Substituted 2-oxy-3,5-dicyano-4aryl-6-aminopyridines and use thereof
View Patent ↗This invention relates to compounds of formula (I) in which the variable groups are as defined in the text and claims. A pharmaceutical composition and methods of using these materials in treatment of various conditions are also disclosed and claimed.
1. A compound of the formula (I)
in which
R 1 and R 2 independently of one another represent hydrogen, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or —NH—C(O)—R 7 , where the alkoxy radials for their part may be substituted by hydroxyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, or cyclopropyl, in which R 7 represents (C 1 -C 8 )-alkyl which may be substituted by hydroxyl or (C 1 -C 4 )-alkoxy; (C 3 -C 7 )-cycloalkyl; or (C 6 -C 10 )-aryl which may be substituted up to three times, independently of one another, by halogen, nitro, (C 1 -C 4 )-alkoxy-, carboxyl, (C 1 -C 4 )-alkoxycarbonyl or mono- or di-(C 1 -C 4 )-alkylamino, or
R 1 and R 2 are attached to adjacent phenyl ring atoms and are linked to represent a group —O—CH 2 —O—, —O—CH 2 —CH 2 —O—, or —O—CH 2 —CH 2 —CH 2 —O—,
R 3 represents hydrogen,
R 4 and R 5 independently of one another represent hydrogen, (C 1 -C 8 )-alkyl which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 6 -C 10 )-aryl or 5- to 6-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S, (C 3 -C 8 )-cycloalkyl which may be substituted by hydroxyl or (C 1 -C 8 )-alkyl, or
R 4 and R 5 together with the nitrogen atom to which they are attached form a 5- to 7-membered saturated or partially unsaturated heterocycle which may contain one or two further heteroatoms from the group consisting of N, O and S in the ring and which may be mono- to trisubstituted, independently of one another, by oxo, fluorine, chlorine, hydroxyl, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-alkoxy, and
R 6 represents (C 3 -C 7 )-cycloalkyl or (C 1 -C 8 )-alkyl, where alkyl may be substituted by (C 3 -C 7 )-cycloalkyl, hydroxyl, (C 1 -C 4 )-alkoxy, (C 2 -C 4 )-alkenyl, (C 6 -C 10 )-aryl or 5- to 10-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S; where aryl and heteroaryl for their part may be substituted by halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino, nitro, cyano or hydroxyl, provided that if R 6 represents (C 1 -C 4 )-alkyl, R 6 is substituted by (C 3 -C 7 )-cycloalkyl, hydroxyl, (C 1 -C 4 )-alkoxy, (C 2 -C 4 )-alkenyl, (C 6 -C 10 )-aryl or 5- to 10-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S; where aryl and heteroaryl for their part may be substituted by halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino, nitro, cyano or hydroxyl,
or a salt thereof.
2. A compound as claimed in claim 1 in which
R 1 and R 2 independently of one another represent hydrogen, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or —NH—C(O)—R 7 , where the alkoxy radials for their part may be substituted by hydroxyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, or cyclopropyl, wherein R 7 represents (C 1 -C 8 )-alkyl which may be substituted by hydroxyl or (C 1 -C 4 )-alkoxy; (C 3 -C 7 )-cycloalkyl; or (C 6 -C 10 )-aryl which may be substituted up to three times, independently of one another, by halogen, nitro, (C 1 -C 4 )-alkoxy-, carboxyl, (C 1 -C 4 )-alkoxycarbonyl or mono- or di-(C 1 -C 4 )-alkylamino, or
R 1 and R 2 are attached to adjacent phenyl ring atoms and are linked to represent a group —O—CH 2 —O—, —O—CH 2 —CH 2 —O—, or —O—CH 2 —CH 2 —CH 2 —O—,
R 3 represents hydrogen,
R 4 and R 5 independently of one another represent hydrogen; (C 1 -C 6 )-alkyl which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy or cyclopropyl, cyclopropyl; benzyl; or pyridylmethyl, or
R 4 and R 5 together with the nitrogen atom to which they are attached form a 5- to 7-membered saturated or partially unsaturated heterocycle which may contain a further heteroatom from the group consisting of N, O and S in the ring and which may be mono- to trisubstituted, independently of one another, by hydroxyl, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy, and
R 6 represents (C 3 -C 7 )-cycloalkyl or (C 1 -C 6 )-alkyl, which is substituted by (C 3 -C 7 )-cycloalkyl, hydroxyl, (C 1 -C 4 )-alkoxy, (C 2 -C 4 )-alkenyl, phenyl or 5- or 6-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S; where phenyl and heteroaryl for their part may be substituted by fluorine, chlorine, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino, nitro, cyano or hydroxyl; or unsubstituted (C 4 -C 6 )-alkyl
or a salt thereof.
