Claims
- 1. A substance which is a compound of formula I,
- 2. A substance according to claim 1 wherein the “Ar” ring represents phenyl or pyridyl.
- 3. A substance according to claim 1 wherein R1 when taken alone is OH, CN, halogen, NO2, NH2, NY2WY1 or Het1.
- 4. A substance according to claim 1 wherein R2 when taken alone is H.
- 5. A substance according to claim 1 wherein R1 and R2 are taken together with the carbon atoms to which they are attached and represent an optionally benzo-fused 5- to 7-membered heteroaryl ring optionally substituted by C1-4 alkyl or C1-4 haloalkyl.
- 6. A substance according to claim 1 wherein X is Cl.
- 7. A substance according to claim 1 wherein n is 0 and q is 0.
- 8. A substance according claim 1 wherein R3 is H, CN, or C1-6 alkyl (optionally substituted by one or more halogen, OH, C1-6 alkoxy, C1-6 alkoxycarbonyl, C2-6 alkanoyl, C2-6 alkanoyloxy, C2-6 alkyloxycarbonyloxy, NR12R13, CONR12R13 and/or NY2WY1).
- 9. A substance according to claim 1 wherein R4 is C1-10 alkyl substituted by one or more substituents selected from:
C2-6 alkoxy [substituted by one or more groups selected from OH, NR25 R26, CONR25R26, halogen, C1-6 alkoxy, C2-4 alkynyl, C2-4 alkenyl, heteroaryl1, aryl1, COCH2CN, CO(heteroaryl1), CO(aryl1), CO2(heteroaryl1), COCH2(aryl1), COCH2(heteroaryl1), CO2CH2(aryl1), CO2CH2(heteroaryl1), S(O)n(C1-6 alkyl), S(O)n(aryl1), S(O)n(heteroaryl1), SO2NR25R26 and cycloalkyl1], S(O)nC1-6 alkyl [optionally substituted by one or more groups selected from OH, NR25R26, CONR25R26, halogen, C1-6 alkoxy, C2-4 alkynyl, C2-4 alkenyl, heteroaryl1, aryl1, COCH2CN, CO(heteroaryl1), CO(aryl1), CO2(heteroaryl1), COCH2(aryl1), COCH2(heteroaryl1), CO2CH2(aryl1), CO2CH2(heteroaryl1), S(O)n(C1-6 alkyl), S(O)n(aryl1), S(O)n(heteroaryl1), SO2NR25R26 and cycloalkyl1], aryl2, CO2CH2(heteroaryl1), CO2CH2(aryl1), cycloalkyl1, CO(heteroaryl1), CO(aryl1), OCO(aryl1), OCO(heteroaryl1), OCO(C1-6 alkyl), OCOCH2CN, CO2(heteroaryl1), CO2(aryl1), COCH2(heteroaryl1), S(O)naryl1, S(O)nCH2aryl1, S(O)n(heteroaryl1), S(O)nCH2(heteroaryl1), NHSO2aryl1, NHSO2(C1-6 alkyl), NHSO2(heteroaryl1), NHSO2CH2(heteroaryl1), NHSO2CH2(aryl1), NHCOaryl1, NHCO(C1-6 alkyl), NHCONHaryl1, NHCONH(C1-6 alkyl), NHCOheteroaryl1, NHCONHheteroaryl1, NHCO2(aryl1), NHCO2(C1-6 alkyl), NHCO2(heteroaryl1), aryl2oxy, heteroaryl1oxy, C1-6 alkoxycarbonyl substituted by C1-6 alkyl, aryl, C1-6 alkoxy, CH2(aryl1), C1-4 haloalkyl, halogen, OH, CN or NR25R26, C2-6 alkanoyl substituted by C1-6 alkyl, aryl, C1-6 alkoxy, CH2(aryl1), C1-4 haloalkyl, halogen, OH, CN or NR25R26, C2-6 alkanoyloxy substituted by C1-6 alkyl, aryl, C1-6 alkoxy, CH2(aryl1), C1-4 haloalkyl, halogen, OH, CN or NR25R26, cycloalkyl1 oxy, COcycloalkyl1, heterocycle substituted by one or more substituent selected from C1-6 alkyl(substituted by OH), CONR25R26, CH2CONR25R26, NR25R26, NHCONR25R26, CO(C1-6 alkyl), SO2NR25R26, SO2(C1-6 alkyl), CO2(C1-6 alkyl), CH2CO2(C1-6 alkyl), OCH2CO2(C1-6 alkyl), aryl, heterocyclyl, aryloxy, aryl(CH2)oxy, aryl(CH2), CN and C3-7 cycloalkyl, heterocyclyloxy substituted by one or more substituent selected from C1-6 alkyl(substituted by OH), CONR25R26, CH2CONR25R26, NR25R26, NHCONR25R26, CO(C1-6 alkyl), SO2NR25R26, SO2(C1-6 alkyl), CO2(C1-6 alkyl), CH2CO2(C1-6 alkyl), OCH2CO2(C1-6 alkyl), aryl, heterocyclyl, aryloxy, aryl(CH2)oxy, aryl(CH2), CN and C3-7 cycloalkyl,
- 10. A substance according to claim 1 wherein R5, R6, R7, R8 R9 and R10 are each taken separately and are all H.
- 11. A substance according claim 1 wherein the “Ar” ring represents a group of formula:
- 12. A substance according to claim 1 wherein R3 is H, CH3, C2H5, i-C3H7, n-C3H7 or CH2OCH3.
- 13. A substance according to claim 1 wherein R1 is OH, CN, I, Cl, NH2, NO2, optionally benzo-fused heteroaryl, NHSO2Y1, NHCOY1 or NHCO2Y1.
- 14. A substance according to claim 1 wherein R4 is C1-10 alkyl substituted by cycloalkyl1.
- 15. A substance according to claim 1 except claims 3, 4 and 13 wherein R1 and R2 are taken together with the carbon atoms to which they are attached are a 5-membered heteroaryl moiety optionally substituted by C1-4 alkyl or C1-4 haloalkyl.
- 16. A substance according to claim 1 wherein R3is CH3 or C2H5.
- 17. A substance according to claim 1 except claims 5 and 15 wherein R1 when taken alone is OH, CN, I, Cl, NH2, NO2,1,2,3-triazolyl, 1,2,4-triazolyl, imidazol-2-yl, pyridin-2-yl, thien-2-yl, imidazol-4-yl, benzimidazol-2-yl, NHSO2(C1-6 alkyl), NHSO2(C1-6 alkyl substituted by methoxy, CONH2, OH, CO2(C2-6 alkyl), phthalimido, NH2 or halogen), NHSO2NH2, NHSO2NH(C1-6 alkyl), NHSO2N(C1-6 alkyl)2, NHSO2Het1a, NHCO(C1-6 alkyl) or NHCO2(C1-6 alkyl).
- 18. A substance according to claim 17 wherein R1 is OH, NHSO2CH3, NHSO2C2H5, NHSO2(n-C3H7), NHSO2(i-C3H7), NHSO2(n-C4H7), NHSO2NH(i-C3H7), NHSO2(N-methylimidazol-4-yl), NHSO2(CH2)2OCH3, NHSO2(CH2)2OH, 1,2,4-triazolyl or imidazol-2-yl.
- 19. A substance according to claim 18 wherein R1 is OH, NHSO2CH3, NHSO2C2H5 or imidazol-2-yl.
- 20. A substance according to claim 15 wherein R1 and R2 when taken together with the carbon atoms to which they are attached are an imidazole group optionally 2-substituted by CF3.
- 21. A substance according to claim 1 wherein R4 is C2-4 alkyl substituted by cycloalkyl1.
