Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents

#1. Field of the Invention

#The present invention provides cyclopentane heptanoic acid, 2 heteroaryl alkyl or alkenyl derivatives which may be substituted in the 1-position with hydroxyl, alkyloxy, amino and amido groups, e.g. 1-OH cyclopentane heptanoic acid, 2 heteroarylalkenyl derivatives. In particular, these derivatives are 7-[5-hydroxy-2-(heteroatom-substituted hydroxyhydrocarbyl)-3hydroxycyclopentyl] heptanoic or heptenoic acids and amine, amide, ether, ester and alcohol derivatives of said acids wherein one or more of said hydroxy groups are replaced with an ether group. These compounds are potent ocular hypotensives and are particularly suited for the management of glaucoma. Moreover, the compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; with additional application in gastrointestinal disease, reproduction, fertility, incontinence, shock, inflammation, immune regulation, disorder of bone metabolism, renal dysfunction, cancer and other hyperproliferative diseases.

#2. Description of Related Art

#FIG. 1 is a schematic of the chemical synthesis of certain 1-carboxylic acid compounds and ester derivatives thereof specifically disclosed as Example 4(a)-(e) and 5(a)-(e) below.

#FIG. 2 is a schematic of the chemical synthesis of certain 1-amido compounds specifically disclosed as Examples 6(b)-(g) below.

#FIG. 3 is a schematic of the chemical synthesis of certain 1-isopropyl ester compounds specifically disclosed as Examples 7(f)-(i), below.

#The present invention relates to the use of cyclopentane heptan(ene)oic acid, 2-heteroaryl alkyl or alkenyl derivatives as therapeutic agents, e.g. as ocular hypotensives. The compounds used in accordance with the present invention are encompassed by the following structural formula I: 3

#wherein the substituents and symbols are as hereinabove defined.

#Preferably, the compounds used in accordance with the present invention have the following structural formula II: 4