Warner-lambert Company

Parke-davis Company

Peter W Woo

Joseph Thomas Repine

James S Kaltenbronn

Ernest D Nicolaides

Theodore H Haskell

James P Hudspeth

Francis John Tinney

Elizabeth Ann Lunney

Marland P Hutt, Jr

Michael Andrew Stier

Timothy R Hurley

Karl-Otto Vollmer

W Howard Roark

Wolfgang Klemisch

Egmont Schaller

Albrecht V Hodenberg

Dino A Sherwood

Gin G Huang

The present invention relates to the + or - pirmenol stereoisomers and to selected metabolites of pirmenol or (+,-)-cis-.alpha.-[3-(2,6-dimethyl-1-piperidinyl))propyl]-.alpha.-phenyl-2 -pyridinemethanol which are active as antiarrhythmic agents. The pharmacological use of the metabolites that is the present invention is as antiarrhythmic agents. Pharmaceutical compositions comprising the metabolites are also within the scope of the invention.

Metabolites of pirmenol

The invention concerns novel renin-inhibiting peptides which are modified as isosteres. These peptides are useful for treating renin-associated hypertension and hyperaldosteronism. Processes for preparing the peptides, compositions containing them and methods for using them are included. Also included is a diagnostic test using the peptides to determine the presence of renin-associated hypertension or hyperaldosteronism.

Renin inhibitors II

The invention concerns novel renin-inhibitory peptides which are useful for treating renin associated hypertension and for treating hyperaldosteronism. Novel intermediates, processes for preparing both the intermediates and the novel peptides, pharmaceutical compositions, and methods of treatment are included.

Renin inhibitors

Novel organic amide compounds which are N-[6-[(acylaminoacylamino or aminoacylamino)phenyl]-1,2-dihydro-2-oxonicotinyl] penicillin compounds having broad spectrum antibacterial utility are provided by (a) reacting the free amino acid of the appropriate penicillin or the acid salt or silylated derivative or complex thereof with a reactive derivative of the corresponding N-6-[(acylaminoacylamino or aminoacylamino)-phenyl]-1,2-dihydro-2-oxonicotinic acid or (b) reacting the free amino acid 6-aminopenicillanic acid or a related compound or the acid salt or silylated derivative thereof with a reactive derivative of the corresponding D-N-[6-[(acylaminoacylamino or aminoacylamino) phenyl]-1,2-dihydro-2-oxonicotinyl]-2-substituted glycine. Pharmaceutical compositions containing said compounds and methods for treating infections using said compositions are also disclosed.

Antibacterial amide compounds and means for using the same

O-2,6-Diamino-2,3,6-trideoxy-.alpha.-D-ribo-hexopyranosyl-(1.fwdarw.4)-O-�. beta.-D-xylofuranosyl-(1.fwdarw.5)!-N.sup.1 -�(S)-4-amino-2-hydroxy-1-oxobutyl!-2-deoxystreptamine, also known as 3'-deoxybutirosin A and acid addition salts of said compound. These compounds exhibit a wide spectrum of antibacterial activity. The above compounds are produced by the reduction of a tetra-N-protected-3'-arylthio-3'-deoxybutirosin A compound having the formula: ##STR1##

Production of 3'-deoxybutirosina A

O-2,6-Diamino-2,3,4,6-tetradeoxy-.alpha.-D-erythro-hexopyranosyl-(1.fwdarw. 4)-O-[5-amino-5-deoxy-.beta.-D-xylofuranosyl-(1.fwdarw.5)]-N.sup.1 -[(S)-4-amino-2-hydroxy-1-oxobutyl]-2-deoxystreptamine, also known as aminotrideoxybutirosin A, and acid-addition salts. They have a wide spectrum of antibacterial activity. The above compounds can be produced from aminodeoxybutirosin A by the sequence of reactions which comprises protecting the five primary amino groups by converting them to arylmethoxycarbonyl derivatives, converting the 3',4'-hydroxyl groups to an acetal, acylating the remaining four hydroxyl groups, and hydrolyzing the acetal to produce a key intermediate which is an O-2,6-dideoxy-2,6-bis[[(arylmethoxy)carbonyl]amino]-.alpha.-D-glucopyranos yl-(1.fwdarw.4)-O-[2,3-di-O-acyl-5-deoxy-5-[[(arylmethoxy)carbonyl]amino]-. beta.-D-xylofuranosyl-(1.fwdarw.5)]-6-O-acyl-N.sup.1 -[(S)-2-acyloxy-1-oxo-4-[[(arylmethoxy)carbonyl]amino]-butyl]-2-deoxy-N.su p.3 -[(arylmethoxy)carbonyl]streptamine, generically also identified as protected 5'-aminodeoxybutirosin A. That compound is reacted with methanesulfonyl chloride in pyridine to introduce 3',4'-methanesulfonyloxy groups which are removed by reaction with zinc and sodium iodide to introduce a double bond at the 3',4' position. The acyl groups are hydrolyzed or cleaved as by reaction with ammonia in methanol and the product is reacted with hydrogen in the presence of a catalyst to remove the arylmethoxycarbonyl groups and hydrogenate the double bond with the formation of aminotrideoxybutirosin A.

Polyamine compounds and methods for their production

Growing community of inventors

Ann Arbor, MI, United States of America

Peter W Woo