L-氢化乳清酸 | 5988-19-2

• 物质功能分类: 生物化工 - 核酸类
• 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: L-氢化乳清酸
• 中文别名: 腺苷-5-磷酸(AMP)；鸟苷磷酸二钠盐(GMP)；核苷酸；核糖核酸(酵母)RNA；L-4,5-二氢乳清酸；(S)-2,6-二氧代六氢-4-嘧啶羧酸
• 英文名称: L-dihydroorotic acid
• 英文别名: L-4,5-dihydroorotic acid；(S)-2,6-dioxohexahydropyrimidine-4-carboxylic acid；(S)-dihydroorotic acid；L-dihydroortotic acid；L-hydroorotic acid；dihydroorotic acid；(4S)-2,6-dioxo-1,3-diazinane-4-carboxylic acid
• CAS: 5988-19-2
• 化学式: C₅H₆N₂O₄
• mdl: MFCD00085339
• 分子量: 158.114
• InChiKey: UFIVEPVSAGBUSI-REOHCLBHSA-N

物化性质

• 熔点：
  254-255 °C (dec.)(lit.)
• 沸点：
  283.16°C (rough estimate)
• 密度：
  1.523
• 溶解度：
  DMSO（微溶）、水（微溶、加热、超声处理）
• 物理描述：
  Solid
• 碰撞截面：
  145.44 Ų [M-H]- [CCS Type: DT, Method: stepped-field]
• 稳定性/保质期：
  常温常压下稳定，结晶。它是生物嘧啶如胸腺嘧啶、尿嘧啶、胞嘧啶、羟甲基胞嘧啶的前体。266℃分解。比旋光度为 [α]D25.3 +33.23°(在1%碳酸氢钠溶液中，C=1.992)。具有刺激性。

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

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
• 危险品运输编号：
  NONH for all modes of transport
• 海关编码：
  2934999001
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338
• 储存条件：
  建议存储于0-5℃环境中，避光、阴凉且干燥的地方，并密封保存。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
L-Dihydroorotic acid
Product Name:
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
P302+P352: IF ON SKIN: Wash with soap and water
P321: Specific treatment (see on this label)
P405: Store locked up

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Section 3. Composition/information on ingredients.
L-Dihydroorotic acid
Ingredient name:
CAS number: 5988-19-2

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H6N2O4
Molecular weight: 158.1

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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

性状

核苷酸为白色结晶性粉末。

生理作用

核苷酸（nucleotides，NTs）是一类具有重要生物学功能的小分子，是生物大分子核酸（nucleic acid，NA），即DNA和RNA的前体物，参与了机体内几乎所有的生物化学反应。生物体既可以进行从头合成也可以利用细胞内代谢产物进行补救合成。同时，核苷酸还是人类饮食中的常见组成成分，它们可以被吸收并结合为机体组织的一部分。

由于膳食核苷酸及核酸在被消化、吸收以及体内代谢上有基本相同的代谢途径，生物学作用也十分相似，所以有理由推测，不论是口服核苷酸还是核酸，它们在体内发挥的营养作用是相似的。

应用

调味剂与增味剂

• 作为调味料：鸟苷酸（GMP）、肌苷酸（IMP）等核苷酸属于呈味性核苷酸，除了本身具有鲜味之外，还可以和左旋谷氨酸（味精）组合时提高鲜味。
• 作为调料、汤料的原料使用。

食品添加剂

母乳中含有尿苷酸（UMP）、胞苷酸（CMP）、腺苷酸（AMP）、鸟苷酸（GMP）、肌苷酸（IMP）等多种核苷酸，为提高婴儿的免疫调节功能和记忆力发挥着作用。在欧美、日本等国家生产的婴儿奶粉中均添加了微量核苷酸，也有添加RNA的例子。

医药原料

核苷酸作为医药用途，可抑制尿道发炎。

食品添加剂最大允许使用量与最大允许残留量标准

• 添加剂中文名称：核苷酸
• 允许使用该种添加剂的食品中文名称：婴幼儿配方粉
• 添加剂功能：营养强化剂
• 最大允许使用量（g/kg）：0.12-0.58g/kg（以核苷酸总量计）

