(R)-2-吡咯烷硼酸蒎烷二醇酯盐酸盐 | 147208-69-3

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: (R)-2-吡咯烷硼酸蒎烷二醇酯盐酸盐
• 英文名称: (R)-boro-Pro (+)-pinanediol ester hydrochloride
• 英文别名: (1S,2S,3R,5S)-pinanediol L-proline boronate hydrochloride；L-boroPro-pn*HCl；L-boroPro-pn hydrochloride；L-boroPro-pn HCI；(2R)-boroPro-(1S,2S,3R,5S)-pinanediol ester hydrochloride；(2R)-boroPro-(1S,2S,3R,5S)-pinanediol ester HCl salt；boroPro-(1S,2S,3R,5S)-pinanediol ester hydrochloride；(R)-boroPro-(+)-pinanediol*HCl；(R)-2-((3aS,4S,6S,7aR)-3a,5,5-Trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)pyrrolidine hydrochloride；(2R)-2-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pyrrolidine;hydrochloride
• CAS: 147208-69-3
• 化学式: C₁₄H₂₄BNO₂*ClH
• 分子量: 285.622
• InChiKey: OVVMNBVQOPZMPY-AKDYBRCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.43
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  30.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (R)-1H-Pyrrolidine-2-boronic acid, pinanediol ester, HCl
(2R)-2-[(1S,2S,8S)-2,9,9-Trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0{ˆ2,6}]decan-4-yl]pyrrolidine 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: (R)-1H-Pyrrolidine-2-boronic acid, pinanediol ester, HCl
CAS number: 147208-69-3

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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, under −20◦C.
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: C14H25BClNO2
Molecular weight: 285.6

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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：

  (R)-2-吡咯烷硼酸蒎烷二醇酯盐酸盐 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 N-methyl-N-{2-oxo-2-[2-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-pyrrolidin-1-yl]-ethyl}-acetamide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of N-acyl-Gly-, N-acyl-Sar- and N-blocked-boroPro inhibitors of FAP, DPP4, and POP

  摘要：

  The structure-activity relationship of various N-acyl-Gly-, N-acyl-Sar-, and N-blocked-boroPro derivatives against three prolyl peptidases was explored. Several N-acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory activity against fibroblast activation protein (FAP) and prolyl oligopeptidase (POP) and selectivity against dipeptidyl peptidase-4 (DPP4). N-Acyl-Sar-boroPro analogs retained selectivity against DPP4 and potent POP inhibitory activity but displayed decreased FAP inhibitory activity.

  DOI：

  10.1016/j.bmcl.2006.11.072
• 作为产物：
  描述：

  (1S,2S,3R,5S)-pinane-2,3-diyl (N-(1,1-dimethylethoxycarbonyl)pyrrolidin-2-yl)boronate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 12.0h， 以3.2 g的产率得到(R)-2-吡咯烷硼酸蒎烷二醇酯盐酸盐
  参考文献：
  名称：

  肽脯氨酸硼酸作为蛋白酶体抑制剂的合成及生物活性

  摘要：

  基于脯氨酸硼酸作为药效基团在激酶抑制剂中的应用以及我们先前的研究结果，以脯氨酸硼酸为战斗部，使用了两个系列的肽脯氨酸硼酸，二肽脯氨酸硼酸（I）和三肽设计并合成了脯氨酸硼酸（II）。首先评估所有合成的化合物对MGC803细胞的生物学活性，然后选择最佳的化合物II-7来测试其在六种人类肿瘤细胞系上的抗肿瘤谱以及对三个亚基的蛋白酶体抑制作用。结果表明，系列II具有比系列I更好的生物学活性。化合物II-7在细胞和蛋白酶体模型中不仅表现出优异的生物学活性（IC 50值为nM），而且亚单位选择性也好得多。因此，脯氨酸硼酸作为战斗部在蛋白酶体抑制剂的设计中是合理的。

  DOI：

  10.1016/j.bmc.2017.05.049
• 作为试剂：
  描述：

  2-[Phenylmethoxycarbonyl-(1-phenylmethoxycarbonylpyrrolidin-3-yl)amino]acetic acid 、 (R)-2-吡咯烷硼酸蒎烷二醇酯盐酸盐 在 (R)-2-吡咯烷硼酸蒎烷二醇酯盐酸盐 作用下， 生成 (R)-3-(Benzyloxycarbonyl-{2-oxo-2-[(R)-2-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-pyrrolidin-1-yl]-ethyl}-amino)-pyrrolidine-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  WO2008109681A2

  摘要：

  公开号：

文献信息

• [EN] FAP-TARGETED RADIOPHARMACEUTICALS AND IMAGING AGENTS, AND USES RELATED THERETO<br/>[FR] AGENTS D'IMAGERIE ET PRODUITS RADIOPHARMACEUTIQUES CIBLANT LA FAP, ET UTILISATIONS ASSOCIÉES
  申请人：TUFTS COLLEGE

  公开号：WO2021195198A1

  公开（公告）日：2021-09-30

  The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts, which are present in more than 90% of epithelial carcinomas, including pancreatic, colon, and breast cancer. Cancer-associated fibroblasts feature high expression of TAP, which is not detectable in adult normal tissue but is associated with a poor prognosis in cancer patients. The present invention provides small-molecule radiopharmaceutical and imaging agents based on a FAP-specific inhibitor.

