di-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) disulfide | 140618-95-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: di-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) disulfide
• 英文别名: bis(3,4-dihydro-2-oxo-1-methylquinol-6-yl) disulfide；di-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) disulphide；1-methyl-6-[(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)disulfanyl]-3,4-dihydroquinolin-2-one
• CAS: 140618-95-7
• 化学式: C₂₀H₂₀N₂O₂S₂
• 分子量: 384.523
• InChiKey: DASYEPCWJXEIDF-UHFFFAOYSA-N

物化性质

• 沸点：
  712.6±60.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  91.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  di-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) disulfide 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N²-[4-tert-butyloxy-2S-isobutyl-3S-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-ylthio)succinyl]-L-tert-leucine-N¹-methylamide
  参考文献：
  名称：

  新的基于α-取代的琥珀酸酯的异羟肟酸作为TNFα转化酶抑制剂。

  摘要：

  肿瘤坏死因子α转化酶（TACE）是负责将前TNFα转化为TNFα的酶，据报道是与基质金属蛋白酶（MMP）密切相关的金属蛋白酶。目前的TACE抑制剂，例如基于Marimastat（TACE IC（50）：3.8 nM;血液IC（50）：7 microM）和BB1101（TACE IC（50）：0.2 nM;血液IC（50）的琥珀酸异羟肟酸） ：2.3 microM）在血液中具有中等效力且体内特性较差。研究了将新的大体积α-取代基引入这些基于琥珀酸酯的异羟肟酸中。与Marimastat相比，诸如硫醚，磺酰胺和醚等取代物对TACE的效力有所改善。尽管这种改善并未转化为硫醚或醚取代基的更好的血液效力，与Marimastat相比，磺酰胺系列药物对TACE和血液的功效均得到改善。该磺酰胺系列的优化最终确定了杂环双环磺酰胺，例如3t（TACE IC（50）：0.57 nM；血液IC（50）：0.28 microM）。

  DOI：

  10.1021/jm990377j
• 作为产物：
  描述：

  1-甲基-2-喹啉酮 、 1-methylquinolin-2(1H)-on-6-yl disulfide 生成 di-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) disulfide
  参考文献：
  名称：

  Substituted-optionally hydrogenated isoquinoline compounds,

  摘要：

  该发明涉及一种异环丙烯衍生物，其化学式为I，其中Ar.sup.1是可选择取代的苯基、萘基或9-或10-成员的双环杂环基；A.sup.1是直接连接到X.sup.1或(1-3C)烷基的链；X.sup.1是氧、硫、亚硫酰基、磺酰基或亚胺基；Ar.sup.2是可选择取代的5-成员杂环基；R.sup.1是(1-4C)烷基、(3-4C)烯基或(3-4C)炔基；而R.sup.2和R.sup.3共同形成一个化学式为--A.sup.2--X.sup.2--A.sup.3--的基团，该基团与A.sup.2和A.sup.3所连接的碳原子一起定义具有5到7个环原子的环，其中A.sup.2和A.sup.3各自是(1-3C)烷基，X.sup.2是氧、硫、亚硫酰基或磺酰基；或其药用可接受盐。该发明的化合物是5-脂氧合酶的抑制剂。

  公开号：

  US05217978A1

文献信息

• Ether derivatives having 5-lipoxygenase inhibitory activity
  申请人：Zeneca Limited

  公开号：US05478842A1

  公开（公告）日：1995-12-26

  The invention concerns ether derivatives of the formula I Q.sup.1 --X--Ar--Q.sup.2 I wherein Q.sup.1 is an optionally substituted 9-, 10- or 11-membered bicyclic heterocyclic moiety containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur; X is oxy, thio, sulphinyl or sulphonyl; Ar is optionally substituted phenylene, pyridinediyl, pyrimidinediyl, thiophenediyl, furandiyl, thiazolediyl, oxazoiediyl, thiadiazoiediyl or oxadiazolediyl; and Q.sup.2 is selected from the groups of the formulae II and III: ##STR1## wherein R.sup.1 is hydrogen, (2-5C)alkanoyl or optionally substituted benzoyl; R.sup.2 is (1-4C)alkyl; and R.sup.3 is hydrogen or (1-4C)alkyl; or R.sup.2 and R.sup.3 are linked to form a methylene, vinylene, ethylene or trimethylene group; or a pharmaceutically-acceptable salt thereof; processes for their preparation; pharmaceutical compositions containing them and their use as 5-lipoxygenase inhibitors.

