(R)-N-FMOC-辛炔二酸 | 220497-96-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (R)-N-FMOC-辛炔二酸
• 中文别名: (R)-N-FMOC-辛基甘氨酸；?-N-FMOC-辛炔二酸；-N-FMOC-辛炔二酸
• 英文名称: 2-(9H-fluoren-9-ylmethoxycarbonylamino)-decanoic acid
• 英文别名: Fmoc-D-Ade-OH；(R)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)decanoic acid；(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)decanoic acid
• CAS: 220497-96-1
• 化学式: C₂₅H₃₁NO₄
• 分子量: 409.525
• InChiKey: LSMLSLHVRMSYPT-HSZRJFAPSA-N

物化性质

• 熔点：
  136.5 °C
• 沸点：
  529.77°C (rough estimate)
• 密度：
  1.1538 (rough estimate)
• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 安全说明：
  S24/25
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存放于阴凉干燥处。

SDS

Name:	(R)-N-FMOC-Octylglycine 95% (98% E.E.) Material Safety Data Sheet
Synonym:	(R)-N-(9-Fluorenylmethoxycarbonyl)-2-Aminodecanoic Acid
CAS:	220497-96-1

Section 1 - Chemical Product MSDS Name:(R)-N-FMOC-Octylglycine 95% (98% E.E.) Material Safety Data Sheet
Synonym:(R)-N-(9-Fluorenylmethoxycarbonyl)-2-Aminodecanoic Acid

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
220497-96-1	(R)-N-FMOC-Octylglycine	95%	unlisted

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

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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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. Wash clothing before reuse.
Ingestion:
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. Wash mouth out with 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.
Notes to Physician:
Treat symptomatically and supportively.

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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 water spray, dry chemical, carbon dioxide, or chemical foam.

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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.

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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.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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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# 220497-96-1: 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:
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: white to off-white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 136.5 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C25H31NO4
Molecular Weight: 409.52

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Incompatible materials, dust generation.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 220497-96-1 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(R)-N-FMOC-Octylglycine - Not listed by ACGIH, IARC, or NTP.

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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.

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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.
WGK (Water Danger/Protection)
CAS# 220497-96-1: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 220497-96-1 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 220497-96-1 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (R)-N-FMOC-辛炔二酸 、 Fmoc-D-亮氨酸 、 N-Fmoc-N'-三苯甲基-D-天冬酰胺 、 芴甲氧羰基-O-叔丁基-D-苏氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 以15 mg的产率得到chlorofusin peptide
  参考文献：
  名称：

  绿藻素类似物的固相合成

  摘要：

  我们报告了一种有效而通用的固相合成方法，通过该方法合成了两个系列的氯夫西林类似物，一个带有变化的生色团，另一个带有环状肽中的多种氨基酸取代基。使用涉及侧链固定，树脂上环化和环化后修饰的策略制备这些肽。这些合成方法的成功证明了该方法的广泛实用性。评价了两个系列的类似物对p53 / MDM2相互作用的抑制活性，但显示在所测试的浓度范围内是无活性的。这表明活性可能需要完整的生色团结构。

  DOI：

  10.1021/jo070450a
• 作为产物：
  描述：

  正辛醛 在 甲酸 、 sodium carbonate 、 C₂₆H₃₄ClIrN₂O₂S 、 C.I.酸性橙108 、 高碘酸 、 1,3-丙二胺 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 甲胺 为溶剂， 反应 51.5h， 生成 (R)-N-FMOC-辛炔二酸
  参考文献：
  名称：

  使用铱基氢转移催化剂进行 α-酮酸的不对称还原胺化：获得未受保护的非天然 α-氨基酸

  摘要：

  描述了由带有手性N- (2-吡啶甲基)磺酰胺基配体的 Cp*Ir 配合物催化的 α-酮酸的直接不对称还原胺化。组合使用光学活性2-苯甘氨醇作为胺化剂对于使用甲酸的化学选择性和立体选择性转移氢化是有效的。随后用原高碘酸消除羟乙基部分可以以令人满意的分离产率（20个实例）提供各种未保护的α-氨基酸，并具有优异的光学纯度（高达> 99% ee）。

  DOI：

  10.1021/acs.orglett.3c04378

文献信息

• [EN] COMPOUNDS AND THERAPEUTIC USES THEREOF<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：CENTAURI THERAPEUTICS LTD

  公开号：WO2018203087A1

  公开（公告）日：2018-11-08

  The invention relates to novel compounds with the ability to link an immune response to a pathogen, to the use of said compounds in a disease or disorder mediated and/or caused by an infective agent, to compositions containing said compounds, processes for their preparation and to novel intermediates used in said process.

