JPS6318584B2 - - Google Patents
Info
- Publication number
- JPS6318584B2 JPS6318584B2 JP15357479A JP15357479A JPS6318584B2 JP S6318584 B2 JPS6318584 B2 JP S6318584B2 JP 15357479 A JP15357479 A JP 15357479A JP 15357479 A JP15357479 A JP 15357479A JP S6318584 B2 JPS6318584 B2 JP S6318584B2
- Authority
- JP
- Japan
- Prior art keywords
- eicosapentaenoic acid
- present
- pyridoxyl
- platelet aggregation
- acid amide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- SBHCLVQMTBWHCD-METXMMQOSA-N (2e,4e,6e,8e,10e)-icosa-2,4,6,8,10-pentaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C(O)=O SBHCLVQMTBWHCD-METXMMQOSA-N 0.000 claims description 8
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims description 7
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims description 7
- HXWJFEZDFPRLBG-UHFFFAOYSA-N Timnodonic acid Natural products CCCC=CC=CCC=CCC=CCC=CCCCC(O)=O HXWJFEZDFPRLBG-UHFFFAOYSA-N 0.000 claims description 5
- NHZMQXZHNVQTQA-UHFFFAOYSA-N pyridoxamine Chemical compound CC1=NC=C(CO)C(CN)=C1O NHZMQXZHNVQTQA-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- WMNJHJBAPOBQHU-UHFFFAOYSA-N n-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]icosa-5,8,11,14,17-pentaenamide Chemical compound CCC=CCC=CCC=CCC=CCC=CCCCC(=O)NCC1=C(CO)C=NC(C)=C1O WMNJHJBAPOBQHU-UHFFFAOYSA-N 0.000 claims description 3
- 235000008151 pyridoxamine Nutrition 0.000 claims description 2
- 239000011699 pyridoxamine Substances 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- -1 2-substituted pyridinium salt Chemical class 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- NCYSTSFUYSFMEO-OBLTVXDOSA-N PGI3 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C\C=C/CC)[C@H](O)C[C@@H]21 NCYSTSFUYSFMEO-OBLTVXDOSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NMZKLLJQNNTBRJ-OIXZZONUSA-N TXA3 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)C\C=C/CC)O[C@@H]2O[C@H]1C2 NMZKLLJQNNTBRJ-OIXZZONUSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- CWRKZMLUDFBPAO-VOTSOKGWSA-N (e)-dec-4-enal Chemical compound CCCCC\C=C\CCC=O CWRKZMLUDFBPAO-VOTSOKGWSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- WALQGLYYNPGHTK-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;methyl sulfate Chemical compound COS([O-])(=O)=O.C[N+]1=CC=CC=C1Cl WALQGLYYNPGHTK-UHFFFAOYSA-M 0.000 description 1
- OVFJVGPVSMMTSA-UHFFFAOYSA-M 4-methylbenzenesulfonate;1-methylpyridin-1-ium Chemical compound C[N+]1=CC=CC=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 OVFJVGPVSMMTSA-UHFFFAOYSA-M 0.000 description 1
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- GUTZMJAHDKIBSN-UHFFFAOYSA-N icosa-5,8,11,14,17-pentaenamide Chemical compound CCC=CCC=CCC=CCC=CCC=CCCCC(N)=O GUTZMJAHDKIBSN-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- ANOICLBSJIMQTA-WXGBOJPQSA-N prostaglandin D3 Chemical compound CC\C=C/C[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O ANOICLBSJIMQTA-WXGBOJPQSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- HNWCOANXZNKMLR-UHFFFAOYSA-N pyridoxamine dihydrochloride Chemical compound Cl.Cl.CC1=NC=C(CO)C(CN)=C1O HNWCOANXZNKMLR-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は医薬として有用なＮ―ピリドキシル
５，８，11，14，17―エイコサペンタエン酸アミ
ドおよびその製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to N-pyridoxyl 5,8,11,14,17-eicosapentaenoic acid amide useful as a pharmaceutical and a method for producing the same.
