N-(6-氨基-1,2,3,4-四氢-3-甲基-2,4-二氧代-嘧啶-5-基)-2,2,2-三氟-N-苄基-乙酰胺 | 140379-38-0

• 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: N-(6-氨基-1,2,3,4-四氢-3-甲基-2,4-二氧代-嘧啶-5-基)-2,2,2-三氟-N-苄基-乙酰胺
• 中文别名: 乙酰胺,N-(6-氨基-1,2,3,4-四氢-3-甲基-2,4-二羰基-5-嘧啶基)-2,2,2-三氟-N-(苯基甲基)-(9CI)
• 英文名称: 6-Amino-3-methyl-5-(N-(phenylmethyl)trifluoracetamido)-pyrimidine-2,4-dione
• 英文别名: N-(6-amino-3-methyl-2,4-dioxo-1H-pyrimidin-5-yl)-N-benzyl-2,2,2-trifluoroacetamide
• CAS: 140379-38-0
• 化学式: C₁₄H₁₃F₃N₄O₃
• 分子量: 342.277
• InChiKey: ORXWIDRGKWBMNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  95.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(6-氨基-1,2,3,4-四氢-3-甲基-2,4-二氧代-嘧啶-5-基)-2,2,2-三氟-N-苄基-乙酰胺 在 三氯氧磷 作用下， 反应 7.0h， 生成 2-Chloro-1-methyl-7-(phenylmethyl)-8-trifluoromethylpurin-6-one
  参考文献：
  名称：

  Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity

  摘要：

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

  DOI：

  10.1021/jm9608467
• 作为产物：
  描述：

  6-amino-5-(benzylamino)-3-methylpyrimidine-2,4(1H,3H)-dione 、 三氟乙酸 在 4-二甲氨基吡啶 、 N-ethyl-N’-(diethylaminopropyl)-carbodiimide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(6-氨基-1,2,3,4-四氢-3-甲基-2,4-二氧代-嘧啶-5-基)-2,2,2-三氟-N-苄基-乙酰胺
  参考文献：
  名称：

  Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity

  摘要：

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

  DOI：

  10.1021/jm9608467

文献信息

• Polycyclic guanine derivatives
  申请人：Schering Corporation

  公开号：US05393755A1

  公开（公告）日：1995-02-28

  Novel polycylic guanine derivatives of the formula: ##STR1## wherein J is oxygen or sulfur, R.sup.1 is hydrogen, alkyl or alkyl substituted with aryl or hydroxy; R.sup.2 is hydrogen, aryl, heteroaryl, cycloalkyl, alkyl or alkyl substituted with aryl, heteroaryl, hydroxy, alkoxy, amino, monoalkyl amino or dialkylamino, or --(CH.sub.2).sub.m TCOR.sup.20 wherein m is an integer from 1 to 6, T is oxygen or --NH-- and R.sup.20 is hydrogen, aryl, heteroaryl, alkyl or alkyl substituted with aryl or heteroaryl; R.sup.3 is hydrogen, halo, trifluoromethyl, alkoxy, alkylthio, alkyl, cycloalkyl, aryl, aminosulfonyl, amino, monoalkylamino, dialkylamino, hydroxyalkylamino, aminoalkylamino, carboxy, alkoxycarbonyl or aminocarbonyl or alkyl substituted with awl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino; R.sup.a, R.sup.b, R.sup.c, and R.sup.d are defined in the specification; and n is zero or one. The compounds of formulas (I) and (I') are useful as antihypertensive, muscle relaxant and bronchodilating agents.

  新颖的多环鸟嘌呤衍生物的化学式为：##STR1## 其中J为氧或硫，R.sup.1为氢，烷基或烷基取代芳基或羟基；R.sup.2为氢，芳基，杂环芳基，环烷基，烷基或烷基取代芳基，杂环芳基，羟基，烷氧基，氨基，单烷基氨基或二烷基氨基，或--(CH.sub.2).sub.m TCOR.sup.20，其中m为1到6的整数，T为氧或--NH--，R.sup.20为氢，芳基，杂环芳基，烷基或烷基取代芳基或杂环芳基；R.sup.3为氢，卤素，三氟甲基，烷氧基，硫烷基，烷基，环烷基，芳基，氨基磺酰基，氨基，单烷基氨基，二烷基氨基，羟基烷基氨基，氨基烷基氨基，羧基，烷氧羰基或氨基羰基或烷基取代芳基，羟基，烷氧基，氨基，单烷基氨基或二烷基氨基；R.sup.a，R.sup.b，R.sup.c和R.sup.d在规范中有定义；n为零或一。化合物的化学式(I)和(I')可用作降压、肌肉松弛和扩张支气管剂。
• POLYCYCLIC GUANINE DERIVATIVES
  申请人：SCHERING CORPORATION

