氮酮 | 59227-89-3

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: 氮酮
• 中文别名: 1-正十二烷基氮杂环庚-2-酮；月桂氮卓酮；月桂氮酮；阿佐恩；1-正十二烷基氮杂环庚烷-2-酮
• 英文名称: Azone
• 英文别名: laurocapram；1-dodecylazepan-2-one
• CAS: 59227-89-3
• 化学式: C₁₈H₃₅NO
• mdl: MFCD00190580
• 分子量: 281.482
• InChiKey: AXTGDCSMTYGJND-UHFFFAOYSA-N

物化性质

• 熔点：
  -7°
• 沸点：
  bp50m 160°
• 密度：
  0.906-0.926
• 溶解度：
  氯仿（微溶）、乙醇（微溶）、甲醇（微溶）
• LogP：
  6.570 (est)
• 颜色/状态：
  Clear, colorless liquid
• 蒸汽压力：
  1.28X10-5 mm Hg at 25 °C (est)
• 折光率：
  Index of refraction: 1.4701

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  20
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.944
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

毒理性

• 相互作用

使用一些新型外用喷雾载体来增强性激素睾酮（Tes）、雌二醇（E2）、黄体酮（Prog）和炔诺酮醋酸酯（NA）的透皮传递的可行性已经得到了研究。新的渗透增强剂，对氨基苯甲酸戊酯（PadO）和辛水杨酸（OSal）被使用并与月桂基乙酰胺（AZ）和油酸（OA）进行了比较。在体外，将每种载体的有限剂量（5微升/平方厘米）应用于蜕皮蛇皮或猪皮上，并使用流过式扩散细胞测量渗透的量。在暴露1分钟后，确定了进入猪皮的分配情况。1分钟后，Tes和PadO迅速进入猪皮，分别有70%和60%的施用剂量残留在皮肤中，未吸收的剂量通过用绝对乙醇冲洗去除。与对照相比，OSal、OA和AZ的Tes在24小时内的累计渗透量（Q24小时）显著增加（p小于0.05），分别增加了6倍、3倍和2倍。使用PadO或AZ时，E2、Prog和NA的Q24小时与对照组相比，范围从三倍增加到十三倍（p小于0.05）。将这些数据外推以预测在人类身上会发生什么，表明应该有可能以每日一次的剂量这种方式递送临床上相关的性激素量。

The feasibility of using some novel topical spray vehicles for enhanced transdermal delivery of the sex hormones, testosterone (Tes), estradiol (E2), progesterone (Prog), and norethindrone acetate (NA) has been investigated. The new penetration enhancers, padimate O (PadO) and octyl salicylate (OSal) were used and compared with laurocapram (AZ) and oleic acid (OA). A finite dose (5 uL/sq cm) of each vehicle was applied to either shed snake skin or swine skin in vitro, and the amount penetrated was measured with flow-through diffusion cells. Partitioning into swine skin was determined after an exposure time of 1 min. Rapid partitioning of Tes and PadO into swine skin occurred after 1 min with 70% and 60% of the applied dose, respectively, remaining in the skin after the unabsorbed dose was removed by rinsing with absolute ethanol. The cumulative amount at 24 hr (Q24 hr) of Tes penetrating across the snake skin was significantly enhanced (p less than 0.05) up to 6-fold for OSal, 3-fold for OA and AZ, and 2-fold for PadO compared to control. Using PadO or AZ, the Q24 hr ranged from three- to thirteen-fold over control (p less than 0.05) for E2, Prog, and NA. Extrapolation of these data to predict what would happen in humans suggests that it should be possible to deliver clinically relevant amounts of sex hormones in this manner with once daily dosing.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

