丙硫异烟胺 | 14222-60-7

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 抗结核麻风分支杆菌类药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 丙硫异烟胺
• 中文别名: 2-丙基硫代异烟酰胺；硫代异烟酰胺
• 英文名称: prothionamide
• 英文别名: protionamide；2-propylpyridine-4-carbothioamide
• CAS: 14222-60-7
• 化学式: C₉H₁₂N₂S
• mdl: MFCD00464119
• 分子量: 180.274
• InChiKey: VRDIULHPQTYCLN-UHFFFAOYSA-N

物化性质

• 熔点：
  140-143°C
• 沸点：
  310.4±44.0 °C(Predicted)
• 密度：
  1.1015 (rough estimate)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 碰撞截面：
  141.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品运输编号：
  NONH for all modes of transport
• 海关编码：
  2933399090
• RTECS号：
  NS0650000
• 危险类别：
  IRRITANT
• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319
• 储存条件：
  | 冰箱 |

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Protionamide
Synonyms: 3-Propylpyridine-4-thiocarboxamide

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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: Protionamide
CAS number: 14222-60-7

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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: C9H12N2S
Molecular weight: 180.3

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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, sulfur 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

药理作用

丙硫异烟胺是异烟酸的一种衍生物，其具体作用机制尚不明确，可能通过抑制肽类合成发挥作用。本品对结核分枝杆菌的疗效取决于感染部位的药物浓度：在低浓度时具有抑菌作用；而在高浓度时则表现为杀菌作用。此外，该药物与乙硫异烟胺存在部分交叉耐药现象。

药代动力学

丙硫异烟胺口服后胃肠道吸收迅速且完全，约90%的药物被吸收，1至2小时内血药浓度达到峰值。药物广泛分布于机体组织和体液中，并能通过血脑屏障进入脑脊液，也能透过胎盘屏障进入胎儿循环。各组织和体液中的药物浓度几乎与血药浓度相同，有效药物浓度可持续6小时以上，半衰期约为3小时。大部分药物在肝脏代谢后随尿液排出，其中约1%为原型药物，5%为活性代谢物，其余均为无活性代谢产物。

适应症

丙硫异烟胺仅对分枝杆菌具有疗效，常与其他一线抗结核药物（如链霉素、异烟肼、利福平和乙胺丁醇）联合使用，适用于这些一线药物治疗无效的结核病患者。

不良反应

1. 较常见的不良反应包括精神忧郁（中枢神经系统毒性）、腹泻、食欲减退、胃痛、胃部不适、呕吐等（胃肠道紊乱）。
2. 少见的不良反应则涉及步态不稳或麻木、针刺感、烧灼感、手足疼痛（周围神经炎），精神错乱或其他精神改变（中枢神经系统毒性），以及黄疸、肝炎等现象。
3. 极少出现的不良反应包括视力模糊或减退、合并或不合并眼痛（视神经炎）、月经失调或怕冷、性欲减退（男性）、皮肤干燥粗糙、甲状腺功能减退、关节疼痛、僵直肿胀。

用途

丙硫异烟胺具有抑制结核菌和在高浓度时表现出杀菌作用。

反应信息

• 作为反应物：
  描述：

  丙硫异烟胺 在 碘 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以69.9%的产率得到3,5-bis(2-propylpyridin-4-yl)-1,2,4-thiadiazole
  参考文献：
  名称：

  Diarylthiazole: An Antimycobacterial Scaffold Potentially Targeting PrrB-PrrA Two-Component System

  摘要：

  Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE)>0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.

  DOI：

  10.1021/jm500833f
• 作为产物：
  描述：

  4-氰基吡啶 在 ammonium persulfate 、 硫酸 、 silver nitrate 、 magnesium chloride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.41h， 生成 丙硫异烟胺
  参考文献：
  名称：

  Diarylthiazole: An Antimycobacterial Scaffold Potentially Targeting PrrB-PrrA Two-Component System

  摘要：

  Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE)>0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.

