公开(公告)号：US4921960A

公开(公告)日：1990-05-01

申请号：US184796

申请日：1988-04-22

申请人： Jozsef Knoll ,  Katalin Budai nee Simonyi ,  Edit Berenyi nee Poldermann ,  Ildiko Miklya ,  Marton Fekete ,  Gabriella Zsilla ,  Berta Knoll ,  Attila Mandi ,  Lujza Petocz ,  Istvan Gyertyan ,  Istvan Gacsalyi

发明人： Jozsef Knoll ,  Katalin Budai nee Simonyi ,  Edit Berenyi nee Poldermann ,  Ildiko Miklya ,  Marton Fekete ,  Gabriella Zsilla ,  Berta Knoll ,  Attila Mandi ,  Lujza Petocz ,  Istvan Gyertyan ,  Istvan Gacsalyi

IPC分类号： A61K31/47 ,  A61P25/20 ,  A61P25/22 ,  C07D215/38

CPC分类号： C07D215/38

摘要： The new compounds of the general Formula I ##STR1## (wherein R.sub.1 stands for C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkinyl, C.sub.3-7 cycloalkyl or optionally substituted phenyl-(C.sub.1-4 alkyl);R.sub.2 represents hydrogen or C.sub.1-5 alkanoyl;X.sub.1 and X.sub.2 can be identical or different and each stands for hydrogen, halogen, trifluoromethyl or C.sub.1-4 alkoxy;(with the proviso that if R.sub.1 stands for ethyl, at least one of R.sub.2, X.sub.1 and X.sub.2 is different from hydrogen) and pharmaceutically acceptable acid additions salts possess valuable anxiolytic properties devoid of sedative effect and can be used in therapy.The compounds of the general Formula I can be prepared by methods known per se.

摘要翻译： 通式Ⅰ的新化合物（Ⅰ）（其中R1代表C1-5烷基，C2-5链烯基，C2-5炔基，C3-7环烷基或任意取代的苯基 - （C 1-4烷基）; R 2表示氢或C 1-5烷酰基; X 1和X 2可以相同或不同，各自表示氢，卤素，三氟甲基或C 1-4烷氧基;（条件是如果R1代表乙基，则R2，X1中的至少一个 和X2不同于氢）和药学上可接受的酸加成盐具有不具有镇静作用的有价值的抗焦虑性质，并且可用于治疗。通式I的化合物可以通过本身已知的方法制备。

公开(公告)号：US4921861A

公开(公告)日：1990-05-01

申请号：US185049

申请日：1988-04-22

申请人： Jozsef Knoll ,  ne Simonyi; Katalin Budai ,  Edit Berenyi ne Poldermann ,  Ildiko Miklya ,  Marton Fekete ,  Gabriella Zsilla ,  Berta Knoll ,  Attila Mandi ,  Lujza Petocz ,  Istvan Gyertyan ,  Istvan Gacsalyi

发明人： Jozsef Knoll ,  ne Simonyi; Katalin Budai ,  Edit Berenyi ne Poldermann ,  Ildiko Miklya ,  Marton Fekete ,  Gabriella Zsilla ,  Berta Knoll ,  Attila Mandi ,  Lujza Petocz ,  Istvan Gyertyan ,  Istvan Gacsalyi

IPC分类号： C07D215/38 ,  A61K31/47 ,  A61P23/00 ,  A61P23/02 ,  A61P25/02 ,  A61P25/20

CPC分类号： A61K31/47

摘要： The 3-amino-4-ethylthio-quinoline of the Formula I ##STR1## and pharmaceutically acceptable acid addition salts thereof possess useful therapeutical properties. They exhibit a potent and highly selective anxiolytic and narcosis potentiating effect and are devoid of sedative and anti-convulsive effect. Consequently, the invention relates to pharmaceutical compositions comprising the compound of Formula I or a salt thereof as active agent.The invention also relates to a new and improved process for the preparation of the compound of Formula I.

