TW200922559A - Compounds for inhibiting KSP kinesin activity - Google Patents

Abstract

The present invention relates to compounds of Formula (I), below, (wherein X, R1, R2, R3, R27, R28, p, E, ring A, and ring B are as defined herein). The present invention also relates to compositions (including pharmaceutically acceptable compositions) comprising these compounds, alone and in combination with one or more additional therapeutic agents, and to methods for their use in inhibiting KSP kinesin activity, and for treating cellular proliferative diseases or disorders associated with KSP kinesin activity.

Description

200922559 IX. INSTRUCTIONS: [Technical field to which the invention pertains] The present invention relates to a cell proliferative disease or disorder in which poetic treatment is associated with the transmission activity of a transmission protein ("KSP"), and KSP transmission Compounds and compositions that are active. The application is based on the US, the priority of the application of the application, and its contents are hereby incorporated by reference. [Prior Art] t the United States and the world, the cancer material is mainly dead U. The 4 inch sign of cancer cells often constitutes a proliferative message, a defect in the cell cycle checkpoint, and a defect in the cell nulling pathway. There is a great need to develop new chemotherapeutic drugs that block cell proliferation and enhance cell zeroing of tumor cells. For the treatment of cancer, ramie t 1 " ^ use, ° treatment" includes red cedars and periwinkle plants, which are based on microtubules. The system is a complete structural element of the mitotic spindle, its system Responsible for the distribution of the color of the woody early body to the daughter cells caused by cell division. ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ „ s s disrupted or interfered with microtubule dynamics to inhibit cells Splitting, and causing cells to be > zero. However, the microtubules are also 7C pieces of structure in the non-proliferating cells. For example, it is required for cell benefit and vesicle delivery within the cell or along the axis. Since the micro-tubes are the standard of the combination of production and production, the old objects will not be distinguished between the different structures. Therefore, there is a possibility to limit the practicality of the plate. Expected side effects. There is a need for a chemotherapeutic agent with improved specificity, to avoid side effects, and to improve the function of the name 135177 200922559 The micro-bureau relies on two materials to deliver protein, material transfer and function. The transporter is a transport protein that moves along the microtubules. It is a conserved transport function site. It is a combination of about 32 amino acid long ft energy sites and hydrolyzed ATP as a source of energy. The eclipse moves along the directionality of the microtubules and also contains microtubule binding interfaces (Manddkow and Mandelk〇w, Trends (5) _, 12 • Measured). The transmission system shows a high degree of functional change, and several transmission systems are particularly needed for mitosis and cell division. Different mitotic transmission lines are involved in all aspects of mitosis' including the formation of bipolar spindles, spindles, kinetics and chromosome movement. ^, the function of interfering with mitotic transducers can disrupt normal mitosis and block cell division. Specifically, mitotic transporter KSP (also known as EG5), which is required for centrosome separation, exhibits essential functions during mitosis. Among them, the KSP function is suppressed, the genus, and the collaterals are contained in the undivided central body in mitosis (Bhngy L:. et al., Cell 1995, 83: 1159-1169). This results in the formation of a single stellate array of microtubules at its ends, and the paired staining system is connected in a rosette leaf configuration. Furthermore, this mitotic containment leads to growth inhibition of tumor cells (Kaiser et al., /. Chest c/zem 1999, 274: 18925 18931). Formulations of Ksp are generally desired for the treatment of proliferative diseases such as cancer. Transkinase inhibitors are known, and several molecules have recently been described in the literature. For example, 'ad〇ciasulfate 2' inhibits the micro-stimulated ATPase activity of several transposons, including CENP-E (Sakowicz et al, Saence 1998, 280: 292-295). Rose red lactone, another non-selective 135177 200922559 formulation, interferes with transkinase function by blocking microtubule binding sites (Hopkins et al, Biochemistry 2000, 39: 2805-2814). Monastrol, a compound that has been isolated using phenotypic screening, is a selective inhibitor of KSP delivery functional sites (Mayer et al, Science 1999, 286: 971-974). Treatment of cells with monastrol will arrest cells that have a monopolar spindle in mitosis. KSP inhibitors have been disclosed in patents or publications, including: W02006/031348, W02(8)6/110390, W02006/068933, W02006/023083, W02006/007491, W02006/086358, W02003/105855, W02006/023440, W02003/079973, W02004/087050, W02004/111193, WO2004/112699, W02006/007497, W02(8)6/101761, W02006/007496, W02005/017190, WO0224/037171, W02005/019205, W02005/019206, W02005/102996, W02006/101780, W02006/ 007501, W02005/018547, W02004/058148, W02004/058700, W02005/018638, W02007/054138, W02006/133805, W02006/002726, WO2006/133821, W02005/108355, W02006/094602, W02005/092011, W02006/031607, W02004/111023, W02006/137490, W02006/101102, W02006/101103, W02006/101104, W02006/101105, W02004/092147, W02005/035512, W02006/044825, W02006/044825, W02006/119146, US2006/0247178, W02006/ 098961, W02006/098962, US2006/0258699, US2007/0213380, US2007/0112044, US2007/0155804, US2008/0194653, W02008/042928, US2007/0249636, US2007/0287703, US2008/0153854 and US2007/0037853. KSP, as well as other mitotic transducers, are attractive targets for the discovery of novel chemotherapeutic agents with anti-proliferative activity. There is a need for 135177 200922559

SUMMARY OF THE INVENTION In a specific embodiment, the present invention provides a compound, or a musically acceptable salt, solvate, ester, prodrug or isomer of the compound, which has the formula (I) The general structure shown in:

y D27 n28 (I) wherein Ri, R2, R3, p, r27, R28, E, ring A and ring B are independently selected from each other, and wherein: p is 0, 1, 2, 3 or 4; (including E and the unsaturation shown) is a 4-8 membered cycloalkenyl or heterocycloalkenyl ring; E is selected from the group consisting of -〇-, -S- '-S(O)-, -S(0)2 -, -C(R4)(R5)-, -N(R6)-, -N(C(Y)R7)-, -N(C(Y)〇R8)-, -N(C(Y)N (R9)(R10))-, -C(〇)-N(Rn)-, -N(Rn)-C(0)-, -S(〇)2-N(Rn)-, -C(( 0)_0—, -0-C(0)-, -0-N(R6)-, -N(R6)-0-, -N(R6)-N(R12)-, -N=N-, -C(R7)=N-, -C(0)-C(R7)=N-, -C(0)-N=N-,-0-C(Y)-N(Rn)-, 1) -C(Y)-〇-, -N(Rn)-C(7)-N(R12)-, -C(7)-N(Rn)-0-, -C(7), -0-N(Rn)-C(Y)- And -N(Ri2 H^R11 )-C(Y)-, wherein each Y is independently selected from the group consisting of (=0), (=S), (=n(R13)), -10-135177 200922559 (=N (CN)), (=n(〇r 丨4)) Ring B is a ^ or a heteroaromatic ring, an unsaturated heterocyclic ring, (=n(r15)(R16)) and (=c(r, (r)%; or partially unsaturated cycloaliphatic ring, or part

, wherein the ring system is unsubstituted or, as the case may be, independently - or a plurality of substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N〇2, alkyl , miscellaneous base, halogenated base, dilute base, dentate base, block base 4 base, aryl, heteroaryl, aryl base... heteroaryl m, base, heterocyclic (tetra), hetero Ring dilute, nitrogen-rich, -_,_0C_R2Q, tear 2lR22, NR23s〇2R24, -NR23C(〇)〇R2〇, .NR2 3C(〇)r24 ^ _s〇2Nr25r26 ^ c(〇)r24 ^ -C_(3), -SR19, _S(〇)Rl9, _s〇2R19, _〇c(〇)R24, 】C(0)NR R 6 , _NR2 3 qN cn)nr2 5 r2 6 and nr2 3 c(9) gauge 2 5 6 ; R system Selected from the group consisting of an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, a heterocycloalkyl group and a heterocycloalkenyl group, wherein each of the aryl groups, each of the heteroaryl groups, each of the ring groups, and the ring The I group, each of the heterocycloalkyl groups and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of , _CN, _N02, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkyne , haloalkynyl, aryl, heteroaryl, aryl-alkyl, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, _ 〇R〗9, _〇c((7)〇R2〇, -NR21R22, -NR23S02R24, _NR23C(0)OR20, -NR23C(0)R24, -S02NR25R26, _c(〇)R24, c(〇)〇r20, _SRl9 , s(〇)Rl9, -S02n19, -0C(0)R2 4, _C(〇)nr25r26, nr23c(n cn)nr25r26 '35177 200922559 &-nr23c(o)nr25r26; base and heterocyclic R2 series Selected from the group consisting of -c(Z)r7, -C(Z)Nr9ri〇kZX)r8, _SQ2NR9Ri〇, alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkane Each Z series is independently selected from the group consisting of (=〇), (=s), (=N(R13)), (=N(CN)), (=N(0R14)), (=N(R15)(R16) And (=c(r17)(r18), wherein each of the alkyl group, each of the heteroalkyl group, each of the aryl groups, each of the heteroaryl groups, each of the alkylene groups, and each of the cycloalkenyl groups The heterocycloalkyl group and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a ketone group (with the attached conditions) Yes, The aryl group and the heteroaryl group are not substituted by a group), _, -CN, -N02, alkyl, heteroalkyl, alkyl, alkenyl, alkenyl, alkynyl, alkynyl, aryl 'Heteroaryl, aryl-alkyl, heteroaryl-alkyl, nonylalkyl, cycloalkenyl'heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -〇C(0) 〇R2〇,·Νκ2,κ22,_NR23sQ2R24, -NR2 3C(〇)〇r20, nr23c(〇)r24, nr25r26, cna24, -c(o)or2〇, _srI9, _s(〇)Rl9, s 〇2Rl9 ' 〇c_24, -C(0)NR2 5 R2 6 , _nr2 3 c(n cn)nr2 5 r2 6 and _nr2 3 c(〇)nr2 5 R2 6 ; R27 (when not bonded to R28) Independently selected from the group consisting of H, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocycloalkenyl Base, halogen, _CN, _N〇2, _〇Rl 9, -OC(0)〇R2〇> -NR21R22 > -NR23S02R24 > -NR23C(0)0R2° ' -NR23C(0)R24, _S〇 2NR2 5R2 6. <(0^2 4, c(〇)〇r20, SR] 9, S(0)R - S02R19 ' -0C(0)R24 ' -C(0)NR25r26 . -NR2 3 C( N-CN)- 135177 200922559 NR25R26&-NR23C(〇)NR2 5R2 6, each of which The alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, each of the heterobasic groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, and each of the cycloalkyl groups and each The cycloaliphatic group, each of the heterocycloalkyl groups and each of the heterocyclic ring-based groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of Keto group, _-, -CN, -N02, alkyl, hetero, kiln, _hetero-k, _alkyl, alkenyl, alkenyl, alkynyl, i-block, aryl, heteroaryl , cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocyclic, azide, _or19, _oc(o)OR20, -NR2 1R2 2, _NR2 3S〇2R24, nr23c(〇)〇r2. , 23c_4, -SO Na妒, _C(Q)R24, .C_R2Q, Guan19, part)R19, -S〇2R- . -〇C(0)R- . -C(0)Nr25r26 . _Nr23C(N .CN) a group of nr25r26 and -NR23C(0)NR25R26, when not bonded to π) is independently selected from the group consisting of a package, an alkyl group, a heteroalkyl group, a dilute group, a heterocyclic group, an alkynyl group, a (tetra) group, and an aryl group. , heteroaryl, cyclononyl, cycloaliphatic, heterocycloalkyl, heterocyclic, halogen, ,, _N02, _W9, -〇C(0)〇R2〇, ,NR2lR22 . .nr23s〇2R24 ^ , nr23C(〇)〇r20 ^ -NR2 3C(0)R24, _s〇2Nr25r26, c_24, rotten (10)2〇, Guan9, -S(0)R19, _sc>2Rl9, _qc(q)r24, c(q)nr25r26 And 23 NR25R26&_NR2 3C(〇)NR2 5R2 6 wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl groups, each of the heteroalkenyl groups, and each of the alkynyl groups Each of the aryl group, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, one or more Can be substituted for the same 135177 200922559 or different substituents, each substituent is independently selected from the group consisting of shouting, element, -CN, -N〇2, alkyl, miscellaneous, ^ Alkyl, alkenyl, functional alkynyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, seven Rl9...〇c(9)〇r2〇 , _NR2lR22, -nr23s〇2R24, -nr23c(o)〇r2〇, _nr23c(〇)r24, -S02NRWR2 6, _c(〇)R24, c(〇)〇R2. , SR19, s浑9, -S〇2R19, -0C(0)R2 4, _c(〇)nr25r26, nr23c (n cn hui 25r26 and -nr23c(o)nr25r26 group, £, R and R and The carbon atoms to which they are attached - which form a cycloalkyl group, the % alkenyl group, the heterocycloalkyl ring - contain one to three heteroatoms selected from the group consisting of N, hydrazine and S or a heterocyclic ring, containing one to three a hetero atom selected from the group consisting of N, hydrazine and s, wherein the heterocycloalkyl ring and the heterocycloalkenyl ring are each unsubstituted or, as the case may be, one or more substituents which may be the same or different Substituted, each substituent is independently selected from the group consisting of a keto group, a halogen, a —CN, a —N〇 2 alkyl group, a halogen-based group, an alkenyl group, an — | alkenyl group, an alkynyl group, a haloalkynyl group, and a heteroaryl group. , aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR1 9, -〇C(0)〇 R2〇, _NR2IR2 2, _NR2 3S〇2R2 4, _NR2 3C(〇)〇R2 0, -NR23C(0)R24, -S〇2NR25R26, -C(〇)R24, -C(0)OR20, -SR19, -S(〇)Rl9, -S02Rl9, -〇C(0)R24, -C(〇)NR25R26, -NR23C(N-CN)-NR2 5 R2 6 and -NR2 3 c(〇)NR2 5 R2 6 ;R3, when present, is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl '135177-14 - 200922559 Heterocyclic, heterocycloalkenyl, halogen, -CN, -N02, -OR1 9, -〇C(〇)〇R2 〇, -NR21R22 ^ -NR23S02R24 . -NR23C(0)0R2° > - NR23C(0)R24 > -S02NR25R26, -C(0)R24, -c(5)R24, -C(0)0R2° ' -SR19, -S(0)R1 9, -S02R19 ' -0C(0)R24 ' - C(0)NR25R26 '-NR2 3 C(N-CN)NR2 5 R2 6 -NR2 3 C(0)NR2 5 R2 6 and -NR2 3 ·〇(ΝΗ)_ν(Κ2 6 )2,

Each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, and each of the cycloalkyl groups Each of the cycloalkenyl groups, each of the heterocycloalkyl groups and each of the heterocycloalkenyl groups is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently Selected from keto, halogen, -CN, -N〇2, deutero, fluorenyl, southern, dilute, dentate, alkynyl, haloalkynyl, aryl, heteroaryl, naphthenic , cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, 〇 〇 Rl9, (9) -NR-R- . -nr23S〇2R24 . , nr23C(〇)〇r20 ^ _nr23c(〇)r24 ^ -S02NR25R26, _C(〇)r24, rotten 〇r2〇, Guan9, -S〇2R- ^ -0C(0)R- . -C(〇)NR-R- , -NR-C(N.CN) a group of NR25R2'6 and -NR2 3 C(〇)NR2 5 R2 6 , : (4) when (4) is bonded to any two R groups of the same ring carbon atom and to the carbon atoms to which they are attached , A Zhao knows to form a 1% alkenyl or spiroheterocycloalkyl ring of spirocyclohexane, containing -

Mb 4x κτττ κ to - an independent w cis -, 1, Na, part) 2. and ring heteroatoms, or spiroheterocycloalkenyl rings, containing '-including or, R2 and (four) materials 卞 135177 -J5· 200922559 Original:; One: V, ring-based, "base, heterocyclic ring" "'NH''_NR6_'_S" 'One to three independently selected from ^Γ cycloalkenyl ring, containing and ring of 4 Heteroatom-, NR-, -s-, Lin, Weng Dang = R5 when joined, including from H, ", miscellaneous silk,

Substrate, heteroblock, aryl, heteroaryl, cycloalkyl, decyl, heterocyclic, dentate, -CN, -N〇2, _ORl9, -〇C(0)OR2〇, _nr2]r22 ^ ,nr23s〇2r24 ^ _nr23c(〇)〇r20 ^ 视23C(〇)R24, _S〇2NR25R26, rotten R24, paste OR2G, _SR19, (〇)RS〇2R, -〇C(〇)R24, ((〇) cis251126, -NR23C(N-CN)_NR2 5 R2 6 and 2 3 c(〇)nr2 5 r2 6 , wherein each of the alkyl group, each of the miscible groups, each of the alkenyl groups, and each The heterocyclic group, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocyclic groups The alkenyl group is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, -CN, -N02, an alkyl group, a heteroalkane. , _alkyl, alkenyl, haloalkenyl, alkynyl, il alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, _0Rl 9. _QC(〇)〇R2 0, -NR21R22, -NR23S02R24, -NR23C(0)〇r2G, _nr2 3c(〇)r24, -S02NR25R2 6, _C(0)R2 4, Groups of _C(〇)〇r20, _SRl9, _s(〇)Ri9, -S02R19, -0C(0)R2 4, -C(0)NR25R2 6, _NR2 3C(n_cn)nr25r26 and -nr23c(o)nr25r26 ; 135177 -16- 200922559 Each R5 (when not bonded to R4) is independently selected from the group consisting of 11, an alkyl group, a heteroalkyl group, a dilute group, a heterocyclic group, an alkynyl group, a heterodoxy group, an aryl group, a heteroaryl group; 'cyclodecyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, _, _CN, _N02, _0R19, -〇C(〇)〇r2〇. _nr21r22 . .nr23s〇2R24 ^ _nr23c(〇)〇 R20 ^ -NR2 3C(〇)R2 4, _s〇2Nr25r26, _c(〇)r24, (10)(10), 观9, -S(〇)R^^-S〇2R^, -〇C(〇)R24 . C(0)Nr25r26^_NR23C(N.CN). NR2 5 R2 6 and _NR2 3 C(〇)nr2 5 r2 6 wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl groups, and each of the heterogeneous groups a base, each of the alkynyl groups, each of the heteroblock groups, each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocyclic groups, and each of the heterocyclic groups Unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, an i-CN CN02, an alkyl group, a heteroalkyl group Halogen, alkenyl, dentate: block, alkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heteropoly, heterocyclic, azide, 〇r19 , K〇)〇r2〇, -NR R2 2 Λ .NR2 3s〇2r24 , -NR2 3C(〇)〇r2〇^ _NR2 3C(〇)R2 4 , -s〇2nr25r26, _C(0)R24, _C_2G, Such as 9, · _ ΐ 9, - 邶 R 】 ^ 0C (0) r24, _c (〇) nr25r26, nr23c (n c_25r26 and -NR23c (0) NR25R26 group; j R 14 R and their connected carbon The atoms together form a cyclodextrin, a ring, a hydrazine-based fluorenyl ring containing one to three heteroatoms or heteronuclear alkenyl rings selected from the group consisting of N, hydrazine and s, containing - to three selected from the group consisting of N, hydrazine and a hetero atom of 5, wherein the heterocyclic ring and the heterocycloalkenyl ring are each unsubstituted, 135177 200922559 or depending on the f month/brother independently - or a plurality of substituents which may be the same or different The substituents are independently selected from the group consisting of ketone groups, i-proteins, -CN, , & bases, _-based groups, dilute bases, thiol groups, dentate radicals, heteroaryls, aromatic Base-alkyl-, heteroaryl-alkyl-, naphthenic cycloalkenyl, heterocycloalkyl, heterocycloalkenyl , Azido, _〇R] 9, 0C (0) 0R, -NR2 1R2 2, nr23s〇2R24, nr23c (square) 〇r2. , NR C(〇)R 4, _S〇2NR25R26, _C(〇)R24, _C(〇)〇R2 0, _SR]9, -S(〇)Rl 9, _S〇2 Rl 9, 〇C(〇 R2 4, -C(〇)NR2 5 R2 6 , -NR2 3 C(N-CN)-NR25R21-NR2 3C(〇)nr25r26; each R6 is independently selected from the group consisting of H, alkyl, _c(〇)r24 , _c(〇)〇r20, _c(5)r24, heteroalkyl, county, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl 'cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl a group, wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl groups, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, and each of the rings The alkyl group, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent Is independently selected from the group consisting of keto, halogen, -CN, -N02, alkyl, heteroalkyl, _alkyl, alkenyl, alkenyl 'alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl , cycloalkenyl, heterocycloalkyl, heterocyclic, azide, 〇Rl 9, 〇 〇 c (〇 > 〇r20, -NR2 1R22, -NR23S02R24, -NR23C(0) 〇 R2〇 _NR2 3C(〇)r24, -S〇2NR2 5R2 6, _C(0)R2 4, _c(s)r24, _c(〇)〇r20, SRI9, -S(〇)Ri 9, and S02 R] 9. a group of -0C(0)R24, -C(0)NR2 5 R2 6, _NR2 3 c(n cn)_ NR25r26 and _NR23C(9)nr25r26; 135177 18 200922559 Each R7 is independently selected from the group consisting of H, alkynyl, alkynyl , alkynyl, aramidyl, alkenyl, heterocyclic, thiol, cycloalkenyl, heterocyclol ==, each of the heteropoly, each of the alkenyl, each of the heteroalkenyl, eve An alkynyl group, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, each of the μ% alkyl groups, each of the cycloalkenyl groups, the group is unsubstituted, and each of the heterocycloenes, or The monthly conditions are independently substituted by one or more substituents which are the same as the lil r, each substituent being independently selected from the group consisting of: ΓΝ0..., group, oxime, ...: group, alkynyl group, haloalkynyl group, Aryl, heterocyclic ρ 杂 heteroaryl, bad alkyl, cycloalkenyl, gangrene, ketone, heterocycloalkenyl, stack

Np2lD22 ί 4 base, -OR19, -〇C(〇)〇R2 0, tear Pm〇2R24, NR23c_R2G, tear 23c(〇)r24 •S〇2NR25R26, -_24, -c_heart, _sr19, part)r19 ' a group of S〇2RI9''〇C(〇)R24'«5r^ and -NR2 3C(〇)Nr25r26;

V

Each R is independently selected from the group consisting of hydrazine, I acetylene, 70 Å, heteroalkyl, alkenyl, heteroalkenyl, yl, heterocyclic, benzyl, pure, sulfhydryl, heterocyclic a heterogeneous group, each of the fluorenyl groups, each of the heterobasic groups, =:, each (four) block group, each of the aryl groups, each of the heteroaryl groups, each of the (tetra) groups, each of the heterocyclic groups, and each of the heterocyclic groups Unsubstituted or, as the case may be, independently - or multiple may be the same: different substituents, each substituent being independently selected from the group consisting of keto, _, -CN, -N02, alkyl, hydrazine' Alkyl, _alkyl, alkenyl, haloalkyl 135177 200922559 base, alkynyl, alkyne, #方方, heteroaryl, cycloalkyl, cycloalkenyl,

Miscellaneous ground, heterocyclic ring, knee I, alkenyl, nitrogen-rich, -OR19, _〇C(〇)〇R20, -NR21 R22 > -NR23q〇d2 4 〇2R , -nr23c(o)〇r2 . , _NR2 3C(〇)r24, -S〇2NR R26, C(〇)R24, -C(0)0R2. a group of _SR19, _s(〇)Rl9, 〇2R 〇C(0)R 4 Λ -C(〇)NR2 5R2 6 λ -NR23C(N-CN)NR25R26 and -NR2 3C(9)NR25r26;

