrolidin-l-yl)ethoxy]quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;

8-(2,2-Dimethoxyethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclohexylmethoxy-4-(2-ethoxyethoxy)quinoline-2-carbbxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cycloheptyloxy-4-(2-ethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cycloheptyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(3-Fluorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(4-Fluorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(3-ChlorobenzyIoxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl -(R)-piperidin-3-yl amide;
4-(3-Methoxypropoxy)-8-(3-trifluoromethylbenzyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Fluorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Benzyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(3-Methoxypropoxy)-8-(tetrahydrofuran-2-ylmethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;

4-(3-Methoxypropoxy)-8-[(R)-(tetrahydrofuran-3-yl)oxy]quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(2,3-Dichlorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(3-Methoxypropoxy)-8-[(S)-l-(tetrahydrofuran-2-yl)methoxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclooctyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Heptyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclohexylmethoxy-4-(3-methoxy propoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cycloheptyloxy-4-(3-ethoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
Carbonic acid-2-[8-cycloheptyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester methyl ester;
Carbonic acid-2-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester methyl ester;
Carbonic acid-2-[8-cyclohexylmethoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyI ester methyl ester;
Carbonic acid-2-[8-isobutoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl)quinolin-4-yloxy] ethyl ester methyl ester;

Carbonic acid-2-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester ethyl ester;
Carbonic acid-2-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester pentyl ester;
Carbonic acid-2-[8-cyclopentyIoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy] ethyl ester isobutyl ester;
Carbonic acid-3-[8-cyclohexylmethoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]propyl ester methyl ester;
Carbonic acid-3-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yIoxy]propyl ester methyl ester;
8-Cycloheptyloxy-4-(2-isobutoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cycloheptyioxy-4-(2-propoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cycloheptyloxy-4-(2-cyclopropylmethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Cyclohexyl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxyethoxy)-8-(4-methyl-2-oxopentyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

4-(2-Methoxyethoxy)-8-(3-methyl-2-oxobutoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Adamantan-l-yl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Cyclopentyl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Cyclopropyl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-[2-(4-Chlorophenyl)-2-oxoethoxy]-4-(2-methoxyethoxy)quino]ine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-[2-Cyclopropyl-l-(2-fluoro phenyl)-2-oxo ethoxy]-4-(2-methoxy ethoxy)quinoline -2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-[2-(3-Chloro phenyl)-2-oxo ethoxy]-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Furan-2-yl-2-oxo ethoxy)-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxy ethoxy)-8-(2-oxo-2-thiophen-2-yl ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Ethoxyethoxy)-8-(4-methyl-2-oxopentyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Cyclopentyl-2-oxoethoxy)-4-(2-ethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-ethoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Ethoxyethoxy)-8-(3-methyl-2-oxobutoxy)quinoline-2-carboxylic acid isopropyl -(R)-piperidin-3-yl amide;
8-(3,3-Dimethyl-2-oxobutoxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Cyclohexyl-2-oxoethoxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(3-Methoxypropoxy)-8-(4-methyl-2-oxopentyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(2-CyclopentyI-2-oxoethoxy)-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(3-Methoxypropoxy)-8-(3-methyl-2-oxobutoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclohexylmethoxy-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Isobutoxy-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cycloheptyloxy-4-(2-methoxymethoxyethoxy)quinoiine-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclopentyloxy-4-(2-methoxymethoxyethoxy)quinoline-2-carboxyIic acid isopropyl-(R)-piperidin-3-yl amide;

8-CycIopentyloxy-4-(2-ethoxymethoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclohexylmethoxy-4-(3-methoxymethoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cycloheptyloxy-4-(3-methoxymethoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-(2-Cyclopentyl-2-oxoethoxy)-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Methoxymethoxyethoxy)-8-(4-methyl-2-oxopentyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-[(R)-2-(2,2-Dimethylpropionylamino)butoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-[(S)-2-(2,2-Dimethyipropionylamino)butoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-((R)-2-Methanesulfonylaminobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
Carbonic acid isobutyl ester-2-((R)-i sop ropy 1 piperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(S)-piperidin-3-yl amide;

8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(S)-piperidin-3-yl amide;
Isobutyricacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
2,2-Dimethyl propionic acid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
Pentanoicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
Hexanoicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
Heptanoicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
Octanoicacid-2-((R)-isopropylpiperidin-3-yI-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
Cyclopropanecarboxylic acid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
Cyclopentanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
Cyclohexanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
l-Methylcyclohexanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;

Adamantane-1 -carboxylic acid-2-((R)-isopropyIpiperidin-3-yI-carbamoyI)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
3-Cyclopentylpropionic acid-2-((R)-isopropyl-piperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy)quinolin-8-yl ester;
4-Fluorobenzoic acid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
Pentanoic acid-2-((R)-isopropyIpiperidin-3-yl-carbamoyl)-4-(3-methoxypropoxy) quinolin-8-yl ester;
Cyclopropanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(3-methoxy propoxy)quinolin-8-yl ester;
CycIopentanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(3-methoxy propoxy)quinoJin-8-yl ester;
Cyclohexanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(3-methoxy propoxy)quinolin-8-yl ester;
Hexanoic acid-2-((R)-isopropyl piperidin-3-yl-carbamoyl)-4-(3-methoxypropoxy) quinolin-8-yl ester;
4-(2-Methoxyethoxy)-8-methoxymethoxy quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Benzyloxymethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Benzyloxyethoxy)-8-cyclohexylmethoxy quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl-amide;

8-Cyclohexylmethoxy-4-[2-(3,3-dimethyl-2-oxobutoxy)ethoxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
Acetic acid-2-[8-cyclohexylmethoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester;
Isobutyric acid-2-[8-cyclohexylmethoxy-2-((R)-isopropyl piperidin-3-yl-carbamoyl) quinolin-4-yIoxy]ethyl ester;
2,2-Dimethyl propionic acid-2-[8-cyclohexylmethoxy-2-((R)-isopropyl piperidin-3-yl carbamoyl)quinolin-4-yloxy]ethyl ester;
8-Cyclopentyloxy-4-(2-methoxybenzyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclopentyloxy-4-(2,3-dichloro benzyIoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclopentyloxy-4-(2-trifluoromethylbenzyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
[8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoIin-2-ylmethyl]isopropyl-(R)-piperidin-3-yl amine;
[8-Cyclopentyloxy-4-(2-methoxyethoxy)quinolin-2-ylmethyl]isopropyl-(R)-piperidin -3-yl amine;
[8-Cycloheptyloxy-4-(2-methoxyethoxy)quinolin-2-ylmethyl]isopropyl-(R)-piperidin -3-yl amine;
4-(2-Acetylaminoethylsulfanyl)-8-cyclopentylmethoxyquinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;

4-(2-Acetylaminoethylsulfanyl)-8-cyclopentyloxyquinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclopentyloxy-4-(2-methanesulfonylaminoethylsulfanyl)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
4-(2-Acetylaminoethylsulfanyl)-8-benzyloxyquinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
4-(2-BenzoylaminoethyIsulfanyl)-8-cyclopentyloxyquinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl-amide;
6-(2-Methoxyethoxy)-2-methyl-furo[3,2-h]quinoline-8-carboxylicacid isopropyl-(R)-piperidin-3-yi-amide;
6-(3-Methoxypropoxy)-2-methyl-furo[3,2-h]quinoline-8-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
6-(2-Methoxyethoxy)-2,2-dimethyl-2,3-dihydrofuro[3,2-h]quinoline-8-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
6-(3-Methoxypropoxy)-2?2-dimethyl-2,3-dihydrofuro[3,2-h]quinoline-8-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(S)-pyrrolidin-3-yl amide;
8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacidisopropyl-(S)-pyrrolidin-3-yl amide;
8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(S)-pyrrolidin-3-yl amide;

8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(S)-1 -pyrrolidin-2-ylmethyl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(S)-l-pyrrolidin-2-ylmethyl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl piperidin-2-ylmethyl amide;
8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl piperidin-2-ylmethyl amide;
8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacidazetidin-3-yl isopropyl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-1 -piperidin-3-ylmethyl amide;
8-(3,3-Diniethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-l-piperidin-3-ylmethyl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoIine-2-carboxylicacid isopropyl piperidin-4-yl amide;
8-Cyclohexylmethoxy-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl piperidin-4-yl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isobutyl-(R)-piperidin-3-yl amide;
8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid cyclopentyl-(R)-piperidin-3-yl amide;

8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isobutyl-(R)-piperidin-3-yl amide;
8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid cyclopentyl-(R)-piperidin-3-yl amide.
The embodiment below are illustrative of the present invention and are not intended to limit the claims to the specific embodiments exemplified.
In one embodiment, as depicted in schemes 1 or 2, the compounds of the formula (la) are obtained by converting compound of formula (1) to compound of formula (2) by alkylation at 8-hydroxy group of quinoline ring. Oxidation of methyl group at 2-position followed by further oxidation of carboxaldehyde derivative gives carboxylic acid derivative of formula (4). The compound of formula (4) is coupled with 3-isopropylamino piperidine-1-carboxylic acid tert-butyl ester to get compound of formula (5). Displacement of halogen at 4-position of quinoline ring by corresponding alkoxyalcohol derivative leads to the compound of formula (6), which on removal of N-protecting group gives compound of formula (la).


Alternatively, compound of the formula (la) can be prepared by following the procedure as depicted in scheme 2. Displacement of halogen at 4-position of compound of formula (2) by corresponding alkoxyalcohol derivative gives compound of formula (7). Oxidation of methyl group at 2-position followed by further oxidation of carboxaldehyde derivative gives carboxylic acid derivative of formula (9). Compound of formula (9) is coupled with 3-isopropylamino piperidine-1-carboxylic acid tert-butyl ester to give compound of formula (6), which on removal of N-protecting group gives compound of formula (la).


Scheme 2
In another embodiment, compound of the formula (lb) can be prepared by following the procedure as depicted in scheme 3. Reductive amination between compound of formula (8) and 3-amino piperidine-1-carboxylic acid tert-buty\ ester gives compound of the formula (10), which upon further reductive amination with acetone gives compound of formula (11). Removal of N-protecting group of compound of formula (11) gives compound of formula (lb).


In yet another embodiment, compound of the formula (Ic) can be prepared by following the procedure as depicted in scheme 4. Displacement of halogen of compound of formula (5) by corresponding mercaptoalkyl amide derivative leads to the compound of formula (12). Removal of N-protecting group of compound of formula (12) gives compound of formula (Ic).

