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1. 发明申请

WO2006090279A1 OXYINDOLE DERIVATIVES AS 5HT4 RECEPTOR AGONISTS 审中-公开
标题翻译：氧化衍生物作为5HT4受体激动剂
公开(公告)号：WO2006090279A1
公开(公告)日：2006-08-31
申请号：PCT/IB2006/000519
申请日：2006-02-10
申请人： PFIZER JAPAN INC. , PFIZER INC. , KAWAMURA, Kiyoshi , SONE, Hiroki , UCHIDA, Chikara
发明人： KAWAMURA, Kiyoshi , SONE, Hiroki , UCHIDA, Chikara
IPC分类号： C07D405/14 , C07D401/14 , C07D401/12 , A61K31/454 , A61P1/04
CPC分类号： C07D401/12 , C07D401/14 , C07D405/14
摘要： This invention relates to compounds of the formula (I): or a pharmaceutically acceptable salt thereof, wherein: A, R 1 , R 2 , R 3 , R4 and R 5 are each as described herein or a pharmaceutically acceptable salt, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5-HT 4 agonisitic activity such as, but not limited to, as gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders, cardiac failure, heart arrhythmia, diabetes or apnea syndrome.
摘要翻译：本发明涉及式（I）化合物或其药学上可接受的盐，其中：A，R 1，R 2，R 3，其中R 4和R 5各自如本文所述或其药学上可接受的盐，以及含有这些化合物的组合物以及这些化合物在治疗病症介导中的用途通过5-HT 4激动剂活性，例如但不限于胃食管反流病，胃肠道疾病，胃动力障碍，非溃疡性消化不良，功能性消化不良，肠易激综合征（IBS），便秘，消化不良，食管炎，胃食管疾病，恶心，中枢神经系统疾病，阿尔茨海默病，认知障碍，呕吐，偏头痛，神经系统疾病，疼痛，心血管疾病，心力衰竭，心律失常，糖尿病或呼吸暂停综合征。

2. 发明申请

WO2005021539A1 BENZIMIDAZOLONE COMPOUNDS HAVING 5-HT4 RECEPTOR AGONISTIC ACTIVITY 审中-公开
标题翻译：具有5-HT4受体激活活性的苯并咪唑化合物
公开(公告)号：WO2005021539A1
公开(公告)日：2005-03-10
申请号：PCT/IB2004/002741
申请日：2004-08-20
申请人： PFIZER JAPAN, INC. , PFIZER INC. , IGUCHI, Satoru , KATSU, Yasuhiro , SONE, Hiroki , UCHIDA, Chikara , KOJIMA, Takashi
发明人： IGUCHI, Satoru , KATSU, Yasuhiro , SONE, Hiroki , UCHIDA, Chikara , KOJIMA, Takashi
IPC分类号： C07D405/14
CPC分类号： C07D413/14 , C04B35/632 , C07D401/12 , C07D405/06 , C07D405/14
摘要： This invention provides a compound of the formula (I) or a pharmaceutically acceptable salt thereof, and compositions containing such compounds and the use of such compounds for the manufacture of medicament for gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders, cardiac failure, heart arrhythmia, diabetes and apnea syndrome. These compounds have 5-HT 4 receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.
摘要翻译：本发明提供式（I）化合物或其药学上可接受的盐，以及含有这些化合物的组合物，以及这些化合物在制备胃食管反流疾病，胃肠道疾病，胃动力障碍，非溃疡性消化不良的药物中的用途，功能性消化不良，肠易激综合征（IBS），便秘，消化不良，食管炎，胃食管疾病，恶心，中枢神经系统疾病，阿尔茨海默病，认知障碍，呕吐，偏头痛，神经系统疾病，疼痛，心血管疾病，心力衰竭，心律失常，糖尿病和呼吸暂停综合征。这些化合物具有5-HT 4受体激动活性，因此可用于治疗哺乳动物特别是人类的胃食管反流病，非溃疡性消化不良，功能性消化不良，肠易激综合征等。