- 22. A substance according to claim 1 wherein R4 is propyl substituted by cycloalkyl1.
- 23. A substance according to claim 1 wherein R4 is propyl substituted by a C3-10 carbocyclic system with one or two rings and which is substituted by OH.
- 24. A substance according to claim 1 wherein R4 is propyl substituted by (cyclohexyl substituted by OH).
- 25. A substance according to claim 1 wherein R4 is (1-hydroxycyclohexyl)prop-3-yl.
- 26. A substance according to claim 1 which has the following relative stereochemistry:
- 27. A pharmaceutical or veterinary composition comprising a substance according to claim 1, and a pharmacutically or veterinarily acceptable carrier.
- 28. A method of treatment of a condition mediated by an opiate receptor or receptors comprising administration of a therapeutically active amount of a substance according to claim 1.
- 29. A process for the preparation of a substance of formula I which comprises:
(a) for compounds of formula I in which q is 0 and R1 represents NY2WY1, reacting a compound of formula II, 215 with a compound of formula III,Z1-WY1 IIIwherein Z1 is a suitable leaving group, such as halogen or Y1SO2O—; (b) for compounds of formula I in which q is 0 and R6 and R7 both represent H, reduction of a compound of formula IV, 216 using a suitable reducing agent; (c) for compounds of formula I in which q is 0 and R9 and R10 both represent H, reduction of a compound of formula V, 217 using a suitable reducing agent; (d) for compounds of formula I in which q is 0 and R1 and R2 are attached to adjacent carbon atoms and are taken together with the carbon atoms to which they are attached to represent Het1a, in which Het1a represents an imidazolo unit, reaction of a corresponding compound of formula VI, 218 with a compound of formula VII,RyCO2H VIIwherein Ry represents H or any of the optional substituents on Het1a (as defined above), preferably H, C1-4 alkyl or C1-4 haloalkyl; (e) where q is 0, reacting a compound of formula VIII, 219 with a compound of formula IX,R4-Lg IXwherein Lg is a leaving group; (f) for compounds of formula I in which q is 0 and R6, R7, R9 and R10 are all H, reduction of a compound of formula X, 220 with a suitable reducing agent; (g) for compounds of formula I in which q is 0 and R1 represents OH, reacting a compound of formula II, where Y2 is H, as defined above, with fluoroboric acid and isoamyl nitrite; (h) for compounds of formula I in which q is 0 and R1 represents Cl, reacting a compound of formula II, where Y2 is H, as defined above, with sodium nitrite in the presence of dilute acid, followed by reaction with copper (I) chloride in the presence of concentrated acid; (i) for compounds of formula I in which q is 1, reacting a compound of formula I where q is 0 with a suitable oxidising agent such as aqueous hydrogen peroxide; or (j) for compounds of formula I where q is 0, by reduction of a corresponding compound of formula XXXI, 221where R4aCH2 takes the same meaning as R4 as defined above, (K) for compounds of formula (I) where q is 0, reductive amination reaction of the amine of formula VIII above with an aldehyde of formula R4a—CHO wherein R4aCH2 takes the same meaning as R4 as defined above, and where desired or necessary converting the resulting compound of formula I into a pharmaceutically or veterinarily acceptable derivative or vice versa.
- 30. A compound of formula II, IV, V, VI, X, Xa, XI, XII, XXI, XXII, XXIII, XXIV, XXIX, XXIXa, XXX, or XXXI, or salt thereof, as described herein.
Priority Claims (1)
Number |
Date |
Country |
Kind |
GB 0015562.2 |
Jun 2000 |
GB |
|
Parent Case Info
[0001] This claims application claims priority under 35 U.S.C. 120 of U.S. Ser. No. 09/883,567, filed Jun. 18, 2001.
Provisional Applications (1)
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Number |
Date |
Country |
|
60218500 |
Jul 2000 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09883567 |
Jun 2001 |
US |
Child |
10117886 |
Apr 2002 |
US |