Medimmune Limited

Spirogen Sarl

Seattle Genetics, Inc.

Spirogen Developments Sàrl

Spirogen Limited

Arnaud Charles Tiberghien

Philip Wilson Howard

Luke Masterson

Scott C Jeffrey

Patrick J Burke

Peter Senter

Stephen John Gregson

Zhizhi Chen

Nazzareno Dimasi

Thais Cailleau

Andrew Duncan Campbell

Jeremy Parker

Balakumar Vijayakrishnan

Jason White

A conjugate of formula (I) wherein Ab is a modified antibody having at least one free conjugation site on each heavy chain. 

Pyrrolobenzodiazepine conjugates

A method of synthesising a compound of formula (I): (I) from a compound of formula (II): (II) where Ris either: (i) Prot; or (ii) a group of formula (A1) in formula (I) and (A2) in formula (II): (A1), (A2). 

Methods

A compound which is selected from A: and salts and solvates thereof. 

Pyrrolobenzodiazepines and conjugates thereof

Pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.

Pyrrolobenzodiazepines used to treat proliferative diseases

A compound with the formula (I), wherein: Ris of formula (II), where X is selected from the group comprising: OH, SH, COH, COH, N&#x2550;C&#x2550;O, NHNH, CONHNH, formula (A), formula (B), NHR, wherein Ris selected from the group comprising H and Calkyl; R, Rand Rare independently selected from H and unsubstituted Calkyl; and either: Ris selected from the group consisting of: (ia) Caryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, Calkyl, Cheterocyclyl and bis-oxy-Calkylene; (ib) Csaturated aliphatic alkyl; (ic) Csaturated cycloalkyl; (id) formula (C), wherein each of R, Rand Rare independently selected from H, Csaturated alkyl, Calkenyl, Calkynyl and cyclopropyl, where the total number of carbon atoms in the Rgroup is no more than 5; (ie) formula (D), wherein one of Rand Ris H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl; and thiophenyl; and (if) formula (E), where Ris selected from: H; Csaturated alkyl; Calkenyl; Calkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl; and thiophenyl; 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; either: (a) Ris H, and Ris OH, OR, where Ris Calkyl; (b) Rand Rform a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) Ris H and Ris SOM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; R&#x2033; is a Calkylene group, which chain may be interrupted by one or more heteroatoms, and/or aromatic rings; Y and Y&#x2032; are selected from O, S, or NH; R, R, Rare selected from the same groups as R, Rand Rrespectively and Rand Rare the same as Rand R, wherein if Rand Rare SOM, M may represent a divalent pharmaceutically acceptable cation. 

Pyrrolobenzodiazepines

A compound of formula I wherein: Ris selected from: OR, where Ris selected from Csaturated alkyl, optionally substituted by phenyl, which may bear a chloro substituent, pyridyl and furanyl; chloro; NH; &#x2014;CH&#x2014;O&#x2014;C(&#x2550;O)Me; Ris OProt, where Protis a silicon-based oxygen protecting group orthogonal to R; Ris selected from H, methyl and methoxy; Ris selected from CF, (CF)CF, CHand (formula 2) and Ris selected from: (i) C(&#x2550;O)&#x2014;OR, where Ris a saturated Calkyl group; (ii) &#x2014;CH&#x2014;O&#x2014;C(&#x2550;O)R, where Ris methyl or phenyl; (iii) CH&#x2014;O&#x2014;Si&#x2014;(R)(R)(R), where R, R, Rare independently selected from Ca saturated alkyl group and a phenyl group; and (iv) C(&#x2014;YR)(&#x2014;YR) where each Y is independently O or S, and where Rand Rare independently a saturated Calkyl group, or together form a Calkylene. 

Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines

A compound of formula (I): which is substantially free of any of the corresponding compound of formula (IB): methods of making such compounds, and the further transformation of such compounds. 

Intermediates useful for the synthesis of pyrrolobenzodiazepines

Pyrrolobenzodiazepine dimers I having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds. 

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. 

Growing community of inventors

Cambridge, United Kingdom

Arnaud Charles Tiberghien