Claims
- 1. A compound represented by Formula I:
- 2. The compound of claim 1, wherein R2 and R3 form a saturated (CH2)m heterocycle.
- 3. The compound of claim 1, wherein said R3 and R4 together form a cyclopropyl ring.
- 4. The compound of claim 1, wherein R1 and R2 are independently chosen from hydrogen or C1-4alkyl;
R3 and R4 are independently chosen from hydrogen or C1-4alkyl, or R2 and R3 together form a saturated (CH2)m heterocycle; R5 is chosen from hydrogen, halogen, or C1-6alkyl; R6 and R7 are independently chosen from hydrogen, halogen, cyano, C1-4alkylthio, C1-4alkyl, or C1-4alkyl substituted by halogen; R8 and R9 are chosen from hydrogen, hydroxyl, C1-6alkyl, C1-6alkoxy, NR10R11, or C1-6alkyl substituted with halogen, hydroxyl, NR10R11, Z-(CH2)m—OR12, or Z-(CH2)pC(═O)NR14R15; R10 and R11 are independently chosen from hydrogen or C1-4alkyl or C(═O)C1-4alkyl or R10 and R11 together complete a saturated 5 or 6-membered heterocyclic ring, which optionally includes an additional heteroatom selected from N, O, or S when a 6-membered ring; A is (CH2)n or CHC1-4alkyl; B is either a single or double bond, wherein when B is a double bond, R8 and R9 is are selected from hydrogen, C1-4alkyl, or C1-4alkyl substituted by halogen, hydroxy, or NR10R11; m=3-4; n=1-2; and X and Y are either N or C, wherein X and Y cannot be the same; and the dashed bonds denote a suitably appointed single and double bond.
- 5. The compound of claim 1, wherein R1 and R2 are independently chosen from hydrogen or C1-4alkyl;
R3 is C1-2alkyl, or R2 and R3 together are (CH2)3 to form pyrrolidine; R4 is hydrogen; R5 is chosen from hydrogen or C1-6alkyl; R6 and R7 are independently chosen from hydrogen, halogen, or C1-4alkyl; R8 and R9 are independently chosen from hydrogen, hydroxyl, C1-6alkoxy, NR10R11, or C1-6alkyl substituted with hydroxyl, NR10R11, Z-(CH2)m—OR12, or Z-(CH2)pC(═O)NR14R15; R10 and R11 are independently chosen from hydrogen, C1-4alkyl or C(═O)C1-4alkyl or R10 and R11 together complete a saturated 5 or 6-membered heterocyclic ring, which optionally includes an additional heteroatom selected from N, O, or S when a 6-membered ring; A is (CH2)n; B is a single bond; n=1; X is C and Y is N; and the dashed bonds denote a suitably appointed single and double bond.
- 6. The compound of claim 1, wherein said compound is:
1-(2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; (S)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-3-methyl-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-(S)-1-Pyrrolidin-2-ylmethyl-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-5-fluoro-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ylamine; [1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-dimethylamine; [1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-methanol; 1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazole-8,9-diol; 1-((S)-2-Aminopropyl)-9-methoxy-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-(2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-(Pyrrolidin-2-ylmethyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-((S)-2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-((S)-2-Aminopropyl)-3-methyl-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; N-[2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydropyrano[2,3-g]indazol-8-yloxy]-ethyl]acetamide; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-ethanol; (S)-2-[(R)-8-(2-Methoxyethoxy)-8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl]-1-methylethylamine; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-acetamide; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-N-hydroxy-acetamide; 1-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-3-ethyl-1-methylurea; (S)-1-Methyl-2-(3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-1-yl)-ethylamine; 2-[(R)-1-((S)-2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-yloxy]-ethanol; [1-((S)-2-Aminopropyl)-7,8-dihydro-1H-furo[2,3-g]indazol-7-yl]-methanol; 2-[(S)-1-((S)-2-Aminopropyl)-7,8-dihydro-3H-furo[3,2-e]indazol-7-yl]-acetamide; or combinations thereof.
- 7. The compound of claim 1, wherein said X is N.
- 8. The compound of claim 1, wherein said X is C.
- 9. A method of controlling normal or elevated intraocular pressure comprising administering a pharmaceutically effective amount of a composition comprising at least one compound of claim 1.
- 10. The method of claim 9, wherein R2 and R3 form a saturated (CH2)m heterocycle.
