本发明涉及登革病毒抑制剂药物
技术领域：
，具体涉及一种八氢喹唑啉-5-酮衍生物在作为登革热病毒抑制剂上的应用。
背景技术：
：登革病毒是黄病毒科黄病毒属中的一个血清型亚群，属于单股正链rna病毒，是一种全球性病毒，每年约有5千万-1亿左右的人感染，其中有近50万人因登革而遭受生命危险，每年因登革而死亡的人数达到了2万多。我国的广东、海南和台湾等地都曾有过登革热的发生和大流行，随着对登革病毒的深入研究，越来越多的登革病毒抑制剂被报道。hong-taoxu等于2015年设计合成了吡啶酰胺化合物dmb220，其抗1-4型登革病毒活性ec50约在5.0-6.7μm左右(antimicrobialagents&che-motherapy,2015,60(1):600)，但该类化合物选择性指数较差，在较低的浓度时就会产生较大的毒性。fatihabenmansour等于2016年设计合成了一类恶二唑类化合物，其抗1-4型登革病毒活性ec50可达到2.0μm左右(europeanjournalofmedicinalchem-istry109(2016)146-156)，但是该合成方法产率较低，部分化合物总产率低至7％。cyrilles.kounde等于2017年报道了一类2-氧哌嗪类化合物，该类化合物对1-4型登革病毒均有着很好的活性，其ec50值达到0.07-0.1μm(bi-oorganic&medicinalchemistryletters27(2017)1385–1389)，但该类化合物表现出非常差的理化性质(如较低的溶解度和较高的亲脂性)，这极大的限制了该类化合物的进一步应用。现有的登革病毒抑制剂存在着各种不足，到目前为止，仍未有公认的登革抑制剂和疫苗可供使用。因此，亟待发展新型登革病毒抑制剂。技术实现要素：本发明的目的是为了克服现有技术的不足，提供一种八氢喹唑啉-5-酮衍生物在作为登革热病毒抑制剂上的应用。目前喹唑啉类衍生物多应用于预防肿瘤上，本发明公开了其在登革热病毒抑制剂上的应用，是一种八氢喹唑啉-5-酮衍生物的新应用。本发明的通过如下技术方案予以实现：一种八氢喹唑啉-5-酮衍生物在作为登革热病毒抑制剂上的应用。优选地，所述八氢喹唑啉-5-酮衍生物的通式为：其中r1是取代的c1-6烷基、c5-6芳香基、取代的c5-6芳香基、c9-10稠二环芳香基；r2是c1-6烷基、取代的c1-6烷基、c5-6芳香基、取代的c5-6芳香基、c9-10稠二环芳香基；r3是c1-6烷基、取代的c1-6烷基、c5-6芳香基、取代的c5-6芳香基、c9-10稠二环芳香基；上述取代基选自下列基团：卤素、全卤代的c1-2烷基、卤代c1-4烷基、羟基、c1-6直链或支链烷氧基、c1-6环烷氧基、硝基、氰基、氨基、c1-6单烷基氨基、c1-6二烷基氨基、c5-8单环烷基氨基、c5-6单杂环基氨基、c5-6单芳基氨基、c1-6烷基酰氨基、c5-6芳基酰氨基、氨基羰基、c1-6单烷基氨基羰基、c1-6二烷基氨基羰基、c1-6烷基酰基、c5-8芳基酰基、氨基砜基、c1-6单烷基氨基砜基、c1-6二烷基氨基砜基、c5-8芳基氨基砜基、c1-6烷基磺酰氨基、羧基、直链或支链烷基、c5-8环烷基、c5-8取代的环烷基、c2-4烯基、c2-4炔基、芳基c1-3烷基、c5-6芳香基、c5-6取代的芳香基、c5-6多取代芳基氨基、c5-6稠二环芳香基、c5-6杂环基、c5-6芳杂环基、c9-10稠二环芳香基或c5-6稠二环芳杂环基。发明人在2016年研究公开了一种简单高效的八氢喹唑啉-5-酮衍生物的合成方法，合成方法具有反应易控制、反应条件简单、原料价廉易得、易于实现产业化等优点，极大的发展了八氢喹唑啉-5-酮衍生物的应用价值。在这之前，喹唑啉类衍生物的应用多是针对于肿瘤细胞的防治，发明人无意中发现由该方法制备的八氢喹唑啉-5-酮衍生物对登革热病毒具有很好的抑制活性，可应用于登革热病毒抑制剂的制备。本发明的八氢喹唑啉-5-酮衍生物的制备方法可以为如下步骤：s1.准确称量5mmol双甲酮，加入20ml水、5.5mmol伯胺、10mmol乙酸，在70℃下搅拌反应2h；s2.将15mmol胺和38％的甲醛溶液7mmol加入到上述反应液中，然后迅速加入醛混合液(20mmol醛+1.5mmol尿素+恰好能溶解醛的二氯甲烷)，70℃下搅拌反应12h；s3.用tlc检测反应结束后，待冷却后加入适量的二氯甲烷萃取反应液，取二氯甲烷层，反复萃取三次。再向取得的二氯甲烷层加入适量的na2so4进行干燥，然后减压蒸馏浓缩。s4.依次按不同比例的流动相石油醚：乙酸乙酯(15:1-10:1-8:1-5:1-3:1-2:1)进行柱层析梯度洗脱，得到拟合成的目标产物并纯化产物。优选地，r1为c6芳香基或取代的c6芳香基。优选地，r2为取代的c1-6烷基、c6芳香基、取代的c6芳香基或c10稠二环芳香基。优选地，r3为取代的c6芳香基。优选地，所述八氢喹唑啉-5-酮衍生物为：2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-氯苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(2-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-三氟甲基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-硝基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-苄氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-异丙氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-叔丁氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-三氟甲氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-叔丁基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-异丙基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(1-萘基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(5-甲基-2-噻吩基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(5-溴-2-噻吩基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-(二苯氨基)苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-2，3-二(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氟苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(3-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-三氟甲基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-苯氧苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-甲氧苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-三氟甲氧基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-甲苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-异丙基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-叔丁基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(2-萘)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-(4-氟苯基)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1，3-二(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-3-(4-氯苯基)-1-(3-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-(4-甲氧苯基)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-(2-萘)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-2-(4-(二苯氨基)苯基)-1,3-二(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-羟基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-甲氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3,5-二甲氧基-4-羟基苯基)-1h-喹唑啉-5-酮2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯-2-(2-噻吩)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-三氟甲基苯基)-1h-喹唑啉-5-酮、4-(2-(1,2,3,4,5,6,7,8-八氢-7,7-二甲基-1,3-二苯基)喹唑啉-5-酮)苯氰、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-硝基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-正丁基-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-异丙基-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,2,3-三(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-(4-甲氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-2,3-二苯基-1-(1-萘)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-(4-苯氨基苯基)-2,3-二苯基-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-苄基-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-2-苯基-1,3-二苄基-1h-喹唑啉-5-酮。