162537-10-2

Usage

Chemical Properties

Light Yellowish Thick-Oil

InChI:InChI=1/C13H16N2O6/c1-8(2)11(12(16)20-3)14-13(17)21-10-6-4-9(5-7-10)15(18)19/h4-8,11H,1-3H3,(H,14,17)/t11-/m0/s1

Upstream product

• 6306-52-1 L-valine methylester hydrochloride 
• 7693-46-1 4-Nitrophenyl chloroformate 
• 4070-48-8 L-Valine methyl ester 
• 5070-13-3 bis-(p-nitrophenyl) carbonate 
• 144-55-8 sodium hydrogencarbonate 

Downstream Products

• 154248-99-4 N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester 
• 155213-67-5 ritonavir 
• 154212-61-0 N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine 

Relevant academic research and scientific papers

Towards a general synthesis of di-aza-amino acids containing peptides

While the incorporation of one aza-amino acid in peptides has been proved to be beneficial for inducing a structure constraint, increasing the resistance towards proteolysis and improving the biological activity, only very rare examples of the incorporation of two or more consecutive aza-amino acids have been reported. In this work, we demonstrate that this fact is probably due to the unsuspected difficulty in synthesizing such peptide analogues, as illustrated by the synthesis of tripeptide derivatives containing two consecutive aza-amino acids. Herein, we report some general guidelines regarding the activation and the coupling of alkyl-hydrazides either mutually or with a natural amino acid, taking into account their nucleophilicity and the nature of their side chains.

HIV protease inhibiting compounds

A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

A novel naphthylmethyleneimino-type photocleavable protecting group for primary amines

A novel naphthylmethyleneimino-type protecting group for aliphatic and aromatic primary amines including α-amino acids was devised and its introduction was accomplished in good to excellent yields. This type of protecting group was found to be cleanly removed photochemically to regenerate the primary amines in good to high yields, regardless of steric and electronic properties. Georg Thieme Verlag Stuttgart.

ACID ADDITION SALT OF 2-ISOPROPYL-4-(((N-METHYL)AMINO)METHYL)THIAZOLE AND ITS?USE IN THE PREPARATION OF RITONAVIR

The present invention relates to a novel acid addition salt of 2-Isopropyl-4-(((N-methyl)amino)methyl)thiazole of Formula (I) which is a useful intermediate for preparing HIV protease inhibitors. The present invention further provides a process for preparing ritonavir, a HIV protease inhibitor, using the compound of Formula (I).

HIV protease inhibiting compounds

A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

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.

Pharmaceutical composition

A solid pharmaceutical composition is disclosed which comprises a pharmaceutically acceptable adsorbent or a mixture of pharmaceutically acceptable adsorbents to which is adsorbed a mixture of (1) a pharmaceutically acceptable organic solvent or a mixture of pharmaceutically acceptable organic solvents, (2) an HIV protease inhibiting compound and (3) one or more pharmaceutically acceptable acids. The solid composition can optionally be encapsulated in a hard gelatin capsule.

Pharmaceutical composition for inhibiting HIV protease

A pharmaceutical composition is disclosed which comprises a solution of an HIV protease inhibiting compound in a pharmaceutically acceptable organic solvent comprising a mixture of (1) (a) a solvent selected from propylene glycol and polyethylene glycol or (b) a solvent selected from polyoxyethyleneglycerol triricinoleate, polyethylene glycol 40 hydrogenated castor oil, fractionated coconut oil, polyoxyethylene (20) sorbitan monooleate and 2-(2-ethoxyethoxy)ethanol or (c) a mixture thereof and (2) ethanol or propylene glycol.

RETROVIRAL PROTEASE INHIBITING COMPOUNDS

A retroviral protease inhibiting compound of the formula: STR1 is disclosed wherein R 1, R 2, R 5, R 6, Y m and Y' n are herein defined.