  本发明涉及具有将免疫应答与病原体连接起来的新化合物，以及在由感染性因子介导和/或引起的疾病或紊乱中使用该类化合物，包含该类化合物的组合物，其制备方法以及在该方法中使用的新中间体。
• BETA-HAIRPIN PEPTIDOMIMETICS AS SELECTIVE ELASTASE INHIBITORS
  申请人：POLYPHOR AG

  公开号：US20160333053A1

  公开（公告）日：2016-11-17

  β-Hairpin peptidomimetics of the general formula cyclo(-Xaa 1 -Xaa 2 -Thr 3 -Xaa 4 -Ser 5 -Xaa 6 -Xaa 7 -Xaa 8 -Xaa 9 -Xaa 10 -Xaa 11 -Xaa 12 -Xaa 13 -) and pharmaceutically acceptable salts thereof, with Xaa 1 , Xaa 2 , Xaa 4 , Xaa 6 , Xaa 7 , Xaa 8 , Xaa 9 , Xaa 10 , Xaa 11 , Xaa 12 and Xaa 13 being amino acid residues of certain types which are defined in the description and the claims, have elastase inhibitory properties, especially against human neutrophil elastase, and can be used for preventing infections or diseases related to such infections in healthy individuals or for slowing infections in infected patients. The compounds of the invention can further be used where cancer, or immunological diseases, or pulmonary diseases, or cardiovascular diseases, or neurodegenerative diseases, or inflammation, or diseases related to inflammation, are mediated or resulting from elastase activity. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

  β-头发环肽类似物的一般公式为cyclo(-Xaa1-Xaa2-Thr3-Xaa4-Ser5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-)及其药学上可接受的盐，其中Xaa1、Xaa2、Xaa4、Xaa6、Xaa7、Xaa8、Xaa9、Xaa10、Xaa11、Xaa12和Xaa13是在描述和权利要求中定义的某些类型的氨基酸残基，具有弹性酶抑制性质，特别是对人类中性粒细胞弹性蛋白酶，可用于预防健康个体中与此类感染相关的感染或疾病，或者用于减缓感染患者中的感染。该发明的化合物还可用于癌症、免疫性疾病、肺部疾病、心血管疾病、神经退行性疾病、炎症或与炎症相关的疾病由弹性酶活性介导或由此导致的情况。这些肽类似物可以通过基于混合固相和溶液相合成策略的过程制造。
• ANTIPROTOZOAL COMPOUNDS
  申请人：Bacoba AG

