Abstract: The invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein A1 is —N? or —C(R3)=; A2 is —N? or —CH?; L is —NH—; B1 and B2 are independently —N? or —C(R2b)=; B3 and B4 are independently —C(R2b)=; no more than one R2b on B1, B2, B3 and B4 is other than hydrogen; R1a is hydrogen, halogen, C1-C3alkyl (n-alkyl) optionally substituted with one R4, or R1a is —NH2, —NH(C1-C3alkyl (n-alkyl)), —NH(C(?O)—C1-C2alkyl), —N(C1-C3alkyl (n-alkyl))2, —OC1-C3alkyl (n-alkyl), C1-C3haloalkyl (n-alkyl) or —OC1-C3haloalkyl (n-alkyl); R1b is hydrogen, halogen, C1-C3alkyl (n-alkyl), —OC1-C3alkyl (n-alkyl), —NH2, —NH(C1-C3alkyl (n-alkyl)) or —N(C1-C3alkyl (n-alkyl))2; R1a and R1b may together form a —CH?CH—CH?CH— moiety in which one or two non-adjacent CH are optionally replaced by N; R2a is halogen, C1-C6alkyl, C1-C6haloalkyl, cyclopropyl, cyclobutyl, —OR6, —NHC(?O)—C3-C6cycloalkyl, Cycle Q, —SF5 or group Y (formula (Y)); wherein X is a 3- or 4-membered carbocyclic ring and R8 is halogen, cy

Abstract: 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 CD40 agonist.

Abstract: 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.

Abstract: 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) (gemcitabine) or a pharmaceutically acceptable salt thereof and the use of the pharmaceutical combinations in the treatment of neoplastic diseases.

Abstract: 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.

Abstract: 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 NH2; R1 and R2, independently of each other, represent hydrogen, N(R3)2, 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, NH2, NH(CH3) or N(CH3)2; X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C?O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a)2— or —(C?O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mon

Abstract: 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 NH2; R1 and R2, independently of each other, represent hydrogen, N(R3)2, 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, NH2, NH(CH3) or N(CH3)2; X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C?O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a)2- or —(C?O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mon

Abstract: The invention provides compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof (I) wherein ring A represents group A-I or A-II (A-I, A-II) A1, A2, A3, A4 represent independently C(R4aa) or N, wherein no more than one of A1, A2, A3, and A4 represents N; A5 represents C(R4b) or N; B1, B2, B3 and B4 represent independently C(R3) or N, wherein no more than two of B1, B2, B3 and B4 represent N; n is 1 or 2; and R1, R2, R3, R4a and R4aa and R4b are as defined in the claims, as well as methods of using the compounds to treat proliferation diseases, in particular cancer.

Abstract: The present invention provides use of EB1 as a biomarker for predicting the response of a brain neoplasm to 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, amino, acetylamino, halogen and nitro; and wherein pyridinyl is optionally substituted by amino or halogen; R1 represents hydrogen or cyano-lower alkyl; or a pharmaceutically acceptable derivative thereof, and wherein the prefix lower denotes a radical having up to and including a maximum of 4 carbon atoms; in particular wherein a higher level of EB1 in the sample from the subject relative to a standard value or set of standard values predicts sensitivity of the brain neoplasm to the compound of formula I or pharmaceutically acceptable derivative thereof. The invention also provides methods of treatment and kits for use according to the invention.

Abstract: 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 NH2; R1 and R2, independently of each other, represent hydrogen, N(R3)2, 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, NH2, NH(CH3) or N(CH3)2; X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C?O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a)2- or —(C?O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mon

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

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

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

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

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

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

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

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

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

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