1,3-二-叔-丁基-1H-吡唑-5-胺 | 787552-38-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1,3-二-叔-丁基-1H-吡唑-5-胺
• 英文名称: 1,3-di-tert-butyl-1H-pyrazol-5-amine
• 英文别名: 5-amino-1,3-di-tert-butyl-1H-pyrazole；2,5-ditert-butylpyrazol-3-amine
• CAS: 787552-38-9
• 化学式: C₁₁H₂₁N₃
• mdl: MFCD12168890
• 分子量: 195.308
• InChiKey: CQCGLMBJVRDWGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.727
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,3-二-叔-丁基-1H-吡唑-5-胺 以 乙腈 为溶剂， 500.0 ℃ 、4.0 Pa 条件下， 反应 1.5h， 生成 1,3-di-tert-butyl-1,7-dihydropyrazolo[3,4-b]pyridin-4-one
  参考文献：
  名称：

  Gas-Phase Synthesis of Pyrazolo[3,4-b]pyridin-4-ones

  摘要：

  Flash vacuum pyrolysis (FVP) at 500-600 degrees C of 1-substituted pyrazolylaminomethylene derivatives of Meldrum's acid provides 1-substituted pyrazolo[3,4-b]pyridin-4-ones in high yields. If the 1-substituent is a tert-butyl group, FVP at 750-850 degrees C causes elimination of 2-methyl-1-propene to give the parent pyrazolo[3,4-b]pyridin-4-one.

  DOI：

  10.1055/s-0034-1378666
• 作为产物：
  描述：

  新戊酰基乙腈 、 叔丁基肼盐酸盐 在 盐酸 作用下， 以 乙醇 为溶剂， 以33%的产率得到1,3-二-叔-丁基-1H-吡唑-5-胺
  参考文献：
  名称：

  V-RAF小鼠肉瘤肉瘤病毒致癌基因同源物B1（BRAF）的新型，高效抑制剂的发展：通过优化远端杂芳族基团来增加细胞效力。

  摘要：

  我们描述了一系列新型V-RAF鼠肉瘤病毒癌基因同源物B1（BRAF）抑制剂的设计，合成和优化，该激酶的突变体形式（V600E）与几种类型的癌症有关，发生频率特别高在黑色素瘤中。我们先前所述的具有三方A-B-C系统的抑制剂（其中A是铰链结合吡啶并[4,5- b ]咪唑啉酮系统，B是芳基间隔基团，C是杂芳族基团）对纯化的V600E有效体外进行BRAF，但在伴随的细胞测定中效力较弱。本文评估将不同的芳族杂环取代为基于苯基的C环，作为提高这些抑制剂细胞效价的潜在手段。取代的吡唑，尤其是3-叔丁基-丁基-1-芳基-1 H-吡唑类可增加细胞效能，而对分离的V600E BRAF的效能无不利影响。因此，已经合成了以低纳摩尔浓度抑制V600E BRAF，其在细胞中的下游信号传导的化合物（如通过细胞外调节激酶（ERK）磷酸化的减少来测量）以及突变型BRAF依赖性细胞的增殖。伴随的好处是良好的口服生物利用度和体内高血浆浓度。

  DOI：

  10.1021/jm900607f

文献信息

• SODIUM CHANNEL INHIBITORS
  申请人：Fulp Alan Bradley

  公开号：US20090023740A1

  公开（公告）日：2009-01-22

  Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels. More particularly, the invention provides substituted sulfonamides, compositions comprising these compounds, as well as methods of using these compounds or compositions in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrence of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a voltage-gated sodium channel.

  提供了在通过抑制电压门控钠通道中的钠离子通量来治疗疾病方面有用的化合物、组合物和方法。更具体地，本发明提供了取代磺胺基的化合物、包含这些化合物的组合物，以及使用这些化合物或组合物治疗中枢或外周神经系统疾病的方法，特别是通过阻断与所示疾病的发作或复发相关的钠通道来治疗疼痛和慢性疼痛。本发明的化合物、组合物和方法特别适用于通过抑制电压门控钠通道中的离子通量来治疗神经病理性或炎症性疼痛。
• [EN] KINASE INHIBITORS BASED UPON N-ALKYL PYRAZOLES<br/>[FR] INHIBITEURS DE KINASE À BASE DE N-ALKYL PYRAZOLES
  申请人：TOPIVERT PHARMA LTD

  公开号：WO2014162121A1

  公开（公告）日：2014-10-09

  There are provided compounds of formula (I), wherein R1 to R5, Ak and X1 to X3 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

  提供了化合物的结构式（I），其中R1至R5，Ak以及X1至X3的含义见说明，这些化合物具有抗炎活性（例如通过抑制p38丝裂原活化蛋白激酶家族中的一个或多个成员；Syk激酶；以及Src酪氨酸激酶家族的成员之一），并且在治疗中有用，包括在药物组合中，特别是用于治疗炎症性疾病，包括肺部、眼部和肠道的炎症性疾病。
• Design and synthesis of aminothiazole modulators of the gamma-secretase enzyme
  作者：Kevin D. Rynearson、Ronald N. Buckle、Keith D. Barnes、R. Jason Herr、Nicholas J. Mayhew、William D. Paquette、Samuel A. Sakwa、Phuong D. Nguyen、Graham Johnson、Rudolph E. Tanzi、Steven L. Wagner

  DOI：10.1016/j.bmcl.2016.07.011

  日期：2016.8

  The design and construction of a series of novel aminothiazole-derived gamma-secretase modulators is described. The incorporation of heterocyclic replacements of the terminal phenyl D-ring of lead compound 1 was conducted in order to align potency with favorable drug-like properties. gamma-Secretase modulator 28 displayed good activity for in vitro inhibition of Abeta42, as well as substantial improvement

  描述了一系列新颖的氨基噻唑衍生的γ-分泌酶调节剂的设计和构建。进行铅化合物1的末端苯基D-环的杂环取代基的掺入，以使效力与有利的类药物性质对准。γ-分泌酶调节剂28表现出良好的体外抑制Abeta42活性，以及​​ADME和理化特性（包括水溶性）的显着改善。化合物28在小鼠中的药代动力学评估显示，其良好的大脑渗透能力以及良好的清除率，半衰期和分布体积共同支持了这类化合物的持续开发。
• Compounds having inhibitive activity of phosphatidylinositol 3-kinase and methods of use thereof
  申请人：Drees E. Beth

  公开号：US20070010548A1

  公开（公告）日：2007-01-11

  Compounds inhibiting phosphatidylinositol 3-kinase (PI 3-K) activities and methods of preparing and using thereof in treating diseases are disclosed. Compounds inhibiting PI 3-K activity and methods of using PI 3-K inhibitory compounds to inhibit cancer cell grwoth or to treat disorders of immunity and inflammation, in which PI 3-K plays a role in leukocyte function are also provided.

  本发明公开了抑制磷脂酰肌醇3-激酶（PI 3-K）活性的化合物及其制备和用于治疗疾病的方法。本发明还提供了抑制PI 3-K活性的化合物及使用PI 3-K抑制剂化合物抑制癌细胞生长或治疗免疫和炎症障碍的方法，其中PI 3-K在白细胞功能中发挥作用。
• Imidazo[4,5-B]Pyridin-2-One and Oxazolo[4,5-B]Pyridin-2-One Compounds and Analogs Thereof as Therapeutic Compounds
  申请人：Niculescu-Duvaz Dan

  公开号：US20070287838A1

  公开（公告）日：2007-12-13

  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 formula (I): 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 P3 , and R P4 is independently —H or a substituent; and additionally R P1 and R P2 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 —; exactly one linker moiety is —NR N —, or: exactly two linker moieties are —NR N —; 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.

  本发明涉及某些咪唑并[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，其中包括抑制RAF（例如B-RAF）活性、抑制细胞增殖、治疗癌症等功能，更具体地，涉及式（I）的化合物：其中：J独立地是—O—或—NRN1—；RN1，如果存在，独立地是—H或取代基；RN2独立地是—H或取代基；Y独立地是—CH═或—N═；Q独立地是—（CH2）j-M-（ ）k—，其中：j独立地是0、1或2；k独立地是0、1或2；j+k为0、1或2；M独立地是—O—、—S—、—NH—、—NMe—或— —；RP1、RP2、RP3和RP4中的每一个独立地是—H或取代基；并且RP1和RP2一起可以是—CH═CH—CH═CH—；L独立地是：由2、3或4个连接基成的连接基团；每个连接基独立地是— —、—NRN—、—C（═X）—或—S（═O）2—；恰好一个连接基是—NRN—，或：恰好两个连接基是—NRN—；恰好一个连接基是—C（═X）—，且没有连接基是—S（═O）2—；或：恰好一个连接基是—S（═O）2—，且没有连接基是—C（═X）—；没有两个相邻的连接基是—NRN—；X独立地是═O或═S；每个RN独立地是—H或取代基；A独立地是：C6-14碳基芳基、C5-14杂环芳基、C3-12环烷基、C3-12杂环基；并且独立地是未取代或取代的；以及其药学上可接受的盐、溶剂化物、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制药组合物，以及这样的化合物和组合物的使用，无论在体内还是体外，用于抑制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，并用于治疗由于抑制RAF、RTK等而改善的疾病和病况，如增殖性疾病，如癌症（例如结肠癌、黑色素瘤）等。