Download Derivatives of Mecamylamine

Derivatives of Mecamylamine
Overview
Technology and Patent Status
Mecamylamine (Inversine ®) is a general nicotinic
acetylcholine receptor (nAChR) antagonist drug that was
previously used to treat high blood pressure prior to the
discovery and clinical use of beta-blockers. More recently
mecamylamine (MA) has been reinvestigated as an antiaddiction agent and to treat conditions such as
depression, ADHD, Tourette’s syndrome amongst others
by action at nicotinic acetylcholine receptors. Despite
such potential over numerous disease states only limited
SAR information is available.
Preliminary testing of the first library is extremely
positive.
The novel compounds are at worst
comparable to MA however, one compound is a
considerably more potent antagonist of the alpha-4beta-2 nicotinic acetylcholine receptor than the lead
compound MA.
Me
Me
NHMe
Preliminary electrophysiological testing of the initial
compound library has shown that most compounds
have similar or slightly improved activity with respect
to MA itself but one compound in particular is a
significantly more potent antagonist than MA.
A priority patent application has been filed with the
EPO.
Me
Applications
mecamylamine
Researchers at Trinity College Dublin have devised a
novel synthetic route facilitating the preparation of a library
of MA derivatives that are inaccessible by prior art
synthetic methods. The novel and inventive compounds
prepared by the method of the present invention may find
utility in the treatment of any condition responsive to the
antagonism of nicotinic acetylcholine receptors
Treatment of a condition responsive to antagonism
of a nicotinic acetylcholine receptor;
Treatment of substance addiction, aiding smoking
cessation;
Treatment of depression
2
R
1
R
4
5
N(R )(R )
Advantages
Novel synthetic route provides for huge array of new
chemical entities, whilst the original route had little scope
to produce such compounds.
MA has an excellent biological profile, good absorption,
pharmacokinetics and crosses the blood-brain-barrier and
millions of doses have been employed in humans.
3
R
General formulae for the invention
The opportunity
Offers potential new therapeutics for addiction and/or
depression along with other CNS issues/disorders for
example Tourette’s Syndrome and ADHD.
These high-growth-potential compounds have been
developed from their inception to be suitable for
clinical development and commercialisation.
The analogues have been prepared with the aim of
providing a more efficacious treatment with reduced sideeffects.
Trinity College Dublin are offering an opportunity to
collaborate and/or licence the technology for further
development
Researcher:
Contact:
Ref:
Dr. Mike Southern and David Mangan
Dr. Emily Vereker, TTO Case Manager [email protected]
MS01-281-01
+ 353 1 896 4152