TRPA1 antagonists
View Patent ↗Compounds of formula (I) wherein R 1 , R 2 , R 3 , and Y are defined in the description are TRPA1 antagonists. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
1. A compound having formula (I) or a pharmaceutically acceptable salt thereof
wherein
R 1 is pyridin-3-yl, or pyridin-4-yl; each of which is substituted with 1, 2, 3, 4 substituents as represented by R j ;
R j , at each occurrence, 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 ) q —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 , and —(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 ethyl
Y is —OR f ,
R 1a , at each occurrence, is independently alkyl or haloalkyl;
R a and R b , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
R d and R e , at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl;
R f , at each occurrence, is independently, alkyl, or haloalkyl; and
q is 1, 2, 3, or 4;
with the proviso that the compound is not
1-(pyridin-3-yl)pent-1-en-3-one oxime;
1-(pyridin-4-yl)pent-1-en-3-one oxime;
1-(5-chloropyridin-3-yl)pent-1-en-3-one oxime; or
1-(3-chloropyridin-4-yl)pent-1-en-3-one oxime.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 2 is C 1-6 alkyl.
3. A pharmaceutical composition comprising therapeutically effective amount of one or more compounds of formula (I)
wherein
R 1 is pyridin-3-yl, or pyridin-4-yl; each of which is substituted with 1, 2, 3, 4 substituents as represented by R j ;
R j , at each occurrence, 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 ) q —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 , and —(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 ethyl;
Y is —OR f ;
R 1a , at each occurrence, is independently alkyl or haloalkyl;
R a and R b , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
R d and R e , at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl;
R f , at each occurrence, is independently, alkyl, or haloalkyl; and
q is 1, 2, 3, or 4;
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
4. The pharmaceutical composition of claim 3 further comprising one or more pain reducing agent.