128300-11-8

Basic information

• Product Name: 3H-Benz[e]indole-3-carboxylic acid, 1-(chloromethyl)-1,2-dihydro-5-(phenylmethoxy)-, 1,1-dimethylethyl ester, (1S)-
• CAS NO: 128300-11-8
• Molecular Formula: C25H26ClNO3
• Molecular Weight: 423.939
• Mol File: 128300-11-8.mol
• Article Data: 10

Chemical Properties

• CAS DataBase Reference: 3H-Benz[e]indole-3-carboxylic acid, 1-(chloromethyl)-1,2-dihydro-5-(phenylmethoxy)-, 1,1-dimethylethyl ester, (1S)-(CAS DataBase Reference)
• NIST Chemistry Reference: 3H-Benz[e]indole-3-carboxylic acid, 1-(chloromethyl)-1,2-dihydro-5-(phenylmethoxy)-, 1,1-dimethylethyl ester, (1S)-(128300-11-8)
• EPA Substance Registry System: 3H-Benz[e]indole-3-carboxylic acid, 1-(chloromethyl)-1,2-dihydro-5-(phenylmethoxy)-, 1,1-dimethylethyl ester, (1S)-(128300-11-8)

Safety Data

• Hazardous Substances Data: 128300-11-8(Hazardous Substances Data)

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 1116653-76-9 (R)-tert-butyl (4-(benzyloxy)-1-iodonaphthalen-2-yl)(oxiran-2-ylmethyl)carbamate 
• 161646-53-3 tert-butyl (4-(benzyloxy)-1-iodonaphthalen-2-yl)carbamate 
• 122745-41-9 tert-butyl (1S)-1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indole-3-carboxylate 
• 100-39-0 benzyl bromide 
• 122745-40-8 tert-Butyl(S)-5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indole-3-carboxylate 
• 227084-59-5 (E/Z)-tert-butyl 4-(benzyloxy)-1-iodonaphthalene-2-yl(3-chloroallyl)carbamate 
• 122745-45-3 N-(tert-butyloxycarbonyl)-N-(2-propynyl)-4-(benzyloxy)-1-bromo-2-naphthylamine 
• 122745-38-4 5-(benzyloxy)-3-(tert-butyloxycarbonyl)-1-methylidene-1,2-dihydro-3H-benzindole 
• 122745-37-3 2-((tert-Butyloxycarbonyl)amino)-4-(benzyloxy)-1-bromonaphthalene 
• 122745-36-2 N-(tert-butyloxycarbonyl)-4-(benzyloxy)-2-naphthylamine 
• 122745-35-1 3-Amino-1-(benzyloxy)naphthalene 
• 128228-76-2 5-(benzyloxy)-3-(tert-butyloxycarbonyl)-1-(hydroxymethyl)-1,2-dihydro-3H-benzindole, (R)-(-)-O-acetylmandelate ester 
• 13802-40-9 1-Methoxy-3-nitronaphthalene 

Downstream Products

• 122745-41-9 tert-butyl (1S)-1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indole-3-carboxylate 

Relevant articles and documents

CYTOTOXIC AGENTS

The present invention provides a compound of formula (I): (T-X4)p-B1-X3-A-X2-L-X1-AM or pharmaceutically acceptable salts, tautomers, stereoisomers or mixtures thereof; wherein AM is (AM1); (AM2); or (AM3); with the proviso that the compound of formula (I) contains at least one sigma hole group; and with the proviso that no more than one of A, B1 and T is a sigma hole group; and each sigma hole group is independently: (SH1); (SH2); (SH3); (SH4); (SH5); (SH6); (SH7); (SH8); (SH9); or (SH10).

Analogues of DNA minor groove cross-linking agents incorporating aminoCBI, an amino derivative of the duocarmycins: Synthesis, cytotoxicity, and potential as payloads for antibody–drug conjugates

A Pd-catalysed amination method is used to convert seco-CBI, a synthetic analogue of the alkylating subunit of the duocarmycin natural products, from the phenol to amino form. This allows efficient enantioselective access to the more potent S enantiomer of aminoCBI and its incorporation into analogues of DNA minor groove cross-linking agents. Evaluation in a panel of nine human tumour cell lines shows that the bifunctional agents containing aminoCBI are generally less cytotoxic than their phenolCBI analogues and more susceptible to P-glycoprotein-mediated resistance. However, all bifunctional agents are potent cytotoxins, some in the sub-pM IC50range, with in vitro properties that compare favourably with established microtubule-targeted ADC payloads.

1-(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE DIMER ANTIBODY-DRUG CONJUGATE COMPOUNDS, AND METHODS OF USE AND TREATMENT

The invention provides antibody-drug conjugates comprising an antibody conjugated to a 1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimer drug moiety via a linker, and methods of using the antibody-drug conjugates.