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    Diazine derivatives
    1.
    发明授权
    Diazine derivatives 失效
    二嗪衍生物

    公开(公告)号：US5252567A

    公开(公告)日：1993-10-12

    申请号：US629502

    申请日：1990-12-18

    申请人： Stuart D. Mills ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin

    发明人： Stuart D. Mills ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin

    IPC分类号： A61K31/505 ,  A61K31/535 ,  A61P9/00 ,  C07D239/48 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04 ,  C07D491/10 ,  A61K31/55 ,  C07D247/02

    CPC分类号： C07D239/48 ,  C07D401/04 ,  C07D403/04 ,  C07D491/10

    摘要： This invention concerns compounds of the formula I: ##STR1## wherein R.sup.1 is (1-10C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-4C)-alkyl, phenyl or phenyl(1-4C)alkyl, the phenyl moiety of the latter two optionally bearing one or more substituents; R.sup.2 is hydrogen, (1-4C)alkyl, amino or (1-4C)alkylamino; R.sup.6 is (1-4C)alkyl, amino or (1-4C)alkylamino; Q is a group of formula II, in which case R.sup.3 and R.sup.4 are independently hydrogen, (1-4C)alkyl, phenyl or benzyl the phenyl moiety of the latter two optionally bearing one or two substituents; R.sup.5 is hydrogen, (1-4C)alkyl or (2-4C)alkenyl; A and B are independently ethylene or trimethylene; Z is a direct bond between A and B, or an oxy, thio, carbonyl, methylene, ethylenedioxymethylene, ethylidene, or isopropylidene link, or Z is a group of the formula .dbd.N.M in which M is hydrogen, (1-6C)alkyl, phenyl or benzyl, the phenyl moiety of the latter two optionally bearing one or two substituents; or Q represents a saturated 9- or 10-membered bicyclic amino group, which is unsubstituted or is substituted by one or two substituents; and Y is a physiologically acceptable anion.The invention also includes certain closely related anhydro-base derivatives which, like the compounds of formula I, possess beneficial effects on the cardiovascular system (and in particular beneficial effects modulated via the sino-atrial node). Also included are pharmaceutical compositions containing compounds of formula I (or a related anhydro-base) as active ingredient, and processes for the manufacture of the various novel compounds.

    1,4-Dihydropyridines substituted by 3-aryloxy-2-hydroxypropyl amino moiety in the 4-phenyl group
    2.
    发明授权
    1,4-Dihydropyridines substituted by 3-aryloxy-2-hydroxypropyl amino moiety in the 4-phenyl group 失效
    在4-苯基中被3-芳氧基-2-羟丙基氨基部分取代的1,4-二氢吡啶类

    公开(公告)号：US4873254A

    公开(公告)日：1989-10-10

    申请号：US828363

    申请日：1986-02-11

    申请人： Rodney B. Hargreaves ,  Bernard J. McLoughlin ,  Stuart D. Mills

    发明人： Rodney B. Hargreaves ,  Bernard J. McLoughlin ,  Stuart D. Mills

    IPC分类号： A61K31/4427 ,  A61K31/443 ,  A61K31/455 ,  A61K31/535 ,  A61P3/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P25/02 ,  C07D209/48 ,  C07D211/82 ,  C07D211/90 ,  C07D319/00 ,  C07D401/12 ,  C07D405/12 ,  C07D413/04 ,  C07D417/12 ,  C07D521/00

    CPC分类号： C07D209/48 ,  C07C205/44 ,  C07D211/90 ,  C07D401/12 ,  C07D405/12 ,  C07D417/12

    摘要： A dihydropyridine of the formula: ##STR1## wherein R.sup.1 and R.sup.2 each is alkyl, alkenyl or alkoxyalkyl, wherein R.sup.3 and R.sup.4 each is alkyl, wherein benzene ring A is unsubstituted or bears one or more additional substituents selected from halogeno, cyano, nitro, trifluoromethyl and alkyl, or bears the substituent .dbd.N--O--N.dbd. attached to the 5- and 6-positions, wherein Ar is as defined in the specification, wherein p is 0 or 1, wherein X is --O-- or --S--, and wherein Y is straight-or branched-chain alkylene or alkenylene each of 2 to 12 carbon atoms which may optionally be interrupted by one or two groups selected from oxygen, sulphur, imino, substituted imino, phenylene, substituted phenylene, pyridylene, cycloalkylene, 1,4-piperazinediyl, 1,4-piperidinediyl and amido groups; or an acid-addition salt thereof, processes for their manufacture and pharmaceutical compositions containing them. The compounds possess either beta-adrenergic blocking or calcium ion slow channel blocking properties, or both such properties, and may be used in the treatment of hypertension.

