9,10-亚甲基油酸 | 738-87-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 9,10-亚甲基油酸
• 中文别名: 苹婆酸；8-(2-辛基环丙-1-烯基)辛酸;；8-(2-辛基环丙-1-烯基)辛酸
• 英文名称: 8-(2-octylcyclopropen-1-yl)octanoic acid
• 英文别名: Sterculic acid
• CAS: 738-87-4
• 化学式: C₁₉H₃₄O₂
• 分子量: 294.5
• InChiKey: PQRKPYLNZGDCFH-UHFFFAOYSA-N

物化性质

• 熔点：
  19 °C
• 沸点：
  418.7±24.0 °C(Predicted)
• 密度：
  0.948±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿：可溶；乙醚：可溶；己烷：可溶；甲醇：可溶
• 碰撞截面：
  172.7 Ų [M-H]- [CCS Type: TIMS, Method: single field calibrated]

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  21
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

毒理性

• 相互作用

AFQ（黄曲霉毒素Q1）是AFB（黄曲霉毒素B1）的一种生物转化代谢物，可以通过人类和猴子肝脏微粒体在体外形成。将AFQ以100 PPB的浓度喂食给两批各80条虹鳟鱼苗，为期10个月，使用半纯化测试饲料。另外的批次则喂食了含有100 PPB AFQ加上50 PPM阿魏酸和50 PPM环丙烯脂肪酸（CPFA）、4 PPB AFB以及基础测试饲料作为对照。12个月时的肝细胞癌发生率为：100 PPB AFQ组为12/114（10.6%）；4 PPB AFB组为55/114（48.2%）；50 PPM CPFA组为44/107（41.1%）；100 PPB AFQ加上50 PPM CPFA（阿魏酸）组为106/119（89.1%）和对照组为0/120（0%）。结果表明AFQ对虹鳟鱼具有致癌性，AFQ和CPFA之间存在协同作用，并且AFQ是一种比AFB致癌性低约100倍的强效肝致癌物。

AFLATOXIN Q1 (AFQ), A BIOTRANSFORMATION METABOLITE OF AFLATOXIN B1 (AFB), IS FORMED IN VITRO BY HUMAN & MONKEY LIVER MICROSOMES. AFQ WAS FED TO DUPLICATE LOTS OF 80 RAINBOW TROUT FINGERLINGS @ 100 PPB IN A SEMI-PURIFIED TEST DIET FOR 10 MONTHS. ADDNL LOTS WERE FED 100 PPB AFQ PLUS 50 PPM STERCULIC ACID, & 50 PPM CYCLOPROPENE FATTY ACID (CPFA), 4 PPB AFB & THE BASAL TEST DIET TO SERVE AS CONTROLS. HEPATOCELLULAR CARCINOMA INCIDENCES @ 12 MONTHS WERE AS FOLLOWS: 100 PPB AFQ- 12/114 (10.6%); 4 PPB AFB- 55/114 (48.2%); 50 PPM CPFA- 44/107 (41.1%); 100 PPB AFQ PLUS 50 PPM CPFA (STERCULIC ACID)- 106/119 (89.1%) & CONTROL 0/120 (0%). RESULTS ESTABLISH THE CARCINOGENICITY OF AFQ TO RAINBOW TROUT, THE SYNERGISTIC INTERACTION BETWEEN AFQ & CPFA & INDICATE THAT AFQ IS A POTENT LIVER CARCINOGEN ABOUT 100 TIMES LESS CARCINOGENIC THAN AFB.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

当饲料中含有20微克/千克赭曲霉毒素A以及硬脂酸时，喂养的虹鳟鱼发展出了肝肿瘤（数量未指定）。而在赭曲霉毒素A单独以16、32或64微克/千克饲料浓度喂养8个月的情况下，没有观察到肿瘤。

