Janssen Pharmaceutica Nv

Other

Marc Rene De Jonge

Jan Heeres

Donald William Ludovici

Lucien Maria Henricus Koymans

Chih Yung Ho

Michael Joseph Kukla

Robert William Kavash

Bart L De Corte

Paul Adriaan Jan Janssen

Koen Jeanne Alfons Van Aken

Koenraad Jozef Lodewijk Marcel Andries

Paul A Janssen

Jean-Marc Edmond Fernand Marie Neefs

Peter Karel Maria Verhasselt

Johann Winkler

Hinrich Wilhelm Helmut Gohlmann

Lucien Maria Koymans

Frederik Frans Daeyaert

Paul Andriaan Jan Janssen

Bart De Cort

This invention provides an isolated mutant atpE protein and departing from said mutant atpE protein the identification of an ATPase binding domain. This invention also provides related nucleic acids, vectors, host cells, pharmaceutical compositions and articles of manufacture. This invention further provides methods for determining whether a test compound interacts with an atpE protein, i.e. with the ATPase binding domain of the present invention, as well as pharmaceuticals compositions comprising said test compound, in particular as antimicrobials, more particular as antimycobacterial agent, even more particular for treating tuberculosis in a subject.

Bacterial ATP synthase binding domain

This invention concerns the use of compounds of formulathe N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a=a-a=a- forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; Ris hydrogen, aryl, formyl, Calkylcarbonyl, Calkyl, Calkyloxycarbonyl, substituted Calkyl, or substituted CalkyloxyCalkylcarbonyl; each Rindependently is hydroxy, halo, optionally substituted Calkyl, Calkenyl or Calkynyl, Ccycloalkyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(Calkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, &#x2014;NHC(&#x2550;O)R, &#x2014;C(&#x2550;NH)Ror a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted Calkyl, Calkenyl, Calkynyl or Ccycloalkyl; or L is &#x2014;X&#x2014;Rwherein Ris optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is &#x2014;NR&#x2014;, &#x2014;NH&#x2014;NH&#x2014;, &#x2014;N&#x2550;N&#x2014;, &#x2014;O&#x2014;, &#x2014;C(&#x2550;O)&#x2014;, &#x2014;CHOH&#x2014;, &#x2014;S&#x2014;, &#x2014;S(&#x2550;O)&#x2014; or &#x2014;S(&#x2550;O)&#x2014;; Q is hydrogen, Calkyl, halo, polyhalo-Calkyl or an optionally substituted amino group; Y represents hydroxy, halo, Ccycloalkyl, optionally substituted Calkyl, Calkenyl or Calkynyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(Calkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, &#x2014;NHC(&#x2550;O)R, &#x2014;C(&#x2550;NH)Ror aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

HIV replication inhibiting pyrimidines

This invention concerns the use of compounds of formula:the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a=-a-a=a- forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; Ris hydrogen, aryl, formyl, Calkylcarbonyl, Calkyl, Calkyloxy-carbonyl, substituted Calkyl, or substituted CalkyloxyCalkylcarbonyl; each Rindependently is hydroxy, halo, optionally substituted Calkyl, Calkenyl or Calkynyl, Ccycloalkyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(Calkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalo-methylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, &#x2014;NHC(&#x2550;O)R, &#x2014;C(&#x2550;NH)Ror a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted Calkyl, Calkenyl, Calkynyl or Ccycloalkyl; or L is &#x2014;X&#x2014;Rwherein Ris optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is &#x2014;NR&#x2014;, &#x2014;NH&#x2014;NH&#x2014;, &#x2014;N&#x2550;N&#x2014;, &#x2014;O&#x2014;, &#x2014;C(&#x2550;O)&#x2014;, &#x2014;CHOH&#x2014;, &#x2014;S&#x2014;, &#x2014;S(&#x2550;O)&#x2014; or &#x2014;S(&#x2550;O)&#x2014;; Q is hydrogen, Calkyl, halo, polyhalo-Calkyl or an optionally substituted amino group; Y represents hydroxy, halo, Ccycloalkyl, optionally substituted Calkyl, Calkenyl or Calkynyl, Calkyloxy, Calkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(Calkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, &#x2014;S(&#x2550;O)R, &#x2014;NH&#x2014;S(&#x2550;O)R, &#x2014;C(&#x2550;O)R, &#x2014;NHC(&#x2550;O)H, &#x2014;C(&#x2550;O)NHNH, &#x2014;NHC(&#x2550;O)R, &#x2014;C(&#x2550;NH)Ror aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

This invention concerns the use of the compounds of formula ##STR1## the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein A is CH, CR.sup.4 or N; n is 0, 1, 2, 3 or 4; R.sup.1 and R.sup.2 are each independently selected from hydrogen, hydroxy, C.sub.1-12 alkyl, C.sub.1-12 alkyloxy, C.sub.1-12 alkylcarbonyl, C.sub.1-12 -alkyloxycarbonyl, aryl, amino, mono- or di(C.sub.1-12 alkyl)amino, mono- or di(C.sub.1-12 alkyl)aminocarbonyl wherein each of the aforementioned C.sub.1-12 alkyl groups may optionally and each individually be substituted; or R.sup.1 and R.sup.2 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, azido or mono- or di(C.sub.1-12 alkyl)aminoC.sub.1-4 alkylidene; R.sup.3 is hydrogen, aryl, C.sub.1-6 alkylcarbonyl, optionally substituted C.sub.1-6 alkyl; and each R.sup.4 independently is hydroxy, halo, C.sub.1-6 alkyl, C.sub.1-6 -alkyloxy, cyano, aminocarbonyl, nitro, amino, trihalomethyl or trihalomethyloxy; L is --X--R.sup.5 or --X--Alk--R.sup.6 ; wherein R.sup.5 and R.sup.6 each independently are indanyl, indolyl or phenyl; each of said indanyl, indolyl or phenyl may be substituted; and X is --NR.sup.3 --, --NH--NH--, --N.dbd.N--, --O--, --S--, --S(.dbd.O)-- or --S(.dbd.O).sub.2 --; aryl is optionally substituted phenyl; Het is an optionally substituted aliphatic or aromatic heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection. It further relates to new compounds being a subgroup of the compounds of formula (I), their preparation and pharmaceutical compositions comprising them.

Trisubstituted 1,3,5-Triazine Derivatives

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Tilburg, Netherlands

Marc Rene De Jonge