公开(公告)号：EP1131294B1

公开(公告)日：2006-12-20

申请号：EP99959340.3

申请日：1999-11-22

申请人： GlaxoSmithKline S.p.A. ,  Laboratoire Glaxosmithkline S.A.S.

发明人： FARINA, Carlo SmithKline Beecham S.p.A. ,  GIARDINA, Giuseppe SmithKline Beecham S.p.A. ,  GRUGNI, Mario SmithKline Beecham S.p.A. ,  NADLER, Guy M. M. G. SmithKline Beecham Lab. Phar. ,  RAVEGLIA, Luca Francesco SmithKline Beecham S.p.A.

IPC分类号： C07D215/52 ,  A61K31/4725 ,  C07D401/06 ,  A61K31/4709 ,  A61P25/00 ,  A61P11/00 ,  A61K31/47

CPC分类号： C07D401/06 ,  C07D215/52 ,  C07D401/14

摘要： A compound, or a solvate or a salt thereof, of formula (I), wherein R is linear or branched alkyl; R1 represents hydrogen or up to four optional substituents selected from the list consisting of: C1-6 alkyl, C1-6 alkenyl, aryl, C1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C1-6 alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino or mono- and di-C1-6 alkylamino; R2 represents a moiety -(CH2)n-NY1Y2 wherein n is an integer in the range of from 1 to 9, Y1 and Y2 are independently selected from hydrogen; C1-6-alkyl; C1-6 alkyl substituted with hydroxy, C1-6 alkylamino or bis (C1-6 alkyl) amino; C1-6-alkenyl; aryl or aryl-C1-6-alkyl or Y1 or Y2 together with the nitrogen atom to which they are attached represent an optionally substituted N-linked single or fused ring heterocyclic group; R3 is branched or linear C1-6 alkyl, C3-7 cycloalkyl, C4-7 cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring aromatic heterocyclic group; and R4 represents hydrogen or alkyl or R4 and R together with the carbon atom to which they are attached form an optionally substituted C3-12 cycloalkyl group; a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds as NK-2 or NK-3 receptor ligands.

公开(公告)号：EP0874827B1

公开(公告)日：2003-05-21

申请号：EP96939926.0

申请日：1996-11-22

申请人： GlaxoSmithKline S.p.A.

发明人： GIARDINA, Giuseppe, Arnaldo, Maria ,  FARINA, Carlo SmithKline Beecham S.p.A. ,  GRUGNI, Mario SmithKline Beecham S.p.A. ,  RAVEGLIA, Luca, Francesco

IPC分类号： C07D215/52 ,  A61K31/47 ,  C07D409/04 ,  C07D401/04 ,  C07D221/18 ,  C07D417/04 ,  C07D405/04 ,  C07D409/12

CPC分类号： C07D417/04 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/473 ,  C07D215/52 ,  C07D221/18 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D409/04 ,  C07D409/12 ,  Y10S514/912

摘要： A method for the treatment and/or prophylaxis of conditions characterized by overstimulation of the tachykinin receptors, which method comprises the administration to a mammal in need thereof of an effective, non-toxic, pharmaceutically acceptable amount of a compound of formula (I), or a pharmaceutically acceptable solvate thereof, or a pharmaceutically acceptable salt thereof, wherein: Ar is an optionally substituted phenyl, naphthyl or C5-7 cycloalkdienyl group, or an optionally substituted single or fused ring heterocyclic group, having aromatic character, containing from 5 to 12 ring atoms and comprising up to four heteroatoms in the or each ring selected from S, O, N; R is linear or branched C1-8alkyl, C3-7cycloalkyl, C4-7cycloalkylalkyl, optionally substituted phenyl or phenyl C1-6alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatoms selected from O and N, hydroxy C1-6alkyl, amino C1-6alkyl, C1-6alkylaminoalkyl, di C1-6alkylaminoalkyl, C1-6acylaminoalkkyl, C1-6alkoxyalkyl, C1-6alkylcarbonyl, carboxy, C1-6alkoxycarbonyl, C1-6alkoxycarbonyl, C1-6alkyl, aminocarbonyl, C1-6alkylaminocarbonyl, di C1-6alkylaminocarbonyl; halogeno C1-6alkyl; or is a group -(CH2)p- when cyclized onto Ar, where p is 2 or 3. R1 and R2, which may be the same or different, are independently hydrogen or C1-6 linear or branched alkyl, or together form a -(CH2)n- group in which n represents 3, 4 or 5; or R1 together with R forms a group -(CH2)q-, in which q is 2, 3, 4 or 5; R3 and R4, which may be the same or different, are independently hydrogen, C1-6 linear or branched alkyl, C1-6alkenyl, aryl, C1-6alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C1-6alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino, mono- and di-C1-6alkylamino, -O(CH2)r-NT2, in which r is 2, 3 or 4 and T is hydrogen or C1-6alkyl or it forms with the adjacent nitrogen a group (a) or (b), in which V and V1 are independently hydrogen or oxygen and u is 0, 1 or 2; -O(CH2)s-OW in which s is 2, 3 or 4 and W is hydrogen or C1-6alkyl; hydroxyalkyl, aminoalkyl, mono- or di-alkylaminoalkyl, acylamino, alkylsulphonylamino, aminoacylamino, mono- or di-alkylaminoacylamino; with up to four R3 substituents being present in the quinoline nucleus; or R4 is a group -(CH2)t- when cyclized onto R5 as aryl, in which t is 1, 2 or 3; R5 is branched or linear C1-6alkyl, C3-7cycloalkyl, C4-7cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring heterocyclic group, having aromatic character, containing from 5 to 12 ring atoms and comprising up to four heteroatoms in the or each ring selected from S, O, N; X is O, S, or N-C N.