RAINBOW TROUT FED A DIET CONTAINING 20 UG OCHRATOXIN A PER KG OF DIET, TOGETHER WITH STERCULIC ACID, DEVELOPED HEPATOMAS (NUMBER UNSPECIFIED). NO TUMORS WERE OBSERVED WHEN OCHRATOXIN A WAS FED ALONE AT CONCN OF 16, 32, OR 64 UG/KG OF DIET FOR 8 MONTHS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

虹鳟鱼喂食含有200 ppm的桐酸和Malvalic酸，这些物质能显著增加鳟鱼肝细胞对黄曲霉毒素B1致癌作用的敏感性。4周后，肝细胞质中出现了一种奇特的类似裂隙的条纹。随着持续喂食这种饮食，这些改变变得越来越多和明显。在8周和12周时，粗糙内质网含有许多平行排列和螺旋状的膜材料。肝脏中的葡萄糖-6-磷酸酶活性显著降低。

RAINBOW TROUT FED A DIET CONTAINING 200 PPM OF STERCULIC ACID & MALVALIC ACID, SUBSTANCES THAT GREATLY INCR THE SENSITIVITY OF TROUT LIVER CELLS TO CARCINOGENIC EFFECTS OF AFLATOXIN B1. AFTER 4 WK, PECULIAR CLEFT-LIKE STRIATIONS APPEARED IN CYTOPLASM OF HEPATOCYTES. THESE ALTERATIONS BECAME PROGRESSIVELY MORE FREQUENT & MARKED WITH CONTINUED FEEDING OF DIET. AT 8 & 12 WK, ROUGH-SURFACED ENDOPLASMIC RETICULUM CONTAINED MANY PARALLEL ARRAYS & WHORLED PROFILES OF MEMBRANE MATERIAL. GLUCOSE-6-PHOSPHATASE ACTIVITY IN LIVER WAS SIGNIFICANTLY DECREASED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在喂食饱和或不饱和脂肪基础饮食的雄性幼年大鼠中，进行了以下添加：基础饮食；黄曲霉毒素B1 @ 1.7 ppm；硬脂酸 @ 210 ppm；以及黄曲霉毒素B1 @ 1.7 ppm 加上硬脂酸 @ 210 ppm。大鼠吃这些饮食2个月，之后直到9个月后被宰杀前，只喂未加补充的基础饮食。所有给予饮食补充的大鼠生长都受到了抑制，但无论脂肪来源如何，都没有观察到协同抑制。黄曲霉毒素使肝脏重量加倍；然而，只有当饮食中含有不饱和脂肪时，硬脂酸与黄曲霉毒素结合才会夸大肝脏重量的增加。在喂食饱和脂肪饮食的大鼠中，给对照组或硬脂酸补充饮食的大鼠施用黄曲霉毒素，导致血浆胆固醇水平显著增加；而补充了黄曲霉毒素的不饱和脂肪饮食则引起了血浆胆固醇含量的轻微增加，这种增加被硬脂酸补充所抵消。

IN MALE WEANLING RATS FED BASAL DIETS OF SATURATED OR UNSATURATED FAT, THE FOLLOWING ADDITIONS WERE MADE: BASAL DIET; AFLATOXIN B1 @ 1.7 PPM; STERCULIC ACID @ 210 PPM; & AFLATOXIN B1 @ 1.7 PPM, PLUS STERCULIC ACID @ 210 PPM. RATS CONSUMED THESE DIETS FOR 2 MONTHS & THEREAFTER WERE FED UNSUPPLEMENTED BASAL DIET UNTIL SACRIFICE 9 MONTHS LATER. GROWTH WAS DEPRESSED IN ALL RATS GIVEN DIETARY SUPPLEMENTS BUT NO SYNERGISTIC INHIBITION WAS OBSERVED, REGARDLESS OF FAT SOURCE. LIVER WEIGHT DOUBLED IN RESPONSE TO AFLATOXIN; HOWEVER, ONLY WHEN DIET CONTAINED UNSATURATED FAT DID STERCULIC ACID, IN COMBINATION WITH AFLATOXIN, EXAGGERATE THE INCREASE IN LIVER WEIGHT. IN RATS FED SATURATED FAT DIET, AFLATOXIN ADMIN TO RATS FED THE CONTROL OR STERCULIC ACID SUPPLEMENT DIETS RESULTED IN MARKED INCREASE IN PLASMA CHOLESTEROL LEVELS; THE UNSATURATED FAT DIETS, SUPPLEMENTED WITH AFLATOXIN, EVOKED A SLIGHT INCREASE IN PLASMA CHOLESTEROL CONTENT WHICH WAS NULLIFIED BY STERCULIC ACID SUPPLEMENTATION.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