优选地，所述八氢喹唑啉-5-酮衍生物为：2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-三氟甲基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-硝基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-苄氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-叔丁氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-三氟甲氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(5-溴-2-噻吩基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-(二苯氨基)苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-2，3-二(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氟苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-苯氧苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-三氟甲氧基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-甲苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(2-萘)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-(4-氟苯基)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-(4-甲氧苯基)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-羟基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-甲氧基基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯-2-(2-噻吩)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-三氟甲基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-正丁基-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-(4-甲氧基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-2,3-二苯基-1-(1-萘)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-2-苯基-1,3-二苄基-1h-喹唑啉-5-酮。更优选地，所述八氢喹唑啉-5-酮衍生物为：2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-三氟甲基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-(二苯氨基)苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氟苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-苯氧苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-三氟甲氧基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-甲苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(2-萘)-2-(4-溴苯基)-1h-喹唑啉-5-酮。更优选地，所述八氢喹唑啉-5-酮衍生物为：2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-三氟甲基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-(二苯氨基)苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氟苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-甲氧基基苯基)-1h-喹唑啉-5-酮、2,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-(4-甲氧基苯基)-1h-喹唑啉-5-酮。与现有技术相比，本发明的有益效果为：本发明提供了一种八氢喹唑啉-5-酮衍生物在作为登革热病毒抑制剂上的应用，该八氢喹唑啉-5-酮衍生物对登革热病毒具有较好的抑制活性，且制备方法简单高效，原料易得，可实现产业化生产，在登革热病毒抑制剂上具有极大的应用价值。具体实施方式下面结合具体实施例对本发明作进一步的解释说明，但具体实施例并不对本发明作任何限定。除非特别说明，实施例中所涉及的试剂、方法均为本领域常用的试剂和方法。八氢喹唑啉-5-酮衍生物的制备方法步骤如下：s1.准确称量双甲酮(5mmol)，加入到干净的锥形瓶中。向锥形瓶中加入20ml水和搅拌子。再加入伯胺(5.5mmol)，乙酸(10mmol)，70℃下搅拌反应2h；s2.将胺(15mmol)，38％的甲醛溶液(7mmol，)加入到上述反应液中，然后迅速加入醛混合液(20mmol醛+1.5mmol尿素+恰好能溶解醛的二氯甲烷)，70℃下搅拌反应12h；s3.反应结束(用tlc检测反应)后，待冷却后加入适量的二氯甲烷萃取反应液，取二氯甲烷层，反复萃取三次。再向取得的二氯甲烷层加入适量的na2so4进行干燥，然后减压蒸馏浓缩。s4.依次按不同比例的流动相石油醚：乙酸乙酯(15:1-10:1-8:1-5:1-3:1-2:1)进行柱层析梯度洗脱，得到拟合成的目标产物并纯化产物。实施例12,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-氯苯基)-1h-喹唑啉-5-酮(2-(4-chlorophenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物1)，73％yield,whitesolid,mp:195–196℃；ir(kbr)νmax＝2955.96,2920.28,2849.63,1633.35,1572.18,1529.75,1493.98,1465.11,1394.63,1347.65,1258.47,1151.60,1081.64,1010.73,923.54,810.02,756.88,698.28；1hnmr(400mhz,chloroform-d)δ7.45–7.37(m,4h),7.30–7.23(m,5h),7.02(d,j＝7.9hz,2h),6.98–6.85(m,3h),6.14(s,1h),4.39(d,j＝17.1hz,1h),3.58(d,j＝17.1hz,1h),2.37(d,j＝16.5hz,2h),2.27(s,2h),2.14(d,j＝16.5hz,1h),1.04(d,j＝4.6hz,6h)；13cnmr(101mhz,cdcl3)δ194.00,155.56,149.14,143.57,137.32,134.21,129.52,129.27,128.93,128.37,126.94,126.45,121.17,118.56,106.31,80.91,50.10,41.62,40.17,33.03,28.76,28.02；hr-esi-ms：calcdforc28h27cln2o([m+h]+)：443.1885，found：443.1889。实施例22,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin5(1h)-one.化合物2)85％yield,whitesolid,mp:166-167℃；1hnmr(400mhz,chloroform-d)δ7.56(d,j＝8.3hz,2h),7.41–7.20(m,7h),7.02(d,j＝8.1hz,2h),6.98–6.88(m,3h),6.13(s,1h),4.40(d,j＝17.1hz,1h),3.59(d,j＝17.1hz,1h),2.38(d,j＝16.5hz,1h),2.29(s,2h),2.15(d,j＝16.5hz,1h),1.05(d,j＝4.5hz,6h)。实施例32,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-溴苯基)-1h-喹唑啉-5-酮(2-(3-bromophenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物3)89％yield,whitesolid,mp:182–183℃；ir(kbr)νmax＝3058.05,2954.81,2867.55,1626.22,1573.78,1493.49,1452.95,1388.23,1292.28,1255.56,1186.69,1072.85,1033.16,1009.02,920.60,887.03,760.80,697.81；1hnmr(400mhz,chloroform-d)δ7.64(s,1h),7.52(d,j＝7.9hz,1h),7.44(d,j＝7.8hz,1h),7.34–7.23(m,6h),7.05–6.87(m,5h),6.14(s,1h),4.39(d,j＝17.1hz,1h),3.60(d,j＝17.2hz,1h),2.40(d,j＝16.4hz,1h),2.28(d,j＝1.9hz,2h),2.14(d,j＝16.5hz,1h),1.05(d,j＝12.3hz,6h)；13cnmr(101mhz,cdcl3)δ194.17,155.59,149.14,143.56,141.18,131.46,130.37,130.12,129.52,129.27,126.87,126.27,125.57,122.87,121.23,118.56,106.57,80.72,53.37,50.08,41.75,40.40,33.18,30.86,29.06,27.68；hr-esi-ms：calcdforc28h27brn2o([m+h]+)：487.1380；found：487.1386。实施例42,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(2-溴苯基)-1h-喹唑啉-5-酮(2-(2-bromophenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物5)66％yield,yellowsolid,mp:118–119℃；ir(kbr)νmax＝3060.06,2956.62,2870.21,1622.86,1571.49,1493.42,1411.81,1389.80,1304.85,1256.78,1191.91,1155.12,1119.58,1075.14,1013.31,917.50,755.74,698.63；1hnmr(400mhz,chloroform-d)δ7.65(m,1h),7.59(m,1h),7.42(m,1h),7.31(m,7h),7.28–7.25(m,1h),6.98(m,1h),6.89–6.81(m,2h),6.39(s,1h),4.56(d,j＝17.4hz,1h),3.61(d,j＝17.3hz,1h),2.40–2.26(m,2h),2.22–2.06(m,2h),1.02(d,j＝47.2hz,6h)；13cnmr(101mhz,cdcl3)δ193.74,156.86,149.05,142.69,136.89,134.06,130.11,129.57,129.16,128.98,127.61,127.58,127.14,123.16,121.24,118.56,103.90,82.01,49.88,41.28,38.95,32.72,28.72,28.07；hr-esi-ms：calcdforc28h27brn2o([m+h]+)：487.1380；found：487.1385。