FR2467847A1 - 1:Acyl 2:hydroxy halo:benzoyl benzimidazole(s) - having vasodilating, anti:hypertensive and sedative properties - Google Patents

1:Acyl 2:hydroxy halo:benzoyl benzimidazole(s) - having vasodilating, anti:hypertensive and sedative properties Download PDF

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FR2467847A1
FR2467847A1 FR7925805A FR7925805A FR2467847A1 FR 2467847 A1 FR2467847 A1 FR 2467847A1 FR 7925805 A FR7925805 A FR 7925805A FR 7925805 A FR7925805 A FR 7925805A FR 2467847 A1 FR2467847 A1 FR 2467847A1
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benzimidazole
vasodilating
hypertensive
acyl
hydroxy
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/12—Radicals substituted by oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

1-Acylated 2-hydroxy halobenzyl benzimidazoles (I) are new (where Hal is F, Cl, or Br in the ortho or para position; A is 1-5C opt. straight hydrocarbon chain; R is H or -COOH). The cpds. are prepd. by the action of an acid or diacid anhydride on the corresp. 1-unsubstd. benzimidazole in an anhydrous, aprotic solvent such as THF and in the presence of a tertiary amine such as triethylamine. (I) may be given orally, transcutaneously, rectally or topically. (I) are long duration vasodilators also having an antihypertensive and sedative affect.

Description

NOUVEAUX DERIVES DE L'(HYDROXYBENZYL)-2 BENZIMIDAZOLE
La pressente invention a pour objet de nouveaux dérivés du benzimidazole, leur procédé de préparation et leur application comme médicament.NEW (HYDROXYBENZYL) -2 BENZIMIDAZOLE DERIVATIVES
The subject of the present invention is new derivatives of benzimidazole, their preparation process and their application as a medicament.

Les nouveaux composés selon l'invention répondent à la formule générale :

Figure img00010001

dans laquelle - le substituant Hal représente un atome de fluor, de chlore ou de
brome situé en ortho ou en para, - A représente une chalande hydrocarbonée linéaire ou ramifiée de I
à 5 atomes de carbone, - R représente l'hydrogène ou un groupe carboxyle.The new compounds according to the invention correspond to the general formula:
Figure img00010001

in which - the substituent Hal represents a fluorine, chlorine or
bromine located in ortho or para, - A represents a linear or branched hydrocarbon chain of I
with 5 carbon atoms, - R represents hydrogen or a carboxyl group.

Ces composés sont dotés de propriétés pharmacologiques intéressantes. Ils présentent notamment une activité vasodilatatrice importante et de longue dure apyres administration par voie intraveineuse, intrapéritonéale ou orale. Ces propriétés s'accompagnent ou sont la cause d'actions antihypertensives et sédatives générales. These compounds have interesting pharmacological properties. They exhibit in particular a significant and long-lasting vasodilating activity after administration by intravenous, intraperitoneal or oral route. These properties are accompanied or are the cause of general antihypertensive and sedative actions.

Ils sont utilisés soit par voie buccale, transcutanée, rectale, soit par voie locale en application topique sur la peau et les muqueuses. They are used either orally, transcutaneously, rectally, or locally as a topical application on the skin and mucous membranes.

Ces produits peuvent se présenter sous forme de solutions ou de suspensions injectables, conditionnées en ampoules, en flacons à prises multiples, de comprimés, de comprimés enrobes, de capsules, de sirops, de suppositoires et de pommades. These products can be in the form of solutions or injectable suspensions, packaged in ampoules, in multiple-take-up vials, tablets, coated tablets, capsules, syrups, suppositories and ointments.

On prépare les composés de l'invention par action d'un anhydride d'acide ou de diacide sur les (hydroxy-benzyl)-2 benzimidazoles convenablement substitués au sein d'un solvant anhydre et aprotique tel que le THF, en présence d'une amine tertiaire telle que la triéthylamine. The compounds of the invention are prepared by the action of an acid or diacid anhydride on the (hydroxy-benzyl) -2 benzimidazoles suitably substituted within an anhydrous and aprotic solvent such as THF, in the presence of a tertiary amine such as triethylamine.

Les exemples suivants illustrent l'invention sans toutefois lui conférer aucun caractère limitatif. The following examples illustrate the invention without, however, giving it any limiting character.

N-Hemisuccinate du (chloro-4 hydroxybenzyl)-2 benzimidazole
On chauffe 4 heures à reflux la solution de 12,94 g (0,05 M) de (chloro-4 hydroxybenzyl)-2 benzimidazole dans 100 cm3 de THF anhydre avec 7 cm3 de triéthylamine (0,05 M) et 5,5 g d'anhydride succinique (0,055 M). On concentre à sec, reprend par de l'acétate d'éthyle, extrait avec de la soude diluée, neutralise à pH 6 avec de l'acide chlorhydrique dilué, extrait à l'acétate d'éthyle, sèche sur Na2504, concentre à petit volume et laisse cristalliser. On obtient 10,6 g de cristaux blancs.(Chloro-4 hydroxybenzyl) -2 benzimidazole N-Hemisuccinate
The solution of 12.94 g (0.05 M) of (4-chloro-hydroxybenzyl) -2 benzimidazole in 100 cm3 of anhydrous THF is heated at reflux with 7 cm3 of triethylamine (0.05 M) and 5.5 g succinic anhydride (0.055 M). Concentrated to dryness, taken up in ethyl acetate, extracted with dilute sodium hydroxide, neutralized to pH 6 with dilute hydrochloric acid, extracted with ethyl acetate, dried over Na2504, concentrated to small volume and leaves to crystallize. 10.6 g of white crystals are obtained.

