Claims
- 1. A compound of the formula (1):
- 2. The compound according to claim 1 wherein
R1 is hydrogen; R2 is chosen from phenyl, naphthyl, and heteroaryl chosen from thienyl, furanyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl, pyrrolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyranyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzothienyl, quinolinyl, quinazolinyl and indazolyl each R2 is optionally substituted with one or more Ra; R3 is C1-10 alkyl chain branched or unbranched optionally substituted with one or more Rb,
or R3 is:
—(CH2)n-L-R6, wherein L is chosen from a bond, —O—C(O)—, —C(O)— and —S(O)m_ wherein m is 0, 1 or 2, and wherein said group is optionally substituted by one or more Rb; wherein R6 is independently chosen from hydroxy, C1-5 alkyl, C1-5 alkoxy, C1-5 alkylthio, phenyl, naphthyl, benzyl, phenethyl, heteroarylC0-5 alkyl, C3-7 cycloalkylC0-5 alkyl, heterocyclylC0-5 alkyl and amino said amino is optionally mono- or di-substituted by C1-5 acyl, C1-5 alkyl, C1-5 alkoxycarbonyl, arylC0-5 alkyl, heteroarylC0-5 alkyl or heterocyclylC0-5 alkyl; and wherein each recited heteroaryl in this paragraph is chosen from thienyl, furanyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl, pyrrolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and pyranyl and wherein each recited heterocyclyl in this paragraph is chosen from pyrrolidinyl, morpholinyl, thiomorpholinyl, dioxalanyl, piperidinyl and piperazinyl; R5 is chosen from phenyl, naphthyl, benzyl, phenethyl, C1-5 alkyl, heteroarylC0-5 alkyl wherein the heteroaryl is chosen from thienyl, furanyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl, pyrrolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and pyranyl, C3-7 cycloalkylC0-5 alkyl and heterocyclylC0-5 alkyl wherein the heterocyclyl is chosen from aziridinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, tetrahydrofuranyl, dioxalanyl, piperidinyl and piperazinyl, each R5 is optionally substituted with one or more Rc;
each Ra, Rb or Rc are independently chosen from hydrogen, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-8 cycloalkyl, phenyl, benzyl, phenoxy, C1-5 alkoxy, C1-5 alkylthio, C1-5 acyl, C1-5 alkoxycarbonyl, C1-5 acyloxy, C1-5 acylamino, C1-5 sulphonylamino, aminosulfonyl, C1-5 alkylsulfonyl, carboxy, carboxamide, hydroxy, halogen, trifluoromethyl, nitro, nitrile and amino optionally mono- or -di-substituted by C1-5 alkyl, C1-5 acyl or C1-5 alkoxycarbonyl, wherein any of the above Ra, Rb or Rc are optionally halogenated where possible; R7 is C3-10 alkenyl or C1-5 alkyl; and Xa and Xb are oxygen.
- 3. The compound according to claim 2 wherein
R2 is chosen from phenyl, naphthyl and heteroaryl chosen from thienyl, furanyl, isoxazolyl, oxazolyl, imidazolyl, thiadiazolyl, pyrazolyl, pyridinyl, quinoxalinyl and benzothienyl each R2 is optionally substituted with one or more Ra; R6 is independently chosen from hydroxy, C1-5 alkyl, C1-5 alkoxy, phenyl, benzyl, phenethyl, heteroarylC0-5 alkyl, heterocyclylC0-5 alkyl, C3-7 cycloalkyl and amino said amino is optionally mono- or di-substituted by C1-5 acyl, C0-5 alkyl, C0-5 alkoxycarbonyl, arylC0-5 alkyl or heteroarylC0-5 alkyl;
and wherein each recited heteroaryl in this paragraph is chosen from thienyl, furanyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl, pyrrolyl and imidazolyl; n is 1-6; R5 is chosen from phenyl, naphthyl, benzyl, phenethyl, C1-5 alkyl, heteroarylC0-5 alkyl wherein the heteroaryl in this paragraph is chosen from thienyl, furanyl, imidazolyl and pyridinyl, C3-7 cycloalkylC0-5 alkyl and heterocyclylC0-5 alkyl wherein the heterocyclyl is chosen from aziridinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyridinyl, morpholinyl, thiomorpholinyl, piperidinyl and piperazinyl, each R5 is optionally substituted with one or more Rc; and and R7 is propenyl or C1-3 alkyl.