3. 发明申请

WO2005123718A2 BENZIMIDAZOLONE CARBOXYLIC ACID DERIVATIVES 审中-公开
标题翻译：苯并咪唑羧酸羧酸衍生物
公开(公告)号：WO2005123718A2
公开(公告)日：2005-12-29
申请号：PCT/IB2005/001825
申请日：2005-06-01
申请人： PFIZER JAPAN INC. , PFIZER INC., , ANDO, Koji , IGUCHI, Satoru , MURASE, Noriaki , MURATA, Yoshinori , NUMATA, Toyoharu , SONE, Hiroki , UCHIDA, Chikara , UEKI, Tatsuo
发明人： ANDO, Koji , IGUCHI, Satoru , MURASE, Noriaki , MURATA, Yoshinori , NUMATA, Toyoharu , SONE, Hiroki , UCHIDA, Chikara , UEKI, Tatsuo
IPC分类号： C07D403/00
CPC分类号： C07D401/12 , C07D211/26 , C07D401/06 , C07D401/14 , C07D405/06 , C07D405/14
摘要： This invention relates to compounds of the formula (I): wherein R 1 , R 2 , R 3 , A and m are each as described herein or a pharmaceutically acceptable salt or solvate thereof, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5-HT 4 receptor activity such as, but not limited to, gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders such as cardiac failure and heart arrhythmia, diabetes and apnea syndrome.
摘要翻译：本发明涉及式（I）的化合物：其中R 1，R 2，R 3，A和m各自如本文所述，或其药学上可接受的盐或溶剂合物，以及含有这些化合物的组合物以及这些化合物在治疗由5-HT4受体活性介导的病症（例如但不限于胃食管反流病，胃肠道疾病，胃动力障碍，非溃疡性消化不良，功能性消化不良，肠易激综合征 IBS），便秘，消化不良，食管炎，胃食管疾病，恶心，中枢神经系统疾病，阿尔茨海默病，认知障碍，呕吐，偏头痛，神经系统疾病，疼痛，心血管疾病如心脏衰竭和心律失常，糖尿病和呼吸暂停综合征。

4. 发明申请

WO2005073222A1 1-ISOPROPYL-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE DERIVATIVES HAVING 5-HT4 RECEPTOR AGONISTIC ACTIVITY 审中-公开
标题翻译：具有5-HT4受体激活活性的1-异丙基-2-氧代-1,2-二氢吡啶-3-羧酰胺衍生物
公开(公告)号：WO2005073222A1
公开(公告)日：2005-08-11
申请号：PCT/IB2005/000173
申请日：2005-01-18
申请人： PFIZER JAPAN, INC. , PFIZER INC. , UCHIDA, Chikara , KAWAMURA, Kiyoshi , KATO, Tomoki
发明人： UCHIDA, Chikara , KAWAMURA, Kiyoshi , KATO, Tomoki
IPC分类号： C07D405/14
CPC分类号： C07D401/12 , C07D405/14
摘要： This invention provides a compound of formula (I): wherein R 1 represents an alkyl group having from 1 to 4 carbon atoms or a halogen atom, R 2 represents an alkyl group having from 1 to 4 carbon atoms, R 3 represents a hydrogen atom or a hydroxy group, and A represents an oxygen atom or a group of the formula -C(R 4 )(R 5 )- (in which R 4 represents a hydrogen atom or an alkyl group having from 1 to 4 carbon atoms and R 5 represents a hydroxy group or an alkoxy group having from 1 to 4 carbon atoms) or a pharmaceutically acceptable salts thereof. These compounds have 5-HT 4 receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.
摘要翻译：本发明提供式（I）的化合物：其中R 1表示具有1至4个碳原子的烷基或卤素原子，R 2表示具有1至4个碳原子的烷基， 3“表示氢原子或羟基，A表示氧原子或式-C（R 4）（R 5） - （其中R 4表示氢原子或式具有1至4个碳原子的烷基，R 5表示羟基或具有1至4个碳原子的烷氧基）或其药学上可接受的盐。这些化合物具有5-HT 4受体激动活性，因此可用于治疗哺乳动物特别是人类的胃食管反流病，非溃疡性消化不良，功能性消化不良，肠易激综合征等。

