Multiple parallel synthesis of N,N-dialkyldipeptidylamines as N-type calcium channel blockers

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 13, 1999, Pages 1813-1818

  Ryder, Todd R ^a   Hu, Lain Yen ^a   Rafferty, Michael F ^a   Millerman, Elizabeth ^b   Szoke, Balazs G ^b   Tarczy Hornoch, Katalin ^b  

^a PFIZER INC   (United States)

^b ELAN PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYL GROUP; AMINE; CALCIUM CHANNEL; CALCIUM CHANNEL BLOCKING AGENT; OMEGA CONOTOXIN MVIIA; PD 151307; PD 173212; POLYMER; UNCLASSIFIED DRUG;

ARTICLE; AUDIOGENIC SEIZURE; DRUG SYNTHESIS; PAIN; STROKE; STRUCTURE ACTIVITY RELATION;

AMINES; CALCIUM CHANNEL BLOCKERS; DIPEPTIDES; INHIBITORY CONCENTRATION 50;

EID: 0033526918     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00284-X     Document Type: Article

References (15)

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10. 2 to give the desired product.
11. 2, Pd/C, THF
12. 7. Booth, R. J.; Hodges, J. C.; J. Am. Chem. Soc. 1997, 119, 4882.
13. 3) ∂ 0.82 (d, 6 H, 5.9 Hz), 1.17 (s, 9 H), 1.21-1.29 (m, 3 H), 1.48 (p, 2 H, J = 6.3 Hz), 1.54 (s, 3H), 1.60 (dd, 1 H, J = 12.9 6.1 Hz), 2.02 (s, 3 H), 2.33 (dd, 2 H, J = 13.2, 6.6 Hz), 2.86 (dd, 1 H, J = 13.9, 8.1 Hz), 2.94-3.00 (m, 2 H), 4.34 (dd, 1 H, J = 15.1, 7.6 Hz), 5.00 (s, 2 H), 5.46 (s, 1 H), 6.86 (d, 2 H, J = 8.3 Hz), 7.10 (d, 2 H, J = 8.3 Hz), 7.26-7.39 (m, 4 H), 7.49 (d, 1 H, J = 8.1 Hz).
14. 2+ indicator Indo-1 in IMR-32 human neuroblastoma cells in the presence of 5 μM nitrendipine to block L-type channels. PD 151307 was run in parallel as a standard in each assay.
15. 10. In the IMR-32 assay, the N,N-dialkyl leucine acid starting materials (1-5) exhibited <25% blockade at 10 μM; the tyrosine amine starting materials (a-f) exhibited 11-67% blockade at 10 μM.