5-amino-1,3-dihydrobenzo[c]isothiazole 2,2-dioxide | 496055-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 5-amino-1,3-dihydrobenzo[c]isothiazole 2,2-dioxide
• 英文别名: 2,2-dioxo-2,3-dihydro-1H-2λ6-benzo[c]isothiazol-5-ylamine；2,2-dioxo-1,3-dihydro-2,1-benzothiazol-5-amine
• CAS: 496055-43-7
• 化学式: C₇H₈N₂O₂S
• mdl: MFCD19105160
• 分子量: 184.219
• InChiKey: ITXAMJIWJHTZRH-UHFFFAOYSA-N

物化性质

• 沸点：
  405.8±55.0 °C(Predicted)
• 密度：
  1.492±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-amino-1,3-dihydrobenzo[c]isothiazole 2,2-dioxide 、 2,4-二氯-5-三氟甲基嘧啶 在 zinc(II) chloride 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 1.0h， 生成 C₁₂H₈ClF₃N₄O₂S
  参考文献：
  名称：

  Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): Structure–activity relationships and strategies for the elimination of reactive metabolite formation

  摘要：

  The synthesis and SAR for a series of diaminopyrimidines as PYK2 inhibitors are described. Using a combination of library and traditional medicinal chemistry techniques, a FAK-selective chemical series was transformed into compounds possessing good PYK2 potency and 10- to 20-fold selectivity against FAK. Subsequent studies found that the majority of the compounds were positive in a reactive metabolite assay, an indicator for potential toxicological liabilities. Based on the proposed mechanism for bioactivation, as well as a combination of structure-based drug design and traditional medicinal chemistry techniques, a follow-up series of PYK2 inhibitors was identified that maintained PYK2 potency, FAK selectivity and HLM stability, yet were negative in the RM assay.

  DOI：

  10.1016/j.bmcl.2008.10.030
• 作为产物：
  描述：

  5-硝基-1,3-二氢-2,1-苯异噻唑 2,2-二氧化物 在 5%-palladium/activated carbon 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以86%的产率得到5-amino-1,3-dihydrobenzo[c]isothiazole 2,2-dioxide
  参考文献：
  名称：

  [DE] SUBSTITUIERTE THIAZOL-BENZOISOTHIAZOLDIOXIDDERIVATIVE, VERFAHREN ZU DEREN HERSTELLUNG UND DEREN VERWENDUNG
  [EN] SUBSTITUTED THIAZOLE-BENZOISOTHIAZOLE DIOXIDE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND USE OF THE SAME
  [FR] DERIVES DE DIOXYDE DE THIAZOL-BENZOISOTHIAZOL SUBSTITUES, PROCEDES POUR LEUR PRODUCTION ET LEUR UTILISATION

  摘要：

  这项发明涉及公式（I）的化合物，其中残基具有所述的含义，以及其生理相容性盐。这些化合物可用作例如降低血糖和预防及治疗糖尿病的药物。

  公开号：

  WO2005012295A1

文献信息

• [DE] SUBSTITUIERTE THIAZOL-BENZOISOTHIAZOLDIOXIDDERIVATIVE, VERFAHREN ZU DEREN HERSTELLUNG UND DEREN VERWENDUNG<br/>[EN] SUBSTITUTED THIAZOLE-BENZOISOTHIAZOLE DIOXIDE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND USE OF THE SAME<br/>[FR] DERIVES DE DIOXYDE DE THIAZOL-BENZOISOTHIAZOL SUBSTITUES, PROCEDES POUR LEUR PRODUCTION ET LEUR UTILISATION
  申请人：AVENTIS PHARMA GMBH

  公开号：WO2005012295A1

  公开（公告）日：2005-02-10

  Die Erfindung betrifft Verbindungen der Formel (I), worin die Reste die angegebenen Bedeutungen haben, sowie deren physiologisch verträgliche Salze. Die Verbindungen eignen sich z.B. als Medikamente zur Blutzuckersenkung und zur Prävention und Behandlung von Diabetes.

