3-<(methanesulfonyl)oxy>-1-azabicyclo<2.2.2>octane | 127424-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-<(methanesulfonyl)oxy>-1-azabicyclo<2.2.2>octane
• 英文别名: 3-[(methanesulfonyl)-oxy]-1-azabicyclo[2.2.2]octane；3-methanesulfonyloxyquinuclidine；(+/-) 3-Methanesulphonyloxy-1-azabicyclo[2.2.2]octane；1-Azabicyclo[2.2.2]oct-3-yl methanesulfonate；1-azabicyclo[2.2.2]octan-3-yl methanesulfonate
• CAS: 127424-06-0
• 化学式: C₈H₁₅NO₃S
• 分子量: 205.278
• InChiKey: QVEMSVFKCNTWFF-UHFFFAOYSA-N

物化性质

• 沸点：
  346.5±21.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-<(methanesulfonyl)oxy>-1-azabicyclo<2.2.2>octane 在 sodium hydride 、 盐酸 作用下， 以 DMF (N,N-dimethyl-formamide) 、 乙醚 、 丙酮 为溶剂， 反应 21.75h， 生成 3-(4-(3,5-difluorophenyl)pyrazol-1-yl]-1-azabicyclo[2.2.2]octane hydrochloride
  参考文献：
  名称：

  Pyrazolyl derivatives, preparation process and intermediates of this process as medicinal products and pharmaceutical compositions containing them

  摘要：

  本发明涉及公式(I)的新颖衍生物，其中A是，如果存在的话，(C1-C6)烷基，(C3-C6)烯基，(C3-C6)炔基，(C3-C7)环烷基或(C5-C7)环烯基，R1是NR6R7，(C4-C7)氮杂环烷基，(C5-C7)氮杂环烯基，(C5-C9)氮杂双环烷基或(C5-C9)氮杂双环烯基；A-R1是这样的，即R1的氮原子和吡唑的1位的氮原子之间至少被两个碳原子分隔，R3是H，卤素，OH，SH，NH2，ORc，SRc，SORa，SO2Ra，NHCHO，NRaRb，NHC(O)Ra，NHC(S)Ra或NHSO2Ra，R4是芳基或杂芳基；R5是H，卤素，CF3，CHF2，CH2F，直链或支链(C1-C6)烷基或(C3-C7)环烷基，它们的外消旋体、对映体和非对映异构体，以及它们的混合物，它们的互变异构体和它们的药学上可接受的盐。

  公开号：

  US20050165005A1
• 作为产物：
  描述：

  甲基磺酰氯 、 奎宁环-3-醇 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到3-<(methanesulfonyl)oxy>-1-azabicyclo<2.2.2>octane
  参考文献：
  名称：

  奎宁环素-3-基三唑和-四唑衍生物的合成和毒蕈碱活性。

  摘要：

  描述了另外被1-氮杂双环[2.2.2] octan-3-基取代的15个甲基或未取代的1,2,3-三唑，1,2,4-三唑和四唑的合成。这些化合物作为毒蕈碱配体的效力和功效是在放射性配体结合测定中使用[3H]氧代苯甲酸和[3H]奎宁环烷基苯磺酸盐测定的。在其中唑部分通过碳原子或氮原子连接至氮杂双环的化合物中发现了效力和功效。计算了C链和新型N链化合物的静电势图。确定了相对于氮杂双环的静电最小值的位置和深度与化合物的效力和功效之间的关系。

  DOI：

  10.1021/jm00085a016

文献信息

• [EN] N-(ARYLALKYL)-N'-PYRAZOLYL-UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS<br/>[FR] COMPOSÉS DE N-(ARYLALKYLE)-N'-PYRAZOLYLE-URÉE, DE THIOURÉE, DE GUANIDINE ET DE CYANOGUANIDINE EN TANT QU'INHIBITEURS DE LA KINASE TRKA
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2014078331A1

  公开（公告）日：2014-05-22

  Compounds of Formula I or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C, X, Ra, Rb, Rc, Rd and n are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.

