methyl 6-hexadecylamino-3-pyridinecarboxylate | 73781-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 6-hexadecylamino-3-pyridinecarboxylate
• 英文别名: 6-Hexadecylamino-nicotinic acid methyl ester；methyl 6-(hexadecylamino)pyridine-3-carboxylate
• CAS: 73781-92-7
• 化学式: C₂₃H₄₀N₂O₂
• 分子量: 376.583
• InChiKey: ZIECLTMQFCNTHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  27
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 6-hexadecylamino-3-pyridinecarboxylate 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以95%的产率得到6-Hexadecylamino-nicotinic acid
  参考文献：
  名称：

  潜在的抗动脉粥样硬化剂。3.替他本的苯甲酸和非苯甲酸类似物。

  摘要：

  描述了一系列类似物的合成，其中cetaben的羧酸基被羧酸酯，羧酰胺或各种其他取代基取代。还报道了类似物的合成，其中cetaben的苯环被其他取代基的存在修饰或被另一部分完全取代。讨论了这些化合物作为降血脂药和作为脂肪酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂的结构活性关系。被设计为产生比西他本更好口服吸收的化合物的类似物合成未能产生任何具有增强生物活性的同类物。相反，针对酸度与西他本相似的非羧酸的类似物合成产生了非常活跃的磺酰胺类。

  DOI：

  10.1021/jm00364a010
• 作为产物：
  描述：

  6-氨基烟酸甲酯 、 溴代十六烷 在 六甲基磷酰三胺 作用下， 反应 22.0h， 以95%的产率得到methyl 6-hexadecylamino-3-pyridinecarboxylate
  参考文献：
  名称：

  潜在的抗动脉粥样硬化剂。3.替他本的苯甲酸和非苯甲酸类似物。

  摘要：

  描述了一系列类似物的合成，其中cetaben的羧酸基被羧酸酯，羧酰胺或各种其他取代基取代。还报道了类似物的合成，其中cetaben的苯环被其他取代基的存在修饰或被另一部分完全取代。讨论了这些化合物作为降血脂药和作为脂肪酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂的结构活性关系。被设计为产生比西他本更好口服吸收的化合物的类似物合成未能产生任何具有增强生物活性的同类物。相反，针对酸度与西他本相似的非羧酸的类似物合成产生了非常活跃的磺酰胺类。

  DOI：

  10.1021/jm00364a010

文献信息

• Hypolipidemic and antiatherosclerotic novel
  申请人：American Cyanamid Company

  公开号：US04382143A1

  公开（公告）日：1983-05-03

  This disclosure described novel (monosubstituted-amino)heteroaryl carboxylic acids and analogs which are useful as hypolipidemic and antiatherosclerotic agents.

  这份披露描述了一种新型（单取代氨基）杂环芳基羧酸及其类似物，可用作降脂和抗动脉粥样硬化药物。
• Amino-substituted phenyl and heteroaryl compounds, process for their preparation and pharmaceutical compositions containing them
  申请人：AMERICAN CYANAMID COMPANY

