(R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸 | 103733-65-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - α-氨基酸
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸
• 中文别名: D-1,2,3,4-四氢异喹啉-3-羧酸；R-1,2,3,4-四氢异喹啉-3-羧酸
• 英文名称: (3R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: (R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid；D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid；(3R)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid；(3R)-1,2,3,4-tetrahydroisoquinolin-2-ium-3-carboxylate
• CAS: 103733-65-9
• 化学式: C₁₀H₁₁NO₂
• mdl: MFCD00144038
• 分子量: 177.203
• InChiKey: BWKMGYQJPOAASG-SECBINFHSA-N

物化性质

• 熔点：
  320-323 °C (decomp)
• 沸点：
  372.0±42.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)
• 溶解度：
  酸水溶液（微溶），碱水溶液（微溶，超声处理）
• 稳定性/保质期：
  在常温常压下保持稳定，应避免与强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933499090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  密封保存，存放在阴凉干燥处，并远离氧化剂。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: D-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid
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: D-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid
CAS number: 103733-65-9

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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: C10H11NO2
Molecular weight: 177.2

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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

(R)-1,2,3,4-四氢-3-异喹啉羧酸是一种phe类似物，具有生物活性。

反应信息

• 作为反应物：
  描述：

  (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸 在 磺酰氯 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  设计，合成和药理评价的ñ - （5-氯-2,4-二羟基苯甲酰） - （[R ）- ñ -arylmethyl - 1,2,3,4-四氢-3- isoquinolinecarboxamides作为有效的Hsp90抑制剂

  摘要：

  使用不同的芳基甲基取代铅Hsp90抑制剂1（N-（5-氯-2,4-二羟基苯甲酰基）-（R）-N-苄基-1,2,3,4-四氢-3-异喹啉甲酰胺），已开发出三十四种衍生物（10 – 43），并表现出改善的Hsp90抑制和抗增殖活性。SAR分析表明，东南芳基取代明显影响了它们的抗增殖活性，对-吡啶基（41）的表现优于所有其他取代方式。在这方面，选择化合物41作进一步评估。CETSA熔体和ITDRF CETSAHsp90α的（等温剂量反应指纹图谱）曲线进一步证明了41与细胞内Hsp90α产生了强大的相互作用。与铅化合物1相比，Hsp90α- 41配合物的对接和MD精炼显示Tyr139的侧链与41的吡啶部分之间具有良好的H键相互作用，这是首次用于间苯二酚基Hsp90抑制剂。具有广谱抗肿瘤活性，化合物41在人乳腺癌MDA-MB-453细胞系上诱导了时间和剂量依赖性的生长抑制和G0 / G1细胞周期停滞

  DOI：

  10.1016/j.ejmech.2017.11.013
• 作为产物：
  描述：

  benzyl (3R)-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 15.0h， 以90%的产率得到(R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸
  参考文献：
  名称：

  Efficient Synthesis of Racemic and Enantiomerically Pure 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid and Esters

  摘要：

  在碱催化下，1,2-双（卤甲基）苯 1 a 或 b 与 2-（乙酰氨基）丙二酸二乙酯（2）发生环化反应，随后发生脱羧反应和酰胺裂解反应，制备出了外消旋和光学纯的 1,2,3,4-四氢异喹啉-3-羧酸及酯。对映体的分解是通过与(-)-薄荷醇酯化，然后柱层析分离非对映异构体混合物，或通过与扁桃酸分离苄酯的双酯盐，以及碱催化两种酯的皂化反应来实现的。

  DOI：

  10.1055/s-1992-26325

文献信息

• N-Acylphenylalanines and related compounds. A new class of oral hypoglycemic agents
  作者：Hisashi Shinkai、Koji Toi、Izumi Kumashiro、Yoshiko Seto、Mariko Fukuma、Katsuaki Dan、Shigeshi Toyoshima

  DOI：10.1021/jm00119a007

  日期：1988.11

  N-Benzoyl-DL-phenylalanine (1) was found to possess hypoglycemic activity. A series of the analogues of compound 1 were prepared and evaluated for their blood glucose lowering activity. Both the steric effects of the phenylalanine moiety and the effects of variations in the acyl moiety were investigated. This study elucidated some of the structure-activity relationships and led to the development of

  N-苯甲酰基-DL-苯丙氨酸（1）被发现具有降血糖活性。制备了一系列化合物1的类似物，并评估了它们的降血糖活性。研究了苯丙氨酸部分的空间影响和酰基部分变化的影响。这项研究阐明了一些构效关系，并导致了N-（4-乙基苯甲酰基）-D-苯丙氨酸（34）的开发，其效力是初始化合物1的50倍。
• Cyclic tetrapeptides with –SS– bridging between amino acid side chains for potent histone deacetylases’ inhibition
  作者：Toru Arai、Md. Ashraful Hoque、Norikazu Nishino、Hyun-Jung Kim、Akihiro Ito、Minoru Yoshida

  DOI：10.1007/s00726-013-1527-8

  日期：2013.10

  Cyclic depsipeptide FK228 with an intramolecular disulfide bond is a potent inhibitor of histone deacetylases (HDAC). FK228 is stable in blood because of its prodrug function, whose –SS– bond is reduced within the cell. Here, cyclic peptides with –SS– bridges between a variety of amino acids were synthesized and assayed for HDAC inhibition. Cyclic peptide 3, cyclo(-l-amino acid-l-amino acid-l-Val-d-Pro-)