    摘要翻译： 下式的二氢吡啶：其中R 1和R 2各自是烷基，烯基或烷氧基烷基，其中R 3和R 4各自是烷基，其中苯环A是未取代的或带有一个或多个选自卤素，氰基，硝基， 三氟甲基和烷基，或带有与5-和6-位连接的取代基= NON =，其中Ar如说明书中所定义，其中p为0或1，其中X为-O-或-S-，其中 Y是2至12个碳原子的直链或支链亚烷基或亚烯基，其可以任选地被选自氧，硫，亚氨基，取代的亚氨基，亚苯基，取代的亚苯基，亚吡啶基，亚环烷基， 4-哌嗪二基，1,4-哌啶二基和酰氨基; 或其酸加成盐，其制备方法和含有它们的药物组合物。 该化合物具有β-肾上腺素能阻断或钙离子缓慢通道阻断性质，或这两种特性，可用于治疗高血压。

    Amino 1,3,5-triazine derivatives as agents for cardiovascular system
    6.
    发明授权
    Amino 1,3,5-triazine derivatives as agents for cardiovascular system 失效
    氨基1,3,5-三嗪衍生物作为心血管系统的药剂

    公开(公告)号：US5574037A

    公开(公告)日：1996-11-12

    申请号：US488458

    申请日：1995-06-07

    申请人： Stuart D. Mills ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin

    发明人： Stuart D. Mills ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin

    IPC分类号： A61K31/53 ,  A61P9/06 ,  A61P9/12 ,  C07D251/18 ,  C07D251/22 ,  C07D251/54 ,  C07D251/70 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04 ,  C07D251/40 ,  C07D251/48

    CPC分类号： C07D401/04 ,  C07D251/18 ,  C07D403/04

    摘要： This invention concerns novel compounds of the formula I: ##STR1## in which P is a group of formula II or a group of formula III; R.sup.1 is alkyl, cycloalkyl, cycloalkylalkyl, phenyl or phenylalkyl; R.sup.2 is hydrogen, alkyl, amino or alkylamino; R.sup.3 and R.sup.4 are independently hydrogen, alkyl, phenyl or benzyl; R.sup.6 is alkyl, amino or alkylamino; C and D are independently ethylene or trimethylene; Z is a direct bond between C and D, or an oxy, thio, carbonyl, methylene, ethylenedioxymethylene, ethylidene, or isopropylidene link, or Z is a group of the formula .dbd.N.R.sup.5 in which R.sup.5 is alkyl, phenyl or benzyl; R8 is hydrogen, cycloalkylalkyl, alkyl, alkenyl, alkynyl or phenylalkyl; or R8 is a alkylene or alkenylene linked to the nitrogen atom of the group Q.A.N--, either of which linking groups may optionally bear a alkyl, phenyl or phenylalkyl substituent and either of which linking groups thereby completes a ring including two adjacent carbon atoms of ring Q, any carbon atoms in A and the adjacent nitrogen atom of the group --A.N--; A is a direct bond to the group --N(R8)-- or is alkylene; Q is a phenyl or pyridyl moiety; Y is a physiologically acceptable anion; and wherein any one or more of said phenyl, benzene or pyridyl moieties may optionally be unsubstituted or bear one or more selected substituents.The invention also includes certain closely related anhydo-base derivatives which, like the compounds of formula I, possess beneficial effects on the cardiovascular system (and in particular beneficial effects modulated via the sino-atrial node). Also included are pharmaceutical compositions containing compounds of formula I (or a related anhydro-base) as active ingredient, and processes for the manufacture of the various novel compounds.

