Ciba-geigy Corporation

Genelabs, Incorporated

Genelabs Technologies, Inc.

Jen Chen

William Choy

Alan J Hutchison

Wilhelm Kump

Kou M Hwang

Su-Ying Liu

You M Qi

Benjamin B Mugrage

John E Francis

Siem J Veenstra

Thomas C Lee

Christian Borel

Bijan Almassian

A method for inhibiting cell infection by an enveloped virus, by administering to an infection site, a therapeutically effective amount of a calix(n)arene compound derivatized, at its ring positions meta to the bridge attachements to the ring, with polar substitutent having a terminal carboxylate, phosphate, or sulfonate groups, including esters and amides which are cleavable in vivo. The compound may be administered orally, or topically, e.g., for treatment of herpes virus.

Treatment of infection by enveloped virus with calix(N)arene compounds

A method of inhibiting thrombus formation in a mammalian subject. The method involves administering to the subject a therapeutically effective dose of a calix(n)arene compound derivatized, at its ring positions meta to the bridge attachments to the ring, with polar substituents having terminal sulfonate groups, including esters and amides which are cleavable in vivo.

Antithrombotic treatment with calix(n)arene compounds

A method of preparing a 4'-0-demethy-4.beta.-NHR podophyllotoxin, where R is an aryl or dialkyl amino alkyl group, is disclosed. The method includes reacting H.sub.2 NR under basic conditions with a mixture of .alpha. and .beta. epimers of 4'-0-demethyl-4-bromo-podophyllotoxin, to form an epimeric mixture of the 4'-0-demethyl-4-NHR-podophyllotoxin compounds, removing acidic impurities which bind to silica gel in a dichloromethane solvent, and crystallizing 4'-0-demethyl-4.beta.-NHR-podophyllotoxin from its .alpha. epimer.

Preparation of 4.beta.- amino podophyllotoxin compounds

The invention relates to novel acyl derivatives of rifamycins of the formula ##STR1## and the salts thereof, in which the structural elements --A.sub.1 --A.sub.2 --, --A.sub.3 --A.sub.4 -- and --A.sub.5 --A.sub.6 -- each denote ethylene or vinylene or the elements --A.sub.1 --A.sub.2 -- and --A.sub.3 --A.sub.4 -- each denote ethylene and --A.sub.5 --A.sub.6 -- denotes vinylene; X represents &gt;C(R.sub.6)-- or &gt;N-- and R.sub.6 denotes hydrogen or alkyl; alk denotes an aliphatic hydrocarbon radical; R.sub.1 denotes hydrogen or acyl; R.sub.2 denotes acyl, or alkyl which is optionally substituted by an aromatic radical, and R.sub.3 and R.sub.3 ' represent a common bond, or R.sub.3 denotes hydrogen or acyl, and R.sub.3 ' is hydrogen; R.sub.4 denotes hydrogen, cycloalkyl or aryl; R.sub.5 denotes hydrogen or acetyl; R.sub.7 denotes hydrogen or alkyl, which can be used as active compounds in medicaments, the preparation and use thereof, and pharmaceutical products and the preparation thereof.

Acyl derivatives of oxazolorifamycins

The compound of the formula I ##STR1## wherein R, R.sub.3 and R.sub.5 independently represent hydrogen or hydroxy provided that at least one of R, R.sub.3 and R.sub.5 represents hydroxy; R.sub.1 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -alkenyl, hydroxy-lower alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, adamantyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl, adamantyl-lower alkyl, aryl-hydroxy-lower alkyl, aryl, aryl-lower alkyl, aryl-C.sub.3 -C.sub.6 -cycloalkyl, 9-fluorenyl, 9-fluorenyl-lower alkyl or cycloalkenyl-lower alkyl; or R.sub.1 represents a bicyclic benzo-fused 5 or 6-membered saturated carbocyclic radical or a benz-fused 5 or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur directly attached to the fused benzene ring, any said bicyclic radicals being optionally substituted on the benzo portion by lower alkyl, lower alkoxy or halogen, or R.sub.1 represents any said bicyclic radical substituted-lower alkyl; R.sub.2 represents hydrogen, halogen, --S--R.sub.1 ', --NR.sub.b --R.sub.1 ', or --NH--R.sub.1 ' in each of which R.sub.1 ' has meaning as defined for R.sub.1 provided that R.sub.1 ' in --SR.sub.1 ' does not represent hydrogen; R.sub.b represents lower alkyl; R.sub.4 represents hydroxymethyl provided that R.sub.2 does not represent either hydrogen or --NHR.sub.1 ' in which R.sub.1 ' represents either hydrogen or lower alkyl; or R.sub.4 represents lower alkoxymethyl or lower alkylthiomethyl; or R.sub.4 represents --CONHR.sub.6 in which R.sub.6 represents lower alkyl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl or hydroxy-lower alkyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; methods for their preparation; and their use as adenosine receptor agonists are disclosed.

