BOC-D-1,2,3,4-四氢异喹啉-3-羧酸 | 115962-35-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - BOC-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: BOC-D-1,2,3,4-四氢异喹啉-3-羧酸
• 中文别名: (R)-N-Boc-1,2,3,4-四氢异喹啉-3-羧酸；(R)-N-叔丁氧羰基-1,2,3,4-四氢异喹啉-3-羧酸；(R)-N-BOC-1,2,3,4-四氢异喹啉-3-羧酸；(R)-2-(叔丁氧羰基)-1,2,3,4-四氢异喹啉-3-甲酸
• 英文名称: (3R)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: D-N-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinolinoline-3-carboxylic acid；(R)-2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid；N-Boc-D-Tic-OH；(3R)-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 115962-35-1
• 化学式: C₁₅H₁₉NO₄
• mdl: MFCD00143818
• 分子量: 277.32
• InChiKey: HFPVZPNLMJDJFB-GFCCVEGCSA-N

物化性质

• 熔点：
  122-123℃
• 沸点：
  420.18°C (rough estimate)
• 密度：
  1.1311 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933499090
• 危险类别：
  IRRITANT
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Boc-d-tic-oh
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: Boc-d-tic-oh
CAS number: 115962-35-1

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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.
Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
Eye contact:
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.
Storage: Store in closed vessels.

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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
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C15H19NO4
Molecular weight: 277.3

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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

用途

BOC-D-1,2,3,4-四氢异喹啉-3-羧酸可用作有机合成中间体。它可以由（3R）-1,2,3,4-四氢异喹啉-3-羧酸盐酸盐通过Boc保护得到，也可以通过L-Phe与甲醛水溶液及叔丁氧酸酐反应制备。

反应信息

• 作为反应物：
  描述：

  BOC-D-1,2,3,4-四氢异喹啉-3-羧酸 在 吡啶 、 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 ((R)-3-Benzyloxycarbamoyl-3,4-dihydro-1H-isoquinolin-2-yl)-(4-methoxy-phenyl)-phosphinic acid butyl ester
  参考文献：
  名称：

  New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids

  摘要：

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

  DOI：

  10.1021/jm0103211
• 作为产物：
  描述：

  (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸 以54%的产率得到
  参考文献：
  名称：

  KAZMIERSKI, WIESLAW;HRUBY, VICTOR J., TETRAHEDRON, 44,(1988) N 3, 697-710

  摘要：

  DOI：

文献信息

• [EN] COMPOSITION AND METHOD FOR NEUROPEPTIDE S RECEPTOR (NPSR) ANTAGONISTS<br/>[FR] COMPOSITION ET MÉTHODE POUR DES ANTAGONISTES DES RÉCEPTEURS DE NEUROPEPTIDE (NPSR)
  申请人：RES TRIANGLE INST

  公开号：WO2013086200A1

  公开（公告）日：2013-06-13

  Neuropeptide S receptor antagonists are provided that bind in functional assays to neuropeptide S receptors; methods are provided for use of these antagonists in treatment of conditions or disease states that are ameliorated by blocking of the neuropeptide S receptor, including substance abuse and substance abuse relapse; and for use of neuropeptide S receptor antagonists in the manufacture of therapeutics and pro-drugs for therapeutics useful in disease states and conditions sensitive to binding of the neuropeptide S receptor.

  神经肽S受体拮抗剂在与神经肽S受体的功能分析中结合；提供了一种使用这些拮抗剂治疗通过阻断神经肽S受体而改善的状况或疾病状态的方法，包括物质滥用和物质滥用复吸；以及使用神经肽S受体拮抗剂在治疗疾病状态和条件中对神经肽S受体结合敏感的药物和前药的制造中的应用。
• 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。
• A progressive synthetic strategy for class B synergimycins
  作者：Jennifer L. Robinson、Rachel E. Taylor、Lisa A. Liotta、Megan L. Bolla、Enrique V. Azevedo、Irene Medina、Shelli R. McAlpine

  DOI：10.1016/j.tetlet.2004.01.048

  日期：2004.3

  four macrocyclic peptides that are the core structure of class B synergimycins, and the synthesis of a final class B derivative. Our synthetic route to these synergimycin derivatives allows the incorporation of amino acid substitutions at all points in the macrocycle, leading to structurally diverse class B analogs.

  描述了作为B类协同霉素核心结构的四个大环肽的合成，以及最终的B类衍生物的合成。我们对这些协同霉素衍生物的合成途径允许在大环的所有点上引入氨基酸取代，从而导致结构上多样化的B类类似物。
• Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of Lead Compound (3<i>R</i>)-<i>N</i>-[1<i>R</i>)-1-(Cyclohexylmethyl)-2-methylpropyl]-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (CDTic)
  作者：Chad M. Kormos、Pauline W. Ondachi、Scott P. Runyon、James B. Thomas、S. Wayne Mascarella、Ann M. Decker、Hernán A. Navarro、Timothy R. Fennell、Rodney W. Snyder、F. Ivy Carroll

  DOI：10.1021/acs.jmedchem.8b00674

  日期：2018.9.13

  analogues were pure opioid receptor antagonists with no agonist activity. Compounds 1, 8, 9, 13, and 14 (Ke values 0.058–0.64 nM) are highly potent and highly selective for the κ relative to the μ and δ opioid receptors. Favorable calculated physiochemical properties were confirmed in rat PK studies, demonstrating brain penetration for selected compounds 1, 9, and 13. High κ opioid receptor potency and selectivity

  动物药理研究表明，强效和选择性κ阿片受体拮抗剂有可能作为针对抑郁症，焦虑症和药物滥用（鸦片，酒精，尼古丁，可卡因）的药物治疗。我们最近报道了仅含一个碱性胺基团的铅化合物1是一类新型的κ阿片受体拮抗剂。合成类似物，并使用[ 35 S]GTPγS结合试验评估其体外阿片受体拮抗剂特性。所有类似物均为纯阿片受体拮抗剂，无激动剂活性。化合物1，8，9，13，和14（ķ Ë相对于μ和δ阿片受体，κ值为0.058–0.64 nM）对κ是高度有效和高度选择性的。有利计算物理化学性质在大鼠PK研究证实，这表明所选择的化合物的脑渗透1，9和13。高κ阿片受体的效能和选择性，以及对脑部渗透的高度有利的经计算的理化和PK特性，建议应考虑将这些化合物用于进一步开发。