甲磺酸异丙酯 | 926-06-7

• 物质功能分类: 有机原料 - 无机酸酯
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 中文名称: 甲磺酸异丙酯
• 英文名称: isopropyl methanesulfonate
• 英文别名: isopropyl mesylate；isopropyl methylsulfonate；propan-2-yl methanesulfonate
• CAS: 926-06-7
• 化学式: C₄H₁₀O₃S
• 分子量: 138.188
• InChiKey: SWWHCQCMVCPLEQ-UHFFFAOYSA-N

物化性质

• 熔点：
  7°C(lit.)
• 沸点：
  82 °C (6 mmHg)
• 密度：
  1.145
• 闪点：
  104 °C
• 溶解度：
  氯仿（微溶）、甲醇（微溶）
• 颜色/状态：
  Clear, colorless liquid
• 蒸汽压力：
  0.436 mm Hg at 25 °C (est)
• 稳定性/保质期：
  避免与不相容的材料接触。

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

低剂量的75毫克/公斤被迅速代谢，产生了尿代谢物，S-异丙基半胱氨酸和S-异丙基半胱氨酸N-乙酸盐，占给药剂量的30%。

... Low quantities of 75 mg/kg were promptly metabolized producing urinary metabolites, S-isopropylcysteine and S-isopropylcysteine N-acetate, accounting for 30% of the administered dose.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 异丙基甲磺酸酯 ... 在大鼠体内被发现会产生异丙醇和甲磺酸。

... Isopropyl methanesulfonate ... in rat was found to yield isopropanol and methanesulfonic acid.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

生殖毒素 - 对生殖系统有毒性的化学物质，包括对后代造成缺陷以及对男性或女性生殖功能的损害。生殖毒性包括发育效应。参见生殖毒性风险评估指南。

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

向雄性小鼠喂食丁基羟基甲苯4周显著提高了小鼠对异丙基甲磺酸酯引起的死亡的保护作用。

Feeding of butylated hydroxytoluene to male mice for 4 wk gave significant protection against the mortality caused by isopropyl methanesulfonate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道（如需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有必要，协助呼吸。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的咳嗽反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。活性炭无效……。不要尝试中和，因为可能会发生放热反应。在去污染后，用干燥的、无菌的敷料覆盖皮肤烧伤……。/有机酸及其相关化合物/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist respirations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Activated charcoal is not effective ... . Do not attempt to neutralize because of exothermic reaction. Cover skin burns with dry, sterile dressings after decontamination ... . /Organic acids and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。一旦出现上呼吸道梗阻的迹象，可能需要尽早进行插管。使用气囊面罩装置的正压通气技术可能有益。考虑对肺水肿进行药物治疗...。对于严重的支气管痉挛，考虑给予β受体激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常...。开始静脉输注D5W/SRP：“保持开放”，最小流量/。如果出现低血容量的迹象，使用0.9%的生理盐水（NS）或乳酸钠林格氏液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。如果病人在正常血容量时出现低血压，考虑使用血管加压药。注意观察液体过载的迹象...。使用丙美卡因盐酸协助眼部冲洗...。/有机酸及其相关化合物/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Early intubation, at the first sign of upper airway obstruction, may be necessary. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organic acids and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：慢性暴露或致癌性 / 六周大的雌性HSD：(ICR)BR小鼠被分为三组：1）车辆对照组（30只小鼠），2）未处理对照组（60只小鼠），3）异丙基甲磺酸处理组（32只小鼠）。第1组每周皮下注射0.05毫升三辛酸酯，持续288天，第2组未接受任何处理，第3组每周皮下注射含有IMS的0.05毫升三辛酸酯。异丙基甲磺酸的剂量为2.8毫克（20微摩尔）持续63天，之后为1.4毫克（10微摩尔）持续57天，最后为0.7毫克（5微摩尔）持续治疗的最后82天。当动物临死时进行解剖。在第288天撰写报告时，第1组或第2组的动物都没有死亡。到第63天时，第3组7只濒死动物中有2只患有淋巴瘤（因此剂量减半）；从63天到120天，15只处理过的小鼠中有10只患有淋巴瘤（再次剂量减半）；到202天时，第3组的其余动物都濒临死亡。在第3组中，有5只动物死亡时没有肿瘤证据，7只动物自溶过多无法解剖。带肿瘤的动物的平均生存时间是治疗开始后的118天。总共32只处理过的小鼠（第3组）中有20只发展出了起源于胸腺的淋巴瘤。

