TW200835487A - 2-substituted pyridines I in therapy - Google Patents

2-substituted pyridines I in therapy Download PDF

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TW200835487A
TW200835487A TW096150617A TW96150617A TW200835487A TW 200835487 A TW200835487 A TW 200835487A TW 096150617 A TW096150617 A TW 096150617A TW 96150617 A TW96150617 A TW 96150617A TW 200835487 A TW200835487 A TW 200835487A
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group
compound
groups
alkyl
cyano
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TW096150617A
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Chinese (zh)
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Barbara Nave
Sven Harmsen
Bernd Mueller
Thomas Grote
Joachim Rheinheimer
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Basf Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—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
    • C07D213/02—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
    • C07D213/04—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
    • 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
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

The present invention relates to the use of 2-substituted pyridines of the formula I and the pharmaceutically acceptable salts of the 2-substituted pyridines of formula I in therapy, in particular in therapy or treatment of cancerous diseases, in which the indices and the substituents are as defined in the claims and the specification.

Description

200835487 九、發明說明： 【發明所屬之技術領域】 本發明係關於用於治療的 口康的式I之2-經取代吡啶及該式I之 2-經取代吼啶的醫藥 卡丄j接文之鹽，具體而言，其分別用 於癌症或癌性疾病之治療或療法。在式ί中 V^R2 上下標及取代基係如下文所定義： Χι Y R1 、=每一情況下，該兩個環成員中的-個為N，另一 個為C-H或素； 係基團-CH-RL、.N_Rl_、m 、R彼此獨立地選自由下列組成之 C2-C1Q-細基、c2_Ciq_块基、 班 環縣，其中RW基團定義之m烧基及C4-C1〇-基團部分可經部分或完全i化或二：及/或環脂族 個或4個基，，該（等）基團rv =個、2個、3 同： 、目同的或彼此不 RV係選自由下列組成之群：_素、 基、c2-c10-埽基、C2_Ci〇_块其 I基、CrCV烧 c4-c6-環烯基、、土、C3'C6·環烷基、 氧基〜氧基、 環稀氧基、c(哪Αΐ Ί乳基、c4-c6_ w )A、N(A2)- 127320.doc 200835487 C(^〇)-A] > N(A3)-C(=0)-N(A2)A1 ShOJm-O-A1 及 s(=0)m-N(A2)A】， 尺亦可能一起為（=〇)或（=s)，或者 Ο ' S(=0)m-A1 > 兩個相鄰基團 或者Rv係苯基，其 中5亥苯基部分基團可攜帶1個、2個或3個基團， 該等基團可為相同的或彼此不同且其係選自由下 列組成之群：鹵素、Cl_C6_烷基、c2_C6-烯基、 cvc6-炔基、c3_C6_環烧基、Ci-(ViS代烷基、 Ci-C6-烷氧基、氰基、硝基、_c( = 〇)_A、 -C(’-0-A、τ(=0)·Ν(Α，)Α、c(A，)(=N 〇A)及 N(A’)A ;其中 m 為〇、1或2 ; A1、A2、A3、A及A，彼此獨立地為氫、 烧基、c2-c6-烯基、c2_c6·快基、c3_C8df 烷基、C3-Cs-環烯基或苯基，其中該等有機 基團可經部分或完全_化或可經_素、硝 基、氰醯基、氰基及/4Ci_C4•烷氧基取 代，或A1及A2、或八及八’分別與其所連接原 子一起為5員或6員飽和、部分不飽和或芳 香族雜環，該雜環可包含丨個、2個、3個或 4個選自由〇、N&s組成之群的雜原子作為 環成員； 中R基團疋義之脂肪族、環脂族及/或芳香 族基團部分可經部分或完全鹵化； R1 亦可為氫； 127320.doc 200835487 R1及R2亦可與其所連接氮原子或碳原子一起形成可含有 〇、S、羰基（〇〇)、次硫醯基（，=〇Η、磺2基 (-SCV)或-(-N(RX)-基團作為環成員之飽和或不飽和5 員或6員環，其中係氫或Ci_C6_烷基，及/或其中所 形成環可包含一個或多個選自由鹵素、Ci_c6_烷基、 ci C6鹵代烷基及氧*_Ci_C3_伸烷氧基組成之群的取 . 代基； R3係選自由下列組成之群：i素、氰基、cvc4-烷基、 c2-cv烯基、c2-c4-炔基、C3-cv環烧基、Ci_C4道氧 基、C3-C4-稀氧基、c3_C4_炔氧基、Ci_c6_烧硫基、 二-(CVCV烷基）胺基及〇1<6_烷基胺基，其中R3基團 疋義之爿曰肪族及/或環脂族基團部分可經部分或完全 齒化或可攜帶1個、2個、3個或4個基團Rt，該等基團 以可為相同的或彼此不同： R係選自由下列組成之群··鹵素、氰基、烷 t. 基、C2_Cl(r烯基、c2-c1(r炔基、經基、 氧基、C3-C6-環燒基、C2-C1(r烯氧基、C2-C1()-炔 氧基、C4-C6-環烯基、c3_c6_環烷氧基、c4'-環 • 稀氧基、-C(=0)-A13、_C〇C〇_〇_A13、 ' N(A )A 、c(A14)(=n_〇A13)、N(A14)AU、 N(A14)-C( = 〇).A13 , N(A15).C( = 0)-N(A14)A13 . S(’。-A13、S(=〇V〇-a1、s(=〇vn(a")a13, 兩個相鄰基團Rt亦可能一起為（=〇)或（=s)，其中 P 係〇、1或2 ; 127320.doc 200835487200835487 IX. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a 2-substituted pyridine of the formula I and a 2-substituted acridine of the formula I for use in the treatment of meto The salts, in particular, are used for the treatment or therapy of cancer or cancerous diseases, respectively. In the formula ί, the V^R2 superscript and substituent are as defined below: Χι Y R1 , = In each case, one of the two ring members is N and the other is CH or a prime; -CH-RL, .N_Rl_, m, R are independently of each other selected from the group consisting of C2-C1Q-fine groups, c2_Ciq_ block groups, Banhuan County, wherein the RW group defines the m-alkyl group and C4-C1〇- The group moiety may be partially or fully i- or di: and/or cycloaliphatic or 4 groups, the (equal) group rv = one, two, three identical:, identical or not RV to each other. Is selected from the group consisting of: _, base, c2-c10-fluorenyl, C2_Ci〇_ block, its I group, CrCV burned c4-c6-cycloalkenyl, earth, C3'C6·cycloalkyl, oxygen 〜~oxy, cyclooxyl, c(ΑΐΑΐ Ί, c4-c6_ w )A, N(A2)- 127320.doc 200835487 C(^〇)-A] > N(A3)-C (=0)-N(A2)A1 ShOJm-O-A1 and s(=0)mN(A2)A], the ruler may also be (=〇) or (=s) together, or Ο 'S(=0 m-A1 > two adjacent groups or Rv-based phenyl groups, wherein the 5 phenyl moiety may carry 1, 2 or 3 groups, and the groups may be the same or different from each other And its Is selected from the group consisting of halogen, Cl_C6_alkyl, c2_C6-alkenyl, cvc6-alkynyl, c3_C6_cycloalkyl, Ci-(ViS alkyl, Ci-C6-alkoxy, cyano, Nitro, _c( = 〇)_A, -C('-0-A, τ(=0)·Ν(Α,)Α, c(A,)(=N 〇A) and N(A')A Wherein m is 〇, 1 or 2; A1, A2, A3, A and A, independently of each other, hydrogen, alkyl, c2-c6-alkenyl, c2_c6· fast radical, c3_C8df alkyl, C3-Cs-ring Alkenyl or phenyl, wherein the organic groups may be partially or fully- or may be substituted by _, nitro, cyano, cyano and /4Ci_C4 alkoxy, or A1 and A2, or VIII And 八' are 5 or 6 member saturated, partially unsaturated or aromatic heterocyclic ring together with the atom to which they are attached, and the heterocyclic ring may comprise 、, 2, 3 or 4 selected from 〇, N&s a hetero atom of the group as a ring member; an aliphatic, cycloaliphatic and/or aromatic moiety of the R group may be partially or completely halogenated; R1 may also be hydrogen; 127320.doc 200835487 R1 and R2 also It may form a ruthenium, S, or carbonyl group together with a nitrogen atom or a carbon atom to which it is attached. A saturated or unsaturated 5- or 6-membered ring of a sulfhydryl group (==〇Η, sulfo-2-yl (-SCV) or —(-N(RX)- group as a ring member, wherein hydrogen or Ci_C6-alkane And the ring formed therein may comprise one or more substituents selected from the group consisting of halogen, Ci_c6-alkyl, ci C6 haloalkyl and oxy*_Ci_C3_aralkyloxy; R3 is selected from a group consisting of: i, cyano, cvc4-alkyl, c2-cv alkenyl, c2-c4-alkynyl, C3-cv cycloalkyl, Ci_C4 oxy, C3-C4-dioxy, c3_C4 _ alkynyloxy, Ci_c6_sulfuryl, bis-(CVCV alkyl)amine and 〇1<6-alkylamino, wherein the R3 group is a alicyclic and/or cycloaliphatic moiety It may be partially or completely dentated or may carry 1, 2, 3 or 4 groups of Rt, which may be the same or different from each other: R is selected from the group consisting of halogens, Cyano, alkyl t., C2_Cl (r alkenyl, c2-c1 (r alkynyl, thiol, oxy, C3-C6-cycloalkyl, C2-C1 (r-alkenyloxy, C2-C1()) -alkynyloxy, C4-C6-cycloalkenyl, c3_c6_cycloalkoxy, c4'-cyclo • diloxy, -C(=0)-A13, _C〇C〇_〇_A13, ' N(A )A , c(A14)(=n_〇A13), N(A14)AU, N(A14)-C( = 〇).A13 , N(A15).C( = 0)-N (A14) A13 . S ('. -A13, S(=〇V〇-a1, s(=〇vn(a")a13, two adjacent groups Rt may also be (=〇) or (=s) together, where P is 〇, 1 Or 2; 127320.doc 200835487

A 13 A彼此獨立地具有如上文所定義 A1、A2及A3之含義； 二 基團疋義之脂肪族、環脂族及/或芳香 族基團部分可經邻 J、工口P刀或元全鹵化或可攜帶丨個、2 個或3個基團ru， R4A 13 A independently of each other has the meanings of A1, A2 and A3 as defined above; the aliphatic, cycloaliphatic and/or aromatic group of the two groups can be passed through the neighboring J, the work P knife or the whole Halogenated or carry one, two or three groups ru, R4

L Θ #基團R可為相同的或彼此 不同且其具有如上文所定義Rt之含義，· 係5員、6員、7昌 、貝、9員或10員飽和、部分不飽 和或方香族單環式- w j次一％雜ί辰，該單環或二環雜環包 1個、2個、3個或4彳is1 、 選自由G、NAS組成之群的雜原 子作為ί衣成員且发中 — /、中雜&邛分可經部分或完全i化或 可攜帶1個、2個、3個七甘 ^ . 3個或4個基團RU，該等基團RU可為 相同的或彼此不同： RU係選自由下列組成之群··齒素、氰基、C1-C10-垸 :C2 C1(r烯基、C2_CiG_炔基、羥基、燒 ^基、CrC6-環垸基、C2-C10-烯氧基、c2-C1〇i 氧基、C4eCV環烯基、c3-c6-環烷氧基、c4-cv環 烯 1 基、-C(==0)-A4、·(：(哪Ο-a、-c(哪 N(A )A、-C(=s)-N(A5)A4、c(A5)(=N-OA4)、 N(A )A ^ N(A )-C(=〇).A4 λ N(A6)-C(=0)-N(A5)A4 > S( 〇)crA、S(==0V〇-A4 及 S(=〇VN(A5)A4，兩 個相鄰基團Ru亦可能一起為卜〇)(脅其中 q 係〇、1或2; A A及A 彼此獨立地具有如上文所定義 A1、A2及A3之含義； 127320.doc 200835487 且其中Ru基團定義之脂肪族、環脂族及/或芳香 族基團部分可經部分或完全鹵化或可攜帶1個、2 個或3個基團rm，該等基團可為相同的或彼此 不同且其具有如上文所定義Ru之含義；L Θ # groups R may be the same or different from each other and have the meaning of Rt as defined above, · 5 members, 6 members, 7 Chang, Bay, 9 members or 10 members saturated, partially unsaturated or square a single-ring type - wj-one-by-half-thirty-thirty-thirty-thirty-thousand-half-half-half-half-half-half-half And the hairs may be partially or completely i- or may carry one, two, three, seven or three groups of RUs, and the groups RU may be The same or different from each other: RU is selected from the group consisting of dentate, cyano, C1-C10-垸: C2 C1 (r-alkenyl, C2_CiG-alkynyl, hydroxy, alkyl, CrC6-cyclic oxime , C2-C10-alkenyloxy, c2-C1〇ioxy, C4eCV cycloalkenyl, c3-c6-cycloalkoxy, c4-cvcycloalkenyl, -C(==0)-A4, ·(:(where Ο-a, -c(which N(A )A, -C(=s)-N(A5)A4, c(A5)(=N-OA4), N(A )A ^ N (A )-C(=〇).A4 λ N(A6)-C(=0)-N(A5)A4 > S( 〇)crA, S(==0V〇-A4 and S(=〇VN (A5) A4, two adjacent groups Ru may also be together (in the case of q, 1, 1 or 2; AA and A are each other) The site has the meanings of A1, A2 and A3 as defined above; 127320.doc 200835487 and wherein the aliphatic, cycloaliphatic and/or aromatic moiety defined by the Ru group may be partially or fully halogenated or may carry 1 , 2 or 3 groups rm, which groups may be the same or different from each other and have the meaning of Ru as defined above;

亦可為：氰基、0：(=^)〇1^、（3(=2州1121^、（3(=2讲112- ORa、C(=Z)NRa-NRzRb、C(=Z)Ra、CRaRb-〇Rz、 CRaRb_NRzRc、〇N(=CRaRb)、〇-C(=Z)Ra、NRaRbl、 NRa(C(=Z)Rb)、NRa(C(=Z)ORb)、NRa(C(=Z)-NRzRb)、 NRa(N=CRcRb)、NRa-NRzRb 或 NRz-ORa，其中 Z 係 〇、S、NRal、NORal 或 N-NRzlRcl ;It can also be: cyano group, 0: (=^) 〇 1^, (3 (= 2 states 1121^, (3 (= 2 speak 112- ORa, C (= Z) NRa-NRzRb, C (= Z) Ra, CRaRb-〇Rz, CRaRb_NRzRc, 〇N(=CRaRb), 〇-C(=Z)Ra, NRaRbl, NRa(C(=Z)Rb), NRa(C(=Z)ORb), NRa(C (=Z)-NRzRb), NRa(N=CRcRb), NRa-NRzRb or NRz-ORa, wherein Z is 〇, S, NRal, NORal or N-NRzlRcl;

Ra、Ral、Rb、Re、Rd彼此獨立地為氫、Ci_C6_烷 基、c2-c6-烯基、c2-c6-炔基、c3-c6-環烷基或 C4-CV環烯基；Ra, Ral, Rb, Re, and Rd are each independently hydrogen, Ci_C6-alkyl, c2-c6-alkenyl, c2-c6-alkynyl, c3-c6-cycloalkyl or C4-CV cycloalkenyl;

Rbl具有如上文所定義Rb之含義，氫除外； RZ、RZl彼此獨立地具有如上文所定義Ra之含義且亦 可為-CO-Ra2，其中Ra2具有如上文所定義Ra之含 義； 其中 Ra、R“、Rb、Rbl、RC、RC1、RZ&RZ1基團定義之 脂肪族、環脂族及/或芳香族基團部分可經部分或完 全鹵化或可攜帶1個、2個、3個或4個基團Rw，該等基 團Rw可為相同的或彼此不同：Rb1 has the meaning of Rb as defined above, except for hydrogen; RZ, RZl, independently of one another, have the meaning of Ra as defined above and may also be -CO-Ra2, wherein Ra2 has the meaning of Ra as defined above; The aliphatic, cycloaliphatic and/or aromatic moiety of the R", Rb, Rbl, RC, RC1, RZ&RZ1 group may be partially or fully halogenated or may carry 1, 2, 3 or 4 groups Rw, these groups Rw may be the same or different from each other:

Rw係i素、氰基、cvcv垸基、c2_Cl()_稀基、 c10-炔基、CVCV烷氧基、C2-Ci(r烯氧基、c” c10-炔氧基、C3-C6-環烷基、c3_c6•環烯基、c3· 127320.doc -ιο· 200835487 烷氧基或CVCV環烯氧基， 且其中基團Ra、Rai、Rb、Rbl 土 兩個與其所連接原子一起可形成5二、，或Μ中的 不飽和或料族雜環，該雜或6貝飽和、部分 Θ 個選自由ο Μ 含1個、2個、3個或4 係％、及8組成之群的雜原子作為環成員，· 之:二:：含1個、2個或3個選自由組成 之群雜原子的5員或6員雜芳基；Rw is i, cyano, cvcv fluorenyl, c2_Cl()-dilute, c10-alkynyl, CVCV alkoxy, C2-Ci(r-alkenyloxy, c"c10-alkynyloxy, C3-C6- Cycloalkyl, c3_c6•cycloalkenyl, c3· 127320.doc -ιο· 200835487 alkoxy or CVCV cycloalkenyloxy, and wherein the groups Ra, Rai, Rb, Rbl are formed together with the atoms to which they are attached 5, or, in the oxime, an unsaturated or a taxocyclic heterocyclic ring, the hetero or 6-shell saturated, partially Θ selected from the group consisting of ο Μ containing 1, 2, 3 or 4%, and 8 a hetero atom as a ring member, wherein: two:: one, two or three heteroaryl groups selected from the group consisting of heteroatoms;

η Lη L

1.,/ 為 1、2、3、4 或 5 ; =自由下列組成之群：“、氰基、氰醯基 \cN)、Cl-Cl0_炫基、C2_Ci〇_稀基、C2_块基、 1-C6·炫氧基、C2-Cl。-烯氧基、c2-Cl。-块氧基、c3· c6-%炫基、c4_cv環稀基、C3_C6_環燒氧基、C4-C6_ 裱烯氧基、硝基、_C( = 〇)_A7、_c( = 〇K)_A7、# = 〇> N(a8)a7、-c(=s)_n(a8)a7、-C(=NAVSV、c(a8) ( = N-0A7)、N(A8)A7 ' N(a8)_c( = 〇) a7、n(a9) c( = 〇)_ N(A8)A7、S( = 〇)r-A7、s( = 〇) _〇 a7 及 s ㈣ N(A8)A7,其中倘若n為2、3、4或5，則L可為等同的 或不同的，且其中 r 係〇、1或2 ; A7、A8、A9彼此獨立地具有如上文所定義Al、a2及 A3之含義； 其中L·基團定義之脂肪族、環脂族及/或芳香族基團部 分可經部分或完全函化或可攜帶丨個、2個、3個或4個 基團RL，該等基團《>可為相同的或彼此不同： 127320.doc -11 · 200835487 自由下列組成之群：鹵素、氰基、Ci_Ci〇•烷 二 CfCio-稀基、C2-C1()-块基、經基、Cl_C6_^ 氧基、c2_c1(r烯氧基、c2_CiG_炔氧基、CrC64 ^基、c4-cv環烯基、c3-c6•環烷氧基、c4_c6_環 烯氧基、-〇( = 0)-八1。、-匚(=〇)-〇-八1()、-〇：( = 0)-N(A )A10 > C(An)(=N-OA10) > N(An)A10 ^ • N(A )-C(=〇).Ai〇 Λ N(A12).C(=〇)-N(A11)A10 - (s S( 〇)’Α °、S—OVO-A10 及 S(=〇)s-N(An)A1()， 兩個相鄰基團rL亦可能一起為（=0)或（=S)，其中 S 為0、1或2 ;且 Α及Α 彼此獨立地具有如上文所定義 A1、A2及A3之含義； /、中R基團定義之脂肪族、環脂族及/或芳香 知基團。卩分可經部分或完全_化或可攜帶1個、2 個、3個或4個基團rla，該等基團rLA可為相同的 〇 ·或彼此不同且其具有如上文所定義妙之含義。 具體而言，本發明係關於式I化合物及其醫藥上可接受 之鹽分別在癌症或癌性疾病之治療或療法中的用途。 _ 本發明亦係關於包含如本文所定義式I之2'經取代吡啶 醫藥上可接受之鹽及（視情況）醫藥上可接受之載劑的 醫樂組合物。進而言之，本發明係關於如本文所定義式I ^ 2 ^取代％ ,定及其醫藥上可接受之鹽在製造藥物（具體而 刀別用於癌症或癌性疾病之治療或療法之藥物）中的 用途本發明亦提供一種用於癌症療法之方法，該方法包 127320.doc •12- 200835487 括對需要其之個體投與有效量的如本文所定義式1之2_經取 代吡啶或其醫藥上可接受之鹽。 【先前技術】 儘管在研究及新穎療法選擇中已取得顯著進步，但癌症 仍為一個主要致死因素。在不同類別癌症中，最經常診斷 出諸如肺癌、乳癌、***癌及結腸癌等癌症以及結腸淋 巴瘤且卵巢癌係繼乳癌後之第二最常見女性生殖性癌症。 已知諸多細胞毒性化合物可有效地抑制腫瘤細胞生長，該 等細胞毒性化合物包括紫杉烷，如紫杉醇（Tax〇le)、多西 他賽（d〇Cetaxel)(TaX〇tere);長春花生物鹼，長春瑞濱 (vinorelbine) > 長春花鹼（vinblastine)、長春地辛 (vindesine)及長春新鹼（vincristine)。然而，此等化合物係 具有複雜結構且因此難以產生之天然產物。 因此，本發明之目標係提供可有效地控制或抑制腫瘤細 胞之生長及/或子代且因此可用於癌症療法之化合物。人 們極為需要可自簡單初始化合物按照有機化學之標準方法 合成此等化合物。 【發明内容】 吾人發現此等及其他目標可藉由開篇處収義2_經取代 吼咬I達成。進而言之，吾人發現—種用於癌症療法之方 法，該方法包括對需要其之個體投與有效量的如本文所定 義2-經取代°比啶I或其醫藥上可接受之鹽。 2-經取代吡啶j已經闡述於w〇 2〇〇6/〇〇〇358中。其中所 揭示化合物對各種植物病原真菌有活性。然而，此文件並 127320.doc -13- 200835487 未闡述或建議此等化人私7 -Γ 士， 口物可有效地治療疾病或甚至治療癌 症。 ” 2、、二取代吡。疋！可藉由揭示於2⑼W000358及其中所 引用文獻中之方法以及藉由標準有機化學方法來製備。 ㈣可使用2.經取代°比"定I之生理學上可耐受之鹽，尤 其是與生理學上可耐受之酸形成的酸加成鹽。適宜生理學 上可耐受之有機酸及無機酸的實例係氮氯酸、氯漠酸、鱗 西夂、硝酸、硫酸、具有i個至12個碳原子之有機磺酸(例 如諸如甲石尹、g夂等之c】_c4燒基續酸、諸如s_(+)_i〇_掉腦 續酸等之《料酸及諸如料酸以料酸等之芳香族 石黃酸）、具有2個至1G個碳原子之二緩酸及三叛酸及經基缓 酸，例如，草酸、呙-舻 ^ ^ 丙一敲、馬來酸、富馬酸、黏酸、乳 酸、酒石酸、擰檬酸、乙醇酸及己二酸以及順式_和反式 肉才土酉夂糠I及苯甲酸。其他可用酸闡述於F。如hriUe der Arzneimittelforschung [Advances in Drug Research] ? 第l〇卷，第224頁及以下各頁，心恤咖ν^，_ _ Stuttgart，i 966。2'經取代吼咬r生理學上彳耐受之鹽 可呈單鹽、雙鹽、奏鹽及肆鹽其中每個式!分子可 含有1個、2個、3個或4個上述酸分子。該等酸分子可呈其 酸形式或呈陰離子出現。該等酸加成鹽可以慣用方式藉由 混合2'經取代之游離驗與對應酸來製備，適當時，呈 水溶液或有機溶劑溶液形式，該有機溶劑係（例如）低碳數 :，例如，甲醇、乙醇、丙醇或異丙醇；㈣，例如，甲基 第三-丁基醚或二異丙基醚；，’例如，丙酮或甲基乙基 127320.dGe .14. 200835487 酮；或酯，例如，乙酸乙酯。可添加不會溶解〗之酸加成 鹽之溶劑（反溶劑）使該鹽沈澱。適宜反溶劑包括Ci-Czr脂 肪酸之c^c：4-烷基酯，例如，乙酸乙酯；脂肪族及環脂族 烴，例如，己烷、環己烷、庚烷等；二弋广烷基醚，例 如’甲基第三-丁基醚或二異丙基醚。 【實施方式】 在上式I所給出符號定義中，使用了統稱，其通常代表 下列取代基： -鹵素：氟、氯、溴或碘； -烷基及烷氧基、烷硫基、烷基羰基、烷氧基羰基、烷 基胺基、二（烷基）胺基、烷基胺基羰基、二（烷基）胺基羰 基、烧基羰基胺基、烧基亞確醯基、烧基續醯基、烧基胺 基磺酿基或二（烷基）胺基磺醯基之烷基部分：具有1個至1〇 個碳原子，較佳具有1個至8個碳原子，更佳具有1個至6個 碳原子’尤其具有1個至4個碳原子之飽和、直鏈或具支鏈 烴基團，例如，甲基、乙基、丙基、1 _甲基乙基、丁基、 1-甲基丙基、2-甲基丙基、ι，ΐ-二甲基乙基、戊基、^甲 基丁基、2 -甲基丁基、3·甲基丁基、2，2-二-甲基丙基、ι_ 乙基丙基、己基、1，1-二甲基丙基、1，2-二甲基丙基、；μ甲 基戊基、2-甲基戊基、3_甲基戊基、4-甲基戊基、u-二 甲基丁基、1，2·二甲基丁基、1，3-二甲基丁基、2,2_二甲基 丁基、2,3-二甲基丁基、3,3-二甲基丁基、乙基丁基、2一 乙基丁基、1，1，2 -二甲基丙基、1，2,2 -三甲基丙基、ι_乙基_ 1-甲基丙基及1-乙基·2-甲基丙基； 127320.doc -15- 200835487 -烯基及烯氧基之烯基部分：具有2個至ι〇個，較佳具有 2個至6個且具體而言，具有2個至4個碳原子且在任一位置 具有雙鍵（尤其是C^C：4-烯基）之不飽和、直鏈或具支鏈烴 基團，例如，乙烯基、1-丙烯基、2-丙烯基、卜甲基乙烯 基、1-丁烯基、2-丁烯基、3-丁烯基、1-甲基-1-丙烯基、 2-甲基-1-丙烯基、1-曱基_2_丙烯基、2-曱基·2_丙烯基、^ 戊烯基、2_戊烯基、3-戊烯基、4·戊烯基、1-甲基-1-丁烯 基、2-甲基-1_ 丁烯基、3·甲基-^ 丁烯基、1β甲基-孓丁烯 基、2-曱基_2_ 丁烯基、3 -曱基-2-丁烯基、1-甲基-3-丁烯 基、2-甲基-3-丁烯基、3_甲基_3_丁烯基、ΐ5ΐ•二甲基丙 烯基、1，2-二甲基-1-丙烯基、；ι，2-二甲基·2_丙烯基、^乙 基丙烤基、1-乙基-2-丙烤基、己稀基、2 -己稀基、3-己烯基、4-己烯基、5-己烯基、1-甲基-1-戊烯基、2-甲基- 1- 戊烯基、3-甲基-1-戊烯基、4-曱基-1-戊烯基、1-甲基-2-戊烯基、2-甲基-2-戊烯基、3-甲基-2-戊烯基、4-甲基-2-戊烯基、：U甲基戊烯基、2-甲基-3-戊烯基、3-曱基-3-戊烯基、4-甲基-3-戊烯基、1-甲基-4-戊烯基、2-甲基-4-戊烯基、3-甲基-4-戊烯基、4-曱基-4-戊烯基、1，1-二甲基_ 2- 丁烯基、ij-二甲基_3-丁烯基、it二甲基-卜丁烯基、 1，2-二甲基_2-丁烯基、1，2-二甲基-3-丁烯基、1，3-二甲基- 1- 丁烯基、1，3·二甲基-2-丁烯基、ι，3-二甲基-3-丁烯基、 2,2_二曱基-3-丁烯基、2,3-二甲基_1-丁烯基、2,3-二甲基- 2- 丁烯基、2,3-二甲基-3-丁烯基、3,3·二甲基-1-丁烯基、 3,一甲基丁烯基、1-乙基-1-丁烯基、1-乙基-2-丁烯 127320.doc •16- 200835487 基、1-乙基-3· 丁烯基、2_乙基·i· 丁烯基、2_乙基_2_ 丁烯 基2_乙基-3· 丁烯基、1，1，2-三甲基-2·丙烯基、ι_乙基_ΐ- 曱基-2-丙稀基、i•乙基_2_甲基小丙稀基及i.乙基_2_甲基· 2-丙晞基； 烯L基·具有4個至8個，具體而言，具有4個至6個 反原子及在任何 >[立置具彳兩個雙鍵之不飽和直鍵或具支鍵 煙基團，例如，丁 -、t岳、Ί。1 U 丁一沐、戊二烯、M-戊二烯、1，3-己 二烯、M-己二烯及丨，^己二烯； -炔基·具有2個至10個，較佳具有2個至6個，具體而 言，具有2個至4個碳原子且在任一位置具有一個三鍵（尤 其是G-C：4-炔基）之直鏈或具支鏈烴基團，例如，乙炔基、 1-丙炔基、2-丙炔基、丨_丁炔基、2_丁炔基、3_丁炔基、^ 甲基-2-丙快基、N戊块基、2_戊块基、3戊炔基、4_戊块 甲基-1-丁炔基、1，1_二甲基_2_丙炔基、卜乙基·2-丙 1-己炔基、2-己炔基、3_己炔基、仁己炔基、5_己 1- 甲基-2-戊炔基、1-甲基_3_戊炔基、丨_甲基_4_戊 2- 甲基-3_戊炔基、2-甲基-4-戊炔基、3_甲基_丨_戊 3- 甲基-4-戊炔基、4-甲基戊炔基、‘甲基·2_戊 1，1-二甲基-2-丁炔基、1J-二甲基丁炔基、 一甲基-3-丁炔基、2,2-一甲基-3-丁炔基、3,3·二甲基_1_丁 炔基、1·乙基-2-丁炔基、1-乙基-3-丁炔基、2_乙基_3_ 丁 快基及1-乙基-1·"甲基-2-丙炔基； -環烷基：具有3個至10個碳原子之單環或二環烴基團； 基、1-甲基-2-丁炔基、1_甲基_3_丁炔基、2_甲基_3_ 丁炔 基、 炔基 炔基 炔基 炔基 炔基 127320.doc -17- 200835487 具有3個至8個，尤其具有3個至6個環成員之單環基團，例 如，CyC8-環燒基，如環丙基、環丁基、環戊基、環己 基、環庚基及環辛基； -i代烧基及_代烷氧基之_代烷基部分：其中存於基 團中之氫原子可部分或完全由如上文所述_素原子代替的 如上文所述具有丨個至10個碳原子，較佳具有丨個至6個碳 原子，尤其具有1個至4個碳原子之直鏈或具支鏈烷基基 團，例如，C^C：4-鹵代烷基，如氯甲基、溴甲基、二氯甲 基、三氣甲基、氟甲基、二氟甲基、三氟甲基、氣氟甲 基、二氯氟甲基、氯二氟甲基、氣乙基、丨_溴乙基、卜 氟^乙基、2-氟乙基、2,2_二氟乙基、2,2,2_三氟乙基、2_氣_ 2-氟乙基、2-氣_2,2-二氟乙基、2,2-二氣氟乙基、2,2,2_ 三氯乙基、五氟乙基、1，U-三氯丙基、以山三氟丙_ b基、l，l，l-三氣丙-2-基及1，1，1_三氟丙基；類似考慮 因素適用於其他-化基團，例如，#中烯基、炔基及環烷 基基團《氫原子可部分或完全經如上文所㈣素原子代替 的鹵代烯基、_代炔基及函代環烷基； •氧基-伸烷氧基：具有2個至3碳原子之二價直鏈烴基 團，例如，och2ch2o或 0CH2CH2CH20; -5貝、6員、7員、8員、9員或10員雜環：含有i個至4個 ^自由氮原子、氧原子及硫原子組成之群的雜原子之同素 環或二環烴基團；不飽和（雜環基）包括部分不飽和（例如， 單-不飽和）及芳香族（雜芳基）；該等雜 127320.doc -18- 200835487 氧原子之5·員雜芳基：除含有碳原子外亦可含u個至*個 氮原子或1個至3個氮原子及丨個硫原子或氧原子作為環成 員之5-員雜芳基基團，例如，2_呋喃基、3_呋喃基、唭 吩基、3-噻吩基、苯硫基、2_吡咯基、3_吡咯基、h異噁 唾基、4-異嚼嗤基、5-異嗎嗤基、3_異嗟嗤基\異= 基、5-異^坐基、丨-吼。坐基、3_。比嗤基、坐基、5_吼 唑基、2+坐基、坐基、5_喔。坐基、2•嗟唾基、*噻 唾基、5-嗟吐基、2-口米唾基、心㈣基、坐 基、1，2,4-噁二唑-5-基、噻二唑基、山·噻二唑_ 5_基、1，2,3-***-基、***·b基、u，***3 基、四唆基、山-嗔二仏基、以“塞二嗤士基及 1，3,4-***-2-基； 1 -含有！個至4個氮原子之6.員雜芳基：_除含有碳原子外 :可含有i個至3個或i個至4個氮原子作為環成員以·員雜 方基基團，例如，2_吼咬基、3十定基、4“比咬基、3_成 噪基、4+秦基、2“㈣基、4•㈣基、5_嘧録、μ 嗪基、1，2,3·三嗪基、us三嗪_2_基及基。 含有!個至4個氮原子或i個至3個氮原子及】個硫原子或 乳原子之9-或10·員雜芳基：除含有碳原子外亦可含有⑽ 至4個氮原子或i個至3個氮原子及1個硫原子或氧原子 :成員之9員或1〇員雜芳基基團，具體而言，含有i個至3 。乳原子或！個氮原子及i個氧原子或硫原子之苯并祠Μ =6貝雜芳基(即，除含有碳原子外亦可含有}個至4個氮 '、或1個至3個虱原子及!個硫原子或氧原子作為環成員 127320.doc -19- 200835487 且其中兩個田比鄰磁戸# 0 衣貝或1個氮原子及1個毗鄰碳環成員 J稽田丁-1，3-二條！ 1 4 團），例如，苯并“—基基團橋接之5員或6員雜芳基基 ^坐-2-基、出-吲嗓小基、m_吲哚_2_ 土、1H令朵_3_基、瓜十坐小基基、苯并 呋喃-2-基及苯并咬喃·3_基；噎啉_2•基、噎啉_3_基、喹 啉-4-基、異啥啉_丨_基、異喧啉_3_基、異喹啉_4_基、呔嗪 基、喹喔啉基、喹唑啉_2_基、喹唑啉_4_基、啐啉·3_基及 碎琳_4-基。1., / is 1, 2, 3, 4 or 5; = free group of the following: ", cyano, cyanonyl \cN), Cl-Cl0_ 炫, C2_Ci 〇 稀, C2_ block Base, 1-C6·Ethyloxy, C2-Cl.-Alkenyloxy, c2-Cl.-Blockoxy, c3·c6-% leucoyl, c4_cv cycloaliphatic, C3_C6_cycloalkoxy, C4- C6_ deceneoxy, nitro, _C(= 〇)_A7, _c( = 〇K)_A7, # = 〇> N(a8)a7, -c(=s)_n(a8)a7, -C( =NAVSV, c(a8) ( = N-0A7), N(A8)A7 ' N(a8)_c( = 〇) a7, n(a9) c( = 〇)_ N(A8)A7, S( = 〇)r-A7, s( = 〇) _〇a7 and s (iv) N(A8)A7, wherein if n is 2, 3, 4 or 5, L may be equivalent or different, and wherein r is 〇 , 1 or 2; A7, A8, A9 have the meanings of Al, a2 and A3 as defined above independently of each other; wherein the aliphatic, cycloaliphatic and/or aromatic moiety defined by the L group may be partially Or fully functional or carry one, two, three or four groups RL, which groups may be the same or different from each other: 127320.doc -11 · 200835487 Free group of the following: Halogen, cyano, Ci_Ci 烷 alkane di CfCio-dilute, C2-C1()-block, Passage group, Cl_C6_^oxy group, c2_c1 (r-alkenyloxy group, c2_CiG_alkynyloxy group, CrC64^ group, c4-cv cycloalkenyl group, c3-c6•cycloalkoxy group, c4_c6_cycloalkenyloxy group, -〇 ( = 0) - 八1., -匚(=〇)-〇-八1(), -〇:( = 0)-N(A )A10 > C(An)(=N-OA10) > N(An)A10 ^ • N(A )-C(=〇).Ai〇Λ N(A12).C(=〇)-N(A11)A10 - (s S( 〇)'Α °, S— OVO-A10 and S(=〇)sN(An)A1(), two adjacent groups rL may also be (=0) or (=S) together, where S is 0, 1 or 2; Α independently of each other has the meanings of A1, A2 and A3 as defined above; /, an aliphatic, cycloaliphatic and/or aromatic group defined by the R group. The moiety may be partially or completely _ or may be Carrying 1, 2, 3 or 4 groups rla, these groups rLA may be the same 〇 or different from each other and have the meaning as defined above. In particular, the invention relates to Use of a compound of I and a pharmaceutically acceptable salt thereof, respectively, in the treatment or therapy of cancer or a cancerous disease. The invention is also directed to a pharmaceutical composition comprising a 2'-substituted pyridine pharmaceutically acceptable salt of formula I as defined herein and, optionally, a pharmaceutically acceptable carrier. Further, the present invention relates to a compound of the formula I ^ 2 ^ as defined herein, and a pharmaceutically acceptable salt thereof for the manufacture of a medicament (specifically, a medicament for the treatment or therapy of cancer or cancerous disease) Uses in the Invention The invention also provides a method for cancer therapy, comprising 127320.doc • 12-200835487 comprising administering to a subject in need thereof an effective amount of a 2-substituted pyridine of formula 1 as defined herein or Its pharmaceutically acceptable salt. [Prior Art] Although significant advances have been made in research and novel therapy options, cancer remains a major cause of death. Among the different types of cancer, cancers such as lung cancer, breast cancer, prostate cancer and colon cancer, as well as colonic lymphoma and ovarian cancer are the second most common female reproductive cancer after breast cancer. Many cytotoxic compounds are known to effectively inhibit tumor cell growth, such as taxanes, such as paclitaxel (Tax〇le), docetaxel (TaX〇tere); vinca Alkali, vinorelbine > vinblastine, vindesine and vincristine. However, such compounds are natural products that have a complex structure and are therefore difficult to produce. Accordingly, it is an object of the present invention to provide compounds which are effective in controlling or inhibiting the growth and/or progeny of tumor cells and which are therefore useful in cancer therapy. It is highly desirable that these compounds be synthesized from simple starting compounds in accordance with standard methods of organic chemistry. SUMMARY OF THE INVENTION We have found that these and other goals can be achieved by replacing the bite I at the beginning. Further, we have discovered a method for cancer therapy which comprises administering to an individual in need thereof an effective amount of a 2-substituted pyridine I or a pharmaceutically acceptable salt thereof as defined herein. 2-Substituted pyridine j has been described in w〇 2〇〇6/〇〇〇358. The compounds disclosed therein are active against a variety of phytopathogenic fungi. However, this document does not address or suggest that such a person can effectively treat a disease or even treat cancer. 127320.doc -13- 200835487 2. Disubstituted pyridinium can be prepared by the method disclosed in 2(9)W000358 and the literature cited therein and by standard organic chemical methods. (4) The physiology of 2. substituted ratio can be used. a tolerable salt, especially an acid addition salt with a physiologically tolerated acid. Examples of suitable physiologically tolerable organic and inorganic acids are chloric acid, chloroform acid, scales. Anthraquinone, nitric acid, sulfuric acid, an organic sulfonic acid having i to 12 carbon atoms (for example, c such as methystine, g夂, etc.) _c4 succinyl acid, such as s_(+)_i〇_ Etc. "Acid acid and aromatic rhein such as acid to acid", bis-acid with 2 to 1G carbon atoms and tri-hazard and basal acid, for example, oxalic acid, cerium-lanthanum ^ ^ C-knock, maleic acid, fumaric acid, mucic acid, lactic acid, tartaric acid, citric acid, glycolic acid and adipic acid, and cis- and trans-fertility I and benzoic acid. Others Acids can be described in F. For example, hriUe der Arzneimittelforschung [Advances in Drug Research] ? Page, page 224 and below, sympathy ν^, _ _ Stuttgart, i 966. 2' Substituted bite r Physiologically tolerant salt can be a single salt, a double salt, a salt and a strontium salt. Each of the molecules can contain 1, 2 , 3 or 4 of the above acid molecules. The acid molecules may be present in their acid form or as an anion. These acid addition salts may be prepared in a conventional manner by mixing 2' substituted free tests with the corresponding acids. Where appropriate, in the form of an aqueous solution or an organic solvent, for example, a low carbon number: for example, methanol, ethanol, propanol or isopropanol; (iv), for example, methyl tert-butyl ether or two Isopropyl ether;, 'for example, acetone or methylethyl 127320.dGe.14. 200835487 ketone; or ester, for example, ethyl acetate. A solvent which does not dissolve the acid addition salt (anti-solvent) can be added. The salt is precipitated. Suitable antisolvents include c^c:4-alkyl esters of Ci-Czr fatty acids, for example, ethyl acetate; aliphatic and cycloaliphatic hydrocarbons, for example, hexane, cyclohexane, heptane, etc. Diterpenoid alkyl ether, such as 'methyl third-butyl ether or diisopropyl ether. [Embodiment] In the above formula I In the definition of symbols, the general term is used, which usually represents the following substituents: - halogen: fluorine, chlorine, bromine or iodine; - alkyl and alkoxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylamine Base, di(alkyl)amino group, alkylaminocarbonyl group, di(alkyl)aminocarbonyl group, alkylcarbonylamino group, alkyl sulfhydryl group, alkyl group, alkyl group sulfonate An alkyl moiety of a bis(alkyl)aminosulfonyl group: having from 1 to 1 carbon atoms, preferably having from 1 to 8 carbon atoms, more preferably from 1 to 6 carbon atoms. a saturated, linear or branched hydrocarbon group having from 1 to 4 carbon atoms, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2- Methylpropyl, ι, ΐ-dimethylethyl, pentyl, methyl butyl, 2-methylbutyl, 3-methylbutyl, 2,2-di-methylpropyl, ι_ Ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, μmethylpentyl, 2-methylpentyl, 3-methylpentyl, 4- Methylpentyl, u-dimethylbutyl, 1,2,dimethylbutyl, 1,3-dimethyl Base, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, ethylbutyl, 2-ethylbutyl, 1,1,2- Dimethylpropyl, 1,2,2-trimethylpropyl, i-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl; 127320.doc -15- 200835487 - Alkenyl moiety of alkenyl and alkenyloxy: having from 2 to 〇, preferably from 2 to 6, and specifically having from 2 to 4 carbon atoms and having a double bond at any position (especially An unsaturated, linear or branched hydrocarbon group of C^C: 4-alkenyl), for example, vinyl, 1-propenyl, 2-propenyl, methylmethyl, 1-butenyl, 2-butene Alkenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-indenyl-2-propenyl, 2-indenyl-2-propenyl, ^ Pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-^ Alkenyl, 1β methyl-nonenbutenyl, 2-mercapto-2-butenyl, 3-mercapto-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3 -butenyl, 3-methyl-3-butenyl, ΐ5ΐ•dimethylpropenyl, 1,2- Methyl-1-propenyl, ι,2-dimethyl-2-propenyl, ethylpropenyl bromide, 1-ethyl-2-propene bake, hexyl, 2-hexyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl , 4-mercapto-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl- 2-pentenyl, :U methylpentenyl, 2-methyl-3-pentenyl, 3-mercapto-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl 4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-mercapto-4-pentenyl, 1,1-dimethyl-2 - butenyl, ij-dimethyl-3-butenyl, it dimethyl-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3 -butenyl, 1,3-dimethyl-1-butenyl, 1,3·dimethyl-2-butenyl, iota, 3-dimethyl-3-butenyl, 2,2 _Dimercapto-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butene Alkenyl, 3,3·dimethyl-1-butenyl, 3,monomethylbutenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butene 127320.doc 16- 200835487 base, 1-ethyl-3-butenyl, 2-ethyl·i·butenyl, 2-ethyl-2-butenyl 2-ethyl-3·butenyl, 1,1 ,2-trimethyl-2·propenyl, ι_ethyl-ΐ-mercapto-2-propenyl, i•ethyl-2-methylpropanyl and i.ethyl_2_A Base · 2-propenyl; olefin L group · having 4 to 8, in particular, having 4 to 6 anti-atoms and in any of the above-mentioned [upright two-bonded unsaturated double bonds Or with a cigarette group, for example, Ding, t, and Ί. 1 U Ding Yi Mu, pentadiene, M-pentadiene, 1,3-hexadiene, M-hexadiene and oxime, hexadiene; - alkynyl group having 2 to 10, preferably a linear or branched hydrocarbon group having 2 to 6, specifically 2 to 4 carbon atoms and having a triple bond at any position (particularly GC: 4-alkynyl), for example, acetylene , 1-propynyl, 2-propynyl, 丨-butynyl, 2-butynyl, 3-butynyl, ^methyl-2-propanyl, N-pentyl, 2-pentyl Block group, 3 pentynyl group, 4-pentylmethyl-1-butynyl group, 1,1 dimethyl-2-propynyl group, ethyl group 2-propan-1-hexynyl group, 2-hexyne , 3-hexynyl, hexenyl, 5-hexyl 1-methyl-2-pentynyl, 1-methyl-3-cyclopentynyl, 丨-methyl _4_pent-2-methyl -3_pentynyl, 2-methyl-4-pentynyl, 3-methyl-oxime-pentyl 3-methyl-4-pentynyl, 4-methylpentynyl, 'methyl·2 1,1,1-dimethyl-2-butynyl, 1J-dimethylbutynyl, monomethyl-3-butynyl, 2,2-methyl-3-butynyl, 3 ,3·Dimethyl-1-butynyl, 1·ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-indolyl and 1-ethyl- 1·&Quota;methyl-2-propynyl; -cycloalkyl: a monocyclic or bicyclic hydrocarbon group having 3 to 10 carbon atoms; a group, 1-methyl-2-butynyl, 1-methyl _3_butynyl, 2-methyl-3-butynyl, alkynyl alkynyl alkynyl 127320.doc -17- 200835487 having 3 to 8, especially 3 to 6 ring members Monocyclic group, for example, CyC8-cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl; -i-alkyl and _alkoxy _ alkyl moiety: wherein the hydrogen atom present in the group may be partially or completely replaced by a _ prime atom as described above having from one to ten carbon atoms as described above, preferably from one to six a carbon atom, especially a linear or branched alkyl group having 1 to 4 carbon atoms, for example, C^C:4-haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, tri Gas methyl, fluoromethyl, difluoromethyl, trifluoromethyl, gas fluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, gas ethyl, hydrazine-bromoethyl, fluoroethyl , 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2_gas_2-fluoro Base, 2-gas 2,2-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 1,U-trichloropropyl, Trifluoropropane-b-based, l,l,l-tri-propan-2-yl and 1,1,1-trifluoropropyl; similar considerations apply to other radicals, for example, # alkenyl , alkynyl and cycloalkyl groups "haloalkenyl, ethynyl and cycloalkyl substituted with a hydrogen atom which may be partially or completely replaced by a (iv) atom as defined above; a divalent straight-chain hydrocarbon group having 2 to 3 carbon atoms, for example, och2ch2o or 0CH2CH2CH20; -5, 6 member, 7 member, 8 member, 9 member or 10 membered heterocyclic ring: containing i to 4 ^ free a homocyclic or bicyclic hydrocarbon group of a hetero atom consisting of a nitrogen atom, an oxygen atom, and a sulfur atom; an unsaturated (heterocyclic group) including a partially unsaturated (for example, mono-unsaturated) and aromatic (heteroaryl) ); such a heterogeneous 127320.doc -18- 200835487 Oxygen atom 5 member heteroaryl: in addition to containing carbon atoms may also contain u to * nitrogen atoms or 1 to 3 nitrogen atoms and a sulfur atom Or a 5-membered heteroaryl group having an oxygen atom as a ring member, for example, 2 _furanyl, 3-furanyl, porphinyl, 3-thienyl, phenylthio, 2-pyrrolyl, 3-pyrrolyl, hisocalinyl, 4-isoxyl, 5-iso Base, 3_isoindolyl group, iso = base, 5-iso^ sityl, 丨-吼. Sitting base, 3_. More than thiol, sitting group, 5_ oxazolyl, 2+ sitting, sitting, 5_喔. Sitrate, 2 嗟 嗟 、, * thiopyranyl, 5- oxime, 2-hydroxy-salt, heart (tetra), sit-based, 1,2,4-oxadiazol-5-yl, thiadipine Azyl, thiadiazole _ 5 —yl, 1,2,3-triazole-yl, triazole·b, u, triazole 3, tetradecyl, s-nonyl, fluorenyl a diterpenoid and 1,3,4-triazol-2-yl; 1 - a heteroaryl containing 6 to 4 nitrogen atoms: _except for containing carbon atoms: may contain i to 3 Or i to 4 nitrogen atoms as a ring member to a member of a heterocyclic group, for example, 2_bite base, 3 decimal base, 4" bite base, 3_noise group, 4+ Qin group, 2"(tetra)yl, 4•(tetra)yl, 5-pyrimidine, μzinyl, 1,2,3.triazinyl, ustriazin-2-yl and phenyl. Containing from 4 to 4 nitrogen atoms or i 9- or 10-membered heteroaryl groups to 3 nitrogen atoms and a sulfur atom or a milk atom: (10) to 4 nitrogen atoms or i to 3 nitrogen atoms and 1 sulfur in addition to carbon atoms Atom or oxygen atom: a 9-member or 1 member heteroaryl group of a member, specifically, a benzopyrene having i to 3. A milk atom or a nitrogen atom and one oxygen atom or a sulfur atom. 6-shell heteroaryl (ie In addition to containing carbon atoms, it may contain from one to four nitrogen's, or one to three helium atoms and one sulfur atom or oxygen atom as a ring member 127320.doc -19- 200835487 and two of them are adjacent magnetic enthalpy # 0 衣贝 or a nitrogen atom and a member of the adjacent carbon ring J JI Tian Ding-1,3-two! 1 4 group), for example, a 5- or 6-membered heteroaryl group of a benzo-based group bridging ^ sit-2-yl, out-吲嗓 small group, m_吲哚_2_ soil, 1H order _3_ base, melon ten sitting small base, benzofuran-2-yl and benzo acetophene 3_yl;porphyrin_2•yl, porphyrin_3_yl, quinolin-4-yl, isoindoline_丨_yl, isoporphyrin_3_yl, isoquinoline_4_yl, hydrazine Azinyl, quinoxalinyl, quinazoline-2-yl, quinazoline-4-yl, porphyrin-3-yl and cleavage-4.

