CN1555364A - 杀虫二酰胺类 - Google Patents

杀虫二酰胺类 Download PDF

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CN1555364A
CN1555364A CNA028182472A CN02818247A CN1555364A CN 1555364 A CN1555364 A CN 1555364A CN A028182472 A CNA028182472 A CN A028182472A CN 02818247 A CN02818247 A CN 02818247A CN 1555364 A CN1555364 A CN 1555364A
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halogen
pyridyl
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CN1298706C (zh
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���Ρ������ա���ķ
乔治·菲利普·拉姆
托马斯·保罗·塞尔比
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    • A01N37/46—N-acyl derivatives
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    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D231/40—Acylated on said nitrogen atom

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Abstract

本发明涉及一种防治无脊椎害虫的方法，包括用生物有效量的式I的化合物(包括所有几何异构体和立体异构体)、其N－氧化物或其适用于农业的盐(例如以包括式I的化合物的组合物)接触无脊椎害虫或其环境，其中J是苯环、萘环系、5－或6－元杂芳环或者芳族8－、9－或10－元稠合杂二环环系，其中每一环或环系取代有1－4个R5;K是－C(＝A)NR2－或－NR2C(＝A)－；L是－NR1C(＝B)－R3或－NR1SO2－R3；A和B独立地是O或S；R1、R2、R3、R4、R5和n的定义如说明书中所述。本发明还公开了一种防治无脊椎害虫的组合物，包括生物有效量的式I的化合物、其N－氧化物或其适用于农业的盐。本发明还公开了某些式I的化合物、其N－氧化物或其适用于农业的盐。

Description

杀虫二酰胺类
                        技术领域
本发明涉及某些二酰胺类、它们的N-氧化物、其适用于农业的盐和组合物，以及它们在农业和非农业环境中防治无脊椎害虫的使用方法。
                        背景技术
无脊椎害虫(例如节肢动物)的防治在实现高效农业中是非常重要的。无脊椎害虫危害农作物的生长和贮存，会导致农作物严重减产，从而增加消费者的费用。在森林、温室作物、观赏植物、苗圃作物、贮存的食品和纤维产品、家畜、家庭、以及公共与动物保健中，防治无脊椎害虫也是重要的。虽然为此目的已可买到许多产品，但是仍然需要更有效、价廉、低毒、对环境更安全或具有不同作用方式的新化合物。
NL 9202078公开了用作杀虫剂的式i的N-酰基邻氨基苯甲酸衍生物
其中，X是直接键；
Y是H或C1-C6烷基；
Z是NH2、NH(C1-C3烷基)或N(C1-C3烷基)2；和
R1-R9独立地是H、卤素、C1-C6烷基、苯基、羟基、C1-C6烷氧基或C1-C7酰氧基。
美国专利US 3,907,892公开了某些N-氟烷酰基-邻-苯二胺类作为杀虫剂。
                         发明概述
本发明涉及式I的化合物(包括所有几何异构体和立体异构体)、及其N-氧化物和其适用于农业的盐
Figure A0281824700131
其中
J是苯环、萘环系、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，其中每一环或环系任选取代有1-4个R5；
K是-C(＝A)NR2-或-NR2C(＝A)-；
L是-NR1C(＝B)-R3或-NR1SO2-R3；
A和B独立地是O或S；
R1是H；或C1-C6烷基、C2-C6链烯基、C2-C6链炔基或C3-C6环烷基，每一个任选取代有一个或多个选自如下的取代基：卤素、CN、NO2、羟基、C1-C4烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C2-C4烷氧基羰基、C1-C4烷基氨基、C2-C8二烷基氨基和C3-C6环烷基氨基；或者
R1是C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基或C3-C8二烷基氨基羰基；
R2是H、C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基、C1-C4烷氧基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C2-C6烷氧基羰基或C2-C6烷基羰基；
R3是C1-C6烷基、C2-C6链烯基、C2-C6链炔基或C3-C6环烷基，每一个任选取代有一个或多个选自如下的取代基：卤素、CN、NO2、羟基、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C2-C6烷氧基羰基、C2-C6烷基羰基、C3-C6三烷基甲硅烷基、苯基、苯氧基和5-或6-元杂芳环，每个苯基、苯氧基和5-或6-元杂芳环任选取代有1-3个独立地选自如下的取代基：R6；C1-C4烷氧基；C1-C4烷基氨基；C2-C8二烷基氨基；C1-C4烷氧基(C1-C4烷基)氨基；C3-C6环烷基氨基；C2-C6烷氧基羰基或C2-C6烷基羰基；或者
R1和R3可以与-NC(＝B)-或-NSO2-部分在一起，它们相连形成一个包括2-6个碳原子并任选还包括一个氮、硫或氧原子的环，所述环任选取代有1-4个选自如下的取代基：C1-C2烷基、卤素、CN、NO2和C1-C2烷氧基；
每个R4独立地是H、C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基、C1-C6卤烷基、C2-C6卤链烯基、C2-C6卤链炔基、C3-C6卤环烷基、卤素、CN、NO2、羟基、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C3-C6三烷基甲硅烷基，或者任选取代有1-3个独立地选自R6的取代基的苯环；
每个R5独立地是C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基、C1-C6卤烷基、C2-C6卤链烯基、C2-C6卤链炔基、C3-C6卤环烷基、卤素、CN、CO2H、CONH2、NO2、羟基、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基、C3-C6三烷基甲硅烷基；或者
每个R5独立地是苯基、苄基、苯甲酰基、苯氧基、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，每个苯基、苄基、苯甲酰基、苯氧基、杂芳环和芳族稠合杂二环环系任选取代有1-3个独立地选自R6的取代基；或者
两个R5基团与相邻碳原子相连时可以在一起为-OCF2O-、-CF2CF2O-或-OCF2CF2O-；
每个R6独立地是C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C2-C4卤链烯基、C2-C4卤链炔基、C3-C6卤环烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C3-C6(烷基)环烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和
n是1、2、3或4；条件是L不是-NHC(＝O)-，并且R3不是取代有一个或多个氟部分的C1-C6烷基。
本发明还提供了一种防治无脊椎害虫的方法，包括用生物有效量的式I的化合物、其N-氧化物或其适用于农业的盐(例如以本文所述的组合物)接触无脊椎害虫或其环境。
本发明还提供了一种防治无脊椎害虫的组合物，包括生物有效量的式I的化合物、其N-氧化物或其适用于农业的盐；和至少一种选自表面活性剂、固体稀释剂和液体稀释剂的其它组分。
本发明还提供了一种组合物，包括生物有效量的式I的化合物、其N-氧化物或其适用于农业的盐；和有效量的至少一种其它生物活性化合物或试剂。
本发明还提供了式I的化合物(包括所有几何异构体和立体异构体)、其N-氧化物或其适用于农业的盐，其中每个R5是R5a或R5b；
J是苯环、萘环系、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，其中每一环或环系取代有一个R5a并任选取代有1-3个R5b；
K是-C(＝A)NR2-或-NR2C(＝A)-；
L是-NR1C(＝B)-R3或-NR1SO2-R3；
A和B独立地是O或S；
R1是H或C1-C4烷基；
R2是H或C1-C4烷基；
R3是任选取代有卤素、CN、OCH3或S(O)pCH3的C1-C4烷基；
R5a和R5b各自独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、苄基或者5-或6-元杂芳环，每个苯基、苄基和杂芳环任选取代有1-3个独立地选自R6的取代基；
R5a在与K相邻的位置与J相连；每个R6独立地是卤素、CN、NO2、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C1-C4烷氧基或C1-C4卤烷氧基；和
p是0、1或2；条件是L不是-NHC(＝O)-和R3不是取代有一个或多个氟部分的C1-C6烷基。
                     发明详述
在上面的陈述中，术语“烷基”既可以单独使用，也可以在组合词中使用，如“烷硫基”或“卤烷基”中使用，它包括直链或支链烷基，如甲基、乙基、正丙基、异丙基、或者不同的丁基、戊基或己基异构体。“链烯基”包括直链或支链链烯基，如1-丙烯基、2-丙烯基、以及不同的丁烯基、戊烯基和己烯基异构体。“链烯基”也包括多烯，如1，2-丙二烯基和2，4-己二烯基。“链炔基”包括直链或支链炔基，如1-丙炔基、2-丙炔基以及不同的丁炔基、戊炔基和己炔基异构体。“链炔基”也可以包括含有多个三键的基团，如2，5-己二炔基。“烷氧基”包括，例如甲氧基、乙氧基、正丙氧基、异丙氧基以及不同的丁氧基、戊氧基和己氧基异构体。“烷氧基烷基”是指在烷基上取代有烷氧基。“烷氧基烷基”的实例包括CH3OCH2、CH3OCH2CH2、CH3CH2OCH2、CH3CH2CH2CH2OCH2和CH3CH2OCH2CH2。“烷硫基”包括支链或直链烷硫基，例如甲硫基、乙硫基以及不同的丙硫基、丁硫基、戊硫基和己硫基异构体。“环烷基”包括，例如，环丙基、环丁基、环戊基和环己基。
术语“杂环环”或“杂环环系”是指是指这样一种环或环系，其中至少一个环原子不是碳并且包括1-4个独立地选自氮、氧和硫的杂原子，条件是每个杂环环含有不超过4个氮、不超过2个氧和不超过2个硫。所述杂环环可以通过任何可以利用的碳或氮将所述碳或氮上的氢替换相连。术语“芳环系”是指完全不饱和碳环和杂环，其中所述多环系是芳族的(其中芳族是指该环系满足Hückel规则)。术语“杂芳环”是指完全芳族的环，其中至少一个环原子不是碳并且包括1-4个独立地选自氮、氧和硫的杂原子，条件是每个杂环环含有不超过4个氮、不超过2个氧和不超过2个硫(其中芳族是指满足Hückel规则)。所述杂环环可以通过任何可以利用的碳或氮将所述碳或氮上的氢替换相连。术语“芳族杂环环系”包括完全芳族的杂环，其中多环系中至少一个环是芳族的(其中芳族是指满足Hückel规则)。术语“稠合的杂二环环系”包括由两个稠合环组成的环系，其中至少一个环原子不是碳并且可以是如上面定义的芳族或非芳族的。
术语“卤素”，可以是单独的或在组合词如“卤烷基”中，包括氟、氯、溴或碘。而且，在组合词如“卤烷基”中使用时，所述烷基可以用卤原子部分或完全地取代，所述卤原子可以相同或不同。“卤烷基”的实例包括F3C、ClCH2、CF3CH2和CF3CCl2。术语“卤链烯基”、“卤链炔基”、“卤烷氧基”等，定义与术语“卤烷基”类似。“卤链烯基”的实例包括(Cl)2C＝CHCH2和CF3CH2CH＝CHCH2。“卤链炔基”的实例包括HC≡CCHCl、CF3C≡C、CCl3C≡C和FCH2C≡CCH2。“卤烷氧基”的实例包括CF3O、CCl3CH2O、HCF2CH2CH2O和CF3CH2O。
取代基中的碳原子总数通过“Ci-Cj”前缀来表示，其中i和j是1-8的数字。例如，C1-C3烷基磺酰基表示甲磺酰基至丙磺酰基；C2烷氧基烷基表示CH3OCH2；C3烷氧基烷基例如表示CH3CH(OCH3)、CH3OCH2CH2或CH3CH2OCH2；C4烷氧基烷基表示总共含有4个碳原子的烷氧基取代的烷基的不同异构体，实例包括CH3CH2CH2OCH2和CH3CH2OCH2CH2。在上述说明中，当式I的化合物含有一个杂环环时，所有取代基都通过取代任何可得到的碳或氮上的氢，经所述碳或氮连接于这些环上。
当一基团含有一取代基(可以是氢)，例如R3，那么当该取代基为氢时，应认为这相当于所述基团未取代。
本发明的化合物可以存在一种或多种立体异构体。各种立体异构体包括对映体、非对映异构体、阻转异构体和几何异构体。本领域技术人员懂得，当一种立体异构体相对于其它异构体含量更多或当从其它异构体分离出来的时候，该立体异构体可以显示更高的活性和/或可以呈现有益的效果。另外，本领域技术人员也知道如何分离、富集和/或选择性地制备所述的立体异构体。因此，本发明的这些化合物可以立体异构体的混合物、单个立体异构体、或以一种光学活性形式存在。
本发明包括选自以下的化合物：式I、其N-氧化物及其适用于农业的盐。本领域技术人员懂得，不是所有含氮杂环都可以形成N-氧化物，因为要氧化成氧化物，氮需要有一对可以利用的孤对电子；本领域技术人员知道，哪些含氮杂环可以形成N-氧化物。本领域技术人员也知道，叔胺可以形成N-氧化物。制备杂环和叔胺的N-氧化物的合成方法是本领域技术人员熟知的，包括用过氧酸(如过氧乙酸和间氯过苯甲酸(MCPBA)、过氧化氢、烷基氢过氧化物如叔丁基氢过氧化物、过硼酸钠)和二环氧乙烷类(如二甲基二环氧乙烷)氧化杂环和叔胺。这些制备N-氧化物的方法已在文献中深入描述或综述，参见文献举例如下：T.L.Gilchrist的“Comprehensive Organic Synthesis”，第7卷，第748-750页，S.V.Ley编辑，Pergamon出版社；M.Tisler和B.Stanovnik的“Comprehensive Heterocyclic Chemistry”，第3卷，第18-19页，A.J.Boulton和A.McKillop编辑，Pergamon出版社；M.R.Grimmett和B.R.T.Keene的“Advances in HeterocyclicChemistry”，第43卷，第139-151页，A.R.Katritzky编辑，Academic出版社；M.Tisler和B.Stanovnik的“Advances in HeterocyclicChemistry”，第9卷，第285-291页，A.R.Katritzky和A.J.Boulton编辑，Academic出版社；和G.W.H.Cheeseman和E.S.G.Werstiuk的“Advances in Heterocyclic Chemistry”，第22卷，第390-392页，A.R.Katritzky和A.J.Boulton编辑，Academic出版社。
本发明化合物的盐包括与无机或有机酸的酸加成盐，所述酸例如有氢溴酸、盐酸、硝酸、磷酸、硫酸、醋酸、丁酸、富马酸、乳酸、马来酸、丙二酸、草酸、丙酸、水杨酸、酒石酸、4-甲苯磺酸和戊酸。
为了获得更高的活性和/或容易合成，优选的方法是：
优选1.包括式I的化合物的方法，其中K是-C(＝A)NR2-，并且A和B都是O。
优选2.包括式I的化合物的方法，其中K是NR2C(＝A)-，并且A和B都是O。
优选3.优选1或优选2的方法，其中
J是苯环或者5-或6-元杂芳环，该杂芳环选自基团J-1、J-2、J-3和J-4，每个J环任选取代有1-3个R5
Q是O、S或NR5c；
W、X、Y和Z独立地是N或CR5c，条件是在J-3和J-4中W、X、Y或Z中至少一个是N；
R1和R2各自独立地是H、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C2-C6烷基羰基或C2-C6烷氧基羰基；
R3是C1-C6烷基、C2-C6链烯基、C2-C6链炔基或C3-C6环烷基，它们各自任选取代有一个或多个选自如下的取代基：卤素、CN、C1-C2烷氧基、C1-C2烷硫基、C1-C2烷基亚磺酰基和C1-C2烷基磺酰基；
每个R4独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基或C1-C4卤烷基磺酰基；
每个R5独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或
每个R5独立地是苯基、苄基或者5-或6-元杂芳环，每个环任选取代有1-3个独立地选自R6的取代基；或者
两个R5基团与相邻碳原子相连时可以在一起为-OCF2O-、-CF2CF2O-或-OCF2CF2O-；
R5c是H或R5；
每个R6独立地是C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C2-C4卤链烯基、C2-C4卤链炔基、C3-C6卤环烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C3-C6(烷基)环烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和
n是1或2。
优选4.优选3的方法，其中
每个R5是R5a或R5b；
J取代有R5a并任选取代有1-2个R5b；
R1和R2各自独立地是H或C1-C4烷基；
R3是任选取代有卤素、CN、OCH3或S(O)pCH3的C1-C4烷基；
R5a基团在与K相邻的位置与J相连；
R5a和R5b各自独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、苄基或者5-或6-元杂芳环，每个环任选取代有1-3个独立地选自R6的取代基；
每个R6独立地是卤素、CN、NO2、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C1-C4烷氧基或C1-C4卤烷氧基；和
p是0、1或2。
优选5.优选4的方法，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
优选6.优选5的方法，其中
R1和R2各自是H；
一个R4选自如下基团：C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和卤素，并且任选的第二个R4选自如下基团：卤素、C1-C3烷基和C1-C3卤烷基。
优选7.优选6的方法，其中
J是J-1；
Q是NR5a；
X是N或CH；
Y是CH；
Z是CR5b；
R5a是苯基或2-吡啶基环，它们取代有一个或者两个选自如下基团的取代基：卤素、C1-C4烷基、C1-C4卤烷基或C1-C4卤烷氧基；和
R5b是卤素或CF3。
本发明的方法包括这样的实施方式，它包括用生物有效量的包含式I的化合物、其N-氧化物或其适用于农业的盐以及生物有效量的至少一种防治无脊椎害虫的其它化合物或试剂的组合物接触无脊椎害虫或其环境，以防治无脊椎害虫。
本发明还涉及一种防治无脊椎害虫的组合物，其包括生物有效量的式I的化合物、其N-氧化物或其适用于农业的盐以及表面活性剂、固体稀释剂和液体稀释剂中的至少一种。本发明的优选组合物是包含上面优选方法的化合物的那些。
本发明还涉及上面定义的一些式I的化合物，包括其所有几何异构体和立体异构体、其N-氧化物或其适用于农业的盐。为了获得更高的活性和/或容易合成，本发明的优选化合物是：
优选A.式I的化合物，其中
J是苯环或者5-或6-元杂芳环，该杂芳环选自基团J-1、J-2、J-3和J-4，每个J环取代有R5a并任选取代有1-2个R5b
Figure A0281824700231
Q是O、S或NR5c；
W、X、Y和Z独立地是N或CR5c，条件是在J-3和J-4中W、X、Y或Z中至少一个是N；
R1和R2各自独立地是H或C1-C4烷基；
R3是C1-C4烷基，它任选取代有卤素、CN、OCH3或S(O)pCH3；
每个R4独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基或C1-C4卤烷基磺酰基；
R5a在与K相邻的位置与J相连；
R5a和R5b各自独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、苄基或者5-或6-元杂芳环，每个环任选取代有1-3个独立地选自R6的取代基；
R5c是H或R5a；
每个R6独立地是卤素、CN、NO2、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C1-C4烷氧基或C1-C4卤烷氧基；
n是1或2；和
p是0、1或2。
优选B.优选A的化合物，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
优选C.优选B的化合物，其中
R1和R2各自是H；
一个R4选自如下基团：C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和卤素，并且任选的第二个R4选自如下基团：卤素、C1-C3烷基和C1-C3卤烷基。
优选D.优选C的化合物，其中
J是J-1；
Q是NR5a；
X是N或CH；
Y是CH；
Z是CR5b；
R5a是苯基或2-吡啶基环，它们取代有一个或者两个选自如下基团的取代基：卤素、C1-C4烷基、C1-C4卤烷基或C1-C4卤烷氧基；和
R5b是卤素或CF3。
如上所述，J是苯环、萘环系、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，其中每一环或环系任选取代有1-4个R5。与这些J基团有关的术语“任选取代的”是指未取代或者具有至少一个非氢取代基的基团，所述取代基不使未取代的类似物所具有的防止无脊椎害虫活性消失。任选取代有1-4个R5的苯基的实例是显示1中如U-1所示的环，其中Rv是R5或H，r是1-4的整数。任选取代有1-4个R5的萘基的实例如显示1中的U-85所述，其中Rv是R5或H，r是1-4的整数。任选取代有1-4个R5的5-或6-元杂芳环的实例包括显示1中所示的U-2至U-53，其中Rv是R5或H，r是1-4的整数。注意上面的J-1至J-4也代表5-或6-元杂芳环。注意U-2至U-20是J-1的实例，U-21至U-35和U-40是J-2的实例，U-41至U-48是J-3的实例，U-49至U-53是J-4的实例。任选取代有1-4个R5的芳族的8-、9-或10-元稠合的杂二环环系的实例包括显示1中所述的U-54至U-84，其中Rv是R5或H，r是1-4的整数。
尽管在结构U-1至U-85显示存在有Rv基团，但是应注意的是它们可以是H，这相当于R5任选不存在。注意当Rv是与一原子相连的H时，这与该原子未被取代相同。需要取代以填充其化合价的这些氮原子取代有H或Rv。注意一些U基团仅可被少于4个Rv基团取代(例如U-14、U-15、U-18至U-21和U-32至U-34仅可被一个Rv取代)。注意当(Rv)r和U基团之间的连接点描述为浮动的时候，(Rv)r可以与U基团上的任何可以利用的碳原子相连。注意当U基团上的连接点描述为浮动的时候，U基团可以通过取代氢原子与式I的剩余部分经U基团的任何可以利用的碳原子相连。
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Figure A0281824700251
Figure A0281824700261
Figure A0281824700271
Figure A0281824700291
如上所述，R3可以(尤其)是C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基，每一个任选取代有一个或多个选自如下的取代基：苯环、苯氧基或者5-或6-元杂芳环，每个环任选取代有1-3个独立地选自R6的取代基；C1-C4烷氧基；C1-C4烷基氨基；C2-C8二烷基氨基；C1-C4烷氧基(C1-C4烷基)氨基；C3-C6环烷基氨基；C2-C6烷氧基羰基或C2-C6烷基羰基。R3的取代环的实例包括如显示1中所述的U-1至U-53和U-86所述的环，不过这些环任选取代有1-3个独立地选自R6(不包括RV)的取代基。
如上所述，每个R5可以独立地(尤其)是苯基、苄基、苯甲酰基、苯氧基、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，每个环任选取代有1-3个独立地选自R6的取代基。这些R5基团的实例包括如显示1中U-1至U-88所述的环或环系，不过这些环任选取代有1-3个独立地选自R6(不包括RV)的取代基。
式I的化合物可以用如下反应式1-34中所述的一种或多种方法和改进方法制备。在下式I和式2-57的化合物中，R1-R6、J、K、L和n的定义如同本发明上面的概述中的定义，式Ia-Ie、2a、5a-e、13a-e和49a-b的化合物分别是式I、2、5、13和49的化合物的不同亚类。
式Ia的化合物可以在有酸清除剂的情况下，将式2的胺与式3的酰基氯偶联制得，如反应式1所示。典型的酸清除剂包括胺碱类，例如三乙胺、N，N-二异丙基乙胺和吡啶；其它清除剂包括氢氧化物如氢氧化钠和氢氧化钾以及碳酸盐如碳酸钠和碳酸钾。在某些情况下，也可以采用聚合物载酸清除剂，如结合在聚合物上的N，N-二异丙基乙胺和结合在聚合物上的4-(二甲基)氨基吡啶。所述偶联作用可以在合适的惰性溶剂如四氢呋喃、二噁烷、二乙醚或二氯甲烷中进行以得到式Ia的酰苯胺。
                         反应式1
如反应式2所述，制备式Ia的化合物的另一方法包括在脱水剂如1，3-二环己基碳二亚胺(DCC)存在下，将式2的胺与式4的酸偶联。这里也可以采用聚合物载试剂，例如结合在聚合物上的1，3-环己基碳二亚胺。反应式1和2的合成方法是用于制备式I化合物的方法的代表性实例，关于这类反应的合成文献很多。
                     反应式2
本领域技术人员还会知道，可通过多种熟知的方法由式4的酸制成式3的酰基氯。例如，在惰性溶剂如甲苯或二氯甲烷中在有催化量的N，N-二甲基甲酰胺的情况下将羧酸4与亚硫酰氯反应可以容易地由式4的羧酸制备式3的酰基氯。
式2a的胺通常可以由式5的相应的硝基化合物经如反应式3所示的硝基催化氢化反应获得。典型的步骤包括在存在金属催化剂(如Pd/C或氧化铂)的情况下并在羟基溶剂如乙醇和异丙醇中用氢还原。它们也可以在乙酸中用锌还原制得。这些步骤充分地公开在化学文献中。在这一阶段通常可以通过通常优选的将该胺还原烷基化的方法引入R1取代基，例如烷基、取代的烷基等。常用步骤是在有还原剂如氰基硼氢化钠的情况下将苯胺2a与醛混合制得式2化合物，其中R1是烷基、链烯基、链炔基或其取代的衍生物。
                     反应式3
如反应式4所述，将式6的胺与式7的酰基氯通过与反应式1所述的类似方法反应可以制得式5a的硝基苯。
                     反应式4
如反应式5所述，式6的胺(其中R2不是H)可以通过将式8的伯胺经与反应式3中所述的类似方法还原烷基化制得。
                     反应式5
反应式6显示了式5b的化合物可以在有碱(如氢化钠或正丁基锂)的情况下在惰性溶剂如四氢呋喃或N，N-二甲基甲酰胺(DMF)中用合适的烷基化试剂烷基化，从而得到式5a的酰苯胺，其中R2不是氢。该步骤特别适用于制备R2是烷基、链烯基或链炔基的式5a化合物。
                     反应式6
Figure A0281824700323
反应式7概括了式5c的硫代酰苯胺的制备方法。式5a的酰苯胺(其中R2是H、烷基等)与五硫化磷或Lawesson试剂(即2，4-二(4-甲氧基苯基)-1，3-二硫代-2，4-diphosphetane-2，4-二硫化物)在合适的溶剂如吡啶中于室温或加热下反应得到式5c的硫代酰苯胺。
                     反应式7
此外，式Ib的硫代酰苯胺可以由式Ia的相应的酰苯胺经反应式8中所述的方法制得。
                     反应式8
式Ic的化合物可以在有酸清除剂的情况下，将式2的胺与式9的磺酰基氯反应制得。典型的酸清除剂包括胺碱类，例如三乙胺、N，N-二异丙基乙胺和吡啶；其它清除剂包括氢氧化物如氢氧化钠和氢氧化钾以及碳酸盐如碳酸钠和碳酸钾。在某些情况下，也可以采用聚合物载酸清除剂，如结合在聚合物上的N，N-二异丙基乙胺和结合在聚合物上的4-(二甲基)氨基吡啶。
                     反应式9
Figure A0281824700333
式5e的硫酰胺可以由式5d的相应的酰胺经与反应式7中所述相似的方法制得。
                     反应式10
Figure A0281824700341
式5d的酰胺(其中R2是H)可以由式10的酰基氯或者由式11的羧酸分别经与反应式1和2中所述相似的方法制得。
                     反应式11
Figure A0281824700342
式5d的酰胺(其中R2不是H)可以由式5d的相应酰胺经与反应式6中所述的类似方法制得。
                     反应式12
Figure A0281824700343
式12的胺可以由式13的羧酸(或者相应的酰基氯衍生物)使用Curtius、Schmitt或Lossen条件制得。这些名称反应在文献中已被充分公开。一些代表性的反应条件例如参见R.C.Larock、ComprehensiveOrganic Transformations，1989，VCH出版社，第431-2页。
                     反应式13
式12的胺也可以将式14的合适硝基化合物通过与反应式3中所述相似的方法还原制得。
                     反应式14
式13a的苯甲酸(J是任选取代的苯基)及其制备步骤在本领域中为公知。本发明的苯甲酸的一个特别有用的亚类是式13a的2-甲基-4-全氟烷基苯甲酸(一个R5是例如CF3、C2F5、C3F7)。反应式15-19概括了这些化合物的合成。式13a的苯甲酸可以由式15的苄腈通过水解制得。所用条件可以包括使用在溶剂如水、乙醇或乙二醇中的碱如碱金属氢氧化物或醇化物(例如氢氧化钾或氢氧化钠)(例如J.Chem.Soc.1948，1025)。或者，可以使用酸(如硫酸或磷酸)在合适的溶剂如水中进行水解(例如Org.Synth.1955，Coll Vol.3，557)。条件的选择依R5对这些反应条件的稳定性而定；通常使用高温获得这种转化。
                     反应式15
式15的腈可以由式16的苯胺通过包括重氮化并用氰化铜盐处理该中间重氮盐的经典步骤制得(例如J.Amer.Chem.Soc.1902，24，1035)。
                     反应式16
式16的苯胺可以由式17的化合物制得。这种转化可以通过一种公知步骤使用阮内镍实现(Org.Synth.Coll.Vol VI，581)。或者，在有氢的情况下采用适当的催化剂例如钯，也可以进行相同的转化。该反应通常在102-105kPa压力下，在适当的有机溶剂如甲苯(但不限于此)中进行。为了完成转化，通常需要80-110℃的高温。作为本领域技术人员将知道，可以对硫醚部分进行许多化学改性，并且在需要促进这种转化时可以采用。
                     反应式17
Figure A0281824700362
式17的化合物可从式18的亚氨基硫化物(iminosulfurane)制得。该转化可以在极性溶剂(如甲醇或水)中，在非质子溶剂(如二氯甲烷或甲苯)中在适当的碱如三乙胺存在下(如Org.Synth.Coll.Vol.VI，581)或甲氧基钠存在下，或在极性溶剂、极性溶剂和碱共同存在下完成。反应进行的温度通常在40-110℃的范围内。本领域技术人员知道，也可以采用式18的化合物的适当的盐，例如，但不限于盐酸盐、硫酸盐或亚硫酸盐，条件是首先用适量的碱以产生游离碱18。这可以作为一个独立的步骤，或者与包括式18的化合物转化成式17的化合物的步骤合为一步。
                     反应式18
Figure A0281824700371
式18的化合物可以由式19的苯胺通过与二甲基硫醚和适当的氯化剂(如(但不限于)N-氯丁二酰亚胺(如Org.Synth.Coll.Vol.VI，581)、氯或N-氯苯并三唑)反应制得。另外，式19的苯胺可以用二甲基砜处理，后者已通过用例如乙酸酐、三氟乙酸酐、三氟甲磺酸酐、环己基碳二亚胺、三氧化硫或五氧化二磷的试剂处理“活化”。该反应在适当的有机溶剂如二氯甲烷或二甲基砜中进行。反应在-70℃至25℃的温度下进行；最佳反应温度取决于所用的溶剂和反应剂。
                     反应式19
Figure A0281824700372
式13的杂环酸(其中J是一任选取代的杂环)可以通过反应式20-25所概括的步骤制得。在以下的概要中可以找到包括噻吩、呋喃、吡啶、嘧啶、三唑、咪唑、吡唑、噻唑、噁唑、异噻唑、噻二唑、噁二唑、三嗪、吡嗪、哒嗪和异噁唑等的多种杂环酸的一般参考文献与专门参考文献：Rodd′s Chemistry of Chemistry of Carbon Compounds，Vol.IVa-IVI.，S.Coffey编辑，Elsevier Scientific Publishing，New York，1973；Comprehensive Heterocyclic Chemistry，Vol.1-7，A.R.Katritzky和C.W.Rees编辑，Pergamon Press，NewYork，1984；ComprehensiveHeterocyclic Chemistry II，Vol.1-9，A.R.Katritzky，C.W.Rees和E.F.Scriven编辑，Pergamon Press，NewYork，1996；及其系列，TheChemistry of Heterocyclic Compounds，E.C.Taylor编辑，Wiley，NewYork。特别有用的本发明的杂环酸包括吡啶酸、嘧啶酸和吡唑酸。在反应式20-25中详述了合成每个代表性实例的方法。在世界专利申请WO 98/57397中可找到各种杂环酸及其常规的合成方法。
式13b的代表性的吡啶酸的合成描述于反应式20。该方法包括已知的由β-酮酯和式23的4-氨基丁酮合成吡啶。取代基R5(d)和R5(e)例如包括烷基和卤烷基。该方法的指导文献参见Synthesis，1999，(7)，1216-1222和Heterocycles，1997，46，129-132。
                     反应式20
式13c的代表性的嘧啶酸的合成描述于反应式21。该方法包括已知的由式26的亚乙烯基-β-酮酯和脒合成嘧啶。取代基R5(d)和R5(e)例如包括烷基和卤烷基。该方法的指导文献参见Bull.Soc.Chim.Fr.，1987，(2)，318-324。
                     反应式21
式13d的代表性的吡唑酸的合成描述于反应式22-25。反应式22中13d的合成包括通过式28的吡啶的烷基化引入R5(e)取代基的关键步骤。烷基化试剂R5(e)-Lg(其中Lg是可离去基团，例如Cl、Br、I、磺酸根如对甲苯磺酸基或甲磺酸基或硫酸根如-OSO2R5(e))包括R5(e)基团，如C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基、C1-C6卤烷基、C2-C6卤链烯基、C2-C6卤链炔基、C3-C6卤环烷基、C2-C6烷基羰基、C2-C6烷氧基羰基、C3-C8二烷基氨基羰基、C3-C6三烷基甲硅烷基；和苯基、苄基、苯甲酰基、5-或6-元杂芳环或芳族的8-、9-或10-元稠合的杂二环环系，每个环或环系经过任选取代。甲基的氧化产生吡唑甲酸。更优选的一些R5(d)基团包括卤烷基。
                     反应式22
Figure A0281824700401
一些吡唑酸可以经式32的吡唑的金属化和羧化作为关键步骤来制备(反应式23)。R5(e)基团以与反应式22类似的方法引入，即用R5(e)烷基化试剂烷基化。代表性的R5(d)基团包括如氰基和卤烷基。
式13d的其它吡唑可以经过任选取代的苯肼33与丙酮酸酯34反应产生吡唑酯35来制备(反应式24)。所得的酯水解产生吡唑酸13d。该方法对于制备R5(e)为任选取代的苯基并且R5(d)是卤烷基的化合物特别有用。
                     反应式23
                     反应式24
Figure A0281824700411
式13d的吡唑酸也可以通过一个适当取代的腈亚胺与式37的取代丙炔酸酯或者式39的丙烯酸酯经3+2环加成来制备，如反应式25中所示。用丙烯酸酯的环加成需要把中间体吡唑啉再氧化成吡唑。酯35水解产生吡唑酸13d。本反应优选的亚胺卤化物包括三氟甲基亚氨基氯化物(40)和亚氨基二溴化物(41)。化合物如40是已知的(J.Heterocycl.Chem.1985，22(2)，565-8)。化合物如41可由已知方法得到(Tetrahedron Letters 1999，40，2605)。这些方法对于制备R5(e)是任选取代的苯基和R5(d)是卤烷基或溴的化合物特别有用。
                     反应式25
式12a的吡唑胺可以通过任选取代的苯肼33与式42的酮腈反应制得。该环化反应在现有技术中已充分公开。指导文献和一些代表性反应条件参见PCT公开WO01/004115和Synthesis，1997，(3)，337-341。反应条件也可以参见本发明的实施例7。
                     反应式26
式Id的化合物可以用胺12处理苯并噁嗪酮43制得，如反应式27所示。苯并噁嗪酮与胺产生苯甲酰亚氨酰胺(anthranilamide)的常规反应在化学文献中已充分公开。关于苯并噁嗪酮化学的综述参见Jakobsen等人，Biorganic and Medicinal Chemistry 2000，8，2095-2103以及其中引证的文献。制备苯并噁嗪酮43的代表性反应方法参见Journal of Heterocyclic Chemistry，2000，37(4)，725-729和Tetrahedron，1995，51(7)，1861-6。
                     反应式27
Figure A0281824700431
式Ie的化合物可以通过反应式28中所述的方法制得。将胺44酰基化，然后将硝基还原，得到式46的胺。胺46与酰基氯7经反应式1中所述的类似方法偶联得到式Ie的化合物。式44的化合物可以经与反应式3中所述的类似方法通过还原烷基化制得。所述酰基化反应可以通过与反应式1和反应式2中所述的类似方法与酰基氯3或酸4偶联实现。
                     反应式28
Figure A0281824700432
式13e的吡唑甲酸，其中R5是CF3，可以通过反应式29中概括的方法制得。
                     反应式29
Figure A0281824700441
式47的化合物(其中R8是C1-C4烷基)与合适的碱在合适的有机溶剂中反应，在用诸如乙酸的酸中和之后，得到式48的环化产物。所述合适的碱例如可以是，但不限于，氢化钠、叔丁氧基钾、甲基亚磺酰钠(CH3S(O)CH2，Na+)、碱金属(如锂、钠或钾)的碳酸盐或氢氧化物、四烷基(如甲基、乙基或丁基)铵氟化物或氢氧化物、或2-叔丁基亚氨基-2-二乙基氨基-1，3-二甲基全氢化-1，3，2-diazaphosphonine。合适的有机溶剂可以是例如，但不限于，丙酮、乙腈、四氢呋喃、二氯甲烷、二甲亚砜或N，N-二甲基甲酰胺。所述环化反应通常在约0-120℃的温度下进行。溶剂、碱、温度和加入时间的影响都是相互依赖的，并且反应条件的选择使副产物的形成最小化是重要的。优选的碱是氟化四丁基铵。
将式48的化合物脱水得到式49的化合物，接着将羧酸酯官能团转化成羧酸，从而得到式13e的化合物。该脱水反应受到用催化量的合适酸处理的影响。该催化酸可以是例如，但不限于，硫酸。该反应通常使用有机溶剂进行。本领域技术人员应了解，脱水反应可以在各种溶剂中于通常在约0-200℃，更优选在约0-100℃的温度范围内进行。就反应式9的方法中的脱水反应而言，优选溶剂包括乙酸，温度为约65℃。通过许多方法可以将羧酸酯化合物转化成羧酸化合物，这些方法包括在无水条件下亲核裂解或者包括使用酸或碱的水解法(参见T.W.Greene和P.G.M.Wuts，Protective Groups in OrganicSynthesis，第2版，John Wiley & Sons，Inc.，New York，1991，第224-269页的方法综述)。就反应式9的方法而言，优选碱催化水解的方法。合适的碱包括碱金属(如锂、钠或钾)氢氧化物。例如，所述酯可以溶解在水和醇如乙醇的混合物中。用氢氧化钠或氢氧化钾处理之后，将该酯皂化得到羧酸的钠或钾盐。用强酸，如盐酸或硫酸酸化，得到式13e的羧酸。该羧酸可以通过本领域技术人员已知的方法分离，这些方法包括结晶、萃取和蒸馏。
式47的化合物可以通过反应式30中概括的方法制备。
                     反应式30
Figure A0281824700451
其中，R5为CF3，R8为C1-C4的烷基。
在溶剂如水、甲醇或乙酸中用式51的酮处理式50的肼化合物得到式52的腙。本领域技术人员将意识到，该反应可能需要任选的酸催化，并且可能还需要高温，这取决于式52的腙的分子取代形式。式52的腙与式53的化合物在合适的有机溶剂(例如，但不限于，二氯甲烷或四氢呋喃)中在有酸清除剂(如三乙胺)的情况下反应得到式47的化合物。该反应通常在约0-100℃的温度下进行。反应式30的方法的进一步试验细节描述在实施例8。式50的肼化合物可以通过标准方法制得，例如通过将相应的2-卤代吡啶与肼接触。
作为反应式29中所述方法的替代，式13e的吡唑甲酸(其中R5是Cl或Br)也可以通过反应式31中概括的方法制得。
                     反应式31
Figure A0281824700461
其中R8是C1-C4烷基。
任选在有酸的情况下将式54的化合物氧化得到式49的化合物，接着将羧酸酯官能团转化成羧酸，从而得到式13e的化合物。氧化剂可以是过氧化氢、有机过氧化物、过硫酸钾、过硫酸钠、过硫酸铵、一过硫酸钾(例如，Oxone_)或高锰酸钾。为了获得完全转化，应使用至少1当量的氧化剂(相对式54的化合物)，优选约1-2当量。这种氧化反应通常是在有一溶剂的情况下进行的。该溶剂可以是醚，例如四氢呋喃、对二噁烷等；有机酯，例如乙酸乙酯、碳酸二甲酯等；或者一极性质子惰性有机溶剂，例如N，N-二甲基甲酰胺、乙腈等。适用于该氧化步骤的酸包括无机酸，例如硫酸、磷酸等；和有机酸，例如乙酸、苯甲酸等。该酸(当使用时)应以相对式54的化合物大于0.1当量使用。为了获得完全转化，可以使用1-5当量的酸。优选的氧化剂是过硫酸钾，并且该氧化反应优选在有硫酸的情况下进行。该反应可以通过将式54的化合物混入所需溶剂和(如果使用的话)酸中进行。然后以方便的速度加入氧化剂。反应温度通常在低至约0℃到高至溶剂沸点的范围内变化，以便获得完成该反应的合理反应时间，优选小于8小时。所需产物，式49的化合物，可以通过本领域技术人员已知的方法分离，这些方法包括结晶、萃取和蒸馏。适用于将式49的酯转化成式13e的羧酸的方法已描述于反应式29。
式54的化合物可以由式55的相应化合物如反应式32中所示制得。
                     反应式32
其中R8是C1-C4烷基。
通常在有一溶剂的情况下，用卤化试剂处理式55的化合物，得到式54的相应卤代化合物。可以使用的卤化试剂包括磷酰卤、三卤化磷、五卤化磷、亚硫酰氯、二卤三烷基磷烷、二卤二苯基磷烷、草酰氯和光气。优选磷酰卤和五卤化磷。为了获得完全的转化，相对式55的化合物，应使用至少0.33当量的磷酰卤，优选约0.33-1.2当量。为了获得完全的转化，相对式55的化合物，应使用至少0.20当量的五卤化磷，优选约0.20-1.0当量。就该反应而言，优选式55的化合物，其中R8是C1-C4烷基。该卤化作用用的典型溶剂包括卤化链烷，例如二氯甲烷、氯仿、氯丁烷等；芳族溶剂，例如苯、二甲苯、氯苯等；醚类，例如四氢呋喃、对二噁烷、二乙醚等；和极性质子惰性溶剂，例如乙腈、N，N-二甲基甲酰胺等。任选，可以加入一种有机碱，例如三乙胺、吡啶、N，N-二甲基苯胺等。加入一种催化剂，例如N，N-二甲基甲酰胺，也是一种选择。优选溶剂是乙腈且没有碱的方法。通常，当使用乙腈溶剂时，要求既没有碱也没有催化剂。优选方法是通过将式55的化合物混入乙腈中来进行的。然后在方便的时间内加入该卤化试剂，然后将该混合物保持在所需温度，直到反应结束。反应温度通常在20℃与乙腈的沸点之间，并且反应时间通常小于2小时。然后将反应物用例如碳酸氢钠、氢氧化钠等的无机碱或者用例如乙酸钠的有机碱中和。目标产物，式54的化合物，可以用本领域技术人员已知的方法(包括结晶、萃取和蒸馏)分离。
或者，式54的化合物(其中R5是Br或Cl)可以通过分别用溴化氢或氯化氢处理式54的相应化合物制得，其中R5是不同的卤素(例如，对于制备式54(其中R5是Br)是Cl)或者是磺酸根基团如对甲苯磺酸基、苯磺酸根和甲磺酸基。通过该方法，将式54的原料化合物上R5卤素或磺酸根取代基分别用来自溴化氢或氯化氢的Br或Cl替换。该反应在合适的溶剂如二溴甲烷、二氯甲烷或乙腈中进行。该反应可以在大气压下或者在大气压附近或者在大于大气压下于压力容器中进行。当式54的原料化合物中的R5是卤素如Cl时，反应优选将反应中产生的卤化氢通过喷射或者其它合适的方式除去。该反应可以在约0-100℃之间进行，最方便地接近室温(例如，约10-40℃)，更优选在约20-30℃之间。加入路易斯酸催化剂(如对制备R5是Br的式54而言为三溴化铝)可以使该反应加速。式54的产物通过本领域技术人员已知的常规方法(包括萃取、蒸馏和结晶)分离。
式54的原料化合物(其中R5是Cl或Br)如已经叙及的可以由式55的相应化合物制得。式54的原料化合物(其中R5是磺酸根基团)同样可以由式54的相应化合物通过标准方法如用磺酰氯(例如对甲苯磺酰氯)和碱如叔胺(例如，三乙胺)在合适的溶剂如二氯甲烷中处理制得。
式13e的吡唑甲酸(其中R5是OCH2CF3)可以通过反应式33中概括的方法制得。
                     反应式33
Figure A0281824700491
其中R8是C1-C4烷基，并且X是离去基团。
在该方法中，不用如反应式32中所示的卤化，而是将式55的化合物氧化成式49a的化合物。该氧化反应的反应条件已在反应式31中将式54的化合物转化成式49的化合物时进行了描述。
然后在有碱的情况下将式49a的化合物与烷基化试剂CF3CH2X(56)接触烷基化形成式49b的化合物。在该烷基化试剂56中，X是一亲核反应离去基团，例如卤素(例如Br、I)、OS(O)2CH3(甲磺酸基)、OS(O)2CF3、OS(O)2Ph-p-CH3(对甲苯磺酸基)等；甲磺酸基是良好的离去基团。反应是在有至少1当量碱的情况下进行的。合适的碱包括无机碱，例如碱金属(如锂、钠或钾)碳酸盐和氢氧化物；以及有机碱，如三乙胺、二异丙基乙基胺和1，8-二氮杂二环[5.4.0]十一碳-7-烯。反应通常是在一溶剂中进行的，该溶剂可以包括醇类，如甲醇和乙醇；卤化链烷，如二氯甲烷；芳族溶剂，如苯、甲苯和氯苯；醚类，如四氢呋喃；和极性质子惰性溶剂，如乙腈、N，N-二甲基甲酰胺等。优选将醇和极性质子惰性溶剂与无机碱一起使用。优选碳酸钾作为碱，并优选乙腈作为溶剂。反应通常在约0-150℃之间进行，最优选在室温-100℃之间。通过常规技术如萃取可以将产物式49b分离。然后可以通过在反应式29中已经描述的将式49转化成式13e的方法将式49b的酯转化成式13e的羧酸。
式55的化合物可以由式50的化合物如反应式34所述制得。
                     反应式34
其中R8(是C1-C4烷基。
在本方法中，在有碱和溶剂的情况下将式50的肼化合物与式57的化合物(可以使用其富马酸酯或马来酸酯或其混合物)接触。碱通常是金属醇盐，如甲醇钠、甲醇钾、乙醇钠、乙醇钾、叔丁醇钾、叔丁醇锂等。相对式50的化合物，应使用大于0.5当量的碱，优选0.9-1.3当量。应使用大于1.0当量的式57的化合物，优选1.0-1.3当量。可以使用极性质子有机溶剂和极性质子惰性有机溶剂，如醇类、乙腈、四氢呋喃、N，N-二甲基甲酰胺、二甲亚砜等。优选溶剂是醇类如甲醇和乙醇。特别优选该醇与构成富马酸酯或马来酸酯以及醇盐碱的醇相同。反应通常通过在该溶剂中将式18的化合物与碱混合来进行。可以将该混合物加热或冷却至所需温度，并在一段时间内加入式57的化合物。典型的反应温度是0℃-所用溶剂的沸点。为了升高溶剂的沸点，反应可以在大于大气压下进行。通常优选温度在约30-90℃。只要热转移允许加入时间越快越好。典型的加入时间在1分钟至2小时之间。最佳反应温度和加入时间随式50和式57的化合物的种类而变化。加入之后，反应混合物可以在该反应温度下保持一段时间。根据该反应温度，所需的保持时间可以在0-2小时。通常保持时间是10-60分钟。然后加入有机酸如乙酸等和无机酸如盐酸、硫酸等，将该反应物酸化。根据反应条件和分离方式，式55的化合物上的-CO2R8官能团可以水解成-CO2H；例如，反应混合物中的水可以促进这种水解。如果形成羧酸(-CO2H)，那么使用本领域公知的酯化法可以将其转化回到-CO2R8，其中R8是C1-C4烷基。目标产物，式55的化合物，可以通过本领域技术人员已知的方法，如结晶、萃取或蒸馏分离。
应理解的是，上面所述制备式I的化合物的一些试剂和反应条件可能与这些中间物中存在的某些官能度不相容。在这些情况下，向该合成中加入保护/去保护序列或官能团将有助于获得所需产物。使用并选择保护基团对化学合成领域的技术人员将是显而易见的(例如参见Greene，T.W.；Wuts，P.G.M.Protective Groups in Organic Synthesis，第2版；Wiley：New York，1991)。本领域技术人员将意识到，在一些情况下，在任何单个反应式中加入如所述的给定试剂之后，可能需要进行未详细描述的其它路径的合成步骤来完成式I的化合物的合成。本领域技术人员还应意识到，在制备式I的化合物时，可能需要以不同与上述顺序的顺序来对上面反应式中所述的步骤进行组合。
本领域技术人员还意识到，式I的化合物和本文所述的中间物可以经受各种亲电、亲核、自由基、有机金属、氧化和还原反应以加入取代基或者改进现有的取代基。
尽管未进一步描述，但是据信本领域技术人员使用前面的描述可以最充分地利用本发明。因此，以下实施例仅仅是描述性的解释，不以任何方式限制其内容。百分比以重量计，除了色谱溶剂混合物或者另有说明的之外。色谱溶剂混合物的份数和百分比以体积计，除非另有说明。1H NMR谱以ppm计从四甲硅烷降场报道的；s是单峰，d是双峰，t是三重峰，q是四重峰，m是多峰，dd是双重的双峰，dt是双重的三重峰，br s是宽单峰。
                          实施例1
1-(2-氯苯基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯基]-3(三氟甲
                  基)-1H-吡唑-5-羧酰胺
步骤A：1-(2-氯苯基)-5-2-呋喃基-3-(三氟甲基)-1H-吡唑的制备
向4，4，4-三氟-1-(2-糠基)-1，3-丁二酮(30.0g，146mmol)的冰醋酸(65mL)溶液中加入乙酸钠(12.1g，148mmol)。将该混合物冷却至约25℃，分份加入2-氯苯基肼盐酸盐(25.6g，145mmol)，接着适当放热，将该混合物加热至60℃持续4小时，然后冷却至25℃。用二氯甲烷(400mL)稀释该混合物，并将有机相用水(3×250mL)、饱和碳酸钠水溶液(2×250mL)和盐水洗涤，然后在硫酸镁上干燥并在减压下蒸发，得到43.2g标题化合物棕色油。
1H NMR(CDCl3)δ7.6(m，5H)，6.9(1H)，5.7(d，1H)。
步骤B：1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备
在约0.25小时内向含有步骤A的标题化合物(43.2g，138mmol)的乙腈(415mL)悬浮液中加入磷酸二氢钠一水合物(92.4g，669mmol)。在室温下搅拌0.5小时之后，将该混合物冷却至约5℃，并在1小时内滴加含有亚氯酸钠(181.7g、2.0mmol)的430mL水的溶液，同时保持反应温度低于10℃。[注：与含水氢氧化钠洗涤塔相连以清洗析出的黄色气体。]加入结束之后，在5℃下将该悬浮液搅拌约1小时，在25℃下过夜，然后通过滴加浓盐酸(150mL)酸化至pH1，然后用乙酸乙酯(1×500mL，然后2×250mL)萃取。在低于20℃的反应温度下将该混合的乙酸乙酯萃取物滴加到焦亚硫酸钠水溶液(228.5g于1.05L水中)中。将该悬浮液分开，含水层用乙酸乙酯(2×100mL)萃取。将有机层混合，在硫酸镁上干燥并在减压下蒸发。残余物与己烷∶二乙醚(99∶1，100mL)一起研磨，得到32.9g标题化合物固体。
1H NMR(DMSO-d6)δ13.9(bs，1H)，7.7(m，5H)。
步骤C：1-(2-氯苯基)-N-(3-甲基-2-硝基苯基)-3-(三氟甲基)-1H-吡唑-5- 羧酰胺的制备
向步骤B的标题化合物(1.2g，3.4mmol)的二氯甲烷(15mL)的混合物中加入草酰氯(0.5g，3.7mmol)，接着加入2滴N，N-二甲基甲酰胺。开始放热之后，在室温、N2下将该悬浮液搅拌0.4小时，然后在减压下蒸发，得到一油状残余物。将该残余物溶解在四氢呋喃(20mL)中，加入2-甲基-6-硝基苯胺(0.5g，152.2mmol)，接着加入N，N-二异丙基乙基胺(0.7g，129.5mmol)，并在室温、N2下将该悬浮液搅拌过夜。在减压下将该粗混合物蒸发，在硅胶上用己烷∶乙酸乙酯(2∶1)作为洗脱剂通过闪蒸塔色谱法将该残余物纯化，得到200mg标题化合物固体；m.p.215-220℃。
1H NMR(CDCl3)δ2.3(s，3H)，6.3-6.6(s，1H)，7.4-7.6(m，7H)，8.0(d，1H)。
步骤D：N-(2-氨基-3-甲基苯基)-1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5- 羧酰胺
将步骤C的标题化合物(1.0g，2.3mmol)溶解在乙酸乙酯(50mL)中并在10％Pd/C(200mg，1.8mmol)上于Parr Shaker(45psi)中氢化3小时。接着将该反应混合物通过Celite_硅藻助滤剂进行过滤，并在减压下将滤液蒸发，将所得油残余物浆化于己烷中并过滤，得到1.0g标题化合物灰白色固体；m.p.165-167℃。
1H NMR(CDCl3)δ2.2(s，3H)，3.6(m，2H)，6.7(m，1H)，6.9(m，1H)，7.1(m，1H)，7.2(m，1H)，7.4(m，2H)，7.5，(m，2H)，8.1(bs，1H)。
步骤E：1-(2-氯苯基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯 基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制备
向含有步骤D的标题化合物(0.6g，1.5mmol)的四氢呋喃(20mL)悬浮液中加入异丁基氯(0.25g，2.3mmol)，接着加入I-二异丙基乙基胺(0.5g，3.9mmol)。在25℃下将该悬浮液搅拌过夜，然后用1NHCl(100mL)和乙酸乙酯(100mL)稀释。分离有机层，用1N HCl、水、饱和碳酸氢钠水溶液和盐水洗涤(每一洗液为约50mL)，然后在硫酸镁上干燥并在减压下蒸发，得到0.6g标题化合物(本发明的化合物)固体；m.p.240-242℃。1H NMR(CDCl3)δ1.3(d，6H)，2.5(s，3H)，2.6(m，1H)，7.0-7.6(m，9H)，9.5(s，1H)。
                         实施例2
2-甲基-6-[(2-甲基-1-氧代丙基)氨基]-N-[2-甲基-4(三氟甲基)苯基]苯甲
                           酰胺
步骤A：2-甲基-N-[2-甲基-4-(三氟甲基)苯基]-6-硝基苯甲酰胺的制备
将2-甲基-6-硝基苯甲酸(9.0g，49.7mmol)和亚硫酰氯(62mL)的混合物在回流下于甲苯(100mL)中加热2.5小时，然后冷却至25℃。在减压下将所得悬浮液蒸发，然后与甲苯共沸。将所得残余物溶解在四氢呋喃(10mL)中，将其滴加到含有2-氨基-5-三氟甲基甲苯(2.89g16.5mmol)和三乙胺(2.02g，20mmol)的四氢呋喃(20mL)溶液中。在25℃下将该悬浮液搅拌72小时，然后倒入水中并用乙酸乙酯(2×20mL)萃取。将该混合有机萃取物蒸发于硅胶上并在硅胶(使用梯度从100％己烷到1∶1己烷∶乙酸乙酯的洗脱剂)上通过中压液相色谱法纯化，得到1.22g标题化合物。
1H NMR(CDCl3)δ2.4(s，3H)，2.6(s，3H)，7.5-7.7(m，5H)，8.1(m，1H)，8.2(m，1H)。
步骤B：2-氨基-6-N-[2-甲基-4-(三氟甲基)苯基]苯甲酰胺的制备
将步骤A的标题化合物(2.73g，7.7mmol)溶解在乙醇(25mL)中并在Pd/C(0.2g)上使用Parr Shaker(350kPa)氢化16小时。将所得反应悬浮液通过Colite_过滤之后，用二乙醚洗涤滤得的白色滤饼。在减压下将这些混合的有机层蒸发，得到2.4g标题化合物半固体。
1H NMR(CDCl3)δ2.4(m，6H)，6.8(m，3H)，7.1(m，1H)，7.4-7.7(m，4H)，8,3(m，1H)。
步骤C：2-甲基-6-[(2-甲基-1-氧代丙基)氨基]-N-[2-甲基-4-三氟甲基) 苯基]苯甲酰胺的制备
将异丁酰氯(51.8mg，0.5mmol)加入到含有步骤B的标题化合物(0.15g，0.5mmol)和N，N-二异丙基乙基胺(0.13g，1.0mmol)的氯仿(5mL)溶液中。在25℃下将该悬浮液搅拌过夜，然后用1N HCl稀释。搅拌约1小时之后，将该悬浮液通过0.45微米PTFE膜过滤，并在减压下将该滤液蒸发，得到0.08g标题化合物(本发明的化合物)固体；m.p.＞230℃。
1H NMR(DMSO-d6)δ1.0(d，6H)，2.5(s，3H)，2.4(s，3H)，2.6(m，1H)，7.1(m，1H)，7.3(m，1H)，7.6(m，2H)，7.9(m，2H)，9.3(bs，1H)，9.9(s，1H)。
                           实施例3
2-甲基-6-[(2-甲基-1-氧代丙基)氨基]-N-[2-甲基-4-(三氟甲氧基)苯基]
                          苯甲酰胺
步骤A：2-甲基-N-[2-甲基-4-(三氟甲氧基)苯基]-6-硝基苯甲酰胺的制 备
通过实施例2的步骤(步骤A)，将2-甲基-4-三氟甲氧基苯胺(3.15g，16.5mmol)与2-甲基-6-硝基苯甲酰氯(3.3g，16.5mmol)和三乙胺(2.02g，20mmol)于四氢呋喃(30mL)中反应。在反应结束之后，将反应悬浮液倒入过量水中，并用乙酸乙酯萃取几次。将这些混合的萃取液在硫酸镁上干燥并在减压下蒸发，得到一固体。将该固体通过与己烷∶二乙醚溶液一起研磨进一步纯化，得到2.73g标题化合物。
1H NMR(CDCl3)δ2.3(s，3H)，2.6(s，3H)，7.1(m，3H)，7.5(m，1H)，7.6(m，1H)，7.9(m，1H)，8.1(m，1H)。
步骤B：2-氨基-6-N-[2-甲基-4-(三氟甲氧基)-苯基]苯甲酰胺的制备
通过实施例2的步骤(步骤B)，将实施例3(步骤A)的标题化合物(2.73g，7.7mmol)氢化，得到2.4g标题化合物半固体。
1H NMR(CDCl3)δ2.3(s，3H)，2.5(s，3H)，6.6(m，2H)，7.1(m，6H)，7.4(bs，1H)，8.0(m，1H)。
步骤C：2-甲基-6-[(2-甲基-1-氧代丙基)氨基-N-[2-甲基-4-(三氟甲氧基) 苯基]苯甲酰胺的制备
将异丁酰氯(0.16g，1.2mmol)加入到含有步骤B的标题化合物(0.2g，0.6mmol)和N，N-二异丙基乙基胺(0.16g，1.2mmol)的二氯甲烷(5mL)溶液中。在25℃下将该反应搅拌过夜之后，将该悬浮液倒入水中并用乙酸乙酯萃取几次。将这些混合的萃取物在硫酸镁上干燥并在减压下蒸发，得到0.13g标题化合物(本发明的化合物)固体；m.p.＞230℃。
1H NMR(DMSO-d6)δ1.0(d，6H)，2.3(s，3H)，2.4(s，3H)，2.6(m，1H)，7.1(m，1H)，7.2-7.4(m，4H)，7.7(m，1H)，9.3(s，1H)，9.8(s，1H)。
                          实施例4
3-氯-2-[(2-甲基-1-氧代丙基)氨基]-N-[4-(三氟甲氧基)苯基]苯甲酰胺
步骤A：3-氯-2-硝基-N-[4-(三氟甲氧基)苯基]苯甲酰胺的制备
将五氯化磷(2.14g，10.2mmol)分份加入到3-氯-2-硝基苯甲酸(2.0g，9.7mmol)的二氯甲烷(30mL)混合物中。加入结束并且气体释放停止之后，在室温下将溶液搅拌0.5小时，然后在减压下蒸发。残余的磷酰氯在减压下用甲苯进一步除去，得到2.1g相应的苯甲酰氯固体。将含有该苯甲酰氯(1.0g，4.4mmol)的二氯甲烷(10mL)溶液滴加到含有4-三氟甲氧基苯胺(0.79g，4.4mmol)和三乙胺(0.45g，4.4mmol)的二氯甲烷(3mL)溶液中。在室温下将该悬浮液搅拌0.5小时，然后倒入过量水中并用乙酸乙酯萃取几次。将该混合的有机萃取物用水洗涤，在硫酸镁上干燥并在减压下蒸发，得到一固体。将该固体用己烷∶二乙醚(1∶1)洗涤，得到1.38g标题化合物固体；m.p.171-172℃。
1H NMR(CDCl3)δ7.2(m，3H)，7.5-7.7(m，4H)，7.8(bs，1H)。
步骤B：2-氨基-3-氯-N-[4-(三氟甲氧基)苯基]苯甲酰胺的制备
向硼氢化钠(26mg，0.68mmol)的乙醇(1mL)溶液中加入含有乙酰丙酮酸铜(II)(20.0mg，0.08mmol)的2-丙醇(1mL)悬浮液，接着加入含有步骤A的标题化合物(0.25g，0.6mmol)的2-丙醇(3mL)悬浮液，接着加入硼氢化钠(2.0mg，78mmol)的乙醇(2mL)溶液。在25℃下将该反应混合物搅拌7小时，然后倒入稀氯化铵水溶液中并用乙酸乙酯萃取几次。将该混合有机萃取物在氯化镁上干燥并在减压下蒸发，得到0.18g标题化合物。
1H NMR(CDCl3)δ7.3(m，5H)，7.4(m，2H)，7.6(m，2H)，7.8(bs，1H)。
步骤C：3-氯-2-[(2-甲基-1-氧代丙基)氨基]-N-[4-(三氟甲氧基)苯基]苯 甲酰胺的制备
将异丁酰氯(57mg，0.5mmol)加入到步骤B的标题化合物(0.18g，0.5mmol)和三乙胺(54.0mg，0.5mmol)的二氯甲烷(3mL)中的混合物中。搅拌1.5小时之后，另外加入5滴丁酰氯和5滴三乙胺。将该悬浮液搅拌2小时，然后倒入水中并用乙酸乙酯萃取几次。混合的萃取物用水洗涤，然后在硫酸镁上干燥并在减压下蒸发。残余物在硅胶上用己烷∶乙酸乙酯(2∶1)作为洗脱剂通过闪蒸塔色谱法进一步纯化，得到40.0mg标题化合物(本发明的化合物)固体；m.p.230-233℃。
1H NMR(DMSO-d6)δ1.0(d，6H)，2.6(m，1H)，7.3-7.4(m，3H)，7.5(m，1H)，7，7(m，1H)，7.8(m，2H)，9.6(s，1H)，10.4(s，1H)。
                       实施例5
1-(3-氯-吡啶基)-N-[2-甲基-6-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟
                    甲基)-1H-吡唑-5-羧酰胺
步骤A：1-(3-氯-吡啶基)-N-(2-甲基-6-硝基苯基)-3-(三氟甲基)1-1H-吡 唑-5-羧酰胺的制备
向0℃下1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸(2.875g，9.86mmol)搅拌于二氯甲烷(30mL)中的悬浮液中加入草酰氯(5.16mL，59.2mmol)，接着滴加N，N-二甲基甲酰胺(1滴)。然后将该搅拌溶液加热至回流并在该温度下搅拌1小时之后，在减压下将该溶液浓缩至干。然后将残余物溶解在四氢呋喃(30mL)中并向该搅拌溶液中加入2-甲基-6-硝基苯胺。然后将该溶液冷却至0℃并滴加N，N-二异丙基乙基胺(8.60mL，49.3mmol)。然后将该搅拌溶液加热至回流，并在该温度下搅拌42小时，然后在减压下浓缩至干。然后将残余物溶解在乙酸乙酯(30mL)中，并将该溶液用1N HCl(10mL)、饱和碳酸氢钠水溶液(10mL)和盐水(10mL)洗涤，干燥(MgSO4)并在减压下浓缩，剩下一黄色固体。将该产物溶解在乙腈(6mL)中，同时搅拌，加入氨水(6mL)，并在室温下将该溶液搅拌2小时，然后在减压下浓缩至干。该产物在硅胶(3∶1 庚烷-乙酸乙酯洗脱剂)上通过闪蒸塔色谱法纯化，得到标题化合物黄色固体(1.53g)。
1H NMR(CDCl3)δ2.21(s，3H)，7.18(s，1H)，7.27(t，1H)，7.38(m，1H)，7.47(d，1H)，7.84(d，1H)，7.85(d，1H)，8.42(dd，1H)，9.16(s，1H)。
步骤B：N-(2-胺-6-甲基苯基)-1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑 -5-羧酰胺的制备
将含有10％Pd/C(69mg)的乙醇(5mL)搅拌悬浮液的烧瓶抽真空/填充氮气(x3)。然后向该悬浮液中加入1-(3-氯-吡啶基)-N-(2-甲基-6-硝基苯基)-3-(三氟甲基)-1H-吡唑-5-羧酰胺(即步骤A的产物)(1.38g，3.25mmol)的乙醇(9mL)溶液。然后将该烧瓶抽真空/填充氮气(x3)然后抽真空/填充氢气(x3)。在室温下将该反应混合物搅拌18小时，然后通过Celite_过滤并将滤床用乙醇(2×3mL)洗涤。在减压下将滤液浓缩，得到标题化合物灰白色固体(1.306g)。
步骤C：1-(3-氯-吡啶基)-N-[2-甲基-6-[(2-甲基-1-氧代丙基)氨基]苯 基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制备
向异丁酰氯(0.053mL，0.505mmol)的四氢呋喃的搅拌溶液中加入N-(2-胺-6-甲基苯基)-1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酰胺(即步骤B的产物)(0.20g，0.505mmol)。然后将该溶液冷却至0℃，并滴加二异丙基乙基胺(0.60mL，3.59mmol)。然后在18小时内将该搅拌溶液加热至室温，然后在减压下浓缩至干。然后将残余物溶解在乙酸乙酯(10mL)中，并将该溶液用1N HCl(10mL)、饱和碳酸氢钠水溶液(10mL)和盐水(10mL)洗涤，干燥(MgSO4)并在减压下浓缩，剩下一黄色固体。该产物通过在热的叔丁基甲基醚(5mL)中浆化纯化，得到标题化合物(本发明的化合物)固体(216mg)，它在215-217℃下熔融。
1H NMR(CDCl3)δ1.11(s，3H)，1.13(s，3H)，2.20(s，3H)，2.44(m，1H)，6.89(dd，1H)，7.05(s，1H)，7.07(d，1H)，7.15(s，1H)，7.35(m，1H)，7.48(s，1H)，7.81(dd，1H)，8.41(dd，1H)，9.06(s，1H)。
                         实施例6
1-(3-氯-2-吡啶基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三
                 氟甲基)-1H-吡唑-5-羧酰胺
步骤A：2-甲基-N-(2-甲基-6-硝基苯基)-丙酰胺的制备
向0℃下2-甲基-6-硝基苯胺(2.5g，16.4mmol)搅拌于二氯甲烷(22.5mL)中的溶液中加入吡啶(2.5mL)，接着滴加异丁酰氯(1.72mL，16.4mmol)。在2小时内将该溶液加热至室温。于室温下再搅拌48小时之后，加入二氯甲烷(10mL)，接着加入饱和碳酸氢钠水溶液(30mL)。然后将水相分离并用二氯甲烷(20mL)萃取。然后将有机萃取物混合，干燥(MgSO4)并在减压下浓缩，得到标题化合物黄色固体(3.54g)。
步骤B：N-(2-氨基-6-甲基苯基)-2-甲基丙酰胺的制备
将含有10％Pd/C(25mg)的乙醇(5mL)的搅拌悬浮液的烧瓶抽真空/填充氮气(x3)。然后向该悬浮液中加入2-甲基-N-(2-甲基-6-硝基苯基)-丙酰胺(即步骤A的产物)(2.54g，11.4mmol)的乙醇(45mL)溶液。然后将该烧瓶抽真空/填充氮气(x3)，然后抽真空/填充氢气(x3)。室温下将该反应混合物搅拌35分钟，然后通过Celite_过滤，并将滤床用乙醇(2×5mL)洗涤。滤液在减压下浓缩，得到标题化合物灰白色固体(2.19g)。
步骤C：1-(3-氯-吡啶基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯 基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制备
向0℃下1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸(0.1g，0.42mmol)搅拌于二氯甲烷(4mL)中的悬浮液中加入草酰氯(0.31g，2.44mmol)，接着滴加N，N-二甲基甲酰胺(1滴)。然后将该搅拌溶液加热至回流，并在该温度下搅拌1小时之后，在减压下将该溶液浓缩至干。然后将该残余物溶解在四氢呋喃(10mL)中并向该搅拌溶液中加入N-(2-氨基-6-甲基苯基)-2-甲基丙酰胺(即步骤B的产物)。然后将该溶液冷却至0℃并滴加N，N-二异丙基乙基胺(0.52mL，2.99mmol)。然后在18小时内将该溶液加热至室温并在减压下浓缩至干。然后将残余物溶解在乙酸乙酯(10mL)中并将该溶液用1N HCl(10mL)、饱和碳酸氢钠水溶液(10mL)和盐水(10mL)洗涤，干燥(MgSO4)并在减压下浓缩，得到一黄色固体。该产物在硅胶(1∶1庚烷-乙酸乙酯洗脱剂)上经闪蒸塔色谱法纯化，然后从乙酸乙酯中再结晶，得到标题化合物(本发明的化合物)固体(70mg)，它在219-220℃下熔融。
1H NMR(CDCl3)δ1.27(s，3H)，1.29(s，3H)，2.29(s，3H)，2.66(m，1H)，7.02(s，1H)，7.08(s，1H)，7.10(d，1H)，7.25(s，1H)，7.33(d，1H)，7.39(m，1H)，7.84(dd，1H)，8.44(dd，1H)，9.50(s，1H)。
                        实施例7
N-[1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-基]-2-甲基-6-[(2-甲基-1-氧
                  代丙基)氨基]苯甲酰胺
步骤A：4，4，4-三氟-3-氧代-丁腈(或者命名为4，4，4-三氟乙酰乙 腈)的制备
向一500mL三颈烧瓶(配备有一个氮气起泡器和两个隔)中加入二异丙基酰胺锂(LDA)(18.4mL，0.172mol，2M于庚烷中)，并将该反应混合物冷却至-72℃。在氮气下使用添加漏斗滴加乙酸三氟甲酯(10.0g，0.078mol)、乙腈(6.41g，0.156mol)和THF(100mL)的0℃溶液。45分钟之后，在1-2小时内将该溶液加热至室温，用冷水(250mL)骤冷，并将有机溶剂蒸发。将含水层用二乙醚(3×250mL)洗涤，用浓HCl酸化至pH2并用二氯甲烷(3×250mL)洗涤。接着，将含水层用二乙醚(3×250mL)萃取。该二乙醚萃取物用硫酸钠干燥并浓缩，得到标题化合物澄清橙色油(1.38g，0.010mol，产率32％)。
1H NMR(CD3OD，300MHz)δ2.96(2H，s)。
步骤B：1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-胺的制备
向一Personal Chemistry(Personal Chemistry Inc.，Boston，MA，USA)10mL反应容器中加入2-氯苯基肼(0.392g，2.19mmol)、乙醇(2.5mL)和5滴冰醋酸。加入4，4，4-三氟-3-氧代-丁腈(即步骤A的产物)(0.300g，2.19mmol)的乙醇(1mL)溶液，然后将该管密封，并在150℃下在微波中加热30分钟。将所得粗混合物浓缩并使用硅胶色谱法(乙酸乙酯/己烷，1∶4)纯化，得到标题化合物黄色固体(0.179g，0.684mmol，31％产率)。
1H NMR(CDCl3，300MHz)δ3.82(2H，br)，5.85(1H，s)，7.45-7.60(4H，m)。
步骤C：5-甲基-2-(1-甲基乙基)-4H-3，1-苯并噁嗪-4-酮的制备
向一500mL圆底烧瓶中加入2-氨基-6-甲基苯甲酸(5.00g，0.033mol)和THF(200mL)。加入异丁酰氯(7.049g，0.066mol)和三乙胺(10.04g，0.099mol)，并在室温下将该反应混合物搅拌过夜。除去溶剂之后，化合物通过硅胶色谱法(乙酸乙酯/己烷，1∶9)纯化，得到标题化合物白色固体(4.85g，0.024mol，72％产率)。
1H NMR(CDCl3、300MHz)δ1.35(6H，d)，2.78(3H，s)，2.90(1H，七重峰)，7.21(1H，d)，7.40(1H，d)，7.64(1H，t)。
步骤D：N-[1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-基]-2-甲基-6-(2-甲 基-1-氧代丙基)氨基]苯甲酰胺的制备
在氮气下将氢化钠(0.2g，7.9mmol，95％纯度)加入到一10mL的装有1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-胺(即步骤B的产物)(0.200g，0.76mmol)和DMF(5mL)的烧瓶中。室温下搅拌5分钟之后，加入5-甲基-2-(1-甲基乙基)-4H-3，1-苯并噁嗪-4-酮(即步骤C的产物)(0.155g，0.76mmol)。反应通过TLC(薄层色谱法)监控，用10滴水骤冷，并直接通过硅胶制备TLC(1∶4乙酸乙酯/己烷)纯化，得到标题化合物(本发明的化合物)白色固体(0.135g，0.29mmol，38％产率)。
1H NMR(CDCl3、300MHz)δ1.08(6H，d)，2.14(3H，s)，2.38(1H，m)，6.91(1H，d)，7.07(1H，s)，7.02(1H，t)，7.41-7.59(5H，m)，8.28(1H，br)，8.36(1H，br)。
下面的实施例8描述了1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备，它可用于通过实施例5中所述的其它步骤制备例如1-(3-氯-吡啶基)-N-[2-甲基-6-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺。
                      实施例8
1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备
步骤A：3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亚乙基)腙的制备
在20-25℃下将1，1，1-三氟丙酮(7.80g，69.6mmol)加入到3-氯-2(1H)-吡啶酮腙(或者命名为(3-氯-吡啶-2-基)-肼)(10g，69.7mmol)中。结束加入之后，将该混合物搅拌约10分钟。在减压下除去该溶剂并在乙酸乙酯(100mL)和饱和碳酸钠水溶液(100mL)之间将混合物分开。将有机层干燥并蒸发。通过硅胶色谱(用乙酸乙酯洗脱)得到灰白色固体产物(11g，66％产率)，m.p.64-64.5℃(从乙酸乙酯/己烷中结晶之后)。
IR(nujol)ν1629，1590，1518，1403，1365，1309，1240，1196，1158，1100，1032，992，800cm-1。
1H NMR(CDCl3)δ2.12(s，3H)，6.91-6.86(m，1H)，7.64-7.61(m，1H)，8.33-8.32(m，2H)。
MS m/z 237(M+)。
步骤B：(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基亚乙基)酰肼乙基氢乙二酸 酯(或者命名为(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基亚乙基)肼)乙基氢乙 二酸酯的制备
0℃下将三乙胺(20.81g，0.206mol)加入到3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亚乙基)腙(即步骤A的产物)(32.63g，0.137mol)的二氯甲烷(68mL)中。在0℃下向该混合物中滴加氯氧代乙酸乙酯(18.75g，0.137mol)的二氯甲烷(69mL)溶液。在约2小时内将该混合物加热至25℃。将该混合物冷却至0℃并滴加另一份氯氧代乙酸乙酯(3.75g，27.47mmol)的二氯甲烷(14mL)。加入约1小时之后，用二氯甲烷(约450mL)稀释该混合物，并且用水(2×150mL)洗涤该混合物。将有机层干燥并蒸发。在硅胶上进行色谱分离(用1∶1乙酸乙酯-己烷洗脱)，得到产物固体(42.06g，90％产率)，m.p.73.0-73.5℃(从乙酸乙酯/己烷结晶之后)。
IR(nujol)ν1751，1720，1664，1572，1417，1361，1330，1202，1214，1184，1137，1110，1004，1043，1013，942，807，836cm-1。
1H NMR(DMSO-d6，115℃)1.19(t，3H)，1.72(br s，3H)，4.25(q，2H)，7.65(dd，J＝8.3，4.7Hz，1H)，8.20(dd，J＝7.6，1.5Hz，1H)，8.55(d，J＝3.6Hz，1H)。
MS m/z 337(M+)。
步骤C：1-(3-氯-2-吡啶基)-4，5-二氢-5-羟基-3-(三氟甲基)-1H-吡唑-5- 甲酸乙酯的制备
在8小时内将(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基-亚乙基)酰肼乙基氢乙二酸酯(即步骤B的产物)(5g，14.8mmol)的二甲亚砜(25mL)溶液加入到氯化四丁基铵(10g)的二甲亚砜(25mL)溶液中。加入结束之后，将该混合物倒入乙酸(3.25g)的水(25mL)溶液中。在25℃下搅拌过夜之后，用甲苯萃取(4×25mL)该混合物，并将该混合的甲苯萃取物用水(50mL)洗涤，干燥并蒸发，得到一固体。在硅胶上进行色谱分离(用1∶2乙酸乙酯-己烷洗脱)，得到产物固体(2.91g，50％产率，含有约5％的3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亚乙基)腙)，m.p.78-78.5℃(从乙酸乙酯/己烷中再结晶之后)。
IR(nujol)ν3403，1726，1618，1582，1407，1320，1293，1260，1217，1187，1150，1122，1100，1067，1013，873，829cm-1。
1H NMR(CDCl3)δ1.19(s，3H)，3.20(1/2的ABZ图谱，J＝18Hz，1H)，3.42(1/2的ABZ图谱，J＝18Hz，1H)，4.24(q，2H)，6.94(dd，J＝7.9，4.9Hz，1H)，7.74(dd，J＝7.7，1.5Hz，1H)，8.03(dd，J＝4.7，1.5Hz，1H)。
MS m/z 319(M+)。
步骤D：1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-甲酸乙酯的制备
将硫酸(浓，2滴)加入到1-(3-氯-2-吡啶基)-4，5-二氢-5-羟基-3-(三氟甲基)-1H-吡唑-5-甲酸乙酯(即步骤C的产物)(1g，2.96mmol)的乙酸(10mL)中，并将该混合物加热至65℃持续约1小时。将该混合物冷却至25℃并在减压下除去大多数乙酸。将该混合物在饱和碳酸钠水溶液(100mL)和乙酸乙酯(100mL)之间分开。将含水层再用乙酸乙酯(100mL)。将混合的有机萃取物干燥并蒸发，得到油状产物(0.66g，77％产率)。
IR(neat)ν3147，2986，1734，1577，1547，1466，1420，1367，1277，1236，1135，1082，1031，973，842，802cm-1。
1H NMR(CDCl3)δ1.23(t，3H)，4.25(q，2H)，7.21(s，1H)，7.48(dd，J＝8.1，4.7Hz，1H)，7.94(dd，J＝6.6，2Hz，1H)，8.53(dd，J＝4.7，1.5Hz，1H)。
MS m/z 319(M+)。
步骤E：1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备
将氢氧化钾(0.5g，85％，2.28mmol)的水(1mL)溶液加入到1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-甲酸乙酯(即步骤D的产物)(0.66g，2.07mmol)的乙醇(3mL)溶液中。约30分钟之后，在减压下除去溶剂，将该混合物溶解在水(40mL)中。将所得溶液用乙酸乙酯(20mL)洗涤。含水层用浓盐酸酸化，并用乙酸乙酯(3×20mL)萃取。将混合的萃取物干燥并蒸发，得到固体产物(0.53g，93％产率)，m.p.178-179 C(从己烷-乙酸乙酯中结晶之后)。
IR(nujol)ν1711，1586，1565，1550，1440，1425，1292，1247，1219，1170，1135，1087，1059，1031，972，843，816cm-1。
1H NMR(DMSO-d6)δ7.61(s，1H)，7.77(m，1H)，8.30(d，1H)，8.60(s，1H)。
通过本文所述的步骤并结合本领域已知的方法，可以制备表1-20的下面的化合物，其中：t是叔，s是仲，n是正，i是异，c是环，Me是甲基，Et是乙基，Pr是丙基，i-Pr是异丙基，Bu是丁基，Ph是苯基，OMe是甲氧基、OEt是乙氧基、SMe是甲硫基，SEt是乙硫基，CN是氰基，并且S(O)2Me是甲基磺酰基。
在如下的表1-20中：propargyl为炔丙基；cyclopropyl为环丙基；pyridyl为吡啶基。
                          表1
Figure A0281824700661
R3         R4a         R4b         Rva         Rvb
Me          3-Me         H            H            CF3
Et          3-Me         5-Me         H            OCF3
i-Pr        3-Me         H            H            OCF3
t-Bu        3-Me         5-Cl         Me           Br
Me          3-Me         H            Et           Br
Et          3-Me         H            Me           Cl
i-Pr        3-Me         5-Br         Et           Cl
R3              R4a          R4b         Rva       Rvb
t-Bu             3-Me          H            Me         I
propargyl        3-Me          H            Me         CF3
cyclopropyl      3-Me          H            Me         OCF3
i-Pr             3-Me          5-Cl         Me         CF3
t-Bu             3-Me          H            Me         SCF3
Me               3-Me          5-CN         Me         SCHF2
Et               3-Me          H            Me         OCHF2
i-Pr             3-Me          H            Me         CF3
t-Bu             3-Me          H            Me         C2F5
propargyl        3-Me          H            Me         C2F5
cyclopropyl      3-Me          H            Et         CF3
i-Pr             3-Me          H            n-Pr       CF3
t-Bu             3-Me          5-Br         i-Pr       CF3
Me               3-Me          H            Cl         CF3
Et               3-Me          H            F          CF3
i-Pr             3-Me          H            Me         SMe
t-Bu             3-Me          5-Cl         Me         OMe
Me               3-Me          H            Me         OEt
Et               3-Me          H            Me         n-C3F7
i-Pr             3-Me          H            Me         i-C3F7
t-Bu             3-Me          5-F          Me         Et
propargyl        3-Me          H            Me         OCF2CHF2
Et               3-Me          H            Me         SCF2CHF2
i-Pr             3-Me          H            Me         SO2Me
t-Bu             3-Me          5-Cl         Me         SO2CF3
Me               3-Me          H            CF3       CF3
Et               3-Me          H            CF3       Me
i-Pr             3-Me          H            OMe        CF3
t-Bu             3-Me          H            H          CF3
cyclopropyl      3-Me          5-Br         H          OCHF2
Et               3-Me          H            H          C2F5
i-Pr             3-Me          5-Me         H          C2F5
t-Bu             3-Me          H            H          OCF3
Me               3-Me          H            H          OCF2CHF2
Et               3-Me          H            H          SCF2CHF2
i-Pr             3-Me          5-Cl         H          n-C3F7
R3            R4a      R4b    Rva              Rvb
t-Bu           3-Me      H       H                 i-C3F7
propargyl      3-Me      H       H                 Br
Et             3-Me      H       H                 Cl
i-Pr           3-Me      H       H                 SCF3
t-Bu           3-Me      5-Br    Ph                CF3
cyclopropyl    3-Me      H       Ph                Cl
Et             3-Me      H       Ph                Br
i-Pr           3-Me      H       2-pyridyl         CF3
t-Bu           3-Me      H       2-pyridyl         Cl
Me             3-Me      H       2-ClPh            CF3
Et             3-Me      5-Cl    2-ClPh            OCF3
i-Pr           3-Me      H       2-ClPh            Br
t-Bu           3-Me      H       2-ClPh            Cl
Me             3-Me      H       2-ClPh            SCHF2
propargyl      3-Me      H       2-BrPh            CF3
i-Pr           3-Me      5-CN    2-MePh            CF3
t-Bu           3-Me      H       2-CNPh            CF3
Me             3-Me      H       2-FPh             CF3
Et             3-Me      H       2，6-F2Ph        CF3
i-Pr           3-Me      5-Br    2，4-F2Ph        CF3
t-Bu           3-Me      H       2，5-F2Ph        CF3
Me             3-Me      5-I     2-MeOPh           CF3
Et             3-Me      H       3-Cl-2-pyridyl    CF3
i-Pr           3-Me      5-Me    3-Cl-2-pyridyl    OCF3
t-Bu           3-Me      H       3-Cl-2-pyridyl    Br
propargyl      3-Me      H       3-Cl-2-pyridyl    Cl
Et             3-Me      5-Br    3-Cl-2-pyridyl    SCHF2
i-Pr           3-Me      H       3-F-2-pyridyl     CF3
t-Bu           3-Me      H       3-CF3-2-pyridyl  CF3
Me             3-Me      H       3-Me-2-pyridyl    CF3
Et             3-Me      H       3-Br-2-pyridyl    CF3
i-Pr           3-Me      5-Cl    3-Br-2-pyridyl    OCF3
t-Bu           3-Me      H       3-Br-2-pyridyl    Br
i-Pr           3-Me      H       3-Br-2-pyridyl    Cl
Me             6-Me      H       H                 CF3
Et             6-Me      4-Me    H                 OCF3
R3            R4a      R4b      Rva      Rvb
