Synthesis of 2-pyridones as tissue factor VIIa inhibitors

Tetrahedron

Volumn 59, Issue 39, 2003, Pages 7695-7701

  Parlow, John J ^a   South, Michael S ^a  

^a PFIZER INC   (United States)

Author keywords

2 pyridones; Tissue factor VIIa

Indexed keywords

2,6 DIBROMOPYRIDINE; 6 BROMO 3 ISOPROPYLAMINOPYRIDIN 2 OL; BLOOD CLOTTING INHIBITOR; PYRIDINE DERIVATIVE; PYRIDONE DERIVATIVE; TISSUE FACTOR VIIA INHIBITOR; UNCLASSIFIED DRUG;

ADDITION REACTION; ALKYLATION; ARTICLE; ENZYME ASSAY; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; SYNTHESIS;

LATEOLABRAX JAPONICUS;

EID: 0042334856     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(03)01239-0     Document Type: Article

References (46)

1. Braunwald E., Califf R.M., Cannon C.P., Fox K.A., Fuster V., Gibler W.B., Harrington R.A., King S.B., Kleiman N.S., Theroux P., Topol E.J., Van de Werf F., White H.D., Willerson J.T. Am. J. Med. 108:2000;41.
2. For reviews see: (a) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79 (b) Betz A. Expert Opin. Therapeutic Patents. 11:2001;1007 (c) Zhu B.Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83 (d) Vacca J.P. Curr. Opin. Chem. Biol. 4:2000;394 (e) Sanderson P.E.J. Med. Res. Rev. 19:1999;179 (f) Fevig J.M., Wexler R.R. Annu. Rep. Med. Chem. 34:1999;81 (g) Ewing W.R., Pauls H.W., Spada A.P. Drug Fut. 24:1999;771.
3. For reviews see: (a) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79 (b) Betz A. Expert Opin. Therapeutic Patents. 11:2001;1007 (c) Zhu B.Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83 (d) Vacca J.P. Curr. Opin. Chem. Biol. 4:2000;394 (e) Sanderson P.E.J. Med. Res. Rev. 19:1999;179 (f) Fevig J.M., Wexler R.R. Annu. Rep. Med. Chem. 34:1999;81 (g) Ewing W.R., Pauls H.W., Spada A.P. Drug Fut. 24:1999;771.
4. For reviews see: (a) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79 (b) Betz A. Expert Opin. Therapeutic Patents. 11:2001;1007 (c) Zhu B.Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83 (d) Vacca J.P. Curr. Opin. Chem. Biol. 4:2000;394 (e) Sanderson P.E.J. Med. Res. Rev. 19:1999;179 (f) Fevig J.M., Wexler R.R. Annu. Rep. Med. Chem. 34:1999;81 (g) Ewing W.R., Pauls H.W., Spada A.P. Drug Fut. 24:1999;771.
5. For reviews see: (a) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79 (b) Betz A. Expert Opin. Therapeutic Patents. 11:2001;1007 (c) Zhu B.Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83 (d) Vacca J.P. Curr. Opin. Chem. Biol. 4:2000;394 (e) Sanderson P.E.J. Med. Res. Rev. 19:1999;179 (f) Fevig J.M., Wexler R.R. Annu. Rep. Med. Chem. 34:1999;81 (g) Ewing W.R., Pauls H.W., Spada A.P. Drug Fut. 24:1999;771.
6. For reviews see: (a) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79 (b) Betz A. Expert Opin. Therapeutic Patents. 11:2001;1007 (c) Zhu B.Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83 (d) Vacca J.P. Curr. Opin. Chem. Biol. 4:2000;394 (e) Sanderson P.E.J. Med. Res. Rev. 19:1999;179 (f) Fevig J.M., Wexler R.R. Annu. Rep. Med. Chem. 34:1999;81 (g) Ewing W.R., Pauls H.W., Spada A.P. Drug Fut. 24:1999;771.
7. For reviews see: (a) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79 (b) Betz A. Expert Opin. Therapeutic Patents. 11:2001;1007 (c) Zhu B.Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83 (d) Vacca J.P. Curr. Opin. Chem. Biol. 4:2000;394 (e) Sanderson P.E.J. Med. Res. Rev. 19:1999;179 (f) Fevig J.M., Wexler R.R. Annu. Rep. Med. Chem. 34:1999;81 (g) Ewing W.R., Pauls H.W., Spada A.P. Drug Fut. 24:1999;771.
