1-叔-丁基-3-(m-苯甲基甲基)吡唑并[3,4-d]嘧啶-4-胺 | 956489-12-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 1-叔-丁基-3-(m-苯甲基甲基)吡唑并[3,4-d]嘧啶-4-胺
• 英文名称: 5-amino-2,3,4-trifluorophenol
• CAS: 956489-12-6
• 化学式: C₆H₄F₃NO
• 分子量: 163.099
• InChiKey: YASSNYOFEPDUIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-叔-丁基-3-(m-苯甲基甲基)吡唑并[3,4-d]嘧啶-4-胺 、 2-氨基-3-硝基-4-氯吡啶 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 以40%的产率得到4-(5-amino-2,3,4-trifluorophenoxy)-3-nitropyridin-2-amine
  参考文献：
  名称：

  BRAF Inhibitors Based on an Imidazo[4,5]pyridin-2-one Scaffold and a Meta Substituted Middle Ring

  摘要：

  We recently reported on the development of a novel series of BRAF inhibitors based on a tripartite A-B-C system characterized by a para-substituted central aromatic core connected to an imidazo-[4,5]pyridin-2-one scaffold and it substituted urea linker. Here, we present it new series of BRAY inhibitors in which the central phenyl ring connects to the hinge binder and substrate pocket of BRAF with a meta-substitution pattern. The optimization of this new scaffold led to the development of low-nanomolar inhibitors that permits the use of a wider range of linkers and terminal C rings while enhancing the selectivity for the BRAF enzyme in comparison to the para series.

  DOI：

  10.1021/jm901509a
• 作为产物：
  描述：

  5-amino-2,3,4-trifluorophenyl ethyl carbonate 在 potassium carbonate 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 1.5h， 以90%的产率得到1-叔-丁基-3-(m-苯甲基甲基)吡唑并[3,4-d]嘧啶-4-胺
  参考文献：
  名称：

  BRAF Inhibitors Based on an Imidazo[4,5]pyridin-2-one Scaffold and a Meta Substituted Middle Ring

  摘要：

  We recently reported on the development of a novel series of BRAF inhibitors based on a tripartite A-B-C system characterized by a para-substituted central aromatic core connected to an imidazo-[4,5]pyridin-2-one scaffold and it substituted urea linker. Here, we present it new series of BRAY inhibitors in which the central phenyl ring connects to the hinge binder and substrate pocket of BRAF with a meta-substitution pattern. The optimization of this new scaffold led to the development of low-nanomolar inhibitors that permits the use of a wider range of linkers and terminal C rings while enhancing the selectivity for the BRAF enzyme in comparison to the para series.

  DOI：

  10.1021/jm901509a

文献信息

• IMIDAZO[4, 5-B]PYRIDIN-2-ONE AND OXAZOLO[4, 5-B]PYRIDIN-2-ONE COMPOUNDS AND ANALOGS THEREOF AS CANCER THERAPEUTIC COMPOUNDS
  申请人：Niculescu-Duvaz Dan

  公开号：US20090325945A1

  公开（公告）日：2009-12-31

  The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: wherein: J is independently —O— or —NR N1− ; R N1 , if present, is independently —H or a substituent; R N2 is independently —H or a substituent; Y is independently —CH═ or —N═; Q is independently —(CH 2 ) j -M-(CH 2 ) k — wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently O—, —S—, —NH—, —NMe-, or —CH 2 —; each of R P1 , R P2 , R P5 , and R P4 is independently —H or a substituent; and additionally R P1 and R P2 taken together may be CH═CH—CH═CH—; and additionally R P1 and R P5 taken together may be CH═CH—CH═CH—; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently CH 2 —, —NR N —, —C(═X)—, or —S(═O) 2 —; either: exactly one linker moiety is —NR N —, or: exactly two linker moieties are —NR N —; either: exactly one linker moiety is —C(═X)—, and no linker moiety is —S(═O) 2 —, or: exactly one linker moiety is —S(═O) 2 —, and no linker moiety is —C(═X)—; no two adjacent linker moieties are —NR N —; X is independently ═O or ═S; each R N is independently —H or a substituent; A is independently: C 6-14 carboaryl, C 5-14 heteroaryl, C 3-12 carbocyclic, C 3-12 heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. 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 RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

