(3S,4R)-4-amino-2,2-dimethylchroman-3-ol | 58740-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (3S,4R)-4-amino-2,2-dimethylchroman-3-ol
• 英文别名: (3S,4R)-4-Amino-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-3-ol；(3S,4R)-4-amino-2,2-dimethyl-3,4-dihydrochromen-3-ol
• CAS: 58740-56-0
• 化学式: C₁₁H₁₅NO₂
• 分子量: 193.246
• InChiKey: CQSLOZRJOIHHAQ-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,4R)-4-amino-2,2-dimethylchroman-3-ol 、 (3R,4R)-4-((E)-2-((tert-butoxycarbonyl)imino)-4,4-diethyl-6-oxotetrahydropyrimidin-1(2H)-yl)-3-(methoxymethyl)chromane-6-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 tert-butyl ((E)-4,4-diethyl-1-((3R,4R)-6-(((3S,4R)-3-hydroxy-2,2-dimethylchroman-4-yl)carbamoyl)-3-(methoxymethyl)chroman-4-yl)-6-oxotetrahydropyrimidin-2(1H)-ylidene)carbamate
  参考文献：
  名称：

  [EN] METHODS OF CHEMOVACCINATION AGAINST PLASMODIUM INFECTIONS
  [FR] MÉTHODES DE CHIMIOVACCINATION CONTRE DES INFECTIONS PAR PLASMODIUM

  摘要：

  一种化学免疫针对疟原虫感染的方法，包括向患者施用有效量的双重抑制剂plasmepsin IX和X，或其药学上可接受的盐。

  公开号：

  WO2022066545A1

文献信息

• [EN] ANTIMALARIAL AGENTS<br/>[FR] AGENTS ANTIPALUDIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2021026884A1

  公开（公告）日：2021-02-18

  Methods for treating malaria comprises administration of compounds of Formula (I) or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the variables are as defined herein. It also provides uses of the compounds of Formula (I), as defined herein, for inhibiting plasmepsin X, plasmepsin IX or plasmepsin X and IX activity, for treating a Plasmodium infection, and for treating malaria. Also provided are methods of treatment further comprising administration of one or more additional anti-malarial compounds.

  治疗疟疾的方法包括将式（I）化合物或其药学上可接受的盐，用于需要该药物的受体中，其中变量如本文所定义。还提供了使用式（I）化合物的用途，如本文所定义，用于抑制血浆蛋白酶X、血浆蛋白酶IX或血浆蛋白酶X和IX的活性，用于治疗疟原虫感染和治疗疟疾。还提供了治疗方法，进一步包括给予一种或多种额外的抗疟疾化合物。
• Pharmaceutically active aminobenzopyrans
  申请人：BEECHAM GROUP PLC

  公开号：EP0095316A1

  公开（公告）日：1983-11-30

  Compounds of formula (I): wherein: either one of R, and R2 is hydrogen and the other is selected from the class of C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C1-6 alkylsulphinyl, C1-6 alkylsulphonyl, C1-6 alkoxysulphinyl, C1-6 alkoxysulphonyl, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonylamino, C1-6 alkyl- thiocarbonyl, C1-6 alkoxy-thiocarbonyl, C1-6 alkyl- thiocarbonyloxy, C1-6 alkyl-thiolmethyl, formyl or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C1-6 alkyl groups, or C1-6 alkylsulphinylamino, C1-6 alkylsulphonylamino C1-6 alkoxysulphinylamino or C1-6 alkoxysulphonylamino or ethylenyl terminally substituted by C1-6 alkylcarbonyl, nitro or cyano, or -C(C1-6 alkyl)NOH or -C(C1-6 alkyl)NNH2, or one of R, and R2 is nitro, cyano or C1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C1-6 alkyl or by C2-7 alkanoyl; one of R3 and R4 is hydrogen or C1-4 alkyl and the other is C1-4 alkyl or R3 and R4 together with the carbon atom to which they are attached are C2-5 polymethylene; either Rs is hydroxy, C1-6 alkoxy or C2-7 acyloxy and R6 is hydrogen or R5 and R6 together are a bond; R7 is hydrogen, C1-6 alkyl optionally substituted by hydroxy, C1-6 alkoxy, C1-6 alkoxycarbonyl or carboxy, or C1-2 alkyl substituted by halogen, or C2.6 alkenyl; R8 is hydrogen or C1-6 alkyl; and X is oxygen or sulphur; the Re-N-CX-R7 group being trans to the R5 group when R5 and R6 together are not a bond; or, when one or the other of R, and R2 is an amino or an amino-containing group, a pharmaceutically acceptable salt thereof, having anti-hypertensive activity.