8. For reviews see: (a) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79 (b) Betz A. Expert Opin. Therapeutic Patents. 11:2001;1007 (c) Zhu B.Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83 (d) Vacca J.P. Curr. Opin. Chem. Biol. 4:2000;394 (e) Sanderson P.E.J. Med. Res. Rev. 19:1999;179 (f) Fevig J.M., Wexler R.R. Annu. Rep. Med. Chem. 34:1999;81 (g) Ewing W.R., Pauls H.W., Spada A.P. Drug Fut. 24:1999;771.
9. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
10. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
11. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
12. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
13. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
14. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
15. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
16. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
17. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
18. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
19. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
20. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
21. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
22. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
23. For reviews see: (a) Robinson L.A., Saiah E.M.K. Annu. Rep. Med. Chem. 37:2002;85 (b) Girard T.J., Nicholson N.S. Curr. Opin. Pharmacol. 1:2001;159 (c) Carroll A.R., Pierens G.K., Fechner G., de Almeida Leone P., Ngo A., Simpson M., Hyde E., Hooper J.N.A., Boström S.-L., Musil D., Quinn R.J. J. Am. Chem. Soc. 124:2002;13340 (d) Hanessian S., Margarita R., Hall A., Johnstone S., Tremblay M., Parlanti L. J. Am. Chem. Soc. 124:2002;13342 (e) Hanessian S., Therrien E., Granberg K., Nilsson I. Bioorg. Med. Chem. Lett. 12:2002;2907 (f) Young W.B., Kolesnikov A., Rai R., Sprengeler P.A., Leahy E.M., Shrader W.D., Sangalang J., Burgess-Henry J., Spencer J., Elrod K., Cregar L. Bioorg. Med. Chem. Lett. 11:2001;2253 (g) Kohrt J.T., Filipski K.J., Rapundalo S.T., Cody W.L., Edmunds J.J. Tetrahedron Lett. 41:2000;6041 (h) Jakobsen P., Horneman A.M., Persson E. Bioorg. Med. Chem. 8:2000;2803 (i) Jakobsen P., Ritsmar Pedersen B., Persson E. Bioorg. Med. Chem. 8:2000;2095 (j) Roussel P., Bradley M., Kane P., Bailey C., Arnold R., Cross A. Tetrahedron. 55:1999;6219 (k) Wang D., Girard T.J., Kasten T.P., LaChance R.M., Miller-Wideman M.A., Durley R.C. J. Nat. Prod. 61:1998;1352 (l) Semple J.E., Rowley D.C., Brunck T.K., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;315 (m) Uchiba M., Okajima K., Abe H., Okabe H., Takatsuki K. Thromb. Res. 74:1994;155 (n) Butenas S., Ribarik N., Mann K.G. Biochemistry. 32:1993;6531 (o) Van der Woerd-De Lange J.A., Van Dam-Mieras M.C.E., Hemker H.C. Haemostasis. 10:1981;315.
24. (a) Houston D.S. Expert Opin. Ther. Targets. 6:2002;159
25. (b) Golino P. Thromb. Res. 106:2002;V257
26. (c) Bajaj M.S., Birktoft J.J., Steer S.A., Bajaj S.P. Thromb. Haemost. 86:2001;959
27. (d) Kaiser B., Hoppensteadt D.A., Fareed J. Expert Opin. Investig. Drugs. 10:2001;1925
28. (e) Kirchhofer D., Nemerson Y. Curr. Opin. Chem. Biotech. 7:1996;386