生物活性

L-Dihydroorotic acid (L-dihydroorotate) 是嘧啶代谢的中间产物，它是二氢乳清酸脱氢酶（线粒体）的底物。

用途

用作增鲜剂、调味剂，可用于家庭、餐饮业等。

反应信息

• 作为反应物：
  描述：

  L-氢化乳清酸 在 dihydroorotate dehydrogenase 、 二氯异丙醚 、 辅酶Q6 、 Triton X-100 作用下， 以 水 为溶剂， 生成 乳清酸
  参考文献：
  名称：

  Stereoselectivity in the enzymic oxidation and nonenzymic hydrogen-exchange reactions of dihydroorotate

  摘要：

  DOI：

  10.1021/ja00288a036
• 作为产物：
  描述：

  乳清酸 生成 L-氢化乳清酸
  参考文献：
  名称：

  Lieberman; Kornberg, 1953, vol. 12, p. 223,227

  摘要：

  DOI：

文献信息

• [EN] FERROPTOSIS INHIBITORS–DIARYLAMINE PARA-ACETAMIDES<br/>[FR] INHIBITEURS DE FERROPTOSE-DIARYLAMINE PARA-ACÉTAMIDES
  申请人：SIRONAX LTD

  公开号：WO2021175200A1

  公开（公告）日：2021-09-10

  Provided are compounds that inhibit ferroptosis activity, or modulate or inhibit a disease associated with ferroptosis dysregulation, such as neuropathy, ischemia reperfusion injury, acute kidney failure and cancer, including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

  提供了抑制铁死亡活性的化合物，或调节或抑制与铁死亡失调相关的疾病，如神经病、缺血再灌注损伤、急性肾衰竭和癌症，包括相应的磺胺类化合物，以及其药用可接受的盐、水合物和立体异构体。这些化合物用于制备药物组合物，并且用于制备和使用方法，包括以有效剂量的化合物或组合物治疗需要的人，并检测人的健康或状况的改善。
• Structural, Electronic, and Electrostatic Determinants for Inhibitor Binding to Subsites S1 and S2 in SARS-CoV-2 Main Protease
  作者：Daniel W. Kneller、Hui Li、Stephanie Galanie、Gwyndalyn Phillips、Audrey Labbé、Kevin L. Weiss、Qiu Zhang、Mark A. Arnould、Austin Clyde、Heng Ma、Arvind Ramanathan、Colleen B. Jonsson、Martha S. Head、Leighton Coates、John M. Louis、Peter V. Bonnesen、Andrey Kovalevsky

  DOI：10.1021/acs.jmedchem.1c01475

  日期：2021.12.9

  acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins is crucial to battle coronavirus disease 2019 (COVID-19). SARS-CoV-2 main protease (Mpro) is an established drug target for the design of protease inhibitors. We performed a structure–activity relationship (SAR) study of noncovalent compounds that bind in the enzyme’s substrate-binding subsites S1 and S2, revealing structural, electronic

  开发针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 蛋白的小分子抗病毒药物对于对抗 2019 年冠状病毒病 (COVID-19) 至关重要。 SARS-CoV-2 主要蛋白酶 (M pro ) 是设计蛋白酶抑制剂的既定药物靶点。我们对与酶的底物结合亚位点 S1 和 S2 结合的非共价化合物进行了构效关系 (SAR) 研究，揭示了这些位点的结构、电子和静电决定因素。该研究以 M pro与 Mcule-5948770040（化合物1 ）复合的 X 射线/中子结构为指导，其中质子化状态直接可视化。采用虚拟现实辅助结构分析和小分子构建来生成1的类似物。体外酶抑制测定和室温 X 射线结构证明了化学修饰对 M pro抑制的影响，表明（1）维持抑制剂 P1 基团的正确几何形状对于保留与质子化的 His163 的氢键至关重要； (2)优选带正电荷的接头； (3) 亚位点 S2 更喜欢体积较小的适度电负性基团。
• Synthesis and central nervous system actions of thyrotropin-releasing hormone analog containing a dihydroorotic acid moiety
  作者：Mamoru Suzuki、Hiroshi Sugano、Kazuo Matsumoto、Michio Yamamura、Ryuichi Ishida