  公开号：EP3345917A1

  公开（公告）日：2018-07-11

  The present invention relates to a compound of formula (I) wherein --A-- represents a peptide chain, wherein said peptide chain consists of 5 to 7 amino acids, wherein said amino acids are selected from any amino acid, wherein at least two, preferably at least three of said 5 to 7 amino acids are α-aminoisobutyric acid (Aib), leucine (Leu) or alanine (Ala); R1 is wherein X is N or CH; R5 is selected from H, C1-C16alkyl, C1-C16alkenyl, C(O)-C1-C16alkyl, C(O)-C1-C16alkenyl, (wherein said C1-C16alkyl, C1-C16alkenyl, C(O)-C1-C16alkyl, C(O)-C1-C16alkenyl are) independently optionally substituted with halogen, NR11R12, -[O-C2H4]n-OCH3 wherein n=2-20; C(O)-R8, C(O)-C1-C3alkylene-R8, N(H)C(O)-R8, or S(O)2-R9, wherein R8 is independently at each occurrence selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C1-C4alkyl, halogen, CF3, OR10, NR11R12, C6H5 and C6H5 substituted with halogen, C1-C3alkyl, OR10, NR11R12; wherein R10, R11, R12 are independently at each occurrence H, C1-C3alkyl; R9 is independently at each occurrence selected from C1-C4alkyl, aryl, heteroaryl, each independently optionally substituted with C1-C4alkyl, halogen, CF3, OR13, NR14R15; wherein R13, R14, R15 are independently at each occurrence H, C1-C3alkyl; R6, R7 are independently at each occurrence selected from H, C1-C4alkyl, C1-C4alkenyl, C(O)-C1-C3alkyl, C(O)-C1-C4alkenyl, (wherein said C1-C4alkyl, C1-C4alkenyl, C(O)-C1-C3alkyl, C(O)-C1-C4alkenyl are) independently optionally substituted with halogen, NR11R12; or R6 and R7 together with the X-C to which they are attached form independently at each occurrence an aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally (further) substituted with C1-C4alkyl, halogen, CF3, OR10, NR11R12, C6H5 and C6H5 substituted with halogen, C1-C3alkyl, OR10, NR11R12; wherein R10, R11, R12 are independently at each occurrence H, C1-C3alkyl; and wherein the arrow indicates the attachment to the NH-moiety depicted in formula (I); R2 is selected from C1-C14alkyl, C2-C14alkyl optionally substituted with OH, C2-C14alkoxy, C2-C14alkenyl optionally substituted with OH; C1-C8alkylene-R23, wherein in alkylene one or two -CH2- moieties are optionally replaced by -CH(NR24R25)-,-CH(OH)-, -C(=O)-, -NR24R25- or -CH(CH3)- moieties, wherein there are no adjacent-C(=O)- moieties or adjacent -NR24R25- moieties, and wherein R23 is independently at each occurrence selected from hydrogen; aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C1-C4alkyl, OR26, NR27R28; wherein R26, R27, R28 are independently at each occurrence H, halogen, CF3, C1-C3alkyl; and wherein R24 and R25 are independently at each occurrence H, C1-C3alkyl; with the proviso that R2 is not -CH2CH(CH3)CH2CH(OH)CH2C(O)C2H5, -CH2CH(CH3)CH2CH=CHC(O)C2H5, -CH2CH(CH3)CH2CH2CH2C(O)C2H5, -CH2CH(CH3)(CH2)3CH(OH)C2H5, -CH2CH(CH3)CH2CH(OCH3)CH2C(O)C2H5; R3 is selected from C2-C12alkyl optionally substituted with OH, C2-C12alkoxy, C2-C12alkenyl optionally substituted with OH, C1-C8alkylene-R29, wherein in alkylene one or two -CH2- moieties are optionally replaced by -CH(NR30R31)-, -CH(OH)-, -C(=O)-, -NR30R31- or -CH(CH3)- moieties, wherein there are no adjacent -C(=O)- moieties or adjacent -NR30R31- moieties, and wherein R29 is independently at each occurrence selected from hydrogen; aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C1-C4alkyl, OR32, NR33R34; wherein R32, R33, R34 are independently at each occurrence H, halogen, CF3, C1-C3alkyl; and wherein R30 and R31 are independently at each occurrence H, C1-C3alkyl; R4 is wherein R35 is independently selected from hydrogen and C1-C3-alkyl; R36 is independently at each occurrence selected from -cycloalkyl-NR41R42, wherein said cycloalkyl moiety is optionally substituted by C1-C4alkyl, hydroxyl, halogen, OR43; -C3-C6alkylene-NR41R42, wherein said C3-C6alkylene moiety is optionally substituted by hydroxyl, OR43, halogen; cycloalkyl optionally substituted with C1-C4alkyl, halogen, OR43; or wherein R35 and R36 together with the nitrogen atom to which they are attached form independently at each occurrence a heteroaryl, a heterocyclyl or a heterocyclic spiranyl, each independently optionally substituted with C1-C4alkyl, halogen, OR43, NR44R45, wherein R43, R44, R45 are independently at each occurrence H, C1-C4alkyl; and wherein R37, R38, R39 and R40 are independently at each occurrence H or C1-C3alkyl, preferably H or methyl, or independently at each occurrence two of said R37, R38, R39 and R40 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, preferably a carbocyclic ring, and wherein R41 and R42 are independently of each other H or C1-C4alkyl optionally substituted with halogen, hydroxyl or C3-C6cycloalkyl; or together with the nitrogen atoms to which they are attached form independently at each occurrence a heteroaryl or a heterocyclyl, each independently optionally substituted with halogen, C1-C4alkyl, OR43, NR44R45; wherein the arrow indicates the attachment to the C(O)-moiety depicted in formula (I); and pharmaceutically acceptable salts of said compound of formula (I). The present invention further relates to pharmaceutical compositions comprising said compounds and to the use of said compounds in a method of treatment of a protozoan disease, wherein preferably said protozoan disease is selected from malaria, human African trypanosomiasis, Chagas disease or leishmaniasis.

