Fluoromethyl-substituted pyrrole carboxamidesThe invention relates to pyrrole carboxamides bearing a fluoromethyl- moiety as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.The compound of general formula (i) is optionally the form of mixtures of single stereoisomers or steric isomer, is the form of free cpds and/or the acceptable salt of its physiology and/or the acceptable solvate of physiology(i), whereinn represents 0,1 or 2;m represents 0 or 1, and condition is n >=m;x is selected from o, s, nh and n-c 1-6-alkyl; r 1, r 2and r 3be independently from each other h separately; f; cl; br; i; no 2; cn; c 1-6-alkyl; cf 3; cf 2h; cfh 2; cf 2cl; cfcl 2; c (=o)-h; c (=o)-c 1-6-alkyl; c (=o)-oh; c (=o)-o-c 1-6-alkyl; c (=o)-n (h) (oh); c (=o)-nh 2; c (=o)-n (h) (c 1-6-alkyl); c (=o)-n (c 1-6-alkyl) 2; c (=n-oh)-h; c (=n-oh)-c 1-6-alkyl; c (=n-o-c 1-6-alkyl)-h; c (=n-o-c 1-6-alkyl)-c 1-6-alkyl; oh; ocf 3; ocf 2h; ocfh 2; ocf 2cl; ocfcl 2; o-c 1-6-alkyl; o-c (=o)-c 1-6-alkyl; o-c (=o)-o-c 1-6-alkyl; o-(c=o)-n (h) (c 1-6-alkyl); o-c (=o)-n (c 1-6-alkyl) 2; o-s (=o) 2-c 1-6-alkyl; o-s (=o) 2-oh; o-s (=o) 2-o-c 1-6-alkyl; o-s (=o) 2-nh 2; o-s (=o) 2-n (h) (c 1-6-alkyl); o-s (=o) 2-n (c 1-6-alkyl) 2; nh 2; n (h) (c 1-6-alkyl); n (c 1-6-alkyl) 2; n (h)-c (=o)-c 1-6-alkyl; n (h)-c (=o)-o-c 1-6-alkyl; n (h)-c (=o)-nh 2; n (h)-c (=o)-n (h) (c 1-6-alkyl); n (h)-c (=o)-n (c 1-6-alkyl) 2; n (c 1-6-alkyl)-c (=o)-c 1-6-alkyl; n (c 1-6-alkyl)-c (=o)-o-c 1-6-alkyl; n (c 1-6-alkyl)-c (=o)-nh 2; n (c 1-6-alkyl)-c (=o)-n (h) (c 1-6-alkyl); n (c 1-6-alkyl)-c (=o)-n (c 1-6-alkyl) 2; n (h)-s (=o) 2oh; n (h)-s (=o) 2-c 1-6-alkyl; n (h)-s (=o) 2-o-c 1-6-alkyl; n (h)-s (=o) 2-nh 2; n (h)-s (=o) 2-n (h) (c 1-6-alkyl); n (h)-s (=o) 2n (c 1-6-alkyl) 2; n (c 1-6-alkyl)-s (=o) 2-oh; n (c 1-6-alkyl)-s (=o) 2-c 1-6-alkyl; n (c 1-6-alkyl)-s (=o) 2-o-c 1-6-alkyl; n (c 1-6-alkyl)-s (=o) 2-nh 2; n (c 1-6-alkyl)-s (=o) 2-n (h) (c 1-6-alkyl); n (c 1-6-alkyl)-s (=o) 2-n (c 1-6-alkyl) 2; sh; scf 3; scf 2h; scfh 2; scf 2cl; scfcl 2; s-c 1-6-alkyl; s (=o)-c 1-6-alkyl; s (=o) 2-c 1-6-alkyl; s (=o) 2-oh; s (=o) 2-o-c 1-6-alkyl; s (=o) 2-nh 2; s (=o) 2-n (h) (c 1-6-alkyl); or s (=o) 2-n (c 1-6-alkyl) 2, wherein c in each case 1-6-alkyl can be side chain or straight chain; do not replace or list-or