ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridine-5-carboxylate | 39057-39-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异恶唑并吡啶类
• 英文名称: ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridine-5-carboxylate
• 英文别名: 4-chloro-3-methyl-isoxazolo[5,4-b]pyridine-5-carboxylic acid ethyl ester；ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridin-5-carboxylate；ethyl 4-chloro-3-methyl-[1,2]oxazolo[5,4-b]pyridine-5-carboxylate
• CAS: 39057-39-1
• 化学式: C₁₀H₉ClN₂O₃
• 分子量: 240.646
• InChiKey: KOMOUKUZGNFOSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridine-5-carboxylate 在 sodium hydroxide 作用下， 以 乙二醇二甲醚 为溶剂， 反应 0.67h， 生成 4-Chloro-3-methyl-[1,2]oxazolo[5,4-b]pyridine-5-carboxylic acid
  参考文献：
  名称：

  N-Arylpiperazinyl-N‘-propylamino Derivatives of Heteroaryl Amides as Functional Uroselective α₁-Adrenoceptor Antagonists

  摘要：

  Novel arylpiperazines were identified as alpha(1)-adrenoceptor(BR) subtype-selective antagonists by functional in vitro screening. 3-[4-(ortho-Substituted phenyl)piperazin-1-yl]propylamines were derivatized with N,N-dimethyl anthranilamides, nicotinamides,;as well as carboxamides of quinoline, I,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4-b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta;a were used as a ''negative screen'' for the test antagonists. Binding to alpha(1)-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g, 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the alpha(1)-AR subtype prevalent in the human lower urinary tract (pA(2) values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the alpha(1D)-AR.

  DOI：

  10.1021/jm970166j
• 作为产物：
  描述：

  diethyl 2-(((3-methylisoxazol-5-yl)amino)methylene)malonate 在 三氯氧磷 作用下， 以 二苯醚 为溶剂， 反应 4.0h， 生成 ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridine-5-carboxylate
  参考文献：
  名称：

  异恶唑并 [5.4-b] 吡啶

  摘要：

  描述了许多新的异恶唑并 [5.4-b] 吡啶-5-羧酸和 5-酮衍生物的合成。大多数化合物在 4 位具有烷氧基或碱性取代基。

  DOI：

  10.1002/ardp.19723051107

文献信息

• 피리미딘카르복스아미드 유도체 및 이를 포함하는 약학적 조성물
  申请人：Wellmarker Bio Co., LTD. 웰마커바이오 주식회사(120180081780) Corp. No ▼ 110111-6267705BRN ▼847-87-00472

  公开号：KR20210027860A

  公开（公告）日：2021-03-11

  본 발명은 피리미딘카르복스아미드 유도체를 유효성분으로 포함하는 조성물에 관한 것으로서, 보다 구체적으로 피리미딘카르복스아미드 유도체, 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, PIM 세린/트레오닌 키나제 효소 과잉 활성과 관련된 질환의 예방, 개선 또는 치료용 조성물에 관한 것이다. 본 발명에 따른 피리딘카르복스아미드 유도체들은 PIM 세린/트레오닌 키나제 효소의 활성을 억제 또는 저해할 수 있어 PIM 세린/트레오닌 키나제 효소의 과잉 활성화와 관련된 질환을 근본적으로 예방 또는 치료할 수 있는 약학적 조성물로 이용될 수 있을 뿐만 아니라, PIM 세린/트레오닌 키나제 효소의 과잉 활성과 관련된 질환의 치료용 생물학적인 제제 개발 및 PIM 세린/트레오닌 키나제 효소의 발현 또는 활성 억제에 관한 다양한 연구에 활용될 수 있다.

