251105-80-3Relevant articles and documents
Preparation method of chiral phenbutamol sulfonamide compound, intermediate for preparing chiral phenbutamol sulfonamide compound and preparation method of chiral phenbutamol sulfonamide compound
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, (2022/04/08)
The invention discloses a preparation method of a chiral phenbutamol sulfonamide compound, which comprises the following steps: carrying out substitution reaction on a compound A, establishing a chiral center by using ketoreductase, and carrying out amidation and Hofmann degradation to obtain the chiral phenbutamol sulfonamide compound, the structural formula of the compound A is as follows: Q1 and Q2 are independently selected from heteroatom groups containing one or more of nitrogen, oxygen and sulfur, or H, or Q1 and Q2 are connected to form a ring, and R1 is selected from alkyl with the carbon atom number of 1-6. The preparation method provided by the invention has the advantages of simple steps, few reaction steps, mild reaction of each step, high safety coefficient and low production cost.
Design and evaluation of novel piperidine HIV-1 protease inhibitors with potency against DRV-resistant variants
Zhu, Mei,Zhou, Huiyu,Ma, Ling,Dong, Biao,Zhou, Jinming,Zhang, Guoning,Wang, Minghua,Wang, Juxian,Cen, Shan,Wang, Yucheng
, (2021/06/02)
A novel class of HIV-1 protease inhibitors with flexible piperidine as the P2 ligand was designed with the aim of improving extensive interactions with the active subsites. Many inhibitors exhibited good to excellent inhibitory effect on enzymatic activity and viral infectivity. In particular, inhibitor 3a with (R)-piperidine-3-carboxamide as the P2 ligand and 4-methoxybenzenesulfonamide as the P2’ ligand showed an enzyme Ki value of 29 pM and antiviral IC50 value of 0.13 nM, more than six-fold enhancement of activity compared to DRV. Furthermore, there was no significant change in potency against DRV-resistant mutations and HIV-1NL4?3 variant for 3a. Besides, inhibitor 3a exhibited potent antiviral activity against subtype C variants with low nanomole EC50 values. In addition, the molecular modeling revealed important hydrogen bonds and other favorable van der Waals interactions with the backbone atoms of the protease and provided insight for designing and optimizing more potent HIV-1 protease inhibitors.
Preliminary SAR and biological evaluation of potent HIV-1 protease inhibitors with pyrimidine bases as novel P2 ligands to enhance activity against DRV-resistant HIV-1 variants
Zhu, Mei,Ma, Ling,Zhou, Huiyu,Dong, Biao,Wang, Yujia,Wang, Zhen,Zhou, Jinming,Zhang, Guoning,Wang, Juxian,Liang, Chen,Cen, Shan,Wang, Yucheng
, (2019/11/28)
Introducing pyrimidine bases, the basic components of nucleic acid, to P2 ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitors because of the carbonyl and amino groups promoting the formation of extensive hydrogen bonding interactions. In this work, we provide evidence that inhibitor 10e, with N-2-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide as the P2 ligand and a 4-methoxylphenylsulfonamide as the P2′ ligand, displayed remarkable enzyme inhibitory and antiviral activity, with the IC50 2.53 nM in vitro and a promising inhibition ratio with 68% against wild-type HIV-1 in vivo, with low cytotoxicity. This inhibitor also exhibited appreciable antiviral activity against DRV-resistant HIV-1 variants, which was of great value for further study.