公开(公告)号：US09440931B2

公开(公告)日：2016-09-13

申请号：US14734012

申请日：2015-06-09

申请人： Koji Nakamichi ,  Takashi Tosaka

发明人： Koji Nakamichi ,  Takashi Tosaka

IPC分类号： C07D241/20 ,  A61K31/4965

CPC分类号： C07D241/20 ,  A61K31/4965 ,  C07B2200/13

摘要： Form-III crystal of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide and a method of producing the crystal are provided. The Form-III crystal exhibits diffraction peaks in its X-ray powder diffraction spectrum at least at the following angles of diffraction 2θ when the spectrum is obtained by using Cu Kα radiation: 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees, and 23.5 degrees. The Form-III crystal can be produced by crystallizing the subject compound from an ester solvent or an aromatic hydrocarbon solvent. The crystal may be administered as an active ingredient to a subject for the purpose of treating or preventing certain diseases, disorders, and symptoms, or for promoting angiogenesis or gene therapy. The targeted diseases and disorders include transient ischemic attack, diabetic neuropathy, diabetic gangrene, peripheral circulatory disturbance, connective tissue disease, reocclusion/restenosis after percutaneous transluminal coronary angioplasty, arteriosclerosis, thrombosis, hypertension, pulmonary hypertension, and diabetic nephropathy.

摘要翻译： 提供2- {4- [N-（5,6-二苯基吡嗪-2-基）-N-异丙基氨基]丁氧基} -N-（甲基磺酰基）乙酰胺的III型晶体及其制备方法。 当使用CuKα辐射：9.3度，9.7度，16.8度，20.6度和23.5度时，至少在以下衍射角2θ时，III型晶体在X射线粉末衍射光谱中表现出衍射峰 度。 III型晶体可以通过将酯化合物从酯溶剂或芳烃溶剂中结晶来制备。 为了治疗或预防某些疾病，病症和症状，或用于促进血管生成或基因治疗，晶体可作为活性成分施用于受试者。 靶向疾病和病症包括短暂性脑缺血发作，糖尿病性神经病变，糖尿病性坏疽，外周循环障碍，结缔组织病，经皮腔内冠状动脉成形术后的再闭塞/再狭窄，动脉硬化，血栓形成，高血压，肺动脉高压和糖尿病肾病。

公开(公告)号：US20150266830A1

公开(公告)日：2015-09-24

申请号：US14734012

申请日：2015-06-09

申请人： Koji NAKAMICHI ,  Takashi TOSAKA

发明人： Koji NAKAMICHI ,  Takashi TOSAKA

IPC分类号： C07D241/20

CPC分类号： C07D241/20 ,  A61K31/4965 ,  C07B2200/13

摘要： Form-III crystal of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide and a method of producing the crystal are provided. The Form-III crystal exhibits diffraction peaks in its X-ray powder diffraction spectrum at least at the following angles of diffraction 2θ when the spectrum is obtained by using Cu Kα radiation: 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees, and 23.5 degrees. The Form-III crystal can be produced by crystallizing the subject compound from an ester solvent or an aromatic hydrocarbon solvent. The crystal may be administered as an active ingredient to a subject for the purpose of treating or preventing certain diseases, disorders, and symptoms, or for promoting angiogenesis or gene therapy. The targeted diseases and disorders include transient ischemic attack, diabetic neuropathy, diabetic gangrene, peripheral circulatory disturbance, connective tissue disease, reocclusion/restenosis after percutaneous transluminal coronary angioplasty, arteriosclerosis, thrombosis, hypertension, pulmonary hypertension, and diabetic nephropathy.

