Arylglycinamide derivatives, methods of producing these substanc

Details Arylglycinamide derivatives, methods of producing these substanc Arylglycinamide derivatives, methods of producing these substanc

1997-10-29

2000-09-26

Ramsuer, Robert W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

544400, A61K 31495, C07D29515

Patent

active

061242969

DESCRIPTION:

BRIEF SUMMARY
SUMMARY OF THE INVENTION

The invention relates to new arylglycinamide derivatives of general formula I ##STR3## and the pharmaceutically acceptable salts thereof, processes for preparing them and pharmaceutical compositions containing these compounds. The compounds are valuable neurokinin (tachykinin) antagonists.


DETAILED DESCRIPTION OF THE INVENTION

The abbreviations used in the specification and claims are explained as follows:


______________________________________ CDI = Carbonyldiimidazole DCCI = Dicyclohexylcarbodiimide HOBt = 1-Hydroxybenzotriazole THF = Tetrahydrofuran DMF = Dimethylformamide RT = Room temperature DMAP = 4-Ditmethylaminopyridine TBTU = O-Benzotriazolyl-tetramethyluronium- tetrafluoroborate ______________________________________
In order to show the formulae, a simplified representation is used. In the representation of the compounds all CH.sub.3 -- substituents are represented by a single bond, and for example the following formula ##STR4## represents ##STR5##
The invention relates to new arylglycinamide derivatives of general formula I ##STR6## or the pharmaceutically acceptable salts thereof, wherein Ar denotes unsubstituted or mono- to penta-substituted phenyl, or unsubstituted or mono- or di-substituted naphthyl, [in which the substituents of the phenyl and naphthyl independently of each other denote halogen (F, Cl, Br, I), OH, (C.sub.1-4)alkyl, O--(C.sub.1-4) alkyl, CF.sub.3, OCF.sub.3 or NR.sup.9 R.sup.10 (wherein R.sup.9 and R.sup.10 independently of each other denote H, methyl or acetyl)] or Ar is phenyl substituted by --OCH.sub.2 O-- or --O(CH.sub.2).sub.2 O--; of the formula ##STR7## wherein p is 2 or 3, may be mono- to tri-substituted by halogen (F, Cl, Br, I) , (C.sub.1-4) alkyl, O--(C.sub.1-4)alkyl, CF.sub.3, OCF.sub.3 or NR.sup.15 R.sup.16 (wherein R.sup.15 and R.sup.16 independently of each other denote H, methyl or acetyl); substituted phenyl, the substituents independently of one another denote halogen (F, Cl, Br, I), (C.sub.1-4)alkyl, O--(C.sub.1-4)alkyl, CF.sub.3 or OCF.sub.3 ], piperidinyl, 1-methylpiperidinyl, ##STR8## if R.sup.8 is H, --CONH.sub.2, --NHC(O)CH.sub.3, --N(CH.sub.3)C(O)CH.sub.3, CN ##STR9## or c) R.sup.7 and R.sup.8 together form the group ##STR10## R.sup.3 denotes H, (C.sub.1-4)alkyl, unsubstituted or mono- to tri-substituted phenyl, wherein the substituents independently of one another represent halogen (F, Cl, Br, I), (C.sub.1-4)alkyl, O--(C.sub.1-4)alkyl, CF.sub.3, OCF.sub.3 or NR.sup.17 R.sup.18 (wherein R.sup.17 and R.sup.18 independently of one another denote H, methyl or acetyl); phenyl may be substituted by 1 to 3 substituents, wherein the substituents independently of one another are halogen (F, Cl, Br, I), (C.sub.1-4)alkyl, O--(C.sub.1-4)alkyl, CF.sub.3, OCF.sub.3 or NR.sup.19 R.sup.20 (wherein R.sup.19 and R.sup.20 independently of one another denote H, methyl or acetyl); and --CH.sub.2 C(O)NH.sub.2, --OH or phenyl(C.sub.1-4)alkyl.
The compounds according to the invention are valuable neurokinin (tachykinin) antagonists which have both substance P-antagonism and also neurokinin A- or neurokinin B-antagonistic properties. They are useful for the treatment and prevention of neurokinin-mediated diseases.
Compounds of general formula I may contain acid groups, chiefly carboxyl groups, and/or basic groups such as, for example, amino functions. Compounds of general formula I may therefore be obtained either as internal salts, as salts with pharmaceutically acceptable inorganic acids such as hydrochloric acid, sulphuric acid, phosphoric acid or sulphonic acid or organic acids (such as, for example, maleic acid, fumaric acid, citric acid, tartaric acid or acetic acid) or as salts with pharmaceutically acceptable bases such as alkali or alkaline earth metal hydroxides or carbonates, zinc or ammonium hydroxides or organic amines such as, for example, diethylamine, triethylamine or triethanolamine, etc.
The compounds according to the invention may occur as racemates but may also be obtained as pure enantiomers

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Shah, K.J. and Trivedi, J.J., "Potential Local Anesthetics. V. Synthesis of Basic N-(Substituted Benzyl)Phenylacetamides," Chem. Abstr. 68:5715. Abstract No. 59230g (1968).
Nagarajan, K. et al., "A Novel Displacement Reaction On .alpha.-Chlorodiphenylacetamides," Tetrahedron Letts. 15:1387-1390 (1967).
Patel, B.M. et al., "Evaluation of New Series of Lignocaine Analogs," Chem. Abstr. 76:7. Abstract No. 54228t (1972).
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An English-language version of the International Search Report for corresponding International Application No. PCT/EP96/01548.

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