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:

Medications to Treat Addictive Disorders: Phase 2 Clinical Trials Initiated for Two Members of Rensselaer's Opioid Library.

The main goal of our research is to design, synthesize and characterize oral, long-acting modulators of opioid G protein-coupled receptors as medications to treat cocaine abuse and other addictive disorders in humans. Our first-generation opioid modulator was the novel carboxamido substituted opioid 8-CAC which displayed unexpectedly high affinity for opioid receptors and a very long duration of action in a mouse antinociception model. A second generation agent is ALKS 33 where the carboxamide group is flanked by a hydroxyl group and more recently, we found that substitution of the nitrogen of 8-CAC with various biphenylethyl groups (e.g., Q) is responsible for extraordinarily high affinity for opioid receptors.

In September 2006 Rensselaer signed a license agreement granting Alkermes Inc. - a biotechnology company based in Massachusetts - exclusive rights to the opioid compounds discovered by our team. As a result of Alkermes' expertise and commitment in preclinical and clinical development of agents to treat central nervous system disorders, Phase 2 clinical trials were initiated for two compounds from Rensselaer's opioid library, ALKS 33 (in a combination with buprenorphine called ALKS 5461) and ALKS 37. The following press releases from Alkermes describe clinical results:

Alkermes Announces Positive Results from Phase 2 Clinical Study of ALKS 5461 for Major Depressive Disorder

Alkermes Announces Results from Phase 2 Study of ALKS 37 for Treatment of Opioid-Induced Constipation

Collaborators: Dr. Jean M. Bidlack and coworkers at University of Rochester and Alkermes, Inc. Acknowledgments: This research was supported by the National Institute of Drug Abuse of the National Institutes of Health under award numbers DA12180 and KO5-DA00360. Funding from AMRI, Inc. is also gratefully acknowledged.

Design and Synthesis of MW06-25, a Novel Probe to Study the Pathways of Morphine's Pain-relieving Properties.

As part of a large collaborative effort headed by Dr. Lindsay Hough of the Albany Medical College, a recent report in Nature Neuroscience describes a neuronal P450 epoxygenase that mediates the pain-relieving properties of morphine. A two-tiered approached was used. The first involved a novel transgenic mutant mouse with brain neuron-specific reductions in P450 activity; compared with controls, these mice showed highly attenuated morphine antinociception. The second was a pharmacologic approach where our research group at Rensselaer designed and synthesized MW06-25, a brain P450 arachidonate epoxygenase inhibitor. MW06-25 produced a similar (to the transgenic mouse) block of morphine antinociception in mice.

Collaborators: Dr. Lindsay B. Hough and coworkers at the Center for Neuropharmacology and Neuroscience, Albany Medical College.

Acknowledgments: This research was supported by the National Institute of Drug Abuse of the National Institutes of Health under award number DA03816. 

Recent Publications (PubMed Database)