Each R9 (when not joined to RW) is intended to be independent of η, alkyl, heteroalkyl,

a vinyl group, a heteroalkenyl group, an alkynyl group, a heterocyclic group, a aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, a heterocycloalkyl group, a heterocycloalkenyl group, ', each of the alkyl groups Each of the heteroalkyl groups, each of the alkenyl groups, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, and each of the heteroaryl groups. Each of the (four) groups, each of the heterocyclic and each of the heterocyclic lines are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent Is independently selected from the group consisting of ketone, halogen CN, -Ν02, fen, chiral, calcinyl, dilute, dentate, fast radical, i alkynyl, aryl, sulfonyl, cycloalkyl, epoxide Alkyl, heterocycloalkyl, heterocycloalkenyl, azido, _or19, _oc(o)OR20, -NR21r22, _NR23s〇2R24, _nr23c_r2Q, NR23c_24, -S〇2NR25R2 6, _C(0)R2 4, _C( 〇)〇R2〇, _sr]9, 妒9, -S〇2R'9, .〇C(〇)R2 4 . -C(〇)NR25R2 6 , .NR23C(N-CN)NR25R2 6 and -NR2 a group of 3 C(0)NR2 5 R2 6 ; each R1〇 (when not bonded to R9) is independently selected from the group consisting of H, alkyl, heteroalkyl alkenyl, heteroalkenyl, alkynyl, heteroalkynyl , aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, 135177 -20- 200922559 2 each of the alkyl groups, each of the saki, ::=, each of the blocks The base, each of the aryl groups, and each of the hetero-substituents are substituted by each of the heterocycles and each of the heterocyclic rings or different substitutions thereof. The conditions are independently one or more may be the same element, _ΓΝ, and each substituent is independently selected from the group consisting of a keto group, a dentate group, a decyl group, a heteroalkyl group, a halogen group, a dilute group, and a dentate group. i 2: alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, variegated, heterocyclic, azide, 〇Rl9, cargo (〇)〇r2〇, police R22,,nr23s〇2R24,_nr23c(wr2Qnr23c(〇)r24, -s〇2nr-r26 , _C(0)r24 ^ _C(〇)〇R2〇^ SR19 ^ S^R19 ^ -S〇2R19 ^ -〇C (〇) R24 . .C(〇)NR25r26 ^ -NR2 3C(n.CN)nr25r26 and -nr23c(〇)nr25r26; or R9 and R1 〇 together with the N atom attached to it Forming a heterocycloalkyl or a whey ring containing - to three heteroatoms selected from the group consisting of N, hydrazine and S, wherein the heterocycloalkyl ring and the heterocycloalkenyl ring system are each unsubstituted, or Optionally, independently or in combination, may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of fluorenyl, narcotics, -cN, _N〇2, alkyl:hetero, and decyl , dilute base, dentate base, block base, functional block base, aryl group, heteroaryl 'aryl group' _,heteroaryl-alkyl group, cycloalkyl, nonenyl, heterocycloalkyl, heterocycloalkenyl, azido, _〇r] 9, -〇C(0)OR2〇^-NR- R- . .Nr23s〇2r24 ^ , nr23c(〇)〇r2〇. -NR2 3C(〇)R2 4 , -S〇2NR25R2 6 . _C(〇)R2 4 , _C(〇)〇R2 0 , _SR1 9 . -S(0)R1 9 . -S〇2 R1 9 , -〇C(〇)R2 4 , _C(〇)nr2 5 r2 6 λ _nr2 3 C(N-CN)-NR25R26&_NR23C(0)NR25R2 6 135177 -21 · 200922559 Heteroalkenyl, heterocycloalkyl, each R 1 is independently selected from the group consisting of H, alkyl, heteroalkyl, alkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, naphthenic Base, cycloalkenyl, heterocycloalkenyl,

Each of the alkyl group, each of the miscible groups, (4) a dilute group, each of the heterobasic groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, each of the fluorene groups, Each of the cyclohexenes I, each of the heterocyclic alkyl groups, and the heterocyclic ring (four), which are unsubstituted or, as the case may be, independently substituted by one or more substituents may be substituted with a different substituent, each substituent being , independently selected from _ group, dentate, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, alkenyl, alkynyl, anthracenyl, aryl, heteroaryl, ring Affiliation, ring-like, heterocyclic, heterocyclic, heterocyclic, fluorene, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine, hydrazine , fly 2,, -S〇2NR2 5R26, paste r24, _c(q)〇r2(), view 19, part) (10) -s〇2R- ^ -0C(0)r24 . _C(0)nr25r26 ^ _nr23C( Groups of N_CN)nr;6 and -NR23C(〇)NR2 5R26; each ulnar is independently extended from Η, 院, 烧 alkyl, alkenyl, heteroalkynyl, heteroalkynyl, aryl, wang# Soil, a base, a heterocyclic ring, a sulfhydryl group, a decyl group, a ring-burning group, a ring-like group, a heterocyclic ring = a hospital: each of the hydrazines, each of the sulphur groups, each of the hetero-alkyl groups, the alkynyl group, each of the alkynyl groups Each of the aryl groups, each of the heteroarylcyclodecyl groups, each of the cycloalkenyl groups, each of the heterocyclic rings, and each of the core systems are unsubstituted or, as the case may be, independently one or more: Substituent substituents 'each substituent is independently selected from the group consisting of -CN, Ν〇2, aryl, (4) yl 1 alkyl, alkenyl, 135177 22- 200922559 base: block group, abusive group, aryl group ,heteroaryl,cycloalkyl,cycloalkylalkylene, azide, 〇Rl 9, 〇〇c(〇)〇r20, -NR R2 2 . -NR2 3S〇2R24 ^ _NR2 3C(〇)〇r20 ^ _NR2 3C(〇)R2 4 . -S〇2NR2 5R2 6, _c(〇)r24, _c(〇)〇r2. , η, 部, 9, S02R19, _oc(9)r24 -C(〇)NR25R2 6 > -NR23C(N-CN)NR25R26 and -NR23C(〇)nr25r26 group; alkyl, heteroalkyl, alkenyl , heteroalkenyl, heteroaryl 'cycloalkyl, cycloalkenyl, heterocycloalkane

Each R13 is independently selected from the group consisting of a decynyl group, a heteroalkynyl group, an aryl group, a group, a heterocycloalkenyl group, wherein each of the (4) groups, each of the hetero-groups, each of the groups, each of the hetero-bases, and the alkyne a group, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocyclic alkyl groups, and each of the heterocyclic ring systems are unsubstituted, Or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, -CN, -Ν02, an anthracene group, a heteroalkyl group, a functional group, a dilute group , dentate, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl 'cycloalkenyl, 'cycloalkyl, heterocycloalkenyl, azido' _ 〇 Rl 9, 〇 〇 c ( 〇)〇r2(), NR2lR22, _NR2 3S〇2R24, nr23c(〇)〇r2〇, NR23c(〇)R24, -S〇2NR25R26, _C(〇)R24, _c(〇)〇r20, SRl9 '柳汛19, -S02R]9, -〇C(〇)R2 4 λ -C(0)NR25R26 > -NR23C(N-CN)NR25R2 6 and -NR2 3 C(0)NR2 5 R2 6 groups; R14 is independently selected from the group consisting of anthracene, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, Alkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, 135177 •23- 200922559 Each of the hysters, the miscellaneous base, each of the rare bases, each of the heterogeneous batches of Ganzi Valley Each of the heteroaryl, each, α, the alkenyl, each of the heterocycloalkyl and each of the heterocycloalkyl are "unsubstituted, or optionally, mono- or di-, --, 丄 = independently selected from 'Base'*H heteroalkyl, cardinyl, dilute, =alkynyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, hydrazine, alkyl, heterocycloalkenyl, stack Nitrogen

Nr21d22 2, with base '-〇R19, -〇C_20, collar P, -NR23S〇2R24, tear 23c(〇)〇r2q, Nor-S〇2NR25R2 6, rrn.D2 4 , claw, s〇r19 'C( 〇)R '«2〇-sR^-s(0)r^ 〇C(〇)R24''C(〇)NR2^ and ~nr23c(〇)nr25r26 group; =(when not with R,6 When bonded) are independently selected from the group consisting of H, alkyl, miscible, cyclodecyl, heterolyl, hetero-based/radical, cycloalkyl,

L: each Na, each of the miscellaneous groups, each of the dilute groups, each of the heterobasic groups, each of the (tetra) groups, each of the aryl groups, each of the heteroaryl groups, and each of the cores: 4% by weight of each of the soils The heterocycloalkyl group and each of the heterocyclic alkene; are unsubstituted or, as the case may be, independently substituted by a plurality of substituents which may be the same differently substituted 'each substituent is independently selected from the group, the letter f, 'Tongji' miscellaneous base, dentate base, dilute base, sulphate, block base, halogen block, Guanqi, w ^ 瘫, cycloalkyl, cycloalkenyl, 2-cycloalkyl, heterocyclic Alkenyl, azido, _〇r19, _〇c(〇)〇r2〇, R22, 撒23咖24, _nr七(打2G, tearing 23c(〇)r24, 135177 •24- 200922559, -SR19, _s(〇)R〗 9, -NR23C(N-CN)NR25R26 -S02NR25R26, -C(〇)R2 4, c(〇)〇r2 0 -so2r19, -oc(o)r2 4, _c(0)nr25r26 And a group of -NR23C(0)NR25R26; each w when not bonded to R15) is independently selected from the group consisting of H, m alkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, hetero Aryl, cycloalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkyl,

And each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, each of the heterobasic groups, each of the alkynyl groups, each of the heteroblock groups, each of the aryl groups, each of the heteroaryl groups, and each of the heterocyclic groups And each of the cycloalkenyl groups, each of the heterocycloalkyl groups and each of the heterocyclic ring groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent Independently selected from (tetra), halogen, -cn, -N〇2, dean, ketone, pyrolyzed, dilute, (tetra), fast-radical, il-block, aryl, heteroaryl, cycloalkyl, ring Dilute, heterocycloalkyl, heterocycloalkenyl, azido, -ORR19, _oc(o)or20, 'NR2,R22'-NR23S〇2R24^-NR23C(〇)〇r20 . _NR23C(〇)R24 . Mom NR25R26, -C(〇)R24, -c(o)or2. , _SR19, 4 barrier 19, -S02R . -0C(0)R24 > -C(0)NR2 5R2 6 n -NR23C(N-CN)NR25R26 and -nr23c(o)nr25r26 group; or 'RMW and The U atoms to which they are attached form a heterocyclic alkyl or heterocyclic ring, containing - to three heteroatoms selected from the group consisting of 1^' and s, wherein the heterocycloalkyl ring and the heterocyclic alkene The base ring systems are each unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a lignin, a _CN, a _N02, an alkyl group, a hetero Affiliation, halogenated base, dilute base, dentate base, block base, tooth block 77-25- 200922559 base, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, ring Alkyl, cycloalkenyl, heterocycloalkyl 'heterocyclenyl, azido, _〇r19, -〇C(〇)〇R2. , _NR21R22, body 3s〇2r24, nr23c(〇)〇r20, NR C(〇)R, -S02 NR2 5 R2 6, _c(Q)R2 4, c(〇)〇r2 0, _sr1 9, -S( 0) Rl 9 . _S〇2 R1 9 . _〇C(〇)R2 4 N,C(〇)nr2 5 r2 6 . _NR2 3 C(N-CN)-NR25R26&_NR2 3C(〇)Nr25r26; 7 (when not bonded to Ri8) is independently selected from the group consisting of H, alkyl, heteroalkyl, dilute, heteroalkenyl, alkynyl, heteroalkynyl, fluorenyl, heteroaryl, cycloalkyl, Glycosyl, heterocycloalkyl, heterocycloalkenyl, _CN, _〇C(〇)〇r2〇, 9, NR R -NR23S02R24 ' -NR2 3 C(0)〇R2 0 > -NR23C(0)R24 > -so2nr25r26, _c(〇)r24, C(0)0R2G, sr19, s(〇)r19, code R19, -〇C(0)R2 4 . .C(〇)Nr2 5R2 6 , -NR2 3 C (N-CN)NR2 5 R2 6 ^ _NR2 3 C(〇)_ NR25R26 , wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl groups, each of the heteroalkenyl groups, each of the alkynyl groups, and each of the hetero An alkynyl group, each of the aryl groups, each of the heteroaryl groups, each of the alkyl groups, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, Substituted by one or more substituents which may be the same or different The base is independently selected from the group consisting of keto, halogen, -CN, -N02, alkyl, heteroalkyl, dentyl, alkenyl, alkenyl, alkynyl, alkynyl, aryl, heteroaryl, naphthenic Base, cycloalkenyl, 'cycloalkyl, heterocycloalkenyl, azide, 〇Rl9, _〇c(〇)〇r2〇, 娜1 R22, -NR23S02R24, -NR23C(0)〇R20,- NR23C(〇)R2 4, -S〇2NR25r26, c(〇)r24, _c(〇)〇r2〇, SRl9, 〇 〇 19, 'S〇2R'9 . -〇C(〇)R2 4 , . C(〇)NR25R26 > -NR23C(N-CN)NR2 5R2 6 135177 -26- 200922559 and a group of -nr23c(o)nr25r26; each R18 (when not joined to R17) is independently selected from the group consisting of Alkyl, heteroalkyl, dilute, hetero, fast, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocyclic, heterocyclic, _CN, _〇 c(〇)〇R20, _〇Rl 9, 妒2妒, _NR23s〇2R24, nr23c(〇)〇r2g, NR% (9) r24 -s〇2nr25r26, _C(0)R24, _c(〇)〇R2G, _SR 9, s(〇)rI9, _s〇2R] 9, 0C(0)R, -C(0)NR2 5 R2 6 , NR25R26, wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group, Each of the heteroalkenyl groups, each of the alkynyl groups, The heteroalkynyl group, each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be Independently substituted by one or more substituents which may be the same or different, each substituent is independently selected from the group consisting of a keto group, a halogen CN N〇2; a k-based 'homo" group, a haloalkyl group, an alkenyl group, a halogen group , alkynyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, 〇Rl 9, 〇〇c(〇)〇r2 〇, _NR2lR22, -NR23S〇2R24, -NR23C(〇)〇R2〇, _NR2 3c(〇)R2 4, -so2nr, 26, _c(〇)r24, c(〇)〇r2〇, Guan19, Na19 , S02R, _〇C(〇)R2 4, _c(〇)NR2 5R2 6 , _nr2 3c(N cn)nr25r26 and -nr23c(〇)nr25r26; group R lean R and their connected carbon The atoms together form a cycloalkyl, n-alkenylalkylene ring containing from one to three heteroatoms selected from N, 0 and S, or a heterocycloalkenyl ring containing from one to three selected from the group consisting of N, 0 and 5 heteroatoms, 135177 -27- 200922559 ^. Each of the heterocycloalkenyl rings and the heterocycloalkenyl ring system are unsubstituted or, as the case may be, independently substituted with or substituted by the same or different substituents, each substituent being independently selected from the group consisting of a ketone group and a halogen. , _CN, _N〇2, ^ group, miscible group, dentate group, alkenyl group, dentate group, block group, tooth fast aryl group, heteroaryl group, aryl-alkyl group, heteroaryl-alkane — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — ) 0R2° > C(〇)R2 4 λ -S〇2NR25R2 6 , _C(〇)R2 4 , _C(〇)〇R2 0 > -SR1 9 > (0)R, -S02 R1 9, - 〇C(〇)R2 4, c(〇)nr2 5 r2 6 , nr2 3 C(N CN) NR25R2 6^.nr23C(〇)nr25r26 ; each Rl9 is independently selected from the group consisting of H, alkyl 'dental alkyl, Heteroalkyl, dentylalkyl=yl, heteroaryl, cycloalkyl, A cycloalkyl; the two independently selected from the group consisting of anthracene, alkyl, south alkyl, heteroalkyl, diasteryl, aryl , heteroaryl, cycloalkyl, cycloalkyl; ^21 (when untouched 22) are independently selected from the group consisting of anthracene, cyclyl, i-alkyl, benzyl, haloalkyl, aryl Heteroaryl 'cycloalkyl, halocycloalkyl; each: 2 (when not bonded to R21) are independently selected from the group consisting of H, alkyl, haloalkyl, jk, chiral, aryl, hetero An aryl group, a ring-based group, a cyclyl group; or t'R2^R22 and the N atoms to which they are bonded, form a heterocyclic or heterocyclic ring, containing - to three selected from the group consisting of N, fluorene And a hetero atom of S; each R2: independently selected from the group consisting of hydrazine, alkyl, _alkyl, heteroalkyl, heteroalkyl, heteroaryl, cycloalkyl, cyclyl; Selected from the group consisting of hydrazine, alkyl, haloalkyl 'heteroalkyl, haloalkyl, heteroaryl, cycloalkyl, _cycloalkyl; 135177 -28- 200922559 when the core is not bonded to R26) Independently selected from the group consisting of anthracene, alkyl, (4), pyridyl, aryl, heteroaryl, weiji, _ ring; and each R26 (when not bonded to R25) is independent , the cargo is independently selected from the group consisting of H, alkyl, and alkyl groups.

a decyl group, a heteroalkyl group, an aryl group, a heteroatom I + a heterocyclic group, a cycloalkyl group, a halocycloalkyl group; = t(tetra) 6 and (d) a bonded heterocyclic alkyl group or an alkenyl group, containing one to Three are selected from heteroatoms including n, 〇M.

As explained in more detail below, it should be understood that ring A may have a

The article provides the unsaturation of the non-saturation of + u ' A thousand knives in the general chemical formula. Also provided is a pharmaceutical formulation or composition comprising a therapeutically effective amount of at least one compound of the invention' and/or a pharmaceutically acceptable salt, solvate, pharmaceutically active salt, or pharmaceutically acceptable salt thereof, and pharmaceutically acceptable A carrier is acceptable. A therapeutically effective amount of at least one compound of the invention (and/or a pharmaceutically acceptable salt, solvate, ester, prodrug or isomer thereof), and a pharmaceutically acceptable carrier, and/or Pharmaceutical formulations or compositions of various other active ingredients are also intended to be encompassed. Also provided are methods of treating a cell proliferative disorder, disorder, and/or inhibition of KSP-transferase activity associated with KSP-transferase activity in a patient, comprising administering to the patient in need of such treatment an effective amount of at least one species The present invention, or a formulation or composition according to the invention. The method according to the present invention can be used in a single-agent regimen, or as part of a multi-agent regimen, as appropriate, as appropriate to those skilled in the art. All of the amounts of ingredients, reaction conditions, etc. used in this patent specification and claims are included in the operating examples or in the claims: 135177 -29- 200922559 目 ' should be understood in all cases Amended by the "about" terminology. DETAILED DESCRIPTION In a specific embodiment, the compound of the present invention has the structure shown in formula (1) and includes a pharmaceutically acceptable salt, solvate, vinegar, prodrug or isomer of the compound. As described in formula (I) (and in other chemistry 1 of the specific examples of the compounds of the invention described herein, m ^ formula), 裱8 is a 4-8 membered cycloalkenyl or hetero P ring dilute base ring. It should be understood that such a cyclo- or heterocyclic-dense ring of ring A may have an unsaturation other than the one shown in the chemical formula provided herein. For the purpose of illustration only, non-limiting examples of such other unsaturations in Ring A include:

