Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

被引：0

作者：

Wang, Xinran ^{[1
]}

Hao, Lijuan ^{[1
]}

Xu, Xuanqi ^{[2
]}

Li, Wei ^{[1
]}

Liu, Chunchi ^{[1
]}

Zhao, Dongmei ^{[1
]}

Cheng, Maosheng ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Liaoning, Peoples R China

[2] Univ Wisconsin, Dept Chem, Madison, WI 53715 USA

来源：

MOLECULES | 2017年 / 22卷 / 10期

基金：

中国国家自然科学基金;

关键词：

synthesis; N; N-substituted amine derivatives; CETP inhibitors; HDL-C; CORONARY-HEART-DISEASE; RANDOMIZED CLINICAL-TRIAL; HIGH-RISK; LDL CHOLESTEROL; HDL CHOLESTEROL; CETP INHIBITOR; DOUBLE-BLIND; TORCETRAPIB; DALCETRAPIB; ATHEROSCLEROSIS;

D O I：

10.3390/molecules22101658

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene ring provide important contributions to the potency. Among these compounds, compound 17 exhibited excellent CETP inhibitory activity (IC50 = 0.38 +/- 0.08 mu M) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study.

引用

页数：15

共 50 条

[41] SYNTHESIS OF NEW N-SUBSTITUTED N-DEMETHYLAPORPHINE DERIVATIVES
BERENYI, S
MAKLEIT, S
RANTAL, F
ACTA CHIMICA HUNGARICA-MODELS IN CHEMISTRY, 1985, 120 (03): : 201 - 205
[42] N-Substituted Isoquinoline Derivatives as Potential AChE Inhibitors
Gitto, Rosaria
De Luca, Laura
Ferro, Stefania
De Grazia, Sara
Di Giorgio, Rosa Maria
Festa, Filomena
De Luca, Grazia
JOURNAL OF HETEROCYCLIC CHEMISTRY, 2010, 47 (01) : 54 - 62
[43] Synthesis of N-substituted morpholine nucleoside derivatives
Nekrasov, Mikhail D.
Lukyanenko, Evgeny R.
Kurkin, Alexander V.
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2020, 39 (09): : 1223 - 1244
[44] SYNTHESIS OF N-SUBSTITUTED DERIVATIVES OF CARNOSINE AND HOMOCARNOSINE
BAILIN, G
LUKTON, A
JOURNAL OF ORGANIC CHEMISTRY, 1962, 27 (02): : 684 - &
[45] Synthesis and properties of N-substituted saccharin derivatives
Soubh, L
Besch, A
Otto, HH
PHARMAZIE, 2002, 57 (06): : 384 - 392
[46] Synthesis of N-substituted tetrahyroisoquinoline derivatives.
Kumpaty, HJ
Bhattacharyya, S
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 223 : B181 - B181
[47] SYNTHESIS OF CYCLOALKYLHYDROXAMIC ACIDS AND THEIR N-SUBSTITUTED DERIVATIVES
ALJALLO, HN
AHMED, SS
SALEH, FI
ABBAS, FM
JOURNAL OF CHEMICAL AND ENGINEERING DATA, 1981, 26 (03): : 338 - 340
[48] Synthesis, Molecular Modeling, and Evaluation of Novel Methylated Benzene Sulfonamide Derivatives as Cholesteryl Ester Transfer Protein (CETP) Inhibitors
Abu Khalaf, Reema
Abuarqoub, Rand
Afaneh, Marah
Habash, Maha
CHEMISTRYSELECT, 2024, 9 (37):
[49] Design, synthesis, biological evaluation and QSAR analysis of novel N-substituted benzimidazole derived carboxamides
Bec, Anja
Mioc, Marija
Bertosa, Branimir
Kos, Marija
Debogovic, Patricia
Kralj, Marijeta
Starcevic, Kristina
Hranjec, Marijana
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2022, 37 (01) : 1327 - 1339
[50] Synthesis, odor characteristics and biological evaluation of N-substituted pyrrolyl chalcones
Hu, Jingyi
Ji, Xiaoming
Su, Fangyao
Zhao, Qianrui
Zhang, Ganlin
Zhao, Mingqin
Lai, Miao
ORGANIC & BIOMOLECULAR CHEMISTRY, 2022, 20 (44) : 8747 - 8755

← 1 2 3 4 5 →