4-氨基水杨酸 | 65-49-6

• 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 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氨基水杨酸
• 中文别名: 对氨基水杨酸；4-氨基-2-羟基苯甲酸；4-氨基柳酸；对氨水杨酸
• 英文名称: 4-Aminosalicylic acid
• 英文别名: 4-amino-2-hydroxybenzoic acid；p-aminosalicylic acid；para-aminosalicylic acid；aminosalicylic acid
• CAS: 65-49-6
• 化学式: C₇H₇NO₃
• mdl: MFCD00007789
• 分子量: 153.137
• InChiKey: WUBBRNOQWQTFEX-UHFFFAOYSA-N

物化性质

• 熔点：
  135-145 °C (lit.)
• 沸点：
  276.03°C (rough estimate)
• 密度：
  1.3585 (rough estimate)
• 溶解度：
  1.69g/l
• 物理描述：
  Solid
• 颜色/状态：
  MINUTE CRYSTALS FROM ALC
• 气味：
  ODORLESS, OR HAS SLIGHT ACETOUS ODOR
• 稳定性/保质期：
  RELATIVELY UNSTABLE IN AQ SOLN & DECOMP WITH EVOLUTION OF CO2 TO FORM M-AMINOPHENOL, PARTICULARLY @ TEMP ABOVE 40 °C
• 解离常数：
  PKA: 3.25

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

乙酰化是许多药物失活的主要途径，例如...对氨基水杨酸...催化这些反应的酶，乙酰辅酶A：N-乙酰转移酶（EC2.3.1.5），位于肝脏细胞质中。

ACETYLATION IS MAJOR ROUTE FOR INACTIVATION OF MANY DRUGS SUCH AS ... P-AMINOSALICYLIC ACID... ENZYMES WHICH CATALYSE THESE REACTIONS, ACETYL COENZYME A:N-ACETYLTRANSFERASES (EC2.3.1.5), ARE LOCATED IN LIVER CYTOSOL.

来源:Hazardous Substances Data Bank (HSDB)

代谢

当管理员口服给药时，它会被迅速吸收，并以未改变的对氨基水杨酸和作为乙酰葡萄糖苷酸、甘氨酰和谷氨酰胺结合物形式随尿液排出。

WHEN ADMIN ORALLY TO MAN IT IS RAPIDLY ABSORBED, & IS EXCRETED IN URINE AS UNCHANGED P-AMINOSALICYLIC ACID & AS ACETYL GLUCURONYL, GLYCYL & GLUTAMINYL CONJUGATES.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在人体内产生5-氨基-2-羧基苯基-β-D-葡萄糖苷酸。在假单胞菌中产生4-氨基儿茶酚。在人体内产生4-氨基水杨酰谷氨酰胺和4-氨基水杨酰甘氨酸。

YIELDS 5-AMINO-2-CARBOXYPHENYL-BETA-D-GLUCURONIDE IN MAN. 4-AMINOCATECHOL IN PSEUDOMONAS. 4-AMINOSALICYLOYLGLUTAMINE & 4-AMINOSALICYLOYLGLYCINE IN MAN. /TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

结核病患者在治疗前、治疗中以及治疗后撤药期间，对五种不同药物组合的血液进行了培养，这些药物包括异烟肼、氨硫脲、对氨基水杨酸和链霉素。用于检测DNA损伤的方法是染色体畸变和姐妹染色单体交换（SCEs）。共分析了179个受试者。这些药物组合显示出协同、相加和拮抗作用，尽管它们单独使用时被发现不具有断裂作用。四种药物组合，异烟肼加氨硫脲、异烟肼加对氨基水杨酸、异烟肼加氨硫脲加链霉素以及异烟肼加对氨基水杨酸加链霉素，显著增加了畸变频率，而异烟肼加链霉素并未诱导畸变。实际上，链霉素似乎减少了畸变的频率。SCEs只在两名患者中增加：一名接受异烟肼加氨硫脲治疗，另一名接受异烟肼加对氨基水杨酸治疗。撤药后畸变的频率降低；它略高于对照组，尽管这并不显著。恢复正常可能是因为损伤细胞的消除或淋巴细胞中DNA的修复。尽管撤药后药物诱导的畸变不会持续存在，但具有染色体损伤的药物组合应谨慎使用，因为不能排除在治疗期间生殖细胞中可能发生减数分裂染色体损伤，并可能传给下一代。

