N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-2-(2-(trifluoromethoxy)benzamido)thiazole-4-carboxamide | 1528742-16-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-2-(2-(trifluoromethoxy)benzamido)thiazole-4-carboxamide
• 英文别名: N-(2,2-Difluoro-5h-[1,3]dioxolo[4,5-F]benzimidazol-6-Yl)-2-{[2-(Trifluoromethoxy)benzoyl]amino}-1,3-Thiazole-4-Carboxamide；N-(2,2-difluoro-5H-[1,3]dioxolo[4,5-f]benzimidazol-6-yl)-2-[[2-(trifluoromethoxy)benzoyl]amino]-1,3-thiazole-4-carboxamide
• CAS: 1528742-16-6
• 化学式: C₂₀H₁₀F₅N₅O₅S
• 分子量: 527.388
• InChiKey: DVVVOLSRHWJCHV-UHFFFAOYSA-N

物化性质

• 密度：
  1.78±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  5-氨基-2,2-二氟-1,3-苯并二噁唑 在 甲醇 、 氢气 、 硝酸 、 sodium methylate 、 镍 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 19.75h， 生成 N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-2-(2-(trifluoromethoxy)benzamido)thiazole-4-carboxamide
  参考文献：
  名称：

  [EN] BIFLUORODIOXALANE-AMINO-BENZIMIDAZOLE KINASE INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNEINFLAMMATION AND CNS DISORDERS
  [FR] INHIBITEURS DE KINASE DIFLUORODIOXALANE-AMINOBENZIMIDAZOLE POUR LE TRAITEMENT D'UN CANCER, D'UNE INFLAMMATION AUTO-IMMUNE ET DE TROUBLES DU SNC

  摘要：

  该发明涉及一般式(I)的化合物或其生理功能衍生物、溶剂或盐，其中(I)中A是键，烷基或烷氧基，可选择地用一个或多个如下所定义的R"取代，*-N(R"')CO-，*-CON(R"')-，*-N(R'")CON(R"')-，-S-，-SO-，*-N(R'")-，*-N(R'")CO-，*-CON(R'")-，-CO-，*-COO-，*-OOC-，*-S02N(R"')-，-S02，或*-N(R"')-SO2-，其中R"'如此定义，*指定连接到X的点；X是芳香族，环烷基，芳基烷基，杂环烷基或杂芳基，可用一个或多个Rx进一步描述；L是键或*-N(RN)CO-，*-CON(RN)-，*-N(RN)-，*-C=N(RN)-，*-N(RN)-烷基-，*-烷基-N(RN)-，*-N(RN)CON(RN)-，*-CO-，*-S02-，烷基，*-烷基-0-烷基-，*-NCO-CH=CH-，*-CH=CH-CONH-，*-S02N(RN)-，*-N(RN)S02-，或杂环烷基，其中*指定连接到X的点；Y是H，烷基，芳基，芳基烷基，环烷基，杂环烷基或杂芳基，可用一个或多个RY进一步描述；R和RN在此进一步描述；以及它们作为药物的用途，包括它们的药物组合物，治疗或预防涉及其管理的医疗状况的方法，以及在制造用于治疗或预防医疗状况的药物中的用途，特别是自身免疫性炎症性疾病、中枢神经系统疾病、睡眠障碍或包括癌症在内的增殖性疾病。该发明还涉及一种特定的制备上述化合物的过程。

  公开号：

  WO2014001464A1

文献信息

• [EN] BIFLUORODIOXALANE-AMINO-BENZIMIDAZOLE KINASE INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNEINFLAMMATION AND CNS DISORDERS<br/>[FR] INHIBITEURS DE KINASE DIFLUORODIOXALANE-AMINOBENZIMIDAZOLE POUR LE TRAITEMENT D'UN CANCER, D'UNE INFLAMMATION AUTO-IMMUNE ET DE TROUBLES DU SNC
  申请人：4SC DISCOVERY GMBH

  公开号：WO2014001464A1

  公开（公告）日：2014-01-03

  The invention relates to a compound of the general formula (I) or a physiologically functional derivative, solvate or salt thereof, (I) wherein A is a bond, alkyl or alkoxy optionally substituted with one or more R" as defined herein, *-N(R"')CO-, *-CON(R"')-, *-N(R'")CON(R"')-, -S-, -SO-, *-N(R'")-, *-N(R'")CO-, *-CON(R'")-, -CO-, *-COO-, *-OOC-, *-S02N(R"')-, -S02, or *-N(R"')-SO2-, wherein R"' is as defined herein and * specifies the point of attachment to X; X is aryl, cycloalkyl, aralkyl, heterocyclyl or heteroaryl, which may be substituted with one or more Rx further described herein; L is a bond or *-N(RN)CO-, *-CON(RN)-, *-N(RN)-, *-C=N(RN)-, *-N(RN)-alkyI-, *-alkyl-N(RN)-, *-N(RN)CON(RN)-, *-CO-, *-S02-, alkyl, *-alkyl-0-alkyl-, *-NCO-CH=CH-, *-CH=CH-CONH-, * -S02N(RN)-, *-N(RN)S02-, or heterocyclyl, wherein * specifies the point of attachment to X; Y is H, alkyl, aryl, aralkyl, cycloalkyl, heterocyclyl or heteroaryl, which may be substituted with one or more RY further described herein; and R and RN are further described herein; as well as their use as a medicament, a pharmaceutical composition comprising them, a method of treatment or prevention of a medical condition entailing the administration thereof, and the use thereof in the manufacture of a medicament for the treatment or prevention of a medical condition, particularly autoimmune inflammatory disorders, CNS disorders, sleeping disorders, or proliferative diseases including cancer. The invention further relates to a specific process for the preparation of said compounds.

