Claims
- 1. A compound having the formula: ##STR94## a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, wherein:
- --A.sup.1 .dbd.A.sup.2 --A.sup.3 .dbd.A.sup.4 -- represents a bivalent radical having the formula
- --N.dbd.CH--CH.dbd.CH-- (a-2),
- --CH.dbd.N--CH.dbd.CH-- (a-3),
- --CH.dbd.CH--N.dbd.CH-- (a-4),
- --CH.dbd.CH--CH.dbd.N-- (a-5),
- --N.dbd.CH--N.dbd.CH-- (a-6),
- or
- --CH.dbd.N--CH.dbd.N-- (a-7),
- wherein one or two hydrogen atoms in said radicals (a-2) to (a-7) may each independently be replaced by halo, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, hydroxy or trifluoromethyl;
- R represents hydrogen or C.sub.1-4 alkyl;
- R.sup.1 represents hydrogen, C.sub.1-6 alkyl or hydroxyC.sub.1-6 alkyl;
- m is 1 or 2;
- D represents C.sub.1-4 alkanediyl;
- B represents NR.sup.2, CH.sub.2, O, S, SO or SO.sub.2 wherein R.sup.2 is hydrogen or C.sub.1-4 alkyl;
- n is 0, 1 or 2; and
- L represents hydrogen; C.sub.1-12 alkyl; C.sub.3-6 cycloalkyl; C.sub.3-6 alkenyl optionally substituted with aryl; C.sub.1-6 alkylcarbonyl; C.sub.1-6 alkyloxy-carbonyl; arylcarbonyl; arylC.sub.1-6 alkyloxycarbonyl; or a radical of the formula:
- --Alk--R.sup.3 (b- 1);
- --Alk--Y--R.sup.4 (b- 2);
- --Alk--Z.sup.1 --C(.dbd.X)--Z.sup.2 --R.sup.5 (b- 3);
- or
- --CH.sub.2 --CHOH--CH.sub.2 --O--R.sup.6 (b- 4);
- wherein
- R.sup.3 represents cyano, aryl or Het;
- R.sup.4 represents hydrogen, aryl, Het or C.sub.1-6 alkyl optionally substituted with aryl or Het;
- R.sup.5 represents hydrogen, aryl, Het or C.sub.1-6 alkyl optionally substituted with aryl or Het;
- R.sup.6 represents aryl or naphthalenyl;
- Y represents O, S, NR.sup.7 said R.sup.7 being hydrogen, C.sub.1-6 alkyl or C.sub.1-6 alkylcarbonyl;
- Z.sup.1 and Z.sup.2 each independently represent O, S, NR.sup.8 or a direct bond, said R.sup.8 being hydrogen or C.sub.1-6 alkyl; and
- X represent O, S or NR.sup.9 ; said R.sup.9 being hydrogen, C.sub.1-6 alkyl or cyano; each Alk independently is C.sub.1-6 alkanediyl;
- wherein each Het represents:
- (i) an optionally substituted five- or six-membered heterocyclic ring containing 1, 2, 3 or 4 heteroatoms selected from oxygen, sulfur and nitrogen, provided that no more than 2 oxygen and/or sulfur atoms are present;
- (ii) an optionally substituted five- or six-membered heterocyclic ring containing 1 or 2 heteroatoms selected from oxygen, sulfur and nitrogen, being fused with an optionally substituted five- or six-membered ring through 2 carbon atoms or 1 carbon and 1 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 oxygen, sulfur and nitrogen, being fused with an optionally substituted five- or six-membered heterocyclic ring through 2 carbon atoms or 1 carbon and 1 nitrogen atom, containing in the remainder of the fused ring 1 or 2 heteroatoms selected from oxygen, sulfur and nitrogen;
- wherein when Het is a monocyclic ring system Het may optionally be substituted with up to 4 substituents; and when Het is a bicyclic ring system Het may optionally be substituted with up to 6 substituents, said substituents being selected from halo, amino, mono- and di(C.sub.1-6 alkyl)amino, arylC.sub.1-6 alkylamino, nitro, cyano, aminocarbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylthio, C.sub.1-6 alkyloxy-carbonyl, C.sub.1-6 alkyloxyC.sub.1-6 alkyl, C.sub.1-6 alkyloxycarbonylC.sub.1-6 alkyl, hydroxy, mercapto, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyloxy, aryl, arylC.sub.1-6 alkyl, carboxyl, C.sub.1-6 alkylaminocarbonylamino, arylaminocarbonylamino, oxo or thio;
- wherein in the foregoing, each aryl is phenyl optionally substituted with 1, 2 or 3 substituents each independently selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylthio, mercapto, amino, mono- and di-(C.sub.1-6 alkyl)-amino, carboxyl, C.sub.1-6 alkyloxycarbonyl and C.sub.1-6 alkylcarbonyl.