环丙烯脂肪酸在200 ppm剂量水平下被添加到木棉籽油中，并喂给幼年虹鳟鱼4周，而500 ppm的剂量则喂给了大鼠2周和4周。所有动物的肝脏都体积增大且适度脂肪化；肝脏重量、肝DNA含量、有丝分裂指数以及肝细胞核DNA中掺入(3)H-胸腺嘧啶的水平显著高于对照组动物。组织学和细胞学改变（含有多数脂肪滴的泡沫状细胞质、大而深染的细胞核、增大且有时多个核仁以及频繁的有丝分裂）在环丙烯脂肪酸喂养2周后变得明显，并且在两种物种中都非常相似。

CYCLOPROPENOID FATTY ACIDS IN STERCULIA FOETIDA OIL AT DOSE LEVEL OF 200 PPM WERE FED TO FINGERLING RAINBOW TROUT FOR 4 WK, & 500 PPM WAS FED TO RATS FOR 2- & 4 WK PERIODS. LIVERS OF ALL ANIMALS WERE LARGE & MODERATELY FATTY; LIVER WEIGHT, CONTENT OF HEPATIC DNA, MITOTIC INDEX, & INCORPORATION OF (3)H-THYMIDINE INTO NUCLEAR DNA OF HEPATOCYTES WERE INCREASED SIGNIFICANTLY ABOVE THOSE OF CONTROL ANIMALS. HISTOLOGIC & CYTOLOGIC ALTERATIONS (FOAMY CYTOPLASM WITH NUMEROUS FAT DROPLETS, LARGE & HYPERCHROMATIC NUCLEI, ENLARGED & SOMETIMES MULTIPLE NUCLEOLI, & FREQUENT MITOSIS) WERE EVIDENT AFTER 2 WK OF CYCLOPROPENOID FATTY ACID FEEDING & VERY SIMILIAR IN BOTH SPECIES.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

STERCULIC ACID 是一种天然存在的环丙烯脂肪酸。研究了在环丙烯环的9,10-亚甲基位标记放射性同位素的STERCULIC ACID在大鳞大麻哈鱼(S GAIRDNERI)体内的分布。在给药剂量中，50%在168小时内通过粪便和尿液排出，但在相同的时间段内，不到1%的剂量以二氧化碳形式呼出。放射性同位素进入大多数器官的高峰在119小时，肝脏中的大部分标记在脂质部分的脂肪酸中。虹鳟鱼容易吸收、运输并将STERCULIC ACID整合到组织脂质中，包括膜脂质，但不能将环丙烯的亚甲基氧化成二氧化碳。

STERCULIC ACID IS A NATURALLY OCCURRING CYCLOPROPENOID FATTY ACID. THE DISTRIBUTION OF RADIOACTIVITY FROM STERCULIC ACID, LABELED ON 9,10-METHYLENE C OF THE CYCLOPROPENE RING, WAS INVESTIGATED IN TROUT, S GAIRDNERI. OF THE ADMIN DOSE, 50% WAS EXCRETED IN FECES & URINE BY 168 HR, BUT LESS THAN 1% OF THE DOSE WAS EXPIRED AS CO2 DURING THE SAME TIME PERIOD. INCORPORATION OF RADIOACTIVITY INTO MOST ORGANS PEAKED AT 119 HR & THE MAJORITY OF THE LABEL IN THE LIVER WAS IN THE FATTY ACID PORTION OF THE LIPID FRACTION. RAINBOW TROUT READILY ABSORB, TRANSPORT & INCORPORATE STERCULIC ACID INTO TISSUE LIPID, INCL MEMBRANE LIPID, BUT CANNOT OXIDIZE THE METHYLENE C OF THE CYCLOPROPENOID TO CO2.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  -20°C，干燥且密封保存。

