6-甲基-2-吡啶-4-基嘧啶-4-胺 | 61310-35-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-甲基-2-吡啶-4-基嘧啶-4-胺
• 英文名称: 4-amino-6-methyl-2-(4-pyridyl)pyrimidine
• 英文别名: 6-methyl-2-pyridin-4-yl-pyrimidin-4-ylamine；4-amino-6-methyl-2-(4-pyridinyl)pyrimidine；4-Amino-6-methyl-2-(4-pyridinyl)pyrimidin；6-Methyl-2-(pyridin-4-yl)pyrimidin-4-amine；6-methyl-2-pyridin-4-ylpyrimidin-4-amine
• CAS: 61310-35-8
• 化学式: C₁₀H₁₀N₄
• 分子量: 186.216
• InChiKey: KNKKGGMVDGAMLG-UHFFFAOYSA-N

物化性质

• 熔点：
  192-194 °C(Solv: isopropanol (67-63-0))
• 沸点：
  288.4±32.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  64.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙氧基甲叉丙二酸二乙酯 、 6-甲基-2-吡啶-4-基嘧啶-4-胺 以76%的产率得到2-(6-methyl-2-pyridin-4-yl-pyrimidin-4-ylamino-methylene)-malonic acid diethyl ester
  参考文献：
  名称：

  5,8-Dihydro-5-oxo-2-(4-or

  摘要：

  抗菌性5,8-二氢-8-(较低烷基)-5-氧代-2-Q-4-R.sub.2-6-Z-吡啶并[2,3-d]嘧啶(I)，其中Z为羧基或较低羧烷氧基，R.sub.2为氢或较低烷基，Q为4(或3)-吡啶基或带有一个或两个较低烷基取代基的4(或3)-吡啶基，通过加热二-(较低烷基)N-(2-Q-6-R.sub.2-4-嘧啶基)氨甲亚甲基丙二酸酯(III)制备，以产生5,8-二氢-5-氧代-2-Q-4-R.sub.2-6-Z-吡啶并[2,3-d]嘧啶(II)，其与5-羟基-2-Q-4-R.sub.2-6-Z-吡啶并[2,3-d]嘧啶(IIA)互变异构，其中Q和R.sub.2与上述I中相同，Z为较低羧烷氧基，将II(或IIA)与较低烷基化试剂反应以产生I，其中Z为较低羧烷氧基，并水解此酯(I)以产生Z为羧基的I。或者，酸(II或IIA，其中Z为COOH)在首先水解酯(II或IIA，其中Z为较低羧烷氧基)后可以被烷基化。给出了中间体III及其制备中使用的中间体的制备方法。

  公开号：

  US03992380A1
• 作为产物：
  描述：

  4-amidinopyridine hydrochloride 在 镍 苯膦酰二氯 、 氢气 、 sodium methylate 、 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 32.0h， 生成 6-甲基-2-吡啶-4-基嘧啶-4-胺
  参考文献：
  名称：

  Novel orally active inhibitors of passive cutaneous anaphylaxis in rats: N-[2-(4-Pyridinyl)-4-pyrimidinyl] ureas and dialkyl [[[2-(4-pyridinyl)-4-pyrimidinyl]amino]methylene]malonates

  摘要：

  4-Chloro-2-(4-pyridinyl)pyrimidines were treated with alkylamines to afford the corresponding N-substituted amino derivatives. 4-Amino-2-(4-pyridinyl)pyrimidines and their N-substituted analogues were converted to amides, carbamates, aminomethylenemalonates, and ureas. Many of these compounds were found to have potential antiallergic activity as indicated by the rat passive cutaneous anaphylaxis screen. The most compounds were found in the last two series.

  DOI：

  10.1021/jm00349a014

文献信息

• N-[2-(pyridinyl)-4-pyrimidinyl]ureas
  申请人：Sterling Drug Inc.

  公开号：US04008235A1

  公开（公告）日：1977-02-15

  Compounds useful as anti-allergic agents are N-R.sub.3 -N-R.sub.4 -N'-R-N'-(2-Q-5-R.sub.1 -6-R.sub.2 -4-pyrimidinyl)ureas (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R.sub.1 is hydrogen, lower-alkyl or cyano, R.sub.2 is hydrogen or lower-alkyl, R.sub.3 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R.sub.4 is hydrogen, lower-alkyl, lower-hydroxyalkyl, lower-alkenyl or lower-cycloalkyl. Said ureas are prepared by reacting 2-Q-4-RNH-5-R.sub.1 -6-R.sub.2 -pyrimidine (II) with a carbamylating agent selected from an R.sub.4 '-isocyanate of the formula R.sub.4 'N=C=O to produce N-R.sub.4 '-N'-R-N'-(2-Q-5-R.sub.1 -6-R.sub.2 -4-pyrimidinyl)urea (IA), an N-R.sub.3 '-N-R.sub.4 '-carbamyl halide of the formula R.sub.3 'R.sub.4 'NC(=O)-halide to produce N-R.sub.3 '-N-R.sub.4 'N'-R-N'-(2-Q-5-R.sub.1 -6-R.sub.2 -4-pyrimidinyl)urea (IB) or 1,1'-carbonyldiimidazole to produce N-(2-Q-5-R.sub.1 -6-R.sub.2 -4-pyrimidinyl)-N-R-imidazole-1-carboxamide and then reacting said 1-carboxamide with R.sub.3 R.sub.4 NH to produce I.

