1H-4(5)-cyclo-substituted imidazole derivatives as histamine H.sub.3
receptor agents
    1.
    发明授权
    1H-4(5)-cyclo-substituted imidazole derivatives as histamine H.sub.3 receptor agents 失效
    1H-4(5) - 环取代的咪唑衍生物作为组胺H3受体剂

    公开(公告)号:US6072057A

    公开(公告)日:2000-06-06

    申请号:US973121

    申请日:1998-02-11

    CPC分类号: C07D233/64 C07D413/04

    摘要: The present invention is directed to 1H-4(5)-substituted imidazole derivates of formula (I), wherein A is (a); (b); or (c) ##STR1## wherein R.sub.1 is lower alkyl or lower alkoxy;R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.7 and R.sub.8 are each independently hydrogen or lower alkyl;R.sub.6 is hydrogen, lower alkyl or lower alkoxy and R.sub.5 and R.sub.6 can be joined to form a 4, 5 or 6 membered ring.The compounds of formula (I) have H.sub.3 histamine receptor agonist activity. The pharmaceutically acceptable salts, and individual stereoisomers of compounds of formula (I) above, as well as mixtures thereof, are also contemplated as falling within the scope of the present invention. The present invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with an effective amount of a compound of formula (1). The present invention also provides a method of treating conditions in which activation of histamine H.sub.3 receptors may be of therapeutic importance such as allergy, inflammation, cardio or cerebrovascular disease, gastrointestinal disorders and CNS disorders involving psychiatric disorders.

    摘要翻译: PCT No.PCT / US96 / 09498 Sec。 371日期1998年2月11日 102(e)1998年2月11日PCT PCT 1996年6月6日PCT公布。 公开号WO96 / 40126 日期:1996年12月19日本发明涉及式(I)的1H-4(5) - 取代咪唑衍生物,其中A为(a); (b); 或(c)其中R1是低级烷基或低级烷氧基; R2,R3,R4,R5,R7和R8各自独立地为氢或低级烷基; R6是氢,低级烷基或低级烷氧基,R5和R6可以连接形成4,5或6元环。 式(I)化合物具有H3组胺受体激动剂活性。 上述式(I)化合物的药学上可接受的盐和单独的立体异构体以及它们的混合物也被认为落入本发明的范围内。 本发明还提供药物组合物,其包含药学上可接受的载体与有效量的式(1)化合物的组合。 本发明还提供了治疗其中组胺H3受体的活化可能具有治疗重要性的病症的方法,例如过敏,炎症,心脑血管疾病,胃肠道疾病和涉及精神疾病的CNS障碍。

    2-(1H-4(5)-imidazoyl) cyclopropyl derivatives
    2.
    发明授权
    2-(1H-4(5)-imidazoyl) cyclopropyl derivatives 失效
    2-(1H-4(5) - 咪唑基)环丙基衍生物

    公开(公告)号:US6008240A

    公开(公告)日:1999-12-28

    申请号:US991030

    申请日:1997-12-15

    摘要: The present invention provides compounds having H.sub.3 histamine receptor antagonist activity of the general formula: ##STR1## R.sub.2 is a hydrogen or a methyl or ethyl group; R.sub.3 is a hydrogen or a methyl or ethyl group;n is 1, 2, 2, 3, 4, 5, or 6; andR.sub.1 is selected from the group consisting of (a) C.sub.3 to C.sub.8 cycloalkyl; (b) phenyl or substituted phenyl; (c) alkyl; (d) heterocyclic; (e) decahydronapthalene; and (f) octahydroindene;with the provisos thatwhen X is H, A can be --CH.sub.2 CH.sub.2 --,--COCH.sub.2 --,--CONH--,--CON(CH.sub.3), CH.dbd.CH, --c.ident.c--,--CH.sub.2 --NH--, --CH.sub.2 --N(CH.sub.3)--,--CH(OH)CH.sub.2 --,--NH--CH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --,--CH.sub.2 O--,--CH.sub.2 S--, and --NHCOO--;when X is NH.sub.2, NH(CH.sub.3), N(CH.sub.3).sub.2, OH, OCH.sub.3, CH.sub.3, SH, and SCH.sub.3 ; A can be --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.dbd.CH--; --COCH.sub.2, --CH.sub.2 CH.sub.2 --,--CH(OH)CH.sub.2, or --C.ident.C--; andwhen R.sub.1 and X taken together denote a 5,6 or 6,6 saturated bicyclic ring structure X NH, O, or S and the pharmaceutically acceptable salts, and individual stereoisomers of compounds of structural formula (1.0) above. This invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with an effective amount of a compound of the above formula and a method of treating conditions in which antagonism of histamine H.sub.3 receptors may be of therapeutic importance.

