公开(公告)号：DE19752904A1

公开(公告)日：1999-07-15

申请号：DE19752904

申请日：1997-11-28

Applicant: BASF AG

Inventor： AMBERG WILHELM DR ,  JANSEN ROLF DR ,  HERGENROEDER STEFAN DR ,  RASCHACK MANFRED DR ,  UNGER LILIANE DR

IPC: C07D239/36 ,  C07D239/52 ,  C07D239/60 ,  C07D401/12 ,  A61K31/505 ,  C07D213/63 ,  C07D239/80 ,  C07D239/96 ,  C07D251/12 ,  C07D491/04

Abstract: Amido-substituted (hetero)aryloxy-alkanoic acid derivatives (I) are new. Carboxylic acid derivatives of formula (I), and their salts and pure enantiomers or diastereomers, are new: R1 = tetrazole or -CO-R; R = OR9, N-bonded 5-membered heteroaryl, -O(CH2)p-S(O)k-R10 or -NHSO2R11; R9 = H; alkali metal, alkaline earth metal or organic ammonium cation; cycloalkyl; alkyl; or (all optionally substituted) benzyl, 3-6C alkenyl, 3-6C alkynyl or phenyl; k = 0-2; p = 1-4; R10 = A, cycloalkyl, 3-6C alkenyl, 3-6C alkynyl or optionally substituted phenyl; A = 1-4C alkyl; R11 = A, 3-6C alkenyl, 3-6C alkynyl or cycloalkyl (all optionally substituted by OA, SA and/or phenyl); or optionally substituted phenyl; R2, R3 = H, OH, NH2, NHA, N(A)2, halo, A', 2-4C alkenyl, 2-4C alkynyl, OA' or SA; A' = A or 1-4C haloalkyl; X, Y = CH or N; Z' = N or CR12; R12 = H, halo or A; or R2+R12 or R3+R12 = alkylene or alkenylene (both optionally substituted and optionally having one or more CH2 replaced by O, S, NH or NA), completing a 5- or 6-membered ring; R4, R5 = phenyl, naphthyl or cycloalkyl (all optionally substituted); or phenyl or naphthyl bonded together in the ortho-position via a direct bond, CH2, CH2CH2, CH=CH, O, S, SO2, NH or N-alkyl (C number not given); R6 = -CO-NR13R14 or -CR21R20-NR18R19; R13, R14 = H (but not both H) or (all optionally substituted) alkyl, cycloalkyl, alkenyl, alkynyl, benzyl, phenyl or naphthyl; or R13+R14 = optionally substituted 3-7C alkylene (optionally with one CH2 replaced by O, S or N or carrying an optionally substituted fused benzene ring); or optionally substituted 3-7C alkenylene carrying an optionally substituted fused benzene ring; R7, R8, R21 = H or A; R18 = H or (all optionally substituted) alkyl, cycloalkyl, alkenyl, alkynyl, phenyl or naphthyl; R19 = alkylcarbonyl, (2-8C) alkenylcarbonyl, (2-8C) alkynylcarbonyl, benzyloxycarbonyl, cycloalkylcarbonyl, benzoyl, naphthoyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, phenylsulfonyl or naphthylsulfonyl (all optionally substituted); or cycloalkylsulfonyl; R20 = H or A (optionally substituted); W = O or S; alkyl moieties = 1-8C and alkenyl, alkynyl or cycloalkyl moieties = 3-8C unless specified otherwise. Independent claims are included for: (i) the use of alcohols of formula (V) as starting materials for the synthesis of endothelin (ET) receptor antagonists; (ii) structural fragments of formula (II); (iii) the use of (II) as a structural component of ET receptor antagonists; (iv) ET receptor antagonists consisting of a fragment of formula (III) covalently bonded with a group having molecular weight at least 30 or a fragment of formula (IV) covalently bonded via N to a group of molecular weight at least 58; and (v) new amines of formula (I'). N.B. The additional CO groups attached to R6 in (V) and (II) have been omitted in the disclosure.