    摘要翻译： 本发明涉及式I的新型化合物：其中P是式II基团或式III基团; R1是烷基，环烷基，环烷基烷基，苯基或苯基烷基; R2是氢，烷基，氨基或烷基氨基; R3和R4独立地是氢，烷基，苯基或苄基; R6是烷基，氨基或烷基氨基; C和D独立地是亚乙基或三亚甲基; Z是C和D之间的直接键，或氧，硫，羰基，亚甲基，亚乙二氧基亚甲基，亚乙基或异亚丙基连接基，或Z是式= N.R5的基团，其中R 5是烷基，苯基或苄基; R8是氢，环烷基烷基，烷基，烯基，炔基或苯基烷基; 或者R8是连接到基团QAN-的氮原子的亚烷基或亚烯基，其中任一个连接基团可以任选地具有烷基，苯基或苯基烷基取代基，并且其中任一个连接基由此完成包含环的两个相邻碳原子的环 Q，A中的任何碳原子和-AN-相邻的氮原子; A是与-N（R 8）基团的直接键合 - 或者是亚烷基; Q是苯基或吡啶基部分; Y是生理上可接受的阴离子; 并且其中所述苯基，苯或吡啶基部分中的任何一个或多个可以任选地是未被取代的或承载一个或多个选定的取代基。 本发明还包括某些密切相关的脱水基衍生物，其与式I化合物一样对心血管系统具有有益作用（尤其是通过窦房结调节的有益作用）。 还包括含有式I化合物（或相关脱氢碱）作为活性成分的药物组合物，以及制备各种新型化合物的方法。

    Amino-1,3,5-triazines and their anhydrobase derivatives as agents for cardiovascular system
    7.
    发明授权
    Amino-1,3,5-triazines and their anhydrobase derivatives as agents for cardiovascular system 失效
    氨基-1,3,5-三嗪及其脱氢基衍生物作为心血管系统的药剂

    公开(公告)号：US5332737A

    公开(公告)日：1994-07-26

    申请号：US621677

    申请日：1990-12-03

    申请人： Stuart D. Mills ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin

    发明人： Stuart D. Mills ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin

    IPC分类号： A61K31/53 ,  A61P9/06 ,  A61P9/12 ,  C07D251/18 ,  C07D251/22 ,  C07D251/54 ,  C07D251/70 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04 ,  C07D251/40 ,  C07D251/48

    CPC分类号： C07D401/04 ,  C07D251/18 ,  C07D403/04

    摘要： This invention concerns novel compounds of the formula I: ##STR1## in which P is a group of formula II or a group of formula III; R.sup.1 is alkyl, cycloalkyl, cycloalkylalkyl, phenyl or phenylalkyl; R.sup.2 is hydrogen, alkyl, amino or alkylamino; R.sup.3 and R.sup.4 are independently hydrogen, alkyl, phenyl or benzyl; R.sup.6 is alkyl amino or alkylamino; C and D are independently ethylene or trimethylene; Z is a direct bond between C and D, or an oxy, thio, carbonyl, methylene, ethylenedioxymethylene, ethylidene, or isopropylidene link, or Z is a group of the formula .dbd.N.R.sup.5 in which R.sup.5 is alkyl, phenyl or benzyl; R8 is hydrogen, cycloalkylalkyl, alkyl, alkenyl, alkynyl or phenylalkyl; or R8 is a alkylene or alkenylene linked to the nitrogen atom of the group Q.A.N--, either of which linking groups may optionally bear a alkyl, phenyl or phenylalkyl substituent and either of which linking groups thereby completes a ring including two adjacent carbon atoms of ring Q, any carbon atoms in A and the adjacent nitrogen atom of the group --A.N--; A is a direct bond to the the group --N(R8)-- or is alkylene; Q is a phenyl or pyridyl moiety; Y is a physiologically acceptable anion; and wherein any one or more of said phenyl, benzene or pyridyl moieties may optionally be unsubstituted or bear one or more selected substituents.The invention also includes certain closely related anhydo-base derivatives which, like the compounds of formula I, possess beneficial effects on the cardiovascular system (and in particular beneficial effects modulated via the sino-atrial node). Also included are pharmaceutical compositions containing compounds of formula I (or a related anhydro-base) as active ingrdient, and processes for the manufacture of the various novel compounds.

