4,5-二氨基-3-异丁基-1-甲基嘧啶-2,6-二酮 | 78033-18-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4,5-二氨基-3-异丁基-1-甲基嘧啶-2,6-二酮
• 英文名称: 1-isobutyl-3-methyl-5,6-diamino uracil
• 英文别名: 3-methyl-1-isobutyl-5,6-diaminouracil；5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione；5,6-diamino-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine；4,5-Diamino-3-isobutyl-1-methylpyrimidine-2,6-dione；5,6-diamino-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione
• CAS: 78033-18-8
• 化学式: C₉H₁₆N₄O₂
• 分子量: 212.252
• InChiKey: VULNACCPMCVPGE-UHFFFAOYSA-N

物化性质

• 熔点：
  180-183°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,5-二氨基-3-异丁基-1-甲基嘧啶-2,6-二酮 在 sodium hydroxide 、 二苯甲基哌嗪 、 氢溴酸 作用下， 以 甲醇 、 水 为溶剂， 反应 66.0h， 生成 8-[2-(4-二苯甲基哌嗪-1-基)乙基]-1-甲基-3-(2-甲基丙基)-7H-嘌呤-2,6-二酮
  参考文献：
  名称：

  New xanthine derivatives with potent and long lasting anti-bronchoconstrictive activity

  摘要：

  DOI：

  10.1016/0223-5234(87)90056-0
• 作为产物：
  描述：

  6-氨基-1-异丁基-3-甲基-5-亚硝基尿嘧啶 在 ammonium hydroxide 、 sodium dithionite 作用下， 生成 4,5-二氨基-3-异丁基-1-甲基嘧啶-2,6-二酮
  参考文献：
  名称：

  Structure-activity relationships in a series of xanthine derivatives with antibronchoconstrictory and bronchodilatory activities

  摘要：

  DOI：

  10.1016/0223-5234(90)90130-u

文献信息

• Adenosine A1 antagonists. 2. Structure-activity relationships on diuretic activities and protective effects against acute renal failure
  作者：Fumio Suzuki、Junichi Shimada、Hideaki Mizumoto、Akira Karasawa、Kazuhiro Kubo、Hiromi Nonaka、Akio Ishii、Takashi Kawakita

  DOI：10.1021/jm00094a022

  日期：1992.8

  Diuretic activities of xanthine or nonxanthine adenosine antagonists and their ameliorative effects against glycerol-induced acute renal failure in rats were investigated in order to clarify the physiological and pathological function of adenosine receptors in the kidney. Diuretic and natriuretic activities of a variety of adenosine antagonists clarified systematically for the first time that the blockade

  为了阐明肾脏中腺苷受体的生理和病理功能，研究了黄嘌呤或非黄嘌呤腺苷拮抗剂的利尿作用及其对甘油诱导的急性肾衰竭的缓解作用。各种腺苷拮抗剂的利尿和利尿作用首次系统性地阐明，在钠和水的排泄中，A1受体的阻滞比A2受体的阻滞更重要，并支持内源性肾内腺苷水平直接增强肾小管钠吸收的假说。 。急性肾衰竭中8取代的黄嘌呤的构效关系研究表明，腺苷A1受体的激活是发展这种肾衰竭的重要因素。一系列8-（3-去甲金刚烷基）黄嘌呤表现出极强的利尿和利尿活性（24; 2.5微克/千克，po，治疗大鼠尿排泄值与对照大鼠尿排泄值之比= 1.69，该比率（治疗大鼠的Na + / K +相对于对照组大鼠的Na + / K + ＝ 1.76）和抗甘油诱导的急性肾衰竭的有效改善作用（24; 10微克/ kg，腹腔注射，抑制55％）。通过对结构-活性关系的详细研究，我们可以推测，肾脏和大脑之间可能存在腺苷A1受体的一些组织差异，并
• Potent and selective xanthine-based inhibitors of phosphodiesterase 5
  作者：Nichola J. Arnold、Ruth Arnold、David Beer、Gurdip Bhalay、Stephen P. Collingwood、Sarah Craig、Nicholas Devereux、Mark Dodds、Andrew R. Dunstan、Robin A. Fairhurst、David Farr、Joseph D. Fullerton、Angela Glen、Sylvie Gomez、Sandra Haberthuer、Julia D.I. Hatto、Colin Howes、Darryl Jones、Thomas H. Keller、Beate Leuenberger、Heinz E. Moser、Irene Muller、Reto Naef、Paul A. Nicklin、David A. Sandham、Katharine L. Turner、Morris F. Tweed、Simon J. Watson、Mauro Zurini

  DOI：10.1016/j.bmcl.2006.11.019

  日期：2007.4

  Inhibitors of PDE5 are useful therapeutic agents for treatment of erectile dysfunction. A series of novel xanthine derivatives has been identified as potent inhibitors of PDE5, with good levels of selectivity against other PDE isoforms, including PDE6. Studies in the dog indicate excellent oral bioavailability for compound 21.