公开(公告)号：DE19738578A1

公开(公告)日：1999-03-11

申请号：DE19738578

申请日：1997-09-04

Applicant: BASF AG

Inventor： AMBERG WILHELM DR ,  JANSEN ROLF DR ,  KLINGE DAGMAR DR ,  RIECHERS HARTMUT DR ,  HERGENROEDER STEFAN DR ,  RASCHACK MANFRED DR ,  UNGER LILIANE DR

IPC: C07D239/34 ,  C07D239/52 ,  C07D277/34 ,  C07D409/12 ,  C07D491/052 ,  C07D239/24 ,  A61K31/215 ,  A61K31/41 ,  A61K31/495 ,  C07C59/64 ,  C07C69/734 ,  C07D233/32 ,  C07D239/80 ,  C07D239/96 ,  C07D263/22

Abstract: Carboxylic acid derivatives (I) and their salts and enantiomers are new. Carboxylic acid derivatives of formula (I) and their salts and enantiomers are new. R = tetrazole or COR1; R1 = OR7, 3-8C cycloalkyl, 1-8C alkyl, optionally substituted phenyl or benzyl, 3-6C alkenyl or optionally substituted 3-6C alkynyl; R7 = H, alkali or alkaline earth metal cation or organic ammonium ion; R2, R3 = H, OH, NH2, mono- or di(1-4C alkyl)amino, halo, 1-4C alkyl, 2-4C alkenyl, 2-4C alkynyl, 1-4C haloalkyl, 1-4C alkoxy, 1-4C haloalkoxy or 1-4C alkylthio; or CR2+CR10 = 5-6-membered ring; X, Y = N or CH; W = N or CR10; R10 = H or 1-4C alkyl; or CR10+CR2 or CR10+CR3 = 5-6-membered alkylene or alkenylene ring (optionally substituted and in which one or more of the methylene groups may be replaced by O, S, NH or N-(1-4C alkyl)); R4, R5 = optionally substituted phenyl or naphthyl (bound via a direct bond, methylene, ethylene, ethenylene, O, S, SO2, NH or N-alkyl) or optionally substituted 3-8C cycloalkyl; R6 = 3-8C cycloalkyl, phenyl, naphthyl or 5-6-membered heteroaromatic group containing 1-3 N atoms and/or an S or O atom (all optionally substituted); Z = O or S; B = 2-4C alkylene; Het = heterocyclic group of formula (i) or (ii); T = O, S or NR8; and R8 = 1-6C alkyl.

公开(公告)号：DE19750529A1

公开(公告)日：1999-05-20

申请号：DE19750529

申请日：1997-11-14

Applicant: BASF AG

Inventor： AMBERG WILHELM DR ,  JANSEN ROLF DR ,  HILLEN HEINZ DR ,  HERGENROEDER STEFAN DR ,  RASCHACK MANFRED DR ,  UNGER LILIANE DR

IPC: C07D249/12 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/42 ,  A61K31/421 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/425 ,  A61K31/426 ,  A61K31/427 ,  A61K31/428 ,  A61K31/433 ,  A61P9/04 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P11/06 ,  A61P13/08 ,  A61P13/12 ,  A61P35/00 ,  A61P43/00 ,  C07D231/20 ,  C07D233/70 ,  C07D261/12 ,  C07D263/38 ,  C07D271/06 ,  C07D271/10 ,  C07D273/01 ,  C07D275/02 ,  C07D275/03 ,  C07D277/20 ,  C07D277/32 ,  C07D277/34 ,  C07D277/60 ,  C07D277/68 ,  C07D285/00 ,  C07D285/08 ,  C07D285/12 ,  C07D291/04 ,  C07D413/12 ,  C07D417/12 ,  C07D263/20 ,  C07D277/72 ,  C07D263/46