  公式I的化合物或立体异构体、互变异构体、或药用可接受的盐、溶剂化物或前药，其中环A、环C、X、Ra、Rb、Rc、Rd和n如本文所述定义，是TrkA激酶的抑制剂，可用于治疗可以用TrkA激酶抑制剂治疗的疾病，如疼痛、癌症、炎症/炎症性疾病、神经退行性疾病、某些传染病、舍格伦综合症、子宫内膜异位症、糖尿病周围神经病变、前列腺炎或骨盆疼痛综合征。
• Pyrazolyl derivatives, preparation process and intermediates of this process as medicinal products and pharmaceutical compositions containing them
  申请人：Genevois-Borella Arielle

  公开号：US20050165005A1

  公开（公告）日：2005-07-28

  The present invention relates to the novel derivatives of formula (I) in which A is, if it is present, a (C1-C6) alkyl, a (C3-C6) alkenyl, a (C3-C6) alkynyl, a (C3-C7) cycloalkyl or a (C5-C7) cycloalkenyl, R1 is an NR6R7, (C4-C7) azacycloalkyl, (C5-C7) azacycloalkenyl, (C5-C9) azabicycloalkyl or (C5-C9) azabicycloalkenyl group; A-R1 is such that the nitrogen of R1 and the nitrogen in the 1-position of the pyrazole are necessarily separated by at least two carbon atoms, R3 is an H, halogen, OH, SH, NH 2 , ORc, SRc, SORa, SO 2 Ra, NHCHO, NRaRb, NHC(O)Ra, NHC(S)Ra or NHSO 2 Ra, R4 is an aryl or heteroaryl; and R5 is an H, halogen, CF 3 , CHF 2 , CH 2 F, linear or branched (C1-C6) alkyl or (C3-C7) cycloalkyl to their racemates, enantiomers and diastereoisomers and to their mixtures, their tautomers and to their pharmaceutically acceptable salts.

  本发明涉及公式(I)的新颖衍生物，其中A是，如果存在的话，(C1-C6)烷基，(C3-C6)烯基，(C3-C6)炔基，(C3-C7)环烷基或(C5-C7)环烯基，R1是NR6R7，(C4-C7)氮杂环烷基，(C5-C7)氮杂环烯基，(C5-C9)氮杂双环烷基或(C5-C9)氮杂双环烯基；A-R1是这样的，即R1的氮原子和吡唑的1位的氮原子之间至少被两个碳原子分隔，R3是H，卤素，OH，SH，NH2，ORc，SRc，SORa，SO2Ra，NHCHO，NRaRb，NHC(O)Ra，NHC(S)Ra或NHSO2Ra，R4是芳基或杂芳基；R5是H，卤素，CF3，CHF2，CH2F，直链或支链(C1-C6)烷基或(C3-C7)环烷基，它们的外消旋体、对映体和非对映异构体，以及它们的混合物，它们的互变异构体和它们的药学上可接受的盐。
• 2-(heterocyclylthio)carbapenem derivatives, their preparation and their
  申请人：Sankyo Company, Limited