  公开号：EP0003663A2

  公开（公告）日：1979-08-22

  The invention provides novel amino-substituted phenyl and heteroaryl compounds which show pharmaceutically useful properties, particularly as hypolipidemic and antiatherosclerotic agents, and processes for the preparation of the novel compounds. The novel compounds have the formula: Q is wherein Y is loweralkyl, loweralkoxy, hydroxy, nitro, acyloxy or halo, and m is an integer of from 0 to 4 inclusive, or a 5- or 6-membered heteroaryl ring containing 1 or more nitrogen, sulfur or oxygen atoms and which may be optionally substituted with one fluorine atom; R is hydrogen or a group convertible in vivo thereinto; Z is: wherein J is selected from the group consisting of hydroxy, loweralkoxy, loweralkoxyloweralkyloxy, diloweralkylaminoloweralkoxy, hydrogen, loweralkyl, (mono-or polyhydroxy)loweralkoxy, (mono- or polycarboxy)loweralkoxy, (mono- or polycarboxy)hydroxyloweralkoxy, allyloxy, 2,3-epoxypropoxy, substituted or unsubstituted(phen- oxy, benzyloxy and 3-pyridyloxy), pyridylmethoxy, tetra- hydropyranyloxy, (mono- or polyhydroxyl)loweralkyl- amino, (mono- or polycarboxy)loweralkylamino, (mono-or polycarboalkoxy)loweralkylamino, allylamino, propargylamino, 2-sulfoethylamino. (substituted or unsubstituted aroyl)amino, loweralkanoylamino, loweralkanesulfonylamino, (substituted or unsubstituted arene)sulfonylamino, loweralkanoylhydrazino, hydroxylamino, polymethyleneimino, (4-carboxy- or 4-carboethoxy)thiazolidino, and loweralkyl bearing one or more carboxy, carboloweralkoxy, carbamoyl, acyl, sulfinyl or sulfonyl groups, or wherein B is a saturated or unsaturated loweralkylene group and K is selected from the group consisting of hydrogen, loweralkyl, loweralkoxyethyl, diloweralkyl aminoethyl, (mono- or polyhydroxy)loweralkyl, (mono- or polycarboxy)loweralkyl, (mono- or polycarb- oxy)hydroxyloweralkyl, allyl, 2,3-epoxypropyl, substituted or unsubstituted (phenyl, benzyl or 3-pyridyl) or pyridylmethyl and tetrahydropyranyl; and wherein Q, Y, m and X are defined as follows: Formula I-A) Q is m is O; X is Sa-Ta- wherein Sa is selected from the group consisting of C3-C16 cycloalkyl or C4-C17 cycloalkenyl and is either unsubstituted or substituted with at least one C1-C13 alkyl, C4-C8 cycloalkyl, decahydronaphthyl, methylene, ethylidene, or isopropylidene group; Ta is a bond or a divalent radical selected from the group consisting of unbranched or branched C,-C,3 alkylene or alkenylene and is either unsubstituted or substituted with at least one C1-C4 alkyl group; with the proviso that the total number of carbon atoms in Sa and Ta shall not exceed twenty; and with the further proviso that when Ta is not a bond, Sa is not an unsubstituted cyclopropyl nor a cyclopropyl substituted with at least one C1-C13 alkyl; Formula I-B) Q is m is O; X is Sb- wherein Sb is a branched or unbranched mono- or polyunsaturated or cyclopropylated C3-C22 alkyl group and can be represented by the formula: wherein R2 and R3 are the same or different and are hydrogen or a saturated or unsaturated C,-Cg alkyl group: R, is a: Formula I-Ba) C2 to C21 E- or Z-alkenyl group unsubstituted or substituted with at least one loweralkyl group; Formula I-Bb) C2 to C20 alkynyl group unsubstituted or substituted with at least one methyl or ethyl group; Formula I-Bc) C. to C20 alkyl group containing at least 2 non-cumulative double bonds, said group being unsubstituted or substituted with at least one methyl or ethyl group; Formula I-Bd) C3 to C,2 allenyl group unsubstituted or substituted with at least one methyl or ethyl group; Formula I-Be) vinyl or C3 to C8 E- or Z-alkenyl group said vinyl or alkenyl group being unsubstituted or substituted with at least one methyl group, and in this Formula I-Be, R2 is a vinyl or C3 to CB E- or Z-alkenyl group unsubstituted or substituted with at least one methyl group; Formula I-Bf) allyl or C. to C8 E- or Z-alkenyl group said allyl or alkenyl group being substituted with at least one exo-(methylene, ethylidene, or isopropylidene), and either further unsubstituted or substituted with at least one methyl group; Formula I-Bg) vinyl or C3 to C8 E- or Z-alkenyl group substituted between the nitrogen and the double bond with at least one loweralkenyl, said vinyl or alkenyl group being