本研究的目标是确定载体和渗透增强剂对甲氨蝶呤（MTX）及其类似物埃达雷克斯（EDAM）经皮吸收的影响，并开发用于治疗类风湿性关节炎（RA）的药物经皮（TD）给药系统。根据之前发表的采用低剂量MTX治疗的药代动力学参数，并考虑到一个50平方厘米的扩散面积，计算出的MTX目标稳态体外TD流量为35微克/平方厘米/小时。修改后的弗朗茨扩散室和无毛小鼠皮肤用于体外皮肤渗透研究。无毛小鼠用于体内研究。通过使用验证的反相高效液相色谱方法分析接收相流体（或血液）来确定MTX和EDAM的给药量。MTX的固有分配系数较低（log P = -1.2）。只有在使用1-15%（v/v）Azone在丙二醇（PG）中时，才能实现大于或等于35微克/平方厘米/小时的MTX流量。EDAM（85微克/平方厘米/小时）的流量高于MTX，来自异丙醇（IPA）-5%（v/v）Azone系统。使用含有大于或等于2.5% Azone的PG中的给药系统，实现了MTX和EDAM的临床上显著的稳态体内血药浓度。MTX的药物浓度-时间曲线下面积（AUC0-24小时）分别为2379和3534纳克小时/毫升，来自PG-2.5% Azone和PG-7.5% Azone系统。使用PG-2.5% Azone系统，EDAM的AUC0-24小时为6893纳克小时/毫升。

... The objective of this study was to determine the effect of vehicles and penetration enhancers on the percutaneous absorption of methotrexate (MTX) and its analog edatrexate (EDAM), and develop transdermal (TD) delivery systems of the drugs for the treatment of rheumatoid arthritis (RA). ... From previously published pharmacokinetic parameters with low-dose MTX therapy, and considering a 50 sq cm diffusional area, the target steady state in vitro TD flux for MTX was calculated to be 35 micrograms/cm2/hr. Modified Franz diffusion chambers and hairless mouse skin were used for in vitro skin permeation studies. Hairless mice were used for in vivo studies. Delivered amounts of MTX and EDAM were determined by assaying the receiver phase fluid (or blood) with validated reversed phase HPLC methods. Intrinsic partition coefficient of MTX was low (log P = -1.2). Target MTX fluxes of greater than or = 35 ug/sq cm/hr were achievable only with 1-15% (v/v) Azone in propylene glycol (PG). Flux of EDAM (85 ug/sq cm/hr) was higher than MTX from an isopropyl alcohol (IPA)-5% (v/v) Azone system. Clinically significant steady state in vivo blood concentration of MTX and EDAM was achieved using delivery systems containing greater than or = 2.5% Azone in PG. Area under the drug concentration-time curves (AUC0-24 hr) for MTX were 2379 and 3534 ng hr/mL from PG-2.5% Azone and PG-7.5% Azone systems respectively. AUC0-24 hr of EDAM was 6893 ng hr/mL using a PG-2.5% Azone system.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

萘普生的渗透通过切除的人体皮肤和隔离灌流的兔耳皮肤已经确定。研究发现，Azone（月桂氮酮）增强了渗透，增强比率高达4倍。这种效果的大小在人体和兔皮肤中相似。从药物饱和溶液中渗透的萘普生通过预先用Azone处理的皮肤与商业制剂（Naprosyn）相似...

