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Drug Design and Discovery |
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The lead structures for these studies are cyclazocine and ethylketocyclazocine
(EKC); cyclazocine is currently being evaluated in clinical trials
by NIDA for remediation of cocaine addiction. Cyclazocine, however,
is short acting in humans and animals via O-glucuronidation. In hopes
of identifying novel isosteric replacements for the phenolic OH of
cyclazocine, Prof. Wentland and coworkers recently reported the synthesis
and biological properties of 8-CAC. This cyclazocine analogue has
a carboxamide group in place of the phenolic OH and displays very
high affinity for opioid receptors and has 15 hour duration of action
in a mouse antinociception model; for comparison, cyclazocine's duration
of action is 2 hours. Currently, the major focus of Prof. Wentland
group's design efforts are centered about exploring new structure-activity
relationships that have emerged from the discovery of 8-CAC.
Main publications in Drug Abuse:
• Bidlack, J.M.;
McLaughlin, J.P.; Wentland, M.P. “Partial Opioids: Medications
for the
Treatment of Pain and Drug Abuse.” Annals New York Academy of
Sciences, 2000, 909, 1-11.
Online resources in Drug Design:
www.nature.com/nrd/
Courses:
Drug Discovery (CHEM-4330, 6330) and Medicinal Chemistry (CHEM-4300,
6300). >>
short description.
Publications of general interest:
Burger's Medicinal Chemistry & Drug Discovery, 6th edition, Donald
J. Abraham, editor; Wiley Interscience, 2003 (ISBN of six volume
hard copy set = 0471-37032-0)
Prof.
Wentland's publications in Drug Design:
Journal articles:
• Wentland, M. P.; Ye, Y.;
Cioffi, C. L.; Lou, R.; Zhou, Q.; Xu, G.; Duan, W.; Dehnhardt, C.
M.; Sun, X.; Cohen, D. J.; Bidlack, J. M. "Syntheses and Opioid
Receptor Binding Affinities of 8-Amino-2,6-methano-3-benzazocines."
J. Med. Chem. 2003, 46, 838-849.
• Lou, R.; VanAlstine,
M.; Sun, X.; Wentland, M. P. "Preparation of N-Hydroxysuccinimido
Esters via Palladium-Catalyzed Carbonylation of Aryl Triflates and
Halides." Tetrahedron Lett. 2003, 44, 2477 - 2480.
• Bidlack, J. M.; Cohen,
D. J.; McLaughlin, J. P.; Lou, R.; Ye, Y.; Wentland, M. P. "8-Carboxamidocyclazocine:
A Long-Acting, Novel Benzomorphan." J. Pharmacol. Exp. Ther.
2002, 302, 374-380.
• Wentland, M. P.; Lou,
R.; Dehnhardt, C. M.; Duan, W.; Cohen, D.J.; Bidlack, J. M. "3-Carboxamido
Analogues of Morphine and Naltrexone: Synthesis and Opioid Receptor
Binding Properties." Bioorgan. Med. Chem. Lett. 2001, 11, 1717-1721.
• Wentland, M. P.; Lou,
R.; Ye, Y.; Cohen, D. J.; Richardson, G. P.; Bidlack, J. M. "8-Carboxamidocyclazocine
Analogues: Redefining the Structure-Activity Relationships of 2,6-Methano-3-benzazocines."
Bioorgan. Med. Chem. Lett. 2001, 11, 623-626.
•
Wentland, M.P.; Duan, W.; Cohen, D.J.; Bidlack, J.M.
"Selective Protection and Functionalization of Morphine: Synthesis
and Opioid Receptor Binding Properties of 3-Amino-3-desoxymorphine
Derivatives." J. Med. Chem. 2000, 43, 3558-3565.
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