25.
    发明专利
    未知

    公开(公告)号:BRPI0403028A

    公开(公告)日:2005-06-14

    申请号:BRPI0403028

    申请日:2004-07-27

    Applicant: SERVIER LAB

    Abstract: Benzoxazole, benzothiazole or indole oxime derivatives (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine) are new. Benzoxazole, benzothiazole or indole oxime derivatives of formula (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine), and their enantiomers, diastereomers and salts are new. [Image] X : O, S, CH 2 or CHR' 2>; R 1>, R 2>H, alkyl, aryl, aralkyl, aryloxy, aralkoxy, alkoxy, OH, NH 2 or mono- or dialkylamino; or R 1> + R 2>=O, =S or =NH; R' 2>group forming an additional bond with R 2>; A : 1-6C alkylene (optionally having one CH 2 replaced by O, S, NRa', phenylene or naphthylene); Ra' : H or alkyl; R 3>, R 4>H, halo, R, OR or NRR'; or R 3> + R 4>group forming an ortho-fused 5- or 6-membered ring (optionally containing an O, S or N heteroatom); R, R', R 5>, R 6>H, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, cycloalkyl, cycloalkylalkyl or polyhaloalkyl; D : benzene ring (in which case X is other than CHR' 2>); or a pyridine, pyrazine, pyrimidine or pyridazine ring; B : alkyl or alkenyl, both substituted by -CHR 7>R 8> or by R 9>; or -CHR 7>R 8> or R 9>; R 7>-C(Z)OR, -C(Z)NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; Z : O or S; R 8>aryl, aralkyl, heteroaryl, heteroaralkyl, CN, tetrazole, OR, NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; R 9>CN, tetrazole, -N(R)C(Z)R', -N(R)C(Z)OR' or -O(CH 2) n-CR 1> 0>R 1> 1>-COOR; n : 0-6; R 1> 0>, R 1> 1>H or alkyl, but not both H; aryl moieties : phenyl, naphthyl or biphenyl (all optionally partially hydrogenated and optionally substituted by 1-3 alkyl, polyhaloalkyl, alkoxy, OH, COOH, CHO, NRaRb, ester, amido, NO 2, CN or halo groups); heteroaryl moieties : 5-10 membered mono- or bicyclic aryl (where one ring is optionally partially hydrogenated in the case of bicyclic systems) containing 1-3 O, S and/or N heteroatom(s) and optionally substituted as for aryl; Rb, Rc : H, alkyl, aryl or heteroaryl; the oxime group -C(R 6>)=NOR 5> has E- or Z-configuration; alkyl moieties have 1-6C, alkenyl or alkynyl moieties 2-6C and cycloalkyl moieties 3-8C. Independent claims are included for: (1) preparation method of (I); and (2) new ketone intermediates of formula (V). [Image] ACTIVITY : Antidiabetic; Antilipemic; Cardiant; Nephrotropic; Ophthalmological; Antipsoriatic; Gynecological; Nootropic; Osteopathic; Antiinflammatory; Antiarteriosclerotic; Anorectic; Cytostatic. In tests in ob/ob mice, oral administration of 10 mg/kg of methyl 3-(4-(2-(6-((methoxyimino)-(phenyl)-methyl)-2-oxo-1,3-benzothiazol-3(2H)-yl)-ethoxy)-phenyl)-2-(2,2,2-trifluoroethoxy)-propanoate (Ia) twice per day for 4 days reduced blood sugar levels by 51% and reduced the weight gain by 80% in comparison with controls, whereas analogous administration of rosiglitazone reduced blood sugar levels by 61% but increased the weight gain by 33% in comparison with controls. MECHANISM OF ACTION : Aldose Reductase Inhibitor; Angiogenesis Inhibitor.