  本发明涉及公式I的醚衍生物 Q.sup.1 --X--Ar--Q.sup.2 I，其中Q.sup.1是可选地取代的含有一个或两个氮杂原子的9-、10-或11-成环杂环部分，并且可选地含有从氮、氧和硫中选择的另外一种杂原子；X是氧乙基、硫乙基、亚磺酰基或磺酰基；Ar是可选地取代的苯基、吡啶基、嘧啶基、噻吩基、呋喃基、噻唑基、恶唑基、噻二唑基或恶二唑基；Q.sup.2是公式II和III的组中选择的：##STR1##，其中R.sup.1是氢、(2-5C)烷酰或可选地取代的苯甲酰；R.sup.2是(1-4C)烷基；R.sup.3是氢或(1-4C)烷基；或者R.sup.2和R.sup.3连接形成一个亚甲基、乙烯基、亚乙基或三亚甲基组；或其药物可接受的盐；其制备过程；包含它们的药物组合物以及它们作为5-脂氧合酶抑制剂的使用。
• Thioxo quinoline compounds, composition and method of use
  申请人：ICI Pharma

  公开号：US05240941A1

  公开（公告）日：1993-08-31

  The invention concerns a thioxo heterocycle of the formula I ##STR1## wherein Q is a 10-membered bicyclic heterocyclic moiety containing 1 or 2 N's which bears 1 or 2 thioxo substituents and which is optionally further substituted; A.sup.1 is a direct link to X.sup.1 or (1-3C)alkylene; X.sup.1 is oxy, thio, sulphinyl, sulphonyl or imino; Ar is optionally substituted phenylene or pyridylene; R.sup.1 is (1-4C)alkyl, (3-4C)alkenyl or (3-4C)alkynyl; and R.sup.2 and R.sup.3 together form a group of the formula --A.sup.2 --X.sup.2 --A.sup.3 -- which, together with the carbon atom to which A.sup.2 and A.sup.3 are attached, defines a ring having 5 to 7 ring atoms, wherein each of A.sup.2 and A.sup.3 is (1-3C)alkylene and X.sup.2 is oxy, thio, sulphinyl or sulphonyl; or a pharmaceutically-acceptable salt thereof. The compounds of the invention are inhibitors of the enzyme 5-lipoxygenase.

  这项发明涉及一种化学式I的噻氧杂环化合物，其中Q是一个包含1或2个N的10元杂环双环脂肪基团，带有1或2个噻氧基取代基，可进一步取代；A.sup.1是直接连接到X.sup.1或(1-3C)烷基的链；X.sup.1是氧、硫、亚砜、砜基或亚胺基；Ar是可选取代的苯基或吡啶基；R.sup.1是(1-4C)烷基、(3-4C)烯基或(3-4C)炔基；R.sup.2和R.sup.3一起形成一个化学式--A.sup.2--X.sup.2--A.sup.3--的基团，与A.sup.2和A.sup.3连接的碳原子一起定义一个具有5到7个环原子的环，其中A.sup.2和A.sup.3各自是(1-3C)烷基，X.sup.2是氧、硫、亚砜或砜基；或其药学上可接受的盐。这些化合物是5-脂氧合酶酶的抑制剂。
• Heterocyclene derivatives
  申请人：Imperial Chemical Industries PLC

  公开号：US05484805A1

  公开（公告）日：1996-01-16

  The invention concerns a heterocyclene derivative of the formula I ##STR1## wherein Ar.sup.1 is optionally substituted phenyl, naphthyl or a 9- or 10-membered bicyclic heterocyclic moiety; A.sup.1 is a direct link to X.sup.1 or (1-3C)alkylene; X.sup.1 is oxy, thio, sulphinyl, sulphonyl or imino; Ar.sup.2 is optionally substituted 5-membered heterocyclene moiety; R.sup.1 is (1-4C)alkyl, (3-4C)alkenyl or (3-4C)alkynyl; and R.sup.2 and R.sup.3 together form a group of the formula --A.sup.2 --X.sub.2 --A.sup.3 -- which, together with the carbon atom to which A.sup.2 and A.sup.3 are attached, defines a ring having 5 to 7 ring atoms, wherein each of A.sup.2 and A.sup.3 is (1-3C)alkylene and X.sup.2 is oxy, thio, sulphinyl or sulphonyl; or a pharmaceutically-acceptable salt thereof. The compounds of the invention are inhibitors of the enzyme 5-lipoxygenase.