  PDE5抑制剂是治疗勃起功能障碍的有用治疗剂。已鉴定出一系列新的黄嘌呤衍生物作为PDE5的有效抑制剂，对其他PDE异构体（包括PDE6）具有良好的选择性。在狗中进行的研究表明，化合物21具有出色的口服生物利用度。
• 8-Quinolinxanthine and 8-isoquinolinxanthine derivatives as pde 5 inhibitors
  申请人：——

  公开号：US20030171384A1

  公开（公告）日：2003-09-11

  A compound of formula (I) in free or salt form, where R 1 is hydrogen or alkyl optionally substituted by hydroxy, alkoxy, or alkylthio, R 2 is hydrogen, alkyl, hydroxyalkyl, alkylcarbonyloxyalkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, cycloalkylalkyl, heterocyclylalkyl, aralkyl in which the aryl ring thereof is optionally fused to a 5-membered heterocyclic group or is optionally substituted by one or more substituents selected from alkoxy, amino, alkylamino, dialkylamino, acylamino, halogen, hydroxy, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonylamino or dialkylaminosulfonylamino, R 3 is hydrogen or alkyl optionally substituted by hydroxy, alkoxy, or alkylthio, R 4 is hydrogen or alkyl, R 5 is a quinolinyl, isoquinolinyl or oxodihydroisoquinolinyl group optionally fused to a 5-membered heterocyclic group and optionally substituted by one or more substituents selected from halogen, cyano, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkoxy, alkylthio, alkenyl, alkoxycarbonyl, alkynyl, carboxyl, acyl, a group of formula —N(R 6 )R 7 , aryl optionally substituted by one or more substituents selected from halogen or alkoxy, or heteroaryl having 5 or 6 ring atoms attached through a ring carbon atom to the indicated carbon atom, and R 6 and R 7 are each independently hydrogen or alkyl optionally substituted by hydroxy or alkoxy or one of R 6 and R 7 is hydrogen and the other is acyl, or R 6 and R 7 together with the nitrogen atom to which they are attached denote a 5- or 6-membered heterocyclyl group.

  化合物的结构式(I)在自由或盐形式下，其中R1为氢或烷基，可以选择地被羟基、烷氧基或烷硫基取代，R2为氢、烷基、羟基烷基、烷基羰基氧基烷基、烷氧基烷基、烷硫基烷基、烯基、环烷基烷基、杂环烷基烷基、芳基烷基，其中芳环可以选择地与一个5-成员杂环基团融合，或可以选择地被烷氧基、氨基、烷基氨基、二烷基氨基、酰胺基、卤素、羟基、氨基磺酰基、烷基氨基磺酰基、二烷基氨基磺酰基、烷基磺酰氨基或二烷基氨基磺酰氨基等一个或多个取代基取代，R3为氢或烷基，可以选择地被羟基、烷氧基或烷硫基取代，R4为氢或烷基，R5为喹啉基、异喹啉基或氧代二氢异喹啉基，可以选择地与一个5-成员杂环基团融合，并可以选择地被卤素、氰基、羟基、烷基、羟基烷基、烷氧基烷基、烷硫基烷基、烷氧基、烷硫基、烯基、烷氧羰基、炔基、羧基、酰基、一个结构式为—N(R6)R7的基团、可以选择地被卤素或烷氧基等一个或多个取代基取代的芳基，或者通过一个环碳原子连接到所指示的碳原子的5个或6个环原子的杂芳基，R6和R7分别独立地为氢或烷基，可以选择地被羟基或烷氧基取代，或者R6和R7中的一个为氢，另一个为酰基，或者R6和R7与它们连接的氮原子一起表示一个5-或6-成员杂环基团。
• Combinations
  申请人：——

  公开号：US20030114469A1

  公开（公告）日：2003-06-19

  The present invention relates to a pharmaceutical composition, comprising (a) a phosphodiesterase 5 inhibitor or a pharmaceutically acceptable salt thereof and (b) at least one of the active ingredients selected from the group consisting of (i) an anti-diabetic agent; (ii) HMG-Co-A reductase inhibitors; (iii) an anti-hypertensive agent; and (iv) a serotonin reuptake inhibitor (SSRI) or, in each case, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. The pharmaceutical composition may be employed for the treatment of sexual dysfunction, hyperglycemia, hyperinsulinaemia, hyperlipidaemia, hypertriglyceridemia, diabetes, insulin resistance, impaired glucose metabolism, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, obesity, diabetic retinopathy, diabetic nephropathy, glomerulosclerosis, diabetic neuropathy, syndrome X, erectile dysfunction, coronary heart disease, hypertension, especially ISH, angina pectoris, myocardial infarction, stroke, vascular restenosis, endothelial dysfunction, impaired vascular compliance, congestive heart failure.