  式(I)化合物： 其中 R 和 R2 中的任一个是氢，另一个选自 C1-6 烷基羰基、C1-6 烷氧基羰基、C1-6 烷基羰氧基、C1-6 烷基羟甲基、硝基、氰基、氯基、三氟甲基、C1-6 烷基亚磺酰基、C1-6 烷基磺酰基、C1-6 烷氧基磺酰基、C1-6 烷基羰基、C1-6 烷氧基磺酰基、C1-6 烷基羰基C1-6烷基磺酰基、C1-6烷氧基磺酰基、C1-6烷氧基磺酰基、C1-6烷基羰基氨基、C1-6烷氧基羰基氨基、C1-6烷基硫代羰基、C1-6烷氧基硫代羰基、C1-6烷基硫代羰氧基、C1-6烷基硫醇甲基、甲酰基或氨基磺酰基、氨基磺酰基或氨基羰基，氨基可选择被一个或两个 C1-6 烷基取代，或 C1-6 烷基亚磺酰氨基、C1-6 烷基磺酰基氨基、C1-6 烷氧基亚磺酰基氨基或 C1-6 烷氧基磺酰基氨基或乙烯基最终被 C1-6 烷基羰基取代、硝基或氰基，或-C(C1-6 烷基)NOH 或-C(C1-6 烷基)NNH2，或 R 和 R2 中的一个是硝基、氰基或 C1-3 烷基羰基，另一个是甲氧基或被一个或两个 C1-6 烷基或 C2-7 烷酰基任选取代的氨基； R3 和 R4 中的一个是氢或 C1-4 烷基，另一个是 C1-4 烷基，或者 R3 和 R4 连同它们所连接的碳原子是 C2-5 聚亚甲基； Rs 为羟基、C1-6 烷氧基或 C2-7 乙酰氧基，R6 为氢，或 R5 和 R6 合在一起为键； R7 是氢、任选被羟基、C1-6 烷氧基、C1-6 烷氧羰基或羧基取代的 C1-6 烷基，或被卤素取代的 C1-2 烷基，或 C2.6 烯基； R8 是氢或 C1-6 烷基；以及 X是氧或硫；当R5和R6合在一起不是键时，Re-N-CX-R7基团反式为R5基团；或者，当R和R2中的一个或另一个是氨基或含氨基的基团时，其为药学上可接受的盐，具有抗高血压活性。
• Chroman and chromene derivatives
  申请人：BEECHAM GROUP PLC

  公开号：EP0126367A1

  公开（公告）日：1984-11-28

  Compounds of formula (I): wherein: either one of R1 and R2 is hydrogen and the other is selected from the class of C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C1-6 alkylsulphinyl, C1-6 alkylsulphonyl, C1-6 alkoxysulphinyl, C1-6 alkoxysulphonyl, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonylamino, C1-6 alkyl-thiocarbonyl, C1-6 alkoxy-thiocarbonyl, C1-6 alkyl-thiocarbonyloxy, C1-6 alkyl-thiomethyl, formyl or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C1-6 alkyl groups, or C1-6 alkylsulphinylamino, C1-6 alkylsulphonylamino, C1-6 alkoxysulphinylamino or C1-6 alkoxysulphonylamino or ethylenyl terminally substituted by Cl-6 alkylcarbonyl, nitro or cyano, or one of R1 and R2 is nitro, cyano or C1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C1-6 alkyl groups or by C2-7 alkanoyl; one of R3 and R4 is hydrogen or Cl-4 alkyl and the other is Cl-4 alkyl or R3 and R4 together are C2-5 polymethylene; either R5 is hydrogen, hydroxy, C1-6 alkoxy or C1-7 acyloxy and R6 is hydrogen or R5 and R6 together are a bond; R7 is selected from the class consisting of C1-6 alkyl substituted by amino optionally substituted by one or two C1-6 alkyl groups which may be the same or different; amino optionally substituted by a C1-6 alkyl or C1-6 alkenyl group or a C5-8 cycloalkyl group or by a phenyl group optionally substituted by C1-6 alkyl, Cl-6 alkoxy or halogen; or C1-6 alkoxy, or phenoxy optionally substituted by C1-6 alkyl, C1-6 alkoxy or halogen; or, when X is oxygen, R7 is selected from the class of carboxy, C1-6 alkoxycarbonyl, or aminocarbonyl optionally substituted by one or two C1-6 alkyl groups which may be the same or different; R8 is hydrogen or C1-6 alkyl; and X is oxygen or sulphur; The R8-N-CX-R7 group being trans to the R5 group when R5 and R6 together are not a bond; or when the compound of formula (I) contains a salifiable group, pharmaceutically acceptable salts thereof, having pharmacological activity, a process for preparing them, pharmaceutical compositions containing them, and their use in the treatment of mammals.

