253265-98-4

Basic information

• Product Name: BIS THF HNS Derivative 1
• Synonyms: BIS THF HNS Derivative 1;1-[[[[(3S,3aR,6aS)-Hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione;VCFNCYVHQSHFRH-XSSZXYGBSA-N
• CAS NO: 253265-98-4
• Molecular Formula: C11H13NO7
• Molecular Weight: 271.22342
• Mol File: 253265-98-4.mol

Chemical Properties

• Boiling Point: 391.8±52.0 °C(Predicted)
• Appearance: /
• Density: 1.51±0.1 g/cm3(Predicted)
• CAS DataBase Reference: BIS THF HNS Derivative 1(CAS DataBase Reference)
• NIST Chemistry Reference: BIS THF HNS Derivative 1(253265-98-4)
• EPA Substance Registry System: BIS THF HNS Derivative 1(253265-98-4)

Safety Data

• Hazardous Substances Data: 253265-98-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
BIS THF HNS Derivative 1 is used as an impurity in the development and production of TMC114, an HIV-aspartyl protease inhibitor. Its presence in the compound may affect the overall efficacy, safety, and pharmacokinetics of the drug. As a result, understanding and controlling the levels of BIS THF HNS Derivative 1 in TMC114 is crucial for ensuring the quality and effectiveness of the HIV treatment.
Used in Research and Development:
BIS THF HNS Derivative 1 serves as a valuable compound for researchers studying the structure-activity relationships of HIV-aspartyl protease inhibitors. By investigating the properties and interactions of this derivative, scientists can gain insights into the design and optimization of more potent and selective inhibitors, potentially leading to the development of improved antiretroviral therapies.
Used in Quality Control and Analysis:
BIS THF HNS Derivative 1 is used as a reference material for quality control and analytical purposes in the pharmaceutical industry. Its unique structural features make it an essential tool for the identification, quantification, and characterization of impurities in HIV-aspartyl protease inhibitors. This helps ensure the safety, purity, and consistency of these drugs, ultimately benefiting patients receiving antiretroviral treatments.

Upstream product

• 162020-29-3 Acetic acid (3S,3aR,6aS)-(hexahydro-furo[2,3-b]furan-3-yl) ester 
• 74124-79-1 di(succinimido) carbonate 
• 156928-10-8 (3S,3aR,6aS)-3-hydroxyhexahydrofuro<2,3-b>furan 

Downstream Products

• 206361-99-1 darunavir 

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.

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.