Recherche dans les collections de brevets nationales et internationales
Une partie du contenu de cette demande n'est pas disponible pour le moment.
Si cette situation persiste, contactez-nous auObservations et contact
1. (WO2008051405) IMIDAZOLES SUBSTITUES UTILISES COMME MODULATEURS SOUS-TYPE 3 DU RÉCEPTEUR DE BOMBÉSINE
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

WHAT IS CLAIMED IS:

1. A compound of formula I:


or a pharmaceutically acceptable salt thereof; wherein
A is a ring selected from the group consisting of:
(1) aryl, and
(2) heteroaryl,
wherein aryl and heteroaryl are unsubstituted or substituted with 0 to 4 substituents selected from

R4;
B is a mono- or bicyclic ring selected from the group consisting of:
(1) -C3-8cycloalkyl,
(2) -Crscycloalkenyl,
(3) -Crsheterocycloalkyl,
(4) -C2-8heterocycloalkenyl,
(5) -aryl, and
(6) -heteroaryl,
wherein cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl are unsubstituted or substituted with 0 to 4 substituents selected from R5;
Rl and R2 are each independently selected from the group consisting of:
(1) hydrogen,
(2) -(CH2)nhalogen,
(3) -(CH2)nOR8,
(4) -(CH2)nCN,
(5) -(CH2)nCF3,
(6) -(CH2)nCHF2,
(7) -(CH2)nCH2F,
(8) -(CH2)nCCl3,
(9) -C-galkyl,
(10) -(CH2)nC2-8alkene,
(11) -(CH2)nC2-8alkyne, (12) -(CH2)nC3-,0cycloalkyl,
(13) -(CH2)nC3-iocycloalkenyl,
(14) -(CH2)nC2-12heterocycloalkyl,
(15) -SC-salkyl,
(16) -SCrgcycloalkyl,
(17) -(CH2)naryl,
(18) -(CH2)nheteroaryl,
(19) -(CH2)nCO2R7, and
(20) -(CH^COCrsalkyl,
provided that Rl and R2 are not both hydrogen, wherein alkyl, alkene, alkyne, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, and (CH2)n are unsubstituted or substituted with

1 to 5 substituents selected from R6, and wherein two R6 substituents together with the atoms to which they are attached may form a 3-6 membered cycloalkyl or cycloalkenyl ring containing 0 to 3 heteroatoms independently selected from oxygen, sulfur, and Nil?, wherein the 3-6 membered cycloalkyl or cycloalkenyl ring is unsubstituted or substituted with 1 to 4 substituents selected from R6;
R3 is selected from the group consisting of:
(1) hydrogen,
(2) -Ci-6alkyl, and
(3) -COC,-6alkyl;
R4 is selected from the group consisting of:
(1) -Cr6alkyl,
(2) -(CH2)nhalogen,
(3) -(CH2)nOR8,
(4) -(CH2)nCN,
(5) -(CH2)nCF3,
(6) -(CH2)nCO2R7,
(7) -(CH2)nN(R8)2,
(8) -(CH2)nNθ2,
(9) -(CH2)nNR7COCi-6alkyl,
(10) -(CH2)nNR7CO2C,-6alkyl,
(H) -(CH2)HNR7SO2C1 -6alkyl, and
(12) -(CH^nSOo^Crealkyl,
wherein alkyl is substituted with 1 to 3 halogens;
R5 is selected from the group consisting of: (D -(CH2)nhalogen,
(2) -d-βalkyl,
(3) -C2-6alkenyl,
(4) -(CH2)nC3-8cycloalkyl,
(5) -(CH2)nheterocycloalkyl,
(6) oxo,
(7) -(CH2)nOR8,
(8) -(CH2)nCN,
(9) -(CH2)nCOR7,
(10) -(CH2)nCO2R8,
(H) -(CH2)nCONR7N(R7)2,
(12) -(CH2)nO(CH2)nCθ2R7,
(13) -(CH2)nNθ2,


(15) -(CH2)nN(R8)2,
(16) -(CH2)nNR7(CH2)nCO2R7,
(17) -(CH2)nNR7COC1-6alkyl,
(18) -(CH2)nSθ2N(R7)2,
(19) -(CH2)nNR7SO2C1-6alkyl,
(20) -(CH2)nSOo-2R8,
(21) -(CH2)nOP(O)2OH,
(22) -CH-N-OH,
(23) -(CH2)naryl,
(24) -(CH2)nheteroaryl, and
(25) -(CH2)nO(CH2)nheteroaryl,
wherein alky] [, alkenyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and -(CH2)n are unsubstituted or substituted with 1 to 3 halogens;
R6 is independently selected from the group consisting of:
(1) halogen,
(2) -OH,
(3) oxo,
(4) -CN,
(5) -CCl3,
(6) -CF3,
(7) -CHF2, (8) -CH2F,
(9) -SO2C,-6alkyl,
(10) -COC-galkyl,
(11) -Cθ2Cr8alkyl,
(12) -CO2H,
(13) -C-galkyl, and
(14) -Crsalkoxy,
wherein alkyl and alkoxy are unsubstituted or substituted with 1 to 4 substituents selected from -C]-6alkyl and halogen, and wherein the -Ci-6alkyl substituent is unsubstituted or substituted with 1 to 3 halogens;
R7 is selected from the group consisting of:
(1) hydrogen, and
(2) -C,-6alkyl,
wherein alkyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen and - OH;
R.8 is selected from the group consisting of:
(1) hydrogen,
(2) -C-ealkyl,
(3) -C3-8cycloalkyl,
(4) -C2-7heterocycloalkyl,
(5) -(CH2)mphenyl, and
(6) -(CH2)mheteroaryl,
wherein alkyl, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with 1 to 3 halogens or -OH, and wherein phenyl and heteroaryl are unsubstituted or substituted with 1 to 3 halogens;
each n is independently 0, 1, 2, 3, 4, or 5; and
each m is independently 1, 2, 3 or 4.

2. The compound of Claim 1 wherein B is a mono- or bicyclic ring selected from the group consisting of: -C3-8cycloalkyl, -C2-8heterocycloalkyl, -C2-8heterocycloalkenyl, -aryl, and -heteroaryl, wherein cycloalkyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl are unsubstituted or substituted with 0 to 4 substituents selected from R5; or a pharmaceutically acceptable salt thereof.

3. The compound of Claim 1 wherein B is a ring selected from the group consisting of: cyclohexyl, piperidine, tetrahydropyrazolopyridine, oxodihydropyridine, tetrahydropyrazine, phenyl, pyrazole, imidazole, pyrazine, pyridazine, pyridine, pyrimidine, thiazole, isothiazole, thiadiazole, triazole, thiene, indazole, isoquinoline, triazolopyridine, pyrrolopyridine, imidazopyrazine, and pyrazolopyridine, wherein the ring is unsubstituted or substituted with 0 to 4 substituents selected from R.5; or a pharmaceutically acceptable salt thereof.

4. The compound of Claim 1 wherein A is phenyl, wherein phenyl is unsubstituted or substituted with 0 to 4 substituents selected from R.4; or a pharmaceutically acceptable salt thereof.

5. The compound of Claim 1 wherein A is unsubstituted phenyl; or a
pharmaceutically acceptable salt thereof.

6. The compound of Claim 1 wherein R.2 and R.3 are hydrogen; or a
pharmaceutically acceptable salt thereof.

7. The compound of Claim 1 wherein Rl is selected from the group consisting of: -(CH2)nhalogen, -(CH2)nOR8, -(CH2)nCN, -(CH2)nCF3, -(CH2)nCCl3, -C,-8alkyl, -C,-8alkoxy, -(CH2)nC2-8alkene, -(CH2)nC3-i0cycloalkyl, -(CH2)nC3-i0cycloalkenyl, -(CH2)nheterocycloalkyl, -(CH2)naryl, -(CH2)nheteroaryl, -(CH2)nCO2R7, and -(CH2)nCOC1-8alkyl, provided that Rl and R2 are not both hydrogen, wherein alkyl, alkene, alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, and (CH2)n are unsubstituted or substituted with 1 to 5 substituents selected from R6; or a pharmaceutically acceptable salt thereof.

8. The compound of Claim 1 wherein R5 is selected from the group consisting of: -(CH2)nhalogen, -C,-6alkyl, -C2-6alkenyl, oxo, -(CH2)nOR8, -CN, -COR7, -(CH2)nCO2R8, -(CH2)nO(CH2)nCθ2R7, -NO2, -(CH2)nN(R8)2, -NH(CH2)nCO2R7, -NHCOC1 -6alkyl, -SO2N(R7)2, -CH=N-OH, -(CH2)nheteroaryl, and -(CH2)nO(CH2)nheteroaryl, wherein alkyl, alkenyl, heteroaryl, and -(CH2)n are unsubstituted or substituted with 1 to 3 halogens; or a pharmaceutically acceptable salt thereof.

9. The compound of Claim 1 of formula IV:

or a pharmaceutically acceptable salt thereof; wherein
B is selected from the group consisting of:
(1) -Cs-scycloalkyl,
(2) -aryl, and
(3) -heteroaryl,
wherein cycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 0 to 4 substituents selected from R.5;
Rl is selected from the group consisting of:
(1) -Crsalkyl, and
(2) -(CH2)nC3-12cycloalkyl,
wherein alkyl, cycloalkyl, and (CH2)n are unsubstituted or substituted with 1 to 5 substituents selected from R.6;
R5 is selected from the group consisting of:
(1) halogen,
(2) -Crealkyl,
(3) -(CH2)nO(CH2)nheteroaryl, and
(4) -(CH2)nCO2H;
R6 is -Ci-6alkyl, wherein alkyl is unsubstituted or substituted with 1 to 4 substituents selected from -Ci-6alkyl and halogen, and wherein the -d-6alkyl substituent is unsubstituted or substituted with 1 to 3 halogens; and
each n is independently 0, 1, 2, 3 or 4.

10. The compound of Claim 1 selected from the group consisting of:




or a pharmaceutically acceptable salt thereof.

11. The compound of Claim 10 which is:



or a pharmaceutically acceptable salt thereof.

12. The compound of Claim 10 which is:
or a pharmaceutically acceptable salt thereof.

13. The compound of Claim 10 which is:


or a pharmaceutically acceptable salt thereof.

14. The compound of Claim 10 which is:


or a pharmaceutically acceptable salt thereof.

15. The compound of Claim 10 which is :



or a pharmaceutically acceptable salt thereof.

16. A composition which comprises a compound of Claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

17. A compound according to Claim 1, or a pharmaceutically acceptable salt thereof, for use in medicine.

18. The use of a compound according to Claim 1 , or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament useful for the treatment or prevention of a disease mediated by the bombesin receptor subtype-3 in a subject in need thereof.

19. The use according to Claim 18 wherein the disease mediated by the bombesin receptor subtype-3 is selected from the group consisting of obesity, diabetes mellitus, a diabetes-related disorder or an obesity-related disorder.