TRPA1 antagonists
View Patent ↗Compounds of formula (I) wherein R 1 , R 2 , R 3 , m, and Y are defined in the specification are TRPA1 antagonists. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
1. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof
wherein
R 1 represent substituents of the phenyl group and each R 1 is independently alkyl, alkenyl, alkynyl, —CN, halogen, —OR a , —NO 2 , —N(R a )(R b ), —N(R b )C(O)R a , —N(R b )S(O) 2 R 1a , —N(R b )C(O)OR a , —N(R b )C(O)N(R a )(R b ), —N(R b )S(O) 2 N(R a )(R b ), —C(O)R a , —C(O)OR a , —C(O)N(R a )(R b ), —SR a , —SF 5 , —S(O)R 1a , —S(O) 2 R 1a , —S(O) 2 OR 1a , —S(O) 2 N(R a )(R b ), —(CR d R e ) q —CN, haloalkyl, —(CR d R e ) q —OR a , —(CR d R e ) q —NO 2 , —(CR d R e ) q —N(R a )(R b ), —(CR d R e ) q —N(R b )C(O)R a , —(CR d R e ) q —N(R b )S(O) 2 R 1a , —(CR d R e ) q —N(R b )C(O)OR a , —(CR d R e ) q —N(R b )C(O)N(R a )(R b ), —(CR d R e ) q —N(R b )S(O) 2 N(R a )(R b ), —(CR d R e ) q —C(O)R a , —(CR d R e )—C(O)OR a , —(CR d R e ) q —C(O)N(R a )(R b ), —(CR d R e ) q —S(O) 2 R 1a , —(CR d R e ) q —S(O) 2 OR 1a , or —(CR d R e ) q —S(O) 2 N(R a )(R b );
R 2 is C 1-6 alkyl or haloalkyl;
R 3 is C 2-6 alkyl;
Y is —OH, —O(C 1-4 alkyl), —N(R f )(R g ), —N(R f )C(O)R g , —N(R f )S(O) 2 R g , or —N(R f )C(O)N(R f )(R g );
R a and R b , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
R 1a , at each occurrence, is independently alkyl or haloalkyl;
R d and R e , at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl; R f and R g , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
m is 1, 2, 3, 4, or 5; and
q is 1, 2, 3, or 4;
with the proviso that the compound is not (Z)-4-(4-chlorophenyl)-3-methylbut-3-en-2-oxime or (E)-4-(4-chlorophenyl)-3-methylbut-3-en-2-oxime; and a pharmaceutically acceptable carrier.
2. The pharmaceutical composition of claim 1 further comprising one or more second pain reducing agent.
3. A compound that is
(1E,3E)-1-(4-fluorophenyl)-2-methylpent-1-en-3-one O-methyloxime;
(1E,3E)-1-(2-fluorophenyl)-2-methylpent-1-en-3-one oxime;
(1E,3E)-1-(4-fluorophenyl)-2-methylhex-1-en-3-one oxime;
(1E,3E)-1-(4-fluorophenyl)-2,4,4-trimethylpent-1-en-3-one oxime;
(1E,3E)-1-(4-fluorophenyl)-2-methylhept-1-en-3-one oxime;
(1E,3Z)-1-(4-fluorophenyl)-2,4-dimethylpent-1-en-3-one oxime;
(1E,3E)-1-(4-fluorophenyl)-2,4-dimethylpent-1-en-3-one oxime;
(1E,3E)-1-(4-fluorophenyl)hex-1-en-3-one oxime;
(1E,3E)-1-(3,4-difluorophenyl)-2-methylpent-1-en-3-one oxime; or
(1E,3E)-2-methyl-1-(3,4,5-trifluorophenyl)pent-1-en-3-one oxime;
or a pharmaceutically acceptable salt thereof.
4. (1E,3E)-1-(4-fluorophenyl)-2-methylpent-1-en-3-one oxime or a pharmaceutically acceptable salt thereof.