The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a subject, pharmaceutical composition comprising such compounds, and their use as MCL-1 inhibitors, useful for treating diseases such as cancer.

The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a subject, pharmaceutical composition comprising such compounds, and their use as MCL-1 inhibitors, useful for treating diseases such as cancer.

The present invention is directed to compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein the substituents A, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b and n are as defined herein. The inventions also directed to pharmaceutical compositions comprising the compounds, methods of treatment using the compounds and methods of preparing the compounds.

##STR00001##

The present invention is directed to compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein the substituents A, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b and n are as defined herein. The inventions also directed to pharmaceutical compositions comprising the compounds, methods of treatment using the compounds and methods of preparing the compounds.

##STR00001##

The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a subject, pharmaceutical composition comprising such compounds, and their use as MCL-1 inhibitors, useful for treating diseases such as cancer.

A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease.

##STR00001##

wherein “” is an optional bond; X, Y, Z.sub.1, and Z.sub.2 are a functional group; m.sub.1 and n are a integer; L.sub.1 and L.sub.2 are a linker.

A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease.

##STR00001##

wherein “” is an optional bond; X, Y, Z.sub.1, and Z.sub.2 are a functional group; m.sub.1 and n are a integer; L.sub.1 and L.sub.2 are a linker.

The present invention relates to macrocyclic pyridotriazine derivatives and the prodrugs thereof, and the pharmaceutically acceptable salts, solvates or polymorph thereof, and the use of such compounds as a medicament, in particular in the prevention and/or treatment of viral infections caused by viruses belonging to the Orthomyxoviridae family. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, and to the compositions or preparations for use as a medicament, more preferably for the prevention or treatment of viral infections caused by viruses belonging to the Orthomyxoviridae family.

The present invention relates to macrocyclic pyridotriazine derivatives and the prodrugs thereof, and the pharmaceutically acceptable salts, solvates or polymorph thereof, and the use of such compounds as a medicament, in particular in the prevention and/or treatment of viral infections caused by viruses belonging to the Orthomyxoviridae family. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, and to the compositions or preparations for use as a medicament, more preferably for the prevention or treatment of viral infections caused by viruses belonging to the Orthomyxoviridae family.

Disclosed are a class of compounds having a highly selective inhibition of ROS1, and the use thereof in the preparation of drugs for treating diseases related to abnormal ROS1 kinase expression. Specifically disclosed are compounds represented by formula (IV) and a pharmaceutically acceptable salt thereof.

##STR00001##