Pfizer Corporation

Intellikine LLC

Sanofi

Millennium Pharmaceuticals Limited

Simon F Campbell

Peter E Cross

John K Stubbs

David A Roberts

David Alker

Yi Liu

Pingda Ren

Liansheng Li

Troy Edward Wilson

Katrina Chan

John C Danilewicz

John E Arrowsmith

Rhona M Plews

Allan L Ham

John D Hardstone

Anthony Wood

Alexander Roderick MacKenzie

Colin W Greengrass

Roger P Dickinson

Alan Stobie

Michael John Humphrey

Anthony G Evans

Alain Pellet

Ryszard Jurek Kobylecki

Albert A Jaxa-Chamiec

Gilles V Courtemanche

David S Morris

Cécile Pascal

Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

Heterocyclic compounds and uses thereof

The present disclosure relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof wherein Rmeans a fluorine atom or a perhalogeno linear alkyl radical containing 1, 2 or 3 carbon atoms; Rmeans a chlorine atom, a linear alkyl radical containing 1, 2 or 3 carbon atoms or a perhalogeno linear alkyl radical containing 1, 2 or 3 carbon atoms, and R means a hydrogen atom or a radical of formula (Ia). The present disclosure also relates to processes for their preparation as well their therapeutic uses, in particular such as for use in the treatment of malaria.

Ethynyl compounds, their preparation and their therapeutic use for the treatment of malaria

The present invention provides substituted benzimidazole compounds of Formula I: wherein the variables R, R, W, W, W, W, W, W, W, W, Wand Ware defined herein. The compounds are useful as phosphoinositide 3-kinase (PI3 kinase) inhibitors.

Substituted benzimidazoles as PI3 kinase inhibitors

The present invention provides substituted benzoxazole compounds of the Formula: wherein the variables R, R, W, W, W, W, W, are Ware defined herein. The compounds are useful as phosphoinositide 3-kinase (PI3 kinase) inhibitors.

Substituted benzoxazoles as PI3 kinase inhibitors

A method of inhibiting phosphatidyl inositol-3 kinase (PI3 kinase), comprising: contacting the PI3 kinase with an effective amount of a compound or pharmaceutically acceptable salt of the formula below, wherein the variables R, R, W, W, W, W, W, are Ware defined herein.

6-heterocyclyl pyrazolo &lsqb;3,4-d&rsqb;pyrimidin-4-one compounds which are selective inhibitors of cGMP PDE are useful in the treatment of erectile dysfunction (impotence) in male animals, including man.

6-heterocyclyl pyrazolo &lsqb;3,4-d&rsqb;pyrimidin-4-one cGMP-PDE inhibitors for the treatment of erectile dysfunction

The use of certain 6-arylpyrazolo&lsqb;3,4-d&rsqb;pyrimidin-4-ones, 2 arylquinazolin-4-ones, 2-arylpurin-6-ones and 2-arylpyrido&lsqb;3,2-d&rsqb;pyrimidin-4-ones, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the curative or prophylactic treatment of erectile dysfunction in a male animal, including man; a pharmaceutical composition for said treatment; and a method of said treatment of said animal with said pharmaceutical composition or with said either entity.

Bicyclic heterocyclic compounds for the treatment of impotence

4-aminoquinazoline derivatives which are selective inhibitors of cGMP PDE are useful in the treatment of erectile dysfunction (impotence) in male animals, including man.

4-aminoquinazoline derivative cGMP-PDE inhibitors for the treatment of erectile dysfunction

A series of novel heterocyclic-substituted 2-(1H)-quinolone compounds have been prepared, including the 3,4-dihydro derivatives thereof, wherein the heterocyclic ring moiety is a pyrrolyl, imidazolyl, pyrazolyl, triazolyl or tetrazolyl group attached by a nitrogen atom of said group to the 5-, 6-, 7- or 8-positions of the quinolone ring. These particular compounds are useful in therapy as highly potent inotropic agents and therefore, are of value in the treatment of various cardiac conditions. Preferred member compounds include 6-(2,4-dimethylimidazol-1-yl)-8-methyl-2-(1H)-quinolone, 6-(2,4-dimethyl-5-nitroimidazol-1-yl)-8-methyl-2-(1H)-quinolone, 8-methyl-6-(tetrazol-1-yl)-2-(1H)-quinolone, 8-methyl-6-(1,2,4-triazol-4-yl)-2-(1H)-quinolone, and 6-(4-cyano-2-methylimidazol-1-yl)-8-methyl-2-(1H)-quinolone, respectively. Methods for preparing these compounds from known starting materials are provided.

precursors to Quinolone inotropic agents

A series of novel heterobicyclic substituted 2-(1H)-quinolone compounds have been prepared, including the 3,4-dihydro derivatives thereof, wherein the heterobicyclic ring moiety is an optionally-substituted indolyl, phthalizinyl, benzimidazolyl, imidazopyridinyl, quinolinyl or isoquinolinyl group attached by an nitrogen or carbon atom of said group to the 6-position of the quinolone ring. The optional substituent is a C.sub.1 -C.sub.14 alkyl group located on either of the two heterobicyclic rings and/or an oxo group situated on the heterocyclic portion of said heterobicyclic ring system. These particular compounds are useful in therapy as cardiac stimulants and therefore, are of value in the treatment of various cardiac conditions. 6-{1(H)-Imidazo[4,5-b]pyridin-6-yl}-8-methyl-2-(1H)-quinolone represents a typical and preferred member compound. Methods for preparing these compounds from known starting materials are provided.

Imidazo[4,5-b]pyridyl quinolone cardiac stimulants

1,4-Dihydropyridine anti-ischaemic and antihypertensive agent of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R is 2-chlorophenyl, 2,3-dichlorophenyl or 2-chloro-3-trifluoromethylphenyl;

Dihydropyridine anti-ischaemic and antihypertensive agents

A series of novel heterocyclic-substituted 2-(1H)-quinolone compounds have been prepared, including the 3,4-dihydro derivatives thereof, wherein the heterocyclic ring moiety is a pyrrolyl, imidazolyl, pyrazolyl, triazolyl or tetrazolyl group attached by a nitrogen atom of said group to the 5-, 6-, 7- or 8-positions of the quinolone ring. These particular compounds are useful in therapy as highly potent inotropic agents and therefore, are of value in the treatment of various cardiac conditions. Preferred member compounds include 6-(2,4-dimethylimidazol-1-yl)-8-methyl-2-(1H)-quinolone, 6-(2,4-dimethyl-5-nitroimidazol-1-yl)-8-methyl-2-(1H)-quinolone, 8-methyl-6-(tetrazol-1-yl)-2-(1H)-quinolone, 8-methyl-6-(1,2,4-triazol-4-yl)-2-(1H)-quinolone, and 6-(4-cyano-2-methylimidazol-1-yl)-8-methyl-2-(1H)-quinolone, respectively. Methods for preparing these compounds from known starting material are provided.

Precursors to quinolone inotropic agents

A compound of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is amino, hydroxy, alkoxy, phenoxy or benzyloxy, useful in the treatment of hypertension, angina, renal impairment or acute renal failure.

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Deal, United Kingdom

Simon F Campbell