1-methylpiperidylidene-2-(3-pyridyl)sulfonamide

• 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: 1-methylpiperidylidene-2-(3-pyridyl)sulfonamide
• 英文别名: (NE)-N-(1-methylpiperidin-2-ylidene)pyridine-3-sulfonamide
• 化学式: C₁₁H₁₅N₃O₂S
• 分子量: 253.325
• InChiKey: IECVSXDZNQQSDC-ACCUITESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  71
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  phenylmagnesium chloride 、 氯甲酸苯酯 、 1-methylpiperidylidene-2-(3-pyridyl)sulfonamide 生成
  参考文献：
  名称：

  Synthesis and antinociceptive activity of 1-methylpiperidylidene-2-(pyridyl)sulfonamides and related dihydropyridyl analogs

  摘要：

  The regiospecific 1,3-dipolar cycloaddition reaction of 1-methyl-1,2-dihydropyridine 2 with 2-, 3- or 4-pyridylsulfonyl azide 3a-c yielded the respective 1-methyl-1,2,3,6-tetrahydropyridylidene-2-(2-, 3- or 4-pyridyl)sulfonamides 5a-c. Hydrogenation of 5a-c afforded the corresponding 1-methylpiperldylidene-2-(pyridyl)sulfonamides 1a-c. Compounds lb and 1c were elaborated to 1',6'- 6a-d and 1',4'- 7a-c, and 1',2'-dihydropyridines 8a-e, respectively by quaternization with phenyl chloroformate followed by in situ reaction with methyl-, n-butyl-, t-butyl- or phenylmagnesium chloride, or sodium borohydride. Antinociceptive activity was determined using the rat sodium chloride-induced writhing assay. The point of attachment of the pyridyl ring was a determinant of activity where the relative activity order was 2-pyridyl la greater-than-or-equal-to 4-pyridyl 1c > 3-pyridyl 1b (ED50) values of 6.2, 9.0 and 6.6 mg/kg sc, respectively), relative to the reference drug meperidine (EC50 = 0.6 mg/kg sc). The pyridyl compounds lb,1c were more potent than their dihydropyridyl derivatives 6a-d, 8a-e. The most active dihydropyridyl derivative, 1-methylpiperidylidene-2-(1',2'-dihydro-2'-t-butyl-1'-phenoxycarbonyl-4'-pyridyl)sulfonamide 8c was more active at 25 mg/kg sc (68% inhibition of writhing) than aspirin at 50 mg/kg sc (58% inhibition of writhing). In the dihydropyridyl series of compounds 6a-d, 8a-e, a t-Bu substituent at the alpha-position of the 1',6'- or 1',2'-dihydropyridyl ring provided superior antinociceptive activity relative to that of a H, Me. n-Bu or Ph substituent.

  DOI：

  10.1016/0223-5234(93)90012-4
• 作为产物：
  描述：

  1-甲基-2H-吡啶 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙醚 为溶剂， 25.0 ℃ 、241.32 kPa 条件下， 反应 12.0h， 生成 1-methylpiperidylidene-2-(3-pyridyl)sulfonamide
  参考文献：
  名称：

  Synthesis and antinociceptive activity of 1-methylpiperidylidene-2-(pyridyl)sulfonamides and related dihydropyridyl analogs