/含有i個至4個氮原子或i個至3個氮原子及i個硫原子或 氧原子之5員、6員及7員雜環基：3-吡唑啶基、4·吡唑啶 基、5-吡唑啶基、2·吡咯啶_2_基、2_吡咯啶_3_基、3_吡咯 。疋-2-基、3-吡咯啶-3-基、吡咯啶酮基、吡咯啶_2_亞硫 醯-1-基、1-六氫吡啶基、2_六氫吡啶基、3_六氫吡啶基、 4-六氫吡啶基、吡啶（1，2_二氫pi,」-基、2_哌嗪基、卜 嘧啶基、2-嘧啶基、嗎啉—4-基、硫嗎啉_4_基、二氫噻唑-2-基、六氫17比咬-2-顚1-1-基、六氫吼淀_2_亞硫酿_1_基、二 氫。比啶基、六氫氮呼-1-基及六氫氮呼_2_亞硫醯基。 本發明之範圍包括具有對掌性中心之式I之（R)及（s)同分 異構體。因此，應理解··任一比例之（R)及（S)同分異構體 化合物之任一混合物（包括外消旋物）亦屬於本發明之範 圍。 就其抑制腫瘤細胞之生長及子代的活性而言，發現若Χι 係N或若X2係N，則2-經取代吡啶I通常為有用的。依照本 發明，X!及X2中只有一個為N，而該吡啶系統之另一環成 127320.doc -20- 200835487 尤其為C- 員係C-Η或C - _素，例如，C-F、C-C1及C-Br Η。 就抑制腫瘤細胞之生長及子代的活性而+ ^丄 丨王阳3，較佳者係2 經取代紙$1，其中Β係苯基。此等化合物對應於式工，/5, 6 and 7 membered heterocyclic groups containing i to 4 nitrogen atoms or i to 3 nitrogen atoms and 1 sulfur atom or oxygen atom: 3-pyrazolidine group, 4·pyrazolidine , 5-pyrazolidine, 2·pyrrolidin-2-yl, 2-pyrrolidinyl-3-yl, 3-pyrrole. Indole-2-yl, 3-pyrrolidin-3-yl, pyrrolidinyl, pyrrolidine-2-sulfin-1-yl, 1-hexahydropyridyl, 2-hexahydropyridyl, 3-6 Hydropyridyl, 4-hexahydropyridyl, pyridine (1,2-dihydropi,"-, 2-piperazinyl, pyrimidinyl, 2-pyrimidinyl, morpholin-4-yl, thiomorpholine _4_yl, dihydrothiazol-2-yl, hexahydro 17-bite-2-顚1-1-yl, hexahydroindole _2_sulfinyl-1-yl, dihydro.pyridyl, Hexahydroazin-1-yl and hexahydroazepine-2-sulfenyl. The scope of the invention includes the (R) and (s) isomers of formula I having a palm center. It is to be understood that any mixture of (R) and (S) isomer compounds (including racemates) in any ratio is also within the scope of the invention to inhibit the growth and progeny of tumor cells. In terms of activity, 2-substituted Pyridine I is generally useful if it is N or if X2 is N. According to the present invention, only one of X! and X2 is N, and the other ring of the pyridine system is 127320. .doc -20- 200835487 Especially for C-cluster C-Η or C-_素, for example, CF, C-C1 and C-Br Η. The growth and activity of the progeny Shang Shu Wang Yang + ^ 3, preferably substituted by 2 paper-based $ 1, wherein the phenyl-based Β. These compounds correspond to the formula work,

η Γ L及η均如上文所定義。 代°比啶，其中Υ係基團-’係-CH-R1-或-N-R1-曰η Γ L and η are as defined above. Pyridine, wherein the lanthanide group -' is -CH-R1- or -N-R1-曰

其中 Xi、χ2、γ、R2，R3、R4、 其他較佳者係式I及Γ之2-經取 CH-R1-、-^、或-〇-，具體而言 更具體而言，係-N-R1-。倘若Υ係基團_CH_Rl_4 -N_r1_， 則R1較佳為氫。在上述化合物丨中，彼等對應於式丨,者為尤 佳0 特別佳者為如下式I及I’之2-經取代吡啶：其中Rl&R2彼 此獨立地為Cl_C8-烷基、Ci-C8· _代烷基、c2_c8_烯基、 c2-c8- _代烯基、C2_C8-快基、C2-(V齒代快基、C3_C8_環 烷基或c^C8-鹵代環烷基，更具體而言，係Ci_C8_烷基、 CrC8·自代院基、C2-C8_稀基、C2_C8_快基、C3_C8_環烷 基、C3-Cr鹵代環烷基，其中脂肪族及/或環脂族基團可攜 可1個或2個（尤其為！個）基團RV，該等基團RV可為相同的或 彼此^不同且其可選自由Ci-G-烷基、Ci-CV_r烷基、C3_ C6 %烷基、C^C：6-鹵代環烷基及苯基組成之群，其中該苯 基邛刀基團可攜帶丨個、2個或3個（尤其為丨個）基團，該等 基團可為相同的或彼此不同且其可選自由下列組成之群·· 127320.doc -21 - 200835487 、.1 燒基、Cl_c：6_i代院基、Ci-C6·院氧基、氰基 及續基。更為特別佳者係其中尺2具有—種上述含義，Y係 NR或CHR1且R1係氫之化合物工。在上述化合物工中，彼等 對應於式I，者為尤佳。 極為特別佳者為如下式I及I，之2-經取代吡啶：其中"Wherein Xi, χ2, γ, R2, R3, R4, and other preferred formulae I and oxime 2- are taken as CH-R1-, -^, or -〇-, specifically, more specifically - N-R1-. In the case of a lanthanide group _CH_Rl_4 - N_r1_, R1 is preferably hydrogen. Among the above-mentioned compound oximes, which correspond to the formula 丨, particularly preferred are those which are particularly preferably 2-substituted pyridines of the following formulae I and I': wherein R1 & R2 are independently of each other, Cl_C8-alkyl, Ci- C8· _alkyl, c2_c8-alkenyl, c2-c8- _alkenyl, C2_C8-fast radical, C2-(V-dentate fast radical, C3_C8_cycloalkyl or c^C8-halocycloalkyl More specifically, it is Ci_C8_alkyl, CrC8·Self-based, C2-C8_thin, C2_C8_fast, C3_C8_cycloalkyl, C3-Cr halocycloalkyl, among which aliphatic and / or a cycloaliphatic group may carry one or two (especially!) groups RV, which may be the same or different from each other and may be optionally free of Ci-G-alkyl, a group consisting of Ci-CV_r alkyl, C3_C6 % alkyl, C^C: 6-halocycloalkyl and phenyl, wherein the phenyl sulfonate group can carry one, two or three (especially a group of groups which may be the same or different from each other and which may be selected from the group consisting of: 127320.doc -21 - 200835487 , .1 burnt base, Cl_c: 6_i generation base, Ci -C6·Oxyl, cyano and contig. More particularly preferred is the ruler 2 Meaning, Y is a compound of NR or CHR1 and R1 is hydrogen. Among the above compounds, those corresponding to formula I are particularly preferred. Very particularly preferred are the following formula I and I, 2-substituted pyridine : where "

C 3 C8烷基、c3_c8_烯基、C3_C8_快基或C3_C8_鹵代烧基， 較佳為CVC8_院基，其分別在α·位置具有支鍵；CA環 烷基：c3-cv画代環烷基，較佳為C3_c8_環烷基，其分別 可‘ π k自由(：3_ϋ基、c3-C6·函代院基及苯基組成之 群的基團Rv(較佳為C3_C6_烧基），其分別細_位置具有支 鏈，其中該苯基部分基團可攜帶H_2個基團，該等基團 可為相同的或彼此不同且其係選自由下列組成之群：鹵 素、q-cv院基、Ci_c6_鹵代烧基、Ci_c6_烧氧基、氣基及 硝基；CVCV烷基或c〗_c0_鹵代烷基，較佳為Ci_c6_烷基， 更佳為C〗-C4-烷基，其分別可攜帶選自由C3_C6-環烷基、 t_C6-函代環烷基及苯基組成之群的基團RV(較佳為 衣烧基及苯基）’#中該苯基部分基團可攜帶i個或2個（較 it為2個）基團，該等基團可為相同的或彼此不同且其係選 自由下列組成之群：齒素、Cl_C6_烷基、Cl々鹵代烷 基、q-C6-烷氧基、氰基及硝基，較佳為C1_C6_烷氧基。 更為特別佳者係其中R2具有一種上述含義，γ係NRi或 CHR1且R1係氫之化合物〗。在上述化合物丨中，彼等對應於 式I者為尤佳。 在其中R係（VCs-烷基或CVC8·鹵代烷基（較佳為C3_C8_ 127320.doc -22- 200835487 烷基）之式I及I，之2-經取代吡啶（其分別在α_位置具有支鏈） 中，較佳者為彼等如下者：其中R2係丙基、丁 基、 戊-2-基、己·2_基、庚_2_基、辛_2_基、（2_甲基）_ 丁 ·2_基、a C 3 C8 alkyl group, a c3_c8-alkenyl group, a C3_C8_fast group or a C3_C8_haloalkyl group, preferably a CVC8_homogeneous group having a branch at the α· position; a CA cycloalkyl group: c3-cv a cycloalkyl group, preferably a C3_c8_cycloalkyl group, which is respectively a group of groups Rv (preferably C3_C6_) which is 'πk free (: 3_fluorenyl, c3-C6. a base having a branch, wherein the phenyl moiety may carry a H 2 group, and the groups may be the same or different from each other and selected from the group consisting of halogen, Q-cv, a Ci_c6_haloalkyl, a Ci_c6_alkoxy group, a gas group and a nitro group; a CVCV alkyl group or a c-_c0_haloalkyl group, preferably a Ci_c6_alkyl group, more preferably a C- a C4-alkyl group which respectively carries a group RV (preferably a ketone group and a phenyl group) in the group consisting of a C3_C6-cycloalkyl group, a t-C6-functional cycloalkyl group and a phenyl group The radical moiety may carry i or 2 (more than 2) groups which may be the same or different from each other and which are selected from the group consisting of dentate, Cl_C6-alkyl, Cl々 haloalkyl, q-C6-alkoxy, And a nitro group, preferably a C1_C6_alkoxy group. More particularly preferred is a compound wherein R2 has one of the above meanings, γ-based NRI or CHR1 and R1 is hydrogen. In the above-mentioned compound oxime, they correspond to It is especially preferred in the formula I. In the R system (VCs-alkyl or CVC8. haloalkyl (preferably C3_C8_127320.doc-22-200835487 alkyl) of the formula I and I, 2-substituted pyridine (which Having a branch at the α_ position, respectively, preferably those of the following: wherein R2 is propyl, butyl, pent-2-yl, hexyl-2-yl, hept-2-yl, xin_2 _ base, (2_methyl)_丁·2_ base,

(2,3-二甲基）_ 丁 _2·基、（3,3_ 二甲基）_丁_2_ 基、仏甲基）_ 戊-2_基、（3-甲基）-戊_2-基、（4_甲基）_戊_2_基、（2,3_二曱 基）-戊-2-基、（2,4-二甲基）_戊_2_基、（3,4_二甲基）_戊-2_ 基、（4,4_二甲基）·戊―2-基、I，1，！·三氯丙-2-基及三氟 丙-2-基，更佳地，R2係丙_2-基、丁 _2_基、戊·2_基、己-^ 基、庚-2-基、辛_2_基、（3,3·二曱基）· 丁 _2_基及甲基> 戊-2-基，甚至更佳地，R2係丙_2•基、丁·2_基、庚_2_基、 (3,3-二2甲基）_ 丁 _2_基及（4_甲基）_戊_2_基。更為特別佳者係 其中R2具有一種上述含義，Y係NR1或CHR丨且Ri係氫之化 合物I。 在其中R2係CVCV環烷基或CVCV鹵代環烷基（較佳為c3_ C8環院基，更佳為CyC6-環烧基）之式I及I，之2_經取代〇比 啶中，較佳者為彼等如下者··其中R2係環丙烷基、環丁烷 基、環戊燒基、環己烷基及環庚烷基，較佳地，R2係環丙 烧基及環己烧基，其在每一情況下可攜帶選自由在α-位置 具支鍵之cvcv燒基（較佳為在位置具支鏈之c广C4_燒 基’尤其為（VC6-烧基及在上述α-位置具支鏈之C3_C6_烷 基基團）及苯基組成之群的基團]^。倘若該基團RV與環己 烧基環連接’則其較佳位於鄰位或對位，更佳位於對位。 特別佳地’ R2係環丙烷基、環己烷基、2_甲基環己烷基、 4-甲基環己烧基、苯基環己烷基、4_苯基環己烷基、（2_ 127320.doc -23- 200835487 第二-丁基）-環己烷基及（4-第三_丁基）環己烷基。更為特別 佳者係其中R2具有一種上述含義，丫係NRl* CHR1且…係 氫之化合物I。 在其中R2係CVCV烷基或Cl-cv鹵代烷基（較佳為Ci_c^ 烷基，具體而言，係甲基、乙基、丙基及丁 _2_基）之式工 及Γ之2-經取代吡啶中，較佳者為彼等攜帶一個選自由下 列組成之群的Rv者：Cs-C6-環烷基，具體而言，係環丙烷 基、環丁烷基、環戊烷基及環己烷基及苯基，其中該苯基 部分基團可攜帶1個或2個（較佳為2個）基團Ci-C6_烷氧基^ 較佳為Ci-Cr烷氧基，具體而言，係甲氧基、乙氧基、丙 氧基及丁氧基。倘若該苯基部分基團攜帶2個(^_(：6_烷氧基 基團，則該等Cl_C6·烷氧基基團較佳與苯環之毗鄰碳原子 連接。特別佳者為1-環丙基-乙基、卜環己基-乙基、2_環 丙基-乙基、2-環己基-乙基、卜笨基-乙基、2_苯基-乙基、 1-(3,4-二甲氧基）苯基.乙基及2-(3,4_二甲氧基）苯基-乙 基。更為特別佳者係其中R2具有一種上述含義，¥係nr1 或CHRl且R1係氫之化合物I。 偏若R1及/或R2含有具有對掌性中心之鹵代烧基或_代 烯基基團，則對於此等基團而言，⑻，分異構體為較 ^。、當具有對掌性中心之不含鹵素的烷基或烯基基團存於 Rl或r2中時，較佳者為（R)-構型同分異構體。 特別佳者亦為如下式，之2-經取代吡啶：其中¥係]^1^1 且/、中R及R與其所連接氮原子一起形成可雜有或 另胺基十N(RX)-基團之飽和或不飽和（較佳飽和）5員或6 127320.doc -24- 200835487 員環，其中Rx係氫或Cl-C6_烷基，及/或其中所形成環可攜 帶一個或多個（例如，1個、2個、3個或4個，較佳為丨個）選 自由鹵素、C丨-(：6·烷基、Ci-CV鹵代烷基及氧基_Ci_c3-伸 烷氧基組成之群的取代基，具體而言，係鹵素、Ci_c6_烷 - 基及C1-C6_鹵代烷基。在上述化合，彼等對應於式工, 、 者為尤佳。 極為特別佳者係如下式I及I，之化合物：其中R1及R2與其 ( ' 所連接氮原子一起形成飽和或不飽和（較佳飽和）5員或ό員 銥，其可雜有氧原子且其可攜帶2個或2個（^_0:6_烷基取代 基，較佳為Ci-CV烷基，例如，甲基、乙基、丙_丨_基及 丙2基’更佳為CrC2-炫基取代基，例如，甲基、乙基， 尤其為甲基。 在其中R1及R2與其所連接氮原子一起形成飽和或不飽和 5貝或6員環之式1及1，之2_經取代吡啶中，尤佳者為彼等如 下者·其中R及R2與其所連接氮原子一起形成除r1&r2所 連接氮原子外不具有其他雜原子之飽和5員或6員環，例 如，吡咯啶及六氫吡啶，如吡咯啶4 —基及六氫吡啶基 且該飽和5員或6員環視情況可經丨個、2個或3個（較佳丨個） • 選自_素、Cl_C4-烷基及Ci-Gi代烷基之基團（較佳為cie _ Cr烷基）取代。更為特別佳者為其中包含Rl、R2及所連接 氮原子之環未經取代或經甲基化（具體而言，係在心位 置，即，靠近吡啶環氮原子之碳原子攜帶曱基，例如， 甲基咣咯咣基及2-曱基哌啶基）之上述2_經取代吡啶j。更 為特別佳者亦為其中Rl、R2與其所連接氮原子-起形成在 127320.doc -25- 200835487 對位（4-位）具有甲基基團之6員飽和環（極為特別佳者為4-甲基哌啶基）的上述2_經取代吡啶I。 式I之2-經取代吡啶之吡啶架構所連接式NR^R2 (即，其 中 Y係-NR1)之較佳基團包括：NH-C2H5、NH(CH(CH3)2)、 NH-CH2CH2CH3、NH(CH(CH3)(C2H5)、(S)-NHCH(CH3) (C2H5) 、 NH-CH(CH3)(CH2CH2CH3) 、 (R)-NHCH(CH3) (c(ch3)3)、nh-ch(ch3)ch(ch3)2、（r)-nhch(ch3)(ch (CH3)2)、（S)-NHCH(CH3)(CH(CH3)2)、NH(環戊基）、 NHCH2CF3、NHCH(CH3)(CF3)、（R)-NHCH(CH3)(CF3)、 (S)-NHCH(CH3)(CF3)、NH-CH(CH3)CH2OCH3 、NH-CH (CH3)CH2OH 、 NH-CH2C(CH3)=CH2 、 n(ch2ch3)2 、 n(ch3)(ch2ch=ch2)、n(ch3)-ch2ch2ch=ch2、n(ch2ch= CH2)2、六氮0比0定-1-基、2-甲基-六氮〇比。定-1-基、3 -甲基· 六氫吡啶-1-基、4-甲基-六氫吡啶-1-基、3,6-二氫-2H-吡 啶-1-基、2-甲基-吡咯啶-1-基、（S)-NHCH(CH3) (C(CH3)3)、-NH-正·丁基、-NH-第三-丁基、-NH-(第二-戊 基）、-NH-2-甲基-環戊基、2-甲基-環氧乙烷基-甲基-胺 基、-N(乙基）（異丙基）、-N(乙基）（第二-丁基）、-N(第二-丁 基）2、NHCH(CH3)-異 丁基、NH-，*、-NHCH(CH3)CH2- ch(ch3)2、-nh-ch(ch3)ch2-c(o)-oh、n(ch2ch3)ch2c (CH3)=CH2、-N(n-Pr)(CH2CH=CH2)、-NH-CH2CH2-CH2-OH、-N(CH3)(CH2CH2OH)、-N(苄基）(CH2CH2OH)、-N(CH2CH2OH) (CH2CH=CH2)-、-N(CH2CH2OSiMe3)(CH2CH=CH2)、-N(CN) (ch2ch=ch2)、-nh-ch(ch3)ch2-och3、-nh-ch(ch3)ch2- 127320.doc -26· 200835487 C(〇)-〇CH3、2_ 丁氧基羰基^比咯啶小基、2,5·二甲基比 咯啶-1-基、2,6-二曱基-嗎啉-4-基及1，1-二氧代基-硫嗎啉_ 4-基。 其他較佳者為如下式I及I，之2-經取代吡啶：其中R3係南 素、氰基、CVCV烷基、cvcv鹵代烷基或Ci-CV烷氧基， 例如，氯、溴、甲基、氰基、甲氧基或乙氧基，尤其為 氯、氰基、甲基或甲氧基。特別佳者為其中R3係氣之化合 物I。在上述化合物I中，彼等對應於式J，者為尤佳。 其他較佳者為如下式I及I’之2-經取代π比啶：其中以4係0比 咯基、吡唑基、咪唑基、H3-***基、U2,4_***基、四 唾基、噁唑基、異噁唑基、1，3,4-噁二唑基、i，2,4-噁二。坐 基、吱喃基、苯硫基、tr塞咬基、異嗟σ坐基、0比σ定基、^密咬 基、吼嗪基、嗒嗪基、1，2,3-三嗪基、1，2,4_三嗪基、σ比咯 啶基、六氫咣啶基、吲唑基、六氫氮呼基、二氫吡啶基、 二氫噻唑基或苯并噻唑基，其中該雜環可藉由c或Ν與吡 啶環連接且可攜帶1個、2個或3個取代基ru，該等取代基 R可為相同的或彼此不同，兩個相鄰基團RU亦可能一起為 (一〇)或（=s)。更佳地，ru係||素、氰基、Ci_C8_烷基、I· C6-烷氧基、-C( = 〇)-A4 …C( = 〇)-〇-A4、卜⑺_n(a5)a4、 c(a5)(=N-0a4)、n(a5)A4、Ν(Αχ(==〇)_Α4，或兩個相鄰 基團R —起為（=0)或（=s)。甚至更佳地，RU係胺基、胺 基、氰基或甲基，或兩個相鄰基團一起為（=〇)或（=s)。 在上述化合物I中，彼等對應於式I，者為尤佳。 特別佳者為如下式I及Γ之2-經取代吡啶：其中R4係吡唑_ 127320.doc -27- 200835487 1-基、3-胺基-吡唑-1-基、[i，2,4]***基、3-氰基_丨，2,4_ ***-1-基、[1，2,3]***_1-基、丨，^^噁二唑_3-基、甲基· 1，2,4-噁二唑_3_基、吡啶-2-基、（6-甲基）_吡啶_2-基、嘧(2,3-dimethyl)-but-2-yl, (3,3-dimethyl)-but-2-yl, fluorenylmethyl)-pent-2-yl, (3-methyl)-pentyl 2-yl, (4-methyl)-pent-2-yl, (2,3-diindenyl)-pentan-2-yl, (2,4-dimethyl)-pent-2-yl, 3,4_Dimethyl)_pent-2-yl, (4,4-dimethyl)penta-2-yl, I,1,! · Trichloropropan-2-yl and trifluoroprop-2-yl, more preferably, R2 is propen-2-yl, but-2-yl, pent-2-yl, hexyl-yl, hept-2- Base, octyl-2-yl, (3,3·didecyl)·butyl-2-yl and methyl>pent-2-yl, even more preferably, R2 is propionyl-2-yl, butyl-2 _ base, hept-2-yl, (3,3-di-2-methyl)-but-2-yl and (4-methyl)-pent-2-yl. More particularly preferred is a compound I wherein R2 has the above meaning, Y is NR1 or CHR丨 and Ri is hydrogen. In the formula I and I wherein R 2 is a CVCV cycloalkyl group or a CVCV halocycloalkyl group (preferably a c3_C8 ring-based group, more preferably a CyC6-cycloalkyl group), in the 2-substituted benzidine, Preferred are those of the following: wherein R 2 is a cyclopropane group, a cyclobutane group, a cyclopentyl group, a cyclohexane group or a cycloheptyl group, preferably, an R 2 ring propylene group and a cyclohexane group. An alkyl group, which in each case can carry a cvcv alkyl group selected from a bond at the α-position (preferably a c-C4_alkyl group at the position of a branch), especially (VC6-alkyl and The above-mentioned α-position branched C3_C6_alkyl group) and the group of the phenyl group] ^. If the group RV is bonded to the cyclohexyl ring, it is preferably located in the ortho or para position More preferably in the para position. Particularly preferred 'R2 cyclopropane, cyclohexane, 2-methylcyclohexane, 4-methylcyclohexyl, phenylcyclohexane, 4-benzene a cyclohexane group, (2_127320.doc -23-200835487 second-butyl)-cyclohexane group and (4-tri-butyl)cyclohexane group. More particularly preferably wherein R2 has One of the above meanings, the lanthanide NRl*CHR1 and ... is a hydrogen compound I. Wherein R 2 is a CVCV alkyl group or a Cl-cv haloalkyl group (preferably a Ci_c^ alkyl group, specifically, a methyl group, an ethyl group, a propyl group and a butyl group 2) group; Among the substituted pyridines, preferred are those which carry a group of Rv selected from the group consisting of Cs-C6-cycloalkyl, specifically, cyclopropane, cyclobutane, cyclopentyl and ring. a hexane group and a phenyl group, wherein the phenyl moiety group may carry one or two (preferably two) groups of Ci-C6-alkoxy groups, preferably Ci-Cr alkoxy groups, specifically Methoxy, ethoxy, propoxy and butoxy. If the phenyl moiety carries 2 (^_(:6-alkoxy) groups, then the C_C6·alkoxy group The group is preferably bonded to the adjacent carbon atom of the benzene ring. Particularly preferred are 1-cyclopropyl-ethyl, cyclohexyl-ethyl, 2-cyclopropyl-ethyl, 2-cyclohexyl-ethyl,笨基基-ethyl, 2-phenyl-ethyl, 1-(3,4-dimethoxy)phenyl.ethyl and 2-(3,4-dimethoxy)phenyl-ethyl More particularly preferred are those in which R2 has one of the above meanings, such as nr1 or CHR1 and R1 is hydrogen. R1 and/or R2 Where there is a haloalkyl or _alkenyl group having a palm center, then for these groups, (8), the isomer is more, and when it has a halogen-free center When the alkyl or alkenyl group is present in R1 or r2, it is preferably an (R)-configuration isomer. Particularly preferred is also a 2-substituted pyridine: wherein ^1^1 and /, R and R together with the nitrogen atom to which they are attached form a saturated or unsaturated (preferably saturated) heterojunction or a different amine group of ten (RX)- groups 5 members or 6 127320.doc -24- 200835487 Member ring wherein Rx is hydrogen or Cl-C6_alkyl, and/or the ring formed therein may carry one or more (eg, 1, 2, 3 or 4, preferably a substituent selected from the group consisting of halogen, C丨-(:6.alkyl, Ci-CV haloalkyl, and oxy-Ci_c3-alkylalkoxy, specifically, halogen, Ci_c6-alkane- And C1-C6_haloalkyl. In the above combination, they correspond to the type of work, and are particularly preferred. Very particularly preferred are compounds of the following formulae I and I: wherein R1 and R2 together with (the attached nitrogen atom form a saturated or unsaturated (preferably saturated) 5 member or member, which may be heteroatomized with oxygen atoms and It may carry 2 or 2 (^_0:6-alkyl substituents, preferably Ci-CV alkyl groups, for example, methyl, ethyl, propyl-fluorenyl and propyl 2 groups) more preferably CrC2 a thiol substituent, for example, methyl, ethyl, especially methyl. In which R1 and R2 together with the nitrogen atom to which they are attached form a saturated or unsaturated 5 or 6 membered ring of formula 1 and 1, 2_ Among the substituted pyridines, those which are preferably those in which R and R2 together with the nitrogen atom to which they are bonded form a saturated 5- or 6-membered ring having no other hetero atom other than the nitrogen atom to which r1 & r2 is attached, for example, Pyrrolidine and hexahydropyridine, such as pyrrolidinyl 4- and hexahydropyridyl, and the saturated 5 or 6 members may be cyclic, 2 or 3 (preferably one) depending on the situation. a group of a Cl_C4-alkyl group and a Ci-Gi-substituted alkyl group (preferably cie_Cr alkyl group) is substituted, and more particularly preferably a ring containing R1, R2 and a nitrogen atom to which it is attached. Substituted or methylated (specifically, at the position of the heart, ie, a carbon atom adjacent to the nitrogen atom of the pyridine ring carries a sulfhydryl group, for example, a methyl fluorenyl group and a 2-mercaptopiperidinyl group) Substituted pyridine j. More particularly preferred is a 6-membered saturated ring in which R1, R2 and its attached nitrogen atom form a methyl group at the 127320.doc -25-200835487 (4-position) methyl group. Particularly preferred is 4-methylpiperidinyl) of the above 2-substituted pyridine I. The pyridine structure of the 2-substituted pyridine of formula I is attached to the formula NR^R2 (ie, wherein Y-NR1) Good groups include: NH-C2H5, NH(CH(CH3)2), NH-CH2CH2CH3, NH(CH(CH3)(C2H5), (S)-NHCH(CH3) (C2H5), NH-CH(CH3) (CH2CH2CH3), (R)-NHCH(CH3) (c(ch3)3), nh-ch(ch3)ch(ch3)2, (r)-nhch(ch3)(ch(CH3)2), (S )-NHCH(CH3)(CH(CH3)2), NH(cyclopentyl), NHCH2CF3, NHCH(CH3)(CF3), (R)-NHCH(CH3)(CF3), (S)-NHCH(CH3) ) (CF3), NH-CH(CH3)CH2OCH3, NH-CH(CH3)CH2OH, NH-CH2C(CH3)=CH2, n(ch2ch3)2, n(ch3)(ch2ch=ch2), n(ch3) -ch2ch2ch=ch2, n(ch2ch=CH2)2, hexanitrogen 0 to 0-1,4-yl, 2- Yl - billion than six nitrogen atoms. Dec-1-yl, 3-methylhexahydropyridin-1-yl, 4-methyl-hexahydropyridin-1-yl, 3,6-dihydro-2H-pyridin-1-yl, 2-methyl -pyrrolidin-1-yl, (S)-NHCH(CH3) (C(CH3)3), -NH-n-butyl, -NH-tert-butyl, -NH-(second-pentyl , -NH-2-methyl-cyclopentyl, 2-methyl-oxiranyl-methyl-amino, -N(ethyl)(isopropyl), -N(ethyl) (second-butyl), -N (second-butyl) 2, NHCH(CH3)-isobutyl, NH-, *, -NHCH(CH3)CH2-ch(ch3)2, -nh-ch (ch3)ch2-c(o)-oh, n(ch2ch3)ch2c (CH3)=CH2, -N(n-Pr)(CH2CH=CH2), -NH-CH2CH2-CH2-OH, -N(CH3) (CH2CH2OH), -N(benzyl)(CH2CH2OH), -N(CH2CH2OH)(CH2CH=CH2)-, -N(CH2CH2OSiMe3)(CH2CH=CH2), -N(CN) (ch2ch=ch2), -nh -ch(ch3)ch2-och3, -nh-ch(ch3)ch2-127320.doc -26· 200835487 C(〇)-〇CH3, 2_ Butoxycarbonyl^pyrrolidinyl, 2,5·2 Methylpyrrolidin-1-yl, 2,6-dimercapto-morpholin-4-yl and 1,1-dioxo-thiomorpholine-4-yl. Further preferred are 2-substituted pyridines of the formulae I and I wherein R3 is a ruthenium, a cyano group, a CVCV alkyl group, a cvcv haloalkyl group or a Ci-CV alkoxy group, for example, chlorine, bromine, methyl A cyano group, a methoxy group or an ethoxy group, especially a chlorine, a cyano group, a methyl group or a methoxy group. Particularly preferred are compounds I wherein R3 is a gas. Among the above compounds I, those corresponding to the formula J are particularly preferred. Other preferred are 2-substituted π-pyridines of the following formulae I and I': wherein 4 is a 0-pyryl group, a pyrazolyl group, an imidazolyl group, a H3-triazolyl group, a U2,4-triazolyl group, Tetrasyl, oxazolyl, isoxazolyl, 1,3,4-oxadiazolyl, i, 2,4-oxadiyl. Sedentary group, fluorenyl group, phenylthio group, tresamine group, isoindole sigma, 0 sigma group, dimethyl group, pyridazinyl group, pyridazinyl group, 1,2,3-triazinyl group, 1,2,4-triazinyl, σ-pyridyl, hexahydroacridinyl, oxazolyl, hexahydroazetyl, dihydropyridyl, dihydrothiazolyl or benzothiazolyl, wherein the hetero The ring may be attached to the pyridine ring by c or hydrazine and may carry 1, 2 or 3 substituents ru, which may be the same or different from each other, and two adjacent groups RU may also be (一〇) or (=s). More preferably, ru is || cyano, cyano, Ci_C8_alkyl, I.C6-alkoxy, -C(= 〇)-A4 ... C( = 〇)-〇-A4, Bu(7)_n(a5) A4, c(a5)(=N-0a4), n(a5)A4, Ν(Αχ(==〇)_Α4, or two adjacent groups R are (=0) or (=s). Even more preferably, the RU is an amine group, an amine group, a cyano group or a methyl group, or two adjacent groups are together (=〇) or (=s). In the above compound I, they correspond to the formula I Particularly preferred are 2-substituted pyridines of the following formula I and oxime: wherein R4 is pyrazole _ 127320.doc -27- 200835487 1-yl, 3-amino-pyrazol-1-yl , [i,2,4]triazolyl, 3-cyano-indole, 2,4-triazol-1-yl, [1,2,3]triazol-1-yl, anthracene, oxadiazole _3-yl, methyl·1,2,4-oxadiazole-3-yl, pyridin-2-yl, (6-methyl)-pyridine-2-yl, pyrimidine