5. 发明申请

WO2005092882A1 4-AMINO-5-HALOGENO-BENZAMIDE DERIVATIVES AS 5-HT4 RECEPTOR AGONISTS FOR THE TREATMENT OF GASTROINTESTINAL, CNS, NEUROLOGICAL AND CARDIOVASCULAR DISORDERS 审中-公开
标题翻译： 4-氨基-5-苯并恶唑衍生物作为治疗胃肠病，中枢神经系统，神经和心脏病的5-HT4受体激动剂
公开(公告)号：WO2005092882A1
公开(公告)日：2005-10-06
申请号：PCT/IB2005/000389
申请日：2005-02-16
申请人： PFIZER JAPAN, INC. , PFIZER INC. , UCHIDA, Chikara , KAWAMURA, Kiyoshi
发明人： UCHIDA, Chikara , KAWAMURA, Kiyoshi
IPC分类号： C07D405/06
CPC分类号： C07D405/14 , C07D211/26 , C07D405/06 , C07D405/12
摘要： This invention provides a compound of the formula (I): wherein R l represents a halogen atom; R 2 represents a hydrogen atom etc.; R 3 represents an alkyl group having from 1 to 4 carbon atoms etc.;R 4 represents a hydrogen atom, a hydroxy group, a carboxy group etc.; A represents an oxygen atom etc. or a pharmaceutically acceptable salts thereof. These compounds have 5-HT4 receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.
摘要翻译：本发明提供式（I）的化合物：其中R 1表示卤素原子; R 2表示氢原子等。 R 3表示具有1〜4个碳原子的烷基等; R 4表示氢原子，羟基，羧基等; A表示氧原子等或其药学上可接受的盐。这些化合物具有5-HT 4受体激动活性，因此可用于治疗哺乳动物特别是人类的胃食管反流病，非溃疡性消化不良，功能性消化不良，肠易激综合征等。

6. 发明申请

WO2005049608A1 QUINOLONECARBOXYLIC ACID COMPOUNDS HAVING 5-HT4 RECEPTOR AGONISTIC ACTIVITY 审中-公开
标题翻译：具有5-HT4受体激活活性的喹喔啉羧酸化合物
公开(公告)号：WO2005049608A1
公开(公告)日：2005-06-02
申请号：PCT/IB2004/003707
申请日：2004-11-10
申请人： PFIZER JAPAN, INC. , PFIZER INC. , KATO, Tomoki , KAWAMURA, Kiyoshi , MORITA, Mikio , UCHIDA, Chikara
发明人： KATO, Tomoki , KAWAMURA, Kiyoshi , MORITA, Mikio , UCHIDA, Chikara
IPC分类号： C07D405/14
CPC分类号： C04B35/632 , C07D401/12 , C07D401/14 , C07D405/14
摘要： This invention provides a compound of the formula (I): wherein Het represents a heterocyclic group having one nitrogen atom, to which B binds directly, and from 4 to 7 carbon atoms, and said heterocyclic group being unsubstituted or substituted by 1 to 4 substituents independently selected from the group consisting of substituents α 1 ;A represents an alkylene group having from 1 to 4 carbon atoms; B represents a covalent bond or an alkylene group having from 1 to 5 carbon atoms; R l represents an isopropyl group, a n-propyl group or a cyclopentyl group; R 2 represents a methyl group, a fluorine atom or a chlorine atom; R 3 independently represents (i) an oxo group, a hydroxy group, an amino group, an alkylamino group or a carboxyl group; (ii) a cycloalkyl group having from 3 to 8 carbon atoms, and said cycloalkyl group being substituted by 1 to 5 substituents, or (iii) a heterocyclic group having from 3 to 8 atoms, and said heterocyclic group being unsubstituted or substituted by 1 to 5 substituents, and n is 1, 2 or 3, or a pharmaceutically acceptable salts thereof. These compounds have 5-HT 4 receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.
摘要翻译：本发明提供式（I）化合物：其中Het表示具有一个氮原子的杂环基团，B直接与该碳原子结合，并且具有4至7个碳原子，所述杂环基团未被取代或被1至4个取代基取代独立地选自取代基α1; A表示具有1至4个碳原子的亚烷基; B表示共价键或具有1至5个碳原子的亚烷基; R 1表示异丙基，正丙基或环戊基; R 2表示甲基，氟原子或氯原子; R 3独立地表示（i）氧代基，羟基，氨基，烷基氨基或羧基; （ii）具有3至8个碳原子的环烷基，所述环烷基被1至5个取代基取代，或（iii）具有3至8个原子的杂环基，所述杂环基未被取代或被1 至5个取代基，n为1,2或3，或其药学上可接受的盐。这些化合物具有5-HT 4受体激动活性，因此可用于治疗哺乳动物特别是人类的胃食管反流病，非溃疡性消化不良，功能性消化不良，肠易激综合征等。