５，８，11，14，17―エイコサペンタエン酸は
古くから魚類に多量に含有されていることが知ら
れている不飽和脂肪酸である。その後この物質の
生理活性についてはあまり研究されていなかつた
が、プロスタグランデイン系の学問の発展にとも
ない、最近プロスタグランデインI3、トロンボキ
サンA3、プロスタグランデインD3等のPG3系の
前駆物質であることが確認された。PG3系すなわ
ち５，８，11，14，17―エイコサペンタエン酸の
代謝産物の研究はPG2系の研究に比べて非常に遅
れており、つい最近トロンボキサンA3はトロン
ボキサンA2と異なり、血小板凝集に対して不活
性であり、プロスタグランデインI3は血小板凝集
を阻害するとの報告がある程度である。従つて、
５，８，11，14，17―エイコサペンタエン酸の合
成による誘導体はほとんど報告されていない。 5,8,11,14,17-eicosapentaenoic acid is an unsaturated fatty acid that has long been known to be contained in large amounts in fish. Since then, not much research has been conducted on the physiological activity of this substance, but with the development of science on prostaglandin, recently, PG 3 such as prostaglandin I 3 , thromboxane A 3 , prostaglandin D 3 It was confirmed that it is a precursor substance. Research on the metabolites of the PG 3 series, namely 5,8,11,14,17-eicosapentaenoic acid, has lagged far behind that of the PG 2 series, and only recently has thromboxane A 3 , unlike thromboxane A 2, been identified. , is inactive against platelet aggregation, and there are some reports that prostaglandin I3 inhibits platelet aggregation. Therefore,
Few synthetic derivatives of 5,8,11,14,17-eicosapentaenoic acid have been reported.
本発明者らは５，８，11，14，17―エイコサペ
ンタエン酸の誘導体を合成し、その薬理作用を検
討していたところ、Ｎ―ピリドキシル５，８，
11，14，17―エイコサペンタエン酸アミドが優れ
た血小板凝集抑制作用を有するとともに、５，
８，11，14，17―エイコサペンタエン酸に比べて
安定でなおかつ吸収性にも優れていることを見い
出し本発明を完成した。 The present inventors synthesized a derivative of 5,8,11,14,17-eicosapentaenoic acid and investigated its pharmacological action.
11,14,17-eicosapentaenoic acid amide has an excellent platelet aggregation inhibitory effect, and also has 5,
The present invention was completed based on the discovery that it is more stable and has better absorbability than 8,11,14,17-eicosapentaenoic acid.
従つて本発明の目的は優れた薬理作用を有する
新規化合物Ｎ―ピリドキシル５，８，11，14，17
―エイコサペンタエン酸アミドを提供せんとする
にある。 Therefore, the object of the present invention is to develop a novel compound N-pyridoxyl 5,8,11,14,17 which has excellent pharmacological action.
- We aim to provide eicosapentaenoic acid amide.
他の目的はＮ―ピリドキシル５，８，11，14，
17―エイコサペンタエン酸アミドを製造する方法
を提供せんとするにある。 Other purposes are N-pyridoxyl 5, 8, 11, 14,
An object of the present invention is to provide a method for producing 17-eicosapentaenoic acid amide.
本発明のＮ―ピリドキシル５，８，11，14，17
―エイコサペンタエン酸アミドは、５，８，11，
14，17―エイコサペンタエン酸またはその反応性
誘導体とピリドキサミンを反応させることにより
製造される。 N-pyridoxyl of the present invention 5, 8, 11, 14, 17
-Eicosapentaenoic acid amide is 5, 8, 11,
It is produced by reacting 14,17-eicosapentaenoic acid or its reactive derivative with pyridoxamine.
５，８，11，14，17―エイコサペンタエン酸の
反応性誘導体としては、酸クロリド、酸ブロミド
等の酸ハライド、Ｎ―ヒドロキシコハク酸イミド
等との活性酸アミド、酸無水物等の一般の酸アミ
ド合成に使用される反応性誘導体が適用可能であ
る。 Reactive derivatives of 5,8,11,14,17-eicosapentaenoic acid include acid halides such as acid chloride and acid bromide, active acid amides with N-hydroxysuccinimide, and general acid anhydrides. Reactive derivatives used in acid amide synthesis are applicable.
