4,6-二氨基喹唑啉 | 159382-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4,6-二氨基喹唑啉
• 英文名称: quinazoline-4,6-diamine
• 英文别名: 4,6-diaminoquinazoline；quinazoline-4,6-diyldiamine；Chinazolin-4,6-diyldiamin；4,6-quinazolinediamine
• CAS: 159382-23-7
• 化学式: C₈H₈N₄
• 分子量: 160.178
• InChiKey: RNWDENXDCQXZLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.79
• 重原子数：
  12.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.82
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4,6-二氨基喹唑啉 在 Raney 30 氢气 、 溶剂黄146 、 三氟乙酸 作用下， 反应 2.0h， 生成 2-desamino-5,8-dideazaisoaminopterin
  参考文献：
  名称：

  Studies on the antitumor effects of analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin

  摘要：

  Six new analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin were synthesized in an effort to obtain enhanced antitumor activity. The modifications included the replacement of the 2-amino group by hydrogen or methyl as well as the inclusion of a methyl substituent at position 9. Based upon activity against L1210 leukemia cells in culture, three of the new analogues together with one compound described previously were evaluated for cytotoxicity in vitro using three human tumor cell lines (Cole 320 DM, Hep G2 and HL-60). The most effective compound was 2-desamino-N-9-methyl-5,8-dideazaisoaminopterin (2c) with the HL-60 cells being the most sensitive to its cytotoxic effects. These analogues were evaluated in vitro as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) from human as well as bacterial (Lactobacillus casei) sources. All four of the 4-amino analogues were most effective toward L. casei DHFR compared with human DHFR, with 2-desamino-2-methyl-5,8-dideazaisoaminopterin (2d) and its 9-methyl derivative (2e) having 818- and 430-fold greater selectivity (L. caseilhuman). Most of the compounds studied were found to be only modest inhibitors of human TS (I-50 values = 1.5 to 20 mu M) and were therefore at least 40-fold less inhibitory than 10-propargyl-5,8-dideazafolic acid. Nevertheless, reversal of cytotoxicity studies with thymidine, hypoxanthine and folinic acid using the HL-60 cell line suggested that TS is the primary target for these analogues.

  DOI：

  10.1016/0006-2952(95)00203-c
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 tin(II) chloride dihdyrate 作用下， 以 甲醇 为溶剂， 反应 13.0h， 生成 4,6-二氨基喹唑啉
  参考文献：
  名称：

  Design and Synthesis of Novel Quinazoline Derivatives and Their Evaluation as PI3Ks Inhibitors

  摘要：

  本研究的目的是合成4-乙酰氨基、4-氨基和4-氧代-6-取代氨基喹唑啉，并评估它们作为磷脂酰肌醇3-激酶（PI3Ks）抑制剂的潜力。相应的化学类型是基于结合两种先前报道的作为强效PI3Kγ抑制剂的结构特征设计的，这两种结构分别是喹唑啉衍生物和氨基杂环衍生物。在10 µM浓度下进行的体外酶活性测定表明，在6位位置上未取代的苯酰胺基团和N4位置上的乙酰基组合在PI3Kγ上表现出最佳的抑制活性。有趣的是，化合物5a和5e对II类PI3K-C2γ表现出显著的抑制作用。这一点非常重要，因为文献中报道的针对该同种型的抑制剂极少。

  DOI：

  10.1248/cpb.c14-00560

文献信息

• NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION, AND APPLICATION
  申请人：SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

  公开号：US20200190091A1

  公开（公告）日：2020-06-18

  A nitrogenous heterocyclic compound, a preparation method, an intermediate, a composition, and an application. The present invention provides a nitrogenous heterocyclic compound as represented by formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, diastereoisomers thereof, tautomers thereof, solvates thereof, metabolites thereof, or prodrugs thereof. The compound has high inhibitory activity against ErbB2 tyrosine kinase, has good inhibitory activity against human breast cancer cells BT-474, human gastric cancer cells NCI-N87 and the like with high expression of ErbB2, and in addition has relatively weak inhibitory activity against EGFR kinase, that is, the compound is an EGFR/ErbB2 double target inhibitor that attenuates EGFR kinase inhibitory activity or a small-molecule inhibitor having selectivity for an ErbB2 target. (I)

