diethyl 2-(((1-phenyl-1H-pyrazol-5-yl)amino)methylene)malonate | 37799-81-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: diethyl 2-(((1-phenyl-1H-pyrazol-5-yl)amino)methylene)malonate
• 英文别名: 2-(((1-phenyl-1H-pyrazol-5-yl)amino)methylene)malonate；<1-Phenyl-pyrazolyl-(5)-aminomethylen>malonsaeurediethylester；diethyl{[(1-phenyl-5-pyrazolyl)-amino]methylene} malonate；[(2-phenyl-2H-pyrazol-3-ylamino)-methylene]-malonic acid diethyl ester；Diethyl {[(1-phenyl-5-pyrazolyl)amino]methylene}malonate；diethyl 2-[[(2-phenylpyrazol-3-yl)amino]methylidene]propanedioate
• CAS: 37799-81-8
• 化学式: C₁₇H₁₉N₃O₄
• 分子量: 329.356
• InChiKey: CUGDMBNWAPLCFO-UHFFFAOYSA-N

物化性质

• 熔点：
  105 °C
• 沸点：
  433.2±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  82.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl 2-(((1-phenyl-1H-pyrazol-5-yl)amino)methylene)malonate 在 邻苯二甲酸二乙酯 作用下， 反应 1.0h， 以70%的产率得到4-oxo-1-phenyl-4,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors

  摘要：

  式1的化合物在由TNF-α介导的疾病条件中很有用，如类风湿关节炎、骨关节炎、败血症、艾滋病、溃疡性结肠炎、多发性硬化症、克罗恩病和软骨退行性损失。

  公开号：

  US20030208066A1
• 作为产物：
  描述：

  5-氨基-4-乙氧羰基-1-苯基吡唑 在 磷酸 作用下， 反应 8.0h， 生成 diethyl 2-(((1-phenyl-1H-pyrazol-5-yl)amino)methylene)malonate
  参考文献：
  名称：

  设计，合成和抗磷。吡唑并吡啶-磺酰胺衍生物的falciparum活性。

  摘要：

  合成了十个通过连接基团连接到在4-位具有不同取代基的苯磺酰胺部分的1-苯基-1H-吡唑并[3,4-b]吡啶衍生物，并针对恶性疟原虫进行了测定。这十种化合物在体外表现出对耐氯喹克隆W2的活性，IC50值为3.46至9.30μM。在苯磺酰胺部分具有取代基R2 = Cl或CH3的活性最高的衍生物表现出最低的IC50。在1H-吡唑并[3,4-b]吡啶环的5位上具有R1 = CO2Et取代基的化合物比具有CN取代基的化合物具有较低的活性。1H-吡唑并[3,4-b]吡啶系统作为克服疟原虫抗药性的抗疟药，有望用于进一步研究。

  DOI：

  10.1016/j.bmc.2016.07.049

文献信息

• Ortho-sulfonamido bicyclic hydroxamic acids as matrix metalloproteinase and TACE inhibitors
  申请人：American Cyanamid Company

  公开号：US06228869B1

  公开（公告）日：2001-05-08

  This invention provides, low molecular weight, non-peptide inhibitors of matrix metalloproteinases and TNF-&agr; converting enzyme (TACE, tumor necrosis factor-&agr; converting enzyme) of formula: B wherein B is P and Q are provided that when P is Q is and vice versa; or a pharmaceutically acceptable salt thereof.

  这项发明提供了一种低分子量、非肽类的基质金属蛋白酶和TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）的抑制剂，其化学式为：B其中B是P和Q，当P为时，Q为，反之亦然；或其药用盐。
• Preparation and use of ortho-sulfonamido bicyclic heteroaryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors
  申请人：——

  公开号：US20010046989A1

  公开（公告）日：2001-11-29

  This invention provides, low molecular weight, non-peptide inhibitors of matrix metalloproteinases and TNF-&agr; converting enzyme (TACE, tumor necrosis factor-&agr; converting enzyme) of formula: B wherein B is 1 2 T, U, W, and X are each, independently, carbon or nitrogen, provided that when T or U is carbon, either may be optionally substituted with R 1 ; Y is carbon, nitrogen, oxygen or sulfur, provided that at least one of T, U, W, X, and Y is not carbon, and further provided that no more than 2 of T, U, W, and X are nitrogen; 3 is a phenyl ring or is a heteroaryl ring of ring 5-6 atoms which may contain 0-2 heteratoms selected from nitrogen, oxygen, and sulfur, in addition to any heteroatoms defined by W or X; wherein the phenyl or heteroaryl ring may be optionally mono-, di-, or tri- substituted with R 1 ; Z is a phenyl, naphthyl, heteroaryl, or heteroaryl fused to phenyl, wherein the heteroaryl moiety contains of 5-6 ring atoms and 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur; wherein the phenyl, naphthyl, heteroaryl, or phenyl fused heteroaryl moieties may be optionally mono-, di-, or tri- substituted with R 1 ; R 1 is hydrogen, halogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cyclocalkyl of 3-6 carbon atoms, —(CH 2 ) n Z, —OR 2 , —CN, —COR 2 , perfluoroalkyl of 1-4 carbon atoms, —CONR 2 R 3 , —S(O) x R 2 —OPO(OR 2 )OR 3 , —PO(OR 2 )R 3 , —OC(O)NR 2 R 3 , —COOR 2 , —CONR 2 R 3 , —SO 3 H, —NR 2 R 3 , —NR 2 COR 3 , —NR 2 COOR 3 , —SO 2 NR 2 R 3 , —NO 2 , —N(R 2 )SO 2 R 3 , —NR 2 CONR 2 R 3 , —NR 2 C(═NR 3 )NR 2 R 3 , —SO 2 NHCOR 4 , —CONHSO 2 R 4 , -tetrazol-5-yl, —SO 2 NHCN, —SO 2 NHCONR 2 R 3 or Z; V is a saturated or partially unsaturated heterocycloalkyl ring of 5-7 ring atoms having 1-3 heteroatoms selected from N, O, or S, which may be optionally mono-, or di-substituted with R 2 ; R 2 and R 3 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R 4 is alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R 5 is hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, Z, or V; n=1-6; x=0-2 or a pharmaceutically acceptable salt thereof.

  这项发明提供了低分子量、非肽类的基质金属蛋白酶和TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）的抑制剂，其化学式为：其中 B 是 12T，U，W 和 X 分别独立地为碳或氮，但当 T 或 U 为碳时，可以选择性地用 R1 取代；Y 为碳、氮、氧或硫，要求 T、U、W、X 和 Y 中至少有一个不是碳，并且进一步要求 T、U、W 和 X 中不超过 2 个是氮；3 为苯环或是由 5-6 个原子组成的杂环，其中可能含有 0-2 个氮、氧或硫等杂原子，除了 W 或 X 定义的杂原子之外；苯或杂环可能选择性地单取代、双取代或三取代的 R1；Z 为苯、萘、杂环或与苯融合的杂环，其中杂环部分含有 5-6 个环原子和 1-3 个氮、氧或硫等杂原子；苯、萘、杂环或苯融合杂环部分可能选择性地单取代、双取代或三取代的 R1；R1 为氢、卤素、1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、3-6 个碳原子的环烷基、—(CH2)nZ、—OR2、—CN、—COR2、1-4 个碳原子的全氟烷基、—CONR2R3、—S(O)xR2—OPO(OR2)OR3、—PO(OR2)R3、—OC(O)NR2R3、—COOR2、—CONR2R3、—SO3H、—NR2R3、—NR2COR3、—NR2COOR3、—SO2NR2R3、—NO2、—N(R2)SO2R3、—NR2CONR2R3、—NR2C(═NR3)NR2R3、—SO2NHCOR4、—CONHSO2R4、-四唑-5-基、—SO2NHCN、—SO2NHCONR2R3 或 Z；V 为由 5-7 个环原子组成、含有 1-3 个氮、氧或硫等杂原子的饱和或部分不饱和杂环烷基，可能选择性地单取代或双取代的 R2；R2 和 R3 分别独立地为氢、1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、3-6 个碳原子的环烷基、1-4 个碳原子的全氟烷基、Z 或 V；R4 为1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、3-6 个碳原子的环烷基、1-4 个碳原子的全氟烷基、Z 或 V；R5 为氢、1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、Z 或 V；n=1-6；x=0-2 或其药用盐。
• NEW TETRACYCLIC HETEROAROMATIC RING SYSTEM 3H-BENZO[b]PYRAZOLO[3,4-h]-1, 6-NAPHTHYRIDINES
  作者：Alexandre Reis de Azevedo、Izabel C.P.P. Frugulhetti、Misbahul Ain Khan、Samia Khakwani、Alice M. Rolim Bernardino

