Merck + Co., Inc.

Douglas J Pettibone

Roger M Freidinger

Ben E Evans

William J Greenlee

Thomas F Walsh

Prasun K Chakravarty

Peter D Williams

Scott William Bagley

Ralph A Rivero

Nancy J Kevin

Daljit S Dhanoa

Kenneth J Fitch

David L Williams

Theodore P Broten

Mark G Bock

James R Tata

Paul S Anderson

Richard B Toupence

Doug W Hobbs

Joseph M Pawluczyk

Jay M Matthews

Otto D Hensens

Jerrold M Liesch

Robert E Schwartz

Michael A Goetz

Kevin F Gilbert

Kenneth E Rittle

Gerard R Kieczykowski

Cheryl D Schwartz

Lawrence R Koupal

Gino M Salituro

George F Lundell

James B Hoffman

Janet M Sigmund

Charles F Hirsch

Roger M Friedinger

Douglas W Hobbs

Gerard J Hickey

Phenoxyphenylacetic acid derivatives

Tocolytic oxytocin receptor antagonists

Phenoxyphenylacetic acids and derivatives of the general structural formula I ##STR1## have endothelin antagonist activity and are useful in treating cardiovascular disorders, such as hypertension, postischemic renal failure, vasospasm, cerebral and cardiac ischemia, myocardial infarction, endotoxic shock, benign prostatic hyperplasia, inflammatory diseases including Raynaud's disease and asthma.

Compounds of the formula ##STR1## X is --O--, --NH-- and --NR.sup.8 --; Y is --CH.sub.2 --, --CHR.sup.8 -- and --C(R.sup.8).sub.2 --; R.sup.1 is camphor-10-yl, C.sub.1-5 alkoxyl, styryl, hydroxystyryl, furyl, unsubstituted or substituted thienyl, naphthyl, indolyl, tetrahydronaphthyl, unsubstituted, mono- or di-substituted pyridyl, pyrazinyl, unsubstituted or substituted cyclohexyl where the substituent is R.sup.4, and unsubstituted or substituted phenyl where the substituents on phenyl are R.sup.5, R.sup.6 and R.sup.7 ; R.sup.2 is hydrogen, C.sub.1-5 alkoxy, C.sub.1-5 alkyl, amino, C.sub.1-5 alkylcarbonylamino, nitro or halogen; R.sup.3 is hydrogen, C.sub.1-5 alkoxycarbonyl, cyano or carbamoyl; R.sup.4 is one to two of hydrogen, oxo, hydroxy, C.sub.1-5 alkoxy, C.sub.1-5 alkoxycarbonylamino-C.sub.1-5 alkyl and amino-C.sub.1-5 alkyl; R.sup.5, R.sup.6 are each independently selected from hydrogen, halogen, C.sub.1-5 alkyl, hydroxyl and C.sub.1-5 alkoxy; R.sup.7 is ##STR2## W is CO or SO.sub.2 ; and m is an integer from 0 to 1. Such compounds as useful as oxytocin and vasopressin receptor antagonists.

Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin

Oxytocin receptor antagonists of the formula ##STR1## wherein R.sup.12 is hydrogen, alkoxycarbonyl or unsubstituted of substituted alkyl; R.sup.13 is hydrogen, alkoxyl, aralkoxyl, alkoxycarbonyl, alkoxycarbonylamino, unsubstituted or substituted cycloalkyl, unsubstituted or substituted phenyl, unsubstituted or substituted amino, unsubstituted or substituted rings of the formulae ##STR2## unsubstituted or substituted alkyl, and the pharmaceutically acceptable salts thereof, are useful for increasing fertility rates, embryonic survival and overall reproductive efficiency in farm animals.

Method for improving reproductive efficiency in farm animals

Biphenyl compounds useful or endothelin antagonists

A method of inhibiting oxytocin from acting at its receptor site by administering oxytocin receptor antagonist compounds of the formula ##STR1## wherein X is oxygen or sulfur; Y is hydrogen or lower alkyl; R.sup.A is ##STR2##

Carbostyril oxytocin receptor antagonists

Compounds of the formula: ##STR1## where R.sup.1 is hydrogen or hydroxy and R.sup.2 is a substituted amino group, a substituted heterocyclic ring or a substituted alkyl. These compounds are oxytocin and vasopressin antagonists useful in the treatment of preterm labor, dysmenorrhea and for the stoppage of labor preparatory to cesarean delivery, timing of parturition, uterine hyperactivity, endometriosis, hypertension, congestive heart failure, hyponatremia and cognitive disorders. Also disclosed are pharmaceutical compositions containing these compounds, methods of their use and methods of their preparation.

Amide-substituted derivatives of spiroindanylcamphorsulfonyl oxytocin

A method for inhibiting oxytocin activity by administering an oxytocin inhibiting amount of a penicillide compound having the formula ##STR1## and compositions for such use are described.

Oxytocin antagonists

Cyclic peptides are produced by the controlled aerobic fermentation of Streptomyces silvensis, ATTCC No. 53525 or ATCC No. 53526. These compounds are antagonists of oxytocin and are useful in the treatment of preterm labor and vasopressin and are thus useful in the treatment and prevention of disease states wherein vasopressin may be involved, for example congestive heart failure, hypertension, edema and hyponatremia.

Oxytocin and vasopressin antagonists

Disclosed are spirocyclic compounds of the formula: ##STR1## The compounds of formula I are oxytocin antagonists useful in the treatment of preterm labor and dysmenorrhea, and for the stoppage of labor preporatory to Caesarian delivery. Also disclosed are pharmaceutical compositions containing these compounds as well as methods for preparing the compounds.

Spirocyclic oxytocin antagonists

Hapalindolinone compounds are produced by the controlled aerobic fermentation of a cyanobacterium of the genus Fischerella, ATCC No. 53558. These compounds are antagonists of vasopressin and are useful in the treatment and prevention of disease states wherein vasopressin may be involved, for example congestive heart failure, hypertension, edema and hyponatremia, and have the formula: ##STR1##

Hapalindolinone compounds as vassopressin antagonists

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Chalfont, PA, United States of America

Douglas J Pettibone