MUSCARINIC MI RECEPTOR POSITIVE ALLQSTERIC MODULATORS
Field of Invention
The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, or pharmaceutically acceptable salts as muscarinic MI receptor positive allosteric modulators (MI PAMs). The present invention also describes method of making such compounds, pharmaceutical compositions comprising such compounds and their use.
Background of the Invention
Muscarinic acetylcholine receptors (mAChRs), which belong to the class A family of G protein-coupled receptors (GPCRs). They are widely expressed throughout the body. Five subtypes termed MI through M5 that respond to the endogenous neurotransmitter acetylcholine (ACh) have been identified till date. They play key role in regulating the activity of many important functions of the central and peripheral nervous system including cognitive function. MI, M3 and M5 couple to Gq, whereas M2 and M4 couple via Gi/o to downstream signaling pathways and associated effector systems {Critical Reviews in Neurobiology, 1996, 10, 69-99; Pharmacology & Therapeutics, 2008,117, 232-243). M2 and M3 are highly expressed in the periphery and are known to be involved in gastrointestinal (GI) motility and parasympathetic responses such as salivation (Life Sciences, 1993, 52, 441-448). The MI muscarinic receptor is predominantly expressed in the brain regions such as cbrtex, hippocampus and amygdala which involved in cognition, and therefore selective activation of the MI receptor would be expected to boost cognitive performance (Annals of Neurology, 2003, 54, 144 - 146).
Xanomeline, a muscarinic acetylcholine receptor agonist with reasonable selectivity for the MI and M4 subtypes, produced significant effects on cognition in a clinical Alzheimer's disease (AD) trial (Ahheimer Disease and Associated Disorders, 1998, 12(4), 304-12) although gastrointestinal' side effects led to a high dropout rate in clinical triáis. There is a high degree of conservation between muscarinic receptor subtypes at their orthosteric acetylcholine ligand binding sites which makes it difficult to identify a Mi selective agonist.
To circumvent this issue of selectivity and safety, an alternative approach consists of developing MI PAMs that act at the less conserved allosteric binding site. Merck reported the development of MI positive allosteric modulator, PQCA (l-{[4-cyano-4-(pyridine-2-yl)piperidin-l-yl]methyl}-4-oxo-4H-quinolizine-3-carboxylic acid). This compound is highly selective for MI over the other muscarinic receptor sub types^arid round to be efficacious in several preclinical models of cognition (Psychopharmacology, 2013, 225(1), 21-30) with no gastrointestinal side effects at doses equal to or less than a fívefold margin from the mínimum effective dose requifed to improve cognition. In preclinical studies it was demonstrated that MI activation increases neurotransmitter acetylcholine concentration in brain. Moreover, the MI activation has potential as disease-modifying therapy for AD by both shifting the APP processing towards the non-amyloidogenic a-secretase pathway and by decreasing the tau hyper-phosphorylation. Positive allosteric modulators at MI receptor have demonstrated tó increase the generation of sAPPa in-vitro {The Journal ofNeuroscience, 2009, 29, 14271— 14286). Therefore, MI PAMs provide an approach to target both symptomatic and disease-modifying treatment of cognitive déficits in AD and schizophrenia.
PCT patent application publications, WO2015049574, WO2015028483, WO2007067489 and WO2011149801 have disclosed some MI PAM compounds. While several MI PAMs have been disclosed in the literature till date, no drug acting as MI PAM is launched in the market. Therefore, there is an un-met need and scope to discover and develop new MI PAMs with novel chemical structures devoid of any side effects for the treatment of disorders, which are regulated by MI receptors.
Summary of the Invention
In fírst aspect, the present invention relates to MI PAMs of compound of formula (I),
wherein:
A1and A2 are each independently represents CH, CF or N;
W is O, S, S(O) or S(0)2;
R'is wherein: * represents point of attachment;
R3 is OH, F, NH2 or H ; R at each occurrence is independently selected from halogen, -O-CH3; -S-CH3, -N(CH3)2, -CH3, -CF3, -CHF2, -CH2F, -OH, -CN, phenyl, pyridyl and hydrogen; wherein phenyl and
pyridyl are optionally substituted with one or more substituents selected from the group cbnsisting of halogen or CH3; XisCH2, OorNH; a is 0 or 1; and b is 1 or 2; or an isotopic form, a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.
In another aspect, the present invention relates to the processes for preparing the compound of formula (I), or a stereoisomer and a pharmaceutically acceptable salt thereof.
In yet another aspect, the present invention relates to pharmaceutical composition containing a therapeutically effective amount of at least one compound of formula (I), or a stereoisomer and a pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients or carriers.
In yet another aspect, the present invention relates to compound of formula (I), or a stereoisomer and a pharmaceutically acceptable salt thereof, for use as MI PAM.

In yet another aspect, the present invention relates to compound of formula (I), or a stereoisomer and a pharmaceutically acceptable salt thereof, for use in the treatment of various disorders selected from AD, schizophrenia, cognitive disorders, pain or sleep disorders.
In another aspect, the present invention relates to a method for the treatment of disorders related to muscarinic MI receptor, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of formula (I), or a stereoisomer and a pharmaceutically acceptable salt thereof.
In yet another aspect, the present invention relates to use of the compound of formula (I), or a stereoisomers and pharmaceutically acceptable salts thereof, for the manufacture of a medicament for the treatment of disorders related to muscarinic MI receptor.
Brief Description of Drawíngs
1. Figure 1: Effect of example 18 with donepezil in time induced memory déficit
2. Figure 2: The discriminative index showing effect of example 18 with donepezil in time
induced memory déficit
3. Figure 3: Effect of example 18 on the scopolamine induced memory déficit
4,. Figure 4: Effect of example 18 on cortical sAPPa levéis in male C57BL/6J mice 5. Figure 5: Effect of example 18 on cortical sAPPa levéis in male Wistar rats
Detailed Description of the Invention
Unless otherwise stated, the following terms used in the specification and claims have the meanings given below:
The term "halogen" means fluorine, chlorine, bromine or iodine.
The phrase, "therapeutically effective amount" is defined as an amount of a compound of the present invention that (i) treats the particular disease, condition or disorder (ii) eliminates one or more symptoms of the particular disease, condition or disorder (iii) delays the onset of one or more symptoms of the particular disease, condition or disorder described herein.
The term, "isotopic form" as used herein refers to the compound of formula (I) wherein one or more atoms of compound of formula (I) are substiruted by their respective isotopes. For example, isotopes of hydrogen include H (deuterium) and H (tntium).
The term, "stereoisomers" as used herein refers to isomers of compound of formula (I) that differ in the arrangement of their atoms iri space. Compounds disclosed herein may exist as single stereoisomers, racemates and/or mixtures of enantiomers and/or diastereomers. All such single stereoisomers, racemates and mixtures thereof are intended to be within the scope of the present invention.
The term, "pharmaceutically acceptable salt" as used herein refers to salts of the active compound Le. the compound of formula I, and are prepared by reaction with the appropriate acid or acid derivative, depending on the particular substituents found on the compounds described herein.
Embodiments
The present invention encompasses all the compounds described by the compound of formula (I) without limitation, however, preferred aspects and elements of the invention are discussed herein in the form of the following embodiments.
In one embodiment, the present invention relates to the compound of formula (I), wherein: W is O; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: W is S or S(O); or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: A1 is CH or CF; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: A1 is N; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: A2 is CH or CF; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: A2 is N; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In yet another embodiment, the present invention relates to the compound of formula (I), wherein: W is O; A1 is CH or CF; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.

In yet another embodiment, the present invention relates to the compound of formula (I), wherein: W is O; A2 is CH or CF; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R1 is
wherein * represents point of attachment; X, R3 and a are as defined in first aspect; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R1 is
wherein * represents point of attachment; X, R and a are as defined in first aspect; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R'is
wherein * represents point of attachment; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R2is
wherein * represents point of attachment; R4 and b are as defíned in the fírst aspect or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R2is
wherein * represents point of attachment; R and b are as defíned in the fírst aspect or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R2is
wherein * represents point of attachment; R4 and b are as defíned in the fírst aspect or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R'is R2is
wherein * represents point of attachment; X is CH2; R3, R4, a and b are as defíned in the first aspect; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R1 is
R2is wherein * represents point of attachment; X is CH2; R3, R4, a and b are as defíned in the first aspect, or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: R1 is

R2is wherein * represents point of attachment; X is NH; R3, R4, a and b are as defined in the fírst aspect, or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: WisO;
A1 and A2 are CH; R1 is
R2is wherein * represents point of attachment; R3, R4, X, a and b are as defined in the first aspect; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: W is S; A1 and A2 are CH;
R'is R2is wherein * represents point of attachment; R3, R4, X, a and b are as defíned in the fírst aspect; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: WisO;
A1 and A2 are CH; R1 is
R2is wherein * represents point of attachment; X is CH2; R3, R4, a and b are as defíned in the fírst aspect; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof.
In another embodiment, the present invention relates to the compound of formula (I), wherein: WisS;

A1 and A2 are CH; R'is R2is wherein * represents point of attachment; X is CH2; R3, R4, a and b are as defined in the first aspect; or an isotopic form, a stereoisomer or a pharmaceutically acceptable salt thereof. In yet another embodiment the representative compounds of the present invention includes but not limited to,
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-8-fluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4- {2-fluorobenzyl}-4H-pyrido[3,2-b] [ 1,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-benzyl-4H-benzo[l,4]oxazine-2-carboxamide; N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(4-methoxybenzyl)-4H-benzo[l,4]oxazine-2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(4-methoxybenzyl)-4H-benzo[l,4]oxazine-2-carboxamide; N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(3-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamide; N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(3-methoxybenzyl)-4H-benzo[ 1,4]oxazine-2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(3-methoxybenzyl)-4H-benzo[l,4]oxazine-2-carboxamide; N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(2-methoxypyridin-4-ylmethyl)-4H-benzo [1,4] oxazine-2 -carboxamide;

N-(2-Hydroxy-2-methylpropyl)-4-(2-methoxypyridin-4-ylmethyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(4-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(4-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-methoxy pyridin-5-ylmethyl)-4H-
benzo[ 1,4]oxazine-2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(2-methoxypyridin-5-ylmethyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3-trifluoromethylbenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2,3-difluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3,4-difluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(3-Hydroxytetrahydrpyran-4-yl)-4-(2,3-difluoro benzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chloropyridin-5-ylmethyl)-4H-benzo[l,4]oxazine-
2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(pyridin-3-ylmethyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(pyridin-4-ylmethyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chloropyridin-4-ylmethyl)-4H-benzo[l,4]oxazine-
2-carboxamide;
Ñ-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(pyridin-2-ylmethyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3,4-dichlorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-methylpyridin-3-ylmethyl)-4H-benzo[l,4]oxazine-
2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2,4-dichlorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;