- 2. A compound according to claim 1 wherein R represents hydrogen; m is 1; and R.sup.1 represents hydrogen or C.sub.1-6 alkyl.
- 3. A compound according to claim 1 wherein --A.sup.1 .dbd.A.sup.2 --A.sup.3 .dbd.A.sup.4 -- represents a bivalent radical having the formula --N.dbd.CH--CH.dbd.CH-- (a-2) wherein one hydrogen atom in said radical (a-2) may be replaced by halo, C.sub.1-6 alkyloxy or hydroxy;
- R represents hydrogen or methyl;
- R.sup.1 represents hydrogen, methyl or hydroxymethyl;
- m is 1 or 2;
- D represents CH.sub.2 ;
- B represents NH, NCH.sub.3, CH.sub.2, O, S or SO;
- n is 0, 1 or 2; and
- L represents hydrogen, C.sub.1-4 alkyl, cyclohexyl, propenyl, 3-phenylpropenyl, C.sub.1-4 alkyloxycarbonyl, or L represents a radical of the formula:
- --Alk--R.sup.3 (b- 1);
- --Alk--Y--R.sup.4 (b- 2);
- --Alk--Z.sup.1 --C(.dbd.X)--Z.sup.2 --R.sup.5 (b- 3);
- or
- --CH.sub.2 --CHOH--CH.sub.2 --O--R.sup.6 (b- 4);
- wherein:
- each Alk independently represents C.sub.1-4 alkanediyl;
- R.sup.3 represents phenyl, hydroxyphenyl, C.sub.1-4 alkyloxyphenyl, 3,4,5-trimethoxyphenyl, pyridinyl, thienyl, 2-methyl-5-oxazolyl, 4,5-dihydro-4-ethyl-5-oxo-1H-tetrazolyl, 2,3-dihydro-6-methyl-3-oxopyridazinyl, 2-oxo-3-oxazolidinyl, 2-(amino or methylamino)-3,4-dihydro-3,6-dimethyl-4-oxo-5-pyrimidinyl, 2-oxo-2H-1-benzopyranyl, 3,7-dihydro-1,3-dimethyl-2,6-dioxo-1H-purin-7-yl, 2,3-dihydro-2-oxo-1-benzimidazolyl,
- or R.sup.3 represents a radical of the formula: ##STR95## wherein G.sup.2 represents --CH.dbd.CH--CH.dbd.CH--, --(CH.sub.2).sub.4 --, --S--(CH.sub.2).sub.2, --S--(CH.sub.2).sub.3 --, --S--CH.dbd.CH--, --N(CH.sub.2).sub.3, --N.dbd.C(CH.sub.3)--CH.sub.2 --, --N(CH.sub.3)--N.dbd.C(CH.sub.3)--; --N(CH.sub.3)--CH.dbd.CH-- or CH.dbd.C(CH.sub.3)--O--;
- Y represents NH, O or S;
- R.sup.4 represents hydrogen, C.sub.1-4 alkyl, halophenyl, pyridinyl, halopyridinyl, pyrimidinyl, 1,4-dihydro-2,4-dioxo-3(2H)-pyrimidinyl, 1,4-dihydro-4-oxopyrimidinyl, pyridazinyl, halo-pyridazinyl, 1-methylimidazolyl, thiazolyl, 2-amino-1,3,4-thiadiazolyl, 6-purinyl or imidazo[4,5-c]-pyridinyl;
- Z.sup.1 and Z.sup.2 each independently represent O, NH or a direct bond;
- X represents O or S;
- R.sup.5 represents hydrogen, C.sub.1-4 alkyl, aminophenyl, C.sub.1-4 alkyl-phenyl, pyridinyl, aminopyridinyl, aminopyrazinyl, 1-methylpyrrolyl, furanyl or 1-methylindolyl; and
- R.sup.6 represents phenyl.
