Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor

European Journal of Medicinal Chemistry

Volumn 108, Issue , 2016, Pages 505-528

  Lin, Wenwei ^a   Yang, Lei ^a   Chai, Sergio C ^a   Lu, Yan ^a   Chen, Taosheng ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

CINPA1; Constitutive androstane receptor; Inverse agonist; TR FRET

Indexed keywords

CLOTRIMAZOLE; CONSTITUTIVE ANDROSTANE RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR INVERSE AGONIST; ETHYL [ (5 DIETHYLGLYCYL) 10,11 DIHYDRO 5H DIBENZO[BF]AZEPIN 3 YL]CARBAMATE DERIVATIVE; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; BENZAZEPINE DERIVATIVE; CELL RECEPTOR; ETHYL (5-(DIETHYLGLYCYL)-10,11-DIHYDRO-5H-DIBENZO(B,F)AZEPIN-3-YL)CARBAMATE;

ARTICLE; BIOCHEMICAL ANALYSIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMAN; HUMAN CELL; IC50; MOLECULAR DOCKING; MOLECULAR MODEL; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; INVERSE AGONISM; METABOLISM; SYNTHESIS;

BENZAZEPINES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INVERSE AGONISM; HUMANS; MOLECULAR STRUCTURE; RECEPTORS, CYTOPLASMIC AND NUCLEAR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84952685060     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2015.12.018     Document Type: Article

References (54)

