Professor, Department of Chemistry and Chemical Biology
Rensselaer Polytechnic Institute

Education:
Ph.D., Rice University, 1970

Career Highlights:
Wentland completed his graduate studies in synthetic organic chemistry in 1970 at Rice University working with the late Professor Robert V. Stevens. He then went to Sterling Winthrop Inc. where he conducted drug discovery research in the medicinal chemistry department for 24 years; his last positions were Sterling Winthrop Fellow and Oncology Discovery Co-Chair. In 1994, he joined the chemistry faculty at Rensselaer. During the period 1971-1994, he was an adjunct professor of chemistry at Rensselaer and taught over 30 graduate-level organic and medicinal chemistry courses.

Research Areas:
Anti-cocaine Medications
The main goal of this research is to design, synthesize and characterize potential medications to treat cocaine abuse in humans. Our working hypothesis for this research is that agents which release dopamine (DA) from the nucleus accumbens (the pleasure seeking area of the human brain) promote drug-seeking behavior and those which prevent release of DA prevent drug-seeking behavior. A growing body of evidence exists indicating that kappa-opioid agonists with varying activity at the mu-opioid receptor are effective in reducing cocaine self-administration in nonhuman primates. Cyclazocine, one of our lead compounds, displays this receptor binding profile and is currently undergoing 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 replace?ments for the phenolic OH of cyclazocine, we recently reported the synthesis and biological properties of 8-CAC. This new cyclazocine analogue has a carboxamide group in place of the phenolic OH and displays unexpectedly high affinity for opioid receptors and has a 15 hour duration of action in a mouse antinociception model. For comparison, cyclazocine's duration of action at the same dose of 1 mg/kg (ip) is 2 hours. We are currently focused on exploring the structure-activity relationships of this new series of carboxamido-substituted opiates and their potential as anti-cocaine medications. (Collaborators: Dr. Jean M. Bidlack and coworkers at University of Rochester; Funding: NIH/NIDA and Albany Molecular Research, Inc.)

Identification of Novel Analgesic Targets
A new class of pain-relieving drugs derived from histamine antagonists has been discovered. Our main goal in this project is to design and synthesize novel brain-penetrating analogues of our lead series and to identify an emerging structure-activity relationship. (Collaborators: Dr. Lindsay B. Hough and coworkers at the Albany Medical College; Funding: NIH/NIDA).

Selected Publications:
Wentland, M. P.;  VanAlstine, M.; Kucejko, R.;  Lou, R; Cohen, D. J.; Parkhill, A. L.; Bidlack, J. M. "Redefining the structure-activity relationships of 2,6-methano-3-benzazocines.  Part 4. Opioid receptor binding properties of 8-[N-(4'-phenyl)-phenethyl)­carboxamido] analogues of cyclazocine and EKC."  J. Med. Chem.  2006, 49, 5635-5639.

Hough, L. B.; Nalwalk, J. W.; Lu, Q.; Shan, Z.; Svokos. K.; Wentland, M. P.; Montero, M. J. "Antinociceptive, Brain-Penetrating Derivatives Related to Improgan, a Non-Opioid Analgesic." Eur. J. Pharm. 2005, 522, 38-46.

Wentland, M. P.;  Sun, X.; Bu, Y.;  Lou, R.; Cohen, D. J.; Bidlack, J. M.  ^"Redefining the Structure-Activity Relationships of 2,6-Methano-3-benzazocines.  Part 3. 8-Thiocarboxamido and 8-Thioformamido Derivatives of Cyclazocine." Bioorg. Med. Chem. Lett.  2005, 15, 2547-2551.

Wentland, M. P.; Lu, Q.; Lou, R.; Knapp, B. I.; Bidlack, J. M.  ^"Synthesis and opioid receptor binding properties of a highly potent 4-hydroxy analogue of naltrexone." Bioorg. Med. Chem. Lett.  2005, 15, 2107-2110.