公开(公告)号：CY1106878T1

公开(公告)日：2012-09-26

申请号：CY071101205

申请日：2007-09-19

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  C07D405/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

Abstract: Ένωσητύπου (Ι):

公开(公告)号：CA2506491C

公开(公告)日：2009-09-01

申请号：CA2506491

申请日：2005-05-05

Applicant: SERVIER LAB

Inventor： HARLEY ELIZABETH ,  COMBETTES MURIELLE ,  BENOIST ALAIN ,  DE NANTEUIL GUILLAUME

IPC: C07D295/18 ,  C07D417/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/04 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12

Abstract: La présente invention vise un composé de formule (I): (voir formule I) dans laquelle: ~ X1 représente un atome ou groupement choisi parmi CR4a R4b, O, S(O)q1 et NR5, OU R4a, R4b, q1 et R5 sont tels que définis dans la description, ~ m1 représente zéro ou un entier compris entre 1 et 4 inclus, ~ m2 représente un entier compris entre 1 et 4 inclus, ~ n1 et n2, identiques ou différents, représentent chacun un entier compris entre 1 et 3 inclus, ~ R1 représente un atome d'hydrogène ou un groupement choisi parmi carboxy, alkoxycarbonyle, carbamoyle éventuellement substitué et alkyle éventuellemen t substitué, ~ R2 représente un atome d'hydrogène ou un groupement alkyle, ~ Ak représente une chaîne alkylène éventuellement substituée, ~ p représente zéro, 1 ou 2, ~ R3 représente un atome d'hydrogène ou un groupement cyano, ~ X2 et X3, identiques ou différents, représentent chacun, soit un groupemen t S(O)q2, soit un groupement CR6a R6b, où q2, R6a et R6b sont tels que définis dans la description, ses isomères optiques lorsqu'ils existent, ainsi que ses sels d'addition à u n acide pharmaceutiquement acceptable. L'invention s'étend à l'utilisation de ces composés, aux compositions pharmaceutiques qui les contiennent ainsi qu'à leurs procédés de préparation.

公开(公告)号：HRP20070376T3

公开(公告)日：2007-12-31

申请号：HRP20070376

申请日：2007-09-03

Applicant: SERVIER LAB

Inventor： NANTEUIL GUILLAUME DE ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  C07D405/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

Abstract: Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives (I), their optical isomers and acid addition salts are new. Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives of formula (I), and their optical isomers and acid addition salts, are new. X 1CR 4aR 4b, O, S(O) q1 or NR 5; R 4a and R 4bhydrogen or 1-6 C linear or branched alkyl or together complete a 3-7C cycloalkyl; q1 : 0-2; R 5hydrogen or 1-6C linear or branched alkyl, optionally substituted by hydroxy; m1 : 0-4; m2 : 1-4; n1 and n2 : 1-3; R 1hydrogen, carboxy, 1-6C linear or branched alkoxycarbonyl, carbamoyl (optionally substituted by 1 or 2 1-6C linear or branched alkyl), or 1-6C linear or branched alkyl (optionally substituted by hydroxy) or amino (optionally substituted by 1 or 2 1-6C linear or branched alkyl); R 2hydrogen or 1-6C linear or branched alkyl; Ak : 1-4C linear or branched alkylene, optionally substituted by one or more halo, particularly fluoro; p : 0-2; R 3hydrogen or cyano; X 2 and X 3S(O) q2 or CR 6aR 6b; R 6a and R 6bhydrogen or halo, preferably fluoro, or R 6a = hydrogen and R 6b = hydroxy; and q2 : 0-2. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Antidiabetic; Anorectic. MECHANISM OF ACTION : Inhibition of dipeptidyl-peptidase IV (DPPIV). The compound (2S)-1-({[9-(hydroxymethyl)-3-oxaspiro[5,5]undec-9-yl]amino}acetyl)-2-pyrrolidinecarbonitrile had IC 50 76.1 nM against porcine renal DPPIV, in an assay based on cleavage of Gly-Pro-p-nitroanilide.

公开(公告)号：UA84553C2

公开(公告)日：2008-11-10

申请号：UAA200504664

申请日：2005-05-18

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/16 ,  C07D277/06 ,  C07D311/96 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

Abstract: Соединениеформулы (І):, (I)где:Хпредставляетсобойатомилигруппу, выбраннуюиз CRR, О, S(O)и NR,где R, R, qи Rявляютсятаковыми, какопределенов описании,mпредставляетсобойнольилицелоечислоот 1 до 4 включительно,mпредставляетсобойцелоечислоот 1 до 4 включительно,nи n, которыемогутбытьодинаковымиилиотличаться, каждыйпредставляетсобойцелоечислоот 1 до 3 включительно,Rпредставляетсобойатомводородаилигруппу, выбраннуюизкарбокси, алкоксикарбонила, необязательнозамещенногокарбамоилаи необязательнозамещенногоалкила,Rпредставляетсобойатомводородаилиалкильнуюгруппу,Ak представляетсобойнеобязательнозамещеннуюалкиленовуюцепь,рпредставляетсобойноль, 1 или 2,Rпредставляетсобоюатомводородаилицианогруппу,ХиХ, которыемогутбытьодинаковымиилиотличаться, каждыйпредс

