2-(4-氧-3,4-二氢邻苯二甲秦)乙酸 | 25947-11-9

• 物质功能分类: 化学试剂 - 有机试剂 - 双环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2-(4-氧-3,4-二氢邻苯二甲秦)乙酸
• 中文别名: (4-氧代-3,4-二氢二氮杂萘-1-基)乙酸；2-(4-羰基-3,4-二氢酞嗪-1-基)乙酸
• 英文名称: 2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid
• 英文别名: 2-(4-oxo-3H-phthalazin-1-yl)acetic acid；1,2-Dihydro-1-oxophthalazin-4-ylacetic acid；(4-Oxo-3,4-dihydrophthalazin-1-yl)acetic acid
• CAS: 25947-11-9
• 化学式: C₁₀H₈N₂O₃
• mdl: MFCD00085017
• 分子量: 204.185
• InChiKey: ZEDQLIHBPGNGEC-UHFFFAOYSA-N

物化性质

• 熔点：
  220 °C
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  78.8
• 氢给体数：
  2
• 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,S36/37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Name:	2-(4-Oxo-3 4-dihydrophthalazin-1-yl)acetic acid 95+% Material Safety Data Sheet
Synonym:
CAS:	25947-11-9

Section 1 - Chemical Product MSDS Name:2-(4-Oxo-3 4-dihydrophthalazin-1-yl)acetic acid 95+% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
25947-11-9	2-(4-Oxo-3,4-dihydrophthalazin-1-yl)ac	95+%	unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 25947-11-9: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: off-white to tan
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 172 - 174 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C10H8N2O3
Molecular Weight: 204

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Oxidizing agents, reducing agents, acid chlorides.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 25947-11-9 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
2-(4-Oxo-3,4-dihydrophthalazin-1-yl)acetic acid - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
No information available.
IMO
No information available.
RID/ADR
No information available.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 25947-11-9: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 25947-11-9 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 25947-11-9 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  2-(4-氧-3,4-二氢邻苯二甲秦)乙酸 在 一水合肼 作用下， 反应 0.5h， 以70%的产率得到2-(4-氧代-3,4-二氢-1-酞嗪)乙酰肼
  参考文献：
  名称：

  Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening

  摘要：

  With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl-phthalazinone acetamide (7114863) increased glucose uptake (EC50 of 0.07 +/- 0.02 mu M) in differentiated skeletal muscle cells in presence of insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-gamma agonist activity thus making it a very interesting scaffold. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.067
• 作为产物：
  描述：

  (4-氧代-3,4-二氢二氮杂萘-1-基)-乙酸乙酯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以44%的产率得到2-(4-氧-3,4-二氢邻苯二甲秦)乙酸
  参考文献：
  名称：

  使用具有二聚体结合模式的变构抑制剂靶向结核分枝杆菌的富马酸水合酶。

  摘要：

  随着结核病（TB）抗生素耐药菌株在全球范围内的日益流行，迫切需要新的靶标来开发具有新作用方式的治疗方法。富马酸水合酶（fumarase）是结核分枝杆菌（Mtb ）柠檬酸循环中的一个脆弱组成部分，是一个可以满足这种未满足需求的代谢目标。结核分枝杆菌延胡索酸酶靶向的一个关键挑战是它与人类同源物的相似性，具有相同的活性位点。先前在结合非保守变构位点的高通量筛选命中中发现了该选择性问题的潜在解决方案。在这项工作中，进行了结构-活性关系研究，并确定了先导系列的进一步结构生物学，提供了具有亚微摩尔抑制的衍生物。此外，针对Mtb的体外筛选确定了具有有效最低抑制浓度的化合物。

  DOI：

  10.1021/acs.jmedchem.9b01203

文献信息

• Discovery and Optimization of Orally Bioavailable Phthalazone and Cinnolone Carboxylic Acid Derivatives as S1P2 Antagonists against Fibrotic Diseases
  作者：Oscar Mammoliti、Koen Jansen、Sandy El Bkassiny、Adeline Palisse、Nicolas Triballeau、Denis Bucher、Brigitte Allart、Alex Jaunet、Giovanni Tricarico、Maxim De Wachter、Christel Menet、Javier Blanc、Vatroslav Letfus、Renata Rupčić、Mario Šmehil、Tanja Poljak、Beatrice Coornaert、Kathleen Sonck、Inge Duys、Ludovic Waeckel、Lola Lecru、Florence Marsais、Catherine Jagerschmidt、Marielle Auberval、Philippe Pujuguet、Line Oste、Monica Borgonovi、Emanuelle Wakselman、Thierry Christophe、Nicolas Houvenaghel、Mia Jans、Bertrand Heckmann、Laurent Sanière、Reginald Brys

  DOI：10.1021/acs.jmedchem.1c01066

  日期：2021.10.14

  effective agents against fibrotic diseases. Our compound collection was mined for molecules possessing substructure features associated with S1P2 activity. The weakly potent indole hit 6 evolved into a potent phthalazone series, bearing a carboxylic acid, with the aid of a homology model. Suboptimal pharmacokinetics of a benzimidazole subseries were improved by modifications targeting potential interactions

  特发性肺纤维化 (IPF) 是一种慢性进行性肺部疾病。目前的治疗只能减缓疾病进展，使新的治疗策略引人注目。越来越多的证据表明，S1P2 拮抗剂可能是对抗纤维化疾病的有效药物。我们的化合物集合被挖掘为具有与 S1P2 活性相关的亚结构特征的分子。弱效吲哚命中6在同源模型的帮助下，演变成一个有效的酞酮系列，带有一个羧酸。基于扩展清除分类系统 (ECCS) 的概念，通过针对与转运蛋白的潜在相互作用的修饰，改善了苯并咪唑子系列的次优药代动力学。作为化学赋能策略的一部分，脚手架跳跃允许快速探索与羧酸相邻的位置。化合物38具有良好的药代动力学和体外效力，在治疗环境中的三种不同的纤维化疾病体内小鼠模型中以 10 mg/kg BID 有效。
• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF FIBROSIS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES DE CEUX-CI DESTINÉS AU TRAITEMENT DE LA FIBROSE
  申请人：GALAPAGOS NV

  公开号：WO2019007696A1

  公开（公告）日：2019-01-10

  The present invention discloses compounds according to Formula (I) Wherein R1, R2, L, A1, A2, A3, Cy and the subscript n are as defined herein. The present invention relates to antagonists compounds of sphingosine 1-phosphate (SIP) receptor, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering the compound of the invention.

