2-(heterocyclylalkyl)imidazopyridines

Claim 1

A method of treating allergic diseases in warm-blooded animals suffering from the same, which method comprises the systemic administration to warm blooded animals of an effective anti-allergic amount of a compound of the formula: ##STR88## a pharmaceutically acceptable acid addition salt or a stereochemically isomeric form thereof, wherein: --A 1 ═A 2 --A 3 ═A 4 -- represents a bivalent radical of the formula: --N═CH--N═CH-- (a-5) or; --CH═N--CH═N-- (a-6), wherein one or two hydrogen atoms in said radicals (a-5) and (a-6) may, each independently from each other, be replaced by halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, or hydroxy; R represents hydrogen or C 1-6 alkyl; R 1 represents hydrogen, C 1-10 alkyl, C 3-6 cycloalkyl, Ar 1 , C 1-6 alkyl substituted with one or two Ar 1 radicals, or a radical of the formula --Alk--G--R 2 , wherein: Ar 1 represents phenyl; phenyl substituted with 1, 2 or 3 substitutents each independently selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, mercapto, amino, mono- and di(C 1-6 alkyl)amino, carboxyl, C 1-6 alkyloxycarbonyl, and C 1-6 alkylcarbonyl; thienyl; halothienyl; furanyl; C 1-6 alkyl substituted furanyl; pyridinyl; pyrimidinyl; pyrazinyl; thiazolyl; imidazolyl; or imidazolyl substituted with C 1-6 alkyl; Alk represents C 1-6 alkanaediyl; G represents O, S, or NR 3 , wherein R 3 represents hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkyloxycarbonyl, or Ar 2 --C 1-6 alkyl; Ar 2 represents phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, mercapto, amino, mono- and di(C 1-6 alkyl)amino, carboxyl, C 1-6 alkyloxycarbonyl, and C 1-6 alkylcarbonyl; and R 2 represents hydrogen; C 2-6 alkenyl; C 2-6 alkenyl substituted with Ar 2 ; C 3-6 alkynyl; Ar 1 ; C 1-6 alkyl; or C 1-6 alkyl substituted with Ar 1 , hydroxy, C 1-6 alkyloxy, carboxyl, C 1-6 alkyloxycarbonyl, Ar 2 -oxycarbonyl, or Ar 2 --C 1-6 alkyloxycarbonyl, wherein Ar 1 and Ar 2 are as defined above; m represents a number having a value of from 1 to 4; n represents a number having a value of from 1 to 2; and L represents hydrogen, C 1-6 alkylcarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyloxycarbonyl, Ar 2 --C 1-6 alkyloxycarbonyl, Ar 2 -carbonyl, Ar 2 -sulfonyl, C 3-6 cycloalkyl, C 2-6 alkenyl, C 2-6 alkenyl substituted with Ar 2 , C 1-12 alkyl, wherein Ar 2 is as defined above, or L represents a radical of the formula: --Alk--R.sup.4 (b- 1); --Alk--Y--R.sup.5 (b- 2); or --Alk--Z.sup.1 --(C═X)--Z.sup.2 --R.sup.6 (b- 3) wherein: Alk is as defined above; Y represents O, S, NR 8 , wherein R 8 represents hydrogen C 1-6 alkyl, C 1-6 alkylcarbonyl, or Ar 1 -carbonyl, wherein Ar 1 is as defined above; Z 1 and Z 2 each independently represent O, S, NR 9 , or a direct bond, wherein R 9 represents hydrogen or C 1-6 alkyl; X represents O, S, or NR 10 , wherein R 10 represents hydrogen, C 1-6 alkyl, or cyano; R 4 represents Het, Ar 2 , cyano, isocyanato, isothiocyanato, Ar 2 -sulfonyl, or halo, wherein Ar 2 is as defined above; R 5 represents hydrogen, Het, Ar 2 , C 1-6 alkyl, or C 1-6 alkyl substituted with halo or Ar 2 , wherein Ar 2 is as defined above; and R 6 represents hydrogen, Het, Ar 2 , C 1-6 alkyl, or C 1-6 alkyl substituted with halo or Ar 2 , wherein Ar 2 is as defined above; wherein Het represents: (i) an optionally substituted five- or six-membered heterocyclic ring containinged 1, 2, 3, or 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, provided that no more than two oxygens or sulfurs are present; or (ii) an optionally substituted five- or six-membered heterocyclic ring containing 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, being fused with an optionally substituted five- or six-membered ring through two ring carbon atoms or one ring carbon and one ring nitrogen atom, containing in the remainder of the fused ring only carbon atoms; or (iii) an optionally substituted five- or six-membered heterocyclic ring containing 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, being fused with an optionally substituted five- or six-membered heterocyclic ring through two ring carbon atoms or one ring carbon and one ring nitrogen atom, containing in the remainder of the fused ring 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen; wherein: Het may optionally be substituted with up to 4 substituents when Het is a monocyclic ring system, and wherein Het may optionally be substituted with up to 5 substituents when Het is a bicyclic ring system, said substitutents of Het being selected from the group consisting of a bivalent radical ═X; halo; isocyanato; isothiocyanato; nitro; cyano; trifluoromethyl; a radical of formula --A; a radical of formula --Y--A; or a radical of formula --Z 1 --C(═X)--Z 2 --A; wherein ═X is as defined above; A represents hydrogen, Ar 2 , or C 1-6 alkyl being optionally substituted with Ar 2 , C 1-6 alkyloxy, Ar 2 --0, hydroxy, or C 1-6 alkyloxycarbonyl; and Y, Z 1 , and Z 2 each have the meaning as defined above; provided that when in the radical --Z 1 --C(═X)--Z 2 --A, A is hydrogen and Z 1 is NR 9 , O, or X, then Z 2 is other than O or S.

