作为趋化因子受体活性调节剂的N－脲基杂环烷基－哌啶,申请号CN01812052.0-传众专利搜索

发明名称	作为趋化因子受体活性调节剂的N－脲基杂环烷基－哌啶
摘要	本发明描述了结构式(I)CCR3的调节物，结构式(I)指(I)或其可药用盐形式，可用于防止哮喘和其他变应性疾病。
申请公布号	CN1440402A	申请公布日期	2003.09.03
申请号	CN01812052.0	申请日期	2001.06.29
申请人	布里斯托尔－迈尔斯斯奎布公司	发明人	S·S·科;J·R·普瑞特;D·A·瓦克;D·G·巴特
分类号	C07D403/12;C07D407/12;C07D409/12;C07D211/56;C07D403/14;C07D413/14;C07D417/14;A61K31/4025;A61K31/4427;A61P37/00	主分类号	C07D403/12
代理机构	中国专利代理(香港)有限公司	代理人	赵苏林;马崇德
主权项	1.结构式(I)的化合物：<img file="A0181205200021.GIF" wi="466" he="249" />或其立体异构体或药用盐，其中：M不存在或者选自<chemistry num="901"><chem file="01812052_cml901.xml" /></chemistry>、<chemistry num="902"><chem file="01812052_cml902.xml" /></chemistry>、<chemistry num="903"><chem file="01812052_cml903.xml" /></chemistry>、<chemistry num="904"><chem file="01812052_cml904.xml" /></chemistry>和<chemistry num="905"><chem file="01812052_cml905.xml" /></chemistry>；Q选自<chemistry num="906"><chem file="01812052_cml906.xml" /></chemistry>、<chemistry num="907"><chem file="01812052_cml907.xml" /></chemistry>、<chemistry num="908"><chem file="01812052_cml908.xml" /></chemistry>、<chemistry num="909"><chem file="01812052_cml909.xml" /></chemistry>和<chemistry num="910"><chem file="01812052_cml910.xml" /></chemistry>；J和K独立地选自<chemistry num="911"><chem file="01812052_cml911.xml" /></chemistry>、<chemistry num="912"><chem file="01812052_cml912.xml" /></chemistry>、<chemistry num="913"><chem file="01812052_cml913.xml" /></chemistry>、<chemistry num="914"><chem file="01812052_cml914.xml" /></chemistry>和<chemistry num="915"><chem file="01812052_cml915.xml" /></chemistry>；L选自<chemistry num="916"><chem file="01812052_cml916.xml" /></chemistry>和<chemistry num="917"><chem file="01812052_cml917.xml" /></chemistry>；条件是：当M不存在时，J选自<chemistry num="918"><chem file="01812052_cml918.xml" /></chemistry>、<chemistry num="919"><chem file="01812052_cml919.xml" /></chemistry>、<chemistry num="920"><chem file="01812052_cml920.xml" /></chemistry>和<chemistry num="921"><chem file="01812052_cml921.xml" /></chemistry>；Z选自<chemistry num="922"><chem file="01812052_cml922.xml" /></chemistry>、<chemistry num="923"><chem file="01812052_cml923.xml" /></chemistry>、<chemistry num="924"><chem file="01812052_cml924.xml" /></chemistry>、<chemistry num="925"><chem file="01812052_cml925.xml" /></chemistry>、<chemistry num="926"><chem file="01812052_cml926.xml" /></chemistry>和<chemistry num="927"><chem file="01812052_cml927.xml" /></chemistry>；R<sup>1a</sup>选自<chemistry num="928"><chem file="01812052_cml928.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、<chemistry num="929"><chem file="01812052_cml929.xml" /></chemistry>、<chemistry num="930"><chem file="01812052_cml930.xml" /></chemistry>、<chemistry num="931"><chem file="01812052_cml931.xml" /></chemistry>、<chemistry num="932"><chem file="01812052_cml932.xml" /></chemistry>和(CH<sub>2</sub>)<sub>w</sub>苯基；R<sup>1b</sup>独立地选自<chemistry num="933"><chem file="01812052_cml933.xml" /></chemistry>、C<sub>1-3</sub>烷基、C<sub>3-6</sub>环烷基和苯基；E是<img file="A0181205200022.GIF" wi="721" he="226" />G选自键、<chemistry num="934"><chem file="01812052_cml934.xml" /></chemistry>和<chemistry num="935"><chem file="01812052_cml935.xml" /></chemistry>；环B是5、6或7元饱和杂环环，其中杂环环包括<chemistry num="936"><chem file="01812052_cml936.xml" /></chemistry>、<chemistry num="937"><chem file="01812052_cml937.xml" /></chemistry>、<chemistry num="938"><chem file="01812052_cml938.xml" /></chemistry>、<chemistry num="939"><chem file="01812052_cml939.xml" /></chemistry>、<chemistry num="940"><chem file="01812052_cml940.xml" /></chemistry>、<chemistry num="941"><chem file="01812052_cml941.xml" /></chemistry>、<chemistry num="942"><chem file="01812052_cml942.xml" /></chemistry>、<chemistry num="943"><chem file="01812052_cml943.xml" /></chemistry>、<chemistry num="944"><chem file="01812052_cml944.xml" /></chemistry>、<chemistry num="945"><chem file="01812052_cml945.xml" /></chemistry>、<chemistry num="946"><chem file="01812052_cml946.xml" /></chemistry>或<chemistry num="947"><chem file="01812052_cml947.xml" /></chemistry>，该杂环环任选被0-2个R<sup>8</sup>取代；R<sup>1</sup>和R<sup>2</sup>独立地选自<chemistry num="948"><chem file="01812052_cml948.xml" /></chemistry>、C<sub>1-8</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基和(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基；R<sup>3</sup>选自0-1个R<sup>10</sup>取代的甲基、0-3个R<sup>7</sup>取代的C<sub>2-8</sub>烷基、0-3个R<sup>7</sup>取代的C<sub>3-8</sub>链烯基、0-3个R<sup>7</sup>取代的C<sub>3-8</sub>炔基、C<sub>2</sub>氟代烷基、C<sub>3-8</sub>卤代烷<!-- SIPO <dp n="1"/>-->基、0-5个R<sup>15</sup>取代的(CR<sup>3′</sup>R<sup>3″</sup>)<sub>r</sub>C<sub>3-10</sub>碳环残基以及0-3个R<sup>15</sup>取代的含有1-4个选自<chemistry num="949"><chem file="01812052_cml949.xml" /></chemistry>、<chemistry num="950"><chem file="01812052_cml950.xml" /></chemistry>和<chemistry num="951"><chem file="01812052_cml951.xml" /></chemistry>的杂原子的(CR<sup>3′</sup>R<sup>3″</sup>)<sub>r</sub>-5-10元杂环体系；R<sup>3′</sup>和R<sup>3″</sup>在每种情况下选自<chemistry num="952"><chem file="01812052_cml952.xml" /></chemistry>、C<sub>1-6</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基和苯基；R<sup>4</sup>不存在，与它所结合的氮形成N-氧化物，或者选自C<sub>1-8</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、<chemistry num="953"><chem file="01812052_cml953.xml" /></chemistry>、<chemistry num="954"><chem file="01812052_cml954.xml" /></chemistry>、<chemistry