133129-29-0Relevant articles and documents
Dihydroisocoumarin derivative and preparation method and application thereof
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Paragraph 0039-0042; 0061-0063; 0066-0067, (2022/01/10)
The present invention discloses a dihydroisocoumarin derivative and preparation method and application thereof, the dihydroisocoumarin derivative having a structure as shown in formula (I) or (II). The method of preparing dihydroisocoumarin derivatives of
Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group
Lee, Won-Gil,Gallardo-Macias, Ricardo,Frey, Kathleen M.,Spasov, Krasimir A.,Bollini, Mariela,Anderson, Karen S.,Jorgensen, William L.
, p. 16705 - 16713 (2013/12/04)
Members of the catechol diether class are highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). The most active compounds yield EC50 values below 0.5 nM in assays using human T-cells infected by wild-type HIV-1. However, these compounds such as rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group. This is an uncommon substructure in drugs that gives reactivity concerns. In the present work, computer simulations were used to design bicyclic replacements for the CVP group. The predicted viability of a 2-cyanoindolizinyl alternative was confirmed experimentally and provided compounds with 0.4 nM activity against the wild-type virus. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. Indolyl and benzofuranyl analogues were also investigated; the most potent compounds in these cases have EC50 values toward wild-type HIV-1 near 10 nM and high-nanomolar activities toward the double-variant. The structural expectations from the modeling were much enhanced by obtaining an X-ray crystal structure at 2.88 A resolution for the complex of the parent 2-cyanoindolizine 10b and HIV-1 RT. The aqueous solubilities of the most potent indolizine analogues were also measured to be ～40 μg/mL, which is similar to that for the approved drug efavirenz and ～1000-fold greater than for rilpivirine.
Synthesis of optically pure (+)-puraquinonic acid and assignment of absolute configuration to natural (-)-puraquinonic acid. Use of radical cyclization for asymmetric generation of a quaternary center
Clive, Derrick L. J.,Yu, Maolin,Sannigrahi, Mousumi
, p. 4116 - 4125 (2007/10/03)
An asymmetric aldol reaction between aldehyde 31 and imide 32, followed at a later stage by ring-closing metathesis (38 → 40), are key reactions used to make optically pure allylic alcohol 40. Radical cyclization of the derived Stork bromo acetals gives lactol ethers 43, which were degraded to generate a quaternary center carrying a methoxycarboxyl group (44 → 47). Compound 47 was converted into (+)-puraquinonic acid; and comparison with a natural sample established that the configuration of the natural compound is 2R (1).