  一种含氮杂环化合物，一种制备方法，一种中间体，一种组合物和一种应用。本发明提供一种由式I表示的含氮杂环化合物，其药学上可接受的盐，其对映体，其非对映异构体，其互变异构体，其溶剂合物，其代谢物或其前药。该化合物对ErbB2酪氨酸激酶具有高抑制活性，对表达ErbB2高的人类乳腺癌细胞BT-474，人类胃癌细胞NCI-N87等具有良好的抑制活性，并且对EGFR激酶具有相对较弱的抑制活性，即该化合物是一种减弱EGFR激酶抑制活性的EGFR/ErbB2双靶点抑制剂或具有选择性作用于ErbB2靶点的小分子抑制剂。 (I)
• Thrombin inhibitors
  申请人：——

  公开号：US20030191139A1

  公开（公告）日：2003-10-09

  The invention relates to compounds of formula I D—CO—B—A-Het and pharmaceutically acceptable salts thereof where substituents in description have the specified meanings. The compounds are used as thrombin inhibitors.

  该发明涉及公式I的化合物D—CO—B—A-Het及其药用可接受的盐，其中描述中的取代基具有指定的含义。这些化合物被用作凝血酶抑制剂。
• [EN] ALKYNE QUINAZOLINE DERIVATIVES AS INHIBITORS OF ERBB2<br/>[FR] DÉRIVÉS DE QUINAZOLINE ALCYNE SERVANT D'INHIBITEURS D'ERBB2
  申请人：ENLIVEN THERAPEUTICS INC

  公开号：WO2022006386A1

  公开（公告）日：2022-01-06

  The present disclosure relates generally to compounds and compositions thereof for inhibition of ErbB2, including mutant forms of ErbB2, particularly those harboring an Exon 20 mutation, methods of preparing said compounds and compositions, and their use in the treatment or prophylaxis of various cancers, such as lung, glioma, skin, head neck, salivary gland, breast, esophageal, liver, stomach (gastric), uterine, cervical, biliary tract, pancreatic, colorectal, renal, bladder or prostate cancer.

  本公开涉及一般用于抑制ErbB2的化合物及其组合物，包括ErbB2的突变形式，特别是那些携带Exon 20突变的形式，制备这些化合物和组合物的方法，以及它们在治疗或预防各种癌症中的应用，如肺癌、胶质瘤、皮肤癌、头颈癌、唾液腺癌、乳腺癌、食道癌、肝癌、胃癌、子宫癌、宫颈癌、胆道癌、胰腺癌、结直肠癌、肾癌、膀胱癌或前列腺癌。
• [EN] QUINAZOLINE ANALOGS AS RECEPTOR TYROSINE KINASE INHIBITORS<br/>[FR] ANALOGUES DE QUINAZOLINE COMME INHIBITEURS DU RECEPTEUR DE LA TYROSINE KINASE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2005016346A1

  公开（公告）日：2005-02-24

  This invention provides quinazoline analogs of Formula (I): where A is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to two independent R3 groups. The invention also includes methods of using compounds of Formula (I) as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

  本发明提供了公式（I）的喹唑啉类似物，其中A与双环环上的5、6、7或8位置中的至少一个碳原子连接，并且该环被最多两个独立的R3基团取代。本发明还包括使用公式（I）化合物作为I型受体酪氨酸激酶抑制剂和治疗癌症等增生性疾病的方法。
• QUINAZOLINE DERIVATIVES SUBSTITUTED BY ANILINE, PREPARATION METHOD AND USE THEREOF
  申请人：Huang Zhenhua

  公开号：US20130184297A1

  公开（公告）日：2013-07-18

  The invention relates to quinazoline derivatives substituted by aniline which are represented by the below formula (I), pharmaceutical acceptable salts and stereoisomer thereof, wherein these groups of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , L and n have the meanings given in the specification. The invention also relates to preparation methods, pharmaceutical compositions, pharmaceutical preparation and the use for preparation of medicine of treating excessive hyperplasia and chronic obstructive pulmonary disease and uses for treating excessive hyperplasia and chronic obstructive pulmonary disease thereof.

  本发明涉及由苯胺取代的喹嗪衍生物，其由下式（I）表示，其药学可接受的盐和立体异构体，其中这些R1、R2、R3、R4、R5、R6、L和n的基团具有规范中给出的含义。本发明还涉及制备方法、制药组合物、制药制剂以及用于治疗过度增生和慢性阻塞性肺疾病的药物制备的用途，以及用于治疗过度增生和慢性阻塞性肺疾病的用途。