num="955"><chem file="01812052_cml955.xml" /></chemistry>和0-3个R<sup>4c</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基；R<sup>4a</sup>和R<sup>4a′</sup>在每种情况下选自<chemistry num="956"><chem file="01812052_cml956.xml" /></chemistry>、C<sub>1-6</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基和苯基；R<sup>4b</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、C<sub>3-8</sub>炔基和苯基；R<sup>4c</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、C<sub>3-6</sub>环烷基、<chemistry num="957"><chem file="01812052_cml957.xml" /></chemistry>、<chemistry num="958"><chem file="01812052_cml958.xml" /></chemistry>、<chemistry num="959"><chem file="01812052_cml959.xml" /></chemistry>、<chemistry num="960"><chem file="01812052_cml960.xml" /></chemistry>、<chemistry num="961"><chem file="01812052_cml961.xml" /></chemistry>、<chemistry num="962"><chem file="01812052_cml962.xml" /></chemistry>、<chemistry num="963"><chem file="01812052_cml963.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="964"><chem file="01812052_cml964.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、<chemistry num="965"><chem file="01812052_cml965.xml" /></chemistry>和(CH<sub>2</sub>)<sub>r</sub>苯基；R<sup>5</sup>选自0-5个R<sup>16</sup>取代的(CR<sup>5′</sup>R<sup>5″</sup>)<sub>t</sub>C<sub>3-10</sub>碳环残基和0-3个R<sup>16</sup>取代的含有1-4个选自<chemistry num="966"><chem file="01812052_cml966.xml" /></chemistry>、<chemistry num="967"><chem file="01812052_cml967.xml" /></chemistry>和<chemistry num="968"><chem file="01812052_cml968.xml" /></chemistry>的杂原子的(CR<sup>5′</sup>R<sup>5″</sup>)<sub>t</sub>-5-10元杂环体系；R<sup>5′</sup>和R<sup>5″</sup>在每种情况下选自<chemistry num="969"><chem file="01812052_cml969.xml" /></chemistry>、C<sub>1-6</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基和苯基；R<sup>6</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、<chemistry num="970"><chem file="01812052_cml970.xml" /></chemistry>、<chemistry num="971"><chem file="01812052_cml971.xml" /></chemistry>、<chemistry num="972"><chem file="01812052_cml972.xml" /></chemistry>、<chemistry num="973"><chem file="01812052_cml973.xml" /></chemistry>、<chemistry num="974"><chem file="01812052_cml974.xml" /></chemistry>、<chemistry num="975"><chem file="01812052_cml975.xml" /></chemistry>、<chemistry num="976"><chem file="01812052_cml976.xml" /></chemistry>、<chemistry num="977"><chem file="01812052_cml977.xml" /></chemistry>、<chemistry num="978"><chem file="01812052_cml978.xml" /></chemistry>、<chemistry num="979"><chem file="01812052_cml979.xml" /></chemistry>、<chemistry num="980"><chem file="01812052_cml980.xml" /></chemistry>、<chemistry num="981"><chem file="01812052_cml981.xml" /></chemistry>、<chemistry num="982"><chem file="01812052_cml982.xml" /></chemistry>、<chemistry num="983"><chem file="01812052_cml983.xml" /></chemistry>、<chemistry num="984"><chem file="01812052_cml984.xml" /></chemistry>、<chemistry num="985"><chem file="01812052_cml985.xml" /></chemistry>和0-3个R<sup>6c</sup>取代的(CH<sub>2</sub>)<sub>t</sub>苯基；R<sup>6a</sup>和R<sup>6a′</sup>在每种情况下选自<chemistry num="986"><chem file="01812052_cml986.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和0-3个R<sup>6c</sup>取代的苯基；R<sup>6b</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和0-3个R<sup>6c</sup>取代的苯基；R<sup>6c</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、<chemistry num="987"><chem file="01812052_cml987.xml" /></chemistry>、<chemistry num="988"><chem file="01812052_cml988.xml" /></chemistry>、<chemistry num="989"><chem file="01812052_cml989.xml" /></chemistry>、<chemistry num="990"><chem file="01812052_cml990.xml" /></chemistry>、<chemistry num="991"><chem file="01812052_cml991.xml" /></chemistry>、<chemistry num="992"><chem file="01812052_cml992.xml" /></chemistry>、<chemistry num="993"><chem file="01812052_cml993.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="994"><chem file="01812052_cml994.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基和<chemistry num="995"><chem file="01812052_cml995.xml" /></chemistry>；R<sup>6d</sup>在每种情况下选自<chemistry num="996"><chem file="01812052_cml996.xml" /></chemistry>、C<sub>1-6</sub>烷基和C<sub>3-6</sub>环烷基；条件是当J或K中的任何一个是<chemistry num="997"><chem file="01812052_cml997.xml" /></chemistry>并且R<sup>6</sup>是氰基或者是通过杂原子键合到它所结合的碳上时，那么另一个R<sup>6</sup>就不是氰基或者不是通过杂原子键合到它所结合的碳上；R<sup>7</sup>选自<chemistry num="998"><chem file="01812052_cml998.xml" /></chemistry>、<chemistry num="999"><chem file="01812052_cml999.xml" /></chemistry>、<chemistry num="1000"><chem file="01812052_cml1000.xml" /></chemistry>、<chemistry num="1001"><chem file="01812052_cml1001.xml" /></chemistry>、<chemistry num="1002"><chem file="01812052_cml1002.xml" /></chemistry>、<chemistry num="1003"><chem file="01812052_cml1003.xml" /></chemistry>、<chemistry num="1004"><chem file="01812052_cml1004.xml" /></chemistry>、<chemistry num="1005"><chem file="01812052_cml1005.xml" /></chemistry>、<chemistry num="1006"><chem file="01812052_cml1006.xml" /></chemistry>、<chemistry num="1007"><chem file="01812052_cml1007.xml" /></chemistry>、<chemistry num="1008"><chem file="01812052_cml1008.xml" /></chemistry>、<chemistry num="1009"><chem file="01812052_cml1009.xml" /></chemistry>、<chemistry num="1010"><chem file="01812052_cml1010.xml" /></chemistry>、<chemistry num="1011"><chem file="01812052_cml1011.xml" /></chemistry>、<chemistry num="1012"><chem file="01812052_cml1012.xml" /></chemistry>、<chemistry num="1013"><chem file="01812052_cml1013.xml" /></chemistry>、<chemistry num="1014"><chem file="01812052_cml1014.xml" /></chemistry>、<chemistry num="1015"><chem file="01812052_cml1015.xml" /></chemistry>、<chemistry num="1016"><chem file="01812052_cml1016.xml" /></chemistry>、<!