Novartis Ag

Torqur Ag

The University of Texas System

University of Pennsylvania

Novartis Corporation

Universitat Basel

Torqur

Gsf-International Research Institute for Environment and Health

Novartis Pharma Gmbh

Doriano Fabbro

Paul William Manley

Jürgen Mestan

Paul Hebeisen

Florent Beaufils

Michael Hallek

Karl-Heinz Altmann

Markus Warmuth

Moshe Talpaz

Nicholas J Donato

John T Seykora

Anton Stütz

Elisabeth Buchdunger

Brett P Monia

Nicholas M Dean

Clarence Frank Bennett

Wolfgang Loscher

Anton Stuetz

Petra Hillmann-Wüllner

Ji Wu

Petra Hillmann-Wuellner

Denise Rageot

Alexander Sele

Leila Alland

Juergen Mestan

Thomas Geiger

Annemarie Ziegler

Marcel Muller

Uwe Zangemeister-Wittke

Wolfgang Löscher

Hoa Huu Phuc Nguyen

Claudia Brandt

Petra Hillmann-wüllner

Petra Hillmann-Wullner

Hoa Huu Nguyen

Alexander Markus Sele

The present invention relates to a compound of formula (I), wherein X, Xand Xare, independently of each other, N or CH; with the proviso that at least two of XXand Xare N; Y is N or CH; W is H or F; with the proviso that when W is F, then X, Xand Xare N; Rand Rare independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein Rand Rare independently of each other H, C-Calkyl optionally substituted with one or two OH, C-Cfluoroalkyl, C-Calkoxy, C-CalkoxyC-Calkyl, CN, or C(0)0-C-Calkyl; or Rand Rform together a bivalent residue —RR— selected from C-Calkylene optionally substituted with 1 to 4 F, —CH-0-CH—, —CH—NH—CH—, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R; wherein Ris independently at each occurrence C-Calkyl optionally substituted with one or two OH, C-Cfluoroalkyl, C-CalkoxyC-Calkyl, C-Ccycloalkyl; or two Rsubstituents form together a bivalent residue —RR— selected from C-Calkylene optionally substituted with 1 to 4 F, —CH-0-CH— or -0-CHCH-0- with the proviso that at least one of Rand Ris a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in a method of treating a skin disorder in a subject, wherein said skin disorder is a genodermatosis, a vascular anomaly or a skin disorder selected from scleroderma, sclerodermatous chronic graft-versus-host disease, lichen sclerosus, lichen planus, lichen ruber planus and scars.

Treatment of skin disorders

The present invention is relates to a compound of formula (I), wherein X, Xand Xare, independently of each other, N or CH; with the proviso that at least two of XXand Xare N; Y is N or CH; W is H or F; with the proviso that when W is F, then X, Xand Xare N; Rand Rare independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein Rand Rare independently of each other H, C-Calkyl optionally substituted with one or two OH, C-Cfluoroalkyl, C-Calkoxy, C1alkoxyC-Calkyl, CN, or C(O)O—C-Calkyl; or Rand Rform together a bivalent residue —RR— selected from C-Calkylene optionally substituted with 1 to 4 F, —CH—O—CH—, —CH—NH—CH—, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R; wherein Ris independently at each occurrence C-Calkyl optionally substituted with one or two OH, C-Cfluoroalkyl, C-CalkoxyC-Calkyl, C-Ccycloalkyl; or two Rsubstituents form together a bivalent residue-RR— selected from Ci-C3alkylene optionally substituted with 1 to 4 F, —CH—O—CH— or —O—CHCH—O—; with the proviso that at least one of Randis a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a skin lesion in a subject.

Treatment of skin lesions

The present invention is relates to a compound of formula (I),

Treatment of neurological disorders

The present invention relates to a compound of formula (I), wherein X, Xand Xare, independently of each other, N or CH; with the proviso that at least two of XXand Xare N; Y is N or CH; W is H or F; with the proviso that when W is F, then Xi, Xand Xare N; Rand Rare independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein Rand Rare independently of each other H, C-Calkyl optionally substituted with one or two OH, C-Cfluoroalkyl, C-Calkoxy, C-CalkoxyC-Calkyl, CN, or C(O)O&#x2014;C-Calkyl; or Rand Rform together a bivalent residue &#x2014;RR&#x2014; selected from C-Calkylene optionally substituted with 1 to 4 F, &#x2014;CH&#x2014;O&#x2014;CH&#x2014;, &#x2014;CH&#x2014;NH&#x2014;CH&#x2014;, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R; wherein Ris independently at each occurrence C-Calkyl optionally substituted with one or two OH, C-Cfluoroalkyl, C-CalkoxyC-Calkyl, C-Ccycloalkyl; or two Rsubstituents form together a bivalent residue &#x2014;RR&#x2014; selected from C-Calkylene optionally substituted with 1 to 4 F, &#x2014;CH&#x2014;O&#x2014;CH&#x2014; or &#x2014;O&#x2014;CHCH&#x2014;O&#x2014;; with the proviso that at least one of Rand Ris a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in a method of treating a skin disorder in a subject, wherein said skin disorder is a genodermatosis, a vascular anomaly or a skin disorder selected from scleroderma, sclerodermatous chronic graft-versus-host disease, lichen sclerosus, lichen planus, lichen ruber planus and scars. 