摘要翻译： 式I的3-氨基-4-乙硫基 - 喹啉（I）及其药学上可接受的酸加成盐具有有用的治疗性质。 它们具有强效和高选择性的抗焦虑和麻醉增效作用，没有镇静和抗惊厥作用。 因此，本发明涉及包含式I化合物或其盐作为活性剂的药物组合物。 本发明还涉及制备式I化合物的新的和改进的方法。

公开(公告)号：US5225410A

公开(公告)日：1993-07-06

申请号：US604488

申请日：1990-10-25

申请人： Jozsef Barkoczy ,  Jozsef Reiter ,  Laszlo Pongo ,  Lujza Petocz ,  Frigyes Gorgenyi ,  Marton Fekete ,  Eniko Szirt nee Kiszelly ,  Maria Szecsey nee Hegedus ,  Istvan Gacsalyi ,  Istvan Gyertyan

发明人： Jozsef Barkoczy ,  Jozsef Reiter ,  Laszlo Pongo ,  Lujza Petocz ,  Frigyes Gorgenyi ,  Marton Fekete ,  Eniko Szirt nee Kiszelly ,  Maria Szecsey nee Hegedus ,  Istvan Gacsalyi ,  Istvan Gyertyan

IPC分类号： A61K31/41 ,  A61K31/50 ,  A61K31/55 ,  A61P1/04 ,  A61P9/08 ,  A61P9/10 ,  C07D249/14 ,  C07D403/04 ,  C07D413/04

CPC分类号： C07D249/14

摘要： This invention relates to novel triazolyl hydrazide derivatives and a process for the preparation thereof.The new triazolyl hydrazide derivatives of the general formula (I). ##STR1## wherein Q represents hydrogen or a heterocyclic group optionally substituted by a C.sub.1-4 alkyl group; or a group of general formula SR.sup.1, whereinR.sup.1 stands for C.sub.1-4 alkyl or phenyl-(C.sub.1-4 alkyl) optionally substituted by halogen, C.sub.1-4 alkyl or nitro substitute therefor substituents; or Q represents a group of the formula NR.sup.2 R.sup.3, wherein R.sup.2 and R.sup.3 each represents hydrogen, straight or branched chain C.sub.1-6 alkyl or C.sub.2-6 alkenyl;Z represents hydrogen or a group of the formula (C.dbd.X)--(N--R.sup.4)--NR.sup.5 R.sup.6, whereinX stands for oxygen or sulfur,R.sup.4, R.sup.5 and R.sup.6 each stand for hydrogen or C.sub.1-4 alkyl;R.sup.7 stands for hydrogen, C.sub.1-4 alkyl or phenyl-(C.sub.1-4 alkyl) optionally substituted by one or more halogen atom(s) or an amino group optionally substituted by one or two C.sub.1-4 alkyl substituents,R.sup.8 stands for hydrogen or a group of the formula --(C.dbd.X)--(N--R.sup.4)--NR.sup.5 R.sup.6, wherein X, R.sup.4, R.sup.5 and R.sup.6 are as stated above,with the proviso that if Z represents a group of the formula --(C.dbd.X)--(N--R.sup.4)--NR.sup.5 R.sup.6, R.sup.8 stands for hydrogen, and if Z represents hydrogen, R.sup.8 stands for a group of the formula (C.dbd.X)--(N--R.sup.4)--NR.sup.5 R.sup.6, and pharmaceutically acceptable acid addition salts thereof excert valuable antianginal and/or gastric ulcer inhibiting properties and are useful in therapy.

公开(公告)号：US5135928A

公开(公告)日：1992-08-04

申请号：US604486

申请日：1990-10-25

申请人： Jozsef Reiter ,  Jozsef Barkoczy ,  Lujza Petocz ,  Frigyes Gorgenyi ,  Marton Fekete ,  Eniko Szirt nee Kiszelly ,  Gabor Gigler ,  Istvan Gacsalyi ,  Istvan Gyertyan ,  Klara Reiter nee Esses

发明人： Jozsef Reiter ,  Jozsef Barkoczy ,  Lujza Petocz ,  Frigyes Gorgenyi ,  Marton Fekete ,  Eniko Szirt nee Kiszelly ,  Gabor Gigler ,  Istvan Gacsalyi ,  Istvan Gyertyan ,  Klara Reiter nee Esses