  本发明涉及式(I)的化合物，其中--A--表示一条肽链，所述肽链由5至7个氨基酸组成，其中所述氨基酸选自任何氨基酸，其中所述5至7个氨基酸中至少有两个、优选至少三个为α-氨基异丁酸(Aib)、亮氨酸(Leu)或丙氨酸(Ala)； R1是： 其中，X为N或CH； R5选自H、C1-C16烷基、C1-C16烯基、C(O)-C1-C16烷基、C(O)-C1-C16烯基(其中所述C1-C16烷基、C1-C16烯基、C(O)-C1-C16烷基、C(O)-C1-C16烯基)各自可独立地被卤素、NR11R12、-[O-C2H4]n-OCH3(其中n=2-20)取代；C(O)-R8、C(O)-C1-C3亚烷基-R8、N(H)C(O)-R8、或S(O)2-R9，其中： R8在每次出现时独立地选自芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、卤素、CF3、OR10、NR11R12、C6H5和被卤素、C1-C3烷基、OR10、NR11R12取代的C6H5取代；其中R10、R11、R12在每次出现时独立地为H、C1-C3烷基； R9在每次出现时独立地选自C1-C4烷基、芳基、杂芳基，各自独立地可被C1-C4烷基、卤素、CF3、OR13、NR14R15取代；其中R13、R14、R15在每次出现时独立地为H、C1-C3烷基； R6、R7在每次出现时独立地选自H、C1-C4烷基、C1-C4烯基、C(O)-C1-C3烷基、C(O)-C1-C4烯基(其中所述C1-C4烷基、C1-C4烯基、C(O)-C1-C3烷基、C(O)-C1-C4烯基)各自独立地可被卤素、NR11R12取代；或R6和R7与所连接的X-C基团共同形成独立地在每次出现时为芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、卤素、CF3、OR10、NR11R12、C6H5和被卤素、C1-C3烷基、OR10、NR11R12取代的C6H5取代；其中R10、R11、R12在每次出现时独立地为H、C1-C3烷基；其中箭头指示连接至式(I)中所示的NH基团； R2选自C1-C14烷基、C2-C14烷基可选地被OH、C2-C14烷氧基、C2-C14烯基可选地被OH取代；C1-C8亚烷基-R23，其中亚烷基中的一或两个-CH2-基团可选地被-CH(NR24R25)-、-CH(OH)-、-C(=O)-、-NR24R25-或-CH(CH3)-基团取代，且不存在相邻的-C(=O)-基团或相邻的-NR24R25-基团，且其中： R23在每次出现时独立地选自氢；芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、OR26、NR27R28取代；其中R26、R27、R28在每次出现时独立地为H、卤素、CF3、C1-C3烷基；且其中R24和R25在每次出现时独立地为H、C1-C3烷基； 条件是R2不为-CH2CH(CH3)CH2CH(OH)CH2C(O)C2H5、-CH2CH(CH3)CH2CH=CHC(O)C2H5、-CH2CH(CH3)CH2CH2CH2C(O)C2H5、-CH2CH(CH3)(CH2)3CH(OH)C2H5、-CH2CH(CH3)CH2CH(OCH3)CH2C(O)C2H5； R3选自C2-C12烷基可选地被OH、C2-C12烷氧基、C2-C12烯基可选地被OH取代，或C1-C8亚烷基-R29，其中亚烷基中的一或两个-CH2-基团可选地被-CH(NR30R31)-、-CH(OH)-、-C(=O)-、-NR30R31-或-CH(CH3)-基团取代，且不存在相邻的-C(=O)-基团或相邻的-NR30R31-基团，且其中： R29在每次出现时独立地选自氢；芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、OR32、NR33R34取代；其中R32、R33、R34在每次出现时独立地为H、卤素、CF3、C1-C3烷基；且其中R30和R31在每次出现时独立地为H、C1-C3烷基； R4为： 其中R35独立地选自氢和C1-C3烷基； R36在每次出现时独立地选自-环烷基-NR41R42的环烷基部分可选地被C1-C4烷基、羟基、卤素、OR43取代；-C3-C6亚烷基-NR41R42的C3-C6亚烷基部分可选地被羟基、OR43、卤素取代；环烷基可选地被C1-C4烷基、卤素、OR43取代；或R35和R36与所连接的氮原子共同形成独立地在每次出现时为杂芳基、杂环基或杂环螺旋基，各自独立地可被C1-C4烷基、卤素、OR43、NR44R45取代，其中R43、R44、R45在每次出现时独立地为H、C1-C4烷基；且其中： R37、R38、R39和R40在每次出现时独立地为H或C1-C3烷基，优选H或甲基，或在每次出现时R37、R38、R39和R40中的两个与所连接的碳原子共同形成碳环或杂环环，优选为碳环，且其中： R41和R42彼此独立地为H或C1-C4烷基(可选地被卤素、羟基或C3-C6环烷基取代)；或与所连接的氮原子共同形成独立地在每次出现时为杂芳基或杂环基，各自独立地可被卤素、C1-C4烷基、OR43、NR44R45取代；其中 箭头指示连接至式(I)中所示的C(O)基团；以及式(I)化合物的药学上可接受的盐。 本发明还涉及包含所述化合物的药物组合物，以及所述化合物在治疗原虫病的方法中的用途，其中优选所述原虫病选自疟疾、人类非洲锥虫病、查加斯病或利什曼病。
• Identification of a new p53/MDM2 inhibitor motif inspired by studies of chlorofusin
  作者：Marco M.D. Cominetti、Sarah A. Goffin、Ewan Raffel、Kerrie D. Turner、Jordann C. Ramoutar、Maria A. O’Connell、Lesley A. Howell、Mark Searcey

