94497-51-5

• 常用中文名：他米巴罗汀
• 常用英文名：Tamibarotene
• CAS号：94497-51-5
• 分子式：C₂₂H₂₅NO₃
• 分子量：351.439
• 相关类别： 生物化工 抑制剂 代谢(Metabolism) Retinoid Receptor 激动剂
• 发布时间：2018-08-08 13:08:57
• 更新时间：2024-01-02 11:06:20
• Tamibarotene是视黄酸受体α/β (RARα/β)的激动剂,比RARγ的选择性高。

名称

• 中文名: 他米巴罗汀
• 英文名: tamibarotene
• 中文别名: 4-[(5,5,8,8-四甲基-6,7-二氢萘-2-基)氨基甲酰]苯甲酸
• 英文别名: 4-[(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbamoyl]benzoic acid; 4-[(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl]benzoic acid; 4-((5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl)benzoic acid; 4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]benzoic acid; tamibarotene; Benzoic acid, 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]carbonyl]-

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 449.6±45.0 °C at 760 mmHg
• 熔点: 231-232ºC
• 分子式: C₂₂H₂₅NO₃
• 分子量: 351.439
• 闪点: 225.7±28.7 °C
• 精确质量: 351.183441
• PSA: 66.40000
• LogP: 6.48
• 外观性状: 结晶固体
• 蒸汽压: 0.0±1.2 mmHg at 25°C
• 折射率: 1.593
• 储存条件: 室温，干燥
• 计算化学:

  1.疏水参数计算参考值（XlogP）:5.4

  2.氢键供体数量:2

  3.氢键受体数量:3

  4.可旋转化学键数量:3

  5.互变异构体数量:2

  6.拓扑分子极性表面积66.4

  7.重原子数量:26

  8.表面电荷:0

  9.复杂度:546

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

• 更多:

  1. 性状：未确定

  2. 密度（g/mL,25℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：231-232

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC，13mmHg）：未确定

  7. 折射率(n20/D)：未确定

  8. 闪点（ºC）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（mmHg,20ºC）：未确定

  12. 饱和蒸气压（kPa,25ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：未确定

生物活性

• 描述: Tamibarotene是视黄酸受体α/β (RARα/β)的激动剂,比RARγ的选择性高。
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> RAR/RXR
  研究领域 >> 癌症
• 靶点:

  RARα/β[1]

• 体外研究: 他米巴罗汀(20,40μM)下调T细胞淋巴瘤细胞中细胞周期基因的表达。他米巴罗汀(5μM)使RARA过表达细胞中的RARE活性增加到比RARAlow细胞更大的程度。此外,RARAwt过表达增加了他米巴罗汀治疗引起的CDK2,CDK4和CDK6抑制的程度[1]。他米巴罗汀直接逆转转化生长因子-β1处理的真皮成纤维细胞的促纤维化表型,抑制内皮细胞中ICAM-1的表达,并促进体外M1巨噬细胞分化[2]。他米巴罗汀(4μM)在VSMC中剂量依赖性地上调apelin mRNA和蛋白质水平。在Tamibarotene刺激后,RARα(视黄酸受体α)通过与KLF5和Sp1相互作用而募集到apelin启动子,预先与apelin启动子的TCE位点结合,形成转录激活复合物,随后导致apelin表达的上调。在VSMC中。 KLF5和Sp1通过它们与apelin启动子上的TCE直接结合,共同介导他米巴罗汀诱导的apelin表达[4]。
• 体内研究: 他米巴罗汀(1mg/kg /天)分别显着减弱博来霉素(BLM)处理的小鼠和紧致皮肤1小鼠的皮肤和皮下纤维化。一致地,他米巴罗汀显着抑制与组织纤维化相关的各种分子的表达,包括转化生长因子-β1,结缔组织生长因子,IL-4,IL-10,IL-13,IL-17A,肿瘤坏死因子-α,IFN -γ和BLM处理小鼠的损伤皮肤中的单核细胞趋化蛋白1。此外,Tamibarotene降低效应T细胞的比例,同时增加BLM处理小鼠引流淋巴结中CD4 + T细胞中幼稚T细胞的比例[2]。与未治疗的小鼠相比,他米巴罗汀(2.5mg/kg,口服)不会导致牙周炎攻击小鼠的AST,ALT或ALP血清水平的任何显着改变。他米巴罗通改善牙槽骨吸收,显着减少小鼠牙龈卟啉单胞菌诱导的破骨细胞数量。与EPD小鼠相比,他米巴罗汀可测量地增加CD4 + Foxp3 + Treg细胞的百分比。他米巴罗汀还有效降低牙龈卟啉单胞菌感染的牙龈组织和CLN中CD4 + ROR-γt+(Th17)细胞的表达[3]。他米巴罗汀(1 mg/kg,po)可增加大鼠球囊损伤动脉的apelin表达,与培养的VSMCs结果一致[4]。在老年SAMP8小鼠中,在施用他米巴罗汀(1mg/kg /天)后海马ADAM10水平改善。在Tamibarotene给药后,Hes5和Ki67恢复,空间工作记忆也得到改善[5]。
• 细胞实验: CellTiter水性非放射性细胞增殖测定试剂盒用于评估细胞生长。简言之，将每孔10,000个细胞接种在96孔板中，并在含有2％活性炭剥离的FBS的RPMI中培养，并指示类视黄醇浓度72小时。在处理期结束时，加入MTS试剂，将细胞再孵育2-4小时，并在490纳米下测量吸光度。
• 动物实验: 对于感染，给小鼠口服悬浮液中的磺胺甲恶唑和甲氧苄氨嘧啶10mL去离子水10天，以减少天然菌群并支持牙龈卟啉单胞菌W83的定植。抗生素治疗结束后4天，通过口服接种建立牙周感染，使用悬浮在100μL4％羧甲基纤维素（CMC）中的1010菌落形成单位的牙龈卟啉单胞菌7天。在第一次口服接种后4周对小鼠实施安乐死。将他米巴罗汀（2.5mg / kg）悬浮在0.5％羧甲基纤维素溶液中。每天以0.1mL / 10g体重的体积将药物口服加入食道。在诱导牙周炎之前1小时施用他米巴罗汀，然后按照方案每天给予直至第28天。患有牙周病的对照小鼠接受相同体积的0.5％羧甲基纤维素溶液。每3天测量每只小鼠的体重。
• 参考文献:

  [1]. Wang X, et al. Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma. Oncotarget. 2017 Apr 18;8(16):26245-26255.

  [2]. Toyama T, et al. Tamibarotene Ameliorates Bleomycin-Induced Dermal Fibrosis by Modulating Phenotypes of Fibroblasts, Endothelial Cells, and Immune Cells. J Invest Dermatol. 2016 Feb;136(2):387-98.

  [3]. Jin Y, et al. Tamibarotene modulates the local immune response in experimental periodontitis. Int Immunopharmacol. 2014 Dec;23(2):537-45.

  [4]. Lv XR, et al. Synthetic retinoid Am80 up-regulates apelin expression by promoting interaction of RARα with KLF5 and Sp1 in vascular smooth muscle cells. Biochem J. 2013 Nov 15;456(1):35-46.

  [5]. Kitaoka K, et al. The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice. Neuropharmacology. 2013 Sep;72:58-65.

MSDS

Material Safety Data Sheet Section1. Identification of the substance Product Name: Tamibarotene Synonyms: Section2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section3. Composition/information on ingredients. Ingredient name:Tamibarotene CAS number:94497-51-5 Section4. 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. Section5. 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. Section6. 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. Section7. 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: Section8. 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. Section9. Physical and chemical properties Appearance:Not specified Boiling point:No data No data Melting point: Flash point:No data Density:No data Molecular formula:C22H25NO3 Molecular weight:351.4 Section10. Stability and reactivity Conditions to avoid: Heat, flames and sparks. Materials to avoid: Oxidizing agents. Possible hazardous combustion products: Carbon monoxide, nitrogen oxides. Section11. Toxicological information No data. Section12. Ecological information No data. Section13. 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. Section14. Transportation information Non-harzardous for air and ground transportation. Section15. 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. SECTION 16 - ADDITIONAL INFORMATION N/A

安全

• 危害码 (欧洲): Xi
• 危险品运输编码: NONH for all modes of transport
• 海关编码: 2924299090

合成路线

1446134-13-9 ~89% 94497-51-5

文献：Fang, Weiwei; Deng, Qinyue; Xu, Mizhi; Tu, Tao Organic Letters, 2013 , vol. 15, # 14 p. 3678 - 3681

94497-53-7 ~% 94497-51-5

文献：Journal of Medicinal Chemistry, , vol. 31, # 11 p. 2182 - 2192

110-03-2 ~% 94497-51-5

文献：Journal of Medicinal Chemistry, , vol. 31, # 11 p. 2182 - 2192

6223-78-5 ~% 94497-51-5

文献：Journal of Medicinal Chemistry, , vol. 31, # 11 p. 2182 - 2192

6683-46-1 ~% 94497-51-5

文献：Journal of Medicinal Chemistry, , vol. 31, # 11 p. 2182 - 2192

102121-55-1 ~% 94497-51-5

文献：Journal of Medicinal Chemistry, , vol. 31, # 11 p. 2182 - 2192

92050-16-3 ~% 94497-51-5

文献：Journal of Medicinal Chemistry, , vol. 31, # 11 p. 2182 - 2192

上下游产品

上游产品  6
94497-53-7 110-03-2 6223-78-5 6683-46-1
102121-55-1 92050-16-3
下游产品  1
94497-53-7

海关

海关编码	2924299090
中文概述	2924299090. 其他环酰胺（包括环氨基甲酸酯）（包括其衍生物以及他们的盐）. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:30.0%
申报要素	品名, 成分含量, 用途, 包装
Summary	2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%