Pyrazole acids as niacin receptor agonists for the treatment of dyslipidemia.
Niacin is an effective drug for raising HDL cholesterol and reducing coronary risks, but patients show low compliance with treatment due to severe facial flushing upon taking the drug. A series of bicyclic pyrazole carboxylic acids were synthesized and tested for their ability to activate the niacin receptor. One analog, 23, showed improved potency and lacked flushing at doses that effectively altered the lipid profile of rats.
Schmidt
Darby
D
Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co, Inc, Rahway, NJ 07065-0900, USA. darbyrschmidt@verizon.net
Smenton
Abigail
A
Raghavan
Subharekha
S
Carballo-Jane
Ester
E
Lubell
Silvi
S
Ciecko
Tanya
T
Holt
Tom G
TG
Wolff
Michael
M
Taggart
Andrew
A
Wilsie
Larissa
L
Krsmanovic
Mihajlo
M
Ren
Ning
N
Blom
Daniel
D
Cheng
Kang
K
McCann
Peggy E
PE
Gerard Waters
M
M
Tata
James
J
Colletti
Steven
S
D000818:Animals; D008076:Cholesterol, HDL / Q000378:metabolism; D050171:Dyslipidemias / Q000188:drug therapy*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009525:Niacin / Q000737:chemistry / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism
D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D018722:Nicotinic Agonists; D011720:Pyrazoles; D043562:Receptors, G-Protein-Coupled; D009525:Niacin