Claims
- 1. A compound represented by Formula I:
- 2. 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, C1-4alkyl or R3, R4 and the carbon atom to which they are attached form a cyclopropyl ring, or R2 and R3 together represent (CH2)m to form a saturated heterocycle; R5 is chosen from hydroxyl, C1-4alkoxy, C1-4alkyl, halogen, or OC(═O)W; R6 is chosen from hydrogen, halogen, C1-4alkyl, C1-4alkyl substituted with halogen; R7 and R8 are hydrogen or C1-4alkyl; W is C1-6alkyl, NR7R8, N(R7)CH2(CH2)nN(R7)(R8), OC1-6alkyl, C1-6alkyl optionally substituted with halogen, hydroxyl, CO2C1-4alkyl, CON(C1-4alkyl)2, C(═NH)NH2, NHC(═NH)NH2, or NH2, C2-4alkenyl optionally substituted by phenyl, unsubstituted or substituted with one or more of C1-4alkyl, C1-4alkoxy or halogen; m is 3 or 4; n is 2 or 3; A is a 5- to 7-membered ring optionally containing one heteroatom chosen from NR7, O, or S; X is either N or C; Y and Z are either N or C, wherein Y and Z are different; and the dashed bonds denote a suitably appointed single and double bond; or pharmaceutically acceptable salts or solvates thereof.
- 3. The compound of claim 1, wherein said R2 and R3 form a saturated (CH2)m heterocycle or said R3 and R4 together form a cycloalkyl ring.
- 4. The compound of claim 1, wherein R1, R2, and R3 are hydrogen;
or R2 and R3 together represent (CH2)m to form a pyrrolidine; R4 is C1-4alkyl; R5 is chosen from hydroxyl, C1-4alkoxy, or OC(═O)W; R6 is chosen from hydrogen, halogen, C1-4alkyl, C1-4alkyl substituted with halogen; R7 and R8 are hydrogen or C1-4alkyl; W is C1-6alkyl, NR7R8, C1-6alkyl optionally substituted with halogen, hydroxyl, or CO2C1-4alkyl; m is 3; A is a 6-membered ring optionally containing one heteroatom chosen from NR7 or O; X is either N or C; Y is N and Z is C; and the dashed bonds denote a suitably appointed single and double bond.
- 5. The compound of claim 1, wherein the compound is:
2-(2-Aminopropyl)-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol; 2-(2-Dimethylaminoethyl)-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol; 2-(2-Aminopropyl)-5-methyl-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol; 2-(2-Aminopropyl)-5-fluoro-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol; 2-(6-Fluoro-7-methoxy-4,5-dihydro-3H-benzo[cd]indazol-1-yl)-1-methylethylamine; Cyclopropanecarboxylic acid 2-(2-aminopropyl)-2,6,7,8-tetrahydro-benzo[cd]indazol-4-yl ester; 1-(2-Aminopropyl)-1,3,4,5-tetrahydro-benzo[cd]indol-7-ol; 1-(2-Aminopropyl)-5H-pyrano[4,3,2-cd]indazol-7-ol; or 1-(2-Aminopropyl)-4-methyl-1,3,4,5-tetrahydro-pyrazolo[4,3,2-de]isoquinol in-7-ol or combinations thereof.
- 6. The compound of claim 1, wherein said X is N.
- 7. The compound of claim 1, wherein said X is C.
- 8. 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.
- 9. The method of claim 8, wherein R2 and R3 form a saturated (CH2)m heterocycle.
- 10. The method of claim 8, wherein said R3 and R4 together form a cycloalkyl ring.
- 11. The method of claim 8, wherein said compound is 2-(2-Aminopropyl)-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol;
2-(2-Dimethylaminoethyl)-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol; 2-(2-(2-Aminopropyl)-5-methyl-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol; 2-(2-Aminopropyl)-5-fluoro-2,6,7,8-tetrahydro-benzo[cd]indazol-4-ol; 2-(6-Fluoro-7-methoxy-4,5-dihydro-3H-benzo[cd]indazol-1-yl)-1-methylethylamine; Cyclopropanecarboxylic acid 2-(2-aminopropyl)-2,6,7,8-tetrahydro-benzo[cd]indazol-4-yl ester; 1-(2-Aminopropyl)-1,3,4,5-tetrahydro-benzo[cd]indol-7-ol; 1-(2-Aminopropyl)-5H-pyrano[4,3,2-cd]indazol-7-ol; or 1-(2-Aminopropyl)-4-methyl-1,3,4,5-tetrahydro-pyrazolo[4,3,2-de]isoquinolin-7-ol; or combinations thereof.
- 12. The method of claim 8, wherein wherein R1, R2, and R3 are hydrogen;
or R2 and R3 together represent (CH2)m to form a pyrrolidine; R4 is C1-4alkyl; R5 is chosen from hydroxyl, C1-4alkoxy, or OC(═O)W; R6 is chosen from hydrogen, halogen, C1-4alkyl, C1-4alkyl substituted with halogen; R7 and R8 are hydrogen or C1-4alkyl; W is C1-6alkyl, NR7R8, C1-6alkyl optionally substituted with halogen, hydroxyl, or CO2C1-4alkyl; m is 3; A is a 6-membered ring optionally containing one heteroatom chosen from NR7 or O; X is either N or C; Y is NandZis C; and the dashed bonds denote a suitably appointed single and double bond.
- 13. The method of claim 9, wherein said X is N.
- 14. The method of claim 9, wherein said X is C.
- 15. A method for the treatment of glaucoma comprising administering a pharmaceutically effective amount of a composition comprising at least one compound of claim 1.
- 16. The method of claim 15, wherein R1, R2, and R3 are hydrogen;
or R2 and R3 together represent (CH2)m to form a pyrrolidine; R4 is C1-4alkyl; R5 is chosen from hydroxyl, C1-4alkoxy, or OC(═O)W; R6 is chosen from hydrogen, halogen, C1-4alkyl, C1-4alkyl substituted with halogen; R7 and R8 are hydrogen or C1-4alkyl; W is C1-6alkyl, NR7R8, C1-6alkyl optionally substituted with halogen, hydroxyl, or CO2C1-4alkyl; m is 3; A is a 6-membered ring optionally containing one heteroatom chosen from NR7 or O; X is either N or C; Y is N and Z is C; and the dashed bonds denote a suitably appointed single and double bond.
- 17. The method of claim 15, 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; [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-(2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[3,2-g]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; or 1-((S)-2-Aminopropyl)-3-methyl-3,7,8,9-tetrahydro-pyrano[3,2-e]indazol-8-ol; or mixtures thereof.
- 18. A pharmaceutical composition comprising the compound of claim 1 and at least one carrier.
- 19. 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 of International Patent Application No. PCT/US02/17114 filed May 30, 2002 and in turn claims the benefit of U.S. Provisional Patent Application No. 60/295,428 filed Jun. 1, 2001, which is incorporated in its entirety by reference herein.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60295428 |
Jun 2001 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/US02/17114 |
May 2002 |
US |
Child |
10721204 |
Nov 2003 |
US |