  可用作抗过敏剂的化合物为N-R.sub.3 -N-R.sub.4 -N'-R-N'-(2-Q-5-R.sub.1 -6-R.sub.2 -4-嘧啶基)脲类化合物（I），其中Q为4-或3-或2-吡啶基或带有一个或两个较低烷基取代基或其N-氧化物，R为氢或较低烷基，R.sub.1为氢、较低烷基或氰基，R.sub.2为氢或较低烷基，R.sub.3为氢、较低烷基或较低羟基烷基，R.sub.4为氢、较低烷基、较低羟基烷基、较低烯基或较低环烷基。所述脲类化合物通过将2-Q-4-RNH-5-R.sub.1 -6-R.sub.2 -嘧啶（II）与选择自R.sub.4 'N=C=O的R.sub.4 '-异氰酸酯的羰基化试剂反应制备，以产生N-R.sub.4 '-N'-R-N'-(2-Q-5-R.sub.1 -6-R.sub.2 -4-嘧啶基)脲（IA），R.sub.3 'R.sub.4 'NC(=O)-卤化物的N-R.sub.3 '-N-R.sub.4 '-脲基卤化物以产生N-R.sub.3 '-N-R.sub.4 'N'-R-N'-(2-Q-5-R.sub.1 -6-R.sub.2 -4-嘧啶基)脲（IB）或1,1'-羰基二咪唑以产生N-(2-Q-5-R.sub.1 -6-R.sub.2 -4-嘧啶基)-N-R-咪唑-1-甲酰胺，然后将所述1-甲酰胺与R.sub.3 R.sub.4 NH反应以产生I。
• 5,8-Dihydro-5-oxo-2-(4-or
  申请人：Sterling Drug Inc.

  公开号：US03992380A1

  公开（公告）日：1976-11-16

  Antibacterial 5,8-dihydro-8-(lower-alkyl)-5-oxo-2-Q-4-R.sub.2 -6-Z-pyrido[2,3-d]pyrimidine (I) where Z is carboxy or lower-carbalkoxy, R.sub.2 is hydrogen or lower-alkyl and Q is 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents is prepared by heating di-(lower-alkyl) N-(2-Q-6-R.sub.2 -4-pyrimidinyl)aminomethylenemalonate (III) to produce 5,8-dihydro-5-oxo-2-Q-4-R.sub.2 -6-Z-pyrido[2,3-d]pyrimidine (II) which is tautomeric with 5-hydroxy-2-Q-4-R.sub.2 -6-Z-pyrido[2,3-d]pyrimidine (IIA) where Q and R.sub.2 are the same as in I above and Z is lower-carbalkoxy, reacting II(or IIA) with a lower-alkylating agent to produce I where Z is lower-carbalkoxy and hydrolyzing this ester (I) to produce I where Z is carboxy. Alternatively, the acid (II or IIA where Z is COOH) can be alkylated after first hydrolyzing the ester (II or IIA where Z is lower-carbalkoxy). The preparations of the intermediate III and intermediates used in its preparation are given.

  抗菌性5,8-二氢-8-(较低烷基)-5-氧代-2-Q-4-R.sub.2-6-Z-吡啶并[2,3-d]嘧啶(I)，其中Z为羧基或较低羧烷氧基，R.sub.2为氢或较低烷基，Q为4(或3)-吡啶基或带有一个或两个较低烷基取代基的4(或3)-吡啶基，通过加热二-(较低烷基)N-(2-Q-6-R.sub.2-4-嘧啶基)氨甲亚甲基丙二酸酯(III)制备，以产生5,8-二氢-5-氧代-2-Q-4-R.sub.2-6-Z-吡啶并[2,3-d]嘧啶(II)，其与5-羟基-2-Q-4-R.sub.2-6-Z-吡啶并[2,3-d]嘧啶(IIA)互变异构，其中Q和R.sub.2与上述I中相同，Z为较低羧烷氧基，将II(或IIA)与较低烷基化试剂反应以产生I，其中Z为较低羧烷氧基，并水解此酯(I)以产生Z为羧基的I。或者，酸(II或IIA，其中Z为COOH)在首先水解酯(II或IIA，其中Z为较低羧烷氧基)后可以被烷基化。给出了中间体III及其制备中使用的中间体的制备方法。
• AMINO ACID COMPOUNDS AND METHODS OF USE
  申请人：Pliant Therapeutics, Inc.