i-Pr           6-Me      H         H         OCF3
t-Bu           6-Me      Cl        Me        Br
Me             6-Me      H         Et        Br
Et             6-Me      H         Me        Cl
i-Pr           6-Me      4-Br      Et        Cl
t-Bu           6-Me      H         Me        I
propargyl      6-Me      H         Me        CF3
cyclopropyl    6-Me      H         Me        OCF3
i-Pr           6-Me      4-Cl      Me        CF3
t-Bu           6-Me      H         Me        SCF3
Me             6-Me      H         Me        SCHF2
Et             6-Me      H         Me        OCHF2
i-Pr           6-Me      4-CN      Me        CF3
t-Bu           6-Me      H         Me        C2F5
propargyl      6-Me      H         Me        C2F5
cyclopropyl    6-Me      H         Et        CF3
i-Pr           6-Me      H         n-Pr      CF3
t-Bu           6-Me      4-Br      i-Pr      CF3
Me             6-Me      H         Cl        CF3
Et             6-Me      H         F         CF3
i-Pr           6-Me      H         Me        SMe
t-Bu           6-Me      4-Cl      Me        OMe
Me             6-Me      H         Me        OEt
Et             6-Me      H         Me        n-C3F7
i-Pr           6-Me      H         Me        i-C3F7
t-Bu           6-Me      4-F       Me        Et
propargyl      6-Me      H         Me        OCF2CHF2
Et             6-Me      H         Me        SCF2CHF2
i-Pr           6-Me      H         Me        SO2Me
t-Bu           6-Me      4-Cl      Me        SO2CF3
Me             6-Me      H         CF3      CF3
Et             6-Me      H         CF3      Me
i-Pr           6-Me      H         OMe       CF3
t-Bu           6-Me      H         H         CF3
cyclopropyl    6-Me      4-Br      H         OCHF2
Et             6-Me      H         H         C2F5
R3            R4a      R4b    Rva               Rvb
i-Pr           6-Me      H       H                  C2F5
t-Bu           6-Me      4-Me    H                  OCF3
Me             6-Me      H       H                  OCF2CHF2
Et             6-Me      H       H                  SCF2CHF2
i-Pr           6-Me      4-Cl    H                  n-C3F7
t-Bu           6-Me      H       H                  i-C3F7
propargyl      6-Me      H       H                  Br
Et             6-Me      H       H                  Cl
i-Pr           6-Me      H       H                  SCF3
t-Bu           6-Me      4-Br    Ph                 CF3
cyclopropyl    6-Me      H       Ph                 Cl
Et             6-Me      H       Ph                 Br
i-Pr           6-Me      H       2-pyridyl          CF3
t-Bu           6-Me      H       2-pyridyl          Cl
Me             6-Me      H       2-ClPh             CF3
Et             6-Me      4-Cl    2-ClPh             OCF3
i-Pr           6-Me      H       2-ClPh             Br
t-Bu           6-Me      4-CN    2-ClPh             Cl
Me             6-Me      H       2-ClPh             SCHF2
propargyl      6-Me      H       2-BrPh             CF3
i-Pr           6-Me      H       2-MePh             CF3
t-Bu           6-Me      H       2-CNPh             CF3
Me             6-Me      H       2-FPh              CF3
Et             6-Me      H       2，6-F2Ph         CF3
i-Pr           6-Me      4-Br    2，4-F2Ph         CF3
t-Bu           6-Me      H       2，5-F2Ph         CF3
Me             6-Me      4-I     2-MeOPh            CF3
Et             6-Me      H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me      H       3-Cl-2-pyridl      OCF3
t-Bu           6-Me      H       3-Cl-2-pyridyl     Br
propargyl      6-Me      H       3-Cl-2-pyridyl     Cl
Et             6-Me      4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me      H       3-F-2-pyridyl      CF3
t-Bu           6-Me      H       3-CF3-2-pyridyl   CF3
Me             6-Me      H       3-Me-2-pyridyl     CF3
Et             6-Me      H       3-Br-2-pyridyl     CF3
R3            R4a      R4b    Rva              Rvb
i-Pr           6-Me      4-Cl    3-Br-2-pyridyl    OCF3
t-Bu           6-Me      H       3-Br-2-pyridyl    Br
i-Pr           6-Me      H       3-Br-2-pyridyl    Cl
Me             3-Cl      H       H                 CF3
Et             3-Br      5-Me    H                 OCF3
i-Pr           3-Cl      H       H                 OCF3
t-Bu           3-Cl      5-Cl    Me                Br
Me             3-Cl      H       Et                Br
Et             3-Cl      H       Me                Cl
i-Pr           3-Cl      5-Br    Et                Cl
t-Bu           3-Cl      H       Me                I
propargyl      3-Cl      H       Me                CF3
cyclopropyl    3-Cl      H       Me                OCF3
i-Pr           3-Cl      5-Cl    Me                CF3
t-Bu           3-Cl      H       Me                SCF3
Me             3-F       H       Me                SCHF2
Et             3-Cl      H       Me                OCHF2
i-Pr           3-Cl      5-CN    Me                CF3
t-Bu           3-Cl      H       Me                C2F5
propargyl      3-Cl      H       Me                C2F5
cyclopropyl    3-Cl      H       Et                CF3
i-Pr           3-Cl      H       n-Pr              CF3
t-Bu           3-Cl      5-Br    i-Pr              CF3
Me             3-Cl      H       Cl                CF3
Et             3-Br      H       F                 CF3
i-Pr           3-Cl      H       Me                SMe
t-Bu           3-Cl      5-Cl    Me                OMe
Me             3-Cl      H       Me                OEt
Et             3-Cl      H       Me                n-C3F7
i-Pr           3-Cl      H       Me                i-C3F7
t-Bu           3-Cl      5-F     Me                Et
propargyl      3-Cl      H       Me                OCF2CH2
Et             3-Cl      H       Me                SCF2CHF2
i-Pr           3-Br      H       Me                SO2Me
t-Bu           3-Cl      5-Cl    Me                SO2CF3
Me             3-Cl      H       CF3              CF3
R3            R4a      R4b    Rva              Rvb
Et             3-CN      H       CF3              Me
i-pr           3-Cl      H       OMe               CF3
t-Bu           3-Cl      H       H                 CF3
cyclopropyl    3-Cl      5-Br    H                 OCHF2
Et             3-Cl      H       H                 C2F5
i-Pr           3-Cl      H       H                 C2F5
t-Bu           3-Cl      H       H                 OCF3
Me             3-F       H       H                 OCF2CHF2
Et             3-Cl      H       H                 SCF2CHF2
i-pr           3-Cl      5-Cl    H                 n-C3F7
t-Bu           3-Cl      H       H                 i-C3F7
propargyl      3-Cl      H       H                 Br
Et             3-Cl      H       H                 Cl
i-pr           3-Cl      H       H                 SCF3
t-Bu           3-Cl      5-Br    Ph                CF3
cyclopropyl    3-Cl      H       Ph                Cl
Et             3-Cl      H       Ph                Br
i-pr           3-Br      H       2-pyridyl         CF3
t-Bu           3-Cl      H       2-pyridyl         Cl
Me             3-Cl      H       2-ClPh            CF3
Et             3-Cl      5-Cl    2-ClPh            OCF3
i-Pr           3-Cl      H       2-ClPh            Br
t-Bu           3-I       H       2-ClPh            Cl
Me             3-Cl      5-Me    2-ClPh            SCHF2
propargyl      3-Cl      H       2-BrPh            CF3
i-Pr           3-Cl      H       2-MePh            CF3
t-Bu           3-Cl      5-CN    2-CNPh            CF3
Me             3-Cl      H       2-FPh             CF3
Et             3-Cl      H       2，6-F2Ph        CF3
i-Pr           3-Cl      5-Br    2，4-F2Ph        CF3
t-Bu           3-F       H       2，5-F2Ph        CF3
Me             3-Cl      5-I     2-MeOPh           CF3
Et             3-Cl      H       3-Cl-2-pyridyl    CF3
i-Pr           3-CN      H       3-Cl-2-pyridyl    OCF3
t-Bu           3-Cl      H       3-Cl-2-pyridyl    Br
propargyl      3-Cl      H       3-Cl-2-pyridyl    Cl
R3            R4a      R4b    Rva                Rvb
Et             3-Cl      5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl      H       3-F-2-pyridyl      CF3
t-Bu           3-Br      H       3-CF3-2-pyridyl   CF3
Me             3-Cl      H       3-Me-2-pyridyl     CF3
Et             3-Cl      H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl      5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Cl      H       3-Br-2-pyridyl     Br
i-Pr           3-Cl      H       3-Br-2-pyridyl     Cl
Me             6-Cl      H       H                  CF3
Et             6-Br      4-Me    H                  OCF3
i-Pr           6-Cl      H       H                  OCF3
t-Bu           6-Cl      Cl      Me                 Br
Me             6-Cl      H       Et                 Br
Et             6-Cl      H       Me                 Cl
i-Pr           6-F       4-Br    Et                 Cl
t-Bu           6-Cl      H       Me                 I
propargyl      6-Cl      H       Me                 CF3
cyclopropyl    6-Cl      H       Me                 OCF3
i-Pr           6-Cl      4-Cl    Me                 CF3
t-Bu           6-Cl      H       Me                 SCF3
Me             6-Cl      H       Me                 SCHF2
Et             6-Cl      H       Me                 OCHF2
i-Pr           6-I       4-CN    Me                 CF3
t-Bu           6-Cl      H       Me                 C2F5
propargyl      6-Cl      H       Me                 C2F5
cyclopropyl    6-Cl      H       Et                 CF3
i-Pr           6-Cl      H       n-Pr               CF3
t-Bu           6-Cl      4-Br    i-Pr               CF3
Me             6-Cl      H       Cl                 CF3
Et             6-F       H       F                  CF3
i-Pr           6-Cl      H       Me                 SMe
t-Bu           6-Cl      4-Cl    Me                 OMe
Me             6-Cl      H       Me                 OEt
Et             6-I       H       Me                 n-C3F7
i-Pr           6-Cl      H       Me                 i-C3F7
t-Bu           6-Cl      4-F     Me                 Et
R3            R4a      R4b    Rva         Rvb
propargyl      6-Cl      H       Me           OCF2CHF2
Et             6-Cl      H       Me           SCF2CHF2
i-Pr           6-Cl      H       Me           SO2Me
t-Bu           6-Cl      4-Cl    Me           SO2CF3
Me             6-Cl      H       CF3         CF3
Et             6-Cl      H       CF3         Me
i-Pr           6-Cl      H       OMe          CF3
t-Bu           6-Br      H       H            CF3
cyclopropyl    6-Cl      4-Br    H            OCHF2
Et             6-Cl      H       H            C2F5
i-Pr           6-Cl      H       H            C2F5
t-Bu           6-F       4-Me    H            OCF3
Me             6-Cl      H       H            OCF2CHF2
Et             6-Cl      H       H            SCF2CHF2
i-Pr           6-CN      4-C     H            n-C3F7
t-Bu           6-Cl      H       H            i-C3F7
propargyl      6-Cl      H       H            Br
Et             6-Cl      H       H            Cl
i-Pr           6-Cl      H       H            SCF3
t-Bu           6-Cl      4-Br    Ph           CF3
cyclopropyl    6-Cl      H       Ph           Cl
Et             6-F       H       Ph           Br
i-Pr           6-Cl      H       2-pyridyl    CF3
t-Bu           6-Cl      H       2-pyridyl    Cl
Me             6-Cl      H       2-ClPh       CF3
Et             6-Br      4-Cl    2-ClPh       OCF3
i-Pr           6-Cl      H       2-ClPh       Br
t-Bu           6-Cl      H       2-ClPh       Cl
Me             6-Cl      H       2-ClPh       SCHF2
propargyl      6-Cl      H       2-BrPh       CF3
i-Pr           6-Br      H       2-MePh       CF3
t-Bu           6-Cl      4-CN    2-CNPh       CF3
Me             6-Cl      H       2-FPh        CF3
Et             6-Cl      H       2，6-F2Ph   CF3
i-Pr           6-Cl      4-Br    2，4-F2Ph   CF3
t-Bu           6-CN      H       2，5-F2Ph   CF3
R3            R4a      R4b    Rva               Rvb
Me             6-Cl      4-I     2-MeOPh            CF3
Et             6-Cl      H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br      H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl      H       3-Cl-2-pyridyl     Br
propargyl      6-Cl      H       3-Cl-2-pyridyl     Cl
Et             6-Cl      4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl      H       3-F-2-pyridyl      CF3
t-Bu           6-Cl      H       3-CF3-2-pyridyl   CF3
Me             6-Cl      H       3-Me-2-pyridyl     CF3
Et             6-Cl      H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl      4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl      H       3-Br-2-pyridyl     Br
i-Pr           6-Cl      H       3-Br-2-pyridyl     Cl
                            Table2
R3            R4a      R4b    Rva               Rvb
Me             3-Me      H       H                  CF3
Et             3-Me      5-Me    H                  OCF3
i-Pr           3-Me      H       H                  OCF3
t-Bu           3-Me      5-Cl    Me                 Br
Me             3-Me      H       Et                 Br
Et             3-Me      H       Me                 Cl
i-Pr           3-Me      5-Br    Et                 Cl
t-Bu           3-Me      H       Me                 I
propargyl      3-Me      H       Me                 CF3
cyclopropyl    3-Me      H       Me                 OCF3
R3            R4a      R4b      Rva    Rvb
i-Pr           3-Me      5-Cl      Me      CF3
t-Bu           3-Me      H         Me      SCF3
Me             3-Me      5-CN      Me      SCHF2
Et             3-Me      H         Me      OCHF2
i-Pr           3-Me      H         Me      CF3
t-Bu           3-Me      H         Me      C2F5
propargyl      3-Me      H         Me      C2F5
cyclopropyl    3-Me      H         Et      CF3
i-Pr           3-Me      H         n-Pr    CF3
t-Bu           3-Me      5-Br      i-Pr    CF3
Me             3-Me      H         Cl      CF3
Et             3-Me      H         F       CF3
i-Pr           3-Me      H         Me      SMe
t-Bu           3-Me      5-Cl      Me      OMe
Me             3-Me      H         Me      OEt
Et             3-Me      H         Me      n-C3F7
i-Pr           3-Me      H         Me      i-C3F7
t-Bu           3-Me      5-F       Me      Et
propargyl      3-Me      H         Me      OCF2CHF2
Et             3-Me      H         Me      SCF2CHF2
i-Pr           3-Me      H         Me      SO2Me
t-Bu           3-Me      5-Cl      Me      SO2CF3
Me             3-Me      H         CF3    CF3
Et             3-Me      H         CF3    Me
i-Pr           3-Me      H         OMe     CF3
t-Bu           3-Me      H         H       CF3
cyclopropyl    3-Me      5-Br      H       OCHF2
Et             3-Me      H         H       C2F5
i-Pr           3-Me      5-Me      H       C2F5
t-Bu           3-Me      H         H       OCF3
Me             3-Me      H         H       OCF2CHF2
Et             3-Me      H         H       SCF2CHF2
i-Pr           3-Me      5-Cl      H       n-C3F7
t-Bu           3-Me      H         H       i-C3F7
propargyl      3-Me      H         H       Br
Et             3-Me      H         H       Cl
R3            R4a      R4b    Rva               Rvb
i-Pr           3-Me      H       H                  SCF3
t-Bu           3-Me      5-Br    Ph                 CF3
cyclopropyl    3-Me      H       Ph                 Cl
Et             3-Me      H       Ph                 Br
i-Pr           3-Me      H       2-pyridyl          CF3
t-Bu           3-Me      H       2-pyridyl          Cl
Me             3-Me      H       2-ClPh             CF3
Et             3-Me      5-Cl    2-ClPh             OCF3
i-Pr           3-Me      H       2-ClPh             Br
t-Bu           3-Me      H       2-ClPh             Cl
Me             3-Me      H       2-ClPh             SCHF2
propargyl      3-Me      H       2-BrPh             CF3
i-Pr           3-Me      5-CN    2-MePh             CF3
t-Bu           3-Me      H       2-CNPh             CF3
Me             3-Me      H       2-FPh              CF3
Et             3-Me      H       2，6-F2Ph         CF3
i-Pr           3-Me      5-Br    2，4-F2Ph         CF3
t-Bu           3-Me      H       2，5-F2Ph         CF3
Me             3-Me      5-I     2-MeOPh            CF3
Et             3-Me      H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me      5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me      H       3-Cl-2-pyridyl     Br
propargyl      3-Me      H       3-Cl-2-pyridyl     Cl
Et             3-Me      5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me      H       3-F-2-pyridyl      CF3
t-Bu           3-Me      H       3-CF3-2-pyridyl   CF3
Me             3-Me      H       3-Me-2-pyridyl     CF3
Et             3-Me      H       3-Br-2-pyridyl     CF3
i-Pr           3-Me      5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me      H       3-Br-2-pyridyl     Br
i-Pr           3-Me      H       3-Br-2-pyridyl     Cl
Me             6-Me      H       H                  CF3
Et             6-Me      4-Me    H                  OCF3
i-Pr           6-Me      H       H                  OCF3
t-Bu           6-Me      Cl      Me                 Br
Me             6-Me      H       Et                 Br
R3            R4a      R4b      Rva      Rvb
Et             6-Me      H         Me        Cl
i-Pr           6-Me      4-Br      Et        Cl
t-Bu           6-Me      H         Me        I
propargyl      6-Me      H         Me        CF3
cyclopropyl    6-Me      H         Me        OCF3
i-Pr           6-Me      4-Cl      Me        CF3
t-Bu           6-Me      H         Me        SCF3
Me             6-Me      H         Me        SCHF2
Et             6-Me      H         Me        OCHF2
i-Pr           6-Me      4-CN      Me        CF3
t-Bu           6-Me      H         Me        C2F5
propargyl      6-Me      H         Me        C2F5
cyclopropyl    6-Me      H         Et        CF3
i-Pr           6-Me      H         n-Pr      CF3
t-Bu           6-Me      4-Br      i-Pr      CF3
Me             6-Me      H         Cl        CF3
Et             6-Me      H         F         CF3
i-Pr           6-Me      H         Me        SMe
t-Bu           6-Me      4-Cl      Me        OMe
Me             6-Me      H         Me        OEt
Et             6-Me      H         Me        n-C3F7
i-Pr           6-Me      H         Me        i-C3F7
t-Bu           6-Me      4-F       Me        Et
propargyl      6-Me      H         Me        OCF2CHF2
Et             6-Me      H         Me        SCF2CHF2
i-Pr           6-Me      H         Me        SO2Me
t-Bu           6-Me      4-Cl      Me        SO2CF3
Me             6-Me      H         CF3      CF3
Et             6-Me      H         CF3      Me
i-Pr           6-Me      H         OMe       CF3
t-Bu           6-Me      H         H         CF3
cyclopropyl    6-Me      4-Br      H         OCHF2
Et             6-Me      H         H         C2F5
i-Pr           6-Me      H         H         C2F5
t-Bu           6-Me      4-Me      H         OCF3
Me             6-Me      H         H         OCF2CHF2
R3            R4a      R4b    Rva               Rvb
Et             6-Me      H       H                  SCF2CHF2
i-Pr           6-Me      4-Cl    H                  n-C3F7
t-Bu           6-Me      H       H                  i-C3F7
propargyl      6-Me      H       H                  Br
Et             6-Me      H       H                  Cl
i-Pr           6-Me      H       H                  SCF3
t-Bu           6-Me      4-Br    Ph                 CF3
cyclopropyl    6-Me      H       Ph                 Cl
Et             6-Me      H       Ph                 Br
i-Pr           6-Me      H       2-pyridyl          CF3
t-Bu           6-Me      H       2-pyridyl          Cl
Me             6-Me      H       2-ClPh             CF3
Et             6-Me      4-Cl    2-ClPh             OCF3
i-Pr           6-Me      H       2-ClPh             Br
t-Bu           6-Me      4-CN    2-ClPh             Cl
Me             6-Me      H       2-ClPh             SCHF2
propargyl      6-Me      H       2-BrPh             CF3
i-Pr           6-Me      H       2-MePh             CF3
t-Bu           6-Me      H       2-CNPh             CF3
Me             6-Me      H       2-FPh              CF3
Et             6-Me      H       2，6-F2Ph         CF3
i-Pr           6-Me      4-Br    2，4-F2Ph         CF3
t-Bu           6-Me      H       2，5-F2Ph         CF3
Me             6-Me      4-I     2-MeOPh            CF3
Et             6-Me      H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me      H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me      H       3-Cl-2-pyridyl     Br
propargyl      6-Me      H       3-Cl-2-pyridyl     Cl
Et             6-Me      4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me      H       3-F-2-pyridyl      CF3
t-Bu           6-Me      H       3-CF3-2-pyridyl   CF3
Me             6-Me      H       3-Me-2-pyridyl     CF3
Et             6-Me      H       3-Br-2-pyridyl     CF3
i-Pr           6-Me      4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me      H       3-Br-2-pyridyl     Br
i-Pr           6-Me      H       3-Br-2-pyridyl     Cl
R3            R4a      R4b      Rva    Rvb
Me             3-Cl      H         H       CF3
Et             3-Br      5-Me      H       OCF3
i-Pr           3-Cl      H         H       OCF3
t-Bu           3-Cl      5-Cl      Me      Br
Me             3-Cl      H         Et      Br
Et             3-Cl      H         Me      Cl
i-Pr           3-Cl      5-Br      Et      Cl
t-Bu           3-Cl      H         Me      I
propargyl      3-Cl      H         Me      CF3
cyclopropyl    3-Cl      H         Me      OCF3
i-Pr           3-Cl      5-Cl      Me      CF3
t-Bu           3-Cl      H         Me      SCF3
Me             3-F       H         Me      SCHF2
Et             3-Cl      H         Me      OCHF2
i-Pr           3-Cl      5-CN      Me      CF3
t-Bu           3-Cl      H         Me      C2F5
propargyl      3-Cl      H         Me      C2F5
cyclopropyl    3-Cl      H         Et      CF3
i-Pr           3-Cl      H         n-Pr    CF3
t-Bu           3-Cl      5-Br      i-Pr    CF3
Me             3-Cl      H         Cl      CF3
Et             3-Br      H         F       CF3
i-Pr           3-Cl      H         Me      SMe
t-Bu           3-Cl      5-Cl      Me      OMe
Me             3-Cl      H         Me      OEt
Et             3-Cl      H         Me      n-C3F7
i-Pr           3-Cl      H         Me      i-C3F7
t-Bu           3-Cl      5-F       Me      Et
propargyl      3-Cl      H         Me      OCF2CHF2
Et             3-Cl      H         Me      SCF2CHF2
i-Pr           3-Br      H         Me      SO2Me
t-Bu           3-Cl      5-Cl      Me      SO2CF3
Me             3-Cl      H         CF3    CF3
Et             3-CN      H         CF3    Me
i-Pr           3-Cl      H         OMe     CF3
t-Bu           3-Cl      H         H       CF3
R3            R4a      R4b    Rva               Rvb
cyclopropyl    3-Cl      5-Br    H                  OCHF2
Et             3-Cl      H       H                  C2F5
i-Pr           3-Cl      H       H                  C2F5
t-Bu           3-Cl      H       H                  OCF3
Me             3-F       H       H                  OCF2CHF2
Et             3-Cl      H       H                  SCF2CHF2
i-Pr           3-Cl      5-Cl    H                  n-C3F7
t-Bu           3-Cl      H       H                  i-C3F7
propargyl      3-Cl      H       H                  Br
Et             3-Cl      H       H                  Cl
i-Pr           3-Cl      H       H                  SCF3
t-Bu           3-Cl      5-Br    Ph                 CF3
cyclopropyl    3-Cl      H       Ph                 Cl
Et             3-Cl      H       Ph                 Br
i-Pr           3-Br      H       2-pyridyl          CF3
t-Bu           3-Cl      H       2-pyridyl          Cl
Me             3-Cl      H       2-ClPh             CF3
Et             3-Cl      5-Cl    2-ClPh             OCF3
i-Pr           3-Cl      H       2-ClPh             Br
t-Bu           3-I       H       2-ClPh             Cl
Me             3-Cl      5-Me    2-ClPh             SCHF2
propargyl      3-Cl      H       2-BrPh             CF3
i-Pr           3-Cl      H       2-MePh             CF3
t-Bu           3-Cl      5-CN    2-CNPh             CF3
Me             3-Cl      H       2-FPh              CF3
Et             3-Cl      H       2，6-F2Ph         CF3
i-Pr           3-Cl      5-Br    2，4-F2Ph         CF3
t-Bu           3-F       H       2，5-F2Ph         CF3
Me             3-Cl      5-I     2-MeOPh            CF3
Et             3-Cl      H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN      H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl      H       3-Cl-2-pyridyl     Br
propargyl      3-Cl      H       3-Cl-2-pyridyl     Cl
Et             3-Cl      5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl      H       3-F-2-pyridyl      CF3
t-Bu           3-Br      H       3-CF3-2-pyridyl   CF3
R3            R4a      R4b    Rva              Rvb
Me             3-Cl      H       3-Me-2-pyridyl    CF3
Et             3-Cl      H       3-Br-2-pyridyl    CF3
i-Pr           3-Cl      5-Cl    3-Br-2-Pyridyl    OCF3
t-Bu           3-Cl      H       3-Br-2-pyridyl    Br
i-Pr           3-Cl      H       3-Br-2-pyridyl    Cl
Me             6-Cl      H       H                 CF3
Et             6-Br      4-Me    H                 OCF3
i-Pr           6-Cl      H       H                 OCF3
t-Bu           6-Cl      Cl      Me                Br
Me             6-Cl      H       Et                Br
Et             6-Cl      H       Me                Cl
i-Pr           6-F       4-Br    Et                Cl
t-Bu           6-Cl      H       Me                I
propargyl      6-Cl      H       Me                CF3
cyclopropyl    6-Cl      H       Me                OCF3
i-Pr           6-Cl      4-Cl    Me                CF3
t-Bu           6-Cl      H       Me                SCF3
Me             6-Cl      H       Me                SCHF2
Et             6-Cl      H       Me                OCHF2
i-Pr           6-I       4-CN    Me                CF3
t-Bu           6-Cl      H       Me                C2F5
propargyl      6-Cl      H       Me                C2F5
cyclopropyl    6-Cl      H       Et                CF3
i-Pr           6-Cl      H       n-Pr              CF3
t-Bu           6-Cl      4-Br    i-Pr              CF3
Me             6-Cl      H       Cl                CF3
Et             6-F       H       F                 CF3
i-Pr           6-Cl      H       Me                SMe
t-Bu           6-Cl      4-Cl    Me                OMe
Me             6-Cl      H       Me                OEt
Et             6-I       H       Me                n-C3F7
i-Pr           6-Cl      H       Me                i-C3F7
t-Bu           6-Cl      4-F     Me                Et
propargyl      6-Cl      H       Me                OCF2CHF2
Et             6-Cl      H       Me                SCF2CHF2
i-Pr           6-Cl      H       Me                SO2Me
R3            R4a      R4b      Rva              Rvb
t-Bu           6-Cl      4-Cl      Me                SO2CF3
Me             6-Cl      H         CF3              CF3
Et             6-Cl      H         CF3              Me
i-Pr           6-Cl      H         OMe               CF3
t-Bu           6-Br      H         H                 CF3
cyclopropyl    6-Cl      4-Br      H                 OCHF2
Et             6-Cl      H         H                 C2F5
i-Pr           6-Cl      H         H                 C2F5
t-Bu           6-F       4-Me      H                 OCF3
Me             6-Cl      H         H                 OCF2CHF2
Et             6-Cl      H         H                 SCF2CHF2
i-Pr           6-CN      4-Cl      H                 n-C3F7
t-Bu           6-Cl      H         H                 i-C3F7
propargyl      6-Cl      H         H                 Br
Et             6-Cl      H         H                 Cl
i-Pr           6-Cl      H         H                 SCF3
t-Bu           6-Cl      4-Br      Ph                CF3
cyclopropyl    6-Cl      H         Ph                Cl
Et             6-F       H         Ph                Br
i-Pr           6-Cl      H         2-pyridyl         CF3
t-Bu           6-Cl      H         2-pyridyl         Cl
Me             6-Cl      H         2-ClPh            CF3
Et             6-Br      4-Cl      2-ClPh            OCF3
i-Pr           6-Cl      H         2-ClPh            Br
t-Bu           6-Cl      H         2-ClPh            Cl
Me             6-Cl      H         2-ClPh            SCHF2
propargyl      6-Cl      H         2-BrPh            CF3
i-Pr           6-Br      H         2-MePh            CF3
t-Bu           6-Cl      4-CN      2-CNPh            CF3
Me             6-Cl      H         2-FPh             CF3
Et             6-Cl      H         2，6-F2Ph        CF3
i-Pr           6-Cl      4-Br      2，4-F2Ph        CF3
t-Bu           6-CN      H         2，5-F2Ph        CF3
Me             6-Cl      4-I       2-MeOPh           CF3
Et             6-Cl      H         3-Cl-2-pyridyl    CF3
i-Pr           6-Br      H         3-Cl-2-pyridyl    OCF3
R3            R4a      R4b      Rva               Rvb
t-Bu           6-Cl      H         3-Cl-2-pyridyl     Br
propargyl      6-Cl      H         3-Cl-2-pyridyl     Cl
Et             6-Cl      4-Br      3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl      H         3-F-2-pyridyl      CF3
t-Bu           6-Cl      H         3-CF3-2-pyridyl   CF3
Me             6-Cl      H         3-Me-2-pyridyl     CF3
Et             6-Cl      H         3-Br-2-pyridyl     CF3
i-Pr           6-Cl      4-Cl      3-Br-2-pyridyl     OCF3
t-Bu           6-Cl      H         3-Br-2-pyridyl     Br
i-Pr           6-Cl      H         3-Br-2-pyridyl     Cl
                            Table 3
R3            R4a      R4b      Rva               Rvb
Me             3-Me      H         H                  CF3
Et             3-Me      5-Me      H                  OCF3
i-Pr           3-Me      H         H                  OCF3
t-Bu           3-Me      5-Cl      Me                 Br
Me             3-Me      H         Et                 Br
Et             3-Me      H         Me                 Cl
i-Pr           3-Me      5-Br      Et                 Cl
t-Bu           3-Me      H         Me                 I
propargyl      3-Me      H         Me                 CF3
cyclopropyl    3-Me      H         Me                 OCF3
i-Pr           3-Me      5-Cl      Me                 CF3
t-Bu           3-Me      H         Me                 SCF3
Me             3-Me      5-CN      Me                 SCHF2
Et             3-Me      H         Me                 OCHF2
i-Pr           3-Me      H         Me                 CF3
R3            R4a      R4b      Rva         Rvb
t-Bu           3-Me      H         Me           C2F5
propargyl      3-Me      H         Me           C2F5
cyclopropyl    3-Me      H         Et           CF3
i-Pr           3-Me      H         n-Pr         CF3
t-Bu           3-Me      5-Br      i-Pr         CF3
Me             3-Me      H         Cl           CF3
Et             3-Me      H         F            CF3
i-Pr           3-Me      H         Me           SMe
t-Bu           3-Me      5-Cl      Me           OMe
Me             3-Me      H         Me           OEt
Et             3-Me      H         Me           n-C3F7
i-Pr           3-Me      H         Me           i-C3F7
t-Bu           3-Me      5-F       Me           Et
propargyl      3-Me      H         Me           OCF2CHF2
Et             3-Me      H         Me           SCF2CHF2
i-Pr           3-Me      H         Me           SO2Me
t-Bu           3-Me      5-Cl      Me           SO2CF3
Me             3-Me      H         CF3         CF3
Et             3-Me      H         CF3         Me
i-Pr           3-Me      H         OMe          CF3
t-Bu           3-Me      H         H            CF3
cyclopropyl    3-Me      5-Br      H            OCHF2
Et             3-Me      H         H            C2F5
i-Pr           3-Me      5-Me      H            C2F5
t-Bu           3-Me      H         H            OCF3
Me             3-Me      H         H            OCF2CHF2
Et             3-Me      H         H            SCF2CHF2
i-Pr           3-Me      5-Cl      H            n-C3F7
t-Bu           3-Me      H         H            i-C3F7
propargyl      3-Me      H         H            Br
Et             3-Me      H         H            Cl
i-Pr           3-Me      H         H            SCF3
t-Bu           3-Me      5-Br      Ph           CF3
cyclopropyl    3-Me      H         Ph           Cl
Et             3-Me      H         Ph           Br
i-Pr           3-Me      H         2-pyridyl    CF3
R3            R4a      R4b      Rva               Rvb
t-Bu           3-Me      H         2-pyridyl          Cl
Me             3-Me      H         2-ClPh             CF3
Et             3-Me      5-Cl      2-ClPh             OCF3
i-Pr           3-Me      H         2-ClPh             Br
t-Bu           3-Me      H         2-ClPh             Cl
Me             3-Me      H         2-ClPh             SCHF2
propargyl      3-Me      H         2-BrPh             CF3
i-Pr           3-Me      5-CN      2-MePh             CF3
t-Bu           3-Me      H         2-CNPh             CF3
Me             3-Me      H         2-FPh              CF3
Et             3-Me      H         2，6-F2Ph         CF3
i-Pr           3-Me      5-Br      2，4-F2Ph         CF3
t-Bu           3-Me      H         2，5-F2Ph         CF3
Me             3-Me      5-I       2-MeOPh            CF3
Et             3-Me      H         3-Cl-2-pyridyl     CF3
i-Pr           3-Me      5-Me      3-Cl-2-pyridyl     OCF3
t-Bu           3-Me      H         3-Cl-2-pyridyl     Br
propargyl      3-Me      H         3-Cl-2-pyridyl     Cl
Et             3-Me      5-Br      3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me      H         3-F-2-pyridyl      CF3
t-Bu           3-Me      H         3-CF3-2-pyridyl   CF3
Me             3-Me      H         3-Me-2-pyridyl     CF3
Et             3-Me      H         3-Br-2-pyridyl     CF3
i-Pr           3-Me      5-Cl      3-Br-2-pyridyl     OCF3
t-Bu           3-Me      H         3-Br-2-pyridyl     Br
i-Pr           3-Me      H         3-Br-2-pyridyl     Cl
Me             6-Me      H         H                  CF3
Et             6-Me      4-Me      H                  OCF3
i-Pr           6-Me      H         H                  OCF3
t-Bu           6-Me      Cl        Me                 Br
Me             6-Me      H         Et                 Br
Et             6-Me      H         Me                 Cl
i-Pr           6-Me      4-Br      Et                 Cl
t-Bu           6-Me      H         Me                 I
propargyl      6-Me      H         Me                 CF3
cyclopropyl    6-Me      H         Me                 OCF3
R3            R4a      R4b      Rva    Rvb
i-Pr           6-Me      4-Cl      Me      CF3
t-Bu           6-Me      H         Me      SCF3
Me             6-Me      H         Me      SCHF2
Et             6-Me      H         Me      OCHF2
i-Pr           6-Me      4-CN      Me      CF3
t-Bu           6-Me      H         Me      C2F5
propargyl      6-Me      H         Me      C2F5
cyclopropyl    6-Me      H         Et      CF3
i-Pr           6-Me      H         n-Pr    CF3
t-Bu           6-Me      4-Br      i-Pr    CF3
Me             6-Me      H         Cl      CF3
Et             6-Me      H         F       CF3
i-Pr           6-Me      H         Me      SMe
t-Bu           6-Me      4-Cl      Me      OMe
Me             6-Me      H         Me      OEt
Et             6-Me      H         Me      n-C3F7
i-Pr           6-Me      H         Me      i-C3F7
t-Bu           6-Me      4-F       Me      Et
propargyl      6-Me      H         Me      OCF2CHF2
Et             6-Me      H         Me      SCF2CHF2
i-Pr           6-Me      H         Me      SO2Me
t-Bu           6-Me      4-Cl      Me      SO2CF3
Me             6-Me      H         CF3    CF3
Et             6-Me      H         CF3    Me
i-Pr           6-Me      H         OMe     CF3
t-Bu           6-Me      H         H       CF3
cyclopropyl    6-Me      4-Br      H       OCHF2
Et             6-Me      H         H       C2F5
i-Pr           6-Me      H         H       C2F5
t-Bu           6-Me      4-Me      H       OCF3
Me             6-Me      H         H       OCF2CHF2
Et             6-Me      H         H       SCF2CHF2
i-Pr           6-Me      4-Cl      H       n-C3F7
t-Bu           6-Me      H         H       i-C3F7
propargyl      6-Me      H         H       Br
Et             6-Me      H         H       Cl
R3            R4a      R4b      Rva               Rvb
i-Pr           6-Me      H         H                  SCF3
t-Bu           6-Me      4-Br      Ph                 CF3
cyclopropyl    6-Me      H         Ph                 Cl
Et             6-Me      H         Ph                 Br
i-Pr           6-Me      H         2-pyridyl          CF3
t-Bu           6-Me      H         2-pyridyl          Cl
Me             6-Me      H         2-ClPh             CF3
Et             6-Me      4-Cl      2-ClPh             OCF3
i-Pr           6-Me      H         2-ClPh             Br
t-Bu           6-Me      4-CN      2-ClPh             Cl
Me             6-Me      H         2-ClPh             SCHF2
propargyl      6-Me      H         2-BrPh             CF3
i-Pr           6-Me      H         2-MePh             CF3
t-Bu           6-Me      H         2-CNPh             CF3
Me             6-Me      H         2-FPh              CF3
Et             6-Me      H         2，6-F2Ph         CF3
i-Pr           6-Me      4-Br      2，4-F2Ph         CF3
t-Bu           6-Me      H         2，5-F2Ph         CF3
Me             6-Me      4-I       2-MeOPh            CF3
Et             6-Me      H         3-Cl-2-pyridyl     CF3
i-Pr           6-Me      H         3-Cl-2-pyridyl     OCF3
t-Bu           6-Me      H         3-Cl-2-pyridyl     Br
propargyl      6-Me      H         3-Cl-2-pyridyl     Cl
Et             6-Me      4-Br      3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me      H         3-F-2-pyridyl      CF3
t-Bu           6-Me      H         3-CF3-2-pyridyl   CF3
Me             6-Me      H         3-Me-2-pyridyl     CF3
Et             6-Me      H         3-Br-2-pyridyl     CF3
i-Pr           6-Me      4-Cl      3-Br-2-pyridyl     OCF3
t-Bu           6-Me      H         3-Br-2-pyridyl     Br
i-Pr           6-Me      H         3-Br-2-pyridyl     Cl
Me             3-Cl      H         H                  CF3
Et             3-Br      5-Me      H                  OCF3
i-Pr           3-Cl      H         H                  OCF3
t-Bu           3-Cl      5-Cl      Me                 Br
Me             3-Cl      H         Et                 Br
R3            R4a      R4b      Rva      Rvb
Et             3-Cl      H         Me        Cl
i-Pr           3-Cl      5-Br      Et        Cl
t-Bu           3-Cl      H         Me        I
propargyl      3-Cl      H         Me        CF3
cyclopropyl    3-Cl      H         Me        OCF3
i-Pr           3-Cl      5-Cl      Me        CF3
t-Bu           3-Cl      H         Me        SCF3
Me             3-F       H         Me        SCHF2
Et             3-Cl      H         Me        OCHF2
i-Pr           3-Cl      5-CN      Me        CF3
t-Bu           3-Cl      H         Me        C2F5
propargyl      3-Cl      H         Me        C2F5
cyclopropyl    3-Cl      H         Et        CF3
i-Pr           3-Cl      H         n-Pr      CF3
t-Bu           3-Cl      5-Br      i-Pr      CF3
Me             3-Cl      H         Cl        CF3
Et             3-Br      H         F         CF3
i-Pr           3-Cl      H         Me        SMe
t-Bu           3-Cl      5-Cl      Me        OMe
Me             3-Cl      H         Me        OEt
Et             3-Cl      H         Me        n-C3F7
i-Pr           3-Cl      H         Me        i-C3F7
t-Bu           3-Cl      5-F       Me        Et
propargyl      3-Cl      H         Me        OCF2CHF2
Et             3-Cl      H         Me        SCF2CHF2
i-Pr           3-Br      H         Me        SO2Me
t-Bu           3-Cl      5-Cl      Me        SO2CF3
Me             3-Cl      H         CF3      CF3
Et             3-CN      H         CF3      Me
i-Pr           3-Cl      H         OMe       CF3
t-Bu           3-Cl      H         H         CF3
cyclopropyl    3-Cl      5-Br      H         OCHF2
Et             3-Cl      H         H         C2F5
i-Pr           3-Cl      H         H         C2F5
t-Bu           3-Cl      H         H         OCF3
Me             3-F       H         H         OCF2CHF2
R3            R4a      R4b      Rva               Rvb
Et             3-Cl      H         H                  SCF2CHF2
i-Pr           3-Cl      5-Cl      H                  n-C3F7
t-Bu           3-Cl      H         H                  i-C3F7
propargyl      3-Cl      H         H                  Br
Et             3-Cl      H         H                  Cl
i-Pr           3-Cl      H         H                  SCF3
t-Bu           3-Cl      5-Br      Ph                 CF3
cyclopropyl    3-Cl      H         Ph                 Cl
Et             3-Cl      H         Ph                 Br
