Novel Bi- and Tri-Cyclic Aza Compounds and Their Uses

Categories: “Neurodegenerative Therapeutics“

Reference #: 1998-034

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP (Directory Information | Send a Message)

Description

Novel tropane derived bi- and tri-cyclic aza compounds that inhibit monoamine neurotransmitter re-uptake, and may treat disorders related to monoamine neurotransmitter re-uptake have been discovered by Georgetown researchers. Specific disorders include cocaine addiction, depression, obsessive compulsive disorder and bulimic disorder. These compounds are of interest because they exhibit selectivity for either the serotonin transporter or the dopamine transporter. This selectivity depends on the structure of the inhibitor compound. For example, certain selected compounds of this invention showed 2.5 to 104-fold greater potency than cocaine for the dopamine transmitter, while others exhibit potent binding (<50nm) of the serotonin transporter. As part of a pharmaceutical composition, these compounds can be used for the treatment disorders associated with the serotonergic and the dopaminergic neural systems of the brain, such as depression and addiction.

Applications

• Use as a Selective Serotonin Reuptake Inhibitor (SSRI)
• Treatments for cocaine addiction, depression, obsessive compulsive and bulimic disorders
• Application for use as PET and SPECT imaging agents
• Tools for diagnosing neurodegenerative diseases

Advantages

• The structurally rigid bi- and tri-cyclic aza derivatives can be structurally tuned to selectively bind either the dopamine or the serotonin transporters.
• These compounds have potentially fewer side-effects (e.g., sleep, gastrointestinal disturbances and sexual dysfunction), than currently used SSRIs
• Ease of synthesis

Stage of Development

In vitro assays validate activity and potency.

Relevant Publications

Tamiz, A.P; Smith, M.P.; Kozikowski, A.P. Bioorganic and Medicinal Chemistry Letter. 2000, 10, pp 297-300.

Smith, M.P.; Johnson, K.M.; Zhang, M.; Flippen Anderson, J.L.; Kozikowskip, A.P. J. Am. Chem. Soc., 1998, 120 (35), pp 9072–9073

INVENTORS: Alan P. Kozikowski et al.

Patent Status

U.S. Patent No. 6,150,376, Filed August 5, 1998, Issued November 21, 2000