1. M. Banerjee, D. Robbins, T. Chen, Targeting xenobiotic receptors PXR and CAR in human diseases, Drug Discov. Today 20 (2015) 618-628.
2. M. Banerjee, D. Robbins, T. Chen, Modulation of xenobiotic receptors by steroids, Molecules 18 (2013) 7389-7406.
3. X. Chai, S. Zeng, W. Xie, Nuclear receptors PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond, Expert. Opin. Drug Metab. Toxicol. 9 (2013) 253-266.
4. Y.M. Wang, S.S. Ong, S.C. Chai, T. Chen, Role of CAR and PXR in xenobiotic sensing and metabolism, Expert. Opin. Drug Metab. Toxicol. 8 (2012) 803-817.
5. J.K. Lamba, Pharmacogenetics of the constitutive androstane receptor, Pharmacogenomics 9 (2008) 71-83.
6. M.T. Cherian, W. Lin, J. Wu, T. Chen, CINPA1 is an inhibitor of constitutive androstane receptor (CAR) that does not activate pregnane x receptor (PXR), Mol. Pharmacol. 87 (2015) 878-889.
7. J. Zhang, W. Huang, S.S. Chua, P. Wei, D.D. Moore, Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR, Science 298 (2002) 422-424.
8. A.A. Takwi, Y.M. Wang, J. Wu, M. Michaelis, J. Cinatl, T. Chen, miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells, Oncogene 33 (2014) 3717-3729.
9. K. Tamura, K. Inoue, M. Takahashi, S. Matsuo, K. Irie, Y. Kodama, T. Gamo, S. Ozawa, M. Yoshida, Involvement of constitutive androstane receptor in liver hypertrophy and liver tumor development induced by triazole fungicides, Food Chem. Toxicol. 78C (2015) 86-95.
10. Y. Sakamoto, K. Inoue, M. Takahashi, Y. Taketa, Y. Kodama, K. Nemoto, M. Degawa, T. Gamou, S. Ozawa, A. Nishikawa, M. Yoshida, Different pathways of constitutive androstane receptor-mediated liver hypertrophy and hepatocarcinogenesis in mice treated with piperonyl butoxide or decabromodiphenyl ether, Toxicol. Pathol. 41 (2013) 1078-1092.
11. W. Huang, J. Zhang, M. Washington, J. Liu, J.M. Parant, G. Lozano, D.D. Moore, Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor, Mol. Endocrinol. 19 (2005) 1646-1653.
12. Y. Kanno, M. Suzuki, Y. Miyazaki, M. Matsuzaki, T. Nakahama, K. Kurose, J. Sawada, Y. Inouye, Difference in nucleocytoplasmic shuttling sequences of rat and human constitutive active/androstane receptor, Biochim. Biophys. Acta 1773 (2007) 934-944.
13. D.J. Kojetin, T.P. Burris, Small molecule modulation of nuclear receptor conformational dynamics: implications for function and drug discovery, Mol. Pharmacol. 83 (2013) 1-8.
14. Y.E. Timsit, M. Negishi, CAR and PXR: the xenobiotic-sensing receptors, Steroids 72 (2007) 231-246.
15. H. Jinno, T. Tanaka-Kagawa, N. Hanioka, S. Ishida, M. Saeki, A. Soyama, M. Itoda, T. Nishimura, Y. Saito, S. Ozawa, M. Ando, J. Sawada, Identification of novel alternative splice variants of human constitutive androstane receptor and characterization of their expression in the liver, Mol. Pharmacol. 65 (2004) 496-502.
16. F.A. Carazo, T. Smutny, L. Hyrsova, K. Berka, P. Pavek, Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR), Toxicol. Lett. 233 (2015) 68-77.
17. L.B. Moore, D.J. Parks, S.A. Jones, R.K. Bledsoe, T.G. Consler, J.B. Stimmel, B. Goodwin, C. Liddle, S.G. Blanchard, T.M. Willson, J.L. Collins, S.A. Kliewer, Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands, J. Biol. Chem. 275 (2000) 15122-15127.
18. M.A. Di, M.E. De, P. Ascenzi, M. Marino, Nuclear receptors CAR and PXR: molecular, functional, and biomedical aspects, Mol. Asp. Med. 30 (2009) 297-343.
19. L.B. Moore, J.M. Maglich, D.D. McKee, B. Wisely, T.M. Willson, S.A. Kliewer, M.H. Lambert, J.T. Moore, Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors, Mol. Endocrinol. 16 (2002) 977-986.
20. J. Jyrkkarinne, B. Windshugel, J. Makinen, M. Ylisirnio, M. Perakyla, A. Poso, W. Sippl, P. Honkakoski, Amino acids important for ligand specificity of the human constitutive androstane receptor, J. Biol. Chem. 280 (2005) 5960-5971.