In a particular embodiment, in Formula 1, Ring A is a heterocyclic ring. In the specific embodiment, in Formula (1), Ring VIII is a 'member ring. In a specific embodiment, in Formula (I), Ring A is a 5-membered ring. In the specific embodiment, in Formula 1, the ring "6_member ring. In the specific embodiment, in the formula (1), the ring VIII is a 7-member ring. 135177 -30- 200922559 In the examples, in Formula (I), Ring A is an 8-membered ring. In one embodiment, in Formula (I), Ring A (including the unsaturation shown) is monounsaturated. In a particular embodiment, in Formula (I), Ring A (including the unsaturation shown) is polyunsaturated. In one embodiment, in Formula (I), E is -C. (R4)(R5)-. In a specific embodiment, in the formula (I), the E is selected from the group consisting of -〇-, -S-, -S(O)-, -S(0)2- , -N(R6)-, -N(C(Y)R7)-, -N(C(7)OR8)-, -N(C(Y)N(R9) (R10))- '-C(0)-N (Rn)- ' -N(Rn)-C(0)- ^ -S(0)2-N(Rn)- ' -N(R] 1 )-S(0)2-, -C(0) -0-, -OC(O)-, -0-N(R6)-, -N(R6)-0-, -N(R6)-N(R12)-, -N=N-, -C( R7 )=N-, -C(0)-C(R7 )=N-, :C(0)-N=N-,-0-C(Y)-N(Rn )-' -Νπ^ΚΧΥΚ» -, -N(R")-C(Y)-N(R12)-, -C(Y)-N(Rn)-0-, -(:(Υ)-Ν(Ι^ 1 )-N( R〗 2) -, -0-N(Rn)-C(Y)- and -N(R) 2)-Ν(Ι^ 1 )-C(Y)-. In the embodiment, in the formula (I), the E is selected from the group consisting of -O-, -S-, -S(O)-, -S(0)2-, and -N(R6)-. In a specific embodiment, 'in formula (I), E is selected from the group consisting of -〇-, -S-, -S(O)-, -S(0)2-, and -N(R6)-' wherein R6 is Selected from the group consisting of η, alkyl, -C(0)R24, -C(0)OR20, and -C(S)R24. In one embodiment, 'in formula (1), E is selected from the group consisting of -0- And -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, _c(0)R24, -C(0)OR20, and -C(S)R24. In a particular embodiment, In I), when E is -N(R6)-, then p is 0 and R3 is absent. In this particular embodiment, non-limiting examples of R6 include deuterium, alkyl '-C (0) R24, -C(0)〇r2〇 and _C(5)R2 4. 135Π7 -31 · 200922559 In a specific embodiment, in the formula (I), E is -0-. In a specific embodiment, In the formula (I), Ε is -S-. In a specific embodiment, in formula (I), Ε is -S(O)-. In a specific embodiment, in Formula (I), E is -S(0)2-. In a particular embodiment, in Formula (I), E is -CH2-. In a particular embodiment, in Formula (I), E is -CHR4-. In a specific embodiment, in Formula (I), E is -CR4R5-. In a specific embodiment, in Formula (I), E is -N(R6)-. In a particular embodiment, in Formula (I), E is -N(C(Y)R7)-. In a specific embodiment, in Formula (I), E is -N(C(Y)OR8)-. In a particular embodiment, in Formula (I), E is -NCCXY^CRlR1 〇)) - In one embodiment, in Formula (I), E is -CCCO-NCR11)-. In a specific embodiment, in Formula (I), E is -N(R! 1 )-C(0)-. In a specific embodiment, in Formula (I), E is -S(0)2-N(Rn)-. In a specific embodiment, in Formula (I), E is -N(I^1)-S(0)2-. In a specific embodiment, in Formula (I), E is -C(0)-0-. In a particular embodiment, in Formula (I), E is -O-C(O)-. In a particular embodiment, in Formula (I), E is-0-N(R6)-. In a specific embodiment, in Formula (I), E is -N(R6)-0-. In a specific embodiment, in Formula (I), E is -N(R6)-N(R)2-. In a specific embodiment, in Formula (I), E is -N=N-. In a specific embodiment, in Formula (I), E is -C(R7)=N-. In a specific embodiment, in Formula (I), E is -C(0)-C(R7)=N-. In a specific embodiment, in Formula (I), E is -C(0)-N=N-. 135177 • 32- 200922559 In a specific embodiment 'In the formula (I), E is -O-CXY^I-NCR11)-. In a particular embodiment, in Formula (I), E is -N(Rn)-C(Y)-0-. In a specific embodiment, in the formula (I), E is -Ν(Ι^ 1 2)-. In a specific embodiment 'in Formula 1, E is _C(Y)_N(Ri 1 . In a specific embodiment, in Formula (I), E is -QD-NOl11)-Ν( Ι^ 2)-. In one embodiment, 'in formula (I), Ε is -O-NCR11)-C(Y)-. In a specific embodiment, in the formula (I), E is _N(Ri 2)_n(ri 1 )_c(7)_. In a specific embodiment, in formula (I), γ is (=〇). In a specific embodiment 'in formula (I), γ is (=S). In a specific embodiment, in the formula (1), γ is (=N(Ri 3)). In a specific embodiment, in formula (I), γ is (=N(CN)). In a specific embodiment, in Formula (I), γ is (sNCOR1 4)). In a specific embodiment, in the formula (I), γ is (=Ν(ί^ 5)(R]6)). In a specific embodiment, in Formula (1), γ is (=c(Ri 7)(ri.) In one embodiment, in Formula (I), Ring A is a 4-7-membered ring. Alkyl ring, and E is -C(R4)(R5)-. In a particular embodiment, in Formula (I), Ring A is a 5-7-membered heterocycloalkyl ring' and the E is Selected from including _〇_, _S_, _S(9)_, _s(〇)2-, -N(R6)-, -N(C(Y)R7)-^-N(C(Y)〇R8). . -N (C(Y)N(R9)(R10))- > -C(0)-N(R] 1)- ' -N(Rn)-C(0)_, -S(〇)2-N (Rn)-, -N(Rn)-S(0)2-, -C(0)-0_, -0-C(0)- ' -0-N(R6)- ^ -N(R6)- 〇- ^ -N(R6)-N(R' 2)- ' -N=N- ' -C(R7)=N-' -C(0)-C(R7 )=N·, -C(〇 )-N=N-,-0-C(Y)-N(Rn)---N(Rn)-C(Y)-0-, -0-N(Rn)-C(Y)-and- I^R1 2)-Ν(Ι^ 1 )-C(Y)-. 135177 -33- 200922559 In a specific embodiment 'in formula (I), ring A is a 5-6-membered heterocyclic ring Burning base % ' and E is selected from the group consisting of -〇-, _; §-, -S(O)-, -S(0)2-, -N(R6), -C(0)-N(Rn) - and -N(R) 1 )-C(0)-. In a particular embodiment, in Formula 1, ring VIII is a 5-6-membered heterocycloalkyl ring, and E is selected from the group consisting of -〇 -, _S-, _s(〇)_, _ disaster) 2_ and _峨6) _. In one such embodiment, in formula (1), r6 is selected from the group consisting of H, alkyl, -C(〇)R2 4, _C(〇)〇R2Q, and _c(s)r24. In one embodiment, 'in Formula 1, Ring A is a 5-6-membered heterocyclic ring' and E is selected from the group consisting of -〇· and _N(R6)_. In one such embodiment, in Formula (I), R6 is selected from the group consisting of η, alkyl, _c(〇)R24, _c(〇)〇r20, and -C(5)R2 4 . In one such specific embodiment, in Formula 1, ring a is a 5-membered heterocycloalkyl ring. In another such specific embodiment, in Formula (1), Ring A is a 6-membered heterocycloalkyl ring. In a specific embodiment, in Formula (I), Ring A is a 4-membered ring and E is -C(R4)(R5)- in one embodiment, in Formula (I) , Ring A is a 4-membered ring, and E is selected from the group consisting of -0, -S-, -S(O)-, -S(0)2-, -N(R6)-, -N(C(Y) ) R7)-, -N(C(Y)OR8)- . -N(C(Y)N(R9)(R10))- ' -C(0)-N(Rn)- > -N(Rn )-C(0)-' -S(0)2-N(R11)- ' -N(R'1 )-S(0)2- ' -C(0)-0- ' -OC(O) - ' -0-N(R6)- ' -N(R6)-0-, -N(R6)-N(R12)-, -N=N-, -C(R7)=N-, -C( 0)-C(R7)=N-, -C(0)-N=N- > ^^(Y^R11)- '-N(RJ 1 )-C(Y)-0- ' -N( R] 1 )-C(Y)-N(R12)-, -C(Y)-N(Rn)-0-, -C(Y)-N(Rn)-N(R12)-,-0- N(Ru)-C(Y)- and -N(R12)-N(Rn)-C(Y)-. In a specific embodiment, in Formula (I), Ring A is a 4-membered ring, and E is 135177-34-200922559 selected from the group consisting of -〇-, -S-, -S(O)-, - S(0)2- and -N(R6)-. In a specific embodiment 'in the formula (1), the ring A is a 4-membered ring, and the ugly is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2- and —N(R6)_, wherein r6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, -C(0)〇R2〇&_C(S)R2 4. In a specific embodiment 'in formula (1), ring A is a 4-membered ring, and e is selected from the group consisting of -0- and -N(R6)-' wherein R6 is selected from the group consisting of η, alkyl, C(0)R24, _C(0)0R20 and -C(S)R24. In a specific embodiment, in Formula (I), Ring A is a 4-membered ring, and E is selected from the group consisting of -0_, _S-, -S(0)-, -S(0)2_, _c (R4) (r5)_, _n(r6)_, -N(C(Y)R7)-, -N(C(Y)0R8)-,. In a particular embodiment, in Formula (I), A is a 4-membered ring and E is selected from the group consisting of -CH2-, -CH(R4)-, -C(R4)(R5)-. In a particular embodiment, in Formula (I), Ring A is a 5-membered ring and E is -C(R4)(R5)-. In a specific embodiment, in Formula (I), Ring A is a 5-membered ring, and E is selected from the group consisting of -0-, -S_, -S(0)-, -S(0)2_, _N(R6)-, _N(C(Y)R7)-, -N(C(Y)0R8)-, -N(C(Y)N(R9)(R1Q))-'-C(0)- N(Rn)-, -N(R")-C(0)-' -S(0)2-N(R'1)- '-N(R] 1 )-S(0)2- ' - C(0)-0- ' -0-C(0)- > -〇-N(R6)- ' -N(R6)-0- ' -N(R6)-N(R12)- ' -N =N- ' -C(R7)=N- ' -C(0)-C(R7 )=N- ' -C(0)-N=N- ' -0-C(Y)-N(R11) - ' -NCR11 >C(Y)-0- ' -NCR11 )-C(Y)-N(R] 2)- ' -C(Y)-N(R'1 )-0- ' -C( Y)-N(R'1)-N(R] 2)- '-O-NCR11 )-C(Y)- and -N(R12)-N(Rn)-C(Y)-. In a specific embodiment, in Formula (I), Ring A is a 5-membered ring and E is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2 -and-N(R6)-. 135177 • 35- 200922559 In a specific embodiment, in Formula (I), Ring A is a 5-membered ring and the E is selected from the group consisting of -0-, -S-, -S(O)-, - S(0)2- and -N(R6)-, wherein r6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, -C(0)OR20, and -C(S)R24. In a specific embodiment, in Formula (I), Ring A is a 5-membered ring and E is selected from the group consisting of -0- and -N(R6)-, wherein R6 is selected from the group consisting of ruthenium and ruthenium. -C(0)R24, -C(0)OR20 and -C(S)R24. In a specific embodiment, in the formula (I), 'ring A is a 5-membered ring, and E is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2 -, -C(R4)(R5)-,)_, -N(C(Y)R7)- > -N(C(Y)〇R8)- '-N(C(Y)N(R9) (R10))- > -C(〇)-N(Ri i).. -N(Rn )-C(0)-, -S(0)2 -N(R]1)-, -N^ 11 )-S(0)2 -, -C(0)-〇-, _ac(〇)_, -0-N(R6)-, -N(R6)-0-, -N(R6)-N (R12)-, _N=N_ and -c(R7)=n_. In a specific embodiment 'in the formula (I), A is a 5-membered ring, and E is _〇... In a specific embodiment, in the formula (I), 'A is a 5-membered ring, And E is _s_. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -S(O)-. In a particular embodiment, in Formula (I), A is a 5-membered ring and E is -S(〇)2-. In a particular embodiment, in Formula (I), A is a 5-membered ring and E is -C(R4)(R5)-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -N(R6)-. In a specific embodiment, in the formula φ, A is a 5-membered ring and E is -N(C(Y)R7)-. And E is a specific embodiment, in the formula (I), A is a 5-membered ring, 135177-36-200922559-N(C(Y)OR8)-. In a particular embodiment, in Formula (I), A is a 5-membered ring and E is -N(C(Y)N(R9)(R1()))-. In a particular embodiment, in Formula (I), A is a 5-membered ring and E is -C(0)-N(Rn)-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -N(Rn)-C(0)-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -S(0)2-N(R")-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -N(Rn)-S(0)2-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -C(0)-0-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -o-c(o)-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -0-N(R6)-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -N(R6)-0-. In a particular embodiment, in Formula (I), A is a 5-membered ring and E is -N(R6)-N(R12)-. In a specific embodiment, in Formula (I), A is a 5-membered ring and E is -N=N-. In a specific embodiment, in Formula 1, A is a 5-membered ring, and E is 135177 - η - 200922559 - C(R7) = N-. In a particular embodiment, in Formula (I), Ring A is a 6-membered ring and e is -C(R4)(R5)-. In a specific embodiment, in Formula (I), Ring A is a 6-membered ring, and E is selected from the group consisting of -0-, -S-, -S(O)-, -S(0)2_ , -N(R6)-, _n(C(Y)R7)-, -N(C(Y)OR8)-, -N(C(Y)N(R9)(R10))-, -C(0 )-N(R]1)-, _N(Rii )_〇;〇)_ ' -S(0)2-N(R'1)- ^ -N(R] 1 )-S(0)2- > -C(0)-0- '-OC(O)- > -〇-N(R6)- > -N(R6)-0-, -N(R6)-N(R12)-, -N=N-, -C(R7)=N-, -C(〇)-C(R7)=N-, -C(0)-N=N- > -0-C(Y)-N (R11)- ^ -N(R! 1 )-C(Y)-〇- > -N(R] 1 )-C(Y)-N(R12)-, -C-wind ruler 11)- 〇-, -〇;丫)-wind ruler 11)-1^佴12)-, -〇_风1111)-(:(丫)- In a specific embodiment, in the formula (I), the ring A is a 6-membered ring and the E is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2-, and -N(R6)-. In one embodiment In the formula (I), the ring A is a 6-membered ring, and the E is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2-, and -N(R6). - wherein r6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, -C(0)0R20 and -C(S)R24. In a particular embodiment, in formula (I), A is a 6-membered ring, and the E is selected from the group consisting of -0- and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, and -C ( 0) R24, -C(0)0R20 and -C(S)R24. In a particular embodiment, in Formula (I), A is a 6-membered ring and the E is selected from the group consisting of -0-, Each, -5 (0)-, -3 (0) 2-, - (: (foot 4) (115) -, - wind 116) -, - wind (: (丫) ruler 7) -, -N ( C(Y)OR8)-, -N(C(Y)N(R9)(R10))-, -C(O)-N(Ru)-, -N(Rn)-C(0)-,- S(0)2-N(Rn)-, -N(RU)-S(0)2-, -C(0)-0- ' -〇-C(0)-, -0-N(R6) -, -N(R6)-0-, -N(R6)-N(R12)-, -N=N-, -C(R7)=N-, 135177 -38- 200922559 -C(0)-C (R7)=N- ' -C(0)-N=N- ' -0-C(Y)-N(R11)- ' ^(R11 )-C(Y)-0- ' -O-NOl1 1 )-C(Y)- and -N^1 2)-N(Rn)-C(Y)-. In a specific embodiment, in Formula (I), Ring A is a 6-membered ring and E is -0- in one embodiment. In Formula (I), Ring A is 6- A member ring, and E is -S- in one embodiment. In the formula (I), ring A is a 6-membered ring and E is -S(0)-. In a specific embodiment, in Formula (I), Ring A is a 6-membered ring and E is -S(0)2-. In a specific embodiment, in Formula 1, Ring A is a 6-membered ring and E is -C(R4)(R5)-. In a specific embodiment, in Formula (1), Ring A is a 6-membered ring and E is -N(R6)-. In the specific embodiment, in the formula (1), the ring VIII is a 6-membered ring, and £ is -N(C(Y)R7)-. In a specific embodiment, in the formula (1), the ring A is a 6-membered ring ' jlE is -N(C(Y)OR8)-. In a specific embodiment -N(C(Y)N(R9)(R10))... In a particular embodiment -C(0)-N(Rn)-〇 is in a specific embodiment In the formula (I), 'ring A is a 6-membered ring, and E is in the formula (I), 'ring A is a 6-membered ring, and e is in the formula (I), and ring A is a 6-membered ring. And e is 135177 •39- 200922559 -N(Rn)-C(0)-. In a specific embodiment, in the formula (I) -S(0)2-N(Rn)-. In one embodiment, in the formula 1, the ring -N(Rn)-S(0)2-. In a specific embodiment -c(o)-o-. In a specific embodiment -O-C(O)-. In one embodiment -0-N(R6)-. In a specific embodiment -N(R6)-0-. In a particular embodiment -N(R6)-N(R12)-. In a specific embodiment -N=N_. In one embodiment -C(R7) = N-. In one embodiment -C(0)-C(R7)=N-. In a specific embodiment -C(0)-N=N-. In a specific embodiment, ring A is 6-membered ring A is 6_member 'in formula (1), ring eight is 6_member ring' in formula (I), ring eight is a member ring, In the formula (1), the ring VIII is a member ring, and in the formula (1), the ring A is a ring of a member, and in the formula (1), the ring is a ring of a 6-member ring in the formula (1). Into the 6_member | 'In the formula (1), the ring eight is the 6_member ring, in the formula (1), the ring A is the 6-membered ring 'in the formula (I) 'the ring A is the 6-member Ring, in formula (I), ring A is a 6-membered ring, and E is, and E is, and day is, and ε is and Ε is, and Ε is, and £ is, and Ε is, and £ For, and Ε, and Ε 135 135177 -40- 200922559 -0-C(Y)-N(Ru)-. In one embodiment, 'in formula (I)' ring A is a 6-membered ring and E is -N(Rn)-C(Y)-0-. In a particular embodiment, in Formula (I), Ring A is a 6-membered ring and e is -N(Rn)-C(Y)-N(R12)-. In a particular embodiment, in Formula (I), Ring A is a 6-membered ring and E is -C(Y)-N(Rn)-0-. In a particular embodiment, in Formula (I), Ring A is a 6-membered ring and e is -C(Y)-N(Rn)-N(R12)-. In a particular embodiment, in Formula (I), Ring A is a 6-membered ring and e is -O-NiR1 1 )-C(Y)-. In a particular embodiment, in Formula (I), Ring A is a 6-membered ring and E is -N(R12)-N(Rn)-C(Y)-. In a particular embodiment, in Formula (I), Ring A is a 7-membered ring and E is -C(R4)(R5)-. In a specific embodiment 'in formula (I), ring A is a 7-membered ring and E is selected from the group consisting of -0-, -S-, -S(O)-, -S(0)2 -, -N(R6)-, _n(C(7)R7)-, -N(C(Y)0R8)- > -N(C(Y)N(R9)(R10))- ^ -C(0)- N(R^)_ , -N(Rn )-C(0)-' -S(0)2-N(R'1)- ^ -N(R' 1 )-S(0)2- ^ - C(0)-0- > -0-C(〇)- . -〇-N(R6)- ^ -N(R6)-0-, -N(R6)-N(R12)-, -N =N-, -C(R7)=N-, -C(〇)-C(R7)=N-, -C(0)-N=N- ' -0-C(Y)-N(R] 1)- ' -N(R'1 )-C(Y)-〇- > .^R11 )-C(Y)-N(R12)- > -C(Y)-N(Rn )-〇 - '-C(Y)-N(Rn)-N(R12)., -O.^R11 >C(Y)- and -N(R12)-N(Rn)-C(Y)-. In a specific embodiment, in Formula (I), Ring A is a 7-membered ring, and E is -41 - 135177 200922559 is selected from the group consisting of -Ο-, -S-, -S(O)-, - S(0)2- and -N(R6)-. In a specific embodiment, in Formula (I), Ring A is a 7-membered ring and E is selected from the group consisting of -0-, -S-, -S(O)-, -S(0)2 - and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, -C(0)OR20 and -C(S)R24. In a specific embodiment, in Formula (I), Ring A is a 7-membered ring, and E is selected from the group consisting of -0- and -N(R6)-, wherein R6 is selected from the group consisting of ruthenium and alkyl. -C(0)R24, -C(0)0R20 and -C(S)R24. In a specific embodiment, in Formula (I), Ring A is a 7-membered ring, and E is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2 -, -C(R4)(R5)-, -N(R6)-, -N(C(Y)R7)-, -N(C(Y)0R8)-, -N(C(Y)N( R9)(R10))-, -C(0)-N(R11)-, -N(R11)-C(0)-, -S(0)2-N(R11)- '-N(R11) -S(0)2-, -C(0)-0-, -0-C(0)-, -0-N(R6)-, -N(R6)-0-, -N(R6)- N(R12)-, -N=N-, -C(R7)=N-, -C(0)-C(R7)=N-, -C(0)-N=N-,-0-C (Y)-N(Rll)-, -N(Rll)-C(Y)-0-, -N(R11)-C(Y)-N(R12)-, -C(Y)-N(R11 )-0-, -C(Y)-N(R11)-N(R12)-, -0-N(Rll)-C(Y)-, and -N(R12)-N(R11)-C(Y )-. In a specific embodiment, in Formula (1), A is a 7-membered ring and E is -0-. In a specific embodiment, in Formula (1), A is a 7-membered ring and E is -S-. In a specific embodiment, in Formula 1, A is a 7-membered ring and E is -S(0)-. In a specific embodiment, in Formula (I), A is a 7-membered ring and E is -S(0)2-. In a particular embodiment, in Formula (I), A is a 7-membered ring and E is -C(R4)(R5)-. In a particular embodiment, in Formula (I), A is a 7-membered ring and E is 135177 42-200922559 r -N(R6)-. In a specific embodiment -N(C(Y)R7)-. In a specific embodiment -N(C(Y)OR8)-. In a specific embodiment - wind (: (丫) 1 ^ (119) (1 ^ 〇)) _. In a specific embodiment -C(0)-N(Rn)-. In the formula (1), 'eight is 7, the member ring is in the formula (I), in the formula (I), in the formula (I), A is a 7-membered ring in a specific embodiment, In Formula 1, A is a 7-membered ring -N(Rn)-C(0)-. In a specific embodiment, in the formula (I), the horse 7~ member ring -S(0)2-N(Rn)-. In a specific embodiment, in the formula (I), A is 7 to bet ring-N(Rn)-S(0)2-. In a specific embodiment, in Formula (I), A氐7 〇8 sentences/-member rings-C(〇)-0- 〇 In a specific embodiment 'in Formula (I), A亘1 QA horse 7-bee ring-OC(O)·. In a specific embodiment, in the formula (I), A is 7-member Jf -0-N(R6)-. In a specific embodiment, in the formula (I), A is a 7-membered ring -N(R6)-0-. In a specific embodiment, 'in formula (I), A is a 7-membered ring, and E is, and E is, and E is, and E is, and E is, and E is, and E is, And E is, and E is, and E is, and E is, and E is 135177 -43- 200922559 -N(R6)-N(R12)-. In a specific embodiment, in the formula Φ, Δ & , and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is 7 is a 7-membered ring - N = N-. 'In the formula (1) 'A is a 7-membered ring' In the formula (1), A is a 7_member ring, and the formula (" 'A is a 7_member ring' in the formula (" 'A is 7_ In the formula (I), A is a 7-membered ring, and in the formula 1, A is a 7-membered ring in a particular embodiment -C(R7)=N-. In a specific embodiment -C(0)-C(R7)=N- in a particular embodiment -C(0)-N=N-. In one embodiment -0-C(Y)-N( Rn)-. In a particular embodiment -N(Rn)-C(Y)-0-. In a particular embodiment -N(Rn)-C(Y)-N(R12)-. In a specific embodiment, in Formula (I), A is 7-membered ring-C(Y)-N(Rn)-0-. In one embodiment, in Formula (I), A Is a 1-membered ring -C(Y)-N(R11)-N(R12)-. In a specific embodiment, in the formula (I), A is a 7-membered ring-0-N(Rn)- C(Y)-. In a particular embodiment, in Formula (I), A is a 7-membered ring-N(R12)-N(Rn)-C(Y)-. In a specific embodiment In Formula 1, Ring A is an 8-membered ring, and e is 135177 200922559 -C(R4)(R5)-. In one embodiment, in Formula (1), 'Ring A is 8- Member ring, and E is selected from the group consisting of -0-, -S-, -S(O)-, -S(0)2- -N(R6)-, -N(C(Y)R7)-, -N(C(Y)OR8)-, -N(C(Y)N(R9)(R10))-, -C(〇 )-N(Rn)-, -N(Rn)-C(0)-' -S(0)2-N(R] 1)- ' -N(R] 1 )-S(0)2- ' -C(0)-0- > -OC(O)- ^ -〇-N(R6)- > -N(R6)-0-, -N(R6)-N(RI2)_, -N =N-, -C(R7)=N-, -C(0)-C(R7)=N-, -C(0)-N=N- '-O-CCY^NiR11)- '-NCR11 ) -C(Y)-0- ^ -NCR11 >C(Y)-N(R12)- ^ -C(Y)-N(R] 1 )-0- ' -C(Y)-N(Rn) -N(R12)- > -〇-N(R] 1 )-C(Y)- and -wind!^2)-^!^1)-^?)-. In a specific embodiment, in Formula (I), Ring A is an 8-membered ring and E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2 -and-N(R6)-. In a specific embodiment, in the formula (I), 'ring A is an 8-membered ring, and E is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2. - and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, -C(0)0R20 and -C(S)R24. In a specific embodiment, in Formula (I), Ring A is an 8-membered ring and E is selected from the group consisting of -0- and -N(R6)-, wherein R6 is selected from the group consisting of ruthenium and alkyl. -C(0)R24, -C(0)0R20 and -C(S)R24. In a specific embodiment, in Formula (I), Ring A is an 8-membered ring and E is selected from the group consisting of -0-, -S-, -S(0)-, -S(0)2 -, -C(R4)(R5)-, -N(R6)-, -N(C(Y)R7)-, -N(C(Y)0R8)-, -N(C(Y)N( R9)(R10))-, -C(〇)-N(Rn)-, -NCR11)-C(0)- > -S(0)2-N(R11)- ^ -N(RJ 1 ) -S(0)2- ^ -C(0)-0- ^ -0-C(0)-,-0-N(R6)-, -N(R6)-0-, -N(R6)- N(R12)-, -N=N-, -C(R7)=N-, -C(0)-C(R7)=N-, -C(0)-N=N-,-0-C (Y)-N(Rn)-, -N(Rn)-C(Y)-0-, -N(Rn)-C(Y)-N(R12)-, -C(Y)-N(Ru )-0-, -C(Y)-N(Rn)-N(R12)-, 135177 • 45· 200922559 -0-Ν(Ι^ 1 )-C(Y)- and -NCR1 'I^R11 ) -C(Y)-. In a specific embodiment, 'in formula (I), A is an 8-member ring in a particular embodiment, and in formula (I), A is an 8-member ring in a particular embodiment, In the formula (I), A is 8-member-S(O)-. In a specific embodiment, in the formula (I), A is 8-member-s(o)2-. In one embodiment, in Formula (I), A is 8-member f-C(R4)(R5)-. In a specific embodiment, in Formula (I), A is 8-member-N(R6)-. In a specific embodiment, in the formula (I), A is 8-member-N(C(Y)R7)-. In a specific embodiment, in Formula (I), A is 8_ member -N(C(7)OR8)-. ^ In a specific embodiment, in Formula (I), A is 8-member \, -N(C(Y)N(R9)(RM))-. In a specific embodiment 'In the formula φ, A is 8-member-C(0)-N(Rn)-. In a specific embodiment, in the formula (I), A is 8-member-N(Rn)-C(0)-. In a specific embodiment 'in Formula 1, A is 8-member-S(0)2-N(Rn)... In a specific embodiment, in Formula (I), A is 8, member And E is -◦-. And E is -S-. a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring, and E is a ring Ring, and E is 135177 -46- 200922559 -N(Rn)-S(0)2-. In a specific embodiment, in Formula (I), A is an 8-membered ring -c(o)-o-. In a specific embodiment, in Formula (I), A is an 8-membered ring -o-c(o)-. In a specific embodiment, in Formula (I), A is 8-membered ring -0-N(R6)-. In a specific embodiment, in Formula (I), A is 8-membered ring 1 _N(R6)-0-. In a particular embodiment, in Formula (I), A is 8-membered ring -N(R6)-N(R12)-. In a specific embodiment, in Formula (I), A is an 8-membered ring -N=N-. In a specific embodiment, in Formula (I), A is an 8-membered ring -C(R7)=N-. In one embodiment, in Formula (I), A is 8-membered ring -C(0)-C(R7)=N-. In a specific embodiment, in Formula (I), A is an 8-membered ring -C(0)-N=N-. In a specific embodiment, in Formula (I), A is 8-membered ring -0-C(Y)-N(Rn)-. In a particular embodiment, in Formula (I), A is 8-membered ring -N(Rn)-C(Y)-0-. In a specific embodiment, in Formula (I), A is an 8-membered ring, and E is, and E is, and E is, and E is, and E is, and E is, and E is, And E is, and E is, and E is, and E is, and E is 135177 -47 - 200922559 -N(Rn)-C(Y)-N(R12)-. A is a 8~ member ring, and E is A is an 8-member ring, and £ is an 8-member ring, and e is A is an 8-member ring, and E is B is unsubstituted and stupid. In a specific embodiment, -C(Y)-N(Rn)-〇- is in Formula 1. In a specific embodiment 'in the formula (I) -C(Y)-N(Rn)-N(R]2)-. In a specific embodiment, in Formula 1, -0-N(Rn)-C(Y)-. In a particular embodiment, in formula (I) -N(R12)-N(Rn)-C(Y)-. Ring B is an unsubstituted or sulfur phenyl ring. In a particular embodiment, the benzo is substituted in formula (I), or unsubstituted or substituted in a particular embodiment, in the formula (1) with or without a substituted thiophenyl ring. In a specific embodiment, in Formula 1, ring B is an unsubstituted aryl, fluorene or an aromatic ring substituted by one or more substituents which may be the same or different, each substituent Independently selected from halogen, _CN, _N〇2 'alkyl, heteroalkyl, _alkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl_ , heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocyclic, heterocycloalkenyl, azido, _〇r19, _〇C(〇)〇r20, _nr21r22, -NR23S〇2r2 4 x -NR23C(0)〇r2〇, -NR23C(0)R24 ' -so2nr25r26 > 'C(〇)R24, -C(0)OR20, -SR19, -S(0)R19, -S02R19,- 0C(0)R24, _C(〇)NR2 5 r2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 . In a specific embodiment, in the formula (I), the ring B is an unsubstituted benzoin % or is substituted by one or more substituents which may be substituted by the same or different substituents 135177 -48- 200922559 'Each substituent is independently selected from the group consisting of halogen, -CN, -N02, alkyl, heteroalkyl, i-alkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl-heteroaryl, aromatic -alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocyclic k-, heterocycloalkenyl, azido, _0RI9, _〇C(〇)〇R20, _NR2 1R22, -NR23S〇2R2 4, _nr23C(〇)〇r2〇, _nr23c(〇)r24, s〇2Nr25r26, _C(〇)R24, -C(〇)〇R20, -SR19, -S(0)R19, -S02R19 , -〇C(0)R24, _C(〇)NR2 5 R2 6, NR 2 3 C(N-CN)NR2 5 R2 6 and _NR2 3 c(〇)NR2 5 r2 6. f -; In a particular embodiment 'in formula (I), ring B is an unsubstituted or substituted heteroaromatic ring, or a substituted heteroaromatic ring, which is one or more Substituted for the same or different substituents, each substituent is independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, i! Alkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, anthracenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkyl, azide, -ORl 9 -〇C(〇)〇R2 0 , -nr21r22 ^ -NR2 3S〇2r2 4 . -nr23c(〇)〇r20 . ~NR23C(0)R24, -S〇2NR25R26, -C(〇)R24,-C (〇)〇R2〇, _SR19, / 'S(0)R19 . _S〇2Ri9 λ -〇C(〇)r2 4 λ _c(〇)NR25R26 , -NR2 3 C(N-CN)- NR 5R26 and _ NR23c (〇) nr25r26. In one such specific embodiment, in Formula (I), Ring B is a 5-6-membered heteroaromatic ring having independently 3 selected heteroatoms of the same or different ring heteroatoms. It includes Ν, 5, 〇, s(〇) and S(〇)2. In a specific embodiment, in Formula (1), Ring B is an unsubstituted or substituted moiety selected from the group consisting of benzo, furyl, thiophenyl, pyrrolyl, oxazolyl, pyrazole Base, imidazolyl, pyrazolyl, isosigma, thiazolidine, oxadiazolyl, oxadiazolyl, pyridyl, hydrazine, pyrimidinyl, pyr 135177 -49- 200922559 Three p well base. 'Ring B is an unsubstituted aryl ring' which is unsubstituted and is stupid in a particular embodiment, in the ring of formula (I). In a specific embodiment, in Formula 1 and %•' and Formula (I) has the following general structure:

FT In the specific embodiment, in Formula 1, the W aromatic ring, which is substituted by the same or different substituents, each substituent is independent * 匕 匕, _CN, _N 〇 2 , yard base, miscellaneous base, south alkyl, dilute, (tetra), alkynyl, halo, aryl, heteroaryl, aryl like...hetero = fluorenyl, cycloaliphatic, heterocyclic Anthracyl, heterocycloalkenyl, stacked bauxite, -〇R, -oc(0)OR2〇, _nr21r22, Na-NR23C(〇)〇R2〇' _nr23c(0)r24, s〇2nr25r26, 2, -C (〇)OR2〇, _SR,^ _S(〇)r19 _s〇2R]9^ -nr23c(N-CN)nr25r26 and -nr23c(〇)nr25r26. In a specific embodiment, in the formula (I), 'B is stupid and produced- or a plurality of substituents which may be the same or different substituents are selected from the group consisting of: -C, -CN, _N〇2, and Base, oxime, second generation base * dilute group, fast group, dentate group, aryl group, heteroaryl group, aryldiyl group, lacquer base group, cycloalkyl group, ring-dense group, heterocyclic group, hetero-: 135177 -50- 200922559 Nitrogen' -OR]9, -OC(0)OR20, -NR21R22, -NR23S〇2R2 4, -NR23C(0)〇R2〇, -NR23C(0)R24, -S02NR25R26, _C( 0) R2 4, -C(0)〇R2〇, _SRl 9, 5(0)Κ1 9, _s〇2Ri 9, 〇〇c(〇)r24, c(〇)nr25r26, -NR2 3 C(N -CN) NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In a particular embodiment, in Formula (I), B is an unsubstituted heteroaromatic ring.

In a specific embodiment, in the formula (I), B is an unsubstituted 5-6-membered heteroaromatic ring 'having _3 ring heteroatoms which may be the same or different, and each hetero atom is independently selected. It includes N, S, Ο, S(0) and S(0)2. In a particular embodiment, in Formula (I), B is a heteroaromatic ring substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of -CN, _N 〇 2, alkyl, heteroalkyl, dentate, alkenyl squary, 'blocky', haloalkynyl, aryl, heteroaryl, aryl, alkyl, aryl-alkyl , cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -OR19, _〇c(〇)〇r20, _nr2!r22, _nr23s〇2R24, -NR2 3C(〇)〇 R2〇. -NR2 3C(〇)R2 4 λ -S〇2NR2 5R2 6 λ _C(〇)r2 4 C(0)〇R2 〇, _SRl 9、·5(〇)κ1 9、s〇2 r1 9. %(9)r2 *, _c(9)nr2 5 ft 2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 ^ _nr2 3 C(〇)nr2 5 R26 〇: In a specific embodiment, in formula (I), 3 For the heteroaromatic ring, it is selected from the group consisting of IT, which are the same or different ring heteroatoms, and each hetero atom is independently: the same or V: And s(0)2, the heteroaromatic ring system is substituted by - or more than 4, _CN, : 〇 = group 'each substituent is independently selected from the group consisting of a peryl group, an alkyne A group, a heteroalkyl group' Alkyl, alkenyl, olefinic, aryl, heteroaryl, aryl-alkyl-, heteroaryl _ 135177 -51 - 200922559 alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkane Base, heterocyclic ring, azide, -◦R19, ·◦(10)(10). ' _NR2 丨, _NR23S〇2R24, tear 23^咖〇, -NR"C(0)r24, code nr25r26, (_24, c(〇)〇r2g, system 9, -S(9)R 丨UQ2R'_(X:(0 R24, _c_r25r26, cis NR2 5 R2 6 and _NR2 3 C(〇)NR2 5 R2 6. In one embodiment, 'in the formula (I) A, B is an unsubstituted 6-membered heteroaromatic ring Having 1-3 ring heteroatoms which may be (four) or different, each hetero atom atom is independently selected from the group consisting of N, S and oxime. In the specific embodiment, in the formula (1), 3 is 6 a heteroaromatic ring having 1-3 ring heteroatoms which may be the same or different, each hetero atom atom is independently selected from the group consisting of N, S and 0'. The heteroaromatic ring system is _ or a plurality of Substituted by the same or different substituents, each substituent is independently selected from the group consisting of (tetra)pyrene-n〇2, alkyl, minus-m', "base, block, aryl, aryl, heteroaryl" , aryl aryl _, heteroaryl ketone ... cycloalkyl, cycloaliphatic, heterocyclic leukoxyl, heterocycloalkenyl, azido, _ 〇 Rl9, κ fly _NR23SQ2R24, view 23c (〇) Qr2, 视~(9)心, -S〇2NR25R26, -C(〇)R24, -C(〇W2Q, -SR19, _s(〇)Rl9, _s〇2R] 9, 〇C(〇)R24, NR25R26, _nr23qn_cn)Nr25r24 2 NR2 5R26. In the embodiment, '纟(I) towel' B is unsubstituted 6

It is known that %' has two ring heteroatoms, and each ring hetero atom is mono-independent. In the specific example, in Formula 1, 3 is a 6-membered heteroaromatic ring having 2 ring heteroatoms, each ring hetero atom is independently selected from ν, dioxa 135177 -52· 200922559 It is understood that one or more substituents may be substituted by the same or different substituents, each substituent being independently selected from the group consisting of halogen, -CN, _N〇2, alkyl, heteroalkyl, south alkyl, alkenyl, dentate Alkenyl, fluorenyl, dentate, aryl, heteroaryl, aryl-alkyl-, heteroarylalkyl...cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero- to-yl, azide Base, move 9' _〇c(〇)〇r2 0, tear 2]r2 2, Na 3 milk... -NR-C(〇)〇R2〇. _NR23C(〇)R24 . _s〇2Nr25r26 ^ . 24 ' - C(0)〇R2〇. _SR> 9 . .S(0)R1 9 . _S〇2Rl 9 , _〇C(〇)r24 ^ _C(〇)nr25r26 ^ -NR2 3 C(N_CN)NR2 5 r2 6 And _nr2 3 c(〇)NR2 5 R2 6. 2: In a specific embodiment, in the formula (1), B is an unsubstituted 5-membered heterodise, which has U ring hetero atoms which may be the same or different, and each sub-system is independently selected from the group consisting of Ν, S and 〇. "In the specific embodiment, 'in the formula 1' 6 is a 5-membered heteroaromatic ring, which is a ring hetero atom which may be the same or different, and each hetero atom is independently selected. , S and 〇 'the heteroaromatic ring system is substituted by one or more substituents which may be the same, each substituent being laterally selected from the group consisting of i, CN, -n〇2, alkyl, (iv), (iv) , (4), aryl, aryl, heteroaryl, aryl, alkyl, heteroaryl, alkyl, cyclohexyl Base, Nau 9, Qing II, -NR^R2 2 . _NR2 3S〇2R24 ^ _nr23c(〇)〇r2〇^ _NR23 4 -s〇2Nr25r26, .c(0)r24, _C(_2G, sr19, s(〇 Ri9 - 〇C(〇)R2 4, _c(〇)nr25r26, nr23c(n c_ 2 NR25r26. and Na 3c(〇)_ In the specific embodiment, in the formula (1), B is unsubstituted , an aromatic ring having one ring hetero atom selected from N, 5 and fluorene. 5·人杂 135177 -53- 200922559 In the specific embodiment, in the formula 1, the mound is a 5-heteroaromatic ring Having a % hetero atom of N, S and 〇, the heteroaromatic ring system is - or a plurality of may be the same or different Substituent substitution, each substitution 1 is independently selected from the group consisting of hexazone, -CN, -N〇2, alkyl, amide, south alkyl, dilute, dentate, fast radical, haloalkynyl, aryl , heteroaryl, aryl-like, heteroaryl, alkyl-, cyclodextrin, cycloaliphatic, heterocyclic, hetero-yl, 4-nitrogen, -〇^--oc(〇)〇R- WlR^.NR23S〇2R^ ( -NR C(0)R24, _S〇2Nr25r26, _c(〇)r24, c(〇)〇r2, plus 9-S coffee 9, _SG2R19, qing) R24, __R25R26, NR23c And NR2 5 R2 6 and Nr2 3 c(〇)nr2 5 r2 6. In a specific embodiment, in the formula (I), the B45_membered heteroaromatic ring has S as a ring hetero atom, The heteroaromatic ring system is substituted by one or more substituents which may be the same or different, and each substituent is independently selected from the group consisting of dentate, N, 2, 2, 2, 2, 2, 2, 2, 4 !_基基基,13⁄4 alkenyl, alkynyl, _aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cyclohexyl, 2-yl, heterocyclic, hetero Cycloalkenyl, azido, collar 19, _oc(o)or20, cis, heart S02R24, cis 23c (_2G, NR23C(0)R24, clarified 5r26, _c(0)r24, ((9)0R2Q, _SR19, s(9)R19 is R19, νΪΪΓ ' 'C(〇)NR25R26 ' 'NR23C(N-CN)NR25R2^_NR2 3C(〇). ′ B is an unsubstituted 5-membered impurity, and B is a thiophenyl group. The 'B' is selected from the group consisting of the formula, in the formula 1, the aromatic ring having s as a ring hetero atom. In the specific embodiment, in the formula 1 in the specific embodiment, in the formula 1 135177 -54- 200922559

In a particular embodiment, in Formula (1), B is pyridine. In a specific embodiment, in the formula (1), β is a partially unsaturated alicyclic ring. The ring system is unsubstituted.

In a specific implementation, in Formula (I), B is a partially unsaturated alicyclic ring which is substituted by one or more substituents which may be the same or different, and each substituent is independently selected from the group consisting of Odonol, _CN, _ν〇2, fluorenyl, heteroalkyl, dentate, alkenyl, alkenyl, alkynyl, dentyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl -alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -〇R]9, -〇c(o)〇r2〇, _nr21r22, -NR2 3S〇 2R2 4, _Nr23c(〇)〇r2. , _nr23c(9)r24 ur25r26, -C(0)R- > -C(0)〇R2〇, _sr19 . _S(〇)r19 ^ _s〇2Rl9 ^ _〇c(〇)r24 ^ -C(0)NR2 5 R2 6. _Nr2 3 c(n_cn)nr2 5 r2 6 and 2 3 c(9)NR2 5 R2 6. In a particular embodiment, in Formula (I), B is a partially unsaturated heterocyclic ring which is unsubstituted. In a specific embodiment, in Formula 1, B is a partially unsaturated heterocyclic ring which is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, _CN. , _N 〇 2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl fluorenyl-, heteroaryl-alkyl- , cycloalkyl, cycloalkenyl 'heterocycloalkyl, heterocycloalkenyl, azide, -OR", _〇C(〇)〇R2 0, _Nr21r22, _nr23sC)2r24, -NR ' C(0) 〇R20, _NR23C(0)R24, -S〇2NR25R26, -C(0)R24, -C(0)〇R2〇, —SR1 9,-SCCOR1 9,-SC^R19, _〇c(〇)r2 4, _c(〇)NR2 5R2 6, 135177 -55- 200922559 -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 R2 6. In a specific embodiment, In Formula 1, Ri is an unsubstituted aryl group, or an aryl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of _, _CN, _N 〇 2, and alkane Base, heteroalkyl, haloalkyl, alkenyl, alkenyl, fast radical, _block, aryl, heteroaryl, aryl-alkyl-, heteroaryl- , cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -〇Rl 9, 〇 〇c(〇)〇r2(), nr2 ! r22, nr23 s〇2R24, - Nr23c(o)〇r2〇, _NR2 3C(〇)r24, _s〇2Nr25r26, _c(9)r24, C(0)0R, -SR1 9, -SCC^R1 9, -S02 R1 9, _〇c(0)R2 4 (9) In the formula (I), R1 For the phenyl group which is substituted by four or the same or different substituents, each substituent is independently selected from the group consisting of a halogen group, -OH, -CN, -N〇2, -NR21R22 and a south alkyl group. In a specific embodiment, in Formula 1, R1 is an unsubstituted aryl group. In a specific embodiment, in Formula (1), R1 is an unsubstituted phenyl group. In a specific embodiment, In the formula (1), R] is an unsubstituted fluorenyl group. In a specific embodiment, in the formula (1), R, a substituted aryl group. In a specific f embodiment, in the formula ( In 1), R1 is a substituted phenyl group. In a specific implementation, in the formula (1), Ri is a substituted tea group. In a specific embodiment, In the formula (1), R1 is an aryl group substituted by one or more substituents which may be the same or different, and each substituent is independently selected from the group consisting of alizarin CN, -N02, alkyl, miscible, and tooth-burning. Base, dilute base, dentate base, block group, i alkynyl group, aryl group, heteroaryl group, aryl group, alkyl group, heteroaryl group, cycloalkyl group, cycloalkenyl group, heterocyclic group, Heterocyclic phenyl group, azido group, 135177 > 56- 200922559 -OR 9, -〇c(0)0r2. , _nr21r22, _nr23s〇2R24, nr23c(〇)〇r20, -NR2 3C(0)R2 4, _s〇2Nr25r26, c(〇)r24, c(7))〇R2〇, now 19, -S(〇)R]9 , -S〇2ri9, _0C(0)R24, _c(〇)Nr25r26, dish 23c (n alone NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In the specific embodiment, 'in the formula In (I), Ri is a phenyl group substituted by one or more substituents which may be the same or different, and each substituent is independently selected from the group consisting of a functional element, -CN, -N〇2, an alkyl group, and a miscible group. , South base, county, alkenyl, block, tooth fast radical, aryl, heteroaryl, aryl _ unified _, heteroaryl _ alkyl, KOH, bad base, heterocycle Affiliation, heterocyclic bake, uranium, -OR19> -OC(O)OR2 0 > -NR^R2 2 , .NR^s〇2R2 4 . .NR2 3C(〇)〇R2 0 . -NR23C (0) R2 4, -S〇2NR2 5r26, _c(〇)r24, c(〇)〇R2〇, _sr19, -S(0)R19, -S02R19, -0C(0)R24, -C(0) NR25r26, _nr23c(n cn) NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In one embodiment, 'in formula (I)' may be the same or different from one to four Substituent substituted phenyl 'each substituent is independently selected from the group consisting of Halogen, -OH, -CN, _N02, -NR21R22 and haloalkyl. In a particular embodiment, in formula (1), R1 is selected from the group consisting of:

In a specific embodiment, in formula (I), R1 is: 135177 -57- 200922559

Halogen in a particular embodiment 'In Formula 1, __^R is a phenyl group substituted with one to three fluoro groups. In a specific embodiment, in the formula (1) Φ nl . Λ w ' R1 is a radical substituted by two fluorine groups. To be replaced by an It base

In a particular embodiment, in formula (I), the phenyl group of R. In the specific embodiment of the invention, in the formula (I), R1 is:

In a specific embodiment, 'in the formula (I), R27 is H. In a particular embodiment, in Formula (I), R27 is alkyl. In a specific embodiment, in the formula (I), R2 8 is H. In one embodiment, in Formula (I), R28 is alkyl. In a particular embodiment, in Formula (I), R27 and R28 are each independently selected from the group consisting of hydrazine and alkyl. In a specific embodiment, in the formula (I), R27 and R28 together with the carbon atom to which they are attached form a cycloalkyl, cycloalkenyl or heterocycloalkyl ring, one to three selected from the group consisting of ruthenium a hetero atom of 0 and S, or a heterocycloalkenyl ring, containing from ~ to three heteroatoms selected from the group consisting of ruthenium, osmium and S. In one embodiment, in formula (I), R2 is selected It includes _c(〇)r7, 'c(〇)NR9 R1 0 and -C(〇)〇r8. 135Π7 •58· 200922559 In a specific embodiment, in a specific embodiment of formula (i), in formula (I), in a specific embodiment, in formula (I) In a particular embodiment, in a particular embodiment of formula (I), in formula (I), in a particular embodiment, in formula (I), in a particular embodiment, In a specific embodiment, in a specific embodiment of formula (I), in a specific embodiment in formula (I), in a specific implementation in formula (I) In a specific embodiment, in Formula (I), in Formula (I), in a specific embodiment, in Formula (I), in a specific embodiment, in Formula (I) In a specific embodiment, in a specific embodiment of formula (I), in formula (1), in a specific embodiment, in formula (I), in a specific embodiment, In a particular embodiment of formula (I), in formula (I), in a particular embodiment, in formula (I) (=〇). In a particular embodiment, in a particular embodiment of Formula (I), in Formula 1 in a particular embodiment, in Formula (I), R2 is -C(Z)R7. , R2 is -C(Z)NR9r10. , R2 is -C(Z)OR8. , R2 is -S02NR9R10. R2 is an alkyl group. R2 is a heteroalkyl group. R2 is an aryl group. R2 is a heteroaryl group. R2 is a cycloalkyl group. R2 is a cycloalkenyl group. R2 is a heterocycloalkyl group. R2 is a heterocycloalkenyl group. Z is (=0). Z is (=s). Z is (=N(R13)). Z is (=N(CN)). Z is (=N(OR14)). Z is (=N(R15)(R16:)) Z is (=c(r17)(r18)), R2 is -C(Z)R7, and R2 is -C(0)H. R2 is -C(O)alkyl. R2 is -C(0)CH3. 135177 -59- 200922559 R:::S In the embodiment, in the formula (1), R2 is -, 7, wherein the substituted oxime; S 个 can be substituted by the same or different substituents, each The substituents are independently selected from the group consisting of keto groups, -CN, -N02, alkyl, heterologous, i-alkyl, alkenyl, alkenyl alkynyl, alkynyl, aryl, hetero Square group, % alkyl group, cycloalkyl group, hetero-f ητ?Ι9 alkyl group, heterocycloalkenyl group, azido group, -OR, 〇C(〇)〇R2 〇, _服2] r2 2 ” NK s〇2R24, -nr23c(o)〇r20, -NR23C(0)R24, 25r26 4, _Q〇)〇R2 0, _SR19,

-S(0)R ' -S〇2R19 x -〇C(O)R24 rvA

} ' -C(〇)NR2 5R2 6 , -NR23C(N-CN)- nr25r26^-nr2 3C(0)nr25r26 In a specific embodiment, in the formula 1, r2 is a radical r7, wherein the R To be: to three of the substituents which may be substituted by the same or different substituents, each substituent is independently selected from the group j壬pyp 1 9 ντ ^ , and the k-head includes -OR , -NRhR22 and a cycloalkyl group. In the specific implementation of 丨Φ, i rr\ i , a & Example A In the formula (I), R 2 is -C(0)R7, wherein the R 7 is an alkyl group wherein the alkyl group is alkyl Replace with the collar. In the formula, in the formula (1), r2 is the political, where

Rm may be a thiol group which may be substituted with the same or different substituents, and each substituent is independently selected from the group consisting of 〇H, 视2 and cyclopropyl. In the formula of the method of octahedron, in the formula (I), R2 is _C(0)R7, wherein the R7 is a group substituted by two substituents which may be the same or different, each substitution The base system is independently selected from the group consisting of -NH2 and cyclopropyl. In the formula "in the formula", in the formula 1, r2 is ((〇) rule 7, wherein the R7 is an alkyl group substituted by -OH. In the specific embodiment A, in the formula 1, r2 is —c(0)r7, wherein R7 is unsubstituted heterocycloalkyl. 135177 -60- 200922559 In a specific embodiment, in formula (1), R2 is -C(〇)R7, wherein The R7 is a substituted heterocycloalkyl group. μ In a specific embodiment, in the formula (1), R2 is ·c(〇)r7, wherein the R7 is - or more may be a phase (5) Each substituent substituted with a different substituent is independently selected from the group consisting of a keto group, a halogen, -CN ' _N〇2, a group, a heteroalkyl group, an i-alkyl group, an alkenyl group, a alkenyl group, an alkyne. , haloalkynyl, yl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -〇C(〇)〇R20, -NR21R22, _nr23SC)2r24, -NR23C(0)OR20, _NR23C(0)R24, -S02NR2sR2 6, _c(〇)R2 4, -C(0)OR2(), -SR1 9, -S(〇)R] 9, -SC^R19, -0C(0)R24, _C(0)NR2 5R2 6, -NR2 3 C(N-CN)NR2 5 R2 6 and _NR2 3 C(0)NR2 5 R2 6. In a specific In the embodiment, in the formula (I) R2 is -C(〇)R7, wherein the R7 is selected from the group consisting of a substituted hexahydro-p ratio. The substituted, substituted hexahydro-p-P well, the substituted ruthenium 11-line, substituted tetrahydro-p The ratio σ and the substitution of one of the four groups. In a specific embodiment, in the formula (I), R 2 is selected from the group consisting of:

In a specific embodiment, in Formula (I), R2 is -QCONI^R1 0. In a particular embodiment, in formula (I) 'R2 is -C(O)NH2. In a specific embodiment, in the formula 00, R2 is -C(0)NR9R10, and R9 and Rio in 135177-61 - 200922559 may be the same or different, each independently selected. In the specific embodiment, in the formula (I), R2 4 κ is -CCCONR9!^. , J: wherein R is an unsubstituted heterocycloalkyl group, and Ri 〇 is /, ^ You include Pi and an alkyl group. In a specific embodiment, in Formula 1, d9^H 4-C(0)NR9r1〇 , Μ.