公开(公告)号：PT1598350E

公开(公告)日：2007-10-04

申请号：PT05291066

申请日：2005-05-18

Applicant: SERVIER LAB

Inventor： NANTEUIL GUILLAUME DE ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  C07D405/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

公开(公告)号：BRPI0501769A

公开(公告)日：2006-01-10

申请号：BRPI0501769

申请日：2005-05-19

Applicant: SERVIER LAB

Inventor： NANTEUIL GUILLAUME DE ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D233/08 ,  A61K31/395 ,  A61P7/12

Abstract: Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives (I), their optical isomers and acid addition salts are new. Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives of formula (I), and their optical isomers and acid addition salts, are new. X 1CR 4aR 4b, O, S(O) q1 or NR 5; R 4a and R 4bhydrogen or 1-6 C linear or branched alkyl or together complete a 3-7C cycloalkyl; q1 : 0-2; R 5hydrogen or 1-6C linear or branched alkyl, optionally substituted by hydroxy; m1 : 0-4; m2 : 1-4; n1 and n2 : 1-3; R 1hydrogen, carboxy, 1-6C linear or branched alkoxycarbonyl, carbamoyl (optionally substituted by 1 or 2 1-6C linear or branched alkyl), or 1-6C linear or branched alkyl (optionally substituted by hydroxy) or amino (optionally substituted by 1 or 2 1-6C linear or branched alkyl); R 2hydrogen or 1-6C linear or branched alkyl; Ak : 1-4C linear or branched alkylene, optionally substituted by one or more halo, particularly fluoro; p : 0-2; R 3hydrogen or cyano; X 2 and X 3S(O) q2 or CR 6aR 6b; R 6a and R 6bhydrogen or halo, preferably fluoro, or R 6a = hydrogen and R 6b = hydroxy; and q2 : 0-2. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Antidiabetic; Anorectic. MECHANISM OF ACTION : Inhibition of dipeptidyl-peptidase IV (DPPIV). The compound (2S)-1-({[9-(hydroxymethyl)-3-oxaspiro[5,5]undec-9-yl]amino}acetyl)-2-pyrrolidinecarbonitrile had IC 50 76.1 nM against porcine renal DPPIV, in an assay based on cleavage of Gly-Pro-p-nitroanilide.

公开(公告)号：NO20052414A

公开(公告)日：2005-11-21

申请号：NO20052414

申请日：2005-05-19

Applicant: SERVIER LAB

Inventor： NANTEUIL GUILLAUME DE ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D207/14

CPC classification number: C07D405/12 ,  C07D207/10 ,  C07D207/16 ,  C07D277/12 ,  C07D295/185 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

公开(公告)号：NO330294B1

公开(公告)日：2011-03-21

申请号：NO20052414

申请日：2005-05-19

Applicant: SERVIER LAB

Inventor： NANTEUIL GUILLAUME DE ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELISZABETH

IPC: C07D207/06 ,  C07D295/18 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

Abstract: Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives (I), their optical isomers and acid addition salts are new. Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives of formula (I), and their optical isomers and acid addition salts, are new. X 1CR 4aR 4b, O, S(O) q1 or NR 5; R 4a and R 4bhydrogen or 1-6 C linear or branched alkyl or together complete a 3-7C cycloalkyl; q1 : 0-2; R 5hydrogen or 1-6C linear or branched alkyl, optionally substituted by hydroxy; m1 : 0-4; m2 : 1-4; n1 and n2 : 1-3; R 1hydrogen, carboxy, 1-6C linear or branched alkoxycarbonyl, carbamoyl (optionally substituted by 1 or 2 1-6C linear or branched alkyl), or 1-6C linear or branched alkyl (optionally substituted by hydroxy) or amino (optionally substituted by 1 or 2 1-6C linear or branched alkyl); R 2hydrogen or 1-6C linear or branched alkyl; Ak : 1-4C linear or branched alkylene, optionally substituted by one or more halo, particularly fluoro; p : 0-2; R 3hydrogen or cyano; X 2 and X 3S(O) q2 or CR 6aR 6b; R 6a and R 6bhydrogen or halo, preferably fluoro, or R 6a = hydrogen and R 6b = hydroxy; and q2 : 0-2. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Antidiabetic; Anorectic. MECHANISM OF ACTION : Inhibition of dipeptidyl-peptidase IV (DPPIV). The compound (2S)-1-({[9-(hydroxymethyl)-3-oxaspiro[5,5]undec-9-yl]amino}acetyl)-2-pyrrolidinecarbonitrile had IC 50 76.1 nM against porcine renal DPPIV, in an assay based on cleavage of Gly-Pro-p-nitroanilide.