  公开号：US20190276449A1

  公开（公告）日：2019-09-12

  The invention relates to compounds of formula (A) and formula (I): or a salt thereof, wherein R 1 , R 2 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , q and p are as described herein. Compounds of formula (A), formula (I), and pharmaceutical compositions thereof are αvβ6 integrin inhibitors that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP).

  该发明涉及以下化合物的公式(A)和公式(I)：或其盐，其中R1、R2、R10、R11、R12、R13、R14、R15、R16、q和p如本文所述。公式(A)、公式(I)的化合物及其药物组合物是αvβ6整合素抑制剂，可用于治疗纤维化疾病，如特发性肺纤维化（IPF）和非特异性间质性肺炎（NSIP）。
• Pyrido 2,3-d pyridimin-5-ones
  申请人：STERLING DRUG INC.

  公开号：EP0108380A2

  公开（公告）日：1984-05-16

  2-Q-6-Q'-8-R-pyrido[2,3-d]pyrimidin-5(8H)-ones (1), where Q is 4 (or 3)-hydroxyphenyl, 4(or 3)-methoxyphenyl, 4 (or 3)-pyridinyl or4(or3)-pyridinyl having one or two lower-alkyl substituents, R' is hydrogen or alkyl having one to four carbon atoms, Q is hydrogen, amino or nitro, and R is alkyl having from one to four carbon atoms, CH(C2H5)2, (CH2)n = CHCH2 where n is 1 or 2, or Y-Z where Y is alkylene having from one to four carbon atoms and having its connecting linkages on different carbon atoms and Z is hydroxy, OR1 or NRIR2 where R1 and R2 are each methyl or ethyl, or acid-addition salts thereof and there preparation by reacting a 2-Q-4-R'-pyrido[2,3-d]pyrimidin-5(8H)-one of the Formula III (herein) where Q is 4 (or 3)-methoxyphenyl, 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents or alkali or alkaline earth metal salt thereof with an alkylating agent. Also shown is the cardiotonic use of I where Q is 4(or 3)-hydroxyphenyl, 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents and Q' is hydrogen or amino. The novel compounds of Formula III and their preparation are also claimed.

  2-Q-6-Q'-8-R 吡啶并[2,3-d]嘧啶-5(8H)-酮 (1)，其中 Q 是 4(或 3)-羟基苯基、4(或 3)-甲氧基苯基、4(或 3)-吡啶基或具有一个或两个低级烷基取代基的 4(或 3)-吡啶基，R'是氢或具有一至四个碳原子的烷基，Q 是氢、R'是氢或具有一至四个碳原子的烷基，Q 是氢、氨基或硝基，R 是具有一至四个碳原子的烷基、CH(C2H5)2、(CH2)n = CHCH2（其中 n 是 1 或 2）或 Y-Z，其中 Y 是具有一至四个碳原子的亚烷基，其连接键位于不同的碳原子上，Z 是羟基、OR1或NRIR2（其中R1和R2各自为甲基或乙基）或其酸加成盐，以及将式III（此处）的2-Q-4-R'-吡啶并[2,3-d]嘧啶-5(8H)-酮（其中Q为4(或3)-甲氧基苯基、4(或3)-吡啶基或具有一个或两个低级烷基取代基的4(或3)-吡啶基或其碱金属或碱土金属盐）与烷化剂反应制备。图中还显示了 I 的强心剂用途，其中 Q 为 4（或 3）-羟基苯基、4（或 3）-吡啶基或具有一个或两个低级烷基取代基的 4（或 3）-吡啶基，Q'为氢或氨基。本发明还要求得到式 III 的新型化合物及其制备方法。
• Dosage forms and regimens for amino acid compounds
  申请人：Pliant Therapeutics, Inc.

  公开号：US11419869B2

  公开（公告）日：2022-08-23

  The invention relates to dosage forms for daily administration of compounds of formula (A) and formula (I): or a salt thereof, wherein R1, R2, R10, R11, R12, R13, R14, R15, R16, q and p are as described herein. Compounds of formula (A), formula (I), and pharmaceutical compositions thereof are αvβ6 integrin inhibitors that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP).

  本发明涉及每日服用式（A）和式（I）化合物的剂型： 或其盐，其中 R1、R2、R10、R11、R12、R13、R14、R15、R16、q 和 p 如本文所述。式（A）、式（I）化合物及其药物组合物是αvβ6整合素抑制剂，可用于治疗纤维化，如特发性肺纤维化（IPF）和非特异性间质性肺炎（NSIP）。