4-(2-甲基-1,3-恶唑-5-基)苯胺 | 89260-50-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(2-甲基-1,3-恶唑-5-基)苯胺
• 英文名称: 4-(2-methyloxazol-5-yl)aniline
• 英文别名: 4-(2-methyl-oxazol-5-yl)-phenylamine；4-(2-methyl-1,3-oxazol-5-yl)aniline；4-(2-methyl-oxazol-5-yl)phenylamine；4-(2-methyloxazol-5-yl)phenylamine
• CAS: 89260-50-4
• 化学式: C₁₀H₁₀N₂O
• mdl: MFCD05258288
• 分子量: 174.202
• InChiKey: AZABYWRROKMRRC-UHFFFAOYSA-N

物化性质

• 沸点：
  318.4±17.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-甲基-1,3-恶唑-5-基)苯胺 、 苯甲酰基异硫氰酸酯 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以17%的产率得到[4-(2-methyl-oxazol-5-yl)-phenyl]-thiourea
  参考文献：
  名称：

  MODULATORS FOR AMYLOID BETA

  摘要：

  该发明涉及以下式中的化合物，其中R1、R2、R3、R4、X和Y的定义如本文所述，并且涉及其药用活性酸盐。这些化合物可用于治疗阿尔茨海默病、脑淀粉样血管病、遗传性脑出血伴淀粉样病变（荷兰型）、多梗塞性痴呆、拳击性痴呆或唐氏综合征。

  公开号：

  US20090181965A1

文献信息

• [EN] NOVEL SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS GAMMA SECRETASE MODULATORS<br/>[FR] NOUVEAUX COMPOSÉS HÉTÉROCYCLIQUES BICYCLIQUES SUBSTITUÉS EN TANT QUE MODULATEURS DE LA GAMMA-SÉCRÉTASE
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2010089292A1

  公开（公告）日：2010-08-12

  The present invention is concerned with substituted bicyclic heterocyclic compounds of Formula (I) wherein Het1, Het2, A1, A2, A3 and A4 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及式（I）的取代双环杂环化合物，其中Het1、Het2、A1、A2、A3和A4的含义如权利要求中所定义。根据本发明的化合物可用作γ-分泌酶调节剂。本发明还涉及制备这种新化合物的方法，包含所述化合物作为活性成分的药物组合物，以及将所述化合物用作药物的用途。
• [EN] NOVEL SUBSTITUTED INDAZOLE AND AZA-INDAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS<br/>[FR] NOUVEAUX DÉRIVÉS SUBSTITUÉS D'INDAZOLE ET D'AZA-INDAZOLE UTILISÉS COMME MODULATEURS DE LA GAMMA SÉCRÉTASE
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2010145883A1

  公开（公告）日：2010-12-23

  The present invention is concerned with novel substituted indazole and aza-indazole derivatives of Formula (I), wherein R1, R2, R3, R4, Y, A1, A2, A3, A4, X1, X2, X3 and Het1 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及具有公式（I）中定义的R1、R2、R3、R4、Y、A1、A2、A3、A4、X1、X2、X3和Het1含义的新型取代的吲唑和氮杂吲唑衍生物。根据本发明的化合物可用作γ-分泌酶调节剂。该发明还涉及制备这种新型化合物的过程，包含该化合物作为活性成分的药物组合物以及将该化合物用作药物的用途。
• Biaryl Amides and Hydrazones as Therapeutics for Prion Disease in Transgenic Mice
  作者：Duo Lu、Kurt Giles、Zhe Li、Satish Rao、Elena Dolghih、Joel R. Gever、Michal Geva、Manuel L. Elepano、Abby Oehler、Clifford Bryant、Adam R. Renslo、Matthew P. Jacobson、Stephen J. DeArmond、B. Michael Silber、Stanley B. Prusiner

  DOI：10.1124/jpet.113.205799

  日期：2013.11

  The only small-molecule compound demonstrated to substantially extend survival in prion-infected mice is a biaryl hydrazone termed “Compd B” (4-pyridinecarboxaldehyde,2-[4-(5-oxazolyl)phenyl]hydrazone). However, the hydrazone moiety of Compd B results in toxic metabolites, making it a poor candidate for further drug development. We developed a pharmacophore model based on diverse antiprion compounds identified by high-throughput screening; based on this model, we generated biaryl amide analogs of Compd B. Medicinal chemistry optimization led to multiple compounds with increased potency, increased brain concentrations, and greater metabolic stability, indicating that they could be promising candidates for antiprion therapy. Replacing the pyridyl ring of Compd B with a phenyl group containing an electron-donating substituent increased potency, while adding an aryl group to the oxazole moiety increased metabolic stability. To test the efficacy of Compd B, we applied bioluminescence imaging (BLI), which was previously shown to detect prion disease onset in live mice earlier than clinical signs. In our studies, Compd B showed good efficacy in two lines of transgenic mice infected with the mouse-adapted Rocky Mountain Laboratory (RML) strain of prions, but not in transgenic mice infected with human prions. The BLI system successfully predicted the efficacies in all cases long before extension in survival could be observed. Our studies suggest that this BLI system has good potential to be applied in future antiprion drug efficacy studies.

