Novartis Pharmaceuticals Corporation

Basilea Pharmaceutica International Ag

Novartis Ag

Novartis Pharma Ag

Novartis Forschungsstiftung Zweigniederlassung Friedrich Miescher Institute for Biomedical Research

Novartis Pharma Gmbh

Novartis International Pharmaceutical Ag

Heidi Lane

Richard William Versace

Terence O'Reilly

Jeanette Marjorie Wood

Terence O'reilly

Felix Bachmann

Jens Pohlmann

David E Lebwohl

William Raj Sellers

George Thomas

Iwan Beuvink

Anne Boulay

Paul McSheehy

Martin Stieger

Stefan Reinelt

Ingrid Elmroth

Michael Stumm

William Berg

John Benedetto

Terence O`Reilly

Gregory Burke

Ronald Richard Linnartz

The present invention provides pharmaceutical combinations comprising (a) a compound of formula (I) wherein R represents phenyl or pyridinyl; wherein phenyl is optionally substituted by one or two substituents independently selected from lower alkyl, lower alkoxy, hydroxyl, amino, lower alkylamino, lower dialkylamino, acetylamino, halogen and nitro; and wherein pyridinyl is optionally substituted by amino or halogen; R1 represents hydrogen or cyano-lower alkyl; and wherein the prefix lower denotes a radical having up to and including a maximum of 4 carbon atoms; or a pharmaceutically acceptable derivative thereof; and (b) a compound of Formula (II) (eribulin) or a pharmaceutically acceptable salt thereof and the use of the pharmaceutical combinations in the treatment of neoplastic diseases. 

Pharmaceutical combinations for use in the treatment of neoplastic diseases

Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH; R1 and R2, independently of each other, represent hydrogen, N(R3), halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH, NH(CH) or N(CH); X represents a group of formula -E- or -E-F&#x2014;, wherein E and F are different from each other and represent a group selected from &#x2014;C(R3a)2-, &#x2014;(C&#x2550;O)&#x2014;, &#x2014;NR3a- and &#x2014;O&#x2014; and F is linked to Y, with the proviso that if X represents -E-F&#x2014; one of E or F represents &#x2014;C(R3a)- or &#x2014;(C&#x2550;O)&#x2014;; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers thereof or mixtures of two tautomeric forms thereof, preferably with the proviso that Y comprises one or more primary amino group &#x2014;NH, when X represents &#x2014;(C&#x2550;O)&#x2014; or &#x2014;(C&#x2550;O)&#x2014;NR3a-, wherein R3a represents hydrogen or C1-C4alkyl; which are useful for the treatment of proliferation disorders or diseases, such as cancer. 

Substituted mono- and polyazanaphthalene derivatives and their use

The present invention is directed to the use of rapamycin derivatives for use in treating solid tumors, optionally in combination with a chemotherapeutic agent.

Treatment of solid tumors with rapamycin derivatives

Rapamycin derivatives have interesting effects in the treatment of solid tumours, optionally in combination with a chemotherapeutic agent.

Rapamycin derivatives have interesting effects in the treatment of solid tumors, optionally in combination with a chemotherapeutic agent.

Cancer treatment

Provided are biomarkers for determining the sensitivity of proliferative diseases such as cancer to therapeutic agents, in particular mTOR inhibitors in combination with a cytotoxic agent, in particular a cytotoxic agent which damages or affects the integrity of DNA.

p53 wild-type as biomarker for the treatment with mTOR inhibitors in combination with a cytotoxic agent

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Basel, Switzerland

Heidi Lane