  公开号：US05104867A1

  公开（公告）日：1992-04-14

  Compounds of formula (I): ##STR1## in which R.sup.a is a group of formula (II): ##STR2## or a group of formula (III): ##STR3## (where one of R' is a bond to the remainder of the compound, one more of R' is R.sup.2 and the others of R' are all hydrogen), R.sup.1 is hydrogen or methyl, R.sup.2 is hydrogen, optionally substiuted alkyl, halogen, hydroxy, alkoxy, amino, alkanoylamino, alkanoyloxy, alkanoyl, carboxy, alkoxycarbonyl, cyano, --S(O).sub.j R.sup.9 (where j is 0, 1 or 2 and R.sup.9 is alkyl), or --CONR.sup.6 R.sup.7 (which is optionally substituted carbamoyl or heterocyclyl-carbonyl), R.sup.2a is hydrogen, alkyl or alkanoyl, --NR.sup.3 R.sup.4 is optionally substituted amino or heterocyclic, and --COOR.sup.5 is carboxy, --COO.sup.-, --COOM.sub.x (where M is a cation and x is the reciprocal of the valence of the cation M) or protected carboxy and, where --COOR.sup.5 is carboxy, --COOM.sub.x or protected carboxy, the compound of formula (I) also contains an anion; l, m and n are independently 0, 1, 2 or 3, provided that (m+n) is an integer from 2 to 6; p is 0, 1 or 2; Y is a single bond, oxygen, sulfur or R.sup.8 N<(wherein R.sup.8 is hydrogen, alkyl or alkanoyl) and pharmaceutically acceptable salts and esters thereof are potentially valuable antibiotics.

  公式（I）的化合物：其中R.sup.a是公式（II）的一个基团：或者是公式（III）的一个基团：（其中R'之一是与化合物的其余部分相连的键，R'中的一个以上是R.sup.2，其余的R'都是氢），R.sup.1是氢或甲基，R.sup.2是氢，可选择地是取代的烷基，卤素，羟基，烷氧基，氨基，烷酰胺基，烷酰氧基，烷酰基，羧基，烷氧羰基，氰基，-S（O）.sub.j R.sup.9（其中j为0、1或2，R.sup.9为烷基），或者-CONR.sup.6 R.sup.7（可选择地是取代的氨基甲酰基或杂环酰基），R.sup.2a是氢，烷基或烷酰基，-NR.sup.3 R.sup.4是可选择地取代的氨基或杂环基，-COOR.sup.5是羧基，-COO^.-，-COOM.sub.x（其中M是阳离子，x是阳离子M的价的倒数）或者保护羧基，其中-COOR.sup.5是羧基，-COOM.sub.x或者保护羧基时，化合物的公式（I）还包含一个阴离子；l、m和n独立地为0、1、2或3，只要（m+n）是从2到6的整数；p为0、1或2；Y是单键，氧，硫或R.sup.8 N<（其中R.sup.8是氢，烷基或烷酰基）及其药学上可接受的盐和酯可能是有价值的抗生素。
• 2-(heterocyclylthio) carbapenem derivatives, their preparation and their
  申请人：Sankyo Company, Limited

  公开号：US05242914A1

  公开（公告）日：1993-09-07

  Compounds of formula (I): ##STR1## in which R.sup.a is a group of formula (II): ##STR2## where one of R' is a bond to the remainder of the compound, one more of R' is R.sup.2 and the others of R' are all hydrogen, R.sup.1 is hydrogen or methyl, R.sup.2 is hydrogen, optionally substituted alkyl, halogen, hydroxy, alkoxy, amino, alkanoylamino, alkanoyloxy, alkanoyl, carboxy, alkoxycarbonyl, cyano, --S(O).sub.j R.sup.9 where j is 0, 1 or 2 and R.sup.9 is alkyl, or --CONR.sup.6 R.sup.7 which is optionally substituted carbamoyl or heterocyclyl-carbonyl, --NR.sup.3 R.sup.4 is optionally substituted amino or heterocyclic, and --COOR.sup.5 is carboxy, --COO.sup.-, --COOM.sub.x, where M is a cation and x is the reciprocal of the valence of the cation M or protected carboxy and, where --COOR.sup.5 is carboxy, --COOM.sub.x or protected carboxy, the compound of formula (I) also contains an anion; l, m and n are independently 0, 1, 2 or 3, provided that (m+n) is an integer from 2 to 6; p is 0, 1 or 2; Y is a single bond, oxygen, sulfur or ##STR3## wherein R.sup.8 is hydrogen, alkyl or alkanoyl, and pharmaceutically acceptable salts and esters thereof. Such compounds are useful as antibiotics.

