Discovery and synthesis of novel substituted benzocoumarins as orally active lipid modulating agents

被引：60
|
作者：
Sashidhara, Koneni V. [1 ]
Kumar, Manoj [1 ]
Modukuri, Ram K. [1 ]
Srivastava, Anuj [2 ]
Puri, Anju [2 ]
机构：
[1] Cent Drug Res Inst CSIR CDRI, Med & Proc Chem Div, Lucknow 226001, Uttar Pradesh, India
[2] Cent Drug Res Inst CSIR CDRI, Div Biochem, Lucknow 226001, Uttar Pradesh, India
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 22期
关键词：
Synthesis; Benzocoumarin; Statins; Antidyslipidemic; LOW-DENSITY-LIPOPROTEIN; DERIVATIVES;
D O I：
10.1016/j.bmcl.2011.09.053
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The synthesis of a series of benzocoumarin keto-enamine schiff bases is reported. The novel compounds were evaluated for their antihyperlipidemic activity in the hyperlipidemic hamster model. The compound 11 at a dose of 10 mg/kg body weight significantly lowered the plasma triglyceride levels (TG) by 70%, total cholesterol (TC) by 47%, accompanied by an increase in HDL-C/TC ratio by 80% in hyperlipidemic hamsters to a greater degree than the reference drugs atorvastatin and lovastatin. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6709 / 6713
页数：5
相关论文
共 50 条
  • [41] Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists
    Riechers, H
    Albrecht, HP
    Amberg, W
    Baumann, E
    Bernard, H
    Bohm, HJ
    Klinge, D
    Kling, A
    Muller, S
    Raschack, M
    Unger, L
    Walker, N
    Wernet, W
    JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (11) : 2123 - 2128
  • [42] DISCOVERY AND SYNTHESIS OF SB-202235, AN ORALLY ACTIVE INHIBITOR OF 5-LIPOXYGENASE
    ADAMS, JL
    GARIGIPATI, RS
    SORENSON, M
    ROSS, S
    SCHMIDT, SJ
    GLEASON, JG
    GRISWOLD, DE
    WEBB, EF
    BRETON, JJ
    MARSHALL, P
    HAY, D
    UNDERWOOD, D
    TORPHY, T
    NEWTON, JF
    TYRRELL, KA
    GARVER, E
    YODIS, L
    BRIAN, WR
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1992, 204 : 21 - MEDI
  • [43] Synthesis of novel benzocoumarin derivatives as lipid lowering agents
    Sashidhara, Koneni V.
    Rosaiah, Jammikuntla N.
    Kumar, Abdhesh
    Bhatia, Gitika
    Khanna, A. K.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (10) : 3065 - 3069
  • [44] Oxyguanidines: Discovery of novel orally active thrombin inhibitors through structure-based drug design and parallel synthesis.
    Markotan, TP
    Lu, TB
    Coppo, F
    Tomczuk, BE
    Crysler, C
    Eisennagel, S
    Spurlino, J
    Soll, RM
    Bone, R
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2003, 226 : U16 - U16
  • [45] Discovery and development of orally active P38 kinase inhibitors as anti-TNF agents
    Devraj, RV
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 229 : U161 - U161
  • [46] Structure based design and synthesis of novel orally active thrombin inhibitors
    Haramura, M
    Shiraishi, T
    Haneishi, T
    Kuromaru, K
    Ohta, M
    Kim, JM
    Nam, WH
    Jung, KY
    Jeon, GH
    Kozono, T
    PEPTIDE SCIENCE - PRESENT AND FUTURE, 1999, : 639 - 641
  • [47] Synthesis and pharmacological evaluation of a novel orally active factor Xa inhibitor
    Nishida, H
    Ohkouchi, M
    Mukaihira, T
    Saitoh, F
    Nakamura, Y
    Miyazaki, Y
    Satoh, T
    Mizuno, M
    Kamino, T
    Hosaka, Y
    Shinozaki, M
    Oono, T
    Muramatsu, H
    Shiromizu, I
    Matsusue, T
    Kamiya, M
    Miyauchi, M
    Yokoyama, T
    Kakinuma, C
    Ogihara, T
    Yanagibashi, K
    Isomura, Y
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 230 : U2660 - U2661
  • [48] Design, synthesis, and evaluation of novel RhoB modulating agents for anticancer chemotherapy
    Lee, Chulho
    Yang, Jee Sun
    Song, Doona
    Kim, Hwan Mook
    Park, Song-Kyu
    Lee, Kiho
    Won, Misun
    Han, Gyoonhee
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2010, 239
  • [49] Arylpiperazinylalkylpyridazinones and analogues as potent and orally active antinociceptive agents: Synthesis and studies on mechanism of action
    Cesari, Nicoletta
    Biancalani, Claudio
    Vergelli, Claudia
    Dal Piaz, Vittorio
    Graziano, Alessia
    Biagini, Pierfrancesco
    Ghelardini, Carla
    Galeotti, Nicoletta
    Giovannoni, Maria Paola
    JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (26) : 7826 - 7835
  • [50] Orally active NGF synthesis stimulators: Potential therapeutic agents in Alzheimer's disease
    Yamada, K
    Nitta, A
    Hasegawa, T
    Fuji, K
    Hiramatsu, M
    Kameyama, T
    Furukawa, Y
    Hayashi, K
    Nabeshima, T
    BEHAVIOURAL BRAIN RESEARCH, 1997, 83 (1-2) : 117 - 122
12345