  本发明涉及公式I的杂环衍生物，其中Ar.sup.1是可选取代的苯基、萘基或9-或10-环杂双环杂环基；A.sup.1是直接连接到X.sup.1或(1-3C)烷基；X.sup.1是氧、硫、亚硫酰基、磺酰基或亚胺基；Ar.sup.2是可选取代的5-环杂杂环基；R.sup.1是(1-4C)烷基、(3-4C)烯基或(3-4C)炔基；R.sup.2和R.sup.3一起形成公式--A.sup.2--X.sub.2--A.sup.3--的基团，其中，与A.sup.2和A.sup.3连接的碳原子一起定义一个具有5至7个环原子的环，其中A.sup.2和A.sup.3各自是(1-3C)烷基，X.sup.2是氧、硫、亚硫酰基或磺酰基；或其药学上可接受的盐。本发明化合物是5-脂氧合酶酶抑制剂。
• Chiral Dioxolane Inhibitors of Leukotriene Biosynthesis: Structure-Activity Relationships and Syntheses Using Asymmetric Dihydroxylation
  作者：Graham C. Crawley、Malcolm T. Briggs

  DOI：10.1021/jm00020a008

  日期：1995.9

  1,3-Dioxolanes have been described as chiral inhibitors of 5-lipoxygenase (5LO). In the present work, this series has been developed further to provide agents which showed comparable or superior potency in vivo to ZD2138, a methoxytetrahydropyran inhibitor of 5LO, which is currently undergoing clinical evaluation. An asymmetric synthesis was developed to these dioxolanes based on asymmetric dihydroxylation. (S)-N-Methyl-4'-[[4-(2,2,4-trimethyl-1,3 dioxolan-4-yl)thien-2-yl]thio]acetanilid ((S)-10d) inhibited leukotriene B-4 (LTB(4)) synthesis in A23187-stimulated human whole blood in vitro with IC50 0.039 mu M, 25-fold more potent than (R)-10d. In vivo, (S)-10d inhibited LTB(4) synthesis by 70% in zymosan-inflamed air pouch exudate in rat 10 h after an oral dose of 1.5 mg/kg. Structure-activity relationship considerations suggested that the dioxolane and methoxytetrahydropyran series are related, a conclusion which can be supported by molecular modeling.
• [EN] THIO DERIVATIVES OF HYDROXAMIC ACIDS<br/>[FR] DERIVES THIO D'ACIDES HYDROXAMIQUES
  申请人：ZENECA LIMITED

  公开号：WO1997042168A1

  公开（公告）日：1997-11-13

  (EN) Compounds of formula (I), wherein R1 is an aryl, arylC1-6alkyl, heteroaryl or heteroarylC1-6alkyl group; R2 is hydrogen, C1-8alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, heteroaryl, heterocyclyl, arylC1-6alkyl, heteroarylC1-6alkyl, heterocyclylC1-6alkyl or C3-8cycloalkylC1-6alkyl; R3 is C1-6alkyl, C2-6alkenyl, aryl, C1-6alkyl, heteroarylC1-6alkyl or the side-chain of a naturally occurring amino acid; R4 is hydrogen, C1-6alkyl, C3-8cycloalkyl, C4-8cycloalkenyl, arylC1-6alkyl, heteroarylC1-6alkyl or heterocyclylC1-6alkyl; R5 is hydrogen or C1-6alkyl; or R4 and R5 together with the nitrogen atom to which they are joined form a heterocyclic ring; wherein any group or ring, in R1-R5, is optionally substituted; or pharmaceutically acceptable salts or $i(in vivo) hydrolysable esters thereof, are described as inhibitors of the production of Tumour Necrosis Factor and/or one or more matrix metalloproteinase enzymes. Compositions containing them and their preparation are also described.(FR) La présente invention concerne des composés de la formule (I), dans laquelle R1 représente un groupe aryle, aryle C1-6alkyle, hétéroaryle ou hétéroaryle C1-6alkyle; R2 représente hydrogène, C1-8alkyle, C2-6alkényle, C2-6alkynyle, C3-8cycloalkyle, hétéroaryle, hétérocyclyle, aryle C1-6alkyle, hétéroaryle C1-6alkyle, hétérocyclyle C1-6alkyle ou C3-8cycloalkyle C1-6alkyle; R3 représente C1-6alkyle, C2-6alkényle, aryle, C1-6alkyle, hétéroaryle C1-6alkyle ou la chaîne latérale d'un aminoacide d'origine naturelle; R4 représente hydrogène, C1-6alkyle, C3-8cycloalkyle, C4-8cycloalkényle, aryle C1-6alkyle, hétéroaryle C1-6alkyle ou hétérocyclyle C1-6alkyle; R5 représente hydrogène ou C1-6alkyle; ou R4 et R5 constituent, avec l'atome d'azote auquel ils sont joints, un anneau hétérocyclique; dans laquelle tout groupe ou tout anneau, compris entre R1 et R5, peut être éventuellement substitué; ou bien leurs sels acceptables sur le plan pharmacologique ou leurs esters hydrolysables $i(in vivo), ces composés étant des inhibiteurs de la production du facteur de nécrose des tumeurs et/ou d'une ou de plusieurs métalloprotéinases matricielles. La présente invention concerne également des compositions contenant ces composés ainsi que leur préparation.