In yet another embodiment, compound of the formula (Id) can be prepared by following the procedure as depicted in scheme 5. Alkylation of o-nitrophenol followed by cyclization at high temperature gives compound of formula (16). Alternatively, Claisen rearrangement of alkylated o-nitrophenol of formula (14) followed by its cyclization gives same cyclized derivative of formula (16). Reduction of nitro group followed by reaction with dimethyl acetylene dicarboxylate leads to the formation of corresponding quinoline derivative of formula (18). Conversion of hydroxyl group to halogen derivative followed by hydrolysis of ester gives compound of formula (20). Compound of the formula (20) is coupled with 3-isopropylamino piperidine-1-carboxylic acid tert-butyl ester to give compound of formula (21). Displacement of halogen by corresponding alkoxyalcohol derivative leads to the formation of compound of formula (22). Removal of N-protecting group of compound of formula (22) gives compound of formula (Id).


In yet another embodiment, compound of the formula (Ie) can be prepared by following the procedure as depicted in scheme 6. The compound of formula (4) is coupled with N-isopropylamino derivative in which the amino group is either directly attached to N-boc protected azetidine and pyrrolidine derivatives or via a methylene group to N-boc protected azetidine, pyrrolidine and piperidine derivatives to get compound of formula (23). Displacement of halogen at 4-position of quinoline ring by corresponding alkoxyalcohol derivative leads to the compound of formula (24), which on removal of N-protecting group gives compound of formula (Ie).


In yet another embodiment, compound of the formula' (If) can be prepared by following the procedure as depicted in scheme 7. The compound of formula (4) is coupled with 3-alkylamino piperidine-1 -carboxylic acid tert-buty\ ester to get compound of formula (25). Displacement of halogen at 4-position of quinoline ring by corresponding alkoxyalcohol derivative leads to the compound of formula (26), which on removal of N-protecting group gives compound of formula (If).


EXPERIMENTAL
The following examples serve to illustrate the invention without limiting the invention in its scope. The methods of preparing some of the starting compounds used in the examples are described as reference examples.
General Method of Preparation
The compounds described herein, including compounds of general formula (la), formula (lb), formula (Ic), formula (Id), formula (Ie), and formula (If) can be prepared by techniques known to in the art, for example, through the reaction scheme depicted in Schemes 1-7. Furthermore, in the following examples, where specific acids, bases, reagents, coupling agents, solvents, etc. are mentioned, it is understood that other

suitable acids, bases, reagents, coupling agents etc. may be used and are included within the scope of the present invention. Modifications to reaction conditions, for example, temperature, duration of the reaction or combinations thereof are envisioned as part of the present invention. The compounds obtained by using the general reaction scheme may be of insufficient purity. These compounds can be purified by any of the methods for purification of organic compounds known in the art, for example, crystallization or silica gel or alumina column chromatography using different solvents in suitable ratios.
Example 1
8-Cycloheptyloxv-4-(2-methoxy ethoxy)quinoline-2-carboxvlic acid isopropyl-(R)-piperidin-3-yl amide dihvdrochloride

Step I: Preparation of 4-chloro-8-cycIoheptyloxy-2-methyl quinoline
Method-A: N,N-Di-isopropyIethylamine (9.5 mL, 0.055 mol) is added to a stirred solution of cycloheptanol (4.2 g, 0.036mol) in dichloromethane (42 mL) at room temperature and stirred for 5 minutes. Reaction mixture is cooled to 0-5°C, methanesulphonylchloride (3.4 mL, 0.044 mol) is added dropwise manner to the reaction mixture and stirred for 30 minutes. D. M. water (40 mL) is added to the reaction mixture, organic layer is separated and aqueous layer is extracted with

dichloromethane (2x40 mL). Combined organic layer is washed with D. M. water (1x40 mL) followed by brine solution (1x40 mL) and dried over anhydrous sodium sulphate. Removal of dichloromethane under reduced pressure gives methanesulfonic acid cycloheptyl ester, which is used for the next step without purification.
Potassium carbonate (4.7 g, 0.034 mol) is added to a stirred solution of 4-chloro-2-methyl quinolin-8-ol (3.0 g, 0.016 mol) in N,N-dimethylforrnamide (30 mL) at room temperature and stirred for 15 minutes. Methanesulfonic acid cycloheptyl ester (4.8 g, 0.025 mol) is added to the reaction mixture and heated at 90°C for 5 hrs. Reaction mixture is cooled to room temperature, filtered to remove potassium carbonate and then washed with ethyl acetate (2x50 mL). D. M. water (60 mL) is added to the combined filtrate, organic layer is separated and aqueous layer is extracted with ethyl acetate (2x60 mL). Combined organic layer is washed with D. M. water (1x50 mL) followed by brine solution (1x80 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 8:92) to get 4-chloro-8-cycloheptyl oxy-2-methyl quinoline.
Method-B: Potassium carbonate (17.5 g, 0.126 mol) is added to a stirred solution of 4-chloro-2-methyl quinolin-8-ol (7.0 g, 0.036 mol) in N,N-dimethy]formamide (105 mL) at room temperature and stirred for 15 minutes. Cycloheptyl bromide (10.4 mL, 0.076 mol) is added to the reaction mixture and then heated at 98°C for 7 hrs. Reaction mixture is cooled to room temperature, filter to remove potassium carbonate and washed with ethyl acetate (2x80 mL). Combined filtrate is concentrated under reduced pressure at 60°C to give crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 8:92) to get 4-chloro-8-cycloheptyl oxy-2-methyl quinoline.
Step II: Preparation of 4-ch1oro-8-cycloheptyloxy quinoline-2-carbaldehyde.

Selenium dioxide (1.35 g, 0.012 mol) is added to a stirred solution of 4-chloro-8-cycloheptyloxy-2-methyl quinoline (2.8 g, 0.009 mol) in 1,4-dioxane (28 mL) at room temperature and then heated at 75°C for 40 minutes. Reaction mixture is cooled to room temperature, filtered through celite bed and washed with 1,4-dioxane (3x20 mL). Combined filtrate is concentrated under reduced pressure to get crude solid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 5:95) to furnish 4-chloro-8-cycloheptyloxy quinoline-2-carbaldehyde.
Step III: Preparation of 4-chloro-8-cyclohepty!oxy quinoline-2-carboxylic acid.
An aqueous solution (50 mL) containing sodium chlorite (2.93 g, 0.026 mol, 80%) and sodium dihydrogen orthophosphate dihydrate (8.1 g, 0.052 mol) is added to a heterogeneous solution of 4-chloro-8-cycIoheptyloxy quinoline-2-carbaldehyde (2.6 g, 0.009 mol) in tert-butanol (50 mL) at room temperature and stirred for 1 hr. Dichloromethane (80 mL) followed by D. M. water (20 mL) is added to the reaction mixture and stirred vigorously for 5 minutes. Organic layer is separated and aqueous layer is extracted with dichloromethane (2x25 mL). Combined organic layer is washed with brine solution (1x50 mL) and dried over anhydrous sodium sulphate. Removal of dichloromethane under reduced pressure fiirnishes 4-chloro-8-cycloheptyloxy quinoline-2-carboxylic acid, which is directly used for the next step without further purification.
Step IV: Preparation of (R)-3-[(4-chIoro-8-cycloheptyloxy quinoline-2-carbonyl)-isopropylamino]-piperidine-l-carboxylic acid tert-butyl ester.
Thionyl chloride (1.12 mL, 0.015 mol) is added drop wise to a stirred solution of 4-chloro-8-cydoheptyloxy quinoline-2-carboxylic acid (2.46 g, 0.008 mol) in dichloromethane (28 mL) at room temperature. N,N-Dimethylformamide (0.15 mL, 0.002 mol) is added to the reaction mixture and stirred for 1 hr and 45 minutes.

Reaction mixture is concentrated under reduced pressure at 40°C to get the acid chloride derivative, which is directly used for the next step.
A solution of (R)-3-isopropylamino piperidine-1-carboxylic acid tert-butyl ester (1.86 g, 0.008 mol) and triethylamine (3.2 mL, 0.023 mol) in tetrahydrofuran (20 mL) is added to a stirred solution of 4-chloro-8-cycloheptyloxy quinoline-2-carbonyl chloride in tetrahydrofuran (20 mL) at room temperature and stirred for 2 hrs. Reaction mixture is quenched with D. M. water (10 mL) and concentrated under reduced pressure. Again, D. M. water (50 mL) is added to the residue and extracted with ethyl acetate (3x75 mL). Combined organic layer is washed with saturated sodium bicarbonate solution (1x50 mL) followed by D. M. water (1x50 mL) and brine solution (1x50 mL). Finally, it is dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 15:85) to furnish (R)-3-[(4-chloro-8-cycloheptyloxy quinoline-2-carbonyl)isopropylamino]piperidine-1-carboxylic acid ter/-butyl ester.
Step V: Preparation of (R)-3-{[8-cycloheptyloxy-4-(2-methoxy ethoxy)quinoIine-2-carbonyl]-isopropylamino}piperidine-l-carboxylic acid tert-butyl ester.
Potassium tert-butoxide (0.07 g, 0.0006 mol) is added to a stirred solution of 2-methoxy ethanol (0.04 mL, 0.0006 mol) in dimethyl sulfoxide (4 mL) at room temperature and stirred for 10 minutes. A solution of (R)-3-[(4-chloro-8-cycloheptyloxy quinoline-2-carbonyl)isopropylamino]piperidine-l-carboxylic acid tert-buty\ ester (0.23 g, 0.0004 mol) in dimethyl sulfoxide (4 mL) is added to the reaction mixture at room temperature and stirred for 1 hr. Reaction mixture is cooled to 10-15°C, ethyl acetate (20 mL) followed by D. M. water (15 mL) is added and stirred vigorously for 5 minutes. Organic layer is separated and aqueous layer is extracted with ethyl acetate (2x20 mL). Combined organic layer is washed with D. M.

water (1x15 mL) followed by brine solution (1x15 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 50:50) to get (R)-3-{[8-cycloheptyIoxy-4-(2-methoxy ethoxy) quinoline-2-carbonyl]isopropylamino}piperidine-l-carboxylic acid tert-butyl ester.
Step VI: Preparation of 8-cycloheptyloxy-4-(2~methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide dihydrochloride.
A solution of 4M hydrochloric acid in 1,4-dioxane (0.8 mL) is added to (R)-3-{[8-cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carbonyl]isopropylamino}piperidine -1-carboxylic acid tert-buty\ ester (0.17 g, 0.0003 mol) and stirred for 30 minutes at room temperature. Reaction mixture is concentrated under reduced pressure, residue is dissolved in dichforomethane (2 mL) and again concentrated under reduced pressure at 55°C. Diethyl ether is added to the residue, content is titurated with spatula and then diethyl ether layer is decant-off. Residue is redissolved in dichloromethane, concentrated and dried under reduced pressure to furnish 8-cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide dihydrochloride.
Examples 2-121 are prepared according to the similar procedure as described in Example 1, using appropriate starting material and reagents.
Table 1:


formula (la)