啶-2-基、吡嗪-2-基、嗒嗪-3-基、（ι，2-二氫）·吡啶-2-酮-1-基、吡咯啶-2-酮-1-基、六氫吡啶_2_酮_卜基、吡咯啶-2-亞 硫醯-1_基、六氫吡啶亞硫醯_丨_基、[ijp塞唑_2-基、 (4,5_二甲基）-[1，3]噻唑-2-基、苯并噻唑_2_基、六氫_ 2H-氮呼-基、六氫-2H_氮呼_2_亞硫醯_卜基或7_胺 基引唾-1-基；更具體而言，係吡唑-基、[丨，2,4]***-^ 基、ϋ比啶-2-基、（6-甲基）-吡啶基、嘧啶_2_基、嗒嗪_3· 基、（1，2-二氫）-吡啶_2-酮_1-基、吡咯啶酮_卜基、[13]噻 唑基、（4,5-二甲基Η1，3]噻唑-2-基或苯并-[1，3]噻唑-2- 基。 更佳者為式I及Γ之化合物，其中R4係2_嘧啶基。 其他較佳者為如下式，之2_經取代吡啶：其中R4係含 有1個：2個$ 3個氮原子或!個氮原子及“固氧原子或硫原 子之苯并稠合5員g 6貝雜芳基，具體而！，係苯并嗟n ^、1H，小基、朵_2_基„·3·基、旧“引 ▲基1Η-吲唑_3_基、苯并呋喃- 基；以及喹啾9装入4 +开天南-3- m 基、噎琳_4·基、異喑琳小 二“啉i基、異喹啉·扣基、呔嗪基、喹喔 唾啉-2-基、喹唑啉4其、 水基、喹 η •基及啐啉I基，… 本开噻唑-2-基。在上述化合物 尤其為 佳。 相應於式I，者為尤 127320.doc -28- 200835487 其他較佳者為如下式I及Γ之2-經取代吡啶：其中R4係氰 基、C( = 0)NRzRb、C(NRal)NRzRb、C(=NORal)NRzRb、 C(=N-NRzlRcl)NRzRb、C(=S)NRzRb、C(=0)Ra、C(=NRal)Ra、 C(=NORal)Ra、C(=N-NRzlRcl)Ra、C(=0)0Ra、C(=NRal)ORa、 C(=N〇Ral)ORa、C( = 0)NRz-0Ra、C(=NRal)NRz-ORa、 C(=NORal)NRz-ORa、C(=0)NRa-NRzRb、CRaRb-NRzRc 或 CRaRb-ORz。在上述化合物I中，彼等對應於式Γ者為尤 佳。 亦為較佳者係其中R4係氰基、0-C(=0)Ra或ON(=CRaRb) 之式I及Γ之2-經取代吡啶。在上述化合物I中，彼等對應於 式Γ者為尤佳。 亦為較佳者係如下式I及Γ之2-經取代吡啶··其中R4係氰 基、NRaRbl、NRa(C( = 0)Rb)、NRa(C(=NRal)Rb)、NRa(C (=NORal)Rb)、NRa(C( = 0)0Rb)、NRa(C( = 0)-NRzRb)、 NRa(C(=NRal)-NRzRb)、NRa(N = CRcRb)、NRa-NRzRb或NRz-ORa。在上述化合物I中，彼等對應於式Γ者為尤佳。 特別佳者為如下式I及Γ之2-經取代吡啶：其中R4係氰 基、C( = S)NRzRb、C( = 0)NRzRb、C(=NORal)NRzRb、 C(NRal)NRzRb、C( = 0)Ra、C(=NORal)Ra、C(=NRal)Ra、 C(=0)0Ra、C(=NORal)ORa、C(=NRal)ORa、C(=0)NRz-ORa、C(=NORal)NRz-ORa、C(=NRal)NRz-ORa、C(=N-NRzlRcl)Ra、CRaRb_NRzRc、ON(=CRaRb)、NRa(C(=0)Rb)、 NRa(C(=0)0Rb)、NRa(N=CRcRb)或 NRz-ORa 〇 在式I及Γ之上述化合物中，彼等如下者為較佳：其中 127320.doc -29- 200835487 R、R 、R、Re及Rcl彼此獨立地為氫、Ci_C6_烷基、Ci一 c6- i代烧基、c2-c6-烯基、c2-c6_ _代烯基、€2弋6_快 基、c2-cv鹵代炔基、c3_C6-環烧基、c3_C6嗰代環烷基、 c4-c6-環烯基或c4-c6-i代環烯基，更佳地，為氫、 烷基、CrQi代烷基、C2_C4-晞基、c2_C4_快基或C3_C6_ 環烧基，尤其為氳或q-C4-烧基。同樣地，彼等其中Rbl具 有如上文所定義Rb之較佳含義(不包括氫)的化合w為較 佳。同樣地，彼等其中RZ及RZ1彼此獨立地具有如上文所 定義V之較佳含義或均為_C〇_Ra2且其中Ra2具有如上文所 定義Ra之較佳含義的化合物I為較佳。 在-個實施例中，極為特別佳者為如下式…，之2_經取 代°比啶.其中R係氰基、c(=z)〇Ra、C(=Z)NRzHb、 C(=S)NRzRb、C(=Z)NRZ_〇Ra 或 c(=z)Ra，較佳地，為 c(=Z)NRZRb、c(=s)NRZRb、或 c㈣NRZ 〇Ra，且立中 z係 〇、NM 或 NOW，較佳為 N〇Ral，例如，c(=〇)〇Ra、Pyridin-2-yl, pyrazin-2-yl, pyridazin-3-yl, (ι,2-dihydro)pyridin-2-one-1-yl, pyrrolidin-2-one-1-yl, Hexahydropyridine-2-ketone-bu-based, pyrrolidine-2-sulfinyl-1-yl, hexahydropyridinium sulfonium-hydrazinyl, [ijp-pyrazole-2-yl, (4,5_2 Methyl)-[1,3]thiazol-2-yl, benzothiazole-2-yl, hexahydro-2H-azepine-yl, hexahydro-2H-azeo- 2 sulfinyl-bry or 7-Amino-inden-1-yl; more specifically, pyrazol-yl, [丨, 2,4]triazole-yl, indolin-2-yl, (6-methyl)- Pyridyl, pyrimidine-2-yl, pyridazine-3-yl, (1,2-dihydro)-pyridine-2-one-1-yl, pyrrolidinone-bu, [13]thiazolyl, (4 , 5-dimethylindole 1,3]thiazol-2-yl or benzo-[1,3]thiazol-2-yl. More preferred are compounds of formula I and indole wherein R4 is 2-pyrimidinyl. Preferably, it is a 2-substituted pyridinium wherein R4 contains 1: 2 of 3 nitrogen atoms or ! nitrogen atoms and "benzoo- or sulfur-bonded benzo-fused 5 members g 6 Bellyrene, specifically!, is a benzopyrene n ^, 1H, a small group, a _2 _ _ _ · · · · base, the old "引 ▲ base 1 Η - carbazole _3_ base, And furan-based; and quinoxaline 9 is charged into 4 + open Tiannan-3- m base, 噎琳_4·yl, isophthalene bis-diphenyl, i-quinoline decarboxyl, pyridazinyl, Quinium quinolate-2-yl, quinazoline 4, water-based, quinolyl and porphyrin-I, ... a thiazol-2-yl group. Particularly preferred in the above compounds. Corresponding to formula I, YU 127320.doc -28- 200835487 Other preferred are 2-substituted pyridines of the following formula I and oxime: wherein R4 is cyano, C(=0)NRzRb, C(NRal)NRzRb, C(=NORal) NRzRb, C(=N-NRzlRcl)NRzRb, C(=S)NRzRb, C(=0)Ra, C(=NRal)Ra, C(=NORal)Ra, C(=N-NRzlRcl)Ra, C( =0) 0Ra, C(=NRal)ORa, C(=N〇Ral)ORa, C(=0)NRz-0Ra, C(=NRal)NRz-ORa, C(=NORal)NRz-ORa, C( =0) NRa-NRzRb, CRaRb-NRzRc or CRaRb-ORz. Among the above compounds I, those corresponding to the formula are particularly preferred. Also preferred is the R4 cyano group, 0-C (=0) Ra or ON (=CRaRb) Formula I and 2-substituted pyridine of hydrazine. Among the above compounds I, those corresponding to the formula are particularly preferred. Also preferred are the following formula I and oxime 2 - substituted pyridine · · wherein R 4 is cyano, NRaRbl, NRa (C ( = 0) Rb), NRa (C (= NRal) Rb), NRa (C (=NORal) Rb), NRa (C (= 0) 0Rb), NRa (C (= 0) - NRzRb), NRa (C (=NRal)-NRzRb), NRa (N = CRcRb), NRa-NRzRb or NRz-ORa. Among the above compounds I, those which correspond to the formula are particularly preferred. Particularly preferred are 2-substituted pyridines of the formula I and fluorene wherein R 4 is cyano, C(=S)NRzRb, C(=0)NRzRb, C(=NORal)NRzRb, C(NRal)NRzRb, C ( = 0) Ra, C (=NORal)Ra, C(=NRal)Ra, C(=0)0Ra, C(=NORal)ORa, C(=NRal)ORa, C(=0)NRz-ORa, C(=NORal)NRz-ORa, C(=NRal)NRz-ORa, C(=N-NRzlRcl)Ra, CRaRb_NRzRc, ON(=CRaRb), NRa(C(=0)Rb), NRa(C(= 0) 0Rb), NRa (N=CRcRb) or NRz-ORa 中 Among the above compounds of formula I and oxime, the following are preferred: 127320.doc -29- 200835487 R, R, R, Re and Rcl is independently of each other hydrogen, Ci_C6_alkyl, Ci-c6-i-alkyl, c2-c6-alkenyl, c2-c6__alkenyl, €2弋6_fast, c2-cvhaloalkyne a group, c3_C6-cycloalkyl, c3_C6 deuterated cycloalkyl, c4-c6-cycloalkenyl or c4-c6-i-cycloalkenyl, more preferably hydrogen, alkyl, CrQi-alkyl, C2_C4- Sulfhydryl, c2_C4_ fast radical or C3_C6_ cycloalkyl, especially hydrazine or q-C4-alkyl. Likewise, it is preferred that they have a compound w of Rb having the preferred meaning of Rb as defined above (excluding hydrogen). Likewise, those compounds in which RZ and RZ1 independently of each other have the preferred meaning of V as defined above or are both _C〇_Ra2 and wherein Ra2 has the preferred meaning of Ra as defined above are preferred. In one embodiment, very particularly preferred is a formula wherein 2_ is substituted by a pyridine. wherein R is a cyano group, c(=z)〇Ra, C(=Z)NRzHb, C(=S NRzRb, C(=Z)NRZ_〇Ra or c(=z)Ra, preferably c(=Z)NRZRb, c(=s)NRZRb, or c(tetra)NRZ 〇Ra, and the z-line 立, NM or NOW, preferably N〇Ral, for example, c(=〇)〇Ra,

C(=NRal)〇Ra > C(=N〇R^)〇Ra , C(=0)NRzRb . C(=NRal) 顺f、C(=N〇R，NRZRb、c(=〇)NRZ-〇Ra、c(=NRai)NRZ 〇Ra、C( = N〇Rai)彫0Ra、c( = 〇)Ra、c( = NRai)Ra 及 C(=N〇Ral)Ra。在此等化合物I中，彼等其中Ral係氫或Cl_ C4-烧基（尤其為Cl_C2·烧基，具體而言，係甲基）者係更為 特別佳的。同樣地，彼等其中(尤其…及…二者 均）為氫之化合物m更為特別佳的。同樣地彼等其中rz 係氫或-CO-R (具體而言，係c(=NH)N(c〇_Ra2)Rb，其中C(=NRal)〇Ra > C(=N〇R^)〇Ra , C(=0)NRzRb . C(=NRal) cis f, C(=N〇R, NRZRb, c(=〇)NRZ -〇Ra, c(=NRai)NRZ 〇Ra, C( = N〇Rai) carved 0Ra, c( = 〇)Ra, c( = NRai)Ra and C(=N〇Ral)Ra. In these compounds In I, those in which Ral is hydrogen or Cl_C4-alkyl (especially Cl_C2·alkyl, specifically methyl) are more particularly preferred. Similarly, among them (especially... and... Both of them) are more particularly preferred for hydrogen compounds m. Similarly, where rz is hydrogen or -CO-R (specifically, c(=NH)N(c〇_Ra2)Rb, wherein

Ra2ARb較佳彼此獨立地為氫st(VC4_烷基，例如，甲基及 127320.doc •30- 200835487 乙基）之化合物以更為特別佳的。極為特別佳者為盆中^ 係氰基、C( = N〇CH3)NH2、C( = NH)NH2、c( = 〇)丽2、 C( = S)NH2 ^ C(=NH)NH-OH . C(=〇)NH-〇H A C(=NH)NH-c(=o)ch3(尤其為氰基、c(=〇)nH2、c(=s_2 = NOCH3)NH2)之2-經取代吡啶！。 在另一實施例中’極為特別佳者為其中R”系氰基、 C(=0)NRzRb、C(=N〇Ral)NRZRb、〔(=職3 丨)y 顺⑽，⑽）、NRZ身、⑽(=CRaRb)、概抑=〇) Rb)、C( = S)NRf或C〇2Ra之式⑴，之2_經取代D比咬。在此 等化合物1中，彼等其中RlRal彼此獨立地為氫或Cl_C4_ 烷基（尤其為Ci-C2_烧基），例如，甲基、乙基、正·丙基、 異-丙基、正-丁基、異·丁基或第三_丁基者係更為特別佳 的：更佳地，"氫、甲基、乙基、正_丙基或異_丙基。 同樣地’ m佳為甲基。而且’彼等其中Rb係氫或 烷基（尤其為^心-烧基，例如，甲基或乙基，具體而言， 係甲基）之化合物I係t為特別佳的。更佳地，氫或甲 基。同樣地’彼等其中RZ係氫、c]_c4_烧基（例如，甲基、 乙基、正-丙基、異-丙基、正_丁基、異·丁基或第三-丁 基，尤其為甲基）或-C0-Ra2(其中Ra2係Ci_c4院基，例如， 曱基或乙基’尤其為甲基)之化合物J係更為特別佳的。更 佳地’ Rz係氣、甲基或-C〇_Ra2，且Ra2係甲基。極為特別 “者為其中 R 係氰基、C( = 〇)NHCH3、c( = N〇CH3)NH2、 C(=NOCH3)CH3 > NH(C(=〇)〇ch3) ^ N(C(=0)CH3)-0CH3 , 〇N(=C(CH3)2) ^ NH(C(=〇)CH3) > C(=〇)NH2 ^ C(=S)NH2 , 127320.doc -31 - 200835487 C(=0)-0(CH3) ^ C(=0).〇(CH2CH3) . C(=〇)-〇(CH2CH2CH3) 或（〇) OCH(CH3)2(尤其為氰基、c(=n〇CH3)nh2、 C(=0)NH2或C( = S)NH2)之2-經取代嘧啶J。 其他較佳者為其中取代基Ln (即，倘、若6為5員或6員 雜芳^則為L1至I/;或若B為苯基，料l^l5)係如下 文所定義之式I及I’之2-經取代吡咬： L係選自由下列組成之群：_素，具體而言，係氟、 氯、溴，較佳為說、氣；氰基；Cpk燒基，具體而 言，係CVCV烷基，尤其為Ci_C4_烷基，例如，甲 基、乙基、丙基及丁基，較佳為曱基；CrCt烤基， 具體而言，係C^cv烯基，尤其為烯基，例 如，乙烯基、丙烯基及丁烯基；C2_Ci(r炔基，具體而 言，係C2-(V炔基，尤其為C2_C4_炔基，例如，乙炔 基、丙炔基及丁炔基；Cl-c0_烧氧基，具體而言，係 Ci-C4-烷氧基，較佳為甲氧基及乙氧基；CyC⑴烯氧 基，具體而言，係烯氧基，例如，乙烯氧基； C2-C1()-炔氧基，具體而言，係C2_C6_炔氧基，例如， 乙炔氧基；硝基；-C( = 〇)-〇-A7，具體而言，係Ci_Cf 烷氧基羰基，尤其為C^C2_烷氧基羰基，例如，甲氧 基羰基；-C(=0)-N(A8)A7，具體而言，係c〇_NH2、 CVCr烧基胺基幾基（例如，c〇_NHCH3及 nhc2h5)及二-(cvcv烷基 > 胺基羰基（例如，c〇_ N(CH3)2); -C(=s)-N(A8)A7，具體而言，係cs_NH2、 CVCzr烷基胺基硫代羰基（例如，cS-NHCH3)及二 127320.doc 32 200835487The Ra2ARb is preferably a compound of hydrogen st (VC4_alkyl, for example, methyl and 127320.doc • 30-200835487 ethyl), which is more preferably independent of each other. Very particularly good is the potted cyano group, C(=N〇CH3)NH2, C(=NH)NH2, c(=〇) Li 2, C( = S)NH2 ^ C(=NH)NH- OH. C(=〇)NH-〇HAC(=NH)NH-c(=o)ch3 (especially 2-substituted by cyano, c(=〇)nH2, c(=s_2 = NOCH3)NH2) Pyridine! . In another embodiment, 'very particularly good is where R" is cyano, C(=0)NRzRb, C(=N〇Ral)NRZRb, [(==3 丨)y cis (10), (10)), NRZ Body, (10) (=CRaRb), 抑=〇) Rb), C(=S)NRf or C〇2Ra (1), 2_substituted D ratio bite. In these compounds 1, these are RlRal Independently from each other, hydrogen or Cl_C4_alkyl (especially Ci-C2_alkyl), for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl or third The butyl group is more particularly preferred: more preferably, "hydrogen, methyl, ethyl, n-propyl or iso-propyl. Similarly, 'm is preferably methyl.' and 'their Rb The compound I is t, which is hydrogen or an alkyl group (especially a methyl group or an alkyl group, for example, a methyl group or an ethyl group, specifically, a methyl group) is particularly preferred. More preferably, hydrogen or a methyl group. Wherein 'the RZ is hydrogen, c]_c4_alkyl (for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl or tert-butyl, Especially methyl) or -C0-Ra2 (wherein the Ra2 is a Ci_c4, for example, a thiol or an ethyl group, especially a methyl group) The product J is more particularly preferred. More preferably, 'Rz is a gas, a methyl group or a -C〇_Ra2, and a Ra2 is a methyl group. Very particular ones are those in which R is a cyano group, C(= 〇)NHCH3, c( = N〇CH3)NH2, C(=NOCH3)CH3 > NH(C(=〇)〇ch3) ^ N(C(=0)CH3)-0CH3 , 〇N(=C(CH3)2) ^ NH(C(=〇)CH3) > C(=〇)NH2 ^ C(=S)NH2 , 127320.doc -31 - 200835487 C(=0)-0(CH3) ^ C(=0). 〇(CH2CH3) . C(=〇)-〇(CH2CH2CH3) or (〇) OCH(CH3)2 (especially cyano, c(=n〇CH3)nh2, C(=0)NH2 or C( = S NH2-) 2-substituted pyrimidine J. Other preferred are those wherein the substituent Ln (i.e., if 6 is 5 or 6 member heteroaryl^, then L1 to I/; or if B is phenyl, material l^l5) is as defined below. 2-Substituted Peptides of Formula I and I': L is selected from the group consisting of: _, specifically, fluorine, chlorine, bromine, preferably, gas; cyano; Cpk alkyl, Specifically, it is a CVCV alkyl group, especially a Ci_C4_alkyl group, for example, a methyl group, an ethyl group, a propyl group, and a butyl group, preferably a mercapto group; a CrCt roast group, specifically, a C^cv alkenyl group; , especially alkenyl, for example, vinyl, propenyl and butenyl; C 2 —Ci (r alkynyl, in particular, C 2 -(V alkynyl, especially C 2 —C 4 —alkynyl, eg ethynyl, propyne And a butynyl group; a Cl-c0_ alkoxy group, specifically, a Ci-C4-alkoxy group, preferably a methoxy group and an ethoxy group; a CyC(1) alkenyloxy group, specifically, an olefinic oxygen group a group, for example, a vinyloxy group; a C2-C1()-alkynyloxy group, specifically, a C2_C6-alkynyloxy group, for example, an acetyleneoxy group; a nitro group; -C(= 〇)-〇-A7, specific In the case of a Ci_Cf alkoxycarbonyl group, especially a C^C2_alkoxycarbonyl group, for example, Oxycarbonyl; -C(=0)-N(A8)A7, specifically, c〇_NH2, CVCr alkylamino group (for example, c〇_NHCH3 and nhc2h5) and di-(cvcv alkane) Aminocarbonyl (for example, c〇_N(CH3)2); -C(=s)-N(A8)A7, specifically, cs_NH2, CVCzr alkylaminothiocarbonyl (for example, cS-NHCH3) and two 127320.doc 32 200835487

Cc烧基胺基硫代羰基（例如，CS-N(CH3)2); C(A )(-N_〇A7)，例如，CH(=N〇H^CH(=N〇CH3); N(A )A ，具體而言，係烷基胺基及二_Ci_C4_ 烷基胺基；N(A8)-C( = 〇)-A7，具體而言，係Cl-C4_烷 基羰基胺基（例如，nh_c( = 〇)CH3：^n_(Ci_cv烷基羰 基 hNJCVCV 烷基胺基（例如，n(CH3)_c( = 〇)CH3); 及/或S(=〇)r-A7,具體而言，係_SH、c〗_c4_烷硫基（例Cc alkylaminothiocarbonyl (for example, CS-N(CH3)2); C(A)(-N_〇A7), for example, CH(=N〇H^CH(=N〇CH3); N (A)A, specifically, an alkylamino group and a di-Ci_C4_alkylamino group; N(A8)-C(=〇)-A7, specifically, a Cl-C4_alkylcarbonylamino group (eg, nh_c(= 〇)CH3:^n_(Ci_cv alkylcarbonyl hNJCVCV alkylamine group (eg, n(CH3)_c(= 〇)CH3); and/or S(=〇)r-A7, specific In terms of _SH, c〗 _c4_ alkylthio (example

如SCH3)4 烷基磺醯基（例如，s〇2cH3);其 中 〃 A7 A8彼此獨立地為氫、 CVCV烷基、c2-C6-烯基、 c^C6-炔基、C3_C8_環烷基或苯基，其中該等有 枝基團可經部分或完全函化或可經i素、氰基 及/或^'4-烷氧基取代；或A7及A8與其所連接 原子一起為包含1個或2個選自由〇、N&s組成 之群雜原子的5員或6員飽和雜環；Such as SCH3) 4 alkylsulfonyl (for example, s〇2cH3); wherein 〃 A7 A8 is independently of each other hydrogen, CVCV alkyl, c2-C6-alkenyl, c^C6-alkynyl, C3_C8_cycloalkyl Or a phenyl group, wherein the branched groups may be partially or completely functionalized or may be substituted by i, cyano and/or ^'4-alkoxy; or A7 and A8 together with the atom to which they are attached One or two 5-membered or 6-membered saturated heterocyclic rings selected from the group consisting of hydrazine, N&s;

I團定義之脂肪族、環脂族及/或芳香族基團 部分可經部分或完全齒化，例如，其中L可為Ci_c6_ 南代院基，尤其為Ci_C2_氣烧基，例如，三氣甲基。 、土在上述化合物1中’彼等對應於式Γ者為尤佳。 之為其中1㈣2個基團L與雜芳基或苯基環系統B 地，個）鄰位連接的式1及Γ之2_經取代°比咬。特別佳 =群f係包含1個、2個或3個選自由〇、咖組成 其群：原子的5員雜芳基或為。比咬基或苯基，尤其為苯 土 *吕之，特別佳者為其中η係卜2或3之2_經取代0比 127320.doc -33- 200835487 啶i。 其他特別佳者為其中取代基、係 之2-經取代吡啶： 了文所疋義之式⑴’ L係鹵素、氰基、Cl_C8-烷基、 ~ 1 C6-烷氧基、-〇：(=〇)_〇_ A 4_C( = 〇)-N(A8)A7。 ) 係下式B基團之2-經取 其他特別佳者為其中基團 代咄啶I :The aliphatic, cycloaliphatic and/or aromatic moiety defined by Group I may be partially or completely dentated, for example, wherein L may be Ci_c6_Southern Institute, especially Ci_C2_gas, for example, three gas methyl. It is preferable that the soil is in the above compound 1 and they correspond to the formula. The formula 1 and the 2'-substituted ratio of 1 (4) 2 groups L and the heteroaryl or phenyl ring system B, and the ortho position are substituted. Particularly preferred = group f consists of one, two or three groups selected from the group consisting of sputum and coffee. More than a bite base or a phenyl group, especially a benzene soil * Lu, especially preferably wherein η is a 2 or 3 of 2_substituted 0 to 127320.doc -33- 200835487 pyridine i. Other particularly preferred ones are 2-substituted pyridines of the formula: (1) 'L-type halogen, cyano, Cl_C8-alkyl, ~ 1 C6-alkoxy, -〇: (= 〇)_〇_ A 4_C( = 〇)-N(A8)A7. A group of the following formula B is taken as a second group. Other particularly preferred ones are those in which the group is acridine I:

B 其中#係嘧啶架構之連接點且其中 L2 L3B where # is the connection point of the pyrimidine structure and where L2 L3

Ll錢、氯、ch3«f3’更料氣或氣； L4/皮此獨立地為氫、ch3或氟，更佳為氫； 係氫氟、氣、溴、氰基、CH3、SCH3、0CH3、 S02CH3 ' CO-NH2 ' CO-NHCH3 ' CO-NHC2H5 ' CO- N(CH3)2、CS-NH2、CS-NHCH3、CS-N(CH3)2、NH· c(=〇)CH3、N(CH3)_C(=0)CH3 或 c〇〇cH3，更佳地， 為氫、l或氣’甚至更佳地，為氫；且 L5係氬、氟、氯或叫丄更佳地，為I或氣。Ll money, chlorine, ch3 «f3' is more gas or gas; L4 / skin is independently hydrogen, ch3 or fluorine, more preferably hydrogen; hydrogen fluoride, gas, bromine, cyano, CH3, SCH3, 0CH3, S02CH3 ' CO-NH2 ' CO-NHCH3 ' CO-NHC2H5 ' CO- N(CH3)2, CS-NH2, CS-NHCH3, CS-N(CH3)2, NH·c(=〇)CH3, N(CH3 )_C(=0)CH3 or c〇〇cH3, more preferably, hydrogen, l or gas 'even more preferably, hydrogen; and L5 is argon, fluorine, chlorine or yttrium, more preferably, I or gas.

係如上文所定義式B基團之 同樣地，其中基團# 式Γ之咣啶及其鹽為較佳。 進而言之，特別佳者為如下式i，之2_經取代吡啶··其中 Y 係 〇、CHR1 或 NR1， 127320.doc -34- 200835487 R、r2 彼此獨立地為cvcv烷基、c2-c8-烯基、c2-c8_炔 基、鹵代烷基、CVCs-鹵代烯基或c2-C8-鹵代炔 基、CVCs-環烧基、C3_C8_ ii代環烧基，其中脂肪族 及/或環脂族基團可攜帶1個或2個取代基RV，該等取 代基Rv可為相同的或彼此不同且其可選自由Ci_C6_燒 基、CVC6-鹵代烷基、c3-c6·環烷基、C3-C6-鹵代環烧 基及苯基組成之群，其中該苯基部分基團可攜帶1 個、2個或3個基團，該等基團可為相同的或彼此不同 且其係選自由下列組成之群：鹵素、烷基、Ci-C6_鹵代烧基、CVC6-烧氧基、氰基及硝基；Similarly, the group of formula B as defined above, wherein the group # is acridine and its salt is preferred. In other words, particularly preferred is the following formula i, 2_substituted pyridine · wherein Y is 〇, CHR1 or NR1, 127320.doc -34- 200835487 R, r2 are each independently cvcv alkyl, c2-c8 Alkenyl, c2-c8-alkynyl, haloalkyl, CVCs-haloalkenyl or c2-C8-haloalkynyl, CVCs-cycloalkyl, C3_C8_ ii cycloalkyl, wherein aliphatic and/or cyclic The aliphatic group may carry one or two substituents RV, which may be the same or different from each other and may be optionally free of Ci_C6_alkyl, CVC6-haloalkyl, c3-c6.cycloalkyl, a group of C3-C6-halocycloalkyl and phenyl groups, wherein the phenyl moiety may carry 1, 2 or 3 groups, which may be the same or different from each other and Selected from the group consisting of halogen, alkyl, Ci-C6-haloalkyl, CVC6-alkoxy, cyano and nitro;

Rl 亦可為氫；或倘若Y為NR1， 則R1及R2亦可與其所連接氮原子一起形成可雜有醚（_〇_)或 另一胺基-(-N(RX))-基團之飽和或不飽和5員或6員 環’其中Rx係氫或Ci-C6·烧基，及/或其中所形成環可 包含一個或多個選自由下列組成之群的取代基：_ 素、Ci-Cp烧基、Ci-C6·鹵代烧基及氧基- C1-C3 -伸烧 氧基； R3 係鹵素、氰基、Ci-cv烷基、cvcv烷氧基 代烷基； R4 係吼17各基、σ比嗤基、味唆基、1，2,3-三吐基、1，2,4_二 唑基、四唑基、噁唑基、異噁唑基、1，3,4-噁二唾 基、1，2,4-噁二唑基、呋喃基、苯硫基、噻唑基、異 噻唑基、吡啶基、嘧啶基、吡嗪基、嗒嗪基、1，253. 三嗓基、1，2,4-三唤基、°比洛啶基、六氫吼咬基、㈣ 127320.doc -35- 200835487 坐基、，、風鼠呼基、二氫π比咬基、二氫嗟唾基或苯并 塞坐基丨中5亥雜環可藉由c或Ν與吼咬環連接且可 攜帶1個、2個或3個基團RU，該等基團RU可為相同的 或彼此不同，其中 係齒素、氰基、燒基、CVCV烧氧基、 (0) A ' -c(=〇)_〇-A4、_c( = 〇)-N(A5)A4、 C(A )(==N-〇A4)、N(A5)A4、N(A5)-C(二0)·Α4，或 其中兩個相鄰基團RU 一起為（=〇)或（==s); 其中特別佳者為其中密咬基之化合物。 η係1 2或3，其中至少一個取代基L位於苯環之鄰位； 係鹵素氰基、Cl_C8_烧基、C2-C10-稀基、c2-C1〇i 基、kcv烧氧基、c2_Ciq^氧基、c2_Cw炔氧基、 硝基、-C( = 〇)-〇_A7、-(：( = 〇),八8)八7、 N(A )A > C(A8)(=N-〇A7) > N(A8)A7 ^ N(A8)-C(-〇). A 或 S( = 〇)r-A7，其中 A7、A8彼此獨立地為氫、Ci_C6_烷基、烯基、 2 C6块基、烧基或苯基，其中該等有 機基團可經部分或完全_化或可經_素、氰基 及/或^^4-烷氧基取代；或A7及A8與其所連接原 子一起為包含1個或2個選自由〇、N&s組成之群 雜原子的5員或6員餘和雜環； 其中L基團定義之脂肪族、環脂族及/或芳香族基團部 分可1部分或完全_化或可攜帶丨個、2個、3個或4個 基團RL，該等基團rl可為相同的或彼此不同。 127320.doc -36- 200835487Rl may also be hydrogen; or if Y is NR1, then R1 and R2 may also form an ether (_〇) or another amine-(-N(RX))- group together with the nitrogen atom to which they are attached. a saturated or unsaturated 5 member or 6 membered ring 'wherein Rx is hydrogen or Ci-C6.alkyl, and/or the ring formed therein may comprise one or more substituents selected from the group consisting of: _, Ci-Cp alkyl, Ci-C6. haloalkyl and oxy-C1-C3 - extended alkyloxy; R3 halogen, cyano, Ci-cv alkyl, cvcv alkoxyalkyl; R4吼17 groups, σ 嗤 、, miso base, 1,2,3-trisyl, 1,2,4-oxadiazolyl, tetrazolyl, oxazolyl, isoxazolyl, 1,3 , 4-oxadisyl, 1,2,4-oxadiazolyl, furyl, phenylthio, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,253 . Triterpenoid, 1,2,4-trioctyl, °piridinyl, hexahydrocarbazide, (iv) 127320.doc -35- 200835487 sitting base,, wind rat, base, dihydro π ratio bite a 5-heterocyclic ring of a hydrazide or a benzoindole or a benzoindole can be attached to the ring by c or hydrazine and can carry 1, 2 or 3 groups of RUs. The groups RU may be the same or different from each other, wherein dentate, cyano, alkyl, CVCV alkoxy, (0) A ' -c(=〇)_〇-A4, _c( = 〇) -N(A5)A4, C(A)(==N-〇A4), N(A5)A4, N(A5)-C(2)·Α4, or two adjacent groups RU together (=〇) or (==s); Among them, particularly preferred are compounds in which the bite group is used. η series 1 2 or 3, wherein at least one substituent L is ortho to the benzene ring; halogen cyano group, Cl_C8_alkyl group, C2-C10-dense group, c2-C1〇i group, kcv alkoxy group, c2_Ciq ^oxy, c2_Cw alkynyloxy, nitro, -C(= 〇)-〇_A7, -(:( = 〇), 八8) 八7, N(A)A > C(A8)(= N-〇A7) > N(A8)A7 ^ N(A8)-C(-〇). A or S(= 〇)r-A7, wherein A7 and A8 are each independently hydrogen, Ci_C6_alkyl, Alkenyl, 2 C6 block, alkyl or phenyl, wherein the organic groups may be partially or fully-substituted or may be substituted by _, cyano and/or oxa-4-alk; or A7 and A8 together with the atom to which it is attached is a 5- or 6-membered residue and a heterocyclic ring containing one or two group heteroatoms selected from the group consisting of hydrazine, N&s; wherein the L group defines an aliphatic group, a cycloaliphatic group and/or Or the aromatic moiety may be partially or fully- or may carry one, two, three or four groups RL, which may be the same or different from each other. 127320.doc -36- 200835487

如上文所定義式B基團者。A group of formula B as defined above.

