Merck Frosst Canada, Inc.

Biomega, Inc.

Bio-mega/boehringer Ingelheim Research Inc.

Lcb Pharma Inc.

Merck + Co., Inc.

Institut De Recherches Cliniques De Montreal

Université D'ottawa

Boehringer Ingelheim Ltd./ Boehringer Ingelheim Ltee

Christiane Yoakim

Paul Cates Anderson

Yvan Guindon

Joshua Rokach

Cheuk K Lau

Rejean Fortin

John W Gillard

Yves Girard

Howard E Morton

Patrice C Belanger

Joseph G Atkinson

Julian Adams

Robert N Young

Michel L Belley

Masatoshi Kakushima

Paul C Anderson

Philippe Mochirian

Haydn R Williams

Mona Nemer

Pierre Louis Beaulieu

Michel Therien

Claude Dufresne

Dominik M Wernic

Sumanas Rakhit

Pierre Lavallee

Robert Deziel

Gregory P Cosentino

Robert D Eziel

Michel Prévost

Brian Fitzsimmons, Deceased

Maryann Fitzsimmons, Heir

John Schiegetz

Thomas R Jones

The compounds are nucleoside and nucleotide analogues that can be used as anticancer or antiviral agents. The compounds include tetrahydrofuranyl or tetrahydrothienyl moieties with quaternary stereogenic all-carbon center at the 3' position and bear a phosphoryl group at either one of, or both of positions C5&#x2032; and/or C3&#x2032;; have a quaternary stereogenic all-carbon center at one of the 3&#x2032; position, 2&#x2032; position, or no quaternary stereogenic center at all, and bear a &#x3b2;-blocked lipoate derivative attached through an amide bond to the primary amine of the nucleobase; or have a quaternary stereogenic all-carbon center at the 2&#x2032; position and bear a phosphorylated prodrug at the C5&#x2032;-position and a &#x3b2;-blocked lipoate derivative attached through an amide bond to the primary amine of the nucleobase 

Nucleoside analogues and methods of use thereof

The compounds are nucleoside and nucleotide analogues that can be used as cardioprotective agents. The compounds include tetrahydrofuranyl or tetrahydrothienyl moieties with quaternary stereogenic all-carbon centers at the 2' position and a phosphonate ester at C5&#x2032; position. 

Nucleoside and nucleotide analogues bearing a quaternary all-carbon stereogenic center at the 2' position and methods of use as a cardioprotective agent

The disclosure provides nucleotide analogues that comprise tetrahydrofuranyl or tetrahydrothienyl moieties with quaternary centers at the 3' position, the pharmaceutical formulations comprising the analogues, and methods of using the analogues and formulations for treating, preventing, and/or inhibiting diseases or conditions associated with cancers and viruses.

Nucleoside analogues with quaternary carbon stereogenic centers and methods of use

The present invention comprises compounds useful as antiviral or antitumor agents. The compounds comprise nucleotide analogues that comprise tetrahydrofuranyl or tetrahydrothienyl moeities with quaternary centers at the 3' position. The nucleotide analogues can be used to inhibit cancer or viruses. Accordingly, the compounds of the present invention are useful for treating, preventing, and/or inhibiting diseases or conditions associated with cancers and viruses. Thus, the present invention also comprising pharmaceutical formulations comprising the compounds and methods of using the compounds and formulations to inhibit viruses or tumors and treat, prevent, or inhibit the foregoing diseases.

Nucleoside and nucleotide analogues with quaternary carbon centers and methods of use

Disclosed herein is a combination of an antiviral nucleoside analog and a ribonucleotide reductase inhibiting peptide derivative. The combination is useful for combatting herpes infections.