摘要翻译： 提供2- {4- [N-（5,6-二苯基吡嗪-2-基）-N-异丙基氨基]丁氧基} -N-（甲基磺酰基）乙酰胺的III型晶体及其制备方法。 至少在以下衍射角2θ时，III型晶体在X射线粉末衍射光谱中显示衍射峰; 当使用CuKα辐射获得光谱时：9.3度，9.7度，16.8度，20.6度和23.5度。 III型晶体可以通过将酯化合物从酯溶剂或芳烃溶剂中结晶来制备。 为了治疗或预防某些疾病，病症和症状，或用于促进血管生成或基因治疗，晶体可作为活性成分施用于受试者。 目标疾病和病症包括短暂性脑缺血发作，糖尿病性神经病变，糖尿病性坏疽，外周循环障碍，结缔组织病，经皮腔内冠状动脉成形术后的再闭塞/再狭窄，动脉硬化，血栓形成，高血压，肺动脉高压和糖尿病肾病。

公开(公告)号：US20140155414A1

公开(公告)日：2014-06-05

申请号：US14160699

申请日：2014-01-22

申请人： Hideyuki ITOU ,  Koji NAKAMICHI ,  Takashi TOSAKA

发明人： Hideyuki ITOU ,  Koji NAKAMICHI ,  Takashi TOSAKA

IPC分类号： C07D241/20

CPC分类号： C07D241/20 ,  A61K31/4965 ,  C07B2200/13

摘要： A main object of the present invention is to provide a novel crystal of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide (hereinafter referred to as “compound A”). A Form-I crystal of compound A shows diffraction peaks at 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees in the powder X-ray diffraction spectrum thereof. A Form-II crystal of compound A shows diffraction peaks at 9.0 degrees, 12.9 degrees, 20.7 degrees and 22.6 degrees in the powder X-ray diffraction spectrum thereof. A Form-III crystal of compound A shows diffraction peaks at 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees and 23.5 degrees in the powder X-ray diffraction spectrum thereof.

摘要翻译： 本发明的主要目的是提供2- {4- [N-（5,6-二苯基吡嗪-2-基）-N-异丙基氨基]丁氧基} -N-（甲基磺酰基）乙酰胺（以下简称为 作为“化合物A”）。 化合物A的I型晶体在其粉末X射线衍射光谱中显示9.4度，9.8度，17.2度和19.4度的衍射峰。 化合物A的II型晶体在其粉末X射线衍射光谱中显示9.0度，12.9度，20.7度和22.6度的衍射峰。 化合物A的III型晶体在其粉末X射线衍射光谱中显示出9.3度，9.7度，16.8度，20.6度和23.5度的衍射峰。

公开(公告)号：US20120101276A1

公开(公告)日：2012-04-26

申请号：US13379531

申请日：2010-06-25

申请人： Hideyuki Itou ,  Koji Nakamichi ,  Takashi Tosaka

发明人： Hideyuki Itou ,  Koji Nakamichi ,  Takashi Tosaka

IPC分类号： C07D241/20

CPC分类号： C07D241/20 ,  A61K31/4965 ,  C07B2200/13

摘要： A main object of the present invention is to provide a novel crystal of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide (hereinafter referred to as “compound A”). A Form-I crystal of compound A shows diffraction peaks at 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees in the powder X-ray diffraction spectrum thereof. A Form-II crystal of compound A shows diffraction peaks at 9.0 degrees, 12.9 degrees, 20.7 degrees and 22.6 degrees in the powder X-ray diffraction spectrum thereof. A Form-III crystal of compound A shows diffraction peaks at 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees and 23.5 degrees in the powder X-ray diffraction spectrum thereof.

摘要翻译： 本发明的主要目的是提供2- {4- [N-（5,6-二苯基吡嗪-2-基）-N-异丙基氨基]丁氧基} -N-（甲基磺酰基）乙酰胺（以下简称为 作为“化合物A”）。 化合物A的I型晶体在其粉末X射线衍射光谱中显示9.4度，9.8度，17.2度和19.4度的衍射峰。 化合物A的II型晶体在其粉末X射线衍射光谱中显示9.0度，12.9度，20.7度和22.6度的衍射峰。 化合物A的III型晶体在其粉末X射线衍射光谱中显示出9.3度，9.7度，16.8度，20.6度和23.5度的衍射峰。