Τ Κ is a substituted heterocycloalkyl group, and R 1 〇 A is at a 5 θ. In the formula, in the formula (I), R 4 -c(o)nr9Ri〇' 1 肀R is one or three which may be the same or different, a base, each substituted A substituent The substituted heterocycloalkyl substituents are independently selected from the group consisting of alkyl groups, and R]0 is present in the group consisting of H and alkyl groups. In a specific embodiment, the formula m is selected from the group consisting of: a calcination group, a -c(o)Nr9r10. The self-burning group, -C(〇)R7, -c(0)0R8 and R々 restrictive examples include the following partial groups:

Ί-2, j. ,

Ά '人.1 < s' 135177 -62- 200922559

In a specific embodiment, in formula (I), R2 is

In a specific embodiment, in Formula 1, R2 is

〇

In a specific embodiment, in a specific embodiment of Formula (I), in Formula (I), in a specific embodiment, in Formula (I), in a specific embodiment, In a specific embodiment of formula (I), in formula (I), R2 is

0 Ο person. 〇 NH; Ο R2 is I 0 in a specific embodiment, in a specific embodiment, in a specific embodiment, in formula (I), R 2 is

Ν - In the formula (I), ρ is 0, and R3 is absent. In the formula (I), Ρ is 1. 135177-63- 200922559 In a specific embodiment 'in the formula (i)' p is 2. In a specific embodiment 'in formula (I), p is 3. In the specific embodiment, 'in the formula (I), p is 4. In a particular embodiment, in Formula 1, p is 2, 3 or 4 and at least two groups R3 are attached to the same ring atom. In a specific embodiment, in the formula (I), p is I 2, 3 or 4, and each R 3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl '_cn, _n 〇 2, -OR19, -oc(o)or2. , -nr2]r22, _c(0)r24, _c(5)r24, c(〇)〇r20 and -C(0)NR2 5 R2 6, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, and each of the The heteroalkenyl group is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a dentate, -CN, -N〇2, an alkane , heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, stack Nitrogen' _〇R]9, _〇c(〇)〇r2〇, -NR21R22, -NR23S02R2 4, _NR2 3c(〇)〇r2. , nr23c(〇)r24, -S02NR25R26, -C(0)R2 4, _c(〇)〇r20, _srI9, sr19, -S02R]9, -0C(0)R24, -C(〇)NR25R2 6, _NR2 A group of 3C(n cn)nr25r26 and -nr23c(o)nr25r26. In a specific shell example, in formula (I), P is 1 and R3 is independently selected from the group consisting of an alkyl group, a heterok group, a fine group, a hetero group, a fast group, a heteroblock group, and an aryl group. , heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halogen, -CN, -N02, -OR19, -〇C(0)〇R2〇, _NR2 1R2 2 ' _nr23s〇 2r24, -nr23c(o)or20, -NR23C(0)R2 4, _s〇2Nr25r26, c(〇)r24, 135177 •64- 200922559 -C(0)0R2°, -SR1 9,3(0)111 9 -SC^R1 9, -OC(〇)R2 4, _c(〇)NR2 5R2 6 , _NR2 3 C(N-CN)NR2 5 R2 6 and _NR2 3 C(0)NR2 5 R2 6. In a specific embodiment, in the formula (I), 'p is 2, 3 or 4, and each R3 is independently selected from the group consisting of a 'alkylene, a dilute, a hetero, a fast, a hetero alkyne. , aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, halogen, -CN, -N02, -OR19, -〇C(〇)〇R20, nr21r22, - NR23S02R24 > -NR23C(0)〇R2° ^ -NR23C(0)R2 4 , .s〇2NR25R26 , -C(0)R24, -C(0)〇R2〇,_SR]9,_S(〇)Rl9 , _s 〇 2Rl9, 〇 c (〇) r24, -C (0) NR2 5 R2 6, NR 2 3 C (N_CN) NR2 5 R2 6 and · nr2 3 c (〇) nr2 5 r2 6. In a particular embodiment, 'p is 2, 3 or 4 in formula (I), and at least two groups R are bonded to the same ring carbon atom 'where each r3, which may be the same or different, Individually selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heteroalkyl, heterocycloalkenyl , halogen, _CN, _N〇2,_0Rl9, ·%(〇)〇_, -NR2, R2 2 , -NR23S02R2 4 , -NR23C(0)0R20 . -NR23C(0)R2 4 -S〇2NR2 5R2 6. ((q)r24, c(〇)〇r2Q, sr19, _s(〇)r19, where Rl9, -〇C(〇)R2 4, _c(〇)nr25r26, _nr23c(n-CN), 25r26 and - service & NR25R2 6 0 ' In a particular embodiment, in Formula 1, p is 2, 3 or 4, and at least two groups R3 are bonded to the same ring carbon atom, wherein two r3 groups, It may be the same or different 'and the carbon atoms to which they are attached to form a ring-based, dilute, heterocyclic alkyl ring containing one to three atoms selected from the group consisting of N, o and S' or a heterocyclic ring. An anthracene ring containing - to three heteroatoms selected from the group consisting of ^, 0 and S. 135177 -65- 200922559 In a particular embodiment, in Formula (I), each R3 (when present) is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, -CN, -N02, -〇R] 9, -0C(0)0R2 0, -NR2 1 R2 2, -NR2 3 S02 R2 4, -NR2 3 C(0)0R2 0, -NR23C(0)R24, -S02NR25R26, _c(〇)r2 4. c(5)R2 4, _c(〇)〇r20, -SR19, -S(0)R19, -S02R]9, -〇c(〇)R24, _c(〇)nr25r2 6 '-NR23C(N-CN)NR25R26,- NR23C(0)NR25R26 and _NR23_c(nh)_nr26r26, wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently one or more The substituents may be independently or differently selected from the group consisting of keto, halo, -CN, -N〇2, alkyl, heteroalkyl 'haloalkyl, alkenyl, haloalkenyl, alkynyl. , haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _0Ri9, _〇c(〇)〇r2〇, -NR2IR22, - NR23S02R24, -NR23C(0)0R2, -NR23C(0)R24, -S02NR25R26, -C(0)R24, _c(〇)〇R2〇, _SRl9, _s(〇)Rl9, -S02R19, -0C(0 )R24, -C(0)NR25R2 6. Groups of _NR23C(N-CN)NR25R26 and -nr23c(o)nr25r26. In a specific embodiment, in Formula (I), each R3 (when present) is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, _CN, -N02, -〇R 〖9, -〇C(0)〇R2〇, _NR21R22, _C(0)R2 4, _c(s)r24, _c(〇)〇r20 and -C(0)NR25R26, wherein each of the alkyl groups The heteroalkyl group, each of the alkenyl group and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a ketone group and a halogen. -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, 135177-66- 200922559 alkynyl, alkynyl, aryl, heteroaryl, cycloalkyl, Cycloalkenyl, heterocyclo, heterocyclenyl, azido, -〇Rl9, _〇q〇)〇R20, -NR2 1 R2 2, -NR2 3 S02 R2 4, _nr2 3 c: (〇) 〇r2 ο, _nr2 3 c(0)R2 4, -S02NR25R26, -C(0)R24, _q〇)〇r2〇, _SRi9, _s(〇)Ri9, -SO2R19, -〇C(〇)R24,- A group of C(〇)NR25R26, -NR23C(N-CN)NR25R26 and -nr23c(o)nr25r26. In a specific embodiment, in formula (I), P is 1 and R3 is selected from the group consisting of an alkyl group, a heterodole group, a dilute group, and a heterogeneous group, f

And wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substitution The base system is independently selected from the group consisting of a keto group, a halogen, -CN, -N02, an alkyl group, a hetero group, a functional group, a dilute group, a (tetra) group, an alkynyl group, a haloalkynyl group, an aryl group, a heteroaryl group, a cycloalkyl group. , cycloalkenyl, heterocycloalkyl 'heterocyclenyl, azido' _ 〇 Rl 9, 〇 〇 c (〇) 〇 r2 〇, -NR2 1R2 2 λ _NR23S 〇 2R2 4 χ _NR23C (〇) 〇 R20 λ -NR23C(0)R24 ^ -S〇2NR25R26 > -C(〇)R2 4 , _C(〇)〇r2 0 . _SR19 N _S(〇)R19 λ -S〇2r19 . .〇C(0)R2 4 x _C(〇)NR2 5R2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 r2 6 groups. In a specific embodiment, in formula (I), P is 2, 3 or 4, and any two r3 groups bonded to the same ring A atom and the carbon atoms to which they are attached are from eucalyptus Used to form a spirocycloalkyl, spirocycloalkenyl, spiroheterocycloalkyl ring containing - to three ring heteroatoms independently selected from the group consisting of -NH_, _nr6_, s_, s), y, and 〇- Or a spiroheterocyclic ring containing - up to three ring heteroatoms independently selected from the group consisting of: -, -NR6_, each, _S(〇>, _S(〇)2_ and _〇_. 135177 -67- 200922559 Two of the R3 groups are therefore non-limiting examples of compounds of the invention that are difficult to use, including:

In the specific embodiment, in ten, m ^ pull ... in the cut +, R2 and R3 silk are connected with the slave atom, even $ 4 to find the base, _ base, miscellaneous « base 3 has Three independent rings including -NH-, _NR6_, _q _S(〇)2 - and -〇-, 弋 left 4)^甘 S(〇) 立...4 or miscellaneous ring 'containing-to Three independent ^ self-included - bribe -, -NR6-, each, the Ministry) ... original +. Glycine ϋ 2 t , S(〇) 2 _ and - 〇 - ring heteroatoms wherein R 2 and R 3 are used together with the present invention M , , and non-limiting derivatives of the compound of the moon, including the following compounds:

In a specific embodiment, in the formula (I), R3 is alkaloid. In a specific embodiment, in the formula (1), R3 is a heterodimeric-based embodiment, in the formula (I), R3 is dilute in a specific embodiment, in the formula (I) In the specific embodiment, R3 is hetero-based, in the formula (I), R3 is a block odor in a specific embodiment, in the formula (I), R3 is a hetero-alkyn based on a specific implementation In the formula (I), R3 is aryl 135177-68- 200922559. In a specific embodiment, in the formula (I), R3 is a heteroaryl group. In a particular embodiment, in Formula (I), R3 is cycloalkyl. In a particular embodiment, in Formula (I), R3 is cycloalkenyl. In a particular embodiment, in Formula (I), R3 is heterocycloalkyl. In a particular embodiment, in Formula (1), R3 is heterocycloalkenyl. In a specific embodiment, in Formula (1), R3 is halogen. In a specific embodiment, in Formula (I), R3 is -CN. In a specific embodiment, in Formula (I), R3 is -N02. In a specific embodiment, in the formula (1), R3 is -OR] 9. In a specific embodiment, in Formula (I), R3 is -OC(0)OR20. In a particular embodiment, in Formula (I), R3 is -NR2 1 R22. In a specific embodiment, in Formula (I), R3 is -NR23S02R24. In a specific embodiment, in Formula (1), R3 is -NR23C(0)OR2〇. In a specific embodiment, in Formula (1), R3 is -NR23C(0)R24. In a specific embodiment, in Formula (I), R3 is -S02NR25R26. In a specific embodiment, in Formula (I), R3 is -C(O)R24. In a specific embodiment, in Formula (I), R3 is -C(S)R24. In a specific embodiment, in Formula (I), R3 is -C(O)OR20. In a specific embodiment, in Formula (I), R3 is -SR1 9. In a specific embodiment, in Formula (I), R3 is 4(0)111 9 . In a specific embodiment, in Formula (I), R3 is -S02R]9. In a specific embodiment, in Formula (I), R3 is -0C(0)R24. In a specific embodiment, in Formula (I), R3 is -C(0)NR25R26. In a particular embodiment, in Formula (I), R3 is -NR23C(N-CN)-135177-69-200922559NR25R26. In a particular embodiment, in Formula (I), R3 is -NR23C(0)NR25R26. Non-limiting examples of R3 include the following: methyl, ethyl, propyl (straight or branched), butyl (straight or branched), pentyl (straight or branched), benzene

In a specific embodiment, in Formula (I), when E is -NR6-, the R3 system is absent. In a specific embodiment, formula (I) has the general structure shown in formula (I.a):

135177 - 70- 200922559 In one embodiment, formula (I) has the general structure shown in formula (I.b):

In a specific embodiment, formula (I) has the general structure shown in formula (I.c):

Where p is 0, 1, 2 or 3. In a specific embodiment, formula (1) has the general structure shown in formula (I.d):

(I.d), 135177 -71 - 200922559 where p is 0, 1, 2 or 3. In a specific embodiment, formula (I) has the general structure shown in formula (I.e):

Where p is 0, 1, 2 or 3. In a specific embodiment, formula (I) has the general structure shown in formula (I, f):

Where p is 0, 1, 2 or 3. In a specific embodiment, formula (I) has the general structure shown in formula (I.g): 135177 -72- 200922559

(i-g). where p is o, 1, 2 or 3. In some embodiments, 'in each of Formulas 1, (Ia), (I b), (Lc), (Ld), () Gf) and (Ig), R is oxime, and the compound of the present invention has General structure shown in formula (Ih):

Where P is 0, 1, 2 or 3. In some embodiments, in each of Equations 1, (La), (Lb), (I c), (id), (Le), (Io, (Ig), and (Ih), p is 〇. With respect to the various embodiments of the invention described herein, it should be understood that any variants of structural formulas that are not explicitly defined therein are defined in the chemical formulas referred to in this particular embodiment. It should also be understood that each R3, when present, 135177 -73- 200922559 and the ring atom or ring heterocycle attached to ring A may be replaced by a hydrogen atom atom. (Lb), (Ic), (Id) in other embodiments In the formulae (1), (Ie), (IO, (Lg) and (Lh): Ring A is a 4-7 membered cycloalkenyl ring; E is -C(R4)(R5)_; Ring B is a stupid ring or a 5-6 membered heteroaromatic ring wherein the ring system is unsubstituted or, as the case may be, independently substituted with the same or different substituents, each substituent being independently selected from the group consisting of dentate , -CN, -N〇m, heteroalkyl, dentate, dilute, functional ': yl, alkynyl, i alkynyl, aryl, heteroaryl, aryl-alkyl...heteroaryl-垸Base-, cycloalkyl, cycloalkenyl, heterocyclic Base, heterocyclenyl, azide, -OR19, -〇C(0)〇R2〇, _nr21r22, _nr23s〇2R24, -NR23C(〇)〇R2〇, 视23c(0)r24, _s〇2Nr25r26, c_R24, -C_R2, 挪9, 丨9, 姆19, 〇c(〇)r24, -C(0)NR2 5 R2 6 . _NR2 3 C(N-CN)NR2 5 R2 6 a _nr2 3 C( 〇)nr2 5 r2 6 In other embodiments, in each of formulas (1), (Ia), (Lb), (Ic), (Id), (Ie), (If), and (Ig): Ring A is a 4-7 membered cycloalkenyl ring; E is -C(R4)(R5)-; and Ring B is a benzo ring or a 5-6 membered heteroaromatic ring wherein the ring system is unsubstituted, Or optionally, independently, substituted to 3 substituents which may be the same or different substituents, each substituent being independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl , 135177 74- 200922559 alkenyl, fast-radical, alkynyl, aryl, heteroaryl, aryl, hetero...cyclodecyl, cycloalkenyl, heterocycloalkyl, heterocyclic, hydrazine Base, -OR丨9, 0 1 )〇R 'NR2 1R2 2 . _NR2 3S〇R2 4 . -NR23C(O)OR20 23 L(〇)R, -S〇2NR25R2 6, _C(〇)R2 4, A ·20, view 9, which is like 9, milk 2 Rl9, _QC(〇)R24, -C(0)NR^R26, -NR^C(N-CN)NR25r26^ _nr23c(〇)nr25r26 ; R1 is the same for one to four rabbits Or a substituted phenyl group, each substituent is independently selected from the group consisting of halo, cn, _N〇2, _nr21r22 and haloalkyl; R2 is selected from the group consisting of: a pyridyl group, a (tetra) group, The group, ((9)R7, -C(0)0R8 and -C(0)NR9R1〇; and each 卟 when present) is independently selected from the group consisting of a top group, a miscible group, an alkenyl group, a heteropoly group, and -CN. -N02, -〇Rl 9, _OC(〇)〇R20, NR2, r22, NR23 s〇2R24, -NR23C_R2. , tear 23c team 24, s〇2NR25R26, c (〇) R24, -C (S,, -CXQ) (10) ◦, view 9, _S (0) R19 ' _SQ2R19, 〇 c (〇) R24, -C (0 NR2 5R26, -Nr23c(n_cn)nr25r26, _NR23c (〇 25 25 at 6 and -NR23-C(NH)-NR26R26, wherein each decyl group, each of the heteroalkyl groups, each of the alkenyl groups and each of the hetero olefins The base is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of keto, _, -CN, -N 〇 2, alkyl, Heteroalkyl, haloalkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide ,_0R19, _〇c(〇)〇R20, -NR21R22 ' -NR23S02R2 4 , -NR23C(0)0R2° ^ -NR23C(0)R24 > 135177 -75· 200922559 -S02NR2 5R2 6, _C(〇)r24 , c(〇)〇r2〇, view 19

a group of -S(0)R 1 9 -S〇2Ri9, _oc(0)r24, _c(0)Nr25r26, nr23c(ncn)nr25r26 and -NR2 3 C(0)NR2 5 R2 6 . In other specific embodiments, in the formulas (I), ((10), (Ib), (ic), (id), (Ie), (If), and (Ig), the ring A is 4-7 members. a cycloalkenyl ring; E is -C(R4)(R5)-;

Ring B is a benzo ring or a 5-6 membered heteroaromatic ring wherein the ring system is unsubstituted or, as the case may be, independently substituted by (1) a substituent which may be the same or different, each substituent being independently selected from the group consisting of Octochrome, -cn'-n〇2, alkyl, miscible, halo, dilute, haloalkenyl, alkynyl, alkynyl, aryl, heteroaryl, aryl-alkyl-, Heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -OR19, _〇C(〇)〇R20, Nr21r22 'nr23s〇2R24, -NR2 3C(〇)〇R2〇. _NR2 3C(〇)r24 ^ _S〇2Nr25r26 ^ c(〇2)r24 ^ -C_R2. , -SR19, _s(〇)Rl9, _s〇2R]9, 〇c(〇)r24, -C(〇)NR^R26 . -NR23C(N.CN)nr25r26^ _nr23c(〇)nr25r26 . R1 is One to four phenyl groups which may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of _ group, (5), , · ν 〇 2, ur UR" and a halogen group; , an alkyl group, a heteroalkyl group, a heterohaloalkyl group, —(10)r7, —C(0)〇r8&_c(〇)Nr9r](); and each when present) are independently selected from the group consisting of alkyl groups and heterocyclones. Base, alkenyl, heteroalkenyl, -CN, -N〇2, 〇Rl9, ·〇(:(_2(), nr21r22, (Na 24, 135177 -76- 200922559 -C(S)R24, -C( 0) 0R2() and -C(〇)NR25R26, wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group, and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently one or more Substituents which may be substituted with the same or different substituents are each independently selected from the group consisting of keto, halo, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl , alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -〇Rl 9, 〇〇c(〇)〇r2 〇, -NR2 1 R2 2, _NR2 3 S02 R2 4, _nr2 3 c(〇)〇R2 〇, _NR2 3 C(0)R2 4, -S02NR25R26, -C(0)R2 4, _c(〇)〇r20 a group of SR1, _s((7)r19, -S02R19, -0C(0)R24, -C(〇)nr25r2 6, _NR2 3c(N cn)nr25r26 and -nr23c(o)nr25r26. In other embodiments, In each of Formulas 1, (La), (Ib), (I c), (I d), (Ie), (If), and (Ig): Ring A is a 4-7 membered cycloalkenyl ring; -C(R4)(R5)-; and