The permeation of naproxen through excised human skin and isolated perfused rabbit ear skin has been determined. It was found that ... Azone ... enhanced the permeation with an enhancement ratio of up to 4-fold. The magnitudes of the effect were similar in human and rabbit skin. The permeation of naproxen from a saturated solution of the drug through skin pre-treated with Azone was similar to that from a commercial preparation (Naprosyn)...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，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，如有需要，辅助通气。通过非循环呼吸面罩以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……。预防癫痫发作，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）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. 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 ... . Anticipate seizures 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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Azone（1-十二烷基氮杂环庚烷-2-酮）是一种已被证明能增强药物经皮吸收的剂。Azone被认为通过分配到皮肤脂质双层中，从而破坏结构而起作用。在一项开放标签研究中，对九名志愿者（两名男性，七名女性；年龄51-76岁）进行了研究，其中Azone乳膏（1.6%；100毫克）在腹部前臂的5 x 10厘米区域连续21天局部给药。在第1天、第8天和第15天，Azone乳膏含有47微居里的(14)C Azone。每次24小时给药后，用肥皂和水清洗皮肤给药部位。通过尿液放射性排泄确定经皮吸收。The (14)C Azone was ring labeled [14C-2-cyclo-heptan]. Radiochemical purity was >98.6% and cold Azone purity was 99%. 第1天第一次给药的经皮吸收为1.84 +/- 1.56%（SD）的给药剂量，对于24小时皮肤给药时间。在第8天重复给药后，经皮吸收显著增加（p<0.002）至2.76 +/- 1.91%。在第15天继续重复给药后，经皮吸收保持不变，为2.72 +/- 1.21%。在人类中，重复使用Azone会导致最初的自我吸收增强，这可能归因于其作用机制。然而，在这个初始变化之后，建立了Azone的稳态经皮吸收。因此，Azone可以增强自身的吸收以及其他化合物的吸收。这对于任何药理或毒理学评估都应考虑相关。用肥皂和水清洗给药部位仅回收了1-2%的给药放射性。以前发表的研究用乙醇洗涤回收了Azone剂量。因此，Azone在皮肤中可能会累积。

Azone (1-dodecylazacycloheptan-2-one) is an agent that has been shown to enhance percutaneous absorption of drugs. Azone is thought to act by partitioning into skin lipid bilayers and thereby disrupting the structure. An open-label study was done with nine volunteers (two males, seven females; aged 51-76 years) in which Azone cream (1.6%; 100 mg) was topically dosed on a 5 x 10-cm area of the ventral forearm for 21 consecutive days. On days 1, 8, and 15, the Azone cream contained 47 uCi of (14)C Azone. The skin application site was washed with soap and water after each 24-hr dosing. Percutaneous absorption was determined by urinary radioactivity excretion. The (14)C Azone was ring labeled [14C-2-cyclo-heptan]. Radiochemical purity was >98.6% and cold Azone purity was 99%. Percutaneous absorption of the first dose (day 1) was 1.84 +/- 1.56% (SD) of applied dose for 24-hr skin application time. Day 8 percutaneous absorption, after repeated application, increased significantly (p<0.002) to 2.76 +/- 1.91%. Day 15 percutaneous absorption, after continued repeated application, stayed the same at 2.72 +/- 1.21%. In humans, repeated application of Azone results in an initial self-absorption enhancement, probably due to its mechanism of action. However, steady-state percutaneous absorption of Azone is established after this initial change. Thus, Azone can enhance its own absorption as well as that of other compounds. This should be considered relevant for any pharmacological or toxicological evaluation. Washing the skin site of application with soap and water only recovered 1-2% of applied radioactivity. Previous published studies recovered the Azone dose with ethanol washes. Thus, there could potentially be an accumulation of Azone in skin.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2933790090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312+P330,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Laurocapram
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: Laurocapram
CAS number: 59227-89-3

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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: C18H35NO
Molecular weight: 281.5

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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

月桂氮酮简介

月桂氮酮是20世纪80年代初由美国人Stoughton首次报道的一种新型皮肤渗透剂。其化学名称为1-正十二烷基氮杂环庚-2-酮，简称氮酮。常温下氮酮呈现无色、无味、无毒的油状透明液体，具有润滑性，并且易于涂层和渗透。它是一种用途广泛的有机化学品，由于其高效的促渗性和良好的安全性，受到了广泛的关注。月桂氮酮对亲水性和疏水性化合物都有显著的促渗作用。

应用 医药、农药、化妆品等

月桂氮酮主要应用于医药、农药、化妆品、印染、制革、石油及化纤等领域。国内已对其生产与应用做了大量的研究，应用领域也在逐步扩大，目前年消耗量以50%的速度递增。随着人们对氮酮的认识日益深入，其工业化前景十分广阔。

推广应用

作为一种高效皮肤渗透促进剂和新型非离子表面活性剂，月桂氮酮在医药、日化、农药、印染、化纤及皮革等行业中的应用范围正不断扩大，使用效果显著，并且还有新的应用领域不断拓展。