γ ·Λ»、V ' miv 乳丄N1Vγ ·Λ», V ' miv nipple N1V

基、Ci-CV鹵代院基、 「規基、c2-c8-稀基、c2-c8-炔 C2 Cg - _代稀基或C2-Cs - _代快 基、c^c：8-環烷基、鹵代環烷基，其中脂肪族 及/或環脂族基團可攜帶丨個或2個取代*RV，該等取 代基Rv可為相同的或彼此不同且其可選自由Ci_C6_烷 基Cl-C6-鹵代烷基、CVCV環烷基、c3-C6-鹵代環烷 基及苯基組成之群，其中該苯基部分基團可攜帶i 個、2個或3個基團，該等基團可為相同的或彼此不同 且其係選自由下列組成之群：鹵素、Ci_C6-烷基、c” C6_鹵代烷基、c^C：6-烷氧基、氰基及硝基；Base, Ci-CV halogenated courtyard, "regular group, c2-c8-sweet, c2-c8-alkyne C2 Cg - _, or C2-Cs - _ fast radical, c^c: 8-ring An alkyl, halocycloalkyl group wherein the aliphatic and/or cycloaliphatic group may carry one or two substituents *RV, which may be the same or different from each other and may be optionally free of Ci_C6_ a group of alkyl Cl-C6-haloalkyl, CVCV cycloalkyl, c3-C6-halocycloalkyl and phenyl, wherein the phenyl moiety can carry i, 2 or 3 groups, The groups may be the same or different from each other and are selected from the group consisting of halogen, Ci_C6-alkyl, c"C6-haloalkyl, c^C:6-alkoxy, cyano and nitro ;

Rl亦可為氫；或倘若Y係nr1， 則R及R2亦可與其所連接氮原子一起形成可雜有醚卜〇_)或 另一胺基-(-N(RX))_基團之飽和或不飽和5員或6員 環，其中Rx係氫或Cl_C6_烷基，及/或其中所形成環可 包含一個或多個選自由_素、Ci_C6_烷基、鹵 代烧基及氧基伸烷氧基組成之群的取代基； R3係鹵素、氰基、cvc4-烷基、CVC4-烷氧基或CkCV齒 代烧基； R4 係氰基、C( = 〇)NRzRb、C(NRal)NRzRb、 127320.doc -37- 200835487 NRzRb 、 C(=N-NRzlRcl)NRzRb 、 C(=S)NRzRb 、 C( = 0)Ra 、C(=NRal)Ra 、C(=NORal)Ra 、C(=N-NRzlRcl)Ra、C( = 0)0Ra、C(=NRal)ORa、C(=NORal) ORa、C( = 0)NRz-0Ra、C(=NRal)NRz-ORa、C(=NORal) NRz-ORa、C( = 0)NRa-NRzRb、CRaRb-NRzRc、CRaRb-ORz、0-C(=0)Ra、ON(=CRaRb)、NRaRbl、NRa(C(=0) Rb)、NRa(C(=NRal)Rb)、NRa(C(=NORal)Rb)、NRa(C (=0)0Rb) 、NRa(C( = 0)-NRzRb) 、NRa(C(=NRa1)- NRzRb)、NRa(N = CRcRb)、NRa-NRzRb 或 NRz-ORa，具 體而言，R4 係氰基、C( = S)NRzRb、C(=0)NRzRb、 C(=NORal)NRzRb、C(NRal)NRzRb、C(=0)Ra、C(= NORal)Ra、C(=NRal)Ra、C(=0)0Ra、C(=NORal) 0Ra、C(=NRal)0Ra、C( = 0)NRz-0Ra、C(=N0Ral)NRz-ORa、C(=NRal)NRz-ORa、C(=N-NRzlRcl)Ra、CRaRb-NRZRC、ON(=CRaRb)、NRa(C(=0)Rb) , NRa(C(=0) ORb)、NRa(N=CRcRb)或 NRz-ORa ; n 係1、2或3，其中至少一個取代基L位於苯環之鄰位； L 係鹵素、氰基、Ci-Cg-烧基、C2-Ci〇-烯基、C2-C10-炔 基、Ci_C6·烧氧基、C2-C1G -烯氧基、C2-C1G -炔氧基、 石肖基、*^(=0)-0-Α7、-C(=0)-N(A8)A7、-C(=S)- n(a8)a7、c(a8)(=n-oa7)、n(a8)a7、n(a8)-c(=o)- A7或 S(=0)rA7，其中 A、A8彼此獨立地為氫、Ci-Cs -烧基、C2-C6 -稀基、 C2-C6-炔基、C3-C8-環烧基或苯基，其中該等有機 127320.doc -38- 200835487 基團可經部分或完全*化或可經鹵素、氰基及/或 1 Cr烷虱基取代；或a7及Μ與其所連接原子一起 :、、、1個或2個選自由〇、s組成之群雜原子 的5員或6員飽和雜環； :中L基團定義之脂肪族、環脂族及/或芳香族基團 口P刀可經部分或完全鹵化或可攜帶i個、2個、3個 或4個基團Rl，該等基團rL可為相同的或彼此不 同0Rl may also be hydrogen; or if Y is nr1, then R and R2 may, together with the nitrogen atom to which they are attached, form a heterodyne-) or another amine-(-N(RX))- group. a saturated or unsaturated 5- or 6-membered ring wherein Rx is hydrogen or Cl_C6-alkyl, and/or wherein the ring formed therein may comprise one or more selected from the group consisting of _, Ci_C6_alkyl, haloalkyl and oxygen a substituent of a group consisting of alkoxy groups; R3 halogen, cyano, cvc4-alkyl, CVC4-alkoxy or CkCV dentate; R4 cyano, C(= 〇)NRzRb, C(NRal NRzRb, 127320.doc -37- 200835487 NRzRb, C(=N-NRzlRcl)NRzRb, C(=S)NRzRb, C(=0)Ra, C(=NRal)Ra, C(=NORal)Ra, C (=N-NRzlRcl)Ra, C(=0)0Ra, C(=NRal)ORa, C(=NORal) ORa, C(=0)NRz-0Ra, C(=NRal)NRz-ORa, C(= NORal) NRz-ORa, C(=0)NRa-NRzRb, CRaRb-NRzRc, CRaRb-ORz, 0-C(=0)Ra, ON(=CRaRb), NRaRbl, NRa(C(=0) Rb), NRa(C(=NRal)Rb), NRa(C(=NORal)Rb), NRa(C(=0)0Rb), NRa(C(=0)-NRzRb), NRa(C(=NRa1)-NRzRb ), NRa (N = CRcRb), NRa-NRzRb or NRz-ORa, specifically, R4 is a cyano group, C(=S)NRzRb, C(=0)NRzR b, C(=NORal)NRzRb, C(NRal)NRzRb, C(=0)Ra, C(= NORal)Ra, C(=NRal)Ra, C(=0)0Ra, C(=NORal) 0Ra, C(=NRal)0Ra, C(=0)NRz-0Ra, C(=N0Ral)NRz-ORa, C(=NRal)NRz-ORa, C(=N-NRzlRcl)Ra, CRaRb-NRZRC, ON(= CRaRb), NRa (C(=0)Rb), NRa(C(=0)ORb), NRa(N=CRcRb) or NRz-ORa; n series 1, 2 or 3, wherein at least one substituent L is located in benzene Ortho position of the ring; L system halogen, cyano group, Ci-Cg-alkyl group, C2-Ci-alkenyl group, C2-C10-alkynyl group, Ci_C6·alkoxy group, C2-C1G-alkenyloxy group, C2- C1G-alkynyloxy, schlossyl, *^(=0)-0-Α7, -C(=0)-N(A8)A7, -C(=S)- n(a8)a7, c(a8)( =n-oa7), n(a8)a7, n(a8)-c(=o)- A7 or S(=0)rA7, wherein A and A8 are independently of each other hydrogen, Ci-Cs-alkyl, C2 -C6 - a dilute group, a C2-C6-alkynyl group, a C3-C8-cycloalkyl group or a phenyl group, wherein the organic 127320.doc-38-200835487 group may be partially or fully oxidized or may be halogen, cyanide And / or 1 Cr alkyl fluorenyl substituted; or a7 and hydrazine together with the atom to which they are attached: ,, 1 or 2, 5 or 6 membered saturated heterocyclic rings selected from the group consisting of hydrazine, s; Aliphatic, ring defined by the L group Aliphatic and / or aromatic groups port P blade may be partially or fully halogenated or may carry i, 2, 3 or 4 groups Rl, rL said groups may be the same or different from each other 0

在此等化合物中，較佳者係彼等其中基團#jQ~Ln 如上文所定義式B基團者。 係 進而言之，尤佳者為如下式丨，之2 γ 係 CHR1 或 NR1，Among these compounds, preferred are those in which the group #jQ~Ln is as defined above for the group B. In other words, the preferred one is the following formula: 2 γ is CHR1 or NR1,

-經取代咄啶··其中 R2 係c3-c8-烧基或c3-c8-鹵代院基，較佳為C3_C8_院基， 其分別在α-位置具有支鏈，較佳者係彼等如下者：其 十R2係丙-2-基、丁 _2_基、戊_2_基、己·2_基、庚冬 基、辛·2_基、(2_ 甲基)_丁-2·基、(2,3-二甲基)_ 丁·2_ 基、（3,3_二甲基）_ 丁 _2·基、（2-甲基）-戊-2-基、（3_甲 基)-戊-2-基、(4-甲基)_戊_2_基、(2,3_二甲基)_戊-2_ 基、（2,4-二甲基）-戊_2_基、（3,4_二甲基）_戊-2•基、 (Μ-二甲基）-戊-2-基、以山三氯丙_2_基或u山三氟 丙-2-基，更佳地 己-2-基、庚-2-基 (‘甲基）-戊-2-基 R2為丙_2-基、丁 基、戊_2·基、 辛基、（3,3-二甲基）_ 丁 _2_基及 甚至更佳地，R2為丙_2_基、丁 _2_ 127320.doc -39- 200835487 基庚2-基、（3,3-—甲基）-丁-2-基或（4_甲基）_戊-2 基， R1係氫；或倘若γ係NR1， R1及R:與氮-起可形成不含其他雜原子之5員或6員飽和雜 環，例如，吡咯啶小基及六氫吡啶小基，且該5員或 6貝飽和雜環視情況可經丨個、2個或3個（較佳為1個）- substituted acridine · wherein R 2 is a c3-c8-alkyl or c3-c8-halo-based group, preferably a C3_C8-house group, which has a branch at the α-position, preferably a The following: its ten R2 is a propan-2-yl group, a butyl-2-yl group, a pentyl-2-yl group, a hexyl-2-yl group, a heptyl group, a sin-2-yl group, a (2-methyl)-but-2 ·, (2,3-dimethyl)-butyl-2-yl, (3,3-dimethyl)-but-2-yl, (2-methyl)-pentan-2-yl, (3_ Methyl)-pentan-2-yl, (4-methyl)-pent-2-yl, (2,3-dimethyl)-pent-2-yl, (2,4-dimethyl)-pentyl 2_yl, (3,4-dimethyl)-pent-2-yl, (Μ-dimethyl)-pent-2-yl, oxalyl-2-yl or u-trifluoropropene- 2-Based, more preferably hex-2-yl, hept-2-yl ('methyl)-pent-2-yl R2 is prop-2-enyl, butyl, pent-2-yl, octyl, ( 3,3-Dimethyl)-but-2-yl and even more preferably, R2 is propen-2-yl, butyl-2_127320.doc-39-200835487 gen hen-2-yl, (3,3-- Methyl)-but-2-yl or (4-methyl)-pent-2-yl, R1 is hydrogen; or if γ is NR1, R1 and R: and nitrogen can form 5 members without other heteroatoms Or a 6-membered saturated heterocyclic ring, for example, pyrrolidine Small group and piperidine group, and the shell 5 or 6 saturated hetero ring optionally may be Shu, 2 or 3 (preferably 1)

選自鹵素、烷基及Ci_C4__代烷基之基團（較佳 為Ci-Cr烷基）取代； R3係i素； R係対基、°比唑基、味唑基、1，2,3_***基、丨，2,4-三 唑基、四唑基、噁唑基、異噁唑基、Μ/-噁’二唑 基丨’2,4·噁二唑基、呋喃基、苯硫基、噻唑基、異 塞坐基、吡啶基、嘧啶基、吡嗪基、嗒嗪基、I，]，％ 一秦基、1，2,4-三嗪基、吡咯啶基、六氫吡啶基、 I If- ^ ί Λ A氫氮呼基、二氫吡啶基、二氫噻唑基或苯并 ^ 基其中該雜環可藉由C或Ν與σ比唆環連接且可 攜π 1個、2個或3個基團RU，該等基團rU可為相 或彼此不同，其中 、 R係鹵幸、惫里 ^ ^ I 虱基、Ci-C8-烷基、Ci-CV烷氧基、 C^〇)-A4 > -C(=0)-〇.A4 > -C(=0)-N(A5)A4 C(A )(’-0A4)、N(A5)A4、N(A5)-C(=0)-A4，或其 苴中兩個相鄰基團RU 一起為（=0)或（=s); /、 其中特別佳者為其中R、2·嘧啶基之化合 基團 /、τ 127320.doc • 40 - 200835487a group selected from the group consisting of a halogen, an alkyl group and a Ci_C4__alkyl group (preferably a Ci-Cr alkyl group); an R3 system i; a R system thiol group, a carbazolyl group, an oxazolyl group, 1, 2, 3_triazolyl, anthracene, 2,4-triazolyl, tetrazolyl, oxazolyl, isoxazolyl, indole/-oxadoxadiazolidine 2,4oxadiazolyl, furyl , phenylthio, thiazolyl, isodecyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, I,], % monomethyl, 1,2,4-triazinyl, pyrrolidinyl, Hexahydropyridinyl, I If-^ ί Λ A hydrazinyl, dihydropyridyl, dihydrothiazolyl or benzoxyl wherein the heterocyclic ring can be attached via C or Ν to σ 唆 ring and can be carried π 1 , 2 or 3 groups RU, the groups rU may be phase or different from each other, wherein R is halogen, 惫 ^ ^ ^ 虱 、, Ci-C8-alkyl, Ci-CV Alkoxy, C^〇)-A4 > -C(=0)-〇.A4 > -C(=0)-N(A5)A4 C(A )('-0A4), N(A5) A4, N(A5)-C(=0)-A4, or two adjacent groups RU in the oxime thereof are (=0) or (=s); /, wherein particularly preferred is R, 2· Compound of pyrimidinyl group /, τ 127320.doc • 40 - 200835487

係如上文所定義式B基團。 進而言之’尤佳者為如下式j，之2·經取代吡啶：其中 Y 係 CHR1 或 NR1，Is a group of formula B as defined above. In other words, the most preferred one is the following formula j, 2, substituted pyridine: where Y is CHR1 or NR1,

R 係烷基或CVCV鹵代烷基，較佳為c3-c8-烷基， 其分別在α-位置具有支鏈，較佳者係彼等如下者：其 中R2係丙-2-基、丁 _2_基、戊·2_基、己_2•基、庚_2_ 基辛-2·基、（2-甲基）-丁-2-基、（2,3-二甲基）_丁_2· 基、（3,3_二甲基）· 丁 _2-基、（2_甲基兴戊_2_基、（3_曱 基）-戊-2-基、（4-甲基）_戊_2_基、（2,3-二曱基）_戊_2-基、（2,4-二甲基）_戊_2•基、（3,4-二甲基）_戊_2·基、 (4,4 一甲基）_戊_2_基、ι，ι，ι_三氯丙_2_基或^，卜三氟 丙-2-基，更佳地，R2係丙基、丁基、戊基、 己2基、庚_2_基、辛·2_基、（3,3-二甲基）_丁_2_基及 (舡甲基）-戊-2-基，甚至更佳地，R2係丙_2_基、丁·2_ 庚2基、（3,3 - 一甲基）-丁-2 -基或（4_甲基）_戊_2_ 基； R 係氫；或，倘若Y係NR1， 、及汉與氮一起可形成不含其他雜原子之5員或6員飽和 雜環，例如，吡咯啶-基及六氫吡啶基，且該5員 或6員飽和雜環視情況經丨個、2個或3個（較佳丨個）選 自南素、烷基及Cl-C4_鹵代烷基之基團（較佳為 烷基）取代； R 係_素； 127320.doc -41 · 200835487 R4 係氰基、C( = 0)NRzRb、C(NRal)NRzRb、C(=NORal) NRzRb、C(=N-NRzlRcl)NRzRb、C( = S)NRzRb、C(=0) Ra、C(=NRal)Ra、C(=NORal)Ra、C(，-NRzlRcl)Ra、 C( = 0)0Ra、C(=NRal)ORa、C(=NORal)ORa、C(=0) NRz-ORa、C(=NRal)NRz-ORa、C(=NORal)NRz-ORa、 C( = 0)NRa-NRzRb、CRaRb-NRzRc、CRaRb-ORz、O-C(=0)Ra、ON( = CRaRb)、NRaRbl、NRa(C(=0)Rb)、 NRa(C(=NRal)Rb) > NRa(C(=NORal)Rb)、NRa(C( = 0) ORb)、NRa(C(=0)-NRzRb)、NRa(C(=NRal)_NRzRb)、 NRa(N=CRcRb)、NRa-NRzRb 或 NRz-ORa，具體而言， R4係氰基、C(=S)NRzRb、C(=0)NRzRb、C(=NORal) NRzRb、C(NRal)NRzRb、C(=0)Ra、C(=NORal)Ra、 C(=NRal)Ra、C(=0)0Ra、C(=NORal)ORa、C(=NRal) ORa、C( = 0)NRz-0Ra、C(=NORal)NRz_ORa、C(=NRal) NRz-ORa、C(=N-NRzlRcl)Ra、CRaRb-NRzRc、ON(= CRaRb)、NRa(C(=0)Rb)、NRa(C(=0)0Rb)、NRa(N=CRcRb) 或 NRz-ORa ; 且其中基團R is an alkyl group or a CVCV haloalkyl group, preferably a c3-c8-alkyl group, which has a branch at the α-position, respectively, preferably those of which: R2 is prop-2-yl, butyl-2 _ base, pentyl-2-yl, hexyl-2-yl, heptyl-2-methyl-2,yl (2-methyl)-butan-2-yl, (2,3-dimethyl)-but 2·yl, (3,3-dimethyl)·butyl-2-yl, (2-methylmethylpenta-2-yl, (3-fluorenyl)-pentan-2-yl, (4-methyl) )_pent-2-yl, (2,3-diindenyl)-pent-2-yl, (2,4-dimethyl)-pent-2-yl, (3,4-dimethyl)_戊_2·yl, (4,4-methyl)-pentyl-2-yl, ι, ι,ι_trichloroprop-2-yl or ^, trifluoropropan-2-yl, more preferably, R2 is propyl, butyl, pentyl, hexyl 2, hept-2-yl, oct-2-yl, (3,3-dimethyl)-but-2-yl and (舡methyl)-pentyl -2-yl, even more preferably, R2 is a propionyl-2-yl group, a butyl-2~heptanyl group, a (3,3-methyl)-but-2-yl group or a (4-methyl)-pentyl group 2_ group; R is hydrogen; or, if Y is NR1, and together with nitrogen, it can form a 5- or 6-membered saturated heterocyclic ring containing no other hetero atom, for example, pyrrolidinyl and hexahydropyridyl, and The 5 members Or a 6-membered saturated heterocyclic ring may be substituted by one, two or three (preferably one) groups selected from the group consisting of a nitrite, an alkyl group and a Cl-C4-haloalkyl group (preferably an alkyl group); _素; 127320.doc -41 · 200835487 R4 is a cyano group, C(=0)NRzRb, C(NRal)NRzRb, C(=NORal) NRzRb, C(=N-NRzlRcl)NRzRb, C( = S)NRzRb , C(=0) Ra, C(=NRal)Ra, C(=NORal)Ra, C(,-NRzlRcl)Ra, C(=0)0Ra, C(=NRal)ORa, C(=NORal)ORa , C(=0) NRz-ORa, C(=NRal)NRz-ORa, C(=NORal)NRz-ORa, C(=0)NRa-NRzRb, CRaRb-NRzRc, CRaRb-ORz, OC(=0) Ra, ON (= CRaRb), NRaRbl, NRa (C(=0)Rb), NRa(C(=NRal)Rb) > NRa(C(=NORal)Rb), NRa(C(= 0) ORb) , NRa(C(=0)-NRzRb), NRa(C(=NRal)_NRzRb), NRa(N=CRcRb), NRa-NRzRb or NRz-ORa, specifically, R4 is cyano, C(=S NRzRb, C(=0)NRzRb, C(=NORal) NRzRb, C(NRal)NRzRb, C(=0)Ra, C(=NORal)Ra, C(=NRal)Ra, C(=0)0Ra , C(=NORal)ORa, C(=NRal) ORa, C(=0)NRz-0Ra, C(=NORal)NRz_ORa, C(=NRal) NRz-ORa, C(=N-NRzlRcl)Ra, CRaRb -NRzRc, ON (= CRaRb), NRa (C (=0) Rb), NRa (C (=0) 0Rb), NRa (N = CRcRb) or NRz-ORa ; and the group

係如上文所定義式B基團。 特定言之，考慮到其作為抗癌劑之用途，較佳者係式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、II、Im、 In、Io、Ip、Ir、Is、It、Iu、Iv、Iw及 lx之化合物，其中 L、η、Y、R2及R3係如本文所定義且較佳具有以較佳或特 127320.doc -42- 200835487 別較佳含義給出之含義。句 主1 r，。。丄，· 攻佳者係化合物If。適宜實例在 表1至188中給出。進而t 口< ’該等表中所述取代基基團本 身獨立於其中述及㈣之組合，所討論取代基之特別佳的 實施例。Is a group of formula B as defined above. In particular, in view of its use as an anticancer agent, preferred la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, II, Im, In, Io, Ip a compound of Ir, Is, It, Iu, Iv, Iw and lx, wherein L, η, Y, R2 and R3 are as defined herein and preferably have a preferred or specific 127320.doc -42-200835487 The meaning of good meaning gives. The sentence is 1 r,. .丄,· The attacker is a compound If. Suitable examples are given in Tables 1 to 188. Further, the substituent groups described in the tables are themselves independent of the combination of the above-mentioned (d), and particularly preferred embodiments of the substituents discussed.

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127320.doc -44 - 200835487127320.doc -44 - 200835487

ο „ 表l 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 ( 物，其中1^係2-氟、6-氯，R3係甲基且每一化合物之YR2 對應於表A之一列。 表2 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,6-二氟，R3係甲基且每一化合物之YR2對 應於表A之一列。 。表3式…、…、…™™、ο „ Table l Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw And a compound of lx, wherein 1 is 2-fluoro, 6-chloro, R3 methyl and each compound YR2 corresponds to one of Table A. Table 2 Formula la, lb, Ic, Id, Ie, If a compound of Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein 1^ is 2,6-difluoro, R3 is a methyl group and YR2 of each compound corresponds to one of Table A. Table 3 is a formula...,...,...TMTM,

Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中LnS2,6-二氯，R3係甲基且每一化合物之YR2對 - 應於表A之一列。 表4 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟、6-甲基，R3係甲基且每一化合物之 127320.doc -45- 200835487 YR2對應於表A之一列。 表5 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,4,6-三氟，113係甲基且每一化合物之丫112對 應於表A之一列。 表6 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-氟，R3係甲基且每一化合物之 YR2對應於表A之一列。 表7 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-曱氧基羰基，R3係甲基且每一化合 物之YR2對應於表A之一列。 表8 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2·氟、4-CN，R3係甲基且每一化合物之YR2 對應於表A之一列。 表9 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc -46- 200835487 物，其中Ln係2,4,5-三氟，R3係甲基且每一化合物之YR2對 應於表A之一列。 表10 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4-二氯，R3係曱基且每一化合物之YR2對 應於表A之一列。 表11 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯，R3係曱基且每一化合物之YR2對應於 表A之一列。 表12 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟，R3係曱基且每一化合物之YR2對應於 表A之一列。 表13 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4-二氟，R3係曱基且每一化合物之YR2對 應於表A之一列。 表14 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 -47- 127320.doc 200835487Compounds of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein LnS2,6-dichloro, R3 methyl and each compound YR2 pair - should be in Table A One of the columns. Table 4 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-fluoro, 6-methyl, R3 methyl and 127320.doc -45-200835487 YR2 of each compound corresponds to one of Table A. Table 5 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is a 2,4,6-trifluoro, 113-methyl group and the oxime 112 of each compound corresponds to one of Table A. Table 6 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, 4-fluoro, R3 methyl and each compound has YR2 corresponding to one of Table A. Table 7 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 4-nonyloxycarbonyl, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 8 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2, fluoro, 4-CN, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 9 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx Compound 127320.doc -46- 200835487, wherein Ln is 2,4,5-trifluoro, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 10 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4-dichloro, R3 is fluorenyl and YR2 of each compound corresponds to one of Table A. Table 11 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, R3 is fluorenyl and YR2 of each compound corresponds to one of Table A. Table 12 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, R3 is fluorenyl and YR2 of each compound corresponds to one of Table A. Table 13 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4-difluoro, R3 is fluorenyl and YR2 of each compound corresponds to one of Table A. Table 14 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, -47- 127320.doc 200835487

Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln*2-氟-4-氯，R3係甲基且每一化合物之YR2對 應於表A之一列。 表15 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯-4-氟，R3係甲基且每一化合物之YR2對 應於表A之一列。 表16 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,3-二氟，R3係甲基且每一化合物之YR2對 應於表A之一列。 表17 式 la、lb、Ic、Id、Ie、If、Ig、In、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,5-二氟，R3係甲基且每一化合物之YR2對 應於表A之一列。 表18 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,3,4-三氟，R3係甲基且每一化合物之YR2對 應於表A之一列。 表19 -48- 127320.doc 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中。係2-甲基，R3係甲基且每一化合物之YR2對應 於表A之一列。 表20 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4-二甲基，R3係曱基且每一化合物之YR2 對應於表A之一列。 表21 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中。係2-甲基-4-氯，R3係甲基且每一化合物之YR2 對應於表A之一列。 表22 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟-4-甲基，R3係甲基且每一化合物之YR2 對應於表A之一列。 表23 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二甲基，R3係甲基且每一化合物之YR2 對應於表A之一列。 -49- 127320.doc 200835487 表24 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,4,6-三甲基，113係甲基且每一化合物之丫112 對應於表A之一列。 表25 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-氰基，R3係甲基且每一化合物之 YR2對應於表A之一列。 表26 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-甲基，R3係甲基且每一化合物之 YR2對應於表A之一列。 表27 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,6-二氟-4-甲氧基羰基，R3係甲基且每一化 合物之YR2對應於表A之一列。 表28 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-甲氧基，R3係甲基且每一化合物之 127320.doc -50- 200835487 YR2對應於表A之一列。 表29 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氯、4-甲基，R3係甲基且每一化合物之 YR2對應於表A之一列。 表30 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik ' IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-曱氧基羰基，R3係甲基且每一化合 物之YR2對應於表A之一列。 表31 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-溴，R3係甲基且每一化合物之YR2 對應於表A之一列。 表32 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-氰基，R3係甲基且每一化合物之 YR2對應於表A之一列。 表33 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc -51 - 200835487 物，其中Ln*2,6-二氟、4-曱氧基，R3係甲基且每一化合 物之YR2對應於表A之一列。 表34 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln* 2-氟、3-甲基，R3係甲基且每一化合物之 YR2對應於表A之一列。 表35 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,5-二甲基，R3係曱基且每一化合物之YR2 對應於表A之一列。 表3 6 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-曱基、4-氰基，R3係甲基且每一化合物之 YR2對應於表A之一列。 表37 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-溴，R3係甲基且每一化合物之 YR2對應於表A之一列。 表38 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 127320.doc -52- 200835487a compound of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein Ln*2-fluoro-4-chloro, R3 is methyl and YR2 of each compound corresponds to the table A column of A. Table 15 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro-4-fluoro, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 16 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,3-difluoro, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 17 Formula la, lb, Ic, Id, Ie, If, Ig, In, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,5-difluoro, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 18 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,3,4-trifluoro, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 19 -48- 127320.doc 200835487 Equation la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, among them. 2-methyl, R3 methyl and each compound YR2 corresponds to one of Table A. Table 20 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4-dimethyl, R3 is fluorenyl and YR2 of each compound corresponds to one of Table A. Table 21 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx a compound of which. 2-methyl-4-chloro, R3 methyl and each compound YR2 corresponds to one of Table A. Table 22 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro-4-methyl, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 23 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-dimethyl, R3 is methyl and YR2 of each compound corresponds to one of Table A. -49- 127320.doc 200835487 Table 24 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw, and lx, wherein 1 is 2,4,6-trimethyl, 113-methyl, and 丫112 of each compound corresponds to one of Table A. Table 25 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro-4-cyano, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 26 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro-4-methyl, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 27 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2,6-difluoro-4-methoxycarbonyl, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 28 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-methoxy, R3 methyl and 127320.doc -50-200835487 YR2 of each compound corresponds to one of Table A. Table 29 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-chloro, 4-methyl, R3 methyl and YR2 of each compound corresponds to one of Table A. Table 30 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik 'IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-decyloxycarbonyl, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 31 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-bromo, R3 methyl and each compound has YR2 corresponding to one of Table A. Table 32 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-cyano, R3 methyl and each compound has YR2 corresponding to one of Table A. Table 33 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx Compound 127320.doc -51 - 200835487, wherein Ln*2,6-difluoro, 4-decyloxy, R3 methyl and each compound YR2 corresponds to one of Table A. Table 34 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln* 2-fluoro, 3-methyl, R3 methyl and each compound YR2 corresponds to one of Table A. Table 35 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,5-dimethyl, R3 is fluorenyl and YR2 of each compound corresponds to one of Table A. Table 3 6 formulas la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and A compound of lx wherein Ln is 2-indenyl, 4-cyano, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 37 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, 4-bromo, R3 methyl and each compound has YR2 corresponding to one of Table A. Table 38 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, 127320.doc -52- 200835487

Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、5-氟，R3係甲基且每一化合物之 YR2對應於表A之一列。 表39 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-曱基、4-甲氧基，R3係甲基且每一化合物 之YR2對應於表A之一列。 表40 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-曱基、4-甲氧基羰基，R3係曱基且每一化 合物之YR2對應於表A之一列。 表41 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,5-二甲基、4-溴，R3係甲基且每一化合物 之YR2對應於表A之一列。 表42 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2_氟、4-溴，R3係甲基且每一化合物之YR2 對應於表A之一列。 表43 127320.doc -53 - 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中LnS 2-氟、4-甲氧基，R3係曱基且每一化合物之 YR2對應於表A之一列。 .表44 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中。係2_氟、5-甲基，R3係甲基且每一化合物之 ( YR2對應於表A之一列。 表45 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係五氟，R3係甲基且每一化合物之YR2對應於 表A之一列。 表46 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 ia compound of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx, wherein Ln is 2-methyl, 5-fluoro, R3 methyl, and YR2 of each compound corresponds to One of the tables in Table A. Table 39 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-indenyl, 4-methoxy, R3 is methyl and YR2 of each compound corresponds to one of Table A. Table 40: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-indenyl, 4-methoxycarbonyl, R3 is indenyl and YR2 of each compound corresponds to one of Table A. Table 41 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,5-dimethyl, 4-bromo, R3 methyl and each compound has YR2 corresponding to one of Table A. Table 42 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 4-bromo, R3 methyl and YR2 of each compound corresponds to one of Table A. Table 43 127320.doc -53 - 200835487 Equation la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein LnS 2-fluoro, 4-methoxy, R3 is fluorenyl and YR2 of each compound corresponds to one of Table A. Table 44 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and Lx compound, of which. 2-fluoro, 5-methyl, R3 methyl and each compound (YR2 corresponds to one of Table A. Table 45 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij a compound of Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein Ln is pentafluoro, R3 is methyl and YR2 of each compound corresponds to the table A column of A. Table 46 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, i

Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2·氣、5_氟、4-甲氧基，R3係甲基且每一化 合物之YR2對應於表A之一列。 表47 式 la、lb ' Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中、係2-氯、5-氟，R3係甲基且每一化合物之YR2 對應於表A之一列。 127320.doc -54- 200835487 表48 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、6-氯，R3係氯且每一化合物之YR2對 . 應於表A之一列。 表49 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 f 物，其中Ln係2,6-二氟，R3係氯且每一化合物之YR2對應 於表A之一列。 表50 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氯，R3係氯且每一化合物之YR2對應 於表A之一列。 表51 1 / . 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟、6-甲基，R3係氣且每一化合物之YR2 對應於表A之一列。 . 表52 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4,6-三氟，R3係氣且每一化合物之YR2對應 127320.doc -55- 200835487 於表A之一列。 表53 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-氟，R3係氯且每一化合物之YR2 . 對應於表A之一列。 表54 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 C Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-曱氧基羰基，R3係氯且每一化合物 之YR2對應於表A之一列。 表55 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-CN，R3係氯且每一化合物之YR2對 應於表A之一列。 ( 表56 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 * 物，其中Ln係2,4,5-三氟，R3係氯且每一化合物之YR2對應 - 於表A之一列。 表57 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc -56- 200835487 物，其中1^係2,4-二氣，R3係氯且每一化合物之YR2對應 於表A之一列。 表58 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合a compound of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx, wherein Ln is 2, gas, 5-fluoro, 4-methoxy, R3 is methyl and each The YR2 of the compound corresponds to one of the columns of Table A. Table 47 Formula la, lb ' Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 2-chloro, 5-fluoro, R3 is methyl and YR2 of each compound corresponds to one of Table A. 127320.doc -54- 200835487 Table 48 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein Ln is 2-fluoro, 6-chloro, R3 is chlorine and the YR2 pair of each compound is listed in Table A. Table 49 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx The compound of the formula wherein Ln is 2,6-difluoro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 50 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-dichloro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 51 1 / . Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Compounds of Iw and lx, wherein 1 is 2-fluoro, 6-methyl, R3 is a gas and YR2 of each compound corresponds to one of Table A. Table 52 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and A compound of lx wherein Ln is 2,4,6-trifluoro, R3 is a gas and YR2 of each compound corresponds to 127320.doc-55-200835487 in one of Table A. Table 53 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, 4-fluoro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 54 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, C Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and A compound of lx wherein Ln is 2-fluoro, 4-nonyloxycarbonyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 55 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 4-CN, R3 is chlorine and YR2 of each compound corresponds to one of Table A. (Table 56: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and a compound of lx, wherein Ln is 2,4,5-trifluoro, R3 is chlorine and YR2 of each compound corresponds to - one of Table A. Table 57 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx 127320.doc -56- 200835487, of which 1^ 2,4-digas, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 58 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Combination of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx

物，其中Ln係2-氯，R3係氯且每一化合物之YR2對應於表A 之一列。 表59 式 la、lb、Ic、Id、Ie、If、Ig ' Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合Where Ln is 2-chloro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 59 Formula la, lb, Ic, Id, Ie, If, Ig 'Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx Combination

物，其中Ln係2-氟，R3係氯且每一化合物之YR2對應於表A 之一列。 表60 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4-二氟，R3係氯且每一化合物之YR2對應 於表A之一列。 表61 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟-4-氯，R3係氯且每一化合物之YR2對應 於表A之一列。 表62 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 -57- 127320.doc 200835487Where Ln is 2-fluoro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 60 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4-difluoro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 61 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-fluoro-4-chloro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 62 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, -57- 127320.doc 200835487

Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯-4-氟，R3係氣且每一化合物之YR2對應 於表A之一列。 表63 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,3-二氟，R3係氯且每一化合物之YR2對應 於表A之一列。 表64 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,5-二氟，R3係氯且每一化合物之YR2對應 於表A之一列。 表65 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,3,4-三氟，R3係氣且每一化合物之YR2對應 於表A之一列。 表66 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基，R3係氯且每一化合物之YR2對應於 表A之一列。 表67 -58- 127320.doc 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4-二甲基，R3係氣且每一化合物之YR2對 應於表A之一列。 表68 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-曱基-4-氣，R3係氯且每一化合物之YR2對 應於表A之一列。 表69 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟-4-甲基，R2係氯且每一化合物之YR2對 應於表A之一列。 表70 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二甲基，R3係氯且每一化合物之YR2對 應於表A之一列。 表71 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4,6-三甲基，R3係氯且每一化合物之YR2對 應於表A之一列。 -59- 127320.doc 200835487 表72 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,6-二氟-4-氰基，R3係氯且每一化合物之 YR2對應於表A之一列。 表73 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-甲基，R3係氯且每一化合物之 YR2對應於表A之一列。 表74 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-甲氧基羰基，R3係氯且每一化合 物之YR2對應於表A之一列。 表75 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-甲氧基，R3係氯且每一化合物之 YR2對應於表A之一列。 表76 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氣、4-曱基，R3係氯且每一化合物之YR2 127320.doc -60- 200835487 對應於表A之一列。 表77 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-甲氧基羰基，R3係氯且每一化合物 之YR2對應於表A之一列。 表78 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4_溴，R3係氯且每一化合物之YR2對 應於表A之一列。 表79 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-氰基，R3係氯且每一化合物之YR2 對應於表A之一列。 表80 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟、4·甲氧基，R3係氣且每一化合物 之YR2對應於表A之一列。 表81 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc -61 - 200835487 物，其中Ln係2-氟、3-曱基，R3係氯且每一化合物之YR2 對應於表A之一列。 表82 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 * Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 , 物，其中Ln係2,5-二甲基，R3係氯且每一化合物之YR2對 應於表A之一列。 表83 ( 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、Compounds of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein Ln is 2-chloro-4-fluoro, R3 is gas and YR2 of each compound corresponds to Table A One of the columns. Table 63: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,3-difluoro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 64: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,5-difluoro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 65 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,3,4-trifluoro, R3 is a gas and YR2 of each compound corresponds to one of Table A. Table 66 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 67 -58- 127320.doc 200835487 Equation la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein Ln is 2,4-dimethyl, R3 is gas and YR2 of each compound corresponds to one of Table A. Table 68 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-mercapto-4-a, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 69 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro-4-methyl, R2 is chlorine and YR2 of each compound corresponds to one of Table A. Table 70 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-dimethyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 71 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4,6-trimethyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. -59- 127320.doc 200835487 Table 72 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein 1 is 2,6-difluoro-4-cyano, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 73 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro-4-methyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 74: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro-4-methoxycarbonyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 75 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-methoxy, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 76 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-gas, 4-mercapto, R3 is chlorine and YR2 127320.doc -60-200835487 of each compound corresponds to one of Table A. Table 77 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-methoxycarbonyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 78 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-bromo, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 79 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-cyano, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 80: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro, 4,methoxy, R3 is a gas and YR2 of each compound corresponds to one of Table A. Table 81 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx Compound 127320.doc -61 - 200835487, wherein Ln is 2-fluoro, 3-mercapto, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 82: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, * Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and A compound of lx, wherein Ln is 2,5-dimethyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 83 (L, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL,

Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-氰基，R3係氯且每一化合物之 YR2對應於表A之一列。 表84 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-曱基、4-溴，R3係氯且每一化合物之YR2 對應於表A之一列。 表85 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 - 物，其中Ln係2-甲基、5·氟，R3係氯且每一化合物之YR2 對應於表A之一列。 表86 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 127320.doc -62- 200835487a compound of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx, wherein Ln is 2-methyl, 4-cyano, R3 is chlorine and YR2 of each compound corresponds to One of the tables in Table A. Table 84 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-indenyl, 4-bromo, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 85 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx The compound, wherein Ln is 2-methyl, 5-fluoro, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 86 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, 127320.doc -62- 200835487

Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-甲基、4·甲氧基，R3係氯且每一化合物之 YR2對應於表A之一列。 表87 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中LnS 2-甲基、4_甲氧基羰基，R3係氯且每一化合 物之YR2對應於表A之一列。 表88 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,5-二甲基、4-溴，R3係氯且每一化合物之 YR2對應於表A之一列。 表89 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-溴，R3係氯且每一化合物之YR2對 應於表A之一列。 表90 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟、4-甲氧基，R3係氣且每一化合物之 YR2對應於表A之一列。 表91 127320.doc •63- 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟、5-甲基，R3係氯且每一化合物之YR2 對應於表A之一列。 表92 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係五氟，R3係氣且每一化合物之YR2對應於表 A之一列。 表93 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、5-氟、4-甲氧基，R3係氯且每一化合 物之YR2對應於表A之一列。 表94 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、5-氟，R3係氣且每一化合物之YR2對 應於表A之一列。 表95 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟、6-氯，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 127320.doc -64- 200835487 表96 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln.2,6-二氟，R3係甲氧基且每一化合物之YR2 對應於表A之一列。 表97 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氯，R3係曱氧基且每一化合物之YR2 對應於表A之一列。 表98 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、6-甲基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表99 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4,6-三氟，R3係甲氧基且每一化合物之YR2 對應於表A之一列。 表100 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-氟，R3係甲氧基且每一化合物之 127320.doc -65- 200835487 YR2對應於表A之一列。 表101 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 .物，其中Ln係2-氟、4-甲氧基羰基，R3係甲氧基且每一化 . 合物之YR2對應於表A之一列。 表102 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 f ^ Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-CN，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表103 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4,5-三氟，R3係曱氧基且每一化合物之YR2 對應於表A之一列。 I’ 表 104 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 • 物，其中1^係2,4-二氯，R3係甲氧基且每一化合物之YR2 對應於表A之一列。 表105 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc -66- 200835487 物，其中Ln係2 -氯，R3待甲I n — 9 ^ 你T虱基且每一化合物之YR2對應 於表A之一列。 表106 式 la、lb、Ic、Id、Ie、If、ig、化、Π、ij、ik、IL、 Im、ln、I〇、Ip、iq、Ir、Is、It、Iu、w、^及匕之化合 物’其中Ln係2-氟’ R3係曱氧基且每一化合物之YR2對應 於表A之一列。 表107 式 la、lb、Ic、Id、Ie、If、Ig、ih、、ij、ik、IL、 In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物’其中一係2,4-二氟，R3係甲氧基且每一化合物之YR2 對應於表A之一列。 表108 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、ij、Ik、IL、Compounds of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein 1^ is 2-methyl, 4·methoxy, R3 is chlorine and YR2 of each compound Corresponds to one of the columns in Table A. Table 87 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein LnS 2-methyl, 4-methoxycarbonyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 88: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,5-dimethyl, 4-bromo, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 89 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 4-bromo, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 90 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-fluoro, 4-methoxy, R3 is a gas and YR2 of each compound corresponds to one of Table A. Table 91 127320.doc •63- 200835487 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein 1 is 2-fluoro, 5-methyl, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 92 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is pentafluoro, R3 is gas and YR2 of each compound corresponds to one of Table A. Table 93 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 5-fluoro, 4-methoxy, R3 is chlorine and YR2 of each compound corresponds to one of Table A. Table 94 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 5-fluoro, R3 is a gas and YR2 of each compound corresponds to one of Table A. Table 95 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-fluoro, 6-chloro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. 127320.doc -64- 200835487 Table 96 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein Ln. 2,6-difluoro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 97 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-dichloro, R3 is decyloxy and YR2 of each compound corresponds to one of Table A. Table 98 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 6-methyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 99 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4,6-trifluoro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 100 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, 4-fluoro, R3 is methoxy and 127320.doc -65-200835487 YR2 of each compound corresponds to one of Table A. Table 101 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx The compound, wherein Ln is 2-fluoro, 4-methoxycarbonyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 102 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, f^ Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw And a compound of lx wherein Ln is 2-fluoro, 4-CN, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 103 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4,5-trifluoro, R3 is decyloxy and YR2 of each compound corresponds to one of Table A. I' Table 104 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw And lx compound, wherein 1^ is 2,4-dichloro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 105 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx Compound 127320.doc -66- 200835487, wherein Ln is 2-chloro, R3 is a, I n - 9 ^, and the YR2 of each compound corresponds to one of Table A. Table 106: la, lb, Ic, Id, Ie, If, ig, chem, ij, ij, IK, IL, Im, ln, I 〇, Ip, iq, Ir, Is, It, Iu, w, ^ and A compound of hydrazine wherein Ln is 2-fluoro' R3 is a decyloxy group and YR2 of each compound corresponds to one of Table A. Table 107 Compounds of the formula la, lb, Ic, Id, Ie, If, Ig, ih, ij, ik, IL, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx' One of them is 2,4-difluoro, the R3 is methoxy and the YR2 of each compound corresponds to one of Table A. Table 108 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, ij, Ik, IL,

Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、iw及 ΐχ之化合 物’其中Ln係2-氟-4-氯，R3係曱氧基且每一化合物之yr2 對應於表A之一列。 表1〇9 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、ij、Ik、IL、a compound of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, iw and oxime, wherein Ln is 2-fluoro-4-chloro, R3 is decyloxy and yr2 of each compound corresponds to One of the tables in Table A. Table 1 〇9 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, ij, Ik, IL,

Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、iw及 ΐχ之化合 物’其中1^係2-氣-4-氟，R3係甲氧基且每一化合物之YR2 對應於表A之一列。 表110 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、ij、Ik、IL、Compounds of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, iw and yttrium] wherein 1^ is 2-gas-4-fluoro, R3 is methoxy and YR2 is corresponding to each compound. In one of the tables A. Table 110 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, ij, Ik, IL,

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Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,3-二氟，R3係曱氧基且每一化合物之YR2 對應於表A之一列。 表111 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,5-二氟，R3係甲氧基且每一化合物之YR2 對應於表A之一列。 表112 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,3,4-三氟，R3係甲氧基且每一化合物之YR2 對應於表A之一列。 表113 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-曱基，R3係甲氧基且每一化合物之YR2對 應於表A之一列。 表114 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4_二甲基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表115 127320.doc -68- 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-甲基-4-氯，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表116 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟_4-甲基，R3係曱氧基且每一化合物之 YR2對應於表A之一列。 表117 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,6-二甲基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表118 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4,6-三甲基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表119 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-氰基，R3係曱氧基且每一化合物 之YR2對應於表A之一列。 -69- 127320.doc 200835487 表120 式 la、lb、Ic、Id、Ie、If、Ig、Ih、π、y、让、乩、 Im、In、I〇、lp、Iq、Ir、Is、It、Iu、Iv、…及 Ιχ之化合 物’其中Ln係2,6-二氟-4-甲基，R3係甲氧基且每一化合物 之YR2對應於表A之一列。 表121 式 la、lb、Ic、Id、Ie、If、Ig、Ih、π、y、比、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、w、^及匕之化合 物’其中Ln係2,6 -二敦-4-甲氧基幾基，r3係甲氧基且每一 化合物之YR2對應於表A之一列。 表122 式 la、lb、Ic、id、Ie、If、Ig、Ih、η、y、Ik、IL、 Im、In、l〇、Ip、Iq、Ir、Is、It、Iu、Iv、卜及 ΐχ之化合 物’其中Ln係2-氯、4-甲氧基，R3係甲氧基且每一化合物 之YR對應於表A之一列。 表123 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、w、^及以之化合 物’其中1^係2-氣、4-甲基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表124 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、ij、ik、il、 Im、ln、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw&Ix之化合 物’其中Ln係2-氣、4-甲氧基羰基，R3係甲氧基且每一化 127320.doc -70- 200835487 合物之YR2對應於表A之一列。 表125 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氯、4-甲氧基，R3係甲氧基且每一化合物 之YR2對應於表A之一列。 表126 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氯、4-氰基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表127 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟、4-曱氧基，R3係甲氧基且每一化 合物之YR2對應於表A之一列。 表128 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、3-甲基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表129 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc •71 - 200835487 物’其中ILn係2,5-二曱基，R3係曱氧基且每一化合物之a compound of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein Ln is 2,3-difluoro, R3 is decyloxy and YR2 of each compound corresponds to the table A column of A. Table 111 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2,5-difluoro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 112 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2,3,4-trifluoro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 113 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-indenyl, R3 is methoxy, and YR2 of each compound corresponds to one of Table A. Table 114: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4-dimethyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 115 127320.doc -68- 200835487 Equation la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein 1 is 2-methyl-4-chloro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 116 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro-4-methyl, R3 is decyloxy and YR2 of each compound corresponds to one of Table A. Table 117 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2,6-dimethyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 118 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4,6-trimethyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 119 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro-4-cyano, R3 is decyloxy and YR2 of each compound corresponds to one of Table A. -69- 127320.doc 200835487 Table 120 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, π, y, let, 乩, Im, In, I 〇, lp, Iq, Ir, Is, It , Iu, Iv, ... and oxime compounds 'where Ln is 2,6-difluoro-4-methyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 121 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, π, y, ratio, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, w, ^, and The compound 'wherein Ln is 2,6-ditun-4-methoxyl, r3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 122 Formula la, lb, Ic, id, Ie, If, Ig, Ih, η, y, Ik, IL, Im, In, l〇, Ip, Iq, Ir, Is, It, Iu, Iv, and A compound of hydrazine wherein Ln is 2-chloro, 4-methoxy, R3 is methoxy and the YR of each compound corresponds to one of Table A. Table 123 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, w, ^ and The compound 'where 1 ' is 2-gas, 4-methyl, R 3 is methoxy and YR 2 of each compound corresponds to one of Table A. Table 124: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, ij, ik, il, Im, ln, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw& Ix The compound 'where Ln is 2-gas, 4-methoxycarbonyl, R3 is methoxy and each YR2 of 127320.doc-70-200835487 corresponds to one of Table A. Table 125 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-chloro, 4-methoxy, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 126 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-chloro, 4-cyano, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 127 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro, 4-decyloxy, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 128: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 3-methyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 129 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx 127320.doc •71 - 200835487 The object 'where ILn is 2,5-dimercapto, R3 is decyloxy and each compound

Yr2對應於表A之一列。 表130 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij ' Ik、IL、Yr2 corresponds to one of the columns of Table A. Table 130 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij 'Ik, IL,

Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-甲基、4-氰基，R3係曱氧基且每一化合物 之¥汉2對應於表A之一列。 表131 式 、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、ln、、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2·甲基、4-溴，R3係曱氧基且每一化合物之 YR2對應於表A之一列。 表132 式1a、lb、ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、I〇、ip、iq、lr、Is、It、Iu、Iv、Iw及 lx之化合 物’其中Ln係2-甲基、5-氟，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表133 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、a compound of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx, wherein 1 is 2-methyl, 4-cyano, R3 is decyloxy and each compound ¥汉2 corresponds to one of the columns in Table A. Table 131 Compounds of the formulas, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, ln, Ir, Is, It, Iu, Iv, Iw and lx, wherein 1^ 2·Methyl, 4-bromo, R3 is a decyloxy group and YR2 of each compound corresponds to one of Table A. Table 132 Formula 1a, lb, ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, I〇, ip, iq, lr, Is, It, Iu, Iv, Iw and The compound of lx wherein Ln is 2-methyl, 5-fluoro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 133 formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL,

Im、In、I〇、ip、iq、lr、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-甲氧基，R3係甲氧基且每一化合 物之YR2對應於表A之一列。 表134 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、ij、Ik、IL、 127320.doc -72- 200835487Compounds of Im, In, I〇, ip, iq, lr, Is, It, Iu, Iv, Iw and lx, wherein Ln is 2-methyl, 4-methoxy, R3 is methoxy and each compound YR2 corresponds to one of the columns of Table A. Table 134 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, ij, Ik, IL, 127320.doc -72- 200835487

Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 Ιχ之化合 物，其中1^係2-甲基、4-曱氧基羰基，R3係甲氧基且每一 化合物之YR2對應於表A之一列。 表135 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,5-二甲基、4-溴，R3係甲氧基且每一化合 物之YR2對應於表A之一列。 表136 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-溴，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表137 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2·氟、4-甲氧基，R3係甲氧基且每一化合物 之YR2對應於表A之一列。 表138 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、5-甲基，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表139 127320.doc -73 - 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係五氟，R3係甲氧基且每一化合物之YR2對應 於表A之一列。 表140 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、5-氟、4-甲氧基，R3係甲氧基且每一 化合物之YR2對應於表A之一列。 表141 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氣、5 -氟，R3係甲氧基且每一化合物之 YR2對應於表A之一列。 表142 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、6-氯，R3係氰基且每一化合物之YR2 對應於表A之一列。 表143 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟，R3係氰基且每一化合物之YR2對 應於表A之一列。 127320.doc -74· 200835487 表144 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中。係2,6-二氣，R3係氰基且每一化合物之YR2對 應於表A之一列。 表145 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 f 物，其中Ln係2-氟、6-甲基，R3係氰基且每一化合物之 YR2對應於表A之一列。 表146 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4,6-三氟，R3係氰基且每一化合物之YR2對 應於表A之一列。 表147 I 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、a compound of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and hydrazine, wherein 1 is 2-methyl, 4-decyloxycarbonyl, R3 is methoxy and each The YR2 of the compound corresponds to one of the columns of Table A. Table 135 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2,5-dimethyl, 4-bromo, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 136 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 4-bromo, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 137 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2·fluoro, 4-methoxy, R 3 is methoxy and YR 2 of each compound corresponds to one of Table A. Table 138 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 5-methyl, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 139 127320.doc -73 - 200835487 Equation la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein 1 is pentafluoro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 140: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 5-fluoro, 4-methoxy, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 141 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-gas, 5-fluoro, R3 is methoxy and YR2 of each compound corresponds to one of Table A. Table 142 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 6-chloro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 143 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. 127320.doc -74· 200835487 Table 144 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, among them. It is 2,6-dialdehyde, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 145 where la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx The compound of the formula wherein Ln is 2-fluoro, 6-methyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 146 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4,6-trifluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 147 I Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL,

Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-氟，R3係氰基且每一化合物之 ‘ YR2對應於表A之一列。 • 表 148 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-甲氧基羰基，R3係氰基且每一化合 127320.doc -75- 200835487 物之YR2對應於表A之一列。 表149 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟、4-CN，R3係氰基且每一化合物之YR2 對應於表A之一列。 表150 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln*2,4,5-三氟，R3係氰基且每一化合物之YR2對 應於表A之一列。 表151 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4_二氯，R3係氰基且每一化合物之YR2對 應於表A之一列。 表152 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯，R3係氰基且每一化合物之YR2對應於 表A之一列。 表153 式 la、lb、Ic、Id、Ie、If、Ig、In、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc -76- 200835487 物，其中1^係2-氟，R3係氰基且每一化合物之YR2對應於 表A之一列。 表154 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,4-二氟，R3係氰基且每一化合物之YR2對 應於表A之一列。 表155 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟-4-氯，R3係氰基且每一化合物之YR2對 應於表A之一列。 表156 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物’其中Ln係2 -氯-4-氟’ R3係氰基且每一化合物之YR2對 應於表A之一列。 表157 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,3-二氟，R3係氰基且每一化合物之YR2對 應於表A之一列。 表158 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 -77- 127320.doc 200835487a compound of Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx, wherein Ln is 2-methyl, 4-fluoro, R3 is a cyano group and the 'YR2' of each compound corresponds In one of the tables A. • Table 148 where la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and A compound of lx wherein Ln is 2-fluoro, 4-methoxycarbonyl, R3 is cyano and YR2 of each compound 127320.doc-75-200835487 corresponds to one of Table A. Table 149 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-fluoro, 4-CN, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 150 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln*2,4,5-trifluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 151 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4-dichloro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 152 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 153 Equations la, lb, Ic, Id, Ie, If, Ig, In, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx Compound 127320.doc-76-200835487, wherein 1^ is 2-fluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 154 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2,4-difluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 155 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-fluoro-4-chloro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 156 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx The compound 'where Ln is 2-chloro-4-fluoro' R3 is a cyano group and YR2 of each compound corresponds to one of Table A. Table 157 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,3-difluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 158 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, -77- 127320.doc 200835487

Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 Ιχ之化合 物，其中Ln係2,5-二氟，R3係氰基且每一化合物之YR2對 應於表A之一列。 表159 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,3,4-三氟，R3係氰基且每一化合物之YR2對 應於表A之一列。 表160 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基，R3係氰基且每一化合物之YR2對應 於表A之一列。 表161 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4-二甲基，R3係氰基且每一化合物之YR2 對應於表A之一列。 表162 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-曱基-4-氯，R3係氰基且每一化合物之YR2 對應於表A之一列。 表163 -78 - 127320.doc 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟-4-甲基，R3係氰基且每一化合物之YR2 對應於表A之一列。 表164 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、Π、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二甲基，R3係氰基且每一化合物之YR2 對應於表A之一列。 表165 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,4,6-三甲基，R3係氰基且每一化合物之YR2 對應於表A之一列。 表166 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-氰基，R3係氰基且每一化合物之 YR2對應於表A之一列。 表167 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-甲基，R3係氰基且每一化合物之 YR2對應於表A之一列。 -79- 127320.doc 200835487 表168 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、I〇、ip、iq、ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟-4-甲氧基羰基，R3係氰基且每一化 - 合物之YR2對應於表A之一列。 表169 式 la、lb、Ic、Id、Ie、If、Ig、In、Ii、Ij、Ik、IL、 Im、In、I〇、ip、iq、ir、Is、It、Iu、Iv、Iw及 lx之化合 ( 物’其中Ln係2_氯、4-甲氧基，R3係氰基且每一化合物之 yr2對應於表A之一列。 表170 式1a、lb、IC、id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im 、I〇、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物’其中、係2-氯、4-甲基，R3係氰基且每一化合物之 yr2對應於表A之一列。 表171 U . 式 la、lb、IC、Η、Ie、K、Ig、Ih、η、][j、Ik、IL、 Im In、、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 * 物’其中1係2-氣、4-曱氧基羰基，R3係氰基且每一化合 ’ 物之YR2對應於表A之一列。 . 表 172 式1a、lb、Ic、id、le、if、Ig、Ih、η、][j、Ik、IL、 I ixx 、 τ n Io ' Ip、Iq、Ir、Is、、Iu、iv、iw及 lx之化合 物’其中1^係2-氯、4-溴，R3係氰基且每一化合物之YR2 127320.doc -80- 200835487 對應於表A之一列。 表173 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、4-氰基，R3係氰基且每一化合物之 . YR2對應於表A之一列。 表174 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 C Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2,6-二氟、4-甲氧基，R3係氰基且每一化合 物之YR2對應於表A之一列。 表175 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中、係2-氟、3-曱基，R3係氰基且每一化合物之 YR2對應於表A之一列。 1, V 表 176 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 - 物，其中Ln係2,5·二甲基，R3係氰基且每一化合物之YR2 、 對應於表A之一列。 表177 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 127320.doc -81 - 200835487 物，其中1^係2-甲基、4·氰基，R3係氰基且每一化合物之 YR2對應於表A之一列。 表178 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中。係2-甲基、4-溴，R3係氰基且每一化合物之 YR2對應於表A之一列。 表179 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、5-氟，R3係氰基且每一化合物之 YR2對應於表A之一列。 表180 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-甲基、4-曱氧基，R3係氰基且每一化合物 之YR2對應於表A之一列。 表181 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-甲基、4-甲氧基羰基，R3係氰基且每一化 合物之YR2對應於表A之一列。 表182 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 127320.doc -82· 200835487Compounds of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and hydrazine, wherein Ln is 2,5-difluoro, R3 is cyano and YR2 of each compound corresponds to Table A One of the columns. Table 159 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2,3,4-trifluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 160: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 161 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4-dimethyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 162 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-mercapto-4-chloro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 163 -78 - 127320.doc 200835487 Equation la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein Ln is 2-fluoro-4-methyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 164 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, Π, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-dimethyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 165 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,4,6-trimethyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 166: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro-4-cyano, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 167 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2,6-difluoro-4-methyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. -79- 127320.doc 200835487 Table 168 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, I〇, ip, iq, ir, Is, It Compounds of Iu, Iv, Iw and lx, wherein Ln is 2,6-difluoro-4-methoxycarbonyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 169 Formula la, lb, Ic, Id, Ie, If, Ig, In, Ii, Ij, Ik, IL, Im, In, I〇, ip, iq, ir, Is, It, Iu, Iv, Iw and a compound of lx (wherein Ln is 2_chloro, 4-methoxy, R3 is cyano and yr2 of each compound corresponds to one of Table A. Table 170 Formula 1a, lb, IC, id, Ie, If , Ig, Ih, Ii, Ij, Ik, IL, Im, I〇, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx compounds, wherein 2-chloro, 4-methyl, R3 is a cyano group and yr2 of each compound corresponds to one of Table A. Table 171 U. Formula la, lb, IC, Η, Ie, K, Ig, Ih, η,] [j, Ik, IL, Im In , Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx compound * where 1 is 2-gas, 4-decyloxycarbonyl, R3 is cyano and each compound is YR2 Corresponds to one of the columns in Table A. Table 172 Formula 1a, lb, Ic, id, le, if, Ig, Ih, η,] [j, Ik, IL, I ixx , τ n Io ' Ip, Iq, Ir, Compounds of Is, Iu, iv, iw and lx wherein 1 is 2-chloro, 4-bromo, R3 is cyano and YR2 127320.doc -80-200835487 of each compound corresponds to one of Table A. Table 173 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 4-cyano, R3 is cyano and each compound. YR2 corresponds to one of Table A. Table 174 Formula la, lb, Ic, Id, Ie, If, Ig, Compounds of Ih, Ii, Ij, Ik, IL, C Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein Ln is 2,6-difluoro, 4-methyl Oxyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 175 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In a compound of Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw and lx, wherein is 2-fluoro, 3-indenyl, R3 is cyano and YR2 of each compound corresponds to Table A One column. 1, V Table 176 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, a compound of Iv, Iw and lx, wherein Ln is 2,5. dimethyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 177 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx 127320.doc -81 - 200835487, wherein 1^ is 2-methyl, 4-cyano, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 178 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx a compound of which. 2-methyl, 4-bromo, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 179 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, 5-fluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 180 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-methyl, 4-decyloxy, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 181 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-methyl, 4-methoxycarbonyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 182 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, 127320.doc -82· 200835487

Im、In、Ιο、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2,5-二甲基、4-溴，113係氰基且每一化合物 之YR2對應於表A之一列。 表183 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氟、4-溴，R3係氰基且每一化合物之YR2 對應於表A之一列。 表184 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、4-曱氧基，R3係氰基且每一化合物之 YR2對應於表A之一列。 表185 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氟、5-甲基，R3係氰基且每一化合物之 YR2對應於表A之一列。 表186 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係五氟，R3係氰基且每一化合物之YR2對應於 表A之一列。 表187 127320.doc -83 - 200835487 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中1^係2-氯、5-氟、4·甲氧基，R3係氰基且每一化 合物之YR2對應於表A之一列。 表188 式 la、lb、Ic、Id、Ie、If、Ig、Ih、Ii、Ij、Ik、IL、 Im、In、Io、Ip、Iq、Ir、Is、It、Iu、Iv、Iw及 lx之化合 物，其中Ln係2-氯、5-氟，R3係氰基且每一化合物之YR2 f 對應於表A之一列。a compound of Im, In, Ιο, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx, wherein 1^ is 2,5-dimethyl, 4-bromo, 113-based cyano and each compound YR2 corresponds to one of the columns of Table A. Table 183 Formula la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is 2-fluoro, 4-bromo, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 184 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 4-decyloxy, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 185: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-fluoro, 5-methyl, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 186 Equations la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein 1 is pentafluoro, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 187 127320.doc -83 - 200835487 Equation la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Compounds of Iu, Iv, Iw and lx, wherein 1 is 2-chloro, 5-fluoro, 4-methoxy, R3 is cyano and YR2 of each compound corresponds to one of Table A. Table 188: la, lb, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, IL, Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, and lx A compound wherein Ln is 2-chloro, 5-fluoro, R3 is cyano and YR2f of each compound corresponds to one of Table A.

表A 編號 YR2 R2 Y [N-R1，CH-R1] A-1 ch2ch3 NH A-2 CH2CH3 nch3 A-3 CH2CH3 NCH2CH3 A-4 CH2CH2CH3 NH A-5 CH2CH2CH3 nch3 A-6 CH2CH2CH3 NCH2CH3 A-7 CH2CH2CH3 NCH2CH2CH3 A-8 ch2ch2f NH A-9 CH2CH2F nch3 A-10 CH2CH2F NCH2CH3 A-11 CH2CF3 NH A-12 ch2cf3 nch3 A-13 CH2CF3 NCH2CH3 A-14 CH2CF3 NCH2CH2CH3 A-15 CH2CC13 NH A-16 CH2CC13 nch3 A-17 CH2CC13 NCH2CH3 A-18 CH2CC13 NCH2CH2CH3 A-19 ch(ch3)2 NH A-20 ch(ch3)2 nch3 A-21 ch(ch3)2 NCH2CH3 127320.doc -84- 200835487Table A No. YR2 R2 Y [N-R1, CH-R1] A-1 ch2ch3 NH A-2 CH2CH3 nch3 A-3 CH2CH3 NCH2CH3 A-4 CH2CH2CH3 NH A-5 CH2CH2CH3 nch3 A-6 CH2CH2CH3 NCH2CH3 A-7 CH2CH2CH3 NCH2CH2CH3 A-8 ch2ch2f NH A-9 CH2CH2F nch3 A-10 CH2CH2F NCH2CH3 A-11 CH2CF3 NH A-12 ch2cf3 nch3 A-13 CH2CF3 NCH2CH3 A-14 CH2CF3 NCH2CH2CH3 A-15 CH2CC13 NH A-16 CH2CC13 nch3 A-17 CH2CC13 NCH2CH3 A-18 CH2CC13 NCH2CH2CH3 A-19 ch(ch3)2 NH A-20 ch(ch3)2 nch3 A-21 ch(ch3)2 NCH2CH3 127320.doc -84- 200835487

編说 Y- R2 R2 Y [N-R1，CH-R1】 A-22 ch(ch3)2 NCH2CH2CH3 A-23 ch2c(ch3)3 NH A-24 ch2c(ch3)3 nch3 A-25 ch2c(ch3)3 NCH2CH3 A-26 ch2ch(ch3)2 NH A-27 ch2ch(ch3)2 nch3 A-28 ch2ch(ch3)2 NCH2CH3 A-29 (±) CH(CH2CH3)CH3 NH A-30 (士）ch(ch2ch3)ch3 nch3 A-31 (±) CH(CH2CH3)CH3 NCH2CH3 A-32 (R) CH(CH2CH3)CH3 NH A-33 (R) CH(CH2CH3)CH3 nch3 A-34 (R) CH(CH2CH3)CH3 NCH2CH3 A-35 (s) ch(ch2ch3)ch3 NH A-36 (S) CH(CH2CH3)CH3 nch3 A-37 (S) CH(CH2CH3)CH3 NCH2CH3 A-38 (士）ch(ch3)-ch(ch3)2 NH A-39 (土) ch(ch3)-ch(ch3)2 nch3 A-40 ㈤ ch(ch3)-ch(ch3)2 NCH2CH3 A-41 (R) CH(CH3)-CH(CH3)2 NH A-42 (R) CH(CH3)-CH(CH3)2 NCH3 A-43 (R) CH(CH3)-CH(CH3)2 NCH2CH3 A-44 (S) CH(CH3)-CH(CH3)2 NH A-45 (S) CH(CH3)-CH(CH3)2 NCH3 A-46 (S) CH(CH3)-GH(CH3)2 NCH2CH3 A-47 (±) CH(CH3)-C(CH3)3 NH A-48 (士) ch(ch3)-c(ch3)3 nch3 A-49 (土) ch(ch3)-c(ch3)3 NCH2CH3 A-50 (R) CH(CH3)-C(CH3)3 NH A-51 (R) CH(CH3)-C(CH3)3 nch3 A-52 (R) CH(CH3)-C(CH3)3 NCH2CH3 A-53 (S) CH(CH3)-C(CH3)3 NH A-54 (s) ch(ch3)-c(ch3)3 nch3 A-55 (s)ch(ch3)-c(ch3)3 NCH2CH3 A-56 (士) ch(ch3)-cf3 NH A-57 (土) ch(ch3)-cf3 nch3 A-58 (士) ch(ch3)-cf3 NCH2CH3 A-59 (R) CH(CH3)-CF3 NH A-60 (R) CH(CH3)-CF3 nch3 127320.doc -85 - 200835487 編號 Υ_ R2 R2 Y [N-R1，CH-R1】 Α-61 (R) CH(CH3)-CF3 nch2ch3 Α-62 (S) CH(CH3)-CF3 NH Α-63 (s) ch(ch3)-cf3 nch3 Α-64 (S) CH(CH3)-CF3 NCH2CH3 Α-65 (士）ch(ch3)-cci3 NH Α-66 (士) ch(ch3)-cci3 ch3 Α-67 (士) ch(ch3)-cci3 nch2ch3 Α-68 (R) CH(CH3)-CC13 NH Α-69 (R) CH(CH3)-CC13 nch3 Α-70 (R) CH(CH3)-CC13 NCH2CH3 Α-71 (s) ch(ch3)-cci3 NH Α-72 (S) CH(CH3)-CC13 nch3 Α-73 (s) ch(ch3)-cci3 NCH2CH3 Α-74 CH2C(CH3)=CH2 NH Α-75 CH2C(CH3)=CH2 nch3 Α-76 CH2C(CH3)=CH2 NCH2CH3 Α-77 CH(CH3)23 0 Α-78 CH(CH3)23 s Α-79 ch2ch(ch3)2 0 Α-80 CH2CH(CH3)2 s Α-81 ch2c(ch3)3 0 Α-82 ch2c(ch3)3 s Α-83 CH(CH2CH3)CH3 0 Α-84 CH(CH2CH3)CH3 s Α-85 CH(CH3)-CH(CH3)2 0 Α-86 ch(ch3)-ch(ch3)2 s Α-87 CH(CH3)-C(CH3)3 0 Α-88 ch(ch3)-c(ch3)3 s Α-89 CH(CH3)-CF3 0 Α-90 CH(CH3)-CF3 s Α-91 CH(CH3)-CC13 0 Α-92 CH(CH3)-CC13 s Α-93 CH2C(CH3)=CH2 0 Α-94 CH2C(CH3)=CH2 s Α-95 環戊基 NH Α-96 環戊基 nch3 Α-97 環戊基 NCH2CH3 Α-98 環己基 NH Α-99 環己基 nch3 127320.doc -86· 200835487 編號 Y-R2 R2 Y [N-R1，CH-R1] A-100 環己基 NCH2CH3 A-101 、nO A-102 \n-^CH3 A-103 (R) A-104 -N^VCH3 (S) V-^ A-105 \N^^〇Me A-106 \N^^r^C2H5 A-107 ch3 〜0^、ch3 A-108 、P ㈤h3c A-109 h3c^n^ch3 ㈤ 丨 A-110 、nO A-111 -〇 A-112 (，N〇 127320.doc •87- 200835487 編號 YR2 R2 Y [N-R1, CH-R1] A-113 -N^>-CH3 A-114 ch3 ㈤d A-115 CH. (R) ^ A-116 CH. r\ (S) ^ A-117 -〇〇 A-118 -〇\ A-119 -oo A-120 -〇 A-121 ch3 A-122 ch2ch3 A-123 CH2CH2CH3 A-124 CH(CH3)2 A-125 ch2ch(ch3)2 A-126 (士）ch(ch3)ch2ch3 A-127 (R) CH(CH3)CH2CH3 A-128 (S) CH(CH3)CH2CH3 A-129 (CH2)3CH3 A-130 C(CH3)3 127320.doc -88 - 200835487 編被 Y-R2 R2 Y [N-R1，CH-R1】 A-131 (CH2)4CH3 A-132 CH(CH2CH3)2 A-133 CH2CH2CH(CH3)2 A-134 (士）ch(ch3)(ch2)2ch3 A-135 (R) CH(CH3)(CH2)2CH3 A-136 (S) CH(CH3)(CH2)2CH3 A-137 (士）ch2ch(ch3)ch2ch3 A-138 (r) ch2ch(ch3)ch2ch3 A-139 (s) ch2ch(ch3)ch2ch3 A-140 (士) ch(ch3)ch(ch3)2 A-141 (R) CH(CH3)CH(CH3)2 A-142 (S) CH(CH3)CH(CH3)2 A-143 (CH2)5CH3 A-144 (士，士）ch(ch3)ch(ch3)ch2ch3 A-145 (士，r) ch(ch3)ch(ch3)ch2ch3 A-146 (±，s) ch(ch3)ch(ch3)ch2ch3 A-147 (士）ch2ch(ch3)cf3 A-148 (R) CH2CH(CH3)CF3 A-149 (S) CH2CH(CH3)CF3 A-150 (±) ch2ch(cf3)ch2ch3 A-151 (r) ch2ch(cf3)ch2ch3 A-152 (s) ch2ch(cf3)ch2ch3 A-153 (士，士) ch(ch3)ch(ch3)cf3 A-154 (士，r) ch(ch3)ch(ch3)cf3 A-155 (士，s) ch(ch3)ch(ch3)cf3 A-156 (±,±) CH(CH3)CH(CF3)CH2CH3 A-157 (士，r) ch(ch3)ch(cf3)ch2ch3 A-158 (土，s) ch(ch3)ch(cf3)ch2ch3 A-159 cf3 A-160 cf2cf3 -89- 127320.doc 200835487 編號 Y-R2 R2 Y [N R1，CH-R1】 A-161 cf2cf2cf3 A-162 C-C3H5 A-163 (1-CH3)-c-C3H4 A-164 C-C5H9 A-165 C-C6H11 A-166 (4-CH3)-c-C6H10 A-167 CH2C(CH3)=CH2 A-168 CH2CH2C(CH3)=CH2 A-169 CHrC(CH3)3 A-170 CH2-Si(CH3)3 A-171 η-〇6Η]3 A-172 (ch2)3-ch(ch3)2 A-173 (CH2)rCH(CH3)-C2H5 A-174 CH2-CH(CH3)-n-C3H7 A-175 CH(CH3)-n-C4H9 A-176 CH2-CH(C2H5)2 A-177 CH(C2H5)-n-C3H7 A-178 CH2-c-C5H9 A-179 ch2-ch(ch3)-ch(ch3)2 A-180 ch(ch3)-ch2ch(ch3)2 A-181 ch(ch3)-ch(ch3)-c2h5 A-182 ch(ch3)-c(ch3)3 A-183 (CH2)rC(CH3)3 A-184 ch2-c(ch3)2-c2h5 A-185 2-CH3-c-C5H8 A-186 3-CH3-c-C5H8 A-187 C(CH3)2-n-C3H7 A-188 (CH2)6-CH3 A-189 (CH2)4-CH(CH3)2 A-190 (CH2)rCH(CH3)_C2H5 -90- 127320.doc 200835487 編號 Y-R2 R2 Y [N-R1，CH-R1] A-191 (CH2)2-CH(CH3)-n，C3H7 A-192 CHrCH(CH3)-n-C4H9 A-193 CH(CH3)-n-C5Hn A-194 (CH2)3C(CH3)3 A-195 (ch2)2ch(ch3)-ch(ch3)2 A-196 (ch2)ch(ch3)-ch2ch(ch3)2 A-197 CH(CH3)(CH2)rCH(CH3)2 A-198 (CH2)2C(CH3)2C2H5 A-199 ch2ch(ch3)ch(ch3)c2h5 A-200 ch(ch3)ch2ch(ch3)c2h5 A-201 CH2C(CH3)2-n-C3H7 A-202 CH(CH3)CH(CH3)_n-C3H7 A-203 C(CH3)rn-C4H9 A-204 (CH2)2CH(C2H5)2 A-205 CH2CH(C2H5)-n-C3H7 A-206 CH(C2H5)-n-C4H9 A-207 CH2CH(CH3)C(CH3)3 A-208 CH(CH3)CH2C(CH3)3 A-209 ch2c(ch3)2ch(ch3)2 A-210 ch2ch(c2h5)ch(ch3)2 A-211 ch(ch3)ch(ch3)ch(ch3)2 A-212 c(ch3)2ch2ch(ch3)2 A-213 ch(c2h5)ch2ch(ch3)2 A-214 ch(ch3)c(ch3)2c2h5 A-215 ch(ch3)ch(c2h5)2 A-216 c(ch3)2ch(ch3)c2h5 A-217 ch(c2h5)ch(ch3)c2h5 A-218 C(CH3)(C2H5)-n-C3H7 A-219 CH(n-C3H7)2 A-220 CH(n-C3H7)CH(CH3)2 -91 - 127320.doc 200835487Edit Y- R2 R2 Y [N-R1,CH-R1] A-22 ch(ch3)2 NCH2CH2CH3 A-23 ch2c(ch3)3 NH A-24 ch2c(ch3)3 nch3 A-25 ch2c(ch3) 3 NCH2CH3 A-26 ch2ch(ch3)2 NH A-27 ch2ch(ch3)2 nch3 A-28 ch2ch(ch3)2 NCH2CH3 A-29 (±) CH(CH2CH3)CH3 NH A-30 (士)ch(ch2ch3 Ch3 nch3 A-31 (±) CH(CH2CH3)CH3 NCH2CH3 A-32 (R) CH(CH2CH3)CH3 NH A-33 (R) CH(CH2CH3)CH3 nch3 A-34 (R) CH(CH2CH3)CH3 NCH2CH3 A-35 (s) ch(ch2ch3)ch3 NH A-36 (S) CH(CH2CH3)CH3 nch3 A-37 (S) CH(CH2CH3)CH3 NCH2CH3 A-38 (士)ch(ch3)-ch( Ch3)2 NH A-39 (earth) ch(ch3)-ch(ch3)2 nch3 A-40 (v) ch(ch3)-ch(ch3)2 NCH2CH3 A-41 (R) CH(CH3)-CH(CH3 2 NH A-42 (R) CH(CH3)-CH(CH3)2 NCH3 A-43 (R) CH(CH3)-CH(CH3)2 NCH2CH3 A-44 (S) CH(CH3)-CH( CH3)2 NH A-45 (S) CH(CH3)-CH(CH3)2 NCH3 A-46 (S) CH(CH3)-GH(CH3)2 NCH2CH3 A-47 (±) CH(CH3)-C (CH3)3 NH A-48 (士) ch(ch3)-c(ch3)3 nch3 A-49 (earth) ch(ch3)-c(ch3)3 NCH2CH3 A-50 (R) CH(CH3)- C(CH3)3 NH A-51 (R) CH(CH3)-C(CH3)3 nch3 A-52 (R) CH(CH3)-C(CH3)3 NCH2CH3 A-53 (S) CH(CH3) -C(CH3)3 NH A-54 (s) ch( Ch3)-c(ch3)3 nch3 A-55 (s)ch(ch3)-c(ch3)3 NCH2CH3 A-56 (s) ch(ch3)-cf3 NH A-57 (earth) ch(ch3)- Cf3 nch3 A-58 (s) ch(ch3)-cf3 NCH2CH3 A-59 (R) CH(CH3)-CF3 NH A-60 (R) CH(CH3)-CF3 nch3 127320.doc -85 - 200835487 No. R2 R2 Y [N-R1,CH-R1] Α-61 (R) CH(CH3)-CF3 nch2ch3 Α-62 (S) CH(CH3)-CF3 NH Α-63 (s) ch(ch3)-cf3 Nch3 Α-64 (S) CH(CH3)-CF3 NCH2CH3 Α-65 (士)ch(ch3)-cci3 NH Α-66 (士) ch(ch3)-cci3 ch3 Α-67 (士) ch(ch3) -cci3 nch2ch3 Α-68 (R) CH(CH3)-CC13 NH Α-69 (R) CH(CH3)-CC13 nch3 Α-70 (R) CH(CH3)-CC13 NCH2CH3 Α-71 (s) ch( Ch3)-cci3 NH Α-72 (S) CH(CH3)-CC13 nch3 Α-73 (s) ch(ch3)-cci3 NCH2CH3 Α-74 CH2C(CH3)=CH2 NH Α-75 CH2C(CH3)=CH2 Nch3 Α-76 CH2C(CH3)=CH2 NCH2CH3 Α-77 CH(CH3)23 0 Α-78 CH(CH3)23 s Α-79 ch2ch(ch3)2 0 Α-80 CH2CH(CH3)2 s Α-81 Ch2c(ch3)3 0 Α-82 ch2c(ch3)3 s Α-83 CH(CH2CH3)CH3 0 Α-84 CH(CH2CH3)CH3 s Α-85 CH(CH3)-CH(CH3)2 0 Α-86 Ch(ch3)-ch(ch3)2 s Α-87 CH(CH3)-C(CH3)3 0 Α-88 ch(ch3)-c(ch3)3 s Α-89 CH(C H3)-CF3 0 Α-90 CH(CH3)-CF3 s Α-91 CH(CH3)-CC13 0 Α-92 CH(CH3)-CC13 s Α-93 CH2C(CH3)=CH2 0 Α-94 CH2C( CH3)=CH2 s Α-95 Cyclopentyl NH Α-96 Cyclopentyl nch3 Α-97 Cyclopentyl NCH2CH3 Α-98 Cyclohexyl NH Α-99 Cyclohexyl nch3 127320.doc -86· 200835487 No. Y-R2 R2 Y [N-R1,CH-R1] A-100 Cyclohexyl NCH2CH3 A-101 , nO A-102 \n-^CH3 A-103 (R) A-104 -N^VCH3 (S) V-^ A- 105 \N^^〇Me A-106 \N^^r^C2H5 A-107 ch3 ~0^, ch3 A-108, P (five) h3c A-109 h3c^n^ch3 (5) 丨A-110, nO A-111 -〇A-112 (,N〇127320.doc •87- 200835487 No. YR2 R2 Y [N-R1, CH-R1] A-113 -N^>-CH3 A-114 ch3 (5)d A-115 CH. ( R) ^ A-116 CH. r\ (S) ^ A-117 -〇〇A-118 -〇\ A-119 -oo A-120 -〇A-121 ch3 A-122 ch2ch3 A-123 CH2CH2CH3 A- 124 CH(CH3)2 A-125 ch2ch(ch3)2 A-126 (士)ch(ch3)ch2ch3 A-127 (R) CH(CH3)CH2CH3 A-128 (S) CH(CH3)CH2CH3 A-129 (CH2)3CH3 A-130 C(CH3)3 127320.doc -88 - 200835487 Edited by Y-R2 R2 Y [N-R1,CH-R1] A-131 (CH2)4CH3 A-132 CH(CH2CH3)2 A-133 CH2 CH2CH(CH3)2 A-134 (士)ch(ch3)(ch2)2ch3 A-135 (R) CH(CH3)(CH2)2CH3 A-136 (S) CH(CH3)(CH2)2CH3 A-137 (士)ch2ch(ch3)ch2ch3 A-138 (r) ch2ch(ch3)ch2ch3 A-139 (s) ch2ch(ch3)ch2ch3 A-140 (s) ch(ch3)ch(ch3)2 A-141 (R CH(CH3)CH(CH3)2 A-142 (S) CH(CH3)CH(CH3)2 A-143 (CH2)5CH3 A-144 (士,士)ch(ch3)ch(ch3)ch2ch3 A -145 (士,r) ch(ch3)ch(ch3)ch2ch3 A-146 (±,s) ch(ch3)ch(ch3)ch2ch3 A-147 (士)ch2ch(ch3)cf3 A-148 (R) CH2CH(CH3)CF3 A-149 (S) CH2CH(CH3)CF3 A-150 (±) ch2ch(cf3)ch2ch3 A-151 (r) ch2ch(cf3)ch2ch3 A-152 (s) ch2ch(cf3)ch2ch3 A -153 (士士士士) ch(ch3)ch(ch3)cf3 A-154 (士,r) ch(ch3)ch(ch3)cf3 A-155 (士,s) ch(ch3)ch(ch3)cf3 A-156 (±,±) CH(CH3)CH(CF3)CH2CH3 A-157 (士,r) ch(ch3)ch(cf3)ch2ch3 A-158 (soil,s) ch(ch3)ch(cf3) Ch2ch3 A-159 cf3 A-160 cf2cf3 -89- 127320.doc 200835487 No. Y-R2 R2 Y [N R1,CH-R1] A-161 cf2cf2cf3 A-162 C-C3H5 A-163 (1-CH3)-c -C3H4 A-164 C-C5H9 A-165 C-C6H11 A-166 (4-CH3)-c-C6H10 A-167 CH2C(CH3)=CH2 A- 168 CH2CH2C(CH3)=CH2 A-169 CHrC(CH3)3 A-170 CH2-Si(CH3)3 A-171 η-〇6Η]3 A-172 (ch2)3-ch(ch3)2 A-173 (CH2)rCH(CH3)-C2H5 A-174 CH2-CH(CH3)-n-C3H7 A-175 CH(CH3)-n-C4H9 A-176 CH2-CH(C2H5)2 A-177 CH(C2H5) -n-C3H7 A-178 CH2-c-C5H9 A-179 ch2-ch(ch3)-ch(ch3)2 A-180 ch(ch3)-ch2ch(ch3)2 A-181 ch(ch3)-ch( Ch3)-c2h5 A-182 ch(ch3)-c(ch3)3 A-183 (CH2)rC(CH3)3 A-184 ch2-c(ch3)2-c2h5 A-185 2-CH3-c-C5H8 A-186 3-CH3-c-C5H8 A-187 C(CH3)2-n-C3H7 A-188 (CH2)6-CH3 A-189 (CH2)4-CH(CH3)2 A-190 (CH2) rCH(CH3)_C2H5 -90- 127320.doc 200835487 No. Y-R2 R2 Y [N-R1,CH-R1] A-191 (CH2)2-CH(CH3)-n,C3H7 A-192 CHrCH(CH3) -n-C4H9 A-193 CH(CH3)-n-C5Hn A-194 (CH2)3C(CH3)3 A-195 (ch2)2ch(ch3)-ch(ch3)2 A-196 (ch2)ch( Ch3)-ch2ch(ch3)2 A-197 CH(CH3)(CH2)rCH(CH3)2 A-198 (CH2)2C(CH3)2C2H5 A-199 ch2ch(ch3)ch(ch3)c2h5 A-200 ch (ch3)ch2ch(ch3)c2h5 A-201 CH2C(CH3)2-n-C3H7 A-202 CH(CH3)CH(CH3)_n-C3H7 A-203 C(CH3)rn-C4H9 A-204 (CH2) 2CH(C2H5)2 A-205 CH2CH(C2H5)-n-C3H7 A-206 CH(C2H5)-n-C4H9 A- 207 CH2CH(CH3)C(CH3)3 A-208 CH(CH3)CH2C(CH3)3 A-209 ch2c(ch3)2ch(ch3)2 A-210 ch2ch(c2h5)ch(ch3)2 A-211 ch (ch3)ch(ch3)ch(ch3)2 A-212 c(ch3)2ch2ch(ch3)2 A-213 ch(c2h5)ch2ch(ch3)2 A-214 ch(ch3)c(ch3)2c2h5 A- 215 ch(ch3)ch(c2h5)2 A-216 c(ch3)2ch(ch3)c2h5 A-217 ch(c2h5)ch(ch3)c2h5 A-218 C(CH3)(C2H5)-n-C3H7 A- 219 CH(n-C3H7)2 A-220 CH(n-C3H7)CH(CH3)2 -91 - 127320.doc 200835487

