Substituted amides, their preparation and use

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

Reexamination Certificate

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C514S253130, C514S318000, C514S343000, C514S355000, C544S131000, C544S365000, C546S146000, C546S194000, C546S276400, C546S277100, C546S316000

Reexamination Certificate

active

10690400

ABSTRACT:
An amide of the formula Iand its tautomeric forms, possible enantiomeric and diastereomeric forms, E and Z forms, and possible physiologically tolerated salts, in which the variables have the following meanings:A —(CH2)p—R1, where R1can be pyrrolidine [sic], morpholine [sic], piperidine [sic], —NR5R6and and R5, R6and R7can, independently of one another, be hydrogen, C1-C4-alkyl, CH2Ph, Ph, CH2CH2Ph, it also being possible for the phenyl rings to be substituted by R6, and p can be 1 and 2, andB can be phenyl [sic], pyridyl [sic], pyrimidyl [sic] and pyridazyl [sic], it also being possible for the rings to be substituted by up to 2 R8radicals, andD can be a bond, —(CH2)m—, —CH═CH—, —C≡C—, andR2is chlorine, bromine, fluorine, C1-C6-alkyl, NHCO—C1-C4-alkyl, NHSO2—C1-C4-alkyl, NO2, —O—C1-C4-alkyl and NH2, andR3is —C1-C6-alkyl, branched or unbranched, and which may also carry a phenyl ring, indolyl ring or cyclohexyl ring which is in turn substituted by by [sic] a maximum of two R8radicals, where R8is hydrogen, C1-C4-alkyl, branched or unbranched, —O—C1-C4-alkyl, OH, Cl, F, Br, I, CF3, NO2, NH2, CN, COOH, COO—C1-C4-alkyl, NHCO—C1-C4-alkyl, —NHSO2-C1-C4-alkyl and —SO2—C1-C4-alkyl; andY is phenyl [sic], pyridine, pyrimidine and pyrazine andR4is hydrogen, COOR9and CO-Z in which Z is NR10R11andR9is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R12radicals, andR10is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which itself may also be substituted by one or two R12radicals, andR11is hydrogen, C1-C6-alkyl, branched or unbranched, which may also be and [sic] substituted by a phenyl ring which may also carry an R9radical, andR12can be hydrogen, C1-C4-alkyl, branched or unbranched, —O—C1-C4-alkyl, OH, Cl, F, Br, J, CF3, NO2, NH2, CN, COOH, COO—C1-C4-alkyl, —NHCO—C1-C4-alkyl, —NHCO-phenyl, —NHSO2—C1-C4-alkyl, NHSO2-phenyl, —SO2—C1-C4-alkyl and —SO2-phenyl,R13is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R12radicals, andR14is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R12radicals, andn is a number 0, 1 or 2, andm, q are, independently of one another, a number 0, 1, 2, 3 or 4.

REFERENCES:
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S. Mehdi, Cell-penetrating Inhibitors of Calpain, Trends in Bio. Sci. 1991, 16, 150-153.
Angelastro et al., Journal of Medicinal Chemistry, 1990, 11-13.
Harbeson et al., Stereospecific Synthesis of Peptidyl a-Keto Amides as Inhibitors of Calpain, Journal of Medicinal Chemistry, 1994, 2918-2929.
Burkhardt, Oxidation of a-Hydroxy Esters to a-Keto Esters Using the Dess-Martin Periodinane Reagent, Tet. Letters vol. 29, No. 28, p. 3433-3436 (1988).

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