N-(cis-lS, 2S-2-Hydroxycyclohexyl)-8-fluoro-4-(2,3-difluorobenzyl)-4H-benzo[l,4]oxazine-
2-carboxamide;
N-(cis-lS, 2S-2-HydroxycycJohexyl)-4-benzyl-4H-pyrido[3,2-b][l,4]oxazine-2-carboxamide;
N-(cis-lS,2S-2-Hydroxycyclohexyl)-l-Benzyl-lH-pyrido[2,3-b][l,4]oxazine-3-
carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-1 -{2,3,difluorobenzyl}-1 H-pyrido[2,3-b][ 1,4]oxazine-
3-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2,3-difluorobenzyl)-4H-pyrido[3,2-b][l,4]oxazine-
2-carboxamide;
N-(cis-lS, 2S-2-Hydróxycyclohexyl)-4-(3-fluoropyridin-4-ylmethyl)-4H-benzo[l,4]oxazine-
2,-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(4-fluorobenzyl)-4H-pyrido[3,2-b][l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-l-(3-fluorobenzyl)-lH-pyrido[2,3-b][l,4]oxazine-3-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-trifluoromethylbenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chlorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(trans-lR, 2R-2-Hydroxycyclopentyl)-4-(2,3-difluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(trans-1R, 2R-2-Hydroxycyclopentyl)-4-(2-fluorobenzyl)-4H-benzo[l ,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chlorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(trans-lR, 2R-2-Hydroxycyclopentyl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-
benzo[l ,4]oxazine-2-carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2-fluorobenzyl)-4H-benzo[ 1,4]oxazine-2-carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2,3-difluorobenzyl)-4H-benzo[l ,4]oxazine-2-carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;

N-(l-Hydroxymethyl-2-methylpropyl)-8-fluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-benzyl-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-1R, 2R-2-Hydroxycyclohexyl)-4- {2-fluorobenzyl} -4H-benzo [ 1,4] oxazine-2-
carboxamide;
N-(cis-lR, 2R-2-Hydroxycyclohexyl)-4-{2-fluorobenzyl}-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{3-fluorobenzyl}-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(2-phenylpyridin-4-ylmethyl)-4H-benzo[l ,4]
oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-8-fluoro-4-(2-phenylpyridin-4-ylmethyl)-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(2-chloropyridin-4-ylmethyl)-8-fluoro-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-fluorobenzyl)-5-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(pyridine-2-ylmethyl)-5-fluoro-4H-benzo[l,4]
oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(pyridine-4-ylmethyl)-8-fluoro-4H-benzo[l,4]
oxazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(6'-Fluoro-5'-methyl-[2,3']bipyridinyl-4-ylmethyl)-
4H-benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-[2-(l-methyl-lH-pyrazol-3-yl)-pyridin-4-ylmethyl]-
4H-benzo [1,4] oxazine-2 -carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(l-methyl-lH-pyrazol-3-ylmethyl)-4H-
b'enzo[l,4]oxazine-2-carboxamide;
N-(cis-,lS, 2S-2-Hydroxycyclohexyl)-4-(2-fluorobenzyl)-5,8-difluoro-4H-benzo[l,4]oxazine-
2-carboxamide;
N-(3-Fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(3-Fluoropiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;

N-(3-Hydroxypiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide; ¡
Ñ-(3-Hydroxypiperidin-4-yl)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2,3-difluorobenzyl)-4H-benzo[l,4]thiazine-2- !
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3-fluorobenzyl)-4H-benzo[l,4]thiazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-benzyl-4H-benzo[l,4]thiazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{4-methoxybenzyl}-4H-benzo[l,4]thiazine-2-
carboxamide;
N-(cis-lS,2S-2-Hydroxycyclohexyl)-4-{4-fluorobenzyl}-4H-benzo[l,4]tbiazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{pyridin-4-yl-methyl}-4H-benzo[l,4]thiazine-2-
carboxamide;
N-(cis-l S, 2S-2-Hydroxycyclohexyl)-4-{2-chloropyridin-5-yl-methyl}-4H-
benzo[l,4]thiazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{pyridin-2-yl-methyl}-4H-benzo[l,4]thiazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2,3-difluorobenzyl)-l-oxo-4H-benzo[l,4]thiazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-benzyl-l-oxo-4H-benzo[l,4]thiazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4- {3-fluorobenzyl}-1 -oxo-4H-benzo[ 1,4]thiazine-2-
carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-{pyridin-2-yl-methyl}-1 -oxo-4H-benzo[ 1,4]thiazine-
2-carboxamide; and
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4- {2-chloropyridin-5-yl-methyl} -1 -oxo-4H-
benzo[l ,4]thiazine-2-carboxamide;
or their pharmaceutically acceptable salt thereof.
In yet another embodiment the representative compounds of pharmaceutically acceptable salt of the present invention includes but not limited to, N-(3-Fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide hydrochloride;
N-(3-Fluoropiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide hydrochloride;

N-(3-Hydroxypiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide trifluoroacetate and
N-(3-Hydroxypiperidin-4-yl)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamide trifluoroacetate.
General Scheme-1 depicts processes for the preparation of the intermediates, wherein WisOandS;A',A¿, andR¿ are as defíned in the first aspect.
Step 1: Preparation of compound óf formula (ii)
The compound of formula (i) is reacted with ethyl bromoacetate in presence of base selected from cesium carbonate, potassium carbonate, sódium carbonate, sodium bicarbonate, sodium hydroxide and potassium hydroxide in a solvent selected from acetonitrile, DCM, DCE, acetone, THF, DMF and DMSO at a temperature range of 80-100 °C for 15-17 hours to obtain the compound of formula (ii). Step 2: Preparation of compound of formula (iii)
The compound of formula (ii) obtained in step 1 is reacted with methyl fórmate in
presence of sodium hydride, sodium tert-butoxide, potassium tert-butoxide, lithium
diisopropylamide (LDA) or lithium hexamethyldisilazide (LiHMDS) at 0 °C to RT for 3-5 •
hours to obtain the compound of formula (iii). Step 3: Preparation of compound of formula (iv)
The compound of formula (iii) obtained in step 2 is reacted with amine, R-CH2-NH2 in a solvent selected from methanol, ethanol and isopropanol at the temperature range of 25-30 °C, for 10-14 hours to obtain the compound of formula (iv). The amines, R-CH2-NH2 were either procured from commercial sources or prepared from either by their respective

halides/mesylates/tosylates through azides or by reduction of respective nitriles. The . halides/mesylates/tosylates were displaced with azide using sodium azide in solvents selected from DMSO, DMF, DMA and NMP at the temperatura range of from RT to 110 °C. The azides and nitriles were reduced to amines using reducing agents selected from PPI13/H2C), Pd/C/H2, Raney nickel and NaBH4/NiCl2 in solvents selected from THF, MeOH, EtOH and H2O at temperatura range of 0 °C to RT. Step 4: Preparation of compound of formula (v)
The compound of formula (iv) obtained in step 3 is reacted with copper iodide, copper chloride or copper bromide in presence of base selected from cesium carbonate, potassium carbonate or potassium phosphate in a solvent selected from DMF, NMP, DMA, DMSO, THF and DCE at temperatura ranging from RT to 90 °C for 5-7 hours to obtain the compound of formula (v). Step 5: Preparation of compound of formula (A)
The compound of formula (v) obtained in step 4 is reacted with sodium hydroxide in a 1:1 mixture of water and methanol under reflux for 3-5 hours to obtain the compound of formula (A).
General Scheme-2 depicts processes for the preparation of compound of formula (I), wherein A1, A2, W, R1, R2, R3 and R4 are as defined above.
Preparation of compound of formula (I)
The compound of formula (A) is coupled with amine, R'-NH2 in presence of coupling reagents such as HATU, DCC, DIC, TBTU or EDC and organic base such as DIPEA, TEA, DABCO and DBU in a solvent selected from DCM, DMF, DMA, NMP and THF at a temperatura range of 25-30 °C for 15-17 hours to obtain the compound of formula (I). The amines of R'-NH2, such as (lS,2S)-2-aminocyclohexanol (CAS No. 13374-30-6), (lR,2R)-2-aminocyclohexanol (CAS No. 931-16-8), l-amino-2-methyl-2-propanol, 2-amino-3-methyl-l'-butanol, 2-aminobenzyl alcohol, (lR,2R)-trans-2-aminocyclopentanol (CAS No. 68327-11-

7) and trans 4-amino tetrahydropyran-3-ol (CAS No. 215940-92-4) were procured from
commercial sources, whereas tert-butyl 4-amino-3-hydroxy piperidine-1-carboxylate was
prepared using the procedures as disclosed in EP0076530A2 and tert-butyl 4-amino-3-fluoro
piperidine-1-carboxylate was prepared using the procedures as disclosed in
WO2012108490A1.
Preparation of compound of formula (I) (wherein W is S(=0))
The compound of formula (I) (wherein W is S) is reacted with NaIÜ4 in a solvent sélected from 1:1:2 mixture of methanol, THF and water at a temperature range of 25-30 °C for 14-17 hours to obtain the compound of formula (I) (wherein W is S(=0)). Preparation of pharmaceutically acceptable salt of compound of formula (I)
The compound of formula (I) can be optionally converted into its pharmaceutically acceptable salt by reaction with the appropriate acid or acid derivative.
Suitable pharmaceutically acceptable salts will be ápparent to those skilled in the art. The salts are formed with inorganic acids e. g. hydrochloric, hydrobromic, sulfuric, nitric & phosphoric acid or organic acids e.g., oxalic, succinic, maleic, acetic, fumaric, citric, malic, tartaric, benzóic, p-toluic, p-toluenesulfonic, benzenesulfonic acid, methanesulfonic or naphthalenesulfonic acid.
In yet another aspect, the present invention relates to the pharmaceutical composition of the compound of formula (I). In order to use the compound of formula (I), or their stereoisomers and pharmaceutically acceptable salts thereof in therapy, they will normally be formulated into a pharmaceutical composition in accordance with standard pharmaceutical practice.
The pharmaceutical compositions of the present invention may be formulated in a conventional manner using one or more pharmaceutically acceptable excipients. The pharmaceutically acceptable excipient is carrier or diluent. Thus, the active compounds of the invention may be formulated for oral dosing. Such pharmaceutical compositions and processes for preparing same are well known in the art.
The dose of the active compounds can vary depending on factors such as age and weight of patient, nature and severity of the disease to be treated and such other factors. Therefore, any reference regarding pharmacologically effective amount of the compounds of general formula (I), stereoisomers and pharmaceutically acceptable salts thereof refers to the aforementioned factors.
In yet another aspect, the present invention relates to method of treatment of disorders related to muscarinic MI receptors.

In another embodiment, the disorders related to muscarinic MI receptors are selected from the group consisting of AD, schizophrenia, cognitive disorders, pain or sleep disorders.
In yet another embodiment, the present invention relates to method of treatment of disorders related to muscarinic MI receptors comprising the compound of formula (I) in combination with other therapeutic agents selected from cholinesterase inhibitors e.g., donepezil, and NMDA receptor antagonist e.g., memantine.
Commercial reagents were used without further purifícation. RT is defined as an ambient temperature range, typically from 25 °C to 35 °C. All mass spectra were obtained using ESI conditions unless otherwise stated. 'H-NMR spectra were recorded at 400 MHz on a Bruker instrument. Deuterated chloroform, methanol or dimethyl sulfoxide was used as solvent. TMS was used as internal reference standard. Chemical shift valúes are expressed in parts per million (8) valúes. The following abbreviations are used for the multiplicity of the NMR signáis: s=singlet, bs=broad singlet, d=doublet, t=triplet, q=quartet, qui=quintet, h-heptet, dd=double doublet, dt=double triplet, tt=triplet of triplets, m=multiplet. Chromatography refers to column chromatography performed using 100 - 200 mesh silica gel and executed under nitrogen pressure (flash chromatography) conditions.
The stereoisomers as a rule are generally obtained as racemates that can be separated into the optically active isomers iri a manner known per se. In the case of the compounds of general formula (I) having an asymmetric carbón atom the present invention relates to the D-form, the L-form and D, L - mixtures and in the case of compound of general formula (I) containing a number of asymmetric carbón atoms, the diastereomeric forms and the invention extends to each of these stereoisomeric forms and to mixtures thereof including racemates. Those compounds of general formula (I) which have an asymmetric carbón and as a rule are obtained as racemates can be separated one from the other by the usual methods, or any given isomer may be obtained by stereo specifíc or asymmetric synthesis. However, it is also possible to employ an optically active compound from the start, a correspondingly optically active enantiomeric or diastereomeric compound then being obtained as the final compound.
The stereoisomers of compounds of general formula (I) may be prepared by one or more ways presented below:
i) One or more of the reagents may be used in their optically active form.
ii) Optically puré catalyst or chiral ligands along with metal catalyst may be employed in
the reduction process. The metal catalyst may be Rhodium, Ruthenium, Indium and

the like. The chiral ligands may preferably be chiral phosphines. (Principies of Asymmetric synthesis, J. E. Baldwin Ed., Tetrahedron series, 14, 311-316).
iii) The mixture of stereoisomers may be resolved by conventional methods such as forming diastereomeric salts with chiral acids or chiral amines or chiral amino alcohols, chiral amino acids. The resulting mixture of diastereomers may then be separated by methods such as fractional crystallization, chromatography and the like, which is followed by an additional step of isolating the optically active product by hydrolyzing the derivative.
iv) The mixture of stereoisomers may be resolved by conventional methods such as microbial resolution, resolving the diastereomeric salts formed with chiral acids or chiral bases. Chiral acids that can be employed may be tartaric acid, mandelic acid, lactic acid,
camphorsulfonic acid, amino acids and the like. Chiral bases that can be employed may be
cinchona alkaloids, brucine or a basic amino acid such as lysine, arginine and the like. In the
case of the compounds of general formula (I) containing geometric isomerism the present
invention relates to all of these geometric isomers.
The following abbreviations are used herein:
Cul : Copperlodide
CS2CO3 : Cesium Carbonate
DCM : Dichloromethane
DCE : Dichloroethane
DCC : N,N'-Dicyclohexylcarbodiimide
DIC : N,N'-Diisopropylcarbodiimide
DIPEA : N,N-Diisopropylethylamine
DBU : l,8-Diazabicyclo[5.4.0]undec-7-ene
DABCO : l,4-Diazabicyclo[2.2.2]octane
DMA : Dimethylacetamide
DMF : N,N-Dimethylformamide
DMSO : Dimethyl sulfoxide
EDC . : Ethylene dichloride
H2 : Hydrogen gas
HATU : 2-(7-Aza-lH-benzotriazole-l-yl)-l,l,3,3-tetramethyluronium
hexafluorophosphate
HC1 : ' Hydrochloric acid

IPA : Isopropyl alcohol
K3PO4 : Potassium phosphate
MeOH : Methanol
NaHC03 : Sodium bicarbonate
NaIÜ4 : Sodium metaperiodate
NaOH : Sodium hydroxide
Na2S04 : Sodium sulfate
NMP : N-Methyl-2-pyrrolidinone
NiCl2 : Nickel chloride
NaBH4 : Sodium borohydride
PPh.3 : Triphenylphosphine
RT Room temperatura (25-30 °C)
TBTU : 0-(Benzotriazol-l-yl)-N,N,N,,N,-tetramethyluroniumtetrafluoroborate
TEA : Triethylamine
THF : Tetrahydrofuran
TMS : Tetramethylsilane
Intermediates preparation:
Intermedíate 1: 2,3-Difluorobenzylamine (1-1)
Step 1: Preparation of l-azidomethyl-2,3-difiuorobénzene
To a stirred solution of l-bromomethyl-2,3-difluorobenzene (50.0 g, 241,5 mmol) in DMF (483.0 mL) at RT, sodium azide (23.5 g, 362.3 mmol) was added over a period of 15 minutes and the reaction mixture was stirred at RT for 16 hours. The reaction mixture was diluted with ether and washed with water. The organic layer was dried over anhydrous Na2SC>4 and the volátiles were removed under reduced pressure to obtain the title compound. Yield: 43.4 g. !H - NMR (400 MHz, CDC13): 5 7.22-7.05 (m, 3H), 4.44 (s, 2H). ¿ ':•* Step 2: Preparation of 2,3-difluorobenzylamine:
To a stirred solution of l-azidomethyl-2,3-difluorobenzene (41.3 g, 244.3 mmol) obtained in the above step in THF (490.0 mL) at 0 °C, triphenylphosphine (70.4 g, 268.8 mmol) and water (13.2 mL, 733.0 mmol) were added. The reaction mixture was stirred at RT for 16 hours and diluted with ethyl acétate. The reaction mass was washed with water and brine, dried over anhydrous Na2SÜ4 and the solvent was removed under reduced pressure.

The crude mass obtained was purifíed by silica gel column chromatography to obtain the title
i
compound.
Yield: 23.1 g; 'H - NMR (400 MHz, CDC13): 5 7.15-7.0 (m, 3H), 3.93 (s, 2H); Mass (m/z):
144.1 (M+H)+.
Using the above experimental procedure, the following substituted benzyl amines were prepared starting from the respective commercially available benzyl halides through azide intermediates.
Intermedíate 2: 3-Trifluoromethylbenzylamine (1-2)
'H - NMR (400 MHz, CDC13): 8 7.60 (s, 1H), 7.58-7.43 (m, 3H), 3.95 (s, 2H); Mass (m/z): 176.4 (M+H)+.
Intermedíate 3: 4-Pyrazol-l-yl benzylamine (1-3)
'H - NMR (400 MHz, CDC13): 8 7.92 (d, J= 2.1 Hz, 1H), 7.72 (s, 1H), 7.67 (d, J= 8.3 Hz, 2H), 7.41(d, J = 8.3Hz, 2H), 6.46 (d, J = 2.1 Hz, 1H), 3.91 (s, 2H); Mass (m/z): 174.0 (M+H)+.
Intermedíate 4: 3,4-Difluorobenzylamine (1-4)
*H - NMR (400 MHz, CDCI3): 8 7.22-7.08 (m, 2H), 7.08-7.03 (m, 1H), 3.85 (s, 2H); Mass (m/z): 144.1 (M+H)+.
Intermedíate 5: 2,4-Dichlorobenzylamine (1-5)
*H - NMR (400 MHz, CDCI3): 8 7.70-7.50 (m, 3H), 3.75 (s, 2H). Mass (m/z): 176.2, 178.1 (M+H)+. Intermedíate 6: 4-Pyridylmethylamine (1-6)
To a stirred solution of 4-cyanopyridine (100.0 mg, 0.96 mmol) in methanol (4.0 mL) at RT, 10 % Pd/C (50.0 mg) was added and stirred for 3 hours under hydrogen atmosphere. The reaction mass was fíltered through a pad of celite and the volátiles were removed under reduced pressure to obtain the title compound.
Yield: 63.6 mg; 'H - NMR (400 MHz, CDCI3): 8 8.52 (d, J = 4.7 Hz, 2H), 7.23 (d, J = 4.7 Hz, 2H), 3.88 (s, 2H); Mass (m/z): 109.2 (M+H)+.
Using the above experimental procedure, the following substituted pyridyl amines were prepared starting from the respective commercially available pyridyl nitriles. Intermedíate 7: 3-Aminomethylpyridine (1-7)
*H - NMR (400 MHz, CDC13): 8 8.58 (s, 1H), 8.52 (d, J= 4.0 Hz, 1H), 7.70 (d, J= 7.5 Hz, 1H), 7.30 (t, J= 5.9 Hz, 1H), 3.92 (s, 2H); Mass (m/z): 109.1 (M+H)+. Intermedíate 8: 2-Aminomethyl-6-methylpyridine (1-8)

'H - NMR (400 MHz, CDC13): 8 7.62-7.51 (m, 1H), 7.20-7.0 (m, 2H), 4.12-4.0 (m, 2H), 2.54
(s, 3H); Mass (m/z): 123.0 (M+H)+.
Intermedíate 9: 3-Fluoro-4-aminomethylpyridine (1-9)
'H - NMR (400 MHz, CDCI3): 8 7.43-7.36 (m, 2H), 7.35-7.26 (m, 1H), 3.91 (s, 2H); Mass
(m/z): 127.1 (M+H)+.
Intermedíate 10: 2-Phenyl-4-aminomethylpyridine (1-10)
Step 1: Preparation of 2-phenyl-4-cyanopyridine
To a stirred solution of 2-chloro-4-cyanopyrdine (500 mg, 3.61 mmol) in a 1:1 mixture of DMF and water (18 mL) at RT, phenylboronic acid (524.1 mg, 4.33 mmol), PPI13 (2.8 mg, 0.01 mmol), Pd2(dba)3 (16.5 mg, 0.018 mmol) were sequentially added. The reaction temperature was then raised to 110 °C and stirred the contents at this temperature for 1 hour. The reaction mass was diluted with ether, washed with water, brine, dried over anhydrous Na2S04 and the solvent was removed under reduced pressure to obtain the title compound. Yield: 43.4 g; 'H - NMR (400 MHz, CDC13): 8 8.86 (d, J= 4.9 Hz, 1H), 8.01 (d, J= 7.8 Hz, 2H), 7.94 (s, 1H), 7.58-7.48 (m, 3H), 7.45 (d, J= 4.9 Hz, 1H); Mass (m/z): 181.2 (M+H)+. Step 2: Preparation of 2-phenyl-4-aminomethylpyridine
To a stirred solution of 2-phenyl-4-cyanopyridine (625.0 mg, 3.4mmol) in methanol (17.0 mL) at RT, 10 % Pd/C (312.0 mg) was added and stirred for 3 hours under hydrogen atmosphere. The reaction mass was filtered through a pad of celite and the volátiles were removed under reduced pressure to obtain the title compound.
Yield: 63.6 mg; 'H - NMR (400 MHz, CDCI3): 8 8.63 (d, J= 5.0 Hz, 1H), 7.71 (s, 1H), 7.50-7.36 (m, 5H), 7.15 (d, J= 7.6 Hz, 1H), 3.97 (s, 2H); Mass (m/z): 185.1 (M+H)+.
Using the above experimental procedure, the following intermedíate was prepared with some non-critical variation.
Intermedíate 11: 2-(2-Fluoro-3-methylpyridine-5-yl)-4-aminomethylpyridine (I-11) 'H - NMR (400 MHz, CDCI3): 8 8.63 (dd, J = 5.0, 7.6 Hz, 1H), 8.58 (d, J= 6.2 Hz, 1H), 8.32-8.26 (m, 1H), 7.74-7.70 (m, 1H), 7.35-7.25 (m, 1H), 3.99 (s, 2H), 2.36 (s, 3H); Mass (m/z): 218.1 (M+H)+. Intermedíate 12: Ethyl 2-bromophenoxy acétate (1-12)

