D-环己基丙氨酸甲酯盐酸盐 | 144644-00-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: D-环己基丙氨酸甲酯盐酸盐
• 中文别名: 3-环己基-D-丙氨酸甲酯盐酸盐
• 英文名称: methyl (R)-2-amino-3-cyclohexylpropanoate hydrochloride
• 英文别名: H-D-Cha-OMe.HCl；methyl (2R)-2-amino-3-cyclohexylpropanoate;hydrochloride
• CAS: 144644-00-8
• 化学式: C₁₀H₁₉NO₂*ClH
• 分子量: 221.727
• InChiKey: YLESODBCBYZUCT-SBSPUUFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22,R41
• 海关编码：
  2922499990
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Cyclohexyl-d-alanine methyl ester, HCl
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: 3-Cyclohexyl-d-alanine methyl ester, HCl
CAS number: 144644-00-8

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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.
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: C10H19NO2.ClH
Molecular weight: 221.7

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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 chloride.

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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：

  D-环己基丙氨酸甲酯盐酸盐 在 水 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 92.5h， 生成 HOCOCH2-D-Cha-Arg-NHBn(4-amidino)
  参考文献：
  名称：

  Design, synthesis, and SAR of a series of activated protein C (APC) inhibitors with selectivity against thrombin for the treatment of haemophilia

  摘要：

  A design strategy was used to identify inhibitors of activated protein C with selectivity over thrombin featured by a basic and/or aromatic functionality for binding to the S2 pocket. Our strongest inhibitor showed an IC50-material value and selectivity for APC vs thrombin similar to a compound previously reported in the literature. However, in contrast to the reference compound, our compound showed a retained coagulant effect of thrombin with increasing substrate concentration in a modified Calibrated Automated Thrombogram (CAT) method. This was likely related to our compound being inactive against FVIIa, while the reference compound showed an IC50 of 8.9 mu M. Thus, the higher selectivity of our compound against all relevant coagulation factors likely explained its higher therapeutic potential in comparison to the reference compound. The data indicate that at least a 100-fold selectivity over other serine proteases in the coagulation cascade will be required for an effective APC inhibitor. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.094
• 作为产物：
  描述：

  D-苯丙氨酸甲酯盐酸盐 在 铑 作用下， 以 甲醇 为溶剂， 以to yield (2R)-2-amino-3-cyclohexyl propanoic acid methyl ester hydrochloride in 97% yield的产率得到D-环己基丙氨酸甲酯盐酸盐
  参考文献：
  名称：

  Hexa- and heptapeptide anaphylatoxin-receptor ligands

  摘要：

  寡肽化合物或寡肽类似物化合物的公式为A-B-D-E-G-J-L-M-Q，是过敏毒素受体的配体，并且在治疗炎症性疾病状态方面非常有用。还公开了过敏毒素受体配体组合物和调节过敏毒素活性的方法。

  公开号：

  US05387671A1

文献信息

• Benzoxazolamines and Benzothiazolamines: Potent, Enantioselective Inhibitors of Leukotriene Biosynthesis with a Novel Mechanism of Action
  作者：Edward S. Lazer、Clara K. Miao、Hin-Chor Wong、Ronald Sorcek、Denice M. Spero、Alex Gilman、Kollol Pal、Mark Behnke、Anne G. Graham

  DOI：10.1021/jm00033a008

  日期：1994.4

  phenylalanine with a cyclohexyl group greatly enhance potency. Several ester bioisosteres that retain potency and enantiomeric selectivity are described. Lead optimization culminated in (S)-N-[2-cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (43b), IC50 0.001 microM. The compounds described are not inhibitors of 5-lipoxygenase but, rather, act at the level of arachidonic acid release.

  描述了一系列抑制白三烯（LT）生物合成的苯并恶唑胺和苯并噻唑胺类似物。最初的铅（S）-N-（苯并噻唑-2-基）苯丙氨酸乙酯（5a）在筛选程序中被发现，该程序可抑制Ca-离子载体-A23187诱导的人多形核白细胞释放LTB4（IC50 0.23 microM ）。通过结构修饰，确定了5-位上的疏水取代基以及苯丙氨酸的苯环被环己基取代极大地增强了效能。描述了几种保留效力和对映异构体选择性的酯类生物甾体。铅优化最终达到（S）-N- [2-环己基-1-（2-吡啶基）乙基] -5-甲基-2-苯并恶唑胺+ ++（43b），IC50 0.001 microM。所述化合物不是5-脂氧合酶的抑制剂，而是
• [EN] BORONIC ACID DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS D'ACIDE BORONIQUE ET LEURS UTILISATIONS
  申请人：INCEPTION 4 INC

  公开号：WO2016100555A1

  公开（公告）日：2016-06-23

  This invention is directed to novel Boronic acid derivatives of Formula I, and pharmaceutically acceptable salts, solvate, solvate of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of Age-related Macular Degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, Wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor ceils. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry -AMD, Wet- AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRA1. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range diseases mediated (in whole or in part) by HTRA1. The compounds of the invention are also useful for inhibiting HTRA1 protease activity in an eye or locus of an arthritis or related condition.