7. 发明申请

WO2003057688A2 OXO OR OXY-PYRIDINE COMPOUNDS AS 5-HT4 RECEPTOR MODULATORS 审中-公开
标题翻译： OXO或OXY-吡啶化合物作为5-HT4受体调节剂
公开(公告)号：WO2003057688A2
公开(公告)日：2003-07-17
申请号：PCT/IB2002/005600
申请日：2002-12-20
申请人： PFIZER PHARMACEUTICALS INC. , PFIZER INC. , UCHIDA, Chikara , MIHARA, Sachiko , MORITA, Mikio , KAWAMURA, Kiyoshi , NUKUI, Seiji , STOBIE, Alan , GYMER, Geoffrey, Edward
发明人： UCHIDA, Chikara , MIHARA, Sachiko , MORITA, Mikio , KAWAMURA, Kiyoshi , NUKUI, Seiji , STOBIE, Alan , GYMER, Geoffrey, Edward
IPC分类号： C07D401/12
CPC分类号： C07D401/06 , C07D401/12 , C07D401/14
摘要： This invention provides compounds of the formula (I) and (II) or the phannaceutically acceptable esters thereof, and the pharmaceutically acceptable salts thereof: wherein R 1 is hydrogen or halo; R 2 and R 3 are independently hydrogen or C 1-6 alkyl; R 4 and R 5 are independently hydrogen or C 1-6 alkyl; R 6 is hydrogen, C l-12 alkyl, C 1-6 alkoxy (C 1-6 )alkyl or C 1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of C 3-8 cycloalkyl, aryl, heteroaryl and heterocyclic; R 7 and R 8 are hydrogen or taken together may form alkylene chain having one or two carbon atoms; R 9 is C 1-6 alkyl or C 3-8 cycloalkyl; R 10 is C 1-6 alkyl or NR 11 R 12 ; L is (CR 11 R 12 )n or NR 11 ; M is NR 11 or (CR 11 R 12 )n ; R 11 and R 12 are independently hydrogen or C 1-6 alkyl; n is an integer from 0 to 5; and. m is an integer from 0 to 2; said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo and C 1-6 alkyl; with the proviso that when R 9 is C 1-6 alkyl, L is not NR 11 . These compounds have 5-HT 4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.
摘要翻译：本发明提供式（I）和（II）化合物或其药学上可接受的酯及其药学上可接受的盐：其中R 1是氢或卤素; R 2和R 3独立地是氢或C 1-6烷基; R 4和R 5独立地是氢或C 1-6烷基; R 6是氢，C 1-12烷基，C 1-6烷氧基（C 1-6）烷基或被至多3个选自C 3-8环烷基，芳基，杂芳基和杂环基; R 7和R 8是氢或一起可以形成具有一个或两个碳原子的亚烷基链; R 9是C 1-6烷基或C 3-8环烷基; R 10是C 1-6烷基或NR 11 R 12; L是（CR 11 R 12）n或NR 11; M是NR 11或（CR 11 R 12）n; R 11和R 12独立地是氢或C 1-6烷基; n为0〜5的整数，和。 m为0〜2的整数; 所述杂环，芳基和杂芳基是未取代的或被至少一个选自卤素和C 1-6烷基的取代基取代; 条件是当R 9为C 1-6烷基时，L不为NR 11。这些化合物具有5-HT 4受体的结合活性，因此可用于治疗哺乳动物，特别是人类的胃食管反流病，非溃疡性消化不良，肠易激综合征等。本发明还提供了包含上述化合物的药物组合物。

8. 发明申请

WO2004094418A1 IMIDAZOPYRIDINE COMPOUNDS HAVING 5-HT4 RECEPTOR AGONISTIC ACTIVITY AND 5-HT3 RECEPTOR ANTAGONISTIC ACTIVITY 审中-公开
标题翻译：具有5-HT4受体激动活性和5-HT3受体拮抗活性的吡嗪类化合物
公开(公告)号：WO2004094418A1
公开(公告)日：2004-11-04
申请号：PCT/IB2004/001269
申请日：2004-04-13
申请人： PFIZER INC. , PFIZER JAPAN, INC. , NOGUCHI, Hirohide , UCHIDA, Chikara
发明人： NOGUCHI, Hirohide , UCHIDA, Chikara
IPC分类号： C07D471/04
CPC分类号： C07D471/04
摘要： This invention provides a compound of the formula (I): wherein R 1 represents a hydrogen atom or a halogen atom; R 2 represents a methyl group or an ethyl group; or pharmaceutically acceptable salts thereof. These compounds have 5-HT 4 receptor agonistic activity and 5-HT 3 receptor antagonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome, diabetes or the like in mammalian, especially humans. The present invention also relates to a pharmaceutical composition, a method of treatment and use, comprising the above compounds.
摘要翻译：本发明提供式（I）的化合物：其中R 1表示氢原子或卤素原子; R 2表示甲基或乙基; 或其药学上可接受的盐。这些化合物具有5-HT 4受体激动活性和5-HT 3受体拮抗活性，因此可用于治疗哺乳动物特别是人类的胃食管反流病，非溃疡性消化不良，功能性消化不良，肠易激综合征，糖尿病等。本发明还涉及包含上述化合物的药物组合物，治疗和使用方法。

