Merck + Co., Inc.

Mu T Wu

Arthur A Patchett

William J Greenlee

Richard L Tolman

Sander G Mills

Malcolm MacCoss

Lihu Yang

Ravi P Nargund

Conrad P Dorn

Wallace T Ashton

James R Tata

Meng Hsin Chen

John J Baldwin

Michael H Fisher

Prasun K Chakravarty

Zhijian Lu

Richard J Budhu

The present invention is directed to certain piperidines, pyrrolidines, and hexahydro-1H-azepines of the general structural formula: ##STR1## wherein B is selected from: ##STR2## and R.sup.1, R.sup.1a, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4, R.sup.4a, R.sup.4b, R.sup.4c, R.sup.5, D, X, Y, n, x and y are as defined herein. These compounds promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Growth hormone releasing compositions containing such compounds as the active ingredient thereof are also disclosed.

Piperidines promote release of growth hormone

Piperidines, pyrrolidines and hexahydro-1H-azepines promote release of

Diacylpiperazines of general structural formula: ##STR1## are: angiotensin II (A-II) antagonists with affinity for both AT.sub.1 and AT.sub.2 receptors useful in the treatment of hypertension, congestive heat failure, cerebrovascular, cognitive, and CNS disorders.

N,N-diacylpiperazines

Diacylpiperazines of general structure ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, and asthma, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.

N,N-diacylpiperazine tachykinin antagonists

Diacylpiperazines of general structure ##STR1## are: angiotensin II (A-II) antagonists selective for the type 2 (AT.sub.2) subtype useful in the treatment of cerebrovascular, cognitive, and CNS disorders; tachykinin receptor antagonists useful in the treatment of inflammatory diseases and pain or migraine; and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.

A series of carboxyl-containing N-alkyldipeptides have been found to posess antiviral potency--specifically against herpes simplex virus--by selectively inhibiting the viral ribonucleotide reductase enzyme.

Antiherpetic agents

There are disclosed certain 2-substituted-4-substituted 6H-7,8-dihydrothiapyrano[3,2-d]pyrimidines which have oral hypoglycemic activity and with such ability to lower blood sugar are useful in the treatment of type II diabetes and/or obesity with associated insulin resistance. Processes for the preparation of such compounds and compositions containing such compounds as the active ingredient thereof are also disclosed. The compounds are also .beta.-adrenergic blocking agonists or .alpha.-adrenergic blocking agents and act as ocular antihypertensives and are useful for the treatment of glaucoma and other eye disorders.

Substituted 6H-7,8-dihydrothiapyrano(3,2-D)-pyrimidines as hyopglycemic

Compounds of the formula: ##STR1## wherein R.sup.2 is --(CH.sub.2).sub.k --X--(CH.sub.2).sub.j --NHR.sup.3 ; wherein k is 0 to 3, j is 1 or 2; X is F or OH; and, R.sup.3 is hydrogen; loweralkyl or loweraralkyl which may be substituted by hydroxy, carboxy, carbamoyl, or carbalkoxy; or, acyl; and, a pharmaceutically acceptable salt thereof; are inhibitors of angiotensin I converting enzyme useful as antihypertensive agents.

N-carboxymethyl substituted lysyl and .alpha.-(.epsilon.-aminoalkyl)

The invention relates to aminoacyl-containing dipeptide derivatives and related compounds which are useful angiotensin converting enzyme inhibitors and as antihypertensives.

Aminoacyl-containing dipeptide derivatives useful as antihypertensives

Compounds of the formula: ##STR1## wherein R.sup.2 is ##STR2## wherein k is 2 to 5; R.sup.3 is hydrogen; loweralkyl and substituted loweralkyl where the substituents are carboxy, hydroxy, and amino; or aralkyl, substituted aralkyl, heteroaralkyl, and substituted heteroaralkyl where the aryl and heteroaryl substituents are carboxy, hydroxy, and amino; and C is COOR; CONH.sub.2 ; or CH.sub.2 OH; and a pharmaceutically acceptable salt thereof; are inhibitors of angiotensin I converting enzyme useful as antihypertensive agents.

N.sup.2 -(Substituted)carboxymethyl-N.sup.6 -(substituted)-lysyl-and

The invention relates to dipeptide compounds containing thialysine and related amino acids which are useful as converting enzyme inhibitors and as antihypertensives.

Dipeptides containing thialysine and related amino acids as

Thiazolines substituted at the 2-position with 2-substituted phenylhydrazino or 2-substituted phenylazo groups are disclosed. The hydrazino group may also be substituted. The compounds are active anthelmintics, antihypertensive and ectoparasiticidal agents.

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Clark, NJ, United States of America

Mu T Wu