发明名称 Bis-quaternary ammonium salts and methods for modulating neuronal nicotinic acetylcholine receptors
摘要 Provided are bis-quaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders.
申请公布号 US9540327(B2) 申请公布日期 2017.01.10
申请号 US200712160713 申请日期 2007.01.16
申请人 University of Kentucky Research Foundation 发明人 Crooks Peter;Dwoskin Linda P.;Zheng Guangrong;Sumithran Sangeetha
分类号 C07D213/24;A61K31/4406;A61K31/444;C07D401/14 主分类号 C07D213/24
代理机构 Crowell & Moring LLP 代理人 Crowell & Moring LLP
主权项 1. A bis-quaternary ammonium compound of Formula (I) X2⊖⊕R2—R—R1⊕⊖X1  (I) wherein X1⊖ and X2⊖ are each independently an organic or inorganic anion; wherein R is selected from the group consisting of —(CH2)12—; wherein R1 and R2 are each six membered rings as shown in formula (IIA), wherein each ring of R1 and R2 has one quaternized nitrogen atom, and the ring atoms from R1 and R2 which are attached to R cannot both be nitrogen atoms: wherein one of A1, A3, and A4, is nitrogen and the remaining A1, A2, A3, A4, A5, and A6 are carbon; wherein R5, R7, R9, R11, and R13 are each independently selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, halo, cyano, nitro, SOY1, SO2Y1, SO2OY1 or SO2NHY1, where Y1 is selected from hydrogen, lower alkyl, alkenyl, alkynyl or aryl, and where Y1 is not hydrogen in SOY1 and if Y1 is alkenyl or alkynyl, the site of unsaturation is not conjugated with a heteroatom; COY2, where Y2 is selected from hydrogen, alkyl, cycloalkyl, alkoxy, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, arylalkenyl, arylalkynyl, or heterocyclic, and where if Y2 comprises alkenyl or alkynyl, the site of unsaturation is not conjugated with the carbonyl group; OY3, where Y3 is selected from hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, arylalkenyl, arylalkynyl, acyl, alkylsulfonyl, or heterocyclic, where if Y3 comprises alkenyl or alkynyl, the site of unsaturation is not conjugated with the oxygen; NY4Y5, where Y4 and Y5 are each independently selected from hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, arylalkenyl, arylalkynyl, acyl, alkylsulfonyl, arylsulfonyl, or heterocyclic, where if Y4 or Y5 comprises alkenyl or alkynyl, the site of unsaturation is not conjugated with the nitrogen; SY6, where Y6 is selected from hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, arylalkenyl, arylalkynyl, or heterocyclic, and where if Y6 comprises alkenyl or alkynyl, the site of unsaturation is not conjugated with the sulfur; and any of R5, R7, R9, R11, or R13 attached to the quaternized nitrogen is independently a straight or branched alkyl group of four carbons or fewer.
地址 Lexington KY US