また、５，８，11，14，17―エイコサペンタエ
ン酸をそのまま使用する場合には、Ｎ，Ｎ―ジシ
クロヘキシルカルボジイミドや２―置換ピリジニ
ウム塩および塩基の存在下に行うのが好ましい。
２―置換ピリジニウム塩としては、２―クロロ―
１―メチルピリジニウムｐ―トルエンスルホネー
ト、２―クロロ―１―メチルピリジニウムブロミ
ド、２―クロロ―１―メチルピリジニウムメチル
サルフエート等が挙げられる。塩基としてはトリ
エチルアミン、トリブチルアミンその他の有機塩
基あるいは炭酸ナトリウム、炭酸カリウム等の無
機塩基が挙げられる。 Furthermore, when 5,8,11,14,17-eicosapentaenoic acid is used as it is, it is preferably carried out in the presence of N,N-dicyclohexylcarbodiimide, a 2-substituted pyridinium salt, and a base.
As the 2-substituted pyridinium salt, 2-chloro-
Examples include 1-methylpyridinium p-toluenesulfonate, 2-chloro-1-methylpyridinium bromide, 2-chloro-1-methylpyridinium methylsulfate, and the like. Examples of the base include triethylamine, tributylamine and other organic bases, and inorganic bases such as sodium carbonate and potassium carbonate.
反応は水またはジクロルメタン、ジクロルエタ
ン、アセトニトリル、ベンゼン、トルエン等の反
応に関与しない有機溶媒中、通常室温から溶媒の
還流温度までの温度で１〜20時間反応させること
により行われる。 The reaction is carried out in water or an organic solvent that does not participate in the reaction, such as dichloromethane, dichloroethane, acetonitrile, benzene, toluene, etc., usually at a temperature from room temperature to the reflux temperature of the solvent, for 1 to 20 hours.
本発明化合物は優れた血小板凝集抑制作用を有
するとともに、５，８，11，14，17―エイコサペ
ンタエン酸に比べて安定であり、さらに吸収性に
も優れており医薬として有用である。 The compounds of the present invention have excellent platelet aggregation inhibiting effects, are more stable than 5,8,11,14,17-eicosapentaenoic acid, and have excellent absorbability, making them useful as pharmaceuticals.
すなわち、ウサギに本発明化合物を投与してお
き、コラーゲン、アドレナリン、アデノシン二燐
酸などの血小板凝集誘起物質による血小板凝集に
対する抑制効果を検討した結果、コントロール群
に比べて本発明化合物投与群が優れた抑制効果を
示した。また試験管内においても本発明化合物が
直接血小板凝集抑制作用を有することを確認し
た。 That is, as a result of administering the compound of the present invention to rabbits and examining the inhibitory effect on platelet aggregation induced by platelet aggregation inducers such as collagen, adrenaline, and adenosine diphosphate, the group administered with the compound of the present invention was superior to the control group. It showed suppressive effect. It was also confirmed that the compound of the present invention has a direct platelet aggregation inhibiting effect even in vitro.
次に実施例を挙げて本発明を詳細に説明する。 Next, the present invention will be explained in detail with reference to Examples.
実施例
ジクロルメタン500mlに５，８，11，14，17―
エイコサペンタエン酸50ｇ、Ｎ，Ｎ―ジシクロヘ
キシルカルボジイミド34ｇおよびＮ―ヒドロキシ
コハク酸イミド19ｇをこの順に加えて溶解し、室
温で３時間撹拌した後、析出した結晶を過し除
去した。液から減圧でジクロルメタンを留去
し、ついでジメチルホルムアミド200mlを加えた。
一方、ジメチルホルムアミド200mlにピリドキサ
ミン２塩酸塩40ｇおよびトリエチルアミン100ml
を加え、２時間撹拌し、この溶液に上記の反応物
のジメチルホルムアミド溶液を撹拌しながら加
え、室温でさらに２時間撹拌した。反応液から減
圧でジメチルホルムアミドを留去し、残渣に酢酸
エチルを加えて水で２回、ついで５％重曹水およ
び水で洗浄し、無水硫酸ナトリウムで乾燥した。
この酢酸エチル溶液を減圧濃縮し、得られた油状
物をシリカゲルクロマトグラフイー（展開液クロ
ロホルム：メタノール＝５：１）で精製しＮ―ピ
リドキシル５，８，11，14，17―エイコサペンタ
エン酸アミド42ｇを得た。Example 5, 8, 11, 14, 17 in 500 ml of dichloromethane
50 g of eicosapentaenoic acid, 34 g of N,N-dicyclohexylcarbodiimide and 19 g of N-hydroxysuccinimide were added and dissolved in this order, and after stirring at room temperature for 3 hours, the precipitated crystals were filtered off. Dichloromethane was distilled off from the liquid under reduced pressure, and then 200 ml of dimethylformamide was added.
