IL29580A - A reaction product from chloral hydrate and 7-chloro-1-methyl-5-phenyl-1,4-3h-benzodiazepin-2(1h)-one and psychotropic compositions containing it - Google Patents
A reaction product from chloral hydrate and 7-chloro-1-methyl-5-phenyl-1,4-3h-benzodiazepin-2(1h)-one and psychotropic compositions containing itInfo
- Publication number
- IL29580A IL29580A IL2958068A IL2958068A IL29580A IL 29580 A IL29580 A IL 29580A IL 2958068 A IL2958068 A IL 2958068A IL 2958068 A IL2958068 A IL 2958068A IL 29580 A IL29580 A IL 29580A
- Authority
- IL
- Israel
- Prior art keywords
- chloro
- phenyl
- chloral hydrate
- solvent
- benzodiazepin
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
-l-ni a-T oy ΒΚΤΊ*Π um a najina ^a nan nsia
n**-(1 Η)2-7»3ΤΚ»τητ33-3 H-4,1- * Js-5- 'na
A reaction product from chloral hydrate and
7-chloro-1 -methyl-5-phenyl-1 ,4-3H-benzodiazepin- 2(lH)-one and psychotropic compositions containing it.
DEL AR CHEMICALS LIMITED
C : 28004
ABSTRACT
A new substance having pharmaceu cal activity is prepared by reacting chloral hydrate and 7-chloro-l-rethyl-5-phenyl-l , -3H-ben2odiazepin-2 (1H) -one. The molecular formula of the new substance} which has a
β
m.p. of about 110 C, is C. ^H. -CI ,Ν.Ο, . I.R. spectrum (see drawing) shows absorption bands among others at about 3430 j and 1670 cm""1.
BACKGROUND OP THE Ii-]V.3NT∑QN
This invention relates to a new substance
and to a process for its preparation. More specifically, this invention relates to 7-chloro-l-mathyI-5-phenyl-l,4-3H-ben2odiasepin~2 (1H) -one chloral hydrate and to a process for its preparation.
SU?-S-IARY OF THE I INV EN IO
An object of the invention is to provide a new and useful substance. Another object is to provide a method for the preparation of said substance.
The product of the present invention is
represented by the general formula: cIQKI5C-^N2°3
has a melting point of about 110 C . It shov/s especially characteristic infra-red absorption bands at about 1670 cm' and at about 3430 cm""5". The complete infra-red spectrum, taken in potassium bromide is shown in the single figure of drawings .
The compound of this invention displays
valuable pharmacological properties. In particular, it exhibits tranquilizing, anti-convulsive and iruscle relaxant properties.
When tested on mice, the effect on the --■ central nervous system of the product of the present invention was found both qualitatively and quantitatively different from that of- 7-chloro-l-methyl-5-phenyl-l, 4- 3H-benzodiazepin-2 (1H) -one and from that of the physical mixtures of the latter with chloral hydrate in 1:1 and 1:2 molar proportions. The compound of the present invention was found to be a potent muscle relaxant as shown in Table I and also an anticonvulsant (against strychnine induced convulsions) as shown in Table II.
In both tables the product of the present invention is represented by A, whereas B represents 7-chloro-l-methyl-5-phenyl-l, 4-3H-benzodiazepin-2 (IK) -one, C represents chloral hydrate, D represents an equimolecular mechanical mixture of B and C and Ξ represents a mechanical mixture of B and C in 1:2 molecular ratio.
TABLE 1. MUSCLE RELAXANT DOSE OF VARIOUS COMPOUNDS IN TUB MOU
Range for 19/20 confidence limit
M.S. - not significant at 19/20 confidence limit
OF VARIOUS COMPOUNDS IN THE MOUSE (PER OS)
" Range for 19/20 confidence limit.
M.S. - not significant at 19/20 confidence limit.
As can be clearly seen from the above descrip tion the pharmacological activity of th . roduct of the present invention is qualitatively and quantitatively different from the activities of either of the starting materials and their mechanical mixtures. These high activities could not be foreseen from the activities of the components and the results obtained on testing are unexpected and surprising.