实施例52,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-三氟甲基苯基)-1h-喹唑啉-5-酮(7,7-dimethyl-1,3-diphenyl-2-(3-(trifluoromethyl)phenyl)-2,3,4,6,7,8-hexahydroq-uinazoli-n-5(1h)-one化合物6)64％yield,whitesolid,mp:174–175℃；ir(kbr)νmax＝3057.65,2959.19,2869.54,1626.35,1574.11,1494.80，1451.83,1392.10,1330.18,1255.94,1166.87,1125.23,1032.35,1009.30,920.40,801.48,755.01,698.23；1hnmr(400mhz,chlorof-orm-d)δ7.79–7.71(m,2h),7.66(d,＝7.8hz,1h),7.58(t,j＝7.7hz,1h),7.35–7.23(m,5h),7.04(d,j＝7.8hz,2h),6.99–6.87(m,3h),6.21(s,1h),4.41(d,j＝17.2hz,1h),3.55(d,j＝17.2hz,1h),2.43(d,j＝16.4hz,1h),2.33–2.25(m,2h),2.15(d,j＝16.4hz,1h),1.05(d,j＝4.1hz,6h)；13cnmr(101mhz,cdcl3)δ194.16,155.52,149.14,143.62,140.06,130.40,129.58,129.43,129.31,126.94,126.24,125.32,125.29,123.85,123.81,121.38,118.66,106.67,80.96,50.10,41.81,40.45,33.15,29.15,27.45；hr-esi-ms：calcdforc29h27f3n2o([m+h]+)：477.2148；found：477.2151。实施例62,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3-硝基苯基)-1h-喹唑啉-5-酮(7,7-dimethyl-2-(3-nitrophenyl)-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物7)，65％yield,yellowsolid,mp:186–187℃；ir(kbr)νmax＝2959.76,2919.81,2849.50,1632.39,1571.76,1529.74,1494.23,1465.95,1392.74,1347.62,1258.29,1198.09,1151.72,1081.87,1030.02,809.49,756.93,698.53；1hnmr(400mhz,chloroform-d)δ8.38(s,1h),8.27(m,1h),7.89(d,j＝7.5hz,1h),7.64(t,j＝7.9hz,1h),7.38–7.27(m,5h),7.10–6.96(m,3h),6.91(d,j＝7.2hz,2h),6.23(s,1h),4.42(d,j＝17.3hz,1h),3.52(d,j＝17.3hz,1h),2.41(d,j＝16.4hz,1h),2.30(s,2h),2.21(d,j＝16.5hz,1h),1.07(d,j＝11.7hz,6h)；13cnmr(101mhz,cdcl3)δ194.27,155.53,148.95,148.63,143.40,141.27,133.17,130.03,129.68,129.39,127.16,126.41,123.51,122.11,121.63,118.72,106.70,80.77,50.09,41.70,40.42,33.10,28.87,27.79；hr-esi-ms：calcdforc28h27n3o3([m+h]+)：454.2125；found：454.2122。实施例72,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-苄氧基苯基)-1h-喹唑啉-5-酮(2-(4-(benzyloxy)phenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazo-lin-5(1h)-one化合物9)，72％yield,whitesolid,mp:101–102℃；ir(kbr)νmax＝3058.99,3038.38,2954.81,2930.67,2868.32,1570.08,1497.25,1454.21,1391.13,1307.80,1255.82,1198.28,1170.79,1123.98,1073.54,1010.92,923.94,825.38,753.12,697.51；1hnmr(400mhz,chloroform-d)δ7.51–7.35(m,7h),7.32(d,j＝7.2hz,2h),7.26(m,3h),7.08–7.00(m,4h),6.94(d,j＝5.7hz,3h),6.16(s,1h),5.11(s,2h),4.40(d,j＝16.9hz,1h),3.65(d,j＝16.9hz,1h),2.37(d,j＝16.5hz,1h),2.28(s,2h),2.15(d,j＝16.5hz,1h),1.05(d,j＝8.7hz,6h)；13cnmr(101mhz,cdcl3)δ193.90,158.81,155.75,149.36,143.73,136.78,131.01,129.41,129.20,128.58,128.18,127.99,127.44,126.78,126.57,120.88,118.57,114.97,106.00,81.11,70.10,50.14,41.65,40.03,33.01,28.81,28.05ppm；hr-esi-ms：calcdforc35h34n2o2([m+h]+)：515.2693；found：515.2691。实施例82,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-异丙氧基苯基)-1h-喹唑啉-5-酮(2-(4-isopropoxyphenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物10)，86％yield,whitesolid,mp:177–178℃；ir(kbr)νmax＝3059.84,2928.02,2863.52,1706.47,1571.48,1498.43,1455.30,1392.28,1297.98,1252.32,1174.43,1116.84,1071.41,1031.29,1008.09,951.57,880.30,825.18,755.55,698.06；1hnmr(400mhz,chloroform-d)δ7.36(d,j＝8.6hz,2h),7.30(s,1h),7.27–7.22(m,4h),7.03(d,j＝8.3hz,2h),6.97–6.88(m,5h),6.14(s,1h),4.68–4.51(m,1h),4.39(d,j＝16.9hz,1h),3.65(d,j＝16.9hz,1h),2.36(d,j＝16.5hz,1h),2.27(s,2h),2.14(d,j＝16.4hz,1h),1.38(d,j＝6.0hz,6h),1.04(d,j＝8.8hz,6h)；13cnmr(101mhz,cdcl3)δ193.87,157.89,155.78,149.37,143.72,130.37,129.35,129.15,128.11,126.72,126.55,120.81,118.54,115.76,105.93,81.12,69.88,50.10,41.63,39.97,32.98,28.79,27.99,22.01ppm；hr-esi-ms：calcdforc31h34n2o2([m+h]+)：467.2693；found：467.2691。实施例92,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-叔丁氧基苯基)-1h-喹唑啉-5-酮(2-(4-(tert-butoxy)phenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5-(1h)-one化合物11)，67％yield,yellowsolid,mp:160–161℃；ir(kbr)νmax＝3059.47,2968.01,2931.05,2869.12,1622.55,1572.15,1497.52,1454.62,1392.55,1298.05,1258.64,1161.84,1071.84,1009.04,925.59,896.75,833.27,757.18,697.96；1hnmr(400mhz,chlorofor-m-d)δ7.37(d,j＝8.3hz,2h),7.30–7.25(m,5h),7.04(m,4h),6.93(t,j＝8.2hz,3h),6.16(s,1h),4.40(d,j＝17.0hz,1h),3.65(d,j＝17.0hz,1h),2.34(d,j＝16.5hz,1h),2.28(s,2h),2.14(d,j＝16.5hz,1h),1.46(d,j＝10.2hz,1h),1.39(s,9h),1.04(d,j＝8.3hz,6h)；13cnmr(101mhz,cdcl3)δ193.93,155.93,155.55,149.34,143.65,133.21,129.38,129.18,127.49,126.83,126.65,123.93,120.92,118.57,105.84,81.31,50.08,41.61,39.88,32.95,28.83,28.72,28.04；hr-esi-ms：calcdforc32h36n2o2([m+h]+)：481.2850：found：481.2854。实施例102,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-三氟甲氧基苯基)-1h-喹唑啉-5-酮(7,7-dimethyl-1,3-diphenyl-2-(4-(trifluoromethoxy)phenyl)-2,3,4,6,7,8-hexah-ydroquinaz-olin-5(1h)-one化合物12)，75％yield,whitesolid,mp:102–103℃；ir(kbr)νmax＝3061.10,2957.38,2870.23,1625.24,1573.10,1496.75,1454.43,1393.78,1259.79,1222.59,1162.90,1071.87,1012.63,924.51,882.00,837.20,756.29,698.10；1hnmr(400mhz,chloroform-d)δ7.53(d,j＝8.6hz,2h),7.31-7.29(m,3h),7.27-7.24(m,3h),7.05–6.90(m,4h),6.17(s,1h),4.40(d,j＝17.1hz,1h),3.58(d,j＝17.1hz,1h),2.38(d,j＝16.5hz,1h),2.28(s,2h),2.15(d,j＝16.5hz,1h),1.05(d,j＝3.9hz,6h)；13cnmr(101mhz,cdcl3)δ194.15,155.77,149.13,143.55,137.40,129.56,129.30,128.47,127.04,126.50,121.28,121.11,118.62,106.29,80.98,50.05,41.61,40.12,33.00,28.67,28.06；hr-esi-ms：calcdforc29h27f3n2o2([m+h]+)：493.2097；found：493.2092。