    摘要翻译: 本发明提供了具有以下通式的H3组胺受体拮抗剂活性的化合物:R2是氢或甲基或乙基; R3是氢或甲基或乙基; n为1,2,3,4,5或6; 并且R 1选自(a)C 3至C 8环烷基; (b)苯基或取代的苯基; (c)烷基; (d)杂环; (e)十氢萘; 和(f)八氢茚; 条件是当X是H时,A可以是-CH 2 CH 2 - , - COCH 2 - , - CONH - , - CON(CH 3),CH = CH,-c = c - , - CH 2 -NH-, - CH 2 -N (CH 3) - , - CH(OH)CH 2 - , - NH-CH 2 - , - N(CH 3)-CH 2 - , - CH 2 O - , - CH 2 S-和-NHCOO-; 当X是NH 2时,NH(CH 3),N(CH 3)2,OH,OCH 3,CH 3,SH和SCH 3; A可以是-NHCO - , - N(CH 3)-CO - , - NHCH 2 - , - N(CH 3)-CH 2 - , - CH = CH-; -COCH 2,-CH 2 CH 2 - , - CH(OH)CH 2或-C = C-; 当R1和X一起表示5,6或6,6饱和双环结构X NH,O或S时,以及上述结构式(1.0)化合物的药学上可接受的盐和单独的立体异构体。 本发明还提供药物组合物,其包含药学上可接受的载体与有效量的上述化合物的组合以及治疗其中组胺H3受体的拮抗作用具有治疗意义的病症的方法。

    2-(1H-4(5)-imidazoyl) cyclopropyl compounds
    3.
    发明授权
    2-(1H-4(5)-imidazoyl) cyclopropyl compounds 失效
    2-(1H-4(5) - 咪唑基)环丙基化合物

    公开(公告)号:US5990317A

    公开(公告)日:1999-11-23

    申请号:US945915

    申请日:1998-02-06

    CPC分类号: C07D233/64

    摘要: The present invention provides compounds having H.sub.3 histamine receptor antagonist activity of formula (1.0) wherein R.sub.2 is a hydrogen or a methyl or ethyl group; R.sub.3 is a hydrogen or a methyl or ethyl group; n is 0, 1, 2, 3, 4, 5, or 6; and R.sub.1 is selected from the group consisting of (a) C.sub.3 to C.sub.8 cycloalkyl; (b) phenyl or substituted pneyly; (c) alkyl; (d) heterocyclic; (e) decahydronaphthalene; and (f) octahydroindene; with the proviso that when X is H, A can be --CH.sub.2 CH.sub.2, --COCH.sub.2 --CON(CH.sub.3)--, --CH.dbd.CH--, .alpha., --CH.sub.2 --NH--, --CH.sub.3 --N(CH.sub.3)--, --CH(OH)CH.sub.2 --, --NH--CH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.sub.2 O--, --CH.sub.2 S--, and --NHCOO--; when X is NH.sub.2, HN(CH.sub.3), N(CH.sub.3).sub.2, OH, OCH.sub.3, CH.sub.3, SH and SCH.sub.3 ; A can be --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.dbd.XH--, --COCH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH( )H)CH.sub.2 --, or .beta.; and when R.sub.1 and X taken together denote a 5,6 or 6,6 saturated bicyclic ring structure, X can be NH, O, or S. The pharmaceutically acceptable salts, hydrates, and individual stereoisomers of compounds of structural formula (1.0), as well as mixtures thereof, are also contemplated as falling within the scope of the present invention. The invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with an effective amount of a compound of said formula and a method of treating conditions in which antagonism of histamine H.sub.3 receptors may be of therapeutic importance.

