2,3-dihydrobenzo[b][1,4]oxathiin-6-ol | 402911-50-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2,3-dihydrobenzo[b][1,4]oxathiin-6-ol
• 英文别名: 2,3-Dihydro-1,4-benzoxathiin-6-ol
• CAS: 402911-50-6
• 化学式: C₈H₈O₂S
• 分子量: 168.216
• InChiKey: YRXYKDKZEOEBCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-dihydrobenzo[b][1,4]oxathiin-6-ol 在 吡啶 、 1,3-双(二苯基膦)丙烷 、 palladium diacetate 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 71.5h， 生成 2,3-dihydrobenzo[b][1,4]oxathiine-6-carbaldehyde
  参考文献：
  名称：

  [EN] OXO-TETRAHYDRO-ISOQUINOLINE CARBOXYLIC ACIDS AS STING INHIBITORS
  [FR] ACIDES OXO-TÉTRAHYDRO-ISOQUINOLINE CARBOXYLIQUES EN TANT QU'INHIBITEURS DE LA PROTÉINE STING

  摘要：

  本发明提供了一种式I的化合物，这些化合物是STING抑制剂，因此可用于治疗STING介导的疾病，如炎症、哮喘、慢性阻塞性肺病（COPD）和癌症。

  公开号：

  WO2019182886A1
• 作为产物：
  描述：

  2-mercaptobenzene-1,4-diol 、 1,2-二溴乙烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 16.33h， 生成 2,3-dihydrobenzo[b][1,4]oxathiin-6-ol
  参考文献：
  名称：

  [EN] OXO-TETRAHYDRO-ISOQUINOLINE CARBOXYLIC ACIDS AS STING INHIBITORS
  [FR] ACIDES OXO-TÉTRAHYDRO-ISOQUINOLINE CARBOXYLIQUES EN TANT QU'INHIBITEURS DE LA PROTÉINE STING

  摘要：

  本发明提供了一种式I的化合物，这些化合物是STING抑制剂，因此可用于治疗STING介导的疾病，如炎症、哮喘、慢性阻塞性肺病（COPD）和癌症。

  公开号：

  WO2019182886A1

文献信息

• Phenyl heterocyclyl ethers
  申请人：——

  公开号：US20030207857A1

  公开（公告）日：2003-11-06

  The invention relates to compounds of formula I 1

  该发明涉及公式I1的化合物。
• Therapeutic diphenyl ether ligands
  申请人：Fliri J. Anton

  公开号：US20060058361A1

  公开（公告）日：2006-03-16

  This invention is directed to compounds of formula Ia, Ib or Ic and to pharmaceutical compositions thereof: or a prodrug thereof and a pharmaceutically acceptable carrier, wherein the R groups are defined in the specification; and, in which the dashed line represents an optional double bond. The invention is also directed to methods of treating, diagnosing, and preventing disorders of the central nervous system that are associated with 5HT receptors, including obesity, attention deficit disorder, migraine, depression, epilepsy, anxiety, Alzheimer's disease, withdrawal from drug abuse, pain, schizophrenia, stress-related disorders, panic disorder, sleep disorders, phobias, obsessive compulsive disorder, post-traumatic-stress syndrome, immune system depression, stress-induced gastrointestinal dysfunction, stress-induced cardiovascular dysfunction, and sexual dysfunction.

  该发明涉及式Ia、Ib或Ic的化合物，以及其药物组成物：或其前药和药用可接受载体，其中R基在规范中定义；以及虚线代表可选的双键。该发明还涉及治疗、诊断和预防与5HT受体相关的中枢神经系统疾病的方法，包括肥胖、注意缺陷障碍、偏头痛、抑郁症、癫痫、焦虑、阿尔茨海默病、戒毒、疼痛、精神分裂症、应激相关疾病、恐慌症、睡眠障碍、恐惧症、强迫症、创伤后应激综合征、免疫系统抑郁、应激引起的胃肠功能障碍、应激引起的心血管功能障碍和性功能障碍。
• Phenoxybenzylamine derivatives as SSRIs
  申请人：Pfizer Inc.