IPC分类号： A61K31/41 ,  A61K31/50 ,  A61K31/535 ,  A61K31/55 ,  A61P9/08 ,  A61P9/10 ,  A61P29/00 ,  C07D249/14 ,  C07D403/04 ,  C07D405/12 ,  C07D413/04 ,  C07D487/04

CPC分类号： C07D405/12 ,  C07D249/14 ,  C07D487/04

摘要： This invention relates to novel triazolo derivatives, a process for the preparation thereof, pharmaceutical compositions comprising the same, to the use of the said triazolo derivatives for the treatment of diseases and also for the preparation of pharmaceutical compositions suitable for the treatment of the said diseases.The new triazolo derivatives of the general formulae (Ia) and (Ib), ##STR1## wherein Q represents hydrogen or a heterocyclic group optionally bearing one or more C.sub.1-4 alkyl substituent(s); or a group of the formula SR.sup.1, whereinR.sup.1 stands for straight or branched chained C.sub.1-4 alkyl or phenyl-(C.sub.1-4 alkyl); or q represents a group of the formula NR.sup.2 R.sup.3, whereinR.sup.2 and R.sup.3 each represent hydrogen, straight or branched chain C.sub.1-12 alkyl, C.sub.2-6 alkenyl or phenyl-(C.sub.1-4 alkyl);R.sup.4 and R.sup.7 each represent hydrogen, C.sub.1-6 alkyl or phenyl-(C.sub.1-4 alkyl) optionally bearing one or more halogen substituent(s);R.sup.5 and R.sup.6 each stand for C.sub.1-4 alkyl optionally substituted by a C.sub.1-4 alkoxycarbonyl group; a heterocyclic group or a phenyl group optionally bearing one or more halogen, hydroxyl, cyano, nitro, alkyl, methylene dioxy and carbamoylmethoxy, di-(C.sub.1-4 alkyl)-amino or C.sub.1-4 alkoxy substituent(s) which latter may carry a di-(C.sub.1-4 alkyl)-amino group; furthermore one of R.sup.5 and R.sup.6 may represent hydrogen, orR.sup.5 and R.sup.6 together stand for C.sub.4-15 alkylene, or together with the adjacent carbon atom they are attached to form a heterocyclic group bearing a phenyl(C.sub.1-4 alkyl) substituent,possess valuable antianginal and tranquillant/sedative properties and are useful in therapy.

公开(公告)号：US4831029A

公开(公告)日：1989-05-16

申请号：US116870

申请日：1987-11-05

申请人： Jozsef Reiter ,  Endre Rivo ,  Klara Reiter nee Esess ,  Marton Fekete ,  Frigyes Gogenyi ,  Lujza Petocz ,  Istvan Gacsalyi ,  Istvan Gyertyan

发明人： Jozsef Reiter ,  Endre Rivo ,  Klara Reiter nee Esess ,  Marton Fekete ,  Frigyes Gogenyi ,  Lujza Petocz ,  Istvan Gacsalyi ,  Istvan Gyertyan

IPC分类号： A61K31/505 ,  A61P23/02 ,  A61P25/02 ,  A61P25/20 ,  C07D471/14 ,  C07D487/04 ,  C07D487/14

CPC分类号： C07D471/14 ,  C07D487/04 ,  C07D487/14

摘要： The invention relates to condensed cyclic triazole derivatives of the general Formula I ##STR1## and pharmaceutically acceptable salts thereof. The compounds of the general Formula I possess useful sedative and tranquillant properties and exhibit particularly spasmolytic, motility inhibiting, and narcosis potentiating, yohimbine potentiating and local anaesthetic and also weak reserpine ptosis inhibiting effect.