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Six-wk-old female HSD:(ICR)BR mice were divided into three groups: 1) vehicle control (30 mice), 2) untreated control (60 mice), and 3) isopropyl methanesulfonate treated (32 mice). Group 1 received 0.05 mL trioctanoin subcutaneously once per week for 288 days, group 2 received no treatment, and group 3 received all injections of IMS in 0.05 mL trioctanoin once per week subcutaneously. The dose of isopropyl methanesulfonate was 2.8 mg (20 micromoles) for 63 days, 1.4 mg (10 micromoles) for the next 57 days, and then 0.7 mg (5 micromoles) for the final 82 days of treatment. Animals were necropsied when moribund. None of the group 1 or group 2 animals had died by day 288, when the report was written. By 63 days, 2 of 7 moribund animals in group 3 had lymphoid neoplasms (therefore the dose was halved); from 63 to 120 days, 10 of 15 treated mice had lymphoid neoplasms (again the dose was halved); and the remainder of the animals in group 3 were moribund by 202 days. Of group 3, 5 animals died with no evidence of neoplasia and 7 animals were too autolysed to autopsy. The mean survival time of tumor bearing animals was 118 days after initiation of treatment. Altogether 20 of 32 treated mice (group 3) developed lymphoid neoplasms of thymus origin.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1
• 危险品标志：
  C
• 安全说明：
  S26,S36/37/39,S45
• 危险类别码：
  R68
• 海关编码：
  2905199090
• 储存条件：
  密封储存于阴凉、干燥的库房，远离腐蚀区域。冷藏时温度应保持在4°C。

SDS

Name:	Isopropyl Methanesulfonate Material Safety Data Sheet
Synonym:	Methanesulfonic Acid, 1-Methylethyl Ester
CAS:	926-06-7

Section 1 - Chemical Product MSDS Name:Isopropyl Methanesulfonate Material Safety Data Sheet
Synonym:Methanesulfonic Acid, 1-Methylethyl Ester

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
926-06-7	Isopropyl Methane Sulphonate	ca 100	213-132-0

Hazard Symbols: C
Risk Phrases: 34 40

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Causes burns. Limited evidence of a carcinogenic effect.Corrosive.
Potential Health Effects
Eye:
Causes eye burns. May cause chemical conjunctivitis and corneal damage.
Skin:
Causes skin burns. May cause skin rash (in milder cases), and cold and clammy skin with cyanosis or pale color.
Ingestion:
May cause severe and permanent damage to the digestive tract. Causes gastrointestinal tract burns. May cause perforation of the digestive tract. May cause systemic effects.
Inhalation:
Causes chemical burns to the respiratory tract. Aspiration may lead to pulmonary edema. May cause systemic effects.
Chronic:
Effects may be delayed.

---

Section 4 - FIRST AID MEASURES
Eyes: Get medical aid immediately. Do NOT allow victim to rub eyes or keep eyes closed. Extensive irrigation with water is required (at least 30 minutes).
Skin:
Get medical aid immediately. Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse. Destroy contaminated shoes.
Ingestion:
Call a poison control center. If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. Get medical aid.
Inhalation:
Get medical aid immediately. Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Do NOT use mouth-to-mouth resuscitation. If breathing has ceased apply artificial respiration using oxygen and a suitable mechanical device such as a bag and a mask.
Notes to Physician:

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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. Use water spray to keep fire-exposed containers cool. Vapors may be heavier than air. They can spread along the ground and collect in low or confined areas. Containers may explode when heated.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Cool containers with flooding quantities of water until well after fire is out.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Absorb spill with inert material (e.g. vermiculite, sand or earth), then place in suitable container. Avoid runoff into storm sewers and ditches which lead to waterways. Clean up spills immediately, observing precautions in the Protective Equipment section. Remove all sources of ignition. Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Use with adequate ventilation. Discard contaminated shoes.
Storage:
Store in a cool, dry place. Keep container closed when not in use.
Corrosives area. Keep refrigerated. (Store below 4C/39F.)

---

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# 926-06-7: 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 minimize contact with skin.
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.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Liquid
Color: colorless
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: 82 deg C @ 6.00mm Hg
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: 104 deg C ( 219.20 deg F)
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C4H10O3S
Molecular Weight: 138.19

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, ignition sources, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of sulfur, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 926-06-7: PB2275000 LD50/LC50:
Not available.
Carcinogenicity:
Isopropyl Methane Sulphonate - 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
Shipping Name: CORROSIVE SOLID, ACIDIC, ORGANIC, N.O.S.*
Hazard Class: 8
UN Number: 3261
Packing Group: III
IMO
Shipping Name: CORROSIVE SOLID, ACIDIC, ORGANIC, N.O.S.
Hazard Class: 8
UN Number: 3261
Packing Group: III
RID/ADR
Shipping Name: CORROSIVE SOLID, ACIDIC, ORGANIC, N.O.S.
Hazard Class: 8
UN Number: 3261
Packing group: III