  DOI：10.1016/j.bmcl.2015.06.014

  日期：2015.11

  Previous studies on the natural product chlorofusin have shown that the full peptide and azaphilone structure are required for inhibition of the interaction between MDM2 and p53. In the current work, we utilized the cyclic peptide as a template and introduced an azidonorvaline amino acid in place of the ornithine/azaphilone of the natural product and carried out click chemistry with the resulting peptide. From this small library the first ever non-azaphilone containing chlorofusin analog with MDM2/p53 activity was identified. Further studies then suggested that the simple structure of the Fmoc-norvaline amino acid that had undergone a click reaction was also able to inhibit MDM2/p53 interaction. This is an example where studies of a natural product have led to the serendipitous identification of a new small molecule inhibitor of a protein-protein interaction. (C) 2015 Elsevier Ltd. All rights reserved.
• Solid-Phase Synthesis of Chlorofusin Analogues
  作者：Esther C. Y. Woon、Mariangela Arcieri、Andrew F. Wilderspin、John P. Malkinson、Mark Searcey

  DOI：10.1021/jo070450a

  日期：2007.7.1

  We report an efficient and versatile solid-phase synthesis through which two series of chlorofusin analogues, one bearing varying chromophores and the other with various amino acid substitutions in the cyclic peptide, were synthesized. These peptides were prepared using a strategy involving side-chain immobilization, on-resin cyclization, and postcyclization modification. The success of these syntheses

  我们报告了一种有效而通用的固相合成方法，通过该方法合成了两个系列的氯夫西林类似物，一个带有变化的生色团，另一个带有环状肽中的多种氨基酸取代基。使用涉及侧链固定，树脂上环化和环化后修饰的策略制备这些肽。这些合成方法的成功证明了该方法的广泛实用性。评价了两个系列的类似物对p53 / MDM2相互作用的抑制活性，但显示在所测试的浓度范围内是无活性的。这表明活性可能需要完整的生色团结构。