unsubstituted or substituted with at least one methyl group; Formula I-Bh) vinyl or C3 to Cs E- or Z-alkenyl group said vinyl or alkenyl group being unsubstituted or substituted with at least one methyl and in this case, R2 is a C2 to C9 alkynyl group unsubstituted or substituted with at least one methyl group; Formula I-B,) C. to C20 alkyl group containing at least one carbon-carbon double bond and at least one carbon-carbon triple bond said group being unsubstituted or substituted with at least one loweralkyl group; or wherein Sb is a; Formula I-Bj) group of the formula wherein R4 is hydrogen or a C, to C15 alkyl group unsubstituted or substituted with at least one methyl group, R5 is hydrogen or methyl and W is a bond or a C, to C15 branched or unbranched alkylene group unsubstituted or substituted with at least one methyl group; Formula I-C) Q is m is O; X is Sc-Tc- wherein Sc is selected from the group consisting of mercapto, lowerakylthio, aralkylthio, arylthio, loweralkylsulinyl, loweralkylsulfonyl, aralkylsulfinyl, aralkylsulfonyl, arylsulfinyl, arylsulfonyl, arylamino, acylamino, loweralkylsulfonylamino, arylsulfonylamino, azido, oxo. oximino, chloro, bromo, and iodo; wherein the substituent Sc may contain q carbon atoms with q being an integer from 0 to 8. inclusive: Te is an unbranched or branched alkylene group, optionally saturated or (mono- or poly-)unsaturated and containing or not containing a cycloalkyl group, represented by the formula CnH2(n-p) with n being an integer from 7 to 18, inclusive, and p being an integer from 0 to 5, inclusive, both being selected in a manner such that the sum of n and q is greater than 6 but less than 19; provided that when Sc is halogen Tc must be a saturated alkylene group; J may not be loweralkyl bearing one or more carboxy. carboloweralkoxy, carbamoyl, acyl, sulfinyl or sulfonyl groups, and Z may not be 0 II -B-C-OK; Formula I-D) Q is m is O; X is Sd-Td- wherein Sd is selected from the group consisting of substituted or unsubstituted aryl and heteroaryl groups; Td is a saturated or unsaturated alkylene group of 1-18 carbon atoms which may be branched or unbranched; such that the total number of carbon atoms in Sd and Td shall not exceed 24; provided that J may not be hydroxyl, loweralkoxy, loweralkoxyloweralkyloxy, diloweralkylaminoloweralkoxy, or substituted or unsubstituted benzyloxy; Formula I-E) Q is m is 1 to 4 inclusive; X is a saturated or unsaturated hydrocarbon radical of 7-19 carbon atoms which may be branched or unbranched and which may contain one or more radicals selected from the group consisting of saturated or unsaturated cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; Y is loweralkyl, loweralkoxy, hydroxy, nitro, acyloxy, or halo; Formula I-F) Q is a 5- or 6-membered heteroaryl ring containing one or more nitrogen, sulfur, or oxygen atoms and optionally unsubstituted or substituted with one fluoro; X is Sf-Tf- wherein Sf is selected from the group consisting of hydrogen, C3-C8 cycloalkyl, and substituted or unsubstituted aryl; Tf is a divalent radical selected from the group consisting of branched or unbranched C6-C,g alkylene, alkenylene, and alkynylene; Formula I-G) Q is m is O; X is Sg-Tg- wherein Sg is selected from the group consisting of carboxy, loweralkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, carbamyl, mono- or diloweralkyl- carbamyl, cyano, sulfo, monoalkyl- or monoarylsulfamyl; Tg is an unbranched or branched alkylene group, optionally saturated or mono- or polyunsaturated, and containing or not containing a cycloalkyl group, represented by the formula CrH2(r-p) with r being an integer from 1 to 18, inclusive, and p being an integer from 0 to 5, inclusive; with the proviso that when Sg is a carbamyl, cyano, or sulfo group, Sg and the nitrogen atom in Formula I may not be bonded to the same carbon atom of the group Tg; Formula I-H) Q is m is O; X is a saturated or unsaturated hydrocarbon radical of 7-19 carbon atoms which may be branched or unbranched and which may contain a saturated or unsaturated cycloalkyl group, said radical containing one or more perfluorinated (-CF2 or -CF3) carbon atoms excluding the carbon adjacent to the nitrogen atom; and the pharmacologically acceptable acid-addition and cationic salts thereof.