Blood from tuberculosis patients was cultured before, during, and after withdrawal of therapy involving five different drug combinations if isoniazid, thiacetazone, p-aminosalicyclic acid, and streptomycin. The approaches used to detect DNA damage were chromosome aberrations and sister chromatid exchanges (SCEs). A total of 179 subjects were analyzed. In combo these drugs showed synergistic, additive, and antagonistic effects, though they were found to be nonclastogenic individually. Four of the drug combinations, isoniazid plus thiacetazone, isoniazid plus p-aminosalicyclic acid, isoniazid plus thiacetazone plus streptomycin, and isoniazid plus p-aminosalicyclic acid plus streptomycin, induced a significant incr in the frequency of aberrations, whereas isoniazid plus streptomycin did not induce aberrations. In fact, streptomycin appeared to reduce the frequency of aberrations. SCEs were incr in only two patients: one treated with isoniazid plus thiacetazone and the other with isoniazid plus p-aminosalicyclic acid. The frequency of aberrations after withdrawal of therapy was decr; it was slightly higher than the controls, though it was insignificant. The return to normalcy could be due to elimination of damaged cells or the repair of DNA in lymphocytes. Though the drug-induced aberrations do not persist after withdrawal of therapy, the chromosome damaging combo of drugs should be used with caution, because the possibility of meiotic chromosome damage in germ cells (during therapy), which might be passed on to the next generation, cannot be ruled out.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 药物性肝损伤

化合物：4-氨基水杨酸

Compound:4-aminosalicylic acid

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：最令人关注的药物性肝损伤

DILI Annotation:Most-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重程度等级：5

Severity Grade:5

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：警告和预防措施

Label Section:Warnings and precautions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-批准的药物标签用于研究药物诱导的肝损伤，《药物发现今天》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: 按照在人类中发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今天》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

生物利用度研究针对12个对象的P-氨基水杨酸及其盐。比色法分析表明，钠、钾、钙盐和P-氨基水杨酸的血药浓度峰值分别出现在0.5、0.75、1.5和3小时。

BIOAVAILABILITY STUDIES ON P-AMINOSALICYLIC ACID & ITS SALTS IN 12 SUBJECTS. COLORIMETRIC ASSAY INDICATED THAT PEAK BLOOD LEVELS OCCURRED @ 0.5, 0.75, 1.5, & 3 HR FOR SODIUM, POTASSIUM, & CALCIUM SALTS & P-AMINOSALICYLIC ACID, RESPECTIVELY.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尿液排泄数据表明吸收基本完全，尽管吸收率有所不同。

URINE EXCRETION DATA SHOWED ABSORPTION TO BE ESSENTIALLY COMPLETE ALTHOUGH RATES OF ABSORPTION DIFFERED.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氨基水杨酸易于从胃肠道吸收。单次口服4克自由酸，约在1.5到2小时内血浆中达到最大浓度，约为75微克/毫升。钠盐的吸收速度更快。药物似乎分布在全身水中，并在胸膜液和干酪样组织中达到高浓度。然而，脑脊液中的值较低，可能是由于活跃的外向运输。

Aminosalicyclic acid is readily absorbed from the gastrointestinal tract. A single oral dose of 4 g of the free acid produces maximal concentrations in plasma of about 75 ug/ml within 1.5 to 2 hours. The sodium salt is absorbed even more rapidly. The drug appears to be distributed throughout the total body water and reaches high concentrations in pleural fluid and caseous tissue. However, values in CSF are low, perhaps because of active outward transport.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

