Discovery of 4-(phenyl)thio-1H-pyrazole derivatives as agonists of GPR109A, a high affinity niacin receptor

Archives of Pharmacal Research

Volumn 38, Issue 6, 2015, Pages 1019-1032

  Kim, Hyeon Young ^a   Jadhav, Vithal B ^a   Jeong, Dae Young ^a   Park, Woo Kyu ^a   Song, Jong Hwan ^a   Lee, Sunkyung ^a,b   Cho, Heeyeong ^a,b  

^a Korea Research Institute of Chemical Technology   (South Korea)

^b University of Science and Technology (UST)   (South Korea)

Author keywords

4 (Phenylthio) 1H pyrazole; Biased agonist; G protein; GPR109A; Niacin; Arrestin

Indexed keywords

1 (PYRIDIN 3 YL)CARBONYL 4 [(2 BROMOPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 1 (PYRIDIN 3 YL)CARBONYL 4 [(2 CHLOROPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 1 (PYRIDIN 3 YL)CARBONYL 4 [(3,5 DICHLOROPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 1 (PYRIDIN 3 YL)CARBONYL 4 [(4 BROMOPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 1 (PYRIDIN 3 YL)CARBONYL 4 [(4 CHLOROPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 3 [(2 BROMOPHENYL)THIO]PENTANE 2,4 DIONE; 3 [(2 CHLOROPHENYL)THIO]PENTANE 2,4 DIONE; 3 [(4 ACETAMIDOPHENYL)THIO]PENTANE 2,4 DIONE; 3 [(4 BROMOPHENYL)THIO]PENTANE 2,4 DIONE; 3 [(4 CHLOROPHENYL)THIO]PENTANE 2,4 DIONE; 3 [[4 (DICHLORO)PHENYL]THIO]PENTANE 2,4 DIONE; 4 (PHENYL)THIO 1H PYRAZOLE DERIVATIVE; 4 (PHENYLTHIO) 5 METHYL 3 PHENYL 1H PYRAZOLE; 4 [(2 BROMOPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 4 [(2 BROMOPHENYL)THIO] 5 METHYL 3PHENYL 1H PYRAZOLE; 4 [(2 CHLOROPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 4 [(2 CHLOROPHENYL)THIO] 5 METHYL 3 PHENYL 1H PYRAZOLE; 4 [(3,5 DICHLOROPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 4 [(3,5 DICHLOROPHENYL)THIO] 5 METHYL 3 PHENYL 1H PYRAZOLE; 4 [(4 ACETAMIDOPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 4 [(4 BROMOPHENYL)THIO] 5 METHYL 3 PHENYL 1H PYRAZOLE; 4 [(4 CHLOROPHENYL)THIO] 3,5 DIMETHYL 1H PYRAZOLE; 4 [[4 (TERT BUTYL)PHENYL]THIO] 3,5 DIMETHYL 1H PYRAZOLE; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; ANTILIPEMIC AGENT; GPR109A RECEPTOR; NICOTINIC ACID; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; BETA ARRESTIN; BETA LACTAMASE; CYCLOHEXANECARBOXYLIC ACID DERIVATIVE; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; G PROTEIN COUPLED RECEPTOR; HCAR2 PROTEIN, HUMAN; MK 6892; NICOTINIC AGENT; NICOTINIC RECEPTOR; OXADIAZOLE DERIVATIVE; RETINA S ANTIGEN;

ARTICLE; BINDING AFFINITY; BIOLOGICAL ACTIVITY; CALCIUM MOBILIZATION; CALCIUM MOBILIZATION ASSAY; CHO CELL LINE; CONTROLLED STUDY; CYCLOADDITION; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG SYNTHESIS; EC50; HUMAN; IMAGE ANALYSIS; LIPOLYSIS; VASODILATATION; AGONISTS; ANIMAL; CALCIUM SIGNALING; CHEMISTRY; CRICETULUS; DRUG EFFECTS; HAMSTER; HIGH THROUGHPUT SCREENING; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANIMALS; ARRESTINS; BETA-LACTAMASES; CALCIUM SIGNALING; CHO CELLS; CRICETINAE; CRICETULUS; CYCLOHEXANECARBOXYLIC ACIDS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INDICATORS AND REAGENTS; NIACIN; NICOTINIC AGONISTS; OXADIAZOLES; PYRAZOLES; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NICOTINIC; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84930865932     PISSN: 02536269     EISSN: 19763786     Source Type: Journal    
DOI: 10.1007/s12272-015-0560-4     Document Type: Article

