N-(3-methyl-benzylidene)-N'-[6-morpholin-4-yl-2-(2-pyridin-3-yloxy)-pyrimidin-4-yl]-hydrazine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-methyl-benzylidene)-N'-[6-morpholin-4-yl-2-(2-pyridin-3-yloxy)-pyrimidin-4-yl]-hydrazine
• 英文别名: N-(3-methyl-benzylidene)-N'-[6-morpholin-4-yl-2-(pyridin-3-yloxy)-pyrimidin-4-yl]-hydrazine；N-[(E)-(3-methylphenyl)methylideneamino]-6-morpholin-4-yl-2-pyridin-3-yloxypyrimidin-4-amine
• 化学式: C₂₁H₂₂N₆O₂
• 分子量: 390.445
• InChiKey: NCIAXDCSYBXVGG-OEAKJJBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  84.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [6-morpholin-4-yl-2-(pyridin-3-yloxy)-pyrimidin-4-yl]-hydrazine 、 3-甲基苯甲醛 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以64%的产率得到N-(3-methyl-benzylidene)-N'-[6-morpholin-4-yl-2-(2-pyridin-3-yloxy)-pyrimidin-4-yl]-hydrazine
  参考文献：
  名称：

  Heterocyclic Compounds For Preventing And Treating Disorders Associated With Excessive Bone Loss

  摘要：

  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）。

  公开号：

  US20080058297A1

文献信息

• [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）。
• Pyrimidine compounds and uses thereof
  申请人：Wada Yumiko

  公开号：US20060135518A1

  公开（公告）日：2006-06-22

  This invention features pyrimidine compounds of formula (I): aryl, or heteroaryl; each of R 2 and R 4 , independently, is R c , halogen, nitro, cyano, isothionitro, SR c , or OR c ; or R 2 and R 4 , taken together, is carbonyl; R 3 is R c , alkenyl, alkynyl, OR c , OC(O)R c , SO 2 R c , S(O)R c , S(O 2 )NR c R d , SR c , NR c R d , NR c COR d , NR c C(O)OR d , NR c C(O)NR c R d , NR c SO 2 R d , COR c , C(O)OR c , or C(O)NR c R d ; R 5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O 2 ), or NR c ; Y is a covalent bond, CH 2 , C(O), C═N—R c , C═N—OR c , C═N—SR c , O, S, S(O), S(O 2 ), or NR c ; Z is N or CH; one of U and V is N, and the other is CR c ; and W is O, S, S(O), S(O 2 ), NR c , or NC(O)R c ; in which each of R a and R b , independently, is H, alkyl, aryl, heteroaryl; and each of R c and R d , independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl. The featured compounds inhibit the production of IL-12, IL-23 and IL-27 and are useful for treating disorders associated with IL-12, IL-23 and IL-27 overproduction or misregulation, such as inflammatory and immune disorders.

  这项发明涉及式(I)的嘧啶化合物：芳基或杂环基；其中R2和R4各自独立地为Rc、卤素、硝基、氰基、异硫氰基、SRc或ORc；或R2和R4一起为羰基；R3为Rc、烯基、炔基、ORc、OC(O)Rc、SO2Rc、S(O)Rc、S(O2)NRcRd、SRc、NRcRd、NRcCORd、NRcC(O)ORd、NRcC(O)NRcRd、NRcSO2Rd、CORc、C(O)ORc或C(O)NRcRd；R5为H或烷基；n为0、1、2、3、4、5或6；X为O、S、S(O)、S(O2)或NRc；Y为共价键、CH2、C(O)、C═N—Rc、C═N—ORc、C═N—SRc、O、S、S(O)、S(O2)或NRc；Z为N或CH；U和V中的一个为N，另一个为CRc；W为O、S、S(O)、S(O2)、NRc或NC(O)Rc；其中每个Ra和Rb各自独立地为H、烷基、芳基或杂环基；每个Rc和Rd各自独立地为H、烷基、芳基、杂环基、环烷基、杂环烷基或烷基羰基。这些特征化合物抑制IL-12、IL-23和IL-27的产生，并可用于治疗与IL-12、IL-23和IL-27过度产生或调节失常有关的疾病，如炎症和免疫性疾病。
• Process for preparing trisubstituted pyrimidine compounds
  申请人：Zhang Shijie

  公开号：US20060122209A1

  公开（公告）日：2006-06-08

  Disclosed herein is a regioselective synthesis of compounds represented by formula (I): or a salt, solvate, clathrate, or prodrug thereof, wherein X, Y, R 2 , R 3 , R 4 , R 7 , R 8 , R 9 , R 10 , m and n are defined as within.

  本文揭示了一种选择区域的合成化合物的方法，该化合物由公式(I)表示：或其盐、溶剂化物、包合物或前药，其中X、Y、R2、R3、R4、R7、R8、R9、R10、m和n如上所定义。
• Pyrimidine compounds
  申请人：Ono Mitsunori

  公开号：US20060025409A1

  公开（公告）日：2006-02-02

  This invention features pyrimidine compounds of formula (I): R 1 is aryl, or heteroaryl; each of R 2 and R 4 , independently, is R c , halogen, nitro, cyano, isothionitro, SR c , or OR c ; or R 2 and R 4 , taken together, is carbonyl; R 3 is R c , alkenyl, alkynyl, OR c , OC(O)R c , SO 2 R c , S(O)R c , S(O 2 )NR c R d , SR c , NR c R d , NR c COR d , NR c C(O)OR d , NR c C(O)NR c R d ; NR c SO 2 R d , COR c , C(O)OR c , or C(O)NR c R d , R 5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O 2 ), or NR c ; Y is a covalent bond, CH 2 , C(O), C═N—R c , C═N—OR c , C═N—SR c , O, S, S(O), S(O 2 ), or NR c ; Z is N or CH; one of U and V is N, and the other is CR c ; and W is O, S, S(O), S(O 2 ), NR c , or NC(O)R c ; in which each of R a and R b , independently, is H, alkyl, aryl, heteroaryl; and each of R c and R d , independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.

  本发明涉及式（I）的嘧啶化合物： R1为芳基或杂环芳基； R2和R4各自独立地为Rc、卤素、硝基、氰基、异硫氰基、SRc或ORc； 或者R2和R4共同为羰基； R3为Rc、烯基、炔基、ORc、OC（O）Rc、SO2Rc、S（O）Rc、S（O2）NRcRd、SRc、NRcRd、NRcCORd、NRcC（O）ORd、NRcC（O）NRcRd、NRcSO2Rd、CORc、C（O）ORc或C（O）NRcRd； R5为H或烷基； n为0、1、2、3、4、5或6； X为O、S、S（O）、S（O2）或NRc； Y为共价键、CH2、C（O）、C═N—Rc、C═N—ORc、C═N—SRc、O、S、S（O）、S（O2）或NRc； Z为N或CH； U和V中的一个为N，另一个为CRc； W为O、S、S（O）、S（O2）、NRc或NC（O）Rc； 其中每个Ra和Rb各自独立地为H、烷基、芳基、杂环芳基；每个Rc和Rd各自独立地为H、烷基、芳基、杂环芳基、环烷基、杂环烷基或烷基羰基。
• 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）。