i-Pr           3-Br      H         2-pyridyl          CF3
t-Bu           3-Cl      H         2-pyridyl          Cl
Me             3-Cl      H         2-ClPh             CF3
Et             3-Cl      5-Cl      2-ClPh             OCF3
i-Pr           3-Cl      H         2-ClPh             Br
t-Bu           3-I       H         2-ClPh             Cl
Me             3-Cl      5-Me      2-ClPh             SCHF2
propargyl      3-Cl      H         2-BrPh             CF3
i-Pr           3-Cl      H         2-MePh             CF3
t-Bu           3-Cl      5-CN      2-CNPh             CF3
Me             3-Cl      H         2-FPh              CF3
Et             3-Cl      H         2，6-F2Ph         CF3
i-Pr           3-Cl      5-Br      2，4-F2Ph         CF3
t-Bu           3-F       H         2，5-F2Ph         CF3
Me             3-Cl      5-I       2-MeOPh            CF3
Et             3-Cl      H         3-Cl-2-pyridyl     CF3
i-Pr           3-CN      H         3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl      H         3-Cl-2-pyridyl     Br
propargyl      3-Cl      H         3-Cl-2-pyridyl     Cl
Et             3-Cl      5-Br      3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl      H         3-F-2-pyridyl      CF3
t-Bu           3-Br      H         3-CF3-2-pyridyl   CF3
Me             3-Cl      H         3-Me-2-pyridyl     CF3
Et             3-Cl      H         3-Br-2-pyridyl     CF3
i-Pr           3-Cl      5-Cl      3-Br-2-pyridyl     OCF3
t-Bu           3-Cl      H         3-Br-2-pyridyl     Br
i-Pr           3-Cl      H         3-Br-2-pyridyl     Cl
R3            R4a      R4b      Rva      Rvb
Me             6-Cl      H         H         CF3
Et             6-Br      4-Me      H         OCF3
i-Pr           6-Cl      H         H         OCF3
t-Bu           6-Cl      Cl        Me        Br
Me             6-Cl      H         Et        Br
Et             6-Cl      H         Me        Cl
i-Pr           6-F       4-Br      Et        Cl
t-Bu           6-Cl      H         Me        I
propargyl      6-Cl      H         Me        CF3
cyclopropyl    6-Cl      H         Me        OCF3
i-Pr           6-Cl      4-Cl      Me        CF3
t-Bu           6-Cl      H         Me        SCF3
Me             6-Cl      H         Me        SCHF2
Et             6-Cl      H         Me        OCHF2
i-Pr           6-I       4-CN      Me        CF3
t-Bu           6-Cl      H         Me        C2F5
propargyl      6-Cl      H         Me        C2F5
cyclopropyl    6-Cl      H         Et        Cf3
i-Pr           6-Cl      H         n-Pr      CF3
t-Bu           6-Cl      4-Br      i-Pr      CF3
Me             6-Cl      H         Cl        CF3
Et             6-F       H         F         CF3
i-Pr           6-Cl      H         Me        SMe
t-Bu           6-Cl      4-Cl      Me        OMe
Me             6-Cl      H         Me        OEt
Et             6-I       H         Me        n-C3F7
i-Pr           6-Cl      H         Me        i-C3F7
t-Bu           6-Cl      4-F       Me        Et
propargyl      6-Cl      H         Me        OCF2CHF2
Et             6-Cl      H         Me        SCF2CHF2
i-Pr           6-Cl      H         Me        SO2Me
t-Bu           6-Cl      4-Cl      Me        SO2CF3
Me             6-Cl      H         CF3      CF3
Et             6-Cl      H         CF3      Me
i-Pr           6-Cl      H         OMe       CF3
t-Bu           6-Br      H         H         CF3
R3            R4a      R4b      Rva               Rvb
cyclopropyl    6-Cl      4-Br      H                  OCHF2
Et             6-Cl      H         H                  C2F5
i-Pr           6-Cl      H         H                  C2F5
t-Bu           6-F       4-Me      H                  OCF3
Me             6-Cl      H         H                  OCF2CHF2
Et             6-Cl      H         H                  SCF2CHF2
i-Pr           6-CN      4-Cl      H                  n-C3F7
t-Bu           6-Cl      H         H                  i-C3F7
propargyl      6-Cl      H         H                  Br
Et             6-Cl      H         H                  Cl
i-Pr           6-Cl      H         H                  SCF3
t-Bu           6-Cl      4-Br      Ph                 CF3
cyclopropyl    6-Cl      H         Ph                 Cl
Et             6-F       H         Ph                 Br
i-Pr           6-Cl      H         2-pyridyl          CF3
t-Bu           6-Cl      H         2-pyridyl          Cl
Me             6-Cl      H         2-ClPh             CF3
Et             6-Br      4-Cl      2-ClPh             OCF3
i-Pr           6-Cl      H         2-ClPh             Br
t-Bu           6-Cl      H         2-ClPh             Cl
Me             6-Cl      H         2-ClPh             SCHF2
propargyl      6-Cl      H         2-BrPh             CF3
i-Pr           6-Br      H         2-MePh             CF3
t-Bu           6-Cl      4-CN      2-CNPh             CF3
Me             6-Cl      H         2-FPh              CF3
Et             6-Cl      H         2，6-F2Ph         CF3
i-Pr           6-Cl      4-Br      2，4-F2Ph         CF3
t-Bu           6-CN      H         2，5-F2Ph         CF3
Me             6-Cl      4-I       2-MeOPh            CF3
Et             6-Cl      H         3-Cl-2-pyridyl     CF3
i-Pr           6-Br      H         3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl      H         3-Cl-2-pyridyl     Br
propargyl      6-Cl      H         3-Cl-2-pyridyl     Cl
Et             6-Cl      4-Br      3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl      H         3-F-2-pyridyl      CF3
t-Bu           6-Cl      H         3-CF3-2-pyridyl   CF3
R3            R4a      R4b      Rva              Rvb
Me             6-Cl      H         3-Me-2-pyridyl    CF3
Et             6-Cl      H         3-Br-2-pyridyl    CF3
i-Pr           6-Cl      4-Cl      3-Br-2-pyridyl    OCF3
t-Bu           6-Cl      H         3-Br-2-pyridyl    Br
i-Pr           6-Cl      H         3-Br-2-pyridyl    Cl
                         Table 4
Figure A0281824700931
R3            R4a      R4b      Rva              Rvb
Me             3-Me      H         H                 CF3
Et             3-Me      5-Me      H                 OCF3
i-Pr           3-Me      H         H                 OCF3
t-Bu           3-Me      5-Cl      Me                Br
Me             3-Me      H         Et                Br
Et             3-Me      H         Me                Cl
i-Pr           3-Me      5-Br      Et                Cl
t-Bu           3-Me      H         Me                I
propargyl      3-Me      H         Me                CF3
cyclopropyl    3-Me      H         Me                OCF3
i-Pr           3-Me      5-Cl      Me                CF3
t-Bu           3-Me      H         Me                SCF3
Me             3-Me      5-CN      Me                SCHF2
Et             3-Me      H         Me                OCHF2
i-Pr           3-Me      H         Me                CF3
t-Bu           3-Me      H         Me                C2F5
propargyl      3-Me      H         Me                C2F5
cyclopropyl    3-Me      H         Et                CF3
i-Pr           3-Me      H         n-Pr              CF3
t-Bu           3-Me      5-Br      i-Pr              CF3
R3            R4a    R4b    Rva         Rvb
Me             3-Me    H       Cl           CF3
Et             3-Me    H       F            CF3
i-Pr           3-Me    H       Me           SMe
t-Bu           3-Me    5-Cl    Me           OMe
Me             3-Me    H       Me           OEt
Et             3-Me    H       Me           n-C3F7
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
R3            R4a    R4b    Rva               Rvb
Me             3-Me    H       2-ClPh             SCHF2
propargyl      3-Me    H       2-BrPh             CF3
i-Pr           3-Me    5-CN    2-MePh             CF3
t-Bu           3-Me    H       2-CNPh             CF3
Me             3-Me    H       2-FPh              CF3
Et             3-Me    H       2，6-F2Ph         CF3
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，5-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
R3            R4a    R4b    Rva         Rvb
t-Bu           6-Me    H       Me           C2F5
propargyl      6-Me    H       Me           C2F5
cyclopropyl    6-Me    H       Et           CF3
i-Pr           6-Me    H       n-Pr         CF3
t-Bu           6-Me    4-Br    i-Pr         CF3
Me             6-Me    H       Cl           CF3
Et             6-Me    H       F            CF3
i-Pr           6-Me    H       Me           SMe
t-Bu           6-Me    4-Cl    Me           OMe
Me             6-Me    H       Me           OEt
Et             6-Me    H       Me           n-C3F7
i-Pr           6-Me    H       Me           i-C3F7
t-Bu           6-Me    4-F     Me           Et
propargyl      6-Me    H       Me           OCF2CHF2
Et             6-Me    H       Me           SCF2CHF2
i-Pr           6-Me    H       Me           SO2Me
t-Bu           6-Me    4-Cl    Me           SO2CF3
Me             6-Me    H       CF3         CF3
Et             6-Me    H       CF3         Me
i-Pr           6-Me    H       OMe          CF3
t-Bu           6-Me    H       H            CF3
cyclopropyl    6-Me    4-Br    H            OCHF2
Et             6-Me    H       H            C2F5
i-Pr           6-Me    H       H            C2F5
t-Bu           6-Me    4-Me    H            OCF3
Me             6-Me    H       H            OCF2CHF2
Et             6-Me    H       H            SCF2CHF2
i-Pr           6-Me    4-Cl    H            n-C3F7
t-Bu           6-Me    H       H            i-C3F7
propargyl      6-Me    H       H            Br
Et             6-Me    H       H            Cl
i-Pr           6-Me    H       H            SCF3
t-Bu           6-Me    4-Br    Ph           CF3
cyclopropyl    6-Me    H       Ph           Cl
Et             6-Me    H       Ph           Br
i-Pr           6-Me    H       2-pyridyl    CF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Me    H       2-pyridyl          Cl
Me             6-Me    H       2-ClPh             CF3
Et             6-Me    4-Cl    2-ClPh             OCF3
i-Pr           6-Me    H       2-ClPh             Br
t-Bu           6-Me    4-CN    2-ClPh             Cl
Me             6-Me    H       2-ClPh             SCHF2
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，5-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
R3            R4a        R4b        Rva    Rvb
i-Pr           3-Cl        5-Cl        Me      CF3
t-Bu           3-Cl        H           Me      SCF3
Me             3-F         H           Me      SCHF2
Et             3-Cl        H           Me      OCHF2
i-Pr           3-Cl        5-CN        Me      CF3
t-Bu           3-Cl        H           Me      C2F5
propargyl      3-Cl        H           Me      C2F5
cyclopropyl    3-Cl        H           Et      CF3
i-Pr           3-Cl        H           n-Pr    CF3
t-Bu           3-Cl        5-Br        i-Pr    CF3
Me             3-Cl        H           Cl      CF3
Et             3-Br        H           F       CF3
i-Pr           3-Cl        H           Me      SMe
t-Bu           3-Cl        5-Cl        Me      OMe
Me             3-Cl        H           Me      OEt
Et             3-Cl        H           Me      n-C3F7
i-Pr           3-Cl        H           Me      i-C3F7
t-Bu           3-Cl        5-F         Me      Et
propargyl      3-Cl        H           Me      OCF2CHF2
Et             3-Cl        H           Me      SCF2CHF2
i-Pr           3-Br        H           Me      SO2Me
t-Bu           3-Cl        5-Cl        Me      SO2CF3
Me             3-Cl        H           CF3    CF3
Et             3-CN        H           CF3    Me
i-Pr           3-Cl        H           OMe     CF3
t-Bu           3-Cl        H           H       CF3
cyclopropyl    3-Cl        5-Br        H       OCHF2
Et             3-Cl        H           H       C2F5
i-Pr           3-Cl        H           H       C2F5
t-Bu           3-Cl        H           H       OCF3
Me             3-F         H           H       OCF2CHF2
Et             3-Cl        H           H       SCF2CHF2
i-Pr           3-Cl        5-Cl        H       n-C3F7
t-Bu           3-Cl        H           H       i-C3F7
propargyl      3-Cl        H           H       Br
Et             3-Cl        H           H       Cl
R3            R4a    R4b    Rva              Rvb
i-Pr           3-Cl    H       H                 SCF3
t-Bu           3-Cl    5-Br    Ph                CF3
cyclopropyl    3-Cl    H       Ph                Cl
Et             3-Cl    H       Ph                Br
i-Pr           3-Br    H       2-pyridyl         CF3
t-Bu           3-Cl    H       2-pyridyl         Cl
Me             3-Cl    H       2-ClPh            CF3
Et             3-Cl    5-Cl    2-ClPh            OCF3
i-Pr           3-Cl    H       2-ClPh            Br
t-Bu           3-I     H       2-ClPh            Cl
Me             3-Cl    5-Me    2-ClPh            SCHF2
propargyl      3-Cl    H       2-BrPh            CF3
i-Pr           3-Cl    H       2-MePh            CF3
t-Bu           3-Cl    5-CN    2-CNPh            CF3
Me             3-Cl    H       2-FPh             CF3
Et             3-Cl    H       2，6-F2Ph        CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph        CF3
t-Bu           3-F     H       2，5-F2Ph        CF3
Me             3-Cl    5-I     2-MeOPh           CF3
Et             3-Cl    H       3-Cl-2-pyridyl    CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl    OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl    Br
propargyl      3-Cl    H       3-Cl-2-pyridyl    Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl    SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl     CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl  CF3
Me             3-Cl    H       3-Me-2-pyridyl    CF3
Et             3-Cl    H       3-Br-2-pyridyl    CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl    OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl    Br
i-Pr           3-Cl    H       3-Br-2-pyridyl    Cl
Me             6-Cl    H       H                 CF3
Et             6-Br    4-Me    H                 OCF3
i-Pr           6-Cl    H       H                 OCF3
t-Bu           6-Cl    Cl      Me                Br
Me             6-Cl    H       Et                Br
R3            R4a        R4b        Rva    Rvb
Et             6-Cl        H           Me      Cl
i-Pr           6-F         4-Br        Et      Cl
t-Bu           6-Cl        H           Me      I
propargyl      6-Cl        H           Me      CF3
cyclopropyl    6-Cl        H           Me      OCF3
i-Pr           6-Cl        4-Cl        Me      CF3
t-Bu           6-Cl        H           Me      SCF3
Me             6-Cl        H           Me      SCHF2
Et             6-Cl        H           Me      OCHF2
i-Pr           6-I         4-CN        Me      CF3
t-Bu           6-Cl        H           Me      C2F5
propargyl      6-Cl        H           Me      C2F5
cyclopropyl    6-Cl        H           Et      CF3
i-Pr           6-Cl        H           n-Pr    CF3
t-Bu           6-Cl        4-Br        i-Pr    CF3
Me             6-Cl        H           Cl      CF3
Et             6-F         H           F       CF3
i-Pr           6-Cl        H           Me      SMe
t-Bu           6-Cl        4-Cl        Me      OMe
Me             6-Cl        H           Me      OEt
Et             6-I         H           Me      n-C3F7
i-Pr           6-Cl        H           Me      i-C3F7
t-Bu           6-Cl        4-F         Me      Et
propargyl      6-Cl        H           Me      OCF2CHF2
Et             6-Cl        H           Me      SCF2CHF2
i-Pr           6-Cl        H           Me      SO2Me
t-Bu           6-Cl        4-Cl        Me      SO2CF3
Me             6-Cl        H           CF3    CF3
Et             6-Cl        H           CF3    Me
i-Pr           6-Cl        H           OMe     CF3
t-Bu           6-Br        H           H       CF3
cyclopropyl    6-Cl        4-Br        H       OCHF2
Et             6-Cl        H           H       C2F5
i-Pr           6-Cl        H           H       C2F5
t-Bu           6-F         4-Me        H       OCF3
Me             6-Cl        H           H       OCF2CHF2
R3            R4a    R4b    Rva               Rvb
Et             6-Cl    H       H                  SCF2CHF2
i-Pr           6-CN    4-Cl    H                  n-C3F7
t-bu           6-Cl    H       H                  i-C3F7
propargyl      6-Cl    H       H                  Br
Et             6-Cl    H       H                  Cl
i-Pr           6-Cl    H       H                  SCF3
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，5-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                   Table 5
R3            R4a    R4b    Rva    Rvb
Me             3-Me    H       H       CF3
Et             3-Me    5-Me    H       OCF3
i-Pr           3-Me    H       H       OCF3
t-Bu           3-Me    5-Cl    Me      Br
Me             3-Me    H       Et      Br
Et             3-Me    H       Me      Cl
i-Pr           3-Me    5-Br    Et      Cl
t-Bu           3-Me    H       Me      I
propargyl      3-Me    H       Me      CF3
cyclopropyl    3-Me    H       Me      OCF3
i-Pr           3-Me    5-Cl    Me      CF3
t-Bu           3-Me    H       Me      SCF3
Me             3-Me    5-CN    Me      SCHF2
Et             3-Me    H       Me      OCHF2
i-Pr           3-Me    H       Me      CF3
t-Bu           3-Me    H       Me      C2F5
propargyl      3-Me    H       Me      C2F5
cyclopropyl    3-Me    H       Et      CF3
i-Pr           3-Me    H       n-Pr    CF3
t-Bu           3-Me    5-Br    i-Pr    CF3
Me             3-Me    H       Cl      CF3
Et             3-Me    H       F       CF3
i-Pr           3-Me    H       Me      SMe
t-Bu           3-Me    5-Cl    Me      OMe
Me             3-Me    H       Me      OEt
R3            R4a    R4b    Rva         Rvb
Et             3-Me    H       Me           n-C3F7
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
Me             3-Me    H       2-ClPh       SCHF2
propargyl      3-Me    H       2-BrPh       CF3
i-Pr           3-Me    5-CN    2-MePh       CF3
t-Bu           3-Me    H       2-CNPh       CF3
Me             3-Me    H       2-FPh        CF3
R3            R4a    R4b    Rva               Rvb
Et             3-Me    H       2，6-F2Ph         CF3
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，6-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
R3            R4a    R4b    Rva         Rvb
Me             6-Me    H       Cl           CF3
Et             6-Me    H       F            CF3
i-Pr           6-Me    H       Me           SMe
t-Bu           6-Me    4-Cl    Me           OMe
Me             6-Me    H       Me           OEt
Et             6-Me    H       Me           n-C3F7
i-Pr           6-Me    H       Me           i-C3F7
t-Bu           6-Me    4-F     Me           Et
propargyl      6-Me    H       Me           OCF2CHF2
Et             6-Me    H       Me           SCF2CHF2
i-Pr           6-Me    H       Me           SO2Me
t-Bu           6-Me    4-Cl    Me           SO2CF3
Me             6-Me    H       CF3         CF3
Et             6-Me    H       CF3         Me
i-Pr           6-Me    H       OMe          CF3
t-Bu           6-Me    H       H            CF3
cyclopropyl    6-Me    4-Br    H            OCHF2
Et             6-Me    H       H            C2F5
i-Pr           6-Me    H       H            C2F5
t-Bu           6-Me    4-Me    H            OCF3
Me             6-Me    H       H            OCF2CHF2
Et             6-Me    H       H            SCF2CHF2
i-Pr           6-Me    4-Cl    H            n-C3F7
t-Bu           6-Me    H       H            i-C3F7
propargyl      6-Me    H       H            Br
Et             6-Me    H       H            Cl
i-Pr           6-Me    H       H            SCF3
t-Bu           6-Me    4-Br    Ph           CF3
cyclopropyl    6-Me    H       Ph           Cl
Et             6-Me    H       Ph           Br
i-Pr           6-Me    H       2-pyridyl    CF3
t-Bu           6-Me    H       2-pyridyl    Cl
Me             6-Me    H       2-ClPh       CF3
Et             6-Me    4-Cl    2-ClPh       OCF3
i-Pr           6-Me    H       2-ClPh       Br
t-Bu           6-Me    4-CN    2-ClPh       Cl
R3            R4a    R4b    Rva               Rvb
Me             6-Me    H       2-ClPh             SCHF2
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-Cl    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
R3            R4a    R4b    Rva         Rvb
t-Bu           3-Cl    H       Me           C2F5
propargyl      3-Cl    H       Me           C2F5
cyclopropyl    3-Cl    H       Et           CF3
i-Pr           3-Cl    H       n-Pr         CF3
t-Bu           3-Cl    5-Br    i-Pr         CF3
Me             3-Cl    H       Cl           CF3
Et             3-Br    H       F            CF3
i-Pr           3-Cl    H       Me           SMe
t-Bu           3-Cl    5-Cl    Me           OMe
Me             3-Cl    H       Me           OEt
Et             3-Cl    H       Me           n-C3F7
i-Pr           3-Cl    H       Me           i-C3F7
t-Bu           3-Cl    5-F     Me           Et
propargyl      3-Cl    H       Me           OCF2CHF2
Et             3-Cl    H       Me           SCF2CHF2
i-Pr           3-Br    H       Me           SO2Me
t-Bu           3-Cl    5-Cl    Me           SO2CF3
Me             3-C     H       CF3         CF3
Et             3-CN    H       CF3         Me
i-Pr           3-Cl    H       OMe          CF3
t-Bu           3-Cl    H       H            CF3
cyclopropyl    3-Cl    5-Br    H            OCHF2
Et             3-Cl    H       H            C2F5
i-Pr           3-Cl    H       H            C2F5
t-Bu           3-Cl    H       H            OCF3
Me             3-F     H       H            OCF2CHF2
Et             3-Cl    H       H            SCF2CHF2
i-Pr           3-Cl    5-Cl    H            n-C3F7
t-Bu           3-Cl    H       H            i-C3F7
propargyl      3-Cl    H       H            Br
Et             3-Cl    H       H            Cl
i-Pr           3-Cl    H       H            SCF3
t-Bu           3-Cl    5-Br    Ph           CF3
cyclopropyl    3-Cl    H       Ph           Cl
Et             3-Cl    H       Ph           Br
i-Pr           3-Br    H       2-pyridyl    CF3
R3           R4a    R4b    Rva               Rvb
t-Bu           3-Cl    H       2-pyridyl          Cl
Me             3-Cl    H       2-ClPh             CF3
Et             3-Cl    5-Cl    2-ClPh             OCF3
i-Pr           3-Cl    H       2-ClPh             Br
t-Bu           3-I     H       2-ClPh             Cl
Me             3-Cl    5-Me    2-ClPh             SCHF2
propargyl      3-Cl    H       2-BrPh             CF3
i-Pr           3-Cl    H       2-MePh             CF3
t-Bu           3-Cl    5-CN    2-CNPh             CF3
Me             3-Cl    H       2-FPh              CF3
Et             3-Cl    H       2，6-F2Ph         CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph         CF3
t-Bu           3-F     H       2，5-F2Ph         CF3
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl     Br
propargyl      3-Cl    H       3-Cl-2-pyridyl     Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF3
Et             3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       H                  CF3
Et             6-Br    4-Me    H                  OCF3
i-Pr           6-Cl    H       H                  OCF3
t-Bu           6-Cl    Cl      Me                 Br
Me             6-Cl    H       Et                 Br
Et             6-Cl    H       Me                 Cl
i-Pr           6-F     4-Br    Et                 Cl
t-Bu           6-Cl    H       Me                 I
propargyl      6-Cl    H       Me                 CF3
cyclopropyl    6-Cl    H       Me                 OCF3
R3            R4a        R4b        Rya    Rvb
i-Pr           6-Cl        4-Cl        Me      CF3
t-Bu           6-Cl        H           Me      SCF3
Me             6-Cl        H           Me      SCHF2
Et             6-Cl        H           Me      OCHF2
i-Pr           6-I         4-CN        Me      CF3
t-Bu           6-Cl        H           Me      C2F5
propargyl      6-Cl        H           Me      C2F5
cyclopropyl    6-Cl        H           Et      CF3
i-Pr           6-Cl        H           n-Pr    CF3
t-B       u    6-Cl        4-Br        i-Pr    CF3
Me             6-Cl        H           Cl      CF3
Et             6-F         H           F       CF3
i-Pr           6-Cl        H           Me      SMe
t-Bu           6-Cl        4-Cl        Me      OMe
Me             6-Cl        H           Me      OEt
Et             6-I         H           Me      n-C3F7
i-Pr           6-Cl        H           Me      i-C3F7
t-Bu           6-Cl        4-F         Me      Et
propargyl      6-Cl        H           Me      OCF2CHF2
Et             6-Cl        H           Me      SCF2CHF2
i-Pr           6-Cl        H           Me      SO2Me
t-Bu           6-Cl        4-Cl        Me      SO2CF3
Me             6-Cl        H           CF3    CF3
Et             6-Cl        H           CF3    Me
i-Pr           6-Cl        H           OMe     CF3
t-Bu           6-Br        H           H       CF3
cyclopropyl    6-Cl        4-Br        H       OCHF2
Et             6-Cl        H           H       C2F5
i-Pr           6-Cl        H           H       C2F5
t-Bu           6-F         4-Me        H       OCF3
Me             6-Cl        H           H       OCF2CHF2
Et             6-Cl        H           H       SCF2CHF2
i-Pr           6-CN        4-Cl        H       n-C3F7
t-Bu           6-Cl        H           H       i-C3F7
propargyl      6-Cl        H           H       Br
Et             6-Cl        H           H       Cl
R3            R4a    R4b    Rva               Rvb
i-Pr           6-Cl    H       H                  SCF3
T-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                  Table 6
Figure A0281824701111
R3            R4a        R4b        Rva    Rvb
Me             3-Me        H           H       CF3
Et             3-Me        5-Me        H       OCF3
i-Pr           3-Me        H           H       OCF3
t-Bu           3-Me        5-Cl        Me      Br
Me             3-Me        H           Et      Br
Et             3-Me        H           Me      Cl
i-Pr           3-Me        5-Br        Et      Cl
t-Bu           3-Me        H           Me      I
propargyl      3-Me        H           Me      CF3
cyclopropyl    3-Me        H           Me      OCF3
i-Pr           3-Me        5-Cl        Me      CF3
t-Bu           3-Me        H           Me      SCF3
Me             3-Me        5-CN        Me      SCHF2
Et             3-Me        H           Me      OCHF2
i-Pr           3-Me        H           Me      CF3
t-Bu           3-Me        H           Me      C2F5
propargyl      3-Me        H           Me      C2F5
cyclopropyl    3-Me        H           Et      CF3
i-Pr           3-Me        H           n-Pr    CF3
t-Bu           3-Me        5-Br        i-Pr    CF3
Me             3-Me        H           Cl      CF3
Et             3-Me        H           F       CF3
i-Pr           3-Me        H           Me      SMe
t-Bu           3-Me        5-Cl        Me      OMe
Me             3-Me        H           Me      OEt
Et             3-Me        H           Me      n-C3F7
R3            R4a    R4b    Rva         Rvb
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
Me             3-Me    H       2-ClPh       SCHF2
propargyl      3-Me    H       2-BrPh       CF3
i-Pr           3-Me    5-CN    2-MePh       CF3
t-Bu           3-Me    H       2-CNPh       CF3
Me             3-Me    H       2-FPh        CF3
Et             3-Me    H       2，6-F2Ph   CF3
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，5-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br--pyridyl      Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
proPargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Cl                 CF3
R3            R4a    R4b    Rva         Rvb
Et             6-Me    H       F            CF3
i-Pr           6-Me    H       Me           SMe
t-Bu           6-Me    4-Cl    Me           OMe
Me             6-Me    H       Me           OEt
Et             6-Me    H       Me           n-C3F7
i-Pr           6-Me    H       Me           i-C3F7
t-Bu           6-Me    4-F     Me           Et
propargyl      6-Me    H       Me           OCF2CHF2
Et             6-Me    H       Me           SCF2CHF2
i-Pr           6-Me    H       Me           SO2Me
t-Bu           6-Me    4-Cl    Me           SO2CF3
Me             6-Me    H       CF3         CF3
Et             6-Me    H       CF3         Me
i-Pr           6-Me    H       OMe          CF3
t-Bu           6-Me    H       H            CF3
cyclopropyl    6-Me    4-Br    H            OCHF2
Et             6-Me    H       H            C2F5
i-Pr           6-Me    H       H            C2F5
t-Bu           6-Me    4-Me    H            OCF3
Me             6-Me    H       H            OCF2CHF2
Et             6-Me    H       H            SCF2CHF2
i-Pr           6-Me    4-Cl    H            n-C3F7
t-Bu           6-Me    H       H            i-C3F7
Propargyl      6-Me    H       H            Br
Et             6-Me    H       H            Cl
i-Pr           6-Me    H       H            SCF3
t-Bu           6-Me    4-Br    Ph           CF3
cyclopropyl    6-Me    H       Ph           Cl
Et             6-Me    H       Ph           Br
i-Pr           6-Me    H       2-pyridyl    CF3
t-Bu           6-Me    H       2-pyridyl    Cl
Me             6-Me    H       2-ClPh       CF3
Et             6-Me    4-Cl    2-ClPh       OCF3
i-Pr           6-Me    H       2-ClPh       Br
t-Bu           6-Me    4-CN    2-ClPh       Cl
Me             6-Me    H       2-ClPh       SCHF2
R3            R4a    R4b    Rva               Rvb
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-CL    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
t-Bu           3-Cl    H       Me                 C2F5
R3            R4a        R4b    Rva         Rvb
propargyl      3-Cl        H       Me           C2F5
cyclopropyl    3-Cl        H       Et           CF3
i-Pr           3-Cl        H       n-Pr         CF3
t-Bu           3-Cl        5-Br    i-Pr         CF3
Me             3-Cl        H       Cl           CF3
Et             3-Br        H       F            CF3
i-Pr           3-Cl        H       Me           SMe
t-Bu           3-Cl        5-Cl    Me           OMe
Me             3-Cl        H       Me           OEt
Et             3-Cl        H       Me           n-C3F7
i-Pr           3-Cl        H       Me           i-C3F7
t-Bu           3-Cl        5-F     Me           Et
propargyl      3-Cl        H       Me           OCF2CHF2
Et             3-Cl        H       Me           SCF2CHF2
i-Pr           3-Br        H       Me           SO2Me
t-Bu           3-Cl        5-Cl    Me           SO2CF3
Me             3-Cl        H       CF3         CF3
Et             3-CN        H       CF3         Me
i-Pr           3-Cl        H       OMe          CF3
t-Bu           3-Cl        H       H            CF3
cyclopropyl    3-Cl        5-Br    H            OCHF2
Et             3-Cl        H       H            C2F5
i-Pr           3-Cl        H       H            C2F5
t-Bu           3-Cl        H       H            OCF3
Me             3-F         H       H            OCF2CHF2
Et             3-Cl        H       H            SCF2CHF2
i-Pr           3-Cl        5-Cl    H            n-C3F7
t-Bu           3-Cl        H       H            i-C3F7
propargyl      3-Cl        H       H            Br
Et             3-Cl        H       H            Cl
i-Pr           3-Cl        H       H            SCF3
t-Bu           3-Cl        5-Br    Ph           CF3
cyclopropyl    3-Cl        H       Ph           Cl
Et             3-Cl        H       Ph           Br
i-Pr           3-Br        H       2-pyridyl    CF3
t-Bu           3-Cl        H       2-pyridyl    Cl
R3           R4a    R4b    Rva               Rvb
Me             3-Cl    H       2-ClPh             CF3
Et             3-Cl    5-Cl    2-ClPh             OCF3
i-Pr           3-Cl    H       2-ClPh             Br
t-Bu           3-I     H       2-ClPh             Cl
Me             3-Cl    5-Me    2-ClPh             SCHF2
propargyl      3-Cl    H       2-BrPh             CF3
i-Pr           3-Cl    H       2-MePh             CF3
t-Bu           3-Cl    5-CN    2-CNPh             CF3
Me             3-Cl    H       2-FPh              CF3
Et             3-Cl    H       2，6-F2Ph         CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph         CF3
t-Bu           3-F     H       2，5-F2Ph         CF3
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl     Br
propargyl      3-Cl    H       3-Cl-2-pyridyl     Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl    CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF3
Et             3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       H                  CF3
Et             6-Br    4-Me    H                  OCF3
i_Pr           6-Cl    H       H                  OCF3
t-Bu           6-Cl    Cl      Me                 Br
Me             6-Cl    H       Et                 Br
Et             6-Cl    H       Me                 Cl
i-Pr           6-F     4-Br    Et                 Cl
t-Bu           6-Cl    H       Me                 I
propargyl      6-Cl    H       Me                 CF3
cyclopropyl    6-Cl    H       Me                 OCF3
i-Pr           6-Cl    4-Cl    Me                 CF3
R3            R4a        R4b    Rva    Rvb
t-Bu           6-Cl        H       Me      SCF3
Me             6-Cl        H       Me      SCHF2
Et             6-Cl        H       Me      OCHF2
i-Pr           6-I         4-CN    Me      CF3
t-Bu           6-Cl        H       Me      C2F5
propargyl      6-Cl        H       Me      C2F5
cyclopropyl    6-Cl        H       Et      CF3
i-Pr           6-Cl        H       n-Pr    CF3
t-Bu           6-Cl        4-Br    i-Pr    CF3
Me             6-Cl        H       Cl      CF3
Et             6-F         H       F       CF3
i-Pr           6-Cl        H       Me      SMe
t-Bu           6-Cl        4-Cl    Me      OMe
Me             6-Cl        H       Me      OEt
Et             6-I         H       Me      n-C3F7
i-Pr           6-Cl        H       Me      i-C3F7
t-Bu           6-Cl        4-F     Me      Et
propargyl      6-Cl        H       Me      OCF2CHF2
Et             6-Cl        H       Me      SCF2CHF2
i-Pr           6-Cl        H       Me      SO2Me
t-Bu           6-Cl        4-Cl    Me      SO2CF3
Me             6-Cl        H       CF3    CF3
Et             6-Cl        H       CF3    Me
i-Pr           6-Cl        H       OMe     CF3
t-Bu           6-Br        H       H       CF3
cyclopropyl    6-Cl        4-Br    H       OCHF2
Et             6-Cl        H       H       C2F5
i-Pr           6-Cl        H       H       C2F5
t-Bu           6-F         4-Me    H       OCF3
Me             6-Cl        H       H       OCF2CHF2
Et             6-Cl        H       H       SCF2CHF2
i-Pr           6-CN        4-Cl    H       n-C3F7
t-Bu           6-Cl        H       H       i-C3F7
propargyl      6-Cl        H       H       Br
Et             6-Cl        H       H       Cl
i-Pr           6-Cl        H       H       SCF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                  Table 7
R3            R4a        R4b        Rva    Rvb
Me             3-Me        H           H       CF3
Et             3-Me        5-Me        H       OCF3
i-Pr           3-Me        H           H       OCF3
t-Bu           3-Me        5-Cl        Me      Br
Me             3-Me        H           Et      Br
Et             3-Me        H           Me      Cl
i-Pr           3-Me        5-Br        Et      Cl
t-Bu           3-Me        H           Me      I
propargyl      3-Me        H           Me      CF3
cyclopropyl    3-Me        H           Me      OCF3
i-Pr           3-Me        5-Cl        Me      CF3
t-Bu           3-Me        H           Me      SCF3
Me             3-Me        5-CN        Me      SCHF2
Et             3-Me        H           Me      OCHF2
i-Pr           3-Me        H           Me      CF3
t-Bu           3-Me        H           Me      C2F5
propargyl      3-Me        H           Me      C2F5
cyclopropyl    3-Me        H           Et      CF3
i-Pr           3-Me        H           n-Pr    CF3
t-Bu           3-Me        5-Br        i-Pr    CF3
Me             3-Me        H           Cl      CF3
Et             3-Me        H           F       CF3
i-Pr           3-Me        H           Me      SMe
t-Bu           3-Me        5-Cl        Me      OMe
Me             3-Me        H           Me      OEt
Et             3-Me        H           Me      n-C3F7
R3            R4a      R4b    Rva         Rvb
i-Pr           3-Me      H       Me           i-C3F7
t-Bu           3-Me      5-F     Me           Et
propargyl      3-Me      H       Me           OCF2CHF2
Et             3-Me      H       Me           SCF2CHF2
i-Pr           3-Me      H       Me           SO2Me
t-Bu           3-Me      5-Cl    Me           SO2CF3
Me             3-Me      H       CF3         CF3
Et             3-Me      H       CF3         Me
i-Pr           3-Me      H       OMe          CF3
t-Bu           3-Me      H       H            CF3
cyclopropyl    3-Me      5-Br    H            OCHF2
Et             3-Me      H       H            C2F5
i-Pr           3-Me      5-Me    H            C2F5
t-Bu           3-Me      H       H            OCF3
Me             3-Me      H       H            OCF2CHF2
Et             3-Me      H       H            SCF2CHF2
i-Pr           3-Me      5-Cl    H            n-C3F7
t-Bu           3-Me      H       H            i-C3F7
propargyl      3-Me      H       H            Br
Et             3-Me      H       H            Cl
i-Pr           3-Me      H       H            SCF3
t-Bu           3-Me      5-Br    Ph           CF3
cyclopropyl    3-Me      H       Ph           Cl
Et             3-Me      H       Ph           Br
i-Pr           3-Me      H       2-pyridyl    CF3
t-Bu           3-Me      H       2-pyridyl    Cl
Me             3-Me      H       2-ClPh       CF3
Et             3-Me      5-Cl    2-ClPh       OCF3
i-Pr           3-Me      H       2-ClPh       Br
t-Bu           3-Me      H       2-ClPh       Cl
Me             3-Me      H       2-ClPh       SCHF2
propargyl      3-Me      H       2-BrPh       CF3
i-Pr           3-Me      5-CN    2-MePh       CF3
t-Bu           3-Me      H       2-CNPh       CF3
Me             3-Me      H       2-FPh        CF3
Et             3-Me      H       2，6-F2Ph    CF3
R3            R4a      R4b      Rva               Rvb
i-Pr           3-Me      5-Br      2，4-F2Ph         CF3
t-Bu           3-Me      H         2，5-F2Ph         CF3
Me             3-Me      5-I       2-MeOPh            CF3
Et             3-Me      H         3-Cl-2-pyridyl     CF3
i-Pr           3-Me      5-Me      3-Cl-2-pyridyl     OCF3
t-Bu           3-Me      H         3-Cl-2-pyridyl     Br
propargyl      3-Me      H         3-Cl-2-pyridyl     Cl
Et             3-Me      5-Br      3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me      H         3-F-2-pyridyl      CF3
t-Bu           3-Me      H         3-CF3-2-pyridyl   CF3
Me             3-Me      H         3-Me-2-pyridyl     CF3
Et             3-Me      H         3-Br-2-pyridyl     CF3
i-Pr           3-Me      5-Cl      3-Br-2-pyridyl     OCF3
t-Bu           3-Me      H         3-Br-2-pyridyl     Br
i-Pr           3-Me      H         3-Br-2-pyridyl     Cl
Me             6-Me      H         H                  CF3
Et             6-Me      4-Me      H                  OCF3
i-Pr           6-Me      H         H                  OCF3
t-Bu           6-Me      Cl        Me                 Br
Me             6-Me      H         Et                 Br
Et             6-Me      H         Me                 Cl
i-Pr           6-Me      4-Br      Et                 Cl
t-Bu           6-Me      H         Me                 I
propargyl      6-Me      H         Me                 CF3
cyclopropyl    6-Me      H         Me                 OCF3
i-Pr           6-Me      4-Cl      Me                 CF3
t-Bu           6-Me      H         Me                 SCF3
Me             6-Me      H         Me                 SCHF2
Et             6-Me      H         Me                 OCHF2
i-Pr           6-Me      4-CN      Me                 CF3
t-Bu           6-Me      H         Me                 C2F5
propargyl      6-Me      H         Me                 C2F5
cyclopropyl    6-Me      H         Et                 CF3
i-Pr           6-Me      H         n-Pr               CF3
t-Bu           6-Me      4-Br      i-Pr               CF3
Me             6-Me      H         Cl                 CF3
R3            R4a      R4b      Rva         Rvb
Et             6-Me      H         F            CF3
i-Pr           6-Me      H         Me           SMe
t-Bu           6-Me      4-Cl      Me           OMe
Me             6-Me      H         Me           OEt
Et             6-Me      H         Me           n-C3F7
i-Pr           6-Me      H         Me           i-C3F7
t-Bu           6-Me      4-F       Me           Et
propargyl      6-Me      H         Me           OCF2CHF2