To a solution of 2-bromophenol (30.2 g, 174.6 mmol), CS2CO3 (85.3 g, 261.8 mmol) in acetonitrile (350 mL), ethyl bromoacetate (23.2 mL, 209.5 mmol) was added over a period of 15 minutes at RT and reaction mixture was stirred at RT for 15 minutes. The temperature of the reaction mixture was gradually raised to reflux and stirred for 16 hours under refluxing until the starting phenol was consumed as indicated by TLC. The reaction mass was cooled to RT, filtered through a pad of celite and the fíltrate was concentrated under vacuum to dryness. The residue was dissolved in ethyl acétate, washed with water and brine, dried pver anhydrous Na2SÜ4 and the solvent was evaporated under reduced pressure to obtain the title compound.
Yield: 43.8 g; *H - NMR (400 MHz, CDC13): 5 7.57 (d,J= 8.0 Hz, 1H), 7.24 (t,J= 8.9 Hz, 1H), 6.88 (t, J= 7.8 Hz, 1H), 6.82 (d, J= 8.3 Hz, 1H), 4.69 (s, 2H), 4.27 (q, 2H), 1.29 (t, J = 7.1 Hz, 3H); Mass (m/z): 281.1, 283.1 (M+Na)+.
Using the above experimental procedure, the following intermediates, 1-13 to 1-17 were prepared. Intermedíate 13: Ethyl 2-bromo-6-fiuoro phenoxy acétate (1-13)
'H - NMR (400 MHz, CDCI3): 5 7.34 (d, J= 7.7 Hz, 1H), 7.15-7.05 (m, 1H), 7.0-6.91 (m, 1H), 4.72 (s, 2H), 4.28 (q, 2H), 1.30 (t, J= 7.0 Hz, 3H); Mass (m/z): 299.0, 301.1 (M+Na)+. Intermedíate 14: Ethyl 3-bromo pyridin-2-yloxy acétate (1-14)
'H - NMR (400 MHz, CDCI3): 5 8.36 (d, J= 1.0 Hz, 1H), 7.95 (d, J= 6.3 Hz, 1H), 7.15-7.05
(m, 1H), 4.94 (s, 2H), 4.25 (q, 2H), 1.29 (t, J = 6.9 Hz, 3H); Mass (m/z): 260.1, 262.1
(M+H)+.
Intermedíate 15: Ethyl 2-fluoro pyridin-3-yloxy acétate (1-15)
'H . NMR (400 MHz, CDCI3): 8 7.82 (d, J= 3.6 Hz, 1H), 7.29 (d, J= 10.8 Hz, 1H), 7.12 (t, J = 2.8 Hz, 1H), 4.71 (s, 2H), 4.24 (q, 2H), 1.27 (t, J= 7.1 Hz, 3H); Mass (m/z): 200.2 (M+H)+. Intermedíate 16: Ethyl 2-bromo-3-fluoro phenoxy acétate (1-16)

'H - NMR (400 MHz, CDCl3):57.25-7.0 (m, 1H), 6.81 (t, J = 8.0 Hz, 1H), 6.60 (d, J= 8.3
Hz, 1H), 4.71 (s, 2H), 4.27 (q, 2H), 1.30 (t, J = 6.9 Hz, 3H); Mass (m/z): 277.0, 279.0
(M+H)+.
Intermedíate 17: Ethyl 2-bromo-3,6-difluoro phenoxy acétate (1-17)
'H - NMR (400 MHz, CDC13): 6 7.10-7.0 (m, 1H), 6.90-6.82 (m, 1H), 4.78 (s, 2H), 4.27 (q, 2H), 1.30 (t, J= 6.9 Hz, 3H); Mass (m/z): 294.0, 296.0 (M+H)*. . Intermedíate 18: Ethyl 2-bromophenylsulfanyl acétate (1-18)
To a solution of 2-bromothiophenol (10.0 g, 52.9 mmol), Cs2C03 (25.8 g, 79.4 mmol) in acetonitrile (210 mL) at RT, ethyl bromoacetate (7.0 mL, 63.5 mmol) was added over a period of 15 minutes. The reaction mixture was stirred at RT for 15 minutes and the reaction mixture was refluxed (80-85 °C) for 16 hours until the starting phenol was consumed as indicated by TLC. The reaction mixture was cooled to RT, filtered through a pad of celite and the fíltrate was concentrated under vacuum to dryness. The residue was dissolved in ethyl acétate, washed with water, brine, dried over anhydrous Na2SC>4 and the solvent was evaporated under reduced pressure to obtain the title compound.
Yield:13.8 g; !H - NMR (400 MHz, CDC13): 8 7.61 (d, J= 5.5 Hz, 1H), 7.42 (d, J= 7.9 Hz, 1H), 7.30 (t, J= 7.2 Hz, 1H), 7.10 (t, J= 8.0 Hz, 1H), 4.21 (q, 2H), 3.70 (s, 2H), 1.26 (t,J = 7.1 Hz, 3H); Mass (m/z): 275.0, 277.1 (M+H)+. Intermedíate 19: Methyl 2-(2-bromophenoxy)-3-hydroxy acrylate (1-19)
To a stirred solution of the intermedíate, 1-12 (18.02 g, 69.5 mmol) in methyl fórmate (105.3 mL) cooled at 0 °C, a suspensión of sodium hydride (11.1 g, 278.0 mmol, 60 % oil

dispersión) was slowly added o ver 0.5 hour and stirred for 4 hours. The reaction mixture was treated with ice cold water (400 mL) and separated aqueous layer. The aqueous layer was acidifíed with 1N HC1 and then extracted with ethyl acétate. The organic layers were combined, washed with water, saturated solution of NaHCÜ3 and fínally with brine. The organic layer was dried over anhydrous Na2SC>4 and the solvent was removed under reduced ' pressure to obtain a crude product (18.9 g) as a mixture of isomers with sufficient purity for use in the next reactions without additional purification. *H - NMR (400 MHz, DMSO-d6): 8 11.1 (bs, 1H), 7.64 (s, 1H), 7.58 (d,J= 7.7 Hz, 1H), 7.25 (t, J= 7.8 Hz, 1H), 6.90 (t, J= 7.5 Hz, 1H), 6.82 (d, J= 8.2 Hz, 1H), 3.61 (s, 3H); Mass (m/z): 271.2, 273.1 (M-H)+.
Using the above reaction procedure the following intermediates, 1-20 to 1-24 were prepared using the intermediates 1-13 to 1-17. Intermedíate 20: Methyl 2-(2-bromo-6-fluorophenoxy)-3-hydroxy acrylate (1-20)
'H - NMR (400 MHz, CDC13): 5 7.45-7.32 (m, 2H), 7.18-6.95 (m, 2H), 3.68 (s, 3H); Mass
(m/z): 313.0,315.1 (M+Na)+.
Intermedíate 21: Methyl 2-(3-bromopyridin-2-yloxy)-3-hydroxy acrylate (1-21)
'H - NMR (400 MHz, CDCI3): 8 8.04 (d, J= 1.2 Hz, 1H), 7.05 (d,J= 6.5 Hz, 1H), 6.84 (t,
1H), 3.78 (s, 3H); Mass (m/z): 246.0,248.1 (M+H)+.
Intermedíate 22: Methyl 2-(2-fluoro pyridin-3-yloxy)-3-hydroxy acrylate (1-22)
Mass (m/z): 213.2 (M+H)+.
Intermedíate 23: Methyl 2-(2-bromo-3-fluorophenoxy)-3-hydroxy acrylate (1-23)

'H - NMR (400 MHz, CDC13): 8 7.26-7.15 (m, 2H), 6.90-6.80 (m, 1H), 6.70-6.60 (m, 1H),
3.82 (s, 3H); Mass (m/z): 289.0, 291.2 (M-H)+.
Intermedíate 24: Methyl 2-(2-bromo-3,6-difluorophenoxy)-3-hydroxy acrylate (1-24)
'H-NMR (400 MHz, CDCI3): 8 7.15-6.80 (m, 3H), 3.90 (s, 3H); Mass (m/z): 307.0, 309.0
(M-H)+.
Intermedíate 25: Methyl 2-(2-bromophenylsulfanyl)-3-hydroxy acrylate (1-25)
To a stirred solution of the intermedíate, 1-18 (16.0 g, 58.2 mmol) in methyl fórmate (88.1 mL) cooled at 0 °C, a suspensión of sodium hydride (9.3 g 232.7 mmol, 60 % oil dispersión) was slowly added over 0.5 h. The reaction mixture was stirred for 4 hours and treated with ice cold water (400 mL). The two layers were separated. The aqueous layer was acidified with IN HC1 and then extracted with ethyl acétate. The organic layers were combined, washed successively with water, saturated solution of NaHCÜ3 and brine. The organic layer was dried over anhydrous Na2SÜ4; the solvent was removed under reduced pressure to obtain the title compound. !H - NMR (400 MHz, CDCI3): 8 12.49 (bs, 1H), 7.73 (s, 1H), 7.51 (d, J= 7.7 Hz, 1H), 7.23 (d, J= 7.2 Hz, 1H), 7.01 (t, J= 7.3 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 3.79 (s, 3H), 2.62 (bs, 1H); Mass (m/z): 287.1, 289.1 (M+H)+. Intermedíate 26: Methyl 4-(2-fiuorobenzyi)-4H-benzo[l,4]oxazine-2-carboxylate (1-26)
To a solution of the intermedíate, 1-19 (1.2 g, 4.4 mmol) in MeOH (18 mL) was added 2-fluorobenzylamine (0.55 g, 4.4 mmol) and stirred for 12 hours at ambient temperature. The

volátiles were evaporated to dryness. The crude residue (1.79 g) was redissolved in DMF (4.4 mL) and Cul (175.6 mg, 0.92 mmol) and CS2CO3 (3.1 g, 9.2 mmol) were added. The reaction mixture was allowed to stir vigorously at 85-90 °C for 6 hours. After completion of the reaction, the mixture was cooled to room temperature and diluted with water and the mixture was extracted with ethyl acétate; The combined organic extracts were washed with 10 % solution of HC1, with brine and dried over anhydrous Na2SÜ4. The solvent was evaporated under reduced pressure to afford the title compound. Yield: 1.48 g; 'H - NMR (400 MHz, CDCI3): 6 7.46 (t, J = 7.7 Hz, 1H), 7.40-7.25 (m, 1H), 7.20-7.0 (m, 3H), 6.70-6.60 (m, 2H), 6.58 (s, 1H), 6.24 (d, J= 7.3 Hz, 1H), 4.45 (s, 2H), 3.75 (s, 3H); Mass (m/z): 300.2 (M+H)+.
Using the above reaction procedure, the following intermediates, 1-27 to 1-31 were prepared by reacting the intermediates 1-20 to 1-24 with appropriate benzyl amines. Intermedíate 27: Methyl 8-fluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxylate (1-27)
'H - NMR (400 MHz, CDC13): 8 7.45 (t, J= 7.3 Hz, 1H), 7.36-7.27 (m, 1H), 7.16 (s, 1H), 7.09 (t, J= 8.9 Hz, 1H), 6.60-6.50 (m, 3H), 6.04 (d, J= 7.5 Hz, 1H), 4.45 (s, 2H), 3.77 (s, 3H); Mass (m/z): 318.2 (M+H)+. Intermedíate 28: Methyl l-benzyl-lH-pyrido[2,3-b][l,4]oxazine-3-carboxylate (1-28)
'H - NMR (400 MHz, CDCI3): 8 7.54 (d, J= 4.2 Hz, 1H), 7.40-7.27 (m, 5H), 6.73 (d, J= 7.5 Hz, 1H), 6.60-6.50 (m, 2H), 4.64 (s, 2H), 3.72 (s, 3H); Mass (m/z): 283.2 (M+H)+. Intermedíate 29: Methyl 4-(2-fluorobenzyl)-4H-pyrido[3,2-b][l,4]oxazine-2-carboxylate (I-29)