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: C
Risk Phrases:
R 34 Causes burns.
R 40 Limited evidence of a carcinogenic effect.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 28A After contact with skin, wash immediately with
plenty of water.
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# 926-06-7: No information available.
Canada
CAS# 926-06-7 is listed on Canada's NDSL List.
CAS# 926-06-7 is listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 926-06-7 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

甲磺酸异丙酯是一种用于有机合成的中间体，在实验室研究中有广泛的应用。

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  乙烷磺酸异丙酯; 乙磺酸异丙酯	2-propyl ethanesulfonate	14245-62-6	C5H12O3S	152.214

反应信息

• 作为反应物：
  描述：

  甲磺酸异丙酯 在 三正丁基氢锡 作用下， 以 various solvent(s) 为溶剂， 生成 methanesulfonyl
  参考文献：
  名称：

  Generation of sulphonyl radicals from sulphonate esters

  摘要：

  DOI：

  10.1016/s0040-4039(00)97388-x
• 作为产物：
  描述：

  甲基磺酰氯 、 异丙醇 在 2,6-二甲基吡啶 、 硫酸 作用下， 反应 2.5h， 以57%的产率得到甲磺酸异丙酯
  参考文献：
  名称：

  Studies on chemical carcinogens and mutagens. XXV. Chemoselectivity of alkyl sulfonates toward 4-(p-nitrobenzyl)pyridine (NBP) in phosphate buffer.

  摘要：

  合成了六种烷基磺酸和五种对取代苯磺酸的甲基、乙基和异丙基酯，并评估了它们在含有60%丙酮的磷酸盐缓冲液（pH 6.0）中对4-(对硝基苄基)吡啶（NBP）的烷基化能力。对NBP的化学选择性常数SNBP被定义为用于NBP烷基化的烷基磺酸的摩尔分数与在缓冲介质中水解的剩余烷基化试剂的摩尔分数之比的对数。研究发现，SNBP不仅显著依赖于分子中烷基部分的结构，还明显依赖于离去的磺酸部分的电子性质。讨论了结构与化学选择性之间的关系。

  DOI：

  10.1248/cpb.32.1326
• 作为试剂：
  描述：

  ethyl 4-[3-([2,2-diphenyl-1,3-benzodioxolan-5-yl]carbonyl)indol-1-yl]butanoate 在 sodium hydroxide 、 甲磺酸异丙酯 、 对甲苯磺酸 作用下， 以 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 5.0h， 生成 4-{3-[(R)-2-(4-Isobutyl-phenyl)-2-methyl-benzo[1,3]dioxole-5-carbonyl]-indol-1-yl}-butyric acid
  参考文献：
  名称：

  The development of non-steroidal dual inhibitors of both human 5α-reductase isozymes

  摘要：

  The design, synthesis and biological properties of homochiral non-steroidal inhibitors of both isozymes of human 5 alpha-reductase are described. The o-hydroxy aniline moiety of the initial lead (1) can be replaced by a 3-acyl indole isostere, whilst the minimum energy conformation of the benzyl ether in the potent inhibitor (3) is mimicked by the conformationally locked benzodioxolane system in the potent non-steroidal inhibitor (7). Pharmacokinetics and oral efficacy in a rat model of BPH are presented for (3) and (7). Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00261-2

文献信息

• INDOL-2-YL-PIPERAZIN-1-YL-METHANONE DERIVATIVES
  申请人：Nettekoven Matthias

  公开号：US20080188484A1

  公开（公告）日：2008-08-07

  The present invention relates to compounds of formula I wherein A and R 1 to R 4 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及公式I的化合物，其中A和R1至R4如描述和声明中所定义，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• Conformational equilibria due to ring inversion in N-alkyl-cis-decahydroisoquinolines
  作者：Judith M. Bailey、Harold Booth、Hatif A. R. Y. Al-Shirayda

  DOI：10.1039/p29840000583

  日期：——

  The position of conformational equilibria due to ring inversion in N-alkyl-cis-decahydroisoquinolines (alkyl = Me, Et, Pri, CH2CF3, or CH2CCl3) has been assessed directly from 13C and/or 19F n.m.r. spectra recorded at temperatures between 173 and 253 K. The measured equilibrium constants are related to the inductive effect of the N-substituent which produces an increase (Me, Et, Pri) or decrease (CH2CF3

  已直接从13 C和/或19 F中评估了N-烷基-顺式-十氢异喹啉（烷基= Me，Et，Pr i，CH 2 CF 3或CH 2 CCl 3）中由于环反转引起的构象平衡位置。在173和253 K之间的温度下记录的nmr光谱。测得的平衡常数与N取代基的感应作用有关，该感应作用产生增加（Me，Et，Pr i）或减少（CH 2 CF 3，CH 2 CCl 3））的大小gauche丙胺型排斥反应。将经历交换的两个双椅构象的碳原子的13 C化学位移列表化。
• 1,1-Dioxo-thiomorpholinyl indolyl methanone derivatives
  申请人：Nettekoven Matthias

  公开号：US20070123526A1

  公开（公告）日：2007-05-31

  The present invention relates to compounds of formula I wherein R 1 , R 2 and G are as defined in the description and claims and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及式I的化合物，其中R1、R2和G如描述和索赔中定义的，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• Histamine-3 Receptor Inverse Agonists for the Treatment of Obesity: Validation of the Target and Identification of Novel Series
  作者：Pascale David Pierson、Christoph Ullmer、Sven Taylor、Tadakatsu Takahashi、Franz Schuler、Monique Schmitt、Rosa María Rodríguez Sarmiento、Olivier Roche、Hans Richter、Susanne Raab、Jean-Marc Plancher、Matthias Nettekoven、Toshito Nakagawa、Peter Mohr、Jörg Huwyler、Cornelia Hertel、Silvia Gatti-Mac Arthur、Christian Freichel、Ruby Wiegand

  DOI：10.2533/chimia.2009.275

  日期：——

  Obesity is a major risk factor for the development of conditions such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease and cancer. Several pieces of evidence, including data in primates, have demonstrated the beneficial effects of histamine-3 receptor (H3R) inverse agonists in the regulation of food intake and body weight. A pharmacophore model based on selected published H3R ligands and validated by previous investigations, was used to identify the 5-oxy-2-carboxamide-indole core as a novel series of H3R inverse agonists. Extensive structure–activity relationship (SAR) investigations were rewarded by the identification of several compounds reversing (R)-?-methyl-histamine-induced water intake increase and reducing food intake/body weight in rodent models of obesity. Among those compounds, (4,4-difluoro-piperidin-1-yl)-[1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone, selected as a lead compound, was exhibiting a promising profile, including excellent pharmacokinetic properties, good in vitro safety profile and high efficacy in a chronic rodent model of obesity.

  肥胖是高血压、高血糖、血脂异常、冠心病和癌症等疾病发展的主要危险因素。包括灵长类动物数据在内的多项证据表明组胺-3受体（H3R）拮抗剂在调节食物摄入和体重方面具有益处。基于选定的已发表H3R配体构建的药效团模型，并经过先前研究验证，用于识别5-氧-2-羧酰胺吲哚核心作为一系列新型H3R拮抗剂。通过广泛的构效关系（SAR）研究，鉴定出几种化合物能够逆转（R）-β-甲基组胺诱导的小鼠摄水量增加，并减少肥胖小鼠模型中的食物摄入/体重。在这些化合物中，（4,4-二氟-哌啶-1-基）-[1-异丙基-5-(1-异丙基-哌啶-4-氧基)-1H-吲哚-2-基]-甲酮，作为首选化合物，表现出有希望的特性，包括优异的药代动力学特性、良好的体外安全性特性以及在慢性肥胖小鼠模型中的高效性。
• Methods of using .alpha.-phosphonosulfonate squalene synthetase
  申请人：Bristol-Myers Squibb Company

  公开号：US05470845A1

  公开（公告）日：1995-11-28

  .alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R.sup.4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.

  提供了抑制酶角鲨烯合酶并从而抑制胆固醇生物合成的.alpha.-磷酸磺酸酯化合物。这些化合物的化学式为##STR1##其中R.sup.2为OR.sup.5或R.sup.5a；R.sup.3和R.sup.5独立地为H、烷基、芳基烷基、芳基或环烷基；R.sup.5a为H、烷基、芳基烷基或芳基；R.sup.4为H、烷基、芳基、芳基烷基或环烷基；Z为H、卤素、低烷基或低烯基；R.sup.1为至少含有7个碳原子的疏水基团，为烷基、烯基、炔基、混合烯基-炔基、芳基、芳基烷基、环烷基、环烷基烷基、杂环芳基、杂环芳基烷基、环杂环烷基、环杂环烷基烷基；如上所述；包括磷酸(亚磷酸)和/或磺酸的药用可接受盐和/或前药酯。

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