Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents

• US 5,607,978 A
• Filed: 01/11/1995
• Issued: 03/04/1997
• Est. Priority Date: 09/21/1992
• Status: Expired due to Term

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan SPA (Abbvie Incorporated)
• Inventors: Andrews, Steven W., Garst, Michael E., Woodward, David F., Burk, Robert M.
• Primary Examiner(s): SIEGEL, ALAN M
• Application Number:
  US08/371,339
• Time in Patent Office: 783 Days
• Field of Search: 514/646, 514/659, 514/514, 514/613, 514/617, 514/471, 514/359, 514/438, 514/548, 514/549, 514/551
• US Class Current: 514/646
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/5585 having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
• CPC Class Codes: A61K 31/559 having heterocyclic rings containing hetero atoms other than oxygen
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07C 215/42 : having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
• CPC Class Codes: C07C 235/34 : having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 247/10 : and containing rings
• CPC Class Codes: C07C 255/36 : the carbon skeleton being further substituted by hydroxy groups
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 35/21 : polycyclic, at least one hydroxy group bound to a non-condensed ring
• CPC Class Codes: C07C 405/00 : Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof

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.

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 I ##STR11## wherein the dashed bonds represent a single or double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical may substituted with one or more hydroxy, oxo, alkyloxy or akylcarboxy groups, B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of phenyl, thienyl, furanyl and pyridyl;

X is a radical selected from the group consisting of amino, radicals;

one of R₁ and R₂ is ═

O,--OH or a --O(CO)R₆ group, and the other one is --OH or --O(CO)R₆, or R₁ is ═

O and R₂ is H, wherein R₆ is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or --(CH₂)m R₇ wherein m is 0-10, and R₇ is cycloalkyl radical, having from three to seven carbon atoms, or an aryl radical, as defined above, or a pharmaceutically-acceptable salt thereof.

2. A method of treating ocular hypertension which comprises applying to the eye an amount sufficient to treat ocular hypertension of a compound is a compound of formula II ##STR12## wherein y is 0 or 1 and either the α

or ω

chain may be unsaturated, Y is a radical selected from the group consisting of halo, nitro, amino, thiol, hydroxy, alkyloxy and alkylcarboxy, n is 0 or an integer of from 1 to 3 R₃ and is ═

O,--OH or --O(CO)R₆.

3. The method of claim 2 wherein said compound is a compound of formula III ##STR13## wherein hatched lines indicate α

configuration and solid triangles indicate β

configuration.

4. The method of claim 3 wherein said compound is a compound of formula IV. ##STR14##

5. The method of claim 4 wherein said compound is a compound of formula V ##STR15## and the 9- and/or 11- and/or 15 esters, thereof.

6. The method of claim 2 wherein X is selected from the group consisting of

--N(R₄)(R₄), wherein R₄ is hydrogen or C₁ to C₃ alkyl.

7. The method of claim 6 wherein R₄ is hydrogen.

8. The method of claim 7 wherein said compound is:

cyclopentane hepteneamine-5-cis-2-(3-α

hydroxy-5-phenyl-1-trans-pentyl)-3, 5 dihydroxy, [1.sub.α

, 2.sub.β

, 3.sub.α

, 5.sub.α

].