  本发明提供了一种新型氨基取代的苯基和杂环芳基化合物，这些化合物具有药学上的有用性质，特别是作为降血脂和抗动脉硬化的药物，并且提供了这些新型化合物的制备方法。新型化合物具有如下通式： Q是 其中，Y是低级烷基、低级烷氧基、羟基、硝基、酰氧基或卤素，m是0到4之间的整数(包括0和4)，或者是一个含有1个或多个氮、硫或氧原子的5-或6-元杂环芳基环，该环可能被一个氟原子取代。R是氢或在体内可转化为氢的基团；Z是： 其中，J选自羟基、低级烷氧基、低级烷氧基低级烷氧基、二低级烷基氨基低级烷氧基、氢、低级烷基、(单或多个羟基)低级烷氧基、(单或多个羧基)低级烷氧基、(单或多个羧基)羟基低级烷氧基、烯丙氧基、2,3-环氧丙氧基、取代或未取代的苯氧基、苄氧基和3-吡啶氧基、吡啶基甲氧基、四氢吡喃氧基、(单或多个羟基)低级烷基氨基、(单或多个羧基)低级烷基氨基、(单或多个羧基烷氧基)低级烷基氨基、烯丙基氨基、炔丙基氨基、2-磺乙基氨基、(取代或未取代的芳酰基)氨基、低级烷酰氨基、低级烷磺酰氨基、(取代或未取代的芳基)磺酰氨基、低级烷酰基肼基、羟胺基、多甲基亚氨基、(4-羧基或4-羧乙氧基)四氢噻唑烷基，以及一个或多个含有羧基、羧低级烷氧基、氨基甲酰基、酰基、亚砜基或砜基的低级烷基；或者 其中，B是饱和或不饱和的低级烷基亚甲基基团，K选自氢、低级烷氧基乙基、双低级烷基氨基乙基、(单或多个羟基)低级烷基、(单或多个羧基)低级烷基、(单或多个羧基烷氧基)低级烷基、烯丙基、2,3-环氧丙基、取代或未取代的(苯基、苄基或3-吡啶基)或吡啶基甲基和四氢吡喃基；并且其中Q、Y、m和X的定义如下： 通式I-A) Q是 m是0；X是Sa-Ta-，其中Sa选自C3-C16环烷基或C4-C17环烯基，并且Sa可以是未取代的或取代有一个或多个C1-C13烷基、C4-C8环烷基、十氢萘基、亚甲基、乙烯基或异丙烯基的环；Ta是一个键或选自直链或支链C1-C3烷基亚基或烯基亚基的二价基团，并且Ta可以是未取代的或取代有一个或多个C1-C4烷基的；并且，Sa和Ta中的碳原子总数不得超过20；并且进一步规定，当Ta不为键时，Sa不是未取代的环丙基，也不是取代有一个或多个C1-C13烷基的环丙基； 通式I-B) Q是 m是0；X是Sb-，其中Sb是直链或支链的单或多不饱和或环丙烷化的C3-C22烷基基团，并且可以用如下通式表示： 其中，R2和R3是相同的或不同的，它们是氢或饱和或不饱和的C1-C8烷基基团；R1是： 通式I-Ba) C2到C21 E或Z-烯基基团，未取代或取代有一个或多个低级烷基的； 通式I-Bb) C2到C20炔基基团，未取代或取代有一个或多个甲基或乙基的； 通式I-Bc) C1到C20烷基基团，含有至少2个非累积性双键，该基团未取代或取代有一个或多个甲基或乙基的； 通式I-Bd) C3到C12炔烯基基团，未取代或取代有一个或多个甲基或乙基的； 通式I-Be) 氯乙烯或C3到C8 E或Z-烯基基团，所述氯乙烯或烯基基团未取代或取代有一个或多个甲基，此时在通式I-Be中，R2是氯乙烯或C3到C8 E或Z-烯基基团，未取代或取代有一个或多个甲基的； 通式I-Bf) 烯丙基或C3到C8 E或Z-烯基基团，所述烯丙基或烯基基团在氮和双键之间被至少一个外位(甲基、乙烯基、或异丙烯基)取代，并且进一步未取代或取代有一个或多个甲基的； 通式I-Bg) 氯乙烯或C3到C8 E或Z-烯基基团，所述氯乙烯或烯基基团在氮和双键之间被至少一个低级烯基取代，所述氯乙烯或烯基基团未取代或取代有一个或多个甲基的； 通式I-Bh) 氯乙烯或C3到C8 