  具有分子内二硫键的环状二肽FK228是组蛋白脱乙酰基酶（HDAC）的有效抑制剂。由于FK228的前药功能，其在细胞内的–SS–键减少，因此在血液中稳定。在这里，合成了在多种氨基酸之间带有–SS–桥的环状肽，并检测了其对HDAC的抑制作用。环肽3，环（ -升-氨基酸升-氨基酸升-Val- d -Pro-），与第一和第二个氨基酸之间的-SS-桥，被发现是一种有效的HDAC抑制剂。环肽7，环（ -升-氨基酸d -氨基酸升-Val- d- Pro-）在第一个和第二个氨基酸之间带有-SS-桥，也是一种有效的HDAC抑制剂。
• Inducible nitric oxide synthase dimerization inhibitors
  申请人：Gahman C. Timothy

  公开号：US20060116515A1

  公开（公告）日：2006-06-01

  The present invention relates to compounds and methods useful as inhibitors of nitric oxide synthase. Certain compounds of the subject invention have the following structural formula: wherein T, X, and Y are independently selected from the group consisting of CR 4 , N, NR 4 , S, and O; U is selected from the group consisting of CR 10 and N; V is selected from the group consisting of CR 4 and N; W and W′ are independently selected from the group consisting of CH 2 , CR 7 R 8 , NR 9 , O, N(O), S(O) q and C(O); n, m and p are independently an integer from 0 to 5; q is 0, 1, or 2; and other substituents are as defined herein. Other compounds of the subject invention have structural formulas as defined herein. Also disclosed herein are pharmaceutical compositions comprising the compounds of the subject invention.

  本发明涉及化合物和方法，用作一氧化氮合酶的抑制剂。本发明的某些化合物具有以下结构式： 其中T、X和Y分别选自CR 4 、N、NR 4 、S和O组成的群；U选自CR 10 和N组成的群；V选自CR 4 和N组成的群；W和W′分别选自CH 2 、CR 7 R 8 、NR 9 、O、N(O)、S(O) q 和C(O)组成的群；n、m和p分别是从0到5的整数；q为0、1或2；其他取代基如本文所定义。本发明的其他化合物具有如本文所定义的结构式。本文还公开了包含本发明化合物的药物组合物。
• [EN] TETRAHYDROISOQUINOLINE DERIVED PRMT5-INHIBITORS<br/>[FR] INHIBITEURS DE PRMT5 DÉRIVÉS DE TÉTRAHYDROISOQUINOLÉINE
  申请人：CTXT PTY LTD

  公开号：WO2016034673A1

  公开（公告）日：2016-03-10

  A compound of formula I wherein: n is 1 or 2: p is 0 or 1; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl.

  式I的化合物，其中：n为1或2；p为0或1；R1可选地为一个或多个卤素或甲基基团；R2a和R2b分别选自以下组：(i) F；(ii) H；(iii) Me；和(iv) CH2OH；R2c和R2d分别选自以下组：(i) F；(ii) H；(iii) Me；和(iv) CH2OH；R3a和R3b分别选自H和Me；R4为H或Me；R5为H或Me；R6a和R6b分别选自H和Me；A为(i)可选地取代的苯基；(ii)可选地取代的萘基；或(iii)可选地取代的C5-12杂环基。
• Metalloprotease inhibitors
  申请人：Adir Et Compagnie

  公开号：US05866587A1

  公开（公告）日：1999-02-02

  Compound of formula (I): ##STR1## in which: m, n, which are identical or different, represent 0, 1 or 2, R.sub.1, R.sub.2, which are identical or different, represent hydrogen, optionally substituted alkyl, aryl, or form with the carbon atom carrying them carbonyl or (C.sub.3 -C.sub.7)cycloalkyl, R.sub.3 represents hydrogen, alkyl, hydroxyl or aryl, R.sub.4 represents any of the groups as defined in the description, X represents --SO.sub.2 --, --CO-- or --SO.sub.2 NH--, R.sub.5 represents optionally substituted alkyl, (C.sub.3 -C.sub.7)cycloalkyl, aryl or heterocyclic, A represents an aryl ring or a heterocycle, its isomers as well as its addition salts with a pharmaceutically acceptable acid or base and medicinal products containing the same are useful as metalloprotease inhibitors.

  化合物的化学式（I）：##STR1## 其中：m，n，相同或不同，表示0，1或2，R.sub.1，R.sub.2，相同或不同，表示氢，可选择地取代的烷基，芳基，或者与携带它们的碳原子形成羰基或（C.sub.3 -C.sub.7）环烷基，R.sub.3表示氢，烷基，羟基或芳基，R.sub.4表示描述中定义的任何基团，X表示--SO.sub.2 --，--CO--或--SO.sub.2 NH--，R.sub.5表示可选择地取代的烷基，（C.sub.3 -C.sub.7）环烷基，芳基或杂环基，A表示芳环或杂环，其异构体以及与药学上可接受的酸或碱形成的加合物盐以及含有它们的药物制剂可用作金属蛋白酶抑制剂。