CN108602817A - 二肽基肽酶-iv 抑制剂的苯甲酸盐的晶型 - Google Patents
二肽基肽酶-iv 抑制剂的苯甲酸盐的晶型 Download PDFInfo
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- CN108602817A CN108602817A CN201680075097.XA CN201680075097A CN108602817A CN 108602817 A CN108602817 A CN 108602817A CN 201680075097 A CN201680075097 A CN 201680075097A CN 108602817 A CN108602817 A CN 108602817A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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Abstract
Description
Claims (20)
- 式(1)所示化合物(R)-2-((7-(3-氨基哌啶-1-基)-3,5-二甲基-2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)甲基)苯甲腈的苯甲酸盐的晶型Ⅰ,其特征在于,使用Cu-Kα辐射,以2θ角度表示的X-射线粉末衍射,在7.9±0.2°、11.2±0.2°、15.0±0.2°、17.5±0.2°处有特征峰:
- 如权利要求1所述的晶型Ⅰ,其特征在于,使用Cu-Kα辐射,以2θ角度表示的X-射线粉末衍射,还在10.6±0.2°、16.6±0.2°、18.1±0.2°处有特征峰。
- 如权利要求2所述的晶型Ⅰ,其特征在于,使用Cu-Kα辐射,以2θ角度表示的X-射线粉末衍射,还在7.4±0.2°、14.2±0.2°、23.4±0.2°处有特征峰。
- 如权利要求3所述的晶型Ⅰ,其特征在于,使用Cu-Kα辐射,以2θ角度表示的X-射线粉末衍射,还在8.9±0.2°、20.9±0.2°处有特征峰。
- 如权利要求4所述的晶型Ⅰ,其特征在于,所述X-射线粉末衍射图谱基本如图1所示。
- 如权利要求1所述的晶型Ⅰ,其特征在于,其差示扫描量热分析图在140℃至210℃范围内具有吸热峰。
- 如权利要求1-6中任一项所述的晶型Ⅰ的制备方法,其特征在于,将化合物(R)-2-((7-(3-氨基哌啶-1-基)-3,5-二甲基-2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)甲基)苯甲腈加入到有机溶剂中,升至一定温度,化合物溶解后,滴加一定摩尔比的苯甲酸,维持一定温度,降温,过滤,干燥而得到所述化合物的苯甲酸盐的晶型Ⅰ。
- 如权利要求7所述的制备方法,其特征在于,将化合物(R)-2-((7-(3-氨基哌啶-1-基)-3,5-二甲基-2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)甲基)苯甲腈加入到有机溶剂中,升至40℃-80℃,优选60℃-80℃,更优选60℃,化合物溶解后,滴加所述化合物(R)-2-((7-(3-氨基哌啶-1-基)-3,5-二甲基-2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)甲基)苯甲腈与苯 甲酸的摩尔比小于或等于1:1、优选1:2-1:1、更优选1:1的苯甲酸,维持40℃-80℃,优选60℃-80℃,更优选60℃,降温,优选降温至室温,过滤,干燥而得到所述化合物的苯甲酸盐的晶型Ⅰ。
- 如权利要求7-8中任一项所述的制备方法,其特征在于,所述有机溶剂选自醇类、酯类、酮类、醚类或者腈类。
- 如权利要求9所述的制备方法,其特征在于,所述醇类为含有至少4个碳原子的醇类,优选正丁醇、异丁醇、正戊醇、异戊醇、正已醇、异己醇、戊二醇、异戊二醇、已二醇、异已二醇,更优选异戊醇。
- 如权利要求9所述的制备方法,其特征在于,所述酯类为甲酸甲酯、甲酸乙酯、甲酸丙酯、甲酸异丙酯、乙酸甲酯、乙酸乙酯、乙酸丙酯、乙酸异丙酯、丙酸甲酯、丙酸乙酯、丙酸丙酯、丙酸异丙酯、乙酸丁酯、乙酸异丁酯,优选乙酸乙酯、乙酸异丙酯。
- 如权利要求9所述的制备方法,其特征在于,所述酮类为丙酮、丁酮、戊酮、甲基丁基酮、甲基异丁基酮,优选丙酮、丁酮。
- 如权利要求9所述的制备方法,其特征在于,所述醚类为异丙醚、甲基叔丁基醚、乙基叔丁基醚、甲基叔戊基醚,优选甲基叔丁基醚。
- 如权利要求9所述的制备方法,其特征在于,所述腈类为乙腈。
- 药物组合物,其含有如权利要求1-6中任一项所述的式(1)所示化合物的苯甲酸盐的晶型Ⅰ以及一种或多种药用载体,所述药物组合物为药学上可接受的任一剂型。
- 权利要求1-6中任一项所述的式(1)化合物的苯甲酸盐的晶型Ⅰ在制备用于治疗和/或预防非胰岛素依赖型糖尿病、高血糖、高血脂、胰岛素抗性疾病的药物中的应用。
- 治疗和/或预防非胰岛素依赖型糖尿病、高血糖、高血脂、胰岛素抗性疾病的方法,包括向需要其的患者施用有效量的权利要求1-6中任一项所述的式(1)化合物的苯甲酸盐的晶型Ⅰ。