21. A.M. Dring, L.E. Anderson, S. Qamar, M.A. Stoner, Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoformspecific nuclear receptor ligands, Chem. Biol. Interact. 188 (2010) 512-525.
22. F. Molnar, J. Kublbeck, J. Jyrkkarinne, V. Prantner, P. Honkakoski, An update on the constitutive androstane receptor (CAR), Drug Metabol. Drug Interact. 28 (2013) 79-93.
23. W. Huang, J. Zhang, P. Wei, W.T. Schrader, D.D. Moore, Meclizine is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for human CAR, Mol. Endocrinol. 18 (2004) 2402-2408.
24. A.J. Lau, G. Yang, G. Rajaraman, C.C. Baucom, T.K. Chang, Differential effect of meclizine on the activity of human pregnane X receptor and constitutive androstane receptor, J. Pharmacol. Exp. Ther. 336 (2011) 816-826.
25. J. Kublbeck, J. Jyrkkarinne, F. Molnar, T. Kuningas, J. Patel, B. Windshugel, T. Nevalainen, T. Laitinen, W. Sippl, A. Poso, P. Honkakoski, New in vitro tools to study human constitutive androstane receptor (CAR) biology: discovery and comparison of human CAR inverse agonists, Mol. Pharm. 8 (2011) 2424-2433.
26. Y. Kanno, N. Tanuma, A. Takahashi, Y. Inouye, TO901317, a potent LXR agonist, is an inverse agonist of CAR, J. Toxicol. Sci. 38 (2013) 309-315.
27. Y. Kanno, N. Tanuma, T. Yatsu, W. Li, K. Koike, Y. Inouye, Nigramide J is a novel potent inverse agonist of the human constitutive androstane receptor, Pharmacol. Res. Perspect. 2 (2014) 2.
28. M.J. Zamek-Gliszczynski, M.A. Mohutsky, J.L. Rehmel, A.B. Ke, Investigational small-molecule drug selectively suppresses constitutive CYP2B6 activity at the gene transcription level: physiologically based pharmacokinetic model assessment of clinical drug interaction risk, Drug Metab. Dispos. 42 (2014) 1008-1015.
29. Y.P. Lim, C.H. Cheng, W.C. Chen, S.Y. Chang, D.Z. Hung, J.J. Chen, L. Wan, W.C. Ma, Y.H. Lin, C.Y. Chen, T. Yokoi, M. Nakajima, C.J. Chen, Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity, Arch. Toxicol. 89 (2015) 57-72.
30. Y. Wang, L. Wang, M. Hu, Y. Li, S. Wang, Q. Ding, D. Hu, H. Yang, J. Zhao, L. Zhang, Y. Li, Method for synthesis of 5-acetyl-3-chloroiminodibenzyl, C.N. Patent 102010349A, April 13, 2011.
31. A. Stark, H. Wunderlich, H. Ehben, R. Mueller, E. Oestreich, W. Kuehne, Preparation of 3-carbethoxyamino-5-dimethylaminoacetyl-10, 11-dihydro- 5H-dibenzo[b, f]azepine and its hydrochloride, D.D. Patent 293346A5, August 29, 1991.
32. H. Wunderlich, A. Stark, E. Carstens, D. Lohmann, A.N. Gritsenko, A.P. Skoldinov, New derivatives of 10, 11-dihydro-5H-dibenz[b, f]azepine with antiarrhythmic efficacy, Pharmazie 40 (1985) 827-830.
33. E. Honda, Y. Ishichi, E. Kimura, M. Yoshikawa, N. Kanzaki, H. Nakagawa, Y. Terao, A. Suzuki, T. Kawai, Y. Arakawa, H. Ohta, J. Terauchi, Design, synthesis, and biological activities of 1-aryl-1, 4-diazepan-2-one derivatives as novel triple reuptake inhibitors, Bioorg. Med. Chem. Lett. 24 (2014) 3898-3902.
34. K. Ikegashira, T. Oka, S. Hirashima, S. Noji, H. Yamanaka, Y. Hara, T. Adachi, J. Tsuruha, S. Doi, Y. Hase, T. Noguchi, I. Ando, N. Ogura, S. Ikeda, H. Hashimoto, Discovery of conformationally constrained tetracyclic compounds as potent hepatitis C virus NS5B RNA polymerase inhibitors, J. Med. Chem. 49 (2006) 6950-6953.
35. D.B. Guthrie, S.J. Geib, D.P. Curran, Synthesis of highly enantioenriched 3, 4- dihydroquinolin-2-ones by 6-exo-trig radical cyclizations of axially chiral alpha-halo-ortho-alkenyl anilides, J. Am. Chem. Soc. 131 (2009) 15492-15500.
36. O. Hromatka, M. Knollmueller, K.A. Maior, F. Gotschy, 1- Acetylaminoanthraquinones with basic substituents, Monatsh. Chem. (1969) 1393-1399.
37. P.J. Flor, A. Marzinzik, J. Nozulak, S. Ofner, B. Roy, C. Spanka, Preparation of substituted diamines as mGluR7 regulators, W.O. Patent 2007025709A2 March 8, 2007.