'H - NMR (400 MHz, CDC13): 8 7.54 (d, J= 4.9 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.38 (t, J= 7.0 Hz, 1H), 7.35-7.20 (m, 1H), 7.10-7.0 (m, 1H), 6.72 (d, J= 7.4 Hz, 1H), 6.61 (s, 1H), 6.54 (dd, J= 5.1, 7.5, Hz, 1H), 4.68 (s, 2H), 3.73 (s, 3H); Mass (m/z): 301.1 (M+H)+. Intermedíate 30: Methyl 5-fluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxylate (1-30)
'H - NMR (400 MHz, CDCI3): 8 7.49 (t, J= 7.3 Hz, 1H), 7.17 (t, J = 6.0 Hz, 1H), 7.08 (t, J= 9.4 Hz, 1H), 6.70-6.62 (m, 1H), 6.55-6.40 (m, 3H), 4.64 (s, 2H), 3.77 (s, 3H); Mass (m/z): 318.3 (M+H)+.
Intermedíate 31: Methyl 5,8-difluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxylate (1-31)
'H - NMR (400 MHz, CDCI3): 8 7.47 (t, J= 7.2 Hz, 1H), 7.36-7.29 (m, 1H), 7.15 (t, J= 7.4 Hz, 1H), 7.09 (t, J= 9.4 Hz, 1H), 6.56-6.38 (m, 3H), 4.64 (s, 2H), 3.76 (s, 3H); Mass (m/z): 336.2 (M+H)+. Intermedíate 32: Methyl 4-(2,3-difluorobenzyl)-4H-benzo[l,4]thiazine-2-carbpxylate (1-32)

To a solution of the intermedíate, 1-25 (0.8 g, 2.77 mmol) in MeOH (11 mL) was added 2,3-difluorobenzylamine, (I-l, 0.4 g, 2.77 mmol). The reaction mixture was stirred for 12 hours at ambient temperature. The volátiles were evaporated to dryness. The crude residue (1.21 g) was redissolved in DMF (5.4 mL) and to the solution Cul (55.6 mg, 0.29 mmol) and K3PO4 (1.24 g, 5.86 mmol) were added. The reaction mixture was allowed to stir vigorously at 100-110 °C for 16 hours. After completion of the reaction, the mixture was cooled to room temperature and diluted with water and the mixture was extracted with ethyl acétate. The combined organic extracts were washed with 10 % solution of HC1, with brine and dried over anhydrous Na2SC>4. The solvent was evaporated under reduced pressure and the crude thus obtained was purifíed by silica gel column chromatography to afford the title compound.
Yield: 0.55 g; *H - NMR (400 MHz, CDCI3): 5 7.20 (t, J = 5.9 Hz, 1H), 7.15 (s, 1H), 7.14-7.08 (m, 2H), 6.90-6.78 (m, 3H), 6.35 (d, J= 7.5 Hz, 1H), 4.70 (s, 2H), 3.74 (s, 3H); Mass (m/z): 333.0 (M+H)+. Intermedíate 33: 4-(2-Fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxylic acid (1-33)
To a stirred solution of the intermedíate, 1-26 (1.45 g, 4.86 mmol) in a 1:1 mixture of methanol and water (24 mL), NaOH (0.39 g, 9.7 mmol) was added. The reaction mixture was refluxed (85-90 °C) for 4 hours. After cooling the reaction mass to RT the volátiles were evaporated to one half of its volume under reduced. pressure. The obtained reaction mass was washed once with ether, cooled to 5 °C, acidified with IN HC1 and extracted with dichloromethane. The combined organic layer was dried over anhydrous Na2SC>4 and the solvent was evaporated under reduced pressure to obtain the title compound. Yield: 0.4 g; 'H - NMR (400 MHz, DMSO-d6): 8 12.1 (bs, 1H), 7.50 (t, J= 7.8 Hz, 1H), 7.36 (dd, J= 6.1, 13.8 Hz, 1H), 7.25 (d, J= 9.7 Hz, 1H), 7.21 (d, J= 6.8 Hz, 1H), 6.88 (s, 1H), 6.70-6.62 (m, 2H), 6.50-6.42 (m, 1H), 6.42-6.36 (m, 1H), 4.61 (s, 2H); Mass (m/z): 286.2 (M+H)+.
Using the above reaction procedure, the following intermediates, 1-34 to 1-38 were prepared by using the intermediates, 1-27 to 1-31.

Intermedíate 34: 8-Fluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxylic acid (I-34)
'H - NMR (400 MHz, DMSO-d6): 5 12.33 (bs, IH), 7.53 (t,J= 7.6 Hz, IH), 7.42-7.33 (m, IH), 7.30-7.20 (m, 2H), 6.92 (s, IH), 6.70-6.62 (m, 2H), 6.28-6.22 (m, IH), 4.64 (s, 2H); Mass (m/z): 304.2 (M+H)+. Intermedíate 35: l-Benzyl-lH-pyrido[2,3-b][l,4]oxazine-3-carboxylic acid (1-35)
'H - NMR (400 MHz, DMSO-d6): 5 12.33 (bs, IH), 7.52 (t, J = 4.2 Hz, IH), 7.42-7.30 (m, 4H), 7.28 (t, J= 6.7 Hz, IH), 6.89 (s, IH), 6.78 (d, J= 7.0 Hz, IH), 6.64 (dd, J= 5.0, 7.7 Hz, IH), 4.66 (s, 2H); Mass (m/z): 269.2 (M+H)+. Intermedíate 36: 4-(2-Fluorobenzyl)-4H-pyrido[3,2-b][l,4]oxazine-2-carboxylic acid (1-36)
'H - NMR (400 MHz, DMSO-d6): 5 7.55 (d, J= 5.2 Hz, IH), 7.49 (t, J= 1A Hz, IH), 7.34-
7.26 (m, IH), 7.18-7.03 (m, 2H), 6.75 (s, IH), 6.71 (d, J = 8.2 Hz, IH), 6.58 (dd, J= 5.1, 7.6
Hz, IH), 4.70 (s, 2H); Mass (m/z): 287.2 (M+H)+.
Intermedíate 37: 5-Fluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxylic acid (I-
37)

'H - NMR (400 MHz, DMSO-d6): 8 12.42 (bs, 1H), 7.53 (t, J= 7.4 Hz, 1H), 7.42-7.32 (m,
1H), 7.28-7.20 (m, 2H), 6.82 (s, 1H), 6.80-6.70 (m, 1H), 6.68-6.58 (m, 1H), 6.38 (d, J= 7.9
Hz, 1H), 4.72 (s, 2H); Mass (m/z): 304.3 (M+H)+.
Intermedíate 38: 5,8-Difluoro-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxylic acid
(1-38)
'H-NMR (400 MHz, DMSO-d6): 5 12.45 (bs, 1H), 7.54 (t, J= 7.2 Hz, 1H), 7.40-7.30 (m, 1H), 7.28-7.18 (m, 2H), 6.87 (s, 1H), 6.82-6.72 (m, 1H), 6.72-6.62 (m, 1H), 4.74.(s, 2H); Mass (m/z): 322.1 (M+H)+. Intermedíate 39: 4-(2,3-Difluorobenzyl)-4H-benzo[l,4]thiazine-2-carboxylic acid (1-39)
To a stirred solution of the intermedíate, 1-32 (0.23 g, 0.69 mmol) in a 1:1 mixture of methanol and water (2.8 mL), NaOH (55.2 mg, 1.4 mmol) was added. The reaction mixture was refiuxed (85-90 °C) for 6 hours. After cooling the reaction mass to RT, the volátiles were evaporated to one half of its volume under reduced pressure. The reaction mass obtained was washed with ether, cooled to 0-5 °C, acidified with IN HC1 and extracted with dichloromethane. The combined organic layer was dried over anhydrous Na2SC>4 and the solvent was evaporated under reduced pressure to obtain the title compound. Yield: 0.21 g; *H - NMR (400 MHz, DMSO-d6): 8 12.36 (bs, 1H), 7,50-7.40 (m, 1H), 7.28 (s, 1H), 7.27-7.20 (m, 2H), 7.40-7.30 (m, 1H), 7.30-7.25 (m, 2H), 6.54 (d, J= 8.0 Hz, 1H), 4.87 (s, 2H); Mass (m/z): 318.3 (M-H)+.

Preparation of representative compounds of formula (I).
Example 1:
N-(cis-lS, 2S-2-HydroxycyclohexyI)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide
To a solution of the intermedíate, 1-33 (100.8 mg, 0.35 mmol) in dichloromethane (2.0 mL) at RT, DIPEA (0.15 mL, 0.88 mmol), HATU (0.15 g, 0.39 mmol) and (1S.2S) 2-aminocyclohexanol hydrochloride (53.5 mg, 0.35 mmol) was added sequentially while stirring vigorously. After completion of addition, the reaction mixture was stirred for 16 hours before diluted with dichloromethane. The reaction mass was washed with water, brine, dried over anhydrous Na2SÜ4 and the solvent was evaporated under vacuum. The crude mass obtained was purified on silica gel column to afford the title compound. Yield: 106.4 mg; rH - NMR (400 MHz, CDC13): 8 7.46 (t, J = 7.4 Hz, 1H), 7.29 (t, J = 6.2 Hz, 1H), 7.17-7.05 (m, 2H), 6.72-6.62 (m, 2H), 6.57 (s, 1H), 6.56-6.49 (m, 1H), 6.30-6.23 (m, 1H), 5.99 (d,J= 6.7 Hz, 1H), 4.46 (s, 2H), 3.83 (t, J= 3.7 Hz, 1H), 3.76-3.65 (m, 1H), 3.45-3.36 (m, 1H), 2.15-2.06 (m, 1H), 2.05-1.95 (m, 1H), 1.82-1.70 (m, 2H), 1.42-1.18 (m, 4H); Mass (m/z): 383.4 (M+H)+.
Examples 2 to 61: The compounds of Examples 2 to 61 were prepared by following the experimental procedures as described in the Example 1 given above, with some non-critical variations using appropriate acids, for example, 1-33 to 1-38 with suitable R1NH2.