Ex. No. n Y R1 R2 MSCES4) Configuration at (*)
1 1 O CH3 Cycloheptyl 484.30 R
2 1 0 CH3 (R)-Tetrahydrofuran-3-yl 458.3 R
3 1 0 CH3 Benzyl 478.3 R
4 1 0 CH3 Tetrahydrofuran-2-yl methyl 472.32 R
5 1 0 CH3 4-Fluorobenzyl 496.28 R
6 1 0 CH3 (S)-l-(Tetrahydrofuran-2-yl)-methyl 472.31 R
7 1 0 CH3 CH2Cyclohexyl 484.36 R
8 1 o CH3 Tetrahydropyran-4-yl methyl 486.27 R
9 1 0 CH3 CH2CH2CH2Cyclopentyl 498.4 R
10 1 0 CH3 CH2CH2Phenyl 492.26 R
11 1 0 CH3 4-Isopropylcyclohexylmethyl 526.34 R
12 1 0 CH3 4-(4-Chlorophenyl) cyclohexyl-methyl 594.23 R
13 1 0 CH3 CH2CH(CH2CH2CH3)2 500.31 R
14 1 0 CH3 Indan-2-yl 504.32 R
15 1 0 CH3 CH2CH2Cyclohexyl 498.27 R
16 1 0 CH3 4-IsobutyIbenzyl 534.30 R
17 1 0 CH3 4-Isopropylbenzyl 520.27 R
18 1 0 CH3 4-Trifluoromethylbenzyl 546.16 R
19 1 0 CH3 4-Cyclohexylbenzyl 560.31 R
20 1 0 CH3 n-Heptyl 486.23 R
21 1 0 CH3 4-Fluorophenethyl 510.26 R
22 1 0 CH3 CH2CH2CH2CH2COCH3 486.16 R
23 1 o CH3 Cyclooctyl 498.31 R
24 1 0 CH3 Pyridin-2-ylmethyl 479.26 R
25 1 0 CH3 Pyridin-3-ylmethyl 479.31 R
26 1 0 CH3 2-(2-Oxo pyrrolidin-l-yl)ethyl 499.13 R
27 1 0 CH3 CH2CH(OCH3)2 476.12 R
28 1 0 C2H5 CH2Cyclohexyl 498.26 R
29 1 0 C2H5 Cycloheptyl 498.31 R
30 2 0 CH3 Cycloheptyl 498.15 R
31 2 0 CH3 3-FluorobenzyI 510.23 R
32 2 0 CH3 4-Fluorobenzyl 510.31 R
33 2 0 CH3 3-Chlorobenzyl 526.31 R
34 2 0 CH3 3-Tri fluoromethylbenzyl 560.34 R

Ex. No.
n Y R' R2 MS(ES+) Configuration at (*)
35 2 0 CH3 2-Fluorobenzyl 510.29 R
36 2 0 CH3 Benzy] 492.32 R
37 2 0 CH3 Tetrahydrofuran-2-ylmethyl 486.21 R
38 2 0 CH3 (R)-Tetrahydrofuran-3-yl 472.19 R
39 2 0 CH3 2,3-Dichlorobenzyl 560.24 R
40 2 0 CH3 (S)-l-(Tetrahydrofuran-2-yl)-m ethyl 486.20 R
41 2 0 CH3 Cyclooctyl 512.19 R
42 2 0 CH3 n-Heptyl 500.21 R
43 2 0 CH3 CH2Cyclohexyl 498.14 R
44 2 0 C2H5 Cycloheptyl 512.20 R
45 1 0 COOCH3 Cycloheptyl 528.32 R
46 1 0 COOCH3 Cyclopentyl 500.18 R
47 1 0 COOCH3 CH2CyclohexyI 528.23 R
48 1 0 COOCH3 CH2CH(CH3)2 488.20 R
49 1 0 COOC2H5 Cyclopentyl 514.28 R
50 1 0 COOC5H1, Cyclopentyl 556.33 R
51 1 0 COOCH2CH(CH3)2 Cyclopentyl 542.31 R
52 2 0 COOCH3 CH2Cyclohexyl 542.33 R
53 2 0 COOCH3 Cyclopentyl 514.14 R
54 1 0 CH2CH(CH3)2 Cycloheptyl 526.34 R
55 1 0 C3H7 Cycloheptyl 512.33 R
56 1 0 CH2CycIopropyl Cycloheptyl 524.31 R
57 1 0 CH3 CH2COCyclohexyl 512.30 R
58 1 0 CH3 CH2COCH2CH(CH3)2 486.27 R
59 1 0 CH3 CH2COC(CH3)3 486.27 R
60 1 0 CH3 CH2COCH(CH3)2 472.31 R
61 1 0 CH3 CH2COAdamantan-l-yl 564.32 R
62 1 0 CH3 CH2COCyclopentyl 498.12 R
63 1 0 CH3 CH2COCyclopropyl 470.13 R
64 1 0 CH3 2-(4-Chlorophenyl)-2-oxoethyl 540.19 R
65 1 0 CH3 2-Cyclopropyl-1 -(2-fluoro-phenyl)-2-oxoethyl 564.25 R
66 1 0 CH3 2-(3-Chlorophenyl)-2-oxoethyl 540.14 R
67 1 0 CH3 CH2COFuran-2-yl 496.16 R
68 1 0 CH3 CH2COThiophene-2-yl 512.17 R
69 1 0 C2H5 CH2COCH2CH(CH3)2 500.15 R
70 1 0 C2H5 CH2COCyclopentyl 512.13 R

Ex. No.
n Y R' R2 MS(ES+) Configuration at (*)
71 1 0 C2H5 CH2COC(CH3)3 500.29 R
72 1 0 C2H5 CH2COCH(CH3)2 486.28 R
73 2 0 CH3 CH2COC(CH3)3 500.15 R
74 2 0 CH3 CH2COCyclohexyl 526.19 R
75 2 0 CH3 CH2COCH2CH(CH3)2 500.02 R
76 2 0 CH3 CH2COCyclopentyl 512.29 R
77 2 0 CH3 CH2COCH(CH3)2 486.28 R
78 1 0 CH2OCH3 CH2Cyclohexyl 514.29 R
79 1 0 CH2OCH3 CH2CH(CH3)2 474.26 R
80 1 0 CH2OCH3 Cycloheptyl 514.33 R
81 1 0 CH2OCH3 Cyclopentyl 486.24 R
82 1 0 CH2OC2H5 Cyclopentyl 500.31 R
83 2 0 CH2OCH3 CH2Cyclohexyl 528.35 R
84 2 0 CH2OCH3 Cycloheptyl 528.30 R
85 1 0 CH2OCH3 CH2COC(CH3)3 516.26 R
86 1 0 CH2OCH3 CH2COCyclopentyl 528.28 R
87 1 0 CH2OCH3 CH2COCH2CH(CH3)2 516.27 R
88 1 0 CH3 (R)-2-(2,2-Dimethylpropionyl-amino)butyl 543.29 R
89 1 0 CH3 (S)-2-(2,2-Dimethylpropionyl-amino)butyl 543.29 R
90 1 0 CH3 (R)-2-Methanesulfonylamino-butyl 537.22 R
91 1 0 CH3 COOCH2CH(CH3)2 488.25 R
92 1 0 CH3 Cycloheptyl 484.25 S
93 1 0 CH3 CH2COC(CH3)3 486.28 S
94 1 0 CH3 COCH(CH3)2 458.37 R
95 1 0 CH3 COC(CH3)3 472.19 R
96 1 0 CH3 COC4H9 472.18 R
97 1 0 CH3 COC5H11 486.19 R
98 1 0 CH3 COC6Hi3 500.20 R
99 1 0 CH3 COC7H15 514.22 R
100 1 0 CH3 COCyclopropyl 456.11 R
101 1 0 CH3 COCyclopentyl 484.18 R
102 1 0 CH3 COCyclohexyl 498.15 R
103 1 0 CH3 1 -Methylcyclohexanecarbonyl 512.15 R
104 I 0 CH3 Adamantane-1 -carbonyl 550.15 R
105 1 o CH3 COCH2CH2Cyclopentyl 512.13 R

Ex. No.
n Y R1 R' MS(ES+) Configura-tion at ( *)
106 1 0 CH3 4-Fluorobenzoyl 510.12 R
107 2 0 CH3 COC4H9 486.16 R
108 2 0 CH3 COCyclopropyl 470.08 R
109 2 0 CH3 COCyclopentyl 498.12 R
110 2 0 CH3 COCyclohexyl 512.12 R
111 2 0 CH3 COC5H11 500.13 R
112 1 0 CH3 CH2OCH3 432.29 R
113 1 0 CH3 CH2OCH2Ph 508.35 R
114 1 0 CH2Ph CH2Cyclohexyl 560.09 R
115 1 0 CH2COC(CH3)3 CH2Cyclohexyl 568.30 R
116 1 0 COCH3 CH2Cyclohexyl 512.34 R
117 1 0 COCH(CH3)2 CH2Cyclohexy] 540.38 R
118 1 o COC(CH3)3 CH2Cyclohexyl 554.40 R
119 0 Ab 2-Methoxyphenyl Cyclopentyl 518.26 R
120 0 Ab 2,3-DichIoro-phenyl Cyclopentyl 556.11 R
121 0 Ab 2-Trifluoromethyl phenyl Cyclopentyl 556.26 R
Y - Ab - Absent
Example 122

Step I: Preparation of 4-chloro-8-cyclohexylmethoxy-2-methyl quinoline.
[8-Cvclohexvlmethoxv-4-f2-methoxy ethoxy)quinolin-2-vl methvllisopropyl-(R)-piperidin-3-yl amine trihydrochloride

Potassium carbonate (5.84 g, 0.042 mol) is added to a stirred solution of 4-chloro-2-methyl quinoIin-8-ol (2.0 g, 0.01 mol) in N,N-dimethyl form amide (30 mL) at room temperature and stirred for 15 minutes. Cyclohexyl methyl bromide (3.56 mL, 0.026 mol) is added to the reaction mixture and then heated at 90°C for 3 hrs and 30 minutes. Reaction mixture is cooled to 10-I5°C, D. M. water (40 mL) is added to the reaction mixture and extracted with ethyl acetate (3x60 mL). Combined organic layer is washed with brine solution (2x30 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 10:90) to get 4-chloro-8-cyclohexyImethoxy-2-methyl quinoline.
Step II: Preparation of 8-cyclohexylmethoxy-4-(2-methoxyethoxy)-2-methyl quinoline.
Potassium tert-butoxide (0.7 g, 0.006 mol) is added to a stirred solution of 2-methoxy ethanof (0.43 mL, 0.005 mol) in dimethyl sulfoxide (10 mL) at room temperature and stirred for 5 minutes. A solution of 4-chloro-8-cyclohexylmethoxy-2-methyl quinoline (1.2 g, 0.004 mol) in dimethyl sulfoxide (10 mL) is added to the reaction mixture at room temperature and then heated at 60°C for 30 minutes. Reaction mixture is cooled 10-15°C, ethyl acetate (20 mL) followed by D. M. water (15 mL) is added and stirred vigorously. Organic layer is separated and aqueous layer is extracted with ethyl acetate (3x20 mL). Combined organic layer is washed with D. M. water (1x15 mL) followed by brine solution (1x15 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 60:40) to furnish 8-cycIohexylmethoxy-4-(2-methoxy ethoxy)-2-methyl quinoline.

