公开(公告)号：US07511041B2

公开(公告)日：2009-03-31

申请号：US10527376

申请日：2003-09-18

申请人： Mitsuyuki Shimada ,  Toshiki Murata ,  Kinji Fuchikami ,  Hideki Tsujishita ,  Naoki Omori ,  Issei Kato ,  Mami Miura ,  Klaus Urbahns ,  Florian Gantner ,  Kevin Bacon

发明人： Mitsuyuki Shimada ,  Toshiki Murata ,  Kinji Fuchikami ,  Hideki Tsujishita ,  Naoki Omori ,  Issei Kato ,  Mami Miura ,  Klaus Urbahns ,  Florian Gantner ,  Kevin Bacon

IPC分类号： A01N43/58 ,  A01N43/60 ,  A61K31/50 ,  A61K31/495 ,  C07D237/26 ,  C07D237/36 ,  C07D241/36 ,  C07D239/00 ,  C07D471/00 ,  C07D471/04 ,  C07D401/04 ,  C07D401/22 ,  C07D487/00 ,  C07D487/04 ,  C07D491/00 ,  C07D495/00 ,  C07D497/00

CPC分类号： C07D471/14 ,  C07D487/04

摘要： The present invention relates to hovel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (PI3K) inhibition, especially for PI3K-γ inhibition and can be used for the prophylaxis and treatment of diseases associated with PI3K and particularly with PI3K-γ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoixnmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to PI3K activity in a human or animal subject.

摘要翻译： 本发明涉及霍夫唑唑吡啶衍生物，其制备方法和含有它们的药物制剂。 本发明的稠合吡唑嘧啶衍生物对于磷脂酰肌醇-3-激酶（PI3K）抑制的效力显着增强，特别是对于PI3K-γ抑制，可用于预防和治疗与PI3K相关的疾病，特别是PI3K-γ活性。 更具体地说，本发明的唑类衍生物可用于治疗和预防以下疾病：炎性和免疫调节性疾病，如哮喘，特应性皮炎，鼻炎，过敏性疾病，慢性阻塞性肺病（COPD），脓毒性休克，关节 疾病，自身免疫性疾病如类风湿性关节炎，格雷夫斯病，癌症，心肌收缩性疾病，心力衰竭，血栓栓塞，缺血和动脉粥样硬化。 本发明的化合物还可用于肺动脉高压，肾衰竭，心脏肥大，以及神经变性疾病如帕金森病，阿尔茨海默病，糖尿病和局灶性缺血，因为这些疾病还涉及人或动物中的PI3K活性 学科。

公开(公告)号：US20060205676A1

公开(公告)日：2006-09-14

申请号：US11240867

申请日：2005-09-30

申请人： Toshiki Murata ,  Masaomi Umeda ,  Sachiko Sakakibara ,  Takashi Yoshino ,  Hiroki Sato ,  Tsutomu Masuda ,  Yuji Koriyama ,  Mitsuyuki Shimada ,  Takuya Shintani ,  Hiroshi Kadono ,  Timothy Lowinger ,  Karl Ziegelbauer ,  Kinji Fuchikami ,  Hiroshi Komura

发明人： Toshiki Murata ,  Masaomi Umeda ,  Sachiko Sakakibara ,  Takashi Yoshino ,  Hiroki Sato ,  Tsutomu Masuda ,  Yuji Koriyama ,  Mitsuyuki Shimada ,  Takuya Shintani ,  Hiroshi Kadono ,  Timothy Lowinger ,  Karl Ziegelbauer ,  Kinji Fuchikami ,  Hiroshi Komura

IPC分类号： A61K31/7052 ,  A61K31/444 ,  A61K31/4436

CPC分类号： C07D213/08 ,  C07D213/10 ,  C07D213/73 ,  C07D213/80 ,  C07D213/85 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D471/08 ,  C07D513/04 ,  C07D515/04