制备方法与用途

甾体酸是一种硬脂酰辅酶A去饱和酶-1（SCD1）抑制剂，能特异性地抑制δ-9去饱和酶（Δ9D）的活性，其IC50值为0.9微摩尔。

反应信息

• 作为产物：
  描述：

  3-(1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)propanoic acid 在 双氧水 、 四丁基碘化铵 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 12.0h， 以99%的产率得到9,10-亚甲基油酸
  参考文献：
  名称：

  原位生成的（次要）碘化物催化剂，用于羧酸与羰基化合物的直接α-羰基化反应

  摘要：

  它是碘：分子内和分子间标题反应是由原位生成的亚碘铵（次同）催化的。H 2 O 2或叔丁基氢过氧化物（TBHP）都可以用作环境友好的氧化剂，并且多种底物反应生成相应的α-酰氧基羰基化合物，收率良好至优异。

  DOI：

  10.1002/anie.201101522

文献信息

• Electrocatalytic Dehydrogenative Esterification of Aliphatic Carboxylic Acids: Access to Bioactive Lactones
  作者：Sheng Zhang、Fei Lian、Mengyu Xue、Tengteng Qin、Lijun Li、Xu Zhang、Kun Xu

  DOI：10.1021/acs.orglett.7b03333

  日期：2017.12.15

  A scalable and efficient electrocatalytic dehydrogenative esterification is reported. With an indirect electrolysis strategy, both intra- and intermolecular-type reactions were amenable to this practical method. With n-Bu4NI as the catalyst, undesired decarboxylation and Baeyer–Villiger oxidation were suppressed. More importantly, this novel method provided reliable and direct access to the natural

  据报道可扩展且有效的电催化脱氢酯化。通过间接电解策略，分子内和分子间反应都适合该实用方法。使用n -Bu 4 NI作为催化剂，可以抑制不希望的脱羧和Baeyer-Villiger氧化。更重要的是，这种新颖的方法可提供以克为单位的对天然产物胞嘧啶酮A的可靠，直接的获取。
• [EN] HETEROCYCLIC DERIVATIVES AND THEIR USE AS STEAROYL-COA DESATURASE INHIBITORS<br/>[FR] DERIVES HETEROCYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA STEAROYL-COA DESATURASE
  申请人：XENON PHARMACEUTICALS INC

  公开号：WO2006034441A1

  公开（公告）日：2006-03-30

  Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I) where x, y, J, K, W, V, R3, R4, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明公开了治疗哺乳动物，尤其是人类患有SCD介导的疾病或症状的方法，其中所述方法包括向需要的哺乳动物施用式(I)的化合物，其中在此处定义了x、y、J、K、W、V、R3、R4、R5、R5a、R6、R6a、R7、R7a、R8和R8a。还公开了包含式(I)化合物的药物组合物。
• [EN] DERIVATIVES OF 2H PYRIDAZIN- 3 -ONES, THEIR PREPARATION AND THEIR USE AS SCD-1 INHIBITORS<br/>[FR] DÉRIVÉS DE 2H-PYRIDAZIN-3-ONES, LEUR PRÉPARATION ET LEUR UTILISATION COMME INHIBITEURS DE LA SCD-1
  申请人：PF MEDICAMENT

  公开号：WO2011015629A1

  公开（公告）日：2011-02-10

  The present invention concerns compounds of general formula (I) characterized in that (formula 1) wherein, in particular: -R1 represents one or more groups such as: trif luoromethyl, halogen such as F, C1, -when n=m=1, W represents CH then Y represents oxygen, -U represents: • either - (C=O) CH2NH- and is branched at position 4 of pyridazinone, then R2 represents H, • or -(C=O)NH- and U is branched at positions (4), (5) or (6) of pyridazinone, then R2 represents H, - R3 represents a hydrogen or methyl and the addition salts with pharmaceutically acceptable bases and acids and the different isomers, and their mixtures in any proportion for use as SCD-1 enyzme inhibitors for the treatment of obesitz, tzpe-2 diabetes and lipid disorders.

