6-Boc-2-氨基-7,8-二氢-5H-吡啶并[4,3-d]嘧啶 | 869198-95-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 6-Boc-2-氨基-7,8-二氢-5H-吡啶并[4,3-d]嘧啶
• 中文别名: 2-氨基-7,8-二氢吡啶并[4,3-D]嘧啶-6(5H)-羧酸叔丁酯
• 英文名称: 6-t-butoxycarbonyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-ylamine
• 英文别名: 6-(tert-butoxycarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine；tert-butyl 2-amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylate；tert-butyl 2-amino-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate
• CAS: 869198-95-8
• 化学式: C₁₂H₁₈N₄O₂
• mdl: MFCD08447402
• 分子量: 250.301
• InChiKey: PGNLVGKPNUNOJE-UHFFFAOYSA-N

物化性质

• 熔点：
  170-172°
• 沸点：
  443.7±55.0 °C(Predicted)
• 密度：
  1.231

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.583
• 拓扑面积：
  81.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: tert-Butyl 2-amino-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: tert-Butyl 2-amino-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate
CAS number: 869198-95-8

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C12H18N4O2
Molecular weight: 250.3

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用广泛的是6-Boc-2-氨基-7,8-二氢-5H-吡啶并[4,3-d]嘧啶，它可用作有机合成中间体和医药中间体，广泛应用于实验室研发过程及化工生产中。

制备过程中，在50 ml圆底烧瓶中加入1-叔丁基-3-((二甲氨基)亚甲基)-4-羰基哌啶-1-羧酸酯、碳酸胍和20 ml乙二醇，采用微波辐射反应5～10分钟。通过薄层色谱监测反应进程，待反应完成后冷却，将反应液倒入冰水中，静置过夜后进行抽滤并用清水洗涤。最终产物经过95％乙醇重结晶，得到化合物2-氨基-7,8-二氢吡啶并[4,3-D]嘧啶-6(5H)-羧酸叔丁酯。

反应信息

• 作为反应物：
  描述：

  6-Boc-2-氨基-7,8-二氢-5H-吡啶并[4,3-d]嘧啶 在 盐酸 、 N,N-二异丙基乙胺 、 cesium fluoride 作用下， 以 1,4-二氧六环 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 39.0h， 生成 ethyl 6-(5'-chloro-3,5-dimethyl-2,4'-bipyridin-2'-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-ylcarbamate
  参考文献：
  名称：

  [EN] HEDGEHOG PATHWAY SIGNALING INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF
  [FR] INHIBITEURS DE LA VOIE SIGNALISATION HEDGEHOG ET LEURS APPLICATIONS THÉRAPEUTIQUES

  摘要：

  刺猬（Hh）信号通路是一条在胚胎发育过程中调节图案形成、生长和细胞迁移的通路，但在成年后仅限于组织维护和修复。抑制性通路组分的突变失活导致刺猬信号通路的成熟配体无关激活，导致基底细胞癌和髓母细胞瘤等癌症的发生。刺猬信号的配体依赖性激活参与前列腺癌、胰腺癌、乳腺癌和血液癌的发生。因此，抑制异常的刺猬信号代表了一种有前途的新型抗癌疗法。该发明提供了一种抑制刺猬通路信号的化合物I的新分子，并为治疗恶性肿瘤（基底细胞癌、髓母细胞瘤、胶质母细胞瘤、非小细胞肺癌、前列腺癌、胰腺癌、血液癌、间叶细胞癌等）、预防肿瘤再生长、增强放疗和化疗的敏感性以及其他疾病（炎症、纤维化和免疫紊乱）的治疗应用。

  公开号：

  WO2014113191A1
• 作为产物：
  描述：

  7,8-二氢-2-(甲磺酰基)吡啶并[4,3-d]嘧啶-6(5H)-甲酸叔丁酯 在 氨 作用下， 以 叔丁醇 为溶剂， 反应 16.0h， 生成 6-Boc-2-氨基-7,8-二氢-5H-吡啶并[4,3-d]嘧啶
  参考文献：
  名称：

  四氢吡啶并[4,3- d ]嘧啶衍生物作为有效的活体拮抗剂的体内活性的设计，合成及构效关系

  摘要：

  髓母细胞瘤是儿童中最普遍的脑肿瘤之一。异常的刺猬（Hh）通路信号被认为与髓母细胞瘤的发生和发展有关。Vismodegib是第一种基于FDA批准的基于抑制异常刺猬信号转导的癌症疗法，其靶点是平滑化（Smo），这是Hh通路的核心G蛋白偶联受体（GPCR）。尽管vismodegib在肿瘤治疗中显示出有希望的治疗效果，但高剂量下的非线性药代动力学（PK）曲线引起了人们的关注，部分原因是水溶性低。许多患者经历不良事件，例如肌肉痉挛和体重减轻。另外，在用vismodegib治疗期间，肿瘤细胞之间经常产生耐药性。显然迫切需要探索具有增强的效力和功效的新型Smo拮抗剂。通过脚手架跳跃策略，我们确定了一系列新型的四氢吡啶并[4,3-d ]嘧啶衍生物，其显示出对Hh信号传导的有效抑制。其中，在NIH3T3-GRE-Luc报告基因检测中，化合物24的效力是vismodegib的三倍。与vismodegib相比，