- 4. The compound according to claim 3 wherein
R2 is chosen from phenyl and heteroaryl chosen from thienyl, furanyl, isoxazolyl, thiadiazolyl, pyrazolyl and pyridinyl each R2 is optionally substituted with one or more Ra; R3 is:
—(CH2)n—C(O)—R6 or —(CH2)n—R6;
wherein R6 is independently chosen from hydroxy, C1-5 alkyl, C1-5 alkoxy, phenyl, thienylC0-5 alkyl, C3-7 cycloalkyl and amino said amino is optionally mono- or di-substituted by C1-5 alkyl or C1-5 alkoxycarbonyl; R5 is chosen from phenyl, benzyl, phenethyl and C3-7 cycloalkylC0-5 alkyl each optionally substituted with one or more Rc; each Ra, Rb or Rc are independently chosen from C1-5 alkyl, C3-8 cycloalkyl, phenyl, C1-5 alkoxy, amino optionally mono- or -di-substituted by C1-5 alkyl, C1-5 alkoxycarbonyl, carboxamide, hydroxy, halogen, trifluoromethyl, nitro and nitrile, wherein any of the above Ra, Rb or Rc are optionally halogenated where possible; and R7 is C1-3 alkyl.
- 5. The compound according to claim 4 wherein
R2 is chosen from phenyl, thienyl, furanyl, isoxazolyl and pyridinyl each optionally substituted with one or more Ra; R5 is chosen from phenyl and cyclohexyl each optionally substituted with one or more Rc; and n is 2-5.
- 6. The compound according to claim 5 wherein
R2 is chosen from phenyl, thien-2-yl, isoxazol-5-yl and pyridin-3-yl each optionally substituted with one or more Ra; R6 is independently chosen from hydroxy, methyl, ethyl, C1-3 alkoxy, phenyl, thienylC0-5 alkyl, C3-7 cycloalkyl and amino said amino is optionally mono- or di-substituted by C1-5 alkyl or C1-5 alkoxycarbonyl; and each Ra, Rb or Rc are independently chosen from C1-3 alkoxy, amino optionally mono- or -di-substituted by C1-3 alkyl, carboxamide, hydroxy, fluoro, chloro, bromo, trifluoromethyl, nitro and nitrile.
- 7. The compound according to claims 1-6 wherein R4 is covalently attached at the indicated 5-position of the formula (I).
- 8. The compound according to claims 1-6 R4 is covalently attached at the indicated 6-position of the formula (I).
- 9. A compound chosen from:
- 10. A compound chosen from:
- 11. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 1 and one or more pharmaceutically acceptable carriers and/or adjuvants.
- 12. A method of treating an immunological disorder, said method comprising administering to a patient in need thereof a therapeutically effect amount of a compound according to claim 1.
- 13. A method of treating an inflammatory disorder, said method comprising administering to a patient in need thereof a therapeutically effect amount of a compound according to claim 1.
- 14. A method of treating an allergic disorder said method comprising administering to a patient in need thereof a therapeutically effect amount of a compound according to claim 1.
- 15. A method of treating a disease chosen from chronic inflammation, contact dermatitis, psoriasis, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, Guillain-Barre syndrome, Crohn's disease, ulcerative colitis, graft versus host disease, lupus erythematosus, asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), bronchitis, conjunctivitis, dermatitis and allergic rhinitis said method comprising administering to a patient in need thereof a therapeutically effect amount of a compound according to claim 1.
- 16. A method of treating cancer said method comprising administering to a patient in need thereof a therapeutically effect amount of a compound according to claim 1.
- 17. A method administering a vaccine to an individual in need thereof comprising co-administration of a vaccine and a pharmaceutically effective amount of a compound according to claim 1.
- 18. A method of making a compound of formula (I) below, wherein R2, R3, R5 and R7 are defined as in claim 1, said method comprising:
APPLICATION DATA
[0001] This application claims benefit to U.S. provisional application No. 60/344,636 filed 11/09/2001.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60344636 |
Nov 2001 |
US |