- 权利要求1-6中任一项所述的式(1)化合物的苯甲酸盐的晶型Ⅰ,用于治疗和/或预防非胰岛素依赖型糖尿病、高血糖、高血脂、胰岛素抗性疾病。
- 式(1)所述的化合物(R)-2-((7-(3-氨基哌啶-1-基)-3,5-二甲基-2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)甲基)苯甲腈的苯甲酸盐的晶型Ⅱ,其特征在于,使用Cu-Kα辐射,以2θ角度表示的X-射线粉末衍射,在5.7±0.2°、6.2±0.2°、9.6±0.2°、11.5±0.2°、12.5±0.2°、16.1±0.2°、21.2±0.2°、22.7±0.2°、23.4±0.2°、25.3±0.2°处有特征峰:
- 式(1)所述的化合物(R)-2-((7-(3-氨基哌啶-1-基)-3,5-二甲基-2-氧代-2,3-二氢-1H-咪唑并[4,5-b]吡啶-1-基)甲基)苯甲腈的苯甲酸盐的晶型Ⅲ,其特征在于,使用Cu-Kα辐射,以2θ角度表示的X-射线粉末衍射,在5.7±0.2°、9.6±0.2°、11.5±0.2°、13.0±0.2°、16.5±0.2°、17.9±0.2°、19.5±0.2°、20.6±0.2°、22.7±0.2°、23.4±0.2°处有特征峰:
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CN201510990347X | 2015-12-24 | ||
PCT/CN2016/111445 WO2017107945A1 (zh) | 2015-12-24 | 2016-12-22 | 二肽基肽酶-iv抑制剂的苯甲酸盐的晶型 |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US20090306379A1 (en) * | 2006-09-13 | 2009-12-10 | Takeda Pharmaceutical Company Limited | POLYMORPHS OF BENZOATE SALT OF 2-[[6-[(3r)-3-AMINO-1- PIPERIDINYL]-3,4-DIHYDRO-3- METHYL-2,4-DIOXO-1(2H)-PYRIMIDINYL]METHYL]-BENZONITRILE AND METHODS OF USE THEREFORE |
CN102127072A (zh) * | 2010-01-15 | 2011-07-20 | 山东轩竹医药科技有限公司 | 吡啶并环衍生物 |
CN102863440A (zh) * | 2011-07-09 | 2013-01-09 | 山东轩竹医药科技有限公司 | 二肽基肽酶-iv抑制剂的盐的晶型 |
WO2013046229A1 (en) * | 2011-09-26 | 2013-04-04 | Hetero Research Foundation | Novel salts of alogliptin |
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- 2016-12-22 CN CN201680075097.XA patent/CN108602817B/zh active Active
- 2016-12-22 WO PCT/CN2016/111445 patent/WO2017107945A1/zh active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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US20090306379A1 (en) * | 2006-09-13 | 2009-12-10 | Takeda Pharmaceutical Company Limited | POLYMORPHS OF BENZOATE SALT OF 2-[[6-[(3r)-3-AMINO-1- PIPERIDINYL]-3,4-DIHYDRO-3- METHYL-2,4-DIOXO-1(2H)-PYRIMIDINYL]METHYL]-BENZONITRILE AND METHODS OF USE THEREFORE |
CN102127072A (zh) * | 2010-01-15 | 2011-07-20 | 山东轩竹医药科技有限公司 | 吡啶并环衍生物 |
WO2011085643A1 (zh) * | 2010-01-15 | 2011-07-21 | 山东轩竹医药科技有限公司 | 吡啶并环衍生物 |
CN102863440A (zh) * | 2011-07-09 | 2013-01-09 | 山东轩竹医药科技有限公司 | 二肽基肽酶-iv抑制剂的盐的晶型 |
WO2013046229A1 (en) * | 2011-09-26 | 2013-04-04 | Hetero Research Foundation | Novel salts of alogliptin |
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