  本发明涉及特定的咪唑并[4,5-b]吡啶-2-酮和噁唑并[4,5-b]吡啶-2-酮化合物及其类似物，其中，它们可以抑制RAF（例如B-RAF）活性，抑制细胞增殖，治疗癌症等。特别是本发明涉及以下式的化合物：其中：J独立地为—O—或—NRN1−；RN1（如果存在）独立地为—H或取代基；RN2独立地为—H或取代基；Y独立地为—CH═或—N═；Q独立地为—（CH2）j-M-（CH2）k—，其中：j独立地为0、1或2；k独立地为0、1或2；j+k为0、1或2；M独立地为O—、—S—、—NH—、—NMe-或—CH2—；RP1、RP2、RP5和RP4中的每一个独立地为—H或取代基；并且另外RP1和RP2一起可以是CH═CH—CH═CH—；并且另外RP1和RP5一起可以是CH═CH—CH═CH—；L独立地为：由2、3或4个连接基成的连接基团；每个连接基单元独立地为CH2—、—NRN—、—C（═X）—或—S（═O）2—；要么：恰好有一个连接基单元为—NRN—，或：恰好有两个连接基单元为—NRN—；要么：恰好有一个连接基单元为—C（═X）—，且没有连接基单元为—S（═O）2—，或：恰好有一个连接基单元为—S（═O）2—，且没有连接基单元为—C（═X）—；没有两个相邻的连接基单元为—NRN—；X独立地为═O或═S；每个RN独立地为—H或取代基；A独立地为：C6-14碳基芳基、C5-14杂环芳基、C3-12环烷基、C3-12杂环烷基；并且独立地未取代或取代；以及其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、N-氧化物、化学保护形式和前药。本发明还涉及包含这样的化合物的药物组合物，以及这样的化合物和组合物的使用，无论是在体外还是在体内，来抑制RAF（例如B-RAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并治疗通过抑制RAF、RTK等而改善的疾病和情况，如癌症（例如结肠癌、黑色素瘤）等。
• Ethylened polymer and molded object obtained therefrom
  申请人：Satoh Yasuo

  公开号：US20060135712A1

  公开（公告）日：2006-06-22

  An ethylene-based polymer which is an ethylene/C4 to C10 α-olefin copolymer and satisfies the following requirements [k1] to [k3]: [k1] melt flow rate (MFR) under a loading of 2.16 kg at 190° C. is in the range of 1.0 to 50 g/10 minutes; [k2] LNR defined as a scale of neck-in upon film molding is in the range of 0.6 to 1.4; and [k3] take-up speed at break [DS (m/min)] at 160° C. and melt flow rate (MFR) satisfy the following relationship (Eq-1): 12×MFR 0.577 ≦DS≦165×MFR 0.577 (Eq-1), and a thermoplastic resin composition containing the ethylene-based polymer, provide a molded product, preferably a film, excellent in moldability and mechanical strength. The ethylene-based polymer can be efficiently obtained by polymerization in the presence of an olefin polymerization catalyst formed from a solid carrier, (A) a solid transition metal catalyst component obtained by contacting (a) a compound of a transition metal of the group 4 in the periodic table, containing at least one ligand having a cyclopentadienyl skeleton, (b) an organoaluminum oxy compound, (c) a multifunctional organic halide, and if necessary (d) an organoaluminum compound, and if necessary (B) organoaluminum compound.

  一种乙烯基聚合物，它是一种乙烯/C4 至 C10 α-烯烃共聚物，并满足以下[k1]至[k3]的要求：[k1] 熔体流动速率（MFR）在 190 摄氏度、负载 2.16 千克的条件下，范围在 1.0 至 50 克/10 分钟之间；[k2] LNR 定义为薄膜成型时的缩颈比例，范围在 0.6 至 1.4 之间；以及 [k3] 160 摄氏度时的断裂收口速度[DS（米/分）]和熔体流动速率（MFR）满足以下关系式（公式-1）：12×MFR 0.577 ≦DS≦165×MFR 0.577 (式-1），以及含有乙烯基聚合物的热塑性树脂组合物，可提供模塑产品，最好是薄膜，具有优异的模塑性和机械强度。乙烯基聚合物可通过在由固体载体、(A)固体过渡金属催化剂组分、(B)有机铝氧化合物、(C)多功能有机卤化物和必要时(D)有机铝化合物以及必要时(B)有机铝化合物形成的烯烃聚合催化剂存在下进行聚合而有效地获得。
• IMIDAZO[4,5-B]PYRIDIN-2-ONE COMPOUNDS AND ANALOGS THEREOF AS CANCER THERAPEUTIC COMPOUNDS
  申请人：Cancer Research Technology Limited

  公开号：EP2013207B1

  公开（公告）日：2012-04-25
• US4129414A
  申请人：——

  公开号：US4129414A

  公开（公告）日：1978-12-12
• US7208559B2
  申请人：——

  公开号：US7208559B2

  公开（公告）日：2007-04-24