丁丙诺啡类似物,申请号CN201180045077.5-传众专利搜索

发明名称	丁丙诺啡类似物
摘要	本发明涉及如下所示式(I)、式(IA)或式(IB)的丁丙诺啡类似物化合物，其中R<sup>1</sup>、R<sup>2</sup>、R<sup>8</sup>、R<sup>3a</sup>、R<sup>3b</sup>、G、X、Z和Y如本文中所定义。本发明化合物可用于治疗疼痛、便秘、以及可被阿片样受体和ORL-1受体之活性所调节的其他病症。<img file="DDA00002937865700011.GIF" wi="1752" he="1100" />
申请公布号	CN103154000A	申请公布日期	2013.06.12
申请号	CN201180045077.5	申请日期	2011.09.20
申请人	普渡制药公司	发明人	唐纳德·J·凯尔;莱基·塔费塞
分类号	C07D489/12(2006.01)I;A61K31/485(2006.01)I;A61P25/04(2006.01)I	主分类号	C07D489/12(2006.01)I
代理机构	北京集佳知识产权代理有限公司 11227	代理人	彭鲲鹏;顾晋伟
主权项	1.式I的化合物，或其可药用盐、前药或溶剂合物：<img file="FDA00002937865400011.GIF" wi="1169" he="828" />其中R<sup>1</sup>选自氢、-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>12</sub>)烯基、-(C<sub>2</sub>-C<sub>12</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、苯基和苄基；其任一个任选地被1、2、或3个独立地选自以下的取代基所取代：-(C<sub>1</sub>-C<sub>6</sub>)烷基、OH、卤素、-C(卤素)<sub>3</sub>、-CH(卤素)<sub>2</sub>、-CH<sub>2</sub>(卤素)、-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-COOR<sup>7</sup>、NH<sub>2</sub>、-NH(C<sub>1</sub>-C<sub>6</sub>)烷基、-NR<sup>9</sup>R<sup>10</sup>、-CN、-CONR<sup>9</sup>R<sup>10</sup>、<sub>-</sub>NR<sup>9</sup>COR<sup>10</sup>、-SR<sup>11</sup>、-(5至12元)碳环、-(5至12元)杂环、苯基、和苄基；R<sup>2</sup>和R<sup>8</sup>各自独立地为氢、-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>12</sub>)烯基、-(C<sub>2</sub>-C<sub>12</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(CH<sub>2</sub>CH<sub>2</sub>O)<sub>s</sub>-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH<sub>2</sub>、-NH(C<sub>1</sub>-C<sub>6</sub>)烷基、CN、-CONR<sup>5</sup>R<sup>6</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-NR<sup>5</sup>R<sup>6</sup>、-COOR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>6</sub>-C<sub>14</sub>)双环烷基、((C<sub>6</sub>-C<sub>14</sub>)双环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>8</sub>-C<sub>20</sub>)三环烷基、((C<sub>8</sub>-C<sub>20</sub>)三环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>7</sub>-C<sub>14</sub>)双环烯基、((C<sub>7</sub>-C<sub>14</sub>)双环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>8</sub>-C<sub>20</sub>)三环烯基、((C<sub>8</sub>-C<sub>20</sub>)三环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环系统、((7至12元)双环系统)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环芳基、((7至12元)双环芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环杂环、((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、苯基、苄基或萘基；其各自任选地被1或2个独立地选自以下的取代基所取代：-OH、(＝O)、卤素、-C(卤素)<sub>3</sub>、-CH(卤素)<sub>2</sub>、-CH<sub>2</sub>(卤素)、-(C<sub>1</sub>-C<sub>6</sub>)烷基、卤素(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>2</sub>-C<sub>6</sub>)烯基、-(C<sub>2</sub>-C<sub>6</sub>)炔基、羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、二羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基、((C<sub>1</sub>-C<sub>6</sub>)烷氧基)CO(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、苯基、苄基、-NH<sub>2</sub>、-NH(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>1</sub>-C<sub>6</sub>)烷基-NH(C<sub>1</sub>-C<sub>6</sub>)烷基-R<sup>14</sup>、-CN、-SH、-OR<sup>4</sup>、-CONR<sup>5</sup>R<sup>6</sup>、-(C<sub>1</sub>-C<sub>6</sub>烷基)-CO-NR<sup>5</sup>R<sup>6</sup>、-COOR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(CH<sub>2</sub>CH<sub>2</sub>O)<sub>s</sub>-(C<sub>1</sub>-C<sub>6</sub>)烷基、((C<sub>1</sub>-C<sub>6</sub>)烷基)磺酰基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-NH-SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基、-N(SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基)<sub>2</sub>、-C(＝NH)NH<sub>2</sub>、-NH-CO-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-CO-NH<sub>2</sub>、-NH-C(＝O)-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-C(＝O)-(5至12元)芳基、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-(5至12元)芳基、