Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator

Journal of Steroid Biochemistry and Molecular Biology

Volumn 134, Issue 1, 2013, Pages 51-58

  Zhang, Xuqing ^a   Allan, George F ^a   Tannenbaum, Pamela ^a   Sbriscia, Tifanie ^a   Linton, Olivia ^a   Lai, Muh Tsann ^a   Haynes Johnson, Donna ^a   Bhattacharjee, Sheela ^a   Lundeen, Scott G ^a   Sui, Zhihua ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

Levator ani; Prostate; Selective androgen receptor modulator; Sexual behavior

Indexed keywords

ESTROGEN; GESTAGEN; GLUCOCORTICOID; GONADOTROPIN; IMIDAZOLOPYRAZOLE; SELECTIVE ANDROGEN RECEPTOR MODULATOR; TESTOSTERONE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG SCREENING; DRUG SYNTHESIS; FEMALE; IN VITRO STUDY; LEVATOR ANI MUSCLE; MALE; NONHUMAN; PHENOTYPE; PROSTATE VENTRAL LOBE; RAT; SEXUAL BEHAVIOR; STRUCTURE ACTIVITY RELATION;

ANDROGEN ANTAGONISTS; ANDROGENS; ANIMALS; BODY WEIGHT; CELL LINE; FEMALE; HORMONES; MALE; MICE; MUSCLES; ORCHIECTOMY; OVARIECTOMY; PROSTATE; PYRAZOLES; RATS; RATS, LONG-EVANS; RECEPTORS, ANDROGEN; SEXUAL BEHAVIOR, ANIMAL;

RATTUS;

EID: 84869108953     PISSN: 09600760     EISSN: 18791220     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2012.10.015     Document Type: Article

References (51)