polysubstituted; not replace in each case or single-or polysubstituted c 3-6alicyclic radical or 3 to 7 yuan of assorted alicyclic radical; r 4represent ch 2f; chf 2or cf 3; r 5represent h; side chain or straight chain, do not replace or the c of single-or multiple-replace 1-6-alkyl; not replace in each case or single-or polysubstituted c 3-6alicyclic radical or 3 to 7 yuan of assorted alicyclic radical; oh; o-c 1-6-alkyl; nh 2; n (h)-c 1-6-alkyl; n (-c 1-6-alkyl) 2or so 2(-c 1-6-alkyl), wherein c in each case 1-6-alkyl can be side chain or straight chain; do not replace or list-or polysubstituted; r 6, r 7and r 8be independently from each other h separately; f; cl; br; i; no 2; cn; c 1-6-alkyl; cf 3; cf 2h; cfh 2; cf 2cl; cfcl 2; c (=o)-h; c (=o)-c 1-6-alkyl; c (=o)-oh; c (=o)-o-c 1-6-alkyl; c (=o)-n (h) (oh); c (=o)-nh 2; c (=o)-n (h) (c 1-6-alkyl); c (=o)-n (c 1-6-alkyl) 2; c (=n-oh)-h; c (=n-oh)-c 1-6-alkyl; c (=n-o-c 1-6-alkyl)-h; c (=n-o-c 1-6-alkyl)-c 1-6-alkyl; oh; ocf 3; ocf 2h; ocfh 2; ocf 2cl; ocfcl 2; o-c 1-6-alkyl; o-c (=o)-c 1-6-alkyl; o-c (=o)-o-c 1-6-alkyl; o-(c=o)-n (h) (c 1-6-alkyl); o-c (=o)-n (c 1-6-alkyl) 2; o-s (=o) 2-c 1-6-alkyl; o-s (=o) 2-oh; o-s (=o) 2-o-c 1-6-alkyl; o-s (=o) 2-nh 2; o-s (=o) 2-n (h) (c 1-6-alkyl); o-s (=o) 2-n (c 1-6-alkyl) 2; nh 2; n (h) (c 1-6-alkyl); n (c 1-6-alkyl) 2; n (h)-c (=o)-c 1-6-alkyl; n (h)-c (=o)-o-c 1-6-alkyl; n (h)-c (=o)-nh 2; n (h)-c (=o)-n (h) (c 1-6-alkyl); n (h)-c (=o)-n (c 1-6-alkyl) 2; n (c 1-6-alkyl)-c (=o)-c 1-6-alkyl; n (c 1-6-alkyl)-c (=o)-o-c 1-6-alkyl; n (c 1-6-alkyl)-c (=o)-nh 2; n (c 1-6-alkyl)-c (=o)-n (h) (c 1-6-alkyl); n (c 1-6-alkyl)-c (=o)-n (c 1-6-alkyl) 2; n (h)-s (=o) 2oh; n (h)-s (=o) 2-c 1-6-alkyl; n (h)-s (=o) 2-o-c 1-6-alkyl; n (h)-s (=o) 2-nh 2; n (h)-s (=o) 2-n (h) (c 1-6-alkyl); n (h)-s (=o) 2n (c 1-6-alkyl) 2; n (c 1-6-alkyl)-s (=o) 2-oh; n (c 1-6-alkyl)-s (=o) 2-c 1-6-alkyl; n (c 1-6-alkyl)-s (=o) 2-o-c 1-6-alkyl; n (c 1-6-alkyl)-s (=o) 2-nh 2; n (c 1-6-alkyl)-s (=o) 2-n (h) (c 1-6-alkyl); n (c 1-6-alkyl)-s (=o) 2-n (c 1-6-alkyl) 2; sh; scf 3; scf 2h; scfh 2; scf 2cl; scfcl 2; s-c 1-6-alkyl; s (=o)-c 1-6-alkyl; s (=o) 2-c 1-6-alkyl; s (=o) 2-oh; s (=o) 2-o-c 1-6-alkyl; s (=o) 2-nh 2; s (=o) 2-n (h) (c 1-6-alkyl); or s (=o) 2-n (c 1-6-alkyl) 2, wherein c in each case 1-6-alkyl can