Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Identification of 2-azabicyclo[4.1.0]heptan-3-imines

Bioorganic and Medicinal Chemistry

Volumn 11, Issue 8, 2003, Pages 1723-1743

  Kawanaka, Yasufumi ^a   Kobayashi, Kaoru ^a   Kusuda, Shinya ^a   Tatsumi, Tadashi ^a   Murota, Masayuki ^a   Nishiyama, Toshihiko ^a   Hisaichi, Katsuya ^a   Fujii, Atsuko ^a   Hirai, Keisuke ^a   Naka, Masao ^a   Komeno, Masaharu ^a   Odagaki, Yshihiko ^a   Nakai, Hisao ^a   Toda, Masaaki ^a  

^a ONO PHARMACEUTICAL CO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

5,7 DIMETHYL 2 AZABICYCLO[4.1.0]HEPTAN 3 IMINE; 5,7,7 TRIMETHYL 2 AZABICYCLO[4.1.0]HEPTAN 3 IMINE; 7 CHLORO 5 METHYL 2 AZABICYCLO[4.1.0]HEPTAN 3 IMINE; 7 FLUORO 5 METHYL 2 AZABICYCLO[4.1.0]HEPTAN 3 IMINE; 7,7 DICHLORO 5 METHYL 2 AZABICYCLO[4.1.0]HEPTAN 3 IMINE; NITRIC OXIDE SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CHEMICAL MODIFICATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACCUMULATION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENANTIOMER; HYDROGENATION; IC 50; INHIBITION KINETICS; ISOMER; MAXIMUM TOLERATED DOSE; MOUSE; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

EID: 12244263550     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0968-0896(03)00034-8     Document Type: Article

References (21)

1. Moncada S., Higgs E.A. FASEB. 9:1995;1319.
2. Kerwin J.F. Jr., Heller M. Med. Res. Rev. 14:1994;23.
3. Griffith O.W., Stuehr D.J. Annu. Rev. Physiol. 57:1995;707.
4. Marletta M.A. J. Biol. Chem. 268:1993;12231.
5. Kerwin J.F. Jr., Lancaster J.R. Jr., Feldman P.L. J. Med. Chem. 38:1995;4343.
6. Olken N.M., Marletta M.A. Biochemistry. 32:1993;9677.
7. Feldman P.L., Griffith O.W., Hong H., Stuehr D.J. J. Med. Chem. 36:1993;491.
8. Rees D.D., Palmer R.M.J., Moncada S. Proc. Natl. Acad. Sci. U.S.A. 86:1989;3375.
9. Misko T.P., Moore W.M., Kasten T.P., Nickols G.A., Corbett J.A., Tilton R.G., McDaniel M.L., Williamson J.R., Currie M.G. Eur. J. Pharmacol. 233:1993;119.
10. Garvey E.P., Oplinger J.A., Tanoury G.J., Sherman P.A., Fowler M., Marshall S., Harmon M.F., Paith J.E., Furfine E.S. J. Biol. Chem. 269:1994;26669.
11. Webber R.K., Metz S., Moore W.M., Connor J.R., Currie M.G., Fok K.F., Hagen T.J., Hansen D.W. Jr., Jerome G.M., Manning P.T., Pitzele B.S., Toth M.V., Trivedi M., Zupec M.E., Tjoeng F.S. J. Med. Chem. 41:1998;96.
12. Hagmann W.K., Galdwell C.G., Chen P., Durette P.L., Esser C.K., Lanza T.J., Kopka I.E., Guthikonda R., Shah S.K., MacCoss M., Chabin R.M., Fletcher D., Grant S.K., Green B.G., Humes J.L., Kelly T.M., Luell S., Meurer R., Moore V., Pacholok S.G., Pavia T., Williams H.R., Wong K.K. Bioorg. Med. Chem. Lett. 10:2000;1975.
13. Kawanaka Y., Kobayashi K., Kusuda S., Tatsumi T., Murota M., Nishiyama T., Hisaichi K., Fujii A., Hirai K., Naka M., Komeno M., Nakai H., Toda M. Bioorg. Med. Chem. Lett. 12:2002;2291.
14. (a) Leotta G.J. III., Overman L.E., Welmaker G.S. J. Org. Chem. 59:1994;1946.
15. (b) Theisen P.D., Heathcock C.H. J. Org. Chem. 58:1993;142.
16. (c) Francis C.J., Jones J.B. J. Chem. Soc., Chem. Commun. 1984;579.
17. Kitatani K., Hiyama T., Nozaki H. J. Am. Chem. Soc. 97:1975;949.
18. Stereochemistry of syn-isomer and anti-isomer was determined using two-dimensional NMR (2D NMR) technique such as nuclear Overhauser effect spectroscopy (NOESY). NOE observed between spatially close protons as illustrated in the analysis of 28d-anti (Fig. 1) supported the described stereochemistry. Same spectral analysis was applied to the corresponding amides prior to the conversion to the amidine derivatives.
19. Naka M., Nanbu T., Kobayashi K., Kamanaka Y., Komeno M., Yanase R., Fukutomi T., Fujimura S., Seo H.G., Fujiwara N., Ohuchida S., Suzuki K., Kondo K., Taniguchi N. Biochem. Biophys. Res. Commun. 270:2000;663.
20. teXsan: Molecular Structure Corporation; 1993.
21. Sheldrick, G. M. In Crystallographic Computing 3; Sheldrick, G. M.; Krüger, C.; Goddard, R., Eds.; Oxford University Press, 1985; pp 175-189.