1. A.D. Mooradian, J.E. Morley, and S.G. Korenman Biological actions of androgens Endocrine Reviews 8 1987 1 28
2. C.J. Bagatell, and W.J. Bremner Androgens in men: uses and abuses New England Journal of Medicine 334 1996 707 714
3. C.D. Liverman, and D.G. Blazer Testosterone and Aging: Clinical Research Directions, Institute of Medicine Report 2004 Natl. Acad. Press Washington, DC
4. Male hypogonadism M.H. Beers, and R.R. Berkow The Merck Manual of Diagnosis and Therapy 17th ed. 2003 Merck Whitehouse Station
5. T.H. Diamond Pharmacotherapy of osteoporosis in men Expert Opinion on Pharmacotherapy 6 2005 45 58
6. D.A. Gruenwald, and A.M. Matsumoto Testosterone supplementation therapy for older men: potential benefits and risks Journal of the American Geriatrics Society 51 2003 101 115 (Pubitemid 36119943)
7. W. Somboonporn, S. Davis, M.W. Seif, and R. Bell Testosterone for peri- and postmenopausal women Cochrane Database of Systematic Reviews 2005 CD004509
8. J.R. Heiman Treating low sexual desire: new findings for testosterone in women New England Journal of Medicine 359 2008 2047 2049
9. S. Davis Androgen replacement in women: a commentary Journal of Clinical Endocrinology and Metabolism 84 1999 1886 1891 (Pubitemid 30647004)
10. M.L. Mohler, C.E. Bohl, A. Jones, C.C. Coss, R. Narayanan, Y. He, D.J. Hwang, J.T. Dalton, and D.D. Miller Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit Journal of Medicinal Chemistry 52 2009 3597 3617
11. D. Yin, W. Gao, J.D. Kearbey, H. Xu, K. Chung, Y. He, C.A. Marhefka, K.A. Veverka, D.D. Miller, and J.T. Dalton Pharmacodynamics of selective androgen receptor modulators Journal of Pharmacology and Experimental Therapeutics 304 2003 1334 1340 (Pubitemid 36254449)
12. W. Gao, P.J. Reiser, C.C. Coss, M.A. Phelps, J.D. Kearbey, D.D. Miller, and J.T. Dalton Selective androgen receptor modulator (SARM) treatment improves muscle strength and body composition, and prevents bone loss in orchidectomized rats Endocrinology 146 2005 4887 4897 (Pubitemid 41446627)
13. K. Hanada, K. Furuya, N. Yamamoto, H. Nejishima, K. Ichikawa, T. Nakamura, M. Miyakawa, S. Amano, Y. Sumita, and N. Oguro Bone anabolic effects of S-40503 a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis Biological and Pharmaceutical Bulletin 26 2003 1563 1569 (Pubitemid 41699636)
14. J.N. Miner, W. Chang, M.S. Chapman, P.D. Finn, M.H. Hong, F.J. Lopez, K.B. Marschke, J. Rosen, W. Schrader, R. Turner, A. van Oeveren, H. Vivero, L. Zhi, and A. Negro-Vilar An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate Endocrinology 148 2007 363 373 (Pubitemid 46021469)
15. E.G. Vajda, F.J. Lopez, P. Rix, R. Hill, Y. Chen, K.-J. Lee, Z. O'Brien, W.Y. Chang, M.D. Meglasson, and Y.-H Lee Pharmacokinetics and pharmacodynamics of LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2- f]quinolin-7(6H)-one], an orally available nonsteroidal-selective androgen receptor modulator Journal of Pharmacology and Experimental Therapeutics 328 2009 663 670
16. J.N. Miner, W. Chang, M.S. Chapman, P.D. Finn, M. Hong, F.J. Lopez, K.B. Marschke, J. Rosen, W. Schrader, R. Turner, A. van Oeveren, H. Viveros, L. Zhi, and A. Negro-Vilar An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate Endocrinology 148 2007 363 373 (Pubitemid 46021469)
17. J. Ostrowski, J.E. Kuhns, J.A. Lupisella, M.C. Manfredi, B.C. Beehler, S.R. Krystek Jr., Y. Bi, C. Sun, R. Seethala, R. Golla, P.G. Sleph, A. Fura, Y. An, K.F. Kish, J.S. Sack, K.A. Mookhtiar, G.J. Grover, L.G. Hamann, and Pharmacological X-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats Endocrinology 148 2007 4 12 (Pubitemid 46023448)
18. G.F. Allan, P. Tannenbaum, T. Sbriscia, O. Linton, M.-T. Lai, D. Haynes-Johnson, S. Bhattacharjee, X. Zhang, Z. Sui, and S.G. Lundeen A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats Endocrine 32 2007 41 51 (Pubitemid 350242546)
19. G.F. Allan, T. Sbriscia, O. Linton, M.-T. Lai, D. Haynes-Johnson, S. Bhattacharjee, R. Ng, Z. Sui, and S.G. Lundeen A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats Journal of Steroid Biochemistry and Molecular Biology 110 2008 207 213
