4-(2-吗啉-4-基-7H-嘌呤-6-基)吗啉 | 7494-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 4-(2-吗啉-4-基-7H-嘌呤-6-基)吗啉
• 英文名称: 4,4'-(9H-purine-2,6-diyl)dimorpholine
• 英文别名: 2,6-di-morpholin-4-yl-7(9)H-purine；4-(2-morpholin-4-yl-7H-purin-6-yl)morpholine
• CAS: 7494-71-5
• 化学式: C₁₃H₁₈N₆O₂
• 分子量: 290.325
• InChiKey: QOMAEQWURQWFMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  79.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(2-吗啉-4-基-7H-嘌呤-6-基)吗啉 、 2,3-二氟苯甲醇 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.0h， 以86%的产率得到4-[9-[(2,3-Difluorophenyl)methyl]-2-morpholin-4-ylpurin-6-yl]morpholine
  参考文献：
  名称：

  Solution-phase synthesis of 2,6,9-trisubstituted purines

  摘要：

  A simple three-step method for the solution-phase combinatorial synthesis of 2,6,9-trisubstituted purines from 2,6-dichloropurine is described. The synthesis exploits the use of resin capture to remove excess reagent used in the final step. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00098-7
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 4-(2-吗啉-4-基-7H-嘌呤-6-基)吗啉
  参考文献：
  名称：

  Solution-phase synthesis of 2,6,9-trisubstituted purines

  摘要：

  A simple three-step method for the solution-phase combinatorial synthesis of 2,6,9-trisubstituted purines from 2,6-dichloropurine is described. The synthesis exploits the use of resin capture to remove excess reagent used in the final step. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00098-7

文献信息

• Heterocyclic Compounds For Preventing And Treating Disorders Associated With Excessive Bone Loss
  申请人：Ono Mitsunori

  公开号：US20080058297A1

  公开（公告）日：2008-03-06

  This invention relates to pyrimidine compounds of formula (I), formula (I′), and formula (I″): and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , U, V, W, X, Y, Z, and n are defined herein. This invention also relates to compositions comprising these compounds and methods for using them. The compounds and compositions of this invention are useful to treat or prevent disorders associated with excessive bone loss, including, without limitation periodontal disease, non-malignant bone disorders (such as osteoporosis, Pagers-disease of bone, osteogenesis imperfecta, fibrous dysplasia, and primary hyperparathyroidism) estrogen deficiency, inflammatory bone loss, bone malignancy, arthritis, osteopetrosis, and certain cancer-related disorders (such as hypercalcemia of malignancy (HCM), osteolytic bone lesions of multiple myeloma and osteolytic bone metastases of breast cancer and other metastatic cancers).

  本发明涉及式(I)、式(I′)和式(I″)的嘧啶化合物，以及其药学上可接受的盐、溶剂合物、包合物和前药，其中R1、R2、R3、R4、R5、U、V、W、X、Y、Z和n在此处有定义。本发明还涉及包含这些化合物的组合物和使用它们的方法。本发明的化合物和组合物可用于治疗或预防与骨量过度流失相关的疾病，包括但不限于牙周病、非恶性骨疾病（如骨质疏松症、帕格氏骨病、遗传性骨发育不全、纤维性骨发育不良和原发性甲状旁腺功能亢进症）、雌激素缺乏、炎症性骨流失、骨恶性肿瘤、关节炎、骨质增生症以及某些与癌症相关的疾病（如恶性高钙血症、多发性骨髓瘤的溶骨性骨病变和乳腺癌及其他转移癌的溶骨性骨转移）。
• Novel compounds
  申请人：——

  公开号：US20040198725A1

  公开（公告）日：2004-10-07

  This invention features a compound of formula (I): 1 R 1 is aryl or heteroaryl; each of R 2 and R 4 , independently, is H, halogen, CN, alkyl, OR a , or NR a R b ; R 3 is H, halogen, CN, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR a , OC(O)R a , OC(O)NR a R b , NR a R b , NR a C(O)R b , NR a S(O)R b , NR a S(O) 2 R b , NR a C(O)NR b R c , NR a C(S)NR b R c , NR a C(NR b )NR c R d , NR a C(O)OR b , S(O)NR a R b , S(O) 2 NR a R b , S(O)R a , S(O) 2 R a , C(O)R a , C(O)OR a , or C(O)NR a R b ; R 5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; A is 0, S, S(O), S(O) 2 , or NR e ; B is N or CR f ; X is O, S, S(O), S(O) 2 , NR c , or C(O); Y is a covalent bond, C(O), C═NR a O, S, S(O), S(O) 2 , or NR e ; Z is N or CH; each of U and V, independently, is N or CR; and W is O, S, or NR e ; in which each of R a , R b , R c , and R d , independently, is H, alkyl, aryl, heteroaryl, cyclyl, or heterocyclyl; R e is H, alkyl, aryl, acyl, or sufonyl; and R f is H, alkyl, aryl, acyl, sulfonyl, alkoxyl, amino, ester, amide, CN, or halogen. The compound is useful for treating an interleukin-12 overproduction-related disorder.