实施例112,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-叔丁基苯基)-1h-喹唑啉-5-酮(2-(4-(tert-butyl)phenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinaz-olin-5(1h)-one化合物13)，72％yield,whitesolid,mp:199–200℃；ir(kbr)νmax＝3059.06,3034.38,2958.43,2868.78,1706.94,1625.96,1572.24,1494.78,1454.19,1392.88,1311.42,1260.63,1072.42,1011.42,946.42,926.44,881.85,822.85,757.59,698.02；1hnmr(400mhz,chloroform-d)δ7.45–7.36(m,4h),7.29–7.23(m,5h),7.02(d,j＝7.9hz,2h),6.91(t,j＝8.1hz,3h),6.16(s,1h),4.36(d,j＝17.0hz,1h),3.60(d,j＝17.0hz,1h),2.36(d,j＝16.5hz,1h),2.26(s,2h),2.14(d,j＝16.4hz,1h),1.35(s,9h),1.03(d,j＝11.3hz,6h)；13cnmr(101mhz,cdcl3)δ193.98,155.85,151.29,149.46,143.82,135.67,129.37,129.19,126.72,126.56,125.63,120.82,118.52,106.10,81.28,50.14,41.65,40.20,34.56,33.01,31.32,28.87,28.04；hr-esi-ms：calcdforc32h36n2o([m+h]+)：465.2900；found：465.2901。实施例122,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-异丙基苯基)-1h-喹唑啉-5-酮(2-(4-isopropylphenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazo-lin-5(1h)-one化合物14)，65％yield,whitesolid,mp:153–154℃；1hnmr(400mhz,chlorof-ormd)δ7.40(d,j＝8.1hz,2h),7.32–7.21(m,7h),7.04(d,j＝7.9hz,2h),6.97–6.90(m,3h),6.18(s,1h),4.39(d,j＝16.9hz,1h),3.63(d,j＝17.0hz,1h),2.96(m,1h),2.38(d,j＝16.4hz,1h),2.19(s,3h),1.30(d,j＝6.9hz,6h),1.05(d,j＝10.3hz,6h)；13cnmr(101mhz,cdcl3)δ193.99,155.88,149.45,149.03,143.81,136.06,129.37,129.19,126.83,126.77,126.72,126.56,120.83,118.53,106.08,81.33,50.12,41.66,40.16,33.76,33.02,30.86,28.87,27.99,23.92；hr-esi-ms：calcdforc31h34n2o([m+h]+)：451.2744；found：451.2749。实施例132,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(1-萘基)-1h-喹唑啉-5-酮(7,7dimethyl-2-(naphthalen-1-yl)-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)–one化合物15)，61％yield,lightyellowsolid,mp:193–194℃；ir(kbr)νmax＝2950.11,2928.21,2885.63,1626.24,1569.00,1495.02,1455.88,1389.73,1263.62,1156.85,1074.72,1029.54,1003.37,924.86,884.62,754.97,697.45；1hnmr(400mhz,chloroform-d)δ8.21–8.13(m,1h),7.96–7.87(m,2h),7.65(d,j＝7.2hz,1h),7.57–7.44(m,3h),7.33(m,2h),7.28–7.18(m,6h),7.03–6.93(m,3h),6.80(s,1h),4.51(d,j＝17.2hz,1h),3.50(d,j＝17.2hz,1h),2.34(d,j＝16.6hz,1h),2.28(s,2h),2.21(d,j＝16.6hz,1h),1.06(d,j＝49.7hz,6h)；13cnmr(101mhz,cdcl3)δ193.99,156.35,148.76,143.51,134.33,132.73,130.58,129.60,128.75,127.17,126.96,126.54,125.96,125.51,124.65,123.69,120.92,118.03,104.58,79.02,50.05,41.64,40.26,32.96,28.83,28.11；hr-esi-ms：calcdforc32h30n2o([m+h]+)：459.2431，found：459.2432。实施例142,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(5-甲基-2-噻吩基)-1h-喹唑啉-5-酮(7,7-dimethyl-2-(5-methylthiophen-2-yl)-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5-(1h)-one化合物17)，64％yield,brownsolid,mp:141–142℃；ir(kbr)νmax＝3060.18,2954.71,2928.05,2866.87,1683.94,1626.14,1575.66,1494.19,1452.63,1397.71,1311.69,1260.23,1150.09,1122.65,1073.23,1032.29,1006.26,923.42,855.77,797.23,753.92,697.89；1hnmr(400mhz,chlorofo-rm-d)δ7.34–7.25(m,5h),7.02(m,4h),6.93(t,j＝7.3hz,1h),6.81(d,j＝3.3hz,1h),6.63(d,j＝2.8hz,1h),6.26(s,1h),4.39(d,j＝16.7hz,1h),3.92(d,j＝16.7hz,1h),2.47(s,3h),2.36–2.26(m,3h),2.09(d,j＝16.6hz,1h),1.04(d,j＝6.0hz,6h)；13cnmr(101mhz,cdcl3)δ194.21,155.19,148.45,143.57,140.49,139.99,129.46,129.20,127.00,126.69,125.65,124.81,121.03,118.34,106.75,77.97,50.20,41.59,40.46,32.91,28.62,28.19,15.38；hr-esi-ms：calcdforc27h28n2os([m+h]+)：429.1995；found：429.1996。实施例15化合物152,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(5-溴-2-噻吩基)-1h-喹唑啉-5-酮(2-(5-bromothiophen-2-yl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroqu-inazolin-5(1h)-one化合物18)，88％yield,whitesolid,mp:75–76℃；1hnmr(400mhz,chlorofor-md)δ7.42–7.22(m,5h),7.08–6.89(m,7h),6.79(d,j＝3.7hz,1h),6.24(s,1h),4.39(d,j＝16.8hz,1h),3.91(d,j＝16.8hz,1h),2.42–2.25(m,3h),2.10(d,j＝16.6hz,1h),1.05(d,j＝2.8hz,7h)。实施例162,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-(二苯氨基)苯基)-1h-喹唑啉-5-酮(2-(4-(diphenylamino)phenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahy-droquinazoli-n-5(1h)-one化合物19)70％yield,whitesolid,mp:204–205℃；ir(kbr)νmax＝2926.99,2863.41,2350.27,2315.15,1706.39,1571.13,1507.18,1493.55,1453.72,1388.96,1292.86,1259.14,1177.47,1073.67,1012.68,923.76,881.05,823.76,750.43,697.70；1hnmr(400mhz,chloroform-d)δ7.53–7.29(m,8h),7.28–7.19(m,5h),7.19–7.00(m,9h),6.96–6.92(m,2h),6.14(s,1h),4.42(d,j＝16.9hz,1h),3.71(d,j＝17.0hz,1h),2.44–2.21(m,3h),2.11(d,j＝16.4hz,1h),1.02(s,6h)；13cnmr(101mhz,cdcl3)δ194.03,155.89,149.36,147.93,147.49,143.75,132.05,129.27,127.69,126.67,124.65,123.04,120.92,118.61,105.96,81.33,50.10,41.62,40.06,32.96,28.79,28.01；hr-esi-ms：calcdforc40h37n3o([m+h]+)：576.3009；found：576.3003。实施例172,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-2，3-二(4-溴苯基)-1h-喹唑啉-5-酮(2,3-bis(4-bromophenyl)-7,7-dimethyl-1-phenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物20)，72％yield,whitesolid,mp:187–189℃；ir(kbr)νmax＝3058.82,2953.98,2928.47,2854.96,1687.71,1571.66,1490.28,1457.21,1391.21,1304.28,1263.20,1172.43,1149.10,1072.81,1008.77,922.27,884.57,819.88,754.30,699.90；1hnmr(400mhz,chloroform-d)δ7.84–7.67(m,2h),7.64–7.51(m,2h),7.49–7.31(m,6h),6.96–6.84(m,3h),6.07(s,1h),4.33(d,j＝17.0hz,1h),3.57(d,j＝17.1hz,1h),2.42–2.27(m,3h),2.15(d,j＝16.3hz,1h),1.03(t,j＝5.7hz,6h)；13cnmr(101mhz,cdcl3)δ194.01,155.50,148.20,143.36,137.45,132.11,131.98,129.64,128.60,127.11,126.37,122.57,120.16,113.37,80.68,50.02,41.58,40.20,33.03,28.77,27.97；hr-esi-ms：calcdforc28h26br2n2o([m+h]+)：565.0485；found：565.0488。