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-CH(NH<sub>2</sub>)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、-(5至12元)芳氧基、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基C(O)NR<sup>5</sup>R<sup>6</sup>、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基C(O)-NR<sup>5</sup>R<sup>6</sup>、-C(O)NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环杂环、和((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；R<sup>3a</sup>和R<sup>3b</sup>各自独立地选自氢、-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>10</sub>)烯基、-(C<sub>2</sub>-C<sub>10</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、OH、羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-C(卤素)<sub>3</sub>、-CH(卤素)<sub>2</sub>、-CH<sub>2</sub>(卤素)、-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CN、-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-，或一起形成(＝O)；R<sup>4</sup>选自-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>2</sub>-C<sub>6</sub>)烯基、-(C<sub>2</sub>-C<sub>6</sub>)炔基、-C(卤素)<sub>3</sub>、-CH(卤素)<sub>2</sub>、-CH<sub>2</sub>(卤素)、羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>6</sub>-C<sub>14</sub>)双环烷基、((C<sub>6</sub>-C<sub>14</sub>)双环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>8</sub>-C<sub>20</sub>)三环烷基、((C<sub>8</sub>-C<sub>20</sub>)三环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>7</sub>-C<sub>14</sub>)双环烯基、((C<sub>7</sub>-C<sub>14</sub>)双环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>8</sub>-C<sub>20</sub>)三环烯基、((C<sub>8</sub>-C<sub>20</sub>)三环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环杂环、或((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；R<sup>5</sup>和R<sup>6</sup>各自独立地为氢、-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>3</sub>-C<sub>8</sub>)环烷基、((C<sub>3</sub>-C<sub>8</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-COOR<sup>7</sup>、-(C<sub>广</sub>C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-CONH<sub>2</sub>、或(C<sub>广</sub>C<sub>6</sub>)烷基-CONH-，或R<sup>5</sup>和R<sup>6</sup>与它们所相连的氮原子一起形成(4至8元)杂环；R<sup>7</sup>选自氢、-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>2</sub>-C<sub>6</sub>)烯基、-(C<sub>2</sub>-C<sub>6</sub>)炔基、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、或((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；R<sup>9</sup>和R<sup>10</sup>各自独立地选自氢、-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>2</sub>-C<sub>6</sub>)烯基、-(C<sub>2</sub>-C<sub>6</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、-(C<sub>3</sub>-C<sub>12</sub>)环烯基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、或((C<sub>3</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；各个R<sup>11</sup>独立地选自氢、-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>10</sub>)烯基、-(C<sub>2</sub>-C<sub>10</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、((C<sub>1</sub>-C<sub>6</sub>)烷基)磺酰基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、或((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；R<sup>12</sup>和R<sup>13</sup>各自独立地选自氢、-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>12</sub>)烯基、-(C<sub>2</sub>-C<sub>12</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>6</sub>-C<sub>14</sub>)双环烷基、((C<sub>6</sub>-C<sub>14</sub>)双环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>8</sub>-C<sub>20</sub>)三环烷基、((C<sub>8</sub>-C<sub>20</sub>)三环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>7</sub>-C<sub>14</sub>)双环烯基、((C<sub>7</sub>-C<sub>14</sub>)双环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>8</sub>-C<sub>20</sub>)三环烯基、((C<sub>8</sub>-C<sub>20</sub>)三环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)(C<sub>1-</sub>C<sub>6</sub>)烷基-、-(7至12元)双环系统、((7至12元)双环系统)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环芳基、((7至12元)双环芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