Ring B is a benzo ring or a 5-6 membered heteroaromatic ring wherein the ring system is unsubstituted or, as the case may be, independently substituted to 3 substituents which may be the same or different substituents, each substituent being independently selected Including dentate, -cn, -N〇2, alkyl, miscible, Nantong, gynecyl, alkenyl, aryl, alkynyl, aryl, heteroaryl, aryl-alkyl a heteroaryl-alkyl group, a ring-based group, a ring-like group, a heterocyclic group, a heterocyclic group, a fluorenyl group, -ORM, _〇c(〇)〇r2〇, nr2]r22, .23岣24, -NR^C(〇)〇R20 . _NR23C(〇)r24 ^ _s〇2Nr25r26 ^ ^ , -〇C(0)R2 4, -C(〇)〇R2〇,_SR]9,_S( 0) R19, _s〇2R]9 135177 -77- 200922559 _C(0)NR2 5 R2 6 , _NR2 3 C(N_CN)NR2 5 R2 6 and _NR2 3 C(〇)nr2 5 R2 6 ; R1 is one to Four phenyl groups which may be substituted by the same or different substituents, each substituent being independently selected from the group consisting of halo, -OH, -CN, -N02, -NR21R22 and haloalkyl; R is selected from the group consisting of: alkyl , haloalkyl, heteroalkyl, heterohaloalkyl, _C(〇)R7, -C(0)0R8 and -C(0)NR9R10; and P is 1, and R3 is selected from the group consisting of alkyl and heterocycloalkyl Base And a heteroalkenyl group, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups and each of the heteroalkenyl groups is unsubstituted or, as the case may be, 1 to 3 substituents which may be the same or different Substituted 'each substituent is independently selected from keto, halo, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, ynkynyl, aryl, Heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, 〇R19, _〇c(〇)〇R20, -NR2 1 R2 2, _NR2 3 S02 R2 4 , -NR2 3 C(〇)〇R2 0, -NR2 3 C(0)R2 4, -S02NR25R26, _c(0)R24, _c(〇)〇r2〇, sr丨9, _s(〇)r19, - S02 R1 9,-0C(0)R2 4 ' -C(〇)NR2 5 R2 6 ' -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 Group . In other specific embodiments, in each of Formulas 1, (I a), (Lb), (Lc), (I d), (Ie), (If), (Ig), and (Ih): Ring A is 5-6 membered heterocycloalkenyl ring; E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(〇)2_, _n(R6)-'-N(C(7)R7)-, -N(C(Y)ORs)- ^ -N(C(Y)N(^)(Ri〇)). , -C(〇)-N(Rn). , -N(R^ )-C( 0)-' -S(0)2-N(R11)- ' -NCR11 )-S(0)2- Λ -C(〇)-〇- . -OC(O)- ' -〇-N(R6 )- ' -N(R6)-0- ' -N(R6 )-N(R! 2)- ' -N=N- ' -C(R7)=N- ' -C(0)-C(R7 )=N- ' 135177 -78- 200922559 -CCOj-NsN-'-O-QYH^RHy'-NCRnKXYya'-N^KXY)- N(R12)- > -C(Y)-N(Rn ). 〇. , -CCY^R^^NCR^). ' -〇-N(R^ )-C(Y)- and -N(R! 2)-Ν(Ι^ 1 )-C(Y)-; And ring B is a benzo ring or a 5-6 membered heteroaromatic ring, / wherein 泫% is unsubstituted or, as the case may be, independently substituted with 3 substituents which may be the same or different, each substituent being independently selected Included from i, -CN, -N〇2, alkyl, ketone, ketone, alkenyl, haloalkenyl, alkyl, dentate, aryl, heteroaryl, aryl sulfhydryl , heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl Base, azide group, -OR19, _OC(o)〇R20, tear 2lR22, _NR23 are called R24, -NR"C_R2., sprinkle 23C(〇)R24, _s〇2Nr25r26, c(〇2)r24, -C( 〇)〇I^, -SR19, -S(0)Rl9, r19, _〇c(〇)R24, -C(0)NR^R26 . -NR23C(N-CN)NR^R26^ -NR2 3C (〇) nr25r26 In other embodiments, in the formulae (I), (I a), (I b), (I c), (I d), (Ie), (If), and (Ig) Wherein: Ring A is a 5-6 membered heterocycloalkenyl ring; and the group E is selected from the group consisting of -〇-, -s-, _S(〇)_, _s(〇)2_a_n (r6, wherein the lanthanide is selected from the group consisting of ruthenium, Alkyl, -C(〇)R2 4, _c(〇)〇r20 and _c(s)r24; Ring B is a benzo ring or a 5-6 membered heteroaromatic ring, wherein the lanthanide is unsubstituted, Or optionally, independently, to 3 substituents which may be the same or different substituents, each substituent being independently selected from the group consisting of dentate, ., 2, to, minus, "base, dilute, tooth, base, Alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, dilute, 135177-79- 200922559 Azido, -OR", _OC(O)〇r20, _nr21r22, nr23s〇2r2 4, -NR - C(0)〇R2 °, _nr2 3 C(0)R2 4, _s〇2 nr2 5 R2 6, -C(0)R2 4, -C(0)0R2°, _SR19, -S (Q)R19, _s〇2R]9, _〇c(〇)R2 4, _C(0)NR R2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and _nr2 3 C(0)NR2 5 R2 6 ; R1 is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of halo '-〇H, _CN, _n〇2, _nr2丨r22 and halane R2 is selected from the group consisting of: alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, _c(〇)R7, -C(0)0R8, and -CCC^NI^RW; and each R3 (when present When selected) are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, -CN, -N02, -〇Ri 9, _〇c(〇)〇r2. , nr2 i r22, ·23 s〇2r24, -NR2 3 C(0)0R2 0, -NR2 3 C(0)R2 4, -S〇2 NR2 5 R2 6, _c(〇)R2 4, _QS)R2 4, -C(0)0R2G, -SRI9, _s(〇)Rl9, s〇2Rl9, 〇c(〇)r24, -C(0)NR25R26, _nr23C(N-CN)NR25R26, _nr23c(o)nr25r26 and -NR23-C(NH)-NR26R26, wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group, and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently one or more may be the same Or substituted with different substituents, each substituent is independently selected from the group consisting of keto, halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, fast-radical, haloalkyne Base, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, _0Rl9, _qc(q) 〇r20, -NR21R22, -NR23S02R24, _NR2 3C(0 )OR20, -NR23C(0)R24, -S02NR25R26, -C(0)R24, -C(0)OR20, -SR19, ·3(0)Κ19, -S02R19, -0C(0)R24, -C( 〇) NR25R26, -NR23C(N-CN)NR25R26 135177 -80- 200922559 and -NR2 3 C(0)NR2 5 R2 6 group.

In other embodiments, each of the ten m WT, /τ, N positions (1), (Ia), (I b), (I c), (I d), (Ie), (If), and (Ig) Wherein: Ring A is a 5-6 membered heterocycloalkenyl ring; E is selected from the group consisting of -〇-, -S-, -S(O)-, _S(0)2_, and 6), wherein r6 Is selected from the group consisting of hydrazine, alkyl, -C(〇)R24, _c(〇)〇r20 and _c(s)r24; ring B is a benzo ring or a 5-6 membered heteroaromatic ring, wherein the bad system Unsubstituted or, as the case may be, independently substituted into 3 substituents which may be the same or different substituents, each substituent being independently selected from the group consisting of a functional element, -CN, -N〇2, alkyl, heteroalkyl, Haloalkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocyclic Alkyl, heterocycloalkenyl, azide, -OR19, -〇C(〇)〇R2〇, -NR21R22, _NR2 3S〇2r2 4, -NR23C(0)OR2° λ -NR23C(0)R24 ' - S02NR25R26 ' -C(0)R24 ^ -C(0)OR20,_SR19,_S(0)R19, -S02R19, -〇C(0)R24, -C(0)NR2 5 R2 6、_NR2 3 C(N -CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 ; R1 is one or four can be the same or not a substituted phenyl group, each substituent being independently selected from the group consisting of halo, 〇H, -CN, -N02, -NR21R22, and haloalkyl; r2 is selected from the group consisting of alkyl, haloalkyl, hetero Alkyl 'heterohaloalkyl, -C(0)R7, -C(0)〇R8 and -C(0)NR9Ri〇; and each R3 (when present) is independently selected from the group consisting of alkyl, heteroalkyl , alkenyl, heteroalkenyl, _CN, -n〇2, -OR19, -OC(0)OR20, -NR21R22, -C(0)R24, -C(S)R24, _C(0)0R2. And _c(〇)nr25r26, 135177 -81- 200922559 wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently one or more It may be substituted with the same or different substituents, each substituent being independently selected from a keto group,! |, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, fast radical, li block, aryl, heteroaryl 'cycloalkyl, cycloalkenyl , heterocycloalkyl, heterocycloalkenyl, azide, -R, R19, _〇c(〇)〇R20, -NR21R22, -NR23S02R24, -NR23C(〇)〇R2G, .NR23C(0)R24, - S〇2NR25R26, 'C(〇)r2 4, _C(〇)〇R2〇, _SRl9, _s(〇)r19, -SC^RO, _〇C(〇)R2 4, _c(〇)nr25r26, nr23c( Nc talks about the group r25r26 and -NR2 3 C(0)NR2 5 r2 6 . In other embodiments, in the formula 1, (La), (Lb), (Ic), ad) ' (Le), (If) and (Ig): Ring A is a 5-6 membered heterocycloalkenyl ring; E is selected from the group consisting of -〇-, _S•, heat, _s(〇)24_n(r, where 妒 is selected from Including hydrazine, alkyl, -C(0)R2 4 ' _c(〇)〇r2〇&_qs)r24; ring B is a benzo ring or a 5-6 membered heteroaromatic ring, wherein the ring system is Substituted, or optionally substituted by the same or different substituents, each substituent being independently selected from the group consisting of: nitrite, -CN, -N〇2, alkyl, miscible, dentate, dilute, South base, block base, _ block base, aryl group , heteroaryl, aryl-alkyl (heteroaryl)-homo-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic/azido...orhoc(o)or20, Liuru, tear 23 is called 2, -NR23C(〇)〇r2〇, -NR-c(〇)R24 . _s〇2Nr25r26 ^ c(〇2 ' Paste 0R2°, -SR, 9, _S(〇)R19, Na) R24 , 135177 -82- 200922559 _C(〇)NR2 5 R2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 ; R can be the same for one to four Or a phenyl group substituted with a different substituent, each substituent is independently selected from the group consisting of halo, 〇H, _CN, _N〇2, _nr2, r2 2 and haloalkyl; R27 and R28 are each independently selected from the group consisting of And an alkyl group; R is selected from the group consisting of: alkyl, decyl, heteroalkyl, heterohaloalkyl, -C(0)R7, -C(0)0R8, and -C(〇)NR9R]; P is 1, and R3 is selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, and a heteroalkenyl group, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, and each of the alkenyl groups is not Substituted, or optionally, independently, substituted to 3 substituents which may be the same or different substituents, each substituent being independently selected from the group consisting of a keto group, a hydroxyl group, -CN, -N〇2, an alkyl group, a heteroalkyl group, a halogen Base, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, 〇Rl 9, _〇c(〇)〇r2 〇, -NR21R22, -NR23S〇2R24, _NR2 3C(〇)〇r2〇, nr23c (〇瓜24, -S02NR25R26, -C(0)R24, _c(〇)〇R2 0 , SR19, _s(〇)Rl9, -S02R19 ' -0C(0)R24 ' -C(0)NR25R26 > -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 Group of R2 6 . In a specific embodiment, the compound of the present invention has the structure shown in the formula (Π) and includes a pharmaceutically acceptable salt, solvate, glycol, prodrug or isomer of the compound. 83- 200922559

R2 (Π) where R1, R2, R27 ' R28, E and ring B are selected independently of each other, A 5 -S*

Wherein E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2-, -C(R4)(R5)_, _N(R6)_, -N(C( Y) R7)-, _N(C(Y)OR8)-, -N(C(Y)N(R9)(R10))-; and ring B, X, R1, R2, R4, r5 'R6, R7 The selected substituents on r8, R9, r1 〇, r27 R28, Y and ring B are all as defined in any of the specific examples described in the above formula (1). In a specific embodiment, in the formula (η): E is selected from the group consisting of _s_, ... s(〇) 2_, _c (r4 Na- and Na ^. Ring B is not fresh a group selected from the group consisting of benzo, tert-butyl, thiophenyl, pyrrolyl, glycerol, carbazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolamide, 1 - hydrazine - oxazolyl, 4 oxadiazolyl, pyridyl, argyl, bromo, and trisyl; R1 is substituted by one to four substituents independently selected from the group I 5 5 different substituents The phenyl group, each and the dentate group; and self-packaging, you-replenish 〒 R is selected from the group consisting of -C(Q)p7)R, pasteification ° and -c(0)0r8. 135177 -84 * 200922559 In a specific embodiment, in the formula (π): R1 is:

In a particular embodiment, the compound of the invention has the structure shown in formula (n.a) 'I" includes pharmaceutically acceptable salts, solvates, esters, prodrugs or isomers of the compound:

R2 (II.a_) wherein R1, R2, R27, R28, E and ring B are independently selected from each other, and wherein: E is selected from the group consisting of -0-, -S-, -S(O)-, - S(0)2-, -C(R4)(R5)_, _n(r6), -N(C(Y)R7)- '-N(C(Y)OR8)- '-N(C(Y N(R9)(R10))-; ring B is a substituted or unsubstituted aromatic ring; and R1, R2, R4, R5, R6, R7, Rs, R9, R10, R27, r28, and The substituents selected on B are all as defined in any of the specific examples described above in formula (I). In one embodiment, the formula (n.a.) has the general structure shown in the formula (II.a.l). 135177 -85- 200922559

R2 (ll_a.1). In a specific embodiment, the formula (Il.a.) has the general structure shown in formula (II.a.2):

R2 (ll.a.2). In some embodiments, in each of Formulas (Il.a.), (Il.a.l), and (II.a.2), E is -C(R4)(R5)-. In some embodiments, in each of the formulas (ILa.), (II.al), and (II.a.2), the E is selected from the group consisting of -〇-, -S-, -S(O)-, -S(0)2- and -N(R6)-. In some embodiments, in each of Formulas (Il.a.), (II.al), and (II.a.2), the E is selected from the group consisting of -0-, -S-, -S(〇) -, -S(0)2- and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24 and -C(S)R24. In some embodiments, in each of Formulas (Il.a.), (II.al), and (II.a.2), the E is selected from the group consisting of -〇- and -N(R6)-, wherein R6 It is selected from the group consisting of hydrazine, alkyl, 135177 -86- 200922559 -C(0)R24 and -C(S)R24. In some embodiments, in each of Formulas (Il.a.), (II.a.l), and (II.a.2), E is -Ο-. In some embodiments, in each of Formulas (Il.a.), (II.a.l), and (II.a.2), Ε is -S-. In some embodiments, in each of Formulas (Il.a.), (ll.a.l), and (II.a.2), E is -S(O)-.

In some embodiments, in each of Formulas (Il.a.), (II.al), and (II.a.2), E is -S(0)2 _ 0 in some embodiments, in In each of the formulas (na·), (nd), and (ILa 2), E is —C(R4)(R5)—. In some embodiments, in each of the formulas (n.a.), (ii.a.i), and (n.a.2), E is -N(R6)-. In some embodiments, in each of the formulas (ILa.), (ILa1), and (ILa 2), E is -N(C(Y)R7)-. In some embodiments, in each of Formulas (ll.a.), (ILa1), and (ILa2), E is -N(C(Y)OR8)-. In some embodiments, in each of the formulas (II.a.), (ILa l), and (II a 2), E is -wind (:(1^)(1^〇))). In some embodiments, in each of the formulae (II.a.), (II al), and (ILa 2), Y is (=0) 一些 in some embodiments, in each formula (II.a· In (ILa l) and (ILa2), Y is (=s). In some embodiments, in each of the formulas (ILa), (ILa l), and (na 2), 200922559 Y is (=N) (R13)) In some embodiments, in the bucket, m, .ττ 1λ. Y (Il.a·), (II.a_l), and (Il.a.2) Y is (= N(CN)). In each of the formulas (Il.a.), (Il.al), and (na2), Y is (=N(OR14)) in some embodiments. In some embodiments Y is (=N(RI5)(R16)) in 夂4, ττ Ώ , in the formulas (Il.a.), (Il.ai), and (na2). In some embodiments,

In each of the formulas (ILa.), (Il.a.l), and (n.a.2), Y is (=C(RI7)(R18)). In some embodiments, the force 々 / ττ, Τ in each of the formulas (n.a.), (II.a.l), and (iLa.2) B is an unsubstituted aromatic ring. In some embodiments, B is an unsubstituted stupid ring in each of the formulas (ILa.), (II_a.l), and (n.a_2) and the formula (Il.a.) has the following general structure:

R2 In some embodiments, B is an unsubstituted benzo ring in each of the formulae (Il.a.), (II.al), and (na2), and the formula (ILa.) has the following general structure: 135177 -88- 200922559

R2. In some embodiments, in each of the formulae (II a), (II.al), and (ILa 2), B is an aromatic % ring which is one or more substituents which may be the same or different. The substituents are independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, heteroalkyl, _alkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, aryl, Heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, -OR19, -〇c(0) OR20, -NR21!?22, -NR S〇2R2 4, NR2 3C(〇)〇R2 0, nr23c(〇)r24, _s〇2Nr25r26, -C(0)R24 λ _C(0)0R2° > - SR19 > -S(0)R19 ^ -S02R19 ' -0C(0)R24 . _C(0)NR2 5 R2 6 , nr2 3 C(N cn)nr2 5 r2 6 and nr2 3 c(9)nr2 5 r2 6. In some embodiments, in each of the formulas (ILa), (ILa1), and (ILa 2), /., VB is a stupid ring and the ring is replaced by one or more substituents which may be the same or different. Each substituent is independently selected from the group consisting of halogen, -CN, -N02, alkyl, alkoxy, i-alkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroarylaryl-alkyl -, Aryl-alkyl-, cycloalkyl, cycloaliphatic, heterocyclic k-, heterocycloalkenyl, azido, -OR19, -OC(0)OR20, -NR21R2 2, -NR23S〇2R2 4, NR2 3C(〇)〇R2 0, _NR2 3C(〇)R2 4, _S〇2nR2 5R2 6, _C(〇)R24, -C(0)〇R20, -SR19, -S(0)R19, -S02R19,- 0C(0)R24, _C(0)NR2 5 R2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. 135177 -89- 200922559 , in some In a specific embodiment, in each of the formulas (ILa.), (II al), and (II a 2), R1 is an unsubstituted aryl group. In some embodiments, in each formula (ILa.) In (II al) and (II a 2), R1 is an unsubstituted phenyl group. In some specific examples, in the formulas (ΙΙ·3.), (II al) and (II a 2) Wherein R1 is an unsubstituted fluorenyl group. In some embodiments, in each of the formulas (ILa.), (nal), and (na 2), R1 is a substituted aryl group. In the examples, in each of the formulas (Ha), (II.ai), and (ILa.2), R is a substituted phenyl group. In each of the specific examples, in each of the formulas (Il.a.), (II.a.i), and (ll.a.2), R1 is a substituted naphthyl group. In some embodiments, in each of (na), (na, and anal & illusion, R1 is an aryl group substituted by one or more substituents which may be the same or different, each substituent being independently selected Including halogen, _CN, _N〇2, alkyl 'heteroalkyl, haloalkyl, alkenyl, nonenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, hetero Aryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, _〇c(〇)〇R20, _nr21r22 '-NR23S02R24 > -NR23C(0 )0R2° ^ -NR23C(0)R24 ' -S02NR25R26 ' -C(0)R24, -C(〇)〇R2〇, _SR19, _s(〇)Rl9, _S〇2r19, _〇c(〇)R2 4 -C(0)NR25R26, -NR23C(N-CN)NR25R26&-NR23C(0)NR25R26. In some embodiments, in each of Formulas (IIa), (II.al), and (ILa 2) And R1 is a phenyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, _n〇2, alkyl, heteroalkyl '135177-90-200922559 Halogenated base, dentate, block, south block, aryl, heteroaryl 'aryl-alkyl-, heteroaryl- , cycloalkyl, cycloalkenyl, heterocycloalkyl, heteroalkenyl, azide, _0Rl9, _〇c(〇)〇r20, -nr21r22, -NR S02R, _NR23C(0)0R2°, _NR2 3c(〇)R2 4, _s〇2Nr25r26, -C_4, -C(〇)〇R2D, Guan〗9, s(〇)r19, Nar]9,%(9)r24 -C(0)NR2 5 R2 6,nr2 3 C(N_CN)NR2 5 r2 6 and tear 2 3 c(9) cis 2 5 r2 6. In the formula (na), (II.al) and (Il.a.2), the phenyl group substituted with the substituent, each -OH, -CN, -N02, -NR21R22

In some embodiments, each of R1 is independently from one to four and may be independently selected from the group consisting of a functional group and a halogen group. (II.a.l) and (II.a.2) In some embodiments, in the formula (n.a.), R1 is selected from the group consisting of:

Haloalkyl.

Halogen

Halogen 〇2n^/=

Halogen Group In some embodiments, in each of formulas (II a ), (ILa l), and (n.a, R1 is:

In some embodiments, in each of Formulas (II.a.), (n.a1), and (II a 2), R1 is a stupid group substituted with one to three fluoro groups. 135177 -91 . 200922559 In some embodiments, in each of the formulas a.) R1 is a phenyl group substituted with two fluoro groups. In some embodiments, R1 in formula (ll.a) is a phenyl group substituted with a fluoro group. In some embodiments, in the formula (ILa) R1 is:

In some embodiments, each of the formulas (ILa), R, and R28 are independently selected from the group consisting of ruthenium and ruthenium. In some embodiments, in each formula (ILa), R2 is -C(Z)R7. In some embodiments, 'in each formula (II a ), R2 is -C(Z)NR9R10. In some embodiments, 'in the formula (ILa), R2 is -C(Z)OR8. In some embodiments, 'in the formula (ILa), R2 is -S02NR9R10. In some embodiments, in each formula (11), R2 is an alkyl group. In some embodiments, 'in each formula (II.a.), R2 is a heteroalkyl group. In some embodiments, in each of the formulas (IIa·), 135177, (II.al), and (II.a.2), (:II.a.1) and (II.a.2) , ' (II.al) and (II.a.2), (II.al) and (II_a.2), (II.a. 1) and (II.a.2), (II. a. 1) and (II.a.2), (II.a. 1) and (II.a.2), (II.a. 1) and (II.a.2), (II .al) and (II.a, 2), (II.al) and (II.a.2), (II.al) and (II.a.2), -92- 200922559 R2 is Fang base. In some embodiments, in each of Formulas (Il.a.), (ll.a.l), and (ll.a.2), R is a heteroaryl group. In some embodiments, in each of Formulas (Il.a.), (ll.a.l), and (ll.a.2), R2 is a cycloalkyl group. In some embodiments, in each of Formulas (Il.a.), (ll.a.l), and (ll.a.2), R2 is cycloalkenyl. < In some embodiments, in each of the formulas (ILa.), (II.a.1), and (ll.a.2), R2 is a heterocycloalkyl group. In some embodiments, in each of Formulas (Il.a.), (Il.a.1), and (ll.a.2), R2 is a heterocyclic heterocyclic group. In the specific embodiments, in each of the formulas (Il.a.), (II.a.l), and (II.a.2), Z is (=0). In some embodiments, in each of Formulas (Il.a.), (II.a.l), and (II.a.2), Z is (=S). I In some embodiments, in each of Formulas (II.a.), (II.a.1), and (II.a.2), Z is (=N(R)3)). In some embodiments, it is (=N(CN)). In some embodiments, it is (=N(OR14)). In some embodiments, it is (=N(R15)(R16)). In some embodiments, 】35177

In each of the formulas (Il.a.), (II.a.1), and (II.a.2), Z is in each of the formulas (Il.a.), (II.al), and (II.a.2). In the formulas (Il.a.), (II.al) and (II.a.2), Z is in the formulae (Il.a.), (II.al) and (II. In a.2), Z -93- 200922559 is (=C(R17)(R18)). In some embodiments, R2 is -C(Z)R7 and Z is (=0) in each formula (u.a). (II.a.1) and (II.a.2), (II.a.1) and (II.a.2), in some embodiments, in each formula (II a) R2 is -C(0)H. In some embodiments, R2 is -C(O)alkyl in formula (IIa). f In some embodiments, R2 is -C(0)CH3 in each formula (II a.). (II.a.1) and (II.a.2), in some concrete combinations (1U.), (II.a.1) and (II.a.2), where (iv) is - or A plurality of alkyl groups which may be substituted with the same or different substituents are each independently selected from the group consisting of a ketone group, a ketone group, a -cn, a -n 〇 2, a decyl group, a (tetra) group, a ketone group 1 group, and (4) Base, block base,

Tetraalkynyl, aryl, heteroaryl, cyclodecyl, cycloaliphatic, heterocyclic, heterocycloalkenyl, azido, -OR19, -OC(O)〇R20, _NR2 丨r22, _nr23 s 〇 2R24, • NR23c (〇) 〇 r2. , _NR23c(〇)R24, _s〇2Nr25r26, ((〇斯4, -C_R2G, -SRHS(0)I^,·δ〇2Κ1 9, 〇〇c(〇)R24, _c(〇)nr25r26, -NR2 3 C(N_CN)NR2 5 R2 6 and _nr2 3 c(〇)nr2 5 R2 6. In some specific examples, in each formula (π.Μ, (ILa l) and (ILa 2), R2 Is -C(〇)R7, wherein R7 is an alkyl group substituted by one to three substituents which may be the same or different, each substituent being independently selected from the group consisting of _0R19, _NR2丨R22 and cycloalkyl.

