Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part I: Exploration of 5-6 fused rings as alternative S1 moieties

Bioorganic and Medicinal Chemistry

Volumn 17, Issue 24, 2009, Pages 8206-8220

  Yoshikawa, Kenji ^a   Yokomizo, Aki ^a   Naito, Hiroyuki ^a   Haginoya, Noriyasu ^a   Kobayashi, Shozo ^a   Yoshino, Toshiharu ^a   Nagata, Tsutomu ^a   Mochizuki, Akiyoshi ^a   Osanai, Ken ^a   Watanabe, Kengo ^a   Kanno, Hideyuki ^a   Ohta, Toshiharu ^a  

^a DAIICHI SANKYO CO   (Japan)

Author keywords

Anticoagulant; Factor Xa inhibitor; Food effect; Solubility

Indexed keywords

ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; CIS 1,2 DIAMINOCYCLOHEXANE; UNCLASSIFIED DRUG;

ANTICOAGULATION; ARTICLE; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; FOOD DRUG INTERACTION; IC 50; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANTICOAGULANTS; ANTITHROMBIN III; BINDING SITES; BINDING, COMPETITIVE; CRYSTALLOGRAPHY, X-RAY; CYCLOHEXYLAMINES; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; INTESTINAL ABSORPTION; KINETICS; MOLECULAR STRUCTURE; PLATELET MEMBRANE GLYCOPROTEINS; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 71849094402     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2009.10.023     Document Type: Article

References (21)

1. Klauss V., and Spannagl M. Curr. Drug Targets 7 (2006) 1285
2. Turpie A.G.G. Eur. Heart J. 29 (2007) 155
3. Garcia D. Thromb. Res. 123 (2009) S50
4. Casimiro-Garcia A., Dudley D.A., Heemstra R.J., Filipski K.J., Bigge C.F., and Edmunds J.J. Exp. Opin. Ther. Pat. 16 (2006) 119
5. Kaiser B. Drugs Future 23 (1998) 423
6. Nagata T., Yoshino T., Haginoya N., Yoshikawa K., Nagamochi M., Kobayashi S., Komoriya S., Yokomizo A., Muto R., Yamaguchi M., Osanai K., Suzuki M., and Kanno H. Bioorg. Med. Chem. 17 (2009) 1193
7. Löbenberg R., and Amidon G.L. Eur. J. Pharm. Biopharm. 50 (2000) 3
8. Fleisher D., Li C., Zhou Y., Pao L.-H., and Karim A. Clin. Pharmacokinet. 36 (1999) 233
9. FDA Guidance for Industry: Food-Effect Bioavailability and Fed Bioequivalence Studies. 2002, Available at http://www.fda.gov/cder/guidance/5194fnl.htm.
10. The permeability assay was conducted using Caco-2 monolayers. The permeability of compound A was more than 30 times higher than that of atenolol. And it is considered that compound A possesses enough permeability.
11. 0 is the volume of water taken with the dose, which is generally set to be 250 mL.
12. Haginoya N., Komoriya S., Osanai K., Yoshino T., Nagata T., Nagamochi M., Muto R., Yamaguchi M., Nagahara T., and Kanno H. Heterocycles 63 (2004) 1555
13. Bernard A.M., Ghiani M.R., Piras P.P., and Rivoldini A. Synthesis 4 (1989) 287
14. Ma{ogonek}kosza M., Danikiewicz W., and Wojciechowski K. Liebigs Ann. Chem. (1988) 203
15. Kurokawa M., and Sugai T. Bull. Chem. Soc. Jpn. 77 (2004) 1021
16. Nazaré M., Will D.W., Matter H., Schreuder H., Ritter K., Urmann M., Essrich M., Bauer A., Wagner M., Czech J., Lorenz M., Laux V., and Wehner V. J. Med. Chem. 48 (2005) 4511
17. Adler M., Kochanny M.J., Ye B., Rumennik G., Light D.R., Biancalana S., and Whitlow M. Biochemistry 41 (2002) 15514
18. Maignan S., Guilloteau J.-P., Choi-Sledeski Y.M., Becker M.R., Ewing W.R., Pauls H.W., Spada A.P., and Mikol V. J. Med. Chem. 46 (2003) 685
19. Chan C., Borthwick A.D., Brown D., Burns-Kurtis C.L., Campbell M., Chaudry L., Chung C., Convery M.A., Hamblin J.N., Johnstone L., Kelly H.A., Kleanthous S., Patikis A., Patel C., Pateman A.J., Senger S., Shah G.P., Toomey J.R., Watson N.S., Weston H.E., Whitworth C., Young R.J., and Zhou P. J. Med. Chem. 50 (2007) 1546
20. Sinha H.K., and Dogra S.K. Bull. Chem. Soc. Jpn. 62 (1989) 2668
21. Artursson P., and Karlsson J. Biochem. Biophys. Res. Commun. 175 (1991) 880