    26.
    发明专利
    未知

    公开(公告)号:FR2858321A1

    公开(公告)日:2005-02-04

    申请号:FR0309214

    申请日:2003-07-28

    Applicant: SERVIER LAB

    Abstract: Benzoxazole, benzothiazole or indole oxime derivatives (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine) are new. Benzoxazole, benzothiazole or indole oxime derivatives of formula (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine), and their enantiomers, diastereomers and salts are new. [Image] X : O, S, CH 2 or CHR' 2>; R 1>, R 2>H, alkyl, aryl, aralkyl, aryloxy, aralkoxy, alkoxy, OH, NH 2 or mono- or dialkylamino; or R 1> + R 2>=O, =S or =NH; R' 2>group forming an additional bond with R 2>; A : 1-6C alkylene (optionally having one CH 2 replaced by O, S, NRa', phenylene or naphthylene); Ra' : H or alkyl; R 3>, R 4>H, halo, R, OR or NRR'; or R 3> + R 4>group forming an ortho-fused 5- or 6-membered ring (optionally containing an O, S or N heteroatom); R, R', R 5>, R 6>H, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, cycloalkyl, cycloalkylalkyl or polyhaloalkyl; D : benzene ring (in which case X is other than CHR' 2>); or a pyridine, pyrazine, pyrimidine or pyridazine ring; B : alkyl or alkenyl, both substituted by -CHR 7>R 8> or by R 9>; or -CHR 7>R 8> or R 9>; R 7>-C(Z)OR, -C(Z)NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; Z : O or S; R 8>aryl, aralkyl, heteroaryl, heteroaralkyl, CN, tetrazole, OR, NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; R 9>CN, tetrazole, -N(R)C(Z)R', -N(R)C(Z)OR' or -O(CH 2) n-CR 1> 0>R 1> 1>-COOR; n : 0-6; R 1> 0>, R 1> 1>H or alkyl, but not both H; aryl moieties : phenyl, naphthyl or biphenyl (all optionally partially hydrogenated and optionally substituted by 1-3 alkyl, polyhaloalkyl, alkoxy, OH, COOH, CHO, NRaRb, ester, amido, NO 2, CN or halo groups); heteroaryl moieties : 5-10 membered mono- or bicyclic aryl (where one ring is optionally partially hydrogenated in the case of bicyclic systems) containing 1-3 O, S and/or N heteroatom(s) and optionally substituted as for aryl; Rb, Rc : H, alkyl, aryl or heteroaryl; the oxime group -C(R 6>)=NOR 5> has E- or Z-configuration; alkyl moieties have 1-6C, alkenyl or alkynyl moieties 2-6C and cycloalkyl moieties 3-8C. Independent claims are included for: (1) preparation method of (I); and (2) new ketone intermediates of formula (V). [Image] ACTIVITY : Antidiabetic; Antilipemic; Cardiant; Nephrotropic; Ophthalmological; Antipsoriatic; Gynecological; Nootropic; Osteopathic; Antiinflammatory; Antiarteriosclerotic; Anorectic; Cytostatic. In tests in ob/ob mice, oral administration of 10 mg/kg of methyl 3-(4-(2-(6-((methoxyimino)-(phenyl)-methyl)-2-oxo-1,3-benzothiazol-3(2H)-yl)-ethoxy)-phenyl)-2-(2,2,2-trifluoroethoxy)-propanoate (Ia) twice per day for 4 days reduced blood sugar levels by 51% and reduced the weight gain by 80% in comparison with controls, whereas analogous administration of rosiglitazone reduced blood sugar levels by 61% but increased the weight gain by 33% in comparison with controls. MECHANISM OF ACTION : Aldose Reductase Inhibitor; Angiogenesis Inhibitor.