  这项发明涉及公式（I）的化合物，其中残基具有所述的含义，以及其生理相容性盐。这些化合物可用作例如降低血糖和预防及治疗糖尿病的药物。
• [EN] PIPERIDINE DERIVATIVES AS NMDA RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PIPERIDINE UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR N-METHYL-D-ASPARTATE (NMDA)
  申请人：RICHTER GEDEON VEGYESZET

  公开号：WO2003010159A1

  公开（公告）日：2003-02-06

  The present invention relates to new carboxylic acid amide derivatives of formula (I), wherein U, V, W, X, Y, Z, n and m are as defined as in Claim 1. A further object of the invention are the processes for producing of carboxylic acid amide compounds of formula (I), and the pharmaceutical manufacture of medicaments containing these compounds, as well as the process of treatments with these compounds, which means administering to a mammal to be treated including human - effective amount/amounts of compounds of formula (I) of the present invention as such or as medicament. The new carboxylic acid amide derivatives of formula (I) of the present invention are highly effective and selective antagonists of NMDA receptor, and moreover most of the compounds are selective antagonist of NR2B subtype of NMDA receptor.

  本发明涉及公式（I）的新羧酸酰胺衍生物，其中U、V、W、X、Y、Z、n和m如权利要求书1中所定义。本发明的另一个目标是制备公式（I）的羧酸酰胺化合物的过程，以及包含这些化合物的药物制剂的制药制造，以及使用这些化合物进行治疗的过程，即向待治疗的哺乳动物（包括人类）施用本发明的公式（I）的化合物或药物的有效量/剂量。本发明的新羧酸酰胺衍生物是高效且选择性的NMDA受体拮抗剂，而且大多数化合物是NMDA受体NR2B亚型的选择性拮抗剂。
• Piperdine derivatives as NMDA receptor antagonists
  申请人：——

  公开号：US20040157886A1

  公开（公告）日：2004-08-12

  The present invention relates to a compound of formula (I): 1 wherein: V and U are hydrogen, halogen, C 1 -C 4 alkylamino, or together form a group that contains one or more heteroatoms, and that taken together with one or more: (a) hydrogen atoms; (b) carbon atoms; (c) —CH═ groups; (d) —CH 2 — groups; or (e) additional heteroatoms of the same or different type; or any combination thereof, form a 4-7 membered homocyclic or heterocyclic ring, wherein the homocyclic or heterocyclic ring may combine with the phenyl group to form a bicyclic ring, and wherein the homocyclic or heterocyclic ring or the bicyclic ring may contain one or more oxo, thioxo, amino, mercapto, trifluoromethyl, C 1 -C 4 alkyl, ═S or —SH groups; W: is —CO—, —CH 2 — or —CH 2 —(C 1 -C 4 alkyl)-; X: is —CO—; Y: is —O—, C 1 -C 4 alkylene, C 1 -C 4 alkynylene, cycloalkylene, aminocarbonyl, —NH—, —N(C 1 -C 4 alkyl)-, —C 1 -C 4 alkylene-N(C 1 -C 4 alkyl)-, —CH 2 O—, —CH(OH)— or —OCH 2 —; Z: is hydrogen, halogen, nitro, amino, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, trifluoromethyl, hydroxyl or carboxyl; R 1 and R 2 : are hydrogen, or together form a C 1 -C 3 bridge; and n and m: independently are 0-3, wherein n and m cannot each be 0; or an optical antipode, racemate or pharmaceutically-acceptable salt thereof. The carboxylic acid amide derivatives of formula (I) are highly effective and selective antagonists of the NMDA receptor.

  本发明涉及化合物式（I）：1其中：V和U为氢、卤素、C1-C4烷基氨基或一起形成一个含有一个或多个杂原子的基团，且与一个或多个：（a）氢原子；（b）碳原子；（c）—CH═基团；（d）—CH2—基团；或（e）同一种或不同种类的其他杂原子；或任意组合，形成一个4-7环的同环或异环环，其中同环或异环环可以与苯基结合形成双环环，且同环或异环环或双环环可以含有一个或多个氧代、硫代、氨基、巯基、三氟甲基、C1-C4烷基、═S或—SH基团；W：为—CO—、—CH2—或—CH2—（C1-C4烷基）-；X：为—CO—；Y：为—O—、C1-C4亚烷基、C1-C4炔基、环烷基、氨基甲酰、—NH—、—N（C1-C4烷基）-、—C1-C4烷基-N（C1-C4烷基）-、—CH2O—、—CH（OH）—或—OCH2—；Z：为氢、卤素、硝基、氨基、C1-C4烷基、C1-C4烷氧基、氰基、三氟甲基、羟基或羧基；R1和R2：为氢，或一起形成一个C1-C3桥；n和m：独立地为0-3，其中n和m不能同时为0；或其光学对映体、外消旋体或药学上可接受的盐。化合物式（I）的羧酸酰衍生物是NMDA受体高效、选择性的拮抗剂。
• Piperidine derivatives as NMDA receptor antagonists
  申请人：Gedeon Richter Vegyeszeti Gyar RT