  式(I)的化合物：##STR1## 其中R.sup.a是式(II)的基团：##STR2## 其中R'中的一个是与化合物的其余部分成键的键，R'中的一个或多个是R.sup.2，其余的R'都是氢，R.sup.1是氢或甲基，R.sup.2是氢、可选取代的烷基、卤素、羟基、烷氧基、氨基、烷酰胺基、烷酰氧基、烷酰基、羧基、烷氧羰基、氰基、--S(O).sub.jR.sup.9（其中j为0、1或2，R.sup.9为烷基）或--CONR.sup.6R.sup.7（可选取代的氨基甲酰基或杂环基甲酰基），--NR.sup.3R.sup.4是可选取代的氨基或杂环基，--COOR.sup.5是羧基、--COO.sup.-、--COOM.sub.x（其中M为阳离子，x为阳离子M的价的倒数）或保护羧基，如果--COOR.sup.5是羧基、--COOM.sub.x或保护羧基，则式(I)的化合物还包含一个阴离子；l、m和n独立地为0、1、2或3，但(m+n)是2到6的整数；p为0、1或2；Y是单键、氧、硫或##STR3## 其中R.sup.8是氢、烷基或烷酰基，以及其药学上可接受的盐和酯。这些化合物可用作抗生素。
• N-linked azabicyclic heterocycles useful for treating dementia
  申请人：Beecham Group p.l.c.

  公开号：US05981545A1

  公开（公告）日：1999-11-09

  A compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## in which one of X and Y represents hydrogen and the other represents Z, where Z is a group ##STR2## in which Q represents a 3-membered divalent residue completing a 5-membered aromatic ring and comprises zero, one or two nitrogen atoms, Q being optionally C-substituted by a group R.sub.1 selected from halogen, CN, OR.sub.2, SR.sub.2, N(R.sub.2).sub.2, NHCOR.sub.2, NHCOOCH.sub.3, NHCOOC.sub.2 H.sub.5, NHOR.sub.2, N.sub.3, NHNH.sub.2, NO.sub.2, COR.sub.2, COR.sub.3, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, cyclopropyl or C.sub.1-2 alkyl optionally substituted with OR.sub.2, N(R.sub.2).sub.2, SR.sub.2, CO.sub.2 R.sub.2, CON(R.sub.2).sub.2 or one, two or three halogen atoms, in which each R.sub.2 is independently hydrogen or C.sub.1-2 alkyl and R.sub.3 is OR.sub.2, NH.sub.2 or NHR.sub.2 ; r represents an integer of 2 or 3, s represents an integer of 1 or 2 and t represents 0 or 1; R.sub.a and R.sub.b each represent hydrogen or, when X is hydrogen, optionally together represent a bond; with the proviso that when Y is hydrogen s is 1.

  化合物公式（I）或其药学上可接受的盐：##STR1## 其中X和Y中的一个代表氢，另一个代表Z，其中Z是一个基团##STR2## 其中Q表示完成5-成员芳香环的3-成员双价残基，包括零个，一个或两个氮原子，Q可以被来自卤素，CN，OR.sub.2，SR.sub.2，N（R.sub.2）.sub.2，NHCOR.sub.2，NHCOOCH.sub.3，NHCOOC.sub.2H.sub.5，NHOR.sub.2，N.sub.3，NHNH.sub.2，NO.sub.2，COR.sub.2，COR.sub.3，C.sub.2-4烯基，C.sub.2-4炔基，环丙基或C.sub.1-2烷基替代的基团R.sub.1选择，其中每个R.sub.2独立地表示氢或C.sub.1-2烷基，R.sub.3表示OR.sub.2，NH.sub.2或NHR.sub.2; r表示2或3的整数，s表示1或2的整数，t表示0或1; R.sub.a和R.sub.b各自表示氢或，当X为氢时，可以选择一起表示键; 假设当Y为氢时，s为1。