-- SIPO <dp n="2"/>--><chemistry num="1017"><chem file="01812052_cml1017.xml" /></chemistry>、C<sub>1-6</sub>卤代烷基；R<sup>7a</sup>和R<sup>7a′</sup>在每种情况下选自<chemistry num="1018"><chem file="01812052_cml1018.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-5个R<sup>7a</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-2个R<sup>7e</sup>取代的含有1-4个选自<chemistry num="1019"><chem file="01812052_cml1019.xml" /></chemistry>、<chemistry num="1020"><chem file="01812052_cml1020.xml" /></chemistry>和<chemistry num="1021"><chem file="01812052_cml1021.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-10元杂环体系；或者，R<sup>7a</sup>和R<sup>7a′</sup>，同它们所结合的<chemistry num="1022"><chem file="01812052_cml1022.xml" /></chemistry>一起结合成含有1-2个选自<chemistry num="1023"><chem file="01812052_cml1023.xml" /></chemistry>、<chemistry num="1024"><chem file="01812052_cml1024.xml" /></chemistry>和<chemistry num="1025"><chem file="01812052_cml1025.xml" /></chemistry>的杂原子并且任选与苯环或6-元芳香杂环稠合的5-6元杂环体系；R<sup>7b</sup>在每种情况下选自<chemistry num="1026"><chem file="01812052_cml1026.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-3个R<sup>7e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>碳环残基和0-2个R<sup>7e</sup>取代的含有1-4个选自<chemistry num="1027"><chem file="01812052_cml1027.xml" /></chemistry>、<chemistry num="1028"><chem file="01812052_cml1028.xml" /></chemistry>和<chemistry num="1029"><chem file="01812052_cml1029.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>7d</sup>在每种情况下选自C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、甲基、<chemistry num="1030"><chem file="01812052_cml1030.xml" /></chemistry>、0-3个R<sup>7e</sup>取代的C<sub>2-6</sub>烷基、0-3个R<sup>7e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-3个R<sup>7e</sup>取代的含有1-4个选自<chemistry num="1031"><chem file="01812052_cml1031.xml" /></chemistry>、<chemistry num="1032"><chem file="01812052_cml1032.xml" /></chemistry>和<chemistry num="1033"><chem file="01812052_cml1033.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>7e</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、C(O)C<sub>1-6</sub>烷基、C(O)OC<sub>1-6</sub>烷基、<chemistry num="1034"><chem file="01812052_cml1034.xml" /></chemistry>、<chemistry num="1035"><chem file="01812052_cml1035.xml" /></chemistry>、<chemistry num="1036"><chem file="01812052_cml1036.xml" /></chemistry>、<chemistry num="1037"><chem file="01812052_cml1037.xml" /></chemistry>、<chemistry num="1038"><chem file="01812052_cml1038.xml" /></chemistry>、<chemistry num="1039"><chem file="01812052_cml1039.xml" /></chemistry>、<chemistry num="1040"><chem file="01812052_cml1040.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="1041"><chem file="01812052_cml1041.xml" /></chemistry>、<chemistry num="1042"><chem file="01812052_cml1042.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、<chemistry num="1043"><chem file="01812052_cml1043.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>苯基和0-1个R<sup>7a</sup>取代的杂环，其中杂环选自咪唑、噻唑、噁唑、吡唑、1，2，4-三唑、1，2，3-三唑、异噁唑和四唑；R<sup>7f</sup>在每种情况下选自<chemistry num="1044"><chem file="01812052_cml1044.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和苯基；R<sup>7g</sup>选自甲基、乙基、乙酰基和<chemistry num="1045"><chem file="01812052_cml1045.xml" /></chemistry>；R<sup>7h</sup>选自<chemistry num="1046"><chem file="01812052_cml1046.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、(CH<sub>2</sub>)<sub>r</sub>苯基、<chemistry num="1047"><chem file="01812052_cml1047.xml" /></chemistry>、<chemistry num="1048"><chem file="01812052_cml1048.xml" /></chemistry>和<chemistry num="1049"><chem file="01812052_cml1049.xml" /></chemistry>；R<sup>7i</sup>在每种情况下选自<chemistry num="1050"><chem file="01812052_cml1050.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基；R<sup>8</sup>选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、C<sub>1-6</sub>卤代烷基、0-3个R<sup>8c</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-2个R<sup>8c</sup>取代的含有1-4个选自<chemistry num="1051"><chem file="01812052_cml1051.xml" /></chemistry>、<chemistry num="1052"><chem file="01812052_cml1052.xml" /></chemistry>和<chemistry num="1053"><chem file="01812052_cml1053.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-10元杂环体系；R<sup>8a</sup>在每种情况下选自<chemistry num="1054"><chem file="01812052_cml1054.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、0-5个R<sup>8e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-3个R<sup>8e</sup>取代的含有1-4个选自<chemistry num="1055"><chem file="01812052_cml1055.xml" /></chemistry>、<chemistry num="1056"><chem file="01812052_cml1056.xml" /></chemistry>和<chemistry num="1057"><chem file="01812052_cml1057.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-10元杂环体系；R<sup>8b</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-2个R<sup>8e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>碳环残基和0-3个R<sup>8e</sup>取代的含有1-4个选自<chemistry num="1058"><chem file="01812052_cml1058.xml" /></chemistry>、<chemistry num="1059"><chem file="01812052_cml1059.xml" /></chemistry>和<chemistry num="1060"><chem file="01812052_cml1060.