    摘要翻译: PCT No.PCT / US96 / 07833 Sec。 371日期1998年2月6日 102(e)1998年2月6日PCT PCT 1996年5月29日PCT公布。 公开号WO96 / 38141 日期:1996年12月5日本发明提供具有式(1.0)的H3组胺受体拮抗剂活性的化合物,其中R 2为氢或甲基或乙基; R3是氢或甲基或乙基; n是0,1,2,3,4,5或6; 并且R 1选自(a)C 3至C 8环烷基; (b)苯基或取代的吡啶基; (c)烷基; (d)杂环; (e)十氢萘; 和(f)八氢茚; 条件是当X是H时,A可以是-CH 2 CH 2,-COCH 2 -CON(CH 3) - , - CH = CH-,α,-CH 2 -NH-, - CH 3 -N(CH 3) - , - CH OH)CH 2 - , - NH-CH 2 - , - N(CH 3)-CH 2 - , - CH 2 O - , - CH 2 S-和-NHCOO-; 当X是NH 2时,HN(CH 3),N(CH 3)2,OH,OCH 3,CH 3,SH和SCH 3; A可以是-NHCO - , - N(CH 3)-CO - , - NHCH 2 - , - N(CH 3)-CH 2 - , - CH = XH-,-COCH 2 - , - CH 2 CH 2 - , - CH - 或beta 当R1和X一起表示5,6或6,6饱和双环结构时,X可以是NH,O或S.结构式(1.0)化合物的药学上可接受的盐,水合物和单个立体异构体, 以及它们的混合物也被认为落入本发明的范围内。 本发明还提供药物组合物,其包含药学上可接受的载体与有效量的所述式的化合物和治疗其中组胺H3受体拮抗作用具有治疗意义的病症的方法。

    2-(4-imidazoyl) cyclopropyl derivatives
    4.
    发明授权
    2-(4-imidazoyl) cyclopropyl derivatives 失效
    2-(4-咪唑基)环丙基衍生物

    公开(公告)号:US5652258A

    公开(公告)日:1997-07-29

    申请号:US453359

    申请日:1995-05-30

    CPC分类号: C07D233/64

    摘要: The present invention provides compounds having H.sub.3 histamine receptor antagonist activity of the general formula: ##STR1## where X is H, A is --CH.sub.2 CH.sub.2 --, --COCH.sub.2 --, --CONH--, --CON(CH.sub.3)--, --CH.dbd.CH--, --C.tbd.C--, --CH.sub.2 --NH--, --CH.sub.2 --NCH.sub.3 --, --CH(OH)CH.sub.2 --, --NH--CH.sub.2 --, --N(CH.sub.3) --CH.sub.2 --, --NHSO.sub.2 --, --CH.sub.2 O--, --CH.sub.2 S--, CH.sub.2 SO.sub.2 --, or --CH.sub.2 S(O)--;R.sub.2 is a hydrogen or a methyl or ethyl group;R.sub.3 is a hydrogen or a methyl or ethyl group;n is 0, 1, 2, 3, 4, 5, or 6; andR.sub.1 is selected from the group consisting of (a) C.sub.3 to C.sub.8 cycloalkyl; (b) H; (c) phenyl or substituted phenyl; (d) alkyl; (e) heterocyclic; and (f) bicyclic alkyl; andwhenX is NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OH, OCH.sub.3, NHR.sub.4, OR.sub.4, SH, SR.sub.4, or SO.sub.2 R.sub.4 ; A is --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --NHSO.sub.2 --, --CH.dbd.CH--, --CH.dbd.CHF--, --COCH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH(OH)CH.sub.2 --, or --C.tbd.C--;R.sub.2 is a hydrogen or a methyl or ethyl group;R.sub.3 is a hydrogen or a methyl or ethyl group;n is 0, 1, 2, 3, 4, 5, or 6;R.sub.1 is selected from the group consisting of (a) C.sub.3 to C.sub.8 cycloalkyl; (b) H; (c) phenyl or substituted phenyl; (d) alkyl; (e) heterocyclic; and (f) bicyclic alkyl andR.sub.4 is designated to mean that X is contained within a ring such as octahydroindole.

