Patent NZ-623918-A (NZ)
Title: Azole derivative
Inventor: KUWADA TAKESHI
IPC: C07D498/08
Filed: 2012-10-25
Abstract: Disclosed are 2-(imidazolyl/1H-1,2,4-triazolyl/1,3-oxazolyl/1,3-thiazolyl/1H-pyrazolyl/2,5-dioxo-2,5-dihydro-1H-pyrrolyl)acetamide derivatives and analogues as represented by the general formula (I), or a pharmaceutically acceptable salt thereof, wherein: R1 represents a hydrogen atom, optionally substituted alkyl, cycloalkyl, or 4- to 8-membered saturated heterocycle; R2 represents a hydrogen atom or alkyl; R3 represents optionally substituted aryl or heteroaryl; R4 and R5 which may be the same or different each represent a hydrogen atom, optionally substituted alkyl, cycloalkyl, or an optionally substituted 4- to 8-membered saturated or unsaturated heterocycle containing one or more nitrogen, oxygen or sulfur atoms in the ring; or R4 and R5 together with the adjoining nitrogen atom, form a 4- to 8-membered saturated or unsaturated heterocycle optionally containing one or more nitrogen, oxygen or sulfur atoms in the ring in addition to the adjoining nitrogen atom, 2-oxa-6-azaspiro[3.3]hept-6-yl or 7-oxa-2-azaspiro[3.5]non-2-yl, wherein the 4- to 8-membered saturated or unsaturated heterocycle is optionally substituted; X1 is a single bond, -CO-, or -CONRx1; X2 is a single bond, alkylene -O-alkylene-; wherein iii) when X1 is a single bond or -CO-, X2 represents alkylene- or -O-alkylene-; and iv) when X1 is -CONRx1-, X2 represents a single bond; the ring A represents a benzene ring, a 6-membered aromatic heterocycle, a 4- to 8-membered saturated or partially unsaturated heterocycle containing one or two nitrogen atoms, or a cycloalkane, wherein the benzene ring, the 6-membered aromatic heterocycle and the 4- to 8-membered saturated or unsaturated heterocycle is optionally substituted, and wherein the remaining substituents are as defined herein. Representative compounds include 2-[2-(3-chlorophenyl)-4-{ 4-[2-(piperidin-1-yl)ethyl]phenyl} -1H-imidazol-1-yl]-N-(propan-2-yl)acetamide; 2-[2-(3-chlorophenyl)-4-{ 4-[2-(morpholin-4-yl)ethyl]phenyl} -1H-imidazol-1-yl]-N-(propan-2-yl)acetamide; 2-[2-(3-chlorophenyl)-4-(4-{ 2-[3-(hydroxymethyl)pyrrolidin-1-yl]ethyl} phenyl)-1H-imidazol-1-yl]-N-(propan-2-yl)acetamide; 2-[2-(4-fluoro-3-methoxyphenyl)-4-{ 4-[2-(3-hydroxy-8-azabicyclo[3.2.1]oct-8-yl)ethyl]phenyl} -1H-imidazol-1-yl]-N-(propan-2-yl)acetamide; 2-[5-(3-chlorophenyl)-3-{ 4-[2-(morpholin-4-yl)ethyl]phenyl } -1H-1,2,4-triazol-1-yl]-N-(propan-2-yl)acetamide; N-tert-butyl-2-[5-(3-methoxyphenyl)-3-{ 5-[2-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)ethyl]pyridin-2-yl} -1H-1,2,4-triazol-1-yl]acetamide; 2-[5-(3-chlorophenyl)-3-{ 4-[2-(morpholin-4-yl)ethyl]phenyl} -2-oxo-2,3-dihydro-1H-imidazol-1-yl]-N-(propan-2-yl)acetamide; 2-[4-(3-chlorophenyl)-2-{ 4-[2-(piperidin-1-yl)ethyl]phenyl} -1,3-oxazol-5-yl]-N-(propan-2-yl)acetamide; 2-[5-(3-chlorophenyl)-2-{ 4-[2-(piperidin-1-yl)ethyl]phenyl} -1,3-thiazol-4-yl]-N-(propan-2-yl)acetamide; 2-[3-(3-chlorophenyl)-1-{ 4-[2-(piperidin-1-yl)ethyl]phenyl} -1H-pyrazol-4-yl]-N-(propan-2-yl)acetamide; 2-[4-(3-chlorophenyl)-1-{ 4-[2-(morpholin-4-yl)ethyl]phenyl} -2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-N-(propan-2-yl)acetamide; N-tert-butyl-2-[4-(3-methoxyphenyl)-1-{ 4-[2-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)ethyl]phenyl} -5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]acetamide; and 2-[2-(3-chlorophenyl)-4-{ 4-[2-(2-oxa-6-azaspiro[3.3]hept-6-yl)ethyl]phenyl} -1H-imidazol-1-yl]-N-(propan-2-yl)acetamide. Also disclosed is a pharmaceutical composition comprising the azole derivative or pharmaceutically acceptable salt thereof as defined above as an active ingredient, for treating or preventing mood disorder, anxiety disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease, Huntington’s chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia.