FR182M - - Google Patents

Description

MINISTRY OF INDUSTRY

• SERVICE. ; .

of INDUSTRIAL PROPERTY

P.V. n ° 835.703> S

International classification: A 61 k

\ W 182 m!

not. _ - „f-

C 07 c

Dibeizo-cycioheptaenic compounds. , ^ -; V * - - .. l

Company known as: F. HOFFMANN-LA ROCHE & CIE Société Anonyme residing in Switzerland.

• Requested on August 12, 1960, at 11h 17m, in Paris.

Issued by decree of February 20, 1961. '•.

{Official Bulletin of Industrial Property [B.S .M. No. 5 of 1961.) [Patent application filed in Switzerland on April 3, 1958, under No. 57.958,

at the nonri of the plaintiff.).

(Patent resulting from the division of the invention patent application, P.V. No. 790,432, filed March 26, 1959.),

The present invention "relates to a di-benzocycloheptaene compound of the general formula '.

-

. in which A represents a saturated non-aromatic radical containing at least 3 carbon atoms and carrying one or more tertiary amirio groups, the 'heptaene nucleus possibly having an additional double bond, optionally' substituted in the nucleus by groups . "alkyls, aralkyls, aryls, alkoxy, aralkoxy, aryloxy, alkylthio, aral-coylthio, aryltbio, halo, acyls, amino, hydroxyls and carboxyls, as well as their dehydration and hydrogenation products, as well as their salts. and their quaternary ammonium compounds.

In particular, the invention relates to novel preparations containing the novel drug represented by the above general formula. - The process for obtaining this drug is described in the patent application filed in France on March 26, 1959 in the name of the applicant for c. Dibenzo-cycloheptaenic compounds and 'preparation thereof'. It is in particular characterized by the fact that the compound of the general formula is reacted.

\AT /\/

in which the heptaene ring may optionally carry an additional double bond, and its derivatives substituted by alkyl, aralkyl, aryl, alkoxy, aralkoxy, aryloxy, alkylthio, aralkoyithio, arylthio, protected halogeno, protected amino, protected hydroxyl and protected carboxyl groups , with a non-aromatic saturated organometallic compound containing at least 3 carbon atoms and bearing one or more tertiary amino groups, the reaction product is hydrolyzed, any protective groups present are removed, and any protective groups present are removed. optionally treated with a dehydrating agent, the semicyclic double bond is hydrogenated and, where appropriate, the bases obtained are transformed into their salts, acid addition or quaternary salts. '• v

The invention also includes the addi- salt. tion of acid or quaternary salts of the above dibenzo (a, e) cyclohepta [l, 5] diene or dibenzo [a, e] cyclohepta [l, 3,5] triene compounds, for example those with inorganic acids , such as hydrochloric acid, hydrobromic acid, sulphuric acid; with organic acids, such as oxalic acid, citric acid, acetic acid, lactic acid, tartaric acid; and those with quatemizing agents, such as alkyl halides, for example methyl bromide, ethyl iodide, dialkyl sulfates, for example dimethyl sulfate, as well as aralkyl halides for example benzyie bromide.

The products of the invention are distinguished by their multiple activities on the nervous system. In particular, it has been observed that they possess a potentiating action on narcosis and an adrenolytic, sedative, antihistamine, antiemetic, antipyretic and hypothermic activity.

The new medicinal preparations according to the invention may contain the active substance in

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admixture with a pharmaceutical vehicle which may be organic or inorganic, solid or liquid, suitable for oral or parenteral administration. As a pharmaceutical carrier, substances which do not react with the new compounds can be 'used', para. example water, gelatin,

* lactose, starch,; stearate, magnesium, talci-vegetable oils "and other vehicles of use, in medicinal preparations. These preparations may be in the form of tablets, dragees or solutions, suspensions.