  本发明揭示了根据式（I）的化合物，其中R1、R2、L、A1、A2、A3、Cy和下标n的定义如本文所述。本发明涉及拮抗神经酰胺1-磷酸（SIP）受体的化合物，其制备方法，包含这些化合物的药物组合物，以及使用这些化合物进行预防和/或治疗涉及纤维化疾病、炎症性疾病、呼吸道疾病、自身免疫疾病、代谢性疾病、心血管疾病和/或增生性疾病的方法，通过给予本发明的化合物。
• Decarboxylative Aldol-Type Reaction of 2-(Trifluoroacetyl)-1,3-diazoles with Activated Acetic Acids
  作者：Dmitriy Volochnyuk、Pavel Khodakovskiy、Andrey Tolmachev

  DOI：10.1055/s-0028-1087985

  日期：2009.4

  The highly electrophilic ketones 2-(trifluoroacetyl)-1,3-diazoles easily undergo a decarboxylative aldol-type reaction with activated acetic acids to afford heterocyclic trifluoromethyl-substituted alcohols bearing various functionalities. heterocycles - 1,3-diazoles - aldol reactions - trifluoro­methyl compounds - alcohols

  高亲电性酮2-（三氟乙酰基）-1,3-二唑容易与活化的乙酸发生脱羧醛醇型反应，从而得到带有各种官能团的杂环三氟甲基取代的醇。 杂环-1,3-二唑-羟醛反应-三氟甲基化合物-醇
• Potent, orally active aldose reductase inhibitors related to zopolrestat: surrogates for benzothiazole side chain
  作者：Banavara L. Mylari、Thomas A. Beyer、Pamela J. Scott、Charles E. Aldinger、Michael F. Dee、Todd W. Siegel、William J. Zembrowski

  DOI：10.1021/jm00081a006

  日期：1992.2

  broad structure-activity program was undertaken in search of effective surrogates for the key benzothiazole side chain of the potent aldose reductase inhibitor, zopolrestat (1). A structure-driven approach was pursued, which spanned exploration of three areas: (1) 5/6 fused heterocycles such as benzoxazole, benzothiophene, benzofuran, and imidazopyridine; (2) 5-membered heterocycles, including oxadiazole

  为了寻找有效的醛糖还原酶抑制剂zopolrestat（1）的关键苯并噻唑侧链的有效替代物，进行了广泛的结构活性程序。追求结构驱动的方法，该方法涵盖了三个领域的探索：（1）5/6稠合杂环，如苯并恶唑，苯并噻吩，苯并呋喃和咪唑并吡啶；（2）5元杂环，包括带有侧基芳基的恶二唑，恶唑，噻唑和噻二唑，以及（3）苯并噻唑的形式当量的硫代苯胺。在糖尿病并发症的一项急性试验中，发现几种苯并恶唑和1,2,4-恶二唑衍生的类似物是有效的人胎盘醛糖还原酶抑制剂，并且在防止大鼠坐骨神经中山梨醇蓄积方面具有口服活性。3,4-Dihydro-4-oxo-3-[（5，（7-二氟-2-苯并恶唑基）甲基] -1-酞嗪乙酸（124）是苯并恶唑系列中最好的（IC50 = 3.2 x 10（-9）M）; 当口服剂量为10 mg / kg时，它可将山梨醇在大鼠坐骨神经中的蓄积抑制78％。化合物139，3,4-二氢-4-氧代-3-[[[（（2-氟苯基）-1
• Synthesis of Peptide Nucleic Acids Containing Pyridazine Derivatives As Cytosine and Thymine Analogs, and Their Duplexes with Complementary Oligodeoxynucleotides
  作者：Takahito Tomori、Yuya Miyatake、Yuta Sato、Takashi Kanamori、Yoshiaki Masaki、Akihiro Ohkubo、Mitsuo Sekine、Kohji Seio

  DOI：10.1021/acs.orglett.5b00522

  日期：2015.3.20

  Synthesis of peptide nucleic acids (PNAs) is reported with new pyridazine-type nucleobases: 3-aminopyridazine (aPz) and 1-aminophthalazine (aPh) as cytosine analogs, and pyridazin-3-one (PzO) and phthalazin-1-one (PhO) as thymine analogs. The PNAs having an aPz or a PzO formed duplexes with each complementary oligodeoxynucleotide forming a base pair with G or A, respectively, as evaluated by using

  肽核酸（PNA）的合成据报道有新的哒嗪类核碱基：胞嘧啶类似物3-氨基哒嗪（aPz）和1-氨基酞嗪（aPh），以及哒嗪-3-one（Pz O）和酞嗪-1-one （Ph O）作为胸腺嘧啶类似物。通过使用紫外熔解分析和圆二色性（CD）光谱评估，具有aPz或Pz O的PNA形成双链体，每个互补的寡聚脱氧核苷酸分别与G或A形成碱基对。