38. H.Y. Song, M.H. Ngai, Z.Y. Song, P.A. MacAry, J. Hobley, M.J. Lear, Practical synthesis of maleimides and coumarin-linked probes for protein and antibody labelling via reduction of native disulfides, Org. Biomol. Chem. 7 (2009) 3400-3406.
39. T. Muto, T. Tanaka, H. Maruoka, S. Imajo, Y. Tomimori, K. Sato, T. Yagi, Preparation of 1, 4-diazepane-3, 5-dione derivatives as chymase inhibitors and pharmaceutical use thereof, W.O. Patent 2007139230A1 December 6, 2007.
40. A. Kathuria, N. Priya, K. Chand, P. Singh, A. Gupta, S. Jalal, S. Gupta, H.G. Raj, S.K. Sharma, Substrate specificity of acetoxy derivatives of coumarins and quinolones towards Calreticulin mediated transacetylation: investigations on antiplatelet function, Bioorg. Med. Chem. 20 (2012) 1624-1638.
41. A.G. Sams, G.K. Mikkelsen, M. Larsen, M. Langgard, M.E. Howells, T.J. Schroder, L.T. Brennum, L. Torup, E.B. Jorgensen, C. Bundgaard, M. Kreilgard, B. Bang- Andersen, Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3, 3-dimethylbutyrylamino)- 3, 5-difluoro-benzoylimino]-thiazol-3-ylmethyl} ester (Lu AA47070): a phosphonooxymethylene prodrug of a potent and selective hA(2A) receptor antagonist, J. Med. Chem. 54 (2011) 751-764.
42. X. Zheng, P. Bauer, T. Baumeister, A.J. Buckmelter, M. Caligiuri, K.H. Clodfelter, B. Han, Y.C. Ho, N. Kley, J. Lin, D.J. Reynolds, G. Sharma, C.C. Smith, Z. Wang, P.S. Dragovich, A. Oh, W. Wang, M. Zak, J. Gunzner-Toste, G. Zhao, P.W. Yuen, K.W. Bair, Structure-based identification of ureas as novel nicotinamide phosphoribosyltransferase (Nampt) inhibitors, J. Med. Chem. 56 (2013) 4921-4937.
43. P.A. Gale, J.R. Hiscock, N. Lalaoui, M.E. Light, N.J. Wells, M. Wenzel, Benzimidazole- based anion receptors: tautomeric switching and selectivity, Org. Biomol. Chem. 10 (2012) 5909-5915.
44. J. Dietrich, C. Hulme, L.H. Hurley, The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec, Nexavar, and BIRB-796, Bioorg. Med. Chem. 18 (2010) 5738-5748.
45. S.H. Kim, J.H. Bok, J.H. Lee, I.H. Kim, S.W. Kwon, G.B. Lee, S.K. Kang, J.S. Park, W.H. Jung, H.Y. Kim, S.D. Rhee, S.H. Ahn, M.A. Bae, D.C. Ha, K.Y. Kim, J.H. Ahn, Synthesis and biological evaluation of cyclic sulfamide derivatives as 11betahydroxysteroid dehydrogenase 1 inhibitors, ACS Med. Chem. Lett. 3 (2012) 88-93.
46. X. Chen, R. Duvadie, T. Harrison, Q. Liu, J.Y.C. Mao, S. Patel, F. Zecri, Preparation of tetrahydropyran compounds as DGAT1 inhibitors, W.O. Patent 2013163508A1, October 31, 2013.
47. T.P. Prakash, E.E. Swayze, W.F. Lima, G.A. Kinberger, Antisense oligonucleotide-conjugate complexes for diagnostic and therapeutic use, W.O. Patent 2013033230A1, March 7, 2013.
48. W.M. Seganish, M.E. Mowery, S. Riggleman, P. DeShong, Palladium-catalyzed homocoupling of aryl halides in the presence of fluoride, Tetrahedron 61 (2005) 2117-2121.
49. H. Foks, A. Czarnocka-Janowicz, W. Rudnicka, H. Trzeciak, Synthesis of new 5- substituted 1, 2, 4-triazole-3-thione derivatives, Phosphorus Sulfur Silicon Relat. Elem. 164 (2000) 67-81.
50. X. Guo, Q. Yang, J. Xu, L. Zhang, H. Chu, P. Yu, Y. Zhu, J. Wei, W. Chen, Y. Zhang, X. Zhang, H. Sun, Y. Tang, Q. You, Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors, Bioorg. Med. Chem. 21 (2013) 6466-6476.
51. J. Zhu, J.B. Lin, Y.X. Xu, X.B. Shao, X.K. Jiang, Z.T. Li, Hydrogen-bondingmediated anthranilamide homoduplexes. Increasing stability through preorganization and iterative arrangement of a simple amide binding site, J. Am. Chem. Soc. 128 (2006) 12307-12313.
52. R.X. Xu, M.H. Lambert, B.B. Wisely, E.N. Warren, E.E. Weinert, G.M. Waitt, J.D. Williams, J.L. Collins, L.B. Moore, T.M. Willson, J.T. Moore, A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer, Mol. Cell 16 (2004) 919-928.
53. O. Trott, A.J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem. 31 (2010) 455-461.
54. R.A. Laskowski, M.B. Swindells, LigPlot+: multiple ligand-protein interaction diagrams for drug discovery, J. Chem. Inf. Model. 51 (2011) 2778-2786.