Claims
1. A compound of formula 00
or a tautomer, stereoisomer (such as an enantiomer or diastereomer), pharmaceutically acceptable salt, pharmaceutically acceptable ester, prodrug or N-oxide thereof, wherein Ring A is independently selected from a substituted or unsubstituted monocyclic aryl and a substituted or unsubstituted monocyclic heteroaryl, wherein each occurrence of X independently is CR4 or N;
Ring B is independently selected from a substituted or unsubstituted monocyclic aryl and a substituted or unsubstituted monocyclic heteroaryl; wherein X1 is CR4 or N;. optionally two R4 substituent ortho to each other may be joined to a form a substituted or unsubstituted saturated or unsaturated 4-10 member ring, which may optionally include heteroatoms which may be same or different and are selected from 0, NR* or S; R is hydrogen, substituted or .unsubstituted (Ci_e)alkyl or -ORa;
R1 is selected from -OH, -NRaOH, -COOH ,-COORa, -CR3/4bOH, -CRACOOH, -SC^R* -CRaRhS02Ra -S(3/4Ra, -CRV-SCbR *, -C (=Y)-NR1,Rb and -S(s=0)q-]S|R% b or an isostere of -COOH group or optionally represent halogen, substituted or unsubstituted (Ci^)alkyl or Cy1; X2 is N or CR2 and X3 is N or CR3, wherein R2 and R3 may be same or different and are independently selected from hydrogen, halogen or substituted or unsubstituted (Ci-e)alkyl or substituted or unsubstituted (CAalkoxy;
L1 and L are independently absent or selected from -(CR*RV, -0-, -S(=0)q- , -NRa- , -C(=Y>, -C(=Y)-CRaRb, -CR,Rb-C(sTf).,-C(ay>C(BY>f -CRaRb-Y-, -C(=Y)-NRaRb-, -SCO^-NR^R"-, -NR3/4 b-C (=Y)-, -NRaRb-S(=0) -, substituted or unsubstituted (Ci_2)alkyl, substimted or unsubstituted (C2)all-enyl, and substituted or unsubstituted (C2)alkynyl; optionally each of substituted or unsubstituted (Ci.2)alkyl, substituted or unsubstituted (Ci-2)alkenyl, and substituted or unsubstituted (Ci.a)alkynyl may be interrupted with -0-, -C(=YK-S(=0)q-and-NRa-;

Cy is selected from substituted or unsubstituted cycloaliyl, substituted or unsubstituted
heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted
heteroaryl;
Cy* is selected from substituted or unsubstituted monocyclic cycloaliyl, substituted or
unsubstituted monocyclic heterocyclic group, substituted or unsubstituted monocyclic aryl
and substituted or unsubstituted monocyclic heteroaryl;
R is independently selected from hydrogen, hydroxy, halogen, cyano, -ORa, -S(s=0)q-Ra , -
NR*Rb, - C(=Y)-R4, -C(=Y)-ORa, -C(=Y>NR*Rb,-S(=0) q-NRaRb, substituted or unsubstirated
alJ^l, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted
or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylaky!, substituted or
unsubstituted cycloalkenyl or when two R4 substituents are present, they may be joined to a
form a substituted or unsubstituted saturated or unsaturated 3-10 member ring, which may
optionally include heteroatoms which may be same or different and are selected from 0 , NRa
or S, or alternatively when two R4 substituent are orfho to each other on an aromatic ring may
be joined to form a substituted or unsubstituted saturated or unsaturated 4-10 member ring,
which may optionally include one or more heteroatoms which may be same or different and
are selected from 0 , NR* or S;
each occurrence of R*and R jjiay be the same or different and are independently selected
from hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted (Cw)alkyl ,-ORc
(wherein Rc is substituted ojr unsubstituted (Chalky!) or when Rl and R are directly bound
to a common atom, they may be joined to form an oxo group (=0) or form a substituted or
unsubstituted saturated or unsaturated 3-10 member ring, which may optionally include
heteroatoms which may be the same or different and are selected from 0, NR* or S;
each occurrence of Y is independently selected from the group consisting of O, S and !NRa;
each occurrence of n independently represents an integer 0, 1, 2, 3, or 4; and
each occurrence of q independently represents an integer 0,1 or 2.
2. A compound according to claim l.whereiii ring A is selected from