制备 固-液相转移催化法

固-液相转移催化法制备月桂氮酮的方法是利用KOH-K2CO3复碱代替氢氧化钾或氢氧化钠作为去质子剂，四丁基溴化钠或聚乙二醇为相转移催化剂。在甲苯或乙烷溶剂中进行反应，一步生成氮酮，收率达93%以上。该方法条件温和，无需N2保护，便于操作，目前是目前国内广泛采用的生产工艺。

渗透促进剂 特性与应用

月桂氮酮又称月桂氮卓酮、月桂纶、N-月桂基己内酰胺、吖酮或氮酮，化学名为1-正十二烷基氮杂环庚-2-酮。这是一种新型高效安全的渗透促进剂，在常温下为无色无味透明液体，稍黏稠，无臭。与水形成乳状液，易溶于各种有机溶剂，具有良好的润滑性。

月桂氮酮能显著提高亲水性和疏水性药物制品的活性或化妆品中营养成分向皮肤内的渗透，大大缩短药物在角质层的滞留时间，显著增强药物疗效和化妆品的使用效果。此外，它还能够减少主药用量、降低成本，并且具有安全低毒无刺激性的特点。

促渗作用

月桂氮酮对亲水性和疏水性药物均有明显的透皮助渗作用，在乳剂状态或胶体状态下都表现良好。它对多种植物提取液和生物碱效果尤为明显，其透皮促渗作用强于二甲基亚砜，并且在含1%氮酮的条件下能产生相当于50%二甲基亚砜的12倍的效果。

安全性

月桂氮酮经亚急毒、皮肤及破损皮肤刺激性和致敏等实验证明无毒，无刺激性，无副作用。对家免眼实验也无刺激性。此外，它化学性质稳定，在室温下避光保存可达四年以上，并具有良好的协同作用。

化学性质

月桂氮酮是一种无色或微黄色透明液体，不溶于水，但可与水形成乳状液，并易溶于各种有机溶剂。

用途 医药、化妆品等

氮酮广泛用于医药、化妆品、农药、气雾剂、印染及石油勘探等行业。它具有渗透作用强、无色、无味、无毒和无刺激性等特点。

表面活性剂

此外，月桂氮酮还用作高效皮肤渗透促进剂，并适用于外用药膏、化妆品以及表面活性剂的应用。

反应信息

• 作为反应物：
  描述：

  氮酮 在 盐酸 作用下， 生成 6-dodecylamino-hexanoic acid
  参考文献：
  名称：

  Synthesis of N-Alkyldimethyl Derivatives of ω-Amino Acids

  摘要：

  DOI：

  10.1021/jo50015a004
• 作为产物：
  描述：

  己内酰胺 在 sodium 、 xylene 作用下， 生成 氮酮
  参考文献：
  名称：

  Synthesis of N-Alkyldimethyl Derivatives of ω-Amino Acids

  摘要：

  DOI：

  10.1021/jo50015a004
• 作为试剂：
  描述：

  溴代十二烷 在 苄基三甲基氯化铵 、 tetra(n-butyl)ammonium hydrogen sulfate sodium hydroxide 作用下， 以 氮酮 、 甲苯 为溶剂， 生成 1-dodecyl-azonan-2-one
  参考文献：
  名称：

  Method of synthesis of 1-dodecylazacycloheptan-2-one

  摘要：

  在一种合成1-取代的氮杂环烷-2-酮的方法中，以一次烷基卤代物和芳基烷基卤代物作为烷基化试剂，改进包括在存在具有以下结构式的相转移催化剂的情况下进行N-烷基化： 其中X是合适的阴离子；R.sub.1、R.sub.2、R.sub.3和R.sub.4分别是具有1-18个碳原子的烷基或芳基基团，或者R.sub.2、R.sub.3和R.sub.4可以形成杂环环的一部分，前提是碳原子的总和在16和40之间。

  公开号：

  US04422970A1

文献信息

• [EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
  申请人：GALLEON PHARMACEUTICALS INC

  公开号：WO2009151744A1

  公开（公告）日：2009-12-17

  The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.