  这项发明涉及一种化合物，其化学式为（I）：1R1是芳基或杂环芳基；R2和R4中的每一个独立地是H、卤素、CN、烷基、ORa或NRaRb；R3是H、卤素、CN、烷基、烯基、炔基、芳基、杂环芳基、环烷基、杂环烷基、ORa、OC（O）Ra、OC（O）NRaRb、NRaRb、NRaC（O）Rb、NRaS（O）Rb、NRaS（O）2Rb、NRaC（O）NRbRc、NRaC（S)NRbRc、NRaC（NRb)NRcRd、NRaC（O）ORb、S（O）NRaRb、S（O）2NRaRb、S（O）Ra、S（O）2Ra、C（O）Ra、C（O）ORa或C（O）NRaRb；R5是H或烷基；n为0、1、2、3、4、5或6；A为0、S、S（O）、S（O）2或NRe；B为N或CRf；X为O、S、S（O）、S（O）2、NRc或C（O）；Y为共价键、C（O）、C═NRaO、S、S（O）、S（O）2或NRe；Z为N或CH；U和V中的每一个独立地是N或CR；W为O、S或NRe；其中Ra、Rb、Rc和Rd中的每一个独立地是H、烷基、芳基、杂环芳基、环烷基或杂环烷基；Re为H、烷基、芳基、酰基或磺酰基；Rf为H、烷基、芳基、酰基、磺酰基、烷氧基、氨基、酯、酰胺、CN或卤素。该化合物可用于治疗与白细胞介素-12过度产生相关的疾病。
• [EN] HETEROCYCLIC COMPOUNDS FOR PREVENTING AND TREATING DISORDERS ASSOCIATED WITH EXCESSIVE BONE LOSS<br/>[FR] COMPOSES HETEROCYCLIQUES PERMETTANT DE PREVENIR ET DE TRAITER DES TROUBLES ASSOCIES A UNE PERTE OSSEUSE EXCESSIVE
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2005000404A2

  公开（公告）日：2005-01-06

  This invention relates to pyrimidine compounds of formula (I), formula (I')’ and formula (I’’): formula (I) and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R1, R2, R3, R4, R5, U, V, W, X, Y, Z, and n are defined herein. This invention also relates to compositions comprising these compounds and methods for using them. The compounds and compositions of this invention are useful to treat or prevent disorders associated with excessive bone loss, including, without limitation periodontal disease, non-malignant bone disorders (such as osteoporosis, Paget's disease of bone, osteogenesis imperfecta, fibrous dysplasia, and primary hyperparathyroidism) estrogen deficiency, inflammatory bone loss, bone malignancy, arthritis, osteopetrosis, and certain cancer-related disorders (such as hypercalcernia of malignancy (HCM), osteolytic bone lesions of multiple myeloma and osteolytic bone metastases of breast cancer and other metastatic cancers).

  本发明涉及式(I)、式(I')和式(I'')的嘧啶化合物，以及其药学上可接受的盐、溶剂化合物、包合物和前药，其中R1、R2、R3、R4、R5、U、V、W、X、Y、Z和n在此定义。本发明还涉及包含这些化合物的组合物和使用它们的方法。本发明的化合物和组合物对于治疗或预防与骨质过度流失相关的疾病有用，包括但不限于牙周疾病、非恶性骨疾病（如骨质疏松症、骨的帕吉特病、不完全性骨发育不良、纤维性骨发育不良和原发性甲状旁腺功能亢进症）、雌激素缺乏、炎症性骨质流失、骨恶性肿瘤、关节炎、骨质硬化和某些与癌症相关的疾病（如恶性高钙血症、多发性骨髓瘤的溶骨性骨病变和乳腺癌和其他转移性癌症的溶骨性骨转移）。
• Heterocyclic compounds
  申请人：Synta Pharmaceuticals Corp.