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；<!-- SIPO <dp n="3"/>-->R<sup>8c</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、<chemistry num="1061"><chem file="01812052_cml1061.xml" /></chemistry>、<chemistry num="1062"><chem file="01812052_cml1062.xml" /></chemistry>、<chemistry num="1063"><chem file="01812052_cml1063.xml" /></chemistry>、<chemistry num="1064"><chem file="01812052_cml1064.xml" /></chemistry>、<chemistry num="1065"><chem file="01812052_cml1065.xml" /></chemistry>、<chemistry num="1066"><chem file="01812052_cml1066.xml" /></chemistry>、<chemistry num="1067"><chem file="01812052_cml1067.xml" /></chemistry>、<chemistry num="1068"><chem file="01812052_cml1068.xml" /></chemistry>、<chemistry num="1069"><chem file="01812052_cml1069.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-4</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-4</sub>烷基、<chemistry num="1070"><chem file="01812052_cml1070.xml" /></chemistry>、<chemistry num="1071"><chem file="01812052_cml1071.xml" /></chemistry>、<chemistry num="1072"><chem file="01812052_cml1072.xml" /></chemistry>、<chemistry num="1073"><chem file="01812052_cml1073.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>C(O)OC<sub>1-4</sub>烷基、<chemistry num="1074"><chem file="01812052_cml1074.xml" /></chemistry>、<chemistry num="1075"><chem file="01812052_cml1075.xml" /></chemistry>、<chemistry num="1076"><chem file="01812052_cml1076.xml" /></chemistry>、<chemistry num="1077"><chem file="01812052_cml1077.xml" /></chemistry>和0-3个R<sup>8e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>苯基；R<sup>8e</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、C<sub>3-6</sub>环烷基、<chemistry num="1078"><chem file="01812052_cml1078.xml" /></chemistry>、<chemistry num="1079"><chem file="01812052_cml1079.xml" /></chemistry>、<chemistry num="1080"><chem file="01812052_cml1080.xml" /></chemistry>、<chemistry num="1081"><chem file="01812052_cml1081.xml" /></chemistry>、<chemistry num="1082"><chem file="01812052_cml1082.xml" /></chemistry>、<chemistry num="1083"><chem file="01812052_cml1083.xml" /></chemistry>、<chemistry num="1084"><chem file="01812052_cml1084.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="1085"><chem file="01812052_cml1085.xml" /></chemistry>、<chemistry num="1086"><chem file="01812052_cml1086.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、<chemistry num="1087"><chem file="01812052_cml1087.xml" /></chemistry>和(CH<sub>2</sub>)<sub>r</sub>苯基；R<sup>8f</sup>在每种情况下选自<chemistry num="1088"><chem file="01812052_cml1088.xml" /></chemistry>、C<sub>1-6</sub>烷基和C<sub>3-6</sub>环烷基；R<sup>9</sup>选自<chemistry num="1089"><chem file="01812052_cml1089.xml" /></chemistry>、<chemistry num="1090"><chem file="01812052_cml1090.xml" /></chemistry>、0-3个R<sup>9a</sup>取代的C<sub>2-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、C<sub>1-6</sub>卤代烷基、0-3个R<sup>9j</sup>取代的(CHR′)<sub>r</sub>C(O)C<sub>1-6</sub>烷基、0-3个R<sup>9b</sup>取代的(CHR′)<sub>r</sub>C(O)OC<sub>1-6</sub>烷基、<chemistry num="1091"><chem file="01812052_cml1091.xml" /></chemistry>、(CHR′)<sub>r</sub>S(O)<sub>2</sub>C<sub>1-6</sub>烷基、S(O)<sub>2</sub>C<sub>1-6</sub>卤代烷基、<chemistry num="1092"><chem file="01812052_cml1092.xml" /></chemistry>、R<sup>9′</sup>、<chemistry num="1093"><chem file="01812052_cml1093.xml" /></chemistry>、<chemistry num="1094"><chem file="01812052_cml1094.xml" /></chemistry>、<chemistry num="1095"><chem file="01812052_cml1095.xml" /></chemistry>和<chemistry num="1096"><chem file="01812052_cml1096.xml" /></chemistry>；R<sup>9′</sup>在每种情况下独立地选自0-3个R<sup>9e</sup>取代的(CHR′)<sub>r</sub>C<sub>3-6</sub>环烷基、0-3个R<sup>9c</sup>取代的(CHR′)<sub>r</sub>苯基、0-3个R<sup>9c</sup>取代的含有1-4个选自<chemistry num="1097"><chem file="01812052_cml1097.xml" /></chemistry>、<chemistry num="1098"><chem file="01812052_cml1098.xml" /></chemistry>和<chemistry num="1099"><chem file="01812052_cml1099.xml" /></chemistry>的杂原子的(CHR′)<sub>r</sub>-5-10元杂环体系；R<sup>9a</sup>在每种情况下独立地选自<chemistry num="1100"><chem file="01812052_cml1100.xml" /></chemistry>、<chemistry num="1101"><chem file="01812052_cml1101.xml" /></chemistry>、OC<sub>1-5</sub>烷基、<chemistry num="1102"><chem file="01812052_cml1102.xml" /></chemistry>、<chemistry num="1103"><chem file="01812052_cml1103.xml" /></chemistry>、OC<sub>1-5</sub>烷基、OC(O)C<sub>1-5</sub>烷基、SC<sub>1-5</sub>烷基、S(O)<sub>p</sub>C<sub>1-5</sub>烷基和<chemistry num="1104"><chem file="01812052_cml1104.xml" /></chemistry>；R<sup>9b</sup>在每种情况下独立地选自C<sub>3-6</sub>环烷基、<chemistry num="1105"><chem file="01812052_cml1105.xml" /></chemistry>、<chemistry num="1106"><chem file="01812052_cml1106.xml" /></chemistry>、(CH<sub>2</sub>)<sub>q</sub>OC<sub>1-5</sub>烷基、<chemistry num="1107"><chem file="01812052_cml1107.xml" /></chemistry>、(CH<sub>2</sub>)<sub>q</sub>SC<sub>1-5</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>S(O)<sub>p</sub>C<sub>1-5</sub>烷基和<chemistry num="1108"><chem file="01812052_cml1108.xml" /></chemistry>；R<sup>9c</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、<chemistry num="1109"><chem file="01812052_cml1109.xml" /></chemistry>、<chemistry num="1110"><chem file="01812052_cml1110.xml" /></chemistry>、<chemistry num="1111"><chem file="01812052_cml1111.xml" /></chemistry>、<chemistry num="1112"><chem file="01812052_cml1112.xml" /></chemistry>、<chemistry num="1113"><chem file="01812052_cml1113.xml" /></chemistry>、<chemistry num="1114"><chem file="01812052_cml1114.xml" /></chemistry>、<chemistry num="1115"><chem file="01812052_cml1115.