Abstract: Heterocyclic alpha -hydroxycarboxylic acid derivatives (I) are new. Heterocyclic alpha -hydroxycarboxylic acid derivatives of formula (I) and their salts, enantiomers and diastereomers are new. R = tetrazolyl or CO-R; R = OR , a 5-membered heteroaromatic group bound via an N atom, -O-(CH2)p-S(O)k-R or -NH-SO2-R ; A = NR R , N3, OR , SR or 1-4C alkyl; X = O, S, CR or NR , provided that if X = CR , then Y = O, S or NR ; Y = O, S, CR or NR ; R , R = independently phenyl or naphthyl (which are optionally substituted or optionally bound via a methylene, ethylene, ethenylene, O, S, SO2, NH or N(1-4C alkyl) group) or 5- or 6C cycloalkyl; R , R = H, halo, or optionally substituted 1-4C alkoxy, 1-4C haloalkoxy, 3-6C alkenyloxy, 3-6C alkynyloxy, 1-4C alkylthio, (1-4C alkyl)carbonyl, (1-4C alkoxy)carbonyl, OH, NH2, NH(1-4C alkyl), N(1-4C alkyl)2, 1-4C alkyl, 2-4C alkenyl, 2-4C alkynyl, or CR and CR together form a 5- or 6-membered alkylene or alkenylene ring, which is optionally substituted and one or more of whose CH2 groups may be replaced by O, S, NH or N(1-4C alkyl); R = H, an alkali or alkaline earth metal cation or an organic ammonium ion, or 3-8C cycloalkyl, 1-8C alkyl, benzyl, 3-8C alkenyl, 3-8C alkynyl or optionally substituted phenyl; k = 0-2; p = 1-4; R = 1-4C alkyl, 3-8C cycloalkyl, 3-8C alkenyl, 3-8C alkynyl or optionally substituted phenyl; R = 1-4C alkyl, 3-8C cycloalkyl, 3-8C alkenyl, 3-8C alkynyl, 1-4C haloalkyl or phenyl (all optionally substituted); R = H, 1-8C alkyl, 3-8C alkenyl, 3-8C alkynyl or (1-5C alkyl)carbonyl, phenyl, naphthyl or 3-8C cycloalkyl (all optionally substituted), or R and R together form a 3-7C alkylene chain which may be substituted and whose alkylene chain may contain O or S atoms; R = H or 1-4C alkyl; R = H, 1-8C alkyl, 3-8C alkenyl, 3-8C alkynyl, phenyl, naphthyl or 3-8C cycloalkyl (all optionally substituted); R = H or 1-4C alkyl, or NR and CR together form a 5- or 6-membered alkylene or alkenylene ring, which is optionally substituted and one or more of whose CH2 groups may be replaced by O or S; R = H, halo, 1-4C alkyl, 2-4C alkenyl or 2-4C alkynyl (all optionally substituted); R = H or 1-4C alkyl.

公开(公告)号：DE19652763A1

公开(公告)日：1998-06-25

申请号：DE19652763

申请日：1996-12-18

Applicant: BASF AG

Inventor： AMBERG WILHELM DR ,  JANSEN ROLF DR ,  KLING ANDREAS DR ,  KLINGE DAGMAR DR ,  RIECHERS HARTMUT DR ,  HERGENROEDER STEFAN DR ,  RASCHACK MANFRED DR ,  UNGER LILIANE DR

IPC: C07D237/14 ,  C07D237/16 ,  C07D241/18 ,  C07D253/07 ,  C07D253/075 ,  C07D253/10 ,  C07D491/04 ,  A61K31/195 ,  A61K31/53 ,  C07D241/14 ,  C07D241/36 ,  C07D255/00 ,  C07D487/06 ,  C07D493/04 ,  C07D495/04