摘要： Pyrimidine compounds of general formula: wherein —R1 represents in which R11 is hydrogen, C1-6 alkyl, halogen, hydroxy, C1-12 alkoxy, nitro, amino, C1-6 alkylsulfonylamino, C1-6 alkoxycarbonyl, C1-6 alkylamino, di (C1-6 alkyl)amino, C1-6 alkanoylamino, phenyl C1-6 alkylamino, phenylsulfonylamino, or —O—(CH2)n—R111; R2 represents hydrogen or halogen; R3 represents hydrogen, —CR31R32R33; R4 is hydrogen, carbamoyl, CN, carboxyl, etc.; R5 is amino, C1-6 alkylamino, di C1-6 alkylamino, etc. or salt thereof. The compound has an excellent anti-inflammatory activity, and other biological activity.

摘要翻译： 其中R 1表示其中R 11为氢，C 1-6烷基，卤素，羟基，C 1 -C 6烷基， 1-12烷氧基，硝基，氨基，C 1-6烷基磺酰基氨基，C 1-6烷氧基羰基，C 1-6烷基， （C 1-6烷基）氨基，C 1-6烷酰基氨基，苯基C 1-6烷基氨基，苯基磺酰基氨基，C 1 -C 6烷基氨基， ，或-O-（CH 2）n - n - R 111; R 2表示氢或卤素; R 3表示氢，-CR 31，32，32，33， R 4是氢，氨基甲酰基，CN，羧基等; R 5是氨基，C 1-6烷基氨基，C 1-6烷基氨基等，或其盐。 该化合物具有优异的抗炎活性和其他生物活性。

公开(公告)号：US20060128732A1

公开(公告)日：2006-06-15

申请号：US10527376

申请日：2003-09-18

申请人： Mitsuyuki Shimada ,  Toshiki Murata ,  Kinji Fuchikami ,  Hideki Tsujishita ,  Naoki Omori ,  Issei Kato ,  Mami Miura ,  Klaus Urbahns ,  florian Gantner ,  Kevin Bacon

发明人： Mitsuyuki Shimada ,  Toshiki Murata ,  Kinji Fuchikami ,  Hideki Tsujishita ,  Naoki Omori ,  Issei Kato ,  Mami Miura ,  Klaus Urbahns ,  florian Gantner ,  Kevin Bacon

IPC分类号： A61K31/519 ,  C07D487/14

CPC分类号： C07D471/14 ,  C07D487/04

摘要： The present invention relates to hovel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (PI3K) inhibition, especially for PI3K-γ inhibition and can be used for the prophylaxis and treatment of diseases associated with PI3K and particularly with PI3K-γ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoixnmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to PI3K activity in a human or animal subject.

公开(公告)号：US07402683B2

公开(公告)日：2008-07-22

申请号：US10512724

申请日：2003-04-14

申请人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Josef Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada ,  Niels Svenstrup ,  Rainer Endermann ,  Peter Nell

发明人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Josef Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada ,  Niels Svenstrup ,  Rainer Endermann ,  Peter Nell

IPC分类号： C07D207/00 ,  C07D215/38 ,  C07D213/00 ,  C07D403/02 ,  C07D231/00 ,  A01N43/36 ,  A01N43/56 ,  A01N43/40 ,  A01N43/42

CPC分类号： C07D207/40 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12

摘要： The present invention relates to compounds, to processes for preparing them, to pharmaceutical compositions comprising them, and to their use in the therapy and/or prophylaxis in illnesses in people or animals, especially diseases of bacterial infection.

摘要翻译： 本发明涉及化合物，其制备方法，包含它们的药物组合物，以及它们在人或动物，特别是细菌感染疾病的治疗和/或预防中的用途。

公开(公告)号：US07045631B2

公开(公告)日：2006-05-16

申请号：US10484133

申请日：2002-07-03

申请人： Ulrich Rosentreter ,  Thomas Kramer ,  Mitsuyuki Shimada ,  Walter Hubsch ,  Nicole Diedrichs ,  Thomas Krahn ,  Kerstin Henninger ,  Johannes-Peter Stasch

发明人： Ulrich Rosentreter ,  Thomas Kramer ,  Mitsuyuki Shimada ,  Walter Hubsch ,  Nicole Diedrichs ,  Thomas Krahn ,  Kerstin Henninger ,  Johannes-Peter Stasch

IPC分类号： C07D213/62 ,  C07D417/12

CPC分类号： C07D417/12 ,  C07D213/85

摘要： Compounds of the formula (I) a process for preparing them, and their use as medicaments are described.

