Claims for Patent: 5,216,167

Summary for Patent: 5,216,167

Title:	Phenylacetic acid benzylamides
Abstract:	Phenylacetic acid benzylamides having the following general structure ##STR1## wherein the substituents are defined herein, are disclosed, which compounds are hypoglcemic agents.
Inventor(s):	Grell; Wolfgang (Biberach, DE), Hurnaus; Rudolf (Biberach, DE), Griss, deceased; Gerhart (late of Biberach, DE), Sauter; Robert (Laupheim, DE), Reiffen; Manfred (Biberach, DE), Rupprecht; Eckhard (Aulendorf-Tannhausen, DE)
Assignee:	Dr. Karl Thomae GmbH (Biberach an der Riss, DE)
Application Number:	07/495,820
Patent Claims:	1. A compound of the formula: ##STR19## wherein R.sub.1 represents an unbranched alkyleneimino group with 4 to 6 carbon atoms optionally mono- or di-(alkyl of 1 to 3 carbon atoms)-substituted; R.sub.2 represents a hydrogen or halogen atom or a methyl or methoxy group; R.sub.3 represents a hydrogen atom, an alkyl group with 1 to 7 carbon atoms, a phenyl group optionally substituted by a halogen atom or a methyl or methoxy group, an alkyl group with 1 or 2 carbon atoms substituted by a hydroxy, alkoxy, alkanoyloxy, tetrahydrofuranyl, tetrahydropyranyl, cycloalkyl or phenyl group, in which the alkoxy part can contain from 1 to 3 carbon atoms, the alkanoyloxy part can contain 2 or 3 carbon atoms and the cycloalkyl part can contain 3 to 7 carbon atoms, an alkenyl group with 3 to 6 carbon atoms, an alkynyl group with 3 to 5 carbon atoms, a carboxy group or an alkoxycarbonyl group with a total of 2 to 5 carbon atoms; R.sub.4 represents a hydrogen atom, a methyl, ethyl or allyl group; and W represents a methyl, hydroxymethyl, formyl, carboxyl, alkoxycarbonyl, cyanomethyl, 2-cyano-ethyl, 2-cyano-ethenyl, carboxymethyl, 2-carboxyethyl, 2-carboxyethenyl, alkoxycarbonylmethyl, 2-alkoxycarbonyl-ethyl or 2-alkoxycarbonylethenyl group, in which each alkoxy part can contain from 1 to 4 carbon atoms and can be substituted by a phenyl group; and when R.sub.3 is other then hydrogen and/or the radical R.sub.1 contains an optically active carbon atom, the enantiomeres and the diastereomeres thereof or their mixtures; when W is carboxyl, a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt thereof formed by an inorganic or organic acid with the amino function in the R.sub.1 -position. 2. A compound of claim 1, wherein R.sub.1 represents a pyrrolidino, piperidino, 4-methyl-piperidino, 3-methyl-piperidino, 3,3-dimethyl-piperidino, 3,5-dimethyl-piperidino or hexamethyleneimino group; R.sub.2 represents a hydrogen, fluorine or chlorine atom; R.sub.3 represents hydrogen atom, an alkyl group with 1 to 6 carbon atoms, a phenyl, methyl-phenyl, chloro-phenyl, methoxy-phenyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, tetrahydrofuran-2-yl-methyl, tetrahydropyran-2-yl-methyl, propargyl, hydroxymethyl, ethoxymethyl, acetoxymethyl, propionyloxymethyl, carboxy, methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl group or an alkenyl group with 3 or 4 carbon atoms; R.sub.4 represents a methyl, ethyl or allyl group; and W represents a methyl, hydroxymethyl, formyl, carboxyl, benzyloxycarbonyl, carboxymethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, cyanomethyl, 2-carboxy-ethyl, 2-ethoxycarbonyl-ethyl, 2-cyano-ethyl, 2-carboxy-ethenyl, 2-ethoxycarbonyl-ethenyl or 2-cyano-ethenyl group or an alkoxycarbonyl group with 1 to 4 carbon atoms in the alkoxy part; and when R.sub.3 is other then hydrogen and/or R.sub.1 represents the 3-methyl-piperidino group, the enantiomeres and the diastereomeres thereof or their mixtures; when W is carboxyl, a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt thereof formed by an inorganic or organic acid with the amino function in the R.sub.1 -position. 