Et             6-Me      H         Me           SCF2CHF2
i-Pr           6-Me      H         Me           SO2Me
t-Bu           6-Me      4-Cl      Me           SO2CF3
Me             6-Me      H         CF3         CF3
Et             6-Me      H         CF3         Me
i-Pr           6-Me      H         OMe          CF3
t-Bu           6-Me      H         H            CF3
cyclopropyl    6-Me      4-Br      H            OCHF2
Et             6-Me      H         H            C2F5
i-Pr           6-Me      H         H            C2F5
t-Bu           6-Me      4-Me      H            OCF3
Me             6-Me      H         H            OCF2CHF2
Et             6-Me      H         H            SCF2CHF2
i-Pr           6-Me      4-Cl      H            n-C3F7
t-Bu           6-Me      H         H            i-C3F7
propargyl      6-Me      H         H            Br
Et             6-Me      H         H            Cl
i-Pr           6-Me      H         H            SCF3
t-Bu           6-Me      4-Br      Ph           CF3
cyclopropyl    6-Me      H         Ph           Cl
Et             6-Me      H         Ph           Br
i-Pr           6-Me      H         2-pyridyl    CF3
t-Bu           6-Me      H         2-pyridyl    Cl
Me             6-Me      H         2-ClPh       CF3
Et             6-Me      4-Cl      2-ClPh       OCF3
i-Pr           6-Me      H         2-ClPh       Br
t-Bu           6-Me      4-CN      2-ClPh       Cl
Me             6-Me      H         2-ClPh       SCHF2
R3            R4a    R4b    Rva               Rvb
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl    CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-Cl    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
t-Bu          3-Cl     H       Me                 C2F5
R3            R4a        R4b    Rva         Rvb
propargyl      3-Cl        H       Me           C2F5
cyclopropyl    3-Cl        H       Et           CF3
i-Pr           3-Cl        H       n-Pr         CF3
t-Bu           3-Cl        5-Br    i-Pr         CF3
Me             3-Cl        H       Cl           CF3
Et             3-Br        H       F            CF3
i-Pr           3-Cl        H       Me           SMe
t-Bu           3-Cl        5-Cl    Me           OMe
Me             3-Cl        H       Me           OEt
Et             3-Cl        H       Me           n-C3F7
i-Pr           3-Cl        H       Me           i-C3F7
t-Bu           3-Cl        5-F     Me           Et
propargyl      3-Cl        H       Me           OCF2CHF2
Et             3-Cl        H       Me           SCF2CHF2
i-Pr           3-Br        H       Me           SO2Me
t-Bu           3-Cl        5-Cl    Me           SO2CF3
Me             3-Cl        H       CF3         CF3
Et             3-CN        H       CF3         Me
i-Pr           3-Cl        H       OMe          CF3
t-Bu           3-Cl        H       H            CF3
cyclopropyl    3-Cl        5-Br    H            OCHF2
Et             3-Cl        H       H            C2F5
i-Pr           3-Cl        H       H            C2F5
t-Bu           3-Cl        H       H            OCF3
Me             3-F         H       H            OCF2CHF2
Et             3-Cl        H       H            SCF2CHF2
i-Pr           3-Cl        5-Cl    H            n-C3F7
t-Bu           3-Cl        H       H            i-C3F7
propargyl      3-Cl        H       H            Br
Et             3-Cl        H       H            Cl
i-Pr           3-Cl        H       H            SCF3
t-Bu           3-Cl        5-Br    Ph           CF3
cyclopropyl    3-Cl        H       Ph           Cl
Et             3-Cl        H       Ph           Br
i-Pr           3-Br        H       2-pyridyl    CF3
t-Bu           3-Cl        H       2-pyridyl    Cl
R3            R4a    R4b    Rva               Rvb
Me             3-Cl    H       2-ClPh             CF3
Et             3-Cl    5-Cl    2-ClPh             OCF3
i-Pr           3-Cl    H       2-ClPh             Br
t-Bu           3-I     H       2-ClPh             Cl
Me             3-Cl    5-Me    2-ClPh             SCHF2
propargyl      3-Cl    H       2-BrPh             CF3
i-Pr           3-Cl    H       2-MePh             CF3
t-Bu           3-Cl    5-CN    2-CNPh             CF3
Me             3-Cl    H       2-FPh              CF3
Et             3-Cl    H       2，6-F2Ph         CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph         CF3
t-Bu           3-F     H       2，6-F2Ph         CF3
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl     Br
propargyl      3-Cl    H       3-Cl-2-pyridyl     Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF3
Et             3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       H                  CF3
Et             6-Br    4-Me    H                  OCF3
i-Pr           6-Cl    H       H                  OCF3
t-Bu           6-Cl    Cl      Me                 Br
Me             6-Cl    H       Et                 Br
Et             6-Cl    H       Me                 Cl
i-Pr           6-F     4-Br    Et                 Cl
t-Bu           6-Cl    H       Me                 I
propargyl      6-Cl    H       Me                 CF3
cyclopropyl    6-Cl    H       Me                 OCF3
i-Pr           6-Cl    4-Cl    Me                 CF3
R3            R4a        R4b        Rva    Rvb
t-Bu           6-Cl        H           Me      SCF3
Me             6-Cl        H           Me      SCHF2
Et             6-Cl        H           Me      OCHF2
i-Pr           6-I         4-CN        Me      CF3
t-Bu           6-Cl        H           Me      C2F5
propargyl      6-Cl        H           Me      C2F5
cyclopropyl    6-Cl        H           Et      CF3
i-Pr           6-Cl        H           n-Pr    CF3
t-Bu           6-Cl        4-Br        i-Pr    CF3
Me             6-Cl        H           Cl      CF3
Et             6-F         H           F       CF3
i-Pr           6-Cl        H           Me      SMe
t-Bu           6-Cl        4-Cl        Me      OMe
Me             6-Cl        H           Me      OEt
Et             6-I         H           Me      n-C3F7
i-Pr           6-Cl        H           Me      i-C3F7
t-Bu           6-Cl        4-F         Me      Et
proPargyl      6-Cl        H           Me      OCF2CHF2
Et             6-Cl        H           Me      SCF2CHF2
i-Pr           6-Cl        H           Me      SO2Me
t-Bu           6-Cl        4-Cl        Me      SO2CF3
Me             6-Cl        H           CF3    CF3
Et             6-Cl        H           CF3    Me
i-Pr           6-Cl        H           OMe     CF3
t-Bu           6-Br        H           H       CF3
cyclopropyl    6-Cl        4-Br        H       OCHF2
Et             6-Cl        H           H       C2F5
i-Pr           6-Cl        H           H       C2F5
t-Bu           6-F         4-Me        H       OCF3
Me             6-Cl        H           H       OCF2CHF2
Et             6-Cl        H           H       SCF2CHF2
i-Pr           6-CN        4-Cl        H       n-C3F7
t-Bu           6-Cl        H           H       i-C3F7
propargyl      6-Cl        H           H       Br
Et             6-Cl        H           H       Cl
i-Pr           6-Cl        H           H       SCF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                     Table 8
Figure A0281824701291
R3            R4a      R4b      Rva      Rvb
Me             3-Me      H         H         CF3
Et             3-Me      5-Me      H         OCF3
i-Pr           3-Me      H         H         OCF3
t-Bu           3-Me      5-Cl      Me        Br
Me             3-Me      H         Et        Br
Et             3-Me      H         Me        Cl
i-Pr           3-Me      5-Br      Et        Cl
t-Bu           3-Me      H         Me        I
propargyl      3-Me      H         Me        CF3
cyclopropyl    3-Me      H         Me        OCF3
i-Pr           3-Me      5-Cl      Me        CF3
t-Bu           3-Me      H         Me        SCF3
Me             3-Me      5-CN      Me        SCHF2
Et             3-Me      H         Me        OCHF2
i-Pr           3-Me      H         Me        CF3
t-Bu           3-Me      H         Me        C2F5
propargyl      3-Me      H         Me        C2F5
cyclopropyl    3-Me      H         Et        CF3
i-Pr           3-Me      H         n-Pr      CF3
t-Bu           3-Me      5-Br      i-Pr      CF3
Me             3-Me      H         Cl        CF3
Et             3-Me      H         F         CF3
i-Pr           3-Me      H         Me        SMe
t-Bu           3-Me      5-Cl      Me        OMe
Me             3-Me      H         Me        OEt
Et             3-Me      H         Me        n-C3F7
R3            R4a    R4b    Rva         Rvb
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
Me             3-Me    H       2-ClPh       SCHF2
propargyl      3-Me    H       2-BrPh       CF3
i-Pr           3-Me    5-CN    2-MePh       CF3
t-Bu           3-Me    H       2-CNPh       CF3
Me             3-Me    H       2-FPh        CF3
Et             3-Me    H       2，6-F2Ph   CF3
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，6-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Cl                 CF3
R3            R4a    R4b    Rva         Rvb
Et             6-Me    H       F            CF3
i-Pr           6-Me    H       Me           SMe
t-Bu           6-Me    4-Cl    Me           OMe
Me             6-Me    H       Me           OEt
Et             6-Me    H       Me           n-C3F7
i-Pr           6-Me    H       Me           i-C3F7
t-Bu           6-Me    4-F     Me           Et
propargyl      6-Me    H       Me           OCF2CHF2
Et             6-Me    H       Me           SCF2CHF2
i-Pr           6-Me    H       Me           SO2Me
t-Bu           6-Me    4-Cl    Me           SO2CF3
Me             6-Me    H       CF3         CF3
Et             6-Me    H       CF3         Me
i-Pr           6-Me    H       OMe          CF3
t-Bu           6-Me    H       H            CF3
cyclopropyl    6-Me    4-Br    H            OCHF2
Et             6-Me    H       H            C2F5
i-Pr           6-Me    H       H            C2F5
t-Bu           6-Me    4-Me    H            OCF3
Me             6-Me    H       H            OCF2CHF2
Et             6-Me    H       H            SCF2CHF2
i-Pr           6-Me    4-Cl    H            n-C3F7
t-Bu           6-Me    H       H            i-C3F7
propargyl      6-Me    H       H            Br
Et             6-Me    H       H            Cl
i-Pr           6-Me    H       H            SCF3
t-Bu           6-Me    4-Br    Ph           Cl
cyclopropyl    6-Me    H       Ph           Cl
Et             6-Me    H       Ph           Br
i-Pr           6-Me    H       2-pyridyl    CF3
t-Bu           6-Me    H       2-pyridyl    Cl
Me             6-Me    H       2-ClPh       CF3
Et             6-Me    4-Cl    2-ClPh       OCF3
i-Pr           6-Me    H       2-ClPh       Br
t-Bu           6-Me    4-CN    2-ClPh       Cl
Me             6-Me    H       2-ClPh       SCHF2
R3            R4a    R4b    Rva               Rvb
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Br           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-Cl    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
t-Bu           3-Cl    H       Me                 C2F5
R3            R4a      R4b    Rva         Rvb
propargyl      3-Cl      H       Me           C2F5
cyclopropyl    3-Cl      H       Et           CF3
i-Pr           3-Cl      H       n-Pr         CF3
t-Bu           3-Cl      5-Br    i-Pr         CF3
Me             3-Cl      H       Cl           CF3
Et             3-Br      H       F            CF3
i-Pr           3-Cl      H       Me           SMe
t-Bu           3-Cl      5-Cl    Me           OMe
Me             3-Cl      H       Me           OEt
Et             3-Cl      H       Me           n-C3F7
i-Pr           3-Cl      H       Me           i-C3F7
t-Bu           3-Cl      5-F     Me           Et
propargyl      3-Cl      H       Me           OCF2CHF2
Et             3-Cl      H       Me           SCF2CHF2
i-Pr           3-Br      H       Me           SO2Me
i-Bu           3-Cl      5-Cl    Me           SO2CF3
Me             3-Cl      H       CF3         CF3
Et             3-CN      H       CF3         Me
i-Pr           3-Cl      H       OMe          CF3
t-Bu           3-Cl      H       H            CF3
cyclopropyl    3-Cl      5-Br    H            OCHF2
Et             3-Cl      H       H            C2F5
i-Pr           3-Cl      H       H            C2F5
t-Bu           3-Cl      H       H            OCF3
Me             3-F       H       H            OCF2CHF2
Et             3-Cl      H       H            SCF2CHF2
i-Pr           3-Cl      5-Cl    H            n-C3F7
t-Bu           3-Cl      H       H            i-C3F7
propargyl      3-Cl      H       H            Br
Et             3-Cl      H       H            Cl
i-Pr           3-Cl      H       H            SCF3
t-Bu           3-Cl      5-Br    Ph           CF3
cyclopropyl    3-Cl      H       Ph           Cl
Et             3-Cl      H       Ph           Br
i-Pr           3-Br      H       2-pyridyl    CF3
t-Bu           3-Cl      H       2-pyridyl    Cl
R3            R4a    R4b    Rva               Rvb
Me             3-Cl    H       2-ClPh             CF3
Et             3-Cl    5-Cl    2-ClPh             OCF3
i-Pr           3-Cl    H       2-ClPh             Br
t-Bu           3-I     H       2-ClPh             Cl
Me             3-Cl    5-Me    2-ClPh             SCHF2
propargyl      3-Cl    H       2-BrPh             CF3
i-Pr           3-Cl    H       2-MePh             CF3
t-Bu           3-Cl    5-CN    2-CNPh             CF3
Me             3-Cl    H       2-FPh              CF3
Et             3-Cl    H       2，6-F2Ph         CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph         CF3
t-Bu           3-F     H       2，6-F2Ph         CF3
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl     Br
propargyl      3-Cl    H       3-Cl-2-pyridyl     Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CF3
Me             3-Cl    H       3-Me-2-pyridyl    CF3
Et             3-Cl    H       3-Br-2-pyridyl    CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl    OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl    Br
i-Pr           3-Cl    H       3-Br-2-pyridyl    Cl
Me             6-Cl    H       H                 CF3
Et             6-Br    4-Me    H                 OCF3
i-Pr           6-Cl    H       H                 OCF3
t-Bu           6-Cl    Cl      Me                Br
Me             6-Cl    H       Et                Br
Et             6-Cl    H       Me                Cl
i-Pr           6-F     4-Br    Et                Cl
t-Bu           6-Cl    H       Me                I
propargyl      6-Cl    H       Me                CF3
cyclopropyl    6-Cl    H       Me                OCF3
i-Pr           6-Cl    4-Cl    Me                CF3
R3            R4a      R4b      Rva      Rvb
t-Bu           6-Cl      H         Me        SCF3
Me             6-Cl      H         Me        SCHF2
Et             6-Cl      H         Me        OCHF2
i-Pr           6-l       4-CN      Me        CF3
t-Bu           6-Cl      H         Me        C2F5
propargyl      6-Cl      H         Me        C2F5
cyclopropyl    6-Cl      H         Et        CF3
i-Pr           6-Cl      H         n-Pr      CF3
t-Bu           6-Cl      4-Br      i-Pr      CF3
Me             6-Cl      H         Cl        CF3
Et             6-F       H         F         CF3
i-Pr           6-Cl      H         Me        SMe
t-Bu           6-Cl      4-Cl      Me        OMe
Me             6-Cl      H         Me        OEt
Et             6-l       H         Me        n-C3F7
i-Pr           6-Cl      H         Me        i-C3F7
t-Bu           6-Cl      4-F       Me        Et
propargyl      6-Cl      H         Me        OCF2CHF2
Et             6-Cl      H         Me        SCF2CHF2
i-Pr           6-Cl      H         Me        SO2Me
t-Bu           6-Cl      4-Cl      Me        SO2CF3
Me             6-Cl      H         CF3      CF3
Et             6-Cl      H         CF3      Me
i-Pr           6-Cl      H         OMe       CF3
t-Bu           6-Br      H         H         CF3
cyclopropyl    6-Cl      4-Br      H         OCHF2
Et             6-Cl      H         H         C2F5
i-Pr           6-Cl      H         H         C2F5
t-Bu           6-F       4-Me      H         OCF3
Me             6-Cl      H         H         OCF2CHF2
Et             6-Cl      H         H         SCF2CHF2
i-Pr           6-CN      4-Cl      H         n-C3F7
t-Bu           6-Cl      H         H         i-C3F7
propargyl      6-Cl      H         H         Br
Et             6-Cl      H         H         Cl
i-Pr           6-Cl      H         H         SCF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                     Table 9
Figure A0281824701381
R3            R4a      R4b      Rva      Rvb
Me             3-Me      H         H         CF3
Et             3-Me      5-Me      H         OCF3
i-Pr           3-Me      H         H         OCF3
t-Bu           3-Me      5-Cl      Me        Br
Me             3-Me      H         Et        Br
Et             3-Me      H         Me        Cl
i-Pr           3-Me      5-Br      Et        Cl
t-Bu           3-Me      H         Me        I
propargyl      3-Me      H         Me        CF3
cyclopropyl    3-Me      H         Me        OCF3
i-Pr           3-Me      5-Cl      Me        CF3
t-Bu           3-Me      H         Me        SCF3
Me             3-Me      5-CN      Me        SCHF2
Et             3-Me      H         Me        OCHF2
i-Pr           3-Me      H         Me        CF3
t-Bu           3-Me      H         Me        C2F5
propargyl      3-Me      H         Me        C2F5
cyclopropyl    3-Me      H         Et        CF3
i-Pr           3-Me      H         n-Pr      CF3
t-Bu           3-Me      5-Br      i-Pr      CF3
Me             3-Me      H         Cl        CF3
Et             3-Me      H         F         CF3
i-Pr           3-Me      H         Me        SMe
t-Bu           3-Me      5-Cl      Me        OMe
Me             3-Me      H         Me        OEt
Et             3-Me      H         Me        n-C3F7
R3            R4a    R4b    Rva         Rvb
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
Me             3-Me    H       2-ClPh       SCHF2
propargyl      3-Me    H       2-BrPh       CF3
i-Pr           3-Me    5-CN    2-MePh       CF3
t-Bu           3-Me    H       2-CNPh       CF3
Me             3-Me    H       2-FPh        CF3
Et             3-Me    H       2，6-F2Ph   CF3
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，6-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Cl                 CF3
R3            R4a      R4b    Rva         Rvb
Et             6-Me      H       F            CF3
i-Pr           6-Me      H       Me           SMe
t-Bu           6-Me      4-Cl    Me           OMe
Me             6-Me      H       Me           OEt
Et             6-Me      H       Me           n-C3F7
i-Pr           6-Me      H       Me           i-C3F7
t-Bu           6-Me      4-F     Me           Et
propargyl      6-Me      H       Me           OCF2CHF2
Et             6-Me      H       Me           SCF2CHF2
i-Pr           6-Me      H       Me           SO2Me
t-Bu           6-Me      4-Cl    Me           SO2CF3
Me             6-Me      H       CF3         CF3
Et             6-Me      H       CF3         Me
i-Pr           6-Me      H       OMe          CF3
t-Bu           6-Me      H       H            CF3
cyclopropyl    6-Me      4-Br    H            OCHF2
Et             6-Me      H       H            C2F5
i-Pr           6-Me      H       H            C2F5
t-Bu           6-Me      4-Me    H            OCF3
Me             6-Me      H       H            OCF2CHF2
Et             6-Me      H       H            SCF2CHF2
i-Pr           6-Me      4-Cl    H            n-C3F7
t-Bu           6-Me      H       H            i-C3F7
propargyl      6-Me      H       H            Br
Et             6-Me      H       H            Cl
i-Pr           6-Me      H       H            SCF3
t-Bu           6-Me      4-Br    Ph           CF3
cyclopropyl    6-Me      H       Ph           Cl
Et             6-Me      H       Ph           Br
i-Pr           6-Me      H       2-pyridyl    CF3
t-Bu           6-Me      H       2-pyridyl    Cl
Me             6-Me      H       2-ClPh       CF3
Et             6-Me      4-Cl    2-ClPh       OCF3
i-Pr           6-Me      H       2-ClPh       Br
t-Bu           6-Me      4-CN    2-ClPh       Cl
Me             6-Me      H       2-ClPh       SCHF2
R3            R4a    R4b    Rva               Rvb
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-Cl    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
t-Bu           3-Cl    H       Me                 C2F5
R3            R4a        R4b    Rva         Rvb
propargyl      3-Cl        H       Me           C2F5
cyclopropyl    3-Cl        H       Et           CF3
i-Pr           3-Cl        H       n-Pr         CF3
t-Bu           3-Cl        5-Br    i-Pr         CF3
Me             3-Cl        H       Cl           CF3
Et             3-Br        H       F            CF3
i-Pr           3-Cl        H       Me           SMe
t-Bu           3-Cl        5-Cl    Me           OMe
Me             3-Cl        H       Me           OEt
Et             3-Cl        H       Me           n-C3F7
i-Pr           3-Cl        H       Me           i-C3F7
t-Bu           3-Cl        5-F     Me           Et
propargyl      3-Cl        H       Me           OCF2CHF2
Et             3-Cl        H       Me           SCF2CHF2
i-Pr           3-Br        H       Me           SO2Me
t-Bu           3-Cl        5-Cl    Me           SO2CF3
Me             3-Cl        H       CF3         CF3
Et             3-CN        H       CF3         Me
i-Pr           3-Cl        H       OMe          CF3
t-Bu           3-Cl        H       H            CF3
cyclopropyl    3-Cl        5-Br    H            OCHF2
Et             3-Cl        H       H            C2F5
i-Pr           3-Cl        H       H            C2F5
t-Bu           3-Cl        H       H            OCF3
Me             3-F         H       H            OCF2CHF2
Et             3-Cl        H       H            SCF2CHF2
i-Pr           3-Cl        5-Cl    H            n-C3F7
t-Bu           3-Cl        H       H            i-C3F7
propargyl      3-Cl        H       H            Br
Et             3-Cl        H       H            Cl
i-Pr           3-Cl        H       H            SCF3
t-Bu           3-Cl        5-Br    Ph           CF3
cyclopropyl    3-Cl        H       Ph           Cl
Et             3-Cl        H       Ph           Br
i-Pr           3-Br        H       2-pyridyl    CF3
t-Bu           3-Cl        H       2-pyridyl    Cl
R3            R4a    R4b    Rva              Rvb
Me             3-Cl    H       2-ClPh            CF3
Et             3-Cl    5-Cl    2-ClPh            OCF3
i-Pr           3-Cl    H       2-ClPh            Br
t-Bu           3-I     H       2-ClPh            Cl
Me             3-Cl    5-Me    2-ClPh            SCHF2
propargyl      3-Cl    H       2-BrPh            CF3
i-Pr           3-Cl    H       2-MePh            CF3
t-Bu           3-Cl    5-CN    2-CNPh            CF3
Me             3-Cl    H       2-FPh             CF3
Et             3-Cl    H       2，6-F2Ph        CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph        CF3
t-Bu           3-F     H       2，5-F2Ph        CF3
Me             3-Cl    5-I     2-MeOPh           CF3
Et             3-Cl    H       3-Cl-2-pyridyl    CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl    OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl    Br
propargyl      3-Cl    H       3-Cl-2-pyridyl    Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl    SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl     CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl  CF3
Me             3-Cl    H       3-Me-2-pyridyl    CF3
Et             3-Cl    H       3-Br-2-pyridyl    CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl    OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl    Br
i-Pr           3-Cl    H       3-Br-2-pyridyl    Cl
Me             6-Cl    H       H                 CF3
Et             6-Br    4-Me    H                 OCF3
i-Pr           6-Cl    H       H                 OCF3
t-Bu           6-Cl    Cl      Me                Br
Me             6-Cl    H       Et                Br
Et             6-Cl    H       Me                Cl
i-Pr           6-F     4-Br    Et                Cl
t-Bu           6-Cl    H       Me                I
propargyl      6-Cl    H       Me                CF3
cyclopropyl    6-Cl    H       Me                OCF3
i-Pr           6-Cl    4-Cl    Me                CF3
R3            R4a        R4b    Rva    Rvb
t-Bu           6-Cl        H       Me      SCF3
Me             6-Cl        H       Me      SCHF2
Et             6-Cl        H       Me      OCHF2
i-Pr           6-I         4-CN    Me      CF3
t-Bu           6-Cl        H       Me      C2F5
propargyl      6-Cl        H       Me      C2F5
cyclopropyl    6-Cl        H       Et      CF3
i-Pr           6-Cl        H       n-Pr    CF3
t-Bu           6-Cl        4-Br    i-Pr    CF3
Me             6-Cl        H       Cl      CF3
Et             6-F         H       F       CF3
i-Pr           6-Cl        H       Me      SMe
t-Bu           6-Cl        4-Cl    Me      OMe
Me             6-Cl        H       Me      OEt
Et             6-I         H       Me      n-C3F7
i-Pr           6-Cl        H       Me      i-C3F7
t-Bu           6-Cl        4-F     Me      Et
propargyl      6-Cl        H       Me      OCF2CHF2
Et             6-Cl        H       Me      SCF2CHF2
i-Pr           6-Cl        H       Me      SO2Me
t-Bu           6-Cl        4-Cl    Me      SO2CF3
Me             6-Cl        H       CF3    CF3
Et             6-Cl        H       CF3    Me
i-Pr           6-Cl        H       OMe     CF3
t-Bu           6-Br        H       H       CF3
cyclopropyl    6-Cl        4-Br    H       OCHF2
Et             6-Cl        H       H       C2F5
i-Pr           6-Cl        H       H       C2F5
t-Bu           6-F         4-Me    H       OCF3
Me             6-Cl        H       H       OCF2CHF2
Et             6-Cl        H       H       SCF2CHF2
i-Pr           6-CN        4-Cl    H       n-C3F7
t-Bu           6-Cl        H       H       i-C3F7
propargyl      6-Cl        H       H       Br
Et             6-Cl        H       H       Cl
i-Pr           6-Cl        H       H       SCF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl      SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                    Table 10
R3            R4a      R4b      R5a      R5b
Me             3-Me      H         H         CF3
Et             3-Me      5-Me      H         OCF3
i-Pr           3-Me      H         H         OCF3
t-Bu           3-Me      5-Cl      Me        Br
Me             3-Me      H         Et        Br
Et             3-Me      H         Me        Cl
i-Pr           3-Me      5-Br      Et        Cl
t-Bu           3-Me      H         Me        I
propargyl      3-Me      H         Me        CF3
cyclopropyl    3-Me      H         Me        OCF3
i-Pr           3-Me      5-Cl      Me        CF3
t-Bu           3-Me      H         Me        SCF3
Me             3-Me      5-CN      Me        SCHF2
Et             3-Me      H         Me        OCHF2
i-Pr           3-Me      H         Me        CF3
t-Bu           3-Me      H         Me        C2F5
propargyl      3-Me      H         Me        C2F5
cyclopropyl    3-Me      H         Et        CF3
i-Pr           3-Me      H         n-Pr      CF3
t-Bu           3-Me      5-Br      i-Pr      CF3
Me             3-Me      H         Cl        CF3
Et             3-Me      H         F         CF3
i-Pr           3-Me      H         Me        SMe
t-Bu           3-Me      5-Cl      Me        OMe
Me             3-Me      H         Me        OEt
Et             3-Me      H         Me        n-C3F7
R3            R4a    R4b    R5a        R5b
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
Me             3-Me    H       2-ClPh       SCHF2
propargyl      3-Me    H       2-BrPh       CF3
i-Pr           3-Me    5-CN    2-MePh       CF3
t-Bu           3-Me    H       2-CNPh       CF3
Me             3-Me    H       2-FPh        CF3
Et             3-Me    H       2，6-F2Ph   CF3
R3            R4a    R4b    R5a               R5b
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，5-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Cl                 CF3
R3            R4a    R4b    R5a        R5b
Et             6-Me    H       F            CF3
i-Pr           6-Me    H       Me           SMe
t-Bu           6-Me    4-Cl    Me           OMe
Me             6-Me    H       Me           OEt
Et             6-Me    H       Me           n-C3F7
i-Pr           6-Me    H       Me           i-C3F7
t-Bu           6-Me    4-F     Me           Et
propargyl      6-Me    H       Me           OCF2CHF2
Et             6-Me    H       Me           SCF2CHF2
i-Pr           6-Me    H       Me           SO2Me
t-Bu           6-Me    4-Cl    Me           SO2CF3
Me             6-Me    H       CF3         CF3
Et             6-Me    H       CF3         Me
i-Pr           6-Me    H       OMe          CF3
t-Bu           6-Me    H       H            CF3
cyclopropyl    6-Me    4-Br    H            OCHF2
Et             6-Me    H       H            C2F5
i-Pr           6-Me    H       H            C2F5
t-Bu           6-Me    4-Me    H            OCF3
Me             6-Me    H       H            OCF2CHF2
Et             6-Me    H       H            SCF2CHF2
i-Pr           6-Me    4-Cl    H            n-C3F7
t-Bu           6-Me    H       H            i-C3F7
propargyl      6-Me    H       H            Br
Et             6-Me    H       H            Cl
i-Pr           6-Me    H       H            SCF3
i-Bu           6-Me    4-Br    Ph           CF3
cyclopropyl    6-Me    H       Ph           Cl
Et             6-Me    H       Ph           Br
i-Pr           6-Me    H       2-pyridyl    CF3
t-Bu           6-Me    H       2-pyridyl    Cl
Me             6-Me    H       2-ClPh       CF3
Et             6-Me    4-Cl    2-ClPh       OCF3
i-Pr           6-Me    H       2-ClPh       Br
t-Bu           6-Me    4-CN    2-ClPh       Cl
Me             6-Me    H       2-ClPh       SCHF2
R3            R4a    R4b    R5a               R5b
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-Cl    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
t-Bu           3-Cl    H       Me                 C2F5
R3            R4a    R4b    R5a         R5b
propargyl      3-Cl    H       Me           C2F5
cyclopropyl    3-Cl    H       Et           CF3
i-Pr           3-Cl    H       n-Pr         CF3
t-Bu           3-Cl    5-Br    i-Pr         CF3
Me             3-Cl    H       Cl           CF3
Et             3-Br    H       F            CF3
i-Pr           3-Cl    H       Me           SMe
t-Bu           3-Cl    5-Cl    Me           OMe
Me             3-Cl    H       Me           OEt
Et             3-Cl    H       Me           n-C3F7
i-Pr           3-Cl    H       Me           i-C3F7
t-Bu           3-Cl    5-F     Me           Et
propargyl      3-Cl    H       Me           OCF2CHF2
Et             3-Cl    H       Me           SCF2CHF2
i-Pr           3-Br    H       Me           SO2Me
t-Bu           3-Cl    5-Cl    Me           SO2CF3
Me             3-Cl    H       CF3         CF3
Et             3-CN    H       CF3         Me
i-Pr           3-Cl    H       OMe          CF3
t-Bu           3-Cl    H       H            CF3
cycloPropyl    3-Cl    5-Br    H            OCHF2
Et             3-Cl    H       H            C2F5
i-Pr           3-Cl    H       H            C2F5
t-Bu           3-Cl    H       H            OCF3
Me             3-F     H       H            OCF2CHF2
Et             3-Cl    H       H            SCF2CHF2
i-Pr           3-Cl    5-Cl    H            n-C3F7
t-Bu           3-Cl    H       H            i-C3F7
propargyl      3-Cl    H       H            Br
Et             3-Cl    H       H            Cl
i-Pr           3-Cl    H       H            SCF3
t-Bu           3-Cl    5-Br    Ph           CF3
cyclopropyl    3-Cl    H       Ph           Cl
Et             3-Cl    H       Ph           Br
i-Pr           3-Br    H       2-pyridyl    CF3
t-Bu           3-Cl    H       2-pyridyl    Cl
R3            R4a    R4b    R5a               R5b
Me             3-Cl    H       2-ClPh             CF3
Et             3-Cl    5-Cl    2-ClPh             OCF3
i-Pr           3-Cl    H       2-ClPh             Br
t-Bu           3-I     H       2-ClPh             Cl
Me             3-Cl    5-Me    2-ClPh             SCHF2
propargyl      3-Cl    H       2-BrPh             CF3
i-Pr           3-Cl    H       2-MePh             CF3
t-Bu           3-Cl    5-CN    2-CNPh             CF3
Me             3-Cl    H       2-FPh              CF3
Et             3-Cl    H       2，6-F2Ph         CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph         CF3
t-Bu           3-F     H       2，5-F2Ph         CF3
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl     Br
propargyl      3-Cl    H       3-Cl-2-pyridyl     Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF3
Et             3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    5-Cl    3-Br-2-Pyridyl     OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       H                  CF3
Et             6-Br    4-Me    H                  OCF3
i-Pr           6-Cl    H       H                  OCF3
t-Bu           6-Cl    Cl      Me                 Br
Me             6-Cl    H       Et                 Br
Et             6-Cl    H       Me                 Cl
i-Pr           6-F     4-Br    Et                 Cl
t-Bu           6-Cl    H       Me                 I
propargyl      6-Cl    H       Me                 CF3
cyclopropyl    6-Cl    H       Me                 OCF3
i-Pr           6-Cl    4-Cl    Me                 CF3
R3            R4a      R4b      R5a      R5b
t-Bu           6-Cl      H         Me        SCF3
Me             6-Cl      H         Me        SCHF2
Et             6-Cl      H         Me        OCHF2
i-Pr           6-I       4-CN      Me        CF3
t-Bu           6-Cl      H         Me        C2F5
propargyl      6-Cl      H         Me        C2F5
cyclopropyl    6-Cl      H         Et        CF3
i-Pr           6-Cl      H         n-Pr      CF3
t-Bu           6-Cl      4-Br      i-Pr      CF3
Me             6-Cl      H         Cl        CF3
Et             6-F       H         F         CF3
i-Pr           6-Cl      H         Me        SMe
t-Bu           6-Cl      4-Cl      Me        OMe
Me             6-Cl      H         Me        OEt
Et             6-I       H         Me        n-C3F7
i-Pr           6-Cl      H         Me        i-C3F7
t-Bu           6-Cl      4-F       Me        Et
propargyl      6-Cl      H         Me        OCF2CHF2
Et             6-Cl      H         Me        SCF2CHF2
i-Pr           6-Cl      H         Me        SO2Me
t-Bu           6-Cl      4-Cl      Me        SO2CF3
Me             6-Cl      H         CF3      CF3
Et             6-Cl      H         CF3      Me
i-Pr           6-Cl      H         OMe       CF3
t-Bu           6-Br      H         H         CF3
cyclopropyl    6-Cl      4-Br      H         OCHF2
Et             6-Cl      H         H         C2F5
i-Pr           6-Cl      H         H         C2F5
t-Bu           6-F       4-Me      H         OCF3
Me             6-Cl      H         H         OCF2CHF2
Et             6-Cl      H         H         SCF2CHF2
i-Pr           6-CN      4-Cl      H         n-C3F7
t-Bu           6-Cl      H         H         i-C3F7
propargyl      6-Cl      H         H         Br
Et             6-Cl      H         H         Cl
i-Pr           6-Cl      H         H         SCF3
R3            R4a    R4b    R5a               R5b
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                     Table 11
R3            R4a      R4b      Rva      Rvb
Me             3-Me      H         H         CF3
Et             3-Me      5-Me      H         OCF3
i-Pr           3-Me      H         H         OCF3
t-Bu           3-Me      5-Cl      Me        Br
Me             3-Me      H         Et        Br
Et             3-Me      H         Me        Cl
i-Pr           3-Me      5-Br      Et        Cl
t-Bu           3-Me      H         Me        I
propargyl      3-Me      H         Me        CF3
cyclopropyl    3-Me      H         Me        OCF3
i-Pr           3-Me      5-Cl      Me        CF3
t-Bu           3-Me      H         Me        SCF3
Me             3-Me      5-CN      Me        SCHF2
Et             3-Me      H         Me        OCHF2
i-Pr           3-Me      H         Me        CF3
t-Bu           3-Me      H         Me        C2F5
propargyl      3-Me      H         Me        C2F5
cyclopropyl    3-Me      H         Et        CF3
i-Pr           3-Me      H         n-Pr      CF3
t-Bu           3-Me      5-Br      i-Pr      CF3
Me             3-Me      H         Cl        CF3
Et             3-Me      H         F         CF3
i-Pr           3-Me      H         Me        SMe
t-Bu           3-Me      5-Cl      Me        OMe
Me             3-Me      H         Me        OEt
Et             3-Me      H         Me        n-C3F7
R3            R4a    R4b    Rva         Rvb
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
Me             3-Me    H       2-ClPh       SCHF2
propargyl      3-Me    H       2-BrPh       CF3
i-Pr           3-Me    5-CN    2-MePh       CF3
t-Bu           3-Me    H       2-CNPh       CF3
Me             3-Me    H       2-FPh        CF3
Et             3-Me    H       2，6-F2Ph   CF3
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，5-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Cl                 CF3
R3            R4a    R4b    Rva         Rvb
Et             6-Me    H       F            CF3
i-Pr           6-Me    H       Me           SMe
t-Bu           6-Me    4-Cl    Me           OMe
Me             6-Me    H       Me           OEt
Et             6-Me    H       Me           n-C3F7
i-Pr           6-Me    H       Me           i-C3F7
t-Bu           6-Me    4-F     Me           Et
propargyl      6-Me    H       Me           OCF2CHF2
Et             6-Me    H       Me           SCF2CHF2
i-Pr           6-Me    H       Me           SO2Me
t-Bu           6-Me    4-Cl    Me           SO2CF3
Me             6-Me    H       CF3         CF3
Et             6-Me    H       CF3         Me
i-Pr           6-Me    H       OMe          CF3
t-Bu           6-Me    H       H            CF3
cyclopropyl    6-Me    4-Br    H            OCHF2
Et             6-Me    H       H            C2F5
i-Pr           6-Me    H       H            C2F5
t-Bu           6-Me    4-Me    H            OCF3
Me             6-Me    H       H            OCF2CHF2
Et             6-Me    H       H            SCF2CHF2
i-Pr           6-Me    4-Cl    H            n-C3F7
t-Bu           6-Me    H       H            i-C3F7
propargyl      6-Me    H       H            Br
Et             6-Me    H       H            Cl
i-Pr           6-Me    H       H            SCF3
t-Bu           6-Me    4-Br    Ph           CF3
cyclopropyl    6-Me    H       Ph           Cl
Et             6-Me    H       Ph           Br
i-Pr           6-Me    H       2-pyridyl    CF3
t-Bu           6-Me    H       2-pyridyl    Cl
Me             6-Me    H       2-ClPh       CF3
Et             6-Me    4-Cl    2-ClPh       OCF3
i-Pr           6-Me    H       2-ClPh       Br
t-Bu           6-Me    4-CN    2-ClPh       Cl
Me             6-Me    H       2-ClPh       SCHF2
R3            R4a    R4b    Rva               Rvb
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-Cl    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
t-Bu           3-Cl    H       Me                 C2F5
R3            R4a    R4b    Rva         Rvb
propargyl      3-Cl    H       Me           C2F5
cyclopropyl    3-Cl    H       Et           CF3
i-Pr           3-Cl    H       n-Pr         CF3
t-Bu           3-Cl    5-Br    i-Pr         CF3
Me             3-Cl    H       Cl           CF3
Et             3-Br    H       F            CF3
i-Pr           3-Cl    H       Me           SMe
t-Bu           3-Cl    5-Cl    Me           OMe
Me             3-Cl    H       Me           OEt
Et             3-Cl    H       Me           n-C3F7
i-Pr           3-Cl    H       Me           i-C3F7
t-Bu           3-Cl    5-F     Me           Et
propargyl      3-Cl    H       Me           OCF2CHF2
Et             3-Cl    H       Me           SCF2CHF2
i-Pr           3-Br    H       Me           SO2Me
t-Bu           3-Cl    5-Cl    Me           SO2CF3
Me             3-Cl    H       CF3         CF3
Et             3-CN    H       CF3         Me
i-Pr           3-Cl    H       OMe          CF3
t-Bu           3-Cl    H       H            CF3
cyclopropyl    3-Cl    5-Br    H            OCHF2
Et             3-Cl    H       H            C2F5
i-Pr           3-Cl    H       H            C2F5
t-Bu           3-Cl    H       H            OCF3
Me             3-F     H       H            OCF2CHF2
Et             3-Cl    H       H            SCF2CHF2
i-Pr           3-Cl    5-Cl    H            n-C3F7
t-Bu           3-Cl    H       H            i-C3F7
propargyl      3-Cl    H       H            Br
