189357-33-3

Basic information

• Product Name: (4R)-N-tert-butyl-3-[(2S,3S)-3-{[(2,6-dimethylphenoxy)acetyl]amino}-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• CAS NO: 189357-33-3
• Molecular Formula: C₃₀H₄₁N₃O₅S
• Molecular Weight: 555.7286
• Mol File: 189357-33-3.mol

Chemical Properties

• Boiling Point: 829.6°C at 760 mmHg
• Flash Point: 455.6°C
• Density: 1.181g/cm³
• Vapor Pressure: 3.61E-29mmHg at 25°C
• Refractive Index: 1.571
• CAS DataBase Reference: (4R)-N-tert-butyl-3-[(2S,3S)-3-{[(2,6-dimethylphenoxy)acetyl]amino}-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: (4R)-N-tert-butyl-3-[(2S,3S)-3-{[(2,6-dimethylphenoxy)acetyl]amino}-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide(189357-33-3)
• EPA Substance Registry System: (4R)-N-tert-butyl-3-[(2S,3S)-3-{[(2,6-dimethylphenoxy)acetyl]amino}-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide(189357-33-3)

Safety Data

• Hazardous Substances Data: 189357-33-3(Hazardous Substances Data)

Upstream product

• 1113-41-3 L-penicillamine 
• 576-26-1 2.6-dimethylphenol 
• 343330-18-7 N-(2-carboxy-ethyl)-succinamic acid 1-(4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl ester 
• 343330-19-8 N-carbamoylmethyl-succinamic acid 1-(4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl ester 
• 343330-17-6 N-carboxymethyl-succinamic acid 1-(4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl ester 
• 288399-78-0 KNI-1047 
• 288399-76-8 KNI-1039 
• 288399-77-9 KNI-1046 
• 288399-75-7 KNI-1038 
• 13335-71-2 2-(2,6-dimethylphenoxy)acetic acid 
• 184955-18-8 (R)-N-tert-butyl-3-<(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl>-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 
• 72778-00-8 (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid 
• 159000-71-2 Boc-Apns-Dmt-NHtBu 
• 148983-13-5 (R)-4-tert-Butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carboxylic acid tert-butyl ester 

Downstream Products

• 343330-25-6 (R)-N-tert-butyl-3-[(2S,3S)-3-(2,6-dimethylphenoxyacetyl)amino-2-glutaryloxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 
• 288399-78-0 KNI-1047 
• 288399-76-8 KNI-1039 
• 288399-77-9 KNI-1046 
• 288399-75-7 KNI-1038 
• 343330-18-7 N-(2-carboxy-ethyl)-succinamic acid 1-(4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl ester 
• 343330-19-8 N-carbamoylmethyl-succinamic acid 1-(4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl ester 
• 343330-17-6 N-carboxymethyl-succinamic acid 1-(4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl ester 
• 343330-26-7 2,2-Dimethyl-succinic acid 4-{(1S,2S)-1-((R)-4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl} ester 
• 343330-15-4 (R)-N-tert-butyl-3-[(2S,3S)-3-(2,6-dimethylphenoxyacetyl)amino-2-succinyloxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 

Relevant articles and documents

Design, synthesis, and biological evaluation of anti-HIV double-drugsconjugates of HIV protease inhibitors with a reverse transcriptase inhibitor through spontaneously cleavable linkers

Based o the prodrug concept as well as the combination of two different classes of anti-HIV agents, we designed and synthesized a series of anti-HIV double-drugs consisitng of HIV protease inhibitors conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoins the two different classes of inhibitors has been investigted. Double-drugs using a succinyl amino acid linker were shown to release the parent drugs via spontaneous imide formation at a faster rate compared ring. Among the double-drugs, KNI-1039 (3B) with a glutaryl-glycine linker exhibited extremely potent anti-HIV activity compared with that of the individual components. Double-drug 3b was relatively stable in culture medium, whereas it regenerated active species in cell homogenate. These results suggested that the synergistic enhancement of anti-HIV activities of 3b may be due to their ability to penetrate into the target cell and subsequent regeneration of two diferent classes of anti-HIV agents in the cytoplasm. Copyright

Controlled drug release: New water-soluble prodrugs of an HIV protease inhibitor

We designed and synthesized a series of highly water-soluble prodrugs of an HIV protease inhibitor, KNI-727 (1), containing tandem-linked two auxiliary units, a solubilizing moiety and a self-cleavable spacer. Prodrugs with an ionized amino group at the solubilizing moiety exhibited a remarkable increase of water-solubility (>104 fold) compared to the parent drug 1. These prodrugs released 1 not enzymatically, but chemically via an intramolecular cyclization-elimination reaction through an imide formation in physiological conditions. Diversified rates of parent drug release were observed when the chemical structure of both the solubilizing and the spacer moieties were modified. This new approach for water-soluble prodrugs will enable to control chemically the release of parent drug as well as to maintain high water-solubility.

'Double-drugs' - A new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker

We designed and synthesized a new series of prodrug-type anti-HIV agents consisting of a peptidomimetic HIV protease inhibitor conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoin the two different classes of inhibitors have been investigated. Conjugates using a succinyl amino acid linker were shown to release the parent components via the spontaneous imide formation at a faster rate compared to conjugates using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Herein, we report a new 'double-drug' 4b (KNI-1039) with a glutarylglycine linker, which exhibited extremely potent anti-HIV activity compared with that of the individual components. (C) 2000 Elsevier Science Ltd. All rights reserved.

Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine

We designed and synthesized a new class of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy- 4-phenylbutyric acid], with a hydroxymethylcarbonyl (HMC) isostere as the active moiety. A systematic evaluation of structure - activity relationships for HIV protease inhibition, anti-HIV activities, and pharmacokinetic profiles has led to the delineation of a set of structural characteristics that appear to afford an orally available HIV protease inhibitor. Optimum structures, exemplified by 21f (JE-2147), incorporated 3-hydroxy-2- methylbenzoyl groups as the P2 ligand, (R)-5,5-dimethyl-1,3-thiazolidine-4- carbonyl (Dmt) residue at the P1' site, and 2-methylbenzylcarboxamide group as the P2' ligand. The present study demonstrated that JE-2147 has potent antiviral activities in vitro and exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals.