克利贝特 | 30299-08-2

• 物质功能分类: 原料药 - 循环系统用药 - 调节血脂药
• 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: 克利贝特
• 中文别名: 环己双妥明
• 英文名称: clinofibrate
• 英文别名: 2,2'-((cyclohexane-1,1-diylbis(4,1-phenylene))bis(oxy))bis(2-methylbutanoic acid)；2,2′-(cyclohexylidene-bis(p-phenyleneoxy))bis(2-methylbutyric acid)；2,2'-(cyclohexylidene-bis(p-phenyleneoxy))bis(2-methylbutyric acid)；Lipoclin；1,1-Bis<4-(1-Carboxy-1-methylpropoxy)phenyl>-cyclohexan-2-<¹⁴C>；2-[4-[1-[4-(2-carboxybutan-2-yloxy)phenyl]cyclohexyl]phenoxy]-2-methylbutanoic acid
• CAS: 30299-08-2
• 化学式: C₂₈H₃₆O₆
• mdl: MFCD00865769
• 分子量: 468.59
• InChiKey: BMOVQUBVGICXQN-UHFFFAOYSA-N

物化性质

• 熔点：
  143-145°C
• 沸点：
  498.6°C (rough estimate)
• 密度：
  1.1005 (rough estimate)
• 溶解度：
  可溶于氯仿（轻微）、甲醇（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

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：
  Refrigerator

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Clinofibrate
2-(4-{1-[4-(1-carboxy-1-methylpropoxy)phenyl]cyclohexyl}phenoxy)-2-methylbutanoic acid
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: Clinofibrate
CAS number: 30299-08-2

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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, refrigerated.
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: C28H36O6
Molecular weight: 468.6

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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.

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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

生物活性

Clinofibrate 抑制羟甲基戊二酰辅酶A还原酶（HMGCR），IC50值为0.47 mM。它是一种降脂剂，用于控制血液中的高胆固醇和甘油三酯水平。

靶点

Target	Value
HMGCR	0.47 mM

体外研究

Clinofibrate 是一种降低血脂的药物，IC50值为40 μM，并且作用于人类肝脏3α-羟类固醇脱氢酶。它还能够刺激AKR1C4的活性达2倍，最高浓度可达50 μM。

体内研究

Clinofibrate 显著降低了动脉粥样硬化大鼠的高血浆胆固醇水平。在处理前，其血浆胆固醇为823 ± 256 mg/dl（平均值±标准差），约为对照组大鼠（85 ± 11 mg/dl）的10倍左右。经过Clinofibrate 处理后，极低密度脂蛋白(VLDL) 分泌显著减少。在附睾脂肪组织中，Clinofibrate 处理的大鼠显示出更高的肝素释放的脂蛋白脂酶活性、肝素血浆中的脂蛋白脂酶活性以及脂肪组织间质血管中的VLDL-三油酸甘油酯水解活性。动脉粥样硬化大鼠中胆固醇脂代谢及酸性胆固醇酯酶活性相关的动脉壁上的酶降低，而Clinofibrate 处理则提高这些活性。此外，动脉粥样硬化大鼠的酰基辅酶A胆固醇酰基转移酶（ACAT）活性与中性胆固醇酯酶活性比率较高，但 Clinofibrate 治疗的大鼠该比率较低。

Clinofibrate 治疗慢性肾衰竭患者时，能够安全有效地降低VLDL。通常每天按600 mg剂量处理，可使血清甘油三酯水平降低36%，VLDL 甘油三酯降低48%。此外，Clinofibrate 还改善了LDL和HDL组分中的成分异常，并显著提高了HDL胆固醇的水平。

反应信息

• 作为反应物：
  描述：

  克利贝特 生成 azane;2-[4-[1-[4-(2-carboxybutan-2-yloxy)phenyl]cyclohexyl]phenoxy]-2-methylbutanoic acid
  参考文献：
  名称：

  XAMMA, NORITAKA

  摘要：

  DOI：
• 作为产物：
  描述：

  环己酮 在 盐酸 、 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 6.5h， 生成 克利贝特
  参考文献：
  名称：

  高纯度克利贝特的制备方法

  摘要：

  本发明涉及一种高纯度克利贝特的制备方法，属于药物化合物的制备领域。环己酮与苯酚在体积比为3:1～7:1的浓盐酸和冰醋酸中反应制得中间体Ⅰ粗品，然后用单一溶剂脱色、降温析晶制得中间体Ⅰ；2-甲基丁酸在三氯化磷中与液溴反应，再与无水乙醇反应，萃取，真空蒸馏，制得中间体Ⅱ；无溶剂条件下中间体Ⅰ和中间体Ⅱ反应，制得中间体Ⅲ；中间体Ⅲ与氢氧化钠水解，萃取、析晶制得克利贝特粗品，再经过无水溶剂重结晶后制得克利贝特。本发明通过调整物料配比来缩短生产操作周期，能耗低，并且溶媒用量小、获得的产品结晶晶粒均匀，纯度高，成本低。

  公开号：

  CN102816060B

文献信息

• 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。
• Aromatic amine derivative and use thereof
  申请人：Taniguchi Takahiko

  公开号：US20090325956A1

  公开（公告）日：2009-12-31

  The present invention provides a novel SCD inhibitor. An SCD inhibitor containing a compound represented by the formula [I] wherein ring A is an optionally substituted aromatic ring, ring B is an optionally substituted ring, ring C is an optionally substituted aromatic ring, R is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, and X is a spacer having 1 to 5 atoms in the main chain, or a salt thereof, or a prodrug thereof.

  本发明提供了一种新型SCD抑制剂。一种包含由下式[I]表示的化合物的SCD抑制剂 其中环A是可选择取代的芳香环，环B是可选择取代的环，环C是可选择取代的芳香环，R是氢原子，可选择取代的碳氢基团或可选择取代的杂环基团，X是具有主链中1到5个原子的间隔物，或其盐，或其前药。
• 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] FUSED RING COMPOUNDS AND USE THEREOF<br/>[FR] COMPOSÉS CYCLIQUES CONDENSÉS ET UTILISATION DE CEUX-CI
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2009125873A1

  公开（公告）日：2009-10-15

  The present invention aims to provide a glucokinase activator useful as a pharmaceutical agent such as an agent for the prophylaxis or treatment of diabetes, obesity and the like. The present invention provides a glucokinase activator containing a compound represented by the formula (I): wherein each symbol is defined in the specification, or a salt thereof or a prodrug thereof.

  本发明旨在提供一种葡萄糖激酶激活剂，可用作药用剂，如用于预防或治疗糖尿病、肥胖等疾病的药剂。本发明提供一种包含由式(I)表示的化合物的葡萄糖激酶激活剂：其中每个符号在规范中有定义，或其盐或前药。
• [EN] FUSED QUINOLINE DERIVATIVE AND USE THEREOF<br/>[FR] DÉRIVÉ DE QUINOLINE FUSIONNÉE ET UTILISATION DE CELUI-CI
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2005105802A1

  公开（公告）日：2005-11-10

  The present invention aims at provision of a quinoline derivative having a neurokinin 2 (NK2) receptor antagonistic action and relates to a compound represented by the formula (I) wherein Rl is a hydrogen atom and the like; R2 is a hydrogen atom, a hydrocarbon group optionally having substituent(s) and the like; R3 is unsubstituted (i.e., absence), a hydrogen atom and the like; R4 and R5 are the same or different and each is a hydrogen atom, a hydrocarbon group optionally having substituent(s), and the like; R6 is (cyclic group optionally having substituent(s)) -carbonyl, and the like; R7, R8, R9 and R10 are the same or different and each is a hydrogen atom, halogen and the like; or R7 and R8, R8 and R9, and R9 and R10 may form a ring together with the adjacent carbon atoms; n is an integer of 1 to 5; --- represents unsubstituted (i.e., absence) or a single bond; and --- represents a single bond or a double bond, or a salt thereof, and the like.

  本发明旨在提供一种具有神经激肽2（NK2）受体拮抗作用的喹啉衍生物，并涉及一种由式（I）表示的化合物，其中R1是氢原子等；R2是氢原子，可选地具有取代基的碳氢基团等；R3是未取代的（即缺失），氢原子等；R4和R5相同或不同，每个是氢原子，可选地具有取代基的碳氢基团等；R6是（环状基团，可选地具有取代基）-羰基等；R7、R8、R9和R10相同或不同，每个是氢原子，卤素等；或R7和R8、R8和R9、以及R9和R10可以与相邻的碳原子一起形成环；n是1到5的整数；---表示未取代的（即缺失）或单键；---表示单键或双键，或其盐等。