Et             3-Cl    H       H            Cl
i-Pr           3-Cl    H       H            SCF3
t-Bu           3-Cl    5-Br    Ph           CF3
cyclopropyl    3-Cl    H       Ph           Cl
Et             3-Cl    H       Ph           Br
i-Pr           3-Br    H       2-pyridyl    CF3
t-Bu           3-Cl    H       2-pyridyl    Cl
R3            R4a    R4b    Rva               Rvb
Me             3-Cl    H       2-ClPh             CF3
Et             3-Cl    5-Cl    2-ClPh             OCF3
i-Pr           3-Cl    H       2-ClPh             Br
t-Bu           3-I     H       2-ClPh             Cl
Me             3-Cl    5-Me    2-ClPh             SCHF2
propargyl      3-Cl    H       2-BrPh             CF3
i-Pr           3-Cl    H       2-MePh             CF3
t-Bu           3-Cl    5-CN    2-CNPh             CF3
Me             3-Cl    H       2-FPh              CF3
Et             3-Cl    H       2，6-F2Ph         CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph         CF3
t-Bu           3-F     H       2，6-F2Ph         CF3
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl     Br
propargyl      3-Cl    H       3-Cl-2-pyridyl     Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF3
Et             3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       H                  CF3
Et             6-Br    4-Me    H                  OCF3
i-Pr           6-Cl    H       H                  OCF3
t-Bu           6-Cl    Cl      Me                 Br
Me             6-Cl    H       Et                 Br
Et             6-Cl    H       Me                 Cl
i-Pr           6-F     4-Br    Et                 Cl
t-Bu           6-Cl    H       Me                 I
propargyl      6-Cl    H       Me                 CF3
cyclopropyl    6-Cl    H       Me                 OCF3
i-Pr           6-Cl    4-Cl    Me                 CF3
R3            R4a        R4b        Rva    Rvb
t-Bu           6-Cl        H           Me      SCF3
Me             6-Cl        H           Me      SCHF2
Et             6-Cl        H           Me      OCHF2
i-Pr           6-I         4-CN        Me      CF3
t-Bu           6-Cl        H           Me      C2F5
propargyl      6-Cl        H           Me      C2F5
cyclopropyl    6-Cl        H           Et      CF3
i-Pr           6-Cl        H           n-Pr    CF3
t-Bu           6-Cl        4-Br        i-Pr    CF3
Me             6-Cl        H           Cl      CF3
Et             6-F         H           F       CF3
i-Pr           6-Cl        H           Me      SMe
t-Bu           6-Cl        4-Cl        Me      OMe
Me             6-Cl        H           Me      OEt
Et             6-I         H           Me      n-C3F7
i-Pr           6-Cl        H           Me      i-C3F7
t-Bu           6-Cl        4-F         Me      Et
propargyl      6-Cl        H           Me      OCF2CHF2
Et             6-Cl        H           Me      SCF2CHF2
i-Pr           6-Cl        H           Me      SO2Me
t-Bu           6-Cl        4-Cl        Me      SO2CF3
Me             6-Cl        H           CF3    CF3
Et             6-Cl        H           CF3    Me
i-Pr           6-Cl        H           OMe     CF3
t-Bu           6-Br        H           H       CF3
cyclopropyl    6-Cl        4-Br        H       OCHF2
Et             6-Cl        H           H       C2F5
i-Pr           6-Cl        H           H       C2F5
t-Bu           6-F         4-Me        H       OCF3
Me             6-Cl        H           H       OCF2CHF2
Et             6-Cl        H           H       SCF2CHF2
i-Pr           6-CN        4-Cl        H       n-C3F7
t-Bu           6-Cl        H           H       i-C3F7
propargyl      6-Cl        H           H       Br
Et             6-Cl        H           H       Cl
i-Pr           6-Cl        H           H       SCF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                    Table 12
Figure A0281824701651
R3            R4a      R4b      R5a      R5b
Me             3-Me      H         H         CF3
Et             3-Me      5-Me      H         OCF3
i-Pr           3-Me      H         H         OCF3
t-Bu           3-Me      5-Cl      Me        Br
Me             3-Me      H         Et        Br
Et             3-Me      H         Me        Cl
i-Pr           3-Me      5-Br      Et        Cl
t-Bu           3-Me      H         Me        I
propargyl      3-Me      H         Me        CF3
cyclopropyl    3-Me      H         Me        OCF3
i-Pr           3-Me      5-Cl      Me        CF3
t-Bu           3-Me      H         Me        SCF3
Me             3-Me      5-CN      Me        SCHF2
Et             3-Me      H         Me        OCHF2
i-Pr           3-Me      H         Me        CF3
t-Bu           3-Me      H         Me        C2F5
propargyl      3-Me      H         Me        C2F5
cyclopropyl    3-Me      H         Et        CF3
i-Pr           3-Me      H         n-Pr      CF3
t-Bu           3-Me      5-Br      i-Pr      CF3
Me             3-Me      H         Cl        CF3
Et             3-Me      H         F         CF3
i-Pr           3-Me      H         Me        SMe
t-Bu           3-Me      5-Cl      Me        OMe
Me             3-Me      H         Me        OEt
Et             3-Me      H         Me        n-C3F7
R3            R4a    R4b    R5a         R5b
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Et
propargyl      3-Me    H       Me           OCF2CHF2
Et             3-Me    H       Me           SCF2CHF2
i-Pr           3-Me    H       Me           SO2Me
t-Bu           3-Me    5-Cl    Me           SO2CF3
Me             3-Me    H       CF3         CF3
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CF3
t-Bu           3-Me    H       H            CF3
cyclopropyl    3-Me    5-Br    H            OCHF2
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            OCF3
Me             3-Me    H       H            OCF2CHF2
Et             3-Me    H       H            SCF2CHF2
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       H            Br
Et             3-Me    H       H            Cl
i-Pr           3-Me    H       H            SCF3
t-Bu           3-Me    5-Br    Ph           CF3
cyclopropyl    3-Me    H       Ph           Cl
Et             3-Me    H       Ph           Br
i-Pr           3-Me    H       2-pyridyl    CF3
t-Bu           3-Me    H       2-pyridyl    Cl
Me             3-Me    H       2-ClPh       CF3
Et             3-Me    5-Cl    2-ClPh       OCF3
i-Pr           3-Me    H       2-ClPh       Br
t-Bu           3-Me    H       2-ClPh       Cl
Me             3-Me    H       2-ClPh       SCHF2
propargyl      3-Me    H       2-BrPh       CF3
i-Pr           3-Me    5-CN    2-MePh       CF3
t-Bu           3-Me    H       2-CNPh       CF3
Me             3-Me    H       2-FPh        CF3
Et             3-Me    H       2，6-F2Ph   CF3
R3            R4a    R4b    R5a               R5b
i-Pr           3-Me    5-Br    2，4-F2Ph         CF3
t-Bu           3-Me    H       2，6-F2Ph         CF3
Me             3-Me    5-I     2-MeOPh            CF3
Et             3-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     Br
propargyl      3-Me    H       3-Cl-2-pyridyl     Cl
Et             3-Me    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Me    H       3-F-2-pyridyl      CF3
t-Bu           3-Me    H       3-CF3-2-pyridyl   CF3
Me             3-Me    H       3-Me-2-pyridyl     CF3
Et             3-Me    H       3-Br-2-pyridyl     CF3
i-Pr           3-Me    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    H       3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Cl                 CF3
R3            R4a    R4b    R5a         R5b
Et             6-Me    H       F            CF3
i-Pr           6-Me    H       Me           SMe
t-Bu           6-Me    4-Cl    Me           OMe
Me             6-Me    H       Me           OEt
Et             6-Me    H       Me           n-C3F7
i-Pr           6-Me    H       Me           i-C3F7
t-Bu           6-Me    4-F     Me           Et
propargyl      6-Me    H       Me           OCF2CHF2
Et             6-Me    H       Me           SCF2CHF2
i-Pr           6-Me    H       Me           SO2Me
t-Bu           6-Me    4-Cl    Me           SO2CF3
Me             6-Me    H       CF3         CF3
Et             6-Me    H       CF3         Me
i-Pr           6-Me    H       OMe          CF3
t-Bu           6-Me    H       H            CF3
cyclopropyl    6-Me    4-Br    H            OCHF2
Et             6-Me    H       H            C2F5
i-Pr           6-Me    H       H            C2F5
t-Bu           6-Me    4-Me    H            OCF3
Me             6-Me    H       H            OCF2CHF2
Et             6-Me    H       H            SCF2CHF2
i-Pr           6-Me    4-Cl    H            n-C3F7
t-Bu           6-Me    H       H            i-C3F7
propargyl      6-Me    H       H            Br
Et             6-Me    H       H            Cl
i-Pr           6-Me    H       H            SCF3
t-Bu           6-Me    4-Br    Ph           CF3
cyclopropyl    6-Me    H       Ph           Cl
Et             6-Me    H       Ph           Br
i-Pr           6-Me    H       2-pyridyl    CF3
t-Bu           6-Me    H       2-pyridyl    Cl
Me             6-Me    H       2-ClPh       CF3
Et             6-Me    4-Cl    2-ClPh       OCF3
i-Pr           6-Me    H       2-ClPh       Br
t-Bu           6-Me    4-CN    2-ClPh       Cl
Me             6-Me    H       2-ClPh       SCHF2
R3            R4a    R4b    R5a               R5b
propargyl      6-Me    H       2-BrPh             CF3
i-Pr           6-Me    H       2-MePh             CF3
t-Bu           6-Me    H       2-CNPh             CF3
Me             6-Me    H       2-FPh              CF3
Et             6-Me    H       2，6-F2Ph         CF3
i-Pr           6-Me    4-Br    2，4-F2Ph         CF3
t-Bu           6-Me    H       2，6-F2Ph         CF3
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     Br
propargyl      6-Me    H       3-Cl-2-pyridyl     Cl
Et             6-Me    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CF3
Me             6-Me    H       3-Me-2-pyridyl     CF3
Et             6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Me    H       3-Br-2-pyridyl     Br
i-Pr           6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       H                  CF3
Et             3-Br    5-Me    H                  OCF3
i-Pr           3-Cl    H       H                  OCF3
t-Bu           3-Cl    5-Cl    Me                 Br
Me             3-Cl    H       Et                 Br
Et             3-Cl    H       Me                 Cl
i-Pr           3-Cl    5-Br    Et                 Cl
t-Bu           3-Cl    H       Me                 I
propargyl      3-Cl    H       Me                 CF3
cyclopropyl    3-Cl    H       Me                 OCF3
i-Pr           3-Cl    5-Cl    Me                 CF3
t-Bu           3-Cl    H       Me                 SCF3
Me             3-F     H       Me                 SCHF2
Et             3-Cl    H       Me                 OCHF2
i-Pr           3-Cl    5-CN    Me                 CF3
t-Bu           3-Cl    H       Me                 C2F5
R3            R4a    R4b    R5a         R5b
propargyl      3-Cl    H       Me           C2F5
cyclopropyl    3-Cl    H       Et           CF3
i-Pr           3-Cl    H       n-Pr         CF3
t-Bu           3-Cl    5-Br    i-Pr         CF3
Me             3-Cl    H       Cl           CF3
Et             3-Br    H       F            CF3
i-Pr           3-Cl    H       Me           SMe
t-Bu           3-Cl    5-Cl    Me           OMe
Me             3-Cl    H       Me           OEt
Et             3-Cl    H       Me           n-C3F7
i-Pr           3-Cl    H       Me           i-C3F7
t-Bu           3-Cl    5-F     Me           Et
propargyl      3-Cl    H       Me           OCF2CHF2
Et             3-Cl    H       Me           SCF2CHF2
i-Pr           3-Br    H       Me           SO2Me
t-Bu           3-Cl    5-Cl    Me           SO2CF3
Me             3-Cl    H       CF3         CF3
Et             3-CN    H       CF3         Me
i-Pr           3-Cl    H       OMe          CF3
t-Bu           3-Cl    H       H            CF3
cyclopropyl    3-Cl    5-Br    H            OCHF2
Et             3-Cl    H       H            C2F5
i-Pr           3-Cl    H       H            C2F5
t-Bu           3-Cl    H       H            OCF3
Me             3-F     H       H            OCF2CHF2
Et             3-Cl    H       H            SCF2CHF2
i-Pr           3-Cl    5-Cl    H            n-C3F7
t-Bu           3-Cl    H       H            i-C3F7
propargyl      3-Cl    H       H            Br
Et             3-Cl    H       H            Cl
i-Pr           3-Cl    H       H            SCF3
t-Bu           3-Cl    5-Br    Ph           CF3
cyclopropyl    3-Cl    H       Ph           Cl
Et             3-Cl    H       Ph           Br
i-Pr           3-Br    H       2-pyridyl    CF3
t-Bu           3-Cl    H       2-pyridyl    Cl
R3            R4a    R4b    R5a               R5b
Me             3-Cl    H       2-ClPh             CF3
Et             3-Cl    5-Cl    2-ClPh             OCF3
i-Pr           3-Cl    H       2-ClPh             Br
t-Bu           3-I     H       2-ClPh             Cl
Me             3-Cl    5-Me    2-ClPh             SCHF2
propargyl      3-Cl    H       2-BrPh             CF3
i-Pr           3-Cl    H       2-MePh             CF3
t-Bu           3-Cl    5-CN    2-CNPh             CF3
Me             3-Cl    H       2-FPh              CF3
Et             3-Cl    H       2，6-F2Ph         CF3
i-Pr           3-Cl    5-Br    2，4-F2Ph         CF3
t-Bu           3-F     H       2，6-F2Ph         CF3
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           3-CN    H       3-Cl-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Cl-2-pyridyl     Br
propargyl      3-Cl    H       3-Cl-2-pyridyl     Cl
Et             3-Cl    5-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF3
Et             3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl     OCF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       H                  CF3
Et             6-Br    4-Me    H                  OCF3
i-Pr           6-Cl    H       H                  OCF3
t-Bu           6-Cl    Cl      Me                 Br
Me             6-Cl    H       Et                 Br
Et             6-Cl    H       Me                 Cl
i-Pr           6-F     4-Br    Et                 Cl
t-Bu           6-Cl    H       Me                 I
propargyl      6-Cl    H       Me                 CF3
cyclopropyl    6-Cl    H       Me                 OCF3
i-Pr           6-Cl    4-Cl    Me                 CF3
R3            R4a        R4b        R5a    R5b
t-Bu           6-Cl        H           Me      SCF3
Me             6-Cl        H           Me      SCHF2
Et             6-Cl        H           Me      OCHF2
i-Pr           6-I         4-CN        Me      CF3
t-Bu           6-Cl        H           Me      C2F5
propargyl      6-Cl        H           Me      C2F5
cyclopropyl    6-Cl        H           Et      CF3
i-Pr           6-Cl        H           n-Pr    CF3
t-Bu           6-Cl        4-Br        i-Pr    CF3
Me             6-Cl        H           Cl      CF3
Et             6-F         H           F       CF3
i-Pr           6-Cl        H           Me      SMe
t-Bu           6-Cl        4-Cl        Me      OMe
Me             6-Cl        H           Me      OEt
Et             6-I         H           Me      n-C3F7
i-Pr           6-Cl        H           Me      i-C3F7
t-Bu           6-Cl        4-F         Me      Et
propargyl      6-Cl        H           Me      OCF2CHF2
Et             6-Cl        H           Me      SCF2CHF2
i-Pr           6-Cl        H           Me      SO2Me
t-Bu           6-Cl        4-Cl        Me      SO2CF3
Me             6-Cl        H           CF3    CF3
Et             6-Cl        H           CF3    Me
i-Pr           6-Cl        H           OMe     CF3
t-Bu           6-Br        H           H       CF3
cyclopropyl    6-Cl        4-Br        H       OCHF2
Et             6-Cl        H           H       C2F5
i-Pr           6-Cl        H           H       C2F5
t-Bu           6-F         4-Me        H       OCF3
Me             6-Cl        H           H       OCF2CHF2
Et             6-Cl        H           H       SCF2CHF2
i-Pr           6-CN        4-Cl        H       n-C3F7
t-Bu           6-Cl        H           H       i-C3F7
propargyl      6-Cl        H           H       Br
Et             6-Cl        H           H       Cl
i-Pr           6-Cl        H           H       SCF3
R3            R4a    R4b    R5a               R5b
t-Bu           6-Cl    4-Br    Ph                 CF3
cyclopropyl    6-Cl    H       Ph                 Cl
Et             6-F     H       Ph                 Br
i-Pr           6-Cl    H       2-pyridyl          CF3
t-Bu           6-Cl    H       2-pyridyl          Cl
Me             6-Cl    H       2-ClPh             CF3
Et             6-Br    4-Cl    2-ClPh             OCF3
i-Pr           6-Cl    H       2-ClPh             Br
t-Bu           6-Cl    H       2-ClPh             Cl
Me             6-Cl    H       2-ClPh             SCHF2
propargyl      6-Cl    H       2-BrPh             CF3
i-Pr           6-Br    H       2-MePh             CF3
t-Bu           6-Cl    4-CN    2-CNPh             CF3
Me             6-Cl    H       2-FPh              CF3
Et             6-Cl    H       2，6-F2Ph         CF3
i-Pr           6-Cl    4-Br    2，4-F2Ph         CF3
t-Bu           6-CN    H       2，6-F2Ph         CF3
Me             6-Cl    4-I     2-MeOPh            CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF3
i-Pr           6-Br    H       3-Cl-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Cl-2-pyridyl     Br
propargyl      6-Cl    H       3-Cl-2-pyridyl     Cl
Et             6-Cl    4-Br    3-Cl-2-pyridyl     SCHF2
i-Pr           6-Cl    H       3-F-2-pyridyl      CF3
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CF3
Me             6-Cl    H       3-Me-2-pyridyl     CF3
Et             6-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           6-Cl    4-Cl    3-Br-2-pyridyl     OCF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     Br
i-Pr           6-Cl    H       3-Br-2-pyridyl     Cl
                  Table 13
R3            R4a        R4b        Rva    Rvb
Me             3-Me        H           H       CF3
Et             3-Me        5-Me        H       OCF3
i-Pr           3-Me        H           H       OCF3
t-Bu           3-Me        5-Cl        Me      Br
Me             3-Me        H           Et      Br
Et             3-Me        H           Me      Cl
i-Pr           3-Me        5-Br        Et      Cl
t-Bu           3-Me        H           Me      I
propargyl      3-Me        H           Me      CF3
cyclopropyl    3-Me        H           Me      OCF3
i-Pr           3-Me        5-Cl        Me      CF3
t-Bu           3-Me        H           Me      SCF3
Me             3-Me        5-CN        Me      SCHF2
Et             3-Me        H           Me      OCHF2
i-Pr           3-Me        H           Me      CF3
t-Bu           3-Me        H           Me      C2F5
propargyl      3-Me        H           Me      C2F5
cyclopropyl    3-Me        H           Et      CF3
i-Pr           3-Me        H           n-Pr    CF3
t-Bu           3-Me        5-Br        i-Pr    CF3
Me             3-Me        H           i-Pr    OCF3
Et             3-Me        H           Me      SMe
i-Pr           3-Me        H           Me      OMe
t-Bu           3-Me        5-Cl        Me      OEt
Me             3-Me        H           Me      n-C3F7
Et             3-Me        H           Me      i-C3F7
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    H       Me                 Et
t-Bu           3-Me    5-F     Me                 OCF2CHF2
propargyl      3-Me    H       Me                 SCF2CHF2
Et             3-Me    H       Me                 SO2Me
i-Pr           3-Me    H       Me                 SO2CF3
t-Bu           3-Me    5-Cl    CHF2              CF3
Me             3-Me    H       CHF2              Me
Et             3-Me    H       Ph                 CF3
i-Pr           3-Me    H       Ph                 Cl
t-Bu           3-Me    H       Ph                 Br
cyclopropyl    3-Me    5-Br    2-pyridyl          CF3
Et             3-Me    H       2-pyridyl          Cl
i-Pr           3-Me    5-Me    2-ClPh             CF3
t-Bu           3-Me    H       2-ClPh             OCF3
Me             3-Me    H       2-ClPh             Br
Et             3-Me    H       2-ClPh             Cl
i-Pr           3-Me    5-Cl    2-ClPh             SCHF2
t-Bu           3-Me    H       2-BrPh             CF3
propargyl      3-Me    H       2-MePh             CF3
Et             3-Me    H       2-CNPh             CF3
i-Pr           3-Me    H       2-FPh              CF3
t-Bu           3-Me    5-Br    2，6-F2Ph         CF3
cyclopropyl    3-Me    H       2，4-F2Ph         CF3
Et             3-Me    H       2，5-F2Ph         CF3
i-Pr           3-Me    H       2-MeOPh            CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     CF3
Me             3-Me    H       3-Cl-2-pyridyl     OCF3
Et             3-Me    5-Cl    3-Cl-2-pyridyl     Br
i-Pr           3-Me    H       3-Cl-2-pyridyl     Cl
t-Bu           3-Me    H       3-Cl-2-pyridyl     SCHF2
Me             3-Me    H       3-F-2-pyridyl      CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF3
i-Pr           3-Me    5-CN    3-Me-2-pyridyl     CF3
t-Bu           3-Me    H       3-Br-2-pyridyl     CF3
Me             3-Me    H       3-Br-2-pyridyl     OCF3
Et             3-Me    H       3-Br-2-pyridyl     Br
R3            R4a    R4b    Rva              Rvb
i-Pr           3-Me    5-Br    3-Br-2-pyridyl    Cl
Me             6-Me    H       H                 CF3
Et             6-Me    4-Me    H                 OCF3
i-Pr           6-Me    H       H                 OCF3
t-Bu           6-Me    Cl      Me                Br
Me             6-Me    H       Et                Br
Et             6-Me    H       Me                Cl
i-Pr           6-Me    4-Br    Et                Cl
t-Bu           6-Me    H       Me                I
propargyl      6-Me    H       Me                CF3
cyclopropyl    6-Me    H       Me                OCF3
i-Pr           6-Me    4-Cl    Me                CF3
t-Bu           6-Me    H       Me                SCF3
Me             6-Me    H       Me                SCHF2
Et             6-Me    H       Me                OCHF2
i-Pr           6-Me    4-CN    Me                CF3
t-Bu           6-Me    H       Me                C2F5
propargyl      6-Me    H       Me                C2F5
cyclopropyl    6-Me    H       Et                CF3
i-Pr           6-Me    H       n-Pr              CF3
t-Bu           6-Me    4-Br    i-Pr              CF3
Me             6-Me    H       Me                SMe
Et             6-Me    H       Me                OMe
i-Pr           6-Me    H       Me                OEt
t-Bu           6-Me    4-Cl    Me                n-C3F7
Me             6-Me    H       Me                i-C3F7
Et             6-Me    H       Me                Et
i-Pr           6-Me    H       Me                OCF2CHF2
t-Bu           6-Me    4-F     Me                SCF2CHF2
propargyl      6-Me    H       Me                SO2Me
Et             6-Me    H       Me                SO2CF3
i-Pr           6-Me    H       CF3              CF3
t-Bu           6-Me    4-Cl    CF3              Me
Me             6-Me    H       Ph                Cf3
Et             6-Me    H       Ph                Cl
i-Pr           6-Me    H       Ph                Br
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Me    H       2-pyridyl          CF3
cyclopropyl    6-Me    4-Br    2-pyridyl          Cl
Et             6-Me    H       2-ClPh             CF3
i-Pr           6-Me    H       2-ClPh             OCF3
t-Bu           6-Me    4-Me    2-ClPh             Br
Me             6-Me    H       2-ClPh             Cl
Et             6-Me    H       2-ClPh             SCHF2
i-Pr           6-Me    4-Cl    2-BrPh             CF3
t-Bu           6-Me    H       2-Meph             CF3
propargyl      6-Me    H       2-CNPh             CF3
Et             6-Me    H       2-FPh              CF3
i-Pr           6-Me    H       2，6-F2Ph         CF3
t-Bu           6-Me    4-Br    2，4-F2Ph         CF3
cyclopropyl    6-Me    H       2，5-F2Ph         CF3
Et             6-Me    H       2-MeOPh            CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     CF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     OCF3
Me             6-Me    H       3-Cl-2-pyridyl     Br
Et             6-Me    4-Cl    3-Cl-2-pyridyl     Cl
i-Pr           6-Me    H       3-Cl-2-pyridyl     SCHF2
t-Bu           6-Me    4-CN    3-F-2-pyridyl      CF3
Me             6-Me    H       3-CF3-2-pyridyl   CF3
propargyl      6-Me    H       3-Me-2-pyridyl     CF3
i-Pr           6-Me    H       3-Br-2-pyridyl     CF3
t-Bu           6-Me    H       3-Br-2-pyridyl     OCF3
Me             6-Me    H       3-Br-2-pyridyl     Br
Et             6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       Me                 Br
Et             3-Br    5-Me    Et                 Br
i-Pr           3-Cl    H       Me                 Cl
t-Bu           3-Cl    5-Cl    Et                 Cl
Me             3-Cl    H       Me                 I
Et             3-Cl    H       Me                 CF3
i-Pr           3-Cl    5-Br    Me                 OCF3
t-Bu           3-Cl    H       Me                 CF3
R3            R4a        R4b    Rva         Rvb
propargyl      3-Cl        H       Me           SCF3
cyclopropyl    3-Cl        H       Me           SCHF2
i-Pr           3-Cl        5-Cl    Me           OCHF2
t-Bu           3-Cl        H       Me           CF3
Me             3-F         H       Me           C2F5
Et             3-Cl        H       Me           C2F5
i-Pr           3-Cl        5-CN    Et           CF3
t-Bu           3-Cl        H       n-Pr         CF3
propargyl      3-Cl        H       i-Pr         CF3
cyclopropyl    3-Cl        H       Me           SMe
i-Pr           3-Cl        H       Me           OMe
t-Bu           3-Cl        5-Br    Me           OEt
Me             3-Cl        H       Me           n-C3F7
Et             3-Br        H       Me           i-C3F7
i-Pr           3-Cl        H       Me           Et
t-Bu           3-Cl        5-Cl    Me           OCF2CHF2
Me             3-Cl        H       Me           SCF2CHF2
Et             3-Cl        H       Me           SO2Me
i-Pr           3-Cl        H       Me           SO2CF3
t-Bu           3-Cl        5-F     CF3         CF3
propargyl      3-Cl        H       CF3         Me
Et             3-Cl        H       Ph           CF3
i-Pr           3-Br        H       Ph           Cl
t-Bu           3-Cl        5-Cl    Ph           Br
Me             3-Cl        H       2-pyridyl    CF3
Et             3-CN        H       2-pyridyl    Cl
i-Pr           3-Cl        H       2-ClPh       CF3
t-Bu           3-Cl        H       2-ClPh       OCF3
cyclopropyl    3-Cl        5-Br    2-ClPh       Br
Et             3-Cl        H       2-ClPh       Cl
i-Pr           3-Cl        H       2-ClPh       OCF3
t-Bu           3-Cl        H       2-BrPh       CF3
Me             3-F         H       2-MePh       CF3
Et             3-Cl        H       2-CNPh       CF3
i-Pr           3-Cl        5-Cl    2-FPh        CF3
t-Bu           3-Cl        H       2，6-F2Ph   CF3
R3            R4a    R4b    Rva               Rvb
propargyl      3-Cl    H       2，4-F2Ph         CF3
Et             3-Cl    H       2，5-F2Ph         CF3
i-Pr           3-Cl    H       2-MeOPh            CF3
t-Bu           3-Cl    5-Br    3-Cl-2-pyridyl     CF3
cyclopropyl    3-Cl    H       3-Cl-2-pyridyl     OCF3
Et             3-Cl    H       3-Cl-2-pyridyl     Br
i-Pr           3-Br    H       3-Cl-2-pyridyl     Cl
t-Bu           3-Cl    H       3-Cl-2-pyridyl     SCHF2
Me             3-Cl    H       3-F-2-pyridyl      CF3
Et             3-Cl    5-Cl    3-CF3-2-pyridyl   CF3
i-Pr           3-Cl    H       3-Me-2-pyridyl     CF3
t-Bu           3-I     H       3-Br-2-pyridyl     CF3
Me             3-Cl    5-Me    3-Br-2-pyridyl     OCF3
propargyl      3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       Et                 Br
Et             6-Br    4-Me    Me                 Cl
i-Pr           6-Cl    H       Et                 Cl
t-Bu           6-Cl    Cl      Me                 I
Me             6-Cl    H       Me                 CF3
Et             6-Cl    H       Me                 OCF3
i-Pr           6-F     4-Br    Me                 CF3
t-Bu           6-Cl    H       Me                 SCF3
propargyl      6-Cl    H       Me                 SCHF2
cyclopropyl    6-Cl    H       Me                 OCHF2
i-Pr           6-Cl    4-Cl    Me                 CF3
t-Bu           6-Cl    H       Me                 C2F5
Me             6-Cl    H       Me                 C2F5
Et             6-Cl    H       Et                 CF3
i-Pr           6-l     4-CN    n-Pr               CF3
t-Bu           6-Cl    H       i-Pr               CF3
propargyl      6-Cl    H       Me                 SMe
cyclopropyl    6-Cl    H       Me                 OMe
i-Pr           6-Cl    H       Me                 OEt
t-Bu           6-Cl    4-Br    Me                 n-C3F7
Me             6-Cl    H       Me                 i-C3F7
R3            R4a    R4b    Rva               Rvb
Et             6-F     H       Me                 Et
i-Pr           6-Cl    H       Me                 OCF2CHF2
t-Bu           6-Cl    4-Cl    Me                 SCF2CHF2
Me             6-Cl    H       Me                 SO2Me
Et             6-I     H       Me                 SO2CF3
i-Pr           6-Cl    H       CF3               CF3
t-Bu           6-Cl    4-F     CF3               Me
propargyl      6-Cl    H       Ph                 CF3
Et             6-Cl    H       Ph                 Cl
i-Pr           6-Cl    H       Ph                 Br
t-Bu           6-Cl    4-Cl    2-pyridyl          CF3
Me             6-Cl    H       2-pyridyl          Cl
Et             6-Cl    H       2-ClPh             CF3
i-Pr           6-Cl    H       2-ClPh             OCF3
t-Bu           6-Br    H       2-ClPh             Br
cyclopropyl    6-Cl    4-Br    2-ClPh             Cl
Et             6-Cl    H       2-ClPh             SCHF2
i-Pr           6-Cl    H       2-BrPh             CF3
t-Bu           6-F     4-Me    2-MePh             CF3
Me             6-Cl    H       2-CNPh             CF3
Et             6-Cl    H       2-FPh              CF3
i-Pr           6-CN    4-Cl    2，6-F2Ph         CF3
t-Bu           6-Cl    H       2，4-F2Ph         CF3
propargyl      6-Cl    H       2，5-F2Ph         CF3
Et             6-Cl    H       2-MeOPh            CF3
i-Pr           6-Cl    H       3-Cl-2-pyridyl     CF3
t-Bu           6-Cl    4-Br    3-Cl-2-pyridyl     OCF3
cyclopropyl    6-Cl    H       3-Cl-2-pyridyl     Br
Et             6-F     H       3-Cl-2-pyridyl     Cl
i-Pr           6-Cl    H       3-Cl-2-pyridyl     SCHF2
t-Bu           6-Cl    H       3-F-2-pyridyl      CF3
Me             6-Cl    H       3-CF3-2-pyridyl   CF3
Et             6-Br    4-Cl    3-Me-2-pyridyl     CF3
i-Pr           6-Cl    H       3-Br-2-pyridyl     CF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     OCF3
Me             6-Cl    H       3-Br-2-pyridyl     Br
R3            R4a    R4b    Rva              Rvb
propargyl      6-Cl    H       3-Br-2-pyridyl    Cl
                       Table 14
Figure A0281824701811
R3            R4a    R4b    Rva              Rvb
Me             3-Me    H       H                 CF3
Et             3-Me    5-Me    H                 OCF3
i-Pr           3-Me    H       H                 OCF3
t-Bu           3-Me    5-Cl    Me                Br
Me             3-Me    H       Et                Br
Et             3-Me    H       Me                Cl
i-Pr           3-Me    5-Br    Et                Cl
t-Bu           3-Me    H       Me                I
propargyl      3-Me    H       Me                CF3
cyclopropyl    3-Me    H       Me                OCF3
i-Pr           3-Me    5-Cl    Me                CF3
t-Bu           3-Me    H       Me                SCF3
Me             3-Me    5-CN    Me                SCHF2
Et             3-Me    H       Me                OCHF2
i-Pr           3-Me    H       Me                CF3
t-Bu           3-Me    H       Me                C2F5
propargyl      3-Me    H       Me                C2F5
cyclopropyl    3-Me    H       Et                CF3
i-Pr           3-Me    H       n-Pr              CF3
t-Bu           3-Me    5-Br    i-Pr              CF3
Me             3-Me    H       i-Pr              OCF3
Et             3-Me    H       Me                SMe
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    H       Me                 OMe
t-Bu           3-Me    5-Cl    Me                 OEt
Me             3-Me    H       Me                 n-C3F7
Et             3-Me    H       Me                 i-C3F7
i-Pr           3-Me    H       Me                 Et
t-Bu           3-Me    5-F     Me                 OCF2CHF2
propargyl      3-Me    H       Me                 SCF2CHF2
Et             3-Me    H       Me                 SO2Me
i-Pr           3-Me    H       Me                 SO2CF3
t-Bu           3-Me    5-Cl    CHF2              CF3
Me             3-Me    H       CHF2              Me
Et             3-Me    H       Ph                 CF3
i-Pr           3-Me    H       Ph                 Cl
t-Bu           3-Me    H       Ph                 Br
cyclopropyl    3-Me    5-Br    2-pyridyl          CF3
Et             3-Me    H       2-pyridyl          Cl
i-Pr           3-Me    5-Me    2-ClPh             CF3
t-Bu           3-Me    H       2-ClPh             OCF3
Me             3-Me    H       2-ClPh             Br
Et             3-Me    H       2-ClPh             Cl
i-Pr           3-Me    5-Cl    2-ClPh             SCHF2
t-Bu           3-Me    H       2-BrPh             CF3
propargyl      3-Me    H       2-MePh             CF3
Et             3-Me    H       2-CNPh             CF3
i-Pr           3-Me    H       2-FPh              CF3
t-Bu           3-Me    5-Br    2，6-F2Ph         CF3
cyclopropyl    3-Me    H       2，4-F2Ph         CF3
Et             3-Me    H       2，5-F2Ph         CF3
i-Pr           3-Me    H       2-MeOPh            CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     CF3
Me             3-Me    H       3-Cl-2-pyridyl     OCF3
Et             3-Me    5-Cl    3-Cl-2-pyridyl     Br
i-Pr           3-Me    H       3-Cl-2-pyridyl     Cl
t-Bu           3-Me    H       3-Cl-2-pyridyl     SCHF2
Me             3-Me    H       3-F-2-pyridyl      CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF3
R3            R4a    R4b    Rva              Rvb
i-Pr           3-Me    5-CN    3-Me-2-pyridyl    CF3
t-Bu           3-Me    H       3-Br-2-pyridyl    CF3
Me             3-Me    H       3-Br-2-pyridyl    OCF3
Et             3-Me    H       3-Br-2-pyridyl    Br
i-Pr           3-Me    5-Br    3-Br-2-pyridyl    Cl
Me             6-Me    H       H                 CF3
Et             6-Me    4-Me    H                 OCF3
i-Pr           6-Me    H       H                 OCF3
t-Bu           6-Me    Cl      Me                Br
Me             6-Me    H       Et                Br
Et             6-Me    H       Me                Cl
i-Pr           6-Me    4-Br    Et                Cl
t-Bu           6-Me    H       Me                I
propargyl      6-Me    H       Me                CF3
cyclopropyl    6-Me    H       Me                OCF3
i-Pr           6-Me    4-Cl    Me                CF3
t-Bu           6-Me    H       Me                SCF3
Me             6-Me    H       Me                SCHF2
Et             6-Me    H       Me                OCHF2
i-Pr           6-Me    4-CN    Me                CF3
t-Bu           6-Me    H       Me                C2F5
propargyl      6-Me    H       Me                C2F5
cyclopropyl    6-Me    H       Et                CF3
i-Pr           6-Me    H       n-Pr              CF3
t-Bu           6-Me    4-Br    i-Pr              CF3
Me             6-Me    H       Me                SMe
Et             6-Me    H       Me                OMe
i-Pr           6-Me    H       Me                OEt
t-Bu           6-Me    4-Cl    Me                n-C3F7
Me             6-Me    H       Me                i-C3F7
Et             6-Me    H       Me                Et
i-Pr           6-Me    H       Me                OCF2CHF2
t-Bu           6-Me    4-F     Me                SCF2CHF2
propargyl      6-Me    H       Me                SO2Me
Et             6-Me    H       Me                SO2CF3
i-Pr           6-Me    H       CF3              CF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Me    4-Cl    CF3               Me
Me             6-Me    H       Ph                 CF3
Et             6-Me    H       Ph                 Cl
i-Pr           6-Me    H       Ph                 Br
t-Bu           6-Me    H       2-pyridyl          CF3
cyclopropyl    6-Me    4-Br    2-pyridyl          Cl
Et             6-Me    H       2-ClPh             CF3
i-Pr           6-Me    H       2-ClPh             OCF3
t-Bu           6-Me    4-Me    2-ClPh             Br
Me             6-Me    H       2-ClPh             Cl
Et             6-Me    H       2-ClPh             SCHF2
i-Pr           6-Me    4-Cl    2-BrPh             CF3
t-Bu           6-Me    H       2-MePh             CF3
propargyl      6-Me    H       2-CNPh             CF3
Et             6-Me    H       2-FPh              CF3
i-Pr           6-Me    H       2，6-F2Ph         CF3
t-Bu           6-Me    4-Br    2，4-F2Ph         CF3
cyclopropyl    6-Me    H       2，5-F2Ph         CF3
Et             6-Me    H       2-MeOPh            CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     CF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     OCF3
Me             6-Me    H       3-Cl-2-pyridyl     Br
Et             6-Me    4-Cl    3-Cl-2-pyridyl     Cl
i-Pr           6-Me    H       3-Cl-2-pyridyl     SCHF2
t-Bu           6-Me    4-CN    3-F-2-pyridyl      CF3
Me             6-Me    H       3-CF3-2-pyridyl   CF3
propargyl      6-Me    H       3-Me-2-pyridyl     CF3
i-Pr           6-Me    H       3-Br-2-pyridyl     CF3
t-Bu           6-Me    H       3-Br-2-pyridyl     OCF3
Me             6-Me    H       3-Br-2-pyridyl     Br
Et             6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       Me                 Br
Et             3-Br    5-Me    Et                 Br
i-Pr           3-Cl    H       Me                 Cl
t-Bu           3-Cl    5-Cl    Et                 Cl
Me             3-Cl    H       Me                 I
R3            R4a        R4b    Rva         Rvb
Et             3-Cl        H       Me           CF3
i-Pr           3-Cl        5-Br    Me           OCF3
t-Bu           3-Cl        H       Me           CF3
propargyl      3-Cl        H       Me           SCF3
cyclopropyl    3-Cl        H       Me           SCHF2
i-Pr           3-Cl        5-Cl    Me           OCHF2
t-Bu           3-Cl        H       Me           CF3
Me             3-F         H       Me           C2F5
Et             3-Cl        H       Me           C2F5
i-Pr           3-Cl        5-CN    Et           CF3
t-Bu           3-Cl        H       n-Pr         CF3
propargyl      3-Cl        H       i-Pr         CF3
cyclopropyl    3-Cl        H       Me           SMe
i-Pr           3-Cl        H       Me           OMe
t-Bu           3-Cl        5-Br    Me           OEt
Me             3-Cl        H       Me           n-C3F7
Et             3-Br        H       Me           i-C3F7
i-Pr           3-Cl        H       Me           Et
t-Bu           3-Cl        5-Cl    Me           OCF2CHF2
Me             3-Cl        H       Me           SCF2CHF2
Et             3-Cl        H       Me           SO2Me
i-Pr           3-Cl        H       Me           SO2CF3
t-Bu           3-Cl        5-F     CF3         CF3
propargyl      3-Cl        H       CF3         Me
Et             3-Cl        H       Ph           CF3
i-Pr           3-Br        H       Ph           Cl
t-Bu           3-Cl        5-Cl    Ph           Br
Me             3-Cl        H       2-pyridyl    CF3
Et             3-CN        H       2-pyridyl    Cl
i-Pr           3-Cl        H       2-ClPh       CF3
t-Bu           3-Cl        H       2-ClPh       OCF3
cyclopropyl    3-Cl        5-Br    2-ClPh       Br
Et             3-Cl        H       2-ClPh       Cl
i-Pr           3-Cl        H       2-ClPh       OCF3
t-Bu           3-Cl        H       2-BrPh       CF3
Me             3-F         H       2-MePh       CF3
R3            R4a    R4b    Rva               Rvb
Et             3-Cl    H       2-CNPh             CF3
i-Pr           3-Cl    5-Cl    2-FPh              CF3
t-Bu           3-Cl    H       2，6-F2Ph         CF3
propargyl      3-Cl    H       2，4-F2Ph         CF3
Et             3-Cl    H       2，5-F2Ph         CF3
i-Pr           3-Cl    H       2-MeOPh            CF3
t-Bu           3-Cl    5-Br    3-Cl-2-pyridyl     CF3
cyclopropyl    3-Cl    H       3-Cl-2-pyridyl     OCF3
Et             3-Cl    H       3-Cl-2-pyridyl     Br
i-Pr           3-Br    H       3-Cl-2-pyridyl     Cl
t-Bu           3-Cl    H       3-Cl-2-pyridyl     SCHF2
