2-(2-chlorophenyl)-6,7-dimethoxy-N-pyridin-4-ylquinazolin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(2-chlorophenyl)-6,7-dimethoxy-N-pyridin-4-ylquinazolin-4-amine
• 化学式: C₂₁H₁₇ClN₄O₂
• 分子量: 392.8
• InChiKey: SKCTXVXYSRKRSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  69.2
• 氢给体数：
  1
• 氢受体数：
  6

文献信息

• Quinazoline derivatives as medicaments
  申请人：——

  公开号：US20030069248A1

  公开（公告）日：2003-04-10

  The invention is directed to methods to inhibit TGF-&bgr;and/or p38-&agr; kinase using compounds of the formula 1 or the pharmaceutically acceptable salts thereof wherein R 3 is a noninterfering substituent; each Z is CR 2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R 2 is independently a noninterfering substituent; L is a linker; n is 0 or 1;and Ar′ is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

  该发明涉及使用式1化合物或其药学上可接受的盐来抑制TGF-β和/或p38-α激酶的方法，其中： R3是非干扰基； 每个Z是CR2或N，其中环A中不超过两个Z位置是N，且环A中相邻的两个Z位置不能是N； 每个R2是独立的非干扰基； L是连接基； n为0或1； Ar′是循环脂肪族、循环杂脂族、芳香族或杂芳香族残基，可选地被1-3个非干扰基取代。
• Hyperglycosylated variants of interferon alfacon-1
  申请人：Alios Biopharma Inc.

  公开号：EP2093235A1

  公开（公告）日：2009-08-26

  The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or nonnative glycosylation sites, as well as erythropoietin and darbepoetin alfa, each of which are linked to a penetrating peptide that facilitates translocation of a substance across a biological barrier as well as pharmaceutical compositions, including oral formulations, of the same. The present invention further provides oral formulations of hyperglycosylated or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.

  本发明提供合成的I型干扰素受体多肽激动剂，包括共识或混合I型干扰素受体多肽激动剂，含有一个或多个原生或非原生糖基化位点。本发明提供合成的 I 型干扰素受体多肽激动剂，包括共识或混合 I 型干扰素受体多肽激动剂，含有一个或多个原生或非原生糖基化位点，以及促红细胞生成素和达贝胎素α，其中每一种都与促进物质通过生物屏障转运的穿透肽相连，以及药物组合物，包括其口服制剂。本发明进一步提供了高糖基化或抗蛋白酶的高糖基化多肽变体的口服制剂，这些多肽变体缺乏母体多肽中的至少一个蛋白酶裂解位点，因此与母体多肽相比表现出更强的抗蛋白酶能力、多肽变体进一步包括(1)与至少一个非原生糖基化位点共价连接的碳水化合物分子，该糖基化位点在母体蛋白治疗剂中未发现；或(2)与至少一个原生糖基化位点共价连接的碳水化合物分子，该糖基化位点在母体蛋白治疗剂中发现但未糖基化。本发明进一步提供了包含合成的 I 型干扰素受体多肽激动剂、高糖基化多肽变体或高糖基化、抗蛋白酶多肽变体的组合物，包括口服药物组合物。本发明进一步提供了包含合成 I 型干扰素受体多肽激动剂、高糖基化多肽变体或高糖基化、抗蛋白酶多肽变体的容器、装置和试剂盒。本发明进一步提供了治疗方法，包括向有需要的个体施用有效量的口服药物组合物，该组合物包含合成的I型干扰素受体多肽激动剂、高糖基化多肽变体或高糖基化、抗蛋白酶多肽变体。
• Treatment of fibroproliferative disorders using TGF-beta inhibitors
  申请人：——

  公开号：US20040038856A1

  公开（公告）日：2004-02-26

  The invention concerns methods of treating fibroproliferative disorders associated with TGF-&bgr; signaling, by administering non-peptide small molecule inhibitors of TGF-&bgr; specifically binding to the type I TGF-&bgr; receptor (TGF&bgr;-R1). Preferably, the inhibitors are quinazoline derivatives. The invention also concerns methods for reversing the effect of TGF-&bgr;-mediated cell activation on the expression of a gene associated with fibrosis, comprising contacting a cell or tissue in which the expression of such gene is altered as a result of TGF-&bgr;-mediated cell activation, with a non-peptide small molecule inhibitor of TGF-&bgr;, specifically binding a TGF&bgr;-R1 receptor kinase present in the cell or tissue.

  本发明涉及治疗与TGF-&bgr;信号传导相关的纤维增生性疾病的方法，方法是施用TGF-&bgr;的非肽小分子抑制剂，特别是与I型TGF-&bgr;受体（TGF&bgr;-R1）结合的抑制剂。抑制剂最好是喹唑啉衍生物。本发明还涉及逆转TGF-&bgr;介导的细胞活化对纤维化相关基因表达的影响的方法，该方法包括将因TGF-&bgr;介导的细胞活化而导致该基因表达改变的细胞或组织与特异性结合细胞或组织中存在的TGF&bgr;-R1受体激酶的TGF-&bgr;非肽小分子抑制剂接触。
• Method for counteracting a pathologic change in the beta-adrenergic pathway
  申请人：——

  公开号：US20040127575A1

  公开（公告）日：2004-07-01

  The invention concerns methods for modulating the &bgr;-adrenergic pathway. In particular, the invention concerns methods for counteracting a pathologic change, such as, for example, a loss in &bgr;-adrenergic sensitivity, in the &bgr;-adrenergic signal transduction pathway by administering an effective amount of a compound capable of inhibiting TGF-&bgr; signaling through a TGF-&bgr; receptor.

  本发明涉及调节&bgr;-肾上腺素能通路的方法。特别是，本发明涉及通过施用有效量的能够通过 TGF-&bgr; 受体抑制 TGF-&bgr; 信号转导的化合物来抵消&bgr;-肾上腺素能信号转导通路中的病理变化，例如，&bgr;-肾上腺素能敏感性丧失的方法。
• Use of TGF-beta inhibitors to counteract pathologic changes in the level or function of steroid/thyroid receptors
  申请人：——

  公开号：US20040138188A1

  公开（公告）日：2004-07-15

  The invention concerns the use of TGF-&bgr; inhibitors to counteract a pathologic change in the expression level, activity and/or signaling of a receptor of the steroid-thyroid hormone receptor superfamily. In particular, the invention concerns a method for counteracting a pathologic change in a signal-transduction pathway involving a member of the steroid/thyroid hormone super-family, comprising administering to a mammalian subject in need an effective amount of a compound capable of inhibiting TGF-&bgr; signaling through a TGF-&bgr; receptor.

  本发明涉及使用 TGF-&bgr; 抑制剂来对抗类固醇-甲状腺激素受体超家族受体的表达水平、活性和/或信号转导的病理变化。特别是，本发明涉及一种抵消涉及类固醇/甲状腺激素超家族成员的信号转导通路中的病理变化的方法，包括向有需要的哺乳动物施用有效量的化合物，该化合物能够抑制通过TGF-&bgr;受体的TGF-&bgr;信号转导。