3. A compound of claim 1, wherein R.sub.1 represents a piperidino group; R.sub.2 represents a hydrogen atom; R.sub.3 represents an alkyl group with 1 to 6 carbon atoms, an alkenyl group with 3 or 4 carbon atoms, a phenyl, tetrahydropyran-2-yl-methyl, cyclopropylmethyl or cyclohexylmethyl group; R.sub.4 represents a methyl, ethyl or allyl group; and W represents a carboxyl, methoxycarbonyl, ethoxycarbonyl or cyanomethyl group; and the enantiomeres thereof or their mixtures; when W is carboxyl, a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt thereof formed by an inorganic or organic acid with the piperidino function. 4. A compound of claim 1, wherein R.sub.1 represents a piperidino group; R.sub.2 represents a hydrogen atom; R.sub.3 represents an alkyl group with 3 to 6 carbon atoms, an alkenyl group with 3 or 4 carbon atoms, a phenyl, cyclopropylmethyl or cyclohexylmethyl group; R.sub.4 represents a methyl or ethyl group; and W represents a carboxyl group; and the enantiomeres thereof or their mixtures; a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt thereof formed by an inorganic or organic acid with the piperidino function. 5. A compound of claim 1, wherein R.sub.1 represents a piperidino group; R.sub.2 represents a hydrogen atom; R.sub.3 represents an alkyl group with 3 to 6 carbon atoms, a 2-methyl-1-propen-1-yl, cyclomethylpropyl or cyclohexylmethyl group; R.sub.4 represents a methyl or ethyl group; and W represents a carboxyl group; and the enantiomeres thereof or their mixtures; a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt thereof formed by an inorganic or organic acid with the piperidino function. 6. A compound of claim 5, wherein R.sub.3 represents a n-propyl, n-butyl, isobutyl, sec.butyl, n-pentyl, 2-methyl-1-propen-1-yl, cyclomethylpropyl or cyclohexylmethyl group; the enantiomeres thereof or their mixtures; a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt thereof formed by an inorganic or organic acid with the piperidino function. 7. A compound of claim 5, wherein R.sub.3 represents a n-propyl, n-butyl, isobutyl, sec.butyl or n-pentyl group; and the enantiomeres thereof or their mixtures; a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt thereof salt thereof formed by an inorganic or organic acid with the piperidino function. 8. The compound of claim 5, which is 2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-1-butyl)-aminocarbonylmethyl]-benzo ic acid; the enantiomeres thereof or their mixtures; a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt formed by an inorganic or organic acid with the piperidino function. 9. The compound of claim 5, which is 2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmeth yl]benzoic acid; the enantiomeres thereof or their mixtures; a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt formed by an inorganic or organic acid with the piperidino function. 10. The compound of claim 5, which is form (A) of 2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmeth yl]-benzoic acid, recrystallized from acetone/petroleum ether, having a melting point of 90.degree.-92.degree. C. 11. The compound of claim 5, which is form (B) of 2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmeth yl]-benzoic acid, recrystallized from ethanol/water, having a melting point of 140.degree.-142.degree. C. 12. The compound of claim 5, which is form (C) of 2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmeth yl]-benzoic acid, recrystallized from methanol, having a melting point of 74.degree.-85.degree. C. 13. The compound of claim 5, which is 2-ethoxy-4-[N-(.alpha.-cyclohexylmethyl-2-piperidino-benzyl)-aminocarbonyl methyl]-benzoic acid; the enantiomeres thereof or their mixtures; a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt formed by an inorganic or organic acid with the piperidino function. 14. The (S)-enantiomer of a compound as claimed in anyone of the claims 1 to 13; when W is carboxy, a non-toxic salt thereof formed with an inorganic or organic base; or a non-toxic acid addition salt formed by an inorganic or organic acid with the amino function in the R.sub.1 -position. 15. A hypoglycemic pharmaceutical composition consisting essentially of an inert pharmaceutical carrier and an effective hypoglycemic amount of a compound of claim 1.