  式(I)化合物： 其中 R1 和 R2 中的任一个为氢，另一个选自 C1-6 烷基羰基、C1-6 烷氧基羰基、C1-6 烷基羰氧基、C1-6 烷基羟甲基、硝基、氰基、氯基、三氟甲基、C1-6 烷基亚磺酰基、C1-6 烷基磺酰基、C1-6 烷氧基磺酰基、C1-6 烷基羰基、C1-6 烷氧基磺酰基、C1-6 烷基羰基C1-6烷基磺酰基、C1-6烷氧基磺酰基、C1-6烷氧基磺酰基、C1-6烷基羰基氨基、C1-6烷氧基羰基氨基、C1-6烷基硫代羰基、C1-6烷氧基硫代羰基、C1-6烷基硫代羰氧基、C1-6烷基硫甲基、甲酰基或氨基磺酰基、氨基磺酰基或氨基羰基，氨基可选择被一个或两个 C1-6 烷基取代，或被 C1-6 烷基亚磺酰氨基、C1-6 烷基磺酰基氨基、C1-6 烷氧基亚磺酰氨基或 C1-6 烷氧基磺酰基氨基或被 Cl-6 烷基羰基最终取代的乙烯基、R1和R2中的一个是硝基、氰基或C1-3烷基羰基，另一个是甲氧基或被一个或两个C1-6烷基或C2-7烷酰基任选取代的氨基；R3 和 R4 中的一个是氢或 Cl-4 烷基，另一个是 Cl-4 烷基，或 R3 和 R4 合在一起是 C2-5 聚亚甲基；R5 是氢、羟基、C1-6 烷氧基或 C1-7 乙酰氧基，R6 是氢，或 R5 和 R6 合在一起是键；R7 选自由氨基任选取代的 C1-6 烷基组成的类别，氨基任选被一个或两个 C1-6 烷基取代，这两个 C1-6 烷基可以相同或不同；被 C1-6 烷基或 C1-6 烯基或 C5-8 环烷基或被 C1-6 烷基、Cl-6 烷氧基或卤素任选取代的苯基任选取代的氨基；或被 C1-6 烷基、C1-6 烷氧基或卤素任选取代的 C1-6 烷氧基或苯氧基；或当 X 为氧时，R7 选自被一个或两个可能相同或不同的 C1-6 烷基任选取代的羧基、C1-6 烷氧基羰基或氨基羰基； R8 是氢或 C1-6 烷基；以及 X 是氧或硫； 当 R5 和 R6 合在一起不是键时，R8-N-CX-R7 基团反式为 R5 基团； 或当式(I)化合物含有可盐基团时，具有药理活性的其药学上可接受的盐、制备它们的工艺、含有它们的药物组合物，以及它们在治疗哺乳动物中的用途。
• ASHWOOC, VALERIE A.;CASSIDY, FREDERICK;COLDWELL, MARTIN C.;EVANS, JOHN M.+, J. MED. CHEM., 33,(1990) N, C. 2667-2672
  作者：ASHWOOC, VALERIE A.、CASSIDY, FREDERICK、COLDWELL, MARTIN C.、EVANS, JOHN M.+

  DOI：——

  日期：——
• ANTIMALARIAL AGENTS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20220331321A1

  公开（公告）日：2022-10-20

  Methods of treating malaria comprising administration of compounds of Formula (I′) or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the variables are as defined herein. It also provides uses of the compounds of Formula (I), as defined herein, for inhibiting plasmepsin X, plasmepsin IX or plasmepsin X and IX activity, for treating a Plasmodium infection, and for treating malaria. Also provided are methods of treatment further comprising administration of one or more additional anti-malarial compounds.