N.sub.9 -cyclopentyl-substituted adenine derivatives useful as adenosine

The invention relates to novel substituted azacyclohexyl derivatives of formula ##STR1## and salts of thereof in which the structural elements --A.sub.1 -A.sub.2, --A.sub.3 -A.sub.4 -- and --A.sub.5 -A.sub.6 -- are each ethylene or vinylene or the elements --A.sub.1 -A.sub.2 -- and --A.sub.3 -A.sub.4 -- are each ethylene and --A.sub.5 -A.sub.6 -- is vinylene, X is &gt;CR.sub.6 -- or &gt;N-- and R.sub.6 is alkyl or hydrogen, alk is an aliphatic hydrocarbon radical or a bond, R.sub.1 is hydrogen or acyl, R.sub.2 is hydrogen or acetyl, R.sub.3 and R.sub.4 together are a bond or each is hydrogen, R.sub.5 is hydrogen, a cycloaliphatic hydrocarbon radical, aryl or heteroaryl and R.sub.7 is hydrogen or alkyl, with the proviso that when --A.sub.1 -A.sub.2 --, --A.sub.3 -A.sub.4 -- and --A.sub.5 -A.sub.6 -- are each vinylene, X is &gt;N--, R.sub.1 is hydrogen or trialkylacetyl, R.sub.2 is hydrogen or acetyl, R.sub.3 and R.sub.4 together are a bond and alk is methylene, R.sub.5 is other than 2,6-dimethyl-4-alkylphenyl, which can be used as active ingredients in medicaments, to their preparation and use and to pharmaceutical preparations.

Substituted azacyclohexyl derivatives of rifamycins

The compound of the formula I ##STR1## wherein R, R.sub.3 and R.sub.5 independently represent hydrogen or hydroxy provided that at least one of R, R.sub.3 and R.sub.5 represents hydroxy; R.sub.1 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -alkenyl, hydroxy-lower alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, adamantyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl, adamantyl-lower alkyl, aryl-hydroxy-lower alkyl, aryl, aryl-lower alkyl, aryl-C.sub.3 -C.sub.6 -cycloalkyl, 9-fluorenyl, 9-fluorenyl-lower alkyl or cycloalkenyl-lower alkyl; or R.sub.1 represents a bicyclic benzo-fused 5 or 6-membered saturated cyabocyclic radical or a benzo-fused 5 or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur directly attached to the fused benzene ring, any said bicyclic radicals being optionally substituted on the benzo portion by lower alkyl, lower alkoxy or halogen, or R.sub.1 represents any said bicyclic radical substituted-lower alkyl; R.sub.2 represents hydrogen, halogen, --S--R.sub.1 ', --NR.sub.b --R.sub.1 ', or --NH--R.sub.1 ' in each of which R.sub.1 ' has meaning as defined for R.sub.1 provided that R.sub.1 ' in --SR.sub.1 ' does not represent hydrogen; R.sub.b represents lower alkyl; R.sub.4 represents hydroxymethyl provided that R.sub.2 does not represent either hydrogen or --NHR.sub.1 ' in which R.sub.1 ' represents either hydrogen or lower alkyl; or R.sub.4 represents lower alkoxymethyl or lower alkylthiomethyl; or R.sub.4 represents --CONHR.sub.6 in which R.sub.6 represents lower alkyl; aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl or hydroxy-lower alkyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; methods for their preparation; and their use as adenosine receptor agonists are disclosed.

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Sunnyvale, CA, United States of America

Jen Chen