  本发明涉及基于巯基和S-亚硝基巯基的SNO化合物及其衍生物，以及它们在治疗正常呼吸控制缺失方面的用途，包括治疗与睡眠、肥胖、某些药物和其他医疗状况相关的呼吸暂停和低通气。
• SYNTHESIS AND USE OF DUAL TYROSYL-DNA PHOSPHODIESTERASE I (TDP1)- TOPOISOMERASE I (TOP1) INHIBITORS
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：US20130345252A1

  公开（公告）日：2013-12-26

  The invention described herein pertains to the synthesis and use of certain N-substituted indenoisoquinoline compounds which inhibit the activity Tyrosyl-DNA Phosphodiesterase I (Tdp1) or Topoisomerase I (Top1) or both, or otherwise demonstrate anticancer activity. Also disclosed are novel N-substituted indenoisoquinoline compounds and pharmaceutical compositions comprising the novel N-substituted indenoisoquinoline compounds.

  本发明涉及合成和使用某些N-取代吲哚异喹啉化合物，这些化合物抑制酪氨酸-DNA磷酸二酯酶I（Tdp1）或拓扑异构酶I（Top1）或两者的活性，或表现出抗癌活性。还公开了新颖的N-取代吲哚异喹啉化合物和包含这些新颖的N-取代吲哚异喹啉化合物的药物组合物。
• [EN] AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS<br/>[FR] DÉRIVÉS AMINOPYRIMIDINIQUES UTILISÉS COMME MODULATEURS DE LRRK2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013079505A1

  公开（公告）日：2013-06-06

  Compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R3 and R4 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

  式(I)的化合物或其药用可接受的盐，其中A、X、R1、R2、R3和R4如本文所定义。还公开了制备这些化合物的方法，并将这些化合物用于治疗与LRRK2受体相关的疾病，如帕金森病。
• [EN] SUBSTITUTED CYCLOPROPYL-2,2'-BIPYRIMIDINYL COMPOUNDS, ANALOGUES THEREOF, AND METHODS USING SAME<br/>[FR] COMPOSÉS DE CYCLOPROPYL-2,2'-BIPYRIMIDINYL SUBSTITUÉS, ANALOGUES DE CEUX-CI, ET PROCÉDÉS LES UTILISANT
  申请人：ARBUTUS BIOPHARMA INC

  公开号：WO2021025976A1

  公开（公告）日：2021-02-11

  The present disclosure includes novel substituted cyclopropyl-2,2'-bipyrimidinyl compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infection and/or hepatitis D virus (HDV) infection in a patient.

  本公开涵盖了新型的取代环丙基-2,2'-双嘧啶基化合物，以及包含这些化合物的组合物，可用于治疗或预防患者体内的乙型肝炎病毒（HBV）感染和/或丙型肝炎病毒（HDV）感染。
• Controlled-release compositions containing opioid agonist and antagonist
  申请人：——

  公开号：US20020010127A1

  公开（公告）日：2002-01-24

  Controlled-release dosage forms containing an opioid agonist; an opioid antagonist; and a controlled release material release during a dosing interval an analgesic or sub-analgesic amount of the opioid agonist along with an amount of said opioid antagonist effective to attenuate a side effect of said opioid agonist. The dosage form provides analgesia for at least about 8 hours when administered to human patients. In other embodiments, the dose of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.

  含有阿片激动剂、阿片拮抗剂和受控释放材料的控释剂型，其在给药间隔期间释放阿片激动剂的镇痛或亚镇痛量以及足以减轻所述阿片激动剂的副作用的阿片拮抗剂的量。当给予人类患者时，该剂型提供至少约8小时的镇痛作用。在其他实施例中，给药间隔期释放的拮抗剂剂量增强了阿片激动剂的镇痛效力。