Patent NZ-336394-A (NZ)
Title: use of tetrazolyl or carboxylic acid derivatives to treat glaucoma
Inventor: CAMERON KIMBERLY O'KEEFE
IPC: A61K31/36
Filed: 1999-06-22
Abstract: A compound of formula (I) A-B-(Q-Z)-K-M or a pharmaceutically acceptable salt thereof is used in the manufacture of a medicament for reducing intraocular pressure in a mammal.  In formula (I) either i): B is N; A is optionally substituted alkylsulphonyl, cycloalkylsulphonyl or cycloalkylalkylsulphonyl; Q is alkylene-W-alkylene, optionally substituted alkylene-, -X-alkylene-, -alkylene-X-, -alkylene-X-alkylene-, -alkylene-W-X-(C0-3)-alkylene-, -(C0-4)-alkylene-X-W-alkylene-, -alkylene-W-X-W-alkylene-, -alkylene-ethenylene-alkylene-, -alkylene-ethenylene-(C0-2C)alkylene-X-(C0-5)alkylene-, -alkylene-ethenylene-(C0-2)alkylene-X-W-alkylene-, -alkylene-ethynylene-alkylene- or -alkylene-ethynylene-X-(C0-3)alkylene- wherein the two occurrences of W are independent of each other; W is oxy, thio, sulphino, sulphonyl, aminosulphonyl-, -mono-N-alkyleneaminosulphonyl-, sulphonylamino, N-alkylenesulphonylamino, carboxamido, N-alkylenecarboxamido, carboxamidooxy, N-alkylenecarboxamidooxy, carbamoyl, -mono-N-alkylenecarbamoyl, carbamoyloxy, or -mono-N-alkylenecarbamoyloxy, wherein said W alkyl groups are optionally substituted on carbon with one to three fluorines;  X is an optionally mono-, or di-substituted five or six membered aromatic ring optionally having one or two heteroatoms selected independently from oxygen, nitrogen, and sulphur; Z is carboxyl, alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl, 5-oxo-1,2,4-oxadiazolyl, alkylsulphonylcarbamoyl or phenylsulphonylcarbamoyl; K is a bond or optionally mono-unsaturated, optionally mono-, di- or tri-substituted alkylene, thioalkylene or oxyalkylene; M is -Ar, -Ar1-V-Ar2, -Ar1-S-Ar2 or -Ar1-O-Ar2 Ar, Ar1 and Ar2 are each independently an optionally substituted optionally unsaturated five to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulphur and nitrogen or a bicyclic ring consisting of two fused optionally unsaturated five or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulphur and oxygen; V is a bond or optionally mono- or di-substituted alkylene with the proviso that when K is alkylene and M is Ar and Ar is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cyclooct-1-yl then the cycloalkyl substituents are not substituted at the one position with hydroxy; or (ii): B is N; A is optionally mono-, di- or tri- substituted alkanoyl, or cycloalkylalkanoyl; Q, W, X, Z, K, M and Ar1 to Ar3 are as defined above; with the proviso that when K is alkylene and M is Ar and Ar is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cyclooct-1-yl then cycloalkyl substituents are not substituted at the one position with hydroxy; and with the proviso that 6-[(3-phenyl-propyl)-(2-propyl-pentanoyl)-amino]-hexanoic acid and its ethyl ester are not included; or (iii): B is C(H); A, Q, W, X, Z, K, M  are as defined above; with the proviso that when K is alkylene and M is Ar and Ar is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cyclooct-1-yl then the cycloalkyl substituents are not substituted at the one position with hydroxy.