References (25)

1. Altschul, R., A. Hoffer, and J.D. Stephen. 1955. Influence of nicotinic acid on serum cholesterol in man. Archives of Biochemistry and Biophysics 54: 558-559.
2. Benyo, Z., A. Gille, J. Kero, M. Csiky, M.C. Suchankova, R.M. Nusing, A. Moers, K. Pfeffer, and S. Offermanns. 2005. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. Journal of Clinical Investigation 115: 3634-3640.
3. Boatman, P.D., B. Lauring, T.O. Schrader, M. Kasem, B.R. Johnson, P. Skinner, J.-K. Jung, J. Xu, M.C. Cherrier, P.J. Webb, G. Semple, C.R. Sage, J. Knudsen, R. Chen, W.-L. Luo, L. Caro, J. Cote, E. Lai, J. Wagner, A.K. Taggart, E. Carballo-Jane, M. Hammond, S.L. Colletti, J.R. Connolly, M.G. Waters, and J.G. Richman. 2012. (1aR,5aR)1a,3,5,5a-Tetrahydro-1H-diaza-cyclopropa[a]pentalene-4-carboxylic acid (MK-1903): A potent GPR109A agonist that lowers free fatty acids in humans. Journal of Medicinal Chemistry 55: 3644-3666.
4. Carlson, L.A. 2005. Nicotinic acid: The broad-spectrum lipid drug. A 50th anniversary review. Journal of Internal Medicine 258: 94-114.
5. Deng, Q., J.L. Frie, D.M. Marley, R.T. Beresis, N. Ren, T.-Q. Cai, A.K.P. Taggart, K. Cheng, E. Carballo-Jane, J. Wang, X. Tong, M.G. Waters, J.R. Tata, and S.L. Colletti. 2008. Molecular modeling aided design of nicotinic acid receptor GPR109A agonists. Bioorganic and Medicinal Chemistry Letters 18: 4963-4967.
6. Eaton, R.P., M. Berman, and D. Steinberg. 1969. Kinetic studies of plasma free fatty acid and triglyceride metabolism in man. Journal of Clinical Investigation 48: 1560-1579.
7. Gaidarov, I., X. Chen, T. Anthony, D. Maciejewski-Lenoir, C. Liaw, and D.J. Unett. 2013. Differential tissue and ligand-dependent signaling of GPR109A receptor: Implications for anti-atherosclerotic therapeutic potential. Cellular Signaling 25: 2003-2016.
8. Ganji, S.H., S. Tavintharan, D. Zhu, Y. Xing, V.S. Kamanna, and M.L. Kashyap. 2004. Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. Journal of Lipid Research 45: 1835-1845.
9. Hanson, J., A. Gille, S. Zwykiel, M. Lukasova, B.E. Clausen, K. Ahmed, S. Tunaru, A. Wirth, and S. Offermanns. 2010. Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. Journal of Clinical Investigation 120: 2910-2919.
10. Jung, J.-K., B.R. Johnson, T. Duong, M. Decaire, J. Uy, T. Gharbaoui, P.D. Boatman, C.R. Sage, R. Chen, J.G. Richman, D.T. Connolly, and G. Semple. 2007. Analogues of acifran: Agonists of the high and low affinity niacin receptors, GPR109a and GPR109b. Journal of Medicinal Chemistry 50: 1445-1448.
11. Kunapuli, P., R. Ransom, K.L. Murphy, D. Pettibone, J. Kerby, S. Grimwood, P. Zuck, P. Hodder, R. Lacson, I. Hoffman, J. Inglese, and B. Strulovici. 2003. Development of an intact cell reporter gene beta-lactamase assay for G protein-coupled receptors for high-throughput screening. Analytical Biochemistry 314: 16-29.
12. Lai, E., M.G. Waters, J.R. Tata, W. Radziszewski, I. Perevozskaya, W. Zheng, L. Wenning, D.T. Connolly, G. Semple, A.O. Johnson-Levonas, J.A. Wagner, Y. Mitchel, and J.F. Paolini. 2008. Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans. Journal of Clinical Lipidology 2: 375-383.
13. Le Goff, W., M. Guerin, and M.J. Chapman. 2004. Pharmacological modulation of cholesteryl ester transfer protein, a new therapeutic target in atherogenic dyslipidemia. Pharmacology and Therapeutics 101: 17-38.
