Piperazine, piperidine and tetrahydropyridine derivative of
indol-3-alkyl as 5-HT.sub.1D-.alpha. agonists
    6.
    发明授权
    Piperazine, piperidine and tetrahydropyridine derivative of indol-3-alkyl as 5-HT.sub.1D-.alpha. agonists 失效
    吲哚-3-烷基的哌嗪,哌啶和四氢吡啶衍生物作为5-HT1D-α激动剂

    公开(公告)号:US5807857A

    公开(公告)日:1998-09-15

    申请号:US737769

    申请日:1996-11-15

    摘要: Compounds of formula (I), or a salt or prodrug thereof, wherein Z represents an optionally substituted five-membered heteroaromatic ring selected from furan, thiophene, pyrrole, oxazole, thiazole, isoxazole, isothiazole, imidazole, pyrazole, oxadiazole, thiadiazole, triazole and tetrazole; E represents a chemical bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms; Q represents a straight or branched alkylene chain containing from 1 to 6 carbon atoms, optionally substituted in any position by a hydroxy group; T represents nitrogen or CH; U represents nitrogen or C--R.sup.2 ; V represents oxygen, sulphur or N--R.sup.3 ; --F--G-- represents --CH2--N--, --CH2--CH-- or --CH.dbd.C--; R.sup.1 represents C.sub.3-6 alkenyl, C.sub.3-6 alkynyl, aryl(C.sub.1-6)alkyl or heteroaryl(C.sub.1-6)alkyl, any of which groups may be optionally substituted; and R.sup.2 and R.sup.3 independently represent hydrogen or C.sub.1-6 alkyl are selective agonists of 5-HT1D receptors, being potent agonists of the human 5-HT1Dalpha receptor subtype, while possessing at least a 10-fold selective affinity for the 5-HT1Dalpha receptor subtype, relative to the 5-HT1Dbeta subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT1D receptors is indicated, while eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT1D receptor agonists.

    摘要翻译: PCT No.PCT / GB95 / 01129 Sec。 371日期1996年11月15日 102(e)日期1996年11月15日PCT提交1995年5月18日PCT公布。 公开号WO95 / 32196 (I)式(I)化合物或其盐或前药,其中Z表示选自呋喃,噻吩,吡咯,恶唑,噻唑,异恶唑的任选取代的五元杂芳环 ,异噻唑,咪唑,吡唑,恶二唑,噻二唑,三唑和四唑; E表示化学键或含有1至4个碳原子的直链或支链亚烷基链; Q表示任选被羟基取代的含有1至6个碳原子的直链或支链亚烷基链; T表示氮或CH; U表示氮或C-R2; V表示氧,硫或N-R3; -F-G-表示-CH 2 -N,-CH 2 -CH-或-CH = C-; R 1表示C 3-6烯基,C 3-6炔基,芳基(C 1-6)烷基或杂芳基(C 1-6)烷基,其中任何基团可以任选被取代; 并且R 2和R 3独立地表示氢或C 1-6烷基是5-HT1D受体的选择性激动剂,它是人5-HT1Dalpha受体亚型的有效激动剂,同时对5-HT1Dalpha受体亚型具有至少10倍的选择性亲和力, 相对于5-HT1Dbeta亚型; 因此,它们可用于治疗和/或预防临床症状,特别是偏头痛和相关疾病,其中指出5-HT1D受体的亚型选择性激动剂,同时引起较少的副作用,特别是不利的心血管事件,比 与非亚型选择性5-HT1D受体激动剂相关的那些。