Claim 2

A method of treating allergic diseases in warm-blooded animals suffering from the same, which method comprises the systemic administration to warm blooded animals of an effective anti-allergic amount of a compound of the formula: ##STR88## a pharmaceutically acceptable acid addition salt or a stereochemically isomeric form thereof, wherein: --A 1 ═A 2 --A 3 ═A 4 -- represents a bivalent radical of the formula: --N═CH--N═CH-- (a-5) or; --CH═N--CH═N-- (a-6), wherein one or two hydrogen atoms in said radicals (a-5) and (a-6) may, each independently from each other, be replaced by halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, or hydroxy; R represents hydrogen or C 1-6 alkyl; R 1 represents hydrogen, C 1-10 alkyl, C 3-6 cycloalkyl, Ar 1 , C 1-6 alkyl substituted with one or two Ar 1 radicals, or a radical of the formula --Alk--G--R 2 , wherein: Ar 1 represents phenyl; phenyl substituted with 1, 2 or 3 substitutents each independently selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, mercapto, amino, mono- and di(C 1-6 alkyl)amino, carboxyl, C 1-6 alkyloxycarbonyl, and C 1-6 alkylcarbonyl; thienyl; halothienyl; furanyl; C 1-6 alkyl substituted furanyl; pyridinyl; pyrimidinyl; pyrazinyl; thiazolyl; imidazolyl; or imidazolyl substituted with C 1-6 alkyl; Alk represents C 1-6 alkanaediyl; G represents O, S, or NR 3 , wherein R 3 represents hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkyloxycarbonyl, or Ar 2 --C 1-6 alkyl; Ar 2 represents phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, mercapto, amino, mono- and di(C 1-6 alkyl)amino, carboxyl, C 1-6 alkyloxycarbonyl, and C 1-6 alkylcarbonyl; and R 2 represents hydrogen; C 2-6 alkenyl; C 2-6 alkenyl substituted with Ar 2 ; C 3-6 alkynyl; Ar 1 ; C 1-6 alkyl; or C 1-6 alkyl substituted with Ar 1 , hydroxy, C 1-6 alkyloxy, carboxyl, C 1-6 alkyloxycarbonyl, Ar 2 -oxycarbonyl, or Ar 2 --C 1-6 alkyloxycarbonyl, wherein Ar 1 and Ar 2 are as defined above; m represents a number having a value of from 1 to 4; n represents a number having a value of from 1 to 2; and L represents hydrogen, C 1-6 alkylcarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyloxycarbonyl, Ar 2 --C 1-6 alkyloxycarbonyl, Ar 2 -carbonyl, Ar 2 -sulfonyl, C 3-6 cycloalkyl, C 2-6 alkenyl, C 2-6 alkenyl substituted with Ar 2 , C 1-12 alkyl, wherein Ar 2 is as defined above, or L represents a radical of the formula: --Alk--R.sup.4 (b- 1); --Alk--Y--R.sup.5 (b- 2); or --Alk--Z.sup.1 --(C═X)--Z.sup.2 --R.sup.6 (b- 3) wherein: Alk is as defined above; Y represents O, S, NR 8 , wherein R 8 represents hydrogen C 1-6 alkyl, C 1-6 alkylcarbonyl, or Ar 1 -carbonyl, wherein Ar 1 is as defined above; Z 1 and Z 2 each independently represent O, S, NR 9 , or a direct bond, wherein R 9 represents hydrogen or C 1-6 alkyl; X represents O, S, or NR 10 , wherein R 10 represents hydrogen, C 1-6 alkyl, or cyano; R 4 represents Het, Ar 2 , cyano, isocyanato, isothiocyanato, Ar 2 -sulfonyl, or halo, wherein Ar 2 is as defined above; R 5 represents hydrogen, Het, Ar 2 , C 1-6 alkyl, or C 1-6 alkyl substituted with halo or Ar 2 , wherein Ar 2 is as defined above; and R 6 represents hydrogen, Het, Ar 2 , C 1-6 alkyl, or C 1-6 alkyl substituted with halo or Ar 2 , wherein Ar 2 is as defined above; wherein Het represents: (i) an optionally substituted five- or six-membered heterocyclic ring containinged 1, 2, 3, or 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, provided that no more than two oxygens or sulfurs are present; or (ii) an optionally substituted five- or six-membered heterocyclic ring containing 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, being fused with an optionally substituted five- or six-membered ring through two ring carbon atoms or one ring carbon and one ring nitrogen atom, containing in the remainder of the fused ring only carbon atoms; or (iii) an optionally substituted five- or six-membered heterocyclic ring containing 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, being fused with an optionally substituted five- or six-membered heterocyclic ring through two ring carbon atoms or one ring carbon and one ring nitrogen atom, containing in the remainder of the fused ring 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen; wherein: Het may optionally be substituted with up to 4 substituents when Het is a monocyclic ring system, and wherein Het may optionally be substituted with up to 5 substituents when Het is a bicyclic ring system, said substitutents of Het being selected from the group consisting of a bivalent radical ═X; halo; isocyanato; isothiocyanato; nitro; cyano; trifluoromethyl; a radical of formula --A; a radical of formula --Y--A; or a radical of formula --Z 1 --C(═X)--Z 2 --A; wherein ═X is as defined above; A represents hydrogen, Ar 2 , or C 1-6 alkyl being optionally substituted with Ar 2 , C 1-6 alkyloxy, Ar 2 --0, hydroxy, or C 1-6 alkyloxycarbonyl; and Y, Z 1 , and Z 2 each have the meaning as defined above; provided that when in the radical --Z 1 --C(═X)--Z 2 --A, A is hydrogen and Z 1 is NR 9 , O, or X, then Z 2 is other than O or S.