BALLARD, THERESA MARIA,FLOHR, ALEXANDER,ZBINDEN, KATRIN GROEBKE,PINARD, EMMANUEL,RYCKMANS, THOMAS,SCHAFFHAUSER, HERVE
申请号：
TW103129408
公开号：
TW201512197A
申请日:
2014.08.26
申请国别(地区):
TW
年份:
2015
代理人:
摘要：
The present invention relates to compounds of formula I wherein R1 halogen, lower alkyl, lower alkoxy, cyano, phenyl, C(O)NHCH3, C(O)NH2, lower alkyl substituted by halogen or is a five-membered heteroaryl group, optionally substituted by lower alkyl； Y1 is N or CH； Y2 is CH； and if Y1 is CH, Y1 and Y2 may form together with the C-atoms to which they are attached a ring, containing -CH=N-N(CH3)-, -CH=N-N(H)-； X is CH or N； R is (CH2)m-cycloalkyl, optionally substituted by hydroxy, lower alkoxy or lower alkyl, or is tetrahydropyran, optionally substituted by hydroxy, or is lower alkoxy, substituted by hydroxy, or is lower alkyl substituted by one or two hydroxy, or is (CH2)m-pyridinyl, optionally substituted by hydroxy, lower alkyl or lower alkyl substituted by hydroxy, or is L-phenyl, optionally substituted by hydroxy, lower alkyl or lower alkyl substituted by hydroxy, and L is a bond, -CH(CH2OH)- or -CH2CH(OH)-； n is 0, 1 or 2； m is 0 or 1； or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds of the present invention are muscarinic M1 receptor positive allosteric modulators (PAM) and hence are useful in the treatment of diseases, mediated by the muscarinic Ml receptor, such as Alzheimer's disease, cognitive impairment, schizophrenia, pain or sleep disorders.本發明係關於如下式之化合物，□其中：R1係鹵素、低碳數烷基、低碳數烷氧基、氰基、苯基、C(O)NHCH3、C(O)NH2、經鹵素取代之低碳數烷基或為視情況經低碳數烷基取代之五員雜芳基；Y1係N或CH；Y2係CH；且若Y1為CH，則Y1及Y2可與其等所附接之C原子一起形成包含-CH=N-N(CH3)-、-CH=N-N(H)-之環。X係CH或N；R係(CH2)m-環烷基，視情況經羥基、低碳數烷氧基或低碳數烷基取代，或為四氫吡喃，視情況經羥基取代，或為低碳數烷氧基，經羥基取代，或為經一個或兩個羥基取代之低碳數烷基，或為(CH2)m-吡啶基，視情況經羥基、低碳數烷基或經羥基取代之低碳數烷基取代，或為L-苯基，視情況經羥基、低碳數烷基或經羥基取代之低碳數烷基取代，及：L係鍵、-CH(CH2OH)-或-CH2CH(OH)-；n係0、1或2；m係0或1；或其醫藥上可接受之酸加成鹽、外消旋混合物或其相應的對映異構體及/或其光學異構體。本發明之化合物為毒蕈鹼M1受體正異位調節劑(PAM)且因此可用於治療由毒蕈鹼M1受體介導之疾病，諸如阿茲海默氏病(Alzheimer's disease)、認知損傷、精神分裂症、疼痛或睡眠障礙。