  这项发明涉及一种新型的化学式I的硼酸衍生物，以及在预防（例如，延缓或减少发展风险）和治疗（例如，控制、缓解或减缓进展）老年性黄斑变性（AMD）及眼部相关疾病中有用的药用盐、溶剂化合物、盐的溶剂化合物和其前体。这些疾病包括干性AMD、湿性AMD、地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受细胞的退化。本公开的发明还涉及预防、减缓进展和治疗干性AMD、湿性AMD和地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受细胞的方法，包括：给予所述发明化合物的治疗有效量。本发明的化合物是HTRA1的抑制剂。因此，本发明的化合物在预防和治疗一系列（全部或部分）由HTRA1介导的疾病中有用。本发明的化合物还可用于抑制眼部或关节炎或相关疾病部位中的HTRA1蛋白酶活性。
• [EN] ALIPHATIC PROLINAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE PROLINAMIDE ALIPHATIQUE
  申请人：INCEPTION 4 INC

  公开号：WO2017222917A1

  公开（公告）日：2017-12-28

  This invention is directed to novel aliphatic prolinamide derivatives of Formula I, and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRAl. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRAl. The compounds of the invention are also useful for inhibiting HTRAl protease activity in an eye or locus of an arthritis or related condition.

  这项发明涉及一种新型的脂肪族脯氨酰胺衍生物，其化学式为I，并且包括药学上可接受的盐、溶剂化合物、盐的溶剂化合物和其前药，用于预防（例如，延缓或减少发展风险）和治疗（例如，控制、缓解或减缓进展）与眼睛相关的年龄相关性黄斑变性（AMD）及相关眼部疾病。这些疾病包括干性AMD、湿性AMD、地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受器细胞的退化。本公开的发明还涉及预防、减缓进展和治疗干性AMD、湿性AMD和地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受器细胞的方法，包括：给予所述发明化合物的治疗有效量。本发明的化合物是HTRAl的抑制剂。因此，本发明的化合物在预防和治疗一系列（全部或部分）由HTRAl介导的疾病中具有用途。本发明的化合物还可用于抑制眼部或关节炎或相关疾病部位的HTRAl蛋白酶活性。
• [EN] CARBOCYCLIC PROLINAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE PROLINAMIDE CARBOCYCLIQUES
  申请人：INCEPTION 4 INC

  公开号：WO2017222914A1

  公开（公告）日：2017-12-28

  This invention is directed to novel carbocyclic prolinamide derivatives of Formula (I), and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRA1. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRA1. The compounds of the invention are also useful for inhibiting HTRA1 protease activity in an eye or locus of an arthritis or related condition.

  这项发明涉及一种新型的Formula (I)的碳环脯氨酰胺衍生物，以及在预防（例如，延缓或降低发展风险）和治疗（例如，控制、缓解或减缓进展）与眼睛相关的年龄相关性黄斑变性（AMD）和相关疾病方面有用的药用盐、溶剂化合物、盐的溶剂化合物和前药。这些疾病包括干性AMD、湿性AMD、地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜脉络膜病变以及视网膜或光感受器细胞的退化。本公开的发明还涉及预防、减缓进展和治疗干性AMD、湿性AMD和地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜脉络膜病变以及视网膜或光感受器细胞的方法，包括：给予所述发明的化合物的治疗有效量。本发明的化合物是HTRA1的抑制剂。因此，本发明的化合物在预防和治疗通过HTRA1（全部或部分）介导的广泛疾病方面有用。本发明的化合物还可用于抑制眼睛或关节炎或相关疾病部位的HTRA1蛋白酶活性。
• [EN] AMINO ACID DEPLETION AGENTS AS ANTIPROLIFERATIVE AGENTS<br/>[FR] AGENTS D'APPAUVRISSEMENT EN ACIDES AMINÉS EN GUISE D'AGENTS ANTIPROLIFÉRATIFS
  申请人：UNIV CENTRAL FLORIDA RES FOUND INC

  公开号：WO2020047361A1

  公开（公告）日：2020-03-05

  Novel compounds are described which decrease the intracellular levels of leucine and methionine. Treatment with these amino acid depletion agents affects many metabolic and life processes which rely upon methionine, leucine and their derivatives. Methionine depletion not only inhibits protein synthesis, but also polyamine biosynthesis and significantly reduces intracellular pools of the native polyamines, spermidine and spermine. Since methionine restriction has been shown to mimic caloric restriction in life extension studies across multiple species, these compounds are also expected to extend lifespan by limiting methionine supply.

  描述了几种新的化合物，这些化合物能够降低细胞内亮氨酸和蛋氨酸的水平。使用这些氨基酸剥夺剂影响许多依赖蛋氨酸、亮氨酸及其衍生物的代谢和生命过程。蛋氨酸剥夺不仅抑制蛋白质合成，还抑制聚胺生物合成，并显著减少细胞内天然聚胺，即亚精胺和精胺的池。由于蛋氨酸限制在多个物种的生命延长研究中已被证明可以模仿卡路里限制，因此预计这些化合物通过限制蛋氨酸供应也能延长寿命。