  本发明涉及包含嘧啶羧酰胺衍生物作为有效成分的组合物，更具体地说，涉及包含嘧啶羧酰胺衍生物及其药学上可接受的盐作为有效成分的，用于预防、改善或治疗与PIM丝氨酸/苏氨酸激酶酶过度活性有关的疾病的组合物。根据本发明的嘧啶羧酰胺衍生物能够抑制或阻碍PIM丝氨酸/苏氨酸激酶酶的活性，因此可以用作药学组合物，从根本上预防或治疗与PIM丝氨酸/苏氨酸激酶酶过度活性有关的疾病。这些嘧啶羧酰胺衍生物不仅可用于开发用于治疗与PIM丝氨酸/苏氨酸激酶酶过度活性有关的疾病的生物制剂，还可用于各种与PIM丝氨酸/苏氨酸激酶酶的表达或活性抑制相关的研究。
• Preparation and use of ortho-sulfonamido bicyclic heteroaryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors
  申请人：——

  公开号：US20010046989A1

  公开（公告）日：2001-11-29

  This invention provides, low molecular weight, non-peptide inhibitors of matrix metalloproteinases and TNF-&agr; converting enzyme (TACE, tumor necrosis factor-&agr; converting enzyme) of formula: B wherein B is 1 2 T, U, W, and X are each, independently, carbon or nitrogen, provided that when T or U is carbon, either may be optionally substituted with R 1 ; Y is carbon, nitrogen, oxygen or sulfur, provided that at least one of T, U, W, X, and Y is not carbon, and further provided that no more than 2 of T, U, W, and X are nitrogen; 3 is a phenyl ring or is a heteroaryl ring of ring 5-6 atoms which may contain 0-2 heteratoms selected from nitrogen, oxygen, and sulfur, in addition to any heteroatoms defined by W or X; wherein the phenyl or heteroaryl ring may be optionally mono-, di-, or tri- substituted with R 1 ; Z is a phenyl, naphthyl, heteroaryl, or heteroaryl fused to phenyl, wherein the heteroaryl moiety contains of 5-6 ring atoms and 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur; wherein the phenyl, naphthyl, heteroaryl, or phenyl fused heteroaryl moieties may be optionally mono-, di-, or tri- substituted with R 1 ; R 1 is hydrogen, halogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cyclocalkyl of 3-6 carbon atoms, —(CH 2 ) n Z, —OR 2 , —CN, —COR 2 , perfluoroalkyl of 1-4 carbon atoms, —CONR 2 R 3 , —S(O) x R 2 —OPO(OR 2 )OR 3 , —PO(OR 2 )R 3 , —OC(O)NR 2 R 3 , —COOR 2 , —CONR 2 R 3 , —SO 3 H, —NR 2 R 3 , —NR 2 COR 3 , —NR 2 COOR 3 , —SO 2 NR 2 R 3 , —NO 2 , —N(R 2 )SO 2 R 3 , —NR 2 CONR 2 R 3 , —NR 2 C(═NR 3 )NR 2 R 3 , —SO 2 NHCOR 4 , —CONHSO 2 R 4 , -tetrazol-5-yl, —SO 2 NHCN, —SO 2 NHCONR 2 R 3 or Z; V is a saturated or partially unsaturated heterocycloalkyl ring of 5-7 ring atoms having 1-3 heteroatoms selected from N, O, or S, which may be optionally mono-, or di-substituted with R 2 ; R 2 and R 3 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R 4 is alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R 5 is hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, Z, or V; n=1-6; x=0-2 or a pharmaceutically acceptable salt thereof.