  DOI：10.1515/hc.2002.8.1.47

  日期：2002.1

  Various derivatives of the tetracyclic ring system 3//-Benzo[A]pyrazolo[3.4-A]1,6-naphthyridine were prepared from 4-anilino-l//-pyrazolo[3.4-Z>]pyridine-5carboxylic acids by intramolecular cyclization employing phophoryl chloride. Η NMR spectra of the various derivatives were recorder.

  4-苯胺基-1//-吡唑并[3.4-Z>]吡啶-5羧酸通过分子内反应制备了四环系统3//-苯并[A]吡唑并[3.4-A]1,6-萘啶的各种衍生物使用磷酰氯环化。各种衍生物的1H NMR光谱被记录。
• Mass Spectrometry of Heterocyclic Compounds: Benzo[b]pyrazolo[3,4-b]-1,6-naphthyridines
  作者：Samia Khakwani、Samina Aslam、Mehrzadi Noureen Shahi、Alice M. Rolim Bernardino、Misbahul Ain Khan

  DOI：10.14233/ajchem.2016.19946

  日期：——

  The mass spectra of a number of benzo[b]pyrazolo[3,4-b]-1,6-naphthyridines are presented. The fragmentation involves elimination of CO molecule followed by other fragments, such as halogen (Cl, Br) or halogen acids (HCl, HBr) and HCN, etc.

  本文展示了一些苯并[b]吡唑并[3,4-b]-1,6-萘啶的质谱。碎裂过程包括消除 CO 分子，然后产生其他碎片，如卤素（Cl、Br）或卤酸（HCl、HBr）和 HCN 等。
• Preparation and use of ortho-sulfonamido bicyclic heteroaryl hydroxamic acids as matrix metalloproteinase and tace inhibitors
  申请人：——

