Merck + Co., Inc.

Merck Sharp + Dohme Corp.

George A Doss

Shieh-Shung T Chen

William K Hagmann

Byron H Arison

Linus S Lin

John G MacConnell

Sanjeev Kumar

Wenji Yin

Thomas F Walsh

Richard L Monaghan

John S Debenham

Christina B Madsen-Duggan

Russell B Lingham

Leeyuan Huang

Laszlo R Treiber

Sheih-Shung T Chen

Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

Substituted naphthyridinone derivatives

Substituted amides

New cholesterol lowering compounds are formed from the photochemical treatment of the zaragozic acids.

Cholesterol lowering compounds

Cholesterol lowering compounds and compositions are formed from the photochemical treatment of the Zaragozic Acids followed by esterification. These compounds and compositions are active squalene synthetase inhibitors useful in the treatment of hypercholesterolemia.

Novel cytochalasins are the biotransformed products after incubation with a substrate in a culture of the microorganism Kibdelosporangium sp. (Merck Culture Collection MA 6559), ATCC No. 53771. The compounds of the present invention inhibit HIV protease and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as a compound, pharmaceutically acceptable salt, pharmaceutical composition ingredient, whether or not as a prodrug or as a combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines.

Inhibitors of HIV protease

Fermentation of the microorganism Streptomyces sp. (MA6804), ATTC No. 55095, in the presence of the HIV reverse transcriptase inhibitor ##STR1## yields a 5-(1-hydroxy)ethyl analog which is useful in the prevention or treatment of infection by HIV and the treatment of AIDS.

Microbial transformation of a substituted pyridinone using streptomyces

Fermentation of the microoganism Actinoplanacete sp. in the presence of the angiotensin II receptor antagonist, 5,7-dimethyl-2-ethyl-3-((2'-tetrazol-5-yl)biphenyl-4-yl)methyl-3H-imidazo[ 4,5-b]pyridine, compound III, ##STR1## yields 2-ethyl-5-hydroxymethyl-7-methyl-3-((2'-tetrazol-5-yl)biphenyl-4-yl)methyl -3H-imidazo[4,5-b]pyridine, compound I, and 2-ethyl-7-hydroxymethyl-5-methyl-3-(2'-tetrazol-3-((2'-tetrazol-5-yl)biphe nyl-4-yl)methy-3H-imidazo[4,5-b]pyridine, compound II, ##STR2## both of which are angiotensin II receptor antagonists useful in the treatment of hypertension and congestive heart failure and other indications known to respond to angiotensin II antagonists.

Microbial transformation process for the preparation of hydroxylanol

Fermentation of the microorganism Actinoplanacete sp. (MA6559), ATTC No. 53771, in the presence of the HIV reverse transcriptase inhibitor ##STR1## yields 3-[2-(benzoxazol-2-yl)ethyl]-5-(1-hydroxyethyl)-6-methyl-2(1H)-pyridinone and 3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-hydroxymethyl-2(1H)-pyridinone, both of which are useful in the prevention or treatment of infection by HIV and the treatment of AIDS.

Microbial transformation of a substituted pyridinone using

Fermentation of the microorganism Streptomyces sp. MA6744 (ATCC No. 55041) in the presence of the Angiotensin II (A II) receptor antagonist ##STR1## yields a 7-hydroxymethyl, a 5,7-dihydroxymethyl, a 7-carboxy and a 1'-hydroxy-5-hydroxymethyl analog, all of which are also A II antagonists useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Microbial transformation process for antihypertensive products

Fermentation of the microorganism Streptomyces sp. MA6751 (ATCC No. 55043) in the presence of the Angiotensin II (A II) receptor antagonist ##STR1## yields an N2-tetrazole .beta.-glucuronide analog which is also an A II antagonist useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Novel biotransformation compounds I, II, III and IV are prepared by fermenting 3-[(2'-tetrazol-5-yl-biphenyl-4-yl) methyl]-7-methyl-2-propyl-3H-imidzao [4,5-b]pyridine in a culture of Streptomyces sp., Accession Number ATCC 55041. ##STR1## These novel compounds are Angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Process for preparation of novel angiotensin II antagonists

Fermentation of the microorganism Streptomyces sp. MA6751 in the presence of ##STR1## yields an anti-hypertensive compound of the structure ##STR2##

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Westfield, NJ, United States of America

George A Doss