Nongenomic actions of bile acids. Synthesis and preliminary characterization of 23- and 6,23-alkyl-substituted bile acid derivatives as selective modulators for the G-protein coupled receptor TGR5

Journal of Medicinal Chemistry

Volumn 50, Issue 18, 2007, Pages 4265-4268

  Pellicciari, Roberto ^a   Sato, Hiroyuki ^b   Gioiello, Antimo ^a   Costantino, Gabriele ^a,e   Macchiarulo, Antonio ^a   Sadeghpour, Bahman M ^a   Giorgi, Gianluca ^c   Schoonjans, Kristina ^b   Auwerx, Johan ^b,d  

^a UNIVERSITY OF PERUGIA   (Italy)

^b INSTITUT DE GÉNÉTIQUE ET DE BIOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

^c UNIVERSITY OF SIENA   (Italy)

^d INSTITUT CLINIQUE DE LA SOURIS   (France)

^e UNIVERSITY OF PARMA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

23 METHYL 3ALPHA,7ALPHA,12ALPHA TRIHYDROXY 5BETA CHOLAN 24 OIC ACID; 6ALPHA ETHYL 23 METHYL 3ALPHA,7ALPHA DIHYDROXY 5BETA CHOLAN 24 OIC ACID; 6ALPHA ETHYLCHENODEOXYCHOLIC ACID; BILE ACID; CHENODEOXYCHOLIC ACID DERIVATIVE; CHOLANE DERIVATIVE; CHOLIC ACID; FARNESOID X RECEPTOR; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR TGR5; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ALKYLATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE ACID SYNTHESIS; BROWN ADIPOSE TISSUE; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; INSULIN RESISTANCE; LIPID METABOLISM; METHYLATION; MOLECULAR DOCKING; MOLECULAR MODEL; MOUSE; NONHUMAN; OBESITY; SUBSTITUTION REACTION;

ANIMALS; BILE ACIDS AND SALTS; CHO CELLS; CRICETINAE; CRICETULUS; CRYSTALLOGRAPHY, X-RAY; DNA-BINDING PROTEINS; HUMANS; LIGANDS; METHYLATION; MODELS, MOLECULAR; MOLECULAR STRUCTURE; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, G-PROTEIN-COUPLED; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTION FACTORS; URSODEOXYCHOLIC ACID;

EID: 34548508190     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070633p     Document Type: Article

References (29)