optionally substituted with one or more R4.
3. A compound according to claim 1 or 2, wherein R1 is -COOH.
4. A compound according to any of the preceding claims, wherein Y is 0 .
5. A compound according to any of the preceding claims, wherein R is H.
6. A compound according to any of the preceding claims, wherein each occurrence of X is CH, C-Cl,C-ForN.
7. A compound according to any of the preceding claims, wherein each occurrence of X1 is CH, N or OF.
8. A compound according to any of the preceding claims, wherein X is CH, C-Cl,C-ForN.
9. A compound according to any of the preceding claims, wherein X3 is CH, C-Cl,C-ForN.
10. A compound according to claim any of the preceding claims, wherein ring B is selected
from
optionally substituted with one or more R4. . •
11. A compound according to any of the preceding claims, wherein Li and Lj are absent,
12. A compound according to any of the preceding claims, wherein Lj is absent and L 2 is -O-CRaRb.
13. A compound according to any of the preceding claims, wherein Cy is

R1 is independently selected from -OH, -NRaOH, -COOH ,-COORa, or an isostere of-COOH group, such as S03H, CONHOH, B-,-C(=Y)-C(=Y)-, -CRl^-Y-, -C(=Y>NRaRb-, -S(=0)q-NRaRb-, -NRaRb-C(=Y)-, -NR^-S^OY. substituted or unsubstituted (Ci.2)alkyl, substituted or unsubstituted (C2)allcenyl, and substituted or unsubstituted (C2)alkynyl; optionally each of substituted or unsubstituted (CiA)alkyl, substituted or unsubstituted (Cj)alkenyl, and substituted or unsubstituted (C2 )alkynyl may be interrupted with -0-, -C(=Y>,-S(=0)q-and-NRa-;
Cy is independently selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
R is independently selected from hydrogen, hydroxy, halogen, cyano, -OR*, -S(=0) q-Ra , -NR*.Rb, -C(=Y)-R a, -C(=Y)-0R 4, -C(=Y)-NRaRb,-S(=0) ,-NRaRb, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalJcyl, substituted or unsubstituted cycloaHsylakyl, or substituted or unsubstituted cycloalkenyl or when two R substituent s are present, they may be joined to a form a substituted or unsubstituted saturated or unsaturated 3-10 member ring, which may optionally include heteroatoias which may be same or different and are selected from 0, NR1 • • or S or alternatively when two R substituent are ortho to each other on an aromatic ring may bejoined to form a substituted or unsubstituted saturated or unsaturated 4-10 member ring, which may optionally include one or more heteroatoms which may be same or different and are selected from 0, NR* or S;

each occurrence of Ra and Rb may be the same or different and are independently selected
from hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted (Ci_$)a]kyl ,-ORe
(wherein Rc is substituted or unsubstituted (CiA)alkyl) or when R4 and R are directly bound
to a common atom, they may bejoined to form an oxo group (=0) or form a substituted or
unsubstituted saturated or unsaturated 3-10 member ring, which may optionally include
heteroatoms which may be the same or different and are selected from O, NRa or S;
Y is selected from 0 , S and NRa;
each occurrence of n independently represents an integer 0, 1, 2, 3, or 4; and
each occurrence of q independently represents an integer 0,1 or 2.
15. A compound compound of formula (IA)
ox a tautomer, stereoisomer (such as an enantiomer or diastereomer), pharmaceutically
acceptable salt, pharmaceutically acceptable ester, prodrugs or N-oxide thereof,
wherein
Ring A including R is selected from

optionally substituted with one or more R , 17. A compound selected from
2A3,5-DiJfluorO'3'-memoxybiphenyl-4-ylcarbamoyl)beiizoic acid 2-(3,5-Difluwc>-3'-me&oxybiphenyA-4-ylcarbamoyl)benzenesulfonic acid 2-(6-(3-Memoxyphenyl)pyridin-3-yl-Abamoyl)benzoic acid 2-(3'-Ethoxy-3-fluorobiphenyl-4-ylcarbamoyi)benzoic acid 2-(3'-Eiihoxy-3,5-aifluoit»biphenylAylcaibamoyl)beii2X)ic acid