    27.
    发明专利
    未知

    公开(公告)号:NO20043188L

    公开(公告)日:2005-01-31

    申请号:NO20043188

    申请日:2004-07-27

    Applicant: SERVIER LAB

    Abstract: Benzoxazole, benzothiazole or indole oxime derivatives (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine) are new. Benzoxazole, benzothiazole or indole oxime derivatives of formula (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine), and their enantiomers, diastereomers and salts are new. [Image] X : O, S, CH 2 or CHR' 2>; R 1>, R 2>H, alkyl, aryl, aralkyl, aryloxy, aralkoxy, alkoxy, OH, NH 2 or mono- or dialkylamino; or R 1> + R 2>=O, =S or =NH; R' 2>group forming an additional bond with R 2>; A : 1-6C alkylene (optionally having one CH 2 replaced by O, S, NRa', phenylene or naphthylene); Ra' : H or alkyl; R 3>, R 4>H, halo, R, OR or NRR'; or R 3> + R 4>group forming an ortho-fused 5- or 6-membered ring (optionally containing an O, S or N heteroatom); R, R', R 5>, R 6>H, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, cycloalkyl, cycloalkylalkyl or polyhaloalkyl; D : benzene ring (in which case X is other than CHR' 2>); or a pyridine, pyrazine, pyrimidine or pyridazine ring; B : alkyl or alkenyl, both substituted by -CHR 7>R 8> or by R 9>; or -CHR 7>R 8> or R 9>; R 7>-C(Z)OR, -C(Z)NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; Z : O or S; R 8>aryl, aralkyl, heteroaryl, heteroaralkyl, CN, tetrazole, OR, NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; R 9>CN, tetrazole, -N(R)C(Z)R', -N(R)C(Z)OR' or -O(CH 2) n-CR 1> 0>R 1> 1>-COOR; n : 0-6; R 1> 0>, R 1> 1>H or alkyl, but not both H; aryl moieties : phenyl, naphthyl or biphenyl (all optionally partially hydrogenated and optionally substituted by 1-3 alkyl, polyhaloalkyl, alkoxy, OH, COOH, CHO, NRaRb, ester, amido, NO 2, CN or halo groups); heteroaryl moieties : 5-10 membered mono- or bicyclic aryl (where one ring is optionally partially hydrogenated in the case of bicyclic systems) containing 1-3 O, S and/or N heteroatom(s) and optionally substituted as for aryl; Rb, Rc : H, alkyl, aryl or heteroaryl; the oxime group -C(R 6>)=NOR 5> has E- or Z-configuration; alkyl moieties have 1-6C, alkenyl or alkynyl moieties 2-6C and cycloalkyl moieties 3-8C. Independent claims are included for: (1) preparation method of (I); and (2) new ketone intermediates of formula (V). [Image] ACTIVITY : Antidiabetic; Antilipemic; Cardiant; Nephrotropic; Ophthalmological; Antipsoriatic; Gynecological; Nootropic; Osteopathic; Antiinflammatory; Antiarteriosclerotic; Anorectic; Cytostatic. In tests in ob/ob mice, oral administration of 10 mg/kg of methyl 3-(4-(2-(6-((methoxyimino)-(phenyl)-methyl)-2-oxo-1,3-benzothiazol-3(2H)-yl)-ethoxy)-phenyl)-2-(2,2,2-trifluoroethoxy)-propanoate (Ia) twice per day for 4 days reduced blood sugar levels by 51% and reduced the weight gain by 80% in comparison with controls, whereas analogous administration of rosiglitazone reduced blood sugar levels by 61% but increased the weight gain by 33% in comparison with controls. MECHANISM OF ACTION : Aldose Reductase Inhibitor; Angiogenesis Inhibitor.