  本发明涉及一种药物组合物，包括(a) 磷酸二酯酶5抑制剂或其药用盐，以及(b) 来自以下组中选择的至少一种活性成分(i) 抗糖尿病药物；(ii) HMG-Co-A还原酶抑制剂；(iii) 抗高血压药物；和(iv) 血清素再摄取抑制剂（SSRI）或在每种情况下，其药用盐；以及药学上可接受的载体。该药物组合物可用于治疗性功能障碍、高血糖、高胰岛素血症、高脂血症、高甘油三酯血症、糖尿病、胰岛素抵抗、糖代谢受损、糖耐量受损（IGT）病状、空腹血糖受损病状、肥胖、糖尿病视网膜病、糖尿病肾病、肾小球硬化、糖尿病神经病变、X综合征、勃起功能障碍、冠心病、高血压，尤其是高收缩压高血压（ISH），心绞痛、心肌梗死、中风、血管再狭窄、内皮功能障碍、血管顺应性受损、充血性心力衰竭。
• 8-Quinolinxanthine and 8-isoquinolinxanthine derivatives as PDE 5 inhibitors
  申请人：Bhalay Gurdip

  公开号：US20060106214A1

  公开（公告）日：2006-05-18

  A compound of formula (I) R 1 is hydrogen or alkyl optionally substituted by hydroxy, alkoxy, or alkylthio, R 2 is hydrogen, alkyl, hydroxyalkyl, alkylcarbonyloxyalkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, cycloalkylalkyl, heterocyclylalkyl, aralkyl in which the aryl ring thereof is optionally fused to a 5-membered heterocyclic group or is optionally substituted by one or more substituents selected from alkoxy, amino, alkylamino, dialkylamino, acylamino, halogen, hydroxy, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsufonylamino or dialkylaminosulfonylamino, R 3 is hydrogen or alkyl optionally substituted by hydroxy, alkoxy, or alkylthio, R 4 is hydrogen or alkyl, R 5 is a quinolinyl, isoquinolinyl or oxodihydroisoquinolinyl group optionally fused to a 5-membered heterocyclic group and optionally substituted by one or more substituents selected from halogen, cyano, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkoxy, alkylthio, alkenyl, alkoxycarbonyl, alkynyl, carboxyl, acyl, a group of formula —N(R 6 )R 7 , aryl optionally substituted by one or more substituents selected from halogen or alkoxy, or heteroaryl having 5 or 6 ring atoms attached through a ring carbon atom to the indicated carbon atom, and R 6 and R 7 are each independently hydrogen or alkyl optionally substituted by hydroxy or alkoxy or one of R 6 and R 7 is hydrogen and the other is acyl, or R 6 and R 7 together with the nitrogen atom to which they are attached denote a 5- or 6- membered heterocyclyl group.

  化合物的式子（I）中，R1是氢或烷基，可以选择性地被羟基、烷氧基或烷基硫代取代，R2是氢、烷基、羟基烷基、烷基羧酸酯基、烷氧基烷基、烷基硫代烷基、烯基、环烷基烷基、杂环烷基烷基、芳基烷基，其中芳环可以选择性地与5元杂环基融合或可以选择性地被一种或多种取代基所取代，这些取代基包括烷氧基、氨基、烷基氨基、二烷基氨基、酰胺基、卤素、羟基、氨基磺酰基、烷基氨基磺酰基、二烷基氨基磺酰基、烷基磺酰氨基或二烷基氨基磺酰氨基，R3是氢或烷基，可以选择性地被羟基、烷氧基或烷基硫代取代，R4是氢或烷基，R5是喹啉基、异喹啉基或氧代二氢异喹啉基，可以选择性地与5元杂环基融合并可以选择性地被一种或多种取代基所取代，这些取代基包括卤素、氰基、羟基、烷基、羟基烷基、烷氧基烷基、烷基硫代烷基、烷氧基、烷基硫代基、烯基、烷氧羰基、炔基、羧基、酰基、式子-N（R6）R7的基团、芳基，其中芳基可以选择性地被一种或多种取代基所取代，这些取代基包括卤素或烷氧基，或者是通过一个环碳原子与所指定的碳原子相连的含有5个或6个环原子的杂环芳基，R6和R7各自独立地是氢或烷基，可以选择性地被羟基或烷氧基取代，或者R6和R7中的一个是氢，另一个是酰基，或者R6和R7连同它们所附着的氮原子一起表示一个含有5个或6个环原子的杂环基团。