  这项发明提供了低分子量、非肽类的基质金属蛋白酶和TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）的抑制剂，其化学式为：其中 B 是 12T，U，W 和 X 分别独立地为碳或氮，但当 T 或 U 为碳时，可以选择性地用 R1 取代；Y 为碳、氮、氧或硫，要求 T、U、W、X 和 Y 中至少有一个不是碳，并且进一步要求 T、U、W 和 X 中不超过 2 个是氮；3 为苯环或是由 5-6 个原子组成的杂环，其中可能含有 0-2 个氮、氧或硫等杂原子，除了 W 或 X 定义的杂原子之外；苯或杂环可能选择性地单取代、双取代或三取代的 R1；Z 为苯、萘、杂环或与苯融合的杂环，其中杂环部分含有 5-6 个环原子和 1-3 个氮、氧或硫等杂原子；苯、萘、杂环或苯融合杂环部分可能选择性地单取代、双取代或三取代的 R1；R1 为氢、卤素、1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、3-6 个碳原子的环烷基、—(CH2)nZ、—OR2、—CN、—COR2、1-4 个碳原子的全氟烷基、—CONR2R3、—S(O)xR2—OPO(OR2)OR3、—PO(OR2)R3、—OC(O)NR2R3、—COOR2、—CONR2R3、—SO3H、—NR2R3、—NR2COR3、—NR2COOR3、—SO2NR2R3、—NO2、—N(R2)SO2R3、—NR2CONR2R3、—NR2C(═NR3)NR2R3、—SO2NHCOR4、—CONHSO2R4、-四唑-5-基、—SO2NHCN、—SO2NHCONR2R3 或 Z；V 为由 5-7 个环原子组成、含有 1-3 个氮、氧或硫等杂原子的饱和或部分不饱和杂环烷基，可能选择性地单取代或双取代的 R2；R2 和 R3 分别独立地为氢、1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、3-6 个碳原子的环烷基、1-4 个碳原子的全氟烷基、Z 或 V；R4 为1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、3-6 个碳原子的环烷基、1-4 个碳原子的全氟烷基、Z 或 V；R5 为氢、1-8 个碳原子的烷基、2-6 个碳原子的烯基、2-6 个碳原子的炔基、Z 或 V；n=1-6；x=0-2 或其药用盐。
• Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors
  申请人：American Cyanamid Company

  公开号：US20030208066A1

  公开（公告）日：2003-11-06

  Compounds of the formula 1 which are useful in disease conditions mediated by TNF-&agr;, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

  式1的化合物在由TNF-α介导的疾病条件中很有用，如类风湿关节炎、骨关节炎、败血症、艾滋病、溃疡性结肠炎、多发性硬化症、克罗恩病和软骨退行性损失。
• Antagonists of MCP-1 function and methods of use thereof
  申请人：——

  公开号：US20030096705A1

  公开（公告）日：2003-05-22

  The present invention relates to chemical compounds, pharmaceutical compositions comprising said compounds, uses of said compounds and compositions, methods of treatment employing said compounds and compositions, and processes for preparing said compounds. Specifically, this invention relates to novel compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection. More specifically, the invention is related to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases.

  本发明涉及化合物、包含该化合物的药物组合物、使用该化合物和组合物的用途、使用该化合物和组合物的治疗方法，以及制备该化合物的过程。具体而言，本发明涉及新型化合物，这些化合物是 MCP-1 功能拮抗剂，可用于预防或治疗慢性或急性炎症性或自身免疫性疾病，特别是那些与淋巴细胞或单核细胞异常积聚有关的疾病，如关节炎、哮喘、动脉粥样硬化、糖尿病肾病、炎性肠病、克罗恩病、多发性硬化、肾炎、胰腺炎、肺纤维化、银屑病、再狭窄和移植排斥反应。更具体地，本发明涉及包含这些化合物的药物组合物以及使用这些化合物和组合物预防或治疗这些疾病。
• Isoxazolo [5.4-b]pyridine
  作者：T. Denzel、H. Höhn

  DOI：10.1002/ardp.19723051107

  日期：——

  Die Synthese einer Reihe neuer Isoxazolo [5.4‐b]pyridin‐5‐carbonsäure‐ und 5‐keton‐Derivate wird beschrieben. Die meisten Verbindungen tragen etweder einen Alkoxy‐ oder einen basischen Substituenten in 4‐Stellung.

  描述了许多新的异恶唑并 [5.4-b] 吡啶-5-羧酸和 5-酮衍生物的合成。大多数化合物在 4 位具有烷氧基或碱性取代基。