762274-65-7

Basic information

• Product Name: L-Proline, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-L-alanyl-3-methyl-L-valyl-, phenylmethyl ester
• CAS NO: 762274-65-7
• Molecular Formula: C27H41N3O6
• Molecular Weight: 503.639
• Mol File: 762274-65-7.mol

Chemical Properties

• CAS DataBase Reference: L-Proline, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-L-alanyl-3-methyl-L-valyl-, phenylmethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: L-Proline, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-L-alanyl-3-methyl-L-valyl-, phenylmethyl ester(762274-65-7)
• EPA Substance Registry System: L-Proline, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-L-alanyl-3-methyl-L-valyl-, phenylmethyl ester(762274-65-7)

Safety Data

• Hazardous Substances Data: 762274-65-7(Hazardous Substances Data)

Upstream product

• 16948-16-6 N-(tert-butoxycarbonyl)-N-methyl-L-alanine 
• 62965-35-9 N-tert-butyloxycarbonyl-L-tert-leucine 
• 13734-31-1 (S)-N-tert-butoxycarbonyl-N-methyl-2-amino-propionic acid 
• 100-51-6 benzyl alcohol 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 37787-77-2 Boc-L-proline benzyl ester 

Downstream Products

• 1363150-47-3 tert-butyl(S)-1-((S)-1-((S)-2-(4-(3-chloro-2,4-difluorophenylamino)-7-methoxyquinazolin-6-ylcarbamoyl)pyrrolidin-1-yl-3,3-dimethyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl)methylcarbamate 
• 1363150-35-9 (S)-N-(4-(3-chloro-2,4-difluorophenylamino)-7-methoxyquinazolin-6-yl)-1-((S)3,3-dimethyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidine-2-carboxamide hydrochloride 

Relevant articles and documents

Design, synthesis and biological evaluation of new bivalent quinazoline analogues as IAP antagonists

We recently reported the biological evaluations of monovalent IAP antagonist 7 with good potency (MDA-MB-231, IC50 = 19 nM). In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized bivalent analogues based on quinazoline structure of 7. Optimization of cellular potency and CYP inhibition led to the identification of 27, which showed dramatic increase of over 100-fold (IC50 = 0.14 nM) and caused substantial tumor regressions in MDA-MB-231 xenograft model. These results strongly support 27 as a promising bivalent antagonist for the development of an effective anti-tumor approaches.

QUINOLINE OR QUINAZOLINE DERIVATIVES WITH APOPTOSIS INDUCING ACTIVITY ON CELLS

Provided is a pharmaceutical composition comprising, as an active ingredient, a quinoline or quinazoline derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate, and a solvate thereof, which is effective in the prevention and treatment of a cancer, inflammation, autoimmune diseases or neurodegenerative disorders which are induced by the overexpression of inhibitor of apoptosis proteins (IAPs).

TETRAPEPTIDE ANALOGS

Compounds, compositions and methods for treatment of hyperproliferative diseases, such as cancer are provided.

Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer

Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.