Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: Highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1″ binding site

Bioorganic and Medicinal Chemistry

Volumn 22, Issue 19, 2014, Pages 5487-5505

  Nara, Hiroshi ^a   Sato, Kenjiro ^a   Naito, Takako ^a   Mototani, Hideyuki ^a   Oki, Hideyuki ^a   Yamamoto, Yoshio ^a   Kuno, Haruhiko ^a   Santou, Takashi ^a   Kanzaki, Naoyuki ^a   Terauchi, Jun ^a   Uchikawa, Osamu ^a   Kori, Masakuni ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

Matrix metalloproteinase; MMP 13; OA; Osteoarthritis; Structure based drug design; Thieno 2 3 d pyrimidin 4 one; X ray crystallography

Indexed keywords

2 (3 METHOXYPHENYL) N (6 METHYL 4 OXO 3,4 DIHYDROQUINAZOLIN 2 YL)ACETAMIDE; 2 (CHLOROMETHYL) 6 METHYLQUINAZOLIN 4(3H) ONE; 2 [1 HYDROXY 3 (3 METHOXYPHENYL)PROPYL] 6 METHYL 3,4 DIHYDROQUINAZOLIN 4 ONE; 2 [3 (3 METHOXYPHENYL)PROPANOYL] 6 METHYL 3,4 DIHYDROQUINAZOLIN 4 ONE; 4 [[[2 [[(3 METHOXYPHENYL)METHYL]CARBAMOYL] 4 OXO 3H,4H THIENO[2,3 D]PYRIMIDIN 5 YL]METHOXY]METHYL]BENZOIC ACID; DISODIUM 4 [[[2 [(3 METHOXYBENZYL)CARBAMOYL] 4 OXO 4H THIENO[2,3 D]PYRIMIDIN 3 ID 5 YL]METHOXY]METHYL]BENZOATE; ETHYL 1,3 DIMETHYL 4 OXO 1H,4H,5H PYRAZOLO[3,4 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 4 OXO 3H,4H PYRIDO[2,3 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 4 OXO 3H,4H PYRIDO[3,4 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 4 OXO 3H,4H THIENO[2,3 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 4 OXO 3H,4H THIENO[3,2 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 5 DIMETHYL 4 OXO 3H,4H THIENO[2,3 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 5,6 DIMETHYL 4 OXO 3H,4H FURO[2,3 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 6 METHYL 4 OXO 3H,4H,7H PYRROLO[2,3 D]PYRIMIDINE 2 CARBOXYLATE; ETHYL 6,7 DIMETHYL 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D]PYRIMIDINE 2 CARBOXYLATE; MATRIX METALLOPROTEINASE INHIBITOR; N [(3 METHOXYPHENYL)METHYL] 1,3 DIMETHYL 4 OXO 1H,4H,5H PYRAZOLO[3,4 D]PYRIMIDINE 6 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 3 METHYL 4 OXO 4H,5H [1,2]OXAZOLO[5,4 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 4 OXO 3H,4H PYRIDO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 4 OXO 3H,4H PYRIDO[3,4 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 4 OXO 3H,4H THIENO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 5 METHYL 4 OXO 3H,4H THIENO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 5 METHYL 4 OXO 3H,4H,7H THIENO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 5,6 DIMETHYL 4 OXO 3H,4H FURO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 5,6 DIMETHYL 4 OXO 3H,4H THIENO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 6 METHYL 4 OXO 3H,4H THIENO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 6 METHYL 4 OXO 3H,4H,7H PYRROLO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 6,7 DIMETHYL 4 OXO 3H,4H THIENO[3,2 D]PYRIMIDINE 2 CARBOXAMIDE; N [(3 METHOXYPHENYL)METHYL] 6,7 DIMETHYL 4 OXO 3H,4H,7H PYRROLO[2,3 D]PYRIMIDINE 2 CARBOXAMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; BENZENE DERIVATIVE; COLLAGENASE 3; PYRIMIDINE DERIVATIVE; THIENO(2,3-D)PYRIMIDINE-2-CARBOXAMIDE;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; BINDING SITE; DRUG BINDING; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; FEMALE; HYDROPHOBICITY; IC50; LIGAND BINDING; MALE; NONHUMAN; PROCESS OPTIMIZATION; PROTEIN INTERACTION; PROTEIN SECRETION; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; HUMAN; METABOLISM; ORAL DRUG ADMINISTRATION; X RAY CRYSTALLOGRAPHY;

ADMINISTRATION, ORAL; BENZENE DERIVATIVES; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MATRIX METALLOPROTEINASE 13; MATRIX METALLOPROTEINASE INHIBITORS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84907539073     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.07.025     Document Type: Article

