N-(1,3-benzothiazol-6-yl)-N-{4-[(4-chlorophenyl)amino]furo[2,3-d]pyridazin-7-yl}amine | 332012-70-1

• 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: N-(1,3-benzothiazol-6-yl)-N-{4-[(4-chlorophenyl)amino]furo[2,3-d]pyridazin-7-yl}amine
• 英文别名: 7-N-(1,3-benzothiazol-6-yl)-4-N-(4-chlorophenyl)furo[2,3-d]pyridazine-4,7-diamine
• CAS: 332012-70-1
• 化学式: C₁₉H₁₂ClN₅OS
• 分子量: 393.856
• InChiKey: KRFWGEWIQQCKDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  7

文献信息

• Barbituric acid analogs as therapeutic agents
  申请人：——

  公开号：US20030229108A1

  公开（公告）日：2003-12-11

  This invention pertains to active barbituric acid analogs which inhibit HIF-1 activity (e.g., the interaction between HIF-1&agr; and p300) and thereby inhibit angiogenesis, tumorigensis, and proliferative conditions, such as cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HIF-1 activity, and to inhibit angiogensis, tumorigensis, and proliferative conditions, such as cancer.

  这项发明涉及活性巴比妥酸类似物，其抑制HIF-1活性（例如，HIF-1α与p300之间的相互作用），从而抑制血管生成、肿瘤发生和增生性疾病，如癌症。本发明还涉及包括这些化合物的药物组合物，以及在体外和体内使用这些化合物和组合物来抑制HIF-1活性，以及抑制血管生成、肿瘤发生和增生性疾病，如癌症。
• [EN] 4H-IMIDAZO[1,5-A]INDOLE DERIVATIVES AND THEIR USE AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) AND/OR TRYPTOPHAN 2,3-DIOXYGENASE (TD02) MODULATORS<br/>[FR] DÉRIVÉS DE 4H-IMIDAZO[1,5-A]INDOLE ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO) ET/OU DE LA TRYPTOPHANE 2,3-DIOXYGÉNASE (TDO2)
  申请人：REDX PHARMA PLC

  公开号：WO2016051181A1

  公开（公告）日：2016-04-07

  This invention relates to novel compounds of formula (I) wherein wherein Ά' is a 5 or 6 membered aryl or heteroaryl group, unsubstituted or substituted with 1, 2 or 3 groups as defined in claim 1; X is a bond or -(CRA1R81)n- (wherein n is selected from 1, 2, 3 and 4); Y is selected from: a bond, -O-, -NRF, -S-, -C(O)-, -C(NRF)-, -C(ORF)Rc-, -C(NRFRG)RC-, -C(O)NRF-, -NRFC(O) -NRFC(O)NRG-, -NRFSO2NRG-, - SO2-, -SO2NRF-, -NRFSO2-, -OC(O)- and -C(O)O-; Z is a bond; R1 is H or a 3 to 16 membered fully saturated, partially unsaturated or aromatic mono-, di- or tri-cyc!ic moiety, which optionally may include 1, 2 or 3 heteroatoms selected from O, N and S, and which is unsubstituted or substituted with 1 to 5 substituents as defined in claim 1; R2 is selected from: H, halo, C1-4alkyl, C1-4haloalkyl, -ORA4 and C1-4alkyl substituted with -ORA4; and R3 and R4 are each independently selected from: H, halo, C1-4halkyl, C1-4haloalkyl, C3-6cycloalkyl, -ORA5, -NRA5RB4, -CN, -SRA5 and C1-4alkyl substituted with -ORA5; and pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as indoieamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxynase (TDO2) modulators (e.g. IDO1, IDO2 and/or TDO2 inhibitors).

  本发明涉及公式（I）的新颖化合物，其中Ά'是一个5或6成员芳基或杂环芳基，未取代或取代为定义在权利要求1中的1、2或3个基团；X是一个键或者-(CRA1R81)n-（其中n选择自1、2、3和4）；Y选择自：一个键，-O-，-NRF，-S-，-C(O)-，-C(NRF)-，-C(ORF)Rc-，-C(NRFRG)RC-，-C(O)NRF-，-NRFC(O)-，-NRFC(O)NRG-，-NRFSO2NRG-，-SO2-，-SO2NRF-，-NRFSO2-，-OC(O)-和-C(O)O-；Z是一个键；R1是H或者一个3到16成员完全饱和、部分不饱和或芳香的单、双或三环！化合物，可选地可能包括1、2或3个来自O、N和S的杂原子，未取代或取代为定义在权利要求1中的1到5个取代基；R2选择自：H，卤素，C1-4烷基，C1-4卤代烷基，-ORA4和C1-4烷基取代的-ORA4；R3和R4各自独立选择自：H，卤素，C1-4烷基，C1-4卤代烷基，C3-6环烷基，-ORA5，-NRA5RB4，-CN，-SRA5和C1-4烷基取代的-ORA5；以及包括这些新型化合物的药物组合物。更具体地，本发明涉及作为印度吲哌啶2,3-双氧酶（IDO）和/或色氨酸2,3-双氧酶（TDO2）调节剂（例如IDO1、IDO2和/或TDO2抑制剂）有用的化合物。
• [EN] 6,7-HETEROCYCLIC FUSED 5H-PYRROLO[1,2-C]IMIDAZOLE DERIVATIVES AND THEIR USE AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) AND/OR TRYPTOPHAN 2,3-DIOXYGENASE (TD02) MODULATORS<br/>[FR] DÉRIVÉS DE 6,7-(HÉTÉROCYCLE FUSIONNÉ)-5H-PYRROLO[1,2-C]IMIDAZOLE ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO) ET/OU DE LA TRYPTOPHANE 2,3-DIOXYGÉNASE (TD02)
  申请人：REDX PHARMA PLC