    摘要翻译： 本发明涉及式I的新型化合物：其中P是式II基团或式III基团; R1是烷基，环烷基，环烷基烷基，苯基或苯基烷基; R2是氢，烷基，氨基或烷基氨基; R3和R4独立地是氢，烷基，苯基或苄基; R6是烷基氨基或烷基氨基; C和D独立地是亚乙基或三亚甲基; Z是C和D之间的直接键，或氧，硫，羰基，亚甲基，亚乙二氧基亚甲基，亚乙基或异亚丙基连接基，或Z是式= N.R5的基团，其中R 5是烷基，苯基或苄基; R8是氢，环烷基烷基，烷基，烯基，炔基或苯基烷基; 或者R8是连接到基团QAN-的氮原子的亚烷基或亚烯基，其中任一个连接基团可以任选地具有烷基，苯基或苯基烷基取代基，并且其中任一个连接基由此完成包含环的两个相邻碳原子的环 Q，A中的任何碳原子和-AN-相邻的氮原子; A是与-N（R 8）基团的直接键合 - 或者是亚烷基; Q是苯基或吡啶基部分; Y是生理上可接受的阴离子; 并且其中所述苯基，苯或吡啶基部分中的任何一个或多个可以任选地是未被取代的或承载一个或多个选定的取代基。 本发明还包括某些密切相关的脱水基衍生物，其与式I化合物一样对心血管系统具有有益作用（尤其是通过窦房结调节的有益作用）。 还包括含有式I化合物（或相关脱氢碱）作为活性成分的药物组合物，以及制备各种新型化合物的方法。

    Pyrimidine derivatives
    8.
    发明授权
    Pyrimidine derivatives 失效
    吡嗪衍生物

    公开(公告)号：US5223505A

    公开(公告)日：1993-06-29

    申请号：US513304

    申请日：1990-04-20

    申请人： Rodney B. Hargreaves ,  Paul W. Marshall ,  Bernard J. McLoughlin ,  Stuart D. Mills

    发明人： Rodney B. Hargreaves ,  Paul W. Marshall ,  Bernard J. McLoughlin ,  Stuart D. Mills

    IPC分类号： C07D239/32 ,  A61K31/505 ,  A61K31/506 ,  A61K31/517 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  C07D211/04 ,  C07D239/00 ,  C07D239/42 ,  C07D239/48 ,  C07D239/50 ,  C07D239/70 ,  C07D239/95 ,  C07D401/00 ,  C07D401/04 ,  C07D401/12 ,  C07D403/00 ,  C07D403/04 ,  C07D405/12 ,  C07D409/12

    CPC分类号： C07D239/48 ,  C07D239/95 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04

    摘要： This invention concerns novel aminopyrimidinium salts of the formula I: ##STR1## in which R.sup.1 is alkyl, alkenyl, cycloalkyl, phenyl, phenylalkyl or cycloalkyl-alkyl; one of R.sup.2 and R.sup.6 is a basic group selected from amino, alkylamino, dialkylamino of up to eight carbon atoms, pyrrolidino, piperidino and morpholino; and the other of R.sup.2 and R.sup.6 is hydrogen, alkyl, alkenyl, alkoxyalkyl, phenyl, phenylalkyl, cycloalkyl or cycloalkyl-alkyl; or both of R.sup.2 and R.sup.6 are basic groups as mentioned above; and R.sup.5 is hydrogen, (1-4C)alkyl or (3-6C)alkenyl; or R.sup.2 is a basic group as mentioned above, and R.sup.5 and R.sup.6 together form alkylene or, together with the appendant carbon atoms of the pyrimidine ring, complete a benzene ring; R.sup.4 is hydrogen, alkyl, cycloalkyl-alkyl, alkenyl, alkynyl or phenylalkyl; or R.sup.4 is an optionally substitutued alkylene or alkenylene linked to the nitrogen atom of the group Q.A.N--, either of which linking groups may thereby completing a ring including two adjacent carbon atoms of Q, the carbon atoms of A and the adjacent nitrogen atom of the group --A.N--; A is a direct bond to the the group --N(R.sup.4)-- or is alkylene or oxyalkylene; Q is a pyridyl, furyl, thienyl or phenyl moiety; and Y is a physiologically acceptable anion; but excluding a number of compounds specified hereinafter.The invention also includes certain closely related anhydro-base derivatives which, like the formula I compounds, possess beneficial effects on the cardiovascular system (and in particular beneficial effects modulated via the sino-atrial node). Also included are pharmaceutical compositions containing the formula I compound (or a related anhydro-base) as active ingredient, and processes for the manufacture of the various novel compounds.

