公开(公告)号：US5973156A

公开(公告)日：1999-10-26

申请号：US68723

申请日：1998-05-13

Applicant: Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Tamara Ladduwahetty ,  Angus Murray MacLeod ,  Kevin John Merchant

Inventor： Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Tamara Ladduwahetty ,  Angus Murray MacLeod ,  Kevin John Merchant

IPC: C07D401/06 ,  C07D413/14 ,  C07D521/00 ,  C07D401/14 ,  A61K31/445 ,  C07D409/14

CPC classification number: C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D413/14

Abstract: A class of substituted piperidine and tetrahydropyridine derivatives, linked through the 4-position thereof via an alkylene chain to a fused bicyclic heteroaromatic moiety such as indolyl, and further substituted at the 1-position by an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl-alkyl, aryl-alkyl or heteroaryl-alkyl moiety, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.spsb..alpha. receptor subtype whilst processing at least a 10-fold selective affinity for the 5-HT.sub.1D.spsb..alpha. receptor subtype relative to the 5-HT.sub.1D.spsb..beta. 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-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.

Abstract translation: PCT No.PCT / GB96 / 02795 Sec。 371日期1998年5月13日 102（e）日期1998年5月13日PCT 1996年11月14日PCT PCT。 公开号WO97 / 19073 日期1997年5月29日一类取代的哌啶和四氢吡啶衍生物，其通过其4-位通过亚烷基链连接到稠合的双环杂芳族部分如吲哚基，并且在1位被进一步被任选取代的烷基，烯基， 炔基，环烷基 - 烷基，芳基 - 烷基或杂芳基 - 烷基部分是5-HT1样受体的选择性激动剂，其是人类5-HT1Dα受体亚型的有效激动剂，同时处理至少10倍的选择性亲和力 5-HT1Dα受体亚型相对于5-HT1Dβ亚型; 因此，它们可用于治疗和/或预防临床状况，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。

公开(公告)号：US5925638A

公开(公告)日：1999-07-20

申请号：US68072

申请日：1998-04-28

Applicant: Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Leslie Joseph Street

Inventor： Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Leslie Joseph Street

IPC: C07D521/00 ,  A61K31/495 ,  C07D403/14

CPC classification number: C07D231/12 ,  C07D233/56 ,  C07D249/08

Abstract: A class of 1-�3-(1H-indol-3-yl)propyl!-4-benzylpiperazine derivatives of formula I, substituted at the 5-position of the indole nucleus by a 1,2,4-triazol-4-yl moiety, and on the methylene linkage of the benzyl moiety by a range of substituted alkyl groups, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. 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-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists. ##STR1##

Abstract translation: PCT No.PCT / GB96 / 02682 Sec。 371日期：1998年4月28日 102（e）1998年4月28日PCT PCT 1996年11月4日PCT公布。 公开号WO97 / 17338 日期1997年5月15日将式I的1- [3-（1H-吲哚-3-基）丙基] -4-苄基哌嗪衍生物在吲哚核的5-位被1,2,4-三唑 三唑-4-基部分，以及苄基部分亚甲基连接的一系列取代的烷基是5-HT1样受体的选择性激动剂，是人5-HT1Dα受体亚型的有效激动剂，同时具有 对5-HT1Dα受体亚型相对于5-HT1Dβ亚型的至少10倍选择性亲和力; 因此，它们可用于治疗和/或预防临床状况，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。

公开(公告)号：US5807857A

公开(公告)日：1998-09-15

申请号：US737769

申请日：1996-11-15

Applicant: Jose Luis Castro Pineiro ,  Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Austin John Reeve ,  Graham Andrew Showell ,  Leslie Joseph Street ,  Victor Giulio Matassa

Inventor： Jose Luis Castro Pineiro ,  Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Austin John Reeve ,  Graham Andrew Showell ,  Leslie Joseph Street ,  Victor Giulio Matassa

IPC: C07D401/14 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/495 ,  A61P9/00 ,  A61P25/04 ,  A61P25/06 ,  A61P43/00 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D471/04 ,  C07D521/00

CPC classification number: C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D471/04

Abstract: 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.

Abstract translation: 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。