环杂环、((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、苯基、苄基或萘基；其各自任选地被1或2个独立地选自以下的取代基所取代：OH、(＝O)、卤素、-C(卤素)<sub>3</sub>、-CH(卤素)<sub>2</sub>、-CH<sub>2</sub>(卤素)、-(C<sub>1</sub>-C<sub>6</sub>)烷基、卤素(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>2</sub>-C<sub>6</sub>)烯基、-(C<sub>2</sub>-C<sub>6</sub>)炔基、羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、苯基、苄基、NH<sub>2</sub>、-NH(C<sub>1</sub>-C<sub>6</sub>)烷基、CN、SH、OR<sup>4</sup>、-CONR<sup>5</sup>R<sup>6</sup>、-COOR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环杂环、和((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；R<sup>14</sup>选自-COOR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-CONH<sub>2</sub>、或(C<sub>1</sub>-C<sub>6</sub>)烷基-CONH-；G选自O、-OCO-、-C(＝O)、NR<sup>9</sup>、NR’、S、SO、或SO<sub>2</sub>；R’是-C(＝O)(C<sub>1</sub>-C<sub>6</sub>)烷基或-SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基；X选自OH、羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、二羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、卤素、-NH<sub>2</sub>、-NR<sup>2</sup>(C＝O)R<sup>12</sup>、-CONR<sup>12</sup>R<sup>13</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CONH<sub>2</sub>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOH、-COOH、-O-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOH、-O-(C<sub>1-</sub>C<sub>6</sub>)烷基-CONH<sub>2</sub>、-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>10</sub>)烯基、-(C<sub>2</sub>-C<sub>10</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-OH、-(CH<sub>2</sub>)<sub>p</sub>CHOHCH<sub>2</sub>OH、CN、-NH-SO<sub>2</sub>R<sup>9</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、-(7至12元)双环杂环、((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、或((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-；Q选自OH、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、-(5至12元)芳基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(CH<sub>2</sub>CH<sub>2</sub>O)<sub>s</sub>-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-OH、-O(C＝O)R<sup>9</sup>、-O-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-O-C(O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(O)OR<sup>7</sup>、-NH-C(O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(O)OR<sup>7</sup>、-O-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(O)NR<sup>9</sup>R<sup>10</sup>、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(O)NR<sup>9</sup>R<sup>10</sup>、-O-C(O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(O)NR<sup>9</sup>R<sup>10</sup>、-NH-C(O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(O)NR<sup>9</sup>R<sup>10</sup>或R<sup>14</sup>；Z是-(CH<sub>2</sub>)<sub>m</sub>-，其任选地被1或2个-(C<sub>1</sub>-C<sub>6</sub>)烷基所取代；Y是-(CH<sub>2</sub>)<sub>n</sub>-CH或直接的键，条件是：当Y是直接的键时，则R<sup>8</sup>不存在；m是整数1、2、3、4、5、或6；n是整数0、1、2、3、4、5或6；p是整数0、1或2；s是整数1、2、3、4、5、6、7、8、9、10、11、12、或13；条件是：当X是OH或-(C<sub>1</sub>-C<sub>6</sub>)烷氧基，Q是OMe，Z未被取代，和G是O时，则为以下任一个：<sub>a</sub>)R<sup>1</sup>选自：i.氢、或(C<sub>1</sub>-C<sub>10</sub>)烷氧基或四唑基-(C<sub>1</sub>-C<sub>6</sub>)烷基，其任一个任选地被1、2、或3个独立地选自以下的取代基所取代：-(C<sub>1</sub>-C<sub>6</sub>)烷基、OH、卤素、-C(卤素)<sub>3</sub>、-CH(卤素)<sub>2</sub>、-CH<sub>2</sub>(卤素)、-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-COOR<sup>7</sup>、NH<sub>2</sub>、-NH(C<sub>1</sub>-C<sub>6</sub>)烷基、NR<sup>9</sup>R<sup>10</sup>、CN、-CONR<sup>9</sup>R<sup>10</sup>、-NR<sup>9</sup>COR<sup>10</sup>、SR<sup>11</sup>、-(5至12元)碳环、-(5至12元)杂环、苯基、和苄基；或ii.