  肿瘤基质占据肿瘤质量的很大一部分，是传递诊断和治疗化合物的一个有吸引力的靶点。在这里，重点特别放在一种称为癌相关成纤维细胞的基质细胞亚群上，这种细胞存在于超过90%的上皮癌中，包括胰腺癌、结肠癌和乳腺癌。癌相关成纤维细胞具有高表达TAP的特征，在成人正常组织中无法检测到，但与癌症患者的不良预后相关。本发明提供基于FAP特异性抑制剂的小分子放射性药物和成像剂。
• Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging
  作者：Romana Meletta、Adrienne Müller Herde、Aristeidis Chiotellis、Malsor Isa、Zoran Rancic、Nicole Borel、Simon Ametamey、Stefanie Krämer、Roger Schibli

  DOI：10.3390/molecules20022081

  日期：——

  Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging.

  对动脉粥样硬化斑块的非侵入性成像研究在临床上具有高度优先性，因为早期识别易损斑块可能减少心血管事件的发生。纤维母细胞活化蛋白α（FAP）最近被提出为一种与炎症相关的蛋白酶，参与斑块易损性的过程。在这项研究中，通过定量聚合酶链反应和免疫组化方法，分别调查了人类动脉切除术中取出的颈动脉斑块中FAP mRNA和蛋白水平。合成了一种已发表的基于硼酸的FAP抑制剂MIP-1232，并用碘-125进行了放射性标记。通过与人类颈动脉斑块进行体外自显影，评估了该放射性示踪剂成像斑块的潜力。特异性通过在小鼠中生长的高FAP水平和低FAP水平的异种移植瘤进行评估。目标表达分析显示动脉粥样硬化斑块中的蛋白水平与正常动脉相比略高，这与斑块的易损性相关。在mRNA水平上未发现表达差异。该放射性示踪剂成功生产，并在体外强烈积累于FAP阳性的SK-Mel-187黑色素瘤异种移植瘤中，而在FAP水平低的NCI-H69异种移植瘤中的积累则微不足道。示踪剂与动脉切除组织的结合在斑块和正常动脉中相似，阻碍了其在动脉粥样硬化成像中的应用。
• [EN] HETEROCYCLIC BORONIC ACID COMPOUNDS<br/>[FR] COMPOSÉS HETEROCYCLIQUES D'ACIDE BORONIQUE
  申请人：PHENOMIX CORP

  公开号：WO2005047297A1

  公开（公告）日：2005-05-26

  Dipeptidyl peptidase IV (DPP-IV)-inhibiting compounds are provided that have formula I: wherein n is 1 to 3; X is CH2; S; O; CF2 or C (CH3)2; Z is H; halogen; hydroxyl; (C1-6)alkoxy; (C1-12)alkyl; (C3-12)cycloalkyl; phenyl; or heteroaryl; where the phenyl and heteroaryl groups are optionally mono- or independently plurisubstituted with R7; optionally, X together with an adjacent ring carbon and Z form a fused cyclopropyl; and optionally, one of the bonds in the ring containing X is a double bond; and CriRii, R1, R1, R3, R4 and R5 are as described herein. Methods for preparing these compounds, and methods for treating diabetes, especially Type II diabetes, and other related diseases are described using the compounds of formula I in pharmaceutical compositions which contain these compounds. Pharmaceutical compositions which contain combinations of these compounds with other antidiabetic agents are also described herein.

  提供具有以下式I的二肽酶IV（DPP-IV）抑制化合物：其中n为1至3；X为CH2；S；O；CF2或C（CH3）2；Z为H；卤素；羟基；（C1-6）烷氧基；（C1-12）烷基；（C3-12）环烷基；苯基；或杂环芳基；其中苯基和杂环芳基可以选择性地为单取代或独立地多取代为R7；可选地，X与相邻环碳和Z一起形成融合的环丙基；并且可选地，含有X的环中的一个键为双键；以及CriRii，R1，R1，R3，R4和R5如本文所述。描述了制备这些化合物的方法，以及使用具有这些化合物的配方I中的药物组合来治疗糖尿病，特别是II型糖尿病，以及其他相关疾病的方法，这些药物组合包含这些化合物。还描述了含有这些化合物与其他抗糖尿病药物组合的药物组合。
• COMPOUNDS AND METHODS FOR SELECTIVE INHIBITION OF DIPEPTIDYL PEPTIDASE-IV
  申请人：Campbell Alan David

  公开号：US20060276410A1

  公开（公告）日：2006-12-07

  Compounds that selectively inhibit dipeptidyl peptidase-IV over closely related dipeptidyl peptidases are those of Formula (I): as well as pharmaceutically acceptable salts thereof, cyclic isomers thereof, prodrugs thereof, and solvates thereof, where all the variables are defined herein. These compounds can be used, alone or in combination with other drugs, for the treatment of diabetes and related diseases.

  选择性抑制二肽基肽酶IV而不抑制密切相关的二肽基肽酶的化合物为公式(I)所示，以及其药学上可接受的盐、环异构体、前药和溶剂化物，其中所有变量均在此定义。这些化合物可以单独或与其他药物联合使用，用于治疗糖尿病和相关疾病。
• Synthesis and structure–activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7
  作者：Yi Hu、Lifu Ma、Min Wu、Melissa S. Wong、Bei Li、Sergio Corral、Zhizhou Yu、Tyzoon Nomanbhoy、Senaiet Alemayehu、Stacy R. Fuller、Jonathan S. Rosenblum、Natasha Rozenkrants、Lauro C. Minimo、William C. Ripka、Anna K. Szardenings、John W. Kozarich、Kevin R. Shreder

  DOI：10.1016/j.bmcl.2005.06.075

  日期：2005.10

  The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N'-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs. (c) 2005 Elsevier Ltd. All rights reserved.