References (27)

1. J. Couzin Science 306 2004 384
2. G.A. FitzGerald N. Engl. J. Med. 351 2004 1709
3. H. Nagase, and J.F. Woessner Jr. J. Biol. Chem. 274 1999 21491
4. R. Visse, and H. Nagase Circ. Res. 92 2003 827
5. J. Gross, and C.M. Lapiere Proc. Natl. Acad. Sci. U.S.A. 48 1962 1014
6. M. Whittaker, C.D. Floyd, P. Brown, and A.J. Gearing Chem. Rev. 99 1999 2735
7. P.G. Mitchell, H.A. Magna, L.M. Reeves, L.L. Lopresti-Morrow, S.A. Yocum, P.J. Rosner, K.F. Geoghegan, and J.E. Hambor J. Clin. Invest. 97 1996 761
8. L.A. Neuhold, L. Killar, W. Zhao, M.L. Sung, L. Warner, J. Kulik, J. Turner, W. Wu, C. Billinghurst, T. Meijers, A.R. Poole, P. Babij, and L.J. DeGennaro J. Clin. Invest. 107 2001 35
9. H. Matter, and M. Schudok Curr. Opin. Drug Discov. Devel. 7 2004 513
10. M. Hidalgo, and S.G. Eckhardt J. Natl Cancer Inst. 93 2001 178
11. E. Breuer, J. Frant, and R. Reich Expert Opin. Ther. Pat. 15 2005 253
12. R. Hoekstra, F.A. Eskens, and J. Verweij Oncologist 6 2001 415
13. L.A. Reiter, R.P. Robinson, K.F. McClure, C.S. Jones, M.R. Reese, P.G. Mitchell, I.G. Otterness, M.L. Bliven, J. Liras, S.R. Cortina, K.M. Donahue, J.D. Eskra, R.J. Griffiths, M.E. Lame, A. Lopez-Anaya, G.J. Martinelli, S.M. McGahee, S.A. Yocum, L.L. Lopresti-Morrow, L.M. Tobiassen, and M.L. Vaughn-Bowser Bioorg. Med. Chem. Lett. 14 2004 3389
14. J.T. Peterson Cardiovasc. Res. 69 2006 677
15. Nara, H.; Sato, K.; Naito, T.; Mototani, H.; Oki, H.; Yamamoto, Y.; Kuno, H.; Santou, T.; Kanzaki, N.; Terauchi, J.; Uchikawa, O.; Kori, M. Discovery of Novel, Highly Potent and Selective Quinazoline-2-carboxamide-based MMP-13 Inhibitors without Zinc Binding Group Using Structure-Based Design Approach. Submitted for publication.
16. Andrianjara, C.; Ortwine, D., Fred; Pavlovsky, A., Gregory; Roark, W., Howard. Matrix Metalloproteinase Inhibitors. WO2002064080.
17. G. Abbenante, and D.P. Fairlie Med. Chem. 1 2005 71
18. T.E. Cawston, A.J. Ellis, G. Humm, E. Lean, D. Ward, and V. Curry Biochem. Biophys. Res. Commun. 215 1995 377
19. K.M. Bottomley, N. Borkakoti, D. Bradshaw, P.A. Brown, M.J. Broadhurst, J.M. Budd, L. Elliott, P. Eyers, T.J. Hallam, B.K. Handa, C.H. Hill, M. James, H.W. Lahm, G. Lawton, J.E. Merritt, J.S. Nixon, U. Rothlisberger, A. Whittle, and W.H. Johnson Biochem. J. 323 Pt 2 1997 483
20. C.C. Cheng, and R.K. Robins J. Org. Chem. 21 1956 1240
21. J.M. Barker, P.R. Huddleston, and M.L. Wood Synth. Commun. 32 2002 2565
22. E. Toja, G. Tarzia, P. Ferrari, and G. Tuan J. Heterocycl. Chem. 23 1986 1555
23. D.L. Temple, J.P. Yevich, R.R. Covington, C.A. Hanning, R.J. Seidehamel, H.K. Mackey, and M.J. Bartek J. Med. Chem. 22 1979 505
24. Temple, J., Davis L. U.S. 4054656.
25. A. Miyashita, K. Fujimoto, T. Okada, and T. Higashino Heterocycles 42 1996 691
26. L.F. Hennequin, F.T. Boyle, J.M. Wardleworth, P.R. Marsham, R. Kimbell, and A.L. Jackman J. Med. Chem. 39 1996 695
27. H. Sato, T. Kinoshita, T. Takino, K. Nakayama, and M. Seiki FEBS Lett. 393 1996 101