848824-84-0

Basic information

• Product Name: Carbamic acid, [(5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-6-[[4-(hydroxymethyl)phen yl]amino]-6-oxohexyl]-, 2-propenyl ester
• CAS NO: 848824-84-0
• Molecular Formula: C22H33N3O6
• Molecular Weight: 435.521
• Mol File: 848824-84-0.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: Carbamic acid, [(5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-6-[[4-(hydroxymethyl)phen yl]amino]-6-oxohexyl]-, 2-propenyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Carbamic acid, [(5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-6-[[4-(hydroxymethyl)phen yl]amino]-6-oxohexyl]-, 2-propenyl ester(848824-84-0)
• EPA Substance Registry System: Carbamic acid, [(5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-6-[[4-(hydroxymethyl)phen yl]amino]-6-oxohexyl]-, 2-propenyl ester(848824-84-0)

Safety Data

• Hazardous Substances Data: 848824-84-0(Hazardous Substances Data)

Upstream product

• 623-04-1 4-aminobenzenemethanol 
• 104669-73-0 N^α-(tert-butoxycarbonyl)-N^ε-(allyloxycarbonyl)-L-lysine 

Downstream Products

• 848824-88-4 1-acetoxymethyl-5-{4-[(6-allyloxycarbonylamino-2-tert-butoxycarbonylamino-hexanoyl)-(2-trimethylsilanyl-ethoxymethyl)amino]-benzyloxy}-1,2-dihydro-pyrrolo-[3,2-f]quinoline-3-carboxylic acid tert-butyl ester 
• 848824-89-5 acetic acid 5-{4-[(6-allyloxycarbonylamino-2-amino-hexanoyl)-hydroxymethyl-amino]-benzyloxy}-2,3-dihydro-1H-pyrrolo[3,2-f]quinolin-1-ylmethyl ester 
• 848824-86-2 {5-tert-butoxycarbonylamino-5-[[4-(tert-butyl-dimethyl-silanyloxymethyl)phenyl]-(2-trimethylsilanyl-ethoxymethyl)carbamoyl]-pentyl}-carbamic acid allyl ester 
• 848824-90-8 acetic acid 5-[4-(6-allyloxycarbonylamino-2-amino-hexanoylamino)benzyloxy]-2,3-dihydro-1H-pyrrolo[3,2-f]quinolin-1-ylmethyl ester 
• 848824-87-3 {5-tert-butoxycarbonylamino-5-[(4-hydroxymethylphenyl)-(2-trimethylsilanyl-ethoxymethyl)carbamoyl]pentyl}-carbamic acid allyl ester 
• 848824-83-9 {5-[(4-bromomethyl-phenyl)-(2-trimethylsilanyl-ethoxymethyl)carbamoyl]-5-tertbutoxycarbonylamino-pentyl}-carbamic acid allyl ester 
• 848824-85-1 {5-allyloxycarbonylamino-1-[4-(tert-butyl-dimethyl-silanyloxymethyl)phenylcarbamoyl]-pentyl}-carbamic acid tert-butyl ester 

Relevant articles and documents

Design, synthesis, and in vitro evaluation of dipeptide-based antibody minor groove binder conjugates

Antibody-drug conjugates (ADCs) were prepared consisting of DNA minor groove binder drugs (MGBs) attached to monoclonal antibodies (mAbs) through peptide linkers designed to release drugs inside the lysosomes of target cells. The site of linker attachment on the MGB was at the 5-position on the B-ring, since model studies showed that attachment of an electron-withdrawing group (i.e., acyl, carbamoyl) at this position increased the stability of the molecule. Because of the hydrophobic nature of the MGBs, several measures were required to overcome their tendencies to induce mAb aggregation upon conjugation. This is exemplified in the series of ADCs containing the amino-CBI drug 1. Initial adducts were prepared using the peptide sequence valine-citrulline, attached to a self-immolative para-aminobenzyl carbamate spacer. The resulting ADCs were completely aggregated. Removal of the self-immolative spacer, introduction of a more hydrophilic valine-lysine sequence, and incorporation of a tetraethyl-eneglycol unit between the mAb and the peptide resulted in conjugates that were nonaggregated, even with as many as eight drugs per mAb. These results were extended to include the hydroxy aza-CBI drug 2, which was linked to the valine-lysine sequence through a para-aminobenzyl ether self-immolative spacer. The resulting mAb conjugates were monomeric and released the hydroxy aza-CBI drug upon treatment with human cathepsin B. In vitro cytotoxicity assays established that the mAb-MGB drug conjugates were highly cytotoxic and effected immunologically specific cell kill at subsaturating doses. The results provide a general strategy for MGB prodrug design and illustrate the importance of linker hydrophilicity in making nonaggregated, active mAb-MGB conjugates.