2-(2^hlon)-3,5-difluorobiphenyl-4-ylcarbamoyl)benzoicacid
2-(3,5-DifluorobiphenylAylcaibamoyl)benzoxc acid
2- [3,5-Difluoro-3-(ttifluorom.ethoxy)biphenyl-4-ylcarbamoyl]benzoic acid
2" [3'-(Beiwyloxy)-3,5-difluorobiphenylAylcaibmoyl]beiizoic acid
4,5 -Dichlor o-2 - (3-chloro- 3 '-ethoxy-5'fluorobiphenyl-4-ylcarbamoyl)benzoic acid
2-(3-Chloro-3'-etho7cy-5-F uorobiphenyl-4-ylcaibamoyl)beflzoic acid
4,5-Dichloro-2-(3,5-4iflooro-3'-methoxybipiieayl-4-ylcaibamoyl)benzoic acid
4,5-P/4cMcxo-2-(3-ethoxy-3,5-2ofurax)-5-yl)-6-fluorophenylcarbamoyl]beiizoic acid
2-[4-(l ,3-Dimethyl-lH-mdazol-5A -2,6-difluorophenylcarbamoylJbenzoic acid
2-(3-Cbloro-3,5-difluoiO-5'-i»etboxybiphenyl4 -ylcaibamoyl)benzoic acid
2-(3-CWoro-5-fluoro-3A4-dimeliioxyb:Lphenyl--4-ylcarbamoyl)betizoic acid
2-(A3 -Dichloro-5-fluoro-5-methoxybiphejjyl-4-ylcarbamoyl)benzoic acid
2-(2',3,5-Trifluoro-5'-methoxybiphenyM-ylcarijamoyl)beii raic acid
2-(4-Chloro-3,5-diF noro-3 -methoxybipheaiyl-4-ylcarbainoyl)benzoic acid
2-(3,4 -Dicbloro-5-fluoro-3 -metixoxybiphenyl-4-ylcarbamoyl)beDzoic acid
2-(3s;Uoro-2^5^difluoro-5-methoxybiphenyl^yIcarbamoyl)beiizoicacid
2-(3,4',5-tr f uOrc-3'-methoxybiphenyl4 -ylcarbarooyl)benzoic acid
2-[2,6-difluoro-4-(3-meiiiyH//-indol-5-yl)phenylcarbamoyl]benzoic acid
2-[2,6-dif uoro-4-(3-meth.yl-lfir-iiidazol-5-yl)plienylcarbamoyl]benzoic acid
2-(3-chloro-3'-etbyl-5-F uorobiphenyl-4-ylcarbamoyl)benzoic acid
2-(3-cbloro-3 -ed),oxy-2',5-difluorobiphenyl-4-ylcarbamoyl)beiizoic acid
2- [2 Ahlor o-4 - (23-dihydrobenzo[6][l,4]dioxin-6-yl>6-fluorophenylcarbainoyl]benzoic
acid
2 - [3 -chloro- 5-fluoro-3'-(2,2,2 -trifluoroethoxy)biphenyl-4-ylcarbamoyl3benzoic acid
2-(3-fluoro-3'-methoxybiphenyl-4-ylcarbaDttoyl)belizOic acid
2-(3'-ethoxybiphenyW-ylcarbamoyl)benzoic acid
2-[3'-(e13iylfhio)-3,5-biphenylAyl<%-ibamoyl)benzoic acid 2-(3'-methoxybiphenyl-4-ylcarbamoyl)benzoic acid 2- [3'- (trii mororoethoxy)biphenyl-4-ylcaibamoyl]ben2oic acid 2-[3'-(ethylthio)-2,6-difluorobiph ;nyl-4-ylcarbamoyl]beozoic acid 2-(3 '-ethylbiphenyl-4 -ylcarbamoyl)benzoic acid 2-(3 '-butoxy'2 ,3,5,6-tetrafluorobiphenylAylcaibamoyl)benzoic acid 2-(3'-bntoxy-3-fluorobipb-myl-4-ylcaibamoyl)benzoic acid 2-[3,5-difluoro-3-(trifluoromethoxy)biphenylAylcarbamoyl]bA nzoic acid 2-(3'-cyclcAropoxy-3-fluorobiphenylAylcaibanioyl )ben2oic acid 2-(3'-cyclopropoxybiphenyW-ylcai%ainoyl)benzoic acid 2 - (3 '-bu. toxybiphenyl-4-y lcarbainoy i) ben2 Oicacid 2-(3'-butoxy-2-flucTObiphenyl4-ylcaibamoyl)benzoicacid 2-(3'-Butoxy-2,6-difluorobiphenylAylcaibamoyl)benzoic acid 2-[2,6-]Auoro A-(3 -propyl-l//-mdol-5-yl)phenylcarbam6yl]beiizoic acid 2 - [2 -Chi or o-4- (3-ethyl-l //-iQdol-5-yl)-6-fluorophenylcarbamoyl]benzoic acid !. A compound selected from
3-(3,5-Dif uoro-3-memoxybiphenylAA Icaibamoyl)pyrazfoe-2-carboxylic acid 3-(3,5-DiflUoro-3'AthoxybipbenylAylcarbamoyl )pyra2me-2-carboxylic acid 3-[3'-(Benzyloxy)-3,5 -difluorobipto ayl^ylcarbamoyl]pyrazine-2-carboxylic acid 3-(3-Cbloro-3'-etboxy-5-fluorobiphenylAylcarbamoyl)pyrazine-2 -carboxylic acid N- (3-Chloro- 3 '-ethoxy- 5 -fluorobiphenAl-4-yl)-2-(hydroxymethyl)benzamide N-(3 '-Ethoxy-3.5-difluarobiphenyl^yl)-2-(hydroxymethyl)benzaniide 2-(3 '-etb.oxy-3,5-difluorobipb.enyl-4-ylc3rbamoyl)nicotiiiic acid 4-(3'-ethoxy-3^-4ifiuorobipheny-4-ylcarbamoyl)nicotinic acid.
19. A pharmaceutical composition, comprising a compound of any one of claims 18 and a phannaceutically acceptable carrier.
20. The pharmaceutical composition of claim 19, further comprising one or more ditional therapeutic agents selected from anti-iiuAaniinatory agent, immunosuppressive

