Details for Patent: 5,352,708
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| Title: | Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| Abstract: | The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives, substituted in the 1-position with halo, methyl, hydroxyl, nitro, amino, amido, azido, oxime, cyano, thiol, either or thioether groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) derivatives. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) derivatives of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) derivatives of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc. |
| Inventor(s): | Woodward; David F. (El Toro, CA), Andrews; Steven W. (Irvine, CA), Burk; Robert M. (Irvine, CA), Garst; Michael E. (Newport Beach, CA) |
| Assignee: | Allergan, Inc. (Irvine, CA) |
| Filing Date: | Sep 21, 1992 |
| Application Number: | 07/948,056 |
| Claims: | 1. A method of treating ocular hypertension which comprises applying to the eye an amount sufficient to treat ocular hypertension of a compound of formula III. ##STR11## wherein hatched lines indicate .alpha. configuration and solid triangles indicate .beta. configuration, and the dashed bonds represent a single or double bond which can be in the cis or trans configuration; X is hydroxyl; one of R.sub.1 and R.sub.2 is .dbd.O, --OH or a --O(CO)R.sub.6 group, and the other one is --OH or --O(CO)R.sub.6, or R.sub.1 is .dbd.O and R.sub.2 is H; wherein R.sub.6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or --(CH.sub.2)mR.sub.7 wherein m is 0-10, and R.sub.7 is cycloalkyl radical, having from to three seven carbon atoms, or a hydrocarbyl aryl or heteroaryl, wherein the heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur atoms and R.sub.3 is hydroxyl. 2. The method of claim 1 wherein said compound is a compound of formula IV ##STR12## 3. The method of claim 2 wherein said compound is a compound of formula V. ##STR13## and the 9- and/or 11 esters, thereof. 4. The method of claim 3 wherein said compound is selected from the group consisting of cyclopentane heptenol-5-cis-2-(3-.alpha.hydroxy-5-phenyl-1-trans-pentenyl)-3, 5 dihydroxy [1.alpha., 2.beta., 3.alpha., 5.alpha.] and cyclopentane heptenol-5-cis-2-(3.alpha. hydroxy-5-phenylpentyl) 3,5 dihydroxy, [1.alpha., 2.beta., 3.alpha., 5.alpha.]. 5. The composition of claim 4 wherein said compound is selected from the group consisting of cyclopentane heptenol-5-cis-2-(3-.alpha. hydroxy-5-phenyl-1-trans-pentenyl)-3, 5 dihydroxy [1.alpha., 2.beta., 3.alpha., 5.alpha.] and cyclopentane heptenol-5-cis-2-(3.alpha. hydroxy-5-phenylpentyl) 3,5 dihydroxy, [1.alpha., 2.beta., 3.alpha., 5.alpha.]. 6. A pharmaceutical composition for treating ocular hypertension which comprises a therapeutically-effective amount of a compound of formula III. ##STR14## wherein hatched lines indicate .alpha. configuration and solid lines indicate .beta. configuration, and the dashed bonds represent a single or double bond which can be in the cis or trans configuration; X is hydroxyl; one of R.sub.1 and R.sub.2 is .dbd.O, --OH or a --O(CO)R.sub.6 group, and the other one is --OH or --O(CO)R.sub.6, or R.sub.1 is .dbd.O and R.sub.2 is H; wherein R.sub.6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or --(CH.sub.2)mR.sub.7 wherein m is 0-10, and R.sub.7 is cycloalkyl radical, having from to three seven carbon atoms, or a hydrocarbyl aryl or heteroaryl, wherein the heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur atoms and R.sub.3 is hydroxyl or a pharmaceutically-acceptable salt thereof in combination with an ophthalmically-acceptable vehicle. 7. The composition of claim 6 wherein said compound is a compound of formula IV. ##STR15## 8. The composition of claim 7 wherein said compound is a compound of formula V. ##STR16## and the 9- and/11 esters, thereof. |