Me             3-Cl    H       3-F-2-pyridyl      CF3
Et             3-Cl    5-Cl    3-CF3-2-pyridyl   CF3
i-Pr           3-Cl    H       3-Me-2-pyridyl     CF3
t-Bu           3-I     H       3-Br-2-pyridyl     CF3
Me             3-Cl    5-Me    3-Br-2-pyridyl     OCF3
propargyl      3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       Et                 Br
Et             6-Br    4-Me    Me                 Cl
i-Pr           6-Cl    H       Et                 Cl
t-Bu           6-Cl    Cl      Me                 I
Me             6-Cl    H       Me                 CF3
Et             6-Cl    H       Me                 OCF3
i-Pr           6-F     4-Br    Me                 CF3
t-Bu           6-Cl    H       Me                 SCF3
propargyl      6-Cl    H       Me                 SCHF2
cyclopropyl    6-Cl    H       Me                 OCHF2
i-Pr           6-Cl    4-Cl    Me                 CF3
t-Bu           6-Cl    H       Me                 C2F5
Me             6-Cl    H       Me                 C2F5
Et             6-Cl    H       Et                 CF3
i-Pr           6-I     4-CN    n-Pr               CF3
t-Bu           6-Cl    H       i-Pr               CF3
propargyl      6-Cl    H       Me                 SMe
cyclopropyl    6-Cl    H       Me                 OMe
R3            R4a    R4b    Rva               Rvb
i-Pr           6-Cl    H       Me                 OEt
t-Bu           6-Cl    4-Br    Me                 n-C3F7
Me             6-Cl    H       Me                 i-C3F7
Et             6-F     H       Me                 Et
i-Pr           6-Cl    H       Me                 OCF2CHF2
t-Bu           6-Cl    4-Cl    Me                 SCF2CHF2
Me             6-Cl    H       Me                 SO2Me
Et             6-I     H       Me                 SO2CF3
i-Pr           6-Cl    H       CF3               CF3
t-Bu           6-Cl    4-F     CF3               Me
propargyl      6-Cl    H       Ph                 CF3
Et             6-Cl    H       Ph                 Cl
i-Pr           6-Cl    H       Ph                 Br
t-Bu           6-Cl    4-Cl    2-pyridyl          CF3
Me             6-Cl    H       2-pyridyl          Cl
Et             6-Cl    H       2-ClPh             CF3
i-Pr           6-Cl    H       2-ClPh             OCF3
t-Bu           6-Br    H       2-ClPh             Br
cyclopropyl    6-Cl    4-Br    2-ClPh             Cl
Et             6-Cl    H       2-ClPh             SCHF2
i-Pr           6-Cl    H       2-BrPh             CF3
t-Bu           6-F     4-Me    2-MePh             CF3
Me             6-Cl    H       2-CNPh             CF3
Et             6-Cl    H       2-FPh              CF3
i-Pr           6-CN    4-Cl    2，6-F2Ph         CF3
t-Bu           6-Cl    H       2，4-F2Ph         CF3
propargyl      6-Cl    H       2，5-F2Ph         CF3
Et             6-Cl    H       2-MeOPh            CF3
i-Pr           6-Cl    H       3-Cl-2-pyridyl     CF3
t-Bu           6-Cl    4-Br    3-Cl-2-pyridyl     OCF3
cyclopropyl    6-Cl    H       3-Cl-2-pyridyl     Br
Et             6-F     H       3-Cl-2-pyridyl     Cl
i-Pr           6-Cl    H       3-Cl-2-pyridyl     SCHF2
t-Bu           6-Cl    H       3-F-2-pyridyl      CF3
Me             6-Cl    H       3-CF3-2-pyridyl   CF3
Et             6-Br    4-Cl    3-Me-2-pyridyl     CF3
R3            R4a    R4b    Rva              Rvb
i-Pr           6-Cl    H       3-Br-2-pyridyl    CF3
t-Bu           6-Cl    H       3-Br-2-pyridyl    OCF3
Me             6-Cl    H       3-Br-2-pyridyl    Br
propargyl      6-Cl    H       3-Br-2-pyridyl    Cl
                         Table 15
R3            R4a    R4b    Rva              Rvb
Me             3-Me    H       H                 CF3
Et             3-Me    5-Me    H                 OCF3
i-Pr           3-Me    H       H                 OCF3
t-Bu           3-Me    5-Cl    Me                Br
Me             3-Me    H       Et                Br
Et             3-Me    H       Me                Cl
i-Pr           3-Me    5-Br    Et                Cl
t-Bu           3-Me    H       Me                I
propargyl      3-Me    H       Me                CF3
cyclopropyl    3-Me    H       Me                OCF3
i-Pr           3-Me    5-Cl    Me                CF3
t-Bu           3-Me    H       Me                SCF3
Me             3-Me    5-CN    Me                SCHF2
Et             3-Me    H       Me                OCHF2
i-Pr           3-Me    H       Me                CF3
t-Bu           3-Me    H       Me                C2F5
propargyl      3-Me    H       Me                C2F5
cyclopropyl    3-Me    H       Et                CF3
i-Pr           3-Me    H       n-Pr              CF3
R3           R4a    R4b    Rva              Rvb
t-Bu           3-Me    5-Br    i-Pr              CF3
Me             3-Me    H       i-Pr              OCF3
Et             3-Me    H       Me                SMe
i-Pr           3-Me    H       Me                OMe
t-Bu           3-Me    5-Cl    Me                OEt
Me             3-Me    H       Me                n-C3F7
Et             3-Me    H       Me                i-C3F7
i-Pr           3-Me    H       Me                Et
t-Bu           3-Me    5-F     Me                OCF2CHF2
propargyl      3-Me    H       Me                SCF2CHF2
Et             3-Me    H       Me                SO2Me
i-Pr           3-Me    H       Me                SO2CF3
t-Bu           3-Me    5-Cl    CHF2             CF3
Me             3-Me    H       CHF2             Me
Et             3-Me    H       Ph                CF3
i-Pr           3-Me    H       Ph                Cl
t-Bu           3-Me    H       Ph                Br
cyclopropyl    3-Me    5-Br    2-pyridyl         CF3
Et             3-Me    H       2-pyridyl         Cl
i-Pr           3-Me    5-Me    2-ClPh            CF3
t-Bu           3-Me    H       2-ClPh            OCF3
Me             3-Me    H       2-ClPh            Br
Et             3-Me    H       2-ClPh            Cl
i-Pr           3-Me    5-Cl    2-ClPh            SCHF2
t-Bu           3-Me    H       2-BrPh            CF3
propargyl      3-Me    H       2-MePh            CF3
Et             3-Me    H       2-CNPh            CF3
i-Pr           3-Me    H       2-FPh             CF3
t-Bu           3-Me    5-Br    2，6-F2Ph        CF3
cyclopropyl    3-Me    H       2，4-F2Ph        CF3
Et             3-Me    H       2，5-F2Ph        CF3
i-Pr           3-Me    H       2-MeOPh           CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl    CF3
Me             3-Me    H       3-Cl-2-pyridyl    OCF3
Et             3-Me    5-Cl    3-Cl-2-pyridyl    Br
i-Pr           3-Me    H       3-Cl-2-pyridyl    Cl
R3            R4a    R4b    Rva               Rvb
t-Bu           3-Me    H       3-Cl-2-pyridyl     SCHF2
Me             3-Me    H       3-F-2-pyridyl      CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF3
i-Pr           3-Me    5-CN    3-Me-2-pyridyl     CF3
t-Bu           3-Me    H       3-Br-2-pyridyl     CF3
Me             3-Me    H       3-Br-2-pyridyl     OCF3
Et             3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    5-Br    3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Me                 SMe
Et             6-Me    H       Me                 OMe
i-Pr           6-Me    H       Me                 OEt
t-Bu           6-Me    4-Cl    Me                 n-C3F7
Me             6-Me    H       Me                 i-C3F7
Et             6-Me    H       Me                 Et
i-Pr           6-Me    H       Me                 OCF2CHF2
t-Bu           6-Me    4-F     Me                 SCF2CHF2
R3            R4a    R4b    Rva               Rvb
propargyl      6-Me    H       Me                 SO2Me
Et             6-Me    H       Me                 SO2CF3
i-Pr           6-Me    H       CF3               CF3
t-Bu           6-Me    4-Cl    CF3               Me
Me             6-Me    H       Ph                 CF3
Et             6-Me    H       Ph                 Cl
i-Pr           6-Me    H       Ph                 Br
t-Bu           6-Me    H       2-pyridyl          CF3
cyclopropyl    6-Me    4-Br    2-pyridyl          Cl
Et             6-Me    H       2-ClPh             CF3
i-Pr           6-Me    H       2-ClPh             OCF3
t-Bu           6-Me    4-Me    2-ClPh             Br
Me             6-Me    H       2-ClPh             Cl
Et             6-Me    H       2-ClPh             SCHF2
i-Pr           6-Me    4-Cl    2-BrPh             CF3
t-Bu           6-Me    H       2-MePh             CF3
propargyl      6-Me    H       2-CNPh             CF3
Et             6-Me    H       2-FPh              CF3
i-Pr           6-Me    H       2，6-F2Ph         CF3
t-Bu           6-Me    4-Br    2，4-F2Ph         CF3
cyclopropyl    6-Me    H       2，5-F2Ph         CF3
Et             6-Me    H       2-MeOPh            CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     CF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     OCF3
Me             6-Me    H       3-Cl-2-pyridyl     Br
Et             6-Me    4-Cl    3-Cl-2-pyridyl     Cl
i-Pr           6-Me    H       3-Cl-2-pyridyl     SCHF2
t-Bu           6-Me    4-CN    3-F-2-pyridyl      CF3
Me             6-Me    H       3-CF3-2-pyridyl   CF3
propargyl      6-Me    H       3-Me-2-pyridyl     CF3
i-Pr           6-Me    H       3-Br-2-pyridyl     CF3
t-Bu           6-Me    H       3-Br-2-pyridyl     OCF3
Me             6-Me    H       3-Br-2-pyridyl     Br
Et             6-Me    H       3-Br-2-pyridyl     Cl
Me             3-Cl    H       Me                 Br
Et             3-Br    5-Me    Et                 Br
R3            R4a    R4b    Rva         Rvb
i-Pr           3-Cl    H       Me           Cl
t-Bu           3-Cl    5-Cl    Et           Cl
Me             3-Cl    H       Me           l
Et             3-Cl    H       Me           CF3
i-Pr           3-Cl    5-Br    Me           OCF3
t-Bu           3-Cl    H       Me           CF3
propargyl      3-Cl    H       Me           SCF3
cyclopropyl    3-Cl    H       Me           SCHF2
i-Pr           3-Cl    5-Cl    Me           OCHF2
t-Bu           3-Cl    H       Me           CF3
Me             3-F     H       Me           C2F5
Et             3-Cl    H       Me           C2F5
i-Pr           3-Cl    5-CN    Et           CF3
t-Bu           3-Cl    H       n-Pr         CF3
propargyl      3-Cl    H       i-Pr         CF3
cyclopropyl    3-Cl    H       Me           SMe
i-Pr           3-Cl    H       Me           OMe
t-Bu           3-Cl    5-Br    Me           OEt
Me             3-Cl    H       Me           n-C3F7
Et             3-Br    H       Me           i-C3F7
i-Pr           3-Cl    H       Me           Et
t-Bu           3-Cl    5-Cl    Me           OCF2CHF2
Me             3-Cl    H       Me           SCF2CHF2
Et             3-Cl    H       Me           SO2Me
i-Pr           3-Cl    H       Me           SO2CF3
t-Bu           3-Cl    5-F     CF3         CF3
propargyl      3-Cl    H       CF3         Me
Et             3-Cl    H       Ph           CF3
i-Pr           3-Br    H       Ph           Cl
t-Bu           3-Cl    5-Cl    Ph           Br
Me             3-Cl    H       2-pyridyl    CF3
Et             3-CN    H       2-pyridyl    Cl
i-Pr           3-Cl    H       2-ClPh       CF3
t-Bu           3-Cl    H       2-ClPh       OCF3
cyclopropyl    3-Cl    5-Br    2-ClPh       Br
Et             3-Cl    H       2-ClPh       Cl
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Cl    H       2-ClPh             OCF3
t-Bu           3-Cl    H       2-BrPh             CF3
Me             3-F     H       2-MePh             CF3
Et             3-Cl    H       2-CNPh             CF3
i-Pr           3-Cl    5-Cl    2-FPh              CF3
t-Bu           3-Cl    H       2，6-F2Ph         CF3
propargyl      3-Cl    H       2，4-F2Ph         CF3
Et             3-Cl    H       2，5-F2Ph         CF3
i-Pr           3-Cl    H       2-MeOPh            CF3
t-Bu           3-Cl    5-Br    3-Cl-2-pyridyl     CF3
cyclopropyl    3-Cl    H       3-Cl-2-pyridyl     OCF3
Et             3-Cl    H       3-Cl-2-pyridyl     Br
i-Pr           3-Br    H       3-Cl-2-pyridyl     Cl
t-Bu           3-Cl    H       3-Cl-2-pyridyl     SCHF2
Me             3-Cl    H       3-F-2-pyridyl      CF3
Et             3-Cl    5-Cl    3-CF3-2-pyridyl   CF3
i-Pr           3-Cl    H       3-Me-2-pyridyl    CF3
t-Bu           3-l     H       3-Br-2-pyridyl    CF3
Me             3-Cl    5-Me    3-Br-2-pyridyl    OCF3
propargyl      3-Cl    H       3-Br-2-pyridyl    Br
i-Pr           3-Cl    H       3-Br-2-pyridyl    Cl
Me             6-Cl    H       Et                Br
Et             6-Br    4-Me    Me                Cl
i-Pr           6-Cl    H       Et                Cl
t-Bu           6-Cl    Cl      Me                I
Me             6-Cl    H       Me                CF3
Et             6-Cl    H       Me                OCF3
i-Pr           6-F     4-Br    Me                CF3
t-Bu           6-Cl    H       Me                SCF3
propargyl      6-Cl    H       Me                SCHF2
cyclopropyl    6-Cl    H       Me                OCHF2
i-Pr           6-Cl    4-Cl    Me                CF3
t-Bu           6-Cl    H       Me                C2F5
Me             6-Cl    H       Me                C2F5
Et             6-Cl    H       Et                CF3
i-Pr           6-I     4-CN    n-Pr              CF3
R3            R4a    R4b    Rva              Rvb
t-Bu           6-Cl    H       i-Pr              CF3
propargyl      6-Cl    H       Me                SMe
cyclopropyl    6-Cl    H       Me                OMe
i-Pr           6-Cl    H       Me                OEt
t-Bu           6-Cl    4-Br    Me                n-C3F7
Me             6-Cl    H       Me                i-C3F7
Et             6-F     H       Me                Et
i-Pr           6-Cl    H       Me                OCF2CHF2
t-Bu           6-Cl    4-Cl    Me                SCF2CHF2
Me             6-Cl    H       Me                SO2Me
Et             6-I     H       Me                SO2CF3
i-Pr           6-Cl    H       CF3              CF3
t-Bu           6-Cl    4-F     CF3              Me
propargyl      6-Cl    H       Ph                CF3
Et             6-Cl    H       Ph                Cl
i-Pr           6-Cl    H       Ph                Br
t-Bu           6-Cl    4-Cl    2-pyridyl         CF3
Me             6-Cl    H       2-pyridyl         Cl
Et             6-Cl    H       2-ClPH            CF3
i-Pr           6-Cl    H       2-ClPh            OCF3
t-Bu           6-Br    H       2-ClPh            Br
cyclopropyl    6-Cl    4-Br    2-ClPh            Cl
Et             6-Cl    H       2-ClPh            SCHF2
i-Pr           6-Cl    H       2-BrPh            CF3
t-Bu           6-F     4-Me    2-MePh            CF3
Me             6-Cl    H       2-CNPh            CF3
Et             6-Cl    H       2-FPh             CF3
i-Pr           6-CN    4-Cl    2，6-F2Ph        CF3
t-Bu           6-Cl    H       2，4-F2Ph        CF3
propargyl      6-Cl    H       2，5-F2Ph        CF3
Et             6-Cl    H       2-MeOPh           CF3
i-Pr           6-Cl    H       3-Cl-2-pyridyl    CF3
t-Bu           6-Cl    4-Br    3-Cl-2-pyridyl    OCF3
cyclopropyl    6-Cl    H       3-Cl-2-pyridyl    Br
Et             6-F     H       3-Cl-2-pyridyl    Cl
i-Pr           6-Cl    H       3-Cl-2-pyridyl    SCHF2
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Cl    H       3-F-2-pyridyl      CF3
Me             6-Cl    H       3-CF3-2-pyridyl   CF3
Et             6-Br    4-Cl    3-Me-2-pyridyl     CF3
i-Pr           6-Cl    H       3-Br-2-pyridyl     CF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     OCF3
Me             6-Cl    H       3-Br-2-pyridyl     Br
propargyl      61-Cl   H       3-Br-2-pyridyl     Cl
                         Table 16
R3            R4a    R4b    Rva               Rvb
Me             3-Me    H       H                  CF3
Et             3-Me    5-Me    H                  OCF3
i-Pr           3-Me    H       H                  OCF3
t-Bu           3-Me    5-Cl    Me                 Br
Me             3-Me    H       Et                 Br
Et             3-Me    H       Me                 Cl
i-Pr           3-Me    5-Br    Et                 Cl
t-Bu           3-Me    H       Me                 I
propargyl      3-Me    H       Me                 CF3
cyclopropyl    3-Me    H       Me                 OCF3
i-Pr           3-Me    5-Cl    Me                 CF3
t-Bu           3-Me    H       Me                 SCF3
Me             3-Me    5-CN    Me                 SCHF2
Et             3-Me    H       Me                 OCHF2
i-Pr           3-Me    H       Me                 CF3
t-Bu           3-Me    H       Me                 C2F5
R3            R4a    R4b    Rva              Rvb
ropargyl       3-Me    H       Me                C2F5
cyclopropyl    3-Me    H       Et                CF3
i-Pr           3-Me    H       n-Pr              CF3
t-Bu           3-Me    5-Br    i-Pr              CF3
Me             3-Me    H       i-Pr              OCF3
Et             3-Me    H       Me                SMe
i-Pr           3-Me    H       Me                OMe
t-Bu           3-Me    5-Cl    Me                OEt
Me             3-Me    H       Me                n-C3F7
Et             3-Me    H       Me                i-C3F7
i-Pr           3-Me    H       Me                Et
t-Bu           3-Me    5-F     Me                OCF2CHF2
propargyl      3-Me    H       Me                SCF2CHF2
Et             3-Me    H       Me                SO2Me
i-Pr           3-Me    H       Me                SO2CF3
t-Bu           3-Me    5-Cl    CHF2             CF3
Me             3-Me    H       CHF2             Me
Et             3-Me    H       Ph                CF3
i-Pr           3-Me    H       Ph                Cl
t-Bu           3-Me    H       Ph                Br
cyclopropyl    3-Me    5-Br    2-pyridyl         CF3
Et             3-Me    H       2-pyridyl         Cl
i-Pr           3-Me    5-Me    2-ClPh            CF3
t-Bu           3-Me    H       2-ClPh            OCF3
Me             3-Me    H       2-ClPh            Br
Et             3-Me    H       2-ClPh            Cl
i-Pr           3-Me    5-Cl    2-ClPh            SCHF2
t-Bu           3-Me    H       2-BrPh            CF3
propargyl      3-Me    H       2-MePh            CF3
Et             3-Me    H       2-CNPh            CF3
i-Pr           3-Me    H       2-FPh             CF3
t-Bu           3-Me    5-Br    2，6-F2Ph        CF3
cyclopropyl    3-Me    H       2，4-F2Ph        CF3
Et             3-Me    H       2，5-F2Ph        CF3
i-Pr           3-Me    H       2-MeOPh           CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl    CF3
R3            R4a    R4b    Rva               Rvb
Me             3-Me    H       3-Cl-2-pyridyl     OCF3
Et             3-Me    5-Cl    3-Cl-2-pyridyl     Br
i-Pr           3-Me    H       3-Cl-2-pyridyl     Cl
t-Bu           3-Me    H       3-Cl-2-pyridyl     SCHF2
Me             3-Me    H       3-F-2-pyridyl      CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF3
i-Pr           3-Me    5-CN    3-Me-2-pyridyl     CF3
t-Bu           3-Me    H       3-Br-2-pyridyl     CF3
Me             3-Me    H       3-Br-2-pyridyl     OCF3
Et             3-Me    H       3-Br-2-pyridyl     Br
i-Pr           3-Me    5-Br    3-Br-2-pyridyl     Cl
Me             6-Me    H       H                  CF3
Et             6-Me    4-Me    H                  OCF3
i-Pr           6-Me    H       H                  OCF3
t-Bu           6-Me    Cl      Me                 Br
Me             6-Me    H       Et                 Br
Et             6-Me    H       Me                 Cl
i-Pr           6-Me    4-Br    Et                 Cl
t-Bu           6-Me    H       Me                 I
propargyl      6-Me    H       Me                 CF3
cyclopropyl    6-Me    H       Me                 OCF3
i-Pr           6-Me    4-Cl    Me                 CF3
t-Bu           6-Me    H       Me                 SCF3
Me             6-Me    H       Me                 SCHF2
Et             6-Me    H       Me                 OCHF2
i-Pr           6-Me    4-CN    Me                 CF3
t-Bu           6-Me    H       Me                 C2F5
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CF3
i-Pr           6-Me    H       n-Pr               CF3
t-Bu           6-Me    4-Br    i-Pr               CF3
Me             6-Me    H       Me                 SMe
Et             6-Me    H       Me                 OMe
i-Pr           6-Me    H       Me                 OEt
t-Bu           6-Me    4-Cl    Me                 n-C3F7
Me             6-Me    H       Me                 i-C3F7
R3            R4a    R4b    Rva               Rvb
Et             6-Me    H       Me                 Et
i-Pr           6-Me    H       Me                 OCF2CHF2
t-Bu           6-Me    4-F     Me                 SCF2CHF2
propargyl      6-Me    H       Me                 SO2Me
Et             6-Me    H       Me                 SO2CF3
i-Pr           6-Me    H       CF3               CF3
t-Bu           6-Me    4-Cl    CF3               Me
Me             6-Me    H       Ph                 CF3
Et             6-Me    H       Ph                 Cl
i-Pr           6-Me    H       Ph                 Br
t-Bu           6-Me    H       2-pyridyl          CF3
cyclopropyl    6-Me    4-Br    2-pyridyl          Cl
Et             6-Me    H       2-ClPh             CF3
i-Pr           6-Me    H       2-ClPh             OCF3
t-Bu           6-Me    4-Me    2-ClPh             Br
Me             6-Me    H       2-ClPh             Cl
Et             6-Me    H       2-ClPh             SCHF2
i-Pr           6-Me    4-Cl    2-BrPh             CF3
t-Bu           6-Me    H       2-MePh             CF3
propargyl      6-Me    H       2-CNPh             CF3
Et             6-Me    H       2-FPh              CF3
i-Pr           6-Me    H       2，6-F2Ph         CF3
t-Bu           6-Me    4-Br    2，4-F2Ph         CF3
cyclopropyl    6-Me    H       2，5-F2Ph         CF3
Et             6-Me    H       2-MeOPh            CF3
i-Pr           6-Me    H       3-Cl-2-pyridyl     CF3
t-Bu           6-Me    H       3-Cl-2-pyridyl     OCF3
Me             6-Me    H       3-Cl-2-pyridyl     Br
Et             6-Me    4-Cl    3-Cl-2-pyridyl     Cl
i-Pr           6-Me    H       3-Cl-2-pyridyl     SCHF2
t-Bu           6-Me    4-CN    3-F-2-pyridyl      CF3
Me             6-Me    H       3-CF3-2-pyridyl   CF3
propargyl      6-Me    H       3-Me-2-pyridyl     CF3
i-Pr           6-Me    H       3-Br-2-pyridyl     CF3
t-Bu           6-Me    H       3-Br-2-pyridyl     OCF3
Me             6-Me    H       3-Br-2-pyridyl     Br
R3            R4a    R4b    Rva              Rvb
Et             6-Me    H       3-Br-2-pyridyl    Cl
Me             3-Cl    H       Me                Br
Et             3-Br    5-Me    Et                Br
i-Pr           3-Cl    H       Me                Cl
t-Bu           3-Cl    5-Cl    Et                Cl
Me             3-Cl    H       Me                I
Et             3-Cl    H       Me                CF3
i-Pr           3-Cl    5-Br    Me                OCF3
t-Bu           3-Cl    H       Me                CF3
propargyl      3-Cl    H       Me                SCF3
cyclopropyl    3-Cl    H       Me                SCHF2
i-Pr           3-Cl    5-Cl    Me                OCHF2
t-Bu           3-Cl    H       Me                CF3
Me             3-F    H        Me                C2F5
Et             3-Cl    H       Me                C2F5
i-Pr           3-Cl    5-CN    Et                CF3
t-Bu           3-Cl    H       n-Pr              CF3
propargyl      3-Cl    H       i-Pr              CF3
cyclopropyl    3-Cl    H       Me                SMe
i-Pr           3-Cl    H       Me                OMe
t-Bu           3-Cl    5-Br    Me                OEt
Me             3-Cl    H       Me                n-C3F7
Et             3-Br    H       Me                i-C3F7
i-Pr           3-Cl    H       Me                Et
t-Bu           3-Cl    5-Cl    Me                OCF2CHF2
Me             3-Cl    H       Me                SCF2CHF2
Et             3-Cl    H       Me                SO2Me
i-Pr           3-Cl    H       Me                SO2CF3
t-Bu           3-Cl    5-F     CF3              CF3
propargyl      3-Cl    H       CF3              Me
Et             3-Cl    H       Ph                CF3
i-Pr           3-Br    H       Ph                Cl
t-Bu           3-Cl    5-Cl    Ph                Br
Me             3-Cl    H       2-pyridyl         CF3
Et             3-CN    H       2-pyridyl         Cl
i-Pr           3-Cl    H       2-ClPh            CF3
R3            R4a    R4b    Rva               Rvb
t-Bu           3-Cl    H       2-ClPh             OCF3
cyclopropyl    3-Cl    5-Br    2-ClPh             Br
Et             3-Cl    H       2-ClPh             Cl
i-Pr           3-Cl    H       2-ClPh             OCF3
t-Bu           3-Cl    H       2-BrPh             CF3
Me             3-F     H       2-MePh             CF3
Et             3-Cl    H       2-CNPh             CF3
i-Pr           3-Cl    5-Cl    2-FPh              CF3
t-Bu           3-Cl    H       2，6-F2Ph         CF3
propargyl      3-Cl    H       2，4-F2Ph         CF3
Et             3-Cl    H       2，5-F2Ph         CF3
i-Pr           3-Cl    H       2-MeOPh            CF3
t-Bu           3-Cl    5-Br    3-Cl-2-pyridyl     CF3
cyclopropyl    3-Cl    H       3-Cl-2-pyridyl     OCF3
Et             3-Cl    H       3-Cl-2-pyridyl     Br
i-Pr           3-Br    H       3-Cl-2-pyridyl     Cl
t-Bu           3-Cl    H       3-Cl-2-pyridyl     SCHF2
Me             3-Cl    H       3-F-2-pyridyl      CF3
Et             3-Cl    5-Cl    3-CF3-2-pyridyl   CF3
i-Pr           3-Cl    H       3-Me-2-pyridyl     CF3
t-Bu           3-I     H       3-Br-2-pyridyl     CF3
Me             3-Cl    5-Me    3-Br-2-pyridyl     OCF3
propargyl      3-Cl    H       3-Br-2-pyridyl     Br
i-Pr           3-Cl    H       3-Br-2-pyridyl     Cl
Me             6-Cl    H       Et                 Br
Et             6-Br    4-Me    Me                 Cl
i-Pr           6-Cl    H       Et                 Cl
t-Bu           6-Cl    Cl      Me                 I
Me             6-Cl    H       Me                 CF3
Et             6-Cl    H       Me                 OCF3
i-Pr           6-F     4-Br    Me                 CF3
t-Bu           6-Cl    H       Me                 SCF3
propargyl      6-Cl    H       Me                 SCHF2
cyclopropyl    6-Cl    H       Me                 OCHF2
i-Pr           6-Cl    4-Cl    Me                 CF3
t-Bu           6-Cl    H       Me                 C2F5
R3            R4a    R4b    Rva              Rvb
Me             6-Cl    H       Me                C2F5
Et             6-Cl    H       Et                CF3
i-Pr           6-I     4-CN    n-Pr              CF3
t-Bu           6-Cl    H       i-Pr              CF3
propargyl      6-Cl    H       Me                SMe
cyclopropyl    6-Cl    H       Me                OMe
i-Pr           6-Cl    H       Me                OEt
t-Bu           6-Cl    4-Br    Me                n-C3F7
Me             6-Cl    H       Me                i-C3F7
Et             6-F     H       Me                Et
i-Pr           6-Cl    H       Me                OCF2CHF2
t-Bu           6-Cl    4-Cl    Me                SCF2CHF2
Me             6-Cl    H       Me                SO2Me
Et             6-I     H       Me                SO2CF3
i-Pr           6-Cl    H       CF3              CF3
t-Bu           6-Cl    4-F     CF3              Me
propargyl      6-Cl    H       Ph                CF3
Et             6-Cl    H       Ph                Cl
i-Pr           6-Cl    H       Ph                Br
t-Bu           6-Cl    4-Cl    2-pyridyl         CF3
Me             6-Cl    H       2-pyridyl         Cl
Et             6-Cl    H       2-ClPh            CF3
i-Pr           6-Cl    H       2-ClPh            OCF3
t-Bu           6-Br    H       2-ClPh            Br
cyclopropyl    6-Cl    4-Br    2-ClPh            Cl
Et             6-Cl    H       2-ClPh            SCHF2
i-Pr           6-Cl    H       2-BrPh            CF3
t-Bu           6-F     4-Me    2-MePh            CF3
Me             6-Cl    H       2-CNPh            CF3
Et             6-Cl    H       2-FPh             CF3
i-Pr           6-CN    4-Cl    2，6-F2Ph        CF3
t-Bu           6-Cl    H       2，4-F2Ph        CF3
propargyl      6-Cl    H       2，5-F2Ph        CF3
Et             6-Cl    H       2-MeOPh           CF3
i-Pr           6-Cl    H       3-Cl-2-pyridyl    CF3
t-Bu           6-Cl    4-Br    3-Cl-2-pyridyl    OCF3
R3            R4a    R4b    Rva               Rvb
cyclopropyl    6-Cl    H       3-Cl-2-pyridyl     Br
Et             6-F     H       3-Cl-2-pyridyl     Cl
i-Pr           6-Cl    H       3-Cl-2-pyridyl     SCHF2
t-Bu           6-Cl    H       3-F-2-pyridyl      CF3
Me             6-Cl    H       3-CF3-2-pyridyl   CF3
Et             6-Br    4-Cl    3-Me-2-pyridyl     CF3
i-Pr           6-Cl    H       3-Br-2-pyridyl     CF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     OCF3
Me             6-Cl    H       3-Br-2-pyridyl     Br
propargyl      6-Cl    H       3-Br-2-pyridyl     Cl
                          Table 17
Figure A0281824702021
R3            R4a    R4b    Rva               Rvb
Me             3-Me    H       H                  CHF2
Et             3-Me    5-Me    H                  CH2CF3
i-Pr           3-Me    H       H                  CH2CF3
t-Bu           3-Me    5-Cl    Me                 CH2CF3
Me             3-Me    H       Et                 CH2CF3
Et             3-Me    H       Me                 CF2CHF2
i-Pr           3-Me    5-Br    Et                 CHF2
t-Bu           3-Me    H       Me                 CHF2
propargyl      3-Me    H       Me                 CBrF2
cyclopropyl    3-Me    H       Me                 CH2F
i-Pr           3-Me    5-Cl    Me                 CH2CF3
t-Bu           3-Me    H       Me                 Et
Me             3-Me    5-CN    Me                 n-Pr
Et             3-Me    H       Me                 CH2C2F5
R3            R4a    R4b    Rva         Rvb
i-Pr           3-Me    H       Me           CH2CF3
t-Bu           3-Me    H       Me           CF3
propargyl      3-Me    H       Me           C2F5
cyclopropyl    3-Me    H       Et           CHF2
i-Pr           3-Me    H       n-Pr         CH2CF3
t-Bu           3-Me    5-Br    i-Pr         CHF2
Me             3-Me    H       Cl           CH2CF3
Et             3-Me    H       F            CH2CF3
i-Pr           3-Me    H       Me           CH2Cl
t-Bu           3-Me    5-Cl    Me           CClF2
Me             3-Me    H       Me           CH2CH2Cl
Et             3-Me    H       Me           n-C3F7
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Allyl
propargyl      3-Me    H       Et           CF2CHF2
Et             3-Me    H       Et           i-C3F7
i-Pr           3-Me    H       n-Pr         CF2CHF2
t-Bu           3-Me    5-Cl    i-Pr         CF2CHF2
Me             3-Me    H       CF3         CF2CHF2
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CH2CF3
t-Bu           3-Me    H       H            CH2CF3
cyclopropyl    3-Me    5-Br    H            CH2CF3
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            C2F5
Me             3-Me    H       H            CF2CHF2
Et             3-Me    H       i-Pr         CH2CF3
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       Ph           CH2CF3
Et             3-Me    H       Ph           CF2CHF2
i-Pr           3-Me    H       Ph           CHF2
t-Bu           3-Me    5-Br    2-pyridyl    CH2CF3
cyclopropyl    3-Me    H       2-pyridyl    CF2CHF2
Et             3-Me    H       2-ClPh       CH2CF3
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    H       2-ClPh             CF2CHF2
t-Bu           3-Me    H       2-ClPh             CHF2
Me             3-Me    H       2-ClPh             Et
Et             3-Me    5-Cl    2-ClPh             CBrF2
i-Pr           3-Me    H       2-BrPh             CH2CF3
t-Bu           3-Me    H       2-MePh             CF2CHF2
Me             3-Me    H       2-CNPh             CH2CF3
propargyl      3-Me    H       2-FPh              CH2CF3
i-Pr           3-Me    5-CN    2，6-F2Ph         CF2CHF2
t-Bu           3-Me    H       2，4-F2Ph         CH2CF3
Me             3-Me    H       2，5-F2Ph         CH2CF3
Et             3-Me    H       2-MeOPh            CF2CHF2
i-Pr           3-Me    5-Br    3-Cl-2-pyridyl     CH2CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     CF2CHF2
Me             3-Me    5-I     3-Cl-2-pyridyl     CF3
Et             3-Me    H       3-Cl-2-pyridyl     CHF2
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     CBrF2
t-Bu           3-Me    H       3-F-2-pyridyl      CH2CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF2CHF2
Et             3-Me    5-Br    3-Me-2-pyridyl     CH2CF3
i-Pr           3-Me    H       3-Br-2-pyridyl     CF3
t-Bu           3-Me    H       3-Br-2-pyridyl     CH2CF3
Me             3-Me    H       3-Br-2-pyridyl     CF2CHF2
Et             3-Me    H       3-Br-2-pyridyl     CClF2
Me             6-Me    H       H                  CHF2
Et             6-Me    4-Me    H                  CH2CF3
i-Pr           6-Me    H       H                  CH2CF3
t-Bu           6-Me    Cl      Me                 CH2CF3
Me             6-Me    H       Et                 CH2CF3
Et             6-Me    H       Me                 CF2CHF2
i-Pr           6-Me    4-Br    Et                 CHF2
t-Bu           6-Me    H       Me                 CHF2
propargyl      6-Me    H       Me                 CBrF2
cyclopropyl    6-Me    H       Me                 CH2F
i-Pr           6-Me    4-Cl    Me                 CH2CF3
t-Bu           6-Me    H       Me                 Et
R3            R4a        R4b        Rva    Rvb
Me             6-Me        H           Me      n-Pr
Et             6-Me        H           Me      CH2C2F5
i-Pr           6-Me        4-CN        Me      CH2CF3
t-Bu           6-Me        H           Me      CF3
propargyl      6-Me        H           Me      C2F5
cyclopropyl    6-Me        H           Et      CHF2
i-Pr           6-Me        H           n-Pr    CH2CF3
t-Bu           6-Me        4-Br        i-Pr    CHF2
Me             6-Me        H           Cl      CH2CF3
Et             6-Me        H           F       CH2CF3
i-Pr           6-Me        H           Me      CH2Cl
t-Bu           6-Me        4-Cl        Me      CClF2
Me             6-Me        H           Me      CH2CH2Cl
Et             6-Me        H           Me      n-C3F7
i-Pr           6-Me        H           Me      i-C3F7
t-Bu           6-Me        4-F         Me      Allyl
propargyl      6-Me        H           Me      CF2CHF2
Et             6-Me        H           Me      i-C3F7
i-Pr           6-Me        H           Me      CF2CHF2
t-Bu           6-Me        4-Cl        Me      CF2CHF2
Me             6-Me        H           CF3    CF2CHF2
Et             6-Me        H           CF3    Me
i-Pr           6-Me        H           OMe     CH2CF3
t-Bu           6-Me        H           H       CH2CF3
cyclopropyl    6-Me        4-Br        H       CH2CF3
Et             6-Me        H           H       C2F5
i-Pr           6-Me        H           H       C2F5
t-Bu           6-Me        4-Me        H       C2F5
Me             6-Me        H           H       CF2CHF2
Et             6-Me        H           H       CH2CF3
i-Pr           6-Me        4-Cl        H       n-C3F7
t-Bu           6-Me        H           H       i-C3F7
propargyl      6-Me        H           H       CH2CF3
Et             6-Me        H           H       CF2CHF2
i-Pr           6-Me        H           H       CHF2
t-Bu           6-Me        4-Br        Ph      CH2CF3
R3            R4a    R4b    Rva               Rvb
cyclopropyl    6-Me    H       Ph                 CF2CHF2
Et             6-Me    H       Ph                 CH2CF3
i-Pr           6-Me    H       2-pyridyl          CF2CHF2
t-Bu           6-Me    H       2-pyridyl          CHF2
Me             6-Me    H       2-ClPh             Et
Et             6-Me    4-Cl    2-ClPh             CBrF2
i-Pr           6-Me    H       2-ClPh             CH2CF3
t-Bu           6-Me    4-CN    2-ClPh             CF2CHF2
Me             6-Me    H       2-ClPh             CH2CF3
propargyl      6-Me    H       2-BrPh             CH2CF3
i-Pr           6-Me    H       2-MePh             CF2CHF2
t-Bu           6-Me    H       2-CNPh             CH2CF3
Me             6-Me    H       2-FPh              CH2CF3
Et             6-Me    H       2，6-F2Ph         CF2CHF2
i-Pr           6-Me    4-Br    2，4-F2Ph         CH2CF3
t-Bu           6-Me    H       2，5-F2Ph         CF2CHF2
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CHF2
i-Pr           6-Me    H       3-Cl-2-pyridyl     CBrF2
t-Bu           6-Me    H       3-Cl-2-pyridyl     CH2CF3
propargyl      6-Me    H       3-Cl-2-pyridyl     CF2CHF2
Et             6-Me    4-Br    3-Cl-2-pyridyl     CH2CF3
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CH2CF3
Me             6-Me    H       3-Me-2-pyridyl     CF2CHF2
Et             6-Me    H       3-Br-2-pyridyl     CClF2
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     CH2CF3
t-Bu           6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    H       3-Br-2-pyridyl     CF2CHF2
Me             3-Cl    H       H                  CHF2
Et             3-Br    5-Me    H                  CH2CF3
i-Pr           3-Cl    H       H                  CH2CF3
t-Bu           3-Cl    5-Cl    Me                 CH2CF3
Me             3-Cl    H       Et                 CH2CF3
Et             3-Cl    H       Me                 CF2CHF2
i-Pr           3-Cl    5-Br    Et                 CHF2
R3            R4a        R4b        Rva    Rvb
t-Bu           3-Cl        H           Me      CHF2
propargyl      3-Cl        H           Me      CBrF2
cyclopropyl    3-Cl        H           Me      CH2F
i-Pr           3-Cl        5-Cl        Me      CH2CF3
t-Bu           3-Cl        H           Me      Et
Me             3-F         H           Me      n-Pr
Et             3-Cl        H           Me      CH2C2F5
i-Pr           3-Cl        5-CN        Me      CH2CF3
t-Bu           3-Cl        H           Me      CF3
propargyl      3-Cl        H           Me      C2F5
cyclopropyl    3-Cl        H           Et      CHF2
i-Pr           3-Cl        H           n-Pr    CH2CF3
t-Bu           3-Cl        5-Br        i-Pr    CHF2
Me             3-Cl        H           Cl      CH2CF3
Et             3-Br        H           F       CH2CF3
i-Pr           3-Cl        H           Me      CH2Cl
t-Bu           3-Cl        5-Cl        Me      CClF2
Me             3-Cl        H           Me      CH2CH2Cl
Et             3-Cl        H           Me      n-C3F7
i-Pr           3-Cl        H           Me      i-C3F7
t-Bu           3-Cl        5-F         Me      Allyl
propargyl      3-Cl        H           Me      CF2CHF2
Et             3-Cl        H           Me      i-C3F7
i-Pr           3-Br        H           Me      CF2CHF2
t-Bu           3-Cl        5-Cl        Me      CF2CHF2
Me             3-Cl        H           CF3    CF2CHF2
Et             3-CN        H           CF3    Me
i-Pr           3-Cl        H           OMe     CH2CF3
t-Bu           3-Cl        H           H       CH2CF3
cyclopropyl    3-Cl        5-Br        H       CH2CF3
Et             3-Cl        H           H       C2F5
i-Pr           3-Cl        H           H       C2F5
t-Bu           3-Cl        H           H       C2F5
Me             3-F         H           H       CF2CHF2
Et             3-Cl        H           H       CH2CF3
i-Pr           3-Cl        5-Cl        H       n-C3F7
R3          R4a    R4b    Rva              Rvb
t-Bu         3-Cl    H       H                 i-C3F7
propargyl    3-Cl    H       H                 CH2CF3
Et           3-Cl    H       H                 CF2CHF2
i-Pr         3-Cl    H       H                 CHF2
t-Bu         3-Cl    5-Br    Ph                CH2CF3
cyclopropyl  3-Cl    H       Ph                CF2CHF2
Et           3-Cl    H       Ph                CH2CF3
i-Pr         3-Br    H       2-pyridyl         CF2CHF2
t-Bu         3-Cl    H       2-pyridyl         CHF2
Me           3-Cl    H       2-ClPh            Et
Et           3-Cl    5-Cl    2-ClPh            CBrF2
i-Pr         3-Cl    H       2-ClPh            CH2CF3
t-Bu         3-I     H       2-ClPh            CF2CHF2
Me           3-Cl    5-Me    2-ClPh            CH2CF3
propargyl    3-Cl    H       2-BrPh            CH2CF3
i-Pr         3-Cl    H       2-MePh            CF2CHF2
t-Bu         3-Cl    5-CN    2-CNPh            CH2CF3
Me           3-Cl    H       2-FPh             CH2CF3
Et           3-Cl    H       2，6-F2Ph        CF2CHF2
i-Pr         3-Cl    5-Br    2，4-F2Ph        CH2CF3
t-Bu         3-F     H       2，5-F2Ph        CF2CHF2
Me           3-Cl    5-I     2-MeOPh           CF3
Et           3-Cl    H       3-Cl-2-pyridyl    CHF2
i-Pr         3-CN    H       3-Cl-2-pyridyl    CBrF2
t-Bu         3-Cl    H       3-Cl-2-pyridyl    CH2CF3
propargyl    3-Cl    H       3-Cl-2-pyridyl    CF2CHF2
Et           3-Cl    5-Br    3-Cl-2-pyridyl    CH2CF3
i-Pr         3-Cl    H       3-F-2-pyridyl     CF3
t-Bu         3-Br    H       3-CF3-2-pyridyl  CH2CF3
Me           3-Cl    H       3-Me-2-pyridyl    CF2CHF2