®MuQT iromunomodiilatory agents, steroids, non-steroidal antiinflammatory agents, ^tUUstamines, analgesics, and suitable mixtures thereof.
21. A method of inhibiting DHODH activity in a mammal comprising adrrnnistering to the mammal a compound of any of claims 1-18, wherein the compound of aay one of claims 1-18 inhibits DHODH activity in the mammal
22. A method of inhibiting cytokine release by inhibiting the DHODH in a ^^mrnaj comprising acLrmnistering to the mammal a compound of any one of claims 1-18, ^herein the compound of any one of claims 1-18 inhibits cytokine release in the mammal.
23. A method of inhibiting cytokine production in a cell, comprising administering to the cell a compound of any one of claims 1-18.
24. The method of claim 22 or 23, wherein the cytokine is selected from IL-17 or
APN-y and combinations thereof.
25. A method of inhibiting lL 17 cytokine release in mammal comprising ftdiiunistering to the mammal a compound of any one of claims 1-18, wherein the compound of any one-of claims 1-19 inhibits cytokine release independent of DHODH irihibition.
26. Use of a compound in any one of claims 1-18 in the manufacture of a Biedicament for the treatment of a disease, disorder, or condition that would benefit from rUhibiting dihydrooratate dehydrogenase..
27. A method of treating autoimmune diseases, immune and inflammatory diseases, destructive bone disorders, variety of cancers & malignant neoplastic diseases, angjogenic-related disorders, viral diseases, or infectious diseases via inhibition of DHODH or IL17 and combination thereof comprising the step of admimstering to a subject in need thereof an effective amount of a compound of any one of claims 1-18.
28. The method of claim 27, wherein the diseases are selected from rheumatoid
arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis,
ankylosing spondilytis, Wegener's granulomatosis, polyarticular juvenile idiopathic arthritis,
inflammatory bowel disease such as ulcerative colitis, Crohn's disease, Reiter's syndrome,
fibromyalgia, chronic pancreatitis, graft versus-host disease, chronic sarcoidosis, transplant
rejection, contact dermatitis, atopic dermatitis allergic rhinitis, allergic conjunctivitis,
Behcet's syndrome, inflammatory eye conditions such as conjunctivitis , uveitis, osteoporosis,
osteoarthritis4y2mangiomas, ocular neovascularization, macular degeneration, HIV infection,
hepatitis and cytoraegdovirus infection, sepsis, septic shock, endotoxic shock, Gram negative
sepsis, toxic shock syndrome, Shigellosis and other protozoal infestations such as malaria.

29. The method of claim 27, wherein the diseases are selected from chronic
obstructive pulmonary disease, rheumatoid arthritis, inflammatory bowel disease, allergic
rhinitis, asthma, multiple sclerosis, psoriasis, Crohn's disease, colitis, ulcerative colitis,
.arthritis, bone diseases associated with increased bone resorption, or chronic obstructive
airway disease, Felty's syndrome, Wegener's granulomatosis, Crohn's disease, sarcoidosis,
Still's disease, pemphigoid, Takayasu arteritis, systemic slerosis, relapsing polychondritis,
refractory IgA nephropathy , SAPHO2 syndrome (SAS), cytomegalovirus infection including
rhinitis or cyst, psoriasis and multiple myeloma.
30. The method of claim 27, wherein the disease is selected from rheumatoid
arthritis, multiple sclerosis or inflammatory bowel disease.