20. A. Schmidt, D.B. Kimmel, C. Bai, A. Scafonas, S. Rutledge, R.L. Vogel, S. McElwee-Witmer, F. Chen, P.V. Nantermet, V. Kasparcova, C. Leu, H.-Z. Zhang, M.E. Duggan, M.A. Gentile, P. Hodor, B. Pennypacker, P. Masarachia, E.E. Opas, S.A. Adamski, T.E. Cusick, J. Wang, H.J. Mitchell, Y. Kim, T. Prueksaritanont, J.J. Perkins, R.S. Meissner, G.D. Hartman, L.P. Freedman, S. Harada, and W.J. Ray Discovery of the selective androgen receptor modulator MK-0773 using a rational development strategy based on differential transcriptional requirements for androgenic anabolism versus reproductive physiology Journal of Biological Chemistry 285 2010 17054 17064
21. C.P. Miller, M. Shomali, C.R. Lyttle, L.S.L. O'Dea, H. Herendeen, K. Gallacher, D. Paquin, D.R. Compton, B. Sahoo, S.A. Kerrigan, M.S. Burge, M. Nickels, J.L. Green, J.A. Katzenellenbogen, A. Tchesnokov, and G. Hattersley Design, synthesis, and preclinical characterization of the selective androgen receptor modulator (SARM) RAD140 ACS Medicinal Chemistry Letters 2 2011 124 129
22. F. Piu, L.R. Gardell, T. Son, N. Schlienger, B.W. Lund, H.H. Schiffer, K.E. Vanover, R.E. Davis, R. Olsson, and S.R. Bradley Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator The Journal of Steroid Biochemistry and Molecular Biology 109 2008 129 137
23. N. Schlienger, B.W. Lund, J. Pawlas, F. Badalassi, F. Bertozzi, R. Lewinsky, A. Fejzic, M.B. Thygesen, A. Tabatabaei, S.B. Bradley, R. Stefania, L.R. Gardell, F. Piu, and R. Olsson Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators Journal of Medicinal Chemistry 52 2009 7186 7191
24. A. Jones, D. Hwang, C.B. Duke III, Y. He, A. Siddam, D.D. Miller, and J.T. Dalton Nonsteroidal selective androgen receptor modulators enhance female sexual motivation Journal of Pharmacology and Experimental Therapeutics 334 2010 439 448
25. A.E. Kudwa, F.J. Lopez, R.F. McGivern, and R.J. Handa A selective androgen receptor modulator enhances male-directed sexual preference, proceptive behavior, and lordosis behavior in sexually experienced, but not sexually naive, female rats Endocrinology 15 2010 2659 2668
26. G. Allan, M.-T. Lai, T. Sbriscia, O. Linton, D. Haynes-Johnson, S. Bhattacharjee, R. Dodds, J. Fiordeliso, J. Lanter, Z. Sui, and S. Lundeen A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy induced bone loss in rats Journal of Steroid Biochemistry and Molecular Biology 103 2007 76 84
27. J.C. Lanter, J.J. Fiordeliso, G.F. Allan, A. Musto, D. Hahn, and Z. Sui A bioisosteric approach to the discovery of indole carbinol androgen receptor ligands Bioorganic and Medicinal Chemistry Letters 16 2006 5646 5649 (Pubitemid 44415444)
28. J. Lanter, J.J. Fiordeliso, W. Jiang, G.F. Allan, M. Lai, D. Hahn, S.G. Lundeen, and Z. Sui The discovery of a potent orally efficacious indole androgen receptor antagonist through in vivo screening Bioorganic and Medicinal Chemistry Letters 17 2007 123 126 (Pubitemid 44959980)
29. J.C. Lanter, J.J. Fiordeliso, V.C. Alford, X. Zhang, K. Wells, R.K. Russell, G.F. Allan, M. Lai, O. Linton, S. Lundeen, and Z. Sui β-Alkylthio indolyl carbinols: potent nonsteroidal antiandrogens with oral efficacy in prostate cancer models Bioorganic and Medicinal Chemistry Letters 17 2007 2545 2548 (Pubitemid 46507777)
30. R.A. Ng, J. Guan, V.C. Alford Jr., J.C. Lanter, G. Allan, T. Sbriscia, O. Linton, and Z. Sui Synthesis SAR of potent and selective androgen receptor antagonists: 5,6-dichloro-benzimidazole derivatives Bioorganic and Medicinal Chemistry Letters 17 2007 784 788 (Pubitemid 46127638)
31. R.A. Ng, J. Guan, V.C. Alford Jr., J.C. Lanter, G. Allan, T. Sbriscia, S. Lundeen, and Z. Sui 2-(2,2,2-Trifluoroethyl)-5,6-dichlorobenzimidazole derivatives as potent androgen receptor antagonists Bioorganic and Medicinal Chemistry Letters 17 2007 955 958 (Pubitemid 46188530)
32. R.A. Ng, J. Lanter, V.C. Alford, G.F. Allan, T. Sbriscia, S. Lundeen, and Z. Sui Synthesis of potent and tissue-selective androgen receptor modulators (SARMs): 2-(2,2,2)-trifluoroethyl-benzimidazole scaffold Bioorganic and Medicinal Chemistry Letters 17 2007 1784 1787
33. X. Zhang, X. Li, G. Allan, A. Musto, S.G. Lundeen, and Z. Sui Discovery of indolecontaining tetracycles as a new scaffold for androgen receptor ligands Bioorganic and Medicinal Chemistry Letters 16 2006 3233 3237 (Pubitemid 44287962)