Et           3-Cl    H       3-Br-2-pyridyl    CClF2
i-Pr         3-Cl    5-Cl    3-Br-2-pyridyl    CH2CF3
t-Bu         3-Cl    H       3-Br-2-pyridyl    CF3
i-Pr         3-Cl    H       3-Br-2-pyridyl    CF2CHF2
Me           6-Cl    H       Et                CHF2
Et           6-Br    4-Me    Me                CH2CF3
R3            R4a        R4b        Rva   Rvb
i-Pr           6-Cl        H           Et     CH2CF3
t-Bu           6-Cl        Cl          Me     CH2CF3
Me             6-Cl        H           Me     CH2CF3
Et             6-Cl        H           Me     CF2CHF2
i-Pr           6-F         4-Br        Me     CHF2
t-Bu           6-Cl        H           Me     CHF2
propargyl      6-Cl        H           Me     CBrF2
cyclopropyl    6-Cl        H           Me     CH2F
i-Pr           6-Cl        4-Cl        Me     CH2CF3
t-Bu           6-Cl        H           Me     Et
Me             6-Cl        H           Me     n-Pr
Et             6-Cl        H           Et     CH2C2F5
i-Pr           6-I         4-CN        n-Pr   CH2CF3
t-Bu           6-Cl        H           i-Pr   CF3
propargyl      6-Cl        H           Cl     C2F5
cyclopropyl    6-Cl        H           F      CHF2
i-Pr           6-Cl        H           Me     CH2CF3
t-Bu           6-Cl        4-Br        Me     CHF2
Me             6-Cl        H           Me     CH2CF3
Et             6-F         H           Me     CH2CF3
i-Pr           6-Cl        H           Me     CH2Cl
t-Bu           6-Cl        4-Cl        Me     CClF2
Me             6-Cl        H           Me     CH2CH2Cl
Et             6-I         H           Me     n-C3F7
i-Pr           6-Cl        H           Me     i-C3F7
t-Bu           6-Cl        4-F         Me     Allyl
propargyl      6-Cl        H           CF3   CF2CHF2
Et             6-Cl        H           CF3   i-C3F7
i-Pr           6-Cl        H           OMe    CF2CHF2
t-Bu           6-Cl        4-Cl        H      CF2CHF2
Me             6-Cl        H           H      CF2CHF2
Et             6-Cl        H           H      Me
i-Pr           6-Cl        H           H      CH2CF3
t-Bu           6-Br        H           H      CH2CF3
cyclopropyl    6-Cl        4-Br        H      CH2CF3
Et             6-Cl        H           H      C2F5
R3          R4a    R4b    Rva              Rvb
i-Pr         6-Cl    H       H                 C2F5
t-Bu         6-F     4-Me    H                 C2F5
Me           6-Cl    H       H                 CF2CHF2
Et           6-Cl    H       H                 CH2CF3
i-Pr         6-CN    4-Cl    H                 n-C3F7
t-Bu         6-Cl    H       Ph                i-C3F7
propargyl    6-Cl    H       Ph                CH2CF3
Et           6-Cl    H       Ph                CF2CHF2
i-Pr         6-Cl    H       2-pyridyl         CHF2
t-Bu         6-Cl    4-Br    2-pyridyl         CH2CF3
cyclopropyl  6-Cl    H       2-ClPh            CF2CHF2
Et           6-F     H       2-ClPh            CH2CF3
i-Pr         6-Cl    H       2-ClPh            CF2CHF2
t-Bu         6-Cl    H       2-ClPh            CHF2
Me           6-Cl    H       2-ClPh            Et
Et           6-Br    4-Cl    2-BrPh            CBrF2
i-Pr         6-Cl    H       2-MePh            CH2CF3
t-Bu         6-Cl    H       2-CNPh            CF2CHF2
Me           6-Cl    H       2-FPh             CH2CF3
propargyl    6-Cl    H       2，6-F2Ph        CH2CF3
i-Pr         6-Br    H       2，4-F2Ph        CF2CHF2
t-Bu         6-Cl    4-CN    2，5-F2Ph        CH2CF3
Me           6-Cl    H       2-MeOPh           CH2CF3
Et           6-Cl    H       3-Cl-2-pyridyl    CF2CHF2
i-Pr         6-Cl    4-Br    3-Cl-2-pyridyl    CH2CF3
t-Bu         6-CN    H       3-Cl-2-pyridyl    CF2CHF2
Me           6-Cl    4-I     3-Cl-2-pyridyl    CF3
Et           6-Cl    H       3-Cl-2-pyridyl    CHF2
i-Pr         6-Br    H       3-F-2-pyridyl     CBrF2
t-Bu         6-Cl    H       3-CF3-2-pyridyl  CH2CF3
propargyl    6-Cl    H       3-Me-2-pyridyl    CF2CHF2
Et           6-Cl    4-Br    3-Br-2-pyridyl    CH2CF3
i-Pr         6-Cl    H       3-Br-2-pyridyl    CF3
t-Bu         6-Cl    H       3-Br-2-pyridyl    CH2CF3
Me           6-Cl    H       3-Br-2-pyridyl    CF2CHF2
                    Table 18
R3            R4a      R4b      Rva    Rvb
Me             3-Me      H         H       CHF2
Et             3-Me      5-Me      H       CH2CF3
i-Pr           3-Me      H         H       CH2CF3
t-Bu           3-Me      5-Cl      Me      CH2CF3
Me             3-Me      H         Et      CH2CF3
Et             3-Me      H         Me      CF2CHF2
i-Pr           3-Me      5-Br      Et      CHF2
t-Bu           3-Me      H         Me      CHF2
propargyl      3-Me      H         Me      CBrF2
cyclopropyl    3-Me      H         Me      CH2F
i-Pr           3-Me      5-Cl      Me      CH2CF3
t-Bu           3-Me      H         Me      Et
Me             3-Me      5-CN      Me      n-Pr
Et             3-Me      H         Me      CH2C2F5
i-Pr           3-Me      H         Me      CH2CF3
t-Bu           3-Me      H         Me      CF3
propargyl      3-Me      H         Me      C2F5
cyclopropyl    3-Me      H         Et      CHF2
i-Pr           3-Me      H         n-Pr    CH2CF3
t-Bu           3-Me      5-Br      i-Pr    CHF2
Me             3-Me      H         Cl      CH2CF3
Et             3-Me      H         F       CH2CF3
i-Pr           3-Me      H         Me      CH2Cl
t-Bu           3-Me      5-Cl      Me      CClF2
Me             3-Me      H         Me      CH2CH2Cl
Et             3-Me      H         Me      n-C3F7
R3            R4a      R4b    Rva         Rvb
i-Pr           3-Me      H       Me           i-C3F7
t-Bu           3-Me      5-F     Me           Allyl
propargyl      3-Me      H       Et           CF2CHF2
Et             3-Me      H       Et           i-C3F7
i-Pr           3-Me      H       n-Pr         CF2CHF2
t-Bu           3-Me      5-Cl    i-Pr         CF2CHF2
Me             3-Me      H       CF3         CF2CHF2
Et             3-Me      H       CF3         Me
i-Pr           3-Me      H       OMe          CH2CF3
t-Bu           3-Me      H       H            CH2CF3
cyclopropyl    3-Me      5-Br    H            CH2CF3
Et             3-Me      H       H            C2F5
i-Pr           3-Me      5-Me    H            C2F5
t-Bu           3-Me      H       H            C2F5
Me             3-Me      H       H            CF2CHF2
Et             3-Me      H       i-Pr         CH2CF3
i-Pr           3-Me      5-Cl    H            n-C3F7
t-Bu           3-Me      H       H            i-C3F7
propargyl      3-Me      H       Ph           CH2CF3
Et             3-Me      H       Ph           CF2CHF2
i-Pr           3-Me      H       Ph           CHF2
t-Bu           3-Me      5-Br    2-pyridyl    CH2CF3
cyclopropyl    3-Me      H       2-pyridyl    CF2CHF2
Et             3-Me      H       2-ClPh       CH2CF3
i-Pr           3-Me      H       2-ClPh       CF2CHF2
t-Bu           3-Me      H       2-ClPh       CHF2
Me             3-Me      H       2-ClPh       Et
Et             3-Me      5-Cl    2-ClPh       CBrF2
i-Pr           3-Me      H       2-BrPh       CH2CF3
t-Bu           3-Me      H       2-MePh       CF2CHF2
Me             3-Me      H       2-CNPh       CH2CF3
propargyl      3-Me      H       2-FPh        CH2CF3
i-Pr           3-Me      5-CN    2，6-F2Ph   CF2CHF2
t-Bu           3-Me      H       2，4-F2Ph   CH2CF3
Me             3-Me      H       2，5-F2Ph   CH2CF3
Et             3-Me      H       2-MeOPh      CF2CHF2
R3            R4a    R4b    Rva               Rvb
i-Pr           3-Me    5-Br    3-Cl-2-pyridyl     CH2CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     CF2CHF2
Me             3-Me    5-I     3-Cl-2-pyridyl     CF3
Et             3-Me    H       3-Cl-2-pyridyl     CHF2
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     CBrF2
t-Bu           3-Me    H       3-F-2-pyridyl      CH2CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF2CHF2
Et             3-Me    5-Br    3-Me-2-pyridyl     CH2CF3
i-Pr           3-Me    H       3-Br-2-pyridyl     CF3
t-Bu           3-Me    H       3-Br-2-pyridyl     CH2CF3
Me             3-Me    H       3-Br-2-pyridyl     CF2CHF2
Et             3-Me    H       3-Br-2-pyridyl     CClF2
Me             6-Me    H       H                  CHF2
Et             6-Me    4-Me    H                  CH2CF3
i-Pr           6-Me    H       H                  CH2CF3
t-Bu           6-Me    Cl      Me                 CH2CF3
Me             6-Me    H       Et                 CH2CF3
Et             6-Me    H       Me                 CF2CHF2
i-Pr           6-Me    4-Br    Et                 CHF2
t-Bu           6-Me    H       Me                 CHF2
propargyl      6-Me    H       Me                 CBrF2
cyclopropyl    6-Me    H       Me                 CH2F
i-Pr           6-Me    4-Cl    Me                 CH2CF3
t-Bu           6-Me    H       Me                 Et
Me             6-Me    H       Me                 n-Pr
Et             6-Me    H       Me                 CH2C2F5
i-Pr           6-Me    4-CN    Me                 CH2CF3
t-Bu           6-Me    H       Me                 CF3
propargyl      6-Me    H       Me                 C2F5
cyclopropyl    6-Me    H       Et                 CHF2
i-Pr           6-Me    H       n-Pr               CH2CF3
t-Bu           6-Me    4-Br    i-Pr               CHF2
Me             6-Me    H       Cl                 CH2CF3
Et             6-Me    H       F                  CH2CF3
i-Pr           6-Me    H       Me                 CH2Cl
t-Bu           6-Me    4-Cl    Me                 CClF2
R3          R4a      R4b    Rva         Rvb
Me           6-Me      H       Me           CH2CH2Cl
Et           6-Me      H       Me           n-C3F7
i-Pr         6-Me      H       Me           i-C3F7
t-Bu         6-Me      4-F     Me           Allyl
propargyl    6-Me      H       Me           CF2CHF2
Et           6-Me      H       Me           i-C3F7
i-Pr         6-Me      H       Me           CF2CHF2
t-Bu         6-Me      4-Cl    Me           CF2CHF2
Me           6-Me      H       CF3         CF2CHF2
Et           6-Me      H       CF3         Me
i-Pr         6-Me      H       OMe          CH2CF3
t-Bu         6-Me      H       H            CH2CF3
cyclopropyl  6-Me      4-Br    H            CH2CF3
Et           6-Me      H       H            C2F5
i-Pr         6-Me      H       H            C2F5
t-Bu         6-Me      4-Me    H            C2F5
Me           6-Me      H       H            CF2CHF2
Et           6-Me      H       H            CH2CF3
i-Pr         6-Me      4-Cl    H            n-C3F7
t-Bu         6-Me      H       H            i-C3F7
propargyl    6-Me      H       H            CH2CF3
Et           6-Me      H       H            CF2CHF2
i-Pr         6-Me      H       H            CHF2
t-Bu         6-Me      4-Br    Ph           CH2CF3
cyclopropyl  6-Me      H       Ph           CF2CHF2
Et           6-Me      H       Ph           CH2CF3
i-Pr         6-Me      H       2-pyridyl    CF2CHF2
t-Bu         6-Me      H       2-pyridyl    CHF2
Me           6-Me      H       2-ClPh       Et
Et           6-Me      4-Cl    2-ClPh       CBrF2
i-Pr         6-Me      H       2-ClPh       CH2CF3
t-Bu         6-Me      4-CN    2-ClPh       CF2CHF2
Me           6-Me      H       2-ClPh       CH2CF3
propargyl    6-Me      H       2-BrPh       CH2CF3
i-Pr         6-Me      H       2-MePh       CF2CHF2
t-Bu         6-Me      H       2-CNPh       CH2CF3
R3             R4a    R4b   Rva              Rvb
Me              6-Me    H      2-FPh             CH2CF3
Et              6-Me    H      2，6-F2Ph        CF2CHF2
i-Pr            6-Me    4-Br   2，4-F2Ph        CH2CF3
t-Bu            6-Me    H      2，5-F2Ph        CF2CHF2
Me              6-Me    4-I    2-MeOPh           CF3
Et              6-Me    H      3-Cl-2-pyridyl    CHF2
i-Pr            6-Me    H      3-Cl-2-pyridyl    CBrF2
t-Bu            6-Me    H      3-Cl-2-pyridyl    CH2CF3
propargyl       6-Me    H      3-Cl-2-pyridyl    CF2CHF2
Et              6-Me    4-Br   3-Cl-2-pyridyl    CH2CF3
i-Pr            6-Me    H      3-F-2-pyridyl     CF3
t-Bu            6-Me    H      3-CF3-2-pyridyl  CH2CF3
Me              6-Me    H      3-Me-2-pyridyl    CF2CHF2
Et              6-Me    H      3-Br-2-pyridyl    CClF2
i-Pr            6-Me    4-Cl   3-Br-2-pyridyl    CH2CF3
t-Bu            6-Me    H      3-Br-2-pyridyl    CF3
i-Pr            6-Me    H      3-Br-2-pyridyl    CF2CHF2
Me              3-Cl    H      H                 CHF2
Et              3-Br    5-Me   H                 CH2CF3
i-Pr            3-Cl    H      H                 CH2CF3
t-Bu            3-Cl    5-Cl   Me                CH2CF3
Me              3-Cl    H      Et                CH2CF3
Et              3-Cl    H      Me                CF2CHF2
i-Pr            3-Cl    5-Br   Et                CHF2
t-Bu            3-Cl    H      Me                CHF2
propargyl       3-Cl    H      Me                CBrF2
cyclopropyl     3-Cl    H      Me                CH2F
i-Pr            3-Cl    5-Cl   Me                CH2CF3
t-Bu            3-Cl    H      Me                Et
Me              3-F     H      Me                n-Pr
Et              3-Cl    H      Me                CH2C2F5
i-Pr            3-Cl    5-CN   Me                CH2CF3
t-Bu            3-Cl    H      Me                CF3
propargyl       3-Cl    H      Me                C2F5
cyclopropyl     3-Cl    H      Et                CHF2
i-Pr            3-Cl    H      n-Pr              CH2CF3
R3            R4a      R4b      Rva         Rvb
t-Bu           3-Cl      5-Br      i-Pr         CHF2
Me             3-Cl      H         Cl           CH2CF3
Et             3-Br      H         F            CH2CF3
i-Pr           3-Cl      H         Me           CH2Cl
t-Bu           3-Cl      5-Cl      Me           CClF2
Me             3-Cl      H         Me           CH2CH2Cl
Et             3-Cl      H         Me           n-C3F7
i-Pr           3-Cl      H         Me           i-C3F7
t-Bu           3-Cl      5-F       Me           Allyl
propargyl      3-Cl      H         Me           CF2CHF2
Et             3-Cl      H         Me           i-C3F7
i-Pr           3-Br      H         Me           CF2CHF2
t-Bu           3-Cl      5-Cl      Me           CF2CHF2
Me             3-Cl      H         CF3         CF2CHF2
Et             3-CN      H         CF3         Me
i-Pr           3-Cl      H         OMe          CH2CF3
t-Bu           3-Cl      H         H            CH2CF3
cyclopropyl    3-Cl      5-Br      H            CH2CF3
Et             3-Cl      H         H            C2F5
i-Pr           3-Cl      H         H            C2F5
t-Bu           3-Cl      H         H            C2F5
Me             3-F       H         H            CF2CHF2
Et             3-Cl      H         H            CH2CF3
i-Pr           3-Cl      5-Cl      H            n-C3F7
t-Bu           3-Cl      H         H            i-C3F7
propargyl      3-Cl      H         H            CH2CF3
Et             3-Cl      H         H            CF2CHF2
i-Pr           3-Cl      H         H            CHF2
t-Bu           3-Cl      5-Br      Ph           CH2CF3
cyclopropyl    3-Cl      H         Ph           CF2CHF2
Et             3-Cl      H         Ph           CH2CF3
i-Pr           3-Br      H         2-pyridyl    CF2CHF2
t-Bu           3-Cl      H         2-pyridyl    CHF2
Me             3-Cl      H         2-ClPh       Et
Et             3-Cl      5-Cl      2-ClPh       CBrF2
i-Pr           3-Cl      H         2-ClPh       CH2CF3
R3            R4a       R4b       Rva              Rvb
t-Bu           3-I        H          2-ClPh            CF2CHF2
Me             3-Cl       5-Me       2-ClPh            CH2CF3
propargyl      3-Cl       H          2-BrPh            CH2CF3
i-Pr           3-Cl       H          2-MePh            CF2CHF2
t-Bu           3-Cl       5-CN       2-CNPh            CH2CF3
Me             3-Cl       H          2-FPh             CH2CF3
Et             3-Cl       H          2，6-F2Ph        CF2CHF2
i-Pr           3-Cl       5-Br       2，4-F2Ph        CH2CF3
t-Bu           3-F        H          2，5-F2Ph        CF2CHF2
Me             3-Cl       5-I        2-MeOPh           CF3
Et             3-Cl       H          3-Cl-2-pyridyl    CHF2
i-Pr           3-CN       H          3-Cl-2-pyridyl    CBrF2
t-Bu           3-Cl       H          3-Cl-2-pyridyl    CH2CF3
propargyl      3-Cl       H          3-Cl-2-pyridyl    CF2CHF2
Et             3-Cl       5-Br       3-Cl-2-pyridyl    CH2CF3
i-Pr           3-Cl       H          3-F-2-pyridyl     CF3
t-Bu           3-Br       H          3-CF3-2-pyridyl  CH2CF3
Me             3-Cl       H          3-Me-2-pyridyl    CF2CHF2
Et             3-Cl       H          3-Br-2-Pyridyl    CClF2
i-Pr           3-Cl       5-Cl       3-Br-2-pyridyl    CH2CF3
t-Bu           3-Cl       H          3-Br-2-pyridyl    CF3
i-Pr           3-Cl       H          3-Br-2-pyridyl    CF2CHF2
Me             6-Cl       H          Et                CHF2
Et             6-Br       4-Me       Me                CH2CF3
i-Pr           6-Cl       H          Et                CH2CF3
t-Bu           6-Cl       Cl         Me                CH2CF3
Me             6-Cl       H          Me                CH2CF3
Et             6-Cl       H          Me                CF2CHF2
i-Pr           6-F        4-Br       Me                CHF2
t-Bu           6-Cl       H          Me                CHF2
propargyl      6-Cl       H          Me                CBrF2
cyclopropyl    6-Cl       H          Me                CH2F
i-Pr           6-Cl       4-Cl       Me                CH2CF3
t-Bu           6-Cl       H          Me                Et
Me             6-Cl       H          Me                n-Pr
Et             6-Cl       H          Et                CH2C2F5
R3            R4a       R4b      Rva         Rvb
i-Pr           6-I        4-CN      n-Pr         CH2CF3
t-Bu           6-Cl       H         i-Pr         CF3
propargyl      6-Cl       H         Cl           C2F5
cyclopropyl    6-Cl       H         F            CHF2
i-Pr           6-Cl       H         Me           CH2CF3
t-Bu           6-Cl       4-Br      Me           CHF2
Me             6-Cl       H         Me           CH2CF3
Et             6-F        H         Me           CH2CF3
i-Pr           6-Cl       H         Me           CH2Cl
t-Bu           6-Cl       4-Cl      Me           CClF2
Me             6-Cl       H         Me           CH2CH2Cl
Et             6-I        H         Me           n-C3F7
i-Pr           6-Cl       H         Me           i-C3F7
t-Bu           6-Cl       4-F       Me           Allyl
propargyl      6-Cl       H         CF3         CF2CHF2
Et             6-Cl       H         CF3         i-C3F7
i-Pr           6-Cl       H         OMe          CF2CHF2
t-Bu           6-Cl       4-Cl      H            CF2CHF2
Me             6-Cl       H         H            CF2CHF2
Et             6-Cl       H         H            Me
i-Pr           6-Cl       H         H            CH2CF3
t-Bu           6-Br       H         H            CH2CF3
cyclopropyl    6-Cl       4-Br      H            CH2CF3
Et             6-Cl       H         H            C2F5
i-Pr           6-Cl       H         H            C2F5
t-Bu           6-F        4-Me      H            C2F5
Me             6-Cl       H         H            CF2CHF2
Et             6-Cl       H         H            CH2CF3
i-Pr           6-CN       4-Cl      H            n-C3F7
t-Bu           6-Cl       H         Ph           i-C3F7
propargyl      6-Cl       H         Ph           CH2CF3
Et             6-Cl       H         Ph           CF2CHF2
i-Pr           6-Cl       H         2-pyridyl    CHF2
t-Bu           6-Cl       4-Br      2-pyridyl    CH2CF3
cyclopropyl    6-Cl       H         2-ClPh       CF2CHF2
Et             6-F        H         2-ClPh       CH2CF3
R3            R4a    R4b    Rva               Rvb
i-Pr           6-Cl    H       2-ClPh             CF2CHF2
t-Bu           6-Cl    H       2-ClPh             CHF2
Me             6-Cl    H       2-ClPh             Et
Et             6-Br    4-Cl    2-BrPh             CBrF2
i-Pr           6-Cl    H       2-MePh             CH2CF3
t-Bu           6-Cl    H       2-CNPh             CF2CHF2
Me             6-Cl    H       2-FPh              CH2CF3
propargyl      6-Cl    H       2，6-F2Ph         CH2CF3
i-Pr           6-Br    H       2，4-F2Ph         CF2CHF2
t-Bu           6-Cl    4-CN    2，5-F2Ph         CH2CF3
Me             6-Cl    H       2-MeOPh            CH2CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF2CHF2
i-Pr           6-Cl    4-Br    3-Cl-2-pyridyl     CH2CF3
t-Bu           6-CN    H       3-Cl-2-pyridyl     CF2CHF2
Me             6-Cl    4-I     3-Cl-2-pyridyl     CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CHF2
i-Pr           6-Br    H       3-F-2-pyridyl      CBrF2
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CH2CF3
propargyl      6-Cl    H       3-Me-2-pyridyl     CF2CHF2
Et             6-Cl    4-Br    3-Br-2-pyridyl     CH2CF3
i-Pr           6-Cl    H       3-Br-2-pyridyl     CF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     CH2CF3
Me             6-Cl    H       3-Br-2-pyridyl     CF2CHF2
                         Table 19
Figure A0281824702191
R3            R4a        R4b    Rva               Rvb
Me             3-Me        H       H                  CHF2
R3            R4a        R4b    Rva    Rvb
Et             3-Me        5-Me    H       CH2CF3
i-Pr           3-Me        H       H       CH2CF3
t-Bu           3-Me        5-Cl    Me      CH2CF3
Me             3-Me        H       Et      CH2CF3
Et             3-Me        H       Me      CF2CHF2
i-Pr           3-Me        5-Br    Et      CHF2
t-Bu           3-Me        H       Me      CHF2
propargyl      3-Me        H       Me      CBrF2
cyclopropyl    3-Me        H       Me      CH2F
i-Pr           3-Me        5-Cl    Me      CH2CF3
t-Bu           3-Me        H       Me      Et
Me             3-Me        5-CN    Me      n-Pr
Et             3-Me        H       Me      CH2C2F5
i-Pr           3-Me        H       Me      CH2CF3
t-Bu           3-Me        H       Me      CF3
propargyl      3-Me        H       Me      C2F5
cyclopropyl    3-Me        H       Et      CHF2
i-Pr           3-Me        H       n-Pr    CH2CF3
t-Bu           3-Me        5-Br    i-Pr    CHF2
Me             3-Me        H       Cl      CH2CF3
Et             3-Me        H       F       CH2CF3
i-Pr           3-Me        H       Me      CH2Cl
t-Bu           3-Me        5-Cl    Me      CClF2
Me             3-Me        H       Me      CH2CH2Cl
Et             3-Me        H       Me      n-C3F7
i-Pr           3-Me        H       Me      i-C3F7
t-Bu           3-Me        5-F     Me      Allyl
propargyl      3-Me        H       Et      CF2CHF2
Et             3-Me        H       Et      i-C3F7
i-Pr           3-Me        H       n-Pr    CF2CHF2
t-Bu           3-Me        5-Cl    i-Pr    CF2CHF2
Me             3-Me        H       CF3    CF2CHF2
Et             3-Me        H       CF3    Me
i-Pr           3-Me        H       OMe     CH2CF3
t-Bu           3-Me        H       H       CH2CF3
cyclopropyl    3-Me        5-Br    H       CH2CF3
R3            R4a    R4b    Rva               Rvb
Et             3-Me    H       H                  C2F5
i-Pr           3-Me    5-Me    H                  C2F5
t-Bu           3-Me    H       H                  C2F5
Me             3-Me    H       H                  CF2CHF2
Et             3-Me    H       i-Pr               CH2CF3
i-Pr           3-Me    5-Cl    H                  n-C3F7
t-Bu           3-Me    H       H                  i-C3F7
propargyl      3-Me    H       Ph                 CH2CF3
Et             3-Me    H       Ph                 CF2CHF2
i-Pr           3-Me    H       Ph                 CHF2
t-Bu           3-Me    5-Br    2-pyridyl          CH2CF3
cyclopropyl    3-Me    H       2-pyridyl          CF2CHF2
Et             3-Me    H       2-ClPh             CH2CF3
i-Pr           3-Me    H       2-ClPh             CF2CHF2
t-Bu           3-Me    H       2-ClPh             CHF2
Me             3-Me    H       2-ClPh             Et
Et             3-Me    5-Cl    2-ClPh             CBrF2
i-Pr           3-Me    H       2-BrPh             CH2CF3
t-Bu           3-Me    H       2-MePh             CF2CHF2
Me             3-Me    H       2-CNPh             CH2CF3
propargyl      3-Me    H       2-FPh              CH2CF3
i-Pr           3-Me    5-CN    2，6-F2Ph         CF2CHF2
t-Bu           3-Me    H       2，4-F2Ph         CH2CF3
Me             3-Me    H       2，5-F2Ph         CH2CF3
Et             3-Me    H       2-MeOPh            CF2CHF2
i-Pr           3-Me    5-Br    3-Cl-2-pyridyl     CH2CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     CF2CHF2
Me            3-Me    5-I     3-Cl-2-pyridyl     CF3
Et             3-Me    H       3-Cl-2-pyridyl     CHF2
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     CBrF2
t-Bu           3-Me    H       3-F-2-pyridyl      CH2CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF2CHF2
Et             3-Me    5-Br    3-Me-2-pyridyl     CH2CF3
i-Pr           3-Me    H       3-Br-2-pyridyl     CF3
t-Bu           3-Me    H       3-Br-2-pyridyl     CH2CF3
Me             3-Me    H       3-Br-2-pyridyl     CF2CHF2
R3            R4a    R4b    Rva              Rvb
Et             3-Me    H       3-Br-2-pyridyl    CClF2
Me             6-Me    H       H                 CHF2
Et             6-Me    4-Me    H                 CH2CF3
i-Pr           6-Me    H       H                 CH2CF3
t-Bu           6-Me    Cl      Me                CH2CF3
Me             6-Me    H       Et                CH2CF3
Et             6-Me    H       Me                CF2CHF2
i-Pr           6-Me    4-Br    Et                CHF2
t-Bu           6-Me    H       Me                CHF2
propargyl      6-Me    H       Me                CBrF2
cyclopropyl    6-Me    H       Me                CH2F
i-Pr           6-Me    4-Cl    Me                CH2CF3
t-Bu           6-Me    H       Me                Et
Me             6-Me    H       Me                n-Pr
Et             6-Me    H       Me                CH2C2F5
i-Pr           6-Me    4-CN    Me                CH2CF3
t-Bu           6-Me    H       Me                CF3
propargyl      6-Me    H       Me                C2F5
cyclopropyl    6-Me    H       Et                CHF2
i-Pr           6-Me    H       n-Pr              CH2CF3
t-Bu           6-Me    4-Br    i-Pr              CHF2
Me             6-Me    H       Cl                CH2CF3
Et             6-Me    H       F                 CH2CF3
i-Pr           6-Me    H       Me                CH2Cl
t-Bu           6-Me    4-Cl    Me                CClF2
Me             6-Me    H       Me                CH2CH2Cl
Et             6-Me    H       Me                n-C3F7
i-Pr           6-Me    H       Me                i-C3F7
t-Bu           6-Me    4-F     Me                Allyl
propargyl      6-Me    H       Me                CF2CHF2
Et             6-Me    H       Me                i-C3F7
i-Pr           6-Me    H       Me                CF2CHF2
t-Bu           6-Me    4-Cl    Me                CF2CHF2
Me             6-Me    H       CF3              CF2CHF2
Et             6-Me    H       CF3              Me
i-Pr           6-Me    H       OMe               CH2CF3
R3            R4a    R4b    Rva              Rvb
t-Bu           6-Me    H       H                 CH2CF3
cyclopropyl    6-Me    4-Br    H                 CH2CF3
Et             6-Me    H       H                 C2F5
i-Pr           6-Me    H       H                 C2F5
t-Bu           6-Me    4-Me    H                 C2F5
Me             6-Me    H       H                 CF2CHF2
Et             6-Me    H       H                 CH2CF3
i-Pr           6-Me    4-Cl    H                 n-C3F7
t-Bu           6-Me    H       H                 i-C3F7
propargyl      6-Me    H       H                 CH2CF3
Et             6-Me    H       H                 CF2CHF2
i-Pr           6-Me    H       H                 CHF2
t-Bu           6-Me    4-Br    Ph                CH2CF3
cyclopropyl    6-Me    H       Ph                CF2CHF2
Et             6-Me    H       Ph                CH2CF3
i-Pr           6-Me    H       2-pyridyl         CF2CHF2
t-Bu           6-Me    H       2-pyridyl         CHF2
Me             6-Me    H       2-ClPh            Et
Et             6-Me    4-Cl    2-ClPh            CBrF2
i-Pr           6-Me    H       2-ClPh            CH2CF3
t-Bu           6-Me    4-CN    2-ClPh            CF2CHF2
Me             6-Me    H       2-ClPh            CH2CF3
propargyl      6-Me    H       2-BrPh            CH2CF3
i-Pr           6-Me    H       2-MePh            CF2CHF2
t-Bu           6-Me    H       2-CNPh            CH2CF3
Me             6-Me    H       2-FPh             CH2CF3
Et             6-Me    H       2，6-F2Ph        CF2CHF2
i-Pr           6-Me    4-Br    2，4-F2Ph        CH2CF3
t-Bu           6-Me    H       2，5-F2Ph        CF2CHF2
Me             6-Me    4-I     2-MeOPh           CF3
Et             6-Me    H       3-Cl-2-pyridyl    CHF2
i-Pr           6-Me    H       3-Cl-2-pyridyl    CBrF2
t-Bu           6-Me    H       3-Cl-2-pyridyl    CH2CF3
propargyl      6-Me    H       3-Cl-2-pyridyl    CF2CHF2
Et             6-Me    4-Br    3-Cl-2-pyridyl    CH2CF3
i-Pr           6-Me    H       3-F-2-pyridyl     CF3
R3            R4a    R4b    Rva               Rvb
t-Bu           6-Me    H       3-CF3-2-pyridyl   CH2CF3
Me             6-Me    H       3-Me-2-pyridyl     CF2CHF2
Et             6-Me    H       3-Br-2-pyridyl     CClF2
i-Pr           6-Me    4-Cl    3-Br-2-puridyl     CH2CF3
t-Bu           6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    H       3-Br-2-pyridyl     CF2CHF2
Me             3-Cl    H       H                  CHF2
Et             3-Br    5-Me    H                  CH2CF3
i-Pr           3-Cl    H       H                  CH2CF3
t-Bu           3-Cl    5-Cl    Me                 CH2CF3
Me             3-Cl    H       Et                 CH2CF3
Et             3-Cl    H       Me                 CF2CHF2
i-Pr           3-Cl    5-Br    Et                 CHF2
t-Bu           3-Cl    H       Me                 CHF2
proparyl       3-Cl    H       Me                 CBrF2
cyclopropyl    3-Cl    H       Me                 CH2F
i-Pr           3-Cl    5-Cl    Me                 CH2CF3
t-Bu           3-Cl    H       Me                 Et
Me             3-F     H       Me                 n-Pr
Et             3-Cl    H       Me                 CH2C2F5
i-Pr           3-Cl    5-CN    Me                 CH2CF3
t-Bu           3-Cl    H       Me                 CF3
propargyl      3-Cl    H       Me                 C2F5
cyclopropyl    3-Cl    H       Et                 CHF2
i-Pr           3-Cl    H       n-Pr               CH2CF3
t-Bu           3-Cl    5-Br    i-Pr               CHF2
Me             3-Cl    H       Cl                 CH2CF3
Et             3-Br    H       F                  CH2CF3
i-Pr           3-Cl    H       Me                 CH2Cl
t-Bu           3-Cl    5-Cl    Me                 CClF2
Me             3-Cl    H       Me                 CH2CH2Cl
Et             3-Cl    H       Me                 n-C3F7
i-Pr           3-Cl    H       Me                 i-C3F7
t-Bu           3-Cl    5-F     Me                 Allyl
propargyl      3-Cl    H       Me                 CF2CHF2
Et             3-Cl    H       Me                 i-C3F7
R3            R4a    R4b    Rva              Rvb
i-Pr           3-Br    H       Me                CF2CHF2
t-Bu           3-Cl    5-Cl    Me                CF2CHF2
Me             3-Cl    H       CF3              CF2CHF2
Et             3-CN    H       CF3              Me
i-Pr           3-Cl    H       OMe               CH2CF3
t-Bu           3-Cl    H       H                 CH2CF3
cyclopropyl    3-Cl    5-Br    H                 CH2CF3
Et             3-Cl    H       H                 C2F5
i-Pr           3-Cl    H       H                 C2F5
t-Bu           3-Cl    H       H                 C2F5
Me             3-F     H       H                 CF2CHF2
Et             3-Cl    H       H                 CH2CF3
i-Pr           3-Cl    5-Cl    H                 n-C3F7
t-Bu           3-Cl    H       H                 i-C3F7
propargyl      3-Cl    H       H                 CH2CF3
Et             3-Cl    H       H                 CF2CHF2
i-Pr           3-Cl    H       H                 CHF2
t-Bu           3-Cl    5-Br    Ph                CH2CF3
cyclopropyl    3-Cl    H       Ph                CF2CHF2
Et             3-Cl    H       Ph                CH2CF3
i-Pr           3-Br    H       2-pyridyl         CF2CHF2
t-Bu           3-Cl    H       2-pyridyl         CHF2
Me             3-Cl    H       2-ClPh            Et
Et             3-Cl    5-Cl    2-ClPh            CBrF2
i-Pr           3-Cl    H       2-ClPh            CH2CF3
t-Bu           3-I     H       2-ClPh            CF2CHF2
Me             3-Cl    5-Me    2-ClPh            CH2CF3
propargyl      3-Cl    H       2-BrPh            CH2CF3
i-Pr           3-Cl    H       2-MePh            CF2CHF2
t-Bu           3-Cl    5-CN    2-CNPh            CH2CF3
Me             3-Cl    H       2-FPh             CH2CF3
Et             3-Cl    H       2，6-F2Ph        CF2CHF2
i-Pr           3-Cl    5-Br    2，4-F2Ph        CH2CF3
t-Bu           3-F     H       2，5-F2Ph        CF2CHF2
Me             3-Cl    5-I     2-MeOPh           CF3
Et             3-Cl    H       3-Cl-2-pyridyl    CHF2
R3            R4a    R4b    Rva               Rvb
i-Pr           3-CN    H       3-Cl-2-pyridyl     CBrF2
t-Bu           3-Cl    H       3-Cl-2-pyridyl     CH2CF3
propargyl      3-Cl    H       3-Cl-2-pyridyl     CF2CHF2
Et             3-Cl    5-Br    3-Cl-2-pyridyl     CH2CF3
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CH2CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF2CHF2
Et             3-Cl    H       3-Br-2-pyridyl     CClF2
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl     CH2CF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    H       3-Br-2-pyridyl     CF2CHF2
Me             6-Cl    H       Et                 CHF2
Et             6-Br    4-Me    Me                 CH2CF3
i-Pr           6-Cl    H       Et                 CH2CF3
t-Bu           6-Cl    Cl      Me                 CH2CF3
Me             6-Cl    H       Me                 CH2CF3
Et             6-Cl    H       Me                 CF2CHF2
i-Pr           6-F     4-Br    Me                 CHF2
t-Bu           6-Cl    H       Me                 CHF2
propargyl      6-Cl    H       Me                 CBrF2
cyclopropyl    6-Cl    H       Me                 CH2F
i-Pr           6-Cl    4-Cl    Me                 CH2CF3
t-Bu           6-Cl    H       Me                 Et
Me             6-Cl    H       Me                 n-Pr
Et             6-Cl    H       Et                 CH2C2F5
i-Pr           6-I     4-CN    n-Pr               CH2CF3
t-Bu           6-Cl    H       i-Pr               CF3
propargyl      6-Cl    H       Cl                 C2F5
cyclopropyl    6-Cl    H       F                  CHF2
i-Pr           6-Cl    H       Me                 CH2CF3
t-Bu           6-Cl    4-Br    Me                 CHF2
Me             6-Cl    H       Me                 CH2CF3
Et             6-F     H       Me                 CH2CF3
i-Pr           6-Cl    H       Me                 CH2Cl
t-Bu           6-Cl    4-Cl    Me                 CClF2
Me             6-Cl    H       Me                 CH2CH2Cl
R3            R4a        R4b    Rva         Rvb
Et             6-I         H       Me           n-C3F7
i-Pr           6-Cl        H       Me           i-C3F7
t-Bu           6-Cl        4-F     Me           Allyl
propargyl      6-Cl        H       CF3         CF2CHF2
Et             6-Cl        H       CF3         i-C3F7
i-Pr           6-Cl        H       OMe          CF2CHF2
t-Bu           6-Cl        4-Cl    H            CF2CHF2
Me             6-Cl        H       H            CF2CHF2
Et             6-Cl        H       H            Me
i-Pr           6-Cl        H       H            CH2CF3
t-Bu           6-Br        H       H            CH2CF3
cyclopropyl    6-Cl        4-Br    H            CH2CF3
Et             6-Cl        H       H            C2F5
i-Pr           6-Cl        H       H            C2F5
t-Bu           6-F         4-Me    H            C2F5
Me             6-Cl        H       H            CF2CHF2
Et             6-Cl        H       H            CH2CF3
i-Pr           6-CN        4-Cl    H            n-C3F3
t-Bu           6-Cl        H       Ph           i-C3F7
propargyl      6-Cl        H       Ph           CH2CF3
Et             6-Cl        H       Ph           CF2CHF2
i-Pr           6-Cl        H       2-pyridyl    CHF2
t-Bu           6-Cl        4-Br    2-pyridyl    CH2CF3
cyclopropyl    6-Cl        H       2-ClPh       CF2CHF2
Et             6-F         H       2-ClPh       CH2CF3
i-Pr           6-Cl        H       2-ClPh       CF2CHF2
t-Bu           6-Cl        H       2-ClPh       CHF2
Me             6-Cl        H       2-ClPh       Et
Et             6-Br        4-Cl    2-BrPh       CBrF2
i-Pr           6-Cl        H       2-MePh       CH2CF3
t-Bu           6-Cl        H       2-CNPh       CF2CHF2
Me             6-Cl        H       2-FPh        CH2CF3
propargyl      6-Cl        H       2，6-F2Ph   CH2CF3
i-Pr           6-Br        H       2，4-F2Ph   CF2CHF2
t-Bu           6-Cl        4-CN    2，5-F2Ph   CH2CF3
Me             6-Cl        H       2-MeOPh      CH2CF3
R3            R4a    R4b    Rva               Rvb
Et             6-Cl    H       3-Cl-2-pyridyl     CF2CHF2
i-Pr           6-Cl    4-Br    3-Cl-2-pyridyl     CH2CF3
t-Bu           6-CN    H       3-Cl-2-pyridyl     CF2CHF2
Me             6-Cl    4-I     3-Cl-2-pyridyl     CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CHF2
i-Pr           6-Br    H       3-F-2-pyridyl      CBrF2
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CH2CF3
propargyl      6-Cl    H       3-Me-2-pyridyl     CF2CHF2
Et             6-Cl    4-Br    3-Br-2-pyridyl     CH2CF3
i-Pr           6-Cl    H       3-Br-2-pyridyl     CF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     CH2CF3
Me             6-Cl    H       3-Br-2-pyridyl     CF2CHF2
                         Table 20
R3            R4a    R4b    Rva               Rvb
Me             3-Me    H       H                  CHF2
Et             3-Me    5-Me    H                  CH2CF3
i-Pr           3-Me    H       H                  CH2CF3
t-Bu           3-Me    5-Cl    Me                 CH2CF3
Me             3-Me    H       Et                 CH2CF3
Et             3-Me    H       Me                 CF2CHF2
i-Pr           3-Me    5-Br    Et                 CHF2
t-Bu           3-Me    H       Me                 CHF2
propargyl      3-Me    H       Me                 CBrF2
cyclopropyl    3-Me    H       Me                 CH2F
i-Pr           3-Me    5-Cl    Me                 CH2CF3
t-Bu           3-Me    H       Me                 Et
R3            R4a    R4b    Rva         Rvb
Me             3-Me    5-CN    Me           n-Pr
Et             3-Me    H       Me           CH2C2F5
i-Pr           3-Me    H       Me           CH2CF3
t-Bu           3-Me    H       Me           CF3
propargyl      3-Me    H       Me           C2F5
cyclopropyl    3-Me    H       Et           CHF2
i-Pr           3-Me    H       n-Pr         CH2CF3
t-Bu           3-Me    5-Br    i-Pr         CHF2
Me             3-Me    H       Cl           CH2CF3
Et             3-Me    H       F            CH2CF3
i-Pr           3-Me    H       Me           CH2Cl
t-Bu           3-Me    5-Cl    Me           CClF2
Me             3-Me    H       Me           CH2CH2Cl
Et             3-Me    H       Me           n-C3F7
i-Pr           3-Me    H       Me           i-C3F7
t-Bu           3-Me    5-F     Me           Allyl
propargyl      3-Me    H       Et           CF2CHF2
Et             3-Me    H       Et           i-C3F7
i-Pr           3-Me    H       n-Pr         CF2CHF2
t-Bu           3-Me    5-Cl    i-Pr         CF2CHF2
Me             3-Me    H       CF3         CF2CHF2
Et             3-Me    H       CF3         Me
i-Pr           3-Me    H       OMe          CH2CF3
t-Bu           3-Me    H       H            CH2CF3
cyclopropyl    3-Me    5-Br    H            CH2CF3
Et             3-Me    H       H            C2F5
i-Pr           3-Me    5-Me    H            C2F5
t-Bu           3-Me    H       H            C2F5
Me             3-Me    H       H            CF2CHF2
Et             3-Me    H       i-Pr         CH2CF3
i-Pr           3-Me    5-Cl    H            n-C3F7
t-Bu           3-Me    H       H            i-C3F7
propargyl      3-Me    H       Ph           CH2CF3
Et             3-Me    H       Ph           CF2CHF2
i-Pr           3-Me    H       Ph           CHF2
t-Bu           3-Me    5-Br    2-pyridyl    CH2CF3
R3            R4a    R4b    Rva               Rvb
cyclopropyl    3-Me    H       2-pyridyl          CF2CHF2
Et             3-Me    H       2-ClPh             CH2CF3
i-Pr           3-Me    H       2-ClPh             CF2CHF2
t-Bu           3-Me    H       2-ClPh             CHF2
Me             3-Me    H       2-ClPh             Et
Et             3-Me    5-Cl    2-ClPh             CBrF2
i-Pr           3-Me    H       2-BrPh             CH2CF3