    摘要翻译: 本发明提供具有以下通式的H3组胺受体拮抗剂活性的化合物:其中X是H,A是-CH 2 CH 2 - , - COCH 2 - , - CONH - , - CON(CH 3) - , - CH = CH - , - C 3-6(C 1 -C 3) - , - CH 2 -NH-,-CH 2 -NCH 3 - , - CH(OH)CH 2 - , - NH-CH 2 - CH 2 O - , - CH 2 S - ,CH 2 SO 2 - 或-CH 2 S(O) - ; R2是氢或甲基或乙基; R3是氢或甲基或乙基; n是0,1,2,3,4,5或6; 并且R 1选自(a)C 3至C 8环烷基; (b)H; (c)苯基或取代的苯基; (d)烷基; (e)杂环; 和(f)双环烷基; 并且当X是NH 2,NHCH 3,N(CH 3)2,OH,OCH 3,NHR 4,OR 4,SH,SR 4或SO 2 R 4时; A是-NHCO-,-N(CH 3)-CO - , - NHCH 2 - , - N(CH 3)-CH 2 - , - NHSO 2 - , - CH = CH-, - CH = CHF-,-COCH 2 - , - CH 2 CH 2 - , - CH(OH)CH 2 - 或-C 3位C; R2是氢或甲基或乙基; R3是氢或甲基或乙基; n是0,1,2,3,4,5或6; R 1选自(a)C 3至C 8环烷基; (b)H; (c)苯基或取代的苯基; (d)烷基; (e)杂环; 和(f)双环烷基和R4表示X包含在环如八氢吲哚中。

    1H-4(5)-substituted imidazole derivatives
    5.
    发明授权
    1H-4(5)-substituted imidazole derivatives 失效
    1H-4(5) - 取代的咪唑衍生物

    公开(公告)号:US6166060A

    公开(公告)日:2000-12-26

    申请号:US948801

    申请日:1997-10-10

    摘要: The present invention provides, in its principal aspect, compounds of the general formula: ##STR1## when A is --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.dbd.CH--, --COCH.sub.2 --, CH.sub.2 CH.sub.2 --, --CH(OH)CH.sub.2 -- or --C.tbd.C--;X can be H, CH.sub.3, NH.sub.2, NH(CH.sub.3),N(CH.sub.3).sub.2, OH, OCH.sub.3, SH,R.sub.2 is hydrogen or a methyl or ethyl group;R.sub.3 is hydrogen or a methyl or ethyl group;n is 0, 1, 2, 3, 4, 5 or 6;R.sub.1 is selected from the group consisting of (a) alkyl; (b) C.sub.3 to C.sub.8 cycloalkyl; (c) phenyl or substituted phenyl; (d) heteroocyclic; and (f) decahydronaphthalene or octahydroindane; andWhen R.sub.1 and X taken together denote a 5, 6 or 6, 6 saturated bicyclic ring structure, X can be NH, O, S, SO.sub.2,When X is constrained in a 5, 6 or 6, 6, saturated bicyclic ring structure, then for example, when X.dbd.NH, R.sub.1 and X taken together mean an octahydroindole ring structure directly attached to A.

    摘要翻译: 本发明在其主要方面提供了以下通式的化合物:当A是-NHCO-,-N(CH 3)-CO-,-NHCH 2 - , - N(CH 3)-CH 2 - , - CH = CH- ,-COCH 2 - ,CH 2 CH 2 - , - CH(OH)CH 2 - 或-C X可以是H,CH 3,NH 2,NH(CH 3),N(CH 3)2,OH,OCH 3,SH,R ​​2是氢或甲基或乙基; R3是氢或甲基或乙基; n为0,1,2,3,4,5或6; R1选自(a)烷基; (b)C3至C8环烷基; (c)苯基或取代的苯基; (d)杂环; 和(f)十氢萘或八氢化茚; 当R 1和X一起表示5,6或6,6个饱和双环结构时,X可以是NH,O,S,SO 2,当X被约束在5,6或6,6饱和双环结构中时 ,那么例如当X = NH时,R 1和X一起表示直接连接到A的八氢吲哚环结构。

