JPS5962586A - Analgesic and antiinflammatory compound, manufacture and dr-ug composition - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel compounds with significant analgesic activity. The compound according to the invention is N-(2-pyridyl)-(:1,4-dimethyl-5-(4-chlorobenzoyl)]-]2-pyrolacetamide having the formula (1).

The present invention also provides a method for producing Compound I, in which 1,4-dimethyl-5-(4-1'lolobensoyl)- The ester of 2-f-rolacetic acid can be conveniently prepared by reacting a molar excess of 2-aminopyridine via the reaction mechanism described below.

This reaction is particularly effective when using CH3(II) (1) cyanomethyl ester (1: R=CH2CN).

Further, according to the present invention, N-(2-pyridyl)-[1.,4
-dimethyl-5-(4-chlorobency#)) -2
- Also provided are pharmaceutical preparations with analgesic, anti-inflammatory and anti-inflammatory action consisting of or containing pyrroleacetamide as an active ingredient.

Hereinafter, the present invention will be explained in more detail with reference to examples.

1 1,4-dimethyl-5-(4-chlorobenzoyl)-2
-750 to 660.9 (2 moles) of viroleacetic acid! 7(
8 mol) of 2-aminopyridine were added and the mixture was then heated to 100° C. in a nitrogen atmosphere. After 1 hour, 8
51 liters of water at 0° C. was added and the mixture was stirred at this temperature until the product was completely crystallized. The mixture was then filtered, washed with water, and wet crystallized from ethyl-hylosolp (2-ethoxyethanol, 7-containing solvent). The N-(2- pyridyl)-[1,4-
C;I chill-5-(4-/lolobensoyl)]-]2
-The melting point of virolacetoacetamide is 182 to 18.
It is c.

Elemental analysis value as C2oH1sN,02C1 (molecular weight 367.82): Calculated value: C65,30H4,93N 11.42C Measured value: C65,72H4-88N 11.09% Compound (1) using the following test method The analgesic and anti-inflammatory effects of codine hydrochloride were measured in comparison with codine hydrochloride.

- Caladenin edema test using rats [Winter (
Winter) et al., Proc, Soc, Exp,
Fljo],,.

111.544.1962]; phenylquinone test using m-mouse [Hendershot and F.
orsaj, th), J, Pharrr+ac
o1. Exp, 'rher, +123+2
7, 1959]; - Randall Selit test [1, o, Randall (Ra
nd, all) and J, J, Sellit (5elit
to ).

Arch, Int, Pharmacodyn,
, U”! 409, 1957] knee-hot
plate test. Male white mice treated with increasing doses of the test compound are placed on 58" (E) pot plates. The time until the mice show no response to pain is then measured. The effective dose (ED) is , defined as the lowest dose that significantly prolongs the reaction time compared to the control; - acute oral toxicity was investigated in mice and rats;
Expressed as LD5o after 4 days of observation.

The results of the above test are shown in Table 7. The doses listed in the table are expressed in mg per 1 Icg of body weight in oral administration.

As can be seen from Gita in Table 1, Compound I has a superior analgesic effect to codine hydrochloride. Moreover, unlike codine hydrochloride, "nalorufin jumping" in mice
It can be concluded that Compound I does not induce physical dependence.

The present invention also relates to the use of N-(2-tlysyl)-41,4-dimethyl-5-(4-chlorobenziyl)'l]-2-virolacetamide in the treatment of humans.
, also relates to all industrially applicable aspects.

Accordingly, an essential aspect of the present invention comprises a predetermined amount of Compound T to treat neoplasms, surgical procedures,
It consists of pharmaceutical preparations useful for the treatment of acute and chronic pain associated with bone arthritis and headaches of various causes.

The compounds of the invention can be used, for example, in tablets, capsules, dragees, syrups, herbal medicines and microclis
It can be administered orally or rectally in the form of m).

By way of further example, the following formulation is described: 25 to 500 m9 of the compound of 2 as active ingredient;
Bulking agents and sentence arrangement commonly used in the field of formulation technology
A tablet containing +'F agent.

Example 111 How much active ingredient can a compound of formula I be added to from 25 to 500 m? Containing one piratine capsule.

Example IV What is the active ingredient of the compound 'r50-100m? Contains suppositories.

Agent Asamura Hao

Claims (1)

[Claims] (1) N-(2-pyrisol)-L having formula 1: 1,4-dimethyl-5(4-/lolobenzoyl)]-]2-pyrolacetamide +2170 to 200°C At a temperature within the range of 1,
/I-dimethyl-5-(4-chlorobenzoyl)-2-
Claim +11 consisting of reacting with 7 molar excess of 2-aminopyridine of t'-roll nitride acetate.
A method for producing compound (I) described in . (:3) The ester used is cyan methyl ester! 14. The method according to claim (2). (4) N-(2-pyridyl)-(1,4
A method for producing -tumethyl-5(4-chlorobenzoyl)]hyrolacetamide. (5) N-(2-birisol)-[1,
4-dimethyl-5-(4-chlorobenzoyl)]-]2
- A pharmaceutical composition comprising pyrroleacetamide and a pharmaceutically acceptable filler or carrier. (31 Pharmaceutical composition according to claim (5) in the form of a tablet, sugar-coated tablet, capsule, syrup, drop, herbal medicine or microcrysm. (7) Any one of Examples n to ■ below) N-(2-pyridyl)-El, 4-dimethyl-5-
A pharmaceutical composition comprising (4-chlorobenzoyl)]-]2-virolacetamide.