    29.
    发明专利
    未知

    公开(公告)号:BRPI0607085A2

    公开(公告)日:2009-08-04

    申请号:BRPI0607085

    申请日:2006-01-26

    Applicant: SERVIER LAB

    Abstract: Heterocyclic oxime derivatives (I), their enantiomers, diastereomers and their acid or basic addition salts are new. Heterocyclic oxime derivatives of formula (I), their enantiomers, diastereomers and their acid or basic addition salts are new. X : O or S; A : 1-6C alkyl (where CH 2 can be replaced by heteroatom (O or S), NR a or a phenyl or naphthyl group); R aH or 1-6C alkyl; R 1>, R 2>, R, R1 : H, 1-6C ((hetero)aryl)alkyl, 2-6C ((hetero)aryl)alkenyl, 2-6C ((hetero)aryl)alkynyl, (hetero)aryl, 3-8C cycloalkyl-1-6C alkyl or polyhalo-1-6C alkyl; either R 3>, R 4>H, halo, R, OR or NRR1; or -C-R 3>-R 4>-C- : 5-6 membered ring (containing heteroatom (O, S or N); B 1>1-6C alkyl, 2-6C alkenyl (both optionally substituted by -CHR 5>R 6> or R 7>), -CHR 5>R 6> or R 7>; R 5>-C(=Z)-OR, -C(=Z)-NRR1, -N(R)-C(=Z)-R1 or -N(R)-C(=Z)-OR1; Z : O or S; R 6>(hetero)aryl, (hetero)aryl-1-6C alkyl, CN, tetrazole, OR, NRR1, -N(R)-C(=Z)-R1, -N(R)-C(=Z)-OR1 or -N(R)-C(=Z)-R; R 7>CN, tetrazole, -N(R)-C(=Z)-R1, -N(R)-C(=Z)-OR1 or -O-(CH 2) n-C(R 8>R 9>)-COOR; n : 1-6; and R 8>, R 9>H or 1-6C alkyl. Provided that both R 8> and R 9> are not simultaneously H. Provided that: the oxime R 1>-C(=N-OR 2>)- can be the Z or E configuration; the aryl are phenyl, naphthyl or biphenyl, which can be partially hydrogenated; the heteroaryl are 5-10 membered mono or bicylic aromatic, where the bicyclics can partially be hydrogenated, and containing 1-3 heteroatom (O, N or S); the (hetero)aryl are optionally substituted by 1-3 of 1-6C (polyhalo)alkyl, 1-6C alkoxy, OH, carboxy, 1-6C alkoxycarbonyl, 1-6C acyloxy, formyl, 1-6C acyl, aryl, NR bR c, amido, nitro, CN or halo, where R b, R c are H, 1-6C alkyl or (hetero)aryl. Independent claims are included for: (1) the preparations of (I); (2) a composition (X) comprising (I) an antioxidant agent. [Image] ACTIVITY : Antidiabetic; Antilipemic; Analgesic; Antianginal; Cardiant; Vasotropic; Cardiovascular-Gen.; Nephrotropic; Ophthalmological; Antipsoriatic; Gynecological; Osteopathic; Gastrointestinal-Gen.; Antiinflammatory; Antiarteriosclerotic; Anorectic; Anabolic; Eating-Disorders-Gen.; Neuroprotective; Cytostatic; Endocrine-Gen.; Neuroleptic. The antidiabetic and hypolipidemic effect of (I) was tested in female mouse. The results showed that (I) exhibited a very good capacity to reduce the glycemia compared with the effects obtained with Rosiglitazone. MECHANISM OF ACTION : Angiogenesis inhibitor.

    NUEVOS DERIVADOS DE OXIMAS HETEROCICLICAS, SU PROCEDIMIENTO DE PREPARACION Y SU UTILIZACION COMO AGENTES HIPOGLUCEMICOS E HIPOLIPIDEMICOS.

