2-(bis(2-chloroethyl)amino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10λ6-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid | 887003-47-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(bis(2-chloroethyl)amino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10λ6-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid
• 英文别名: 2-[Bis-(2-chloroethyl)amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid；8-[bis(2-chloroethyl)amino]-10-chloro-1-methyl-5,5-dioxo-6H-benzo[b][1,5]benzoxathiepine-3-carboxylic acid
• CAS: 887003-47-6
• 化学式: C₁₉H₁₈Cl₃NO₅S
• 分子量: 478.781
• InChiKey: AWZPONZVNZMHSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-噻吩甲胺 、 2-(bis(2-chloroethyl)amino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10λ6-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid 在 四丁基碘化铵 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  WO2006/51476

  摘要：

  公开号：
• 作为产物：
  描述：

  2-(bis(2-chloroethyl)amino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10λ6-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester 在 sodium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以97%的产率得到2-(bis(2-chloroethyl)amino)-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10λ6-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid
  参考文献：
  名称：

  WO2006/51476

  摘要：

  公开号：

文献信息

• Fused Tricyclic Compounds as Inhibitors of Tumor Necrosis Factor-Alpha
  申请人：Lal Bansi

  公开号：US20070299050A1

  公开（公告）日：2007-12-27

  Compounds of formula 1: are disclosed, wherein V is CH 2 ; W is S(O) m ; m is the integer 0, 1 or 2; U is O, C(O), CR 13 R 14 or NR 15 ; where R 13 is H, alkyl; R 14 is H, OH, OR 13 or OCOR 13 ; R 15 is H, alkyl, cycloalkyl, alkenyl, C(O)R 13 , C(O)OR 13 or alkylaminocarbonyl; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

  本文披露了式子1的化合物，其中V为CH2；W为S(O)m；m为0、1或2的整数；U为O、C(O)、CR13R14或NR15；其中R13为H、烷基；R14为H、OH、OR13或OCOR13；R15为H、烷基、环烷基、烯基、C(O)R13、C(O)OR13或烷基氨基甲酰基；R1、R2、R3、R4、R5、R6、R7和R8的定义如本文所述。这些化合物是肿瘤坏死因子-alpha（TNF-α）的抑制剂，并可用作药物治疗和预防由增加的TNF-α活性引起的疾病，特别是炎症。
• Tricyclic Guanidine Derivatives as Sodium-Proton Exchange Inhibitors
  申请人：Lal Bansi

  公开号：US20070299051A1

  公开（公告）日：2007-12-27

  Guanidine derivatives having a condensed tricyclic ring of formula 1: are disclosed, wherein U is C(O), CR a R b , O, NR a or S(O) m ; V is CR a R b or NR a ; W is S(O) m ; wherein R a is H, alkyl, cycloalkyl, alkenyl or aralkyl; R b is H, alkyl, OH, OR a or OCOR a , and m is the integer 0, 1 or 2; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidino carbonyl. These derivatives are sodium-proton exchange inhibitors and are useful as medicaments for the treatment of, for example, organ disorders associated with ischemia and reperfusion, cardiac arrhythmia, cardiac hypertrophy, hypertension, cell proliferative disorders and diabetes.

  本发明公开了具有式1的紧凑三环环的胍衍生物，其中U为C（O），CRaRb，O，NRa或S（O）m; V为CRaRb或NRa; W为S（O）m;其中Ra为H，烷基，环烷基，烯基或芳基烷基; Rb为H，烷基，OH，ORa或OCORa，m为整数0、1或2; R1、R2、R3、R4、R5、R6、R7和R8如定义所述，但至少其中之一为胍基或胍基羰基。这些衍生物是钠-质子交换抑制剂，可用作治疗与缺血再灌注相关的器官疾病、心律失常、心肌肥大、高血压、细胞增殖性疾病和糖尿病等疾病的药物。
• Fused tricyclic compounds as inhibitors of tumor necrosis factor-α
  申请人：Piramal Life Sciences Limited

  公开号：US07964631B2

  公开（公告）日：2011-06-21

  Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

  公式1的化合物被披露，其中V是CH2; W是S（O）m; m是整数0、1或2; U是O、C（O）、CR13R14或NR15;其中R13是H、烷基; R14是H、OH、OR13或OCOR13; R15是H、烷基、环烷基、烯基、C（O）R13、C（O）OR13或烷基氨基甲酰基; R1、R2、R3、R4、R5、R6、R7和R8如本文所定义。这些化合物是肿瘤坏死因子-alpha（TNF-α）的抑制剂，并且可用作治疗和预防由增加的TNF-α活性引起的疾病的药物，特别是炎症。
• Tricyclic guanidine derivatives as sodium-proton exchange inhibitors
  申请人：Piramal Life Sciences Limited

  公开号：US08183234B2

  公开（公告）日：2012-05-22

  Guanidine derivatives having a condensed tricyclic ring of formula 1: are disclosed, wherein U is C(O), CRaRb, O, NRa or S(O)m; V is CRaRb or NRa; W is S(O)m; wherein Ra is H, alkyl, cycloalkyl, alkenyl or aralkyl; Rb is H, alkyl, OH, ORa or OCORa, and m is the integer 0, 1 or 2; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidinocarbonyl. These derivatives are sodium-proton exchange inhibitors and are useful as medicaments for the treatment of, for example, organ disorders associated with ischemia and reperfusion, cardiac arrhythmia, cardiac hypertrophy, hypertension, cell proliferative disorders and diabetes.

  揭示了具有公式1的紧凑三环环的胍衍生物，其中U为C（O），CRaRb，O，NRa或S（O）m；V为CRaRb或NRa；W为S（O）m；其中Ra为H，烷基，环烷基，烯基或芳基烷基；Rb为H，烷基，OH，ORa或OCORa，m为整数0、1或2；R1、R2、R3、R4、R5、R6、R7和R8如此定义，但其中至少有一个是胍基或胍基羰基。这些衍生物是钠-质子交换抑制剂，可用作治疗与缺血再灌注相关的器官疾病、心律失常、心肌肥大、高血压、细胞增殖性疾病和糖尿病等疾病的药物。
• Fused tricyclic compounds as inhibitors of tumor necrosis factor-alpha
  申请人：Piramal Life Sciences Limited

  公开号：US07834052B2

  公开（公告）日：2010-11-16

  Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

  公式1的化合物被披露，其中V为CH2；W为S(O)m；m为0、1或2的整数；U为O、C(O)、CR13R14或NR15；其中R13为H、烷基；R14为H、OH、OR13或OCOR13；R15为H、烷基、环烷基、烯基、C(O)R13、C(O)OR13或烷基氨基甲酰基；R1、R2、R3、R4、R5、R6、R7和R8如本文所定义。这些化合物是肿瘤坏死因子-α（TNF-α）的抑制剂，并可用作治疗和预防由TNF-α活性增加引起的疾病，特别是炎症的药物。