  摘要：

  The regiospecific 1,3-dipolar cycloaddition reaction of 1-methyl-1,2-dihydropyridine 2 with 2-, 3- or 4-pyridylsulfonyl azide 3a-c yielded the respective 1-methyl-1,2,3,6-tetrahydropyridylidene-2-(2-, 3- or 4-pyridyl)sulfonamides 5a-c. Hydrogenation of 5a-c afforded the corresponding 1-methylpiperldylidene-2-(pyridyl)sulfonamides 1a-c. Compounds lb and 1c were elaborated to 1',6'- 6a-d and 1',4'- 7a-c, and 1',2'-dihydropyridines 8a-e, respectively by quaternization with phenyl chloroformate followed by in situ reaction with methyl-, n-butyl-, t-butyl- or phenylmagnesium chloride, or sodium borohydride. Antinociceptive activity was determined using the rat sodium chloride-induced writhing assay. The point of attachment of the pyridyl ring was a determinant of activity where the relative activity order was 2-pyridyl la greater-than-or-equal-to 4-pyridyl 1c > 3-pyridyl 1b (ED50) values of 6.2, 9.0 and 6.6 mg/kg sc, respectively), relative to the reference drug meperidine (EC50 = 0.6 mg/kg sc). The pyridyl compounds lb,1c were more potent than their dihydropyridyl derivatives 6a-d, 8a-e. The most active dihydropyridyl derivative, 1-methylpiperidylidene-2-(1',2'-dihydro-2'-t-butyl-1'-phenoxycarbonyl-4'-pyridyl)sulfonamide 8c was more active at 25 mg/kg sc (68% inhibition of writhing) than aspirin at 50 mg/kg sc (58% inhibition of writhing). In the dihydropyridyl series of compounds 6a-d, 8a-e, a t-Bu substituent at the alpha-position of the 1',6'- or 1',2'-dihydropyridyl ring provided superior antinociceptive activity relative to that of a H, Me. n-Bu or Ph substituent.

  DOI：

  10.1016/0223-5234(93)90012-4

文献信息

• WARREN, B. K.;KNAUS, E. E., J. HETEROCYCL. CHEM., 1982, 19, N 5, 1259-1260
  作者：WARREN, B. K.、KNAUS, E. E.

  DOI：——

  日期：——
• WARREN, BRENT K.;KNAUS, EDWARD E., J. HETEROCYCL. CHEM., 24,(1987) N 5, 1413-1416
  作者：WARREN, BRENT K.、KNAUS, EDWARD E.

  DOI：——

  日期：——
• Synthesis and antinociceptive activity of 1-methylpiperidylidene-2-(pyridyl)sulfonamides and related dihydropyridyl analogs
  作者：JK Buolamwini、EE Knaus

  DOI：10.1016/0223-5234(93)90012-4

  日期：1993.1

  The regiospecific 1,3-dipolar cycloaddition reaction of 1-methyl-1,2-dihydropyridine 2 with 2-, 3- or 4-pyridylsulfonyl azide 3a-c yielded the respective 1-methyl-1,2,3,6-tetrahydropyridylidene-2-(2-, 3- or 4-pyridyl)sulfonamides 5a-c. Hydrogenation of 5a-c afforded the corresponding 1-methylpiperldylidene-2-(pyridyl)sulfonamides 1a-c. Compounds lb and 1c were elaborated to 1',6'- 6a-d and 1',4'- 7a-c, and 1',2'-dihydropyridines 8a-e, respectively by quaternization with phenyl chloroformate followed by in situ reaction with methyl-, n-butyl-, t-butyl- or phenylmagnesium chloride, or sodium borohydride. Antinociceptive activity was determined using the rat sodium chloride-induced writhing assay. The point of attachment of the pyridyl ring was a determinant of activity where the relative activity order was 2-pyridyl la greater-than-or-equal-to 4-pyridyl 1c > 3-pyridyl 1b (ED50) values of 6.2, 9.0 and 6.6 mg/kg sc, respectively), relative to the reference drug meperidine (EC50 = 0.6 mg/kg sc). The pyridyl compounds lb,1c were more potent than their dihydropyridyl derivatives 6a-d, 8a-e. The most active dihydropyridyl derivative, 1-methylpiperidylidene-2-(1',2'-dihydro-2'-t-butyl-1'-phenoxycarbonyl-4'-pyridyl)sulfonamide 8c was more active at 25 mg/kg sc (68% inhibition of writhing) than aspirin at 50 mg/kg sc (58% inhibition of writhing). In the dihydropyridyl series of compounds 6a-d, 8a-e, a t-Bu substituent at the alpha-position of the 1',6'- or 1',2'-dihydropyridyl ring provided superior antinociceptive activity relative to that of a H, Me. n-Bu or Ph substituent.