摘要翻译： 本发明涉及通式I（I）的缩合环状三唑衍生物及其药学上可接受的盐。 通式I的化合物具有有用的镇静和镇静特性，并且显示出特别的解痉，运动性抑制和麻醉增强，育亨宾加强和局部麻醉以及弱的利血平下垂抑制作用。

公开(公告)号：US5276030A

公开(公告)日：1994-01-04

申请号：US755219

申请日：1991-09-09

申请人： Josef Barkoczy ,  Josef Reiter ,  Laszlo Pongo ,  Lujza Petocz ,  Marton Fekete ,  Frigyes Gorgenyi ,  Gabor Gigler ,  Istvan Gacsalyi ,  Istvan Gyertyan

发明人： Josef Barkoczy ,  Josef Reiter ,  Laszlo Pongo ,  Lujza Petocz ,  Marton Fekete ,  Frigyes Gorgenyi ,  Gabor Gigler ,  Istvan Gacsalyi ,  Istvan Gyertyan

IPC分类号： A61K31/41 ,  A61K31/4196 ,  A61K31/4427 ,  A61K31/445 ,  A61K31/495 ,  A61K31/535 ,  A61P13/06 ,  A61P25/08 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/26 ,  A61P29/00 ,  C07D249/14 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/04 ,  C07D413/14

CPC分类号： C07D249/14

摘要： The invention relates to novel triazolyl thioamides of the general formula (I), ##STR1## wherein Q represents hydrogen or a heterocyclic group optionally bearing one or more C.sub.1-4 alkyl substituent(s), or a group of the formula SR.sup.1, whereinR.sup.1 stands for straight or branched chained alkyl group comprising 1 to 6 carbon atom(s), or a group of the formula NR.sup.2 R.sup.3, whereinR.sup.2 and R.sup.3 each represent hydrogen, straight or branched chained C.sub.1-4 alkyl or C.sub.2-6 alkenyl group,Y denotes C.sub.1-4 alkyl bearing one or more hydroxyl or C.sub.1-4 alkoxy substituent(s), phenyl-(C.sub.1-4 alkyl) optionally bearing on the phenyl ring one or more C.sub.1-4 alkoxy group(s), or phenoxy-(C.sub.1-4 alkyl) optionally substituted on the phenyl ring by a C.sub.1-4 alkyl bearing a heterocyclic group containing a nitrogen atom, with the proviso that if Q represents methylthio, dimethylamino, piperidino or morpholino, Y is other than benzyl,and pharmaceutically acceptable acid additional salts thereof.Furthermore the invention relates to a process for preparing these compounds.The compounds according to the invention possess tranquillant, antidepressant, spasmolytic, antiinflammatory, analgesic and antiperistaltic effects.

摘要翻译： 本发明涉及通式（I）的新型三唑基硫代酰胺，其中Q表示氢或任选带有一个或多个C 1-4烷基取代基的杂环基或式SR1的基团，其中R 1 代表包含1至6个碳原子的直链或支链烷基或式NR2R3基团，其中R2和R3各自表示氢，直链或支链C 1-4烷基或C 2-6烯基，Y 表示具有一个或多个羟基或C 1-4烷氧基取代基的C 1-4烷基，任选地在苯环上带有一个或多个C 1-4烷氧基的苯基 - （C 1-4烷基）或苯氧基 - （ C 1-4烷基），其任选在苯环上被带有含氮原子的杂环基的C 1-4烷基取代，条件是如果Q表示甲硫基，二甲基氨基，哌啶子基或吗啉代，则Y不是苄基， 其酸加成盐。 此外，本发明涉及一种制备这些化合物的方法。 根据本发明的化合物具有镇静，抗抑郁，解痉，抗炎，止痛和抗静脉作用。

公开(公告)号：US5175163A

公开(公告)日：1992-12-29

申请号：US617126

申请日：1990-11-21

申请人： Jozsef Barkoczy ,  Jozsef Reiter ,  Laszlo Pongo ,  Lujza Petocz ,  Marton Fekete ,  Frigyes Gorgenyi ,  Gabor Gigler ,  Istvan Gacsalyi ,  Istvan Gyertyan

发明人： Jozsef Barkoczy ,  Jozsef Reiter ,  Laszlo Pongo ,  Lujza Petocz ,  Marton Fekete ,  Frigyes Gorgenyi ,  Gabor Gigler ,  Istvan Gacsalyi ,  Istvan Gyertyan

IPC分类号： A61K31/41 ,  A61K31/4196 ,  A61K31/4427 ,  A61K31/445 ,  A61K31/495 ,  A61K31/535 ,  A61P13/06 ,  A61P25/08 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/26 ,  A61P29/00 ,  C07D249/14 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/04 ,  C07D413/14