, i. sions or emulsions. If desired, the preparations may be sterilized and / or may contain. auxiliary substances, para. example preservatives, stabilizers, wetting or emulsifying. They can also contain salts: regulating the osmotic pressure or compounds: buffer. These preparations are obtained by the usual methods, illustrated by the following examples. • Example 1. - 100 g of 5- (w-dimethylamino-propylidene) -dibenzo [a, e] - cyclo- • heptà [1,5] diene hydrochloride, 150 g of aerosil compositum, 420 g. "Corn starch, 300 g of .lactose 'and 30 g of talc are thoroughly mixed and triturated, then pressed into 100 mg tablets. These tablets decompose" *; - dahsTeau' in the space of. 3 1: 5 mins.

Example 2. - 50 g of 3-chloro- hydrochloride. 5 - (& vdimethylamino-propylidene) -dibenzo [a, e] cy-clohepta [l, 5] diene, 110 g of corn starch, 120 g> 'of lactose and 20'g of talc are intimately mixed

* and 'triturated, then pressed into tablets of 300 mg. r vi These tablets decompose in water within 4 minutes. . ' ^ • s. '

Example 3. - A solution is prepared with

* 0.8 g of 5- (w-dimethyl-amino-propylidene) -dibenzo- [a, e] cyclohepta [l, 5] diene (hydrochloride), 0.08 g of "Nipagine" (methyl p-aminobenzoate) ), 0.01 g of "Nipasol" (propyl p-aminobenzoate) and

^ 100 ml of redistilled water. This solution is placed in 2.2 ml ampoules under a nitrogen atmosphere.

" ' ABSTRACT . '

The subject of the invention is:.

. As a new medicinal product: '1 ° The dibenzo-cycloheptaenic compounds of the general formula / ■ "

HO

V \

in which A represents a non-aromatic radical

tiquëMturé "containing * ^^ 5irif3âtome ^ d ^^^ ®i (and: poiteot.vdeg

"Nopa: heptaéiûque'ï capable", ëyentueliemfa ^^ é-senter urié additional double bond,

lement: substituted 'in the nucleus' by.

/ ments alkyls, aralkyls, * ar ^ es, '. alcbxyï; ^ ralcqçy5 "aryloxy, alkylthio, aralkoyithio, aryîthio, - halo, acyls, aminos, hydroxyls et carboxylés, as well as their dehydration and hydrogenation products , as well as their salts and their quaternary ammonium compounds;

-r-2 ° The dibenzo-cycloheptaenic compounds of the general formula::; . ': f £,' f>. : "

-W '

; / \

\AT

in which A represents a dialkyl - minoalkyl group, the heptaene ring possibly having an additional double bond, optionally substituted in the ring by halogen atoms, as well as - their dehydration or hydrogenation products and their ^ âels d 'addition of acids and their "quaternary ammonium salts; •.' •> -

3 ° The dibenzo-cycloheptaenic compounds described in paragraph 2 °, in which A represents a. dialkoylaminopropyl group; ';; 4 ° 5-hydroxy- 5- ("y-dimethylamino - propyl) - (ifc benzo [a, e] cyclohepta [l, 5] diene; 5 ° 3-chloro-5-hydroxy: 5- ("Y-dimethylammo3 propyl) -dibenzo [a, e] cyclohepta [l, 5] diene,! 6 ° 5-hydroxy- 5 - (" y-dimethylamino - propyl) -dir benzo [a "e] cyclohepta [ l, 3,5] triene; "'■ .. -

7. 5 - (w-dimethylamin6-propylidene) - dibenzo [a, e] -cyclohepta [l, 3, 5] -diene; . ->

8. 3-Chloro-5- (γ-dimethylamino-propylidene) _- dibenzo [a, e] cyclohepta [1,5] -diene; •• '' r

9 ° 5- (iw-dimethylammo-pro'pylidene) -diberizo [a, e] -cyclohepta [1,3,5] -triene; ■ - '' •

10. The '5- (û) -dimethylaminopropyl); dibenzo [a,' 'e] cyclohepta [1,5] -diene; ■ ■

'11 ° Medicinal preparations containing dibenzocycloheptaenic compounds defined in paragraphs 1 to 10 °.

Society known as: "r. •

F. HOFFMANN-LA. ROCHE & CIE.

Anonimous society -

Vicarious : '.

Étieime Coulomb>

For the sale of fascicuJÉjg ,. contact the Imprimerie Nationale, 27, rue de la Convention, Paris (15 *).