5-溴-n-环丙基烟酰胺 | 385382-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-溴-n-环丙基烟酰胺
• 中文别名: 5-溴-N-环丙基尼克酰胺
• 英文名称: 5-bromo-N-cyclopropylnicotinamide
• 英文别名: 5-bromo-N-cyclopropylpyridine-3-carboxamide
• CAS: 385382-48-9
• 化学式: C₉H₉BrN₂O
• mdl: MFCD03017678
• 分子量: 241.087
• InChiKey: SYKDJEARKMRQGE-UHFFFAOYSA-N

物化性质

• 沸点：
  377.9±27.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: N-Cyclopropyl 5-bromonicotinamide
Synonyms: 5-Bromo-N-cyclopropylnicotinamide

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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: N-Cyclopropyl 5-bromonicotinamide
CAS number: 385382-48-9

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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.
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: C9H9BrN2O
Molecular weight: 241.1

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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, hydrogen bromide.

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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

反应信息

• 作为反应物：
  描述：

  5-溴-n-环丙基烟酰胺 在 N-甲基吗啉 、 四(三苯基膦)钯 、 caesium carbonate 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 49.0h， 生成 (R)-5-(4-((1-((4-chloro-3-(trifluoromethyl)phenyl)amino)-1-oxopropan-2-yl)carbamoyl)phenyl)-N-cyclopropylnicotinamide
  参考文献：
  名称：

  以氨基酸为柔性接头的新型 Bcr-AblT315I 抑制剂的设计、合成和生物学评价

  摘要：

  尽管伊马替尼通过 Bcr-Abl 抑制在 CML 治疗中取得了成功，但随着时间的推移，患者会出现获得性耐药性。特别是T315I突变引起的耐药性在临床上仍然是一个挑战。在此，我们开始了一项结构优化活动，旨在基于先前报道的二苯甲酰哌嗪衍生物发现针对 T315I 突变体的新型 Bcr-Abl 抑制剂。我们提出，通过避免与 Ile315 庞大侧链的空间冲突，柔性接头的掺入可以实现对 Bcr-Abl T315I的有效抑制。已经开发和评估了一个包含 28 种以氨基酸为接头的化合物的文库。其中，化合物AA2对 Bcr-Abl WT和 Bcr-Abl T315I的活性最强，以及朝向 Bcr-Abl 驱动的 K562 和 K562R 细胞。进一步的研究表明AA2可以诱导K562细胞凋亡并下调Bcr-Abl的磷酸化。综上所述，氨基酸作为新型柔性接头的化合物表现出一定的抗肿瘤活性，为发现新型 Bcr-Abl 抑制剂克服

  DOI：

  10.1016/j.bmc.2021.116398
• 作为产物：
  描述：

  5-溴烟酸 在 氯化亚砜 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 5-溴-n-环丙基烟酰胺
  参考文献：
  名称：

  Discovery of novel Bcr-Abl inhibitors with diacylated piperazine as the flexible linker

  摘要：

  设计、合成并评估了含有灵活的二酰基哌嗪连接剂的四十种化合物，作为新型的Bcr-Abl抑制剂。

  DOI：

  10.1039/c5ob00430f

文献信息

• Design, synthesis, and biological evaluation of 8-biarylquinolines: A novel class of PDE4 inhibitors
  作者：Michel Gallant、Nathalie Chauret、David Claveau、Stephen Day、Denis Deschênes、Daniel Dubé、Zheng Huang、Patrick Lacombe、France Laliberté、Jean-François Lévesque、Susana Liu、Dwight Macdonald、Joseph Mancini、Paul Masson、Anthony Mastracchio、Donald Nicholson、Deborah A. Nicoll-Griffith、Hélène Perrier、Myriam Salem、Angela Styhler、Robert N. Young、Yves Girard

  DOI：10.1016/j.bmcl.2008.01.004

  日期：2008.2

  of a novel series of 8-biarylquinolines acting as type 4 phosphodiesterase (PDE4) inhibitors is described herein. Prototypical compounds from this series are potent and non-selective inhibitors of the four distinct PDE4 (IC(50)<10 nM) isozymes (A-D). In a human whole blood in vitro assay, they inhibit (IC(50)<0.5 microM) the LPS-induced release of the cytokine TNF-alpha. Optimized inhibitors were evaluated

  本文描述了充当4型磷酸二酯酶（PDE4）抑制剂的一系列新的8-联芳基喹啉系列的结构-活性关系。该系列的典型化合物是四种不同PDE4（IC（50）<10 nM）同功酶（AD）的有效和非选择性抑制剂。在人类全血体外测定中，它们抑制（IC（50）<0.5 microM）LPS诱导的细胞因子TNF-α释放。在清醒的豚鼠中，在卵清蛋白诱导的支气管收缩模型中评估了优化的抑制剂的体内功效。通过在松鼠猴中进行药代动力学研究，评估了它们产生催吐反应的倾向。这项工作已导致鉴定出几种具有优异的体外和体内特性的化合物，其中包括治疗呕吐的良好治疗窗口。
• [EN] 8-(BIARYL) QUINOLINE PDE4 INHIBITORS<br/>[FR] INHIBITEURS DE PDE4 8-(BIARYLE)QUINOLINES
  申请人：MERCK FROSST CANADA INC

