UREA-SUBSTITUTED AND URETHANE-SUBSTITUTED ACYLUREAS, METHODS FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICAMENTS
(19)AUSTRALIAN PATENT OFFICE (54) TitleUREA-SUBSTITUIbD AND URETHANE-SUBSTITUTED ACYLUREAS, METHODS FOR THEPRODUCTION THEREOF AND THEIR USE AS MEDICAMENTS (51)6 International Patent Classification(s) CO 7 C 275/54 A61P 003/10 A61 K 031/17 C07D 239/96 (21) Application No: 2003281027 (22) Application Date: 2003.06.30 (87) WIPONo: WO04/007437 (30) Priority Data (31) Number (32) Date (33) Country 102 31371.7 2002.07.11DE (43) Publication Date : 2004.02.02 (43) Publication Journal Date : 2004.03.18 (71) Applicant(s)AVENTIS PHARMA DEUTSCHLAND GMBH (72) Inventor(s)DEFOSSA, Elisabeth; KADEREIT,Dieter; KLABUNDE, Thomas; BURGER,Hans-Joerg ; HERLING, Andreas;WENDT, Karl-Ulrich; VON ROEDERN,Erich; SCHOENAFINGER, Karl (H) Application NoAU2003281027 A1(19)AUSTRALIAN PATENT OFFICE (54) TitleUREA-SUBSTITUIbD AND URETHANE-SUBSTITUTED ACYLUREAS, METHODS FOR THEPRODUCTION THEREOF AND THEIR USE AS MEDICAMENTS (51)6 International Patent Classification(s) CO 7 C 275/54 A61P 003/10 A61 K 031/17 C07D 239/96 (21) Application No: 2003281027 (22) Application Date: 2003.06.30 (87) WIPONo: WO04/007437 (30) Priority Data (31) Number (32) Date (33) Country 102 31371.7 2002.07.11DE (43) Publication Date : 2004.02.02 (43) Publication Journal Date : 2004.03.18 (71) Applicant(s)AVENTIS PHARMA DEUTSCHLAND GMBH (72) Inventor(s)DEFOSSA, Elisabeth; KADEREIT,Dieter; KLABUNDE, Thomas; BURGER,Hans-Joerg ; HERLING, Andreas;WENDT, Karl-Ulrich; VON ROEDERN,Erich; SCHOENAFINGER, Karl The invention relates to urea-substituted and urethane-substituted acylureas, to physiologically compatible salts thereof and to their physiologically functional derivatives. The invention thus relates to compounds of formula (I), wherein the radicals have the cited meanings. The invention also relates to the physiologically compatible salts of these compounds and to methods for the production thereof. The inventive compounds are suited for use, for example, as antidiabetics.
A compound of the formula Ia
in which the meanings are
R9, R10, R11 independently of one another F or Cl;
R12 H;
R13 independently of one another H or (C1-C6)-alkyl;
R3, R4, R5 independently of one another H, COOR13;
R6 Cl, OCF3, COOR13, N(R14) (R15), (C2-C6) -alkenyl, O-(C1-C10)-alkyl, where alkyl, alkenyl may be substituted more than once by F, COOR13 or CON(R14) (R15) ;
R14, R15 (C1-C6)-alkyl, where alkyl may be substituted by N(R13)2;
or the radicals R14 and R15 form with the nitrogen atom to which they are bonded a 5-membered, saturated heterocyclic ring;
R8 N(R18) (R19) or OR20;
R18, R19 independently of one another H, (C1-C10)-alkyl, (C2-C10) -alkenyl, where alkyl may be substituted by COOR13, N(R13)2 or phenyl, or (C3-C7)-cycloalkyl or (C6-C10)-aryl, where aryl may be substituted more than once by F, Cl, CN, (C1-C6) -alkyl, O-(C1-C6)-alkyl, CO-(C1-C6)-alkyl, where alkyl may be substituted more than once by F, or O-phenyl, phenyl, pyridyl or COOR13;
R20 (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl or phenyl, where phenyl may be substituted by Cl or (C1-C6) -alkyl;
and its physiologically tolerated salts.
A medicament comprising one or more of the compounds as claimed in claim 1
A medicament comprising one or more of the compounds as claimed in claim 1 and at least one other active ingredient.
A medicament as claimed in claim 3, wherein the other active ingredient comprises one or more antidiabetics, hypoglycemic active ingredients, HMGCoA reductase inhibitors, cholesterol absorption inhibitors, PPAR gamma agonists, PPAR alpha agonists, PPAR alpha/gamma agonists, fibrates, MTP inhibitors, bile acid absorption inhibitors, CETP inhibitors, polymeric bile acid adsorbents, LDL receptor inducers, ACAT inhibitors, antioxidants, lipoprotein lipase inhibitors, ATP-citrate lyase inhibitors, squalene synthetase inhibitors, lipoprotein(a) antagonists, lipase inhibitors, insulins, sulfonylureas, biguanides, meglitinides, thiazolidinediones, α-glucosidase inhibitors, active ingredients which act on the ATP-dependent potassium channel of the beta cells, CART agonists, NPY agonists, MC4 agonists, orexin agonists, H3 agonists, TNF agonists, CRF agonists, CRF BP antagonists, urocortin agonists, β3 agonists, MSH (melanocyte-stimulating hormone) agonists, CCK agonists, serotonin reuptake inhibitors, mixed sertoninergic and noradrenergic compounds, 5HT agonists, bombesin agonists, galanin antagonists, growth hormones, growth hormone-releasing compounds, TRH agonists, uncoupling protein 2 or 3 modulators, leptin agonists, DA agonists (bromocriptine, Doprexin), lipase/amylase inhibitors, PPAR modulators, RXR modulators or TR-β agonists or amphetamines.
The use of the compounds as claimed in claim 1 for producing a medicament for reducing blood glucose.
The use of the compounds as claimed in claim 1 for producing a medicament for the treatment of type II diabetes.
The use of the compounds as claimed in claim 1 for producing a medicament for the treatment of disturbances of lipid and carbohydrate metabolism.
The use of the compounds as claimed in claim 1 for producing a medicament for the treatment of arteriosclerotic manifestations.
The use of the compounds as claimed in claim 1 for producing a medicament for the treatment of insulin resistance.
A process for producing a medicament comprising one or more of the compounds as claimed in claim 1, which comprises mixing the active ingredient with a pharmaceutically suitable carrier and converting this mixture into a form suitable for administration.