F. inst. = 202 -3 C18 H15 Cl N204 z 358,78 eh cal. : C 60,25 H 4,21 Cl 9,88 N 7,81 017,84 % tr. : 60,00 3,91 9,96 7,95 17,75 Acétyl-1 (chloro-4 hydroxybenzyl )-a benzimidazole
On chauffe 4 heures à reflux la solution de 8,1 g (0,031 M) de (chloro-4 hydroxybenzyl)-2 benzimidazole dans 80 cm3 de THF anhydre avec 4,4 cm3 (0,032 M) de triéthylamine et 3 cm3 (0,032 M) d'anhydride acétique. On concentre à sec et recristallise le résidu dans l'éthanol. On obtient 6,35 g de cristaux blancs
F. inst. = 2280
C16 H13 Cl N2 02 = 300,74 cal. : C 63,90 H 4,36 N 9,32 % tr. : 64,10 4,22 9,25 Acéty1-1 (chloro-2 hvdroxybenzyl )-2 benzimidazole
On chauffe 4 heures à reflux la solution de 8 g (0,031 M) de (chloro-2 hydroxybenzyl)-2 benzimidazole dans 80 cm3 de THF anhydre avec 4,4 cm3 (0,032 M) de triéthylamine et 3 cm3 (0,032 M) d'anhydride acétique. On concentre à sec et recristallise le rEsi- du dans ltéthanol. On obtient 5,7 g de cristaux blancs.F. inst. = 202 -3 C18 H15 Cl N204 z 358.78 eh cal. : C 60.25 H 4.21 Cl 9.88 N 7.81 017.84% tr. : 60.00 3.91 9.96 7.95 17.75 Acetyl-1 (4-chloro hydroxybenzyl) -a benzimidazole
The solution of 8.1 g (0.031 M) of (4-chloro-hydroxybenzyl) -2 benzimidazole in 80 cm3 of anhydrous THF with 4.4 cm3 (0.032 M) of triethylamine and 3 cm3 (0.032 M) is heated at reflux for 4 hours. ) acetic anhydride. The mixture is concentrated to dryness and the residue is recrystallized from ethanol. 6.35 g of white crystals are obtained
F. inst. = 2280
C16 H13 Cl N2 02 = 300.74 cal. : C 63.90 H 4.36 N 9.32% tr. : 64.10 4.22 9.25 Acety1-1 (2-chloro hvdroxybenzyl) -2 benzimidazole
The solution of 8 g (0.031 M) of (2-chloro hydroxybenzyl) -2 benzimidazole in 80 cm3 of anhydrous THF with 4.4 cm3 (0.032 M) of triethylamine and 3 cm3 (0.032 M) d is heated at reflux for 4 hours. acetic anhydride. Concentrate to dryness and recrystallize the residue from ethanol. 5.7 g of white crystals are obtained.

F. inst. 3 2420
C16 H13 Cl N2 02 = 300,74 % cal. : C 63,90 H 4,36 N 9,32 eS tr. : 63,90 4,25 9,21 F. inst. 3 2420
C16 H13 Cl N2 02 = 300.74% cal. : C 63.90 H 4.36 N 9.32 eS tr. : 63.90 4.25 9.21

Claims (3)

REVENDICATIONS 1 - Les composés répondant à la formule générale - A représente une chaîne hydrocarbonée linéaire ou ramifiée de de brome situé en ortho ou en para, - le substituant Hal représente un atome de fluor, de chlore ou dans laquelleCLAIMS 1 - The compounds corresponding to the general formula - A represents a linear or branched hydrocarbon chain of bromine located in ortho or para, - the substituent Hal represents a fluorine, chlorine atom or in which 1 à 5 atomes de carbone, 1 to 5 carbon atoms, - R représente l'hydrogène ou un groupe carboxyle. - R represents hydrogen or a carboxyl group. ble. corn. la revendication 1 et un excipient pharmaceutiquement accepta claim 1 and a pharmaceutically acceptable excipient 2 - Les compositions pharmaceutiques comprenant un composé selon2 - Pharmaceutical compositions comprising a compound according to d'activité similaire et/ou complémentaire  of similar and / or complementary activity revendication 1 et un ou plusieurs autres principes actifs claim 1 and one or more other active ingredients 3 - Les compositions pharmaceutiques comportant on composé selon la3 - Pharmaceutical compositions comprising a compound according to the
FR7925805A 1979-10-17 1979-10-17 1:Acyl 2:hydroxy halo:benzoyl benzimidazole(s) - having vasodilating, anti:hypertensive and sedative properties Granted FR2467847A1 (en)

Priority Applications (1)

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FR2467847B1 FR2467847B1 (en) 1981-10-02

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2166117A1 (en) * 1971-12-28 1973-08-10 Hoechst Ag
FR2257269A1 (en) * 1973-10-03 1975-08-08 Delalande Sa
FR2292473A1 (en) * 1974-11-28 1976-06-25 Expandia Sa 2-(Alpha-hydroxy-halobenzyl) benzimidazoles - and their salts, with antihypertensive activity

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2166117A1 (en) * 1971-12-28 1973-08-10 Hoechst Ag
FR2257269A1 (en) * 1973-10-03 1975-08-08 Delalande Sa
FR2292473A1 (en) * 1974-11-28 1976-06-25 Expandia Sa 2-(Alpha-hydroxy-halobenzyl) benzimidazoles - and their salts, with antihypertensive activity

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