Example 62:
N-(3-Fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide hydrochloride
Step 1: Preparation of N-(l-tertbutoxycarbonyl-3-fluoropiperidin-4-yl)-4-(2-fluoro benzyl)-8-fluoro-4H-benzo[ 1 J4]oxazine-2-carboxamide
4-(2-Fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxylic acid (1-34) was treated with tert-butyl 4-amino-3-fluoropiperidine-l-carboxylate in presence of HATU by following the procedure as described in the preparation of example 1 to obtain the title compound.
'H - NMR (400 MHz, CDC13): 5 7.44 (t, J = 7.2 Hz, IH), 7.36-7.28 (rn, IH), 7.14 (t, J = 7.5 Hz, IH), 7.08 (t, J = 8.9 Hz, IH), 6.67-6.50 (m, 3H), 6.49 (d, J = 8.2 Hz, IH), 6.05 (d, J = 7.9 Hz, IH), 4.74 (d, J = 52.0 Hz, IH), 4.46 (s, 2H), 4.38-4.10 (m, 3H), 3.10-2.80 (m, 2H), 1.91-1.72 (m, 2H), 1:47 (s, 9H); Mass (m/z): 504.4 (M+H)+.
Step 2: Preparation of N-(3-Fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzofl ,4]oxazine-2-carboxamide hydrochloride

To a stirred solution of the compound obtained in the above step 1 (50.0 mg, 0.1 mmol) in IPA (1.0 mL) cooled at 0 °C, a solution of 3N HCl in IPA (0.5 mL) was added. The reaction mixture was stirred for 1 hour and the volátiles were removed under reduced pressure to obtain a mass which was washed several times with ether to afford the title compound.
Yield: 43 mg; 'H - NMR (400 MHz, DMSO-d6): 5 9.22 (bs, 1H), 8.63 (bs, 1H),7.51 (t, J = 7.2 Hz, 1H), 7.42-7.36 (m, 1H), 7.32-7.18 (m, 2H), 7.12 (d, J = 7.6 Hz, 1H), 6.80 (s, 1H), 6.78-6.62 (m, 2H), 6.28 (d, J = 7.3 Hz, 1H), 5.03 (d, J = 47.6 Hz, 1H), 4.62 (s, 2H), 4.50-4.40 (m, 1H), 4.40-4.15 (m, 2H), 3.20-3.0 (m, 2H), 2.10-1.96 (m, 1H), 1.90-1.80 (m, 1H); Mass (m/z): 404.2 (M+H)+.
Example 63:
N-(3-Fluoropiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide hydrochloride
Step 1: Preparation of N-(l-tertbutoxycarbonyl-3-fluoropiperidin-4-yl)-4-(2,3-difluoro benzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide
This compound was prepared using step 1 procedure of example 62. lH - NMR (400 MHz, CDC13): 5 7.28-7.20 (m, 1H), 7.20-7.06 (m, 2H), 6.68-6.50 (m, 3H), 6.34 (d, J = 8.3 Hz, 1H), 6.02 (d, J = 7.9 Hz, 1H), 4.73 (d, J = 49.8 Hz, 1H), 4.48 (s, 2H), 4.40-4.10 (m, 3H), 3.12-2.78 (m, 2H), 1.92-1.78 (m, 2H), 1.46 (s, 9H); Mass (m/z): 522.3 (M+H)+.
Step 2: Preparation of N-(3-fluoro piperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l ,4]oxazine-2-carboxamide hydrochloride
This compound was prepared using step 2 procedure of example 62. [H - NMR (400 MHz, DMSO-d6): 5 9.16 (bs, 1H), 8.62 (bs, 1H), 7.50-7.10 (m, 3H), 6.81 (s, 1H), 6.80-6.70 (m, 2H), 6.68-6.40 (m, 1H), 6.29 (d, J = 7.1 Hz, 1H), 5.03 (d, J = 48.3 Hz,

IH), 4.71 (s, 2H), 4.35-4.10 (m, 2H), 3.20-3.0 (m, 2H), 2.10-1.98 (m, IH), 1.90-1.80 (m, IH); Mass (m/z): 422.3 (M+H)+.
Example 64:
N-(3-Hydroxypiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-cárboxamide trifluoroacetate
Step 1: Preparation of N-(l-tertbutoxycarbonyl-3-hydroxypiperidin-4-yl)-4-(2,3-difluoro benzyl)-8-fluoro-4H-benzo[l ,4]oxazine-2-carboxamide
The title compound was prepared using step 1 procedure of example 62. 'H - NMR (400 MHz, CDC13): 8 7.25-7.16 (m, IH), 7.16-7.05 (m, 2H), 6.70-6.50 (m, 3H), 6.12-6.02 (m, 2H), 4.49 (s, 2H), 4.40-4.10 (m, 3H), 3.88-3.78 (m, IH), 3.50-3.38 (m, IH), 2.80-2.70 (m, IH), 2.70-2.55 (m, IH), 1.98-1.90 (m, IH), 1.60-1.50 (m, IH), 1.45 (s, 9H); Mass (m/z): 520.2 (M+H)+.
Step 2: Preparation of N-(3-hydroxypiperidin-4-yl)-4-(2,3-difluoro benzyl)-8-fluoro-4H-benzofl ,4]oxazine-2-carboxamide trifluoroacetate
To the stirred solution of compound obtained in step 1 (75.0 mg, 0.14 mmol) in DCM (0.7 mL) cooled at 0 °C trifluoroacetic acid (0.7 mL) was added. The reaction mixture was stirred at RT for an hour and the volátiles were removed under reduced pressure to obtain a crude mass which was triturated several times with ether to obtain the title compound. 'H - NMR (400 MHz, DMSO-d6): 8 8.64 (bs, 2H), 7.50-7.10 (m, 3H), 6.80-6.70 (m, 3H), 6'.35-6.25 (m, IH), 5.60-5.50 (m, IH), 4.70 (s, 2H), 3.90-3.70 (m, 2H), 3.60-3.20 (m, 3H), 3.20-3.0 (m, 2H), 2.10-1.98 (m, IH), 1.90-1.80 (m, IH); Mass (m/z): 420.3 (M+H)+.
Example 65:
N-(3-Hydroxypiperidin-4-yl)-4-(2-fluorobenzyI)-4H-benzo[l,4]oxazine-2-carboxamide
trifluoroacetate

Step 1: Preparation of N-(l-tertbutoxycarbonyl-3-hydroxypiperidin-4-yl)-4-(2-fluoro benzyl)-4H-benzo[l,4]oxazine-2-carboxamide
The.title compound was prepared using step 1 procedure of example 62. 'H - NMR (400 MHz, CDC13): 5 7.50-7.40 (m, IH), 7.20-7.20 (m, IH), 7.18-7.02 (m, 2H), 6.72-6.62 (m, 2H), 6.59 (s, IH), 6.55-6.48 (m, IH), 6.32-6.25 (m, IH), 6.02 (d, J = 5.9 Hz, IH), 4.46 (s, 2H), 4.40-4.10 (m, 3H), 3.83-3.75 (m, IH), 3.50-3.40 (m, IH), 2.80-2.70 (m, IH), 2.70-2.57 (m, IH), 1.98-1.90 (m, IH), 1.60-1.50 (m, IH), 1.45 (s, 9H); Mass (m/z): 484.3 (M+H)+.
Step 2: Preparation of N-(3-Hydroxypiperidin-4-yl)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-carboxamidetrifluoroacetate
The title compound was prepared using step 2 procedure of example 64. 'H - NMR (400 MHz, DMSO-d6): 6 8.61 (bs, 2H), 7.70-7.10 (m, 5H), 6.80-6.60 (m, 3H), 6.50-6.40 (m, IH), 5.50 (d, J = 3.9 Hz, IH), 4.61 (s, 2H), 3.90-3.70 (m, 2H), 3.40-3.25 (m, 3H), 3.10-2.90 (m, 2H), 2.88-1.78 (m, IH), 1.70-1.60 (m, IH); Mass (m/z): 384.3 (M+H)+.
Example 66:
N-(3-Fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide
To a stirred solution of N-(3-fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide hydrochloride (example 62, 20.0 mg, 0.045 mmol) in ethyl acétate (2.0 mL), cooled at 0 °C, a solution of NaOH (IN, 0.5 mL) was added. The reaction mixture was stirred for 5 minutes and the two layers were. separated. The organic layer was

washed with brine, dried over anhydrous Na2SÜ4 and the solvent was removed under reduced
pressüre to obtain the title compound.
Yield: 15.0 mg; 'H - NMR (400 MHz, CDC13): 8 7.44 (t, J'= 7.3 Hz, 1H), 7.35-7.25 (m, 1H),
7.13 (t, J = 7.4 Hz, 1H), 7.08 (t, J = 9.4 Hz, 1H), 6.63-6.43 (m, 3H), 6.33 (d, J = 8.6 Hz, 1H),
6.05 (d, J = 7.9 Hz, 1H), 4.70 (d, J = 50.1 Hz, 1H), 4.46 (s, 2H), 4.23-4.10 (m, 1H), 3.40-3.28
(m, 1H), 3.20-3.10 (m, 1H), 2.90-2.65 (m, 2H), 1.70-1.60 (m, 2H); Mass (m/z): 404.3
(M+H)+.
Examples 67 to 69: The compounds of Example 67 to 69 were prepared by following the experimental procedures as described in the Example 66 given above, with some non-critical variations.

Example 70:
N-(cís-l S, 2S-2-HydroxycyclohexyI)-4-(2,3-difluorobenzyl)-4H-benzo [1,4] thiazine-2-
carboxamide
To a solution of the intermedíate, 1-39 (200.8 mg, 0.63 mmol) in dichloromethane (2.0 mL) at RT, DIPEA (0.27 mL, 01.56 mmol), HATU (0.29 g, 0.75 mmol) and (1S,2S) 2-amino cyclohexanol hydrochloride (94.5 mg, 0.63 mmol) was added sequentially while stirring vigorously. Añer completion of addition, the reaction mixture was stirred for 16 hours and diluted with dichloromethane. The reaction mass was washed with water, brine, dried over anhydrous Na2SC>4 and the solvent was evaporated under vacuum. The crude mass obtained was purified using silica gel column chromatography to afford the title compound. Yield: 210.0 mg; *H - NMR (400 MHz, CDC13): 5 7.39 (s, 1H), 7.18-7.03 (m, 3H), 7.03-6.91 (m, 3H), 6.55 (d, J= 7.9 Hz, 1H), 6.0 (d, J = 6.7 Hz, 1H), 4.83 (s, 2H), 3.77 (d, J= 3.8 Hz, 1H), 3.80-3.67 (m, 1H), 3.45-335 (m, 1H), 2.17-2.08 (m, 1H), 2.05-1.98 (m, 1H), 1.82-1.72 (m, 2H), 1.43-1.22 (m, 4H); Mass (m/z): 417.3 (M+H)+.

Examples 71 to 77: The compounds of Examples 71 to 77 were prepared by following the experimental procedures as described in the Example 70 given above, with some noncritical variations

Example 78:
N-(cis-lS, 2S-2-HydroxycycIohexyl)-4-(2,3-difluorobenzyI)-l-oxo-4H-benzo[l,4]
thiazine-2-carboxamide
To a stirred solution of compound of example 70 (136.0 mg, 0.33 mmol) in 1:1 mixture of methanol and THF (1.4 mL) at RT, solution of NaI04 (76.5 mg, 0.36 mmol) in water (1.6 mL) was added over a period of 15 minutes. The reaction mass was stirred for 16 hours at RT and filtered through a pad of celite. The fíltrate was evaporated under reduced pressure. The crude mass was dissolved in dichloromethané and washed with water and brine solution. The organic layer was dried over anhydrous N^SCU and the solvent was removed under reduced pressure to obtain the title compound.
Yield: 115 mg; 'H - NMR (400 MHz, CDC13): 8 8.33 (s, IH), 8.02 (d, J= 7.7 Hz, IH), 7.59 (t, J= 7.7 Hz, IH), 7.43 (d, J= 7.4 Hz, IH), 7.20-7.10 (m, 2H), 7.06-6.97 (m, IH), 6.74 (t, J = 6.9 Hz, IH), 6.57 (d,J= 6.4 Hz, IH), 5.53 (d,J= 17.2 Hz, IH), 5.31 (d,J= 17.2 Hz, IH), 3.95-3.85 (m, 2H), 3.51-3.42 (m, IH), 2.20-2.06 (m, 2H), 1.83-1.72 (m, 2H), 1.50-1.20 (m, 4H); Mass (m/z): 433.3 (M+H)+.
Examples 79 to 82: The compounds of Examples 79 to 82 were prepared by following the experimental procedures as described in the Exampíe 78 given above, with some noncritical variations.