- 11. The method of claim 9, wherein said R3 and R4 together form a cyclopropyl ring.
- 12. The method of claim 9, wherein R1 and R2 are independently chosen from hydrogen or C1-4alkyl;
R3 and R4 are independently chosen from hydrogen or C1-4alkyl, or R2 and R3 together form a saturated (CH2)m heterocycle; R5 is chosen from hydrogen, halogen, or C1-6alkyl; R6 and R7 are independently chosen from hydrogen, halogen, cyano, C1-4alkylthio, C1-4alkyl, or C1-4alkyl substituted by halogen; R8 and R9 are chosen from hydrogen, hydroxyl, C1-6alkyl, C1-6alkoxy, NR10R11, or C1-6alkyl substituted with halogen, hydroxyl, NR10R11, Z-(CH2)m—OR12, or Z-(CH2)pC(═O)NR14R5; R10 and R11 are independently chosen from hydrogen or C1-4alkyl or C(═O)C1-4alkyl or R10 and R11 together can complete a saturated 5 or 6-membered heterocyclic ring, which can include an additional heteroatom selected from N, O, or S when a 6-membered ring; A is (CH2)n or CHC1-4alkyl; B is either a single or double bond, wherein when B is a double bond, R8 and R9 are selected from hydrogen, C1-4alkyl, or C1-4alkyl substituted by halogen, hydroxy, or NR10R11; m=3-4; n=1-2; and X and Y are either N or C, wherein X and Y cannot be the same; and the dashed bonds denote a suitably appointed single and double bond.
- 13. The method of claim 9, wherein R1 and R2 are independently chosen from hydrogen or C1-4alkyl;
R3 is C1-2alkyl, or R2 and R3 together are (CH2)3 to form pyrrolidine; R4 is hydrogen; R5 is chosen from hydrogen or C1-6alkyl; R6 and R7 are independently chosen from hydrogen, halogen, or C1-4alkyl; R8 and R9 are independently chosen from hydrogen, hydroxyl, C1-6alkoxy, NR10R11, or C1-6alkyl substituted with hydroxyl, NR10R11, Z-(CH2)m—OR12, or Z-(CH2)pC(═O)NR14R15; R10 and R11 are independently chosen from hydrogen, C1-4alkyl or C(═O)C1-4alkyl or R10 and R11 together complete a saturated 5 or 6-membered heterocyclic ring, which optionally includes an additional heteroatom selected from N, O, or S when a 6-membered ring; A is (CH2).; B is a single bond; n=1; X is C and Y is N; and the dashed bonds denote a suitably appointed single and double bond.
- 14. The method of claim 9, wherein said compound is:
1-(2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g] indazol-8-ol; (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g] indazol-8-ol; (S)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-3-methyl-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-(S)-1-Pyrrolidin-2-ylmethyl-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-5-fluoro-1,7,8,9-tetrahydro-pyrano[2,3-g] indazol-8-ol; (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g] indazol-8-ylamine; [1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-dimethylamine; [1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-methanol; 1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazole-8,9-diol; 1-((S)-2-Aminopropyl)-9-methoxy-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-(2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-(Pyrrolidin-2-ylmethyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-((S)-2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-((S)-2-Aminopropyl)-3-methyl-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; N-[2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydropyrano[2,3-g]indazol-8-yloxy]-ethyl]acetamide; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-ethanol; (S)-2-[(R)-8-(2-Methoxyethoxy)-8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl]-1-methylethylamine; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-acetamide; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-N-hydroxy-acetamide; 1-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-3-ethyl-1-methylurea; (S)-1-Methyl-2-(3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-1-yl)-ethylamine; 2-[(R)-1-((S)-2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-yloxy]-ethanol; [1-((S)-2-Aminopropyl)-7,8-dihydro-1H-furo[2,3-g]indazol-7-yl]-methanol; 2-[(S)-1-((S)-2-Aminopropyl)-7,8-dihydro-3H-furo[3,2-e]indazol-7-yl]-acetamide; or combinations thereof.
- 15. The method of claim 9, wherein said X is N.
- 16. The method of claim 9, wherein said X is C.
- 17. A method for the treatment of glaucoma comprising administering a pharmaceutically effective amount of a composition comprising at least one compound of claim 1.