    摘要翻译： 本发明涉及式I的新的氨基嘧啶鎓盐：其中R 1是烷基，烯基，环烷基，苯基，苯基烷基或环烷基 - 烷基; R 2和R 6中的一个是选自氨基，烷基氨基，至多8个碳原子的二烷基氨基，吡咯烷子基，哌啶子基和吗啉代基团的碱基; R2和R6中的另一个是氢，烷基，烯基，烷氧基烷基，苯基，苯基烷基，环烷基或环烷基 - 烷基; 或者R 2和R 6都是如上所述的碱性基团; R5为氢，（1-4C）烷基或（3-6C）烯基; 或R 2是如上所述的碱性基团，并且R 5和R 6一起形成亚烷基，或与嘧啶环的上述碳原子一起形成苯环; R4是氢，烷基，环烷基 - 烷基，烯基，炔基或苯基烷基; 或R4是与QAN-的氮原子连接的任选取代的亚烷基或亚烯基，其中连接基团可以由此完成包含Q的两个相邻碳原子的环，A的碳原子和相邻的氮原子 组-AN-; A是与-N（R 4）基团的直接键合 - 或者是亚烷基或氧亚烷基; Q是吡啶基，呋喃基，噻吩基或苯基部分; Y是生理上可接受的阴离子; 但不包括以下指定的许多化合物。 本发明还包括与式I化合物一样具有对心血管系统的有益作用的某些密切相关的脱氢基衍生物（特别是通过窦房结调节的有益作用）。 还包括含有式I化合物（或相关脱氢碱）作为活性成分的药物组合物，以及制备各种新型化合物的方法。

    1,2,4-Triazin-3(2H) ones
    9.
    发明授权
    1,2,4-Triazin-3(2H) ones 失效
    1,2,4-三嗪-3（2H）酮

    公开(公告)号：US4495185A

    公开(公告)日：1985-01-22

    申请号：US436801

    申请日：1982-10-26

    申请人： David Brown ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin ,  Stuart D. Mills

    发明人： David Brown ,  Rodney B. Hargreaves ,  Bernard J. McLoughlin ,  Stuart D. Mills

    IPC分类号： A61K31/535 ,  A61K31/5375 ,  A61K31/54 ,  A61P9/04 ,  A61P9/12 ,  C07C45/00 ,  C07C45/64 ,  C07C49/82 ,  C07C67/00 ,  C07C239/00 ,  C07C243/38 ,  C07C281/04 ,  C07D253/06 ,  C07D273/04 ,  C07D285/16 ,  C07D295/18 ,  C07D295/21 ,  A61K31/53