Equally surprising is the easy formation of the product of this invention, especially in. view of the fact that benzodiazepinones not substituted in position 1 or substituted with substituents such as a phenyl group in position 3 do not react with chloral hydrate under the conditions used for the preparation of our new product.
The compound of this invention may be
prepared for administration by formulation with the usual pharmaceutical carriers, for oral administration.
For example, an amount of the product of the invention ranging from about 2 milligrams to about 200 milligrams, individually selected according to the condition to be treated, may be formulated into dosage units with any of the usual pharmaceutical carriers, as for example, lactose, starch, gelatin, etc.
The product cf the invention is recdily obtained in excellent yields by reacting together
7-chloro-i-i^ethyl-5-phsnyl-i ,4-2H-ben.¾oeias i -2 {IE) -one and chloral hydrate. Best results are obtained by bringing the reactants together in approximately equi olar quantities". It is preferred to bring the reaction about by heating e.g. above room temperature bu j if a solvent is used, the reaction vili take place even at room temperature. A mere mechanical mixture of the two reactants in the absence of a solvent will not yield the desired product at room temperature. The reaction is preferably carried out - in a medium of a substantially non-polar organic solvent, e.g. benzene, toluene 3 xylene, or hexane. However, the product of the invention is also obtained v;hen the tv;o reactants are melted together in the absence cf a solvent. ' ,
The nature of the bond obtained in the reaction.is not clear. Possibly, the strong partial positive charge cf the carbon atom v;hich is substituted by three chlorine atoms in chloral hydrate is partially compensated by the partial negative charge of the imino nitrogen of the other reactant. Another hypothesis is that the- imino dipole is discharged by addition of a hydroxy! group from the chloral hydrate. Eovrever, the present invention is not restricted to any theoretical interpretation of the reaction.
In order that the nature of the present
invention be more fully understood, the following
examples are given for illustration, but they
should not be construed as limiting the scope of
the invention.
EXAMPLE 1
To a stirred solution of 6.8 g' of chloral
hydrate in 12 ml of benzene at a temperature of about
40°C were added 10 g of 7-chloro-l-roethyl-5-phenyl-l,4-3K-benzodiazepin-2 (1H) -one. The latter compound went immediately into solution and the reaction product
precipitated from the reaction mixture in a short time.
It was collected by filtration, washed with benzene and dried at room temperature. The yield was about 15 g.
An analytical sample was prepared by recrystallization from benzene and had a melting point of about 110 C.
Analysis: calculated for °ΐ8Η16014Ν203 : C 4δ·02? κ 3·5δ> CI 31.51, N 6.22%; found C 48.01, K 3.77, CI 31.52, N 6,10%.
EXAMPLE 2
The process was carried out as described in
Example 1, except that toluene was used instead of
benzene as solvent. The same product as in Example 1 was obtained in the amount of 13.2 g.
EXAMPLE 3
Using xylene instead of benzene as reaction medium, the otherwise same--process... as described in .
Example 1 was carried out. The same product as in
Examj^le 1 was obtained. The yield was 13 g.
EXAMPLE 4
To a boiling solution of 6.8 g of chloral
hydrate in 100 ml- of hexane were added 10 g of 7-chloro-l-methyl-5-phenyl-l , 4-3H-benzodiazepin-2 (IK) -one. The latter starting material dissolved immediately and the reaction product precipitated on cooling. The yield was 14.1 g and the product was found identical with that described in Example 1.
EXAMPLE 5
An intimate mixture of 1.4 g of chloral hydrate and 2 g of 7-chloro-l-methyl-5-phenyl-l , 4-3H-benzodiazepin-2(lH)-one was heated to 100°C and ke t at that temperature for 10 minutes. After cooling, the product was triturated with benzene and collected by filtration.
The yield was 2.25 g and the product was found identical with the one described in Example 1.
EXAMPLE 6
To a stirred. solution of 6.8 g of chloral hydrate in—15 ml. benzene, 10 g of 7-chloro-l-methyl-5-phenyl-l , 4-3H-benzodiazepin-2 (1H) -one- were added at room temperature. The latter compound went immediately into solution and the reaction product' precipitated from the reaction mixture in a short time. It was collected by filtration, washed with benzene and dried at room temperature. The yield was 14.3 g and the product was found identical with that described in Example 1.