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、(CHR′)<sub>r</sub>C(O)C<sub>1-5</sub>烷基、(CHR′)<sub>r</sub>C(O)OC<sub>1-5</sub>烷基、<chemistry num="1116"><chem file="01812052_cml1116.xml" /></chemistry>、<chemistry num="1117"><chem file="01812052_cml1117.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>S(O)<sub>p</sub>C<sub>1-5</sub>烷基和<chemistry num="1118"><chem file="01812052_cml1118.xml" /></chemistry>；条件是如果R<sup>9c</sup>结合到与环B上的氮结合的碳上，那么R<sup>9c</sup>选自<chemistry num="1119"><chem file="01812052_cml1119.xml" /></chemistry>、(CH<sub>2</sub>)<sub>q</sub>OC<sub>1-5</sub>烷基、(CH<sub>2</sub>)<sub>q</sub>SC<sub>1-5</sub>烷基、(CH<sub>2</sub>)<sub>q</sub>S(O)<sub>q</sub>C<sub>1-5</sub>烷基和<chemistry num="1120"><chem file="01812052_cml1120.xml" /></chemistry>；R<sup>9d</sup>和R<sup>9d′</sup>在每种情况下独立地选自<chemistry num="1121"><chem file="01812052_cml1121.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和苯基；或者，R<sup>9d</sup>和R<sup>9d′</sup>同它们所结合的<chemistry num="1122"><chem file="01812052_cml1122.xml" /></chemistry>一起结合成含有1-2个选自<chemistry num="1123"><chem file="01812052_cml1123.xml" /></chemistry>、<chemistry num="1124"><chem file="01812052_cml1124.xml" /></chemistry>和<chemistry num="1125"><chem file="01812052_cml1125.xml" /></chemistry>的杂原子并且任选与苯环或6-元芳香杂环稠合的5-6元杂环体<!-- SIPO <dp n="4"/>-->系；R<sup>9e</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、<chemistry num="1126"><chem file="01812052_cml1126.xml" /></chemistry>、<chemistry num="1127"><chem file="01812052_cml1127.xml" /></chemistry>、<chemistry num="1128"><chem file="01812052_cml1128.xml" /></chemistry>、<chemistry num="1129"><chem file="01812052_cml1129.xml" /></chemistry>、<chemistry num="1130"><chem file="01812052_cml1130.xml" /></chemistry>、<chemistry num="1131"><chem file="01812052_cml1131.xml" /></chemistry>、<chemistry num="1132"><chem file="01812052_cml1132.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、(CHR′)<sub>r</sub>C(O)OC<sub>1-5</sub>烷基、<chemistry num="1133"><chem file="01812052_cml1133.xml" /></chemistry>、<chemistry num="1134"><chem file="01812052_cml1134.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>S(O)<sub>p</sub>C<sub>1-5</sub>烷基和<chemistry num="1135"><chem file="01812052_cml1135.xml" /></chemistry>，或者同一碳原子上的两个R<sup>9e</sup>形成<chemistry num="1136"><chem file="01812052_cml1136.xml" /></chemistry>；R<sup>9h</sup>选自<chemistry num="1137"><chem file="01812052_cml1137.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、(CH<sub>2</sub>)<sub>r</sub>苯基、<chemistry num="1138"><chem file="01812052_cml1138.xml" /></chemistry>、<chemistry num="1139"><chem file="01812052_cml1139.xml" /></chemistry>和<chemistry num="1140"><chem file="01812052_cml1140.xml" /></chemistry>；R<sup>9i</sup>在每种情况下选自C<sub>1-6</sub>烷基和C<sub>3-6</sub>环烷基；R<sup>9j</sup>在每种情况下选自C<sub>3-6</sub>环烷基、<chemistry num="1141"><chem file="01812052_cml1141.xml" /></chemistry>、<chemistry num="1142"><chem file="01812052_cml1142.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="1143"><chem file="01812052_cml1143.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>S(O)<sub>p</sub>C<sub>1-5</sub>烷基和<chemistry num="1144"><chem file="01812052_cml1144.xml" /></chemistry>；R<sup>10</sup>选自<chemistry num="1145"><chem file="01812052_cml1145.xml" /></chemistry>、<chemistry num="1146"><chem file="01812052_cml1146.xml" /></chemistry>、<chemistry num="1147"><chem file="01812052_cml1147.xml" /></chemistry>、<chemistry num="1148"><chem file="01812052_cml1148.xml" /></chemistry>、<chemistry num="1149"><chem file="01812052_cml1149.xml" /></chemistry>、<chemistry num="1150"><chem file="01812052_cml1150.xml" /></chemistry>、<chemistry num="1151"><chem file="01812052_cml1151.xml" /></chemistry>、<chemistry num="1152"><chem file="01812052_cml1152.xml" /></chemistry>、<chemistry num="1153"><chem file="01812052_cml1153.xml" /></chemistry>；R<sup>10a</sup>和R<sup>10a′</sup>在每种情况下选自<chemistry num="1154"><chem file="01812052_cml1154.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-5个R<sup>10e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-2个R<sup>10e</sup>取代的含有1-4个选自<chemistry num="1155"><chem file="01812052_cml1155.xml" /></chemistry>、<chemistry num="1156"><chem file="01812052_cml1156.xml" /></chemistry>和<chemistry num="1157"><chem file="01812052_cml1157.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-10元杂环体系；或者，R<sup>10a</sup>和R<sup>10a′</sup>同它们所结合的<chemistry num="1158"><chem file="01812052_cml1158.xml" /></chemistry>一起结合成含有1-2个选自<chemistry num="1159"><chem file="01812052_cml1159.xml" /></chemistry>、<chemistry num="1160"><chem file="01812052_cml1160.xml" /></chemistry>和<chemistry num="1161"><chem file="01812052_cml1161.xml" /></chemistry>的杂原子并且任选与苯环或6-元芳香杂环稠合的5-6元杂环体系；R<sup>10b</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-3个R<sup>10e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>碳环残基和0-2个R<sup>10e</sup>取代的含有1-4个选自<chemistry num="1162"><chem file="01812052_cml1162.xml" /></chemistry>、<chemistry num="1163"><chem file="01812052_cml1163.xml" /></chemistry>和<chemistry num="1164"><chem file="01812052_cml1164.