Step III: Preparation of 8-cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carbaldehyde.
Selenium dioxide (0.35 g, 0.003 mol) is added to a stirred solution of 8-cyclohexylmethoxy-4-(2-methoxy ethoxy)-2-methyl quinoline (0.7 g, 0.002 mol) in 1,4-dioxane (10 mL) at room temperature and then heated at 70°C for 30 minutes. Reaction mixture is cooled to room temperature, filtered through celite bed and washed with 1,4-dioxane (3x30 mL). Combined filtrate is concentrated under reduced pressure to get crude solid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 30:70) to furnish 8-cycIohexylmethoxy-4-(2-methoxy ethoxy)quinoline -2-carbaldehyde.
Step IV: Preparation of (R)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy) quinolin-2-ylmethyl]amino}piperidine-l-carboxylic acid tert-buty\ ester.
Glacial acetic acid (0.04 mL, 0.0006 mol) followed by (R)-3-amino piperidine-1-carboxylic acid tert-butyl ester (0.3 g, 0.002 mol) is added to a stirred solution of 8-cyclohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carbaldehyde (0.52 g, 0.002 mol) in dichloromethane (20 mL) at room temperature and stirred for 1 hr. Sodium cyanoborohydride (0.19 g, 0.003 mol) is added to the reaction mixture at room temperature and then stirred for 2 hrs. Reaction mixture is quenched with D. M. water (20 mL), organic layer is separated and aqueous layer is extracted with dichloromethane (2x30 mL). Combined organic layer is washed with brine solution (1x10 mL) and dried over anhydrous sodium sulphate. Removal of dichloromethane under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:methanol, 90:10) to get (R)-3-{[8-cyc!ohexylmethoxy-4-(2-methoxy ethoxy)quinolin-2-ylmethyl]amino}piperidine-1-carboxylic acid tert-butyl ester.

Step V: Preparation of (R)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy) quinolin-2-yl methyl] isopropylamino} piperidine-1-carboxylic acid tert-butyl ester.
Glacial acetic acid (0.04 mL, 0.0006 mol) followed by acetone (0.52 mL) is added to a stirred solution of (R)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy)quinolin-2-ylmethyl]amino}piperidine-l-carboxylic acid tert-butyl ester (0.26 g, 0.0005 mol) in dichloromethane (10 mL) at room temperature and stirred for 1 hr. Sodium cyanoborohydride (0.06 g, 0.001 mol) is added to the reaction mixture at room temperature and then stirred for 2 hrs. Reaction mixture is concentrated under reduced pressure at 45°C, D. M. water (15 mL) is added to the residue and this aqueous layer is extracted with dichloromethane (2x30 mL). Combined organic layer is washed with brine solution (1x10 mL) and dried over anhydrous sodium sulphate. Removal of dichloromethane under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:methanol, 96:4) to get (R)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy) quinolin-2-yl methyl] isopropyl amino} piperidine-1-carboxylic acid tert-butyl ester.
Step VI: Preparation of [8-cyclohexylmethoxy-4-(2-methoxyethoxy)quinolin-2-yl methyl]isopropyI-(R)-piperidin-3-yI amine trihydrochloride.
A solution of 4M hydrochloric acid in 1,4-dioxane (1 mL) is added to (R)-3-{[8-cyclo hexy!methoxy-4-(2-methoxyethoxy)quinolin-2-yl methyl]isopropylamino}piperidine-1-carboxylic acid tert-butyl ester (0.18 g, 0.0003 mol) at room temperature and stirred for 30 minutes. Reaction mixture is concentrated under reduced pressure, residue is dissolved in dichloromethane (2 mL) and again concentrated under reduced pressure at 55°C. Diethyl ether is added to the residue, content is titurated with spatula and then diethyl ether layer is decant-off. Residue is redissolved in dichloromethane, concentrated and dried under reduced pressure to furnish [8-cyclohexylmethoxy-4-(2-

methoxy ethoxy) quinolin-2-ylmethyl] isopropyl-(R)-piperidin-3-yl amine trihydrochloride.
Examples 123 and 124 are prepared according to the similar procedure as described in Example 122, using appropriate starting material and reagents.

Ex. No. D Y R1 R2 MS(ES+) Configuration at (*)
122 1 0 CH3 CH2Cyclohexyl 470.19 R
123 1 0 CH3 Cyclopentyl 442.15 R
124 1 o CH3 Cycloheptyl 470.20 R
Example 125
4-(2-Acetylamino ethvlsulfanyl)-8-cyclopentylmethoxy quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-vl amide dihvdrochloride


Step I: Preparation of 4-chloro-8-cyclopentylmethoxy-2-methyl quinoline.
N,N-Di-isopropylethylamine (1.8 mL, 0.011 mol) is added to a stirred solution of cyclopentylmethanol (0.7 g, 0.007 mol) in dichloromethane (10 mL) at room temperature and stirred for 5 minutes. Reaction mixture is cooled to 0-5°C, methanesulphonylchloride (0.65 mL, 0.008 mol) is added dropwise to the reaction mixture and stirred for 30 minutes. D. M. water (10 mL) is added to the reaction mixture, organic layer is separated and aqueous layer is extracted with dichloromethane (2x20 mL). Combined organic layer is washed with D. M. water (1x10 mL) followed by brine solution (1x10 mL) and dried over anhydrous sodium sulphate. Removal of dichloromethane under reduced pressure gives methane sulfonic acid cyclopentylmethyl ester, which is used directly for the next step.
Potassium carbonate (1.5 g, 0.011 mol) is added to a stirred solution of 4-chloro-2-methyl quinolin-8-oI (1.05 g, 0.005 mol) in N,N-dimethylformamide (8 mL) at room temperature and stirred for 15 minutes. A solution of methanesulfonic acid cyclopentylmethyl ester (1.25 g, 0.007 mol) in N,N-dimethyl formamide (7 mL) is added to the reaction mixture and then heated at 90°C for 5 hrs. Reaction mixture is cooled to 10-15°C, D. M. water (25 mL) is added and extracted with ethyl acetate (3x30 mL). Combined organic layer is washed with brine solution (2x30 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel

230-400 mesh, ethyl acetate:n-hexane, 10:90) to get 4-chloro-8-cyclopentylmethoxy-2-methyl quinoline.
Step II: Preparation of 4-chloro-8-cyclopentylmethoxy quinoline-2-carbaldehyde.
Selenium dioxide (0.5 g, 0.004 mol) is added to a stirred solution of 4-chloro-8-cyclopentylmethoxy-2-methyl quinoline (1.05 g, 0.004 mol) in 1,4-dioxane (15 mL) at room temperature and then heated at 80°C for 15 minutes. Reaction mixture is cooled to room temperature, filtered through celite bed and washed with 1,4-dioxane (3x20 mL). Combined filtrate is concentrated under reduced pressure to get crude solid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 6:94) to furnish 4-chloro-8-cyclopentylmethoxy quinoline-2-carb aldehyde.
Step III: Preparation of 4-chloro-8-cyclopentylmethoxy quinoline-2-carboxyIic acid.
An aqueous solution (8 mL) containing sodium chlorite (0.67 g, 0.006 mot, 80%) and sodium dihydrogen orthophosphate dihydrate (1.87 g, 0.012 mol) is added to a heterogeneous solution of 4-chloro-8-cyclopentylmethoxy quinoline-2-carbaldehyde (0.58 g, 0.002 mol) in tert-butanol (15 mL) at room temperature and stirred for 2 hrs. Dichloromethane (25 mL) followed by D.M. water (20 mL) is added to the reaction mixture and stirred for 5 minutes. Organic layer is separated and aqueous layer is extracted with dichloromethane (2x25 mL). Combined organic layer is washed with brine solution (1x25 mL) and dried over anhydrous sodium sulphate. Removal of dichloromethane under reduced pressure furnishes 4-chloro-8-cyclopentylmethoxy quinoline-2-carboxylic acid, which is directly used for the next step without purification.

Step IV: Preparation of (R)-3-[(4-chIoro-8-cyclopentylmethoxy quinoIine-2-carbonyl)isopropylamino]piperidine-l-carboxylic acid tert-butyl ester.
Oxalyl chloride (0.32 mL, 0.004 mol) is added dropwise to a stirred solution of 4-chloro-8-cyclopentylmethoxy quinoline-2-carboxyIic acid (0.54 g, 0.002 mol) in dichloro methane (20 mL) at room temperature. N,N-Dimethylformamide (0.02 mL, 0.0003 mol) is added to the reaction mixture and stirred for 30 minutes. Reaction mixture is concentrated under reduced pressure at 40°C to get acid chloride derivative, which is directly used for the next step.
A solution of (R)-3-isopropylamino piperidine-1-carboxylic acid tert-buty\ ester (0.5 g, 0.002 mol) and triethylamine (0.79 mL, 0.006 mol) in tetrahydrofiiran (10 mL) is added to a stirred solution of 4-chloro-8-cyclopentylmethoxy quinoiine-2-carbonyl chloride in tetrahydrofiiran (5 mL) at room temperature and stirred for 2 hrs. Reaction mixture is quenched with D. M. water (5 mL) and concentrated under reduced pressure. Again, D. M. water (15 mL) is added to the residue and extracted with ethyl acetate (3x25 mL). Combined organic layer is washed with saturated sodium bicarbonate solution (1x20 mL) followed by D. M. water (1x20 mL) and brine solution (1x20 mL). Finally, it is dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate :n-hexane, 25:75) to furnish (R)-3-[(4-chloro-8-cyclopentylmethoxy quinoline-2-carbonyl) isopropylamino]-piperidine-1-carboxylic acid tert-butyl ester.
Step V: Preparation of (R)-3-{[4-(2-acetylamino ethylsulfanyl)-8-cyclopentyI methoxy quinoline-2-carbonyl]isopropylamino}piperidine-l-carboxylic acid tert-butyl ester.
Potassium tert-butoxide (0.09 g, 0.0008 mol) is added to a stirred solution of N-(2-mercaptoethyl) acetamide (0.09 g, 0.0008 mol) in dimethylsulfoxide (3 mL) at room