  公开号：US07122665B2

  公开（公告）日：2006-10-17

  This invention features a compound of formula (I): R1 is aryl or heteroaryl; each of R2 and R4, independently, is H, halogen, CN, alkyl, ORa, or NRaRb; R3 is H, halogen, CN, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, ORa, OC(O)Ra, OC(O)NRaRb, NRaRb, NRaC(O)Rb, NRaS(O)Rb, NRaS(O)2Rb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(NRb)NRcRd, NRaC(O)ORb, S(O)NRaRb, S(O)2NRaRb, S(O)Ra, S(O)2Ra, C(O)Ra, C(O)ORa, or C(O)NRaRb; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; A is O, S, S(O), S(O)2, or NRe; B is N or CRf; X is O, S, S(O), S(O)2, NRe, or C(O); Y is a covalent bond, C(O), C═NRa, O, S, S(O), S(O)2, or NRe; Z is N or CH; each of U and V, independently, is N or CR; and W is O, S, or NRe; in which each of Ra, Rb, Rc, and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, or heterocyclyl; Re is H, alkyl, aryl, acyl, or sufonyl; and Rf is H, alkyl, aryl, acyl, sulfonyl, alkoxyl, amino, ester, amide, CN, or halogen. The compound is useful for treating an interleukin-12 overproduction-related disorder.

  本发明涉及一种化合物，其化学式为(I)：其中，R1为芳基或杂环芳基；R2和R4分别独立地为H、卤素、CN、烷基、ORa或NRaRb；R3为H、卤素、CN、烷基、烯基、炔基、芳基、杂环芳基、环烷基、杂环烷基、ORa、OC（O）Ra、OC（O）NRaRb、NRaRb、NRaC（O）Rb、NRaS（O）Rb、NRaS（O）2Rb、NRaC（O）NRbRc、NRaC（S）NRbRc、NRaC（NRb）NRcRd、NRaC（O）ORb、S（O）NRaRb、S（O）2NRaRb、S（O）Ra、S（O）2Ra、C（O）Ra、C（O）ORa或C（O）NRaRb；R5为H或烷基；n为0、1、2、3、4、5或6；A为O、S、S（O）、S（O）2或NRe；B为N或CRf；X为O、S、S（O）、S（O）2、NRe或C（O）；Y为共价键、C（O）、C═NRa、O、S、S（O）、S（O）2或NRe；Z为N或CH；U和V分别独立地为N或CR；W为O、S或NRe；其中，Ra、Rb、Rc和Rd分别独立地为H、烷基、芳基、杂环芳基、环烷基或杂环烷基；Re为H、烷基、芳基、酰基或磺酰基；Rf为H、烷基、芳基、酰基、磺酰基、烷氧基、氨基、酯基、酰胺基、CN或卤素。该化合物可用于治疗与白细胞介素-12过度产生相关的疾病。
• HETEROCYCLIC COMPOUNDS FOR PREVENTING AND TREATING DISORDERS ASSOCIATED WITH EXCESSIVE BONE LOSS
  申请人：Ono Mitsunori

  公开号：US20100120722A1

  公开（公告）日：2010-05-13

  This invention relates to pyrimidine compounds of formula (I), formula (I′), and formula (I″): and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , U, V, W, X, Y, Z, and n are defined herein. This invention also relates to compositions comprising these compounds and methods for using them. The compounds and compositions of this invention are useful to treat or prevent disorders associated with excessive bone loss, including, without limitation periodontal disease, non-malignant bone disorders (such as osteoporosis, Pagers-disease of bone, osteogenesis imperfecta, fibrous dysplasia, and primary hyperparathyroidism) estrogen deficiency, inflammatory bone loss, bone malignancy, arthritis, osteopetrosis, and certain cancer-related disorders (such as hypercalcemia of malignancy (HCM), osteolytic bone lesions of multiple myeloma and osteolytic bone metastases of breast cancer and other metastatic cancers).

  本发明涉及式(I)、式(I′)和式(I″)的嘧啶化合物，以及其药学上可接受的盐、溶剂化合物、笼合物和前药，其中R1、R2、R3、R4、R5、U、V、W、X、Y、Z和n在此被定义。本发明还涉及包含这些化合物的组合物和使用它们的方法。本发明的化合物和组合物可用于治疗或预防与过度骨质流失相关的疾病，包括但不限于牙周病、非恶性骨疾病（如骨质疏松症、骨的Pagers病、不完全性骨发育不良、纤维性骨发育异常和原发性甲状旁腺功能亢进症）、雌激素缺乏、炎症性骨流失、骨恶性肿瘤、关节炎、骨质硬化和某些与癌症相关的疾病（如恶性高钙血症（HCM）、多发性骨髓瘤的溶骨性骨病变和乳腺癌和其他转移性癌症的溶骨性骨转移）。