Abstract: Heterocyclic compounds of formula (I) and their salts are new. R1 = tetrazolyl, or COR; R = OR6, O(CH2)pS(O)kR7, NHS(O)2R8 or a 5-membered azaheteroaryl; R2 = 1-4C alkyl, 2-4C alkenyl, 2-4C alkynyl (all optionally substituted), H, halo, 1-4C alkoxy, 1-4C haloalkoxy, 3-6C alkenyloxy, 3-6C alkynyloxy, 1-4C alkylthio, 1-4C alkylcarbonyl, 1-4C alkoxycarbonyl, NH(1-4C alkyl), N(1-4C alkyl)2, OH, carboxy or amino; R3, R4 = phenyl, naphthyl or 3-8C cycloalkyl (all optionally substituted); or R3+R4 = two of phenyl, naphthyl linked at the o-position by a bond, methylene, ethylene, ethenyl, S, SO2, NH or N-alkyl; R5 = H, 1-8C alkyl, 3-8C alkenyl, 3-8C alkynyl, Ph, naphthyl, 5-6 membered heteroaromatic (containing 1-3 N, S and/or O), or 3-8C cycloalkyl (all optionally substituted); R6 = H, alkali metal or earth-alkali metal, organic ammonium, 3-8C cycloalkyl, 1-8C alkyl, or (all optionally substituted) benzyl, 3-8C alkenyl, 3-8C alkynyl or phenyl; R7 = 1-4C alkyl, 3-8C cycloalkyl, 3-8C alkenyl, 3-8C alkynyl or optionally substituted phenyl; R8 = 1-4C alkyl, 3-8C alkenyl, 3-8C alkynyl, 3-8C cycloalkyl (all optionally substituted by 1-4C alkoxy, 1-4C alkylthio and/or phenyl), 1-4C haloalkyl or optionally substituted phenyl; X = N, Y = N or CR9 and Z = N; or X = CH, Y = N or CR9 and Z = N or CR10 provided that Y or Z = N; R9, R10 = 1-4C alkyl, 2-4C alkenyl or 2-4C alkynyl (all optionally substituted), H, OH, NH2, NH(1-4C alkyl), N(1-4C alkyl)2, halo, 1-4C alkoxy, 1-4C haloalkoxy or 1-4C alkylthio; or CR2+CR9 or CR2+CR10 completes a 5-6 membered alkylene or alkenyl ring (optionally substituted) with one or more CH2 optionally replaced by O, S, NH or N(1-4C alkyl); Q = N and W = bond; or Q = O and W = S, O or a bond; k = 0-2; and p = l-4.

公开(公告)号：DE19636046A1

公开(公告)日：1998-03-12

申请号：DE19636046

申请日：1996-09-05

Applicant: BASF AG

Inventor： AMBERG WILHELM DR ,  JANSEN ROLF DR ,  KLING ANDREAS DR ,  KLINGE DAGMAR DR ,  RIECHERS HARTMUT DR ,  HERGENROEDER STEFAN DR ,  RASCHACK MANFRED DR ,  UNGER LILIANE DR

IPC: A61K31/505 ,  A61K31/506 ,  A61K31/519 ,  A61P9/04 ,  A61P9/08 ,  A61P9/12 ,  A61P43/00 ,  C07C59/66 ,  C07C69/734 ,  C07D239/34 ,  C07D239/52 ,  C07D239/60 ,  C07D239/70 ,  C07D491/04 ,  C07D491/048 ,  C07D405/10 ,  C07D403/12 ,  C07D251/12 ,  C07C59/64 ,  A61K31/41

Abstract: Carboxylic acid derivatives have the formula (I), in which R stands for tetrazole or a group (a); R stands for hydrogen, hydroxy, NH2, NH(C1-c4-alkyl), N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkinyl, C1-C4-alkyl halide, C1-C4-alkoxy, C1-C4-alkoxy halide or C1-C4-alkylthio, or CR is linked with CR , as indicated below, into a 5- or 6-membered ring; X stands for nitrogen or methine; Y stands for nitrogen or methine; Z stands for nitrogen or CR , wherein R is hydrogen or C1-C4-alkyl or CR forms together with CR or CR an optionally substituted 5- or 6-membered alkylene or alkenylene ring, and wherein one or more methylene groups can be substituted by hydrogen, sulphur, -NH or -N(C1-C4-alkyl); R stands for hydrogen, hydroxy, NH2, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkinyl, C1-C4-hydroxyalkyl, C1-C4-alkyl halide, C1-C4-alkoxy, C1-C4-alkoxy halide, C1-C4-alkylthio; or CR is linked to CR as indicated above into a 5- or 6-membered ring, R and R (which may be identical or different) stand for optionally substituted phenyl or naphthyl, or for phenyl or naphthyl which are linked to each other at the ortho-position by a direct bond, a methylene, ethylene or ethenylene group, an oxygen or sulphur atom or an SO2, NH or N-alkyl group; optionally substituted C3-C8-cycloalkyl; R stands for optionally substituted C3-C8-cycloalkyl; optionally substituted phenyl or naphthyl, a 5- or 6-membered, optionally substituted heteroaromatic compound containing one to three nitrogen atoms and/or one sulphur or oxygen atom; W stands for sulphur or oxygen; Q is a spacer with a length that corresponds to a C2-C4 chain. Also disclosed are the physiologically tolerable salts of these compounds, as well as their pure enantiomer and diastereoisomer forms, their preparation and use as mixed ETA/ETB-receptor antagonists.