temperature and stirred for 10 minutes. A solution of (R)-3-[(4-chloro-8-cyclopentyl methoxy quinoline-2-carbonyl)isopropyl amino]piperidine-l-carboxylic acid tert-butyl ester (0.2 g, 0.0004 mol) in dimethylsulfoxide (3 mL) is added to the reaction mixture at room temperature and then heated at 60°C for 30 minutes. Reaction mixture is cooled to 10-15°C, ethyl acetate (15 mL) followed by D. M. water (15 mL) is added and stirred for 5 minutes. Organic layer is separated and aqueous layer is extracted with ethyl acetate (3x25 mL). Combined organic layer is washed with D. M. water (1x20 mL) followed by brine solution (1x20 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure at 50°C gives crude solid, which is purified by column chromatography (silica gel 230-400 mesh, dichloromethane:methanol, 96:4) to get (R)-3-{[4-(2-acetylamino ethylsulfanyl)-8-cyclopentyl methoxy quinoline-2-carbonyl]isopropyl amino}piperidine-l-carboxylic acid tert-butyl ester.
Step VI: Preparation of 4-(2-acetylaminoethylsulfanyl)-8-cycIopentylmethoxy quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yI amide dihydrochloride.
A solution of 4M hydrochloric acid in 1,4-dioxane (1.8 mL) is added to (R)-3-{[4-(2-acetylaminoethylsulfanyl)-8-cyclopentylmethoxy quinoline-2-carbonyl] isopropyl-amino}piperidi.ne-l-carboxylic acid tert-butyl ester (0.18 g, 0.0003 mol) at room temperature and stirred for 30 minutes. Reaction mixture is concentrated under reduced pressure, residue is dissolved in dichloromethane:methnol mixture (50:50, 2 mL) and again concentrated under reduced pressure at 58°C. Diethyl ether is added to the residue, content is titurated with spatula and then diethyl ether layer is decant-off. Residue is redissolved in dichloromethane:methnol mixture (50:50, 2 mL), concentrated and dried under reduced pressure to furnish 4-(2-acetylamino ethylsulfanyl)-8-cyclopentylmethoxy quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide dihydrochloride.

Examples 126-129 are prepared according to the similar procedure as described in Example 125, using appropriate starting material and reagents.
Table 3:

Ex. No. n R' R2 MS (ES+) Configura-tion ai ( * )
125 COCH3 CH2Cyclopentyl 513.33 R
126 COCH3 Cyclopentyl 499.22 R
127 SO2CH3 Cyclopentyl 535.26 R
128 COCH3 Benzyl 521.21 R
129 COPh Cyclopentyl 561.35 R
Example 130
6-(2-Methoxv ethoxy)-2-methyl furo[3,2-hlquinoline-8-carboxylic acid isopropvl-(R)-piperidin-3-vlamide dihydrochloride

Step I: Preparation of l-nitro-2-prop-2-ynyloxy benzene.
Potassium carbonate (19.8 g, 0.144 mol) is added to a stirred solution of 2-nitro phenol (10.0 g, 0.071 mol) in N,N-dimethylformarnide (100 m L) at room temperature

and stirred for 15 minutes. Propargyl bromide (10.4 mL, 0.093 mol) is added to the reaction mixture and then heated at 65°C for 30 minutes. Reaction mixture is cooled to room temperature, filtered to remove potassium carbonate and then washed with ethyl acetate (2x50 mL). D. M. water (100 mL) is added to the combined filtrate, organic layer is separated and aqueous layer is extracted with ethyl acetate (2x100 mL). Combined organic layer is washed with D. M. water (1x50 mL) followed by brine solution (1x80 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure at 50°C to get l-nitro-2-prop-2-ynyloxy benzene, which is used for the next step without purification.
Step II: Preparation of 2-methyl-7-nitro benzofuran.
A stirred solution of l-nitro-2-prop-2-ynyloxy benzene (15.6 g, 0.088 mol) in polyethylene glycol-200 (39 mL) is heated at 220°C for 1 hr and 30 minutes under nitrogen atmosphere. Reaction mixture is cooled to room temperature, poured into ice-water mixture (-100 mL) and then aqueous layer is extracted with diethyl ether (3x200 mL). Combined organic layer is dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain crude solid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 8:92) to get 2-methyl-7-nitro benzofuran.
Step III: Preparation of 2-methyl benzofuran-7-ylamine.
Stannous chloride (13.2 g, 0.07 mol) is added to a stirred solution of 2-methyl-7-nitro benzofuran (4.1 g, 0.023 mol) in methanol (41 mL) at room temperature. Concentrated hydrochloric acid (20.6 mL) is added to the reaction mixture and then heated at 75°C for 30 minutes. Methanol is removed under reduced pressure, D. M. water (30 mL) is added to the residue and reaction mixture is basified (pH~9) using aqueous sodium hydroxide solution (25%, 75 mL) at 0-5°C. It is then extracted with ethyl acetate (3x100 mL). Combined organic layer is washed with brine solution

(1x50 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:toluene, 2:98) to get 2-methyl benzofuran-7-ylamine.
Step IV: Preparation of 6-hydroxy-2-methyI furo[3,2-h]quinoline-8-carboxyIic acid methyl ester.
Dimethyl acetylenedicarboxylate (2.33 mL, 0.019 mol) is added to a solution of 2-methyl benzofuran-7-ylamine (2.8 g, 0.019 mol) in methanol (42 mL) at room temperature and stirred for 30 minutes. Reaction mixture is concentrated under reduced pressure at 50°C, the resulting liquid is added dropwise to a pre-heated solution of diphenyl ether (23 mL) at 250°C and then heating is continued for 15 minutes. Reaction mixture is cooled to room temperature, petroleum ether (40 mL) is added to it and stirred for 10 minutes. Petroleum ether layer is decanted and the crude material is purified by column chromatography (silica gel 230-400 mesh, dichloromethane:methanol, 98:2) to get 6-hydroxy-2-methyl furo[3,2-h]quinoline-8-carboxylic acid methyl ester.
Step V: Preparation of 6-chloro-2-methyl furo[3,2-h]quinoline-8-carboxylic acid methyl ester.
Thionyl chloride (1.0 mL, 0.014 mol) is added dropwise to a solution of 6-hydroxy-2-methyl furo[3,2-h]quinoline-8-carboxylic acid methyl ester (2.2 g, 0.008 mol) in dichloromethane (22 mL) at room temperature. N,N-Dimethylformarnide (0.97 mL, 0.013 mol) is added to the reaction mixture and then heated at 55°C for 1 hr and 30 minutes. Reaction mixture is cooled to room temperature and slowly added to saturated sodium bicarbonate solution (30 mL) at 0-5°C. Organic layer is separated and aqueous layer is extracted with dichloromethane (2x50 mL). Combined organic layer is washed with brine solution (1x50 mL) and dried over anhydrous sodium

sulphate. Removal of dichloromethane under reduced pressure gives crude solid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 50:50) to get 6-chloro-2-methyI furo[3,2-h]quinoIine-8-carboxylic acid methyl ester.
Step VI: Preparation of 6-chloro-2-methyl furo[3,2-h]quinoline-8-carboxylic acid.
An aqueous solution (22.4 mL) of lithium hydroxide monohydrate (0.54 g, 0.013 mol) is added to a stirred solution of 6-chloro-2-methyl furo[3,2-h]quinoline-8-carboxylic acid methyl ester (1.45 g, 0.005 mol) in methanol (33.7 mL) at room temperature and then heated at 60°C for 1 hr. Methanol is removed under reduced pressure, D. M. water (12 mL) is added to the residue and aqueous layer is acidified (pH~6) using IN hydrochloric acid solution at 0-5°C. Solid precipitate thus obtained is filtered, washed with acetone (1x10 mL) and dried under reduced pressure to get 6-chloro-2-methyl furo[3,2-h]quinoline-8-carboxylic acid, which is used directly for the next step.
Step VII: Preparation of (R)-3-[(6-chloro-2-methyI furo[3,2-h]quinoline-8-carbonyl)isopropylamino]piperidine-l-carboxylic acid tert-butyl ester.
Oxalyl chloride (0.3 mL, 0.003 mol) is added dropwise to a stirred solution of 6-chIoro-2-methyl furo[3,2-h]quinoline-8-carboxyIic acid (0.45 g, 0.002 mol) in dichloromethane (10 mL) at room temperature. N,N-Dimethylformamide (0.02 mL, 0.0003 mol) is added to the reaction mixture and stirred for 30 minutes. Reaction mixture is concentrated under reduced pressure at 40°C to get acid chloride derivative, which is directly used for the next step.
A solution of (R)-3-isopropylamino piperidine-1-carboxylic acid tert-buty\ ester (0.4 g, 0.002 mol) and triethylamine (0.7 mL, 0.005 mol) in tetrahydrofuran (5 mL) is

added to a stirred solution of 6-chloro-2-methyl furo[3,2-h]quinoIine-8-carbonyl chloride in tetrahydrofuran (5 mL) at room temperature and stirred for 2 hrs. Reaction mixture is quenched with D. M. water (5 mL) and concentrated under reduced pressure. Again, D. M. water (15 mL) is added to the residue and aqueous layer is extracted with ethyl acetate (3x40 mL). Combined organic layer is washed with saturated sodium bicarbonate solution (1x20 mL) followed by D. M. water (1x20 mL) and brine solution (1x20 mL). Removal of ethyl acetate layer under reduced pressure after drying over anhydrous sodium sulphate gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate :n-hexane, 30:70) to furnish (R)-3-[(6-chloro-2-methyl furo[3,2-h]quinoline-8-carbonyl)isopropylamino]-piperidine-1-carboxylic acid tert-butyl ester.
Step VIII: Preparation of (R)-3-{isopropyl-[6-(2-methoxy ethoxy)-2-methyl furo [3,2-h]quinoline-8-carbonyl]amino}piperidine-l-carboxylic acid tert-butyl ester.
Potassium tert-butoxide (0.08 g, 0.0007 mol) is added to a stirred solution of 2-methoxy ethanol (0.05 mL, 0.0007 mol) in dimethyl sulfoxide (4 mL) at room temperature and stirred for 5 minutes. A solution of (R)-3-[(6-chloro-2-methyl furo[3,2-h]quinoline-8-carbonyl)isopropylamino]piperidine-l-carboxylic acid tert-butyl ester (0.25 g, 0.0005 mol) in dimethyl sulfoxide (4 mL) is added to the reaction mixture at room temperature and stirred for 1 hr. Reaction mixture is cooled to 10-15°C, ethyl acetate (25 mL) followed by D. M. water (12 mL) is added to the reaction mixture and stirred vigorously for 5 minutes. Organic layer is separated and aqueous layer is extracted with ethyl acetate (2x25 mL). Combined organic layer is washed with D. M. water (1x20 mL) followed by brine solution (1x20 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure at 50°C gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 65:35) to get (R)-3-{isopropyl-[6-(2-methoxy ethoxy)-

