5-HT3 receptor antagonists
AssigneeTakeda Pharmaceutical Company Limited
InventorsStephen Hitchcock, Holger Monenschein, Holly Reichard, Huikai Sun, Todd Macklin, Maria Hopkins, Shota Kikuchi
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Abstract
The present invention provides 5-HT3 receptor antagonists of Formula (I): which are useful for the treatment of diseases treatable by inhibition of 5-HT3 receptor such as emesis, pain, drug addiction, neurodegenerative and psychiatric disorders, and GI disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
Claims14
A method of treating in a subject at least one disease, disorder, or condition treatable by inhibition of the 5-HT3 receptor, wherein the at least one disease, disorder, or condition treatable by inhibition of the 5-HT3 receptor is select from the group consisting of:
- emesis, migraine, substance abuse and addiction, anxiety, depression, eating disorders, schizophrenia, Parkinson's disease, cognitive dysfunction associated with Parkinson's disease, Huntington's Chorea, pre-senile dementia, Alzheimer's disease, pain, dyspepsia, gastroesophageal reflux disease, irritable bowel syndrome, atherosclerosis, tendomyopathies, and fibromyalgia, the method comprising
- (a) administering to the subject a compound of Formula (I):
- wherein:
- Z is O or NRa where Ra is hydrogen or C1-6 alkyl;
- R1 is a ring of the formula (a)-(h) below:
- R2 is hydrogen, C1-6 alkyl, or C1-6 haloalkyl;
- each R3 is independently hydrogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, or halo and can be present on any carbon atom in the rings;
- R4 is pyridinyl or pyrazolyl optionally substituted with one or two substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy, cyano, or halo;
- all of X1, X2, X3, and X4 are CR5;
- each R5 is independently hydrogen, C1-6 alkyl, halo, hydroxy, or cyano provided that at least one of R5 is hydrogen;
- and
- X5 is CR6 where R6 is hydrogen, C1-6 alkyl, or halo;
- or a pharmaceutically acceptable salt thereof or N-oxide thereof.
A method of inhibiting the 5-HT3 receptor in a subject, the method comprising
- (a) administering to the subject a compound of Formula (I):
- wherein:
- Z is O or NRa where Ra is hydrogen or C1-6 alkyl;
- R1 is a ring of the formula (a)-(h) below:
- R2 is hydrogen, C1-6 alkyl, or C1-6 haloalkyl;
- each R3 is independently hydrogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, or halo and can be present on any carbon atom in the rings;
- R4 is pyridinyl or pyrazolyl optionally substituted with one or two substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy, cyano, or halo;
- all of X1, X2, X3, and X4 are CR5;
- each R5 is independently hydrogen, C1-6 alkyl, halo, hydroxy, or cyano provided that at least one of R5 is hydrogen;
- and
- X5 is CR6 where R6 is hydrogen, C1-6 alkyl, or halo;
- or a pharmaceutically acceptable salt thereof or N-oxide thereof.
Dependencies are inferred from the claim text.