Literature DB >> 24900295

Discovery of a potent nicotinic Acid receptor agonist for the treatment of dyslipidemia.

Jun Qin1, Ashwin Rao1, Xiao Chen1, Xiaohong Zhu1, Zhidan Liu1, Xianhai Huang1, Sylvia Degrado1, Ying Huang1, Dong Xiao1, Robert Aslanian1, Boonlert Cheewatrakoolpong2, Hongtao Zhang2, Scott Greenfeder2, Constance Farley2, John Cook2, Stan Kurowski2, Qiu Li2, Margaret van Heek2, Madhu Chintala2, Ganfeng Wang3, Yunsheng Hsieh3, Fangbiao Li3, Anandan Palani1.   

Abstract

Nicotinic acid has been used clinically for decades to control serum lipoproteins. Nicotinic acid lowers very low-density lipoprotein (VLDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and lipoprotein-a (LPa), and it is also effective in raising high-density lipoprotein (HDL)-cholesterol. However, nicotinic acid has several side effects in clinical use. The most notable is intense cutaneous vasodilation "flushing" on the upper body and face. We discovered a pyranopyrimidinedione series to be nicotinic acid receptor agonists. A potent nicotinic acid receptor agonist from this series {5-(3-cyclopropylpropyl)-2-(difluoromethyl)-3H-pyrano[2,3-d]pyrimidine-4,7-dione}with reduced flushing side effect in dogs was identified.

Entities:  

Keywords:  HDL; Nicotinic acid; VLDL; agonist; dyslipidemia; flushing

Year:  2010        PMID： 24900295      PMCID： PMC4017979          DOI： 10.1021/ml100251u

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  30 in total

1.  Low high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report.

Authors:  A M Gotto
Journal:  Circulation       Date:  2001-05-01       Impact factor: 29.690

2.  INITIAL DISTRIBUTION IN MICE OF 3H-LABELED NICOTINIC ACID STUDIED WITH AUTORADIOGRAPHY.

Authors:  L A CARLSON; A HANNGREN
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3.  Studies on the effect of nicotinic acid on catecholamine stimulated lipolysis in adipose tissue in vitro.

Authors:  L A CARLSON
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Review 4.  Nicotinic acid receptor agonists.

Authors:  P Douglas Boatman; Jeremy G Richman; Graeme Semple
Journal:  J Med Chem       Date:  2008-12-25       Impact factor: 7.446

5.  Effects of lipolytic and antilipolytic substances on adenosine 3',5'-monophosphate levels in isolated fat cells.

Authors:  R W Butcher; C E Baird; E W Sutherland
Journal:  J Biol Chem       Date:  1968-04-25       Impact factor: 5.157

6.  Hepatotoxicity associated with sustained-release niacin.

Authors:  T A Dalton; R S Berry
Journal:  Am J Med       Date:  1992-07       Impact factor: 4.965

7.  Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins.

Authors:  Allen J Taylor; Lance E Sullenberger; Hyun J Lee; Jeannie K Lee; Karen A Grace
Journal:  Circulation       Date:  2004-11-10       Impact factor: 29.690

8.  Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin.

Authors:  J A Etchason; T D Miller; R W Squires; T G Allison; G T Gau; J K Marttila; B A Kottke
Journal:  Mayo Clin Proc       Date:  1991-01       Impact factor: 7.616

9.  PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect.

Authors:  Sorin Tunaru; Jukka Kero; Annette Schaub; Christian Wufka; Andree Blaukat; Klaus Pfeffer; Stefan Offermanns
Journal:  Nat Med       Date:  2003-02-03       Impact factor: 53.440

10.  Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia.

Authors:  John F Paolini; Yale B Mitchel; Robert Reyes; Uma Kher; Eseng Lai; Douglas J Watson; Josephine M Norquist; Alan G Meehan; Harold E Bays; Michael Davidson; Christie M Ballantyne
Journal:  Am J Cardiol       Date:  2007-12-21       Impact factor: 2.778
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  3 in total

1.  Discovery of SCH 900271, a Potent Nicotinic Acid Receptor Agonist for the Treatment of Dyslipidemia.

Authors:  Anandan Palani; Ashwin U Rao; Xiao Chen; Xianhai Huang; Jing Su; Haiqun Tang; Ying Huang; Jun Qin; Dong Xiao; Sylvia Degrado; Michael Sofolarides; Xiaohong Zhu; Zhidan Liu; Brian McKittrick; Wei Zhou; Robert Aslanian; William J Greenlee; Mary Senior; Boonlert Cheewatrakoolpong; Hongtao Zhang; Constance Farley; John Cook; Stan Kurowski; Qiu Li; Margaret van Heek; Gangfeng Wang; Yunsheng Hsieh; Fangbiao Li; Scott Greenfeder; Madhu Chintala
Journal:  ACS Med Chem Lett       Date:  2011-11-24       Impact factor: 4.345

2.  Design and synthesis of nucleolipids as possible activated precursors for oligomer formation via intramolecular catalysis: stability study and supramolecular organization.

Authors:  Kishore Lingam Gangadhara; Puneet Srivastava; Jef Rozenski; Henri-Philippe Mattelaer; Volker Leen; Wim Dehaen; Johan Hofkens; Eveline Lescrinier; Piet Herdewijn
Journal:  J Syst Chem       Date:  2014-12-09

Review 3.  Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part II: Novel Niacin Mimetics.

Authors:  Harsh Goel; Richard L Dunbar
Journal:  Curr Atheroscler Rep       Date:  2016-04       Impact factor: 5.113
  3 in total

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