The present invention is relates to a compound of formula (I), wherein wherein the arrow denotes the bond in formula (I); andwherein Rand Rare independently of each other H, C-Calkyl optionally substituted with one or two OH, C-Cfluoroalkyl, C-Calkoxy, C-CalkoxyC-Calkyl, CN, or C(O)O&#x2014;C-Calkyl; or Rand Rform together a bivalent residue &#x2014;RR&#x2014; selected from C-Calkylene optionally substituted with 1 to 4 F, &#x2014;CH&#x2014;O&#x2014;CH&#x2014;, &#x2014;CH&#x2014;NH&#x2014;CH&#x2014;, or any of the structures wherein the arrows denote the bonds in formula (II); or

The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of systemic mastocytosis.

Pyrimidylaminobenzamide derivatives for systemic mastocytosis

The invention relates to a combination which comprises (a) at least one compound decreasing the c-Src activity and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine or the monomethanesulfonate salt thereof; to pharmaceutical compositions comprising said combinations; and to a method of treating a warm-blooded animal having leukaemia, especially chronic myelogenous leukaemia, comprising administering to the animal at least one compound inhibiting the activity of a member of the Src kinase family, the Btk kinase family, the Tec kinase family or a Raf kinase inhibitor, in particular inhibiting the c-Src protein tyrosine kinase activity or inhibiting simultaneously the c-Src protein tyrosine kinase activity and the Bcr-Abl tyrosine kinase activity, alone or in combination with a Bcr-Abl inhibitor, in particular N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine.

Use of c-Src inhibitors alone or in combination with STI571 for the treatment of leukaemia

The present invention relates to the treatment of KIT dependent diseases that are characterized by a mutant form of KIT whereby the mutant KIT is identified and an appropriate inhibitor of the mutant KIT is administered.

Inhibitors of the mutant form of kit

The present invention relates to the treatment of KIT dependent diseases that are characterized by a mutant form of KIT whereby the mutant KIT is identified and an appropriate inhibitor of the mutant KIT selected form midostaurin, vatalanib and compound A is administered. 

The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of FIP1L1-PDGFR&#x3b1;-induced or TEL-PDGFR&#x3b2;-induced myeloproliferative diseases, especially for the curative and/or prophylactic treatment of hypereosinophilic syndrome and hypereosinophilic syndrome with resistance to imatinib, and to a method of treating hypereosinophilic syndrome, chronic eosinophilic leukemia and hypereosinophilic syndrome with resistance to imatinib, or other diseases associated with FIP1L1-PDGFR&#x3b1;, TEL-PDGFR&#x3b2; or similar mutations that activate PDGFR.

Pyrimidylaminobenzamide derivatives for hypereosinophilic syndrome

The present invention relates to an oligonucleotide derivative which is specifically hybridizable to a region of a RNA deriving from the gene encoding human Bcl-2 protein, the region being selected from the group consisting of a region comprising a sequence corresponding to a sequence ranging from base position no. 1880 (5&prime;) to no. 1899 (3&prime;), or comprising at least a part thereof, of the human Bcl-2 cDNA, and a region comprising the translation termination codon of the RNA.

Oligonucleotide derivatives

The invention relates to combinations of PKC-targeted (especially PKC-.alpha.-targeted) deoxyribo- and ribo-oligonucleotides and derivatives thereof with other chemotherapeutic compounds, as well as to pharmaceutical preparations and/or therapies, in relation to disease states which respond to such oligonucleotides or oligonucleotide derivatives, especially to to modulation of the activity of a regulatory protein. In particular, the invention relates to products or combinations comprising antisense oligonucleotides or oligonucleotide derivatives targeted to nucleic acids encoding human PKC and other (preferably standard) chemotherapeutics, either in fixed combination or for chronologically staggered or simultaneous administration, and the combined use of both classes of compounds, either in fixed combination or for chronologically staggered or simultaneous administration, for the treatment of proliferative diseases, especially tumor diseases, that can be treated by inhibition of PKC activity, that is, where the antisense oligonucleotides or oligonucleotide derivatives are targeted to nucleic acids encoding the regulatory protein PKC or active mutated derivatives thereof.

Combination for treatment of proliferative diseases

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Arlesheim, Switzerland

Doriano Fabbro