206362-00-7

Basic information

• Product Name: N-[1(S)-Benzyl-2(R)-hydroxy-3-[N-isobutyl-N-(4-methoxyphenylsulfonyl)amino]propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester
• Synonyms: UIC-PI; UIC-94-003; (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl [(2S,3R)-3-hydroxy-4-{[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino}-1-phenylbutan-2-yl]carbamate
• CAS NO: 206362-00-7
• Molecular Formula: C₂₈H₃₈N₂O₈S
• Molecular Weight: 562.6749
• Mol File: 206362-00-7.mol

Chemical Properties

• Density: 1.31g/cm³
• Refractive Index: 1.601
• CAS DataBase Reference: N-[1(S)-Benzyl-2(R)-hydroxy-3-[N-isobutyl-N-(4-methoxyphenylsulfonyl)amino]propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester(CAS DataBase Reference)
• NIST Chemistry Reference: N-[1(S)-Benzyl-2(R)-hydroxy-3-[N-isobutyl-N-(4-methoxyphenylsulfonyl)amino]propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester(206362-00-7)
• EPA Substance Registry System: N-[1(S)-Benzyl-2(R)-hydroxy-3-[N-isobutyl-N-(4-methoxyphenylsulfonyl)amino]propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester(206362-00-7)

Safety Data

• Hazardous Substances Data: 206362-00-7(Hazardous Substances Data)

Upstream product

• 159005-71-7 N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-methoxybenzenesulfonamide 
• 253265-97-3 1-[[[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy]pyrrolidine-2,5-dione 
• 799241-79-5 N-((2R,3S)-3-(dibenzylamino)-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-methoxybenzenesulfonamide 
• 98-68-0 4-methoxy-phenyl-sulphonyl chloride 
• 169331-42-4 βS--αR-<<(2-methylpropyl)amino>methyl>-benzenepropanol 
• 159006-03-8 tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propylcarbamate 
• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 160232-08-6 (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol 

Downstream Products

• 1005324-19-5 C₂₈H₃₆N₂O₈S 

Relevant articles and documents

FITNESS ASSAY AND ASSOCIATED METHODS

The present invention provides an assay for determining the biochemical fitness of a biochemical species in a mutant replicating biological entity relative to its predecessor. The present invention further provides a continuous fluorogenic assay for measuring the anti-HIV protease activity of protease inhibitor. The present invention also provides a method of administering a therapeutic compound that reduces the chances of the emergence of drug resistance in therapy. The present invention also provides a compound of formula (I) or a pharmaceutically acceptable salt, a prodrug, a composition, or an ester thereof, wherein A is a group of formulas (A), (B), (C) or (D); R1, R2, R3, R5 or R6 is H, or an optionally substituted and/or heteroatom-bearing alkyl, alkenyl, alkynyl, or cyclic group; Y and/or Z are CH2, O, S, SO, SO2, amino, amides, carbamates, ureas, or thiocarbonyl derivatives thereof, optionally substituted with an alkyl, alkenyl, or alkynyl group; n is from 1 to 5; X is a bond, an optionally substituted methylene or ethylene, an amino, O or S; Q is C(O), C(S), or SO2; m is from 0 to 6; R4 is OH, ═O (keto), NH2, or alkylamino, including esters, amides, and salts thereof; and W is C(O), C(S), S(O), or SO2. Optionally, R5 and R6, together with the N—W bond of formula (I), comprise a macrocyclic ring.

METHOD AND COMPOSITIONS FOR TREATING HIV INFECTIONS

Described herein are compounds and compositions that are useful in the treatment of HIV, AIDS, and AIDS-related diseases. In addition, compounds are described herein that are capable of inhibiting the dimerization of HIV proteases.

Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor

The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2′ substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.

Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere

Design and synthesis of a series of very potent nonpeptide HIV protease inhibitors are described. The inhibitors are derived from novel high affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere.