2-(BENZHYDRYLSULFONYL)ACETAMIDE, PROCEDE POUR SA PREPARATION ET SES UTILISATIONS THERAPEUTIQUES

2-(BENZHYDRYLSULFONYL)ACETAMIDE, A PROCESS FOR ITS PREPARATION AND ITSTHERAPEUTIC USE

Abrégé anglais

ABSTRACT OF THE DISCLOSURE
The subject of the present invention is
2-(benzhydrylsulfonyl) acetamide, which is a compound
of the Formula I:
<IMG> - SO 2 - CH2 - CONH2 I
This compound exhibits an activity on the central
nervous system and may be used in therapy. There is
also disclosed a process for the preparation and the
usage of this compound as an active ingredient in
therapeutic compositions.

Revendications

WHAT IS CLAIMED IS:
1. 2-(benzhydrylsulfonyl) acetamide.
2. Process for the preparation of 2-(benz-
hydrylsulfonyl) acetamide, comprising the oxidation of
2-(benzhydrylthio) acetamide.
3. Therapeutic composition comprising a
compound according to Claim 1 as active ingredient and
a pharmaceutically acceptable carrier.
-4-

Description

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-- 1 -
The present invention ralates to 2-(benzhydrylsulfonyl)
acetamide, a process for its preparation and its therapeutic use.
Thus, the subject of the present invention is 2 (benzhydryl-
sulfonyl) acetamide which is a compound of f~rmula:
~\
CH - S02 - CH - CONH
~Y
The applicant has di~covered that this compound exhibitQ an
activity on the central nervous system and may be used in therapy.
2-(benzhydrylsulfonyl) acetamide can be prepared by oxlda~ion.
in particular by hydrogen peroxide, from 2-(benzhydrylthio) acetamide~
the latter itself being prepared by reaction of ammonia with 2-(benzhydrylthio)
acetyl chloride.
Therapeutic compositions containing 2-(benzhydrylsulfonyl)
acetamide as active ingredient are also a subject of the present invention.
The following example illustrates the preparation of the compound:
a) Preparation of 2-(benzhydry~ o) acetamide
21 g (0.076 mole) of benzhydrylthioacetyl chloride dissolved in
100 ml of methylene chloride are added drop-wise with stirring to 40 ml of
ammonia and 40 ml of water. After being stirred for 1 hour, the organic
pha~e i~ separated, washed with water and dried over Na2S04. The solvent iq
e~aporated in a vacuum, the residue is crystallized from isopropyl ether and
recrystallized from ethyl acetate. The compound is obtained in a yield of
45~.
It is a white powder, soluble in alcohols, acetone, ethyl
acetate; insoluble in water, isopropyl ether. It melts at 107-108C.
b) Preparation of 2-(benzhydrylsulfonYl) acetamide (Code ~o. CRL 41 056)
12.85 g (0.05 mole) of 2-(benzhydrylthio) acetamide dissolved In
50 m} of acetic acid are oxidized by the drop-wise addition of 15 ml
(0.15 mole) of 110 Yolumes strength hydrogen peroxide bet~een 20 and 30C.
After being ~tirred for 5 hours9 the mixture is left ~o stand for 48 hour3.
The sulfone is filtered off, washed with water, dried and recry~tallized
from ethanol.
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The compound is obtained in an overall yield of 36%.
It exists in the form of white needles, soluble in alcohols,
acetone; slightly soluble in chloroform, ethyl acetate; insoluble in
ethyl ether, water. It melts at 194C.
The results of the pharmacological studies on the compound
(CRL 41 056) demonstrating its properties will be given below.
A suspension of CRL 41 056 in a solution of gum arabic was
administered by the intraperitoneal route in a volume of 20 ml/kg to the
mouse (male, NMRI, Evic Ceba) and 5 ml/kg to the rat (male, CDl,
SPRAGUE DAWLEY, Charles).
I - Pretoxicity (3 mice per dose)
- At doses of 64,_128 and 256 mg/kg appearance of stomach
cramps
- At a dose of 512 mg/kg: stomach cramps, dyspnea.
- At a dose of 1024 mg/kg: stomach cramps, dyspnea, sedation,
no deaths.
II - General behaviour and reactivity
Groups of 3 rats were observered before and then at 15 mn,
;~ 30 mn, 1 h, 2 h, 3 h and 24 h after administration of CRL 41 056.
4 mg/kg: hypo-reactivity on being touched
(30 mn)
25- 16 mg/kg: hypo-reactivity on being touched
(30 mn)
: mydriasis for 2 to 3 hours
- 64 mg/kg: hypo-reactivity on being touched (30
to 60 mn)
:: :
: muscular hypotonia (15 mn)
: mydriasis for 1 hour
- 256 mg/kg: hypo-reactivity on being touched and
muscular hypotonia for 30 mn.
: mydriasis for 1 to 3 hours
: dyspnea for 2 hours.
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III - Action on spontaneous motility
A half-hour after being given CRL 41 056, the mice (6 per
dose, 12 controls) are placed in an actimeter where their motility is
recorded for 30 minutes.
At doses of 12~ and 512 mg/kg, CRL 41 056 brings about a
diminution in spontaneous motor activity.
Conclusion
CRL 41 056 shows a sedative effect associated with hypo-
motility and hypo-reactivity.
CRL 41 056 has proved to be a good sedative in man when two
tablets each containing 100 mg are taken per day.
The therapeutic compositions according to the invention may
be administered to man or animals by the oral and parentera7 routes.
They may be available in the form of solid or semi-solid
preparations. As examples may be cited tablets, capsules, suppositories
as well as delayed-release forms.
In these compositions, the active ingredient is usually
mixed with one or more of the pharmaceutically acceptable excipients
usually used and well-known to the specialist.
The quantity of active ingredient administered obviously
depends on the patient who is being treated, the route of administration
and the severity of the disease.

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