Example 83
Determination of allosteric potency EC50 valúes for Muscarinic MI receptor:
A stable CHO cell line expressing recombinant human Muscarinic MI receptor and pCRE-Luc repórter system was used for cell-based assay. The assay offers a non-radioactive based approach to determine binding of a compound to GPCRs. In this spe.cific assay, the level of intracellular cyclic AMP which is modulated by activation or inhibition of the receptor is measured. The recombinant cells harbor luciferase repórter gene under the control of cAMP response element.
The above cells were grown in 96 well clear bottom white plates in Hams F12 médium containing 10 % fetal bovine serum (FBS). Prior to the addition of compounds or standard agonist, cells were serum starved overnight. Increasing concentrations of test compounds were added along with EC20 of acetylcholine in OptiMEM médium to the cells. The incubation was continued at 37 °C in CO2 incubator for 4 hours. Médium was removed and cells were washed with phosphate buffered saline. The cells were lysed and luciferase activity was measured in a Luminometer. Luminescence units were plotted against the compound concentrations using Graphpad software. EC50 valúes. of the compounds were defined as the concentration required in stimulating the luciferase activity by 50 % in presence of EC20 of acetylcholine.

Example 84
Object Recognition Task Model
The cognition enhancing properties of compounds of this invention were estimated by using this model.
Male Wístar rats (8- 10 weeks oíd) were used as experimental animáis. Four animáis were housed in each cage. Animáis were kept on 20 % food deprivation from a day prior to experimentation. Water was provided ad libitum throughout the experiment. Animáis were maintained on a 12 hours light/dark cycle in temperature and humidity controlled room. The

experiment was carried out in an open fíeld made up of acrylic. Rats were habituated to individual arenas (open fíeld) for 1 hour in the absence of any objects on day 1.
One group of 12 iats lecewed velñcle and anothei set of animáis received test compounds or test compounds and Donepezil, before the familiar (Ti) and choice (T2) triáis. During the familiarization phase, (Ti), the rats were placed individually in the arena for 3 minutes, in which two identical objects (ai and a2) were positioned 10 cm from the wall. 24 hours after Ti, trial for long-term memory test was performed. The same rats were placed in the same arena as they were placed in Ti trial. During the choice phase (T2) rats were allowed to explore the arena for 3 minutes in presence of a copy of familiar object (a3) and one novel object (b). During the Ti and T2 trial, explorations of each object (defined as sniffing, licking, chewing or having moving vibrissae whilst directing the nose towards the object at a distance of less than 1 cm) were recorded using stopwatch. Ti is the total time spent exploring the familiar objects (al + a2). T2 is the total time spent exploring the familiar object and novel object (a3 +b). Discriminative index = Time spent with novel object / (time spent with novel and familiar object).
The object recognition test was performed as described in Behavioural Brain Research, 1988,31,47-59.
Effect of Example 18 in combination with Donepezil
Procognitive effects observed with combination of test compound, example 18 and donepezil is better than the either treatment. The results are shown in figures 1 and 2.
Example 85
Object Recognition Task Model - Scopolamine challenge

The cognition enhancing properties of compounds óf this invention were estimated by using this model.
Male Wistar rats (8- 10 weeks oíd) were used as experimental animáis. Four animáis
i
were housed in each cage. Animáis were kept on 20 % food deprivation from a day prior to experimentation. Water was provided ad libitum throughout the experiment. Animáis were maintained on a 12 hours light/dark cycle in temperature and humidity controlled room. The experiment was carried out in an open field made up of acrylic. Rats were habituated to individual arenas (open field) for 1 hour in the absence of any objects on day. 1.
Rats received vehicle or vehicle and scopolamine or cómpound of the formula (I) and scopolamine, before the familiar (Ti). During the familiarization phase, (Ti), the rats were placed individually in the arena for 3 minutes, in which two identical objects (aj and &2) were positioned 10 cm from the wall. 3 minutes after Ti, trial for memory test was performed. The same rats were placed in the same arena as they were placed in Ti trial. During the choice phase (T2) rats were allowed to explore the arena for 3 minutes in presence of a copy of familiar object (a3) and one novel object (b). During the Ti and T2 trial, explorations of each object (defined as sniffing, licking, chewing or having moving vibrissae whilst directing the nose towards the object at a distance of less than 1 cm) were recorded using stopwatch. Ti is the total time spent exploring the familiar objects (al + a2). T2 is the total time spent exploring the familiar object and novel object (a3 +b). Discriminative index = Time spent with novel object / (time spent with novel and familiar object).
Example 86
Contextual fear conditioning task
Experiment was carried out o ver a period of two days. On day 1, rats were placed in the operant behavior chamber and allowed to acclimatize for 2 minutes. Rats received an unavoidable foot shock (unconditioned stimulus (US): electric shock of 0.5 - 0.7 mA for 3 sec). Following a 1 minute interval, shocks were repeated to deliver a total of three US. Rats were administered with vehicle or test cómpound post training. Scopolamine (0.3 mg/kg, s.c.) was administered 120 minutes after training.

On day 2, rats were placed in the operant behavior chamber and total freezing time was scored for a period of 5 minutes. Test compound, example 18 reversed the scopolamine induced memory déficit and the result is shown in figure 3.
Example 87
Rodent Pharmacokinetic Study
Male Wistar rats (260 ± 50 grams) were used as experimental animáis. Animáis were housed individually in polypropylene cage. Two days prior to study, male Wistar rats were anesthetized with isofiurane for surgical placement of jugular vein catheter. Rats were randomly divided for oral (3 mg/kg) and intravenous (1 mg/kg) dosing (n = 3/group) and fasted overnight before oral dosing (p.o.). However, rats allocated to intravenous (z'.v.) dosing food and water was provided ad libitum.
At pre-determined point, blood was collected through jugular vein and replenished with an equivalent volume of normal saline. Collected blood was transferred into a labeled eppendorf tube containing 10 uL of heparin as an anticoagulant. Typically blood samples were collected at following time points: 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours post dose. Blood was centrifuged at 4000 rpm for 10 minutes. Plasma was separated and stored frozen at -80 °C until analysis. The concentrations of the test compounds were quantified in plasma by qualified LC-MS/MS method using suitable extraction technique. The test compounds were quantified in the calibration range around 1-1000 ng/mL in plasma. Study samples were analyzed using calibration samples in the batch and quality control samples spread across the batch.
Pharmacokinetic parameters Cmax, Tmax, AUQ, T1/2, clearance, Vz and bioavailability were calculated by non-compartmental model using standard non-compartmental model by using Phoenix WinNonlin 6.0.2 or 6.0.3 versión Software package.

Example 88
Rodent Brain Penetration Study
Male Wistar rats (260 ± 40 grams) were used as experimental animáis. Three animáis were housed in each cage. Animáis were given water and food ad libitum throughout the experiment and maintained on a 12 hours light/dark cycle.
Brain penetration was determined in discrete manner in rats. One day prior to dosing day, male Wistar rats were acclimatized and randomly grouped according to their weight. At each time point (0.50, 1 and 2 hours) n = 3 animáis were used.
The test compounds were suitably preformulated and administered orally at (free base equivalent) 3 mg/kg. Blood samples were removed via cardiac punchare by using isoflurane anesthesia. The animáis were sacrificed to collect brain tissue. Plasma was separated and brain samples were homogenized and stored frozen at -20 °C until analysis. The concentrations of the test compounds in plasma and brain were determined using LC-MS/MS method.
The test compounds were quantified in plasma and brain homogenate by qualified LC-MS/MS method using suitable extraction technique. The test compounds were quantified in the calibration range of 1-500 ng/mL in plasma and brain homogenate. Study samples were analyzed using calibration samples in the batch and quality control samples spread across the batch. Extent of brain-plasma ratio was calculated (Ct,/Cp).

Example 89
Modulation of soluble amyloid precursor protein a (sAPPa) levéis in cortex
In addition to providing symptomatic treatment for cognitive déficits in Alzheimer's desease, activation of the MI receptor also has disease modifying effects in AD patients. Positive allosteric modulators at MI receptor have demonstrated to increase the generation of sAPPa in-vitro indicating processing of amyloid precursor protein through the non-amyloidogenic pathway. Experimental Procedure: Estimation of. cortical sAPPa levéis in rat brain
Male Wistar rats (250 ± 40 grams) were randomly divided (n=8 group) into different treatment groups. Control group of rats were intraperitoneally (/'./?.) administered with vehicle (99.75 % of 0.25 % HEC HHX + 0.25 % tween 80). Rats from treatment groups received a single intraperitoneal injection of test compound (dose volume of 2 mL/kg). Rats were sacrificed by cervical dislocation at 60 minutes after administration of test compound. Brains were quickly isolated and the cortex was dissected at -20 °C. The cortex was immediately kept.on a dry ice and weighed before being stored at -80 °C until quantification of sAPPa using Enzyme-linked immunosorbent assay (ELISA). Estimation of cortical sAPPa levéis in mice brain
Male C57BL/6J mice (25 ± 5 grams) were randomly divided (n=8 group) into five groups. Control group of mice were intraperitoneally (i.p.) administered with vehicle (99.75 % of 0.25 % HEC HHX + 0.25 % tween 80) and the treatment group of mice received a single intraperitoneal injection of example 18 (dose volume of 10 mL/kg). Mice were sacrificed by cervical dislocation at 60 minutes after administration of test compound. Brains were quickly isolated and the cortex was dissected at -20 °C. The cortex was immediately kept on a dry ice and weighed before being stored at -80 °C until quantification of sAPPa using Enzyme-linked immunosorbent assay (ELISA). Sample Prepara tion:
1. Protease inhibitor cocktail tablets (complete mini, Make- Roche; 1 tablet for 8 mL) were added to the Tris Buffer Saline (TBS) prior to using the buffer for the tissue processing.

2. Cortical tissues were thawed and homogenized in fíve volumes of TBS and the solution was centrifuged at 15,000 rpm at 4 °C for 90 minutes.
3. The supematant was discarded and homogenized in five volumes of TBS. Samples were centrifuged at 15,000 rpm at 4 °C for 30 minutes.
4'. Supematant was discarded and precipitated was sonicated in ten volumes of 6 M
Guanidine-HCl (in 50 mM Tris buffer, pH: 7.6). Sonication was repeated four times with
duration of five seconds every time.
5. Resulting mixture was incubated at the room temperature for 30 minutes and centrifuged at
15,000 rpm at 4 °C for 30 minutes. Supematant was diluted 100 times with EIA buffer prior
to addition in the pre-coated ELISA plates.
Measurement of sAPPa by ELISA Kit:
To investígate the role of an acute treatment of test compound on sAPPa levéis, the expression of this protein was measured in homogenates obtained from the cortex of treated and untreated rats by employing ELISA assay. The entire procedure was followed as described in the ELISA kit manual (Mouse/Rat sAPPa ELISA, Catalog Number: JP27419, Immuno-Biological Laboratories, Hamburg, Germany). Statistical analysis:
Statistical analyses were performed using the Graph Pad Prism (Versión 4). Results are expressed as Mean ± SEM levéis of sAPPa expressed as percentage of control valúes (rats treated with vehicle). Statistical significance after treatment was assessed using One-Way ANO VA followed by Dunnett's post test and the significance level was set below p valué less than 0.05. References:
Neurotherapeutics, 2008, 5, 433-442 Current Alzheimer Research, 2009, 6, 112-117 The Journal ofNeuroscience, 2009, 29, 14271-14286
Journal of Pharmacology and Experimental Therapeutics, 2003, 305, 864 - 871 Result:
After sixty minutes post treatment, the test compound, example 18 produced significant increases in the cortical sAPPa levéis in mice brain with mean increase of 38 % observed at a dose 10 mg/kg, i.p. and the result are shown in figure 4. Similarly, Example 18 produced dose-dependent increase in the rat brain cortical sAPPa levéis with mean máximum increase of 26 % observed at a dose 10 mg/kg, i.p. and the result is shown in figure 5.