29. (f) Girard T.J. Tissue Factor Pathway Inhibitor. Sasahara A.A., Loscalzo J. Atherosclerosis. Atherosclerosis. Vol. 139:1998;199 Shannon, Ireland.
30. (a) Parlow J.J., Case B.L., Dice T.A., Fenton R.L., Hayes M.J., Jones D.E., Neumann W.L., Wood R.S., Lachance R.M., Girard T.J., Nicholson N.S., Clare M., Stegeman R.A., Stevens A.M., Stallings W.C., Kurumbail R.G., South M.S. J. Med. Chem. 2003;. in press
31. (b) South M.S., Case B.L., Wood R.S., Jones D.E., Hayes M.J., Girard T.J., Lachance R.M., Nicholson N.S., Clare M., Stevens A.M., Stegeman R.A., Stallings W.C., Kurumbail R.G., Parlow J.J. Bioorg. Med. Chem. Lett. 13:2003;2319-2325.
32. (a) Parlow J.J., Stegeman R.A., Stevens A.M., Stallings W.C., Kurumbail R.G., South M.S. J. Med. Chem. 2003;. in press
33. (b) South, M.S., Zeng, Q., Rueppel, M.L., WO 0069826, 2000.
34. (a) Damewood J.R. Jr., Edwards P.D., Feeney S., Gomes B.C., Steelman G.B., Tuthill P.A., Williams J.C., Warner P., Woolson S.A., Wolanin D.J., Veale C.A. J. Med. Chem. 37:1994;3303
35. (b) Warner P., Green R.C., Gomes B., Strimpler A.M. J. Med. Chem. 37:1994;3090
36. (c) Brown F.J., Andisik D.W., Bernstein P.R., Bryant C.B., Ceccarelli C., Damewood J.R. Jr., Edwards P.D., Earley R.A., Feeney S., Green R.C., Gomes B., Kosmider B.J., Krell R.D., Shaw A., Steelman G.B., Thomas R.M., Vacek E.P., Veale C.A., Tuthill P.A., Warner P., Williams J.C., Wolanin D.J., Woolson S.A. J. Med. Chem. 37:1994;1259.
37. (a) Sanderson P.E.J., Cutrona K.J., Dyer D.L., Krueger J.A., Kuo L.C., Lewis S.D., Lucas B.J., Yan Y. Bioorg. Med. Chem. Lett. 13:2003;161
38. (b) Reiner J.E., Siev D.V., Araldi G.-L., Cui J.J., Ho J.Z., Reddy K.M., Mamedova L., Vu P.H., Lee K.-S.S., Minami N.K., Gibson T.S., Anderson S.M., Bradbury A.E., Nolan T.G., Semple J.E. Bioorg. Med. Chem. Lett. 12:2002;1203
39. (c) Sanderson P.E.J., Cutrona K.J., Dorsey B.D., Dyer D.L., Mcdonough C.M., Naylor-Olsen A.M., Chen I.W., Chen Z., Cook J.J., Gardell S.J., Krueger J.A., Lewis S.D., Lin J.H., Lucas B.J. Jr., Lyle E.A., Lynch J.J. Jr., Stranieri M.T., Vastag K., Shafer J.A., Vacca J.P. Bioorg. Med. Chem. Lett. 8:1998;817
40. (d) Isaacs R.C.A., Cutrona K.J., Newton L., Sanderson P.E.J., Solinsky M.G., Baskin E.P., Chen I.W., Cooper C.M., Cook J.J., Gardell S.J., Lewis S.D., Lucas R.J. Jr., Lyle E.A., Lynch J.J. Jr., Naylor-Olsen A.M., Stranieri M.T., Vastag K., Vacca J.P. Bioorg. Med. Chem. Lett. 8:1998;1719
41. (e) Sanderson P.E.J., Lyle T.A., Cutrona K.J., Dyer D.L., Dorsey B.D., McDonough C.M., Naylor-Olsen A.M., Chen I.W., Chen Z., Cook J.J., Cooper C.M., Gardell S.J., Hare T.R., Krueger J.A., Lewis S.D., Lin J.H., Lucas B.J. Jr., Lyle E.A., Lynch J.J., Stranieri M.T., Vastag K., Yan Y., Shafer J.A., Vacca J.P. J. Med. Chem. 41:1998;4466
42. (f) Sanderson P.E.J., Dyer D.L., Naylor-Olsen A.M., Vacca J.P., Gardell S.J., Lewis S.D., Lucas B.J. Jr., Lyle E.A., Lynch J.J. Jr., Mulichak A.M. Bioorg. Med. Chem. Lett. 7:1997;1497
43. (g) Tamura S.Y., Semple J.E., Reiner J.E., Goldman E.A., Brunck T.K., Lim-Wilby M.S., Carpenter S.H., Rote W.E., Oldeshulte G.L., Richard B.M., Nutt R.F., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;1543.
44. Duffy J.L., Laali K.K. J. Org. Chem. 56:1991;3006.
45. Advanced Chemistry Development Inc. HNMR predictor.
46. Barney C.L., Huber E.W., McCarthy J.R. Tetrahedron Lett. 31:1990;5547.