be side chain or straight chain; do not replace or single-or multiple-replace; not replace in each case or single-or polysubstituted c 3-6alicyclic radical or 3 to 7 yuan of assorted alicyclic radical; r 9represent h; side chain or straight chain, do not replace or the c of single-or multiple-replace 1-10aliphatic residue; c 3-10alicyclic radical or 3 to 10 yuan of assorted alicyclic radical, do not replace in each case or single-or multiple-replace and in each case optional via side chain or straight chain ,-or polysubstituted c can not replaced or single again 1-...
플루오로메틸-치환된 피롤 카복스아미드본 발명은, 전압 개폐 칼슘 채널 차단제(voltage gated calcium channel blocker)로서의 플루오로메틸-모이어티(moiety)를 갖는 피롤 카복스아미드, 상기 화합물을 함유하는 약제학적 조성물, 및 통증 및 추가의 질환 및/또는 장애의 치료 및/또는 예방에 사용하기 위한 상기 화합물에 관한 것이다.임의로 단일 입체이성체 형태 또는 입체이성체들의 혼합물 형태, 유리 화합물 및/또는 생리학적으로 허용되는 염 및/또는 생리학적으로 허용되는 용매화물 형태인 화학식 I의 화합물.화학식 I[이미지]위의 화학식 I에서, n은 0, 1 또는 2이고; m은 0 또는 1이며, 단 n ≥ m이고;X는 O, S, NH 또는 N-C1-6-알킬로 이루어진 그룹으로부터 선택되고;R1, R2 및 R3은, 각각, H; F; Cl; Br; I; NO2; CN; C1-6-알킬; CF3; CF2H; CFH2; CF2Cl; CFCl2; C(=O)-H; C(=O)-C1-6-알킬; C(=O)-OH; C(=O)-O-C1-6-알킬; C(=O)-N(H)(OH); C(=O)-NH2; C(=O)-N(H)(C1-6-알킬); C(=O)-N(C1-6-알킬)2; C(=N-OH)-H; C(=N-OH)-C1-6-알킬; C(=N-O-C1-6-알킬)-H; C(=N-O-C1-6-알킬)-C1-6-알킬; OH; OCF3; OCF2H; OCFH2; OCF2Cl; OCFCl2; O-C1-6-알킬; O-C(=O)-C1-6-알킬; O-C(=O)-O-C1-6-알킬; O-(C=O)-N(H)(C1-6-알킬); O-C(=O)-N(C1-6-알킬)2; O-S(=O)2-C1-6-알킬; O-S(=O)2-OH; O-S(=O)2-O-C1-6-알킬; O-S(=O)2-NH2; O-S(=O)2-N(H)(C1-6-알킬); O-S(=O)2-N(C1-6-알킬)2; NH2; N(H)(C1-6-알킬); N(C1-6-알킬)2; N(H)-C(=O)-C1-6-알킬; N(H)-C(=O)-O-C1-6-알킬; N(H)-C(=O)-NH2; N(H)-C(=O)-N(H)(C1-6-알킬); N(H)-C(=O)-N(C1-6-알킬)2; N(C1-6-알킬)-C(=O)-C1-6-알킬; N(C1-6-알킬)-C(=O)-O-C1-6-알킬; N(C1-6-알킬)-C(=O)-NH2; N(C1-6-알킬)-C(=O)-N(H)(C1-6-알킬); N(C1-6-알킬)-C(=O)-N(C1-6-알킬)2; N(H)-S(=O)2OH; N(H)-S(=O)2-C1-6-알킬; N(H)-S(=O)2-O-C1-6-알킬; N(H)-S(=O)2-NH2; N(H)-S(=O)2-N(H)(C1-6-알킬); N(H)-S(=O)2N(C1-6-알킬)2; N(C1-6-알킬)-S(=O)2-OH; N(C1-6-알킬)-S(=O)2-C1-6-알킬; N(C1-6-알킬)-S(=O)2-O-C1-6-알킬; N(C1-6-알킬)-S(=O)2-NH2; N(C1-6-알킬)-S(=O)2-N(H)(C1-6-알킬); N(C1-6-알킬)-S(=O)2-N(C1-6-알킬)2; SH; SCF3; SCF2H; SCFH2; SCF2Cl; SCFCl2; S-C1-6-알킬; S(=O)-C1-6-알킬; S(=O)2-C1-6-알킬; S(=O)2-OH; S(=O)2-O-C1-6-알킬;S(=O)2-NH2; S(=O)2-N(H)(C1-6-알킬); 또는 S(=O)2-N(C1-6-알킬)2(여기서, 각각의 경우 C1-6-알킬은 분지되거나 분지되지 않을 수 있고, 치환되지 않거나 일치환 또는 다치환될 수 있다); C3-6 지환족 잔기 또는 3원 내지 7원 헤테로지환족 잔기(각각의 경우 치환되지 않거나 일치환 또는 다치환된다)로 이루어진 그룹으로부터 서로 독립적으로 선택되고;R4는 CH2F; CHF2, 또는 CF3이고;R5는 H; 분지되거나 분지되지 않은, 치환되지 않거나 일치환 또는 다치환된 C1-6-알킬; C3-6 지환족 잔기 또는 3원 내지 7원 헤테로지환족 잔기(각각의 경우 치환되지 않거나 일치환 또는 다치환된다); OH; O-C1-6-알킬; NH2; N(H)-C1-6-알킬; N(-C1-6-알킬)2 또는 SO2(-C1-6-알킬)(여기서, 각각의 경우 C1-6-알킬은 분지되거나 분지되지 않을 수 있고, 치환되지 않거나 일치환 또는 다치환될 수 있다)이고;R6, R7 및 R8은, 각각, H; F; Cl; Br; I; NO2; CN; C1-6-알킬; CF3; CF2H; CFH2; CF2Cl; CFCl2; C(=O)-H; C(=O)-C1-6-알킬; C(=O)-OH; C(=O)-O-C1-6-알킬; C(=O)-N(H)(OH); C(=O)-NH2; C(=O)-N(H)(C1-6-알킬); C(=O)-N(C1-6-알킬)2; C(=N-OH)-H; C(=N-OH)-C1-6-알킬; C(=N-O-C1-6-알킬)-H; C(=N-O-C1-6-알킬)-C1-6-알킬; OH; OCF3; OCF2H; OCFH2; OCF2Cl; OCFCl2; O-C1-6-알킬; O-C(=O)-C1-6-알킬; O-C(=O)-O-C1-6-알킬; O-(C=O)-N(H)(C1-6-알킬); O-C(=O)-N(C1-6-알킬)2; O-S(=O)2-C1-6-알킬; O-S(=O)2-OH; O-S(=O)2-O-C1-6-알킬; O-S(=O)2-NH2; O-S(=O)2-N(H)(C1-6-알킬); O-S(=O)2-N(C1-6-알킬)2; NH2; N(H)(C1-6-알킬); N(C1-6-알킬)2; N(H)-C(=O)-C1-6-알킬; N(H)-C(=O)-O-C1-6-알킬; N(H)-C(=O)-NH2; N(H)-C(=O)-N(H)(C1-6-알킬); N(H)-C(=O)-N(C1-6-알킬)2; N(C1-6-알킬)-C(=O)-C1-6-알킬; N(C1-6-알킬)-C(=O)-O-C1-6-알킬; N(C1-6-알킬)-C(=O)-NH2; N(C1-6-알킬)-C(=O)-N(H)(C1-6-알킬); N(C1-6-알킬)-C(=O)-N(C1-6-알킬)2; N(H)-S(=O)2OH; N(H)-S(=O)2-C1-6-알킬; N(H)-S(=O)2-O-C1-6-알킬; N(H)-S(=O)2-NH2; N(H)-S(=O)2-N(H)(C1-6-알킬); N(H)-S(=O)2N(C1-6-알킬)2; N(C1-6-알킬)-S(=O)2-OH; N(C1-6-알킬)-S(=O)2-C1-6-알킬; N(C1-6-알킬)-S(=O)2-O-C1-6-알킬; N(C1-6-알킬)-S(=O)2-NH2; N(C1-6-알킬)-S(=O)2-N(H)(C1-6-알킬); N(C1-6-알킬)-S(=O)2-N(C1-6-알킬)2; SH; SCF3; SCF2H; SCFH2; SCF2Cl; SCFCl2; S-C1-6-알킬; S(=O)-C1-6-알킬; S(=O)2-C1-6-알킬; S(=O)2-OH; S(=O)2-O-C1-6-알킬;S(=O)2-NH2; S(=O)2-N(H)(C1-6-알킬); 또는 S(=O)2-N(C1-6-알킬)2(여기서, 각각의 경우 C1-6-알킬은 분지되거나 분지되지 않을 수 있고, 치환되지 않거나 일치환 또는 다치환될 수 있다); C3-6 지환족 잔기 또는 3원 내지 7원 헤테로지환족 잔기(각각의 경우 치환되지 않거나 일치환 또는 다치환된다)로 이루어진 그룹으로부터 서로 독립적으로 선택되고;R9는 H; 분지되거나 분지되지 않은, 치환되지 않거나 일치환 또는 다치환된 C1-10 지방족 잔기; C3-10 지환족 잔기 또는 3원 내지 10원 헤테로지환족 잔기(각각의 경우 치환되지 않거나 일치환 또는 다치환되고, 각각의 경우, 분지되거나 분지되지 않은 C1-8 알킬렌 그룹을 통해 임의로 연결되며, 상기 알킬렌 그룹은 치환되지 않거나 일치환 또는 다치환될 수 있다)이고;R10은 H; 분지되거나 분지되지 않은, 치환되지 않거나 일치환 또는 다치환된 C1-10 지방족 잔기; C3-10 지환족 잔기, 3원 내지 10원 헤테로지환족 잔기 또는 헤테로아릴 잔기(각각의 경우 치환되지 않거나 일치환 또는 다치환되고, 각각의 경우, 분지되거나 분지되지 않은 C1-8 알킬렌 그룹을 통해 임의로 연결되며, 상기 알킬렌 그룹은 치환되지 않거나 일치환 또는 다치환될 수 있다)이거나; R9와 R10은, 이들을 연결하는 질소 원자와 함께, 치환되지 않거나 일치환 또는 다치환될 수 있는 3원 내지 10원 헤테로지환족 잔기를 형성한다.