  公开号：US20010025047A1

  公开（公告）日：2001-09-27

  This invention provides, low molecular weight, non-peptide inhibitors of matrix metalloproteinases and TNF-&agr; converting enzyme (TACE, tumor necrosis factor-&agr; converting enzyme) of formula: B wherein B is 1 P and Q are 2 provided that when P is 3 and vice versa; T, U, W, and X are each, independently, carbon or nitrogen, provided that when T or U is carbon, either may be optionally substituted with R 1 ; Y is carbon, nitrogen, oxygen or sulfur, provided that at least one of T, U, W, X, and Y is not carbon, and further provided that no more than 2 of T, U, W, and X are nitrogen; 4 is a phenyl ring or is a heteroaryl ring of ring 5-6 atoms which may contain 0-2 heteratoms selected from nitrogen, oxygen, and sulfur, in addition to any heteroatoms defined by W or X; wherein the phenyl or heteroaryl ring may be optionally mono-, di-, or tri-substituted with R 1 ; Z is a phenyl, naphthyl, heteroaryl, or heteroaryl fused to phenyl, wherein the heteroaryl moiety contains of 5-6 ring atoms and 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur; wherein the phenyl, naphthyl, heteroaryl, or phenyl fused heteroaryl moieties may be optionally mono-, di-, or tri-substituted with R 1 ; R 1 is hydrogen, halogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cyclocalkyl of 3-6 carbon atoms, —(CH 2 ) n Z, —OR 2 , —CN, —COR 2 , perfluoroalkyl of 1-4 carbon atoms, —CONR 2 R 3 , —S(O) X R 2 —OPO(OR 2 )OR 3 , —PO(OR 2 )R 3 , —OC(O)NR 2 R 3 , —COOR 2 , —CONR 2 R 3 , —SO 3 H, —NR 2 R 3 , —NR 2 COR 3 , —NR 2 COOR 3 , —SO 2 NR 2 R 3 , —NO 2 , —N(R 2 )SO 2 R 3 , —NR 2 CONR 2 R 3 ,—NR 2 C(═NR 3 )NR 2 R 3 , —SO 2 NHCOR 4 , —CONHSO 2 R 4 , -tetrazol-5-yl, —SO 2 NHCN, —SO 2 NHCONR 2 R 3 , or Z; V is a saturated or partially unsaturated heterocycloalkyl ring of 5-7 ring atoms having 1-3 heteroatoms selected from N, O, or S, which may be optionally mono-, or di-substituted with R 2 ; R 2 and R 3 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R 4 is alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R 5 is hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, Z, or V; n=1-6; X=0-2 or a pharmaceutically acceptable salt thereof.

  该发明提供了低分子量、非肽类的基质金属蛋白酶和TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）抑制剂，其化学式为：B其中，B为1。P和Q为2，但当P为3时，反之亦然；T、U、W和X各自独立地为碳或氮，但当T或U为碳时，可以任选一个用R1取代；Y为碳、氮、氧或硫，但至少有一个T、U、W、X和Y不为碳，并且进一步提供不超过2个T、U、W和X为氮；4为苯环或环5-6原子的杂环环，除了由W或X定义的任何杂原子外，还可以包含0-2个从氮、氧和硫中选择的杂原子，其中苯环或杂环环可以选择性地单取代、二取代或三取代R1；Z为苯、萘、杂环或与苯融合的杂环，其中杂环基团包含5-6个环原子和1-3个从氮、氧或硫中选择的杂原子；其中苯、萘、杂环或苯融合的杂环基团可以选择性地单取代、二取代或三取代R1；R1为氢、卤素、1-8个碳原子的烷基、2-6个碳原子的烯基、2-6个碳原子的炔基、3-6个碳原子的环烷基、-(CH2)nZ、-OR2、-CN、-COR2、1-4个碳原子的全氟烷基、-CONR2R3、-S(O)XR2-OPO(OR2)OR3、-PO(OR2)R3、-OC(O)NR2R3、-COOR2、-CONR2R3、-SO3H、-NR2R3、-NR2COR3、-NR2COOR3、-SO2NR2R3、-NO2、-N(R2)SO2R3、-NR2CONR2R3、-NR2C(═NR3)NR2R3、-SO2NHCOR4、-CONHSO2R4、-四唑-5-基、-SO2NHCN、-SO2NHCONR2R3或Z；V为5-7个环原子的饱和或部分不饱和的杂环烷基环，其中有1-3个从N、O或S中选择的杂原子，可以选择性地单取代或二取代R2；R2和R3各自独立地为氢、1-8个碳原子的烷基、2-6个碳原子的烯基、2-6个碳原子的炔基、3-6个碳原子的环烷基、1-4个碳原子的全氟烷基、Z或V；R4为1-8个碳原子的烷基、2-6个碳原子的烯基、2-6个碳原子的炔基、3-6个碳原子的环烷基、1-4个碳原子的全氟烷基、Z或V；R5为氢、1-8个碳原子的烷基、2-6个碳原子的烯基、2-6个碳原子的炔基、Z或V；n为1-6；X为0-2或其药学上可接受的盐。