超过80%的药物通过尿液排出；其中50%以上以乙酰化合物的形式存在。剩余部分中最大的一部分是由自由酸组成。

Over 80% of the drug is excreted in the urine; more than 50% is in the form of the acetylated compound. The largest portion of the remainder is made up of the free acid.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xi
• 安全说明：
  S26,S37/39,S45,S53
• 危险类别码：
  R36/37/38
• WGK Germany：
  2
• 海关编码：
  29225000
• 危险品运输编号：
  UN 1789 8/PG 3
• RTECS号：
  VO1225000
• 危险标志：
  GHS07
• 危险性描述：
  H319
• 危险性防范说明：
  P305 + P351 + P338
• 储存条件：
  本品应密封避光保存。

SDS

Name:	4-Aminosalicylic acid 99% Material Safety Data Sheet
Synonym:	PAS; 4-Amino-2-hydroxybenzoic aci
CAS:	65-49-6

Section 1 - Chemical Product MSDS Name:4-Aminosalicylic acid 99% Material Safety Data Sheet
Synonym:PAS; 4-Amino-2-hydroxybenzoic aci

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
65-49-6	4-aminosalicylic acid	99.0	200-613-5

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Light sensitive.Air sensitive.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract.
Inhalation:
May cause respiratory tract irritation.
Chronic:
No information found.

---

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. Get medical aid if irritation develops or persists. Wash clothing before reuse.
Ingestion:
If victim is conscious and alert, give 2-4 cupfuls of milk or water.
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or 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 if cough or other symptoms appear. Get medical aid.
Notes to Physician:
Antidote: None reported.

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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. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire.

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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. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation. Place under an inert atmosphere.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation. Store protected from light. Handle under an inert atmosphere. Store protected from air.
Storage:
Store in a cool, dry, well-ventilated area away from incompatible substances. Do not expose to air. Store protected from light. Store under an inert atmosphere.

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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# 65-49-6: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use. 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: Not available.
Odor: Odorless or slight acetous
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 147 deg C dec
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: practically insoluble in benzene
Specific Gravity/Density:
Molecular Formula: C7H7NO3
Molecular Weight: 153.14

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, light, exposure to air.
Incompatibilities with Other Materials:
Air.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported.

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 65-49-6: VO1225000 LD50/LC50:
CAS# 65-49-6: Draize test, rabbit, eye: 100 mg/24H Moderate; Oral, mouse: LD50 = 4 gm/kg; Oral, rabbit: LD50 = 3650 mg/kg.
Carcinogenicity:
4-aminosalicylic acid - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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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
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 65-49-6: No information available.
Canada
CAS# 65-49-6 is listed on Canada's NDSL List.
CAS# 65-49-6 is listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 65-49-6 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

4-氨基水杨酸（Para-aminosalicylic acid，Aminosalicylic acid，4-aminosalicylate）是一种抗结核药物，对结核杆菌具有抑菌活性。

化学性质

白色结晶。熔点为150-151℃（分解）。无臭或微有丙酮气味。溶于稀硝酸、稀氢氧化钠、丙酮、碳酸氢钠和磷酸，稍溶于乙醇，微溶于乙醚，不溶于水及苯。在40℃时该品水溶液不稳定，分解放出二氧化碳而生成氨基酚。暴露于空气中变为棕色。

用途

医药中间体，用于合成抗结核病药对氨柳酸钠；也用于分析试剂、酸碱荧光指示剂；还可作为镀锌光亮剂、整平剂和匀镀剂，用于碱性镀锌。

生产方法

由间氨基酚经羟化而得。具体步骤如下：将水、间氨基酚和碳酸氢钠依次投入反应罐内，通入二氧化碳置换空气后密闭升温至110±1℃，罐内压力保持在0.6-0.8MPa反应6h，冷却至-5℃，加亚硫酸钠，过滤，水洗，合并洗滤液供酸化用。滤饼为间氨基酚回收物，可重复使用。

将上述洗滤液升温至10-15℃，用30-40%硫酸中和至pH为6.4-7.0，加入适量的亚硫酸钠与硫化钠溶液后经树脂脱色。于30℃用30-40%硫酸调节pH至3-3.5放置，甩滤，水洗至硫酸根合格，甩干得对氨基水杨酸。