    公开(公告)号:ES2318727T3

    公开(公告)日:2009-05-01

    申请号:ES06709172

    申请日:2006-01-26

    Applicant: SERVIER LAB

    Abstract: Compuesto de fórmula (I) :** ver fórmula** donde - X representa un átomo de óxigeno o de azufre - A representa una cadena alquileno(C1-C6) de la cual un grupo CH2 puede ser opcionalmente sustituido por un heteroátomo seleccionado entre oxígeno o azufre o por un grupo NRa (donde Ra representa un átomo de hidrógeno o un grupo alquilo(C 1-C 6) lineal o ramificado), o por un grupo fenileno o naftileno, - R 1 y R 2 , idénticos o diferentes, representan un átomo de hidrógeno o un grupo alquilo(C1-C6) lineal o ramificado, alquenilo(C2-C6) lineal o ramificado, alquinilo (C2-C6) lineal o ramificado, arilo, arilalquilo(C1- C 6) lineal o ramificado, arilalquenilo(C 2-C 6) lineal o ramificado, arilalquinilo(C 2-C 6) lineal o ramificado, heteroarilo, heteroarilalquilo(C 1-C 6) lineal o ramificado, heteroarilalquenilo(C 2-C 6) lineal o ramificado, heteroarilalquinilo(C2-C6) lineal o ramificado, cicloalquilo(C3-C8), cicloalquil(C3-C8)alquilo(C1-C6) lineal o ramificado o polihaloalquilo(C1-C6) lineal o ramificado, - R 3 y R 4 , idénticos o diferentes, representan un átomo de hidrógeno o de halógeno, o un grupo R, OR o NRR'', donde R y R'', idénticos o diferentes, representan un átomo de hidrógeno o un grupo alquilo(C1-C6) lineal o ramificado, alquenilo(C2-C6) lineal o ramificado, alquinilo(C2-C6) lineal o ramificado, arilo, arilalquilo (C1-C6) lineal o ramificado, arilalquenilo(C2-C6) lineal o ramificado, arilalquinilo(C2-C6) lineal o ramificado, heteroarilo, heteroarilalquilo(C 1-C 6) lineal o ramificado, heteroarilalquenilo(C 2-C 6) lineal o ramificado, heteroarilalquinilo(C 2-C 6) lineal o ramificado, cicloalquilo(C 3-C 8), cicloalquil(C 3-C 8)alquilo(C 1-C 6) lineal o ramificado o polihaloalquilo (C1-C6) lineal o ramificado, o R 3 y R 4 forman, junto con los átomos de carbono que los portan, cuando son portados por dos átomos de carbono adyacentes, un ciclo que comprende 5 ó 6 eslabones y pudiendo opcionalmente contener un heteroátomo seleccionado entre oxígeno, azufre y nitrógeno, - B representa un grupo alquilo(C1-C6) lineal o ramificado o alquenilo(C2-C6) lineal o ramificado, estando estos grupos sustituidos: con un grupo de fórmula (II): ** ver fórmula** donde** ver fórmula** -R 5 representa un grupo ** ver fórmula** donde Z representa un átomo de oxígeno o de azufre y R y R'', idénticos o diferentes, son tales como se han definido anteriormente, y -R 6 representa un grupo arilo, arilalquilo cuya parte alquilo contiene de 1 a 6 átomos de carbono y que puede ser lineal o ramificada, heteroarilo, heteroarilalquilo cuya parte alquilo contiene de 1 a 6 átomos de carbono y puede ser lineal o ramificada, CN, tetrazol, -OR, -NRR'' ** ver fórmula**, donde Z es tal como se ha definido anteriormente y R y R'', idénticos o diferentes, pueden tomar los mismos valores que se han definido anteriormente, o con un grupo R 7 donde R 7 representa un grupo CN, tetrazol, donde Z es tal como se ha definido anteriormente y R y R'', idénticos o diferentes, pueden tomar los mismos valores que se han definido anteriormente, n representa 0, 1, 2, 3, 4, 5 ó 6, y R 8 y R 9 , idénticos o diferentes, representan un átomo de hidrógeno o un grupo alquilo(C 1-C 6) lineal o ramificado, entendiéndose que R 8 y R 9 no pueden representar simultáneamente un átomo de hidrógeno, - o B representa un grupo de fórmula (II) o un grupo R 7 tal como se ha definido anteriormente, entendiéndose que: - la oxima R 1 -C(=N-OR 2 )- puede ser de configuración Z ó E, - por arilo se entiende un grupo fenilo, naftilo o bifenilo, pudiendo estos grupos estar opcionalmente parcialmente hidrogenados, - por heteroarilo se entiende todo grupo aromático mono o bicíclico que contiene de 5 a 10 eslabones, pudiendo estar opcionalmente parcialmente hidrogenado en uno de los ciclos en el caso de los heteroarilos bicíclicos, y conteniendo de 1 a 3 heteroátomos seleccionados entre oxígeno, nitrógeno y azufre, donde los grupos arilo y heteroarilo así definidos pueden estar opcionalmente sustituidos con 1 a 3 grupos, idénticos o diferentes, seleccionados entre alquilo(C 1-C 6) lineal o ramificado, polihaloalquilo(C 1-C 6) lineal o ramificado, alcoxi(C 1-C 6) lineal o ramificado, hidroxilo, carboxilo, formilo, acilo(C 1-C 6) lineal o ramificado, aroilo, NRbRc (donde Rb y Rc, idénticos o diferentes, representan un átomo de hidrógeno, un grupo alquilo (C1-C6) lineal o ramificado, arilo o heteroarilo), éster, amido, nitro, ciano, o átomos de halógeno, sus enantiómeros y diastereoisómeros, así como sus sales de adición de un ácido o de una base farmacéuticamente aceptables.

Patent Agency Ranking