34. X. Zhang, X. Li, G.F. Allan, T. Sbriscia, O. Linton, S.G. Lundeen, and Z. Sui Synthesis SAR of novel hydantoin derivatives as selective androgen receptormodulators Bioorganic and Medicinal Chemistry Letters 16 2006 5763 5766 (Pubitemid 44486745)
35. X. Zhang, X. Li, G.F. Allan, T. Sbriscia, O. Linton, S.G. Lundeen, and Z. Sui Serendipitous discovery of novel imidazolopyrazole scaffold as selective androgen receptor modulators Bioorganic and Medicinal Chemistry Letters 17 2007 439 443 (Pubitemid 46073744)
36. X. Zhang, X. Li, G.F. Allan, T. Sbriscia, O. Linton, S.G. Lundeen, and Z. Sui Design, synthesis and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators Journal of Medicinal Chemistry 50 2007 3857 3869 (Pubitemid 47292049)
37. Y. Cheng, and W.H. Prusoff Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 percent inhibition (I50) of an enzymatic reaction Biochemical Pharmacology 22 1973 3099 3108
38. J.T. Wu, P. Zhang, M.E. Astill, L.W. Wilson, B.W. Lyons, L.L. Wu, and R. Stephenson PSA immunoreactivity detected in LNCaP cell medium, breast tumor cytosol, and female serum Journal of Clinical Laboratory Analysis 9 1995 243 251
39. G.F. Allan, E. Lombardi, D. Haynes-Johnson, S. Palmer, M. Kiddoe, P. Kraft, C. Campen, P. Rybczynski, D.W. Combs, and A. Phillips Induction of a novel conformation in the progesterone receptor by ZK299 involves a defined region of the carboxyl-terminal tail Molecular Endocrinology 10 1996 1206 1213 (Pubitemid 26330953)
40. W. Jiang, J.J. Fiordeliso, G. Allan, O. Linton, P. Tannenbaum, J. Xu, P. Zhu, J. Gunnet, K. Demarest, S. Lundeen, and Z. Sui Discovery of novel phosphorus-containing steroids as selective glucocorticoid receptor antagonist Bioorganic and Medicinal Chemistry Letters 17 2007 1471 1474
41. M.S. Erskine Solicitation behavior in the estrous female rat: a review Hormones and Behavior 23 1989 473 502 (Pubitemid 20028502)
42. J.S. Sack, K.F. Kish, C. Wang, R.M. Attar, S.E. Kiefer, Y. An, G.Y. Wu, J.E. Scheffler, M.E. Salvati, S.R. Krystek Jr., R. Weinmann, and H.M. Einspah Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone Proceedings of the National Academy of Sciences of the United States of America 98 2001 4904 4909 (Pubitemid 32397055)
43. L.G. Hershberger, E.G. Shipley, and R.K. Meyer Myotrophic activity of 19-nortestosterone and other steroids determined by modified levator ani muscle method Proceedings of the Society for Experimental Biology and Medicine 83 1953 175 180
44. J. Veldscholte, C.A. Berrevoets, C. Ris-Stalpers, G.G. Kuiper, G. Jenster, J. Trapman, A.O. Brinkmann, and E. Mulder The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens Journal of Steroid Biochemistry and Molecular Biology 41 1992 665 669
45. K. Yamasaki, S. Masakuni, N. Shoji, M. Takako, T. Saori, M. Hideo, S. Satoko, N. Makoto, and Y. Yoshikuni Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals Toxicology 195 2004 177 186 (Pubitemid 38125118)
46. W. Gao, J.D. Kearbey, V.A. Nair, K. Chung, A.F. Parlow, D.D. Miller, and J.T. Dalton Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia Endocrinology 145 2004 5420 5428 (Pubitemid 39564578)
47. J. Chen, D.J. Hwang, C.E. Bohl, D.D. Miller, and J.T. Dalton A selective androgen receptor modulator for hormonal male contraception Journal of Pharmacology and Experimental Therapeutics 312 2005 546 553 (Pubitemid 40189551)
48. A. Jones, J. Chen, D.J. Hwang, D.D. Miller, and J.T. Dalton Preclinical characterization of a (S)-N-(4-cyano-3-trifluoromethylphenyl)-3-(3-fluoro, 4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide: a selective androgen receptor modulator for hormonal male contraception Endocrinology 150 2009 385 395
49. F.H. De Jonge, and N.E. van de Poll On the involvement of progesterone in sexually rewarded choice behavior of the female rat Physiology and Behavior 37 1986 93 98 (Pubitemid 16121803)
50. D.A. Edwards, and J.K. Pfeifle Hormonal control of receptivity proceptivity and sexual motivation Physiology and Behavior 30 1983 437 443 (Pubitemid 13057267)
51. K. Wallen Desire and ability: hormones and the regulation of female sexual behavior Neuroscience and Biobehavioral Reviews 14 1990 233 241 (Pubitemid 20159559)