Meanwhile, 40 g of pyridoxamine dihydrochloride and 100 ml of triethylamine in 200 ml of dimethylformamide.
was added and stirred for 2 hours, and a dimethylformamide solution of the above reactant was added to this solution with stirring, and the mixture was further stirred at room temperature for 2 hours. Dimethylformamide was distilled off from the reaction solution under reduced pressure, and ethyl acetate was added to the residue, which was washed twice with water, then with 5% aqueous sodium bicarbonate and water, and dried over anhydrous sodium sulfate.
This ethyl acetate solution was concentrated under reduced pressure, and the resulting oil was purified by silica gel chromatography (developing solution: chloroform:methanol = 5:1) to produce N-pyridoxyl 5,8,11,14,17-eicosapentaenoic acid amide. Obtained 42g.
性状：エーテル、ｎ―ヘキサンに難溶、エタノー
ル、ベンゼン、クロロホルム、酢酸エチルに易
溶の油状物。Properties: Oily substance, slightly soluble in ether and n-hexane, easily soluble in ethanol, benzene, chloroform, and ethyl acetate.
UVスペクトル λmax：285mμ（エタノール中） IRスペクトル νKBr nax（neat）cm-1：1630、1540（CONH） 1440（メチレン） 1360，1020 MS／ｍ／ｅ：452（M+）、151 NMR（CDCl3）δ： 7.18（1H，ｓ，核プロトン） 6.08（1H，ｔ，アミドプロトン） 5.28（10H，ｍ，オレフインプロトン） 4.42（2H，ｓ，ヒドロキシメチレン） 4.25（2H，ｄ，アミドメチレン） 2.70（8H，ｍ，オレフイン間メチレン） 2.32（3H，ｓ，核メチル） 0.90（3H，ｔ，末端メチル） 2.2〜1.1（8H、上記以外のメチレン）。UV spectrum λmax: 285 mμ (in ethanol) IR spectrum ν KBr nax (neat) cm -1 : 1630, 1540 (CONH) 1440 (methylene) 1360, 1020 MS/m/e: 452 (M + ), 151 NMR (CDCl 3 ) δ: 7.18 (1H, s, nuclear proton) 6.08 (1H, t, amide proton) 5.28 (10H, m, olefin proton) 4.42 (2H, s, hydroxymethylene) 4.25 (2H, d, amide methylene) 2.70 (8H, m, interolefin methylene) 2.32 (3H, s, nuclear methyl) 0.90 (3H, t, terminal methyl) 2.2-1.1 (8H, methylene other than the above).
Claims (1)
コサペンタエン酸アミド。 ２ ５，８，11，14，17―エイコサペンタエン酸
またはその反応性誘導体とピリドキサミンを反応
させることを特徴とする、Ｎ―ピリドキシル５，
８，11，14，17―エイコサペンタエン酸アミドの
製造法。[Claims] 1 N-pyridoxyl 5,8,11,14,17-eicosapentaenoic acid amide. 2 N-pyridoxyl 5, characterized by reacting 5,8,11,14,17-eicosapentaenoic acid or its reactive derivative with pyridoxamine.
Method for producing 8,11,14,17-eicosapentaenoic acid amide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15357479A JPS5677259A (en) | 1979-11-29 | 1979-11-29 | N-pyridoxyl 5,8,11,14,17-eicosapentaenoic acid amide, and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15357479A JPS5677259A (en) | 1979-11-29 | 1979-11-29 | N-pyridoxyl 5,8,11,14,17-eicosapentaenoic acid amide, and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5677259A JPS5677259A (en) | 1981-06-25 |
| JPS6318584B2 true JPS6318584B2 (en) | 1988-04-19 |
Family
ID=15565460
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15357479A Granted JPS5677259A (en) | 1979-11-29 | 1979-11-29 | N-pyridoxyl 5,8,11,14,17-eicosapentaenoic acid amide, and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5677259A (en) |
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-
1979
- 1979-11-29 JP JP15357479A patent/JPS5677259A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5677259A (en) | 1981-06-25 |
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