-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>12</sub>)烯基、-(C<sub>2</sub>-C<sub>12</sub>)炔基、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((3至12元)杂环)-、(5至12元)杂芳基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、(3至12元)杂环-(C<sub>1</sub>-C<sub>6</sub>)烷基-、苯基、或苄基；其各自被1、2、或3个独立地选自-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-COOR<sup>7</sup>、NR<sup>9</sup>R<sup>10</sup>、-CONR<sup>9</sup>R<sup>10</sup>、-NR<sup>9</sup>COR<sup>10</sup>、和SR<sup>11</sup>的取代基所取代，条件是：NR<sup>9</sup>R<sup>10</sup>不是NH<sub>2</sub>或-NH(C<sub>1</sub>-C<sub>6</sub>)烷基，且SR<sup>11</sup>不是SH；或b)R<sup>2</sup>和R<sup>8</sup>中至少一个选自：i.-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(CH<sub>2</sub>CH<sub>2</sub>O)<sub>s</sub>-(C<sub>1</sub>-C<sub>6</sub>)烷基、或-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>；其各自任选地被1或2个独立地选自以下的取代基所取代：OH、(＝O)、卤素、-C(卤素)<sub>3</sub>、-CH(卤素)<sub>2</sub>、-CH<sub>2</sub>(卤素)、-(C<sub>1</sub>-C<sub>6</sub>)烷基、卤素(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>2</sub>-C<sub>6</sub>)烯基、-(C<sub>2</sub>-C<sub>6</sub>)炔基、羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、二羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基、((C<sub>1</sub>-C<sub>6</sub>)烷氧基)CO(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、苯基、苄基、NH<sub>2</sub>、-NH(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>1</sub>-C<sub>6</sub>)烷基-NH(C<sub>1</sub>-C<sub>6</sub>)烷基-R<sup>14</sup>、CN、SH、OR<sup>4</sup>、-CONR<sup>5</sup>R<sup>6</sup>、-(C<sub>1</sub>-C<sub>6</sub>烷基)-CO-NR<sup>5</sup>R<sup>6</sup>、-COOR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(CH<sub>2</sub>CH<sub>2</sub>O)<sub>s</sub>-(C<sub>1</sub>-C<sub>6</sub>)烷基、((C<sub>1</sub>-C<sub>6</sub>)烷基)磺酰基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-NH-SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基、-N(SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基)<sub>2</sub>、-C(＝NH)NH<sub>2</sub>、-NH-CO-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-CO-NH<sub>2</sub>、-NH-C(＝O)-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-C(＝O)-(5至12元)芳基、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-(5至12元)芳基、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-CH(NH<sub>2</sub>)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、-(5至12元)芳氧基、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基C(O)NR<sup>5</sup>R<sup>6</sup>、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基C(O)-NR<sup>5</sup>R<sup>6</sup>、-C(O)NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环杂环、和((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；或ii.-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、-((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、-(C<sub>6</sub>-C<sub>14</sub>)双环烷基、-(C<sub>8</sub>-C<sub>20</sub>)三环烷基、-(C<sub>7</sub>-C<sub>14</sub>)双环烯基、-(C<sub>8</sub>-C<sub>20</sub>)三环烯基、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环系统、-(7至12元)双环芳基、-(5至12元)杂芳基、-(3至12元)杂环、-(7至12元)双环杂环、苯基、苄基、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>6</sub>-C<sub>14</sub>)双环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>8</sub>-C<sub>20</sub>)三环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>7</sub>-C<sub>14</sub>)双环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>8</sub>-C<sub>20</sub>)三环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((7至12元)双环系统)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((7至12元)双环芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、或萘基；其各自被1或2个独立地选自以下的取代基所取代：-CONHR<sup>6</sup>、二羟基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>1</sub>-C<sub>6</sub>)烷基-NH(C<sub>1</sub>-C<sub>6</sub>)烷基-R<sup>14</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(CH<sub>2</sub>CH<sub>2</sub>O)<sub>s</sub>-(C<sub>1</sub>-C<sub>6</sub>)烷基、((C<sub>1</sub>-C<sub>6</sub>)烷基)磺酰基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-NH-SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基、-N(SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基)<sub>2</sub>、-C(＝NH)NH<sub>2</sub>、-NH-CO-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-CO-NH<sub>2</sub>、-NH-C(＝O)-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-C(＝O)-(5至12元)芳基、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-(5至12元)芳基、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-CH(NH<sub>2</sub>)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基C(O)NR<sup>5</sup>R<sup>6</sup>、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基C(O)-NR<sup>5</sup>R<sup>6</sup>、-C(O)NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(7至12元)双环杂环、和((7至12元)双环杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-；或iii.-(C<sub>1</sub>-C<sub>10</sub>)烷基、-(C<sub>2</sub>-C<sub>12</sub>)烯基、或-(C<sub>2</sub>-C<sub>12</sub>)炔基，其各自被1或2个独立地选自以下的取代基所取代：-CONHR<sup>6</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷基-NH(C<sub>1</sub>-C<sub>6</sub>)烷基-R<sup>14</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>、-(OCH<sub>2</sub>CH<sub>2</sub>)<sub>s</sub>-O(C<sub>1</sub>-C<sub>6</sub>)烷基、-(CH<sub>2</sub>CH<sub>2</sub>O)<sub>s</sub>-(C<sub>1</sub>-C<sub>6</sub>)烷基、((C<sub>1</sub>-C<sub>6</sub>)烷基)磺酰基(C<sub>1</sub>-C<sub>6</sub>)烷基-、-NH-SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基、-N(SO<sub>2</sub>(C<sub>1</sub>-C<sub>6</sub>)烷基)<sub>2</sub>、-C(＝NH)NH<sub>2</sub>、-NH-CO-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-CO-NH<sub>2</sub>、-NH-C(＝O)-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基、-NH-C(＝O)-(5至12元)芳基、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-(5至12元)芳基、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-NH-C(＝O)-CH(NH<sub>2</sub>)-(C<sub>1</sub>-C<sub>6</sub>)烷基-CO-OR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基C(O)NR<sup>5</sup>R<sup>6</sup>、-NH-(C<sub>1</sub>-C<sub>6</sub>)烷基C(O)-NR<sup>5</sup>R<sup>6</sup>、和-C(O)NH-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>；或iv.2，3-二羟基丙基；或v.被1或2个烷基所取代的4-异<img file="FDA00002937865400071.GIF" wi="56" he="55" />唑基、4-异<img file="FDA00002937865400072.GIF" wi="56" he="55" />唑基(C<sub>1</sub>-C<sub>6</sub>)烷基、5-异<img file="FDA00002937865400073.GIF" wi="56" he="55" />唑基、或5-异<img file="FDA00002937865400074.GIF" wi="56" he="55" />唑基(C<sub>1</sub>-C<sub>6</sub>)烷基，或vi.-C(＝O)NH<sub>2</sub>或-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(＝O)NH<sub>2</sub>；或c)R<sup>3a</sup>或R<sup>3b</sup>中至少一个独立地选自-(C<sub>7</sub>-C<sub>10</sub>)烷基、-(C<sub>7</sub>-C<sub>10</sub>)烯基、-(C<sub>7</sub>-C<sub>10</sub>)炔基、-(C<sub>1</sub>-C<sub>10</sub>)烷氧基、-(C<sub>1</sub>-C<sub>6</sub>)烷基-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-C(＝O)-(C<sub>1</sub>-C<sub>6</sub>)烷基、-(C<sub>1</sub>-C<sub>6</sub>)烷基-CN、-(C<sub>1</sub>-C<sub>6</sub>)烷基-COOR<sup>7</sup>、-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-COOR<sup>7</sup>、-(C<sub>3</sub>-C<sub>12</sub>)环烷基、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((C<sub>3</sub>-C<sub>12</sub>)环烷基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(C<sub>4</sub>-C<sub>12</sub>)环烯基、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((C<sub>4</sub>-C<sub>12</sub>)环烯基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)芳基、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((5至12元)芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(5至12元)杂芳基、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、((5至12元)杂芳基)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-、-(3至12元)杂环、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷基-、((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-、或((3至12元)杂环)-(C<sub>1</sub>-C<sub>6</sub>)烷氧基-(C<sub>1</sub>-C<sub>6</sub>)烷基-；或条件是：当X是OH或-(C<sub>1</sub>-C<sub>6</sub>)烷氧基，Q是OMe，R<sup>3a</sup>和R<sup>3b</sup>均是氢，Z被取代，G是O，和Y是直接的键时，则R<sup>2</sup>不是氢。
地址	美国康涅狄格州