  公开号：EP0538332B1

  公开（公告）日：1997-07-23
• US5393755A
  申请人：——

  公开号：US5393755A

  公开（公告）日：1995-02-28
• [EN] POLYCYCLIC GUANINE DERIVATIVES
  申请人：SCHERING CORPORATION

  公开号：WO1991019717A1

  公开（公告）日：1991-12-26

  (EN) Novel polycyclic guanine derivatives of formula (I) and (I'), wherein J is oxygen or sulfur, R1 is hydrogen, alkyl or alkyl substituted with aryl or hydroxy; R2 is hydrogen, aryl, heteroaryl, cycloalkyl, alkyl or alkyl substituted with aryl, heteroaryl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino, or -(CH2)mTCOR20 wherein m is an integer from 1 to 6, T is oxygen or -NH- and R20 is hydrogen, aryl, heteroaryl, alkyl or alkyl substituted with aryl or heteroaryl; R3 is hydrogen, halo, trifluoromethyl, alkoxy, alkylthio, alkyl, cycloalkyl, aryl, aminosulfonyl, amino, monoalkylamino, dialkylamino, hydroxyalkylamino, aminoalkylamino, carboxy, alkoxycarbonyl or aminocarbonyl or alkyl substituted with aryl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino; Ra, Rb, Rc and Rd independently represent hydrogen, alkyl, cycloalkyl or aryl; or (Ra and Rb) or (Rc and Rd) or (Rb and Rc) can complete a saturated ring of 5- to 7- carbon atoms, or (Ra and Rb) taken together and (Rb and Rc) taken together, each complete a saturated ring of 5- to 7- carbon atoms, wherein each ring optionally can contain a sulfur or oxygen atom and whose carbon atoms may be optionally substituted with one or more of the following: alkenyl, alkynyl, hydroxy, carboxy, alkoxycarbonyl, alkyl or alkyl substituted with hydroxy, carboxy or alkoxycarbonyl; or such saturated ring can have two adjacent carbon atoms which are shared with an adjoining aryl ring; and n is zero or one. The compounds of formulas (I) and (I') are useful as antihypertensive, muscle relaxant and bronchodilating agents.(FR) Nouveaux dérivés polycycliques de guanine ayant les formules (I et I'), dans lesquelles J représente oxygène ou soufre, R1 représente hydrogène, alkyle ou alkyle remplacé par de l'aryle ou hydroxy; R2 représente hydrogène, aryle, hétéroaryle, cycloalkyle, alkyle ou alkyle remplacé par de l'aryle, hétéroaryle, hydroxy, alcoxy, amino, monoalkylamino ou dialkylamino, ou -(CH2)mTCOR20 où m représente un nombre entier compris entre 1 et 6, T représente oxygène ou -NH- et R20 représente hydrogène, aryle, hétéroaryle, alkyle ou alkyle remplacé par de l'aryle ou hétéroaryle; R3 représente hydrogène, halo, trifluorométhyle, alcoxy, alkylthio, alkyle, cycloalkyle, aryle, aminosulfonyle, amino, monoalkylamino, dialkylamino, hydroxyalkylamino, aminoalkylamino, carboxy, alcoxycarbonyle ou aminocarbonyle ou alkyle remplacé par de l'aryle, hydroxy, alcoxy, amino, monoalkylamino, ou dialkylamino; Ra, Rb, Rc et Rd représentent indépendamment hydrogène, alkyle, cycloalkyle ou alkyle; ou (Ra et Rb) ou (Rc et Rd) ou (Rb et R6) peuvent compléter un anneau saturé de 5 à 7 atomes de carbone, ou (Ra et Rb) pris ensemble et (Rb et Rc) pris ensemble complètent chacun un anneau saturé de 5 à 7 atomes de carbone, dans lesquels chaque atome peut facultativement contenir un atome de soufre ou d'oxygène et dont les atomes de carbone peuvent être facultativement remplacés par un ou plusieurs des éléments suivants: alcényle, alkynyle, hydroxy, carboxy, alcoxycarbonyle, alkyle ou alkyle remplacé par hydroxy, carboxy ou alcoxycarbonyle; ou ledit anneau saturé peut comporter deux atomes de carbone adjacent partagés avec un anneau aryle adjacent; et n représente 0 ou 1. Les composés des formules (I) et (I') sont utiles en tant qu'agents antihypertensifs, relaxant musculaire et bronchodilatateurs.
• Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity
  作者：Ho-Sam Ahn、Ana Bercovici、George Boykow、Alan Bronnenkant、Samuel Chackalamannil、Jason Chow、Renee Cleven、John Cook、Michael Czarniecki、Carol Domalski、Ahmad Fawzi、Michael Green、Asli Gündes、Ginny Ho、Malvina Laudicina、Neil Lindo、Ke Ma、Mahua Manna、Brian McKittrick、Bita Mirzai、Terry Nechuta、Bernard Neustadt、Chester Puchalski、Kathryn Pula、Lisa Silverman、Elizabeth Smith、Andrew Stamford、Richard P. Tedesco、Hsingan Tsai、Deen Tulshian、Henry Vaccaro、Robert W. Watkins、Xiaoyu Weng、Joseph T. Witkowski、Yan Xia、Hongtao Zhang

  DOI：10.1021/jm9608467

  日期：1997.7.1

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).