169280-63-1

Upstream product

• 799241-80-8 N-(3-dibenzylamino-2-hydroxy-4-phenyl-butyl)-N-isobutyl-3-nitro-benzenesulfonamide 
• 143224-62-8 (2R,3S)-3-benzyloxycarbonylamino-2-hydroxy-1-(N-isobutylamino)-4-phenylbutane 
• 169331-42-4 βS--αR-<<(2-methylpropyl)amino>methyl>-benzenepropanol 
• 160232-08-6 (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol 
• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 475292-71-8 {(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-(3-nitro-benzenesulfonyl)-amino]-propyl}-carbamic acid tert-butyl ester 
• 169280-89-1 {(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-(3-nitro-benzenesulfonyl)-amino]-propyl}-carbamic acid benzyl ester 
• 121-51-7 3-nitrobenzenesulphonyl chloride 

Downstream Products

• 181124-54-9 carbamic acid, 2R-hydroxy-3-[[(3-aminophenyl)sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, phenylmethyl ester 

Relevant academic research and scientific papers

Discovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV

A new series of HIV protease inhibitors has been designed and synthesized based on the combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavir. The series was optimized by replacing the 6-membered cyclic urea linker with an imidazolidine-2,4-dione which readily underwent N-alkylation to incorporate various methylene-linked heterocycle groups that bind favorably in site 3 of HIV protease. Significant improvements compared to lopinavir were seen in cell culture activity versus wild-type virus (pNL4-3) and the lopinavir-resistant mutant virus A17 (generated by in vitro serial passage of HIV-1 (pNL4-3) in MT-4 cells). Select imidazolidine-2,4-dione containing PIs were also more effective at inhibiting highly resistant patient isolates Pt1 and Pt2 than lopinavir. Pharmacokinetic data collected for compounds in this series varied considerably when coadministered orally in the rat with an equal amount of ritonavir (5 mg/kg each). The AUC values ranged from 0.144 to 12.33 μg h/mL.

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.

Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1 protease

The human immunodeficiency virus (HIV) has been shown to be the causative agent for AIDS. The HIV virus encodes for a unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors have been useful in combating the disease. The inhibitors incorporate a variety of isosteres including the hydroxyethylurea at the protease cleavage site. We have shown that the replacement of t-butylurea moiety by benzothiazolesulfonamide provided inhibitors with improved potency and antiviral activities. Some of the compounds have shown good oral bioavailability and half-life in rats. The synthesis of benzothiazole derivatives led us to explore other heterocycles. During the course of our studies, we also developed an efficient synthesis of benzothiazole-6-sulfonic acid via a two-step procedure starting from sulfanilamide.

HETEROCYCLECARBONYL AMINO ACID HYDROXYETHYLAMINO SULFONAMIDE RETROVIRAL PROTEASE INHIBITORS

Selected heterocyclecarbonyl amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

Hydroxyethylamino sulphonamides useful as retroviral protease inhibitors

PCT No. PCT/US94/09139 Sec. 371 Date Jan. 24, 1996 Sec. 102(e) Date Jan. 24, 1996 PCT Filed Aug. 23, 1994 PCT Pub. No. WO95/06030 PCT Pub. Date Mar. 2, 1995The invention relates to sulfonamide-containing hydroxyethylamine protease inhibitor compounds, their process of making, composition and method of use for inhibiting retroviral proteases such as human immunodeficiency virus.

Bis-sulfonamide hydroxyethylamino retroviral protease inhibitors

PCT No. PCT/US96/00607 Sec. 371 Date Feb. 26, 1998 Sec. 102(e) Date Feb. 26, 1998 PCT Filed Jan. 18, 1996 PCT Pub. No. WO96/22287 PCT Pub. Date Jul. 25, 1996Bis-sulfonamido hydroxyethylamino compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to retroviral protease inhibiting compounds of the formula: or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein the variables are as defined herein.

Synthesis of benzo fused heterocyclic sulfonyl chlorides

A process for preparing a benzo fused heterocyclic sulfonyl halide comprising reacting a benzo fused heterocyclic compound with an SO3 complex in the presence of a water immiscible, non-reactive solvent, at a temperature of from about 0 DEG C. to about 75 DEG C., cooling, if necessary, to a temperature of from about -25 DEG C. to about 65 DEG C. and then adding oxalyl halide.

AMINO ACID HYDROXYETHYLAMINO SULFONAMIDE RETROVIRAL PROTEASE INHIBITORS

Described herein is a retroviral protease inhibiting compound of the formula: STR1 or a pharmaceutically acceptable salt, prodrug or ester thereof.

SULFONYLALKANOYLAMINO HYDROXYETHYLAMINO SULFONAMIDE RETROVIRAL PROTEASE INHIBITORS

Selected sulfonylalkanoylamino hydroxyethylamine sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.