Janssen Pharmaceutica Nv

Mcneil Ab

Robert W Tuman

Dana L Johnson

Raymond A Stokbroekx

Marc Willems

Jan L Sechler

Marcel Jozef Maria Van Der Aa

Robert A Galemmo

Marcel Gerebernus Maria Luyckx

Tianbao Lu

Kristi A Leonard

Maxwell David Cummings

Thomas P Markotan

Richard Scott Alexander

Richard William Connors

Jay Mei

Christian Andrew Baumann

Marc Andr&eacute; Ceusters

Anna C Maroney

Jeremy Mark Travins

Henry Joseph Breslin

Donald William Ludovici

Michael Joseph Kukla

Chris R Rasmussen

Chih Yung Ho

Stuart Emanuel

Robert A Galemmo, Jr

Umar Maharoof

Heather Rae Hufnagel

Michael Gaul

Eric D Strobel

Ehab Khalil

Wu-Nan Wu

Hwa Kwo Yen

Bengt Anders Brunmark

Kung-Tat Ng

Joyce E Epps

Lieven Meerpoel

Carl R Illig

Mark James Wall

Sanath K Meegalla

Kevin Douglas Kreutter

Jinsheng Chen

Guozhang Xu

Marcel J Van Der Aa

Shelley K Ballentine

Kenneth J Wilson

Marcel G Luyckx

Alexander Y Kim

M Jonathan Rudolph

Nand Baindur

Marc André Ceusters

Umar S M Maharoof

Saneth Meegalla

Jingsheng Chen

Kenneth Wilson

The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from compounds of Formula I': Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.

Synergistic modulation of FLT3 kinase using a FLT3 inhibitor and a farnesyl transferase inhibitor

The invention is directed to triazolopyridazine compounds of Formula I: where R, R, R, R, R, and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

Triazolopyridazine compounds

The invention is directed to alkylquinoline and alkylquinazoline compounds of Formula I: wherein R, R, R, B, Z, G, Q and X are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and/or c-kit and/or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and/or c-kit and/or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 and/or c-kit and/or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

Alkylquinoline and alkylquinazoline kinase modulators

Triazolopyridazines as kinase modulators

The invention is directed to compounds having the following structures: N-(3-ethoxyphenyl)-1,4-dihydro-6-ethoxy-7-(3-hydroxypropoxy)-1-methylindeno[1,2-c]pyrazole-3-amine; 3-[3-(3-Bromo-phenylamino)-6-ethoxy-1-methyl-1,4-dihydro-indeno[1,2-c]pyrazol-7-yloxy]-propan-1-ol;or 3-[3-(2-Chloro-pyridin-4-ylamino)-6-ethoxy-1-methyl-1,4-dihydro-indeno[1,2-c]pyrazol-7-yloxy]-propan-1-ol, and N-oxides, pharmaceutically acceptable salts, solvates, tautomers and stereochemical isomers thereof and the uses of such compounds as inhibitors of tubulin polymerization and for the treatment of solid tumors. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

N-substituted tricyclic 3-aminopyrazoles as anti-mitotic tubulin polymerization inhibitors

A method of reducing or inhibiting kinase activity of FLT3 in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof.The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.

Method of inhibiting FLT3 kinase

The invention is directed to N-substituted tricyclic 3-AMINOPYRAZOLE derivatives, which are useful as inhibitors of platelet-derived growth factor receptor (PDGF-R) kinase, and methods for the preparation of said derivatives. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as tumors and other cell proliferative disorders.

N-substituted tricyclic 1-aminopyrazoles as inhibitors for the treatment of cell proliferative disorders

The invention is directed to acylhydrazones compounds of Formula I: where R, Rand A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

Acylhydrazones as kinase modulators

This invention concerns compounds of formula the N-oxide forms, the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof, wherein X is CH or N; Ris hydrogen, Calkyl, Calkyloxy, Calkylthio, amino, mono- or di(Calkyl)amino, Ar, ArNH&#x2014;, Ccycloalkyl, hydroxymethyl or benzoyloxymethyl; Ris hydrogen, Calkyl, amino, aminocarbonyl, mono- or di(Calkyl)amino, Calkyloxycarbonyl, Calkylcarbonylamino, hydroxy or Calkyloxy; R, Rand Rare each independently selected from hydrogen, halo, Calkyl, Calkyloxy, trifluoromethyl, nitro, amino, cyano, azido, CalkyloxyCalkyl, Calkylthio, Calkyloxycarbonyl or Het; is Ar, ArCH&#x2014; or Het; Arand Aroptionally substituted phenyl; Hetand Hetare optionally substituted monocyclic heterocycles; having angiogenesis inhibiting activity; their preparation, compositions containing them and their use as a medicine.

Angiogenesis inhibiting 5-substituted-1,2,4-thiadiazolyl derivatives

N-substituted tricyclic 3-aminopyrazoles as inhibitors for the treatment of cell proliferative disorders

Angiogenesis inhibiting 5-substituted-1,2,4,-thiadiazolyl derivatives

Angiogenesis inhibiting thiadiazolyl pyridazine derivatives

This invention concerns compounds of formula

This invention concerns compounds of formula the N-oxide forms, the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof, wherein X is CH or N; m is 2 or 3 and n is 1, 2 or 3; wherein 1 or 2 C-atoms of the CH.sub.2 groups of the ##STR1## moiety which may also contain one double bond, may be substituted with C.sub.1-6 alkyl, amino, aminocarbonyl, mono- or di(C.sub.1-6 alkyl)amino, C.sub.1-6 alkyloxycarbony, C.sub.1-6 alkylcarbonylamino, hydroxy or C.sub.1-6 alkyloxy; and/or 2 C-atoms of said CH.sub.2 groups may be bridged with C.sub.2-4 alkanediyl; R.sup.1 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylthio, amino, mono- or di(C.sub.1-6 alkyl)amino, Ar, ArNH--, C.sub.3-6 cycloalkyl, hydroxymethyl or benzyloxymethyl; R.sup.2 and R.sup.3 are hydrogen, or taken together may form a bivalent radical of formula --CH.dbd.CH--CH.dbd.CH--; in case X represents CH then L is a radical L.sup.1, L.sup.2 or L.sup.3 ; or in case X represents N then L is a radical L.sup.2 or L.sup.3 ; L.sup.1 is Ar-C.sub.1-6 alkyloxy, Ar-oxy, Ar-thio, Ar-carbonylamino, di-Ar-methyloxy-, N-Ar-piperazinyl, N-Ar-homopiperazinyl, 2-benzimidazolinonyl, Ar--NR.sup.4 --, Ar-Alk-NR.sup.4 --, Ar--NR.sup.4 -Alk-NR.sup.5 -- or Het-NR.sup.4 --; L.sup.2 is Ar, Ar-carbonyl, Ar--CH.dbd.CH--CH.sub.2 --, naphtalenyl or Het; L.sup.3 is C.sub.1-6 alkyl substituted with one or two radicals selected from Ar, Ar-oxy, or Ar-thio, further optionally substituted with cyano or hydroxy; 2,2-dimethyl-1,2,3,4-tetrahydro-naphtalenyl; 2,2-dimethyl-1H-2,3-dihydroindenyl;Ar-piperidinyl or Ar--NR.sup.4 -Alk-; R.sup.4 and R.sup.5 are each independently selected from hydrogen or C.sub.1-6 alkyl; Alk is C.sub.1-6 alkanediyl; their preparation, compositions containing them and their use as a medicine.

Angiogenesis inhibiting pyridazinamines

This invention relates to new heterocyclic derivatives of guanidine and more particularly to such derivatives which have hypoglycemic activity, their methods of use for treating hyperglycemia and novel intermediate compounds for their preparation.

Guanidine derivatives

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Chalfont, PA, United States of America

Robert W Tuman