9. 发明申请

WO2003057688A3 OXO OR OXY-PYRIDINE COMPOUNDS AS 5-HT4 RECEPTOR MODULATORS 审中-公开
公开(公告)号：WO2003057688A3
公开(公告)日：2003-07-17
申请号：PCT/IB2002/005600
申请日：2002-12-20
申请人： PFIZER PHARMACEUTICALS INC. , PFIZER INC. , UCHIDA, Chikara , MIHARA, Sachiko , MORITA, Mikio , KAWAMURA, Kiyoshi , NUKUI, Seiji , STOBIE, Alan , GYMER, Geoffrey, Edward
发明人： UCHIDA, Chikara , MIHARA, Sachiko , MORITA, Mikio , KAWAMURA, Kiyoshi , NUKUI, Seiji , STOBIE, Alan , GYMER, Geoffrey, Edward
IPC分类号： C07D401/12
摘要： This invention provides compounds of the formula (I) and (II) or the phannaceutically acceptable esters thereof, and the pharmaceutically acceptable salts thereof: wherein R 1 is hydrogen or halo; R 2 and R 3 are independently hydrogen or C 1-6 alkyl; R 4 and R 5 are independently hydrogen or C 1-6 alkyl; R 6 is hydrogen, C l-12 alkyl, C 1-6 alkoxy (C 1-6 )alkyl or C 1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of C 3-8 cycloalkyl, aryl, heteroaryl and heterocyclic; R 7 and R 8 are hydrogen or taken together may form alkylene chain having one or two carbon atoms; R 9 is C 1-6 alkyl or C 3-8 cycloalkyl; R 10 is C 1-6 alkyl or NR 11 R 12 ; L is (CR 11 R 12 )n or NR 11 ; M is NR 11 or (CR 11 R 12 )n ; R 11 and R 12 are independently hydrogen or C 1-6 alkyl; n is an integer from 0 to 5; and. m is an integer from 0 to 2; said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo and C 1-6 alkyl; with the proviso that when R 9 is C 1-6 alkyl, L is not NR 11 . These compounds have 5-HT 4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.

10. 发明申请

WO2006090224A1 BENZISOXAZOLE DERIVATIVES 审中-公开
标题翻译：苯并噻唑衍生物
公开(公告)号：WO2006090224A1
公开(公告)日：2006-08-31
申请号：PCT/IB2006/000313
申请日：2006-02-15
申请人： PFIZER JAPAN INC. , PFIZER INC. , NOGUCHI, Hirohide , SAKURADA, Isao , UCHIDA, Chikara , WAIZUMI, Nobuaki
发明人： NOGUCHI, Hirohide , SAKURADA, Isao , UCHIDA, Chikara , WAIZUMI, Nobuaki
IPC分类号： C07D413/12 , C07D413/14 , A61K31/454 , A61P9/00 , A61P25/00 , A61P25/28
CPC分类号： C07D413/12 , C07D413/14
摘要： This invention relates to compounds of the formula (I): wherein A, B, R 1 , R 4 , m, and n are each as described herein or a pharmaceutically acceptable salt thereof, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5-HT 4 receptor activity such as, but not limited to, gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central 10 nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders such as cardiac failure and heart arrhythmia, diabetes and apnea syndrome.
摘要翻译：本发明涉及式（I）化合物：其中A，B，R 1，R 4，m和n各自如本文所述，或药学上可接受的其盐和含有这些化合物的组合物以及这些化合物在治疗5-HT 4受体活性介导的病症中的用途，例如但不限于胃食管反流病，胃肠道疾病，胃动力障碍，非溃疡性消化不良，功能性消化不良，肠易激综合征（IBS），便秘，消化不良，食管炎，胃食管疾病，恶心，中枢10神经系统疾病，阿尔茨海默病，认知障碍，呕吐，偏头痛，神经系统疾病，疼痛，心血管疾病如心力衰竭和心律失常，糖尿病和呼吸暂停综合征。

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