29580/2
Claims (1)
- CLAIMS 1. A chemical substance having a molecular formula of C. QH. gCl. O-, further characterized by a melting point in potassium bromide of about 118 C and by infra-red absorption bands/at about -1 -1 3430 cm and 1670 cm , said substance resulting from are brought together in a medium of a \substantially non-polar organic solvent. 5. A process according to Claim 4t wherein the solvent is benzene. '{ 6. A process according to Claim 4, wherein the solvent is toluene. < 7. A process according to Claim 4, wherein the solvent A is xylene. ! \ 8. A process according to'( Claim 4, wherein the solvent is n-hexane. 29580/.Γ ( 9. A process according to Claim 4, wherein the reaction is carried out at a temperature higher than room temperature, 10. A pharmaceutical composition _having psychotropic activity comprising a pharmaceutical carrier and an effective amount of the product of Claim 1.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US62079967A | 1967-03-06 | 1967-03-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
IL29580A true IL29580A (en) | 1971-12-29 |
Family
ID=24487444
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL2958068A IL29580A (en) | 1967-03-06 | 1968-03-05 | A reaction product from chloral hydrate and 7-chloro-1-methyl-5-phenyl-1,4-3h-benzodiazepin-2(1h)-one and psychotropic compositions containing it |
Country Status (13)
Country | Link |
---|---|
AT (1) | AT286991B (en) |
BE (1) | BE711676A (en) |
CH (1) | CH505117A (en) |
DK (1) | DK121234B (en) |
FI (1) | FI48351C (en) |
FR (2) | FR1583753A (en) |
GB (1) | GB1183060A (en) |
IE (1) | IE31974B1 (en) |
IL (1) | IL29580A (en) |
LU (1) | LU55619A1 (en) |
NL (2) | NL6803061A (en) |
NO (1) | NO119841B (en) |
SE (1) | SE342629B (en) |
-
0
- NL NL138681D patent/NL138681C/xx active
-
1968
- 1968-03-05 FI FI60168A patent/FI48351C/en active
- 1968-03-05 CH CH324468A patent/CH505117A/en not_active IP Right Cessation
- 1968-03-05 DK DK90368A patent/DK121234B/en unknown
- 1968-03-05 IE IE25668A patent/IE31974B1/en unknown
- 1968-03-05 SE SE289068A patent/SE342629B/xx unknown
- 1968-03-05 LU LU55619D patent/LU55619A1/xx unknown
- 1968-03-05 NO NO82568A patent/NO119841B/no unknown
- 1968-03-05 FR FR1583753D patent/FR1583753A/fr not_active Expired
- 1968-03-05 BE BE711676D patent/BE711676A/xx unknown
- 1968-03-05 NL NL6803061A patent/NL6803061A/xx unknown
- 1968-03-05 IL IL2958068A patent/IL29580A/en unknown
- 1968-03-06 AT AT219668A patent/AT286991B/en not_active IP Right Cessation
- 1968-03-06 GB GB1099268A patent/GB1183060A/en not_active Expired
- 1968-06-05 FR FR153796A patent/FR7640M/fr not_active Expired
Also Published As
Publication number | Publication date |
---|---|
AT286991B (en) | 1971-01-11 |
LU55619A1 (en) | 1969-10-02 |
DE1670593A1 (en) | 1972-01-27 |
FI48351C (en) | 1974-09-10 |
FR7640M (en) | 1970-02-02 |
SE342629B (en) | 1972-02-14 |
FR1583753A (en) | 1969-12-05 |
NO119841B (en) | 1970-07-13 |
GB1183060A (en) | 1970-03-04 |
CH505117A (en) | 1971-03-31 |
NL6803061A (en) | 1968-09-09 |
IE31974L (en) | 1968-09-06 |
BE711676A (en) | 1968-09-05 |
FI48351B (en) | 1974-05-31 |
IE31974B1 (en) | 1973-03-07 |
DE1670593B2 (en) | 1975-12-04 |
DK121234B (en) | 1971-09-27 |
NL138681C (en) |
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