实施例18化合物182,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氟苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-fluorophenyl)-7,7-dimethyl-1-phenyl-2,3,4,6,7,8-hexahydroqui-nazolin-5(1h)-one化合物21)75％yield,whitesolid,mp:202–203℃；ir(kbr)νmax＝2956.65,2931.86,2845.90,1706.46,1624.36,1572.42,1505.46,1454.60,1391.29,1303.04,1261.87,1231.29,1159.65,1072.57,1009.08,925.85,883.21,827.27,755.03,700.19；1hnmr(400mhz,chloroform-d)δ7.57(d,j＝8.0hz,2h),7.41–7.26(m,5h),7.06–6.91(m,4h),6.86(d,j＝7.6hz,2h),5.98(s,1h),4.28(d,j＝17.1hz,1h),3.57(d,j＝17.2hz,1h)2.37(d,j＝16.5hz,1h),2.28(s,2h),2.14(d,j＝16.5hz,1h),1.05(d,j＝3.4hz,6h)；13cnmr(101mhz,cdcl3)δ193.98,158.95,156.56,155.64,145.61,143.45,137.65,131.93,129.57,128.69,127.05,126.44,122.47,120.61,120.54,115.86,115.64,105.84,82.12,50.08,41.58,40.44,33.00,28.74,28.04；hr-esi-ms：calcdforc28h26brfn2o([m+h]+)：505.4314；found：505.1286。实施例19化合物192,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-chlorophenyl)-7,7-dimethyl-1-phenyl-2,3,4,6,7,8-hexahydroqui-nazolin-5(1h)-one化合物22)，71％yield,lightyellowsolid,mp:161–162℃；ir(kbr)νmax＝2955.73,2868.71,1624.86,1572.84,1491.71,1456.50,1391.26,1304.38,1261.60,1198.90,1172.46,1070.97,1008.26,924.82,883.10,822.93,754.49,699.11；1hnmr(400mhz,chloroform-d)δ7.56(d,j＝8.2hz,2h),7.33–7.21(m,7h),6.92(m,4h),6.06(s,1h),4.33(d,j＝17.2hz,1h),3.56(d,j＝17.1hz,1h),2.37(d,j＝16.6hz,1h),2.28(s,2h),2.14(d,j＝16.5hz,1h),1.04(d,j＝5.0hz,6h；13cnmr(101mhz,cdcl3)δ193.99,155.55,147.77,143.35,137.49,131.97,129.65,129.19,128.63,127.13,126.40,126.02,122.55,119.86,118.56,105.89,80.94,50.04,41.57,40.22,33.02,28.75,28.01；hr-esi-ms：calcdforc28h26brcln2o([m+h]+)：521.0990；found：521.0999。实施例202,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(3-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(3-chlorophenyl)-7,7-dimethyl-1-phenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物23)，76％yield,whitesolid,mp:178–179℃；1hnmr(400mhz,chloroform-d)δ7.56(d,j＝8.3hz,2h),7.34(m,5h),7.18(t,j＝8.1hz,1h),7.01–6.85(m,5h),6.09(s,1h),4.35(d,j＝17.0hz,1h),3.59(d,j＝17.0hz,1h),2.41(d,j＝16.5hz,1h),2.29(s,2h),2.15(d,j＝16.5hz,1h),1.05(s,6h)；13cnmr(101mhz,cdcl3)δ193.97,150.31,143.34,137.38,135.00,132.00,130.26,129.67,128.57,127.11,126.29,122.59,121.02,118.37,116.38,106.32,80.09,49.99,41.62,40.57,33.06,28.73,27.95。实施例212,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-三氟甲基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-7,7-dimethyl-1-phenyl-3-(4-(trifluoromethyl)phe-nyl)-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物26)，67％yield,whitesol-id,mp:188–189℃；ir(kbr)νmax＝3056.52,2954.90,2928.39,2861.30,1705.09,1612.08,1573.79,1522.46,1490.97,1454.79,1393.98,1325.90,1262.09,1164.05,1115.71,1070.87,1009.30,925.20,885.25,824.14,755.21,695.98；1hnmr(400mhz,chloroform-d)δ7.57(d,j＝8.5hz,2h),7.50(d,j＝8.6hz,2h),7.41–7.30(m,5h),7.06–6.94(m,4h),6.23(s,1h),4.45(d,j＝17.0hz,1h),3.63(d,j＝17.0hz,1h),2.42(d,j＝16.5hz,1h),2.31(s,2h),2.15(d,j＝16.5hz,1h),1.04(d,j＝3.8hz,6h)；13cnmr(101mhz,cdcl3)δ194.07,155.33,151.53,143.33,137.27,132.08,129.74,128.50,127.16,126.69,126.65,126.61,126.58,126.11,122.70,117.05,106.55,79.14,50.01,41.64,40.40,33.11,28.86,27.80；hr-esi-ms：calcdforc29h26brf3n2o([m+h]+)：555.1253；found：555.1259。实施例222,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-苯氧苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-7,7-dimethyl-3-(4-phenoxyphenyl)-1-phenyl-2,3,4,6,7,8-hexahydro-quinazolin-5(1h)-one化合物28)，77％yield,whitesolid,mp:131–132℃；ir(kbr)νmax＝2925.68,2852.08,1706.06,1571.20,1493.61,1450.93,1394.09,1261.46,1158.94,1014.95,915.19,886.32,818.18,753.98,697.71；1hnmr(400mhz,chloroform-d)δ7.46–7.37(m,4h),7.32–7.26(m,4h),7.19–7.01(m,7h),6.94(t,j＝7.3hz,3h),6.17(s,1h),4.41(d,j＝17.0hz,1h),3.68(s,1h),2.36(d,j＝16.5hz,1h),2.28(s,2h),2.14(d,j＝16.4hz,1h),1.04(d,j＝3.8hz,6h)；13cnmr(101mhz,cdcl3)δ194.00,157.54,156.66,155.77,149.29,143.69,133.21,129.79,129.44,129.23,128.36,126.85,126.57,123.61,121.01,119.29,118.57,106.10,81.13,50.10,41.63,40.08,32.99,28.77,28.06。实施例232,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-甲氧苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-methoxyphenyl)-7,7-dimethyl-1-phenyl-2,3,4,6,7,8-hexahydro-quinazolin-5(1h)-one化合物29)，63％yield,brownsolid,mp:130–131℃；ir(kbr)νmax＝2953.30,2930.53,2866.67,1705.28,1622.49,1571.49,1508.82,1456.28,1390.83,1260.06,1176.22,1071.82,1305.29,1009.34,926.87,883.54,825.12,754.97,699.70；1hnmr(400mhz,chloroform-d)δ7.56(d,j＝8.2hz,2h),7.37(d,j＝8.2hz,2h),7.31–7.26(m,2h),6.99(d,j＝8.8hz,2h),6.89–6.68(m,5h),5.94(s,1h),4.26(d,j＝17.2hz,1h),3.80(s,3h),3.55(d,j＝17.2hz,1h),2.36(d,j＝16.5hz,1h),2.28(s,2h),2.14(d,j＝16.5hz,1h),1.05(d,j＝3.0hz,6h)；13cnmr(101mhz,cdcl3)δ193.93,155.70,154.53,143.54,143.04,137.89,131.83,129.48,128.78,126.93,126.60,122.30,120.68,114.75,114.42,105.94,82.44,55.68,50.11,41.59,40.46,32.96,28.75,28.10；hr-esi-ms：calcdforc29h29brn2o2([m+h]+)：517.1485；found：517.1491。