  DOI：10.1021/jm00170a014

  日期：1990.8

  A series of thyrotropin-releasing hormone (TRH) analogues in which the pyroglutamic acid residue was replaced by (S)-4,5-dihydroorotic acid (Dio-OH) and the related derivatives were prepared. Their central nervous system actions based on spontaneous locomotor activity, antagonistic effect on reserpine-induced hypothermia, and antagonistic effect on pentobarbital anesthesia were evaluated and the structure-activity

  制备了一系列促甲状腺激素释放激素（TRH）类似物，其中焦谷氨酸残基被（S）-4,5-二氢乳清酸（Dio-OH）取代，并且相关衍生物也存在。基于自发运动能力，对利血平诱导的体温过低的拮抗作用以及对戊巴比妥麻醉的拮抗作用，评估了它们的中枢神经系统作用，并讨论了其构效关系。其中，（1-甲基-（（S）-4,5-二氢原基））-L-组氨酸-L-脯氨酰胺（14b）显示出最有效的活性，比TRH的活性高30-90倍。此外，14b的促甲状腺素释放活性比TRH弱约50倍，因此选择了化合物14b（TA-0910）作为有效的候选药物。
• Practical syntheses of optically pure 1- and 3-substituted dihydroorotic acids.
  作者：Mamoru SUZUKI、Hiroshi MAEDA、Kazuhiko KONDO、Hiroshi SUGANO、Kazuo MATSUMOTO

  DOI：10.1248/cpb.37.1764

  日期：——

  Various optically pure 3-substituted dihydroorotic acids (9, 12) were synthesized by the N-alkylation and Mitsunobu reaction of optically active benzyl or tert-butyl dihydroorotate (6, 10), followed by deprotection of the ester group.Moreover, optically pure 1-methyl (16, 17) and 1-ethyl (19) dihydroorotic acids were obtained by an optical resolution method.

  通过对具有光学活性的二氢乳清酸苄酯或叔丁酯（6、10）进行 N-烷基化和三丁反应，然后对酯基进行脱保护，合成了各种光学纯度的 3-取代二氢乳清酸（9、12）。
• Gonadotropin-releasing hormone receptor-targeted paclitaxel-degarelix conjugate: synthesis and <i>in vitro</i> evaluation
  作者：Chenhong Wang、Yongtao Ma、Siliang Feng、Keliang Liu、Ning Zhou

  DOI：10.1002/psc.2769

  日期：2015.7

  degarelix. The in vitro cytostatic effects of the conjugates were determined by a (3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium) (MTS) assay, and the 50% inhibitory concentration value of the conjugates on 3T3 mouse embryonic fibroblast cells were one order of magnitude higher than the 50% inhibitory concentration values of the conjugates on MCF‐7 human breast

  为了增加化学治疗剂的选择性，已经开发了受体介导的肿瘤靶向方法。这里，地加瑞克[的Ac- d -Nal- d -Cpa- d -PAL-SER-APH（大号-Hor） - d -Aph（CBM）-Leu-ILys-亲d -Ala-NH 2]，一种促性腺激素释放激素拮抗剂，被用作紫杉醇（PTX）的靶向部分。合成了五种PTX-degarelix共轭物，其中PTX通过二硫键连接到degarelix序列中的不同位置。在人血清中测定的所有PTX–degarelix结合物的半衰期均大于10小时。荧光成像板读数器测定表明，缀合物LK‐MY‐9和LK‐MY‐10具有与地加瑞克相似的拮抗作用。在体外通过（3-（4,5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑鎓）（MTS）测定确定缀合物的细胞抑制作用结合物对3T3小鼠胚胎成纤维细胞的抑制浓度值为50％，比结合物对MCF

表征谱图