Claims
- 1. A method of decreasing intraocular pressure or improving ocular accommodation in an animal, including a human, comprising administering an intraocular pressure decreasing or accommodation improving amount of (A) a compound of formula (I):
- 2. The method of claim 1, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula I, wherein Y is according to formula —CH(R5)R6.
- 3. The method of claim 2, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula I, wherein Y is according to formula —CH(R5)—W—R7.
- 4. The method of claim 2, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula I, wherein Y is according to formula —CH(R5)—W—Rs.
- 5. The method of claim 1, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula I, wherein:
c. Ar can substituted on ring carbon atoms
1. with one or more substituents independently selected from the group consisting hydrogen, acylamino, alkanoyl, alkanoylalkyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, ω-alkylenesulfonic acid, carbamoyl, carboxy, carboxyalkyl, cycloalkyl, halo, hydroxy, (C2-C6)hydroxyalkyl, mercapto, nitro, sulfamoyl, sulfonic acid (—SO3H), alkylsulfonyl (alkylSO2—), alkylsulfinyl (alkylSO—), alkylthio, trifluoromethyl, Ar*, Ar*-alkyl-, Ar*—O—, Ar*SO2—, Ar*SO—, Ar*S—, Ar*SO2NH—, Ar*NH, (N—Ar*)(N-alkyl)N—, Ar*C(O)—, Ar*C(O)NH—, Ar*NH—C(O)—, and (N—Ar*)(N-alkyl)N—C(O)—, wherein Ar* may be substituted by one or more substituents as set forth above; or 2. two adjacent substitutions together with their ring carbons form a C6- or C10-aromatic fused ring system; or 3. two adjacent substitutions together with their ring carbons form a C5-C7 fused cycloalkyl ring having no double bonds except the fused double bond of the Ar group, which cycloalkyl ring can be substituted by one or more of the group consisting of alkyl, amino, aminocarbonyl, carboxy, fluoro, or oxo, wherein multiple substituents are located on different carbon atoms of the cycloalkyl ring, except in the case of alkyl, and fluoro substituents, which can be located on the same or different carbon atoms; d. Y is:
1. a group of the formula —CH(R5)—R6 (a) R5 is hydrogen or alkyl; (b) wherein R6 is
(1) hydrogen, alkyl, alkenyl, alkynyl, cyano, cyanoalkyl, or Rs, wherein Rs is a [C6 or C10]aryl or a heterocycle containing 4-10 ring atoms of which 1-3 are heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur; or (2) a group of the formula —W—R7, wherein R7 is alkyl, alkoxy, hydroxy, or Rs, wherein W is —C(═O)— or —S(O)2—; (3) a group of the formula —W—OR8 wherein R8 is hydrogen or alkyl, (4) a group of the formula —CH(OH)Rs; or (5) a group of the formula —W—N(R9)R10, wherein
(a) R9 is hydrogen and R10 is an alkyl or cycloalkyl, optionally substituted by (i) [C6 or C10]aryl, or (ii) a 5- or 6-membered heteroaryl ring containing at least one and up to three atoms of N for the 6-membered heteroaryl ring and from one to three atoms of N or one atom of O or S and zero to two atoms of N for the 5-membered heteroaryl ring; said heteroaryl ring can be optionally substituted with one or more halo or (C1-C3)alkylenedioxy groups, or fused to a phenyl ring, or (b) R9 is hydrogen or alkyl and R10 is Ar*; or (e) R9 and R10 together with N form a heterocycle containing 4-10 ring atoms which can incorporate up to one additional heteroatom selected from the group of N, O or S in the ring, wherein the heterocycle is optionally substituted with (C6-or C10)aryl, (C6-or C10)arylalkyl, or a 5- or 6-membered heteroaryl ring containing at least one and up to three atoms of N for the 6-membered heteroaryl rings and from one to three atoms of N or one atom of O or S and zero to two atoms of N for the 5-membered heteroaryl rings, each such heteroaryl can be optionally substituted with one or more halo or (C1-C3)alkylenedioxy; or (f) R9 and R10 are both hydrogen; or 2.—NH2, and e. X is a pharmaceutically acceptable anion, which may be absent if the compound provides a neutralizing salt, (B) a pharmaceutically acceptable salt of the compound, wherein aryl, Ar or Ar* can be substituted with, in addition to any substitutions specifically noted, with one or more substituents selected from the group consisting of acylamino, acyloxyalkyl, alkanoyl, alkanoylalkyl, alkenyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, (C1-C3)alkylenedioxy, alkylsulfonyl, alkylsulfinyl, ω-alkylenesulfonic acid, alkylthio, allyl, Ar*C(O)—, Ar*C(O)NH—, Ar*O—, Ar*—, Ar*-alkyl-, carboxy, carboxyalkyl, cycloalkyl, halo, trifluoromethyl, hydroxy, (C2-C6)hydroxyalkyl, mercapto, nitro, sulfamoyl, sulfonic acid (SO3H); and wherein heterocycles, except those of Ar or Ar*, can be substituted with, in addition to any substitutions specifically noted, acylamino, alkanoyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylsulfonyl, alkylsulfinyl, alkylthio, Ar*C(O)—, Ar*O—, Ar*—, carboxy, fluoro, fluoroalkyl, difluoroalkyl, hydroxy, mercapto, sulfamoyl, or trifluoromethyl, wherein multiple substituents are located on different atoms of the heterocyclic ring, with the proviso that alkyl, alkylcarbonyl, and fluoro substituents can be substituted on the same carbon atom of the heterocyclic ring.
- 6. The method of claim 5, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula I, wherein Y is according to formula —CH(R5)R6.
- 7. The method of claim 6, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula I, wherein Y is according to formula —CH(R5)—W—R7.
- 8. The method of claim 6, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula I, wherein Y is according to formula —CH(R5)—W—Rs.
- 9. The method of claim 1, wherein Y—Ar⊕.X− is
- 10. The method of claim 9, wherein Ar is not tetrazole, or pyrrole.
- 11. The method of claim 9, comprising administering an intraocular pressure decreasing or accommodation improving amount of a compound of formula II, wherein R6 is according to —CH(R5)—W—Rs
- 12. The method of claim 9, wherein aryl, Ar or Ar* is substituted with, in addition to any substitutions specifically noted, one or more substituents selected from the group consisting of hydrogen, alkyl, amino, dialkylamino, 1-pyrrolidinyl, 4-[C6 or C10]arylpiperazin-1-yl, 4-[C6 or C10]arylpiperidin-1-yl, azetidin-1-yl, and morpholin-4-yl, piperidin-1-yl.
- 13. The method of claim 9, wherein Y—Ar⊕.X− is
- 14. The method of claim 9, wherein Y—Ar⊕.X− is
- 15. The method of claim 9, wherein Y—Ar⊕.X− is
- 16. The method of claim 1, wherein Y—Ar⊕.X− is
- 17. The method of claim 1, wherein Ar is substituted on a said ring nitrogen with amino.
- 18. The method of claim 17, wherein Ar is further substituted with up to two aminos.
Parent Case Info
[0001] The present application claims the priority of U.S. application Ser. No. 60/259,429, filed Dec. 29, 2000 and No. 60/296,317, filed Jun. 6, 2001.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60259429 |
Dec 2000 |
US |
|
60296317 |
Jun 2001 |
US |