SOSA approach of minaprine drug

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BANGLADESH UNIVERSITY
Topic: SOSA Approcess of Minaprine
Prepared by,
Mohammed Tareq Aziz
Student, Department of PHARMACY,
Bangladesh University,
Iqbal road, Mohammadpur,
Dhaka-1207

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Index
S/N Contents Page no.
1 Definition of SOSA. 02
1.1 Rationale of the SOSA approach 02
2
Indication & side effects of
Minaprine
02
2.1 SOSA approach of Minaprine 03

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1. Definition of SOSA.
Selective optimization of side activities of drug molecules can be
abbreviated as SOSA.
SOSA approach is an intelligent and potentially more efficient strategy than
HTS for the generation of new biological activities. Only a limited number of
highly diverse drug molecules are screened, for which bioavailability and
toxicity studies have already been performed and efficacy in humans has
been confirmed. Once the screening has generated a hit it will be used as
the starting point for a drug discovery program. Using traditional medicinal
chemistry as well as parallel synthesis, the initial 'side activity' is
transformed into the 'main activity' and, conversely, the initial 'main activity'
is significantly reduced or abolished. This strategy has a high probability of
yielding safe, bioavailable, original and patentable analogues.
1.1 Rationale of the SOSA approach
The rationale behind the SOSA approach lies in the fact that, in addition to
their main activity, almost all drugs used inhuman therapy show one or
several side effects.
In other words, if they are able to exert a strong interaction with the main
target, they exert also less strong interactions with some other biological
targets. Most of these targets are unrelated to the primary therapeutic
activity of the compound.
The objective is then to proceed to a reversal of the affinities, the identified
side effect is becoming the main effect and vice-versa.
2. Indication & side effects of Minaprine
Minaprine (INN, USAN, BAN) (brand names Brantur, Cantor) is
a monoamine oxidase inhibitor antidepressant drug that was used for the
treatment of depression until it was withdrawn from the market in 1996
because it caused convulsions.
Selective optimization of side activities

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A study found that it acts as a reversible inhibitor of MAO-A (RIMA) in rats.
In a study it has also been found to weakly inhibit acetyl cholinesterase in
rat brain (striatum) homogenates.
2.1 SOSA approach of Minaprine (From minaprine to cholinergic agents)
In the early 1980s we prepared the atypical antidepressant drug
minaprine dihydrochloride (Cantor®,Isopulsan®). It was the result of a
collaborative research on psychoactive pyridazines undertaken with
Dr. Henri Laborit and the scientists of the Sanofi Group.
Minaprine proved to be active on animal models of depression and its
mechanism of action was attributed to an enhancement of the
dopaminergic transmission and to a lesser extend of the serotoninergic
transmission.
Soon it was observed that, besides its dopaminergic and serotoninergic
profile , it also exhibits some cholinergic activity. This was an interesting
observation, because according to the cholinergic hypothesis , memory
impairment in patients with senile dementia of the Alzheimer type result
from a deficit of cholinergic functions of the brain.
Then, Scientists undertook the synthesis of minaprine analogs with
increased cholinomimetic properties and if possible with less
dopaminergic serotoninergic activities.
Taken together , we observed that three simple modifications
(01)Methyl shift.
(02)Lipophilic cationic head
(03)presence of an orthohydroxylic functions
The lucky serendipitous result was that the compounds were totally
devoid of any dopaminergic and serotoninergic properties.
This result in first perception of the selective optimization of the side
activity.

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