Antiherpes compositions and method of use

Disclosed herein is a stereospecific synthesis amenable to the large scale preparation of a hydrochloric acid addition salt of a chlorohydrin of the formula ##STR1## wherein R.sup.1 and R.sup.2 are amino protective groups and R.sup.3 is an amino acid side chain or a protected amino acid side chain. The synthesis involves reacting an aldehyde of the formula ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined hereinbefore with (chloromethyl)lithium at -20.degree. C. or below and contacting the resulting diastereoisomeric mixture of lithium alcoholates with aqueous hydrochloric acid to obtain a separable mixture of the hydrochloric acid addition salts of the chlorohydrin and its corresponding hydroxy diastereoisomer. The hydrochloric acid addition salt of the chlorohydrin is transformed readily into corresponding optionally amino-protected aminoepoxides; for example, 3(S)-(tert-butyloxycarbonylamino)-l,2(S)-epoxy-4-phenyl-butane.

Process for key intermediates for HIV protease inhibitors

Disclosed herein is a combination of an antiviral nucleoside analog and a ribonucleotide reductase inhibiting peptide derivative. The combination is useful for treating herpes infections.

Synergistic combination for treating herpes infections

A group of known naphthoquinone derivatives have been found to be useful for preventing or relieving herpes viral infections.

Methods and compositions for combatting herpes viruses

A group of known naphthalene derivatives have been found to be useful for preventing or relieving herpes viral infections.

Treating herpes Viral infections

Compounds having the formula: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti asthmatic, anti allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

3-hetero-substituted-N-benzyl-indoles and medical methods of use therefor

Disclosed herein are peptide derivatives which inhibit the activity of human immunodeficiency virus (HIV) protease. The peptide derivatives can be represented by general formula R.sup.1 --R.sup.2 --Y--R.sup.3 --R.sup.4 wherein R.sup.1 is an optionally substituted 3-(1,2,3,4-tetrahydroisoquinolyl)carbonyl residue, R.sup.2 and R.sup.3 are amino acid or analogous amino acid residues (R.sup.3 may optionally be absent), Y is a non-peptide linking unit, e.g. statyl, and R.sup.4 is [--NR.sup.17 CH(R.sup.18)C(O)].sub.p --Z wherein R.sup.17 is hydrogen or lower alkyl, R.sup.18 is an amino acid or analogous amino acid side chain, p is zero or 1 and Z is a terminal group (e.g. hydroxy or amino), or R.sup.4 is --NR.sup.17 CR.sup.18 (R.sup.21)CH.sub.2 --OH wherein R.sup.17 and R.sup.18 are as noted hereinabove and R.sup.21 is hydrogen, lower alkyl or hydroxy(lower)alkyl. The derivatives also inhibit renin activity. Accordingly, the derivatives can be used for combating HIV infections or for treating hypertension or congestive heart failure.

Enzyme inhibitors

Compounds of the Formulae: ##STR1## are antagonists of leukotrienes of C.sub.4, D.sub.4 and E.sub.4, the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.

Leukotriene antagonists

Disclosed herein are peptide derivatives which inhibit the activities of human immunodeficiency virus (HIV) protease and renin. The peptide derivatives can be represented by general formula R.sup.1 --R.sup.2 --Y--R.sup.3 --R.sup.4 wherein R.sup.1 is a derived amino acid based on an O.sup.4 -(carboxymethyl)-tyrosyl residue, R.sup.2 and are amino acid or analogous amino acid residues (R.sup.3 may optionally be absent), Y is a non-peptide linking unit, e.g. statyl, and R.sup.4 is [--NR.sup.17 CHR.sup.18 --C(O)].sub.p --Z wherein R.sup.17 is hydrogen or lower alkyl, R.sup.18 is an amino acid or analogous amino acid side chain, p is zero or one and Z is a terminal group (e.g. hydroxy or amino), or R.sup.4 is --NR.sup.17 CR.sup.18 (R.sup.21)CH.sub.2 OH wherein R.sup.17 and R.sup.18 are as noted hereinabove and R.sup.21 is hydrogen, lower alkyl or hydroxy(lower)alkyl. The derivatives are useful as agents for combatting HIV infections and for treating renin-associated hypertension and congestive heart failure.

Enzyme inhibiting peptide derivatives

Compounds of the formula: ##STR1## where R.sup.2 contains certain aryls or heteroaryls are effective leukotriene inhibitors.

5-hydroxy-2,3-dihydrobenzofuran analogs as leukotriene biosynthesis

Compounds having the formula: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

Growing community of inventors

Montreal, Canada

Yvan Guindon