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>10d</sup>在每种情况下选自C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、甲基、<chemistry num="1165"><chem file="01812052_cml1165.xml" /></chemistry>、0-3个R<sup>10e</sup>取代的C<sub>2-6</sub>烷基、0-3个R<sup>10e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-3个R<sup>10e</sup>取代的含有1-4个选自<chemistry num="1166"><chem file="01812052_cml1166.xml" /></chemistry>、<chemistry num="1167"><chem file="01812052_cml1167.xml" /></chemistry>和<chemistry num="1168"><chem file="01812052_cml1168.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>10e</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、C(O)C<sub>1-6</sub>烷基、C(O)OC<sub>1-6</sub>烷基、<chemistry num="1169"><chem file="01812052_cml1169.xml" /></chemistry>、<chemistry num="1170"><chem file="01812052_cml1170.xml" /></chemistry>、<chemistry num="1171"><chem file="01812052_cml1171.xml" /></chemistry>、<chemistry num="1172"><chem file="01812052_cml1172.xml" /></chemistry>、<chemistry num="1173"><chem file="01812052_cml1173.xml" /></chemistry>、<chemistry num="1174"><chem file="01812052_cml1174.xml" /></chemistry>、<chemistry num="1175"><chem file="01812052_cml1175.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="1176"><chem file="01812052_cml1176.xml" /></chemistry>、<chemistry num="1177"><chem file="01812052_cml1177.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、<chemistry num="1178"><chem file="01812052_cml1178.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>苯基和0-1个R<sup>10g</sup>取代的杂环，其中杂环选自咪唑、噻唑、噁唑、吡唑、1，2，4-三唑、1，2，3-三唑、异噁唑和四唑；R<sup>10f</sup>在每种情况下选自<chemistry num="1179"><chem file="01812052_cml1179.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和苯基；R<sup>10g</sup>选自甲基、乙基、乙酰基和<chemistry num="1180"><chem file="01812052_cml1180.xml" /></chemistry>；R<sup>10h</sup>选自<chemistry num="1181"><chem file="01812052_cml1181.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、(CH<sub>2</sub>)<sub>r</sub>苯基、<chemistry num="1182"><chem file="01812052_cml1182.xml" /></chemistry>、<chemistry num="1183"><chem file="01812052_cml1183.xml" /></chemistry><!-- SIPO <dp n="5"/>-->和<chemistry num="1184"><chem file="01812052_cml1184.xml" /></chemistry>；R<sup>10i</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基；R<sup>13</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、C<sub>3-6</sub>环烷基、<chemistry num="1185"><chem file="01812052_cml1185.xml" /></chemistry>、<chemistry num="1186"><chem file="01812052_cml1186.xml" /></chemistry>、<chemistry num="1187"><chem file="01812052_cml1187.xml" /></chemistry>、<chemistry num="1188"><chem file="01812052_cml1188.xml" /></chemistry>、<chemistry num="1189"><chem file="01812052_cml1189.xml" /></chemistry>、<chemistry num="1190"><chem file="01812052_cml1190.xml" /></chemistry>、<chemistry num="1191"><chem file="01812052_cml1191.xml" /></chemistry>、<chemistry num="1192"><chem file="01812052_cml1192.xml" /></chemistry>、<chemistry num="1193"><chem file="01812052_cml1193.xml" /></chemistry>、<chemistry num="1194"><chem file="01812052_cml1194.xml" /></chemistry>、<chemistry num="1195"><chem file="01812052_cml1195.xml" /></chemistry>、<chemistry num="1196"><chem file="01812052_cml1196.xml" /></chemistry>、<chemistry num="1197"><chem file="01812052_cml1197.xml" /></chemistry>、<chemistry num="1198"><chem file="01812052_cml1198.xml" /></chemistry>、<chemistry num="1199"><chem file="01812052_cml1199.xml" /></chemistry>和0-3个R<sup>13c</sup>取代的(CH<sub>2</sub>)<sub>w</sub>苯基；R<sup>13a</sup>和R<sup>13a′</sup>在每种情况下选自<chemistry num="1200"><chem file="01812052_cml1200.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和0-3个R<sup>13c</sup>取代的苯基；R<sup>13b</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和0-3个R<sup>13c</sup>取代的苯基；R<sup>13c</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、<chemistry num="1201"><chem file="01812052_cml1201.xml" /></chemistry>、<chemistry num="1202"><chem file="01812052_cml1202.xml" /></chemistry>、<chemistry num="1203"><chem file="01812052_cml1203.xml" /></chemistry>、<chemistry num="1204"><chem file="01812052_cml1204.xml" /></chemistry>、<chemistry num="1205"><chem file="01812052_cml1205.xml" /></chemistry>、<chemistry num="1206"><chem file="01812052_cml1206.xml" /></chemistry>、<chemistry num="1207"><chem file="01812052_cml1207.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="1208"><chem file="01812052_cml1208.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基和<chemistry num="1209"><chem file="01812052_cml1209.xml" /></chemistry>；R<sup>13d</sup>在每种情况下选自<chemistry num="1210"><chem file="01812052_cml1210.xml" /></chemistry>、C<sub>1-6</sub>烷基和C<sub>3-6</sub>环烷基；R<sup>15</sup>在每种情况下选自<chemistry num="1211"><chem file="01812052_cml1211.xml" /></chemistry>、C<sub>1-8</sub>烷基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、<chemistry num="1212"><chem file="01812052_cml1212.xml" /></chemistry>、<chemistry num="1213"><chem file="01812052_cml1213.xml" /></chemistry>、<chemistry num="1214"><chem file="01812052_cml1214.xml" /></chemistry>、<chemistry num="1215"><chem file="01812052_cml1215.xml" /></chemistry>、<chemistry num="1216"><chem file="01812052_cml1216.xml" /></chemistry>、<chemistry num="1217"><chem file="01812052_cml1217.xml" /></chemistry>、<chemistry num="1218"><chem file="01812052_cml1218.xml" /></chemistry>、<chemistry num="1219"><chem