Spirogen Sarl

Spirogen Limited

Spirogen Developments Sàrl

Medimmune Limited

Zhizhi Chen

Philip Wilson Howard

Stephen John Gregson

Luke Masterson

Arnaud Charles Tiberghien

Compounds of the formula I: or solvate thereof, wherein:

Pyrrolobenzodiazepines

Methods of preparing ZC-423 (I) which result in varying enantiomeric ratios. 

The invention relates to certain pyrrolobenzodiazepines (PBDs), and in particular pyrrolobenzodiazepine dimers bearing C2 substitutions, including compounds of formula (T): wherein: Ris CHR, and Ris independently selected from H, R, COR, COR, CHO, COH, and halo; Rand Rare independently selected from H, R, OH, OR, SH, SR, NH, NHR, NRR', NO, MeSn and halo; Ris independently selected from H, R, OH, OR, SH, SR, NH, NHR, NRR&#x2032;, NO, MeSn and halo; Ris independently selected from H, R, OH, OR, SH, SR, NH, NHR, NRR&#x2032;, NO, MeSn and halo; R is independently selected from optionally substituted Calkyl, Cheterocyclyl and Caryl groups; or the compound is a dimer with each monomer being of formula (M), where the Rgroups or Rgroups of each monomer form together a dimer bridge having the formula &#x2014;X&#x2014;R&#x2033;&#x2014;X&#x2014; linking the monomers; wherein R&#x2033; is a Calkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H), and/or aromatic rings, e.g. benzene or pyridine; and each X is independently selected from O, S, or N(H); or any pair of adjacent groups from Rto Rtogether form a group &#x2014;O&#x2014;(CH)&#x2014;O&#x2014;, where p is 1 or 2, and salts and solvates thereof, and their use as intermediates for the preparation of other PBD compounds. 

Compounds of the formula: (I) or solvate thereof, wherein: Ris an optionally substituted Caryl group; Rand Rare independently selected from H, R, OH, OR, SH, SR, NH, NHR, NRR', nitro, MeSn and halo; where R and R&#x2032; are independently selected from optionally substituted Calkyl, Cheterocyclyl and Caryl groups; Ris selected from H, R, OH, OR, SH, SR, NH, NHR, NHRR&#x2032;, nitro, MeSn and halo; R&#x2033; is a Calkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R&#x2032;, R&#x2032;, R&#x2032;, R&#x2032;, X&#x2032; and M&#x2032; are selected from the same groups as R, R, R, R, X and M respectively, or M and M&#x2032; may together represent a divalent pharmaceutically acceptable cation. 

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London, United Kingdom

Zhizhi Chen