Synthesis of cystamidin A (pyrrole-3-propanamide), a reported calpain inhibitor

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 13, 1996, Pages 1541-1542

  Bihovsky, Ron ^a   Pendrak, Israil ^b  

^a CEPHALON INC   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CALPASTATIN; CYSTAMIDIN A; PYRROLE 3 PROPANAMIDE; PYRROLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BRAIN ISCHEMIA; DEGENERATIVE DISEASE; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG USE; MUSCULAR DYSTROPHY;

EID: 0030576305     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00269-7     Document Type: Article

References (19)

1. 1. Mellgren, R. L.; Murachi, T. Intracellular Calcium-Dependent Proteolysis; CRC: Boca Raton, 1990. Siman, R. In Neurotoxicity of Excitatory Amino Acids; Guidotti, A., Ed.; Raven: New York, 1990; pp 145-161. Croall, D. E.; DeMartino, G. N. Physiol. Rev. 1991, 71, 813.
2. 1. Mellgren, R. L.; Murachi, T. Intracellular Calcium-Dependent Proteolysis; CRC: Boca Raton, 1990. Siman, R. In Neurotoxicity of Excitatory Amino Acids; Guidotti, A., Ed.; Raven: New York, 1990; pp 145-161. Croall, D. E.; DeMartino, G. N. Physiol. Rev. 1991, 71, 813.
3. 1. Mellgren, R. L.; Murachi, T. Intracellular Calcium-Dependent Proteolysis; CRC: Boca Raton, 1990. Siman, R. In Neurotoxicity of Excitatory Amino Acids; Guidotti, A., Ed.; Raven: New York, 1990; pp 145-161. Croall, D. E.; DeMartino, G. N. Physiol. Rev. 1991, 71, 813.
4. 2. Wang, K. K. W.; Yuen, P.-W. Trends Pharmacol. Sci. 1994, 15, 412. Wang, K. K. W. Trends Pharmacol. Sci. 1990, 11, 139.
5. 2. Wang, K. K. W.; Yuen, P.-W. Trends Pharmacol. Sci. 1994, 15, 412. Wang, K. K. W. Trends Pharmacol. Sci. 1990, 11, 139.
6. 3. Mehdi, S. Trends Biol. Sci. 1991,16, 150.
7. 4. Li, Z.; Patil, G. S.; Golubski, Z. E.; Hori, H.; Tehrani, K.; Foreman, J. E.; Eveleth, D. D.; Bartus, R. T.; Powers, J. C. J. Med Chem. 1993, 36, 3472.
8. 5. Omura, S.; Tanaka, H.; Shiomi, K. U.S. Patent 5 336 783, 1994. Casein was utilized as the substrate.
9. 6. Bray, B. L.; Mathies, P. H.; Naef, R.; Solas, D. R.; Tidwell, T. T.; Artis, D. R.; Muchowski, J. M. J. Org. Chem. 1990, 55, 6317. Bray, B. L.; Muchowski, J. M. J. Org. Chem. 1988, 53, 6115.
10. 6. Bray, B. L.; Mathies, P. H.; Naef, R.; Solas, D. R.; Tidwell, T. T.; Artis, D. R.; Muchowski, J. M. J. Org. Chem. 1990, 55, 6317. Bray, B. L.; Muchowski, J. M. J. Org. Chem. 1988, 53, 6115.
11. 7. Bates, H. A.; Rapoport, H. J. Amer. Chem. Soc. 1979, 101, 1259. Labouta, I. H.; Jacobsen, P.; Thorbek, P.; Krogsgaard-Larsen, P.; Hieds, H. Acta Chem. Scand B 1982, 36, 669.
12. 7. Bates, H. A.; Rapoport, H. J. Amer. Chem. Soc. 1979, 101, 1259. Labouta, I. H.; Jacobsen, P.; Thorbek, P.; Krogsgaard-Larsen, P.; Hieds, H. Acta Chem. Scand B 1982, 36, 669.
13. 8. Cavalleri, B.; Volpe, G.; Pallanza, R. Farmaco Ed. Sci. 1975, 30, 110. Keller-Schierlein, W.; Müller, A.; Hagmann, L.; Schneider, U.; Zähner, H. Helv. Chim. Acta 1985, 68, 559.
14. 8. Cavalleri, B.; Volpe, G.; Pallanza, R. Farmaco Ed. Sci. 1975, 30, 110. Keller-Schierlein, W.; Müller, A.; Hagmann, L.; Schneider, U.; Zähner, H. Helv. Chim. Acta 1985, 68, 559.
15. 9. Högberg, T.; Ström, P.; Ebner, M.; Rämsby, S. J. Org. Chem. 1987, 52, 2033.
16. 2O: C, 60.85; H, 7.30; N, 20.28; found: C, 60.77; H, 7.34; N, 20.30. Interestingly, the melting point of synthetic cystamidin A (recrystallized from chloroform, mp 76-8 °C) differs from that reported for the natural product (mp 146-8 °C), suggesting polymorphous crystal forms.
17. 2O: C, 60.85; H, 7.30; N, 20.28; found: C, 60.98; H, 6.75; N, 19.97. mp 97-8 °C.
18. 50S consistent with literature values, for example: Ac-Leu-Leu-Nle-H, 7 nM; Z-Leu-Phe-CONHEt, 11 nM; human calpastatin domain I, 7 nM.
19. Bioorganic & Medicinal Chemistry Letters, Vol. 6, No. 13, pp. 1543-1546, 1996