file="01812052_cml1219.xml" /></chemistry>、<chemistry num="1220"><chem file="01812052_cml1220.xml" /></chemistry>、<chemistry num="1221"><chem file="01812052_cml1221.xml" /></chemistry>、<chemistry num="1222"><chem file="01812052_cml1222.xml" /></chemistry>、<chemistry num="1223"><chem file="01812052_cml1223.xml" /></chemistry>、<chemistry num="1224"><chem file="01812052_cml1224.xml" /></chemistry>、<chemistry num="1225"><chem file="01812052_cml1225.xml" /></chemistry>、<chemistry num="1226"><chem file="01812052_cml1226.xml" /></chemistry>、<chemistry num="1227"><chem file="01812052_cml1227.xml" /></chemistry>、<chemistry num="1228"><chem file="01812052_cml1228.xml" /></chemistry>、<chemistry num="1229"><chem file="01812052_cml1229.xml" /></chemistry>、<chemistry num="1230"><chem file="01812052_cml1230.xml" /></chemistry>、<chemistry num="1231"><chem file="01812052_cml1231.xml" /></chemistry>、<chemistry num="1232"><chem file="01812052_cml1232.xml" /></chemistry>、<chemistry num="1233"><chem file="01812052_cml1233.xml" /></chemistry>、<chemistry num="1234"><chem file="01812052_cml1234.xml" /></chemistry>、<chemistry num="1235"><chem file="01812052_cml1235.xml" /></chemistry>、<chemistry num="1236"><chem file="01812052_cml1236.xml" /></chemistry>、C<sub>1-6</sub>卤代烷基、0-3个R′取代的C<sub>2-8</sub>链烯基、0-3个R′取代的C<sub>2-8</sub>炔基、0-3个R<sup>15e</sup>取代的(CHR′)<sub>r</sub>苯基和0-2个R<sup>15e</sup>取代的含有1-4个选自<chemistry num="1237"><chem file="01812052_cml1237.xml" /></chemistry>、<chemistry num="1238"><chem file="01812052_cml1238.xml" /></chemistry>和<chemistry num="1239"><chem file="01812052_cml1239.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-10元杂环体系；R′在每种情况下选自<chemistry num="1240"><chem file="01812052_cml1240.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基和R<sup>15e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>苯基；R<sup>15a</sup>和R<sup>15a′</sup>在每种情况下选自<chemistry num="1241"><chem file="01812052_cml1241.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-5个R<sup>15e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-2个R<sup>15e</sup>取代的含有1-4个选自<chemistry num="1242"><chem file="01812052_cml1242.xml" /></chemistry>、<chemistry num="1243"><chem file="01812052_cml1243.xml" /></chemistry>和<chemistry num="1244"><chem file="01812052_cml1244.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-10元杂环体系；或者，R<sup>15a</sup>和R<sup>15a′</sup>同它们所结合的<chemistry num="1245"><chem file="01812052_cml1245.xml" /></chemistry>一起结合成含有1-2个选自<chemistry num="1246"><chem file="01812052_cml1246.xml" /></chemistry>、<chemistry num="1247"><chem file="01812052_cml1247.xml" /></chemistry>和<chemistry num="1248"><chem file="01812052_cml1248.xml" /></chemistry>的杂原子并且任选与苯环或6-元芳香杂环稠合的5-6元杂环体系；<!-- SIPO <dp n="6"/>-->R<sup>15b</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-3个R<sup>15e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>碳环残基和0-2个R<sup>15e</sup>取代的含有1-4个选自<chemistry num="1249"><chem file="01812052_cml1249.xml" /></chemistry>、<chemistry num="1250"><chem file="01812052_cml1250.xml" /></chemistry>和<chemistry num="1251"><chem file="01812052_cml1251.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>15d</sup>在每种情况下选自C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、甲基、<chemistry num="1252"><chem file="01812052_cml1252.xml" /></chemistry>、0-3个R<sup>15e</sup>取代的C<sub>2-6</sub>烷基、0-3个R<sup>15e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-3个R<sup>15e</sup>取代的含有1-4个选自<chemistry num="1253"><chem file="01812052_cml1253.xml" /></chemistry>、<chemistry num="1254"><chem file="01812052_cml1254.xml" /></chemistry>和<chemistry num="1255"><chem file="01812052_cml1255.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>15e</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、C(O)C<sub>1-6</sub>烷基、C(O)OC<sub>1-6</sub>烷基、<chemistry num="1256"><chem file="01812052_cml1256.xml" /></chemistry>、<chemistry num="1257"><chem file="01812052_cml1257.xml" /></chemistry>、<chemistry num="1258"><chem file="01812052_cml1258.xml" /></chemistry>、<chemistry num="1259"><chem file="01812052_cml1259.xml" /></chemistry>、<chemistry num="1260"><chem file="01812052_cml1260.xml" /></chemistry>、<chemistry num="1261"><chem file="01812052_cml1261.xml" /></chemistry>、<chemistry num="1262"><chem file="01812052_cml1262.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="1263"><chem file="01812052_cml1263.xml" /></chemistry>、<chemistry num="1264"><chem file="01812052_cml1264.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、<chemistry num="1265"><chem file="01812052_cml1265.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>苯基和0-1个R<sup>15g</sup>取代的杂环，其中杂环选自咪唑、噻唑、噁唑、吡唑、1，2，4-三唑、1，2，3-三唑、异噁唑和四唑；R<sup>15f</sup>在每种情况下选自<chemistry num="1266"><chem file="01812052_cml1266.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基和苯基；R<sup>15g</sup>选自甲基、乙基、乙酰基和<chemistry num="1267"><chem file="01812052_cml1267.xml" /></chemistry>；R<sup>15h</sup>选自<chemistry num="1268"><chem file="01812052_cml1268.