編號 Y-R2 R2 Y [N-R1，CH R1】 A-221 C(CH3)2C(CH3)3 A-222 c(ch3)(c2h5)-ch(ch3)2 A-223 c(c2h5)3 A-224 (3-CH3)-c-C6H10 A-225 (2-CH3)-c-C6H10 A-226 n-CsHi7 A-227 CH2C(=NO-CH3)CH3 A-228 ch2c(=no-c2h5)ch3 A-229 CH2C(=NO-n-C3H7)CH3 A-230 CH2C(=NO-i-C3H7)CH3 A-231 CH(CH3)C(=NOCH3)CH3 A-232 ch(ch3)c(=noc2h5)ch3 A-233 CH(CH3)C(=NO-n-C3H7)CH3 A-234 CH(CH3)C(=NO-i-C3H7)CH3 A-235 C(=NOCH3)C(=NOCH3)CH3 A-236 c(=noch3)c(=noc2h5)ch3 A-237 C(=NOCH3)C(=NO-n-C3H7)CH3 A-238 C(=NOCH3)C(=NO-i-C3H7)CH3 A-239 C(=NOC2H5)C(=NOCH3)CH3 A-240 c(=noc2h5)c(=noc2h5)ch3 A-241 C(=NOC2H5)C(=NO-n-C3H7)CH3 A-242 C(=NOC2H5)C(=NO-i-C3H7)CH3 A-243 CH2C(=NO-CH3)C2H5 A-244 ch2c(=no-c2h5)c2h5 A-245 CH2C(=NO-n-C3H7)C2H5 A-246 CH2C(=NO-i-C3H7)C2H5 A-247 CH(CH3)C(=NOCH3)C2H5 A-248 ch(ch3)c(=noc2h5)c2h5 A-249 CH(CH3)C(=NO-n-C3H7)C2H5 A-250 CH(CH3)C(=NO-n-C3H7)C2H5 127320.doc -92- 200835487No. Y-R2 R2 Y [N-R1, CH R1] A-221 C(CH3)2C(CH3)3 A-222 c(ch3)(c2h5)-ch(ch3)2 A-223 c(c2h5)3 A-224 (3-CH3)-c-C6H10 A-225 (2-CH3)-c-C6H10 A-226 n-CsHi7 A-227 CH2C(=NO-CH3)CH3 A-228 ch2c(=no-c2h5 Ch3 A-229 CH2C(=NO-n-C3H7)CH3 A-230 CH2C(=NO-i-C3H7)CH3 A-231 CH(CH3)C(=NOCH3)CH3 A-232 ch(ch3)c( =noc2h5)ch3 A-233 CH(CH3)C(=NO-n-C3H7)CH3 A-234 CH(CH3)C(=NO-i-C3H7)CH3 A-235 C(=NOCH3)C(=NOCH3 CH3 A-236 c(=noch3)c(=noc2h5)ch3 A-237 C(=NOCH3)C(=NO-n-C3H7)CH3 A-238 C(=NOCH3)C(=NO-i-C3H7 CH3 A-239 C(=NOC2H5)C(=NOCH3)CH3 A-240 c(=noc2h5)c(=noc2h5)ch3 A-241 C(=NOC2H5)C(=NO-n-C3H7)CH3 A- 242 C(=NOC2H5)C(=NO-i-C3H7)CH3 A-243 CH2C(=NO-CH3)C2H5 A-244 ch2c(=no-c2h5)c2h5 A-245 CH2C(=NO-n-C3H7) C2H5 A-246 CH2C(=NO-i-C3H7)C2H5 A-247 CH(CH3)C(=NOCH3)C2H5 A-248 ch(ch3)c(=noc2h5)c2h5 A-249 CH(CH3)C(= NO-n-C3H7)C2H5 A-250 CH(CH3)C(=NO-n-C3H7)C2H5 127320.doc -92- 200835487

編號 Y-R2 R2 Y [N-R1，CH-R1] A-251 C(=NOCH3)C(=NOCH3)C2H5 A-252 c(=noch3)c(=noc2h5)c2h5 A-253 C(=NOCH3)C(=NO-n-C3H7)C2H5 A-254 C(=NOCH3)C(=NO-i-C3H7)C2H5 A-255 C(=NOC2H5)C(=NOCH3)C2H5 A-256 c(=noc2h5)c(=noc2h5)c2h5 A-257 C(=NOC2H5)C(=NO_n-C3H7)C2H5 A-258 C(=NOC2H5)C(=NO-i-C3H7)C2H5 A-259 CH=CH-CH2CH3 A-260 ch2-ch=ch-ch3 A-261 ch2-ch2-ch=ch2 A-262 c(ch3)2ch2ch3 A-263 CH=C(CH3)2 A - 264 C(=CH2)-CH2CH3 A-265 C(CH3)=CH-CH3 A-266 CH(CH3)CH=CH2 A-267 CH=CH-n-C3H7 A-268 ch2-ch=ch-c2h5 A-269 (CH2)2-CH=CH-CH3 A-270 (CH2)3-CH=CH2 A-271 ch=ch-ch(ch3)2 A-272 ch2-ch=c(ch3)2 A-273 (CH2)rC(CH3)=CH2 A-274 CH=C(CH3)-C2H5 A-275 ch2-c(=ch2)-c2h5 A-276 CH2-C(CH3)=CH-CH3 A-277 CH2-CH(CH3)-CH=CH2 A-278 C(=CH2)-CH2-CH2-CH3 A-279 C(CH3)=CH-CHrCH3 A-280 CH(CH3)-CH=CH-CH3 127320.doc -93- 200835487 編號 Y-R2 R2 Y [N-R1，CH-R1] A-281 CH(CH3)-CH2-CH=CH2 A-282 C(=CH2)CH(CH3)2 A-283 C(CH3)=C(CH3)2 A-284 CH(CH3)-C(=CH2)-CH3 A-285 C(CH3)2-CH=CH2 A-286 C(C2H5)=CH-CH3 A-287 CH(C2H5)-CH=CH2 A-288 CH=CH-CHrCH2-CHrCH3 A-289 CH2-CH=CH-CH2-CH2-CH3 A-290 CHrCH2-CH=CH-CH2-CH3 A-291 CHrCHrCHrCH=CH-CH3 A-292 ch2-ch2-ch2-ch2-ch=ch2 A-293 CH=CH-CHrCH(CH3)CH3 A-294 CHrCH=CH-CH(CH3)CH3 A-295 ch2-ch2-ch=c(ch3)ch3 A-296 CH2-CH2-CH2-C(CH3)=CH2 A-297 CH=CH-CH(CH3)-CHrCH3 A-298 CHrCH=C(CH3)-CH2-CH3 A-299 CHrCH2-C(=CH2)-CH2-CH3 A-300 CH2-CH2-C(CH3)=CH-CH3 A-301 CH2-CH2-CH(CH3)-CH=CH2 A-302 CH=C(CH3)-CH2-CH2-CH3 A-303 CHrC(=CH2)-CH2-CHrCH3 A-304 ch2 - c(ch3)=ch-ch2-ch3 A-305 CH2-CH(CH3)-CH=CH-CH3 A-306 CH2-CH(CH3)»CH2-CH=CH2 A-307 c(=ch2)-ch2-ch2-ch2-ch3 A-308 C(CH3)=CH-CHr CHr CH3 A-309 CH(CH3)-CH=CH-CH2-CH3 A-310 CH(CH3)-CH2-CH=CH-CH3 -94- 127320.doc 200835487 編號 Y-R2 R2 Y [N R1，CH-R1】 A-311 CH(CH3)-CHrCHrCH=CH2 A-312 ch=ch-c(ch3)3 A-313 CH=C(CH3)-CH(CH3)-CH3 A-314 ch2-c(=ch2)-ch(ch3)-ch3 A-315 ch2-c(ch3)=c(ch3)-ch3 A-316 CH2-CH(CH3)-C(=CH2)-CH3 A-317 C(=CH2)-CHrCH(CH3)-CH3 A-318 c(ch3)=ch-ch(ch3)-ch3 A-319 CH(CH3)-CH=C(CH3)-CH3 A-320 CH(CH3)-CHrC(=CH2)-CH3 A-321 CH=C(CHrCH3)-CHrCH3 A-322 CH2-C(=CH-CH3)-CHrCH3 A-323 ch2-ch(ch=ch2)-ch2-ch3 A-324 c(=ch-ch3)-ch2-ch2-ch3 A-325 ch(ch=ch2)-ch2-ch2-ch3 A-326 c(ch2-ch3)=ch-ch2-ch3 A-327 CH(CH2-CH3)-CH=CH-CH3 A-328 ch(ch2-ch3)-ch2-ch=ch2 A-329 CHrC(CH3)2-CH=CH2 A-330 C(=CH2)-CH(CH3)-CHrCH3 A-331 C(CH3)=C(CH3)-CHrCH3 A-332 CH(CH3)-C(=CH2)-CHrCH3 A-333 CH(CH3)-C(CH3)=CH-CH3 A-334 CH(CH3)-CH(CH3)-CH=CH2 A-335 C(CH3)2-CH=CH-CH3 A-336 C(CH3)2-CH2-CH=CH2 A-337 c(=ch2)-c(ch3)3 A-338 C(=CH-CH3)-CH(CH3)-CH3 A-339 CH(CH=CH2)-CH(CH3)-CH3 A-340 c(ch2-ch3)=c(ch3)-ch3 -95- 127320.doc 200835487 編號 Y-R2 R2 Y [N-R1，CH-R1】 A-341 ch(ch2-ch3)-c(=ch2)-ch3 A-342 C(CH3)2-C(=CH2)-CH3 A-343 C(CH3)(CH=CH2)-CHrCH3 A-344 C(CH3)(CH2CH3)-CHrCH2-CH3 A-345 CH(CH2CH3)-CH(CH3)-CHrCH3 A-346 CH(CH2CH3)-CH2-CH(CH3)-CH3 A-347 c(ch3)2-c(ch3)3 A-348 C(CHrCH3)-C(CH3)3 A-349 c(ch3)(ch2-ch3)-ch(ch3)2 A-350 ch(ch(ch3)2)-ch(ch3)2 A-351 CH=CH-CH2-CH2-CHrCH2-CH3 A-352 CHrCH=CH-CHrCHrCHrCH3 A-353 CHrCHrCH=CH-CHrCHrCH3 A-354 CH2-CH2-CH2-CH=CH-CHrCH3 A-355 CH2-CH2-CHrCH2_CH=CH-CH3 A-356 ch2-ch2-ch2-ch2-ch2-ch=ch2 A-357 ch=ch-ch2-ch2-ch(ch3)-ch3 A-358 ch2-ch=ch-ch2-ch(ch3)-ch3 A-359 CHrCH2-CH=CH-CH(CH3)-CH3 A-360 ch2-ch2-ch2-ch=c(ch3)-ch3 A-361 CH2-CH2-CH2-CHrC(=CH2)-CH3 A-362 CH=CH-CH2-CH(CH3)-CH2-CH3 A-363 CHrCH=CH-CH(CH3)-CH2-CH3 A-364 CH2-CH2-CH=C(CH3)-CHrCH3 A-365 CHrCHrCHrC(=CH2)-CH2-CH3 A-366 CH2-CH2-CHrC(CH3)=CH-CH3 A-367 CH2-CH2-CH2-CH(CH3)-CH=CH2 A-368 CH=CH-CH(CH3)-CH2-CH2-CH3 A-369 CH2-CH=C(CH3)-CHrCHrCH3 A-370 CH2-CH2-C(=CH2)-CHrCH2-CH3 -96- 127320.doc 200835487No. Y-R2 R2 Y [N-R1, CH-R1] A-251 C(=NOCH3)C(=NOCH3)C2H5 A-252 c(=noch3)c(=noc2h5)c2h5 A-253 C(=NOCH3 C(=NO-n-C3H7)C2H5 A-254 C(=NOCH3)C(=NO-i-C3H7)C2H5 A-255 C(=NOC2H5)C(=NOCH3)C2H5 A-256 c(=noc2h5 )c(=noc2h5)c2h5 A-257 C(=NOC2H5)C(=NO_n-C3H7)C2H5 A-258 C(=NOC2H5)C(=NO-i-C3H7)C2H5 A-259 CH=CH-CH2CH3 A -260 ch2-ch=ch-ch3 A-261 ch2-ch2-ch=ch2 A-262 c(ch3)2ch2ch3 A-263 CH=C(CH3)2 A - 264 C(=CH2)-CH2CH3 A-265 C(CH3)=CH-CH3 A-266 CH(CH3)CH=CH2 A-267 CH=CH-n-C3H7 A-268 ch2-ch=ch-c2h5 A-269 (CH2)2-CH=CH- CH3 A-270 (CH2)3-CH=CH2 A-271 ch=ch-ch(ch3)2 A-272 ch2-ch=c(ch3)2 A-273 (CH2)rC(CH3)=CH2 A- 274 CH=C(CH3)-C2H5 A-275 ch2-c(=ch2)-c2h5 A-276 CH2-C(CH3)=CH-CH3 A-277 CH2-CH(CH3)-CH=CH2 A-278 C(=CH2)-CH2-CH2-CH3 A-279 C(CH3)=CH-CHrCH3 A-280 CH(CH3)-CH=CH-CH3 127320.doc -93- 200835487 No. Y-R2 R2 Y [N -R1,CH-R1] A-281 CH(CH3)-CH2-CH=CH2 A-282 C(=CH2)CH(CH3)2 A-283 C(CH3)=C(CH3)2 A-284 CH (CH3)-C(=CH2)-CH3 A-285 C(CH3)2-CH=CH2 A-286 C(C2H5)=CH-CH3 A-287 CH(C2H5)-CH=CH2 A-288 CH=CH-CHrCH2-CHrCH3 A-289 CH2-CH=CH-CH2-CH2-CH3 A-290 CHrCH2-CH=CH-CH2-CH3 A-291 CHrCHrCHrCH=CH -CH3 A-292 ch2-ch2-ch2-ch2-ch=ch2 A-293 CH=CH-CHrCH(CH3)CH3 A-294 CHrCH=CH-CH(CH3)CH3 A-295 ch2-ch2-ch=c (ch3)ch3 A-296 CH2-CH2-CH2-C(CH3)=CH2 A-297 CH=CH-CH(CH3)-CHrCH3 A-298 CHrCH=C(CH3)-CH2-CH3 A-299 CHrCH2- C(=CH2)-CH2-CH3 A-300 CH2-CH2-C(CH3)=CH-CH3 A-301 CH2-CH2-CH(CH3)-CH=CH2 A-302 CH=C(CH3)-CH2 -CH2-CH3 A-303 CHrC(=CH2)-CH2-CHrCH3 A-304 ch2 - c(ch3)=ch-ch2-ch3 A-305 CH2-CH(CH3)-CH=CH-CH3 A-306 CH2 -CH(CH3)»CH2-CH=CH2 A-307 c(=ch2)-ch2-ch2-ch2-ch3 A-308 C(CH3)=CH-CHr CHr CH3 A-309 CH(CH3)-CH= CH-CH2-CH3 A-310 CH(CH3)-CH2-CH=CH-CH3-94- 127320.doc 200835487 No. Y-R2 R2 Y [N R1,CH-R1] A-311 CH(CH3)-CHrCHrCH =CH2 A-312 ch=ch-c(ch3)3 A-313 CH=C(CH3)-CH(CH3)-CH3 A-314 ch2-c(=ch2)-ch(ch3)-ch3 A-315 Ch2-c(ch3)=c(ch3)-ch3 A-316 CH2-CH(CH3)-C(=CH2)-CH3 A-317 C(=CH2)-CHrCH(CH3)-CH3 A-318 c( Ch3)=ch-ch(ch3)-ch3 A-319 CH(CH3)-CH=C(CH3)-CH3 A-320 CH(CH3)-CHrC(=CH2)-CH3 A-321 CH=C(CHrCH3)-CHrCH3 A-322 CH2-C(=CH-CH3)-CHrCH3 A-323 ch2-ch(ch=ch2 )-ch2-ch3 A-324 c(=ch-ch3)-ch2-ch2-ch3 A-325 ch(ch=ch2)-ch2-ch2-ch3 A-326 c(ch2-ch3)=ch-ch2- Ch3 A-327 CH(CH2-CH3)-CH=CH-CH3 A-328 ch(ch2-ch3)-ch2-ch=ch2 A-329 CHrC(CH3)2-CH=CH2 A-330 C(=CH2 )-CH(CH3)-CHrCH3 A-331 C(CH3)=C(CH3)-CHrCH3 A-332 CH(CH3)-C(=CH2)-CHrCH3 A-333 CH(CH3)-C(CH3)= CH-CH3 A-334 CH(CH3)-CH(CH3)-CH=CH2 A-335 C(CH3)2-CH=CH-CH3 A-336 C(CH3)2-CH2-CH=CH2 A-337 c(=ch2)-c(ch3)3 A-338 C(=CH-CH3)-CH(CH3)-CH3 A-339 CH(CH=CH2)-CH(CH3)-CH3 A-340 c(ch2 -ch3)=c(ch3)-ch3 -95- 127320.doc 200835487 No. Y-R2 R2 Y [N-R1, CH-R1] A-341 ch(ch2-ch3)-c(=ch2)-ch3 A -342 C(CH3)2-C(=CH2)-CH3 A-343 C(CH3)(CH=CH2)-CHrCH3 A-344 C(CH3)(CH2CH3)-CHrCH2-CH3 A-345 CH(CH2CH3) -CH(CH3)-CHrCH3 A-346 CH(CH2CH3)-CH2-CH(CH3)-CH3 A-347 c(ch3)2-c(ch3)3 A-348 C(CHrCH3)-C(CH3)3 A-349 c(ch3)(ch2-ch3)-ch(ch3)2 A-350 ch(ch(ch3)2)-ch(ch3)2 A-351 CH=CH-CH2-CH2-CHrCH2-CH3 A -352 CHrC H=CH-CHrCHrCHrCH3 A-353 CHrCHrCH=CH-CHrCHrCH3 A-354 CH2-CH2-CH2-CH=CH-CHrCH3 A-355 CH2-CH2-CHrCH2_CH=CH-CH3 A-356 ch2-ch2-ch2-ch2- Ch2-ch=ch2 A-357 ch=ch-ch2-ch2-ch(ch3)-ch3 A-358 ch2-ch=ch-ch2-ch(ch3)-ch3 A-359 CHrCH2-CH=CH-CH( CH3)-CH3 A-360 ch2-ch2-ch2-ch=c(ch3)-ch3 A-361 CH2-CH2-CH2-CHrC(=CH2)-CH3 A-362 CH=CH-CH2-CH(CH3) -CH2-CH3 A-363 CHrCH=CH-CH(CH3)-CH2-CH3 A-364 CH2-CH2-CH=C(CH3)-CHrCH3 A-365 CHrCHrCHrC(=CH2)-CH2-CH3 A-366 CH2 -CH2-CHrC(CH3)=CH-CH3 A-367 CH2-CH2-CH2-CH(CH3)-CH=CH2 A-368 CH=CH-CH(CH3)-CH2-CH2-CH3 A-369 CH2- CH=C(CH3)-CHrCHrCH3 A-370 CH2-CH2-C(=CH2)-CHrCH2-CH3-96- 127320.doc 200835487

編號 YR2 R2 Y [N-R1，CH-R1] A-371 CHrCHrC(CH3)=CH-CHrCH3 A-372 ch2-ch2-ch(ch3)-ch=ch-ch3 A-373 CHrCH2-CH(CH3)-CH2-CH=CH2 A-374 CH=C(CH3) - CH2-CHrCHrCH3 A-375 ch2-c(=ch2)-ch2-ch2-ch2-ch3 A-376 ch2-c(ch3)=ch-ch2-ch2-ch3 A-377 CHrCH(CH3)-CH=CH-CHrCH3 A-378 CHrCH(CH3)-CH2-CH=CH-CH3 A-379 CHrCH(CH3)-CHrCHrCH=CH2 A-380 C(=CH2)-CHrCHrCHrCH2-CH3 A-381 C(CH3)=CH-CHrCHrCHrCH3 A-382 CH(CH3)-CH=CH-CHrCHrCH3 A-383 CH(CH3)-CHrCH=CH-CHrCH3 A-384 CH(CH3)-CH2-CH2-CH=CH-CH3 A-385 ch(ch3)_ch2-ch2-ch2-ch=ch2 A-386 ch=ch-ch2-c(ch3)3 A-387 CH2-CH=CH-C(CH3)3 A-388 CH=CH-CH(CH3)-CH(CH3)2 A-389 ch2-ch=c(ch3)-ch(ch3)2 A-390 ch2-ch2-c(=ch2)-ch(ch3)2 A-391 ch2-ch2-c(ch3)=c(ch3)2 A-392 CH2-CH2-CH(CH3)-C(=CH2)-CH3 A-393 CH=C(CH3)-CH2-CH(CH3)2 A-394 CHrC(=CH2)-CH2-CH(CH3)2 A-395 CHrC(CH3)=CH-CH(CH3)2 A-396 CHrCH(CH3)-CH=C(CH3)2 A-397 CH2-CH(CH3)-CHrC(=CH2)-CH3 A-398 C(=CH2)-CH2-CH2-CH(CH3)2 A-399 c(ch3)=ch-ch2-ch(ch3)2 A-400 CH(CH3)-CH=CH-CH(CH3)2 127320.doc -97- 200835487 編號 Y-R2 R2 Y [N-R1，CH-R1] A-401 CH(CH3)-CHrCH=C(CH3)2 A-402 CH(CH3)-CHrCHrC(=CH2)-CH3 A-403 CH=CH-C(CH3)rCH2-CH3 A-404 ch2-ch2-c(ch3)2-ch=ch2 A-405 ch=c(ch3)-ch(ch3)-ch2-ch3 A-406 CH2-C(=CH2)-CH(CH3)-CHrCH3 A-407 ch2-c(ch3)=c(ch3)-ch2-ch3 A-408 ch2-ch(ch3)-c(=ch2)-ch2-ch3 A-409 CHrCH(CH3)-C(CH3)=CH-CH3 A-410 CH2-CH(CH3)-CH(CH3)-CH=CH2 A-411 C(=CH2)-CHrCH(CH3)-CHrCH3 A-412 C(CH3)=CH-CH(CH3)-CHrCH3 A-413 ch(ch3)-ch=c(ch3)-ch2_ch3 A-414 CH(CH3)-CH2-C(=CH2)-CHrCH3 A-415 CH(CH3)-CHrC(CH3)=CH-CH3 A-416 CH(CH3) - CHrCH(CH3)-CH=CH2 A-417 CH2-C(CH3)2-CH=CH-CH3 A-418 ch2-c(ch3)2-ch2-ch=ch2 A-419 C(=CH2)-CH(CH3)-CH2-CHrCH3 A-420 c(ch3)=c(ch3)-ch2-ch2-ch3 A - 421 CH(CH3)-C(=CH2)-CH2-CHrCH3 A-422 CH(CH3)-C(CH3)=CH-CHrCH3 A-423 CH(CH3)-CH(CH3)-CH=CH-CH3 A-424 CH(CH3)-CH(CH3)-CH2-CH=CH2 A-425 C(CH3)2-CH=CH-CH2-CH3 A-426 C(CH3)rCH2-CH=CH-CH3 A-427 C(CH3)2-CH2-CHrCH=CH2 A-428 CH=CH-CH(CH2-CH3)-CHrCH3 A-429 CHrCH=C(CHrCH3)-CHrCH3 A-430 ch2-ch2-c(=ch-ch3)-ch2-ch3 •98- 127320.doc 200835487 編说 Y-R2 R2 Y [N R1，CH-R1] A-431 CH2-CH2-CH(CH=CH2)-CH2-CH3 A-432 ch=c(ch2-ch3)-ch2-ch2-ch3 A-433 ch2-c(=ch，ch3)-ch2-ch2-ch3 A-434 ch2-ch(ch=ch2)-ch2-ch2-ch3 A-435 CHrC(CHrCH3)=CH-CH2-CH3 A-436 ch2-ch(ch2-ch3)-ch=ch-ch3 A-437 ch2-ch(ch2-ch3)-ch-chch2 A-438 C(=CH-CH3)-CHrCH2-CH2-CH3 A-439 CH(CH=CH2)-CHrCHrCH2-CH3 A-440 C(CH2-CH3)=CH-CHrCHrCH3 A-441 CH(CHrCH3)-CH=CH-CHrCH3 A-442 CH(CH2-CH3)-CH2-CH=CH-CH3 A-443 CH(CH2-CH3)-CHrCHrCH=CH2 A-444 C(=CH-CH2-CH3)-CH2-CHrCH3 A-445 C(CH=CH-CH3)-CHrCH2-CH3 A-446 C(CH2-CH=CH2)-CH2-CHrCH3 A-447 CH=C(CH3)-C(CH3)3 A-448 ch2-c(=ch2)-c(ch3)3 A-449 ch2-c(ch3)2-ch(=ch2)-ch3 A-450 c(=ch2)-ch(ch3)-ch(ch3)-ch3 A-451 c(ch3)=c(ch3)-ch(ch3)-ch3 A-452 ch(ch3)-c(=ch2)-ch(ch3)-ch3 A-453 ch(ch3)-c(ch3)=c(ch3)-ch3 A-454 ch(ch3)-ch(ch3)-c(=ch2)-ch3 A-455 C(CH3)rCH=C(CH3)-CH3 A-456 C(CH3)2-CHrC(=CH2)-CH3 A-457 C(CH3)2-C(=CH2)-CH2-CH3 A-458 c(ch3)2-c(ch3)=ch-ch3 A-459 c(ch3)2-ch(ch3)ch=ch2 A-460 ch(ch2-ch3)-ch2-ch(ch3)-ch3 -99- 127320.doc 200835487 編號 Y-R2 R2 Y [N-R1，CH-R1】 A-461 CH(CH2-CH3)-CH(CH3)-CHrCH3 A-462 C(CH3)(CHrCH3)-CH2-CH2-CH3 A-463 CH(i-C3H7)-CH2-CH2-CH3 A-464 CH=C(CH2-CH3)-CH(CH3)>CH3 A-465 ch2_c(=ch-ch3)-ch(ch3)-ch3 A-466 ch2-ch(ch=ch2)-ch(ch3)-ch3 A-467 CH2-C(CHrCH3)=C(CH3)-CH3 A-468 CHrCH(CH2-CH3)-C(=CH2)-CH3 A-469 CH2-C(CH3)(CH=CH2)-CHrCH3 A-470 C(=CH2)-CH(CH2-CH3)-CH2-CH3 A-471 C(CH3)=C(CHrCH3)-CH2-CH3 A-472 ch(ch3)-c(=ch-ch3)-ch2-ch3 A-473 CH(CH3)-CH(CH=CH2)-CHrCH3 A-474 ch=c(ch2-ch3)-ch(ch3)-ch3 A-475 ch2-c(=ch-ch3)-ch(ch3)-ch3 A-476 CHrCH(CH=CH2)-CH(CH3)-CH3 A-477 ch2-c(ch2-ch3)=c(ch3)-ch3 A-478 CHrCH(CH2-CH3)-C(=CH2)-CH3 A-479 C(=CH-CH3)-CHrCH(CH3)-CH3 A-480 ch(ch=ch2)-ch2-ch(ch3)-ch3 A-481 c(ch2-ch3)=ch-ch(ch3)-ch3 A-482 ch(ch2-ch3)ch=c(ch3)-ch3 A-483 CH(CH2-CH3)CHrC(=CH2)-CH3 A-484 C(=CH-CH3)CH(CH3)-CH2-CH3 A-485 ch(ch=ch2)ch(ch3) - ch2-ch3 A-486 C(CHrCH3)=C(CH3)-CHrCH3 A-487 CH(CH2-CH3)-C(=CH2)-CHrCH3 A-488 ch(ch2-ch3)-c(ch3)=ch-ch3 A-489 CH(CH2-CH3)-CH(CH3)-CH=CH2 A-490 C(CH3)(CH=CH2)-CH2-CH2-CH3 -100- 127320.doc 200835487 編號 Y-R2 R2 Y [N-R1，CH-R1] A-491 C(CH3)(CHrCH3)-CH=CH-CH3 A-492 C(CH3)(CHrCH3)-CHrCH=CH2 A-493 C[=C(CH3)-CH3]-CHrCHrCH3 A-494 CH[C(=CH2)-CH3]-CHrCH2-CH3 A-495 C(i-C3H7)=CH-CHrCH3 A-496 CH(i-C3H7)-CH=CH-CH3 A-497 CH(i-C3H7)-CH2-CH=CH2 A-498 C(=CH-CH3)-C(CH3)3 A-499 CH(CH=CH2)-C(CH3)3 A-500 c(ch3)(ch=ch2)ch(ch3)-ch3 A-501 C(CH3)(CHrCH3)C(=CH2)-CH3 A-502 2-CHr環己-1-烯基 A-503 [2-(=CH2)]-c-C6H9 A-504 2-CHr環己-2-烯基 A-505 2-CH3-環己-3-烯基 A-506 2-CHr環己-4-烯基 A-507 2-CH3-環己-5-烯基 A-508 2-CH3-環己-6-烯基 A-509 3-CH3-環己-1-烯基 A-510 3-CHr環己-2-烯基 A-511 [3-(=CH2)]-c-C6H9 A-512 3-CHr環己-3-烯基 A-513 3-CH3-環己-4-烯基 A-514 3-CHr環己-5-烯基 A-515 3-CHr環己-6-烯基 A-516 4-CHr環己小烯基 A-517 4-CHr環己-2-烯基 A-518 4-CHr環己-3-烯基 A-519 [4-(=CH2)]-c-C6H9 2-經取代吡啶I，具體而言，係式la、Ic、le、If、Ig、 -101 - 127320.doc 200835487 ° Iq、Ir及18之化合物可有效地抑制腫瘤細胞之生 長及/或子代’如藉由對諸如HeLa、mcf_7&c〇l〇 2〇5等 腫瘤細胞系之標準測試所證實。特^言之，2_經取代喷幻 在HeLa細胞中對細胞週期抑制通常顯示<i〇6 m〇i/i (即， <ι μΜ)^ι〇50^ , ^^Λ<10-7 m〇1/1 (^<l〇〇 nM)^ICs〇 值，如藉由下文概述測試程序所測定。 根據此等私準藥理測試程序之結果，2'經取代吡啶可用No. YR2 R2 Y [N-R1, CH-R1] A-371 CHrCHrC(CH3)=CH-CHrCH3 A-372 ch2-ch2-ch(ch3)-ch=ch-ch3 A-373 CHrCH2-CH(CH3) -CH2-CH=CH2 A-374 CH=C(CH3) - CH2-CHrCHrCH3 A-375 ch2-c(=ch2)-ch2-ch2-ch2-ch3 A-376 ch2-c(ch3)=ch-ch2 -ch2-ch3 A-377 CHrCH(CH3)-CH=CH-CHrCH3 A-378 CHrCH(CH3)-CH2-CH=CH-CH3 A-379 CHrCH(CH3)-CHrCHrCH=CH2 A-380 C(=CH2 )-CHrCHrCHrCH2-CH3 A-381 C(CH3)=CH-CHrCHrCHrCH3 A-382 CH(CH3)-CH=CH-CHrCHrCH3 A-383 CH(CH3)-CHrCH=CH-CHrCH3 A-384 CH(CH3)- CH2-CH2-CH=CH-CH3 A-385 ch(ch3)_ch2-ch2-ch2-ch=ch2 A-386 ch=ch-ch2-c(ch3)3 A-387 CH2-CH=CH-C( CH3)3 A-388 CH=CH-CH(CH3)-CH(CH3)2 A-389 ch2-ch=c(ch3)-ch(ch3)2 A-390 ch2-ch2-c(=ch2)- Ch(ch3)2 A-391 ch2-ch2-c(ch3)=c(ch3)2 A-392 CH2-CH2-CH(CH3)-C(=CH2)-CH3 A-393 CH=C(CH3) -CH2-CH(CH3)2 A-394 CHrC(=CH2)-CH2-CH(CH3)2 A-395 CHrC(CH3)=CH-CH(CH3)2 A-396 CHrCH(CH3)-CH=C (CH3)2 A-397 CH2-CH(CH3)-CHrC(=CH2)-CH3 A-398 C(=CH2)-CH2-CH2-CH(CH3)2 A-399 c(ch3)=ch-ch2 -ch(ch3)2 A-400 CH(CH3)-CH=CH-CH(CH3)2 127320.doc -97- 200835487 Y-R2 R2 Y [N-R1,CH-R1] A-401 CH(CH3)-CHrCH=C(CH3)2 A-402 CH(CH3)-CHrCHrC(=CH2)-CH3 A-403 CH=CH -C(CH3)rCH2-CH3 A-404 ch2-ch2-c(ch3)2-ch=ch2 A-405 ch=c(ch3)-ch(ch3)-ch2-ch3 A-406 CH2-C(= CH2)-CH(CH3)-CHrCH3 A-407 ch2-c(ch3)=c(ch3)-ch2-ch3 A-408 ch2-ch(ch3)-c(=ch2)-ch2-ch3 A-409 CHrCH (CH3)-C(CH3)=CH-CH3 A-410 CH2-CH(CH3)-CH(CH3)-CH=CH2 A-411 C(=CH2)-CHrCH(CH3)-CHrCH3 A-412 C( CH3)=CH-CH(CH3)-CHrCH3 A-413 ch(ch3)-ch=c(ch3)-ch2_ch3 A-414 CH(CH3)-CH2-C(=CH2)-CHrCH3 A-415 CH(CH3 )-CHrC(CH3)=CH-CH3 A-416 CH(CH3) - CHrCH(CH3)-CH=CH2 A-417 CH2-C(CH3)2-CH=CH-CH3 A-418 ch2-c(ch3 ) 2-ch2-ch=ch2 A-419 C(=CH2)-CH(CH3)-CH2-CHrCH3 A-420 c(ch3)=c(ch3)-ch2-ch2-ch3 A - 421 CH(CH3) -C(=CH2)-CH2-CHrCH3 A-422 CH(CH3)-C(CH3)=CH-CHrCH3 A-423 CH(CH3)-CH(CH3)-CH=CH-CH3 A-424 CH(CH3 )-CH(CH3)-CH2-CH=CH2 A-425 C(CH3)2-CH=CH-CH2-CH3 A-426 C(CH3)rCH2-CH=CH-CH3 A-427 C(CH3)2 -CH2-CHrCH=CH2 A-428 CH=CH-CH(CH2-CH3)-CHrCH3 A-429 CHrCH=C(CHrCH3)-CHrCH3 A-430 ch2-ch2-c(=ch-ch3)-ch2-ch3 •98- 127 320.doc 200835487 Edit Y-R2 R2 Y [N R1,CH-R1] A-431 CH2-CH2-CH(CH=CH2)-CH2-CH3 A-432 ch=c(ch2-ch3)-ch2- Ch2-ch3 A-433 ch2-c(=ch,ch3)-ch2-ch2-ch3 A-434 ch2-ch(ch=ch2)-ch2-ch2-ch3 A-435 CHrC(CHrCH3)=CH-CH2- CH3 A-436 ch2-ch(ch2-ch3)-ch=ch-ch3 A-437 ch2-ch(ch2-ch3)-ch-chch2 A-438 C(=CH-CH3)-CHrCH2-CH2-CH3 A -439 CH(CH=CH2)-CHrCHrCH2-CH3 A-440 C(CH2-CH3)=CH-CHrCHrCH3 A-441 CH(CHrCH3)-CH=CH-CHrCH3 A-442 CH(CH2-CH3)-CH2- CH=CH-CH3 A-443 CH(CH2-CH3)-CHrCHrCH=CH2 A-444 C(=CH-CH2-CH3)-CH2-CHrCH3 A-445 C(CH=CH-CH3)-CHrCH2-CH3 A -446 C(CH2-CH=CH2)-CH2-CHrCH3 A-447 CH=C(CH3)-C(CH3)3 A-448 ch2-c(=ch2)-c(ch3)3 A-449 ch2- c(ch3)2-ch(=ch2)-ch3 A-450 c(=ch2)-ch(ch3)-ch(ch3)-ch3 A-451 c(ch3)=c(ch3)-ch(ch3) -ch3 A-452 ch(ch3)-c(=ch2)-ch(ch3)-ch3 A-453 ch(ch3)-c(ch3)=c(ch3)-ch3 A-454 ch(ch3)-ch (ch3)-c(=ch2)-ch3 A-455 C(CH3)rCH=C(CH3)-CH3 A-456 C(CH3)2-CHrC(=CH2)-CH3 A-457 C(CH3)2 -C(=CH2)-CH2-CH3 A-458 c(ch3)2-c(ch3)=ch-ch3 A-459 c(ch3)2-ch(ch3)ch=ch2 A-460 ch(ch2- Ch3)-ch2-ch (ch3)-ch3 -99- 127320.doc 200835487 No. Y-R2 R2 Y [N-R1,CH-R1] A-461 CH(CH2-CH3)-CH(CH3)-CHrCH3 A-462 C(CH3) (CHrCH3)-CH2-CH2-CH3 A-463 CH(i-C3H7)-CH2-CH2-CH3 A-464 CH=C(CH2-CH3)-CH(CH3)>CH3 A-465 ch2_c(=ch -ch3)-ch(ch3)-ch3 A-466 ch2-ch(ch=ch2)-ch(ch3)-ch3 A-467 CH2-C(CHrCH3)=C(CH3)-CH3 A-468 CHrCH(CH2 -CH3)-C(=CH2)-CH3 A-469 CH2-C(CH3)(CH=CH2)-CHrCH3 A-470 C(=CH2)-CH(CH2-CH3)-CH2-CH3 A-471 C (CH3)=C(CHrCH3)-CH2-CH3 A-472 ch(ch3)-c(=ch-ch3)-ch2-ch3 A-473 CH(CH3)-CH(CH=CH2)-CHrCH3 A-474 Ch=c(ch2-ch3)-ch(ch3)-ch3 A-475 ch2-c(=ch-ch3)-ch(ch3)-ch3 A-476 CHrCH(CH=CH2)-CH(CH3)-CH3 A-477 ch2-c(ch2-ch3)=c(ch3)-ch3 A-478 CHrCH(CH2-CH3)-C(=CH2)-CH3 A-479 C(=CH-CH3)-CHrCH(CH3) -CH3 A-480 ch(ch=ch2)-ch2-ch(ch3)-ch3 A-481 c(ch2-ch3)=ch-ch(ch3)-ch3 A-482 ch(ch2-ch3)ch=c (ch3)-ch3 A-483 CH(CH2-CH3)CHrC(=CH2)-CH3 A-484 C(=CH-CH3)CH(CH3)-CH2-CH3 A-485 ch(ch=ch2)ch( Ch3) - ch2-ch3 A-486 C(CHrCH3)=C(CH3)-CHrCH3 A-487 CH(CH2-CH3)-C(=CH2)-CHrCH3 A-488 ch(ch2-ch3)-c(ch3 )=ch -ch3 A-489 CH(CH2-CH3)-CH(CH3)-CH=CH2 A-490 C(CH3)(CH=CH2)-CH2-CH2-CH3 -100- 127320.doc 200835487 No. Y-R2 R2 Y [N-R1,CH-R1] A-491 C(CH3)(CHrCH3)-CH=CH-CH3 A-492 C(CH3)(CHrCH3)-CHrCH=CH2 A-493 C[=C(CH3) -CH3]-CHrCHrCH3 A-494 CH[C(=CH2)-CH3]-CHrCH2-CH3 A-495 C(i-C3H7)=CH-CHrCH3 A-496 CH(i-C3H7)-CH=CH-CH3 A-497 CH(i-C3H7)-CH2-CH=CH2 A-498 C(=CH-CH3)-C(CH3)3 A-499 CH(CH=CH2)-C(CH3)3 A-500 c (ch3)(ch=ch2)ch(ch3)-ch3 A-501 C(CH3)(CHrCH3)C(=CH2)-CH3 A-502 2-CHrcyclohex-1-enyl A-503 [2- (=CH2)]-c-C6H9 A-504 2-CHrcyclohex-2-enyl A-505 2-CH3-cyclohex-3-enyl A-506 2-CHrcyclohex-4-enyl A -507 2-CH3-cyclohex-5-enyl A-508 2-CH3-cyclohex-6-enyl A-509 3-CH3-cyclohex-1-enyl A-510 3-CHr cyclohexene- 2-Alkenyl A-511 [3-(=CH2)]-c-C6H9 A-512 3-CHrcyclohex-3-enyl A-513 3-CH3-cyclohex-4-enyl A-514 3 -CHr cyclohex-5-alkenyl A-515 3-CHr cyclohex-6-alkenyl A-516 4-CHr cyclohexenyl alkenyl A-517 4-CHr cyclohex-2-enyl A-518 4 -CHrcyclohex-3-enyl A-519 [4-(=CH2)]-c-C6H9 2-substituted pyridine I, in particular The compounds la, Ic, le, If, Ig, -101 - 127320.doc 200835487 ° Iq, Ir and 18 are effective in inhibiting the growth and/or progeny of tumor cells as by, for example, HeLa, mcf_7 & This was confirmed by standard tests of tumor cell lines such as c〇l〇2〇5. In particular, the cell cycle inhibition in HeLa cells is usually shown by <i〇6 m〇i/i (ie, <ι μΜ)^ι〇50^ , ^^Λ<10 -7 m 〇 1 / 1 (^ < l 〇〇 nM) ^ ICs 〇 value, as determined by the test procedure outlined below. According to the results of these proprietary pharmacological test procedures, 2' substituted pyridine is available

