783350-37-8Relevant articles and documents
Design, synthesis and biological evaluation of protease inhibitors containing morpholine cores with remarkable potency against both HIV-1 subtypes B and C
Cen, Shan,Ding, Jiwei,Dong, Biao,Ma, Ling,Shan, Qi,Wang, Juxian,Wang, Minghua,Wang, Yucheng,Zhang, Guoning,Zhou, Huiyu,Zhou, Jinming,Zhu, Mei
, (2022/03/15)
By following up on the design vector of optimizing amine-based HIV-1 protease inhibitors, we have designed and biologically evaluated a novel class of inhibitors with the free nitrogen or sulphone in morpholine cores as P2 ligands in combination with diverse substituted phenylsulfonamide P2′ ligands. As it turns out, a majority of these inhibitors exhibit prominent enzymatic inhibitory activity in low nanomolar ranges with relatively low cytotoxicity. Particularly, inhibitor 1e containing a morpholine carboxamide P2 ligand and a 4-hydroxyphenylsulfonamide P2′ ligand illustrates a robust enzyme inhibitory IC50 value of 90 pM. Furthermore, 1e demonstrates impressive in vivo antiviral activity with EC50 value of 89 nM and a degree of inhibitory potency against the DRV-resistant variant. More importantly, 1e exhibits remarkable activity with EC50 values of 13.59 nM and 8.23 nM against subtype C HIV-1 strains ZM246 and Indie, respectively. Furthermore, the in silico studies provide molecular insights into binding features of inhibitors with HIV-1 protease, and furnish a valuable forecast on further process.
Dihydropyrimidine compounds and their use in medicine (by machine translation)
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Paragraph 0353; 0355, (2018/03/25)
The invention relates to a dihydropyrimidine compounds and their use as medicaments, in particular for the treatment and prevention of hepatitis b use of the medicament. In particular, the invention relates to the general formula (I) or (Ia) compound of formula or its enantiomer, non-enantiomeric isomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt, wherein the variables are defined in the specification. The invention also relates to the general formula (I) or (Ia) compound of formula or its enantiomer, non-enantiomeric isomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt as the pharmaceutical use, especially for the treatment and prevention of hepatitis b use of the medicament. (by machine translation)
NOVEL PYRAZOLO PYRIMIDINE DERIVATIVES AND THEIR USE AS MALT1 INHIBITORS
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Page/Page column 53; 54, (2015/12/31)
The present invention describes new pyrazolo-pyrimidine derivatives of formula (I) or a pharmaceutically acceptable salt thereof; (I) wherein, R1 is halogen, cyano, or C1-C3alkyl optionally substituted by halogen; R2 is C1-C6alkyl optionally substituted one or more times by C1-C6alkyl, C2-C6alkenyl, hydroxyl, N,N-di-C1-C6alkyl amino, N-mono-C1-C6alkyl amino, O-Rg, Rg, phenyl, or by C1-C6alkoxy wherein said alkoxy again may optionally be substituted by C1-C6alkoxy, N,N-di-C1-C6alkyl amino, Rg or phenyl; C3-C6cycloalkyl optionally substituted by C1-C6alkyl, N,N-di-C1-C6alkyl amino or C1-C6alkoxy-C1-C6alkyl, and/or two of said optional substituents together with the atoms to which they are bound may form an annulated or spirocyclic 4 - 6 membered saturated heterocyclic ring comprising 1 - 2 O atoms; phenyl optionally substituted by C1-C6alkoxy; a 5 - 6 membered heteroaryl ring having 1 to 3 heteroatoms selected from N and O said ring being optionally substituted by C1-C6alkyl which may be optionally substituted by amino or hydroxy; Rg; or N,N-di-C1-C6alkyl amino carbonyl; and R is phenyl independently substituted two or more times by Ra, 2-pyridyl independently substituted one or more times by Rb, 3-pyridyl independently substituted one or more times by Rc, or 4-pyridyl independently substituted one or more times by Rd; which are generally interacting with MALT1 proteolytic and/or autoproteolytic activity, and in particular which may inhibit said activity. The present invention further describes the synthesis of said new pyrazolo-pyrimidine derivatives, their use as a medicament, especially by interacting with MALT1 proteolytic and/or autoproteolytic activity.