2-methyl furo[3,2-h]quinoline-8-carbonyl]amino}piperidine-l-carboxylic acid tert-butyl ester.
Step IX: Preparation of 6-(2-methoxy ethoxy)-2-methyl furo[3,2-h]quinoline-8-carboxylic acid isopropyl-(R)-piperidin -3-yl amide dihydrochloride.
A solution of 4M hydrochloric acid in 1,4-dioxane (0.9 mL) is added to (R)-3-{isopropyl-[6-(2-methoxy ethoxy)-2-methyl furo[3,2-h]quinoline-8-carbonyl]amino} piperidine-1-carboxylic acid tert-butyl ester (0.16 g, 0.0003 mol) at room temperature and stirred for 30 minutes. Reaction mixture is concentrated under reduced pressure, residue is dissolved in dichloromethane:methanol mixture(50:50, 2 mL) and again concentrated under reduced pressure at 55°C. Diethyl ether is added to the residue, content is titurated with spatula and then diethyl ether layer is decant-off. Residue is redissolved in dichloromethane:methanol mixture(50:50, 2 mL), concentrated and dried under reduced pressure to furnish 6-(2-methoxy ethoxy)-2-methyl furo[3,2-h] quinoline-8-carboxylic acid isopropyl-(R)-piperidin -3-yl amide dihydrochloride.
Examples 131-133 are prepared according to the similar procedure as described in Example 130, using appropriate starting material and reagent.
Table 4:


Ex. No. n Y R1 Ring 'c' MS(ES+) Configuration at (* )
130 1 O CH3 426.26 R
131 2 O CH3 440.15 R
132 1 0 CH3 442.32 R
133 2 0 CH3 456.19 R
Example 134
8-Cyclohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid
isopropvl-(S)-pyrrolidin-3-yl amide dihydrochloride

Step I: Preparation of (S)-3-[(4-chIoro-8-cyclohexylmethoxyquinoline-2-carbonyl)-isopropylamino]pyrrolidine-l-carboxyIic acid tert-butyl ester.
Thionyl chloride (0.18 mL, 0.003 mol) is added dropwise to a stirred solution of 4-chloro-8-cyclohexylmethoxy quinoline-2-carboxylic acid (0.4 g, 0.001 mol) in dichloromethane (8 mL) at room temperature. N,N-Dimethylforrnamide (0.05 mL,

0.0006 mol) is added to the reaction mixture and heated at 50°C for 1 hr. Reaction mixture is concentrated under reduced pressure at 40°C to get acid chloride derivative, which is directly used for the next step.
A solution of (S)-3-isopropylamino pyrrolidine-1-carboxylic acid tert-butyl ester (0.29 g, 0.001 mol) and triethylamine (0.52 mL, 0.004 mol) in tetrahydrofuran (5 mL) is added to a stirred solution of 4-chloro-8-cyclohexylmethoxy quinoline-2-carbonyl chloride in tetrahydrofuran (5 mL) at room temperature and stirred for 2 hrs. Reaction mixture is quenched with D. M. water (5 mL) and concentrated under reduced pressure. Again, D. M. water (10 mL) is added to the residue and extracted with ethyl acetate (3x25 mL). Combined organic layer is washed with saturated sodium bicarbonate solution (1x20 mL) followed by D. M. water (1x20 mL) and brine solution (1x20 mL). Finally, it is dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 20:80) to furnish (S)-3-[(4-chloro-8-cyclohexylmethoxy quinoline-2-carbonyl) isopropylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester.
Step II: Preparation of (S)-3-{[8-cyclohexyImethoxy-4-(2-methoxy ethoxy) quinoIine-2-carbonyl]isopropylamino}pyrroIidine-l-carboxylic acid tert-butyl ester.
Potassium tert-butoxide (0.11 g, 0.001 mol) is added to a stirred solution of 2-methoxy ethanol (0.07 mL, 0.0009 mol) in dimethyl sulfoxide (3 mL) at room temperature and stirred for 10 minutes. A solution of (S)-3-[(4-chloro-8-cyclohexylm ethoxy quinoline-2-carbonyl)isopropylamino]pyrrolidine-l-carboxylic acid tert-butyl ester (0.39 g, 0.0007 mol) in dimethyl sulfoxide (4 mL) is added to the reaction mixture at room temperature and stirred for 1 hr. Reaction mixture is cooled to 10-15°C, ethyl acetate (20 mL) followed by D. M. water (15 mL) is added and

stirred vigorously for 5 minutes. Organic layer is separated and aqueous layer is extracted with ethyl acetate (2x20 mL). Combined organic layer is washed with D. M. water (1x15 mL) followed by brine solution (1x15 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 60:40) to get (S)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carbonyl]isopropyIamino}pyrrolidine-l-carboxyIic acid ter/-butyl ester.
Step III: Preparation of 8-cyclohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(S)-pyrrolidin-3-yl amide dihydrochloride,
A solution of 4M hydrochloric acid in 1,4-dioxane (1.3 mL) is added to (S)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carbonyl]isopropylamino}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.26 g, 0.0005 mol) at room temperature and stirred for 30 minutes. Reaction mixture is concentrated under reduced pressure, residue is dissolved in dichloromethane (2 mL) and again concentrated under reduced pressure at 55°C. Diethyl ether is added to the residue, content is titurated with spatula and then diethyl ether layer is decant-off. Residue is redissolved in dichloromethane, concentrated and dried under reduced pressure to furnish 8-cyclohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(S)-pyrro!idin-3-yl amide dihydrochloride.
Examples 135-145 are prepared according to the similar procedure as described in Example 134, using appropriate starting material and reagent.
Table 5:

Ex.No. n Y ml m2 m3 R1 R2 MS(ES4) Configuration at (*)
134 1 0 0 2 1 CH3 CH2CyclohexyI 470.23 S
135 1 0 0 2 1 CH3 Cycloheptyl 470.27 S
136 1 0 0 2 1 CH3 CH2COC(CH3)3 472.20 S
137 1 0 1 3 0 CH3 Cycloheptyl 484.24 s
138 1 0 1 3 0 CH3 CH2Cyclohexyl 484.25 s
139 1 0 1 4 0 CH3 CH2Cyclohexyl 498.30 RS
140 1 0 1 4 0 CH3 Cycloheptyl 498.21 RS
141 1 0 0 1 1 CH3 Cycloheptyl 456.23 ~
142 1 0 1 3 1 CH3 CH2Cyclohexyl 498.26 R
143 1 0 1 3 1 CH3 CH2COC(CH3)3 500.38 R
144 1 0 0 2 2 CH3 CH2Cydohexyl 484.08 —
145 2 0 0 2 2 CH3 CH2CycIohexyl 498.13 __
Example 146
8-CYclohexylmethoxv-4-(2-methoxv ethoxv)quinoline-2-carboxylic acid isobutyl-(R)-piperidin-3-vl amide dihydrochloride

Step I: Preparation of (R)-3-[(4-chloro-8-cycIohexylmethoxy quinoline-2-carbonyl) isobutylamino] piperidine-l-carboxylic acid tert-butyl ester.

Thionyl chloride (0.2 mL, 0.003 mo!) is added dropwise to a stirred solution of 4-chloro-8-cyclohexylmethoxy quinoline-2-carboxylic acid (0.3 g, 0.0009 mol) in dichloromethane (10 mL) at room temperature. N,N-Dimethylformamide (0.01 mL, 0.0002 mol) is added to the reaction mixture and heated at 60°C for 1 hr. Reaction mixture is concentrated under reduced pressure at 40°C to get the acid chloride derivative, which is directly used for the next step.
A solution of (R)-3-isobutylamino piperidine-1-carboxylic acid tert-buty\ ester (0.24 g, 0.0009 mol) and triethylamine (0.4 mL, 0.003 mol) in tetrahydrofuran (6 mL) is added to a stirred solution of 4-chloro-8-cyclohexylmethoxy quinoline-2-carbonyl chloride in tetrahydrofuran (6 mL) at room temperature and stirred for 2 hrs. Reaction mixture is quenched with D. M. water (10 mL) and concentrated under reduced pressure. Again, D. M. water (50 mL) is added to the residue and extracted with ethyl acetate (3x75 mL). Combined organic layer is washed with saturated sodium bicarbonate solution (1x50 mL) followed by D. M. water (1x50 mL) and brine solution (1x50 mL). Finally, it is dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 20:80) to furnish (R)-3-[(4-chloro-8-cyclohexylmethoxy quinoline-2-carbonyl) isobutylamino] piperidine-1-carboxylic acid tert-buty\ ester.
Step II: Preparation of (R)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy) quinoIine-2-carbonyl]isobutylamino}piperidine-l-carboxylic acid tert-buty\ ester.
Potassium tert-butoxide (0.08 g, 0.0007 mol) is added to a stirred solution of 2-methoxy ethanol (0.06 mL, 0.0008 mol) in dimethyl sulfoxide (4 mL) at room temperature and stirred for 10 minutes. A solution of (R)-3-[(4-chloro-8-cyclohexylmethoxy quinoline-2-carbonyl)isobutylamino]piperidine-l-carboxylic acid

tert-butyl ester (0.32 g, 0.0006 mol) in dimethyl sulfoxide (4 mL) is added to the reaction mixture at room temperature and stirred for 1 hr. Reaction mixture is cooled to 10-15°C, ethyl acetate (20 mL) followed by D. M. water (15 mL) is added and stirred vigorously for 5 minutes. Organic layer is separated and aqueous layer is extracted with ethyl acetate (2x20 mL). Combined organic layer is washed with D. M. water (1x15 mL) followed by brine solution (1x15 mL) and dried over anhydrous sodium sulphate. Removal of ethyl acetate under reduced pressure gives crude liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane, 50:50) to get (R)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy) quinoline-2-carbonyl]isobutylamino}piperidine-l-carboxylic acid tert-butyl ester.
Step III: Preparation of 8-cydohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isobutyl-(R)-piperidin-3-yl amide dihydrochloride.
A solution of 4M hydrochloric acid in 1,4-dioxane (1.3 mL) is added to (R)-3-{[8-cyclohexylmethoxy-4-(2-methoxy ethoxy) quinoline-2-carbonyl] isobutylamino} piperidine-1-carboxylic acid tert-butyl ester (0.26 g, 0.0004 mol) and stirred for 30 minutes at room temperature. Reaction mixture is concentrated under reduced pressure, residue is dissolved in dichloromethane (2 mL) and again concentrated under reduced pressure at 55°C. Diethyl ether is added to the residue, content is titurated with spatula and then diethyl ether layer is decant-off. Residue is redissolved in dichloromethane, concentrated and dried under reduced pressure to furnish 8-cyclohexylmethoxy-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isobutyl-(R)-piperidin-3-yl amide dihydrochloride.
Examples 147-149 are prepared according to the similar procedure as described in Example 146, using appropriate starting material and reagents.
Table 6:

