Abstract: Non-human transgenic animals, such as transgenic mice, are generated which incorporate the a non-native form of the bradykinin B1 receptor gene against a null phenotype for the native form of the bradykinin B1 receptor. An exemplified portion of the invention disclosed a transgenic mouse wherein a targeting construct containing a transgene encoding the human B1 bradykinin receptor gene is inserted downstream of and operatively linked to the native mice bradykinin B1 promoter. This targeting construct also contains a fluxed neomycin resistance gene. The resulting transgenic animals are “humanized” for the bradykinin B1 receptor and are effectively on a null background for native, functional B1 receptor activity. These animals may be crossed with a Cre-deleter strain to generate transgenic offspring which absent of the floxed marker gene.

Abstract: Transgenic rats are generated which incorporate a primate B1 bradykinin receptor transgene(s) into their genome. This B1 bradykinin receptor gene is expressed in these transgenic rats, which results in binding of compounds which are selective for the primate form (such as the human form) of the receptor and not the rat form of the receptor. Therefore, the expressed transgenes within these transgenic lines mimic antagonist and agonist selectivity of the wild type primate B1 bradykinin receptor. These transgenic animals are useful as a specific receptor occupancy model for modulators of the B1 bradykinin receptor from the human or closely related species, as well as providing for an animal model system for assessment of the pharmacodynamic properties of such a B1 bradykinin modulator(s).

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

Abstract: Compounds of the formula X-Y-Z-R.sup.1 wherein:X is ##STR1## Y is --CO-- or --SO.sub.2 --; Z is an optional substituent selected from --NH--, --O--, --CHR--, --CH.dbd.CH--, --CH.dbd., --(CH.sub.2).sub.m -- or--CHCHOH--; andR.sup.1 is --CH.sub.3 --, --CH(CH.sub.3).sub.2, or substituted phenyl are tocolytic oxytocin antagonists useful in the treatment of pre-term labor, stripping labor preparatory to Caesarean delivery and dysmenorrhea.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Hapalindolinone compounds are produced by the controlled aerobic fermentation of a cyanobacterium of the genus Fischerella, ATCC No. 53558.