260417-95-6Relevant academic research and scientific papers
Synthesis and in vitro evaluation of SG3227, a pyrrolobenzodiazepine dimer antibody-drug conjugate payload based on sibiromycin
Kemp, Gary C.,Tiberghien, Arnaud C.,Patel, Neki V.,D'Hooge, Francois,Nilapwar, Sanjay M.,Adams, Lauren R.,Corbett, Simon,Williams, David G.,Hartley, John A.,Howard, Philip W.
, p. 1154 - 1158 (2017)
A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro.
PYRROLOBENZODIAZEPINE DERIVATIVES, COMPOSITIONS COMPRISING THE SAME AND METHODS RELATED THERETO
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Page/Page column 34, (2008/06/13)
Disclosed are compounds of Formula (I) wherein X, Y, R1-R7, T1, T2, Z, and p are as described herein; a pharmaceutical composition comprising a compound of Formula (I) and a carrier; a method of inhibiting growth of a cell, which method comprises administering in an amount effective to inhibit growth a compound of Formula (I); a method of treating cancer in a mammal, which method comprises administering in an amount effective to treat cancer a compound of Formula (I); a method of treating a viral, parasitic, or bacterial infection of a cell, which method comprises administering in an amount effective to treat a viral, parasitic, or bacterial infection a compound of Formula (I); and a method of preparing a compound of Formula (I) as described herein.
Linker Length Modulates DNA Cross-Linking Reactivity and Cytotoxic Potency of C8/C8′ Ether-Linked C2-exo-Unsaturated Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Dimers
Gregson, Stephen J.,Howard, Philip W.,Gullick, Darren R.,Hamaguchi, Anzu,Corcoran, Kathryn E.,Brooks, Natalie A.,Hartley, John A.,Jenkins, Terence C.,Patel, Sejal,Guille, Matthew J.,Thurston, David E.
, p. 1161 - 1174 (2007/10/03)
A C2/C2′-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer 4b (DRG-16) with a C8-O(CH2)nO-C8′ diether linkage (n = 5) has been synthesized that shows markedly superior in vitro cytotoxic potency (e.g., > 3400-fold in IGRO
Pyrrolobenzodiazepines
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Page 37, 105, (2010/11/29)
Compounds of the formulae Ia and Ib: wherein:A is CH2, or a single bond;R2 is selected from: R, OH, OR, CO2H, CO2R, COH, COR, SO2R, CN;R6, R7 and R9 are independently selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn;and R8 is selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn, where R is as defined above, or the compound is a dimer with each monomer being the same or different and being of formula Ia or Ib, where the R8 groups of the monomers form together a bridge having the formula -X-R'-X- linking the monomers, where R' is an alkylene chain containing from 3 to 12 carbon atoms, which chain may be interrupted by one or more hetero-atoms and/or aromatic rings and may contain one or more carbon-carbon double or triple bonds, and each X is independently selected from O, S, or N; except that in a compound of formula Ia when A is a single bond, then R2 is not CH=CH(CONH2) or CH=CH(CONMe2). Other related compounds are also disclosed.
Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer.
Gregson,Howard,Corcoran,Jenkins,Kelland,Thurston
, p. 2859 - 2862 (2007/10/03)
We report the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer 16 synthesised through a new and efficient route, thus establishing that C2-C3-endo unsaturation enhances both cytotoxicity and DNA-binding affin