- 4. A compound according to claim 3 wherein:
- --A.sup.1 .dbd.A.sup.2 --A.sup.3 .dbd.A.sup.4 -- represents a bivalent radical having the formula --N.dbd.CH--CH.dbd.CH-- (a-2);
- R represents hydrogen;
- the oxazolyl moiety has the formula: ##STR96## B represents NH, S or CH.sub.2 ; n is 1; and
- L represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, propenyl, 3-phenylpropenyl or a radical of the formula:
- --Alk--R.sup.3 (b- 1);
- --Alk--Y--R.sup.4 (b- 2);
- --Alk--NH--C(.dbd.O)--R.sup.5-a (b- 3-a);
- or
- --Alk--C(.dbd.O)--Z.sup.2 --R.sup.5-b (b- 3-b);
- wherein:
- each Alk independently represents C.sub.1-3 alkanediyl;
- R.sup.3 represents phenyl, 4-methoxy-phenyl, 4-hydroxyphenyl, pyridinyl, thienyl, 4,5-dihydro-4-ethyl-5-oxo-1H-tetrazolyl, 2-oxo-2H-1-benzopyranyl, 2-(amino- or methylamino)-3,4-dihydro-3,6-dimethyl-4-oxo-5-pyrimidinyl, 6-purinyl,
- or R.sup.3 represents a radical of the formula: ##STR97## wherein G.sup.2 represents --CH.dbd.CH--CH.dbd.CH--, --(CH.sub.2).sub.4 --, --S--(CH.sub.2).sub.2.sub.--, --S--(CH.sub.2).sub.3 --, --S--CH.dbd.CH-- or --N(CH.sub.3)--N.dbd.C(CH.sub.3)--CH.sub.2 --;
- Y represents NH or O;
- R.sup.4 represents pyrimidinyl, 5-amino-1,3,4-thiadiazolyl, pyridazinyl, imidazo[4,5-c]pyridinyl or 1,4-dihydro-4-oxo-2-pyrimidinyl;
- R.sup.5-a represents aminopyrazinyl or furanyl;
- Z.sup.2 represents O; and
- R.sup.5-b represents hydrogen.
- 5. A compound according to claim 4 wherein said compound is a member selected from the group consisting of:
- 3-[(2-methyl-5-oxazolyl)methyl]-N-(4-piperidinyl)-3H-imidazo[4,5-b]pyridin-2-amine hemihydrate;
- N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-3-[(2-methyl-5-oxazolyl)methyl]-3H-imidazo[4,5-b]pyridin-2-amine;
- 3-[(2-methyl-5-oxazolyl)methyl]-N-[1-[2-(2-thienyl)ethyl]-4-piperidinyl]-3H-imidazo[4,5-b]pyridin-2-amine;
- 2-[[2-[4-[[3-[(2-methyl-5-oxazolyl)methyl]-3H-imidazo[4,5-b]-pyridin-2-yl]amino]-1-piperidinyl]ethyl]amino]-4(1H)-pyrimidinone (E)-2-butenedioate (2:5); and
- 9-[(2-methyl-5-oxazolyl)methyl9 -N-(1-methyl-4-piperidinyl)-9H-purin-8-amine.
- 6. An antiallergic composition comprising a pharmaceutically acceptable carrier and as active ingredient an effective anti-allergic amount of a compound as claimed in claim 1.
- 7. An antiallergic composition comprising a pharmaceutically acceptable carrier and as active ingredient an effective anti-allergic amount of a compound as claimed in claim 2.
- 8. An antiallergic composition comprising a pharmaceutically acceptable carrier and as active ingredient an effective anti-allergic amount of a compound as claimed in claim 3.
- 9. An antiallergic composition comprising a pharmaceutically acceptable carrier and as active ingredient an effective anti-allergic amount of a compound as claimed in claim 4.
- 10. An antiallergic composition comprising a pharmaceutically acceptable carrier and as active ingredient an effective anti-allergic amount of a compound as claimed in claim 5.
- 11. A method of treating warm-blooded animals suffering from allergic diseases comprising administering to said warm-blooded animals an effective antiallergic amount of a compound as claimed in claim 1.
- 12. A method of treating warm-blooded animals suffering from allergic diseases comprising administering to said warm-blooded animals an effective antiallergic amount of a compound as claimed in claim 2.
- 13. A method of treating warm-blooded animals suffering from allergic diseases comprising administering to said warm-blooded animals an effective antiallergic amount of a compound as claimed in claim 3.
- 14. A method of treating warm-blooded animals suffering from allergic diseases comprising administering to said warm-blooded animals an effective antiallergic amount of a compound as claimed in claim 4.
- 15. A method of treating warm-blooded animals suffering from allergic diseases comprising administering to said warm-blooded animals an effective antiallergic amount of a compound as claimed in claim 5.
CROSS-REFERENCE TO RELATED APPLICATION
This application is a division of copending application Ser. No. 723,862, filed Jul. 1, 1991, now U.S. Pat. No. 5,217,980, which in turn was a continuation-in-part of application Ser. No. 554,326, filed Jul. 19, 1990, now abandoned.
US Referenced Citations (9)
Number |
Name |
Date |
Kind |
4556660 |
Janssens et al. |
Dec 1985 |
|
4588772 |
Bohmer et al. |
May 1986 |
|
4634704 |
Janssens et al. |
Jan 1987 |
|
4695569 |
Janssens et al. |
Sep 1987 |
|
4695575 |
Janssens et al. |
Sep 1987 |
|
4835161 |
Janssens et al. |
May 1989 |
|
4897401 |
Janssens et al. |
Jan 1990 |
|
4988689 |
Janssens et al. |
Jan 1991 |
|
5041448 |
Janssens et al. |
Aug 1991 |
|
Divisions (1)
|
Number |
Date |
Country |
Parent |
723862 |
Jul 1991 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
554326 |
Jul 1990 |
|