CPC分类号： C07D249/14

摘要： The invention relates to novel triazolyl thioamides of the general formula (I), ##STR1## wherein Q represents hydrogen or a heterocyclic group optionally bearing one or more C.sub.1-4 alkyl substituent(s), or a group of the formula SR.sup.1, whereinR.sup.1 stands for straight or branched chained alkyl group comprising 1 to 6 carbon atom(s), or a group of the formula NR.sup.2 R.sup.3, whereinR.sup.2 and R.sup.3 each represent hydrogen, straight or branched chained C.sub.1-4 alkyl or C.sub.2-6 alkenyl group,Y denotes C.sub.1-4 alkyl optionally bearing one or more hydroxyl or C.sub.1-4 alkoxy substituent(s), phenyl-(C.sub.1-4 alkyl) optionally bearing on the phenyl ring one or more C.sub.1-4 alkoxy group(s), or phenoxy-(C.sub.1-4 alkyl) optionally substituted on the phenyl ring by a C.sub.1-4 alkyl bearing a heterocyclic group containing a nitrogen atom,and pharmaceutically acceptable acid addition salts thereof.Furthermore the invention relates to a process for preparing these compounds.The compounds according to the invention possess tranquillant, antidepressant, spacmolytic, antiinflammatory, analgesic and antiperistaltic effects.

摘要翻译： 本发明涉及通式（I）的新型三唑基硫代酰胺，其中Q表示氢或任选带有一个或多个C 1-4烷基取代基的杂环基或式SR 1的基团 其中R1代表包括1至6个碳原子的直链或支链烷基或式NR2R3基团，其中R2和R3各自表示氢，直链或支链C 1-4烷基或C 2-6烯基 基团，Y表示任选带有一个或多个羟基或C 1-4烷氧基取代基的C 1-4烷基，任选地在苯环上带有一个或多个C 1-4烷氧基的苯基 - （C 1-4烷基） 或在苯环上被含有含有氮原子的杂环基的C 1-4烷基任选取代的苯氧基 - （C 1-4烷基）及其药学上可接受的酸加成盐。 此外，本发明涉及一种制备这些化合物的方法。 根据本发明的化合物具有镇静，抗抑郁，间质，抗炎，止痛和抗静脉作用。

公开(公告)号：US4965259A

公开(公告)日：1990-10-23

申请号：US292450

申请日：1988-12-30

申请人： Laszlo Rozsa ,  Lujza Petocz ,  Eniko Szirt nee Kiszelly ,  Marton Fekete ,  Maria Szecsey nee Hegedus ,  Gabor Gigler ,  Istvan Gacsalyi

发明人： Laszlo Rozsa ,  Lujza Petocz ,  Eniko Szirt nee Kiszelly ,  Marton Fekete ,  Maria Szecsey nee Hegedus ,  Gabor Gigler ,  Istvan Gacsalyi

IPC分类号： A61K31/357 ,  A61K31/395 ,  A61P9/06 ,  A61P21/02 ,  A61P23/00 ,  A61P23/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/08 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/26 ,  C07D273/00 ,  C07D273/01

CPC分类号： C07D273/00

摘要： Dioxazocine derivatives, their preparation and composition containing them, said derivatives being represented by the formula I ##STR1## wherein R.sub.1 represents hydrogen or alkyl having from 1 to 4 carbon atoms,R.sub.2 represents alkyl having from 1 to 4 carbon atoms, andn is equal to 0 or 1,and pharmaceutically acceptable acid addition salts thereof formed with an inorganic or organic acid.Two different reactions are described for making these compounds. They can be formulated into pharmaceutical compositions in the usual manner and exhibit central nervous system affecting activities.