  公开号：US06610747B2

  公开（公告）日：2003-08-26

  A compound of general formula (I) wherein R1 and R2 are H, C1-C6alkyl or (CH2)d(C3-C6cycloalkyl) wherein d=0, 1, 2 or 3; or R1 and R2 together with the nitrogen to which they are attached form an azetidine ring; Z or Y is —SR3 and the other Z or Y is halogen or —R3; wherein R3 is C1-C4 alkyl optionally substituted with fluorine; except that R3 is not CF3; or Z and Y are linked so that, together with the interconnecting atoms, Z and Y form a fused 5 to 7-membered carbocyclic or heterocyclic ring, and wherein when Z and Y form a heterocyclic ring, in addition to carbon atoms, the linkage contains one or two heteroatoms independently selected from oxygen, sulfur and nitrogen; R4 and R5, which may be the same or different, are: A—X, wherein A=—CH═CH— or —(CH2)p— where p is 0, 1 or 2; X is hydrogen, F, Cl, Br, I, CONR6R7, SO2NR6R7, SO2NHC(═O)R6, OH, C1-4alkoxy, NR8SO2R9, NO2, NR6R11, CN, CO2R10, CHO, SR10, S(O)R9 or SO2R10; or a 5- or 6-membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, S and O, optionally substituted independently by one or more R13; wherein R13 is hydroxy, C1-C4alkoxy, F, C1-C6alkyl, haloalkyl, haloalkoxy, —NH2, —NH(C1-C6alkyl) or —N(C1-C6alkyl)2.

  通式（I）的化合物，其中R1和R2为H、C1-C6烷基或（CH2）d（C3-C6环烷基），其中d=0、1、2或3；或者R1和R2与它们连接的氮形成一个氮杂杂环；Z或Y为-SR3，另一个Z或Y为卤素或-R3；其中R3为C1-C4烷基，可选地取代氟；但R3不是CF3；或者Z和Y连接在一起，与连接的原子一起形成一个融合的5到7环碳环或杂环，当Z和Y形成杂环时，除了碳原子外，连接还包含一个或两个独立选择的杂原子，选自氧、硫和氮；R4和R5，可以相同也可以不同，为A-X，其中A=-CHCH-或-( )p-，其中p为0、1或2；X为氢、F、Cl、Br、I、CONR6R7、SO2NR6R7、SO2NHC(O)R6、OH、C1-4烷氧基、NR8SO2R9、NO2、NR6R11、CN、CO2R10、CHO、SR10、S(O)R9或SO2R10；或者为一个5-或6-杂环，其中包含1、2或3个选自N、S和O的杂原子，可选地独立地被一个或多个R13取代；其中R13为羟基、C1-C4烷氧基、F、C1-C6烷基、卤代烷基、卤代烷氧基、-NH2、-NH(C1-C6烷基)或-N(C1-C6烷基)2。
• Oxo-tetrahydro-isoquinoline carboxylic acids as STING inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US11311528B2

  公开（公告）日：2022-04-26

  The instant invention provides compounds of formula I which are STING inhibitors, and as such are useful for the treatment of STING-mediated diseases such as inflammation, asthma, COPD and cancer.

  本发明提供的式 I 化合物是 STING 抑制剂，因此可用于治疗 STING 介导的疾病，如炎症、哮喘、慢性阻塞性肺病和癌症。
• Discovery of a Novel cGAMP Competitive Ligand of the Inactive Form of STING
  作者：Tony Siu、Michael D. Altman、Gretchen A. Baltus、Matthew Childers、J. Michael Ellis、Hakan Gunaydin、Harold Hatch、Thu Ho、James Jewell、Brian M. Lacey、Charles A. Lesburg、Bo-Sheng Pan、Berengere Sauvagnat、Gottfried K. Schroeder、Serena Xu

  DOI：10.1021/acsmedchemlett.8b00466

  日期：2019.1.10

  Drugging large protein pockets is a challenge due to the need for higher molecular weight ligands, which generally possess undesirable physicochemical properties. In this communication, we highlight a strategy leveraging small molecule active site dimers to inhibit the large symmetric binding pocket in the STING protein. By taking advantage of the 2:1 binding stoichiometry, maximal buried interaction with STING protein can be achieved while maintaining the ligand physicochemical properties necessary for oral exposure. This mode of binding requires unique considerations for potency optimization including simultaneous optimization of protein ligand as well as ligand ligand interactions. Successful implementation of this strategy led to the identification of 18, which exhibits good oral exposure, slow binding kinetics, and functional inhibition of STING-mediated cytokine release.