US 6,720,328 B2 · Non-imidazole compounds

Abstract

Disclosed are novel compounds of the formula In Formula I, M1 is carbon, M2, M3 and M4 are carbon or nitrogen and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of Formula I. Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I. Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I in combination with a H1 receptor antagonist.

A compound of the formula:

or a pharmaceutically acceptable salt or solvate thereof, wherein:
(1) R1 is selected from:
(a) aryl;
(b) heteroaryl;
(c) heterocycloalkyl
(d) alkyl;
(e) cycloalkyl;
or
(f) alkylaryl;
wherein said R1 groups are optionally substituted with 1 to 4 substituents independently selected from:
(1) halogen;
(2) hydroxyl;
(3) lower alkoxy;
(4) —CE3;
(5) CF3O—;
(6) —NR4R5;
(7) phenyl;
(8) —NO2,
(9) —CO2R4;
(10) —CON(R4)2 wherein each R4 is the same or different;
(11) —S(O)mN(R20)2 wherein each R20 is the same or different H or alkyl group;
(12) —CN;
or
(13) alkyl;
or
(2) R1 and X taken together form a group selected from:
wherein {circle around (N)} represents a nitrogen atom located at one of the 4 non-fused positions of the ring;
(3) X is selected from:
═C(O), ═C(NOR3), ═C(NNR4R5),
(4) M1 is carbon;
(5) M2is N;
(6) one of M3 and M4 is C and the other is N;
(7) Y is selected from:
is —CH2—, ═C(O), ═C(NOR20) (wherein R20 is as defined above), or ═C(S);
(8) Z is a C1-C6 alkyl group;
(9) R2 is a five or six-membered heteroaryl ring, said six-membered heteroaryl ring comprising 1 or 2 nitrogen atoms with the remaining ring atoms being carbon, and said five-membered heteroaryl ring containing 1 or 2 heteroatoms selected from:
nitrogen, oxygen, or sulfur with the remaining ring atoms being carbon;
said five or six membered heteroaryl rings being optionally substituted with 1 to 3 substituents independently selected from:
halogen, hydroxyl, lower alkyl, lower alkoxy, —CF3, CF3O—, —NR4R5, phenyl, —NO2, —CO2R4, —CON(R4)2 wherein each R4 is the same or different, —CH2NR4R5, —(N)C(NR4R5)2, or —CN;
(10) R3 is selected from:
(a) hydrogen;
(b) C1-C6 alkyl;
(c) aryl;
(d) heteroaryl;
(e) heterocycloalkyl;
(f) arylalkyl;
(g) —(CH2)e—C(O)N(R4)2 wherein each R4 is the same or different,
(h) —(CH2)e—C(O)OR4;
(i) —(CH2)e—C(O)R30 wherein R30 is a heterocycloalkyl group, or
(j) —CF3;
or
(k) —CH2CF3;
wherein said aryl, heteroaryl, heterocycloalkyl, and the aryl portion of said arylalkyl are optionally substituted with 1 to 3 substituents selected from:
halogen, —OH, —OCF3, —CF3, —CN, —N(R45)2, —CO2R45, or —C(O)N(R45)2, wherein each R45 is independently selected from:
H, alkyl, alkylaryl, or alkylaryl wherein said aryl moiety is substituted with 1 to 3 substituents independently selected from —CF3, —OH, halogen, alkyl, —NO2, or —CN;
(11) R4 is selected from:
hydrogen, C1-C6 alkyl, aryl, alkylaryl, said aryl and alkylaryl groups being optionally substituted with 1 to 3 substituents selected from:
halogen, —CF3, —OCF3, —OH, —N(R45)2, —CO2R45, —C(O)N(R45)2, or —CN;
wherein R45 is as defined above;
(12) R5 is selected from:
hydrogen, C1-C6 alkyl, —C(O)R4, —C(O)2R4, or —C(O)N(R4)2 wherein each R4 is independently selected, and R4 is as defined above;
(13) or R4 and R5 taken together with the nitrogen atom to which they are bound forms a five or six membered heterocycloalkyl ring;
(14) R6 is selected from:
alkyl, aryl, alkylaryl, halogen, hydroxyl, lower alkoxy, —CF3, CF3O—, —NR4R5, —NO2, —CO2R4, —CON(R4)2 wherein each R4 is the same or different, or —CN;
(15) R12 is selected from:
alkyl, hydroxyl, alkoxy, or fluoro;
(16) R13 is selected from:
alkyl, hydroxyl, alkoxy, or fluoro;
(17) a is 0 to 2;
(18) b is 0 to 2;
(19) c is 0 to 2;
(20) e is 0 to 5;
(21) m is 1 or 2;
(22) n is 2, and
(23) p is 2.

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Non-imidazole compounds

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Non-imidazole compounds

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Abstract

Claims43