t-Bu           3-Me    H       2-MePh             CF2CHF2
Me             3-Me    H       2-CNPh             CH2CF3
propargyl      3-Me    H       2-FPh              CH2CF3
i-Pr           3-Me    5-CN    2，6-F2Ph         CF2CHF2
t-Bu           3-Me    H       2，4-F2Ph         CH2CF3
Me             3-Me    H       2，5-F2Ph         CH2CF3
Et             3-Me    H       2-MeOPh            CF2CHF2
i-Pr           3-Me    5-Br    3-Cl-2-pyridyl     CH2CF3
t-Bu           3-Me    H       3-Cl-2-pyridyl     CF2CHF2
Me             3-Me    5-I     3-Cl-2-pyridyl     CF3
Et             3-Me    H       3-Cl-2-pyridyl     CHF2
i-Pr           3-Me    5-Me    3-Cl-2-pyridyl     CBrF2
t-Bu           3-Me    H       3-F-2-pyridyl      CH2CF3
propargyl      3-Me    H       3-CF3-2-pyridyl   CF2CHF2
Et             3-Me    5-Br    3-Me-2-pyridyl     CH2CF3
i-Pr           3-Me    H       3-Br-2-pyridyl     CF3
t-Bu           3-Me    H       3-Br-2-pyridyl     CH2CF3
Me             3-Me    H       3-Br-2-pyridyl     CF2CHF2
Et             3-Me    H       3-Br-2-pyridyl     CClF2
Me             6-Me    H       H                  CHF2
Et             6-Me    4-Me    H                  CH2CF3
i-Pr           6-Me    H       H                  CH2CF3
t-Bu           6-Me    Cl      Me                 CH2CF3
Me             6-Me    H       Et                 CH2CF3
Et             6-Me    H       Me                 CF2CHF2
i-Pr           6-Me    4-Br    Et                 CHF2
t-Bu           6-Me    H       Me                 CHF2
propargyl      6-Me    H       Me                 CBrF2
cyclopropyl    6-Me    H       Me                 CH2F
R3            R4a        R4b        Rva    Rvb
i-Pr           6-Me        4-Cl        Me      CH2CF3
t-Bu           6-Me        H           Me      Et
Me             6-Me        H           Me      n-Pr
Et             6-Me        H           Me      CH2C2F5
i-Pr           6-Me        4-CN        Me      CH2CF3
t-Bu           6-Me        H           Me      CF3
propargyl      6-Me        H           Me      C2F5
cyclopropyl    6-Me        H           Et      CHF2
i-Pr           6-Me        H           n-Pr    CH2CF3
t-Bu           6-Me        4-Br        i-Pr    CHF2
Me             6-Me        H           Cl      CH2CF3
Et             6-Me        H           F       CH2CF3
i-Pr           6-Me        H           Me      CH2Cl
t-Bu           6-Me        4-Cl        Me      CClF2
Me             6-Me        H           Me      CH2CH2Cl
Et             6-Me        H           Me      n-C3F7
i-Pr           6-Me        H           Me      i-C3F7
t-Bu           6-Me        4-F         Me      Allyl
propargyl      6-Me        H           Me      CF2CHF2
Et             6-Me        H           Me      i-C3F7
i-Pr           6-Me        H           Me      CF2CHF2
t-Bu           6-Me        4-Cl        Me      CF2CHF2
Me             6-Me        H           CF3    CF2CHF2
Et             6-Me        H           CF3    Me
i-Pr           6-Me        H           OMe     CH2CF3
t-Bu           6-Me        H           H       CH2CF3
cyclopropyl    6-Me        4-Br        H       CH2CF3
Et             6-Me        H           H       C2F5
i-Pr           6-Me        H           H       C2F5
t-Bu           6-Me        4-Me        H       C2F5
Me             6-Me        H           H       CF2CHF2
Et             6-Me        H           H       CH2CF3
i-Pr           6-Me        4-Cl        H       n-C3F7
t-Bu           6-Me        H           H       i-C3F7
propargyl      6-Me        H           H       CH2CF3
Et             6-Me        H           H       CF2CHF2
R3            R4a    R4b    Rva               Rvb
i-Pr           6-Me    H       H                  CHF2
t-Bu           6-Me    4-Br    Ph                 CH2CF3
cyclopropyl    6-Me    H       Ph                 CF2CHF2
Et             6-Me    H       Ph                 CH2CF3
i-Pr           6-Me    H       2-pyridyl          CF2CHF2
t-Bu           6-Me    H       2-pyridyl          CHF2
Me             6-Me    H       2-ClPh             Et
Et             6-Me    4-Cl    2-ClPh             CBrF2
i-Pr           6-Me    H       2-ClPh             CH2CF3
t-Bu           6-Me    4-CN    2-ClPh             CF2CHF2
Me             6-Me    H       2-ClPh             CH2CF3
propargyl      6-Me    H       2-BrPh             CH2CF3
i-Pr           6-Me    H       2-MePh             CF2CHF2
t-Bu           6-Me    H       2-CNPh             CH2CF3
Me             6-Me    H       2-FPh              CH2CF3
Et             6-Me    H       2，6-F2Ph         CF2CHF2
i-Pr           6-Me    4-Br    2，4-F2Ph         CH2CF3
t-Bu           6-Me    H       2，5-F2Ph         CF2CHF2
Me             6-Me    4-I     2-MeOPh            CF3
Et             6-Me    H       3-Cl-2-pyridyl     CHF2
i-Pr           6-Me    H       3-Cl-2-pyridyl     CBrF2
t-Bu           6-Me    H       3-Cl-2-pyridyl     CH2CF3
propargyl      6-Me    H       3-Cl-2-pyridyl     CF2CHF2
Et             6-Me    4-Br    3-Cl-2-pyridyl     CH2CF3
i-Pr           6-Me    H       3-F-2-pyridyl      CF3
t-Bu           6-Me    H       3-CF3-2-pyridyl   CH2CF3
Me             6-Me    H       3-Me-2-pyridyl     CF2CHF2
E，            6-Me    H       3-Br-2-pyridyl     CClF2
i-Pr           6-Me    4-Cl    3-Br-2-pyridyl     CH2CF3
t-Bu           6-Me    H       3-Br-2-pyridyl     CF3
i-Pr           6-Me    H       3-Br-2-pyridyl     CF2CHF2
Me             3-Cl    H       H                  CHF2
Et             3-Br    5-Me    H                  CH2CF3
i-Pr           3-Cl    H       H                  CH2CF3
t-Bu           3-Cl    5-Cl    Me                 CH2CF3
Me             3-Cl    H       Et                 CH2CF3
R3            R4a        R4b        Rva   Rvb
Et             3-Cl        H           Me     CF2CHF2
i-Pr           3-Cl        5-Br        Et     CHF2
t-Bu           3-Cl        H           Me     CHF2
propargyl      3-Cl        H           Me     CBrF2
cyclopropyl    3-Cl        H           Me     CH2F
i-Pr           3-Cl        5-Cl        Me     CH2CF3
t-Bu           3-Cl        H           Me     Et
Me             3-F         H           Me     n-Pr
Et             3-Cl        H           Me     CH2C2F5
i-Pr           3-Cl        5-CN        Me     CH2CF3
t-Bu           3-Cl        H           Me     CF3
propargyl      3-Cl        H           Me     C2F5
cyclopropyl    3-Cl        H           Et     CHF2
i-Pr           3-Cl        H           n-Pr   CH2CF3
t-Bu           3-Cl        5-Br        i-Pr   CHF2
Me             3-Cl        H           Cl     CH2CF3
Et             3-Br        H           F      CH2CF3
i-Pr           3-Cl        H           Me     CH2Cl
t-Bu           3-Cl        5-Cl        Me     CClF2
Me             3-Cl        H           Me     CH2CH2Cl
Et             3-Cl        H           Me     n-C3F7
i-Pr           3-Cl        H           Me     i-C3F7
t-Bu           3-Cl        5-F         Me     Allyl
propargyl      3-Cl        H           Me     CF2CHF2
Et             3-Cl        H           Me     i-C3F7
i-Pr           3-Br        H           Me     CF2CHF2
t-Bu           3-Cl        5-Cl        Me     CF2CHF2
Me             3-Cl        H           CF3   CF2CHF2
Et             3-CN        H           CF3   Me
i-Pr           3-Cl        H           OMe    CH2CF3
t-Bu           3-Cl        H           H      CH2CF3
cyclopropyl    3-Cl        5-Br        H      CH2CF3
Et             3-Cl        H           H      C2F5
i-Pr           3-Cl        H           H      C2F5
t-Bu           3-Cl        H           H      C2F5
Me             3-F         H           H      CF2CHF2
R3            R4a    R4b    Rva               Rvb
Et             3-Cl    H       H                  CH2CF3
i-Pr           3-Cl    5-Cl    H                  n-C3F7
t-Bu           3-Cl    H       H                  i-C3F7
propargyl      3-Cl    H       H                  CH2CF3
Et             3-Cl    H       H                  CF2CHF2
i-Pr           3-Cl    H       H                  CHF2
t-Bu           3-Cl    5-Br    Ph                 CH2CF3
cyclopropyl    3-Cl    H       Ph                 CF2CHF2
Et             3-Cl    H       Ph                 CH2CF3
i-Pr           3-Br    H       2-pyridyl          CF2CHF2
t-Bu           3-Cl    H       2-pyridyl          CHF2
Me             3-Cl    H       2-ClPh             Et
Et             3-Cl    5-Cl    2-ClPh             CBrF2
i-Pr           3-Cl    H       2-ClPh             CH2CF3
t-Bu           3-I     H       2-ClPh             CF2CHF2
Me             3-Cl    5-Me    2-ClPh             CH2CF3
propargyl      3-Cl    H       2-BrPh             CH2CF3
i-Pr           3-Cl    H       2-MePh             CF2CHF2
t-Bu           3-Cl    5-CN    2-CNPh             CH2CF3
Me             3-Cl    H       2-FPh              CH2CF3
Et             3-Cl    H       2，6-F2Ph         CF2CHF2
i-Pr           3-Cl    5-Br    2，4-F2Ph         CH2CF3
t-Bu           3-F     H       2，5-F2Ph         CF2CHF2
Me             3-Cl    5-I     2-MeOPh            CF3
Et             3-Cl    H       3-Cl-2-pyridyl     CHF2
i-Pr           3-CN    H       3-Cl-2-pyridyl     CBrF2
t-Bu           3-Cl    H       3-Cl-2-pyridyl     CH2CF3
propargyl      3-Cl    H       3-Cl-2-pyridyl     CF2CHF2
Et             3-Cl    5-Br    3-Cl-2-pyridyl     CH2CF3
i-Pr           3-Cl    H       3-F-2-pyridyl      CF3
t-Bu           3-Br    H       3-CF3-2-pyridyl   CH2CF3
Me             3-Cl    H       3-Me-2-pyridyl     CF2CHF2
Et             3-Cl    H       3-Br-2-pyridyl     CClF2
i-Pr           3-Cl    5-Cl    3-Br-2-pyridyl     CH2CF3
t-Bu           3-Cl    H       3-Br-2-pyridyl     CF3
i-Pr           3-Cl    H       3-Br-2-pyridyl     CF2CHF2
R3            R4a        R4b        Rva    Rvb
Me             6-Cl        H           Et      CHF2
Et             6-Br        4-Me        Me      CH2CF3
i-Pr           6-Cl        H           Et      CH2CF3
t-Bu           6-Cl        Cl          Me      CH2CF3
Me             6-Cl        H           Me      CH2CF3
Et             6-Cl        H           Me      CF2CHF2
i-Pr           6-F         4-Br        Me      CHF2
t-Bu           6-Cl        H           Me      CHF2
propargyl      6-Cl        H           Me      CBrF2
cyclopropyl    6-Cl        H           Me      CH2F
i-Pr           6-Cl        4-Cl        Me      CH2CF3
t-Bu           6-Cl        H           Me      Et
Me             6-Cl        H           Me      n-Pr
Et             6-Cl        H           Et      CH2C2F5
i-Pr           6-I         4-CN        n-Pr    CH2CF3
t-Bu           6-Cl        H           i-Pr    CF3
propargyl      6-Cl        H           Cl      C2F5
cyclopropyl    6-Cl        H           F       CHF2
i-Pr           6-Cl        H           Me      CH2CF3
t-Bu           6-Cl        4-Br        Me      CHF2
Me             6-Cl        H           Me      CH2CF3
Et             6-F         H           Me      CH2CF3
i-Pr           6-Cl        H           Me      CH2Cl
t-Bu           6-Cl        4-Cl        Me      CClF2
Me             6-Cl        H           Me      CH2CH2Cl
Et             6-I         H           Me      n-C3F7
i-Pr           6-Cl        H           Me      i-C3F7
t-Bu，         6-Cl        4-F         Me      Allyl
propargyl      6-Cl        H           CF3    CF2CHF2
Et             6-Cl        H           CF3    i-C3F7
i-Pr           6-Cl        H           OMe     CF2CHF2
t-Bu           6-Cl        4-Cl        H       CF2CHF2
Me             6-Cl        H           H       CF2CHF2
Et             6-Cl        H           H       Me
i-Pr           6-Cl        H           H       CH2CF3
t-Bu           6-Br        H           H       CH2CF3
R3            R4a    R4b    Rva               Rvb
cyclopropyl    6-Cl    4-Br    H                  CH2CF3
Et             6-Cl    H       H                  C2F5
i-Pr           6-Cl    H       H                  C2F5
t-Bu           6-F     4-Me    H                  C2F5
Me             6-Cl    H       H                  CF2CHF3
Et             6-Cl    H       H                  CH2CF3
i-Pr           6-CN    4-Cl    H                  n-C3F7
t-Bu           6-Cl    H       Ph                 i-C3F7
propargyl      6-Cl    H       Ph                 CH2CF3
Et             6-Cl    H       Ph                 CF2CHF2
i-Pr           6-Cl    H       2-pyridyl          CHF2
t-Bu           6-Cl    4-Br    2-pyridyl          CH2CF3
cyclopropyl    6-Cl    H       2-ClPh             CF2CHF2
Et             6-F     H       2-ClPh             CH2CF3
i-Pr           6-Cl    H       2-ClPh             CF2CHF2
t-Bu           6-Cl    H       2-ClPh             CHF2
Me             6-Cl    H       2-ClPh             Et
Et             6-Br    4-Cl    2-BrPh             CBrF2
i-Pr           6-Cl    H       2-MePh             CH2CF3
t-Bu           6-Cl    H       2-CNPh             CF2CHF2
Me             6-Cl    H       2-FPh              CH2CF3
propargyl      6-Cl    H       2，6-F2Ph         CH2CF3
i-Pr           6-Br    H       2，4-F2Ph         CF2CHF2
t-Bu           6-Cl    4-CN    2，5-F2Ph         CH2CF3
Me             6-Cl    H       2-MeOPh            CH2CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CF2CHF2
i-Pr           6-Cl    4-Br    3-Cl-2-pyridyl     CH2CF3
t-Bu           6-CN    H       3-Cl-2-pyridyl     CF2CHF2
Me             6-Cl    4-I     3-Cl-2-pyridyl     CF3
Et             6-Cl    H       3-Cl-2-pyridyl     CHF2
i-Pr           6-Br    H       3-F-2-pyridyl      CBrF2
t-Bu           6-Cl    H       3-CF3-2-pyridyl   CH2CF3
Propargyl      6-Cl    H       3-Me-2-pyridyl     CF2CHF2
Et             6-Cl    4-Br    3-Br-2-pyridyl     CH2CF3
i-Pr           6-Cl    H       3-Br-2-pyridyl     CF3
t-Bu           6-Cl    H       3-Br-2-pyridyl     CH2CF3
R3       R4a        R4b       Rva              Rvb
Me        6-Cl        H          3-Br-2-pyridyl    CF2HCF2
                         本发明的生物学实施例
剂型/应用
本发明的化合物一般与农业上适宜的载体一起作为剂型或组合物来应用，适宜的载体包括至少一种液体稀释剂、固体稀释剂或表面活性剂。剂型或组合物成分的选择应与有效成分的物理性质、应用方式和环境因素例如土壤类型、湿度与温度相一致。有用的剂型包括液体如溶液(包括可乳化的浓缩物)、悬浮剂、乳液(包括微乳剂和/或悬浮剂)等等，它们可任选被粘稠成胶状物。有用的剂型也包括固体如粉剂、粉末、颗粒剂、片剂、丸剂、薄膜等，它们可以是水分散性的(“可湿的”)或水溶性的。有效成分可被(微)囊化，进一步制成悬浮剂或固体剂型；另外也可对有效成分的整个剂型进行胶囊化(或“外涂敷”)。成胶囊可以控制或延缓有效成分的释放。可喷雾剂型可在适当的介质中冲稀，使用的喷雾体积为每公顷大约1百至几百升。高浓度的组合物主要用作进一步配制的中间体。
这些剂型一般含有有效量的有效成分、稀释剂和表面活性剂，其中大约按以下范围，各组分含量总和为100％(重量计)。
               重量百分数
  有效成分    稀释剂  表面活性剂
水分散性和水溶性颗粒剂、片剂和粉剂     5-90    0-94     1-15
悬浮剂、乳液、溶液(包括可乳化的浓缩物)     5-50    40-95     0-15
粉     1-25    70-99     0-5
颗粒剂和丸剂     0.01-99    5-99.99     0-15
高浓度组合物     90-99    0-10     0-2
典型的固体稀释剂在Watkins等人，Handbook of Insecticide DustDiluents and Carriers，2nd Ed.，Dorland Books，Caldwell，NewJersey中作了介绍。典型的液体稀释剂在Marsden，Solvents Guide，2nd Ed.，Interscience，New York，1950中作了介绍。McCutcheon′s Detergents andEmulsifiers Annual，Allured Publ.Corp.，Ridgewood，New Jersey以及Sisely and Wood，Encyclopedia of Surface Active Agents，Chemical Publ.Co.，Inc.，New York，1964，列出了表面活性剂和推荐应用。所有剂型都可含有少量的添加剂，以减少泡沫、结块、腐蚀、微生物的生长等，或加增稠剂以增加粘度。
表面活性剂包括，例如，聚乙氧基化醇、聚乙氧基化烷基酚、聚乙氧基化脱水山梨糖醇脂肪酸酯、磺化丁二酸二烷基酯、硫酸烷基酯、烷基苯磺酸盐、有机聚硅氧烷、N，N-二烷基牛磺酸酯、木质素磺酸盐、萘磺酸盐甲醛缩合物、聚羧酸酯和聚氧乙烯/聚氧丙烯嵌段共聚物。固体稀释剂包括，例如，粘土如膨润土、蒙脱石、硅镁土和高岭土、淀粉、糖、二氧化硅、滑石、硅藻土、尿素、碳酸钙、碳酸钠和碳酸氢钠以及硫酸钠，液体稀释剂包括，例如，水、N，N-二甲基甲酰胺、二甲亚砜、N-烷基吡咯烷酮、乙二醇、聚丙二醇、石蜡、烷基苯、烷基萘、橄榄油、蓖麻油、亚麻籽油、桐油、芝麻油、玉米油、花生油、棉籽油、大豆油、菜籽油和椰子油，脂肪酸酯、酮类如环己酮、2-庚酮、异佛尔酮和4-羟基-4-甲基-2-戊酮、和醇类如甲醇、环己醇、十二烷醇和四氢呋喃醇。
溶液，包括可乳化的浓缩物，可以通过简单地混合各组分制得。粉剂和细粉可通过混合和通常在捶磨或液能磨中通过研磨来制备。悬浮剂一般通过湿磨来制备；参见，例如，US 3,060,084。颗粒剂和丸剂通过将有效物质喷到预先制成的颗粒载体上或通过造粒技术来制备。参见Browning，″Agglomeration″，Chemical Engineering，1967年12月4日，第147-48页、Perry′s Chemical Engineer′s Handbook，4th Ed.，McGraw-Hill，New York，1963第8-57页和随后部分，以及PCT公开WO 91/13546。丸剂的制备如US 4,172,714中所述。水分散性和水溶性颗粒剂如US 4,144,050、US 3,920,442和DE 3,246,493中教导制备。片剂可如US 5,180,587、US 5,232,701和US 5,208,030中教导制备。薄膜可按照GB 2,095,558和US 3,299,566中教导制备。
有关剂型技术的更多信息可参见T.S.Woods，″The Formulator′sToolbox-Product Forms for Modern Agriculture″in Pesticide Chemistryand Bioscience，The Food-Environment Challenge，T.Brooks和T.R.Roberts编辑，Proceedings of the 9th International Congress on PesticideChemistry，The Royal Society of Chemistry，Cambridge，1999第120-133页。还参见US 3,235,361第6栏第16行至第7栏第19行和实施例10-41；US 3,309,192第5栏第43行至第7栏第62行和实施例8、12、15、39、41、52、53、58、132、138-140、162-164、166、167和169-182；US 2,891,855第3栏第66行至第5栏第17行和实施例1-4；Klingman，Weed Control as a Science，John Wiley和Sons，Inc.，New York.1961第81-96页；和Hance等，Weed Control Handbook，8th Ed.，BlackwellScientific Publications，Oxford，1989。
在以下实施例中，所有百分数均以重量计，所有剂型都用常规方法制备。化合物号参见在索引表A中的化合物。
                         实施例A
可湿性粉剂
化合物1                                            65.0％
十二烷基酚聚乙二醇醚                               2.0％
木质素磺酸钠                                       4.0％
硅铝酸钠                                           6.0％
蒙脱石(煅烧的)                                     23.0％
                         实施例B
颗粒剂
化合物7                                           10.0％
硅镁土颗粒(低挥发物，0.71/0.30mm；U.S.25-50号筛)  90.0％
                         实施例C
挤压丸
化合物1                                           25.0％
无水硫酸钠                                        10.0％
粗木质素磺酸钙                                    5.0％
烷基萘磺酸钠                                      1.0％
钙/镁膨润土                                       59.0％
                         实施例D
可乳化的浓缩物
化合物7                                           20.0％
油状可溶性磺酸酯和聚氧乙基醚的混合物              10.0％
异佛尔酮                                          70.0％
                         实施例E
颗粒剂
化合物1                                           0.5％
纤维素                                            2.5％
乳糖                                              4.0％
玉米粉                                            93.0％
本发明的化合物的特征在于有利的新陈代谢和/或土壤残留物形式，并显示对一定范围的农业和非农业无脊椎害虫的防治活性。(在本说明书的上下文中“无脊椎害虫防治”意思是抑制无脊椎害虫生长(包括致死)，从而显著减少其摄食量或减少害虫引起的其它损失；相关的表述定义类似。)正如本说明书中所述，术语“无脊椎害虫”包括具有经济重要性的节肢动物类、腹足动物类和线虫类害虫。术语“节肢动物”包括昆虫、螨、蜘蛛、蝎子、蜈蚣、千足虫、球潮虫和综合纲。术语“腹足动物”包括蜗牛、鼻涕虫和其它柄眼目。术语“线虫”包括所有的寄生虫，例如：蛔虫、大恶丝虫和植食性线虫(线虫纲)、吸虫(Tematoda)、棘头纲和绦虫(多节绦虫亚纲)。本领域技术人员将理解，不是所有的化合物对所有害虫都有相等的药效。然而，本发明化合物显示了对经济上具重要性的农业、林业、温室、苗圃、观赏植物、食物和纤维、公共卫生和动物保健、家庭和商用建筑、家用品、和贮藏产品的害虫的活性。这些包括鳞翅目的幼虫，例如夜蛾科的粘虫、切根虫、尺蠖和heliothines(例如，草地粘虫(Spodoptera fugiperdaJ.E.Smith)、甜菜夜蛾(Spodoptera exigua Hubner)、小地老虎(Agrotisipsilon Hufnagel)、粉纹夜蛾(Trichoplusia ni Hubner)、美洲夜烟蛾(Heliothis virescens Fabricius))；螟蛾科的钻蛀虫、鞘蛾幼虫、结网毛虫、锥形虫、卷叶菜虫和雕叶虫(例如，欧洲玉米钻蛀虫(Ostrinianubilalis Hubner)、脐橙螟(Amyelois transitella Walker)、玉米根结网毛虫(Crambus caliginosellus Clemens)、草地结网毛虫(Herpetogrammalicarsisalis Walker))；卷蛾科中的卷叶蛾、蚜虫、种子蠕虫、和水果蠕虫(例如，苹果蠹蛾(Cydia pomonella Linnaeus)、葡萄小食心虫(Endopiza viteana Clemens)、梨小食心虫(Grapholita molesta Busck))；和许多其它经济上重要的鳞翅目(例如，菜蛾(Plutella xylostellaLinnaeus)、红铃虫(Pectinophora gossypiella Saunders)、舞毒蛾(Lymantria dispar Linnaeus))；蜚镰目的蛹和成虫，包括来自小蠊科和蠊科的(例如，东方蜚镰(Blatta orientalis Linnaeus)、亚洲蜚镰(Blatellaasahinai Mizukubo)、德国蜚镰(Blattella germanica Linnaeus)、长须鲱蠊(Supella longipalpa Fabricius)、美洲栗(Periplaneta americanaLinnaeus)、褐色大蠊(Periplaneta brunnea Burmeister)、马德拉蜚镰(Leucophaea maderae Fabricius))；鞘翅目的食叶幼虫和成虫，包括来自长脚象虫科、豆象科和象虫科的象鼻虫(例如，棉籽象鼻虫(Anthonomus grandis Boheman)、稻象甲(Lissorhoptrus oryzophilusKuschel)、谷象(Sitophilus granarius Linnaeus)、米象(Sitophilus oryzaeLinnaeus))；叶甲科中的跳甲、黄瓜甲虫、根虫、叶虫、薯虫、和潜叶蛾(例如，科罗拉多薯虫(Leptinotarsa decemlineata Say)、玉米根叶甲(Diabrotica virgifera virgifera LeConte))；来自金龟子科的金龟子和其它甲虫(例如，日本金龟子(Popillia Japonica Newman)和欧洲金龟子(Rhizotrogus majalis Razoumowsky))；来自皮蠹科的红缘皮蠹；来自叩头虫科的线虫；来自刺胫小蠹科的树皮甲虫和来自拟步行虫科的粉甲虫。此外农业和非农业害虫包括：革翅目的成虫和幼虫，包括来自球螋科的蠼螋(例如，欧洲球螋(Forficula auricularia Linnaeus)、黑球螋(Chelisoches morio Fabricius))；半翅目和同翅目的成虫和蛹，例如，来自盲蝽科的盲蝽、来自蝉科的蝉、来自大叶蝉科的叶蝉(例如微叶蝉亚种)、来自樗鸡科和飞虱科的樗鸡、来自角蝉科的角蝉、来自木虱科的木虱、来自粉虱科的粉虱、来自蚜科的蚜虫、来自根瘤蚜科的根瘤蚜、来自粉蚧科的水蜡虫、来自蚧科、盾蚧科和珠棉蚧亚科的介壳虫、来自网蝽科的网蝽、来自蝽象科的蝽象、来自长蝽科的麦长蝽(例如，长蝽亚种)和其它实蝽、来自沫蝉科的沫蝉、来自缘蝽科的缘蝽、以及来自红蝽科的红蝽和红甲虫。还包括螨目的成虫和幼虫，例如叶螨科的蛛螨和红蜘蛛(例如，欧洲红蜘蛛(Panonychus ulmi Koch)、两斑纹蛛螨(Tetranychus urticae Koch)、麦克旦尼氏螨(Tetranychusmcdanieli McGregor))、细须螨科的flat mites(例如，桔短须螨(Brevipalpus lewisi McGregor))、瘿螨科的锈螨和芽螨以及其它食叶螨和在人和动物健康中重要的螨，即表皮螨科的尘螨、蠕形螨科的毛囊螨、食甜螨科的干酪螨、蜱目的蜱(例如，鹿蜱(Ixodes scapulars Say)、澳洲瘫痪蜱(Ixodes holocyclus Neumann)、美洲犬蜱(Dermacentorvariabilis Say)、美洲花蜱(Amblyomma americanum Linnaeus)以及痒螨科、蒲螨科和疥螨科的马痒螨和疥螨；直翅目的成虫和未成年虫，包括蚂蚱、蝗虫和蟋蟀(例如，迁徙蚂蚱(例如，Melanoplus sanguinipesFabricius、M.differentialis Thomas)、美洲蚂蚱(例如，Schistocercaamericana Drury)、沙漠蝗(Schistocerca gregaria Forskal)、飞蝗(Locustamigratoria Linnaeus)、家蟋蟀(Acheta domesticus Linnaeus)、蝼蛄(蝼蛄属亚种))；双翅目的成虫和未成年虫，包括潜叶蛾、蠓、果蝇(实蝇科)、瑞典杆蝇(例如，Oscinella frit Linnaeus)、土壤蛆、家蝇(例如，Muscadomestica Linnaeus)、小加蝇(例如，Fannia canicularis Linnaeus、F.femoralis Stein)、厩螫蝇(例如，Stomoxys calcitrans Linnaeus)、秋家蝇、角蝇、丽蝇(例如，金蝇属亚种、伏蝇属亚种)、和其它蝇状飞虫(muscoidfly pests)、马蝇(例如，虻属亚种)、肤蝇(例如，马胃蝇属亚种、牛虻属亚种)、牛皮蝇(例如，下皮属亚种)、鹿虻(例如，斑虻属亚种)、羊蜱蝇(例如，Melophagus ovinus Linnaeus)和其它短角亚目、蚊子(例如，伊蚊属亚种、按蚊属亚种、库蚊属亚种)、黑蝇(例如，原蚋属亚种、蚋属亚种)、蠓、沙蝇、尖眼蕈蚊、和其它长角亚目；缨翅目的成虫和未成年虫，包括葱蓟马(Thrips tabaci Lindeman)和其它食叶蓟马；膜翅目的昆虫，包括蚂蚁(例如，红木蚁(Camponotus ferrugineusFabricius)、黑木蚁(Camponotus pennsylvanicus De Geer)、厨蚁(Monomorium pharaonis Linnaeus)、小火蚁(Wasmannia auropunctataRoger)、火蚁(Solenopsis geminata Fabricius)、外引红火蚁(Solenopsisinvicta Buren)、阿根廷蚁(Iridomyrmex humilis Mayr)、家褐蚁(Paratrechina longicornis Latreille)、铺道蚁(Tetramorium caespitumLinnaeus)、玉米田蚁(Lasius alienus Forster)、香家蚁(Tapinoma sessileSay))、蜜蜂(包括木蜂)、大黄蜂、胡蜂和黄蜂；等翅目的昆虫，包括东美散白蚁蚁(Reticulitermesflavipes Kollar)、西美散白蚁(Reticulitermeshesperus Banks)、台湾乳白蚁(Coptotermes formosanus Shiraki)、移栖楹白蚁(Incisitermes immigrans Snyder)和其它经济上重要的白蚁；缨尾目的昆虫，例如蠹虫(Lepisma saccharina Linnaeus)和家衣鱼(Thermobia domestica Packard)；食毛目的昆虫并包括头虱(Pediculushumanus capitis De Geer)、体虱(Pediculus humanus humanusLinnaeus)、鸡体虱(Menacanthus stramineus Nitszch)、狗羽虱(Trichodectes canis De Geer)、食毛鸟虱(Goniocotes gallinae De Geer)、羊体虱(Bovicola ovis Schrank)、牛盲虱(Haematopinus eurysternusNitzsch)、犊长颚虱(Linognathus vituli Linnaeus)和其它攻击人和动物的吸和咬的寄生虱；蚤目的昆虫，包括东方鼠蚤(Xenopsylla cheopisRothschild)、猫蚤(Ctenocephalides felis Bouche)、狗蚤(Ctenocephalidescanis Curtis)、鸡蚤(Ceratophyllus gallinae Schrank)、禽毒蚤(Echidnophaga gallinacea Westwood)、人蚤(Pulex irritans Linnaeus)和其它折磨动物和鸟的蚤。包含的其它节肢动物害虫包括：蜘蛛目的蜘蛛，例如褐皮花蛛(Loxosceles reclusa Gertsch & Mulaik)和黑寡妇蜘蛛(Latrodectus mactans Fabricius)，以及蚰蜒形目的蜈蚣，例如家蚰蜒(Scutigera coleoptrata Linnaeus)。本发明的化合物还对线虫纲、多节绦虫亚纲、吸虫纲和棘头纲的成员有活性，这些成员包括圆线虫目、蛔虫目、蛲虫目、杆状线虫目、旋尾目和嘴刺目的经济上重要的成员，例如但不限于经济上重要的农业害虫(即，根结线虫属的根癌线虫、草地垫刀线虫属的lesion nematodes、根线虫属的鬃根线虫，等。)以及危害动物和人健康的害虫(即，所有经济上重要的吸虫、绦虫和蛔虫，例如马内的寻常圆线虫、狗内的犬弓首蛔虫、羊内的捻转血矛线虫、狗内的Dirofrlaria immitis Leidy、马内的叶形裸头绦虫、反刍动物内的肝片吸虫，等。)。
本发明的化合物对以下害虫显示了特别高的活性：鳞翅目(例如，Alabama argillacea Hubner(棉叶波纹夜蛾)、Archips argyrospilaWalker(果树卷叶虫)、A.rosana Linnaeus(欧洲卷叶虫)和其它黄卷蛾属种、Chilo suppressalis Walker(二化螟)、Cnaphalocrosis medinalisGuenee(稻纵卷叶螟)、Crambus caliginosellus Clemens(玉米根草螟)、Crambus teterrellus Zincken(早熟禾草螟)、Cydia pomonella Linnaeus(苹果蠹蛾)、Earias insulana Boisduval(棉斑实蛾)、Earias vittellaFabricius(棉斑实蛾)、Helicoverpa armigera Hbner(美洲棉铃虫)、Helicoverpa zea Boddie(玉米穗夜蛾)、Heliothis virescens Fabricius(美洲夜烟蛾)、Herpetogramma licarsisalis Walker(草皮结网毛虫)、Lobesiabotrana Denis & Schiffermuller(葡萄小食心虫)、Pectinophoragossypiella Saunders(红铃虫)、Phyllocnistis citrella Stainton(桔细潜蛾)、Pieris brassicae Linnaeus(大菜粉蝶)、Pieris rapae Linnaeus(小菜粉蝶)、Plutella xylostella Linnaeus(菜蛾)、Spodoptera exigua Hubner(甜菜夜蛾)、Spodoptera litura Fabricius(斜纹夜蛾、cluster caterpillar)、Spodopteraftugiperda J.E.Smith(草地粘虫)、Trichoplusia ni Hubner(粉纹夜蛾)和Tuta absoluta Meyrick(番茄潜叶蛾))。本发明的化合物还对来自同翅目的成员具有商业上显著的活性，这些同翅目成员包括：Acyrthisiphon pisum Harris(豌豆蚜)、Aphis craccivora Koch(豇豆蚜)、Aphis fabae Scopoli(豆蚜)、Aphis gossypii Glover(棉蚜、甜瓜蚜)、Aphispomi De Geer(苹果蚜)、Aphis spiraecola Patch(绣线菊蚜)、Aulacorthumsolani Kaltenbach(毛地黄蚜)、Chaetosiphon fragaefolii Cockerell(草莓蚜)、Diuraphis noxia Kurdjumov/Mordvilko(俄罗斯小麦蚜)、Dysaphisplantaginea Paaserini(苹粉红劣蚜)、Eriosoma lanigerum Hausmann(苹绵蚜)、Hyalopteruspruni Geoffroy(梅大尾蚜)、Lipaphis erysimiKaltenbach(萝卜蚜)、Metopolophium dirrhodum Walker(谷类蚜)、Macrosipum euphorbiae Thomas(马铃薯蚜)、Myzus persicae Sulzer(桃-薯蚜、桃蚜)、Nasonovia ribisnigri Mosley(莴苣蚜)、天庖疮亚种(根蚜和缨蚜)、Rhopalosiphum maidis Fitch(玉米叶蚜)、Rhopalosiphum padiLinnaeus(粟缢蚜)、Schizaphis graminum Rondani(麦二叉蚜)、Sitobionavenae Fabricius(英国谷物蚜)、Therioaphis maculata Buckton(苜蓿斑翅蚜)、Toxoptera aurantii Boyer de Fonscolombe(桔二叉蚜)、和Toxopteracitricida Kirkaldy(桔二岔蚜)；球蚜属亚种(球蚜)；Phylloxera devastatrixPergande(美核桃根瘤蚜)；Bemisia tabaci Gennadius(菸草粉虱、棉粉虱)、Bemisia argentifolii Bellows & Perring(银叶粉虱)、Dialeurodes citriAshmead(桔粉虱)和Trialeurodes vaporariorum Westwood(温室白粉虱)；Empoasca fabae Harris(马铃薯微叶蝉)、Laodelphax striatellusFallen(灰飞虱)、Macrolestes quadrilineatus Forbes(紫莞叶蝉)、Nephotettix cinticeps Uhler(大青叶蝉)、Nephotettix nigropictus Stal(黑尾叶蝉)、Nilaparvata lugens Stal(稻褐飞虱)、Peregrinus maidisAshmead(菲岛玉米蜡蝉)、Sogatella furcifera Horvath(白背飞虱)、Sogatodes orizicola Muir(美洲稻飞虱)、Typhlocyba pomaria McAtee(苹白小叶蝉)、红斑叶蝉属亚种(葡萄二星斑叶蝉)；Magicidadaseptendecim Linnaeus(十七年蟑)；Icerya purchasi Maskell(吹棉蚧)、Quadraspidiotus pemiciosus Comstock(梨圆盾蚧)；Planococcus citriRisso(桔粉蚧)；粉蚧属亚种(其它水蜡虫复合物)；CacopsyllapyricolaFoerster(木虱)、Trioza diospyri Ashmead(柿木虱)。这些化合物也对来自半翅目的成员有活性，这些成员包括：Acrosternum hilare Say(喜绿蝽)、Anasa tristis De Geer(南瓜缘蝽)、Blissus leucopterus leucopterusSay(麦长蝽)、Corythuca gossypii Fabricius(棉网蝽)、Cyrtopeltis modestaDistant(番茄蝽)、Dysdercus suturellus Herrich-Sch ffer(红甲虫)、Euchistus servus Say(褐臭蝽)、Euchistus variolarius Palisot de Beauvois(一点褐蝽)、Graptosthetus亚种(实蝽的复合物)、Leptoglossus corculusSay(松籽喙缘蝽)、Lygus lineolaris Palisot de Beauvois(牧草盲蝽)、Nezara viridula Linnaeus(稻绿蝽)、Oebalus pugnax Fabricius(美洲稻盾蝽)、Oncopeltus fasciatus Dallas(大马利筋长蝽)、Pseudatomoscelisseriatus Reuter(棉跳盲蝽)。通过本发明化合物防治的其它昆虫目包括缨翅目(例如，Frankliniella occidentalis Pergande(苜蓿蓟马)、Scirthothrips citri Moulton(桔实蓟马)、Sericothrips variabilis Beach(大豆蓟马)、和Thrips tabaci Lindeman(葱蓟马)；和鞘翅目(例如，Leptinotarsa decemlineata Say(科罗拉多薯虫)、Epilachna varivestisMulsant(墨西哥豆瓢虫)和叩甲属(Agriotes)、叩甲属(Athous)或草金针金属的金针虫)。
本发明的化合物也可与一种或多种其它生物活性化合物包括杀虫剂、杀真菌剂、杀线虫剂、杀细菌剂、杀螨剂、生长调节剂如根刺激剂、化学消毒剂、化学信息素、驱避剂、诱引剂、信息激素、摄食刺激剂、其它生物活性化合物或食虫菌、病毒或真菌混合形成多组分农药，给出更广谱的农业保护作用。因此本发明的组合物还可以包括生物有效量的至少一种其它生物活性化合物或试剂。可与本发明化合物一起加工的这些生物活性化合物的实例是：杀虫剂如阿维菌素、乙酰甲胺磷、吡虫清、齐墩螨素、艾扎丁、保棉磷、氟氯菊酯、联苯肼酯、噻嗪酮、呋喃丹、氟唑虫清、定虫隆、毒死蜱、甲基毒死蜱、chromafenozide、clothianidin、氟氯氰菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、灭蝇胺、溴氰菊酯、杀螨硫隆、二嗪农、氟脲杀、乐果、噁茂醚、emamectin、硫丹、高杀灭菊酯、ethiprole、苯硫威、苯氧威、甲氰菊酯、唑螨酯、杀灭菊酯、锐劲特、flonicamid、氟氰戊菊酯、τ-氟胺氰菊酯、氟虫脲、地虫磷、特丁苯酰肼、氟铃脲、吡虫啉、噁二唑虫、丙胺膦、氟丙氧脲、马拉硫磷、四聚乙醛、甲胺磷、杀扑磷、灭多虫、烯虫酯、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝虫噻嗪、甲氨叉威、杀线威、对硫磷、甲基对硫磷、氯菊酯、甲拌磷、伏杀硫磷、亚胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蝇醚、鱼藤酮、艾克敌105、乙丙硫磷、双苯酰肼、伏虫隆、七氟菊酯、特丁硫磷、杀虫畏、thiacloprid、thiamethoxam、硫双威、杀虫双、四溴菊酯、敌百虫和杀虫隆；杀真菌剂如噻二唑素、腈嘧菌酯、苯菌灵、杀稻瘟菌素-S、波尔多液(碱式硫酸铜)、糠菌唑、氯环丙酰胺、敌菌丹、克菌丹、多菌灵、地茂散、百菌清、氧氯化铜、铜盐、cyflufenamid、霜脲氰、环丙唑醇、嘧菌环胺、(S)-3，5-二氯-N-(3-氯-1-乙基-1-甲基-2-氧丙基)-4-甲基苯甲酰胺(RH 7281)、双氯氰菌胺(S-2900)、哒菌清、氯硝胺、噁醚唑、(S)-3，5-二氢-5-甲基-2-(甲硫基)-5-苯基-3-(苯氨基)-4H-咪唑-4-酮(RP 407213)、烯酰吗啉、dimoxystrobin、烯唑醇、烯唑醇-M、多果定、敌瘟磷、氧唑菌、噁唑酮菌、fenamidone、氯苯嘧啶醇、腈苯唑、fencaramid(SZX0722)、拌种咯、苯锈啶、丁苯吗啉、薯瘟锡、毒菌锡、氟啶胺、咯菌腈、氟联苯菌(RPA 403397)、氟喹唑、氟硅唑、氟酰胺、粉唑醇、灭菌丹、三乙膦酸铝、呋霜灵、呋吡唑灵(S-82658)、己唑醇、种菌唑、异稻瘟净、异菌脲、稻瘟灵、春雷霉素、亚胺菌、代森锰锌、代森锰、mefenoxam、灭锈胺、甲霜灵、叶菌唑、叉氨苯酰胺(SSF-126)、腈菌唑、田安(甲胂酸铁)、恶霜灵、戊菌唑、戊菌隆、烯丙苯噻唑、咪鲜胺、霜霉威、丙环唑、啶斑肟、pyraclostrobin、二甲嘧菌胺、咯喹酮、喹氧灵、螺噁茂胺、硫磺粉、戊唑醇、四氟醚唑、噻菌灵、噻呋酰胺、甲基硫菌灵、福美双、tiadinil、三唑酮、三唑醇、三环唑、肟菌酯、灭菌唑、有效霉素和乙烯菌核利；杀线虫剂如涕灭威、甲氨叉威和克线磷；杀细菌剂如链霉素；杀螨剂如杀螨脒、灭螨猛、乙酯杀螨醇、三环锡、开乐散、除螨灵、特苯噁唑、喹螨醚、杀螨锡、甲氰菊酯、唑螨酯、噻螨酮、克螨特、哒螨酮和吡螨胺；和生物制剂如苏云金杆菌，包括鲇泽亚种和库尔斯塔克亚种，苏云金杆菌δ毒素、杆状病毒以及食虫细菌、病毒和真菌。
有关这些农业保护剂的常规参考文献是The Pesticide Manual，第12版，C.D.S.Tomlin出版，British Crop Protection Council，Farnham，Surrey，U.K.，2000。
其中重要的组合物包括(除了式I组份和任意表面活性剂和/或稀释剂之外)至少一种选自以下的生物活性化合物或试剂：阿维菌素、乙酰甲胺磷、吡虫清、amidoflument、齐墩螨素、艾扎丁、保棉磷、氟氯菊酯、联苯肼酯、噻嗪酮、呋喃丹、氟唑虫清、定虫隆、毒死蜱、甲基毒死蜱、chromafenozide、clothianidin、氟氯氰菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、灭蝇胺、溴氰菊酯、杀螨硫隆、二嗪农、氟脲杀、乐果、噁茂醚、emamectin、硫丹、高杀灭菊酯、ethiprole、苯硫威、苯氧威、甲氰菊酯、杀灭菊酯、锐劲特、flonicamid、氟氰戊菊酯、τ-氟胺氰菊酯、氟虫脲、地虫磷、特丁苯酰肼、氟铃脲、吡虫啉、噁二唑虫、丙胺膦、氟丙氧脲、马拉硫磷、四聚乙醛、甲胺磷、杀扑磷、灭多虫、烯虫酯、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝虫噻嗪、甲氨叉威、杀线威、对硫磷、甲基对硫磷、氯菊酯、甲拌磷、伏杀硫磷、亚胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蝇醚、鱼藤酮、艾克敌105、乙丙硫磷、双苯酰肼、伏虫隆、七氟菊酯、特丁硫磷、杀虫畏、thiacloprid、thiamethoxam、硫双威、杀虫双、四溴菊酯、敌百虫和杀虫隆、涕灭威、甲氨叉威、克线磷、杀螨脒、灭螨猛、乙酯杀螨醇、三环锡、开乐散、除螨灵、特苯噁唑、喹螨醚、杀螨锡、甲氰菊酯、唑螨酯、噻螨酮、克螨特、哒螨酮、吡螨胺；苏云金杆菌，包括鲇泽亚种和库尔斯塔克亚种，苏云金杆菌δ毒素、杆状病毒以及食虫细菌、病毒和真菌。
用于与本发明化合物混合的优选的杀虫剂和杀螨剂包括拟除虫菊酯类，如氯氰菊酯、氯氟氰菊酯、氟氯氰菊酯、β-氟氯氰菊酯，高杀灭菊酯、杀灭菊酯和四溴菊酯；氨基甲酸酯类如苯硫威、灭多虫、甲氨叉威和硫双灭多虫；类烟碱类如噻虫胺、吡虫啉和噻虫啉；神经钠通道阻断剂如噁二唑虫、杀虫的大环内酯如艾克敌105、阿维菌素、齐墩螨素和emamectin；-氨基丁酸(GABA)拮抗剂如硫丹、ethiprole和锐劲特；杀虫的脲类如氟虫脲和杀虫隆；保幼激素模拟物如噁茂醚和蚊蝇醚；拒嗪酮；和虫螨脒。用于与本发明化合物混合的优选生物制剂包括苏云金杆菌和苏云金杆菌δ毒素以及天然存在和遗传改性的病毒杀虫剂，包括杆状病毒类以及食虫真菌。
最优选的混合物包括本发明化合物与氟氯氰菊酯的混合物；本发明化合物与β-氯氟氰菊酯的混合物；本发明的化合物与高杀灭菊酯的混合物；本发明的化合物与灭多虫的混合物；本发明化合物与吡虫啉的混合物；本发明化合物与噻虫啉的混合物；本发明化合物与噁二唑虫的混合物；本发明化合物与阿维菌素的混合物；本发明化合物与硫丹的混合物；本发明化合物与ethiprole的混合物；本发明化合物与锐劲特的混合物；本发明化合物与氟虫脲的混合物；本发明化合物与蚊蝇醚的混合物；本发明化合物与拒嗪酮的混合物；本发明化合物与虫螨脒的混合物；本发明化合物与苏云金杆菌的混合物和本发明化合物与苏云金杆菌δ毒素的混合物。
在某些情况下，和其它具有类似的防治谱，但作用方式不同的无脊椎害虫防治化合物或试剂混合将特别有利于抗性管理。因此，本发明的化合物还可以包括生物有效量的至少一种具有类似防治谱，但作用方式不同的其它无脊椎害虫防治化合物或试剂。将生物有效量的本发明化合物与经基因改性以表达植物保护化合物(例如蛋白质)的植物或该植物的部位接触，也可以提供更广谱的植物保护并有利于抗性管理。
在农业和非农业领域，通过将一种或多种有效量的本发明化合物施加于无脊椎害虫的环境(包括农业和/或非农业的害虫侵染地)、施用于被保护的区域，或者直接施用于被防治的害虫上，都可以防治无脊椎害虫。因此，本发明进一步包括一种防治农业和/或非农业领域中无脊椎害虫的方法，该方法包括用有效量的一种或多种本发明的化合物，或者用含有至少一种这种化合物的组合物或含有至少一种这种化合物和有效量的至少一种其它生物活性化合物或试剂的组合物与这些无脊椎害虫或其环境接触。包括本发明化合物和有效量的至少一种其它生物活性化合物或试剂的适宜组合物的实例包括颗粒组合物，其中其它生物活性化合物存在于与本发明化合物相同的颗粒上，或者存在于于本发明化合物颗粒分开的颗粒上。
接触的优选方法是喷雾。此外，含有本发明化合物的颗粒组合物可施用于植物的叶面或土壤。本发明的化合物还通过以液体剂型进行土壤浸湿、以颗粒剂型用于土壤、在移植中用于护理盒处理或浸渍，将植物与含有本发明化合物的组合物接触，经植物摄取有效地供给。通过将含有本发明化合物的组合物局部施用到侵染部位也可以发挥化合物的效力。其它接触方法包括通过直接或滞留喷雾、飞机喷洒、凝胶、种子包衣、微胶囊化、全身性摄入、饵、耳标、丸剂、迷雾器、熏蒸剂、气雾剂、粉剂和许多其它方式施用本发明的化合物或组合物。本发明的化合物也可掺入制备无脊椎害虫防治设备(例如昆虫网捕)的材料中。
本发明化合物可掺入无脊椎害虫消耗的饵剂中或例如捕获器等设备中。含有0.01-5％活性组分，0.05-10％保水剂和40-99％蔬菜粉的颗粒或饵剂以非常低的施用比率防治土壤昆虫是有效的，特别是对于通过消化而不是通过直接接触致死的活性组分的剂量。
本发明的化合物可以它们的纯净状态被施用，但最普遍使用的是含有一种或多种化合物与适当的载体、稀释剂和表面活性剂的剂型，并可以与食品混合，这取决于预期的最终用途。优选的施用方法包括喷洒化合物的水分散液或精炼油溶液。与喷雾油、喷雾油浓制剂、铺展增稠剂、助剂、其它溶剂和增效剂如胡椒基丁醚一起，常常可提高化合物的功效。
有效防治所需的施药量(即“生物有效量”)取决于以下因素：被防治的无脊椎害虫的品系、害虫的生命周期、生命阶段、它的大小、地点、一年中的时期、寄生作物或动物、喂饲行为、交配行为、空气湿度、温度等。在通常环境下，每公顷大约0.01-2kg有效成分的施药量对农业生态系中的害虫防治是足够的，但少至0.0001kg/公顷可能是有效的，或多至8kg/公顷可能是需要的。对于非农业应用，有效使用量范围是大约1.0-50mg/m2，但少至0.1mg/m2可能是有效的，或多至150mg/m2可能是需要的。本领域技术人员可以容易地确定对所需的无脊椎害虫的防治水平所需的生物有效量。
本发明生物学实施例的以下试验表明了本发明方法防止特定无脊椎害虫妨害植物的功效。“防治功效”代表对无脊椎害虫发育的抑制(包括死亡)，抑制会引起明显的摄食减少。由这些化合物产生的害虫防治保护并不限于这些品系。关于化合物的说明见索引表A。在该索引表中采用的缩写如下：t是叔，n是正，i是异，s是仲，c是环，Me是甲基，Et是乙基，Pr是丙基，Bu是丁基；因此i-Pr是异丙基，s-Bu是仲丁基等。缩写“Ex.”代表“实施例”，其后跟着的数字表示化合物在该实施例中被制备。
                      索引表A
化合物      R 3         R 4      R 5            熔点℃
1          t-Bu        H        2，3-diMe       208-209
2          i-Pr        H        4-OCF3         160-161
3(Ex.4)    i-Pr        5-Cl     4-OCF3         230-233
4          Me          5-Me     4-OCF3         224-225
5          Me          5-Me     2-Me，4-Cl      114-116
6          i-Pr        5-Cl     2-Me，4-Cl      ＞250
7(Ex.3)    i-Pr        2-Me     2-Me，4-OCF3   230
8          t-Bu        2-Me     2-Me，4-OCF3   200-203
9(Ex.2)    i-Pr        2-Me     2-Me，4-CF3    230
10         i-Pr        5-NO2    4-CF3          Solid
11         4-CF3-Ph   5-Me     2-Me            ＞250
                       索引表B
化合物     R 3     R 4     J                        熔点℃
12        t-Bu    H       2，3-diMe-Ph              161-164
13        t-Bu    H       2-CF3-Ph                 173-174
14        i-Pr    H       2，4-F-Ph                 148
15        i-Pr    H       2，3-diMe-Ph              169-171
16        t-Bu    H       2，4-diF-Ph               146-149
17        i-Pr    5-Me    2，3-diMe-Ph              202-205
18        i-Pr    5-Me    2，6-diCl-Ph              230
19        i-Pr    5-Me    2，4-diF-Ph               196
20        Me      H       2-F-Ph                    固体
21        i-Pr    5-Cl    2-Me，4-Cl，6-NC(O)CF3   203
22        i-Pr    5-Cl    2-Me，4-Cl，6-NC(O)CH3   ＞250
23        t-Bu    5-Me    3-CF3-Ph                 固体
24        t-Bu    5-Me    2-F，5-CF3-Ph            固体
25        t-Bu    5-Me    4-CF3-Ph                 固体
26        t-Bu    5-Me    4-OCF3-Ph                固体
27        i-Pr    5-Me    4-CF3-Ph                 固体
28        i-Pr    5-Me    3-CF3-Ph                 固体
29        t-Bu    5-Me    4-CF3-Ph                 固体
30        t-Bu    5-Me    4-OCF3-Ph                固体
31        i-Pr    5-Me    2-F，5-CF3-Ph            固体
32        i-Pr    5-Me    4-OCF3-Ph                固体
33        i-Pr    5-Me    4-CF3-Ph                 固体
34        t-Bu    5-Me    3-CF3-Ph                 固体
                         索引表C
Figure A0281824702541
化合物      R 3       R 4     R 5a              R 5b  熔点℃
35(Ex.1)    i-Pr      5-Me    2-Cl-Ph           CF3   Solid
36          Me        5-Me    3-Cl-2-Pyridyl    CF3   204-205
37(Ex.6)    i-Pr      5-Me    3-Cl-2-Pyridyl    CF3   219-220
38          NHEt      5-Me    3-Cl-2-Pyridyl    CF3   185-186
39          NHi-Pr    5-Me    3-Cl-2-Pyridyl    CF3   191-192
40          t-Bu      5-Me    3-Cl-2-Pyridyl    CF3   205-206
41          Me        5-Me    3-Cl-2-Pyridyl    Cl     201-202
42          i-Pr      5-Me    3-Cl-2-Pyridyl    Cl     229-230
43          NHEt      5-Me    3-Cl-2-Pyridyl    Cl     187-188
44          NHi-Pr    5-Me    3-Cl-2-Pyridyl    Cl     195-196
45          t-Bu      5-Me    3-Cl-2-Pyridyl    Cl     201-202
46          Me        5-Me    3-Cl-2-Pyridyl    Br     176-177
47          i-Pr      5-Me    3-Cl-2-Pyridyl    Br     237-238
48          NHEt      5-Me    3-Cl-2-Pyridyl    Br     176-177
49          NHi-Pr    5-Me    3-Cl-2-Pyridyl    Br     192-193
50          t-Bu      5-Me    3-Cl-2-Pyridyl    Br     196-197
51          i-Pr      2-Me    3-Cl-2-Pyridyl    Br     190-191
52          i-Pr      2-Me    3-Cl-2-Pyridyl    Cl     185-186
53(Ex.5)    i-Pr      2-Me    3-Cl-2-Pyridyl    CF3   215-217
54          Me        2-Me    3-Cl-2-Pyridyl    CF3   167-168
其中，pyridyl为吡啶基
                        索引表D
Figure A0281824702551
化合物      R 3     R 4     R 5a              R 5b  熔点℃
55          Me      5-Me    2-Cl-Ph           CF3   194-195
56          i-Pr    5-Me    2-Cl-Ph           CF3   244-246
57          t-Bu    5-Me    2-Cl-Ph           CF3   260
58          Et      5-Me    2-Cl-Ph           CF3   236-237
59          i-Pr    2-Me    2-Cl-Ph           CF3   203-205
60          t-Bu    2-Me    2-Cl-Ph           CF3   232-233
61          Et      2-Me    2-Cl-Ph           CF3   170-172
62          Me      2-Me    2-Cl-Ph           CF3   212-213
63          Me      5-Me    3-Cl-2-Pyridyl    CF3   192-193
64          Me      2-Me    3-Cl-2-Pyridyl    CF3   236
65(Ex.7)    i-Pr    2-Me    3-Cl-2-Pyridyl    CF3   198
其中，pyridyl为吡啶基
                 本发明的生物实施例
                        试验
为了评价对菜蛾(Plutella xylostella)的防治，试验单元由小开口容器组成，其中装有12-14-天大的萝卜植物。预先对该单元进行侵染：用核芯取样器从生长有许多幼虫的硬化害虫饲料薄片上取下一芯杆，其上的害虫饲料带有10-15只婴幼虫，将带有幼虫和饲料的芯杆转移到试验单元。随着饲料芯杆的干透，幼虫转移到试验植物上。
除非另有说明，试验化合物被配制成一溶液，其中含有10％丙酮、90％水和300ppm含有烷基芳基聚氧乙烯、游离脂肪酸、二醇和异丙醇的X-77_ Spreader Lo-Foam Formula非离子表面活性剂(LovelandIndustries，Inc.)。将经配制的化合物以1mL液体的形式，通过SUJ2雾化喷嘴喷出，其中1/8JJ通体(Spraying Systems Co.)被固定在每个试验单元的顶部上方1.27cm(0.5英寸)处。本筛选中的所有试验化合物都以50ppm喷雾，重复3次。将配制的试验化合物喷洒之后，将每个试验单元干燥1小时，然后将一个黑色筛帽放于上面。这些试验单元在25℃和70％相对湿度的生长室内保持6天。然后目测植物受到的侵食危害。
以下试验的化合物提供了优异的植物保护水平(30％或更低的侵食危害)：11，37，39，43，47，48，51，52，53和63。

Claims (18)

1、一种防治无脊椎害虫的方法，包括用生物有效量的式I的化合物，包括其所有几何异构体和立体异构体、其N-氧化物或其适用于农业的盐，来接触所述无脊椎害虫或其环境：
Figure A028182470002C1
其中
J是苯环、萘环系、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，其中每一环或环系任选取代有1-4个R5；
K是-C(＝A)NR2-或-NR2C(＝A)-；
L是-NR1C(＝B)-R3或-NR1SO2-R3；
A和B独立地是O或S；
R1是H；或C1-C6烷基、C2-C6链烯基、C2-C6链炔基或C3-C6环烷基，每一个任选取代有一个或多个选自如下的取代基：卤素、CN、NO2、羟基、C1-C4烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C2-C4烷氧基羰基、C1-C4烷基氨基、C2-C8二烷基氨基和C3-C6环烷基氨基；或者
R1是C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基或C3-C8二烷基氨基羰基；
R2是H、C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基、C1-C4烷氧基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C2-C6烷氧基羰基或C2-C6烷基羰基；
R3是C1-C6烷基、C2-C6链烯基、C2-C6链炔基或C3-C6环烷基，每一个任选取代有一个或多个选自如下的取代基：卤素、CN、NO2、羟基、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C2-C6烷氧基羰基、C2-C6烷基羰基、C3-C6三烷基甲硅烷基、苯基、苯氧基和5-或6-元杂芳环，每个苯基、苯氧基和5-或6-元杂芳环任选取代有1-3个独立地选自如下的取代基：R6；C1-C4烷氧基；C1-C4烷基氨基；C2-C8二烷基氨基；C1-C4烷氧基(C1-C4烷基)氨基；C3-C6环烷基氨基；C2-C6烷氧基羰基或C2-C6烷基羰基；或者
R1和R3可以与-NC(＝B)-或-NSO2-部分在一起，它们相连形成一个包括2-6个碳原子并任选还包括一个氮、硫或氧原子的环，所述环任选取代有1-4个选自如下的取代基：C1-C2烷基、卤素、CN、NO2和C1-C2烷氧基；
每个R4独立地是H、C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基、C1-C6卤烷基、C2-C6卤链烯基、C2-C6卤链炔基、C3-C6卤环烷基、卤素、CN、NO2、羟基、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C3-C6三烷基甲硅烷基，或者任选取代有1-3个独立地选自R6的取代基的苯环；
每个R5独立地是C1-C6烷基、C2-C6链烯基、C2-C6链炔基、C3-C6环烷基、C1-C6卤烷基、C2-C6卤链烯基、C2-C6卤链炔基、C3-C6卤环烷基、卤素、CN、CO2H、CONH2、NO2、羟基、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基、C3-C6三烷基甲硅烷基；或者
每个R5独立地是苯基、苄基、苯甲酰基、苯氧基、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，每个苯基、苄基、苯甲酰基、苯氧基、杂芳环和芳族稠合杂二环环系任选取代有1-3个独立地选自R6的取代基；或者
两个R5基团与相邻碳原子相连时可以在一起为-OCF2O-、-CF2CF2O-或-OCF2CF2O-；
每个R6独立地是C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C2-C4卤链烯基、C2-C4卤链炔基、C3-C6卤环烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C3-C6(烷基)环烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和
n是1、2、3或4；
条件是L不是-NHC(＝O)-，并且R3不是取代有一个或多个氟部分的C1-C6烷基。
2、如权利要求1的方法，其中K是-C(＝A)NR2-，并且A和B都是O。
3、如权利要求1的方法，其中K是-NR2C(＝A)-，并且A和B都是O。
4、如权利要求2或权利要求3的方法，其中
J是苯环或者5-或6-元杂芳环，该杂芳环选自基团J-1、J-2、J-3和J-4，每个J环任选取代有1-3个R5
Q是O、S或NR5c；
W、X、Y和Z独立地是N或CR5c，条件是在J-3和J-4中W、X、Y或Z中至少一个是N；
R1和R2各自独立地是H、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C2-C6烷基羰基或C2-C6烷氧基羰基；
R3是C1-C6烷基、C2-C6链烯基、C2-C6链炔基或C3-C6环烷基，它们各自任选取代有一个或多个选自如下的取代基：卤素、CN、C1-C2烷氧基、C1-C2烷硫基、C1-C2烷基亚磺酰基和C1-C2烷基磺酰基；
每个R4独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基或C1-C4卤烷基磺酰基；
每个R5独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或
每个R5独立地是苯基、苄基或者5-或6-元杂芳环，每个环任选取代有1-3个独立地选自R6的取代基；或者
两个R5基团与相邻碳原子相连时可以在一起为-OCF2O-、-CF2CF2O-或-OCF2CF2O-；
R5c是H或R5；
每个R6独立地是C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C2-C4卤链烯基、C2-C4卤链炔基、C3-C6卤环烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C3-C6(烷基)环烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和
n是1或2。
5、如权利要求4的方法，其中
每个R5是R5a或R5b；
J取代有R5a并任选取代有1-2个R5b；
R1和R2各自独立地是H或C1-C4烷基；
R3是任选取代有卤素、CN、OCH3或S(O)pCH3的C1-C4烷基；
R5a基团在与K相邻的位置与J相连；
R5a和R5b各自独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、苄基或者5-或6-元杂芳环，每个环任选取代有1-3个独立地选自R6的取代基；
每个R6独立地是卤素、CN、NO2、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C1-C4烷氧基或C1-C4卤烷氧基；和
p是0、1或2。
6、如权利要求5的方法，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
7、如权利要求6的方法，其中
R1和R2各自是H；
一个R4选自如下基团：C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和卤素，并且任选的第二个R4选自如下基团：卤素、C1-C3烷基和C1-C3卤烷基。
8、如权利要求7的方法，其中
J是J-1；
Q是NR5a；
X是N或CH；
Y是CH；
Z是CR5b；
R5a是苯基或2-吡啶基环，它们取代有一个或者两个选自如下基团的取代基：卤素、C1-C4烷基、C1-C4卤烷基或C1-C4卤烷氧基；和
R5b是卤素或CF3。
9、一种式I的化合物，包括其所有几何异构体和立体异构体、其N-氧化物或其适用于农业的盐
Figure A028182470007C1
其中
J是苯环、萘环系、5-或6-元杂芳环或者芳族8-、9-或10-元稠合杂二环环系，其中每一环或环系取代有一个R5a并任选取代有1-3个R5b；
K是-C(＝A)NR2-或-NR2C(＝A)-；
L是-NR1C(＝B)-R3或-NR1SO2-R3；
A和B独立地是O或S；
R1是H或C1-C4烷基；
R2是H或C1-C4烷基；
R3是任选取代有卤素、CN、OCH3或S(O)pCH3的C1-C4烷基；
每个R4独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基或C1-C4卤烷基磺酰基；
R5a和R5b各自独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、苄基或者5-或6-元杂芳环，每个苯基、苄基和杂芳环任选取代有1-3个独立地选自R6的取代基；
R5a在与K相邻的位置与J相连；
每个R6独立地是卤素、CN、NO2、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C1-C4烷氧基或C1-C4卤烷氧基；
n是1、2、3或4；和
p是0、1或2；
条件是L不是-NHC(＝O)-，并且R3不是取代有一个或多个氟部分的C1-C6烷基。
10、如权利要求9的化合物，其中
J是苯环或者5-或6-元杂芳环，该杂芳环选自基团J-1、J-2、J-3和J-4，每个J环取代有R5a并任选取代有1-2个R5b
Q是O、S或NR5c；
W、X、Y和Z独立地是N或CR5c，条件是在J-3和J-4中W、X、Y或Z中至少一个是N；
R1和R2各自独立地是H或C1-C4烷基；
R3是C1-C4烷基，它任选取代有卤素、CN、OCH3或S(O)pCH3；
每个R4独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰X基或C1-C4卤烷基磺酰基；
R5a在与K相邻的位置与J相连；
R5a和R5b各自独立地是C1-C4烷基、C1-C4卤烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4卤烷硫基、C1-C4卤烷基亚磺酰基、C1-C4卤烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、苄基或者5-或6-元杂芳环，每个环任选取代有1-3个独立地选自R6的取代基；
R5c是H或一个R5a取代基；
每个R6独立地是卤素、CN、NO2、C1-C4烷基、C2-C4链烯基、C2-C4链炔基、C3-C6环烷基、C1-C4卤烷基、C1-C4烷氧基或C1-C4卤烷氧基；和
n是1或2。
11、权利要求10的化合物，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
12、权利要求11的化合物，其中
R1和R2各自是H；
一个R4选自如下基团：C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和卤素，并且任选的第二个R4选自如下基团：卤素、C1-C3烷基和C1-C3卤烷基。
13、权利要求12的化合物，其中
J是J-1；
Q是NR5a；
X是N或CH；
Y是CH；
Z是CR5b；
R5a是苯基或2-吡啶基环，它们取代有一个或者两个选自如下基团的取代基：卤素、C1-C4烷基、C1-C4卤烷基或C1-C4卤烷氧基；和
R5b是卤素或CF3。
14、一种防治无脊椎害虫的组合物，其包括：
生物有效量的如权利要求1的式I的化合物、其N-氧化物或其适用于农业的盐；和
至少一种选自表面活性剂、固体稀释剂和液体稀释剂的其它组分。
15、权利要求14的组合物，其还包括有效量的至少一种其它生物活性化合物或试剂。
16、权利要求15的组合物，其中至少一种其它生物活性化合物或试剂选自拟除虫菊酯类、氨基甲酸酯类、新类烟碱类、神经钠通道阻断剂、杀虫的大环内酯、γ-氨基丁酸(GABA)拮抗剂、杀虫的脲类和保幼激素模拟物。
17、权利要求14的组合物，还包括至少一种选自以下的其它生物活性化合物或试剂：阿维菌素、乙酰甲胺磷、吡虫清、amidoflumet、齐墩螨素、艾扎丁、甲基保棉磷、氟氯菊酯、联苯肼酯、噻嗪酮、呋喃丹、氟唑虫清、定虫隆、毒死蜱、甲基毒死蜱、chromafenozide、clothianidin、氟氯氰菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、灭蝇胺、溴氰菊酯、杀螨硫隆、二嗪农、氟脲杀、乐果、噁茂醚、emamectin、硫丹、高杀灭菊酯、ethiprole、苯硫威、苯氧威、甲氰菊酯、杀灭菊酯、锐劲特、flonicamid、氟氰戊菊酯、τ-氟胺氰菊酯、氟虫脲、地虫磷、特丁苯酰肼、氟铃脲、吡虫啉、噁二唑虫、丙胺膦、氟丙氧脲、马拉硫磷、多聚乙醛、甲胺磷、杀扑磷、灭多虫、烯虫酯、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝虫噻嗪、甲氨叉威、甲氨叉威、对硫磷、甲基对硫磷、氯菊酯、甲拌磷、伏杀硫磷、亚胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蝇醚、鱼藤酮、艾克敌105、乙丙硫磷、双苯酰肼、伏虫隆、七氟菊酯、特丁硫磷、杀虫畏、thiacloprid、thiamethoxam、硫双威、杀虫双、四溴菊酯、敌百虫和杀虫隆、涕灭威、甲氨叉威、克线磷、杀螨脒、灭螨猛、乙酯杀螨醇、三环锡、开乐散、除螨灵、特苯噁唑、喹螨醚、杀螨锡、甲氰菊酯、唑螨酯、噻螨酮、克螨特、哒螨酮、吡螨胺；苏云金杆菌，包括鲇泽亚种和库尔斯塔克亚种，苏云金杆菌δ毒素、杆状病毒以及食虫细菌、病毒和真菌。
18、权利要求14的组合物，其还包括至少一种选自以下的其它生物活性化合物或试剂：氯氰菊酯、氯氟氰菊酯、氟氯氰菊酯和β-氟氯氰菊酯、高氰戊菊酯、杀灭菊酯、四溴菊酯、苯硫威、灭多虫、甲氨叉威、硫双灭多虫、噻虫胺、吡虫啉、噻虫啉、噁二唑虫、艾克敌105、阿维菌素、齐墩螨素、emamectin、硫丹、ethiprole、锐劲特、氟虫脲、杀虫隆、噁茂醚、蚊蝇醚、拒嗪酮、虫螨脒、苏云金杆菌、苏云金杆菌δ毒素和食虫真菌。
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