In some embodiments, in each of Formulas (Il.a.), dLU), and (ILa 2), R 2 is -C(O)R7, wherein R 7 is alkyl, wherein the alkyl is alkyl Replaced with _〇H 135177 94- 200922559. And R. And the alkyl group of the ring -T is substituted with the same or different substituents. Each substituent is independently selected from a propyl group. In some specific embodiments, in various forms, called · township f

RK(_, wherein R7 is a group substituted by _ to two substituents which may be the same or different, each substituent being independently selected from the group consisting of na and cyclopropyl. In some embodiments, In the formulae (ILa.), (IU丨) and ([a 2), R2 is -C(0)R7, wherein the R7 is an alkyl group substituted by _〇H. In some embodiments, in various formulas (II.a.), (II al) and (II a.2), R 2 is -C(0)R7, wherein R 7 is an unsubstituted heterocycloalkyl group. In some specific examples, In each of Formulas (Il.a.), (nai), and (II a.2), R2 is -C(0)R7, wherein R7 is substituted heterocycloalkyl. In some embodiments In each of the formulas (na), (ii.ai) and (II a 2), R is -C(0)R7 ' wherein R7 is a heterocyclic ring substituted by one or more substituents which may be the same or different substituents The alkyl 'each substituent is independently selected from the group consisting of keto, halo, -CN, -N02, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, fast radical, ynkynyl, aryl' Heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -〇Ri9, _〇C(0)OR2g, -NR21R22, -NR23S〇2R 2 4 , _nr23C(0)0R2° ' -NR23C(0)R24 ' -S02NR25r2 6 , -C(〇)R2 4, c(〇)〇r20, _SRl9 ' s(〇)r19, _s〇2R19,〇c (〇) r24, -C(0)NR2 5 R2 6, _nr2 3 C(N_CN)NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 R2 6. In some embodiments, in each formula (Il .a.), (Il.a. 1) and (ll.a.2) 135177 -95- 200922559 R2 is -C(0)R7 ' wherein the R7 is selected from the group consisting of substituted hexahydropyridines, Substituted /, nitrogen P ratio 11 well, substituted ruthenium P forest, substituted tetrahydro P ratio and substituted one nitrogen four garden. In some embodiments, in each formula (II.a· In (II a) and (ILa 2), R2 is selected from:

In some embodiments, R2 is -C(0)NR9 R1 0 in each of the formulas (ILa·), (II.a l), and (ILa.2). In some specific λ examples, in each of the formulas (n.a.), (n.a.i), and (n.a.2), R2 is -C(0)NH2. In some specific examples, 'in each formula (ILa), (ILa and (Il a 2), R2 is -C(〇)NR9 R1 °, where R9 and W ° can be _ U, each independently selected Self-calcinating. Some specific examples t' in the formulae (II a ), (na l) and (ILa 2) R are -C(0)NR R, wherein R9 is an unsubstituted heterocycloalkyl group, And the ruler is selected from the group consisting of hydrazine and alkyl. In some embodiments, 'in each of the formulas (na), (lLa i) and (HU), C(0)NR R, wherein R 9 is substituted a heterocyclic compound, and the y lanthanide is selected from the group consisting of ruthenium and alkyl. In some embodiments, 'in the valleys (ILa.), (II.al), and (II.a.2), R Is -C(〇)NR9R10, wherein R9 A s -7 is one or two heterocycloalkyl groups which may be substituted by the same or different substituents, each of which is independently selected from an alkyl group, and R10 is selected from the group consisting of ruthenium and alkyl. 135177 - 96- 200922559 In some embodiments, in each of the formulas (Il.a.), (Il.al), and (II.a.2), the R2 system is selected. Self-contained: alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, -C(0)R7, -C(0)0R8 and -C(0)NR9 R1 0. R2 is not limited Examples based moiety include the following:

135177 -97 200922559

Ο L—ΝΗ. and Ο

Ν - in some embodiments 尺 In each of the formulas (ILa.), (Il.al), and (II.a.2), the ruler 2 is \CF3. In some embodiments, in each of the formulas (Il.a) .), (Il.al) and (II.a.2) 0 R2 is

In some embodiments, in each of the formulas (ILa.), (Il.a.l), and (II.a.2), R2 is

In some embodiments, in the various formulas (ILa.), (II.al), and (II.a.2), in some embodiments, in the various formulas (ILa.), (II. Al) and (II.a.2) 〇, A^〇\ f In some embodiments, in the various formulas (Il.a.), (II.al) and (II.a.2) , ο 2 〇ΝΗ In some embodiments, in the various formulas (Il.a.), (II.al), and (II.a.2)

Ν' R2 is 丨 In the various formulas (ILa.), (II.a.l), and (II.a.2), in some embodiments, human R2 is I, ~/. In a particular embodiment, the compound of the invention has the structure of 135177 98-200922559 as shown in formula (Il.b) and comprises a pharmaceutically acceptable salt, solvate, ester, prodrug or Isomer:

R2 (Il.b.) wherein R], R2, E, R, R2 8 and ring B are independently selected from each other, and wherein: E is selected from the group consisting of -0-, -S-, -S(O) -, -S(0)2-, _C(R4)(r5)_, _n(r6)_, -N(C〇〇r7)_, -N(C(Y)OR8)-, -N(C (Y)N(R9)(R10"_ ; Ring B is a substituted or unsubstituted heteroaromatic ring; and, R2, R4' R5, R6, R7, R8, R9, Rl〇, r27, r28, The selected substituents on γ and ring B are as defined in any of the specific embodiments described above in Formula 1. In one embodiment, the formula has the general structure shown in formula (nb l):

(ll.b.1) '35177 -99- 200922559 In a specific embodiment, the formula (Il.b.) has the general structure shown in the formula (n.b.2):

R2 (ll.b.2). In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (ll.b.2), E is -C(R4)(R5)-. In some embodiments, in each of the formulas (ILb), (Il.bl), and (II.b_2), the E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S ( 0) 2- and -N(R6)-. In some embodiments, in each of Formulas (Il.b), (Il.bl), and (II.b.2), E is selected from the group consisting of -Ο-, -S-, -S(O)- And -S(0)2- and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24 and -C(5)R24. In some embodiments, in each of Formulas (Il.b), (Il.bl), and (II.b.2), E is selected from the group consisting of -Ο- and -N(R6)-, wherein R6 is It is selected from the group consisting of hydrazine, alkyl, 'C(〇)R24 and _C(S)R24. In some embodiments, in each of the formulas (ILb), (Il.b.l), and (ll.b.2), E is -〇. In some embodiments, 'in each of formulas (n.b), (Il.b.l), and (ll.b.2), E is ? -S- 〇 In some embodiments, in each of Formulas (Il.b), (ILb.l), and (II.b.2), E is -S(O)-. 135177 -100- 200922559 In some embodiments, in each of (II b), (ILb l), and (II.b 2), E is -S(0)2 - in some specific embodiments In each of the formulas (ILb), (ILb l), and (ILb 2), E is -C(R4)(R5)-. In some embodiments, in each of the formulas (ILb), (ILb l), and (ILb 2), E is -N(R6)-. In some specific examples, in each of the formulas (ILb), (ILb l), and (n b 2), E is -N(C(Y)R7)-. In some specific embodiments, in each of the formulas (II b), (nb U and (nb 2), E is -N(C(Y)OR8)-. In some specific embodiments, in various formulas In (ILb), (ILb l), and (nb 2), E is -N(C(Y)N(R9)(Ri〇))-. In some specific examples, in each formula (ILb), In (π Μ) and (II.b 2), γ is (=〇). In some embodiments, in each of the formulas (nb), (nb l), and (n b.2), γ is ( = s) In some embodiments, in each of the formulas (ILb), (nb l), and (ILb 2), γ is (=N(R) 3)). In some specific embodiments, In each of the formulas (nb), (ILb l), and (nb 2), γ is (=N(CN)). In some embodiments, in each of the formulas _, (nbl), and (nb 2), γ (=N(OR14)). In some embodiments, in each of the formulas (nb), (nb l), and (n b.2), γ is (=N(R15)(R16)). -101 - 200922559 In some embodiments, in each of the formulas (ILb), (II.bl), and (ILb 2), γ is (=C(R17)(R18)).

In some embodiments, in each of the formulas (ILb), (IIb υ, and (ILb 2), B is an unsubstituted heteroaromatic ring. In some embodiments, in each formula (IIb), (ILb l) and (ILb.2), B is an unsubstituted 5-6-membered heteroaromatic ring having μ3 ring heteroatoms which may be the same or different, and each hetero atom atom is independently selected from the group consisting of n, s, 〇, s(〇) and s(o)2.

In some embodiments, in each of Formulas (II.b), (II b 1}, and (II b.2), B is a heteroaryl sulphonium, which may be the same or different by one or more Substituent Substituents Each substituent is independently selected from the group consisting of halogen, -CN, -N02, alkyl, heteroalkyl, haloalkyl, alkenyl, alkenyl, alkynyl, ynkynyl, aryl, heteroaryl , aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR1 9,-0C(0)0R2() , -NR2丨R22, NR S〇2r2 4 , -NR23C(0)〇R2〇λ -NR23C(0)R24 ' -S02NR25R26 ' C(0)R, _C(〇)〇R2 0,_SR19,_s(9)R,9 , s〇2r19, 〇c(〇)r24, C(〇)NR 5R26 , -NR2 3C(N-CN)NR25R26^ _NR23C(0)NR25R26 〇, in some embodiments, in each formula (nb), In (ILb") and (nb 2), B is a 56-membered aromatic ring which has 1-3 ring heteroatoms which may be the same or different, and each hetero atomic atom is independently selected from the group consisting of N, s, and 〇. , s(〇) and s(〇h, the heteronuclear % are substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of _-, -CN, -N02 , alkyl, heteroalkyl, alkenyl alkenyl, alkenyl, alkynyl, ii alkynyl, aryl, heteroaryl, arylalkyl-, heteroaryl-alkyl-, cycloalkyl, Cycloalkenyl, heterocycloalkyl, hetero 135177 -102- 200922559 cycloalkenyl, azido, _〇Rl 9, 〇〇c(〇)〇r20, nr2 1 R22, _NR23s〇2R24, -NR23C(〇) 〇R2〇, _NR2 3C(〇)R2 4, _s〇2NR2 5R2 6 ' c(〇)r24, -C(〇)〇R2 〇, _SR1 9, _s(〇)R]9, _s〇2 Rl 9, 〇c(〇)r2 4, c(〇)nr2 5 妒6, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 R2 6. In some embodiments, In each of the formulae (Hb), (II.bl) and (nb2), B is an unsubstituted 6-membered heteroaromatic ring having 1-3 ring heteroatoms which may be the same or different, each The ring atomic system is independently selected from the group consisting of N, S and oxime. In specific embodiments, in the formulae (Il.b), (II.bl) and (II.b 2)

a 6-membered heteroaromatic ring having 1-3 ring heteroatoms which may be the same or different, each hetero atom atom is independently selected from the group consisting of N, 5 and fluorene, the heteroaromatic ring system being one or more Substituted for the same or different substituents, each substituent being independently selected from the group consisting of dentate, -CN, .2, alkyl, heteroalkyl, dentate, dilute, terrarenyl, alkynyl, haloalkyne , aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, gamma 9, - OC(0)〇R2〇, _nr2】r22, nr23s〇2R24 -NR^C(〇)〇R2〇, _NR23C(〇)r24 ^ _s〇2Nr25r26 ^ c(〇)r24 ^ -C(0)OR2〇 -SR-. .S(0)R»9, .S〇2Ri9, _〇C(〇)R24. . -NR2 3 C(N_CN)NR2 5 r2 6 and _nr2 3 c(〇)NR2 5 R2 6.

In some embodiments, 'in each of Formulas (II.b), (II.bl), and (II.b.2), the B heteroaromatic ring 'has two ring heteroatoms'. Independently selected from Ν, s and 〇. Specific Examples _, A Jiudou, m In each of the formulas (ILb), (Hbl), and (II.b.2), the b = member heteroaromatic ring 'has two ring heteroatoms, each ring hetero atom system Independently selected from N, S and 〇', the heteroaromatic ring system is substituted by one or more substituents which may be the same or different 135177-103-200922559. Each substituent is independently selected from the group consisting of halogen, _CN, _N〇2 , alkyl, heteroalkyl, i alkyl, _0Rl 9, _NR2, R22, _C(〇)R24, _C(〇)〇r2 〇, -sr, -s(o)r]9, _s〇2Ri9, 〇 c(〇)r24&_c(〇)nr25r26. In some embodiments, in each of the formulas (Hb), (Il.bl), and (nb2), B is an unsubstituted 5-membered heteroaromatic ring having _2 of the same or different The hetero atom of each of the heteroatoms is independently selected from the group consisting of N, § and 〇.

In the specific examples, 'in each formula (Hb), (II.bl) and (II.b.2), :B is 5 members of the 嘁芳奴%' has a ring that can be the same or different An atom, each of which is selected from the group consisting of N, S, and oxime, wherein the heteroaromatic ring system is substituted with or substituted by the same substituents, each substituent being independently selected from the group consisting of halogens, _CN, Μη ' - Ν 02, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, south, also from aryl, aryl, heteroaryl, aryl -, heterogas ^, 1919 alkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, stacked λ 〇C(0)OR20, -NR21R22, -NR23S02R24,

-NR23C(O)OR20, NC(0)R, -S02NR25R26, _c(〇)r2 4 -C(〇)〇R2〇..Sr]9_ () ()R, -S02 R1 9,-0C(0 R2 4, -C(0)NR2 5 R2 6 , ^3C(K-CN)NR25r26^Nr23w - some of the specific examples are unsubstituted 5_members' Λ' _' (ΙΙΛ1) and (ILb· 2) The 'β atom. ...the slave nucleus, having one ring selected from Ν, S, and Ο as Γη. In some specific examples, 'in various formulas _, _, and ah, Β is a 5-shell heteroaromatic ring, "Τ Β The aromatic ring system is replaced by a / / ring hetero atom selected from Ν, S and 0. The heterogeneous group is independently substituted from h (four) or a different substituent, each of which includes _ 素, -CN, -N〇2, alkyl 'heteroalkyl, tooth 135177 • 104. 200922559 alkyl, -OR1 9, _NR2 1 R22, _C(〇)r24, c(〇)〇r2〇, system 9, but 9 S 〇 2Rl9, -〇C(0)R24 and -C(0)NR25r2 6.

In some embodiments, in each of the formulas (ILb), (ILb l), and (II b 2), B is a heteroaromatic ring having s as a ring heteroatom, the heteroaromatic ring system being Or a plurality of substituents may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of i, s, s, 2, ketone, (4), haloalkyl, _0R19, RR, 'C(〇)R24, -C(0)0R2°, -SR19, -S(0)R丨9, -S〇2r19, -〇C(〇)R2 4 and c(〇)nr25r26. In some embodiments, in the formulas _, dLb.D and (n.b.2), the 5-membered heterocyclic ring substituted with B has s as a ring hetero atom. ζΛζΛ. —'τ- « ___ V...

2

R

s 2 or

R

2 The following general structure

S N

R or

R 2 In some embodiments, in each of formulas (Il.b), (n.b.l), and (ll.b.2), Ϊ35177-105-200922559 R1 is an unsubstituted aryl group. In some embodiments, in each of Formulas (IIb), (II b丨), and (II b 2), R1 is an unsubstituted phenyl group. In some embodiments, in each of the formulas (ILb), (II.b l), and (ILb.2), R1 is an unsubstituted thiol group. In some embodiments, in each of the formulas (ILb), (ILb l), and (II b.2), R1 is a substituted aryl group. r In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (ll.b.2), R1 is a substituted phenyl group. In some embodiments, in each of Formulas (IIb), (ILb), and (ILb 2), R1 is a substituted naphthyl group. In some embodiments, in each of Formulas (Ii b), b, and Ba.2), R is an aryl group substituted with one or more substituents which may be the same or different, each substituent being independently selected. Self-including halogen, _CN, _n02, alkyl, heteroalkyl, haloalkyl, alkenyl, ! Ialkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, I aryl-alkyl-, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl , azido group, _〇R19, ·〇(:(〇)〇κ20, _nr21r22, -NR23S02R24, -NR23C(0)OR20, -NR23C(0)R24, -S〇2NR25R26, -C(〇)R24, -C(〇)〇R2 0, _SR19, _s(〇)Rl9, _s〇2r19, 〇c(〇)r24, -C(0)NR2 5 R2 6, _NR2 3 C(N-CN)NR2 5 r2 6 And _nr2 3 c(〇) nr2 5 r2 6. In some embodiments, in each of formula (II b), (ILb l), and shell b 2), R1 is one or more may be the same or a substituent substituted with a different substituent, each substituent being independently selected from the group consisting of halogen, -CN '-N02, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl' Aryl, heteroaryl, 135177 -106- 200922559 ^yl-fluorenyl-, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, - 〇Rl9, _〇C(〇)〇R2Q, _NR2iR22, -nr23so2r24, -nr23c(o)or20, -NR23C(0)R24, -S02NR25R26, -C(0)R24, -C(0)〇R2〇, -SR19, -S(0)R19, -S02R19 -0C (0) R24, -C (0) NR2 5 R2 6, -NR2 3 C (N-CN) NR2 5 R2 6 and _NR2 3 c (square) NR2 5 r2 6. In some embodiments, 'in each formula (Hb), (Il.bl), and (ll.b.2), R1 is phenyl substituted by one to four substituents which may be the same or different, each substitution The base system is independently selected from the group consisting of halo, 〇H, -CN, -N〇2, -NR21R2 2 and a halogen group. In some embodiments, in each of Formulas (Il.b), (mi), and (n.b.2), the R1 is selected from the group consisting of:

In some embodiments, 'in each of formulas (H.b), (Il.b.l), and (ll.b.2), R1 is:

In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (ILb.2), R1 is a stupid group substituted with one to three fluoro groups. In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (II.b.2), 135177-107-200922559 R1 is a stupid base substituted with two fluoro groups. In some embodiments, in each of Formulas (II.b), (n.bj), and (11.2), R1 is phenyl substituted with a fluoro group. In some embodiments, in each of (II.b), Beichang, and (n.b.2), R1 is:

In some embodiments, in each of Formulas (IIb), (II.b l), and (II b.2), R27 and R28 are each independently selected from the group consisting of ruthenium and ruthenium. In some embodiments, 'in each of formulas (II b), (II b and (II b 2), R 2 is -C(Z)R7. In some embodiments, in each formula (II b), In (ILb l) and (ILb.2), R2 is -C(Z)NR9R10. In some embodiments, in each of formulas (IIb), (II b and (II b 2), R2 is - C(Z)OR8. In some embodiments, in each of Formulas (IIb), (ILb1), and (ILb2), R2 is -S02NR9Ri〇. In some embodiments, 'in various formulas (ILb) In (ILb l) and (ILb 2), R 2 is a calcining group. In some embodiments, in each of the formulas (ILb), (ILb 1), and (ILb 2), R 2 is a miscible group. In some embodiments, in each of Formulas (IIb), (ILb1), and (ILb2), R2 is aryl. 135177-108- 200922559 In some embodiments, R is a heteroaryl group. R2 is cycloalkyl. In some embodiments R2 is cycloalkenyl. In some embodiments R2 is heterocycloalkyl. f In some embodiments R2 is heterocycloalkenyl. In the specific embodiment, it is (=0). In some embodiments, (=s) In some embodiments ((=N(R)3)). In some embodiments (=N(CN)). In some embodiments bNCOR1 4)). In some embodiments, it is (=N(R15)(R16)). In some embodiments, it is 0=(:(1117)(1118)).] 35177 'in each formula (ILb), (Il. In bl) and (II.b.2), in each of formulas (Il.b), (Il.bl), and (II.b.2), 'in each formula (ILb), (Il.bl) And (II.b.2), in each of the formulas (Il.b), (Il.bl) and (II.b.2),

'In each of the formulas (Il.b), (Il.bl), and (II.b.2), in each of the formulas (ILb), (Il.bl), and (II.b.2), Z ' In each of the formulas (ILb), (Il.bl), and (II.b.2), Z' is in each of the formulas (Il.b), (Il.bl), and (II.b.2), Z' In each of the formulas (Il.b), (Il.bl), and (II.b.2), Z, in each of the formulas (Il.b), (Il.bl), and (II.b.2), Z 'in each of the formulas (Il.b), (Il.bl), and (II.b.2), Z, in each of the formulas (Il.b), (Il.bl), and (II.b.2) , Z-109-200922559 In some embodiments, in each of the formulas (Il.b), (Il.bl), and (II.b.2), R2 is -C(Z)R7, and Z is (=0). In some embodiments, in each of Formulas (II.b), (ILb l), and (ILb.2), R2 is -C(0)H. In some embodiments, in each of Formulas (ll.b), (ll.b.l), and (IIb2), R2 is -C(O)alkyl. In some embodiments, in each of Formulas (II.b), (ILb l), and (ILb 2), R2 is -C(0)CH3. In some embodiments, in each of Formulas (Il.b), (ILb l), and (ILb 2), R2 is -C(0)R7, wherein the R7 is one or more may be the same or different The substituents substituted by the substituent 'each substituent are independently selected from the group consisting of keto, halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, Haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR1 9, -〇C(〇)〇r20, _NR2 1 R22, _NR23 S〇2R24, -NR2 3C(〇)OR2〇, _NR2 3c(〇)r24, _s〇2Nr25r26, _c(〇)r24, -C(0)〇R20, -SR1 9,4(0)111 9, -SC^R1 9, -〇C(0)R24, -C(0)NR25R26, -NR2 3 C(N_CN)NR2 5 R2 6 and _Nr2 3 c(〇)nr2 5 r2 6. In some embodiments, 'in each of Formulas (Il.b), (Il.bl), and (II.b.2), R2 is -C(0)R7' wherein the R7 is one to three The alkyl group substituted with the same or different substituents, each substituent being independently selected from the group consisting of 〇κΐ9, _NR2iR22 and a cycloalkyl group. In some embodiments, 'in each of (nb), (II.bl), and (ILb 2), R2 is -C(0)R7' wherein R7 is alkyl, wherein the alkyl is alkyl Replace with _〇H. -1) 0- 135177 200922559 In some embodiments, in the Shibuya type (ILb), (Il. bl), and (II.b.2), R2 is -C(0)R7, wherein the R7 In order to be substituted by a main alkyl group which may be substituted by the same or different substituents, each of the substituents is independently selected from the group consisting of -OH, -NH2 and cyclopropyl. In some embodiments, in each of the mh, the coupled formulas (II.b), (Il.bl), and (II.b.2), R2 is -C(0)R7, wherein the R7 is - Up to two alkyl groups which may be substituted with the same or different substituents, each of which is independently included from -NH2 and cyclopropyl. In some embodiments, in each of the formulas (ILb), (Il.bl), and (II.b.2), R2 is -C(0)R7, wherein the R7 is replaced by _〇H Alkyl group. In some embodiments, in each of formulas (n.b), (n b i), and (reg. 2), R 2 is —C(O)R 7 , wherein R 7 is unsubstituted heterocycloalkyl. In some specific embodiments, in each of formula (II b), (II b l), and melon b 2), R is -C(O)R7, wherein R7 is a substituted heterocycloalkyl.