实施例242,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-三氟甲氧基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-7,7-dimethyl-1-phenyl-3-(4-(trifluoromethoxy)phenyl)-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物30)，71％yield,whitesolid,mp:185–186℃；ir(kbr)νmax＝2955.47,2929.73,2870.36,1626.61,1574.28,1507.93,1491.62,1390.59,1367.94,1258.13,1223.73,1160.44,1071.44,1010.21,920.00,882.88,813.75,763.51,750.31,699.57；1hnmr(400mhz,chloroform-d)δ7.83–7.52(m,4h),7.33(m,5h),7.20–7.09(m,2h),7.08–6.93(m,2h),6.89(d,j＝7.0hz,1h),6.07(s,1h),4.35(d,j＝16.9hz,1h),3.66–3.55(m,1h),2.49–2.28(m,3h),2.14(d,j＝16.3hz,1h),1.07–0.94(m,6h)；13cnmr(101mhz,cdcl3)δ194.09,155.56,147.93,143.44,143.04,137.48,132.01,129.62,128.60,127.08,126.23,122.59,122.08,119.48,106.16,80.99,50.02,41.64,40.53,33.06,28.85,27.85；hr-esi-ms：calcdforc29h26brf3n2o2([m+h]+)：571.1203；found：571.1209。实施例252,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-甲苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-7,7-dimethyl-1-phenyl-3-(p-tolyl)-2,3,4,6,7,8-hexahydro-quinazolin-5(1h)-one化合物31，75％yield,whitesolid,mp:102–103℃；ir(kbr)νmax＝3058.33,3033.09,2955.28,2928.24,2856.95,1682.37,1623.72,1572.89,1490.71,1455.51,1391.13,1302.65,1260.00,1198.23,1172.51,,1125.22,1071.17,1008.67,927.41,881.90,817.19,756.22,699.80；1hnmr(400mhz,chloroform-d)δ7.55(d,j＝8.0hz,2h),7.40–7.26(m,5h),7.06(d,j＝8.1hz,2h),6.95–6.86(m,4h),6.06(s,1h),4.34(d,j＝17.2hz,1h),3.56(d,j＝17.1hz,1h),2.36(d,j＝16.5hz,1h),2.30(s,3h),2.27(s,2h),2.14(d,j＝16.5hz,1h),1.04(d,j＝4.4hz,6h)；13cnmr(101mhz,cdcl3)δ193.95,155.54,146.81,143.55,137.96,131.84,130.63,129.76,129.49,128.76,126.90,126.53,122.30,118.72,106.20,81.28,50.10,41.62,40.31,33.01,28.80,28.04,20.50；hr-esi-ms：calcdforc29h29brn2o([m+h]+)：501.1636；found：501.1538。实施例262,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-异丙基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-isopropylphenyl)-7,7-dimethyl-1-phenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物32)，70％yield,whitesolid,mp:196–197℃；ir(kbr)νmax＝2956.99,2928.03,2857.18,1706.14,1572.78,1492.15,1455.36,1393.39,1306.61,1262.91,1164.99,1118.24,1071.64,1009.74,925.99,883.62,822.69,755.55,698.87；1hnmr(400mhz,chlorofo-rm-d)δ7.55(d,j＝7.9hz,2h),7.41–7.25(m,5h),7.11(d,j＝8.1hz,2h),6.92(m,4h),6.06(s,1h),4.35(d,j＝17.0hz,1h),3.58(d,j＝17.1hz,1h),2.96–2.78(m,1h),2.40(d,j＝16.4hz,1h),2.26(s,2h),2.13(d,j＝16.4hz,1h),1.24(d,j＝6.9hz,6h),1.04(s,6h)；13cnmr(101mhz,cdcl3)δ194.02,155.47,147.10,143.68,141.79,138.03,131.85,129.42,128.74,127.04,126.76,126.35,122.28,118.60,106.65,80.99,50.10,41.70,40.62,33.18,33.04,28.94,27.84,24.02；hr-esi-ms：calcdforc31h33brn2o([m+h]+)：529.1849；found：529.1853。实施例27化合物272,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(4-叔丁基苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-(tert-butyl)phenyl)-7,7-dimethyl-1-phenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物33)，75％yield,whitesolid,mp:201–202℃；ir(kbr)νmax＝3058.10,2957.20,2899.73,2868.78,1627.61,1572.64,1513.45,1491.03,1455.70,1390.23,1302.68,1259.71,1170.98,1153.32,1070.25,1009.21,927.10,882.18,826.89,754.74,699.71；1hnmr(400mhz,chloroform-d)δ7.54(d,j＝8.2hz,2h),7.36(d,j＝8.2hz,2h),7.31–7.25(m,5h),6.91(t,j＝8.6hz,4h),6.06(s,1h),4.35(d,j＝17.2hz,1h),3.57(d,j＝17.1hz,1h),2.41(d,j＝16.5hz,1h),2.25(d,j＝3.1hz,2h),2.12(d,j＝16.4hz,1h),1.30(s,9h),1.03(s,6h)；13cnmr(101mhz,cdcl3)δ194.05,155.43,146.70,143.98,143.69,138.06,131.85,129.43,128.74,126.73,126.27,125.96,122.28,118.14,106.79,80.65,50.09,41.75,40.72,34.01,33.08,31.37,29.03,27.76；hr-esi-ms：calcdforc32h35brn2o([m+h]+)：543.2006；found：543.2009。实施例282,3,4,6,7,8-八氢-7,7-二甲基-1-苯基-3-(2-萘)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-7,7-dimethyl-3-(naphthalen-2-yl)-1-phenyl-2,3,4,6,7,8-hexa-hydroqu-inazolin-5(1h)-one化合物35)，69％yield,brownsolid,mp:155–156℃；ir(kbr)νmax＝3056.64,2956.91,2929.37,2861.97,1626.86,1572.11,1491.00,1390.89,1300.56,1261.85,1173.08,1069.77,1009.56,950.98,925.67,880.00,813.74,751.92,699.35；1hnmr(400mhz,chloroform-d)δ7.75(d,j＝8.7hz,2h),7.59(m,j＝15.4,8.3hz,3h),7.48–7.21(m,9h),6.94(d,j＝7.1hz,2h),6.25(s,1h),4.53(d,j＝17.0hz,1h),3.67(d,j＝17.0hz,1h),2.38(d,j＝16.5hz,1h),2.30(s,2h),2.17(d,j＝16.5hz,1h),1.05(d,j＝7.4hz,6h)；13cnmr(101mhz,cdcl3)δ194.10,155.46,146.49,143.45,137.68,134.35,131.94,129.59,129.13,129.07,128.69,127.39,127.03,126.92,126.53,126.40,123.95,122.47,120.40,113.35,106.15,80.43,50.12,41.63,40.61,33.05,28.70,28.05；hr-esi-ms：calcdforc32h29brn2o([m+h]+)：537.1536；found：537.1542。实施例292,3,4,6,7,8-八氢-7,7-二甲基-1-(4-氟苯基)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-chlorophenyl)-1-(4-fluorophenyl)-7,7-dimethyl-2,3,4,6,7,8-hex-ahydroquinazolin-5(1h)-one化合物36)，77％yield,yellowsolid,mp:177–178℃；1hnmr(400mhz,chloroform-d)δ7.57(d,j＝8.4hz,2h),7.32(d,j＝8.4hz,2h),7.23(d,j＝8.9hz,2h),7.09–6.90(m,4h),6.86(m,2h),6.00(s,1h),4.32(d,j＝17.1hz,1h),3.54(d,j＝17.2hz,1h),2.28(d,j＝18.3hz,3h),2.11(d,j＝16.5hz,1h),1.05(d,j＝10.8hz,6h)；13cnmr(101mhz,cdcl3)δ193.95,155.54,155.53,147.67,139.41,137.16,132.05,129.26,128.52,126.25,122.67,119.94,116.70,116.47,105.90,81.48,49.93,41.49,39.83,32.91,28.62,28.13。