  公开号：US07435744B2

  公开（公告）日：2008-10-14

  The present invention relates to a compound of formula (I): wherein: V and U are hydrogen, halogen, C1-C4 alkylamino, or together form a group that contains one or more heteroatoms, and that taken together with one or more: (a) hydrogen atoms; (b) carbon atoms; (c) —CH═ groups; (d) —CH2— groups; or (e) additional heteroatoms of the same or different type; or any combination thereof, form a 4-7 membered homocyclic or heterocyclic ring, wherein the homocyclic or heterocyclic ring may combine with the phenyl group to form a bicyclic ring, and wherein the homocyclic or heterocyclic ring or the bicyclic ring may contain one or more oxo, thioxo, amino, mercapto, trifluoromethyl, C1-C4 alkyl, ═S or —SH groups; W: is —CO—, —CH2— or —CH2—(C1-C4 alkyl)-; X: is —CO—; Y: is —O—, C1-C4 alkylene, C1-C4 alkynylene, cycloalkylene, aminocarbonyl, —NH—, —N(C1-C4 alkyl)-, -C1-C4 alkylene-N(C1-C4 alkyl)-, —CH2O—, —CH(OH)— or —OCH2—; Z: is hydrogen, halogen, nitro, amino, C1-C4 alkyl, C1-C4 alkoxy, cyano, trifluoromethyl, hydroxyl or carboxyl; R1 and R2: are hydrogen, or together form a C1-C3 bridge; and n and m: independently are 0-3, wherein n and m cannot each be 0; or an optical antipode, racemate or pharmaceutically-acceptable salt thereof. The carboxylic acid amide derivatives of formula (I) are highly effective and selective antagonists of the NMDA receptor.

  本发明涉及式(I)的化合物：其中：V和U是氢、卤素、C1-C4烷基氨基或共同形成包含一个或多个杂原子的基团，与一个或多个：(a)氢原子；(b)碳原子；(c) -CH═基团；(d) -CH2-基团；或(e)相同或不同类型的其他杂原子；或任意组合，形成一个4-7环的同环或异环，其中同环或异环可以与苯基结合形成双环，同环或异环或双环可能包含一个或多个氧代、硫代、氨基、巯基、三氟甲基、C1-C4烷基、═S或-SH基团；W：是-CO-、-CH2-或-CH2-(C1-C4烷基)-；X：是-CO-；Y：是-O-、C1-C4亚烷基、C1-C4炔基、环烷基、氨基甲酰基、-NH-、-N(C1-C4烷基)-、-C1-C4亚烷基-N(C1-C4烷基)-、-CH2O-、-CH(OH)-或-OCH2-；Z：是氢、卤素、硝基、氨基、C1-C4烷基、C1-C4烷氧基、氰基、三氟甲基、羟基或羧基；R1和R2：是氢，或共同形成C1-C3桥；n和m：独立地为0-3，其中n和m不能同时为0；或其光学对映体、外消旋体或药学上可接受的盐。式(I)的羧酸酰胺衍生物是NMDA受体的高效选择性拮抗剂。
• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：ACEA BIOSCIENCES INC.

  公开号：US20150133457A1

  公开（公告）日：2015-05-14

  The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.

  本发明涉及制药化合物、组合物和方法，特别是涉及用于治疗和/或预防增殖障碍、癌症、肿瘤、炎症性疾病、自身免疫疾病、银屑病、干眼症或免疫相关疾病的组合物和方法，以及在某些实施方式中与激酶失调相关的疾病或疾病，例如但不限于EGFR（包括HER）、Alk、PDGFR、BLK、BMX/ETK、FLT3（D835Y）、ITK、TEC、TXK、BTK或JAK及其相应的通路。