762245-27-2Relevant academic research and scientific papers
Design, synthesis and evaluation of novel, potent DNA alkylating agents and their antibody-drug conjugates (ADCs)
Reid, Emily E.,Archer, Katie E.,Shizuka, Manami,McShea, Molly A.,Maloney, Erin K.,Ab, Olga,Lanieri, Leanne,Wilhelm, Alan,Ponte, Jose F.,Yoder, Nicholas C.,Chari, Ravi V.J.,Miller, Michael L.
, p. 2455 - 2458 (2019)
Antibody-drug conjugates (ADCs) incorporating potent indolinobenzodiazepine (IGN) DNA alkylators as the cytotoxic payload are currently undergoing clinical evaluation. The optimized design of these payloads consists of an unsymmetrical dimer possessing both an imine and an amine effectively eliminating DNA crosslinking and demonstrating improved tolerability in mice. Here we present an alternate approach to generating DNA alkylating ADCs by linking the IGN monomer with a biaryl system which has a high DNA binding affinity to potentially enhance tolerability. These BIA ADCs were found to be highly cytotoxic in vitro and demonstrated potent antitumor activity in vivo.
POLYCYCLIC AMIDES AS CYTOTOXIC AGENTS
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, (2020/03/29)
The invention relates to a compound of formula (I): or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; wherein the fused ring moiety is a non-alkylating moiety; and wherein the compounds are useful as medicaments, in particular for use as a drug in an antibody-drug conjugate and in the treatment of a proliferative disease, a bacterial infection, a malarial infection and inflammation.
BENZODIAZEPINE DERIVATIVES
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Page/Page column 138; 139; 190; 191, (2019/07/17)
The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formulae (I), (II) and (III). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.
CYTOTOXIC AGENTS
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, (2019/03/17)
The invention relates to a compound of formula (I) or formula (II) or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; which are useful as medicaments, in particular as anti-proliferative agents and for use as a d
CYTOTOXIC BENZODIAZEPINE DERIVATIVES AND CONJUGATES THEREOF
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Page/Page column 118; 119, (2018/11/22)
The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formulae (I) and (II). The invention also provides conjugates of the benzodiazepine compounds linked to a
ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
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, (2018/04/27)
Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.
ASYMMETRIC CONJUGATE COMPOUNDS
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, (2017/12/01)
The invention relates to compound of formula (I): A-X1-L-X2-B and salts, solvates and tautomers thereof, which are useful as medicaments, in particular as anti-proliferative agents and for use as a drug in an antibody-drug conjugate;
Synthesis of a novel tetrahydroisoquinolino[2,1-c][1,4]benzodiazepine ring system with DNA recognition potential
Kothakonda, Kiran Kumar,Bose, D. Subhas
, p. 4371 - 4373 (2007/10/03)
The first stereospecific synthesis of a novel tetrahydroisoquinolino[2,1-c] [1,4]benzodiazepine ring system with DNA recognition potential starting from (S)-1,2,3,4-tetrahydroisoquinoline carboxylic acid has been reported. We report the first stereospecif
