Phenylacetamide derivatives

Details Phenylacetamide derivatives Phenylacetamide derivatives

1998-06-21

1999-10-26

Leary, Louise N.

Organic compounds -- part of the class 532-570 series

Organic compounds

Amino nitrogen containing

514466, C07C23300, A01N 4330

Patent

active

059732016

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to phenylacetamide derivatives and pharmaceutically acceptable salts thereof, which have potent analgesic and anti-inflammatory activities.


BACKGROUND OF THE INVENTION

Capsaicin, N-vanillyl-trans-8-methyl-6-nonenamide, is a hot substance found in the fruit juice of a plant belonging to the genus Capsicum. U.S. Pat. No. 4,313,958 issued to LaHann, and European Patent No. 0 282 127 granted to Garnder, disclose as having analgesic activities such natural capsaicin and synthetic capsaicin derivatives, e.g., N-{4-(2-aminoethoxy)- 3-methoxybenzyl}amide derivatives.
Also reported in LaHann et al., U.S. Pat. No. 4,424,205; Gardner et al., U.S. Pat. No. 5,045,565; and Park et al., U.S. Pat. No. 5,242,944 are various homovanillic amides, i.e., phenylacetamide derivatives, as having pharmacologically and physiologically activities superior to the conventional capsaicin derivatives. However, each of thoese disclosed in the prior art still exhibits some of the skin irritability and toxicity unique to a capsaicin.


SUMMARY OF THE INVENTION

It is, therefore, a primary object of the present invention to provide a phenylacetamide derivative having potent analgesic and anti-inflammatory activities which is less irritable and toxic.
It is another obbject of the present invention to provide a pharmaceutical composition comprising said compound as an active ingredient.
In accordance with one aspect of the present invention, there is provided et phenylacetamide compound of formula (I) and a pharmaceutically acceptable salt thereof: ##STR2## wherein: X is hydrogen, halogen, hydroxy or C.sub.1-3 alkoxy group; and wherein R.sup.1 and R.sup.2 are each independently hydrogen, C.sub.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 aminoalkyl, formyl, C.sub.1-3 alkylcarbonyl or C.sub.1-3 alkoxycarbonyl group; group consisting of C.sub.1-5 alkyl, halogen, hydroxy, C.sub.1-5 alkoxy and alkylenedioxy group;
In accordance with another aspect of the present invention, there is also provided a pharmaceutical composition containing the compound of formula (I) as an active ingredient.


DETAILED DESCRIPTION OF THE INVENTION

The compound of formula (I) is structurally distinct from the phenylacetamide derivatives of the prior art; it has a unique feature that the aralkyl substituent attached to the nitrogen atom carries an ether or thioether group therewithin. Presumably due to this structural feature, the inventive compound of formula (I) possesses a much reduced level of toxicity and skin irritability, while retaining all the analgesic and anti-inflammatory potency. Moreover, the inventive compound exhibits improved physical properties, e.g., improved solubilities in mixed solvents, as compared with the compound of the prior art. It is therefore possible to use the compound of formula (I) or a pharmaceutically acceptable salts thereof as a highly effective analgesic and anti-inflammatory agent.
The inventive compound of formula (I) may form salts when Y is hydrogen or a group containing one or more amine groups. In case when one or more amine groups are present, pharmaceutically acceptable salts thereof may be made using an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, sodium hydrogen sulfate, carbonic acid, or using an organic acid such as formic acid, acetic acid, oxalic acid, benzoic acid, citric acid, tartaric acid, gluconic acid, gentisic acid, fumaric acid, lactobionic acid, salicylic acid, acetylsalicylic acid (aspirin). In addition, the compound of formula (I) and a salt thereof may exhibit polymorphism.
The phenylacetamide derivative of formula (I) of the present invention may be prepared in accordance with a process which comprises: (i) reacting a compound of formula (II) with an amine compound of formula (III) to produce a compound of formula (IV), and (ii) reacting the compound of formula (IV) with a compound suitable for constructing a desired substituent Y to provide the compound (I): ##STR3## wherein: R is H, CH.sub.2 CH.sub.2 Cl, CH.sub.2 CH.

REFERENCES:
patent: 4313958 (1982-02-01), LaHann
patent: 4424205 (1984-01-01), LaHann et al.
patent: 5045565 (1991-09-01), Gardner et al.
patent: 5242944 (1993-09-01), Park et al.

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