作治療、抑制或控制有需要的個體之癌性腫瘤細胞之生長 或子代及相關疾病的藥劑。因此，此等化合物可用： 溫血脊椎動物之癌症治療，該等溫血脊椎動物即哺乳動物 及鳥類’尤其為人類但亦可為具有生態及/或社會重要性 之其他哺乳動物’例如，諸如貓及狗等食肉動物、豬科 (母豬公豬及野豬）、反芻動物（例如，畜牛、公牛、綿 羊、鹿、山羊、野牛）及馬或鳥，尤其為諸如火雞、小 雞、鴨、鶴、珠雞及諸如此類等禽類。本文所用術語"療 法”及’’治療”係同義詞。 ’、 特定言之，2-經取代吡啶丨可用於癌症或癌性疾病之治 療’包括乳癌、肺癌、結腸癌、***癌、黑素瘤癌、表 皮癌、腎膀胱癌、口腔癌、喉癌、食道癌、胃癌、卵巢 癌、胰腺癌、肝癌、皮膚癌及腦癌。 所用活性成份之有效劑量可視所用特定化合物、投與方 式及所治療病況之嚴重程度而有所變化。然而，一般而 言，當本發明之化合物以介於約0·10至約1〇〇毫克/公^體 重/天之量投與時可獲得令人滿意的結果。最優結：之較 127320.doc •102- 200835487 佳方案可為自約1¾克至約20毫克/公斤體重/天且對於體重 為約70公斤之個體而言，可在24小時時間内投與總量為自 約70毫克至約1400毫克活性化合物之此等劑量單元。An agent for treating, inhibiting or controlling the growth or progeny of a cancerous tumor cell or a related disease in an individual in need thereof. Thus, such compounds are useful in the treatment of cancer of warm-blooded vertebrates, ie, mammals and birds, especially humans, but may also be other mammals of ecological and/or social importance, such as, for example, Carnivores such as cats and dogs, pigs (sow boars and wild boars), ruminants (for example, cattle, bulls, sheep, deer, goats, bison) and horses or birds, especially such as turkeys, chickens, ducks , cranes, pheasants and the like. The terms "therapy" and 'therapeutic" are used synonymously herein. 'Specifically, 2-substituted pyridinium can be used for the treatment of cancer or cancerous diseases' including breast cancer, lung cancer, colon cancer, prostate cancer, melanoma cancer, epidermal cancer, renal bladder cancer, oral cancer, laryngeal cancer , esophageal cancer, stomach cancer, ovarian cancer, pancreatic cancer, liver cancer, skin cancer and brain cancer. The effective dose of the active ingredient employed will vary depending upon the particular compound employed, the mode of administration, and the severity of the condition being treated. However, in general, satisfactory results are obtained when the compound of the present invention is administered in an amount of from about 0.10 to about 1 mg/cm body weight per day. Optimal knot: 127320.doc •102- 200835487 The best solution can be from about 13⁄4 grams to about 20 mg/kg body weight/day and for individuals weighing about 70 kg, it can be administered within 24 hours. The total amount is from about 70 mg to about 1400 mg of such dosage unit of the active compound.

C 可調整治療哺乳動物之劑量療程，以提供最優治療反 應。舉例而言，每日可投與若干分開劑量或者該劑量可依 照治療情形之緊急程度所示按比例減少。其操作優勢顯著 在於此等活性化合物可以諸如經口、靜脈内、肌内或皮下 途徑等任一方便方式投與。該等活性組合物可（例如）藉助 惰性稀釋劑或藉助可同化之食用載劑經口投與，或可將其 封入硬殼或軟殼明膠膠囊中，或可將其壓製成錠劑，或可 將其直接納入飲食之食物中。經口治療投藥時，可將此等 活性化合物與賦形劑一起納入並以可食用之錠劑、*** 片、糖錠、膠囊、醜劑、懸浮劑、糖漿、寺需米紙囊劑及諸 如此類等形式使用。此等組合物及製劑應包含至少之 活性化合物。當然，該等組合物及製劑之百分比可有所變 化且宜佔單元重量之介於約2%至約6〇%之間。活性化合物 於此等適用於治療之組合物中之含量應能獲得適宜劑量。 製備本發明之較佳組合物或製劑以使口服劑量單元形式含 有介於10 *克與1000毫克間之活性化合物。 該等錠劑、糖錠、丸劑、膠囊及諸如此類亦可包含下 述：黏合劑’例如，黃㈣、***膠、玉米殺粉、或明 膠’賦形劑’例如，磷酸二鈣；崩解劑，你】如玉米澱粉、 馬鈴薯澱粉、海藻酸及諸如此類；潤滑劑，例如，硬脂酸C can be adjusted to treat mammals in doses to provide optimal therapeutic response. For example, several separate doses may be administered daily or the dose may be proportionally reduced as indicated by the urgency of the treatment situation. The operational advantages are significant in that the active compounds can be administered in any convenient manner, such as orally, intravenously, intramuscularly or subcutaneously. The active compositions may be administered orally, for example, by means of an inert diluent or by means of an assimilable edible carrier, or may be enclosed in a hard or soft shell gelatin capsule, or may be compressed into a lozenge, or It can be incorporated directly into the food of the diet. When administered orally, the active compound may be incorporated together with excipients in the form of edible lozenges, buccal tablets, troches, capsules, ugly agents, suspending agents, syrups, temple rice paper containers and Use in the form of, etc. Such compositions and preparations should contain at least the active compound. Of course, the percentages of such compositions and formulations may vary and preferably range from about 2% to about 6% by weight of the unit. The active compound should be present in such compositions as are suitable for therapeutic use in such compositions. Preferred compositions or formulations of the invention are prepared such that the oral dosage unit form contains between 10 <RTIgt; Such lozenges, lozenges, pills, capsules and the like may also comprise the following: binders 'for example, yellow (four), gum arabic, corn flour, or gelatin 'excipients', for example, dicalcium phosphate; disintegrants , you] such as corn starch, potato starch, alginic acid and the like; lubricants, for example, stearic acid

鎂；及甜味劑，你H 1、；丄#， 又伽I 例如，可添加庶糖、乳糖或糖精；或矯味 127320.doc 200835487 J例如’薄何、冬青油、或樓桃調味料。 式為膠囊時，其除含有上述類型材料之"單元形 劑。可包含作為包衣或改進劑量單元理U含液體裁 :材料。舉例而言，錠劑、丸劑、或膠囊可=種: 劑）、對Λ苯;ΓΛ性化合物、絲（作為增甜 劑）、料4^1 歸(作為保存 如，櫻桃味或撥味調味劑）。當然， 、任何劑ϊ單元形式中所用任—材料廡具 所採用之量應實質上無毒。此外，可將此二:二又且 入緩釋製劑及調配物中。 ，化合物納 =活性化合物亦可以非經腸或腹膜腔内方式投與。此 /化合物（作為游離驗或藥理學上可接受之 或懸浮液可於適當地與表面活 ^吟液 混合的水中進行^。八例如’經丙基纖維素） I備刀散液亦可在甘油、液體聚乙二 ，、於油中之混合物中製備。在普通儲存及使用停件 下、，此等製劑包含保存劑以防止微生物生長。 條件 =合於注射使用的醫藥形式包括無菌水性溶液或分散液 用主於即時製備無菌注射溶液或分散液之無菌粉劑。在所 有十月形中，該形式必須無菌且其流動程度必須使其具有易 庄射性。其在製造與儲存條件下必須穩定且必須防止其受 到4如細菌及真菌等微生物之污染作用。載劑 分散介質，包含Γp ^ ^ 一 > 、Μ例如）水、乙醇、多元醇（例如，甘油、丙 -醇及液體聚乙二醇)、其適宜混合物，以及植物油。 表B中所給出了列實例Μ至！-55藉由闡述於 127320.doc -104- 200835487 W02006/000358中之方法加以製備。該等實例係可用作抗 癌劑之本發明代表性化合物。 127320.doc -105- 200835487 荟^^^^:PQ< 物理數據* ^-NMR (CDC13) δ = 1.20 (t); 3.87 (d); 4.30 (m); 6.45 (m); 7.20 ⑴;7.40 (m); 7.73 (m); 8.52 (m). ^-NMR (CDCI3) δ =122 (m); 3.75 (m); 3.88 (m); 6.45 (m); 7.15-7.40 (m); 7.75 (m); 8.55 (m). m.p. 170°C m.p. 78〇C ^-NMR (CDCI3) δ = 0.85 (s); 1.05 (d); 3.50 (m); 3.88 (d); 6.42 ⑴；7.20 (m); 7.40 (m); 7.75 (d); 8·55 (d)[旋轉異構體之混合物]。 ^-NMR (CDCI3) δ = 0.85 and 0.87 (s); 1.05 and 1.06 (d); 3.90 (d); 4.20 (m); 6.47 (m); 7.20 (m); 7.40 (m); 7·73 (m); 8.50 (m)[旋轉異構體之混合 物]0 ^-NMR (CDCI3) δ = 0.75-2.25 (m); 3.22 (m); 3.78 (d); 6.45 (m); 7.18 (m); 7.40 (m); 7.74 (m); 8.55 (m) m.p. 126〇C 1爷_ 1 3觫 |ϊι V· m Ξ t ”。 "g m 〇〇 鬥 β 蕊 S旦旦φ d S g瘐 卜$ w 晉觀 ISt & Θ 2-氯-6-氟苯基 2-氯-6-氟苯基 2_氯-6-氟苯基 2-氯-6-氟苯基 2-氯-6-氟苯基 2-氯-6-氟苯基 2-氯-6-氟苯基 2-氣-6-氟苯基 2-氯-6-氟苯基 η X 〇 U U U U U U Z z υ ¢5 1 < i -丨-H 1 ""< ΐ" 1 Η 1 H YR2 2-丙基胺基 2-丙基胺基 4-苯基環己基胺 基胺基 4-苯基環己基胺 基胺基 3,3-二甲基丁烧-2-胺基 3,3-二甲基丁烷-2-胺基 4-第三丁基環己 胺基 4-第三丁基環己 胺基 1，3-二甲基丁烧-1-氟苯基 °比嗤-卜基 σ比峻-1-基 〇比〇坐-1-基 °比唾-1-基 1 °比唾-1-基 σ比唾-1-基 吡唑-1-基 口比口坐-1-基 〇比唾-1-基 編號 ▼—Η (Ν cn in VO 1> HH 00 127320.doc -106- 200835487 物理數據* ^-NMR (CDC13) δ = 0.88 (m); 1.13 (m); 1.30 (m); 1.60 (m); 3.80 (m); 4.33 (m); 6.45 (m); 7.20 (m); 7.40 (m); 7.73 (m); 8.55 (m)[旋轉異構體之混合 物]0 ^-NMR (CDCI3) δ = 0.88 (m); 1.16 (m); 1.25 (m); 1.40 (m); 1.63 (m); 3.70 (m); 6.45 (m); 7.20 (m); 7.40 (m); 7.73 (m); 8.55 (m)[旋轉異構體之混合 物]。 m.p. 152〇C m.p. 152〇C m.p. 108°C m.p. 114°C ^-NMR (CDCI3) δ = 0.25 (m); 0.47 (m); 0.80 (m); 1.25 (m); 3.23 (m); 3.95 (m); 6.45 (m); 7.20 (m); 7.40 (m); 7.73 (m); 8.55 (m)[旋轉異構體之混合 物]。 ^-NMR (CDCI3) δ = 0.88 (m); 1.15 (m); 1.30 (m); 1.50 (m); 3.85 (m); 4.20 (m); 6.45 (m); 7.20 (m); 7.40 (m); 7.73 (m); 8.55 (m)[旋轉異構體之混合 物]0 m.p. 120°C m.p. 158〇C m.p. 161°C m.p. 164〇C m.p. 103°C 讀 讀 C 」 +*4 νό VO ^0 νό 'sO 1 ^s〇 雇 喊 喊 κ I (N (N CN A (N CN (N (Ν A (Ν (N (N (N ffi K ffi ffi ffi U u u U ζ u u X E ffi ffi ffi X u 7U u U Z u U υ u —t 1 < ψ · H f—Η 1 i Μ 111 4 1 < .......i h l4 1 Q; hH 丨1鍥 cA ^ νε V? •^3 ve CN 1 1-H r-H (N (N (N CN <N <N 4 二 1 ▼"Η I 1 1 1 1 1 Ψ nl i w\ 1 謙 K 1 1 K 賺 1 i ΐ ri 4 rsi i Ψ 41 i r-H ΐ r—( r-H i f f V N v N 1—H uj f f f f f f f f 編號 0 r-H r-H 二 (N m r-H 寸 H ^T) r-H \o t-H 二 卜 1-H 〇〇 H ηΛ OS r—Η 1—H (N (N (N 二 -107- 127320.doc 200835487 物理數據* m.p. 162〇C m.p. 181°C ^-NMR (CDC13) δ = 0.85 (s); 0.95-2.25 (m); 3.80 (d); 4.00 (m); 7.10 ⑴；7.37 (m); 7.85 ⑴；7.90 (s); 8.43 (d); 8.63 (m). m.p. 163〇C ^-NMR (CDCI3) δ = 1.20 (m); 3.72 (d); 3.96 (m); 7.13 ⑴；7.33 (m); 7.40 (m); 7.75 (s); 7.80 (t); 8.45 (d); 8.70 (m). ^-NMR (CDCI3) δ = 0.90 (s); 1.10 (m); 3.85 (d); 4.30 (m); 7.20 (m); 7.33 (m); 7.43 (m); 7.83 (m); 7.90 (s); 8.45 (d); 8.70 (m). ^-NMR (CDCI3) δ = 0.88 (d); 0.95 (m); 1.50 (m); 2.80 (m); 7.10 (m); 7.33 (m); 7.80 ⑴；8.10 (s); 8.45 (d); 8.70 (m). m.p. 119°C ^-NMR (CDCI3) δ = 0.25 (m); 0.45 (m); 0.80 (m); 1.22 (m); 3.30 (m); 3.90 (m); 7.13-7.45 (m); 7.70 (s); 7.80 (t); 8·45 (d); 8.70 (m)(旋轉異構體之混合 物）0 ^-NMR (CDCI3) δ = 0.82 (m); 1.10-1.50 (m); 3.70 C 」 $4 +4 i4 ί*4 ^0 vo \〇 滅 1 (N CN CN (N CN CN (N (N (N (N A X ffi ffi ffi X ffi r N U u 〇 z u U U ffi X X X o 〇 z z u u u 9 i F "'^ 1 1 1 < 1 i 1 i 1 1 '< ，i »—Η i rO rO 〇 〇 rO n3 iiiiH 1 1 h Η 4C 'Ί , 、丨1 > ve 蝣鍩 浓硪 cAj ^ g辦 z OJS 4 ^ 4 ^ 4鍩 4 ^ (N cn <N 4 二 4 二 二鍩 A -V3 (N (N CN (Ν (N (N (N (N (N (N (N 編號 (N CN (N 〇 cn r-H cn cn 127320.doc -108- 200835487 物理數據* (m); 3.80 (m); 7.13-7.45 (m); 7.75 (s); 7.80 (t); 8.45 (d); 8.67 (m). ^-NMR (CDCls) δ = 1.00-1.75 (m); 2.10 (m); 3.90 (d); 4.15 (m); 7.13-7.45 (m); 7.80 (t); 7.87 (s); 8.40 (d); 8.70 (m). m.p. 83〇C ^-NMR (CDCls) δ = 0.90 (m); 1.18 (m); 1.25 (m); 1.40 (m); 1.67 (m); 3.75 (m); 4.45 (m); 7.15-7.45 (m); 7.80 (t); 7.90 (s); 8.42 (d); 8.67 (m). ^-NMR (CDC13) δ = 0.90 (m); 1.18 (m); 1.25-1.40 (m); 1.62 (m); 3.63 (m); 3.85 (m); 7.15-7.45 (m); 7.76 (s); 7.80 ⑴；8.42 (d); 8.67 (m). m.p. 67〇C m.p. 155〇C ^-NMR (CDCI3) δ = 0.90 (m); 1.20 (m); 1.55 (m); 3.80 (寬)；4.27 (m); 7.15-7.45 (m); 7.80 ⑴；7.90 (s); 8.42 (d); 8.67 (m). ^-NMR (CDCls) δ = 0.90 (m); 1.20 (m); 1.50 (m); 3.67 (寬)；3·77 (m); 7.15-7.45 (m); 7.75 (s); 7.82 ⑴;8.42 (d); 8.67 (m). m.p. 152〇C m.p. 112°C m.p. 131°C ^-NMR (CDCI3) δ = L22 (t); 2.67 (s); 3.63 (m); 3.75 (m); 7.15-7.45 (m); 7.70 (t); 7.77 (s); 8.20 (d). ^-NMR (CDC13) δ = 1.22 (t); 3.90 (d); 4.33 (m); 7.20 (t); 7.40 (m); 7.63 (s); 7.90 (d). m.p. 78°C 械1 +4 ο» | | \6 | ^0 VO ^0 VO 滅 (N (N (N (N (N (N <N (N CN <N (N (N (N K ffi ffi ffi ffi U z u Z z u u u u K X ffi ffi X ffi ffi u u u U u z u 三 u u ，_ 1 < 1 ' i I· i -圓H ......i F__ H 1 1 i I1 Λ 1 | Γ" 讀 % A nJ rO Λ ¥ 1-H ^ cA ^ 卜 rO rO CN 1 r-H (N 1 r-H (N (N (N (N CN 讀 砩 1 福 κ ¥ 砩 I 1 r—Η 1 (N -λ£ ft ¢- fi fi (N (Ν (N <N (N CN (N (N f (N (N ψ Ψ 編號 1-34 cn 1-36 1-37 _____1 1-40 1-41 Ml 1-45 1-46 |l-47 1 127320.doc -109- 200835487 鳍 Bv 0。 00 r Ή ?—Η d ε m.p. 183〇C m.p. 129〇C m.p. 129〇C ^-NMR (CDCI3) δ = 2.90 (t); 3.77 (m); 3.86 (s); 3.88 (s); 4.13 (m); 6.70 (m); 7.10 (t); 7.35 (m); 7.80 ⑴；7.90 (s); 8.47 (d); 8·73 (m). 。〇 d a m.p. 59〇C m.p· 201 〇C Θ 滅 (Ν (Ν CN (N i4 (Ν νό (N ^0 CN i4 'O (N X ffi u ffi U ffi u Z E U >< X ο ffi U ffi 〇 ffi 〇 Z βί —4 i i i tai ρ·Η 1 < 1 _< 1 \ »ί (Ν (N 4 二 6- ^ 4 二 '1 Ο -A i ^jA (N代 \\ ° 墨 (Ν ^ M 〇 "4 A- cn' ν Ώ (N M ^ 1 4<j>< (N代 Ψ ψ »- Μ 4 *> I m (Ν ψ 、1 4 ^ rs | cn (N ψ (Ν φ (Ν -aJ (N (Ν 1 (N -〇 1 (N jlJ m ΗΗ HH Ο un 二 Λ d.a ^ -110- 127320.doc 200835487 細胞週期抑制在HeLa細胞中之量測-測試程序： 在37C、92¾濕度及7% C〇2下，使HeLa B細胞在存於 180 cm2 Flasks 中、補充有 1〇% 胎牛血清（FCS，Life Technologies 目錄編號 10270-106)之 DMEM (Life Technologies 目錄編號21969_〇35)中生長。 在2心孔平板中以5x104個細胞每孔播種細胞。在20小時 後’添加該等化合物以使最終濃度為1χ1〇·6、3.3χ1〇·7、 l.lxlO·7、3·7χ1〇_8、及 1χ1〇·9 Μ，最終體積 5〇〇 μΐ。向6個孔中僅添加DMSO作為對照。按照上文所述將細 胞與化合物一起培育20小時。隨後在顯微鏡下觀察細胞以 檢查細胞死亡且隨後於2〇t下以12〇〇 rpm將該24_孔平板 離心5分鐘，加速位7且暫停位5 (Eppendorf離心機 5804R) 〇 去除上清液並用〇·5 ml RNase Buffer (10 mM擰檬酸鋼， 0.1% Nonidet NP40，5〇 gg/mi RNase，10 pg/ml埃化丙 I定）每 孔裂解該等細胞。隨後將該等平板在黑暗中於RT下培育至 少30分鐘且隨後將該等試樣轉移至fACS試管。在Facs機 器（Beckton Dickinson)中於下列設定下量測試樣： FACS Calibur之儀器設定： 運行模數：高 參數 電壓 放大器增益 模式 FSC E01 2,5 lin SSC 350 1 lin FI 1 FI2 430 2 lin 127320.doc 200835487 FI3 FI2-A … 1 lin FI 2-W … 3 lin DDM參數 FI 2 口十开Go/Gi-期與gvm期之細胞比例並與僅添加dmso之 對照的數值比較。結果作為IC5G值（自針對細胞週期比所繪 製》辰度曲線計算得）在表C中給出且表明在用該化合物處理 後細胞週期之50%細胞生長停滯時之化合物濃度。以相同 方式對其他細胞系（MCF-7及COLO 205)進行測試，只是該 等細胞系用美國組織培養物保藏中心（American Tissue Culture collection)所推薦適於其細胞類別之生長培養基培 育。Magnesium; and sweeteners, you H 1 , ; 丄 #, 伽 I For example, you can add sugar, lactose or saccharin; or flavor 127320.doc 200835487 J such as 'thin, wintergreen oil, or floor peach seasoning. When the formula is a capsule, it contains a "cell type agent of the above type of material. It can be included as a coating or as a modified dosage unit. For example, lozenges, pills, or capsules can be: a variety of agents: acetonide; anthraquinone compounds; silky compounds, as a sweetener, and 4^1 (as a preserve, such as cherry or flavor) Agent). Of course, the amount of material used in any of the dosage unit forms should be substantially non-toxic. In addition, these two: two can be incorporated into sustained release formulations and formulations. Compound Na = Active compound can also be administered parenterally or intraperitoneally. This / compound (as a free or pharmacologically acceptable or suspension can be carried out in water suitably mixed with the surface active solution. VIII, for example, 'propylcellulose') Glycerin, liquid polyethylene, and in a mixture of oils. Under ordinary storage and use of the stop, these formulations contain a preservative to prevent microbial growth. Conditions = Pharmaceutical forms for injection include sterile aqueous solutions or dispersions Sterile powders for the preparation of sterile injectable solutions or dispersions. In all October forms, the form must be sterile and must be fluid to the extent that it is easy to smear. It must be stable under the conditions of manufacture and storage and must be protected from the contaminating action of microorganisms such as bacteria and fungi. Carrier Dispersion medium comprising Γp ^ ^ a >, for example, water, ethanol, polyols (e.g., glycerol, propanol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils. The column examples given in Table B are up! -55 was prepared by the method set forth in 127320.doc-104-200835487 W02006/000358. These examples are representative compounds of the invention useful as anti-cancer agents. 127320.doc -105- 200835487 荟^^^^:PQ< physical data* ^-NMR (CDC13) δ = 1.20 (t); 3.87 (d); 4.30 (m); 6.45 (m); 7.20 (1); 7.40 (m); 7.73 (m); 8.52 (m). ^-NMR (CDCI3) δ = 122 (m); 3.75 (m); 3.88 (m); 6.45 (m); 7.15-7.40 (m); 7.75 (m); 8.55 (m). mp 170°C mp 78〇C ^-NMR (CDCI3) δ = 0.85 (s); 1.05 (d); 3.50 (m); 3.88 (d); 6.42 (1); 7.20 ( m); 7.40 (m); 7.75 (d); 8·55 (d) [mixture of rotamers]. ^-NMR (CDCI3) δ = 0.85 and 0.87 (s); 1.05 and 1.06 (d); 3.90 (d); 4.20 (m); 6.47 (m); 7.20 (m); 7.40 (m); (m); 8.50 (m) [mixture of rotamers] 0 ^-NMR (CDCI3) δ = 0.75-2.25 (m); 3.22 (m); 3.78 (d); 6.45 (m); 7.18 (m 7.40 (m); 7.74 (m); 8.55 (m) mp 126〇C 1 _ 1 3 觫|ϊι V· m Ξ t ”. "gm 〇〇 β β S S dan φ d S g瘐布$w 晋观ISt & Θ 2-chloro-6-fluorophenyl 2-chloro-6-fluorophenyl 2_chloro-6-fluorophenyl 2-chloro-6-fluorophenyl 2-chloro- 6-fluorophenyl 2-chloro-6-fluorophenyl 2-chloro-6-fluorophenyl 2-gas-6-fluorophenyl 2-chloro-6-fluorophenyl η X 〇 UUUUUUZ z υ ¢ 5 1 < i -丨-H 1 ""<ΐ" 1 Η 1 H YR2 2-propylamino 2-propylamino 4-phenylcyclohexylaminoamino 4-phenylcyclohexylamine Amino 3,3-dimethylbutan-2-amine 3,3-dimethylbutan-2-amino 4-tert-butylcyclohexylamino 4-tert-butylcyclohexylamine 1,3-dimethylbutyring-1-fluorophenyl 嗤- 卜 σ σ 峻 -1- 〇 〇 〇 〇 〇 -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -base σ than sial-1-ylpyrazole - 1-Base mouth ratio -1-base 〇 唾 基 基 基 ▼ Η Η Ν Ν Ν Ν Ν Ν Ν Ν cn cn cn cn cn cn cn cn cn cn cn cn VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO VO (m); 1.13 (m); 1.30 (m); 1.60 (m); 3.80 (m); 4.33 (m); 6.45 (m); 7.20 (m); 7.40 (m); 7.73 (m); 8.55 (m) [mixture of rotamers] 0 ^-NMR (CDCI3) δ = 0.88 (m); 1.16 (m); 1.25 (m); 1.40 (m); 1.63 (m); 3.70 (m); 6.45 (m); 7.20 (m); 7.40 (m); 7.73 (m); 8.55 (m) [mixture of rotamers]. Mp 152 〇C mp 152〇C mp 108°C mp 114°C ^-NMR (CDCI3) δ = 0.25 (m); 0.47 (m); 0.80 (m); 1.25 (m); 3.23 (m); (m); 6.45 (m); 7.20 (m); 7.40 (m); 7.73 (m); 8.55 (m) [mixture of rotamers]. ^-NMR (CDCI3) δ = 0.88 (m); 1.15 (m); 1.30 (m); 1.50 (m); 3.85 (m); 4.20 (m); 6.45 (m); 7.20 (m); 7.40 ( m); 7.73 (m); 8.55 (m) [mixture of rotamers] 0 mp 120°C mp 158〇C mp 161°C mp 164〇C mp 103°C read C ” +*4 νό VO ^0 νό 'sO 1 ^s employment shouting κ I (N (N CN A (N CN (N (N (N (N ffi K ffi ffi Uuu U ζ uu XE ffi ffi ffi X u 7U u UZ u U υ u —t 1 < ψ · H f—Η 1 i Μ 111 4 1 < .......ih l4 1 Q; hH 丨1锲cA ^ νε V? • ^3 ve CN 1 1-H rH (N (N CN <N <N 4 2 1 ▼"Η I 1 1 1 1 1 Ψ nl iw\ 1 谦 K 1 1 K earn 1 i ΐ ri 4 rsi i Ψ 41 i rH ΐ r—( rH iff VN v N 1—H uj ffffffff No. 0 rH rH 二(N m rH 寸 H ^T) rH \o tH 二卜 1-H 〇〇H η OS r - Η 1 - H (N (N 2 - 107 - 127320.doc 200835487 Physical Data * mp 162 〇 C mp 181 ° C ^-NMR (CDC13) δ = 0.85 (s); 0.95-2.25 (m 3.80 (d); 4.00 (m); 7.10 (1); 7.37 (m); 7.85 (1); 7.90 (s); 8.43 (d); 8.63 (m). mp 163〇C ^-NMR (CDCI3) δ = 1.20 (m); 3.72 (d); 3.96 (m); 7.13 (1); 7.33 (m); 7.40 (m); 7.75 (s); 7.80 (t); 8.45 (d); 8.70 (m). NMR (CDCI3) δ = 0.90 (s); 1.10 (m); 3.85 (d); 4.30 (m); 7.20 (m); 7.33 (m); 7.43 (m); 7.83 (m); 7.90 (s) 8.45 (d); 8.70 (m). ^-NMR (CDCI3) δ = 0.88 (d); 0.95 (m); 1.50 (m); 2.80 (m); 7.10 (m); 7.33 (m); 7.80 (1); 8.10 (s); 8.45 (d); 8.70 (m). mp 119 ° C ^-NMR (CDCI3) δ = 0.25 (m); 0.45 (m); 0.80 (m); 1.22 (m); (m); 3.90 (m); 7.13-7.45 (m); 7.70 (s); 7.80 (t); 8·45 (d); 8.70 (m) (mixture of rotamers) 0 ^-NMR ( CDCI3) δ = 0.82 (m); 1.10-1.50 (m); 3.70 C ” $4 +4 i4 ί*4 ^0 vo \〇灭1 (N CN CN (N CNN (N (N (N (N (N (N (N) Ffi ffi X ffi r NU u Zu UU ffi XXX o 〇zzuuu 9 i F "'^ 1 1 1 < 1 i 1 i 1 1 '< ,i »—Η i rO rO 〇〇rO n3 iiiiH 1 1 h Η 4C 'Ί , ,丨1 > ve 蝣鍩 硪 cAj ^ g do z OJS 4 ^ 4 ^ 4鍩4 ^ (N cn <N 4 2 4 2 A A-V3 (N (N CN (Ν (N (N (N (N N (N (N (N (N (N (N (N (N) (N 〇Nr (N 〇cn rH cn cn 127320.doc -108- 200835487 Physical Data* (m); 3.80 (m); 7.13-7.45 (m); 7.75 (s) 7.80 (t); 8.45 (d); 8.67 (m). ^-NMR (CDCls) δ = 1.00-1.75 (m); 2.10 (m); 3.90 (d); 4.15 (m); 7.13-7.45 ( m); 7.80 (t); 7.87 (s); 8.40 (d); 8.70 (m). mp 83〇C ^-NMR (CDCls) δ = 0.90 (m); 1.18 (m); 1.25 (m); 1.40 (m); 1.67 (m); 3.75 (m); 4.45 (m); 7.15-7.45 (m); 7.80 (t); 7.90 (s); 8.42 (d); 8.67 (m). ^-NMR (CDC13) δ = 0.90 (m); 1.18 (m); 1.25-1.40 (m); 1.62 (m); 3.63 (m); 3.85 (m); 7.15-7.45 (m); 7.76 (s); 7.80 (1); 8.42 (d); 8.67 (m). mp 67〇C mp 155〇C ^-NMR (CDCI3 δ = 0.90 (m); 1.20 (m); 1.55 (m); 3.80 (width); 4.27 (m); 7.15-7.45 (m); 7.80 (1); 7.90 (s); 8.42 (d); 8.67 ( m). ^-NMR (CDCls) δ = 0.90 (m); 1.20 (m); 1.50 (m); 3.67 (width); 3.77 (m); 7.15-7.45 (m); 7.75 (s); 7.82 (1); 8.42 (d); 8.67 (m). mp 152 〇C mp 112 ° C mp 131 ° C ^-NMR (CDCI3) δ = L22 (t); 2.67 (s); 3.63 (m); 3.75 ( m); 7.15-7.45 (m); 7.70 (t); 7.77 (s); 8.20 (d). ^-NMR (CDC13) δ = 1.22 (t); 3.90 (d); 4.33 (m); 7.20 ( t); 7.40 (m); 7.63 (s); 7.90 (d). mp 78°C 1 +4 ο» | | \6 | ^0 VO ^0 VO Off (N (N (N (N (N (N (N (N <N (N CN <N (N (N (N (N), N (N), N (N), N, N, N, H, H, H, H, H, H ......i F__ H 1 1 i I1 Λ 1 | Γ" Read % A nJ rO Λ ¥ 1-H ^ cA ^ 卜rO rO CN 1 rH (N 1 rH (N (N (N (N (N (N砩1 福 ¥ ¥ 砩I 1 r—Η 1 (N -λ£ ft ¢- fi fi (N (Ν (N <N (N CN (N (N f (N (N N Ψ 编号号 1-34) Cn 1-36 1-37 _____1 1-40 1-41 Ml 1-45 1-46 |l-47 1 127320.doc -109- 200835487 Fin Bv 0. 00 r Ή Η Η mp 183 〇 C mp 129 〇 C mp 129 〇 C ^-NMR (CDCI3) δ = 2.90 (t); 3.77 (m); 3.86 (s); 3.88 (s); 4.13 ( m); 6.70 (m); 7.10 (t); 7.35 (m); 7.80 (1); 7.90 (s); 8.47 (d); 8.73 (m). 〇da mp 59〇C mp· 201 〇C Θ Ν (Ν CN (N i4 (Ν νό (N ^0 CN i4 'O (NX ffi u ffi U ffi u ZEU >< X ο ffi U ffi 〇ffi 〇Z βί —4 iii tai ρ·Η 1 < 1 _< 1 \ »ί (Ν (N 4 2 6- ^ 4 2'1 Ο -A i ^jA (N generation \\ ° ink (Ν ^ M 〇"4 A- cn' ν Ώ (NM ^ 1 4<j><(N Ψ ψ »- Μ 4 *> I m (Ν ψ , 1 4 ^ rs | cn (N ψ ( Ν φ (Ν -aJ (N (Ν 1 (N -〇1 (N jlJ m ΗΗ HH Ο un Λ da ^ -110- 127320.doc 200835487 Cell cycle inhibition in HeLa cells - Test procedure: 37C, 923⁄4 humidity and 7% C〇2, HeLa B cells were stored in 180 cm2 Flasks supplemented with 1% fetal bovine serum (FCS, Life Technologies catalog number 10270-106) in DMEM (Life Technologies catalog number) Growth in 21969_〇35). Seeds were seeded at 5x104 cells per well in a 2-well plate. After 20 hours, the compounds were added to give a final concentration of 1χ1〇·6, 3.3χ1〇·7, l. lxlO·7,3·7χ1〇_8, and 1χ1〇·9 Μ, the final volume is 5〇〇μΐ. To 6 Only DMSO was added to the wells as a control. Cells were incubated with the compounds for 20 hours as described above. The cells were then observed under a microscope to examine cell death and then the 24-well plates were plated at 12 rpm at 2 Torr. Centrifuge for 5 minutes, Acceleration 7 and Pause 5 (Eppendorf Centrifuge 5804R) 〇 Remove the supernatant and use 〇·5 ml RNase Buffer (10 mM citric acid, 0.1% Nonidet NP40, 5 〇 gg/mi RNase, 10 The cells were lysed per well in pg/ml. The plates were then incubated at RT for at least 30 minutes in the dark and the samples were subsequently transferred to fACS tubes. On the Facs machine (Beckton Dickinson) Test the sample in the following settings: FACS Calibur instrument settings: Operating module: High parameter voltage amplifier gain mode FSC E01 2,5 lin SSC 350 1 lin FI 1 FI2 430 2 lin 127320.doc 200835487 FI3 FI2-A ... 1 lin FI 2-W ... 3 lin DDM parameter FI 2 The ratio of cells in the Go/Gi-phase to the gvm phase is compared with the value of the control in which only dmso is added. The results are given in Table C as IC5G values (calculated from the plot for the cell cycle ratio plotted) and indicate the concentration of the compound at 50% cell growth arrest after treatment with the compound. Other cell lines (MCF-7 and COLO 205) were tested in the same manner except that the cell lines were cultured in a growth medium suitable for their cell type as recommended by the American Tissue Culture Collection.