Example
No. n Y R R1 R2 MS(ES+) Configura-tion at ( *)
146 1 0 CH2CH(CH3)2 CH3 CH2Cyclohexyl 498.25 R
147 1 0 Cyclopentyl CH3 CH2Cyclohexyl 510.28 R
148 1 0 CH2CH(CH3)2 CH3 CH2COC(CH3)3 50031 R
149 1 0 Cyclopentyl CH3 CH2COC(CH3)3 512.35 R
Measurement of human renin inhibition :
The inhibitory effect of the NCEs on Human Renin was evaluated using the SensoLyte®520 Renin Assay Kit (Catalog No.- 72040) from Anaspec. Test compound/vehicle was preincubated with recombinant human renin for 30 minutes at 37°C in a 96-well plate. Renin Substrate was added and incubated for another 15 minutes, after which the fluorescence intensity was measured on Multimode Reader at 490nm as Excitation/Emission = 490nm/520nm. All the reagents were prepared and used according to the kit literature. The results of some representative compounds of the present invention measured according to the above-mentioned method are shown in Table 7.
Table 7: Human renin inhibitory activity

Example No. % inhibition
1 93.53a

17 86.39a
29 97 97 a
75 84.41a
80 98.46a
124 56.64 b
125 93.21a
131 58.67b
133 49.90b
134 45.23 b
147 81.05b
149 71.11 b
a% inhibition at 10 nM; b% inhibition at/ 100 nM
All publications and patent applications cited in this application are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated herein by reference.

We claim:
1. A compound of formula (I),

or pharmaceutically acceptable salt thereof,
wherein;
X is selected from O or S;
Y is bond or a group selected from 0 or NH, with the proviso that Y is NH when X is S;
Z is a group selected from -CO, -CH2;
R is selected from the group consisting of substituted or unsubstituted -C1-5-linear or
branched alkyl -C3-8-cycloalkyl and cycloalkylalkyl; wherein cycloalkyl group
may be optionally substituted with C1-3 -linear or branched alkyl group;
R1 is selected from the group consisting of substituted or unsubstituted -C].8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-aIkyl, -(CH2)qO-C3.i2-cycloalkyl, -(CH2)qCO-C1-8-alkyt, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3_12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02Ct.8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical, and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, and 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6
R2 is selected from the group consisting of substituted or unsubstituted -C1-12-linear or branched alkyl - -(CH2)q-C3-]2-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloaIkyl, -(CH2)qCO-aryl, - (CH2)qCO-heteroaryl, -COC1-8-alkyl, -COC-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyI, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6, with proviso that R2 is -C7-12-linear or branched alkyl when Z is -CO,;

R3 is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted -C1-8-alkyl, -C3-12-cycloalkyl;
or OR and R together with the carbon atom to which they are attached form a 3 to 6-
membered cyclic ring system, ring 'c' of the formula with optional
one or more double bond, R" is a substitutent selected from -C1-8-alkyl or -C3-12-cycloalkyl and 'p' is an integer selected from 0, 1 or 2;
V is an integer selected from 0, 1 and 2;
'm1', 'm2 and 'm3' are integers independently selected from 0, 1, 2, 3 and 4;
( * ) at the ring carbon, indicate (R) or (S) configuration or a racemate (RS). 2. A compound of formula (la),

or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl) cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alky1, -COOC3-I2-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-linear or
branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-

cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8alkyl, -(CH2)qCO-C3-l2-cycloa!kyl, -(CH2)qCO-aryl, - (CH2)qCO-heteroaryl, -COCus-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3,4, 5 or 6;
'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (5) configuration or racemate (RS).
3. A compound of formula (lb),

or pharmaceutical^ acceptable salt thereof,
wherein;
Y is bond or oxygen (0);
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or
branched alkyl, -(CH2)q-C3_12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-
cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryI, -COC1-8-alkyl, -COC3-12-cycloalkyI, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;

V is an integer selected from 0, 1 and 2; ( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS).
4. A compound of formula (Ic),

or pharmaceutically acceptable salt thereof,
wherein;
R is selected from the group consisting of substituted or unsubstituted -Ci.s-Hnear or branched alkyl, -C3.12-cycloalkyl, cycloalkylalkyl, -(CH2)qO-C1-8-alkyI, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryI, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-aIkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
R is selected from the group consisting of substituted or unsubstituted -C1-8-Hnear or
branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-
cycloalkyl, -(CH2)qO-ara1kyl, -(CH2)qCO-C1-8-alkyl) -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-a1kyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
V is an integer selected from 0, 1 and 2; ( * ) at the piperidin-3-yl carbon, indicate (R) or (5) configuration or racemate (RS).
5. A compound of formula (Id),


or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (0);
R1 is selected from the group consisting of substituted or uns'ubstituted -Cus-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl,-(CH2)qO-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COCus-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
ring 'c' of the formula , contains optionally one or more double bond;
R" is a substituted selected from -C1-8-alkyl or -C3-12-cycloa|kyl and 'p' is an integer selected from 0, 1 or 2;
'n' is an integer selected from 0, 1 and 2;
( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS).
6. A compound of formula (Ie),


formula (Ie)
or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (0);
X is selected from 0 or S;
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)q(D-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -toC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1,2, 3, 4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-linear or
branched alkyl, -(CH2)q-C3-12-cycloalkyl, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-
cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycIoalkyl, -(CH2)qCO-ary!, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from O, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3, 4, 5 or 6;
'n' is an integer selected from 0, I and 2;
'm1', 'm2' and 'm are integers independently selected from 0, I, 2, 3 and 4;
( * ) at the ring carbon indicate (R) or (5) configuration or racemate (RS). 7. A compound of formula (If),


or pharmaceutically acceptable salt thereof,
wherein;
Y is bond or oxygen (O);
R is selected from the group consisting of substituted or unsubstituted -C1-5-linear or branched alkyl, -C3-8-cycloalkyl and cycloalkylalkyl; wherein cycloalkyl group may be optionally substituted with C1-3-linear or branched alkyl group.
R1 is selected from the group consisting of substituted or unsubstituted -C1-8-linear or branched alkyl, -C3-12-cycloalkyl, cycloalkylalkyl, -(CH2)q(j)-C1-8-alkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-12-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, -S02C1-8-alkyl, -S02-aryl, aryl, aralkyl, heteroaryl, and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, 1, 2, 3,4, 5 or 6;
R2 is selected from the group consisting of substituted or unsubstituted -C7-12-linear or branched alkyl, -(CH2)q-C3-12-cycloalkyl -, -(CH2)qO-C1-8-alkyl, -(CH2)qO-C3-12-cycloalkyl, -(CH2)qO-aralkyl, -(CH2)qCO-C1-8-alkyl, -(CH2)qCO-C3-12-cycloalkyl, -(CH2)qCO-aryl, -COC1-8-alkyl, -COC3-2-cycloalkyl, -CO-aryl, -COOC1-8-alkyl, -COOC3-12-cycloalkyl, aralkyl aryl, heteroaryl and a heterocyclic radical and may contain one or more heteroatom selected from 0, S and N in the cycloalkyl or heterocyclic ring system, 'q' is an integer selected from 0, I, 2, 3, 4, 5 or 6;
'n' is an integer selected from 0, 1 and 2; ( * ) at the piperidin-3-yl carbon, indicate (R) or (S) configuration or racemate (RS).
8. A compound according to any one of the preceeding claims, selected from the group consisting of:
• 8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-cnrboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-[(R)-(tetrahydrofuran-3-yl)oxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 8-Benzyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-(tetrahydrofuran-2-ylmethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(4-Fluorobenzyloxy)-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-[(S)-1 -(tetrahydrofuran-2-yl)methoxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyI-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-(tetrahydropyran-4-ylmethoxy)quinoIine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(3-CyclopentyIpropoxy)-4-(2-methoxyethoxy)quinoIine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
i
• 4-(2-Methoxyethoxy)-8-phenethyloxyquinoline-2-carboxylic acid isopropyl-
(R)-piperidin-3-yl amide;
• 8-(4-Isopropyl cycIohexylmethoxy)-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-[4-(4-ChIorophenyl)cyclohexylmethoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-(2-propylpentyloxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;

• 8-(Indan-2-yloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl piperidin-3-yl amide;
• 8-(2-Cyclohexylethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(4-Isobutylbenzyloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
• 8-(4-Isopropylbenzyloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-(4-trifluoromethylbenzyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(4-Cyclohexylbenzyloxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Heptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-[2-(4-Fluorophenyl)ethoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yI amide;
• 4-(2-Methoxyethoxy)-8-(5-oxohexyloxy)quinoline-2-carboxylic acid isopropyI-(R)-piperidin-3-yl amide;
• 8-Cyclooctyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-(pyridin-2-ylmethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 4-(2-Methoxyethoxy)-8-(pyridin-3-ylmethoxy)quinoline-2-carboxylic acid isopropy]-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-[2-(2-oxopyrrolidin-l-yl)ethoxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2,2-Dimethoxyethoxy)-4-(2-methoxyethoxy)quinoiine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclohexylmethoxy-4-(2-ethoxyethoxy)quinoline-2-carboxyIicacid isopropyl-(R)-piperidin-3-yl amide;
• 8-CycIoheptyloxy-4-(2-ethoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cycloheptyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(3-Fluorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(4-FIuorobenzyIoxy)-4-(3-methoxypropoxy)quino]ine-2-carboxyIicacid isopropyl-(R)-piperidin-3-yl amide;
• 8-(3-Chlorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl -(R)-piperidin-3-yl amide;
• 4-(3-Methoxypropoxy)-8-(3-trifluoromethylbenzyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-Fluorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 8-Benzyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yJ amide;
• 4-(3-Methoxypropoxy)-8-(tetrahydrofuran-2-ylmethoxy)quinoline-2-carboxylic acid isopropyi-(R)-piperidin-3-yl amide;
• 4-(3-Methoxypropoxy)-8-[(R)-(tetrahydrofuran-3-yl)oxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2,3-Dichlorobenzyloxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(3-Methoxypropoxy)-8-[(S)-l-(tetrahydrofuran-2-yl)methoxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclooctyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Heptyloxy-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclohexylmethoxy-4-(3-methoxy propoxy)qumofine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cycloheptyloxy-4-(3-ethoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• Carbonic acid-2-[8-cycloheptyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester methyl ester;
• Carbonic acid-2-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinoiin-4-y!oxy]ethyl ester methyl ester;