We claim:
A compound of formula (I),
wherein:
A and A are each independently represents CH, CF or N;
W is O, S, S(O) or S(0)2;
R'is
wherein * represents point of attachment; R3 is OH, F, NH2 or H;

ORIGINAL
R4 at each occurrence is independently selected from halogen, -O-CH3; -S-CH3,
-N(CH3)2, -CH3, -CF3, -CHF2, -CH2F, -OH, -CN, phenyl, pyridyl and hydrogen;
wherein phenyl and pyridyl are optionally substituted with one or more substituents
selected from the group consisting of halogen or CH3;
X is CH2, O or NH;
a is 0 or 1; and b is 1 or 2;
or an isotopic form, a stereoisomer, a tautomer or a pharmaceutically acceptable salt
thereof.
The compound of formula (I) as claimed in claim 1, wherein:
WisO;
A1 and A2 are CH;
R1 is
R2is
The compound of formula (I) as claimed in claim 1, wherein:
WisS;
A1 and A2 are CH;
R1 is
R2is

4. The compound of formula (I) as claimed in claim 1, wherein:
WisO;
A1 and A2 are CH; R'is
R2is
X is CH2.
5. The compound of formula (I) as claimed in claim 1, wherein:
WisS;
A1 and A2 are CH; R'is
R2is

X is CH2.
The compound as claimed in any one of the claims 1 to 5, wherein the compound is
selected from the group consisting of:
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS,2S-2-Hydroxycycíohexyl)-8-fluoro-4-(2-fluorobenzyl)-4H-
benzp[ 1,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{2-fluorobenzyl}-4H-pyrido[3,2-
b] [ 1,4]oxazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-benzyl-4H-benzo[ 1,4]oxazine-2-
carboxamide;
N-(cis-l S, 2S-2-Hydroxycyclohexyl)-4-(4-methoxybenzyl)-4H-benzo[l ,4]oxazine-
2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(4-methoxybenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(3 -fluorobenzyl)-4H-benzo [ 1,4] oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4T(3-methoxybenzyl)-4H-benzo[l,4]oxazine-
2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(3-methoxybenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(2-methoxypyridin-4-ylmethyl)-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(2-methoxypyridin-4-ylmethyl)-4H-
benzo[l ,4]oxazine-2-carboxamide;

N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(4-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(4-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(cis-l.S, 2S-2-Hydroxycyclohexyl)-4-(2-methoxypyridin-5-ylmethyl)-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(2-Hydroxy-2-methylpropyl)-4-(2-methoxypyridin-5-ylmethyl)-4H-
benzo[l ,4]oxazine-2-carboxamide;
N-(cis-l S, 2S-2-Hydroxycyclohexyl)-4-(3-trifluoromethylbenzyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2,3-difluoro benzyl)-4H-
benzo[l ,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3,4-difluoro benzyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(3-Hydroxytetrahydrpyran-4-yl)-4-(2,3-difluorobenzyl)-4H-benzo[l,4]oxazine-
2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(2-chloropyridin-5-ylmethyl)-4H-
benzo[l ,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(pyridin-3-ylmethyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-l S, 2S-2-Hydroxycyclohexyl)-4-(pyridin-4-ylmethyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chloropyridin-4-ylmethyl)-4H-
benzo[l ,4]oxazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(pyridin-2-yimethyl)-4H-
benzo[l ,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3,4-dichloro benzyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-methylpyridin-3-ylmethyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-l S, 2S-2-Hydroxycyclohexyl)-4-(2,4-dichlorobenzyl)-4H-
benzofl ,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-8-fluoro-4-(2,3-difluorobenzyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;

N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-benzyl-4H-pyrido[3,2-b] [ 1,4]oxazine-2-
carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-1 -Benzyl-1 H-pyrido[2,3-b] [ 1,4]oxazine-3-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-l-{2,3-difluorobenzyl}-lH-pyrido[2,3-
b] [ 1,4]oxazine-3-carboxamide;
N-(cis-lS,2S-2-Hydroxycyclohexyl)-4-(2,3-difluorobenzyl)-4H-pyrido[3,2-
b] [ 1,4]oxazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(3-fluoropyridin-4-yImethyl)-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(4-fluorobenzyl)-4H-pyrido[3,2-
b] [ 1,4] oxazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-1 -(3-fluorobenzyl)-1 H-pyrido[2,3 -
b] [ 1,4]oxazine-3-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-(2-trifluoromethylbenzyl)-4H-
benzo[ 1,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chlorobenzyl)-8-fluoro-4H-
benzo [1,4] oxazine-2 -carboxamide;
N-(trans-lR,2R-2-Hydroxycyclopentyl)-4-(2,3-difluorobenzyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(trans-lR,2R-2-Hydroxycyclopentyl)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-
2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chlorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(trans-1R, 2R-2-Hydroxycyclopentyl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2-fluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-
benzo[ 1,4]oxazine-2-carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2,3-difluorobenzyl)-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(2-Hydroxymethylphenyl)-4-(2-fluorobenzyl)-8 -fluoro-4H-benzo [ 1,4] oxazine-2-
carboxamide;

N'(l-Hydroxymethyl-2-methylpropyl)-8-fluoro-4-(2-fluorobenzyl)-4H-
benzo[l,4]oxazine-2-carboxamide;
N'(c.is-\S,2S-2-HydTOxycycVohexy\)-4-benzy\-&-í\viOTO-4H-benzo[\^ox2ame.-2-
carboxamide;
N-(cis-lR, 2R-2-Hydroxycyclohexyl)-4-{2-fluorobenzyl}-4H-benzo[l,4]oxazine-2-
carboxamide;
N*(cis-1R, 2R-2-Hydroxycyclohexyl)-4-{2-fluorobenzyl}-8-fluoro-4H-
benzo[ 1,4]oxazine-2-carboxamide;
N'(cis-lS,2S-2-Hydroxycyclohexyl)-4-{3-fluorobenzyl}-8-fluoro-4H-
benzo [1,4] oxazine-2-carboxamide;
N'(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-phenylpyridin-4-ylmethyl)-4H-
benzo[l,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-8-fluoro-4-(2-phenylpyridin-4-ylmethyl)-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-chloropyridin-4-ylmethyl)-8-fluoro-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-fluorobenzyl)-5-fluoro-4H-
benzo[l ,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(pyridine-2-ylmethyl)-5-fluoro-4H-
benzo[l,4] oxazine-2-carboxamide;N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-
(pyridine-4-ylmethyl)-8-fluoro-4H-benzo[l,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(6'-Fluoro-5,-methyl-[2,3']bipyridinyl-4-
ylmethyl)-4H-benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-[2-(l-methyl-lH-pyrazol-3-yl)-pyridin-4-
ylmethyl]-4H-benzo[l,4]oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(l-methyl-lH-pyrazol-3-ylmethyl)-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2-fluorobenzyl)-5,8-difluoro-4H-
benzo [ 1,4] oxazine-2-carboxamide;
N-(3-Fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-
carboxamide;
N-(3-Fluoropiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-
2-carboxamide;

N-(3-Hydroxypiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-
benzo[l,4]oxazine-2-carboxamide;
N-(3 -Hydroxypiperidin-4-yl)-4-(2-fluorobenzyl)-4H-benzo [ 1,4] oxazine-2-
carboxamide;
N-(cis-lS, 2S-2-hydroxy cyclohexyl)-4-(2,3-difluorobenzyl)-4H-
benzo[ 1,4]thiazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(3-fluorobenzyl)-4H-benzo[l,4]thiazine-2-
carboxamide;
Ñ-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-benzyl-4H-benzo[l,4]thiazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{4-methoxybenzyl}-4H-benzo[l,4]thiazine-
2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{4-fluorobenzyl}-4H-benzo[l,4]tbiazine-2-
carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-{pyridin-4-yl-methyl}-4H-
benzo[ 1,4]thiazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{2-chloropyridin-5-yl-methyl}-4H-
benzo[ 1,4]thiazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{pyridin-2-yl-methyl}-4H-
benzo[l ,4]thiazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-(2,3-difluorobenzyl)-l-oxo-4H-
benzo[l ,4]thiazine-2-carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-benzyl-l-oxo-4H-benzo[l,4]thiazine-2-
carboxamide;
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{3-fluorobenzyl}-l-oxo-4H-
benzo[l,4]thiazine-2-carboxamide;
N-(cis-1S, 2S-2-Hydroxycyclohexyl)-4-{pyridin-2-yl-methyl}-1 -oxo-4H-
benzo[l,4]thiazine-2-carboxamide; and
N-(cis-lS, 2S-2-Hydroxycyclohexyl)-4-{2-chloropyridin-5-yl-methyl}-l-oxo-4H-
benzo[ 1,4]thiazine-2-carboxamide;
or a pharmaceutically acceptable salt thereof.
7. The compound as claimed in any one of the claims 1 to 6, wherein the
pharmaceutically acceptable salt is selected from the group consisting of:

N-(3-Fluoropiperidin-4-yl)-4-(2-fluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide hydrochloride;
N-(3-Fluoropiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide hydrochloride;
N-(3-Hydroxypiperidin-4-yl)-4-(2,3-difluorobenzyl)-8-fluoro-4H-benzo[l,4]oxazine-2-carboxamide trifluoroacetate; and N-(3-Hydroxypiperidin-4-yl)-4-(2-fluorobenzyl),-4H-benzo[l,4]oxazine-2-carboxamide trifluoroacetate.
8. A pharmaceutical composition comprising a compound as claimed in any one of the claims 1 to 7, and pharmaceutically acceptable excipients or carriers.
9. The pharmaceutical composition as claimed in claim 8, for the treatment of disorder related to muscarinic MI receptor selected from the group consisting of Alzheimer's disease, schizophrenia, cognitive disorders, pain or sleep disorders.
10. A method for treating a disorder related to muscarinic MI receptor comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7.

11. The method as claimed in claim 10, wherein disorder related to muscarinic MI receptor is selected from the group consisting of Alzheimer's disease, schizophrenia, cognitive disorders, pain or sleep disorders.
12. Use of the compound as claimed in any one of the claims 1 to 7, for the manufacture of medicament for the treatment of disorder related to Muscarinic MI receptor.
13. The compound as claimed in any one of the claims 1 to 7, for use in the treatment of disorder related to muscarinic MI receptor selected from the group consisting of Alzheimer's disease, schizophrenia, cognitive disorders, pain or sleep disorders.