实施例302,3,4,6,7,8-八氢-7,7-二甲基-1，3-二(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-1,3-bis(4-chlorophenyl)-7,7-dimethyl-2,3,4,6,7,8-hexahydr-oquinazo-lin-5(1h)-one化合物37)，75％yield,whitesolid,mp:184–185℃；1hnmr(400mhz,chloroform-d)δ7.57(d,j＝8.5hz,2h),7.30(m,4h),7.21(d,j＝9.0hz,2h),6.96–6.89(m,2h),6.87–6.79(m,2h),6.01(s,1h),4.31(d,j＝17.2hz,1h),3.55(d,j＝17.2hz,1h),2.36(d,j＝16.5hz,1h),2.28(s,2h),2.11(d,j＝16.5hz,1h),1.04(d,j＝1.7hz,6h；13cnmr(101mhz,cdcl3)δ194.11,154.90,147.65,142.00,137.18,132.76,132.09,129.81,129.26,128.50,127.51,126.24,122.71,119.84,106.69,81.13,50.02,41.61,40.18,33.08,28.80,27.92。实施例31化合物312,3,4,6,7,8-八氢-7,7-二甲基-3-(4-氯苯基)-1-(3-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-1-(3-chlorophenyl)-3-(4-chlorophenyl)-7,7-dim-ethyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物38)，69％yield,whitesolid,mp:187–188℃；1hnmr(400mhz,chloroform-d)δ7.57(d,j＝8.1hz,2h),7.32(d,j＝8.3hz,2h),7.23(m,4h),6.92(d,j＝8.4hz,3h),6.77m,1h),6.04(s,1h),4.30(d,j＝17.3hz,1h),3.55(d,j＝17.2hz,1h),2.42(d,j＝16.4hz,1h),2.28(d,j＝3.7hz,2h),2.12(d,j＝16.4hz,1h),1.05(d,j＝5.0hz,6h)；13cnmr(101mhz,cdcl3)δ194.28,154.58,147.58,144.77,137.15,135.15,132.12,130.51,129.25,128.47,127.11,126.11,124.36,122.73,119.74,107.43,80.93,50.09,41.69,40.37,33.22,28.89,27.80。实施例322,3,4,6,7,8-八氢-7,7-二甲基-1-(4-甲氧苯基)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-chlorophenyl)-1-(4-methoxyphenyl)-7,7-dimethyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物40)，78％yield,wh-itesolid,mp:188–189℃；1hnmr(400mhz,chloroform-d)δ7.56(d,j＝8.5hz,2h),7.32(d,j＝8.4hz,2h),7.26–7.19(m,2h),7.03–6.92(m,2h),6.81(d,j＝1.6hz,4h),6.01(s,1h),4.33(d,j＝17.0hz,1h),3.81(s,3h),3.53(d,j＝17.0hz,1h),2.25(d,j＝20.2hz,3h),2.13(d,j＝16.7hz,1h),1.03(d,j＝16.8hz,6h)；13cnmr(101mhz,cdcl3)δ193.65,158.57,156.47,147.77,137.38,135.93,131.92,129.20,128.63,128.06,126.05,122.51,119.98,114.73,104.78,81.48,55.43,49.85,41.38,39.71,32.77,28.53,28.27。实施例332,3,4,6,7,8-八氢-7,7-二甲基-1-(2-萘)-3-(4-氯苯基)-2-(4-溴苯基)-1h-喹唑啉-5-酮(2-(4-bromophenyl)-3-(4-chlorophenyl)-7,7-dimethyl-1-(naphthalen-2-yl)-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物42)，74％yield,brownsolid,mp:176–177℃；1hnmr(400mhz,chloroform-d)δ7.89–7.83(m,1h),7.80(d,j＝8.7hz,1h),7.76–7.70(m,1h),7.60(d,j＝8.5hz,2h),7.53(d,j＝9.3hz,2h),7.44–7.37(m,3h),7.21(d,j＝9.0hz,2h),6.97(t,j＝9.0hz,3h),6.17(s,1h),4.37(d,j＝17.2hz,1h),3.61(d,j＝17.2hz,1h),2.46(d,j＝16.5hz,1h),2.30(s,2h),2.20(d,j＝16.5hz,1h),1.04(s,6h).13cnmr(101mhz,cdcl3)δ194.09,155.53,147.79,140.94,137.57,133.44,132.07,131.80,129.66,129.23,128.69,127.72,127.67,127.09,126.59,126.06,124.71,124.10,122.63,119.84,106.45,81.10,50.12,41.86,40.42,33.15,28.84,27.95。实施例342,3,4,6,7,8-八氢-7,7-二甲基-2-(4-(二苯氨基)苯基)-1,3-二(4-溴苯基)-1h-喹唑啉-5-酮(1,3-bis(4-bromophenyl)-2-(4-(diphenylamino)phenyl)-7,7-dimethyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物45)，75％yield,yellowsolid,mp:102–103℃；1hnmr(400mhz,chloroform-d)δ7.45(d,j＝8.7hz,4h),7.38–7.29(m,5h),7.27–7.19(m,4h),7.20–6.96(m,6h),6.84(m,3h),6.03(s,1h),4.33(d,j＝17.1hz,1h),3.67(d,j＝17.1hz,1h),2.45–2.19(m,3h),2.08(d,j＝16.3hz,1h),1.10–0.86(m,6h)。实施例352,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-羟基苯基)-1h-喹唑啉-5-酮(2-(4-hydroxyphenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物49)，68％yield,whitesolid,mp:179–180℃；1hnmr(400mhz,cdcl3)δ＝8.05(s,1h),7.35–7.22(m,7h),7.04(t,j＝6.9hz,2h),6.99–6.84(m,5h),6.11(s,1h),4.44(d,j＝16.8hz,1h),3.69(d,j＝16.8hz,1h),2.37–2.27(m,3h),2.16(d,j＝16.8hz,1h),1.04(d,j＝11.3hz,6h)。实施例362,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-甲氧基基苯基)-1h-喹唑啉-5-酮(2-(4-methoxyphenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物50)，71％yield,whitesolid,mp:169–170℃；1hnmr(400mhz,cdcl3)δ＝7.40(d,j＝8.6hz,2h),7.28(m,5h),7.04(d,j＝8.2hz,2h),7.00–6.86(m,5h),6.16(s,1h),4.40(d,j＝16.9hz,1h),3.85(s,3h),3.64(d,j＝16.9hz,1h),2.37(d,j＝16.5hz,1h),2.28(s,2h),2.15(d,j＝16.5hz,1h),1.05(d,j＝10.1hz,6h)。实施例372,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(3,5-二甲氧基-4-羟基苯基)-1h-喹唑啉-5-酮(2-(4-hydroxy-3,5-dimethoxyphenyl)-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物52)，61％yield,whitesolid,mp:194–195℃；1hnmr(400mhz,cdcl3)δ＝7.32(m,2h),7.28–7.21(m,3h),7.09–6.88(m,5h),6.73(s,2h),6.13(s,1h),5.62(s,1h),4.42(d,j＝16.9hz,1h),3.87(s,6h),3.71(d,j＝16.9hz,1h),2.44(d,j＝16.4hz,1h),2.32(d,j＝16.5hz,1h),2.24(d,j＝16.5hz,1h),2.09(d,j＝16.4hz,1h),1.06(d,j＝16.0hz,6h)。实施例382,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯-2-(2-噻吩)-1h-喹唑啉-5-酮(7,7-dimethyl-1,3-diphenyl-2-(thiophen-2-yl)-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物53)，,80％yield,argenteoussolid；mp:164–165℃；1hnmr(400mhz,cdcl3)δ＝7.31(m,6h),7.11–7.02(m,4h),7.02–6.97(m,2h),6.94(t,j＝7.3hz,1h),6.35(s,1h),4.40(d,j＝16.7hz,1h),3.88(d,j＝16.7hz,1h),2.34(d,j＝16.5hz,1h),2.29(s,2h),2.11(d,j＝16.5hz,1h),1.05(d,j＝5.1hz,6h)。实施例392,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-三氟甲基苯基)-1h-喹唑啉-5-酮(7,7-dimethyl-1,3-diphenyl-2-(4-(trifluoromethyl)phenyl)-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物54)，84％yield,whitesolid；mp:192–193℃；1hnmr(400mhz,cdcl3)δ＝7.70(d,j＝8.3hz,2h),7.63(d,j＝8.3hz,2h),7.36–7.23(m,5h),7.04(d,j＝8.1hz,2h),6.97(t,j＝7.3hz,1h),6.91(d,j＝7.3hz,2h),6.21(s,1h),4.41(d,j＝17.2hz,1h),3.55(d,j＝17.2hz,1h),2.40(d,j＝16.5hz,1h),2.29(s,2h),2.17(d,j＝16.5hz,1h),1.06(d,j＝4.8hz,6h)。实施例404-(2-(1,2,3,4,5,6,7,8-八氢-7,7-二甲基-1,3-二苯基)喹唑啉-5-酮)苯氰(4-(7,7-dimethyl-5-oxo-1,3-diphenyl-1,2,3,4,5,6,7,8-octahydroquinazolin-2-yl)benzonitrile化合物55)，74％yield,whitesolid,mp:184–185℃；1hnmr(400mhz,cdcl3)δ＝7.78–7.68(m,2h),7.60(d,j＝8.1hz,2h),7.28(m,5h),7.05–6.80(m,5h),6.16(s,1h),4.37(d,j＝17.3hz,1h),3.49(d,j＝17.3hz,1h),2.35(d,j＝16.5hz,1h),2.26(s,2h),2.14(d,j＝16.5hz,1h),1.02(d,j＝1.2hz,6h)。