  该发明涉及一般式(I)的化合物或其生理功能衍生物、溶剂或盐，其中(I)中A是键，烷基或烷氧基，可选择地用一个或多个如下所定义的R"取代，*-N(R"')CO-，*-CON(R"')-，*-N(R'")CON(R"')-，-S-，-SO-，*-N(R'")-，*-N(R'")CO-，*-CON(R'")-，-CO-，*-COO-，*-OOC-，*-S02N(R"')-，-S02，或*-N(R"')-SO2-，其中R"'如此定义，*指定连接到X的点；X是芳香族，环烷基，芳基烷基，杂环烷基或杂芳基，可用一个或多个Rx进一步描述；L是键或*-N(RN)CO-，*-CON(RN)-，*-N(RN)-，*-C=N(RN)-，*-N(RN)-烷基-，*-烷基-N(RN)-，*-N(RN)CON(RN)-，*-CO-，*-S02-，烷基，*-烷基-0-烷基-，*-NCO-CH=CH-，*-CH=CH-CONH-，*-S02N(RN)-，*-N(RN)S02-，或杂环烷基，其中*指定连接到X的点；Y是H，烷基，芳基，芳基烷基，环烷基，杂环烷基或杂芳基，可用一个或多个RY进一步描述；R和RN在此进一步描述；以及它们作为药物的用途，包括它们的药物组合物，治疗或预防涉及其管理的医疗状况的方法，以及在制造用于治疗或预防医疗状况的药物中的用途，特别是自身免疫性炎症性疾病、中枢神经系统疾病、睡眠障碍或包括癌症在内的增殖性疾病。该发明还涉及一种特定的制备上述化合物的过程。
• BIFLUORODIOXALANE-AMINO-BENZIMIDAZOLE KINASE INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNEINFLAMMATION AND CNS DISORDERS
  申请人：4SC DISCOVERY GMBH

  公开号：US20150158878A1

  公开（公告）日：2015-06-11

  The invention relates to a compound of the general formula (I) or a physiologically functional derivative, solvate or salt thereof, wherein A, X, L, Y, R, and R N are as defined herein. The invention further relates to the use of the compounds of formula (I) as a medicament, a pharmaceutical composition comprising them, a method of treatment or prevention of a medical condition entailing the administration thereof, and the use thereof in the manufacture of a medicament for the treatment or prevention of a medical condition, particularly autoimmune inflammatory disorders, CNS disorders, sleeping disorders, or proliferative diseases including cancer. The invention further relates to a specific process for the preparation of said compounds.

  本发明涉及一种通式(I)的化合物或其生理功能衍生物、溶剂或盐，其中A、X、L、Y、R和RN如本文所定义。本发明还涉及将通式(I)的化合物用作药物，包括它们的制药组合物，以及治疗或预防需要其给药的医疗状况的方法，以及将其用于制造治疗或预防医疗状况的药物，尤其是自身免疫炎症性疾病、中枢神经系统疾病、睡眠障碍或增殖性疾病，包括癌症。本发明还涉及一种特定的制备上述化合物的方法。
• US9580438B2
  申请人：——

  公开号：US9580438B2

  公开（公告）日：2017-02-28
• Difluoro-dioxolo-benzoimidazol-benzamides As Potent Inhibitors of CK1δ and ε with Nanomolar Inhibitory Activity on Cancer Cell Proliferation
  作者：Julia Richter、Joachim Bischof、Mirko Zaja、Hella Kohlhof、Olaf Othersen、Daniel Vitt、Vanessa Alscher、Irmgard Pospiech、Balbina García-Reyes、Sebastian Berg、Johann Leban、Uwe Knippschild

  DOI：10.1021/jm500600b

  日期：2014.10.9

  Deregulation of CK1 (casein kinase 1) activity can be involved in the development of several pathological disorders and diseases such as cancer. Therefore, research interest in identifying potent CK1 specifc inhibitors is still increasing. A previously published potent and selective benzimidazole-derived CK1 delta/epsilon specific inhibitor compound with significant effects on several tumor cell lines was further modified to difluoro-dioxolo-benzoimidazole derivatives displaying remarkable inhibitory effects and increased intracellular availability. In the present study, we identified two heterocyclic molecules as new CK-specific inhibitor compunds with favorable physicochemical properties and notable selectivity in a kinom-wide screen Being compared to other CK1 isoforms these compounds exhibited advanced isoform selectivity toward CK1 delta Moreover, newly designed compounds showed increased growth inhibitory activity in a panel of different tumor cell lines as determined by analyses of cell viability and cell cycle distribution. In summary presented lead optimization. resulted in new highly elective CK1 delta-specific small molecule inhibitors with increased biological activity.