表C 實例 ic50_ 1-51 45 127320.doc 112-Table C Example ic50_ 1-51 45 127320.doc 112-

Claims (1)

200835487 十、申請專利範圍： •種用於/σ療的式1之2-經取代π比ϋ定化合物及該式I之2_ 經取代。比啶的醫藥上可接受之鹽， R R3 I 其中上下払及取代基係如下文所定義： X,、X2在每一情況下，該兩個環成員中的一個為N ,另 一個為C-H或C-鹵素； Υ係基團-CH-R1-、-N-R1-、·〇_或-s_; R彼此獨立地選自由下列組成之群：院基、 c2 C10-烯基、c2_Ci〇_炔基、C3_Ci2_環烧基及Κι〇_ 環稀基，其中Rl及R2基團定義之脂肪族及/或環脂族 基團可經部分或完全齒化或可攜帶丄個、2個、3個 或4個基團RV’該等基團Rv可為相同或彼此不同： RV係選自由下列組成之群：.素、氰基、Cl_c8_ 烷基、C2-Cl『稀基、C2_Ci〇_快基、C3_C6_環^ 基、C4-C6-環稀基、經基、c】_c6_烧氧基、C，· C-稀氧基、C2-Cl。，氧基、C3々環燒二 基、C4-C6-環烯氧基、_c(=〇)_Al、卜⑺… 八1、-C(，(a2)a1、c(a2)(=n· 、· n(a2)a1、、n(a3)_c N(A2)Al、S(=〇)m-Al、ShOh-O-A1 及 S( N(A2)V，兩個相鄰基團RV亦可能一起為（二) 127320.doc 200835487 或（=S)，或Rv係苯基，其中該苯基部分基團可 攜帶1個、2個或3個基團，該等基團可為相同 的或彼此不同且其係選自由下列組成之群：鹵 素、基、C2-C6-稀基、c2-C6-块基、 C3-c6-環烧基、cvc6_齒代烧基、Ci_C6_燒氧 基、氰基、硝基、-C(=〇)-A、-C( = 〇)-〇-a、 <(”Α’)Α、c(A，)(=N_〇A：^N(Af)A ;其中 m 係 〇、1 或 2 ; ' A 、八2、八3、八及八，彼此獨立地為氫、^_^_烷 基' c2_c6-烯基、C2_C6_炔基、c3_C8_環烷基、 環烯基或苯基，其中該等有機基團可經 部分或完全齒化或者可經_素、硝基、氰醯 基、氰基及/或^/^烷氧基取代；或者A1及 A、或A及A’分別與其所連接原子一起為5員或 員飽和、部分不飽和或芳香族雜環，該雜環 包含1個、2個、3個或4個選自由〇、N&s組成 之群的雜原子作為環成員； ’、中R基團定義之脂肪族、環脂族及/或芳香族 基團部分可經部分或完全齒化； R1 亦可為氫； ’、可/、其所連接氮原子或碳原子一起形成飽和或 不飽和5員或6員環，該環可包含〇、s、幾基 (〇)-人硫醯基（_S[=0]-)、磺醯基（-S02-)或 N(RX)-土團作為％成員’其中RX係氫或cvc6-烷基，及/或 127320.doc 200835487 其中所形成環可包含-個或多個選自由i素、Cl_ CV烷基、Cl_C6__代烷基及氧基_C1_C3_伸烷氧基組 成之群的取代基； R3 係選自由下而I h JU、 田卜列組成之群：鹵素、氰基、Ci_c4_烷 基、C2_C4_烯基、c2-c4-快基、c3-c6-環燒基、Ci_ C4_烷氧基、C3_C4-烯氧基、C3-C4-炔氧基、Cl_C6_ 烷硫基、二-(Cl_C6_烷基）胺基及Ci_Cr烷基胺基， 其中R3基團定義之脂肪族及/或環脂族基團部分可經 部分或完全_化或可攜帶1個、2個、3個或4個基團 R ’该等基團Rt可為相同的或彼此不同·· R係選自由下列組成之群：鹵素、氰基、Ci_c『烷 基、C2-C1(r烯基、C2-CiG_炔基、經基、 烷氧基、c3-cv環烷基、c2_Ci(r烯氧基、c2_ 快氧基、cvcv環烯基、C3-C6_環烷氧基、 C4-C6-環烯氧基…c( = 〇)_a13、_c( = 〇)_〇_a13、 _c(哪n(a14)a13、C(A14)(=N_0A13)、N(Ai4)Al3、 N(A14)_c(=〇)-A13、N(A15)-C(=0)-N(A14)A13、 S〇0)rA13、S(=〇)p-〇-A13及 s( = 〇)p—N(A14)A13， 兩個相鄰基團Rt亦可能一起為（ = 〇)或（ = s)，其中 p 係ο、1或2 ; A 、A及A15彼此獨立地具有如上文所定義 A1、A2及A3之含義； 且其中Rt基團定義之脂肪族、環脂族及/或芳香 族基團部分可經部分或完全鹵化或可攜帶丨個、 127320.doc 200835487 R4 2個或3個基圏Ru，該等基團Rta可為相同的或彼 此不同且其具有如上文所定義…之含義；200835487 X. Patent Application Range: • The 2-substituted π-pyrozyl compound of Formula 1 for the treatment of σ and the 2_ of the Formula I are substituted. A pharmaceutically acceptable salt of pyridine, R R3 I wherein the upper and lower oximes and substituents are as defined below: X, X2 In each case, one of the two ring members is N and the other is CH Or a C-halogen; a lanthanide group -CH-R1-, -N-R1-, 〇- or -s_; R independently of each other selected from the group consisting of: affiliation, c2 C10-alkenyl, c2_Ci〇 Alkynyl, C3_Ci2_cycloalkyl and Κι〇_ ring, wherein the aliphatic and/or cycloaliphatic groups defined by the R1 and R2 groups may be partially or fully dentated or may carry one or two , 3 or 4 groups RV' such groups Rv may be the same or different from each other: RV is selected from the group consisting of: cyano, cyano, Cl_c8_alkyl, C2-Cl", C2_Ci〇 _ fast group, C3_C6_ ring group, C4-C6-ring dilute group, trans group, c]_c6_ alkoxy group, C, · C-diloxy group, C2-Cl. ,oxy, C3 anthracycline, C4-C6-cycloalkenyloxy, _c(=〇)_Al, Bu(7)... VIII, -C(, (a2)a1, c(a2)(=n· , n(a2)a1, n(a3)_c N(A2)Al, S(=〇)m-Al, ShOh-O-A1 and S(N(A2)V, two adjacent groups RV It may also be (2) 127320.doc 200835487 or (=S), or an Rv-based phenyl group, wherein the phenyl moiety may carry 1, 2 or 3 groups, and the groups may be the same Or different from each other and selected from the group consisting of halogen, base, C2-C6-dilute, c2-C6-block, C3-c6-cycloalkyl, cvc6-dentate, Ci_C6_ Oxy, cyano, nitro, -C(=〇)-A, -C( = 〇)-〇-a, <("Α')Α, c(A,)(=N_〇A: ^N(Af)A; wherein m is 〇, 1 or 2; 'A, 八2, 八3, 八和八, independently of each other, hydrogen, ^_^_alkyl' c2_c6-alkenyl, C2_C6_alkyne a group, c3_C8_cycloalkyl, cycloalkenyl or phenyl, wherein the organic groups may be partially or completely dentated or may be _, nitro, cyano, cyano and/or Oxygen substitution; or A1 and A, or A and A' are 5 together with the atom to which they are attached a member of a saturated or partially unsaturated or aromatic heterocyclic ring containing 1, 2, 3 or 4 heteroatoms selected from the group consisting of ruthenium and N&s as ring members; The aliphatic, cycloaliphatic and/or aromatic moiety of the group may be partially or completely dentated; R1 may also be hydrogen; ', /, the nitrogen or carbon atom to which it is attached may form a saturated or not Saturated 5- or 6-membered ring, which may contain 〇, s, a few (〇)-human thiol (_S[=0]-), sulfonyl (-S02-) or N (RX)- a group as a % member 'wherein RX is hydrogen or cvc6-alkyl, and/or 127320.doc 200835487 wherein the ring formed may comprise one or more selected from the group consisting of i, Cl_CV alkyl, Cl_C6__alkyl and oxygen a substituent of the group consisting of _C1_C3_alkyleneoxy; R3 is selected from the group consisting of I h JU, Tambo: halogen, cyano, Ci_c4_alkyl, C2_C4_alkenyl, c2-c4 - fast radical, c3-c6-cycloalkyl, Ci_C4_alkoxy, C3_C4-alkenyloxy, C3-C4-alkynyloxy, Cl_C6_alkylthio, bis-(Cl_C6-alkyl)amine and Ci_Cr An alkylamino group, wherein the R3 group is defined The aliphatic and/or cycloaliphatic moiety may be partially or fully- or may carry 1, 2, 3 or 4 groups R' such groups Rt may be the same or different from each other. R is selected from the group consisting of halogen, cyano, Ci_c "alkyl, C2-C1 (r-alkenyl, C2-CiG-alkynyl, thiol, alkoxy, c3-cv cycloalkyl, c2_Ci ( r alkenyloxy, c2_ fastoxy, cvcv cycloalkenyl, C3-C6-cycloalkoxy, C4-C6-cycloalkenyloxy...c(= 〇)_a13, _c( = 〇)_〇_a13, _c(which n(a14)a13, C(A14)(=N_0A13), N(Ai4)Al3, N(A14)_c(=〇)-A13, N(A15)-C(=0)-N(A14 ) A13, S〇0)rA13, S(=〇)p-〇-A13 and s(=〇)p-N(A14)A13, two adjacent groups Rt may also be (= 〇) or ( = s), wherein p is ο, 1 or 2; A, A and A15 have, independently of one another, the meanings of A1, A2 and A3 as defined above; and wherein the Rt group defines an aliphatic, cycloaliphatic and/or The aromatic moiety may be partially or fully halogenated or may carry one, 127320.doc 200835487 R4 2 or 3 based on Ru, the groups Rta may be the same or different from each other and have ... the meaning defined above; 係5員、^、7員、8員、9員或10員餘和、部分不 飽和或芳香族單環或二環雜環，該單環或二環雜環 包含1個、2個、3個或4個選自由〇、N及S組成之群 的雜原子作為環成員，且其中該雜環部分可經部分 或完全齒化或可攜帶！個、2個、3個或4個基團ru， 該等基團Ru可為相同的或彼此不同·· RU係選自由下列組成之群：函素、氰基 烧基、c2-CiG-烯基、c2_Cig_炔基、羥基、Ci_ c6-烷氧基、c3-C6-環烷基、c2_Ci(r烯氧基、 c2 c1(r快氧基、c4_c6_環稀基、C3_C6_環烷氧 基、C4_CV環烯氧基、{(=〇)-Α4、_c(=〇)4 A 、，C(=〇)_N(A5)A4、-C(=S)-N(A5)A4、 C(A5)(=N-OA4)、N(A5)A4、N(A5)-C(=0)-A4、 n(a6)-c(=o)-n(a5)a4、s(=o)q-A4、s(=o)q-〇- A及S( = 〇)q-N(A5)A4，兩個相鄰基團ru亦可能 一起為（=0)或（=s)，其中 q 係ο、1或2; A、Α及Α彼此獨立地具有如上文所定義八1、 A2及A3之含義； 且其中Ru基團定義之脂肪族、環脂族及/或芳 香族基團部分可經部分或完全鹵化或可攜帶1 個、2個或3個基團Rua，該等基團Rua可為相同 127320.doc 200835487 的或彼此不同且其具有如上文所定義Ru之含 義； r4 亦可為：氰基、C(=Z)ORa、C(=Z)NRzRb、C(=Z)NRz-〇Ra、C(=Z)NRa-NRzRb、C(=Z)Ra、CRaRb-ORz、 CRaR、NRzRc、ON(=CRaRb)、0-C(=Z)Ra、NRaRbl、 NRa(C(=Z)Rb) 、 NRa(C(=Z)ORb) 、 NRa(C(=Z)-NRzRb)、NRa(N=CRcRb)、NRa-NRzRb 或 NRz-ORa， 其中 Z 係 〇、S、NRal、NORal 或 N-NRzlRcl ; Ra、Ral、Rb、Re、Rel彼此獨立地為氫、Cl-C6-烷 基、C2-C6-烯基、C2-C6·炔基、C3-C6-環烷基或 C4-C6-環稀基； R 具有如上文所定義Rb之含義，氫除外；且 RZ、RZl彼此獨立地具有如上文所定義Ra之含義且亦 可為-C〇-Ra2，其中Ra2具有如上文所定義Ra之 含義； 其中 Ra、Ral、Rb、Rbl、RC、RCl、RZ&RZl基團定義 之脂肪族、環脂族及/或芳香族基團部分可經部分或 完全齒化或可攜帶1個、2個、3個或4個基團Rw，該 等基團R、為相同的或彼此不同： RW係i素、氰基、Ci-Cv烧基、C2-CiG_烯基、& Ci〇一块基、（VC6-烧氧基、C2-C1()-稀氧基、C2-Cl0_块氧基、C3-C6-環烷基、c3-CV環烯基、 c^c6-環烷氧基、C3_C6_環烯氧基， 127320.doc 200835487 且其中基團Ra、Ral、 b bl K R 、Rc、rc1、RZ或 RZ1 中 的兩個與其所連接原子—起可形成5員或6貝飽和、 …飽和或芳香族雜環，該雜環可包含丨個、2 個、3個或4個選自由〇、M , S組成之群的雜原子作 ® 為環成員； 係苯基或係包含1個、2個或3個選自由0、咖組成 之群之雜原子作為環成員的5員或6員雜芳基； η L 係 1、2、3、4 或 5 ; 係選自由下列組成之群：齒素、氛基、氛醯基 (〇cn)、Ci-Ci。.院基、c2_c㈣基、c2_^块基、 q-cv烧氧基、c2_Ci『烯氧基、c2_Ci。-快氧基、q- C6-環烧基、c4_c6_環埽基、c3_c6-環院氧基、C4_ C6-環烯氧基、硝基、_c(=〇)_a7、_c_q_a7、 -C(=〇)-N(A8)A7 ^ -C(=S)-N(A8)A7 ^ -C(=NA8)- SA7 ^ C(A8)(=N-OA7) > N(A8)A7 , N(A8)-C(=〇)-A7 > N(A9)-C(=〇)-N(A8)A7、S(=〇)r-A7、S(=0)r_0_Ai S(=0)r-N(A8)A7 ’其中倘若n係2、3、4或5，則[可 為相同的或不同的’且其中 r 係0、1或2 ; A7、A8、A9彼此獨立地具有如上文所定義Al、A2及 A3之含義； 其中L基團定義之脂肪族、環脂族及/或芳香族基團 部分可經部分或完全_化或可攜帶丨個、2個、3個 或4個基團rl，該等基團rl可為相同的或彼此不 127320.doc 200835487 同： R 係選自由下列組成之 ^ ^ > c c m a 努、氰基、Ci-c10- | c2_c10_ 烯基 ^ A ^ 2 in 炔基、羥基、cv 6垸虱基、c2-c…歸^ c3-c6-環烷基、c 1。炔乳丞 4 烯基、Γ γ ρ知 基、c4-c6-環烯氧A ^ c3_c6_壞烷乳 A，0 礼基、-C(=〇)-A10、-C(=〇)-〇- 、-C(=0)-N(A")AU) u N(An} ^ ^·〇Α，°^ N(Au、Ai〇 V n(a12)-c(=〇)- α )A 、S(=0)s_Al。 S(=〇)s NfAn)A，o S(〜〇)s-0-A1G 及 ，兩個相鄰基圏M亦可能一 起為（=〇)或（=s)，其中 s 係0、1或2 ;且 A1 〇、A11及A12彼此想 《此獨立地具有如上文所定義 A1、A2及A3之含義· 且其中RL基團定義之貝匕 我之知肪私、環脂族及/或芳 香族基團部分可經部分或完全齒化或可攜❸ 個' 2個、3個或4個基團rLA，該等基團rLa可 為相同的或彼此不同且其具有如上文所定義以 之含義。 2·如2求項1之化合物，其中式I中之B係苯基。 月求項2之化合物，其對應於式I， ^R2a 5-, ^, 7-, 8-, 9- or 10-membered, partially unsaturated or aromatic monocyclic or bicyclic heterocyclic ring containing 1, 2, 3 Or 4 heteroatoms selected from the group consisting of ruthenium, N and S as ring members, and wherein the heterocyclic moiety may be partially or completely toothed or portable! , 2, 3 or 4 groups ru, the groups Ru may be the same or different from each other · The RU system is selected from the group consisting of: a troponin, a cyanoalkyl group, a c2-CiG-ene , c2_Cig_alkynyl, hydroxy, Ci_ c6-alkoxy, c3-C6-cycloalkyl, c2_Ci (r-alkenyloxy, c2 c1 (r-oxyl, c4_c6-cycloalkyl, C3_C6_cycloalkoxy) Base, C4_CV cycloalkenyloxy, {(=〇)-Α4, _c(=〇)4 A ,, C(=〇)_N(A5)A4, -C(=S)-N(A5)A4, C (A5) (=N-OA4), N(A5)A4, N(A5)-C(=0)-A4, n(a6)-c(=o)-n(a5)a4, s(=o q-A4, s(=o)q-〇- A and S(= 〇)qN(A5)A4, two adjacent groups ru may also be (=0) or (=s) together, where q Or Α, 1 or 2; A, Α and Α independently of each other have the meanings of VIII, A2 and A3 as defined above; and wherein the Ru group defines an aliphatic, cycloaliphatic and/or aromatic moiety Partially or completely halogenated or may carry 1, 2 or 3 groups Rua, which may be the same 127320.doc 200835487 or different from each other and have the meaning of Ru as defined above; r4 also It can be: cyano group, C(=Z)ORa, C(=Z)NRzRb, C(=Z)NRz-〇Ra, C(=Z)NRa-NRzRb, C(=Z)Ra, CRaRb-ORz, CRaR, NRzRc, ON(=CRaRb), 0-C(=Z)Ra, NRaRbl, NRa(C(=Z)Rb) , NRa(C(=Z)ORb), NRa(C(=Z)-NRzRb), NRa(N=CRcRb), NRa-NRzRb or NRz-ORa, where Z is 〇, S, NRal, NORal or N- NRzlRcl ; Ra, Ral, Rb, Re, Rel are each independently hydrogen, Cl-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl or C4-C6- a ring-like group; R has the meaning of Rb as defined above, except for hydrogen; and RZ, RZ1 independently of each other have the meaning of Ra as defined above and may also be -C〇-Ra2, wherein Ra2 has Ra as defined above Meaning; wherein the aliphatic, cycloaliphatic and/or aromatic moiety defined by the Ra, Ral, Rb, Rbl, RC, RCl, RZ & RZl groups may be partially or fully toothed or may carry one, 2, 3 or 4 groups Rw, which are identical or different from each other: RW-based i-, cyano, Ci-Cv alkyl, C2-CiG-alkenyl, & Ci〇 Block, (VC6-alkoxy, C2-C1()-diloxy, C2-Cl0_blockoxy, C3-C6-cycloalkyl, c3-CV cycloalkenyl, c^c6-cycloalkane Oxygen, C3_C6_ ring Oxyl, 127320.doc 200835487 and wherein two of the radicals Ra, Ral, b bl KR , Rc, rc1, RZ or RZ1 may form 5 or 6 moles of saturated, saturated or aromatic a heterocyclic ring which may comprise one, two, three or four heteroatoms selected from the group consisting of ruthenium, M, S as a ring member; a phenyl group or a system comprising one, two or 3 or 5 member heteroaryl groups selected from the group consisting of 0, coffee, or a hetero atom; or η L system 1, 2, 3, 4, or 5; selected from the group consisting of dentate, Aroma, 醯cn, Ci-Ci. Affiliation, c2_c(tetra)yl, c2_^block, q-cv alkoxy, c2_Ci"alkenyloxy, c2_Ci. - alkoxy, q-C6-cycloalkyl, c4_c6-cyclodecyl, c3_c6-cyclohexyloxy, C4_C6-cycloalkenyloxy, nitro, _c(=〇)_a7, _c_q_a7, -C(= 〇)-N(A8)A7 ^ -C(=S)-N(A8)A7 ^ -C(=NA8)- SA7 ^ C(A8)(=N-OA7) > N(A8)A7 , N (A8)-C(=〇)-A7 > N(A9)-C(=〇)-N(A8)A7, S(=〇)r-A7, S(=0)r_0_Ai S(=0) rN(A8)A7 'wherein n is 2, 3, 4 or 5, then [may be the same or different ' and wherein r is 0, 1 or 2; A7, A8, A9 have each other independently as above Defining the meanings of Al, A2 and A3; wherein the aliphatic, cycloaliphatic and/or aromatic moiety defined by the L group may be partially or completely- or may carry one, two, three or four The group rl, these groups rl may be the same or not each other 127320.doc 200835487 The same: R is selected from the group consisting of ^ ^ > ccma Nu, cyano, Ci-c10- | c2_c10_ alkenyl ^ A ^ 2 in alkynyl, hydroxy, cv 6 fluorenyl, c2-c... ^ c3-c6-cycloalkyl, c 1 . Alkyne emulsifier 4 alkenyl, Γ γ ρ ki, c4-c6-cycloal oxy A ^ c3_c6 _ bad alkane A, 0 ritual, -C(=〇)-A10, -C(=〇)-〇 - , -C(=0)-N(A")AU) u N(An} ^ ^·〇Α,°^ N(Au, Ai〇V n(a12)-c(=〇)- α )A , S(=0)s_Al. S(=〇)s NfAn)A,o S(~〇)s-0-A1G and, two adjacent bases M may also be (=〇) or (=s ), where s is 0, 1 or 2; and A1 〇, A11 and A12 are mutually intended to "this independently has the meanings of A1, A2 and A3 as defined above and wherein the RL group defines The private, cycloaliphatic and/or aromatic moiety may be partially or fully dentated or carry a '2, 3 or 4 group rLA, which may be the same or different from each other And it has the meaning as defined above. 2. The compound of claim 1, wherein the B in the formula I is a phenyl group. Compound of item 2, which corresponds to formula I, ^R2 127320.doc 200835487 其中 Y 係基團-CH-R1-、-N-R1·或; R1、R2彼此獨立地選自由下列組成之群·· Ci-C8-烷基、 c2-c8_烯基、c2-C8-炔基、CrCViR烧基、c2-c8- 鹵代烯基或CVCV鹵代炔基、c3-c8-環烷基及c3-c8-鹵代環烷基，其中脂肪族及/或環脂族基團可攜帶i 個或2個基團R%該等基團RV可為相同的或彼此不 同且其可選自由CVCV烷基、Cl_c6_鹵代烷基、c3_ 環烧基、鹵代環烷基及苯基組成之群，其 中5亥笨基部分基團可攜帶1個、2個或3個基團，該 等基團可為相同的或彼此不同且其係選自由下列組 成之群：鹵素、q-cv烷基、Cl-c6_鹵代烷基、Ci_ C(5 -烧氧基、氰基及硝基； R1亦可為氫； R1及R2亦可與其所連接氮原子一起形成可雜有醚（_〇_)或 另胺基-(-N(R ))_基團之飽和或不飽和5員或6員 環，其中R係氫或C^C：6·烧基，及/或其中所形成環 可包含一個或多個選自由_素、Ci_c6-烷基、c” C：6·鹵代烷基及氧基-Cl-C3-伸烷氧基組成之群的取 代基； R係_素、氰基、Cl_c4-烷基、Κ4-烷氧基或 鹵代烧基； R 係選自由下列纟且成之群：吼洛基、π比嗤基、味味 基、1，2,3-二唑基、1，2,4-***基、四唑基、噁唑 127320.doc 200835487 基、異噁唑基、i，3,44二唑基、·嗔二唑基、 呋喃基、苯硫基、噻唑基、異噻唑基、吡啶基、嘧 啶基、吼嗪基、嗒嗪基、丨，2,3_三嗪基、丨，2,4_三嗪 基、吡咯啶基、六氫吡啶基、叫丨唑基、六氫氮呼 基、二氫处啶基、二氫噻唑基及苯并噻唑基，其中 4雜壞可藉由C或N與該吡啶環連接且可攜帶丨個、2 個或3個基團Ru，該等基團Ru可為相同的或彼此不 同，其中 係函素、氰基、Cl-c8-烧基、Cl_C6_烧氧基、 -C(=0)-A4、<(=0)-0-Α4、<( = 〇)_ν(α5)α4、 c(a5)(=n-oa4)、n(a5)a4、n(a5)-c(=o)-a4， 或其中兩個相鄰基團Ru—起為（ = 〇)或（ = S); 或R係選自由下列組成之群：氰基、C(=〇)NRzRb、 C(NRal)NRzRb、C(=NORal)NRzRb、c(=N-NRzlRcl) NRzRb、C(=S)NRzRb、C(=0)Ra、C(=NRal)Ra、 C(=NORal)Ra、C(=N-NRzlRcl)Ra、C(=0)0Ra、 C(=NRal)ORa、C(=NORal)ORa、C( = 0)NRz-0Ra、 C(，Ral)NRz-0Ra、C(=N0Ral)NRz-0Ra、C(=0)NRa-NRzRb、CRaRb_NRzRC、CRaRb_ORz、0-C( = 0)Ra、 ON(=CRaRb)、NRaRbl、NRa(C(=0)Rb)、NRa(C(=NRal) Rb)、NRa(C(=N0Ral)Rb)、NRa(C(=0)0Rb)、NRa(C(=0)_ NRzRb)、NRa(C(=NRal)-NRzRb)、NRa(N=CRcRb)、 NRa-NRzRb及 NRz_ORa ; n 係1、2或3，其中至少一個取代基L位於苯環之鄰 127320.doc -9- 200835487 位； L·係選自由下列組成之群：齒素、氰基、Ci_Cs_燒 基、c2-c1()-烯基、c2-c1()，基、CrCr烧氧基、 C1(r烯氧基、（VC1()-炔氧基、硝基、_c卜⑺_〇_ A7、-C( = 0)-N(A8)A7、τ(4)·ν(α8)α7、c(a8)卜冰 〇A7)、N(A8)A7、N(A8H^〇)W及 S(=0)r-A7，其中 A7、A8彼此獨立地為氫、CVCV烷基、（：2<6_烯 基、cvcv炔基、環烷基或苯基，其中 該等有機基團可經部分或完全A化或可經_ 素、氰基及/或(^-(：4-烷氧基取代；或A7及A8與 其所連接原子一起為包含丨個或2個選自由〇、 N及S組成之群之雜原子的5員或6員飽和雜 環； 其中L基團定義之脂肪族、環脂族及/或芳香族基團 可經部分或完全_化或可攜帶丨個、2個、3個或4個 基團R，該等基團rl可為相同的或彼此不同。 4.如上述請求項中任一項之化合物，其中： R係選自由下列組成之群··吡唑-1-基、3-胺基-吡唑_ 1基[丨，2,4]二唑_1-基、3-氰基_1，2,4_***-1-基、 [1，2,3]***基、1，2,4-噁二唑 _3_ 基 ' 5_ 甲基-1，2,4-噁二唑_3_基、吡啶·2_基、（6_甲基）_吡啶-2_ 基、嘧啶-2-基、吡嗪基、σ荅嗪_3_基、（1，2-二 氫）-吡啶-2-酮_1_基、吡咯啶_2_酮-丨-基、六氫吡啶_ 2-酮-1-基、吡咯啶_2-亞硫醯4•基、六氫吡啶亞 127320.doc -10- 200835487 硫醯-1-基、[1，3]噻唑-2-基' (4,5-二甲基）-[1，3]噻 唑-2-基、苯并_[1，3]噻唑基、（4,5·二甲基）-(1，2_ 二氫Hl，3]噻唑_2·基、六氫-2H-氮呼-2-酮-1·基、六 氣- 2H -氣呼-2-亞硫酿-1-基及7 -胺基引唾-1-基。 5·如請求項4之化合物，其中R4係嘧咬基。 6·如請求項1至3中任一項之化合物，其中乂以系ν且义2係 CH， R4 係氰基、C(=Z)ORa、C(=Z)NRzRb、C(=S)NRzRb、 C卜Z)NRz-ORa或 C(=Z)Ra;且 z 係 〇、NRal 或 NORal， 其中R、Rb、Rz及Ral係如請求項1中所定義。 如上述晴求項中任一項之化合物，其中： Y 係基團-CHR1或-NR1，其中R1係η ;且 R2係選自由下列組成之群：CrCV烷基、C3-C8-烯 基、炔基或C^-C：8-鹵代烷基，其分別在α_位置 白具有支鏈；CVCs-環烧基或CVC8·鹵代環烧基， 其分別可攜帶選自由分別在(X—位置具有支鏈的C3_ C6_院基、C3-C6_鹵代烷基及苯基組成之群的基團 R ，CrCV烷基或CVCV鹵代烷基，其分別可攜帶 選自由C3_C0-環烷基、C3_C6_鹵代環烷基及苯基組 成之群的基團Rv，其中該苯基部分基團可攜帶1個 或2個取代基，該等取代基可為相同的或彼此不同 且其係選自由下列組成之群：_素、Ci_c6_烷基、 Ci-C6·鹵代烷基、Cl_C6_烷氧基、氰基及硝基。 127320.doc -11 - 200835487 8·如請求項1至6中任一項之化合物，其中 Υ 係基團_NRl，其中R1及R2與其所連接氮原子一起形 成可攜帶選自由鹵素、Cl_c6_烷基及Ci-c6-鹵代烷 基組成之群之取代基的飽和5員或6員環。 9.如上述請求項中任一項之化合物，其中Xl係N且χ2係 CH 〇 10·如上述請求項中任一項之化合物，其中基團@—Ln對應 於式B :127320.doc 200835487 wherein the Y group is -CH-R1-, -N-R1· or; R1, R2 are independently of each other selected from the group consisting of Ci-C8-alkyl, c2-c8-alkenyl, a C2-C8-alkynyl group, a CrCViR alkyl group, a c2-c8-haloalkenyl group or a CVCV haloalkynyl group, a c3-c8-cycloalkyl group, and a c3-c8-halocycloalkyl group, wherein an aliphatic group and/or The cycloaliphatic group may carry i or 2 groups R%. The groups RV may be the same or different from each other and may be optionally free of CVCV alkyl, Cl_c6-haloalkyl, c3_cycloalkyl, halo ring a group consisting of an alkyl group and a phenyl group, wherein the 5 moiety may carry 1, 2 or 3 groups, and the groups may be the same or different from each other and selected from the group consisting of Halogen, q-cv alkyl, Cl-c6-haloalkyl, Ci_C (5-alkoxy, cyano and nitro; R1 may also be hydrogen; R1 and R2 may also form together with the nitrogen atom to which they are attached a saturated or unsaturated 5- or 6-membered ring of an ether (_〇_) or another amine-(-N(R))- group, wherein R is hydrogen or C^C:6·alkyl, / or wherein the ring formed therein may comprise one or more selected from the group consisting of _, Ci_c6-alkyl, c" C: 6 · a substituent of a group consisting of a haloalkyl group and an oxy-Cl-C3-alkyleneoxy group; an R-line compound, a cyano group, a C1-c4-alkyl group, a fluorenyl 4-alkoxy group or a halogenated alkyl group;纟 成 成 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 吼 127 127 127 127 127 127 127 127 127 127 127 127 127 127 127 127 127 127 127 , isoxazolyl, i, 3,44 oxadiazolyl, oxadiazolyl, furyl, phenylthio, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyridazinyl, anthracene , 2,3_triazinyl, anthracene, 2,4-triazinyl, pyrrolidinyl, hexahydropyridyl, oxazolyl, hexahydroazetyl, dihydropyridyl, dihydrothiazolyl and Benzothiazolyl, wherein 4 heterozygous may be attached to the pyridine ring by C or N and may carry one, two or three groups of Ru, which may be the same or different from each other, wherein Element, cyano group, Cl-c8-alkyl group, Cl_C6_alkoxy group, -C(=0)-A4, <(=0)-0-Α4, <( = 〇)_ν(α5)α4 , c(a5)(=n-oa4), n(a5)a4, n(a5)-c(=o)-a4, or two of the adjacent groups Ru- (a 〇) or ( = S); or R system The following groups of components are selected: cyano group, C(=〇)NRzRb, C(NRal)NRzRb, C(=NORal)NRzRb, c(=N-NRzlRcl) NRzRb, C(=S)NRzRb, C(=0 )Ra, C(=NRal)Ra, C(=NORal)Ra, C(=N-NRzlRcl)Ra, C(=0)0Ra, C(=NRal)ORa, C(=NORal)ORa,C( = 0) NRz-0Ra, C(, Ral) NRz-0Ra, C(=N0Ral)NRz-0Ra, C(=0)NRa-NRzRb, CRaRb_NRzRC, CRaRb_ORz, 0-C(=0)Ra, ON(=CRaRb ), NRaRbl, NRa (C(=0)Rb), NRa (C(=NRal) Rb), NRa (C(=N0Ral)Rb), NRa(C(=0)0Rb), NRa(C(=0) _ NRzRb), NRa (C (= NRal) - NRzRb), NRa (N = CRcRb), NRa-NRzRb and NRz_ORa; n series 1, 2 or 3, wherein at least one substituent L is located adjacent to the benzene ring 127,320. Doc -9- 200835487; L· is selected from the group consisting of dentate, cyano, Ci_Cs_alkyl, c2-c1()-alkenyl, c2-c1(), yl, CrCr alkoxy, C1(r-alkenyloxy, (VC1()-alkynyloxy, nitro, _cb(7)_〇_ A7, -C(=0)-N(A8)A7, τ(4)·ν(α8)α7 , c(a8), blister A7), N(A8)A7, N(A8H^〇)W, and S(=0)r-A7, wherein A7 and A8 are each independently hydrogen, CVCV alkyl, (: 2<6-alkenyl, cvcv alkynyl, cycloalkyl or phenyl, Wherein the organic groups may be partially or fully A- or may be substituted by _, cyano and/or (^-(: 4-alkoxy; or A7 and A8 together with the atom to which they are attached) 2 or 6 membered saturated heterocyclic rings selected from heteroatoms consisting of ruthenium, N and S; wherein the aliphatic, cycloaliphatic and/or aromatic groups defined by the L group may be partially or completely _ Or may carry one, two, three or four groups R, which may be the same or different from each other. 4. A compound according to any one of the preceding claims, wherein: R is selected from the group consisting of pyrazol-1-yl, 3-amino-pyrazole-1-yl [丨, 2, 4] Azole-1-yl, 3-cyano-1,2,4-triazol-1-yl, [1,2,3]triazolyl, 1,2,4-oxadiazole_3_yl' 5_ A Base-1,2,4-oxadiazole_3_yl, pyridine-2-yl, (6-methyl)-pyridine-2-yl, pyrimidin-2-yl, pyrazinyl, σ-pyridazine_3_ , (1,2-dihydro)-pyridin-2-one-1-yl, pyrrolidine-2-one-fluorenyl, hexahydropyridine-2-ket-1-yl, pyrrolidine-2- Thiopurine 4·yl, hexahydropyridine 127320.doc -10- 200835487 thiopurine-1-yl, [1,3]thiazol-2-yl' (4,5-dimethyl)-[1,3] Thiazol-2-yl, benzo-[1,3]thiazolyl, (4,5·dimethyl)-(1,2-dihydro-Hl,3]thiazole-2·yl, hexahydro-2H-aza -2-keto-1·yl, hexa- 2H-gash-2-sulfinyl-1-yl and 7-aminopyran-1-yl. 5. The compound of claim 4, wherein R4 is The compound according to any one of claims 1 to 3, wherein the oxime is a ν and a genus 2 is a CH, an R 4 is a cyano group, a C(=Z)ORa, a C(=Z)NRzRb, C (=S)NRzRb, C Bu Z)NRz-ORa C (= Z) Ra; and z-based square, NRal or NORal, wherein R, Rb, Rz and Ral system as defined in one request item. A compound according to any one of the preceding claims, wherein: Y group -CHR1 or -NR1, wherein R1 is η; and R2 is selected from the group consisting of CrCV alkyl, C3-C8-alkenyl, Alkynyl or C^-C: 8-haloalkyl, which has a branch at the α_ position, respectively; CVCs-cycloalkyl or CVC8·halocycloalkyl, which can be carried separately from (X-position) a group R, a CrCV alkyl group or a CVCV haloalkyl group having a branched C3_C6_house group, a C3-C6_haloalkyl group and a phenyl group, which may be respectively carried from a C3_C0-cycloalkyl group, a C3_C6_halogen a group Rv of a group consisting of a cycloalkyl group and a phenyl group, wherein the phenyl moiety group may carry one or two substituents, which may be the same or different from each other and are selected from the group consisting of Groups: _, Ci_c6_alkyl, Ci-C6. haloalkyl, Cl_C6_alkoxy, cyano and nitro. 127320.doc -11 - 200835487 8 pursuant to any one of claims 1 to 6 A compound, wherein the lanthanide group _NR1, wherein R1 and R2 together with the nitrogen atom to which they are attached, is portable and consists of a halogen, a Cl_c6-alkyl group and a Ci-c6-haloalkyl group. A compound of any one of the preceding claims, wherein the compound of any one of the preceding claims, wherein X1 is N and χ2 is CH 〇10. Group @-Ln corresponds to Equation B: 其中#係與σ比啶架構之連接點且 Ll係氟、氯、CH3或CF3 ; L2、L4彼此獨立地為氫、ch3或氟； L 係氫、氟、氯、溴、硝基、氰基、CH3、SCH3、 0CH3、S02CH3、C0-NH2、C0-NHCH3、C0-NHC2H5、CO-N(CH3)2、CS-NH2、CS-NHCH3、CS-n(ch3)2、NH-C(=〇)CH3、n(ch3)-c(=o)ch3 或 cooch3 ;且 L5係氫、氟、氣或CH3。 11.如明求項1至10中任一項所定義之式J之2_經取代吡啶化 合物及其醫藥上可接受之鹽，其用於癌症治療。 12· —種醫藥組合物，其包含如上述請求項中任一項所定義 之式I之2 -經:取代吼咬化合物或其醫藥上可接受之鹽。 127320.doc -12- 200835487 種如明未項1至10中任_項 口定介八仏 只W疋義之式I之2-經取代吡 療。 之现的用途，其用於疾病治 14.如請求項13之 苴 /、Y °亥疾病係癌症。 15· —種如請求項丨至1〇中任— 咬化合物及其醫筚上可接/式1之2_經取代°tb 物。 ·了接雙之鹽的用途，其用於製造藥 16 ·如請求項15之用^伞 甘 用返其用於製造用於癌症療法之藥物。 17· 一種用於動物、太、 尤八疋人類癌症療法之方法，其包 需要其之個體投與有效量之如請求項1至10中任一項 定義式I之2-經取代吼咬化合物或其醫藥上可接受之鹽所 U 127320.doc -13 - 200835487 七、指定代表圖： (一) 本案指定代表圖為：（無） (二) 本代表圖之元件符號簡單說明： 八、本案若有化學式時，請揭示最能顯示發明特徵的化學式：Wherein # is the point of attachment to the σ-pyridine structure and L1 is fluorine, chlorine, CH3 or CF3; L2, L4 are each independently hydrogen, ch3 or fluorine; L is hydrogen, fluorine, chlorine, bromine, nitro, cyano , CH3, SCH3, 0CH3, S02CH3, C0-NH2, C0-NHCH3, C0-NHC2H5, CO-N(CH3)2, CS-NH2, CS-NHCH3, CS-n(ch3)2, NH-C(= 〇) CH3, n(ch3)-c(=o)ch3 or cooch3; and L5 is hydrogen, fluorine, gas or CH3. 11. The 2-substituted pyridine compound of formula J as defined in any one of claims 1 to 10, and a pharmaceutically acceptable salt thereof, for use in the treatment of cancer. A pharmaceutical composition comprising a formula I 2 as defined in any one of the preceding claims, wherein: a substituted bite compound or a pharmaceutically acceptable salt thereof. 127320.doc -12- 200835487 Kind of illuminating items 1 to 10, _ kou 定 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏 仏The current use for disease treatment 14. As claimed in item 13 /, Y ° Hai disease cancer. 15·—As for the request item 丨 to 1〇—the bite compound and its doctor's order can be connected to the formula 1 of the 2_ substituted °tb. The use of a salt of a double salt for the manufacture of a medicament 16 • The use of the herb of claim 15 for the manufacture of a medicament for cancer therapy. 17. A method for the treatment of human, cancer, or yuba, human cancer therapy, wherein the individual in need thereof is administered an effective amount of a 2-substituted bite compound of formula I as defined in any one of claims 1 to 10. Or its pharmaceutically acceptable salt station U 127320.doc -13 - 200835487 VII. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbolic symbol of the representative figure is simple: VIII. If there is a chemical formula, please reveal the chemical formula that best shows the characteristics of the invention: 127320.doc127320.doc
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Publication number Priority date Publication date Assignee Title
YU35699A (en) * 1997-02-10 2002-06-19 Pfizer Products Inc. 2-amino-6-(2-substituted-4-phenoxy)-substituted pyridines
EP1273580B1 (en) * 2001-07-05 2005-06-15 Pfizer Products Inc. Sulfonyl heteroaryl triazoles as anti-inflammatory and analgesic agents
EP1697375A2 (en) * 2003-12-02 2006-09-06 Vertex Pharmaceuticals Incorporated Heterocyclic protein kinase inhibitors and uses thereof
BRPI0512306A (en) * 2004-06-25 2008-02-26 Basf Ag compounds, processes for their preparation, pesticides, and processes for combating phytopathogenic fungi and pests of agricultural animals

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