1-acylpiperidine compounds

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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514311, 514314, 514318, 514319, 514320, 514321, 514323, 514324, 514326, 514330, 514331, 544180, 546152, 546168, 546174, 546175, 546176, 546192, 546194, 546195, 546196, 546198, 546201, 546202, 546205, 546208, 546212, 546213, 546214, 546225, 546226, 546227, 546229, 546230, 546232, 546233, 546234, 546235, 546237, 546238, 546239, A61K 3147, C07D21512, C07D40900

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active

056461445

ABSTRACT:
1-Acylpiperidine compound of the formula I ##STR1## in which R.sub.1 is an optionally substituted aralkyl, aryloxyalkyl, heteroaralkyl, aroyl, heteroaroyl, cycloalkylcarbonyl, aralkanoyl, heteroarylalkanoyl, aralkoxycarbonyl or arylcarbamoyl radical or the acyl radical of an .alpha.-amino acid which is optionally N-substituted by lower alkanoyl or carbamoyl-lower-alkanoyl, R.sub.2 is cycloalkyl or an optionally substituted aryl or heteroaryl radical, R.sub.3 is hydrogen, alkyl, carbamoyl or an alkanoyl or alkenoyl radical which is optionally substituted by carboxyl or esterified or amidated carboxyl, R.sub.4 is an optionally substituted aryl or optionally partially hydrogenated heteroaryl radical, X.sub.1 is methylene, ethylene, a direct linkage, an optionally ketalized carbonyl group or an optionally etherified hydroxymethylene group, X.sub.2 is alkylene, carbonyl or a direct linkage, and X.sub.3 is carbonyl, oxo-lower-alkylene, oxo(aza)-lower-alkylene or an alkylene radical which is optionally substituted by phenyl, hydroxymethyl, optionally esterified or amidated carboxyl or, in higher than the .alpha. position, by hydroxyl, and its salts have substance-P-antagonistic properties and can be used as pharmaceutically active substances in pharmaceuticals for the treatment of disorders in whose development substance P plays an essential part.

REFERENCES:
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patent: 5145967 (1992-09-01), Lin et al.
Garret et al; "Pharmacological Properties of a Potent and Selective Nonpeptide Substance P or Antagonist", Proc. Natl. Acad Sci USA vol. 88 10208-10212, Nov. 9.
Snider et al; "A Potent Nonpeptide Antagonist of the Substance P (Nk.sub.1) Receptor", Science 251, pp. 435-437 Jan. 25, 1991.
McLean et al; "Activity and Distribution of Binding Sites in Brain of a Nonpeptide Substance P (Nk.sub.1) Receptor Antagonist"; Science 251, pp. 437-439; Jan. 25, 1991.
Chem Abstr. 68: 38700v (1968) of Becker et al, J. Prakt. Chem. 37 (1-2), 47-58 (1968); Synthesis in the Isoquinoline Series. IV.
Chem Abstr. 63: 11494c (1965) of Becker et al, J. Prakt. Chem. 29 (3-6), 142-57 (1965), Synthesis in the Isoquinoline Series III.
Chem Abstr 56: 7263i (1961) of Becker et al, Z Chem. 1, 157 (1961); New Synthesis of Derivatives of 4-Piperidone.

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