3. A compound as claimed in claim 1 , in which
R 1 and R 2 independently of one another represent hydrogen, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or —NH—C(O)—CH 3 , where the alkoxy radicals for their part may be substituted by hydroxyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or cyclopropyl, or R 1 and R 2 are attached to adjacent phenyl ring atoms and are linked to represent a group —O—CH 2 —O—,
R 3 represents hydrogen,
R 4 represents hydrogen, methyl, ethyl, n-propyl, isopropyl, where the alkyl radicals for their part may be substituted by hydroxyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or cyclopropyl,
R 5 represents hydrogen or a methyl group, and
R 6 represents methyl or ethyl which are substituted by pyridyl, phenyl hydroxyl, methoxy, ethoxy, n-propoxy, isopropoxy, or n-butoxy, wherein said pyridyl and phenyl groups for their parts may be substituted by cyano, nitro, methyl, ethyl, propyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or amino, or
a salt thereof.
4. A compound of the formula (I)
in which
R 1 , R 2 and R 3 independently of one another represent (C 1 -C 8 )-alkyl which may be substituted up to three times, independently of one another, by hydroxyl, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 2 -C 4 )-alkenyl, (C 2 -C 4 )-alkynyl, halogen or (C 6 -C 10 )-aryloxy; (C 6 -C 10 )-aryl which may be substituted up to three times, independently of one another, by halogen, nitro, (C 1 -C 4 )-alkoxy, carboxyl, (C 1 -C 4 )-alkoxycarbonyl or mono- or di-(C 1 -C 4 )-alkylamino; (C 1 -C 8 )-alkoxy which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, (C 3 -C 6 )-cycloalkyl, (C 2 -C 4 )-alkenyl, (C 6 -C 10 )-aryl, 5- to 10-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S, (C 6 -C 10 )-aryloxy, halogen, cyano, (C 1 -C 4 )-alkoxycarbonyl, amino or mono- or di-(C 1 -C 4 )-alkylamino; hydrogen; hydroxyl; halogen; nitro; cyano; or —NH—C(O)—R 7 , in which R 7 represents (C 1 -C 8 )-alkyl which may be substituted by hydroxyl or (C 1 -C 4 )-alkoxy; or (C 3 -C 7 )-cycloalkyl or (C 6 -C 10 )-aryl which may be substituted up to three times, independently of one another, by halogen, nitro, (C 1 -C 4 )-alkoxy-, carboxyl, (C 1 -C 4 )-alkoxycarbonyl or mono- or di-(C 1 -C 4 )-alkylamino; provided that R 1 , R 2 , and R 3 cannot all be hydrogen; or
R 1 and R 2 are attached to adjacent phenyl ring atoms and, together with the two ring carbon atoms, form a 5- to 7-membered saturated or partially unsaturated heterocycle having one or two heteroatoms from the group consisting of N, O and S, which may be substituted by (C 1 -C 4 )-alkyl or oxo,
R 4 represents hydrogen; (C 1 -C 8 )-alkyl which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 6 -C 10 )-aryl or 5- to 6-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S; or (C 3 -C 8 )-cycloalkyl which may be substituted by hydroxyl or (C 1 -C 8 )-alkyl, and
R 5 represents (C 1 -C 8 )-alkyl which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 6 -C 10 )-aryl or 5- to 6-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S; or (C 3 -C 8 )-cycloalkyl which may be substituted by hydroxyl or (C 1 -C 8 )-alkyl, provided that, if R 4 and R 5 are the same, R 1 and R 2 are attached to adjacent phenyl ring atoms and, together with the two ring carbon atoms, form a 5- to 7-membered saturated or partially unsaturated heterocycle having one or two heteroatoms from the group consisting of N, O and S, which may be substituted by (C 1 -C 4 )-alkyl or oxo, or
R 4 and R 5 together with the nitrogen atom to which they are attached form a 5- to 7-membered saturated or partially unsaturated heterocycle which may contain one or two further heteroatoms from the group consisting of N, O and S in the ring and which may be mono- to trisubstituted, independently of one another, by oxo, fluorine, chlorine, hydroxyl, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-alkoxy, and
R 6 represents (C 3 -C 7 )-cycloalkyl or (C 1 -C 8 )-alkyl, where alkyl may be substituted by (C 3 -C 7 )-cycloalkyl, hydroxyl, (C 1 -C 4 )-alkoxy, (C 2 -C 4 )-alkenyl, (C 6 -C 10 )-aryl or 5- to 10-membered heteroaryl having up to three heteroatoms from the group consisting of N, O and S, where aryl and heteroaryl for their part may be substituted by halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino, nitro, cyano or hydroxyl,
or a salt thereof.
5. A pharmaceutical composition, comprising at least one compounds of the formula (1) as defined in claim 1 and a pharmaceutically acceptable carrier.