摘要翻译： 二恶唑辛衍生物及其制备方法和含有它们的组合物，所述衍生物由式I（I）表示，其中R 1表示氢或具有1至4个碳原子的烷基，R 2表示具有1至4个碳原子的烷基，以及 n等于0或1，并且其药学上可接受的酸加成盐与无机或有机酸形成。 描述了制备这些化合物的两种不同的反应。 它们可以以通常的方式配制成药物组合物，并显示中枢神经系统影响活性。

公开(公告)号：US4883798A

公开(公告)日：1989-11-28

申请号：US221529

申请日：1988-07-20

申请人： Lujza Petocz ,  Istvan Simonyi ,  Ivan Beck ,  Gabor Gigler ,  Marton Fekete ,  Eniko Szirt nee Kiszelly ,  Attila Mandi ,  Frigyes Gorgenyi ,  Andras Dietz ,  Elemer Jakfalvi ,  Katalin Zukovics nee Sumeg ,  Klara Gado ,  Maria Hegedus

发明人： Lujza Petocz ,  Istvan Simonyi ,  Ivan Beck ,  Gabor Gigler ,  Marton Fekete ,  Eniko Szirt nee Kiszelly ,  Attila Mandi ,  Frigyes Gorgenyi ,  Andras Dietz ,  Elemer Jakfalvi ,  Katalin Zukovics nee Sumeg ,  Klara Gado ,  Maria Hegedus

IPC分类号： A61K31/505 ,  A61P25/04 ,  A61P29/00 ,  A61P43/00 ,  C07D239/49 ,  C07D405/06

CPC分类号： A61K31/505

摘要： The compounds of the general Formula I ##STR1## (wherein R.sup.1 and R.sup.2 may be the same or different and each stands for hydrogen, hydroxy, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy-C.sub.1-6 alkoxy, C.sub.2-6 alkenyloxy or phenyl-(C.sub.1-3 alkoxy), or R.sup.1 and R.sup.2 together form C.sub.1-2 alkylenedioxy; with the proviso that at least one of symbols R.sup.1 and R.sup.2 is other than hydrogen and with the further proviso that R.sup.1 and R.sup.2 can not represent 3,4-dimethoxy substitution) andtheir pharmaceutically acceptable acid addition salts exhibit useful analgesic, antipyretic, anti-inflammatory, anti-anginal and antioxidant effect.

摘要翻译： 通式I的化合物（I）（其中R 1和R 2可以相同或不同，各自代表氢，羟基，C 1-6烷氧基，C 1-6烷氧基-C 1-6烷氧基，C 2-6 烯基氧基或苯基 - （C1-3烷氧基），或R1和R2一起形成C1-2亚烷基二氧基;条件是符号R1和R2中的至少一个不是氢，另外条件是R1和R2不能表示 3,4-二甲氧基取代）及其药学上可接受的酸加成盐显示出有用的镇痛，解热，抗炎，抗心绞痛和抗氧化作用。

公开(公告)号：US4873249A

公开(公告)日：1989-10-10

申请号：US17090

申请日：1987-02-20

申请人： Lujza Petocz ,  Istvan Simonyi ,  Ivan Beck ,  Gabor Gigler ,  Marton Fekete ,  Eniko Kiszelly ,  Attila Mandi ,  Frigyes Gorgenyi ,  Andras Dietz ,  Katalin Sumeg nee Zukovics ,  Elemer Jakfalvi

发明人： Lujza Petocz ,  Istvan Simonyi ,  Ivan Beck ,  Gabor Gigler ,  Marton Fekete ,  Eniko Kiszelly ,  Attila Mandi ,  Frigyes Gorgenyi ,  Andras Dietz ,  Katalin Sumeg nee Zukovics ,  Elemer Jakfalvi

IPC分类号： C07D239/49 ,  A61K31/505 ,  A61P25/04 ,  A61P29/00

CPC分类号： A61K31/505 ,  Y10S514/825

摘要： The invention relates to pharmaceutical compositions having analgesic and/or anti-inflammatory effect comprising as active ingredient 2,4-diamino-5-(3,4-dimethoxy-benzyl)-pyrimidine or a pharmaceutically acceptable acid addition salt thereof.The pharmaceutical compositions of the present invention exhibit the desired analgesic and anti-inflammatory effect without causing undesired ulcerogenic side-effects.

摘要翻译： 本发明涉及包含作为活性成分2,4-二氨基-5-（3,4-二甲氧基 - 苄基） - 嘧啶或其药学上可接受的酸加成盐的镇痛和/或抗炎作用的药物组合物。 本发明的药物组合物显示出期望的止痛和抗炎作用，而不引起不希望的溃疡发生副作用。