Merck + Co., Inc.

Other

Paul J Reider

Ralph P Volante

Kai Rossen

David Askin

Edward J Grabowski

Richard John Varsolona

Woo-Baeg Choi

Kenneth M Wells

Joseph E Lynch

Philip J Pye

Andrew S Thompson

Ichiro Shinkai

Guy R Humphrey

Robert D Larsen

Richard D Tillyer

Steven A Weissman

Joseph S Amato

Kan K Eng

Jess Sager

Hywyn R Churchill

Thomas R Verhoeven

Feng Xu

Peter Emmanuel Maligres

Michel M Chartrain

Mark A Huffman

Lushi Tan

Edward G Corley

David L Hughes

R Scott Hoerrner

Cheng Yi Chen

James M McNamara

Robert A Reamer

Ioannis N Houpis

Audrey Molina

Chris H Senanayake

Brian Heimbuch

F Edward Roberts

Yongkui Sun

Mandana Asgharnejad

Jaemoon Lee

Edward J J Grabowski

Randolph L Greasham

Johnnie L Leazer, Jr

James J Bergan

Neal C Connors

Veena Upadhyay

Carl LeBlond

Robert M Purick

Roger C Olewinski, Jr

Barbara A Jackey

Francis P Gailliot

Jose M Vega

Chanyong Lee

Barry C Buckland

The instant invention provides methods and pharmaceutical compositions for inhibiting HMG-CoA reductase, as well as for treating and/or reducing the risk for diseases and conditions affected by inhibition of HMG-CoA reductase, comprising orally administering a therapeutically effective amount of a compound selected from a dihydroxy open acid statin and a pharmaceutically acceptable salt or ester thereof in a delayed-release pharmaceutical dosage form to a patient in need of such treatment wherein substantial release of the compound from the dosage form is delayed until after passage of the dosage form through the stomach.

Dihydroxy open-acid and salts of HMG-CoA reductase inhibitors

Process for the synthesis of carbapenem intermidiates, and compounds produced

A process for making a beta methyl carbapenem intermediate is disclosed. A compound of formula I:

Preparation of betamethyl carbapenem intermediates

An improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butylcarboxamide, an intermediate for an HIV protease inhibitor.

Process for preparing

The instant invention relates to a compound of the formula: ##STR1## wherein R.sub.a and P are: (a) hydrogen,

Preparation of beta-methyl carbapenem intermediates

This invention relates to a sulfate salt of an HIV protease inhibitor, Compound A, of formula: ##STR1## Compound A is useful in the treatment of AIDS, ARC or HIV infection in adults and children. Processes for making the sulfate salt of Compound A are also disclosed.

HIV protease inhibitor

The invention relates to an improved stereoselective heterogenous catalytic reductive amination between ethyl 2-oxo-4-phenylbutyrate and alanylproline using hydrogen, a catalyst and one or more additives to produce the ACE inhibitor, enalapril.

Stereoselective process for enalapril

A method of preparing intermediates for carbapenem antibiotics characterized by treating a N-deprotected acetoxy conpound of the formula: ##STR1## in the presence of a Lewis acid or a silylating agent to yeild an intermediate; and cyclizing the intermediate in the presence of rhodium (II) acetate to form a bicyclic ketoester.

Antibiotic synthesis

An improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butylcarboxaimide, an intermediate for an HIV protease inhibitor.

A process for enhancing the purity of 2R-�1-hydroxy-1-trifluoromethyl-3-cyclopropylpropyn-2-yl!-4-chloroaniline comprising the formation of an acid addition salt which is capable of rejecting the racemate in the selected organic solvent.

Process for enhancing the optical purity

Intermediates of structural formula ##STR1## can be made by reacting a primary or secondary amine with glycosidol or an activated derivative thereof. The process and intermediates are useful for synthesizing HIV protease inhibitor compounds.

Process for making HIV protese inhibitors

A process is disclosed that bioconverts indene to (1S)-amino-(2R)-indanol substantially free of any of its stereoisomers, by the action of a strain of P. putida or Rhodococcus sp., followed by various chemical step(s), e.g., chiral specific crystallization, treatment with strong acid in the presence of acetonitrile.

Conversion of indene to (1S)-amino-(2R)-indanol free of any

A process for the preparation of Phosphodiesterase IV inhibitors is described. The process consists of eight chemical steps involving five isolations to prepare the title compound from readily available isovanillin in 35% overall yield (Scheme 1). The process is highlighted by: a) a highly diastereoselective Michael addition of phenyllithium using (1R, 2S) cis-aminoindanol as a chiral auxiliary, b) highly crystalline intermediates providing for efficient purifications, c) crystallization of the final compound as its CSA salt for excellent enantiomeric purity.

Method of preparing phosphodiesterase IV inhibitors

A process for synthesizing the epoxide of the formula ##STR1## consists of, at a minimum, formation of a halohydrin from the allyl acetonide reactat, followed by base-induced cyclization, the epoxide product I being useful as an intermediate for the synthesis of inhibitors of renin or HIV protease or other proteases.

Process for making an epoxide

An improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butyl-carboxamide, an intermediate for an HIV protease inhibitor.

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Westfield, NJ, United States of America

Paul J Reider