14. Li, G., Y. Shi, H. Huang, Y. Zhang, K. Wu, J. Luo, Y. Sun, J. Lu, J.L. Benovic, and N. Zhou. 2010. Internalization of the human nicotinic acid receptor GPR109A is regulated by G(i), GRK2, and arrestin3. Journal of Biological Chemistry 285: 22605-22618.
15. Muhammad, A.R., N. Rasool, M. Adeel, H. Reinke, C. Fischer, and P. Langer. 2008. Synthesis and functionalized diaryl sulfides based on regioselective one-pot cyclization of 1,3-bis(trimethylsilyloxy)-1,3-butadienes. Tetrahedron 64: 3782-3793.
16. Offermanns, S. 2006. The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends in Pharmacological Sciences 27: 384-390.
17. Palani, A., A.U. Rao, X. Chen, X. Huang, J. Su, H. Tang, Y. Huang, J. Qin, D. Xiao, S. Degrado, M. Sofolarides, X. Zhu, Z. Liu, B. Mckittrick, W. Zhou, R. Aslania, W.J. Greenlee, M. Senior, B. Cheewatrakoolpong, H. Zhang, C. Farley, J. Cook, S. Kurowski, Q. Li, M. Heek, G. Wang, Y. Hsieh, F. Li, S. Greenfeder, and M. Chintala. 2012. Discovery of SCH 900271, a potent nicotinic acid receptor agonist for the treatment of dyslipidemia. ACS Medicinal Chemistry Letters 3: 63-68.
18. Parsons Jr., W.B., and J.H. Flinn. 1959. Reduction of serum cholesterol levels and beta-lipoprotein cholesterol levels by nicotinic acid. AMA Archives of Internal Medicine 103: 783-790.
19. Richman, J.G., M. Kanemitsu-Parks, I. Gaidarov, J.S. Cameron, P. Griffin, H. Zheng, N.C. Guerra, L. Cham, D. Maciejewski-Lenoir, D.P. Behan, D. Boatman, R. Chen, P. Skinner, P. Ornelas, M.G. Waters, S.D. Wright, G. Semple, and D.T. Connolly. 2007. Nicotinic acid receptor agonists differentially activate downstream effectors. Journal of Biological Chemistry 282: 18028-18036.
20. Shen, H.C., F.X. Ding, S. Raghavan, Q. Deng, S. Luell, M.J. Forrest, E. Carballo-Jane, L.C. Wilsie, M.L. Krsmanovic, A.K. Taggart, K.K. Wu, T.J. Wu, K. Cheng, N. Ren, T.Q. Cai, Q. Chen, J. Wang, M.S. Wolff, X. Tong, T.G. Holt, M.G. Waters, M.L. Hammond, J.R. Tata, and S.L. Colletti. 2010. Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): A potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate. Journal of Medicinal Chemistry 53: 2666-2670.
21. Soga, T., M. Kamohara, J. Takasaki, S. Matsumoto, T. Saito, T. Ohishi, H. Hiyama, A. Matsuo, H. Matsushime, and K. Furuichi. 2003. Molecular identification of nicotinic acid receptor. Biochemical and Biophysical Research Communications 303: 364-369.
22. Soudijn, W., I. Wijngaarden, and A.P. Izerman. 2007. Nicotinic acid receptor subtypes and their ligands. Medicinal Research Reviews 27: 417-433.
23. Tunaru, S., J. Kero, A. Schaub, C. Wufka, A. Blaukat, K. Pfeffer, and S. Offermanns. 2003. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nature Medicine 9: 352-355.
24. Walters, R.W., A.K. Shukla, J.J. Kovacs, J.D. Violin, S.M. DeWire, C.M. Lam, J.R. Chen, M.J. Muehlbauer, E.J. Whalen, and R.J. Lefkowitz. 2009. Beta-arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. Journal of Clinical Investigation 119: 1312-1321.
25. Wise, A., S.M. Foord, N.J. Fraser, A.A. Barnes, N. Elshourbagy, M. Eilert, D.M.P. Ignar, R. Murdock, K. Steplewski, A. Green, A.J. Brown, S.J. Dowell, P.G. Szekeres, D.G. Hassall, F.H. Marshall, S. Wilson, and N.B. Pike. 2003. Molecular identification of high and low affinity receptors for nicotinic acid. Journal of Biological Chemistry 278: 9869-9874.