从苯乙酸出发也可以合成得到对氨基水杨酸。先使苯乙酸在浓硫酸和浓硝酸中60℃下硝化，然后倾入冰水中，过滤析出2,4-二硝基苯乙酸[643-43-6]。硝化产率95%。

将得到的产物加入10倍甲醇中均匀混合后通入干燥的氯化氢，加热至沸，冷却后析出2,4-二硝基苯乙酸甲酯晶体[58605-12-2]。酯化产率为80%。

将酯化物溶解于热甲醇中，加入亚硝酸丁酯再加入甲醇钠，静置数小时直至完全析出深红色沉淀物，分离沉淀物得中间产物。将其溶于稀氢氧化钾溶液中，加入盐酸酸化至呈酸性。逸出二氧化碳气体，析出4-硝基-2-羟基苯腈产率为80%，将此腈化物与水、浓硫酸、冰醋酸混合加热至沸即可析出4-硝基水杨酸[619-19-2]。

将4-硝基水杨酸溶解于25%碳酸钠溶液中，加入硫酸亚铁水溶液再加适量的碳酸钠溶液，加热至沸，分离析出铁盐。过滤，滤液用乙酸调pH=3,4-氨基水杨酸则析出。再过滤干燥即得产品。工业品对氨基水杨酸含量大于70%，氯化物小于50ppm，硫酸根小于500ppm。

类别

有毒物品；

毒性分级

中毒；

急性毒性

腹腔-小鼠LD50: 4250毫克/公斤；口服-小鼠LD50: 4000毫克/公斤；

刺激数据

眼睛-兔子100毫克/24小时 中度；

可燃性危险特性

可燃;燃烧产生有毒氮氧化物烟雾；

储运特性

库房通风低温干燥；

灭火剂

干粉、泡沫、砂土、二氧化碳，雾状水。

反应信息

• 作为反应物：
  描述：

  4-氨基水杨酸 在 sodium tungstate sodium sulfide 、 四丁基溴化铵 、 水 、 双氧水 、 溴 、 氯甲酸乙酯 、 三乙胺 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 6.0h， 生成 阿米舒必利
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR PREPARATION OF AMISULPRIDE
  [FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION D'AMISULPRIDE

  摘要：

  本发明涉及一种制备阿米舒普利（I）的新工艺，包括：用二甲基硫酸酯和碱甲基化4-氨基水杨酸（VI），可选地在TBAB存在下，以获得4-氨基-2-甲氧基甲基苯甲酸酯（VII）和（ii）在钨酸钠或钼酸铵存在下，用氧化剂氧化4-氨基-2-甲氧基-5-乙基硫基苯甲酸（IX）或4-氨基-2-甲氧基-5-乙基硫基甲基苯甲酸酯（X），分别得到2-甲氧基-4-氨基-5-乙基磺酰基苯甲酸（IV）或2-甲氧基-4-氨基-5-乙基磺酰基甲基苯甲酸酯（XI）。

  公开号：

  WO2011158084A1
• 作为产物：
  描述：

  sodium 4-aminosalicylate dihydrate 在 硫酸 作用下， 生成 4-氨基水杨酸
  参考文献：
  名称：

  一种对氨基水杨酸的晶型及其制备方法与应 用

  摘要：

  本发明涉及药物化学领域，具体涉及对氨基水杨酸的一种新的晶型及其制备方法，所述新晶型的晶体进行X‑ray粉末衍射，以衍射峰位置2θ为光谱图特征参数，所述2θ依次为：7.36±0.2，14.61±0.2，17.01±0.2，21.91±0.2，29.28±0.2；其制备是将对氨基水杨酸和有机溶剂混合，再利用温差法析晶，固液分离并干燥固体，得到所述新晶型的晶体；本发明还涉及包含所述新晶型的制剂或组合物及新晶型在制备用于治疗结核病的药物中的应用。本发明提供的对氨基水杨酸的新晶型稳定性好，不仅具有储存和运输的优势，还极大的方便了工业生产。

  公开号：

  CN104402749B
• 作为试剂：
  描述：

  Quadricyclane 在 tetrasodium (5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato)cobalt(II) aluminum oxide 、 4-氨基水杨酸 作用下， 以 正戊烷 为溶剂， 生成 2,5-降冰片二烯
  参考文献：
  名称：

  用于将四环烷转化为降冰片二烯的氧化铝锚定钴卟啉催化剂

  摘要：

  描述了用于制备锚定在涂有聚胺砜-A 的氧化铝珠上的钴 (II) 氘代卟啉和钴 (II) 四（对磺基苯基）卟啉的方法。波长色散 X 射线微量分析表明，钴 (II) 卟啉分布在约 100 微米的催化剂外表面层内。100 微米深度。该催化剂对于四环烷环转化为降冰片二烯具有高活性。使用等温循环反应器的异构化的详细动力学给出了 Langmuir-Hinshelwood 类型的速率表达式。催化剂逐渐失去活性，可通过在真空中将催化剂加热至 200 °C 使其完全再生。

  DOI：

  10.1246/bcsj.61.973

文献信息

• Novel indole derivatives as selective androgen receptor modulators (SARMS)
  申请人：Lanter C. James

  公开号：US20050245485A1

  公开（公告）日：2005-11-03

  The present invention is directed to novel indole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the androgen receptor.

  本发明涉及新型吲哚衍生物，含有它们的药物组合物以及它们在治疗由雄激素受体调节的疾病和症状中的应用。
• [EN] THIOPHENE DERIVATIVES FOR THE TREATMENT OF DISORDERS CAUSED BY IGE<br/>[FR] DÉRIVÉS DE THIOPHÈNE POUR LE TRAITEMENT DE TROUBLES PROVOQUÉS PAR IGE
  申请人：UCB BIOPHARMA SRL

  公开号：WO2019243550A1

  公开（公告）日：2019-12-26

  Thiophene derivatives of formula (I) and a pharmaceutically acceptable salt thereof are provided. These compounds have utility for the treatment or prevention of disorders caused by IgE, such as allergy, type 1 hypersensitivity or familiar sinus inflammation.

  提供了公式（I）的噻吩衍生物及其药用可接受的盐。这些化合物对于治疗或预防由IgE引起的疾病具有用途，如过敏、1型超敏反应或家族性鼻窦炎。
• [EN] SUBSTITUTED 4-PYRIDONES AND THEIR USE AS INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY<br/>[FR] 4-PYRIDONES SUBSTITUÉES ET LEUR UTILISATION COMME INHIBITEURS DE L'ACTIVITÉ DE L'ÉLASTASE NEUTROPHILE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2014029831A1

  公开（公告）日：2014-02-27

  This invention relates to substituted 4-pyridones of formula 1 and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other auto-immune and allergic disorders, allograft rejection, and oncological diseases.

  这项发明涉及式1的取代4-吡啶酮及其作为中性粒细胞弹性蛋白酶活性抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗和/或预防肺部、胃肠道和泌尿系统疾病、皮肤和眼部炎症性疾病以及其他自身免疫和过敏性疾病、移植物排斥和肿瘤性疾病的药剂的方法。
• SUBSTITUTED 4-PYRIDONES AND THEIR USE AS INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY
  申请人：OOST Thorsten

  公开号：US20140057916A1

  公开（公告）日：2014-02-27

  This invention relates to substituted 4-pyridones of formula 1 and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other auto-immune and allergic disorders, allograft rejection, and oncological diseases.

  这项发明涉及式1的取代4-吡啶酮及其作为中性粒细胞弹性蛋白酶活性抑制剂的用途，包含这些化合物的药物组合物，以及将其用作治疗和/或预防肺部、胃肠道和泌尿系统疾病、皮肤和眼睛的炎症性疾病以及其他自身免疫和过敏性疾病、移植物排斥反应和肿瘤性疾病的药剂的方法。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。

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