1. Houten, S. M.; Watanabe, M.; Auwerx, J. Endocrine functions of bile acids. EMBO J. 2006, 25, 1419-1425.
2. Makishima, M.; Okamoto, A. Y.; Repa, J. J.; Tu, H.; Learned, R. M.; Luk, A.; Hull, M. V.; Lustig, K. D.; Mangelsdorf, D. J.; Shan, B. Identification of a nuclear receptor for bile acids. Science 1999, 284, 1362-1365.
3. Parks, D. J.; Blanchard, S. G.; Bledsoe, R. K.; Chandra, G.; Consler, T. G.; Kliewer, S. A.; Stimmel, J. B.; Willson, T. M.; Zavacki, A. M.; Moore, D. D.; Lehmann, J. M. Bile acids: Natural ligands for an orphan nuclear receptor. Science 1999, 284, 1365-1368.
4. Wang, H.; Chen, J.; Hollister, K.; Sowers, L. C.; Forman, B. M. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol. Cell 1999, 3, 543-553.
5. Pellicciari, R.; Costantino, G.; Fiorucci, S. Farnesoid X receptor: From structure to potential clinical applications. J. Med. Chem. 2005, 48, 5383-5403.
6. Maruyama, T.; Miyamoto, Y.; Nakamura, T.; Tamai, Y.; Okada, H.; Sugiyama, E.; Nakamura, T.; Itadani, H.; Tanaka, K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem. Biophys. Res. Commun. 2002, 298, 714-719.
7. Kawamata, Y.; Fujii, R.; Hosoya, M.; Harada, M.; Yoshida, H.; Miwa, M.; Fukusumi, S.; Habata, Y.; Itoh, T.; Shintani, Y.; Hinuma, S.; Fujisawa, Y.; Fujino, M. A G-protein-coupled receptor responsive to bile acids. J. Biol. Chem. 2003, 278, 9435-9440.
8. Keane, R. M.; Gadacz, T. R.; Munster, A. M.; Birmingham, W.; Winchurch, R. A. Impairment of human lymphocyte function by bile salts. Surgery 1984, 95, 439-443.
9. Kimmings, A. N.; van Deventer, S. J.; Obertop, H.; Rauws, E. A.; Gouma, D. J. Inflammatory and immunologic effects of obstructive jaundice: Pathogenesis and treatment. J. Am. Coll. Surg. 1995, 181, 567-581.
10. Drivas, G.; James, O.; Wardle, N. Study of reticuloendothelial phagocytic capacity in patients with cholestasis. Br. Med. J. 1976, 1, 1568-1569.
11. Pain, J. A.; Cahill, C. J.; Bailey, M. E. Perioperative complications in obstructive jaundice: Therapeutic considerations. Br. J. Surg. 1985, 72, 942-945.
12. Greve, J. W.; Gouma, D. J.; Buurman, W. A. Bile acids inhibit endotoxin-induced release of tumor necrosis factor by monocytes: An in vitro study. Hepatology 1989, 10, 454-458.
13. Calmus, Y.; Weill, B.; Ozier, Y.; Chereau, C.; Houssin, D.; Poupon, R. Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse. Gastroenterology 1992, 103, 617-621.
14. Ikemoto, S.; Takahashi, M.; Tsunoda, N.; Maruyama, K.; Itakura, H.; Kawanaka, K.; Tabata, I.; Higuchi, M.; Tange, T.; Yamamoto, T. T.; Ezaki, O. Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-CoA synthetase mRNA decrease. Am. J. Physiol. 1997, 273, E37-45.
15. Watanabe, M.; Houten, S. M.; Mataki, C.; Christoffolete, M. A.; Kim, B. W.; Sato, H.; Messaddeq, N.; Harney, J. W.; Ezaki, O.; Kodama, T.; Schoonjans, K.; Bianco, A. C.; Auwerx, J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006, 439, 484-489.
16. Maruyama, T.; Tanaka, K.; Suzuki, J.; Miyoshi, H.; Harada, N.; Nakamura, T.; Miyamoto, Y.; Kanatani, A.; Tamai, Y. Targeted disruption of G-protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. J. Endocrinol. 2006, 191, 197-205.
17. Ito, F.; Hinuma, K.; Kanzaki, N.; Miki, T.; Kawamata, Y.; Oi, S.; Tawaeaishi, T.; Ishichi, Y.; Hirohashi, M. Preparation of aromatic ring-fused cyclic compounds as TGR5 receptor agonists, Takeda Chemical Industries Ltd., Japan, PN: WO2004067008.
18. Pellicciari, R.; Fiorucci, S.; Camaioni, E.; Clerici, C.; Costantino, G.; Maloney, P. R.; Morelli, A.; Parks, D. J.; Willson, T. M. 6α-Ethyl- chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J. Med. Chem. 2002, 45, 3569-3572.
19. Pellicciari, R.; Costantino, G.; Camaioni, E.; Sadeghpour, B. M.; Entrena, A.; Willson, T. M.; Fiorucci, S.; Clerici, C.; Gioiello, A. Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid. J. Med. Chem. 2004, 47, 4559-4569.
20. Pellicciari, R.; Gioiello, A.; Costantino, G.; Sadeghpour, B. M.; Rizzo, G.; Meyer, U.; Parks, D. J.; Entrena-Guadix, A.; Fiorucci, S. Back door modulation of the farnesoid X receptor: Design, synthesis, and biological evaluation of a series of side chain modified chenodeoxycholic acid derivatives. J. Med. Chem. 2006, 49, 4208-4225.
21. Pellicciari, R.; Cecchetti, S.; Natalini, B.; Roda, A.; Grigolo, B.; Fini, A. Bile acids with cyclopropane-containing side chain. 2. Synthesis and properties of 3α,7β-dihydroxy-22,23-methylene-5β-cholan-24-oic acid (2-sulfoethyl)amide. J. Med. Chem. 1985, 28, 239-242.
22. Pellicciari, R.; Natalini, B.; Cecchetti, S.; Porter, B.; Roda, A.; Grigolo, B.; Balducci, R. Bile acids with a cyclopropyl-containing side chain. 3. Separation, identification, and properties of all four stereoisomers of 3α,7β-dihydroxy-22,23-methylene-5β-cholan-24-oic acid. J. Med. Chem. 1988, 31, 730-736.
23. Roda, A.; Grigolo, B.; Aldini, R.; Simoni, P.; Pellicciari, R.; Natalini, B.; Calducci, R. Bile acids with a cyclopropyl-containing side chain. IV. Physicochemical and biological properties of the four diastereoisomers of 3α,7β-dihydroxy-22,23-methylene-5β-cholan-24-oic acid. J. Lipid Res. 1987, 28, 1384-1397.
24. Roda, A.; Aldini, R.; Grigolo, B.; Simoni, P.; Roda, E.; Pellicciari, R.; Lenzi, P. L.; Natalini, B. 23-Methyl-3α,7β-dihyuroxy-5β-cholan- 24-oic acid: Dose-response study of biliary secretion in rat. Hepatology 1988, 8, 1571-1576.
25. Roda, A.; Grigolo, B.; Minutello, A.: Pellicciari, R.; Natalini, B. Physicochemical and biological properties of natural and synthetic C-22 and C-23 hydroxylated bile acids. J. Lipid Res. 1990, 31, 289-298.
26. Clerici, C.; Dozzini, G.; Distrutti, E.; Gentili, G.; Sadeghpour, B. M.; Natalini, B.; Pellicciari, R.; Rizzoli, R.; Roda, A.; Pelli, M. A. Effect of intraduodenal administration of 23-methyl-UDCA diastereoisomers on bile flow in hamsters. Dig. Dis. Sci. 1992, 37, 791-798.
27. Aldini, R.; Roda, A.; Montagnani, M.; Cerre, C.; Pellicciari, R.; Roda, E. Relationship between structure and intestinal absorption of bile acids with a steroid or side-chain modification. Steroids 1996, 61, 590-597.
28. Castagnola, V.; Frigerio, E. G.; Pellicciari, R.; Roda, A. Derivatives of biliary acids, process for the production thereof and corresponding pharmaceutical compositions, Gipharmex S.p.A., Italy, PN: US4892868.
29. Kutner, A.; Jaworske, R. Synthesis and absolute configuration at C-23 of [23R and 23S]-3α,7α,23-trihydroxy-5β-cholan-24-oic and 3α,7α,12α,23-trihydroxy-5β-cholan-24-oic acids. Steroids 1982, 40, 11-22.