公开(公告)号：DK1598350T3

公开(公告)日：2007-11-12

申请号：DK05291066

申请日：2005-05-18

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  C07D405/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

Abstract: Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives (I), their optical isomers and acid addition salts are new. Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives of formula (I), and their optical isomers and acid addition salts, are new. X 1CR 4aR 4b, O, S(O) q1 or NR 5; R 4a and R 4bhydrogen or 1-6 C linear or branched alkyl or together complete a 3-7C cycloalkyl; q1 : 0-2; R 5hydrogen or 1-6C linear or branched alkyl, optionally substituted by hydroxy; m1 : 0-4; m2 : 1-4; n1 and n2 : 1-3; R 1hydrogen, carboxy, 1-6C linear or branched alkoxycarbonyl, carbamoyl (optionally substituted by 1 or 2 1-6C linear or branched alkyl), or 1-6C linear or branched alkyl (optionally substituted by hydroxy) or amino (optionally substituted by 1 or 2 1-6C linear or branched alkyl); R 2hydrogen or 1-6C linear or branched alkyl; Ak : 1-4C linear or branched alkylene, optionally substituted by one or more halo, particularly fluoro; p : 0-2; R 3hydrogen or cyano; X 2 and X 3S(O) q2 or CR 6aR 6b; R 6a and R 6bhydrogen or halo, preferably fluoro, or R 6a = hydrogen and R 6b = hydroxy; and q2 : 0-2. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Antidiabetic; Anorectic. MECHANISM OF ACTION : Inhibition of dipeptidyl-peptidase IV (DPPIV). The compound (2S)-1-({[9-(hydroxymethyl)-3-oxaspiro[5,5]undec-9-yl]amino}acetyl)-2-pyrrolidinecarbonitrile had IC 50 76.1 nM against porcine renal DPPIV, in an assay based on cleavage of Gly-Pro-p-nitroanilide.

公开(公告)号：DE602005001576D1

公开(公告)日：2007-08-23

申请号：DE602005001576

申请日：2005-05-18

Applicant: SERVIER LAB

Inventor： DE NANTEUIL GUILLAUME ,  BENOIST ALAIN ,  COMBETTES MURIELLE ,  HARLEY ELIZABETH

IPC: C07D295/18 ,  C07D405/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/426 ,  A61K31/427 ,  A61K31/438 ,  A61P3/10 ,  A61P43/00 ,  C07D207/06 ,  C07D207/10 ,  C07D207/16 ,  C07D277/06 ,  C07D277/12 ,  C07D295/185 ,  C07D311/96 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

Abstract: Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives (I), their optical isomers and acid addition salts are new. Spiro-cycloalkyl N-acyl pyrrolidine or thiazolidine derivatives of formula (I), and their optical isomers and acid addition salts, are new. X 1CR 4aR 4b, O, S(O) q1 or NR 5; R 4a and R 4bhydrogen or 1-6 C linear or branched alkyl or together complete a 3-7C cycloalkyl; q1 : 0-2; R 5hydrogen or 1-6C linear or branched alkyl, optionally substituted by hydroxy; m1 : 0-4; m2 : 1-4; n1 and n2 : 1-3; R 1hydrogen, carboxy, 1-6C linear or branched alkoxycarbonyl, carbamoyl (optionally substituted by 1 or 2 1-6C linear or branched alkyl), or 1-6C linear or branched alkyl (optionally substituted by hydroxy) or amino (optionally substituted by 1 or 2 1-6C linear or branched alkyl); R 2hydrogen or 1-6C linear or branched alkyl; Ak : 1-4C linear or branched alkylene, optionally substituted by one or more halo, particularly fluoro; p : 0-2; R 3hydrogen or cyano; X 2 and X 3S(O) q2 or CR 6aR 6b; R 6a and R 6bhydrogen or halo, preferably fluoro, or R 6a = hydrogen and R 6b = hydroxy; and q2 : 0-2. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Antidiabetic; Anorectic. MECHANISM OF ACTION : Inhibition of dipeptidyl-peptidase IV (DPPIV). The compound (2S)-1-({[9-(hydroxymethyl)-3-oxaspiro[5,5]undec-9-yl]amino}acetyl)-2-pyrrolidinecarbonitrile had IC 50 76.1 nM against porcine renal DPPIV, in an assay based on cleavage of Gly-Pro-p-nitroanilide.