E或Z-烯基基团，所述氯乙烯或烯基基团未取代或取代有一个或多个甲基，并且此时R2是C2到C9炔基基团，未取代或取代有一个或多个甲基的； 通式I-Bi) C1到C20烷基基团，含有至少一个碳-碳双键和至少一个碳-碳三键，所述基团未取代或取代有一个或多个低级烷基的； 或者，Sb是： 通式I-Bj) 其中，R4是氢或C1到C15烷基基团，未取代或取代有一个或多个甲基的；R5是氢或甲基；W是键或C1到C15直链或支链烷基亚甲基基团，未取代或取代有一个或多个甲基的； 通式I-C) Q是 m是0；X是Sc-Tc-，其中Sc选自巯基、低级烷基巯基、芳烷基巯基、芳基巯基、低级烷基亚砜基、低级烷基砜基、芳烷基亚砜基、芳烷基砜基、芳基亚砜基、芳基砜基、芳基氨基、酰基氨基、低级烷基砜基氨基、芳基砜基氨基、叠氮基、氧基、氧亚氨基、氯、溴和碘；其中，取代基Sc可能含有的碳原子数q是0到8之间的整数；Tc是直链或支链的烷基亚甲基基团，可以是饱和的或单或双不饱和的，并且可能含有或不含环烷基基团，用通式CnH2(n-p)表示，其中n是从7到18的整数，p是从0到5的整数，两个选择使得n和q的和大于6但小于19；并且规定，当Sc是卤素时，Tc必须是饱和的烷基亚甲基基团；并且J不能是含有一个或多个羧基、羧低级烷氧基、氨基甲酰基、酰基、亚砜基或砜基的低级烷基基团，Z不能是0—N—B—O—K； 通式I-D) Q是 m是0；X是Sd-Td-，其中Sd选自取代或未取代的芳基和杂环芳基基团；Td是含有1到18个碳原子的饱和或不饱和烷基亚甲基基团，可以是支链的或直链的；并且Sd和Td中的碳原子总数不得超过24；并且规定，J不能是羟基、低级烷氧基、低级烷氧基低级烷氧基、双低级烷基氨基低级烷氧基，或取代或未取代的苄氧基； 通式I-E) Q是 m是1到4之间的整数(包括1和4)；X是含有7到19个碳原子的饱和或不饱和的碳氢化合物基团，可以是支链的或直链的，并且可能含有一个或多个选自饱和或不饱和环烷基、取代或未取代的芳基和取代或未取代的杂环芳基的基团；Y是低级烷基、低级烷氧基、羟基、硝基、酰氧基或卤素； 通式I-F) Q是含有一个或多个氮、硫或氧原子的5-或6-元杂环芳基环，并且可能未取代或取代有一个氟原子；X是Sf-Tf-，其中Sf选自氢、C3-C8环烷基，以及取代或未取代的芳基；Tf是直链或支链C6-C8烷基亚基、烯基亚基或炔基亚基； 通式I-G) Q是 m是0；X是Sg-Tg-，其中Sg选自羧基、低级烷氧基羰基、芳氧基羰基、杂环芳氧基羰基、氨基甲酰基、单或双低级烷基氨基甲酰基、氰基、亚砜基、单烷基或单芳基磺酰氨基；Tg是直链或支链烷基亚甲基基团，可以是饱和的或单或双不饱和的，并且可能含有或不含环烷基基团，用通式CrH2(r-p)表示，其中r是从1到18的整数，p是从0到5的整数；并且规定，当Sg是氨基甲酰基、氰基或亚砜基时，Sg和通式I中的氮原子可能不与Tg上的同一碳原子键合； 通式I-H) Q是 m是0；X是含有7到19个碳原子的饱和或不饱和的碳氢化合物基团，可以是支链的或直链的，并且可能含有一个饱和或不饱和的环烷基基团，所述基团含有一个或多个全氟化的(-CF2或-CF3)碳原子，不包括与氮原子相邻的碳原子；以及其药理学上可接受的酸加成盐和阳离子盐。
• 6-Amino pyridine carboxylic acid derivatives, a process for their preparation and pharmaceutical compositions containing them
  申请人：BEECHAM GROUP PLC