  DOI：

  10.1021/jm500833f

文献信息

• [EN] OXAZOLIDINONE COMPOUNDS AND METHODS OF USE THEREOF AS ANTIBACTERIAL AGENTS<br/>[FR] COMPOSÉS OXAZOLIDINONE ET PROCÉDÉS D'UTILISATION DE CES DERNIERS EN TANT QU'AGENTS ANTIBACTÉRIENS
  申请人：MERCK SHARP & DOHME

  公开号：WO2017066964A1

  公开（公告）日：2017-04-27

  The present invention relates to oxazolidinone compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, E, and R1 are as defined herein. The present invention also relates to compositions which comprise at least one oxazolidinone compound of the invention. The invention also provides methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosiscomprising administering a therapeutically effective amount of an oxazolidinone of the invention and/or apharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.

  本发明涉及式(I)的噁唑烷酮化合物及其药学上可接受的盐，其中A、E和R1如本文所定义。本发明还涉及包含本发明至少一种噁唑烷酮化合物的组合物。该发明还提供了抑制分枝杆菌细胞生长的方法，以及通过给予治疗有效量的本发明的噁唑烷酮和/或其药学上可接受的盐，或包含该化合物和/或盐的组合物来治疗结核分枝杆菌感染的方法。
• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• [EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
  申请人：STC UNM

  公开号：WO2018148113A1

  公开（公告）日：2018-08-16

  The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

  本发明涉及13C和/或2H同位素增强的氨溴索（“同位素增强的氨溴索”）及其在治疗自噬感染，特别是结核分枝杆菌和其他感染、疾病状态和/或肺部疾病条件中的用途，如肺结核，特别是包括耐药和多重耐药结核病。包括同位素增强的氨溴索的药物组合物，单独或与额外的生物活性剂（特别是利福霉素类抗生素，包括额外的自噬调节剂（一种能够促进或抑制自噬的剂），因此对抗自噬介导的疾病状态和/或条件有用），特别是在肺部发生的自噬介导的疾病状态和/或条件，例如分枝杆菌感染。慢性阻塞性肺病（COPD）、哮喘、肺纤维化、囊性纤维化、干燥综合征和肺癌（小细胞和非小细胞肺癌等其他肺部疾病状态和/或条件，特别是肺部疾病状态和/或条件。治疗自噬疾病状态和/或条件的方法，特别包括治疗主要发生在患者肺部的自噬疾病状态或条件的方法，代表本发明的另一实施例。另一实施例包括根据本发明在此披露的其他方法合成化合物的方法。
• COMPOUNDS HAVING A POTENTIATING EFFECT ON THE ACTIVITY OF ETHIONAMIDE AND USES THEREOF
  申请人：Deprez Benôit

  公开号：US20110136823A1

  公开（公告）日：2011-06-09

  The present invention relates to the use of compounds with a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, for the preparation of a medicament for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy, to pharmaceutical compositions comprising them in combination with an antibiotic that is activatable via the EthA pathway, to compounds having a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, to pharmaceutical compositions comprising them and to their use as medicaments, especially medicaments for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy.

  本发明涉及具有增强抗生素活性的化合物，这些抗生素通过EthA酶途径可激活，用于制备预防和/或治疗如结核病和麻风病等分枝杆菌感染的药物；涉及包含这些化合物与通过EthA途径可激活的抗生素组合的药物组合物；涉及具有增强通过EthA酶途径可激活抗生素活性的化合物；涉及包含这些化合物的药物组合物；以及涉及它们作为药物，特别是用于预防和/或治疗如结核病和麻风病等分枝杆菌感染的药物的使用。
• BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1422228A1

  公开（公告）日：2004-05-26

  The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.

  本发明提供了一种新型的苯并氮杂环衍生物，其由以下公式表示： 其中，R1是一个5-或6-成员的芳香环，R2是低级烷基团等，Y是可选地取代的亚氨基，环A和环B是独立地选自一个可选地取代的芳香环，W是公式-W1-X2-W2-（W1和W2是独立地为S(O)m1（m1是0、1或2）等，X2是一个可选地取代的亚烷基团等），其制备方法及其用途。