- Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors
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Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus. This inhibitor was also shown to be moderately effective against polyomaviruses, another family of opportunistic viruses. We have developed a panel of analogues for this inhibitor and have shown that these analogues maintain their high efficacy against HCMV, while substantially lowering the concentration required to inhibit polyomavirus replication. By targeting a host protein these compounds are able to inhibit the replication of two very different viruses. These observations open up the possibility of pan-viral inhibitors for immunosuppressed individuals that are effective against multiple, diverse opportunistic viruses.
- Desai, Dhimant,Lauver, Matthew,Ostman, Alexandria,Cruz, Linda,Ferguson, Kevin,Jin, Ge,Roper, Brianne,Brosius, Daniel,Lukacher, Aron,Amin, Shantu,Buchkovich, Nick
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Read Online
- Divergent 2-Chloroquinazolin-4(3H)-one Rearrangement: Twisted-Cyclic Guanidine Formation or Ring-Fused N-Acylguanidines via a Domino Process
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A highly efficient 2-chloroquinazolin-4(3H)-one rearrangement was developed that predictably generates either twisted-cyclic or ring-fused guanidines in a single operation, depending on the presence of a primary versus secondary amine in the accompanying diamine reagent. Exclusive formation of twisted-cyclic guanidines results from pairing 2-chloroquinazolinones with secondary diamines. Use of primary amine-containing diamines permits a domino quinazolinone rearrangement/intramolecular cyclization, gated through (E)-twisted-cyclic guanidines, to afford ring-fused N-acylguanidines. This scalable, structurally tolerant transformation generated 55 guanidines and delivered twisted-cyclic guanidines with robust plasma stability and an abbreviated total synthesis of an antitumor ring-fused guanidine (4 steps, 55 % yield).
- Yan, Gang,Zekarias, Bereket L.,Li, Xiaoyu,Jaffett, Victor A.,Guzei, Ilia A.,Golden, Jennifer E.
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supporting information
p. 2486 - 2492
(2020/02/13)
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- One-Pot, Multistep Reactions for the Modular Synthesis of N, N′-Diarylindazol-3-ones
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The pot-economic synthesis of N,N′-diarylindazol-3-ones has been developed using readily available isatoic anhydrides, aryl amines, and aryl boronic acids. A Cu-catalyzed oxidative C-N cross-coupling and dehydrogenative N-N formation sequence under an air atmosphere affords indazol-3-one derivatives in good to excellent yields. Such process merges well with the preceding decarboxylative amination reaction, resulting in a more modular and straightforward approach.
- Liu, Shuai,Xu, Liang,Wei, Yu
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p. 1596 - 1604
(2019/02/07)
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- NaNO2/I2 as an alternative reagent for the synthesis of 1,2,3-benzotriazin-4(3H)-ones from 2-aminobenzamides
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An efficient transformation of 2-aminobenzamides to 1,2,3-benzotriazin-4(3H)-ones in the presence of sodium nitrite (NaNO2) and Iodine (I2) is described. The reaction is proposed to proceed via formation of nitrosyl halide that induces nitrosylation of the amino group of 2-aminobenzamide leading to diazotization followed by intramolecular cyclization.
- Barak, Dinesh S.,Mukhopadhyay, Sushobhan,Dahatonde, Dipak J.,Batra, Sanjay
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p. 248 - 251
(2019/01/04)
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- NONTOXIC COMPOUNDS FOR THE TREATMENT AND PREVENTION OF HERPESVIRUS INFECTIONS
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Compositions for preventing or treating virus infections inhibit the biogenesis of cytoplasmic viral assembly compartment (cVAC). The preferred compounds are dihydroquinazolinones.
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Page/Page column 56; 57
(2018/02/14)
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