  DOI：

  10.1021/acschemneuro.7b00153

文献信息

• NITROGEN-CONTAINING FUSED HETEROCYCLIC COMPOUND, AS WELL AS PREPARATION METHOD, INTERMEDIATE, COMPOSITION AND APPLICATION THEREOF
  申请人：SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

  公开号：US20190010153A1

  公开（公告）日：2019-01-10

  The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.

  本发明公开了一种含氮融合杂环化合物，以及其制备方法、中间体、组合物和应用。本发明的含氮融合杂环化合物如公式(I)所示，以及其药学上可接受的盐、对映体、二对映体、互变异构体、溶剂合物、代谢物或药物前体，在分子水平上对CDK4和CDK6表现出高选择性和高抑制活性，在细胞水平上对乳腺癌细胞表现出优异的抑制活性，并在动物水平上显著抑制与细胞周期依赖性激酶活性相关的肿瘤细胞增殖。该发明还在人类或小鼠肝微粒体中表现出良好的稳定性，没有显著抑制代谢酶，对小鼠和大鼠体内吸收良好，具有高生物利用度和良好的药物可用性。
• 取代的环化合物及其使用方法和用途
  申请人：广东东阳光药业有限公司

  公开号：CN104016979B

  公开（公告）日：2017-05-03

  本发明提供了取代的环化合物及其使用方法和用途。所述化合物为式(I)所示的化合物或式(I)所示化合物的立体异构体、几何异构体、互变异构体、氮氧化物、溶剂化物、代谢产物、药学上可接受的盐或它的前药。本发明还提供了包含所述化合物的药物组合物，所述化合物和所述药物组合物可以调节生物样本内的蛋白激酶活，用于防护、处理、治疗或减轻患者增殖性疾病。
• [EN] SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS CYCLIQUES SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：CALITOR SCIENCES LLC

  公开号：WO2014089324A1

  公开（公告）日：2014-06-12

  The present invention provides novel substituted alkynyl compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明提供了新颖的取代炔基化合物，药用可接受的盐及其制剂，用于调节蛋白酪氨酸激酶活性，并调节细胞活动，如增殖、分化、凋亡、迁移和侵袭。该发明还提供了包括这些化合物的药用可接受的组合物，以及在治疗哺乳动物，特别是人类的增生性疾病中使用这些组合物的方法。
• METHOD OF TREATING CONDITIIONS WITH KINASE INHIBITORS
  申请人：ALLERGAN, INC.

  公开号：US20130237537A1

  公开（公告）日：2013-09-12

  The present invention relates to a method of treating ophthalmic diseases and conditions, e.g. diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, etc., in a subject comprising administering to said subject a therapeutically effective amount of at least one compound of formula I or a prodrug, pharmaceutically acceptable salt, racemic mixtures or enantiomers of said compound. The compounds of formula I are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.

  本发明涉及一种治疗眼科疾病和病况的方法，例如糖尿病视网膜病变、老年性黄斑变性、早产儿视网膜病变等，在一个受试者中，包括向该受试者施用至少一种式I的化合物的治疗有效量，或者该化合物的前药、药学上可接受的盐、拉丁混合物或对映体。式I的化合物能够调节酪氨酸激酶信号传导，以调节、调制和/或抑制异常细胞增殖。
• Piperidylpyrimidine derivatives as modulators of protein kinase inhibitors and of vascular endothelial growth factor receptor 2
  申请人：Allergan, Inc.

  公开号：US09296747B1

  公开（公告）日：2016-03-29

  This invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein X, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. The compounds of Formula I are useful as protein kinase (PK) inhibitors and can be used to treat such diseases as cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders, metabolic diseases inflammatory disorders and neurodegenerative disorders.

  这项发明涉及一种具有以下结构的化合物 或其药学上可接受的盐，其中X、R1、R2、R3、R4、R5、R6和R7如本文所定义。公式I的化合物可用作蛋白激酶（PK）抑制剂，并可用于治疗癌症、血管增生性疾病、纤维化疾病、系膜细胞增生性疾病、代谢性疾病、炎症性疾病和神经退行性疾病。