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、(CH<sub>2</sub>)<sub>r</sub>苯基、<chemistry num="1269"><chem file="01812052_cml1269.xml" /></chemistry>、<chemistry num="1270"><chem file="01812052_cml1270.xml" /></chemistry>和<chemistry num="1271"><chem file="01812052_cml1271.xml" /></chemistry>；R<sup>15i</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基；R<sup>16</sup>在每种情况下选自C<sub>1-8</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、<chemistry num="1272"><chem file="01812052_cml1272.xml" /></chemistry>、<chemistry num="1273"><chem file="01812052_cml1273.xml" /></chemistry>、<chemistry num="1274"><chem file="01812052_cml1274.xml" /></chemistry>、<chemistry num="1275"><chem file="01812052_cml1275.xml" /></chemistry>、<chemistry num="1276"><chem file="01812052_cml1276.xml" /></chemistry>、<chemistry num="1277"><chem file="01812052_cml1277.xml" /></chemistry>、<chemistry num="1278"><chem file="01812052_cml1278.xml" /></chemistry>、<chemistry num="1279"><chem file="01812052_cml1279.xml" /></chemistry>、<chemistry num="1280"><chem file="01812052_cml1280.xml" /></chemistry>、<chemistry num="1281"><chem file="01812052_cml1281.xml" /></chemistry>、<chemistry num="1282"><chem file="01812052_cml1282.xml" /></chemistry>、<chemistry num="1283"><chem file="01812052_cml1283.xml" /></chemistry>、<chemistry num="1284"><chem file="01812052_cml1284.xml" /></chemistry>、<chemistry num="1285"><chem file="01812052_cml1285.xml" /></chemistry>、<chemistry num="1286"><chem file="01812052_cml1286.xml" /></chemistry>、<chemistry num="1287"><chem file="01812052_cml1287.xml" /></chemistry>、<chemistry num="1288"><chem file="01812052_cml1288.xml" /></chemistry>、<chemistry num="1289"><chem file="01812052_cml1289.xml" /></chemistry>、<chemistry num="1290"><chem file="01812052_cml1290.xml" /></chemistry>、<chemistry num="1291"><chem file="01812052_cml1291.xml" /></chemistry>、<chemistry num="1292"><chem file="01812052_cml1292.xml" /></chemistry>、<chemistry num="1293"><chem file="01812052_cml1293.xml" /></chemistry>、C<sub>1-6</sub>卤代烷基、0-3个R′取代的C<sub>2-8</sub>链烯基、0-3个R′取代的C<sub>2-8</sub>炔基和0-3个R<sup>16e</sup>取代的(CHR′)<sub>r</sub>苯基；R<sup>16a</sup>和R<sup>16a′</sup>在每种情况下选自<chemistry num="1294"><chem file="01812052_cml1294.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-5个R<sup>16e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-2个R<sup>16e</sup>取代的含有1-4个选自<chemistry num="1295"><chem file="01812052_cml1295.xml" /></chemistry>、<chemistry num="1296"><chem file="01812052_cml1296.xml" /></chemistry>和<chemistry num="1297"><chem file="01812052_cml1297.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-10元杂环体系；或者，R<sup>16a</sup>和R<sup>16a′</sup>同它们所结合的<chemistry num="1298"><chem file="01812052_cml1298.xml" /></chemistry>一起结合成含有1-2个选自<chemistry num="1299"><chem file="01812052_cml1299.xml" /></chemistry>、<chemistry num="1300"><chem file="01812052_cml1300.xml" /></chemistry>和<chemistry num="1301"><chem file="01812052_cml1301.xml" /></chemistry>的杂原子并且任选与苯环或6-元芳香杂环稠合的5-6元杂环体系；R<sup>16b</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-3个R<sup>16e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>碳环残基和0-2个R<sup>16e</sup>取代的含有1-4个选自<chemistry num="1302"><chem file="01812052_cml1302.xml" /></chemistry>、<chemistry num="1303"><chem file="01812052_cml1303.xml" /></chemistry>和<chemistry num="1304"><chem file="01812052_cml1304.xml" /></chemistry>的<!-- SIPO <dp n="7"/>-->杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>16d</sup>在每种情况下选自C<sub>3-8</sub>链烯基、C<sub>3-8</sub>炔基、0-3个R<sup>16e</sup>取代的C<sub>1-6</sub>烷基、0-3个R<sup>16e</sup>取代的(CH<sub>2</sub>)<sub>r</sub>C<sub>3-10</sub>碳环残基和0-3个R<sup>16e</sup>取代的含有1-4个选自<chemistry num="1305"><chem file="01812052_cml1305.xml" /></chemistry>、<chemistry num="1306"><chem file="01812052_cml1306.xml" /></chemistry>和<chemistry num="1307"><chem file="01812052_cml1307.xml" /></chemistry>的杂原子的(CH<sub>2</sub>)<sub>r</sub>-5-6元杂环体系；R<sup>16e</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>2-8</sub>链烯基、C<sub>2-8</sub>炔基、(CH<sub>2</sub>)<sub>r</sub>C<sub>3-6</sub>环烷基、<chemistry num="1308"><chem file="01812052_cml1308.xml" /></chemistry>、<chemistry num="1309"><chem file="01812052_cml1309.xml" /></chemistry>、<chemistry num="1310"><chem file="01812052_cml1310.xml" /></chemistry>、<chemistry num="1311"><chem file="01812052_cml1311.xml" /></chemistry>、<chemistry num="1312"><chem file="01812052_cml1312.xml" /></chemistry>、<chemistry num="1313"><chem file="01812052_cml1313.xml" /></chemistry>、<chemistry num="1314"><chem file="01812052_cml1314.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>OC<sub>1-5</sub>烷基、<chemistry num="1315"><chem file="01812052_cml1315.xml" /></chemistry>、<chemistry num="1316"><chem file="01812052_cml1316.xml" /></chemistry>、(CH<sub>2</sub>)<sub>r</sub>SC<sub>1-5</sub>烷基、<chemistry num="1317"><chem file="01812052_cml1317.xml" /></chemistry>和(CH<sub>2</sub>)<sub>r</sub>苯基；R<sup>16f</sup>在每种情况下选自<chemistry num="1318"><chem file="01812052_cml1318.xml" /></chemistry>、C<sub>1-5</sub>烷基、C<sub>3-6</sub>环烷基和苯基；R<sup>16h</sup>选自<chemistry num="1319"><chem file="01812052_cml1319.xml" /></chemistry>、C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基、(CH<sub>2</sub>)<sub>r</sub>苯基、<chemistry num="1320"><chem file="01812052_cml1320.xml" /></chemistry>、<chemistry num="1321"><chem file="01812052_cml1321.xml" /></chemistry>和<chemistry num="1322"><chem file="01812052_cml1322.xml" /></chemistry>；R<sup>16i</sup>在每种情况下选自C<sub>1-6</sub>烷基、C<sub>3-6</sub>环烷基；m在每种情况下独立地选自0、1和2；t在每种情况下独立地选自1和2；w在每种情况下独立地选自0和1；r在每种情况下独立地选自0、1、2、3、4和5；q在每种情况下独立地选自1、2、3、4和5；并且p在每种情况下独立地选自0、1和2。
地址	美国新泽西州