Patent DE-102006052755-A1 (DE)
Title: New peptide derivatives and peptidomimetics are transglutaminase inhibitors useful for the treatment or prophylaxis of e.g. celiac disease, fibrosis, thrombosis, neurodegenerative disorders, Huntington's chorea and Parkinson disease
Inventor: OERTEL KAI
IPC: C07K5/00
Filed: 2006-11-08
Abstract: Peptide derivatives and peptidomimetic (D) and their stereoisomer forms, E/Z-isomers, enantiomers, enantiomeric mixture, diastereomers, diastereomeric mixture, racemates, tautomers, anomers, keto-enol-forms, betaine forms, prodrugs, solvate, hydrate or their salts, are new. Peptide derivatives and peptidomimetic (D) of formula (I-III), and their stereoisomer forms, E/Z-isomers, enantiomers, enantiomeric mixture, diastereomers, diastereomeric mixture, racemates, tautomers, anomers, keto-enol-forms, betaine forms, prodrugs, solvate, hydrate or their salts, are new, where (I) excludes compounds having X and X1a are hydrogen and Y 1>is hydroxy. MS : acceptor substituted olefin of formula (-CH(R 1>)(R 2>)-CH(R 3>)(R 4>)-(CO) m-CH(Z 3>)=C(Z 1>)(Z 2>)); E : e.g. -CH 2-, -CF 2-, -C 2H 4-, -CH 2-CF 2-, -CF 2-CH 2-, -CH=CH-, -CH(OH)-CH 2-, -C(=O)-CH 2-, -CH 2-NH-, -CH 2-O-, -CH(OH)-CH 2-NH-, -P(=O)(OH)-NH-, -P(=O)(OH)-O- or -P(=O)(OH)-S-; m : 0 or 1; either Z 1>-Z 3>e.g. CO-(1-6C-alkyl), -COO-(1-6C-alkyl) (both preferred), -CO-R 6>, -CO-R 7>, -CO-(1-6C-haloalkyl), -CO-(3-10C-heteroaryl), -CO-(6-15C-aryl), -COO-(1-6C-haloalkyl), -COO-(3-10C-heteroaryl), -COO-(6-15C-aryl), -CN, -F, -Cl, -COOH, -CO-NH(1-6C-alkyl), -CO-N(1-6C-alkyl)(1-6C-alkyl), -CO-NH 2, -CH 2CN, -CH 2F, -CHF 2, -CF 3, -OCF 3, -CH 2-CF 3, -CF 2-CF 3, -NO 2, -CS-(1-6C-alkyl), -CS-N(1-6C-alkyl)(1-6C-alkyl), -OS-NH 2, -SO-N(1-6C-alkyl)(1-6C-alkyl), -SO 2-N(1-6C-alkyl)(1-6C-alkyl), SO 2-OH, -O-P(O)(OH) 2, -O-P(O)(O-1-6C-alkyl)(O-1-6C-alkyl), -P(O)(O-1-6C-alkyl)(O-1-6C-alkyl) or -CF 2-P(O)(O-1-6C-alkyl)(O-1-6C-alkyl); or Z 2>+Z 3>e.g. -CO-O-CH 2-, -CO-O-CO- or -CO-NH-CO-; either Q, Q 1>a side chain residue of a natural amino acid; or Q+X1a, Q 1>+X1b : a propylenyl group; Y 1>e.g. OH, amino, 1-6C-alkylamino, 1-6C-dialkylamino, 1-6C-alkoxy, 1-6C-alkyl, 1-6C-haloalkyl, 3-10C-heteroaryl, 6-15C aryl, a peptidomimetic group of up to 60 carbon atoms or amine bond bounded peptide residue of up to 6 amino acids; either X1a, X1b : H or 1-6C alkyl; or N+X+X1a : e.g. amino, 1-10C alkylamino, 6-12C aralkyloxycarbonylamino, 1-10C-dialkylamino, 2-6C-nitrogen heterocycle, 3-5C nitrogen heteroaryl or a part of peptidomimetic residue of up to 60 carbon atoms; and X : amine bond bounded peptide residue of up to 6 amino acids; and R 1>-R 4>e.g. H, -OH, -OCH 3, -OC 2H 5, -OC 3H 7, -O-cyclo-C 3H 5, -OCH(CH 3) 2, -OC(CH 3) 3, -OC 4H 9, -OPh, -OCH 2-Ph, -OCPh 3, -SH, -SCH 3, -SC 2H 5, -SC 3H 7, -S-cyclo-C 3H 5, -SCH(CH 3) 2, -SC(CH 3) 3, -NO 2, -F, -Cl, -Br, -I, -N 3, -CN, -OCN, -NCO, -SCN, -NCS, -CHO, -COOH 3, -COC 2H 5or -COC 3H 7. Independent claims are included for: (1) tetrapeptide derivatives of formula (IV); and (2) a pharmaceutical composition comprising (A) and at least a carrier, auxiliary material or solvent. Either Q, Q 1>, Q 2>a side chain residue of a natural amino acid; or Q+X1b, Q 1>+X1c, Q 2>+X1d : a propylenyl residue; and X1b, X1c, X1d : H or 1-6C alkyl. [Image] [Image] ACTIVITY : Immunosuppressive; Gastrointestinal-Gen; Antiinflammatory; Thrombolytic; Anticoagulant; Neuroprotective; Anticonvulsant; Nootropic; Antiparkinsonian; Ophthalmological; Antiseborrheic; Dermatological; Antipsoriatic; Fungicide. MECHANISM OF ACTION : Transglutaminase inhibitor. Test details are described but no results given.