  公开号：WO2004000814A1

  公开（公告）日：2003-12-31

  8-(biaryl) quinolines wherein the bi-aryl group at the 8-position is in a meta relationship to the quinoline group, are PDE4 inhibitors useful in the treatment of asthma, chronic bronchitis, chronic obstructive pulmonary disease, eosinophilic granuloma, psoriasis and other benign or malignant proliferative skin diseases, endotoxic shock, laminitis in horses, colic in horses, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, inflammatory arthritis, chronic glomerulonephritis, atopic dermatitis, urticaria, adult respiratory distress syndrome, chronic obstructive pulmonary disease in animals, diabetes insipidus, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, arterial restenosis, ortherosclerosis, atherosclerosis, neurogenic inflammation, pain, cough, rheumatoid arthritis, ankylosing spondylitis, transplant rejection, graft versus host disease, hypersecretion of gastric acid, bacterial, fungal induced sepsis, viral induced sepsis, fungal induced septic shock, viral induced septic shock, inflammation-mediated chronic tissue degeneration, cytokine-mediated chronic tissue degeneration, osteoarthritis, cancer, cachexia, muscle wasting, depression, memory impairment, tumour growth, or cancerous invasion of normal tissues.In another aspect, the present invention is directed to a method of enhancing cognition in a healthy subject comprising administering a safe cognition enhancing amount of phosphodiesterase-4 inhibitor. In particular, this invention is directed to a method of enhancing memory, learning, retention, recall, awareness and judgement in health subjects comprising administering a safe and cognition enhancing amount of a phosphodiesterase-4 inhibitor.

  8-(联苯基)喹啉类化合物，其中在8位的联苯基与喹啉基团呈间位关系，是磷酸二酯酶4抑制剂，在治疗哮喘、慢性支气管炎、慢性阻塞性肺疾病、嗜酸性肉芽肿、牛皮癣和其他良性或恶性增生性皮肤疾病、内毒素休克、马蹄炎、马胃肠炎、脓毒性休克、溃疡性结肠炎、克罗恩病、心肌和脑再灌注损伤、炎症性关节炎、慢性肾小球肾炎、特应性皮炎、荨麻疹、成人呼吸窘迫综合征、动物慢性阻塞性肺疾病、尿崩症、过敏性鼻炎、过敏性结膜炎、春季结膜炎、动脉再狭窄、动脉粥样硬化、动脉粥样硬化、神经源性炎症、疼痛、咳嗽、类风湿性关节炎、强直性脊柱炎、移植排斥反应、移植物抗宿主病、胃酸过多分泌、细菌、真菌诱导的败血症、病毒诱导的败血症、真菌诱导的脓毒性休克、病毒诱导的脓毒性休克、炎症介导的慢性组织退行性变、细胞因子介导的慢性组织退行性变、骨关节炎、癌症、虚弱、肌肉消耗、抑郁症、记忆障碍、肿瘤生长或癌细胞侵袭正常组织。另一方面，本发明涉及一种增强健康受试者认知能力的方法，包括给予安全的增强认知量的磷酸二酯酶4抑制剂。具体而言，本发明涉及一种增强健康受试者记忆、学习、保留、回忆、意识和判断能力的方法，包括给予安全且增强认知量的磷酸二酯酶4抑制剂。
• NEW BICYCLIC DIHYDROISOQUINOLINE-1-ONE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130143863A1

  公开（公告）日：2013-06-06

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A 1 , A 2 , A 3 , A 4 , A 5 and n are as described herein, compositions including the compounds and methods of using the compounds. The compounds are useful, for example, as aldosterone synthase (CYP11B2 or CYP11B1) inhibitors for the treatment or prophylaxis of chronic kidney disease, congestive heart failure, hypertension, primary aldosteronism and Cushing syndrome.

  这项发明提供了具有一般式(I)的新化合物，其中R1、R2、R3、R4、R5、R6、A1、A2、A3、A4、A5和n如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。这些化合物可用作醛固酮合酶（CYP11B2或CYP11B1）抑制剂，用于治疗或预防慢性肾脏疾病、充血性心力衰竭、高血压、原发性醛固酮增多症和库欣综合征。
• 一种羟脯氨酸类肽衍生物及其制备方法和应 用
  申请人：西安交通大学

  公开号：CN109796439B

  公开（公告）日：2020-05-19

  一种羟脯氨酸类肽衍生物及其制备方法和应用，以联苯吡啶为铰链区结合片段，并采用片段药物的设计策略，引入L‑羟脯氨酸为柔性Linker，以构建具有激酶抑制活性的类肽类小分子化合物库，并通过ADP‑Glo等活性试验筛选发现具有Bcr‑Abl激酶抑制活性以及抗肿瘤细胞增殖的类肽类酪氨酸激酶抑制剂。该化合物能够用于制备抗肿瘤药物中，具有抑制Bcr‑Abl、Bcr‑AblT315I激酶活性，并且对K562细胞具有细胞增值抑制活性。引入L‑羟脯氨酸扩展Bcr‑Abl抑制剂结构多样性，活性结果显示脯氨酸的引入对化合物的抑制活性具有一定作用，可以作为Bcr‑Abl酪氨酸激酶抑制剂的新型药效片段。
• 一种含有叔丁基取代的丝氨酸的类肽类化合 物及其制备方法和应用
  申请人：西安交通大学

  公开号：CN109734660B

  公开（公告）日：2020-07-28

  一种含有叔丁基取代的丝氨酸的类肽类化合物及其制备方法和应用，利用酰化、Suzuki偶联、缩合等反应合成目标化合物，并构建了化合物库，该类化合物是具有新型分子结构的Bcr‑Abl小分子酪氨酸激酶抑制剂。本发明采用基于片段的药物设计策略，以联苯吡啶为铰链区结合片段，引入叔丁基取代的L‑丝氨酸为柔性Linker，以构建具有激酶抑制活性的类肽类小分子化合物库，并通过ADP‑Glo的激酶活性筛选发现具有Bcr‑Abl激酶抑制活性的酪氨酸激酶抑制剂。激酶筛选试验表明此类化合物对Abl激酶、T315I突变Abl激酶均具有一定的抑制活性。