  公开号：WO2016059412A1

  公开（公告）日：2016-04-21

  This invention relates to novel compounds of formula (I) wherein 'A' is a 5 or 6 membered heteroaryl group, unsubstituted or substituted with 1, 2 or 3 groups as defined in claim 1; X is a bond or -(CRA1RB1)n-; Y is selected from: a bond, -(CRDRE)m-, -O-, -NRF, -S-, -C(O)-, -C(NRF) -, -C(ORF)Rc-, -C(NRFRG)RC-, -C(O)NRF, -NRFC(O)-, -NRFC(O)NRG-, - NRFSO2NRG-, -SO2-, -SO2NRF-, -NRFSO2-, -OC(O)- and -C(O)O-; Z is a bond or -(CRA2RB2)k-; wherein m, n and k are each independently selected from 1, 2, 3 and 4; R1 is H or a 3 to 16 membered fully saturated, partially unsaturated or aromatic mono-, di- or tri-cyclic moiety, which optionally may include 1, 2 or 3 heteroatoms selected from O, N and S, and which is unsubstituted or substituted with 1 to 5 substituents as defined in claim 1; R2 is selected from: H, halo, C1-4alkyl, C1-4 haloalkyl, -ORA4 and C1-4alkyl substituted with -ORA4; and R3 and R4 are each independently selected from: H, halo, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, -ORA4, -NRA5RB4, -CN, -SRAS and C1-4alkyl substituted with -ORA5; and pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3- dioxygenase (TD02) modulators (e.g. IDOl, and ID02 and/or TD02 inhibitors).

  该发明涉及具有以下结构的新化合物（I）：其中“A”是一个5或6成员的杂芳基团，未取代或取代为定义在权利要求1中的1、2或3个基团；X是一个键或-(CRA1RB1)n-；Y选自：键，-(CRDRE)m-，-O-，-NRF，-S-，-C(O)-，-C(NRF)-，-C(ORF)Rc-，-C(NRFRG)RC-，-C(O)NRF，-NRFC(O)-，-NRFC(O)NRG-，-NRFSO2NRG-，-SO2-，-SO2NRF-，-NRFSO2-，-OC(O)-和-C(O)O-；Z是一个键或-(CRA2RB2)k-；其中m、n和k分别独立选择自1、2、3和4；R1是H或一个3到16成员的完全饱和、部分不饱和或芳香单、二或三环的基团，可选地可能包括1、2或3个从O、N和S中选择的杂原子，并且未取代或取代为定义在权利要求1中的1到5个取代基；R2选自：H，卤素，C1-4烷基，C1-4卤代烷基，-ORA4和用-ORA4取代的C1-4烷基；R3和R4分别独立选择自：H，卤素，C1-4烷基，C1-4卤代烷基，C3-6环烷基，-ORA4，-NRA5RB4，-CN，-SRAS和用-ORA5取代的C1-4烷基；以及包含这些新化合物的药物组合物。更具体地，该发明涉及作为吲哚胺2,3-二氧化酶（IDO）和/或色氨酸2,3-二氧化酶（TD02）调节剂（例如IDO1和IDO2和/或TD02抑制剂）有用的化合物。
• Anti-angiogenesis combination therapies comprising pyridazine or pyridine derivatives
  申请人：Adams E. Paul

  公开号：US20050019424A1

  公开（公告）日：2005-01-27

  The invention relates generally to the use of certain substituted fused or unfused pyridazine or pyridine derivatives which are KDR inhibitors in combination with other chemotherapeutic agents for use in treatment of diseases associated with abnormal angiogenesis and/or hyperpermeability and/or hyperproliferative diseases, such as cancer.

  本发明总体上涉及某些取代的融合或未融合哒嗪或吡啶衍生物的用途，这些衍生物是 KDR 抑制剂，与其他化疗药物联用，用于治疗与异常血管生成和/或高渗透性和/或高增殖性疾病（如癌症）相关的疾病。
• SUBSTITUTED PYRIDINES AND PYRIDAZINES WITH ANGIOGENESIS INHIBITING ACTIVITY
  申请人：BAYER CORPORATION

  公开号：EP1228063B1

  公开（公告）日：2009-02-11