  唯一被证实能大幅延长朊病毒感染小鼠存活时间的小分子化合物是一种双芳基腙，称为 "Compd B"（4-吡啶甲醛，2-[4-(5-恶唑基)苯基]腙）。然而，Compd B 的腙分子会产生有毒的代谢物，因此不适合进一步开发药物。我们根据高通量筛选出的多种抗磷脂化合物建立了一个药理模型；在此基础上，我们生成了康普迪 B 的双芳基酰胺类似物。通过药物化学优化，多个化合物的药效增强、脑浓度提高、代谢稳定性提高，表明它们有望成为抗磷脂治疗的候选药物。将 Compd B 的吡啶环替换为含有电子供能取代基的苯基可提高药效，而在噁唑分子上添加芳基可提高代谢稳定性。为了测试 Compd B 的功效，我们应用了生物发光成像（BLI）技术，该技术以前曾被证明能比临床症状更早地检测到活体小鼠朊病毒病的发病。在我们的研究中，Compd B 在感染了小鼠适应的洛基山实验室（Rocky Mountain Laboratory，RML）朊病毒株的两系转基因小鼠中表现出良好的疗效，但在感染了人类朊病毒的转基因小鼠中却没有表现出良好的疗效。早在观察到存活期延长之前，BLI 系统就成功预测了所有病例的疗效。我们的研究表明，BLI 系统在未来的抗朊病毒药物疗效研究中具有良好的应用潜力。
• [EN] MODULATORS FOR AMYLOID BETA<br/>[FR] MODULATEURS POUR L'AMYLOÏDE-BÊTA
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009087127A1

  公开（公告）日：2009-07-16

  The invention relates to compounds of formula (I) R1 is -C(O)O-lower alkyl, cyano or is hetaryl; hetaryl is a five-or six membered heteraryl group, optionally substituted by R'; R' is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy or lower alkoxy substituted by halogen; R2 is hydrogen, lower alkoxy, lower alkyl, halogen or cyano; R3 is -(CH2)n-C(O)O-lower alkyl, lower alkyl, lower alkoxy, hydroxy, -O-Si(CH3)2-lower alkyl, -C(O)-N(lower alkyl)2, -O-S(O)2-lower alkyl, C3-7-cycloalkyl, S(O)2-aryl, heterocyclyl, -C(O)-heterocyclyl, or is aryl or hetaryl, which aryl or hetaryl rings are optionally substituted by one or more R'; R4 is hydrogen, lower alkyl, hydroxy or CH2CN; X is S or -N=C(R5)-; R5 is hydrogen, lower alkyl or hydroxy, is a bond, -O-, -CH2-, -CH2-CH2-, formula (II) or or -N(R)-; R is hydrogen, lower alkyl, C(O)O-lower alkyl, C(O)-lower alkyl, S(O)2-lower alkyl, or benzyl; n is 0 or 1 or to pharmaceutically active acid addition salts. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

  本发明涉及式(I)的化合物，其中R1为-C（O）O-较低烷基，氰基或是杂芳基；杂芳基是五元或六元的杂芳基团，可选择性地由R'取代；R'为卤素，较低烷基，由卤素取代的较低烷基，较低烷氧基或由卤素取代的较低烷氧基；R2为氢，较低烷氧基，较低烷基，卤素或氰基；R3为-(CH2)n-C（O）O-较低烷基，较低烷基，较低烷氧基，羟基，-O-Si（CH3）2-较低烷基，-C（O）-N(较低烷基)2，-O-S（O）2-较低烷基，C3-7-环烷基，S（O）2-芳基，杂环基，-C（O）-杂环基，或是芳基或杂芳基，其中芳基或杂芳基环可以选择性地由一个或多个R'取代；R4为氢，较低烷基，羟基或CH2CN；X为S或-N=C（R5）-；R5为氢，较低烷基或羟基，是一个键，-O-，-CH2-，-CH2-CH2-，式（II）或或-N（R）-；R为氢，较低烷基，C（O）O-较低烷基，C（O）-较低烷基，S（O）2-较低烷基或苄基；n为0或1或是药物活性酸盐。这些化合物可用于治疗阿尔茨海默病、脑淀粉样血管病、遗传性脑出血伴有淀粉样蛋白病、荷兰型（HCHWA-D）、多发性脑梗死、拳击性痴呆或唐氏综合症。
• Modulators for amyloid beta
  申请人：Hoffmann-La Roche Inc.

  公开号：US07923450B2

  公开（公告）日：2011-04-12

  The invention relates to compounds of formula wherein R1, R2, R3, R4, X and Y are as defined herein and to pharmaceutically active acid addition salts thereof. The compounds can be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

  本发明涉及式中R1、R2、R3、R4、X和Y如此定义的化合物，以及其药学上活性的酸加盐。这些化合物可用于治疗阿尔茨海默病、脑淀粉样血管病、遗传性脑出血伴有淀粉样变（荷兰型）、多梗塞性痴呆、拳击痴呆或唐氏综合症。