实施例412,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-(4-硝基苯基)-1h-喹唑啉-5-酮(7,7-dimethyl-2-(4-nitrophenyl)-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物56)。65％yield,yellowsolid,mp:182–183℃；1hnmr(400mhz,cdcl3)δ＝8.35–8.25(m,2h),7.69(d,j＝8.4hz,2h),7.36–7.26(m,5h),7.07–6.86(m,5h),6.23(s,1h),4.41(d,j＝17.3hz,1h),3.52(d,j＝17.3hz,1h),2.39(d,j＝16.6hz,1h),2.29(s,2h),2.18(d,j＝16.6hz,1h),1.06(d,j＝4.5hz,6h)。实施例422,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-正丁基-1h-喹唑啉-5-酮(2-butyl-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物57).85％yield,whitesolid,mp:110–111℃；1hnmr(400mhz,cdcl3)δ＝7.42–7.22(m,5h),7.08–6.75(m,5h),5.02(m,1h),4.50(d,j＝17.1hz,1h),4.05(d,j＝17.1hz,1h),2.32(d,j＝16.4hz,1h),2.23(d,j＝16.4hz,1h),2.14–2.00(m,2h),1.91–1.75(m,2h),1.62–1.46(m,1h),1.45–1.25(m,3h),0.93(m,9h)。实施例432,3,4,6,7,8-八氢-7,7-二甲基-1,3-二苯基-2-异丙基-1h-喹唑啉-5-酮(2-isopropyl-7,7-dimethyl-1,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物58).83％yield,whitesolid；mp:135–136℃；1hnmr(400mhz,cdcl3)δ＝7.26(m,2h),7.18(m,3h),6.82(m,5h),4.66(d,j＝9.8hz,1h),4.36(d,j＝17.1hz,1h),4.04(d,j＝17.1hz,1h),2.47–2.20(m,3h),2.08(m,2h),1.13(d,j＝6.7hz,3h),0.98(m,9h)。实施例442,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-(4-溴苯基)-1h-喹唑啉-5-酮(3-(4-bromophenyl)-7,7-dimethyl-1,2-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物59)，82％yield,whitesolid；mp:169–170℃；1hnmr(400mhz,cdcl3)δ＝7.50–7.24(m,10h),7.03–6.86(m,4h),6.14(d,j＝1.2hz,1h),4.34(d,j＝17.0hz,1h),3.60(d,j＝17.0hz,1h),2.38(d,j＝16.5hz,1h),2.28(s,2h),2.17(d,j＝16.5hz,1h),1.05(d,j＝9.2hz,6h)。实施例452,3,4,6,7,8-八氢-7,7-二甲基-1,2,3-三(4-溴苯基)-1h-喹唑啉-5-酮(1,2,3-tris(4-bromophenyl)-7,7-dimethyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物60).66％yield,whitesolid,mp:178–179℃；1hnmr(400mhz,cdcl3)δ＝7.56(ppm)(d,j＝8.5hz,2h),7.45(d,j＝8.7hz,2h),7.39–7.29(m,4h),6.86(d,j＝8.9hz,2h),6.78(d,j＝8.6hz,2h),6.02(s,1h),4.30(d,j＝17.2hz,1h),3.54(d,j＝17.2hz,1h),2.38(d,j＝16.5hz,1h),2.27(d,j＝1.5hz,2h),2.11(d,j＝16.5hz,1h),1.04(s,6h)实施例462,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-(4-甲氧基苯基)-1h-喹唑啉-5-酮(3-(4-methoxyphenyl)-7,7-dimethyl-1,2-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物61).80％yield,whitesolid,mp:134–135℃；1hnmr(400mhz,cdcl3)δ＝7.56–7.33(m,5h),7.31–7.20(m,3h),7.07–6.97(m,2h),6.95–6.74(m,4h),6.02(s,1h),4.27(d,j＝17.1hz,1h),3.80(s,3h),3.59(d,j＝17.1hz,1h),2.44–2.23(m,3h),2.17(d,j＝16.4hz,1h),1.03(t,j＝17.8hz,6h)。实施例472,3,4,6,7,8-八氢-7,7-二甲基-2,3-二苯基-1-(1-萘)-1h-喹唑啉-5-酮(7,7-dimethyl-1-(naphthalen-1-yl)-2,3-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物62)，74％yield,whitesolid,mp:191–192℃；1hnmr(400mhz,cdcl3)δ＝7.89(d,j＝8.2hz,1h),7.84(d,j＝8.2hz,1h),7.50(t,j＝7.5hz,1h),7.47–7.23(m,10h),7.21(d,j＝7.2hz,1h),7.09(d,j＝8.0hz,2h),6.97(t,j＝7.3hz,1h),6.11(s,1h),4.54(d,j＝16.4hz,1h),3.76(d,j＝16.4hz,1h),2.39(d,j＝16.3hz,1h),2.31(d,j＝16.3hz,1h),2.25(d,j＝16.9hz,1h),1.85(d,j＝16.9hz,1h),1.02(s,3h),0.95(s,3h)。实施例482,3,4,6,7,8-八氢-7,7-二甲基-1-(4-苯氨基苯基)-2,3-二苯基-1h-喹唑啉-5-酮(7,7-dimethyl-2,3-diphenyl-1-(4-(phenylamino)phenyl)-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物63)，70％yield,yellowsolid,mp:192–193℃；1hnmr(400mhz,cdcl3)δ＝7.57–7.20(m,9h),7.16–6.84(m,8h),6.78(d,j＝8.4hz,2h),6.17(s,1h),5.84(s,1h),4.41(d,j＝16.9hz,1h),3.60(d,j＝16.9hz,1h),2.38–2.15(m,4h),1.06(d,j＝20.1hz,6h)。实施例492,3,4,6,7,8-八氢-7,7-二甲基-1,2-二苯基-3-苄基-1h-喹唑啉-5-酮(3-benzyl-7,7-dimethyl-1,2-diphenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物64).72％yield,whitesolid,mp:102–103℃；1hnmr(400mhz,cdcl3)δ＝7.56–6.93(m,15h),5.19(s,1h),3.91(s,2h),3.64(d,j＝17.1hz,1h),3.37(d,j＝17.1hz,1h),2.61(d,j＝16.4hz,1h),2.33(d,j＝16.8hz,1h),2.26(d,j＝16.8,1h),2.25(d,j＝16.4,1h),1.12(d,j＝24.5hz,6h)。实施例502,3,4,6,7,8-八氢-7,7-二甲基-2-苯基-1,3-二苄基-1h-喹唑啉-5-酮(1,3-dibenzyl-7,7-dimethyl-2-phenyl-2,3,4,6,7,8-hexahydroquinazolin-5(1h)-one化合物65).67％yield,whitesolid,mp:157–158℃；1hnmr(400mhz,cdcl3)δ＝7.52–7.06(m,15h),4.86(d,j＝16.7hz,2h),3.99(d,j＝16.7hz,1h),3.74(d,j＝13.5hz,1h),3.63(m,2h),3.25(d,j＝16.4hz,1h),2.69(d,j＝16.2hz,1h),2.58(d,j＝16.2hz,1h),2.35(d,j＝16.3hz,1h),2.28(d,j＝16.3hz,1h),1.23(d,j＝23.3hz,6h)。结果检测利用ldh法对本发明所述的八氢喹唑啉-5-酮衍生物作为制备治疗由登革病毒引发的各种疾病的药物用途的药理研究。ldh法原理：乳酸脱氢酶(ldh)在胞质内含量非常高，细胞处于正常状态下其不能通过细胞膜，但当细胞受到损伤或死亡时便可释放到细胞外，此时细胞培养液中ldh的活性与细胞的死亡数目成正比，通过比色法测定并与靶细胞对照孔的ldh活性进行比较，可计算出效应细胞对靶细胞的杀伤百分数，进而通过计算可得化合物对登革病毒的抑制活性。ldh法实验步骤：bhk-21细胞以每孔1×104个细胞铺在96孔板中。等细胞贴壁后，pbs洗两次，加入2型登革病毒液在37℃中孵育1小时。随后用pbs洗掉没有吸附的病毒，再加入维持培养基配置的相应浓度的化合物，在37℃5％co2中培养到96小时。收取培养上清，按照乳酸脱氢酶试剂盒操作步骤检测ldh含量。在显微镜下观察细胞形态，并拍照。按下列公式计算细胞生长抑制率：抑制率＝[(ac-as)/(ac-ab)]×100％ac：病毒孔(感染病毒，无药物)ab：空白孔(未感染病毒)as：实验孔(感染病毒，含有药物)根据药物在不同剂量下对细胞增殖的抑制率，通过graphpadprism5软件计算出ec50值(表2)。实施例1～50的化合物对登革病毒的抑制作用如表2和表3所示，可知该类化合物对感染2型登革病毒的细胞有较好的抑制作用。表1.化合物1-34作用于登革病毒的ec50值实施例ec50(μm)实施例ec50(μm)实施例ec50(μm)15.96133.87241.8422.85143.24251.9831.31152.64265.5543.88161.33275.3351.32172.33281.7762.83181.25-2.5292.6472.61191.38304.3385.03204.73315.692.63214.02322.6102.52221.853313.49118.61235.42344.76123.6表2.化合物35-50作用于登革病毒的抑制率上述结果表明，本发明保护的化合物具有良好的抗登革病毒作用，而且通过本发明的合成方法可以高效、简便、原子经济、能实现产物结构多样性和复杂性的来合成这一类化合物，易于实现产业化，具有广泛的应用价值。当前第1页12