- 18. The method of claim 17, wherein R1 and R2 are independently chosen from hydrogen or C1-4alkyl;
R3 and R4 are independently chosen from hydrogen or C1-4alkyl, or R2 and R3 together form a saturated (CH2)m heterocycle; R5 is chosen from hydrogen, halogen, or C1-6alkyl; R6 and R7 are independently chosen from hydrogen, halogen, cyano, C1-4alkylthio, C1-4alkyl, or C1-4alkyl substituted by halogen; R8 and R9 are chosen from hydrogen, hydroxyl, C1-6alkyl, C1-6alkoxy, NR10R11, or C1-6alkyl substituted with halogen, hydroxyl, NR10R11, Z-(CH2)m—OR12, or Z-(CH2)pC(═O)NR14R15; R10 and R11 are independently chosen from hydrogen or C1-4alkyl or C(═O)C1-4alkyl or R10 and R11 together can complete a saturated 5 or 6-membered heterocyclic ring, which can include an additional heteroatom selected from N, O, or S when a 6-membered ring; A is (CH2)n or CHC1-4alkyl; B is either a single or double bond, wherein when B is a double bond, R8 and R9 are selected from hydrogen, C1-4alkyl, or C1-4alkyl substituted by halogen, hydroxy, or NR10R11; m=3-4; n=1-2; and X and Y are either N or C, wherein X and Y cannot be the same; and the dashed bonds denote a suitably appointed single and double bond.
- 19. The method of claim 17, wherein R1 and R2 are independently chosen from hydrogen or C1-4alkyl;
R3 is C1-2alkyl, or R2 and R3 together are (CH2)3 to form pyrrolidine; R4 is hydrogen; R5 is chosen from hydrogen or C1-6alkyl; R6 and R7 are independently chosen from hydrogen, halogen, or C1-4alkyl; R8 and R9 are independently chosen from hydrogen, hydroxyl, C1-6alkoxy, NR10R11, or C1-6alkyl substituted with hydroxyl, NR10R11, Z-(CH2)m—OR12, or Z-(CH2)pC(═O)NR14R15; R10 and R11 are independently chosen from hydrogen, C1-4alkyl or C(═O)C1-4alkyl or R10 and R11 together complete a saturated 5 or 6-membered heterocyclic ring, which optionally includes an additional heteroatom selected from N, O, or S when a 6-membered ring; A is (CH2)n; B is a single bond; n=1; X is C and Y is N; and the dashed bonds denote a suitably appointed single and double bond.
- 20. The method of claim 17, wherein said compound is:
1-(2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; (S)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-3-methyl-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-(S)-1-Pyrrolidin-2-ylmethyl-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-((S)-2-Aminopropyl)-5-fluoro-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ylamine; [1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-dimethylamine; [1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-methanol; 1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazole-8,9-diol; 1-((S)-2-Aminopropyl)-9-methoxy-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol; 1-(2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-(Pyrrolidin-2-ylmethyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-((S)-2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; 1-((S)-2-Aminopropyl)-3-methyl-3,7,8,9-tetrahydro-pyrano[3,2-e] indazol-8-ol; N-[2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydropyrano[2,3-g]indazol-8-yloxy]-ethyl]acetamide; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-ethanol; (S)-2-[(R)-8-(2-Methoxyethoxy)-8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl]-1-methylethylamine; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-acetamide; 2-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yloxy]-N-hydroxy-acetamide; 1-[(R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-yl]-3-ethyl-1-methylurea; (S)-1-Methyl-2-(3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-1-yl)-ethylamine; 2-[(R)-1-((S)-2-Aminopropyl)-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-yloxy]-ethanol; [1-((S)-2-Aminopropyl)-7,8-dihydro-1H-furo[2,3-g]indazol-7-yl]-methanol; 2-[(S)-1-((S)-2-Aminopropyl)-7,8-dihydro-3H-furo[3,2-e]indazol-7-yl]-acetamide; or combinations thereof.
- 21. A pharmaceutical composition comprising the compound of claim 1 and at least one carrier.
- 22. A method to block or bind to serotonin receptors comprising administering an effective amount of at least one compound of claim 1 to a patient.
Parent Case Info
[0001] This application is a continuation-in-part of PCT application Serial No. PCT/US02/16861, filed May 30, 2002, which claims the benefit of U.S. Provisional Patent Application No. 60/295,429 filed Jun. 1, 2001, both of which are incorporated in their entirety by reference herein.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60295429 |
Jun 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
PCT/US02/16861 |
May 2002 |
US |
Child |
10316600 |
Dec 2002 |
US |