• Carbonic acid-2-[8-cyclohexylmethoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyI ester methyl ester;,
• Carbonic acid-2-[8-isobutoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl)quinolin-4-yloxy]ethyl ester methyl ester;
• Carbonic acid-2-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester ethyl ester;
• Carbonic acid-2-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester pentyl ester;
• Carbonic acid-2-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester isobutyl ester;
• Carbonic acid-3-[8-cyclohexylmethoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinoIin-4-yIoxy]propyl ester methyl ester;
• Carbonic acid-3-[8-cyclopentyloxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]propyl ester methyl ester;
• 8-Cycloheptyloxy-4-(2-isobutoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cycloheptyloxy-4-(2-propoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cycloheptyloxy-4-(2-cyclopropylmethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-Cyclohexyl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 4-(2-Methoxyethoxy)-8-(4-methyl-2-oxopentyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Methoxyethoxy)-8-(3-methyl-2-oxobutoxy)quinpline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-Adamantan-l-yl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yI amide;
• 8-(2-Cyclopentyl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-Cyclopropyl-2-oxoethoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl! amide;
• 8-[2-(4-ChIorophenyI)-2-oxoethoxy]-4-(2-methoxyethoxy)quinoline-2-carboxyiic acid isopropyl-(R)-piperidin-3-yi amide;
• 8-[2-Cyclopropyl-l-(2-fluoro phenyI)-2-oxo ethoxy]-4-(2-methoxy ethoxy)quinoline -2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-[2-(3-Chloro phenyl)-2-oxo ethoxy]-4-(2-methoxy ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-Furan-2-yl-2-oxo ethoxy)-4-(2-methoxy ethoxy)quinoiine-2-carboxyiic acid isopropyi-(R)-piperidin-3-yi amide;
• 4-(2-Methoxy ethoxy)-8-(2-oxo-2-thiophen-2-yl ethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 4-(2-Ethoxyethoxy)-8-(4-methyl-2-oxopentyloxy)quinoline-2-carboxylic acid isopropy]-(R)-piperidin-3-y] amide;
• 8-(2-Cyclopentyl-2-oxoethoxy)-4-(2-ethoxyethoxy)quinoIine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-ethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Ethoxyethoxy)-8-(3-methyl-2-oxobutoxy)quinoline-2-carboxylic acid isopropyl -(R)-piperidin-3-yl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-CyclohexyI-2-oxoethoxy)-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyI-(R)-piperidin-3-yl amide;
• 4-(3-Methoxypropoxy)-8-(4-methyl-2-oxopentyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-CycIopentyI-2-oxoethoxy)-4-(3-methoxypropoxy)quinoIine-2-carboxyiic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(3-Methoxypropoxy)-8-(3-methyl-2-oxobutoxy)quinoIine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Isobutoxy-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 8-Cycloheptyloxy-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclopentyloxy-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
i
• 8-Cyclopentyloxy-4-(2-ethoxymethoxyethoxy)quinolihe-2-carboxylic acid
isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclohexylmethoxy-4-(3-methoxymethoxypropoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cycloheptyloxy-4-(3-methoxymethoxypropoxy)quinoline-2-carboxylicacid
isopropyl-(R)-piperidin-3-yl amide;
i
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxymethoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-(2-Cyclopentyl-2-oxoethoxy)-4-(2-methoxymethoxyethoxy)quinoline-2-carboxyiic acid isopropyi-(R)-piperidin-3-yi amide;
• 4-(2-Methoxymethoxyethoxy)-8-(4-methyl-2-oxopentyIoxy)quinoline-2-carboxylic acid isopropyI-(R)-piperidin-3-yl amide;
• 8-[(R)-2-(2,2-Dimethylpropionylamino)butoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-[(S)-2-(2,2-Dimethylpropionylamino)butoxy]-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 8-((R)-2-Methanesulfonylaminobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• Carbonic acid isobutyl ester-2-((R)-isopropyl piperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
• 8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(S)-piperidin-3-yl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxyiic acid isopropyl-(S)-piperidin-3-yl amide;
• Isobutyric acid-2-((R)-isopropyl piperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yI ester;
• 2,2-Dimethyl propionic acid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quino!in-8-yI ester;
• Pentanoicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
• Hexanoic acid-2-((R)-isopropylpiperidin-3-yI-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
• Heptanoicacid-2-((R)-isopropylpiperidin-3-yi-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
• Octanoicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy) quinolin-8-yl ester;
• Cyclopropanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;

• Cyclopentanecarboxylic acid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-y| ester;
• Cyclohexanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyI)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
• 1 - Methylcyclohexanecarboxylic acid-2-((R)-isopropylpiperidin-3-y]-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
• Adamantane-1 -carboxyl ic acid-2-((R)-isopropy lpiperidin-3-y l-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-yl ester;
• 3-Cyclopentylpropionicacid-2-((R)-isopropyl-piperidin-3-yl-carbamoyl)-4-(2-methoxyethoxy)quinolin-8-yl ester;
• 4-Fluorobenzoicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(2-methoxy ethoxy)quinolin-8-y| ester; :
• Pentanoicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(3-methoxypropoxy) quinolin-8-yl ester;
• Cyclopropanecarboxylic acid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(3-methoxy propoxy)quinolin-8-yl ester;
• Cyclopentanecarboxylicacid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(3-methoxy propoxy)quinolin-8-yl ester;
• Cyclohexanecarboxylic acid-2-((R)-isopropylpiperidin-3-yl-carbamoyl)-4-(3-methoxy propoxy)quinolin-8-yl ester;
• Hexanoic acid-2-((R)-isopropyl piperidin-3-yl-carbamoyl)-4-(3-methoxypropoxy) quinolin-8-yl ester;

• 4-(2-Methoxyethoxy)-8-methoxymethoxyquinoline-2-carboxylicacid isopropyl-(R)-piperidin-3-yl amide;
• 8-Benzyloxymethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyI-(R)-piperidin-3-yl amide;
• 4-(2-Benzyloxyethoxy)-8-cyclohexylmethoxy quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl-amide;
• 8-Cyclohexylmethoxy-4-[2-(3,3-dimethyl-2-oxobutoxy)ethoxy]quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• Acetic acid-2-[8-cyclohexylmethoxy-2-((R)-isopropylpiperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester;
• Isobutyric acid-2-[8-cyclohexylmethoxy-2-((R)-isoprppyl piperidin-3-yl-carbamoyl) quinolin-4-yloxy]ethyl ester; .
• 2,2-Dimethyl propionic acid-2-[8-cyclohexylmethoxy-2-((R)-isopropyl piperidin-3-yl carbamoyl)quinolin-4-yloxy]ethyl ester;
• 8-Cyclopentyloxy-4-(2-methoxybenzyloxy)quinoline-2-carboxyiicacid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclopentyloxy-4-(2,3-dichloro benzyloxy)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclopentyloxy-4-(2-trifluoromethylbenzyloxy)quinoline-2-carboxylic acid . isopropyI-(R)-piperidin-3-yl amide;
• [8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinolin-2-ylmethyl]isopropyl-(R)-piperidin-3-yl amine;

• [8-Cyclopentyloxy-4-(2-methoxyethoxy)quinolin-2-ylmethyl]isopropyl-(R)-piperidin -3-y] amine;
• [8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoIin-2-ylmethyl]isopropyl-(R)-piperidin -3-yl amine;
• 4-(2-Acetylaminoethylsulfanyl)-8-cyclopentylmethoxyquinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Acetylaminoethylsulfanyl)-8-cyclopentyloxyquinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 8-Cyclopentyloxy-4-(2-methanesulfonylaminoethylsulfanyl)quinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Acetylaminoethylsulfanyl)-8-benzyloxyquinoline-2-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 4-(2-Benzoylaminoethylsulfanyl)-8-cyclopentyloxyquinoIine-2-carboxylic acid isopropyl-(R)-piperidin-3-yl-amide;
• 6-(2-Methoxyethoxy)-2-methyl-furo[3,2-h]quinoiine-8-carboxylic acid isopropyl-(R)-piperidin-3-yl-amide;
• 6-(3-Methoxypropoxy)-2-methyl-furo[3,2-h]quinoline-8-carboxylic acid isopropyI-(R)-piperidin-3-yl amide;
• 6-(2-Methoxyethoxy)-2,2-dimethyl-2,3-dihydrofuro[3,2-h]quinoline-8-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;
• 6-(3-Methoxypropoxy)-2,2-dimethyl-2,3-dihydrofuro[3,2-h]quinoline-8-carboxylic acid isopropyl-(R)-piperidin-3-yl amide;

• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid
isopropyl-(S)-pyrrolidin-3-yl amide;
i
• 8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(S)-pyrrolidin-3-yl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(S)-pyrrolidin-3-yl amide;
• 8-Cycioheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(S)-l-pyrrolidin-2-ylmethyl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(S)-1 -pyrrolidin-2-yImethyl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid
isopropyl piperidin-2-ylmethyl amide;
• 8-Cycloheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl
piperidin-2-ylmethyl amide;
• 8-CycIoheptyloxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid azetidin-3-yl isopropyl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylicacid isopropyl-(R)-l-piperidin-3-ylmethyl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl-(R)-l-piperidin-3-ylmethyl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isopropyl piperidin-4-yl amide;

• 8-Cyclohexylmethoxy-4-(3-methoxypropoxy)quinoline-2-carboxylic acid isopropyl piperidin-4-yl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid isobutyl-(R)-piperidin-3-yl amide;
• 8-Cyclohexylmethoxy-4-(2-methoxyethoxy)quinoline-2-carboxylic acid
cyclopentyI-(R)-piperidin-3-yl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic
acid isobutyl-(R)-piperidin-3-yl amide;
• 8-(3,3-Dimethyl-2-oxobutoxy)-4-(2-methoxyethoxy)quinoline-2-carboxylic
acid cyclopentyl-(R)-piperidin-3-yl amide.