    CPC分类号： C07D253/06 ,  C07C243/38 ,  C07C45/64 ,  C07D273/04 ,  C07D285/16 ,  C07D295/21

    摘要： Heterocyclic compounds of the formula ##STR1## wherein either X is --CR.sup.1 R.sup.2 and Y is --O--, --S-- or --NR.sup.3 --, wherein R.sup.1, R.sup.2 and R.sup.3, which may be the same or different, each is hydrogen or alkyl of up to 4 carbon atoms;or X is --O--, --S-- or --NH-- and Y is --CR.sup.1 R.sup.2 -- wherein R.sup.1 and R.sup.2 have the meanings stated above;wherein either R.sup.4 is hydrogen, fluoro or chloro, or alkyl, alkenyl, halogenoalkyl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or alkoxy each of up to 6 carbon atoms, and R.sup.5, R.sup.6 and R.sup.7, which may be the same or different, each is hydrogen, fluoro, chloro, bromo or iodo, or alkyl, alkenyl, halogenoalkyl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or alkoxy each of up to 6 carbon atoms, provided that R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are not all hydrogen;or R.sup.4 is bromo and R.sup.5, R.sup.6 and R.sup.7 have the meanings stated above, provided that R.sup.5, R.sup.6 and R.sup.7 are not all hydrogen;or R.sup.4 and R.sup.5 together, or R.sup.5 and R.sup.6 together, or R.sup.4 and R.sup.7 together, form the --CH.dbd.CH--CH.dbd.CH-- group and the other two or R.sup.4, R.sup.5, R.sup.6 and R.sup.7 have the meanings stated above; processes for their manufacture and pharmaceutical compositions containing them. The compounds possess cardiotonic and/or antihypertensive activity.

    摘要翻译： 其中X是-CR 1 R 2和Y的杂环化合物是其中R 1，R 2和R 3可以相同或不同，各自为氢或烷基， 最多4个碳原子; 或X是-O - ， - S-或-NH-，Y是-CR 1 R 2 - ，其中R 1和R 2具有上述含义; 其中R 4是氢，氟或氯，或至多6个碳原子的烷基，烯基，卤代烷基，氨基烷基，羟基烷基，烷氧基烷基或烷氧基，以及可以相同或不同的R 5，R 6和R 7各自为氢 ，氟，氯，溴或碘，或各自具有至多6个碳原子的烷基，烯基，卤代烷基，氨基烷基，羟基烷基，烷氧基烷基或烷氧基，条件是R4，R5，R6和R7不全部为氢; 或R 4为溴，R 5，R 6和R 7具有上述含义，条件是R 5，R 6和R 7不全为氢; 或R 4和R 5一起，或R 5和R 6一起，或者R 4和R 7一起形成-CH = CH-CH = CH-基，而另外两个或者R 4，R 5，R 6和R 7具有上述含义; 其制造方法和含有它们的药物组合物。 该化合物具有强心剂和/或抗高血压活性。

    Morpholine derivatives
    10.
    发明授权
    Morpholine derivatives 失效
    吗啉衍生物

    公开(公告)号：US4088814A

    公开(公告)日：1978-05-09

    申请号：US735125

    申请日：1976-10-22

    申请人： Bernard J. McLoughlin ,  Allen J. Guildford

    发明人： Bernard J. McLoughlin ,  Allen J. Guildford

    IPC分类号： C07D265/30 ,  C07D265/32 ,  C07F9/6533

    CPC分类号： C07D265/30 ,  C07D265/32 ,  C07F9/6533

    摘要： Morpholine derivatives, typically those of the formula: ##STR1## wherein A is an ethylene or vinylene radical and X is a phenyl radical optionally substituted by one or two substituents selected from halogen atoms, alkyl and alkoxy radicals of 1 to 6 carbon atoms and aryloxy radicals of 1 to 6 carbon atoms, the aryloxy radicals themselves being optionally substituted by one or two substituents selected from halogen atoms and alkyl radicals of 1 to 4 carbon atoms, and the pharmaceutically-acceptable acid-addition salts thereof. Processes for making these compounds, pharmaceutical compositions containing them and a method of restoring to normal abnormal mental states in warm-blooded animals are also disclosed.

    摘要翻译： 吗啉衍生物，通常是下式的那些：其中A是乙烯或亚乙烯基，X是任选地被一个或两个选自卤素原子，1-6个碳原子的烷基和烷氧基的取代基取代的苯基和芳氧基 1至6个碳原子的基团，芳氧基本身任选被一个或两个选自卤素原子和1-4个碳原子的烷基的取代基取代，及其药物上可接受的酸加成盐。 还公开了制备这些化合物的方法，含有它们的药物组合物和在温血动物中恢复正常的异常精神状态的方法。