144186-12-9

Basic information

• Product Name: carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester
• Synonyms: carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester
• CAS NO: 144186-12-9
• Molecular Weight: 389.365
• Mol File: 144186-12-9.mol

Chemical Properties

• CAS DataBase Reference: carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester(144186-12-9)
• EPA Substance Registry System: carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester(144186-12-9)

Safety Data

• Hazardous Substances Data: 144186-12-9(Hazardous Substances Data)

Upstream product

• 5070-13-3 bis-(p-nitrophenyl) carbonate 
• 169280-83-5 (5-hydroxymethylpyridin-2-yl)-carbamic acid t-butyl ester 
• 144186-11-8 methyl 6-<(tert-butyloxycarbonyl)amino>nicotinoate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 36052-24-1 methyl 6-aminonicotinoate 
• 7693-46-1 4-Nitrophenyl chloroformate 

Relevant articles and documents

Structural Basis for Genetic-Code Expansion with Bulky Lysine Derivatives by an Engineered Pyrrolysyl-tRNA Synthetase

Yanagisawa et al. analyzed the Y306A/Y384F mutant of Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS) with 17 non-natural, bulky oxycarbonyllysine derivatives for tRNAPyl aminoacylation and site-specific incorporation into proteins. Fourteen crystal structures of the amino acid-bound PylRS mutant revealed the structural bases of the binding. This information facilitates the structure-based design of novel amino acids. Pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl have been extensively used for genetic-code expansion. A Methanosarcina mazei PylRS mutant bearing the Y306A and Y384F mutations (PylRS(Y306A/Y384F)) encodes various bulky non-natural lysine derivatives by UAG. In this study, we examined how PylRS(Y306A/Y384F) recognizes many amino acids. Among 17 non-natural lysine derivatives, N?-(benzyloxycarbonyl)lysine (ZLys) and 10 ortho/meta/para-substituted ZLys derivatives were efficiently ligated to tRNAPyl and were incorporated into proteins by PylRS(Y306A/Y384F). We determined crystal structures of 14 non-natural lysine derivatives bound to the PylRS(Y306A/Y384F) catalytic fragment. The meta- and para-substituted ZLys derivatives are snugly accommodated in the productive mode. In contrast, ZLys and the unsubstituted or ortho-substituted ZLys derivatives exhibited an alternative binding mode in addition to the productive mode. PylRS(Y306A/Y384F) displayed a high aminoacylation rate for ZLys, indicating that the double-binding mode minimally affects aminoacylation. These precise substrate recognition mechanisms by PylRS(Y306A/Y384F) may facilitate the structure-based design of novel non-natural amino acids.

Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy

The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption. Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 μM) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.