    1H-4(5)-substituted imidazole derivatives
    6.
    发明授权
    1H-4(5)-substituted imidazole derivatives 失效
    1H-4(5) - 取代的咪唑衍生物

    公开(公告)号:US06448282B1

    公开(公告)日:2002-09-10

    申请号:US09631189

    申请日:2000-08-02

    IPC分类号: A61K31417

    摘要: The present invention provides, in its principal aspect, compounds of the general formula: where A is —NHCO—, —N(CH3)—CO—, —NHCH2—, —N(CH3)—CH2—, —COCH2—, —CH2CH2—, or —CH(OH)CH2—, X is H, CH3, NH2, NH(CH3), N(CH3)2, OCH3, or SH; R2 is hydrogen or a methyl or ethyl group; R3 is hydrogen or a methyl or ehtyl group; n is 0, 1, 2, 3, 4, 5 or 6; R1 is selected from the group consisting of (a) alkyl; (b) C3 to C8 cycloalkyl; (c) phenyl or substituted phenyl; (d) heterocyclic; (e) decahydronaphthalene and (f) octahydroindane; or R1 and X may be taken together to denote a 5,6 or 6,6 saturated bicycle ring structure. The compounds of the present invention have H3 histamine receptor antagonist activity. This invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with an effective amount of a compound of formula 1.0. The present invention also provides a method of treating conditions in which antagonism of histamine H3 receptors may of therapeutic importance.

    摘要翻译: 本发明主要由下列通式表示:其中A是-NHCO - , - N(CH 3)-CO - , - NHCH 2 - , - N(CH 3)-CH 2 - , - COCH 2 - , - CH 2 CH 2 - 或-CH(OH)CH 2 - ,X是H,CH 3,NH 2,NH(CH 3),N(CH 3)2,OCH 3或SH; R 2是氢或甲基或乙基; R 3是氢或 甲基或庚基; n为0,1,2,3,4,5或6; R 1选自(a)烷基; (b)C3至C8环烷基; (c)苯基或取代的苯基; (d)杂环; (e)十氢萘和(f)八氢化茚; 或R 1和X可以一起表示5,6或6,6饱和自由基环结构。本发明化合物具有H3组胺受体拮抗剂活性。 本发明还提供药物组合物,其包含药学上可接受的载体与有效量的式1.0化合物的组合。 本发明还提供了治疗组胺H 3受体的拮抗作用具有治疗意义的病症的方法。

    Perforating and fracturing system
    8.
    发明授权
    Perforating and fracturing system 有权
    穿孔和压裂系统

    公开(公告)号:US08365824B2

    公开(公告)日:2013-02-05

    申请号:US12503577

    申请日:2009-07-15

    申请人: James G. Phillips

    发明人: James G. Phillips

    IPC分类号: E21B43/11 E21B43/1185

    摘要: A system for use in borehole completion is provided and includes a perforating sub, a firing sub having a first port and an interior and including a firing assembly disposable within the interior and operably coupled to the perforating sub and a drilling fluid barrier, which is formed with a second port and is displaceable toward a position at which the first and second ports align to form a fluid path through the interior that is sufficiently pressurizable to actuate the firing assembly, a drop plug selectively engageable with the drilling fluid barrier to enable displacement thereof to the position in response to applied pressures and an isolation sub, into which the drop plug is receivable following disengagement thereof from the drilling fluid barrier.

    摘要翻译: 提供了一种用于钻孔完井的系统,包括一个穿孔子,一个具有第一端口和内部的点火组件,其包括一个在内部中一次性的可操作地连接到穿孔子和一个钻井液屏障的点火组件, 具有第二端口并且可朝着第一和第二端口对准的位置移动以形成穿过内部的流体路径,该流体路径被足够加压以致致动点火组件;液滴塞可以选择性地与钻井液屏障接合以使其能够移位 到达所施加的压力和隔离子的位置,在其脱离钻井液屏障之后,液滴塞可以被接收到该位置。