  公开号：EP0013153A1

  公开（公告）日：1980-07-09

  This invention provides a series of novel nicotinic acid derivatives, a method for their preparation and their use as hypolipidaemic agents. The compounds of the invention have formula (I):- wherein R1CH2- is a C9 to C25 alkyl or alkenyl group which is optionally branched or unbranched or includes a carbocyclic ring and R2 is -CO2H or -CH2CO2H or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable group which is convertable in the human body into a-CO2H or -CH2CO2H group.

  本发明提供了一系列新型烟酸衍生物、其制备方法及其作为降脂药的用途。 本发明的化合物具有式 (I) 其中 R1CH2- 是 C9 到 C25 的烷基或烯基，可选择支化或不支化或包括碳环，R2 是-CO2H 或-CH2CO2H 或其药学上可接受的盐或药学上可接受的基团，该基团可在人体内转化为-CO2H 或-CH2CO2H 基团。
• US4382143A
  申请人：——

  公开号：US4382143A

  公开（公告）日：1983-05-03
• Potential antiatherosclerotic agents. 3. Substituted benzoic and nonbenzoic acid analogs of cetaben
  作者：J. Donald Albright、Vern G. DeVries、Mila T. Du、Elwood E. Largis、Thomas G. Miner、Marvin F. Reich、Robert G. Shepherd

  DOI：10.1021/jm00364a010

  日期：1983.10

  acid group of cetaben is replaced by carboxylate ester, carboxamide, or a variety of other substituent groups is described. Also reported are the syntheses of analogues in which the phenyl ring of cetaben is either modified by the presence of additional substituents or replaced entirely by another moiety. Structure-activity relationships of these compounds both as hypolipidemic agents and as inhibitors

  描述了一系列类似物的合成，其中cetaben的羧酸基被羧酸酯，羧酰胺或各种其他取代基取代。还报道了类似物的合成，其中cetaben的苯环被其他取代基的存在修饰或被另一部分完全取代。讨论了这些化合物作为降血脂药和作为脂肪酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂的结构活性关系。被设计为产生比西他本更好口服吸收的化合物的类似物合成未能产生任何具有增强生物活性的同类物。相反，针对酸度与西他本相似的非羧酸的类似物合成产生了非常活跃的磺酰胺类。