摘要翻译： 描述了式（I）化合物的制备方法及其作为药物的用途。

公开(公告)号：US20090149528A1

公开(公告)日：2009-06-11

申请号：US12217248

申请日：2008-07-02

申请人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Joseph Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada ,  Niels Svenstrup ,  Rainer Endermann ,  Peter Nell

发明人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Joseph Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada ,  Niels Svenstrup ,  Rainer Endermann ,  Peter Nell

IPC分类号： A61K31/4025 ,  C07D207/333 ,  A61P31/04

CPC分类号： C07D207/40 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12

摘要： The present invention relates to compounds, to processes for preparing them, to pharmaceutical compositions comprising them, and to their use in the therapy and/or prophylaxis in illnesses in people or animals, especially diseases of bacterial infection.

摘要翻译： 本发明涉及化合物，其制备方法，包含它们的药物组合物，以及它们在人或动物尤其是细菌感染疾病的治疗和/或预防中的用途。

公开(公告)号：US20060178369A1

公开(公告)日：2006-08-10

申请号：US10512724

申请日：2003-04-14

申请人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Josef Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada ,  Niels Svenstrup ,  Rainer Endermann

发明人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Josef Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada ,  Niels Svenstrup ,  Rainer Endermann

IPC分类号： A61K31/506 ,  A61K31/501 ,  A61K31/497 ,  A61K31/4709 ,  A61K31/4439 ,  A61K31/4245 ,  A61K31/4178 ,  A61K31/4025

CPC分类号： C07D207/40 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12

摘要： The present invention relates to compounds, to processes for preparing them, to pharmaceutical compositions comprising them, and to their use in the therapy and/or prophylaxis in illnesses in people or animals, especially diseases of bacterial infection.

公开(公告)号：US20060100246A1

公开(公告)日：2006-05-11

申请号：US11240728

申请日：2005-09-30

申请人： Toshiki Murata ,  Masaomi Umeda ,  Sachiko Sakakibara ,  Takashi Yoshino ,  Hiroki Sato ,  Tsutomu Masuda ,  Yuji Koriyama ,  Mitsuyuki Shimada ,  Takuya Shintani ,  Hiroshi Kadono ,  Timothy Lowinger ,  Karl Ziegelbauer ,  Kinji Fuchikami ,  Hiroshi Komura

发明人： Toshiki Murata ,  Masaomi Umeda ,  Sachiko Sakakibara ,  Takashi Yoshino ,  Hiroki Sato ,  Tsutomu Masuda ,  Yuji Koriyama ,  Mitsuyuki Shimada ,  Takuya Shintani ,  Hiroshi Kadono ,  Timothy Lowinger ,  Karl Ziegelbauer ,  Kinji Fuchikami ,  Hiroshi Komura

IPC分类号： A61K31/444 ,  A61K31/4436 ,  C07D409/02 ,  C07D401/02

CPC分类号： C07D213/08 ,  C07D213/10 ,  C07D213/73 ,  C07D213/80 ,  C07D213/85 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D471/08 ,  C07D513/04 ,  C07D515/04

摘要： This invention is to provide a process for producing 2-amino-4,6-disubstituted nicotinic acid ester analogs and salts thereof, comprising the reaction shown by the following scheme. The ester analogs can be prepared in one pot, and in good yield by using tertiary alkyl cyanoacetate. Furthermore, the method is useful for preparing derivatives of various analogs of the ester, e.g. alkyl substituted and aryl substituted analogs.

摘要翻译： 本发明提供一种制备2-氨基-4,6-二取代的烟酸酯类似物及其盐的方法，其包括如下方案所示的反应。 酯类似物可以在一锅中制备，并且通过使用氰基乙酸叔烷酯以良好的产率制备。 此外，该方法可用于制备酯的各种类似物的衍生物，例如。 烷基取代和芳基取代的类似物。

公开(公告)号：US07544709B2

公开(公告)日：2009-06-09

申请号：US10496058

申请日：2002-11-07

申请人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Josef Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada

发明人： Nina Brunner ,  Christoph Freiberg ,  Thomas Lampe ,  Ben Newton ,  Michael Otteneder ,  Josef Pernerstorfer ,  Jens Pohlmann ,  Guido Schiffer ,  Mitsuyuki Shimada

IPC分类号： A61K31/4015 ,  C07D207/40

CPC分类号： C07D207/40

摘要： The invention relates to compounds of general formula (I), to a method for the production thereof, to pharmaceutical compositions containing them, and to their use in the treatment and/or prophlaxis of diseases in humans or animals, particularly bacterial infections diseases. The compounds are derivatives of the natural substances andrimide and moiramide B.

摘要翻译： 本发明涉及通式（I）的化合物，其制备方法，含有它们的药物组合物，以及它们在人或动物疾病，特别是细菌感染疾病的治疗和/或前体中的应用。 这些化合物是天然物质和杀虫剂和莫拉滨B的衍生物。

公开(公告)号：US20090048258A1

公开(公告)日：2009-02-19

申请号：US11883357

申请日：2006-01-31

申请人： Masaki Ogino ,  Yoshihisa Nakada ,  Mitsuyuki Shimada ,  Kouhei Asano ,  Norikazu Tamura ,  Minori Masago

发明人： Masaki Ogino ,  Yoshihisa Nakada ,  Mitsuyuki Shimada ,  Kouhei Asano ,  Norikazu Tamura ,  Minori Masago

IPC分类号： A61K31/5375 ,  C07D277/46 ,  A61K31/426 ,  A61K31/167 ,  A61P3/10 ,  A61P3/04 ,  C07C233/11 ,  C07D265/30

CPC分类号： C07D277/46 ,  C07C235/78 ,  C07D207/34 ,  C07D213/75 ,  C07D215/38 ,  C07D231/14 ,  C07D231/38 ,  C07D239/42 ,  C07D295/12 ,  C07D333/36 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

摘要： The present invention relate to a compound represented by the formula (I) or (II) wherein ring A is an optionally substituted ring (the ring should not be pyrrolidine, piperidine and piperazine), ring B is an optionally substituted aromatic ring, ring D is an optionally substituted ring, R1 and R2 are each independently a hydrogen atom or a substituent, R3 is a hydrogen atom or a C1-6 alkyl group, or R3 is bonded to ring A to form a non-aromatic ring, ring Aa is an optionally substituted aromatic hydrocarbon, Y is CH or N, Ra1 is an optionally substituted hydrocarbon group, and Ra2 and Ra3 are each independently a hydrogen atom or a substituent, or a salt thereof. The present invention provides a compound having a DGAT inhibitory activity, which is useful for the treatment or amelioration of diseases or pathologies caused by high expression or high activation of DGAT.

摘要翻译： 本发明涉及由式（I）或（II）表示的化合物，其中环A为任选取代的环（该环不应为吡咯烷，哌啶和哌嗪），环B为任选取代的芳环，环D 是任选取代的环，R 1和R 2各自独立地为氢原子或取代基，R 3为氢原子或C 1-6烷基，或R 3与环A键合形成非芳香环，环A a为 任选取代的芳烃，Y是CH或N，Ra1是任选取代的烃基，Ra2和Ra3各自独立地是氢原子或取代基，或其盐。 本发明提供具有DGAT抑制活性的化合物，其可用于治疗或改善由高表达或高活化DGAT引起的疾病或病理。