The invention discloses a process for the preparation of maytansinoid esters of formula (I) comprising a thiol or disulphide group wherein R.sup.1, R.sup.4 and R.sup.5 and the asterisk are as defined in the description, by reacting maytansinol with an enantiopure alpha-azido acid, followed by reduction of the azido group and reacting the obtained amino-ester with a compound of formula (IX) (IX) R.sup.3—S—S—X—COOH wherein X and R.sup.3 are as defined in the description, or with a reactive derivative thereof and optionally reducing the obtained disulfide-containing maytansinoid ester to give a maytansinoid ester wherein R.sup.1 is a —X—SH group. ##STR00001##

The invention discloses a process for the preparation of maytansinoid esters of formula (I) comprising a thiol or disulphide group wherein R.sup.1, R.sup.4 and R.sup.5 and the asterisk are as defined in the description, by reacting maytansinol with an enantiopure alpha-azido acid, followed by reduction of the azido group and reacting the obtained amino-ester with a compound of formula (IX) (IX) R.sup.3—S—S—X—COOH wherein X and R.sup.3 are as defined in the description, or with a reactive derivative thereof and optionally reducing the obtained disulfide-containing maytansinoid ester to give a maytansinoid ester wherein R.sup.1 is a —X—SH group. ##STR00001##

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

The present disclosure provides fused 1,4-diazepines represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, E, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and Ar are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds having Formula (I) to treat diseases, conditions, or disorders responsive to inhibition of BET bromodomain proteins such as cancer. ##STR00001##

The present disclosure provides fused 1,4-diazepines represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, E, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and Ar are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds having Formula (I) to treat diseases, conditions, or disorders responsive to inhibition of BET bromodomain proteins such as cancer. ##STR00001##

The present invention provides improved, commercially viable and consistently reproducible processes for the preparation of pure and stable crystalline Raltegravir potassium Form 3 and pharmaceutical composition thereof.

The present invention provides improved, commercially viable and consistently reproducible processes for the preparation of pure and stable crystalline Raltegravir potassium Form 3 and pharmaceutical composition thereof.

The present disclosure provides fused 1,4-diazepines represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A. E, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and Ar are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds having Formula (I) to treat diseases, conditions, or disorders responsive to inhibition of BET bromodomain proteins such as cancer.

##STR00001##

The present disclosure provides fused 1,4-diazepines represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A. E, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and Ar are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds having Formula (I) to treat diseases, conditions, or disorders responsive to inhibition of BET bromodomain proteins such as cancer.

##STR00001##