  本发明涉及一般式(I)的化合物，其特征在于（式1），其中，特别是： -R1代表三氟甲基、氟、C1等一种或多种基团， -当n=m=1时，W代表CH，Y代表氧， -U代表： • 要么是-(C=O)CH2NH-并且在吡啶并酮的4位分支，然后R2代表H， • 要么是-(C=O)NH-并且U在吡啶并酮的(4)、(5)或(6)位分支，然后R2代表H， -R3代表氢或甲基，以及与药用可接受的碱和酸形成的加合物，以及不同的异构体，以及它们在任何比例下的混合物，用作SCD-1酶抑制剂，用于治疗肥胖症、2型糖尿病和脂质紊乱。
• [EN] DERIVATIVES OF TRIAZINES AND URACILS, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPEUTICS<br/>[FR] DÉRIVÉS DE TRIAZINES ET D'URACILES, LEUR PRÉPARATION ET LEURS APPLICATIONS EN THÉRAPEUTIQUE HUMAINE
  申请人：PF MEDICAMENT

  公开号：WO2010006962A1

  公开（公告）日：2010-01-21

  The present invention relates to derivatives of general formula I wherein : - W represents nitrogen, - R1 represents: • a hydrogen or a linear or branched C1-C5 alkyl radical or, • a C1-C3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C1-C3 alcoxy, C3-C6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C1-C3 N-alkylcarbamoyl groups or, • a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C1-C4 alkyl, linear or branched C1-C3 alkoxy groups, • a C6 2-oxocycloalkyl radical - R2 represents a methyl or heptyl, - m, n are equal to 1, - V represents CH2, - X-Y represents -N- (C=O) -, -CH-O-, - Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C1-C4 alkyl groups.

  本发明涉及一般式I的衍生物，其中： - W代表氮， - R1代表： • 氢或直链或支链C1-C5烷基基团，或者 • 被三氟甲基、腈、羟基、C1-C3烷氧基、C3-C6烷氧基烷氧基、吲哚基、噻吩基、氧硫吩基、C1-C3 N-烷基氨基羰基基团取代的C1-C3烷基基团，或者 • 苯基或吡啶基或萘基，或者选择性地被一个或多个卤素原子、硝基、腈、三氟甲基、乙烯、甲硫基、直链或支链C1-C4烷基、直链或支链C1-C3烷氧基基团取代的噻吩基， • C6 2-氧代环烷基基团 - R2代表甲基或庚基， - m，n等于1， - V代表CH2， - X-Y代表-N- (C=O) -，-CH-O-，- Z代表被一个或多个三氟甲基基团、卤素原子或直链C1-C4烷基基团取代的苯基。
• [EN] HETEROCYCLIC DERIVATIVES AND THEIR USE AS MEDIATORS OF STEAROYL-COA DESATURASE<br/>[FR] DERIVES HETEROCYCLIQUES ET LEUR UTILISATION EN TANT QUE MODULATEURS DE STEAROYLE-COA DESATURASE
  申请人：XENON PHARMACEUTICALS INC

  公开号：WO2006034338A1

  公开（公告）日：2006-03-30

  Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): Formula (I) where x, y, G, J, L, M, V, W, R2, R3, R4, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明揭示了治疗哺乳动物，尤其是人类患有SCD介导的疾病或症状的方法，其中所述方法包括向需要的哺乳动物施用以下化合物（I）的方法：化合物（I）其中x、y、G、J、L、M、V、W、R2、R3、R4、R5、R5a、R6、R6a、R7、R7a、R8和R8a在此处被定义。还揭示了包含化合物（I）的药物组合物。