In some specific embodiments, in each of the formulas (II b), (ILb l), and (n b.2), R is -C(0)R7, wherein the R7 is one or more may be the same Or a heterocycloalkyl substituted with a different substituent, each substituent being independently selected from the group consisting of keto, halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkyl , alkynyl, i alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, -〇Rl 9, 〇〇c(〇)〇r2 0, _nr2 1 r2 2, -NR23S02R24 ' -NR23C(0)0R2° ' -NR23C(0)R24 ' -S02NR25R26 ' , C(0)R24, -C(0)〇R20, -SR19, -S(0 R19, -S02R19, -0C(0)R24, -C(0)NR2 5 R2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 . In some embodiments, in each of Formulas (Il.b), (Il.bl), and (ILb.2), R2 is -C(0)R7' wherein R7 is selected from the group consisting of substituted hexahydro Pyridine, hexahydropyrazine substituted by 135177-111 - 200922559, substituted morpholine, substituted tetrahydropyrrole and substituted one nitrogen tetraindole. In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (n.b.2), R2 is selected from:

In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (II.b.2), R2 is -c(o)nr9r10. In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (II.b.2), R2 is -c(〇)nh2. In some embodiments, in each of Formulas (Il.b), (Il.bl), and (II.b.2), R2 is -C(0)NR9R]〇, wherein R9 and Rio may be the same or Different, each is independently selected from the appearance base. In some embodiments, in each of Formulas (Il.b), (Il.bl), and (ΙΙ·Κ2), R2 is -c(o)nr9r]〇, wherein R9 is unsubstituted heterocycloalkane And R10 is selected from the group consisting of ruthenium and alkyl. In some embodiments, in each of the formulas (ILb), (ILb l), and shell b 2), R2 is -C(〇)Nr9r1〇, wherein R9 is a substituted heterocyclic alkyl group, and R1〇 The choice is from hydrazine to alkyl. Play some specific facts...叨, (Il.b.l) and (II.b.2): 2 is -CXCWRI. 'wherein 妒 is - to three heterocyclic groups which may be the same or different =, each substituent is independently selected from the group, and R1 is selected from the group consisting of hydrazine and alkyl. In the examples, in the formulas _, (10)") and (10).2), 135177 Π2- 200922559 R2 is selected from the group consisting of: alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, -C(0)R7 , -C(0)0R8 and -C(0)NR9 R1 0. Non-limiting examples of R2 include the following partial groups:

135177 - 113- 200922559 In the various formulas (Il.b), (Il.b.l) and (ll.b.2), in some embodiments, R2 is Y^CF3. In some embodiments, in each of Formulas (Il.b), (Il.b.l), and (II.b.2), R2 is

In some embodiments, in each of the formulas (Il.b), (Il.b.l), and (II.b.2), 0 R2 is

0 f-' In some embodiments, in each of the formulas (Il.b), (Il.bl), and (II.b.2), in some embodiments, in each of the formulas (Il.b) , (Il.bl) and (II.b.2) in some specific examples, in the various formulas (Il.b), (Il.bl) and (II.b.2) ΝΗ 2 〇 In some embodiments 2 Ί R2 is I. In some embodiments, 'R2 is in each of the formulae (Il.b), (Il.bl), and (II.b.2) in the formulae (Il.b), (Il.bl), and (II) .b.2) 中Ν-N— In a specific embodiment, the compound of the present invention has the structure shown in formula (III.1) and includes pharmaceutically acceptable salts, solvates, esters of the compound , prodrug or isomer: 135177 -114- 200922559

(ΠΙ. I) wherein R], R2, R3, R27, R28, p, E and ring B are independently selected from each other, and wherein: E is selected from the group consisting of -0-, -S-, -S(O )-, -s(0)2-, -C(R4)(R5)..._N(R6)_, -N(C(Y)R7)-, -N(C(Y)OR8)-, and -N (C(Y)N(R9)(R)0))-; and p is α l or 2; and %Β, R1, R2, R4, R5, R6, R7, r8, r9, Rl0, r27, r28 The selected substituents on Y, Y and % B are as defined in any of the specific examples described in Formula 1 above. i In the specific embodiment, 'in the formula (Πΐ, ι): E is selected from including you 4) (r5)_, _〇_, each, _s(〇)_, _s(〇)2_iN(R6) _; « is an unsubstituted or substituted aromatic ring, or an unsubstituted or substituted 5-6-membered heteroaromatic ring having μ3 ring heteroatoms, which may be opposite or different ' Each ring hetero atom is independently selected from the group consisting of N, s, 〇' s (9) and 'the substituent on the ring or the heteroaromatic ring (when present) = is selected from the group consisting of, including, burning,嶋, (4), alkynyl, aryl 'heteroaryl, aryl-alkyl, ...%, alkyl, heterocyclic, heterocyclic, heterocyclic, Π5177 -115- 200922559 azide, - OR19, -〇C(〇)〇R20, _NR21R22, _nr23S〇2r24, -NR23C(0)0R2° > -NR23C(0)R24 > -S02NR25R26 ' -C(0)R24 ' -C(0)0R2 . , -SR1 9, -S(〇)Ri 9, _s〇2Ri 9, _〇c(〇)R2 4, _c(〇)nr25R26, -NR2 3 C(N-CN)NR2 5 R2 6 and _nr2 3 C(0)NR2 5 R2 6 ; R1 is an unsubstituted aryl group' or an aryl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of _, _CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl , cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, 〇Rl9, _〇C(〇)〇R2〇, _NR2 1R2 2 , -NR23S02R2 4 , -NR23C(0) 0R2° > -NR23C(0)R24 ^ -S02NR25R26, -C(0)R24, _c(〇)〇R2 0, _SR19, _s(〇)Ri9, s〇2Rl9, -〇C(0)R2 4 , -C(〇)NR25R2 6 , -NR23C(N-CN)NR25R26^-NR23C(〇)- NR25R26 ; R2 is selected from the group consisting of -C(0)R7, _匸(〇辉91^ 0 and -C(0) ) 0R8 ; P is 0 or 1; and each ignition is independently selected from the group consisting of alkyl, heteroalkyl 'sweet, heteroalkenyl, -CN, -N02, -0R19, _〇QC)K) R2(), nr21r22, \ -C(S)R2 4, _C(〇)〇R2 0 and _c(〇)Nr25r26, each of which is burned Each of the heterozygous filaments, each of the dilute bases, and each of the heterogeneously baked bases are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be different from each other. Each substituent is independently selected from the group consisting of S. , dentate, -CN, trap 2, alkyl, rhodothene, alkyl, dilute, dentyl, alkynyl, _, aryl, aryl, cycloalkyl, cyclyl, Miscellaneous soil base, heterocyclic dilute base, azide base, see 19, cargo (〇) 〇r2〇, 135177 200922559 -NR2, R2 2, _Nr23s〇2R24, _nr23c(〇)〇r2〇, nr23c(〇)r24 -S02NR25R2 6 n -C(〇)r2 4 x _C(0)OR20 ' -SR19 ' -S(0)R19 χ -S〇2Rl9, -〇C(0)R24, -C(0)NR25R26,- Group of NR23C(N-CN)NR25R2 6 and -NR23C(〇)NR2 5R26. In a specific embodiment, in Formula (III1): B is an unsubstituted or substituted moiety selected from the group consisting of benzo, furanyl, thiophenyl, pyrrolyl, oxazolyl, Pyrazolyl, imidazolyl, pyrazole f, isoxazolyl, isoxazolyl, triazolyl, thiadiazolyl, pyridyl, hydrazine, pyrimidinyl, pyridinyl and tri-farming;

R1 is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of fluorenyl, 〇H, _CN, _n〇2, _nr21r22 and haloalkyl; each of R7 and R28 Independently selected from H and alkyl; R is selected from the group consisting of -c(〇)r7, _c(〇)nr9r10&c(〇)〇r8; P is 0 or 1; and (each R3 (when present)) Independently selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, and a heterocyclic group, wherein each of the hydroxy groups, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently One or more substituents may be substituted with the same or different substituents. Each substituent is independently selected from the group consisting of a keto group, a halogen, —CN, — — 02, an alkyl group, a hetero group, a halogen group, an alkenyl group, a dentate group, Block group, i block group, aryl group, heteroaryl group, cycloalkyl group, cycloalkyl group, heteroalkyl group, heterocycloalkenyl group, azido group, _or19, -oc(o)or20, NR R '-NR23S 〇2R2 4 ^ _NR2 3C(〇)〇R2 0 , -NR2 3C(〇)R2 4 λ 135177 *117- 200922559 -so2nr25r26, -C(0)R24, -C(0)〇r2〇, -SR19, _S (0) R19, -S〇2 R1 9 ' -0C(0)R2 4 ' -C(0)NR2 5 R2 6 ^ -NR2 3 C(N-CN)NR2 5 R2 6 and a group of -NR2 3 C(0)NR2 5 R2 6 . In one such embodiment, in the formula (ΠΙ.1): R1 is:

f ' r6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, _c(〇)〇R2〇 and _c(S)R24. In a particular embodiment, the compound of the invention has the structure shown in formula (III 2) and includes a pharmaceutically acceptable salt, solvate, ester, prodrug or isomer of the compound:

Select, and wherein: E is selected from the group consisting of -〇-, -S-, -S(0)_, _s(〇)2_, c(r4)(r5)_, _n(r6)_, -N(C (Y) R7)-, -N(C(Y)OR8)j_N(c(7)n(r9)(r1〇w; and p is 0, 1 or 2, and ring B, R1, R2, R4, R5, R6, The selected substituents on r7, r8, r9, R] 〇, 妒7, r28, Y and ring B are all as defined in the specific examples of 135177 • 118 - 200922559 as described in Formula 1 above. In the embodiment, in the formula (4)): E is selected from the group consisting of -c(r4)(r5)_, _〇_, s_ to earn R rabbit soil π π (υ · -S(0)2- and -N( R6)-; % B is unsubstituted 5 6 member...a 戈 ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... The hetero atom is independently selected from the group consisting of N, s, 〇, s(9) and an aromatic ring or the substituent on the heteroaromatic ring (when present) r "includes *, _CN, .2, alkyl, miscellaneous Base, ship, olefinic, alkynyl, alkynyl, aryl, heteroaryl, aryl-alkyl-, heteroarylalkyl 5, cycloalkenyl, heterocycloalkyl, hetero Ring dilute, azide group, -OR19, _〇C(〇)〇r20 Nr21r22, NR23s〇2R24, - service 乂(9)(10), tear 23c(〇)r24, s〇2nr25r26, c(〇)r24, -C'm —SR' .s(〇)Rl9, _s〇2r19, 〇c( 〇)r24, c(〇)nr25r26, -NR2 3 C(N-CN)NR2 5 r2 6 and _nr2 3 c(〇)nr2 5 r2 6 ; R1 is an unsubstituted aryl group, or is one or more An aryl group which may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, heteroalkyl 'haloalkyl, alkenyl, haloalkenyl, alkyne , haloalkynyl, aryl, heteroaryl 'aryl-alkyl-, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl 'azide, _ 〇Ri 9, _〇C(〇)〇R2〇, -NR21R22, -NR23S02R24, _NR23C(0)OR20, -NR23C(0)R24, -S02NR25R26, -C(0)R24, -C(〇)〇R2 〇, _SR", _S(〇)R19, _S〇2R19, -0C(0)R24, -C(0)NR25R26, _NR2 3C(N_CN)NR2 5R2 6&_NR2 3C(〇)_ nr25r26 ; R2 is selected from Including -C(〇)R7, -C(0)NR9R10 and -C(0)0R8; 135177-119- 200922559 p is 〇 or l; and each R3 (when present) is independently selected from the group consisting of alkyl, hetero Alkyl, alkenyl, heteroalkenyl, -CN -N02, -〇Ri9 ' 〇c(〇)〇r20, nr21r22, c(〇)r24, -C(S)R2 4, -c(〇)〇r2 o and _c(〇)nr2 5 r2 6, Wherein each of the alkyl groups, each of the heteroalkyl groups, each of the dilute groups, and the heterocyclic group are unsubstituted or, as the case may be, independently substituted or substituted with the same or different substituents, each substituent Independently selected from the group consisting of keto, dentate, CN N〇2, alkyl, heterophenyl, haloalkyl, alkenyl, dentate, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl , cycloalkenyl, heteroalkyl, heterocycloalkenyl, azido, _〇R]9, _〇c(〇)〇r2〇, NR R, -NR23S〇2R24, _NR2 3C(〇)〇R2 0, _Nr23c(〇)r24, S〇2NR25R26, _c(〇)R24, _c(〇)〇r2Q, SR19, S_19, -S02R > -0C(0)R2 4 , -C(〇)NR25R2 6 . A group of NR23C(N-CN)NR25R26 and -NR2 3C(〇)Nr25r26. In a specific embodiment, in the formula (Π1.2):

The ring is an unsubstituted or substituted part of the base ring, selected from the group consisting of benzoate, bitter base, thiophenyl, pyrrolyl " oxazolyl" oxazolyl", isoxazolyl, thiazole , 咄, /, 1 丄 oxadiazolyl, thiadiazolyl, pyridyl, hydrazine, pyrimidinyl, pyridinyl and tri-farming; RI is: to four can be the same or different a substituent substituted phenyl, each substituent is independent; AI ^ includes i group, 0H, _CN, _n 〇 2, 21 21r22 and a halogen group; R7 and R28 are each independently selected from the group consisting of ruthenium and alkyl; R2 It is selected from the group consisting of -C(0)R7, -C(〇)nr9r]0 and _c(〇辉8; 135177-120-200922559 P is 0 or 1; and heteroalkyl, alkenyl, hetero-R3 ( When present, are independently selected from the group consisting of alkyl groups, wherein each of the alkyl groups, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently Substituents may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of a keto group, a phytosin, a haloalkyl group, an alkenyl group, a benzyl group, a -N02 group, an alkyl group, a heteroalkyl group, an alkynyl group, Haloalkynyl, aryl, heteroaryl, cycloalkyl, Alkenyl, heterocycloalkyl, heterocycloalkenyl, azido' _ 〇 Rl9, _〇C(〇)〇R2〇, -NR R2 2, -NR S02 R2 4, —NR2 3 C(0)〇 R2 0, -NR2 3 C(0)R2 4, -so2nr25r26, -C(0)R2 4, _c(〇)〇r20, SRl9, _s(〇)Rl9, -S02R19, -0C(0)R24, - A group of C(0)NR25R26, -NR23C(N-CN)NR25R26 and -nr23c(o)nr25r26. In one such specific embodiment, in the formula (111, 2): R1 is:

R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R2 4, _C(〇)〇R2(^_C(5)R2 4. In a particular embodiment, the compound of the invention has the formula (Ill.a) Structure, and including pharmaceutically acceptable salts, solvates, esters, prodrugs or isomers of the compound: 135177 -121 - 200922559

The ground is selected, and wherein: 垓A (including E and the unsaturation shown) is a cycloalkenyl or heterocycloalkenyl ring; E is selected from the group consisting of -0-, -S-, -s(0) )-, -s(0)2-, -C(R4)(R5)-, _n(R6)-, -n(c(y)r7)_, _n(c(y)or8)_, _n( c(y)n(r9)(r1(}))_, _c(〇)_n(r11)_, -N(R> I ).C(0)- > -S^^NCR11)- > -N(RJ i )-S(〇)2- ^ -C(0)-0- > -OC(O)-, -〇-N(R6)-, -N(R6)-〇-,- N(R6)-N(R12)-, -N=N- and -C(R7)=N-; ring B is a substituted or unsubstituted aromatic ring; P, Rl, R2, R3, R4, The optional substituents on R5, R6, R7, R8, R9, R1 0, R1 1, R1 2, R27, R28, Y and ring B are all as defined in any of the specific examples described above in formula (I). In a specific embodiment, the formula (Ill.a) has the following general structure:

R3) Ϊ 35Ι77 -122- 200922559 In one embodiment, the formula (Hl.a) has the following general structure:

In a specific embodiment, in the formula (Ill.a.), p is 〇, 1 or 2; in one embodiment, 'in the formula (Ill.a.), ring a is a ring-like group Ring, and E is -C(R4)(R5)-. In a specific embodiment 'in the formula (Ill.a.), ring A is a heterocyclic heterocyclic group, and E is selected from the group consisting of -C(0)-N(Rn)-, -N^y-QO )-, _S(〇)2_N(Rll)_, -N(Rn)-S(0)2-, -C(0)-〇-, -〇-C(0)-,-0-N(R6 )_, _n(r6)〇, -N(R6)-N(R] 2)-, -N=N-, and -C(R7)=N-. By way of non-limiting example, examples of compounds of formula (IILa.) wherein E is -C(0)-N(Rn)- include:

0 0 In a specific embodiment, in Formula (Ill.a.), Ring A is a heterocycloalkenyl ring, and E is selected from the group consisting of -〇-, -S-, -S(0)-, -S(0)2- and -N(R6)-. In a specific embodiment, in the formula (IILa.), the E is selected from the group consisting of -〇_, -S-, -S(〇)-, -S(0)2-, and -N(R6)- Wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24 and -C(S)R24. In a specific embodiment 'in the formula (Ill.a.), the E is selected from the group consisting of -0- and -N(R6)-, wherein the lanthanide is selected from the group consisting of ruthenium, alkyl, and -C(0) R24 and -C(S)R24. 135177 -123- 200922559 In a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), in a specific embodiment, In a specific embodiment, in a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), in a specific implementation In the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), In a specific embodiment, in the formula (Ill.a.), E is in a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill. In a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), in a specific embodiment, In a specific embodiment, in a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), in a specific implementation In the example, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), in a concrete In the formula (Ill.a.), in a specific embodiment, in the formula (IILa.), in a specific embodiment, in the formula (Ill.a.), In a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.), in a specific embodiment, in the formula (Ill.a.) , E is -0-. E is -S-. E is -S(O)-. E is -S(0)2-. E is -C(R4)(R5)-. E is -N(R6)-. E is -N(C(Y)R7)-. E is -N(C(Y)OR8)-. -N(C(Y)N(R9 XR1 G))-. E is -C(0)-N(Rn)-. E is -N(R] 1 )-C(0)-. E is -S(0)2-N(Rn)-. E is -NKR1 y-SCOh-. E is -C(0)-0-. E is -O-C(O)-. E is -0-N(R6)-. E is -N(R6)-0-. E is -N(R6)-N(R12)-. E is -N=N-. E is -C(R7)=N-. Y is (=0). Y is (=s). Y is (=N(R]3)). Y is (=N(CN)). 135177 - 124- 200922559 In a specific embodiment, in the formula (m.a.), γ is (^(ORM)). In a specific embodiment, in the formula (nl.a.), γ is (=N(Rl5)(Rl6). In a specific embodiment, in the formula (III.a·), γ is (=C(R1 7)(r1 8)). In a specific embodiment 'in the formula (III.a.), B is an unsubstituted aromatic ring. In a specific embodiment, In the formula (IILa), B is an unsubstituted benzo ring ' and the formula (IH.a.) has the following general structure:

In the embodiment of the invention, in the formula (IILa), B is an aromatic ring, and the i is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of i, _CN , _NQ2, (4), (4), (10), baking base 'i dilute, block, 4, aryl, heteroaryl, aryl-like heteroaryl, · ring, base, «base, miscellaneous Cycloalkyl, heterocyclic dilute, fluorenyl, -OR19, _〇c(9)〇r20, nr21r22, na, -nr23C(〇)〇r2〇, _nr23c(〇)r24 ^ _s〇2Nr25r26 ^ 2 ' 'C( 〇)〇R2°' 'SR19' 'S(0)R19' 9 ^ -〇C(〇)R- ^ -C(〇)nr25r26 . -NR2 3 C(N-CN)NR2 5 R2 6 and rhyme 2 3 c(〇)nr2 5 r2 6. In one embodiment, one or more may be the same or in the formula (IILa.), B is a benzo ring, and the substituents are different. 'Substituents are 135177 > 125- 200922559 Included from the group consisting of halogen, -CN, -Ν〇2, alkyl, heteroalkyl, _inhoyl, dilute, haloalkenyl, alkynyl, ynkynyl, aryl, heteroaryl, aryl Aryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclomethine, azide, -OR19, -OC(0)OR20, -NR2]R22, _Nr23srr24, -NR23C(0 ) 0R2° > -NR2 3C(〇)R24 . -S02NR2 5r2 6 n _C(〇)r24 -C(0)0R2 Q, -SR1 9, _S(0)R1 9, -S〇2 Rl 9, _ 〇c(〇)r2 4, c(〇)nr2 5 r2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and _NR2 3 C(0)NR2 5 R2 6 R is an unsubstituted ί In a specific embodiment, in formula (IILa.), the group. In a specific embodiment, in the formula (III.a.), ~ is an unsubstituted stupid group. In a specific embodiment, in the formula (ni.a.), Ri is an unsubstituted naphthyl group. In one embodiment, 'R' is a substituted aryl group in formula (IILa.). In a particular embodiment, in the formula (III.a.), 'R1 is a substituted phenyl group. (In the specific embodiment, 'in the formula _.) 'Ri is a substituted stupid group. In the specific embodiment, 'in the formula (111)', R1 is an aryl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of li-, -CN, -N02, alkyl, heteroalkyl, _alkyl, alkenyl, haloalkenyl, alkynyl, alkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl, ring Alkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, gamma 9, -CC-R2. , _NR2lR22, _NR23s〇2R24, _nr23c(〇)〇r2〇, -nr23c(0)r24, _s〇2Nr25r26, _c(0)r24, _c(〇)〇R2G, SR]9, -S(0)R' 9 . -S〇2R19 > -〇C(〇)R24 , .C(〇)NR25R26 λ „NR23C(N.CN). 135177 -126· 200922559 NR25R26&-NR23C(0)NR25R2 6. In a specific In the embodiment, in the formula (m_a·), R] is a phenyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N〇2 , alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, ynkynyl, aryl, heteroaryl, aryl-alkyl-, heteroarylalkyl, cycloalkyl ,cycloalkenyl,heterocycloalkyl,heterocyclenyl,azido'-OR19,-0C(0)0R2G, -NR21R22, -NR23S02R24, -NR23C(0)〇R2〇, -NR23C(0)R24 , -S02NR25R26, _c(0)R24, -C(〇)〇R2〇, _SR19, -S(〇)R] 9 ' -S02R19 ' -0C(0)R24 > -C(0)NR25R26 > - NR2 3 C(N-CN)· NR2 5 R2 6 and —NR 2 3 C(0)NR 2 5 R 2 6. In one embodiment, 'in the formula (III.a.), Ri is one to four Benzene which may be substituted for the same or different substituents Each substituent is independently selected from the group consisting of halo, -OH, -CN, -N〇2, -NR2 1R2 2, and haloalkyl. In a particular embodiment, 'in formula (III.a.), R] is selected from the group consisting of:

In a specific embodiment, 'in the formula (ni.a.), Ri is:

In a specific embodiment, in the formula (m.a.), R1 is a phenyl group substituted with one to three fluorines 135177 -127- 200922559. In a specific embodiment, in the formula (IILa.), R1 is a phenyl group substituted by two fluorine groups. In a specific embodiment, in the formula (Ill.a.), R1 is a phenyl group substituted by a fluorine group. In a specific embodiment, in the formula (Ill.a.), R1 is:

In a specific embodiment, in the formula (Ill.a.), R27 and R28 are each independently selected from the group consisting of ruthenium and alkyl. In a specific embodiment, in Formula (Ill.a.), R2 is -C(Z)R7. In a specific embodiment, in the formula (Ill.a.), R2 is -C^NR9:^0. In a specific embodiment, in the formula (Ill.a.), R2 is -C(Z)OR8. In a specific embodiment, in the formula (Ill.a.), R2 is -SC^NR9!^. In a particular embodiment, in Formula (Ill.a.), R2 is an alkyl group. In a particular embodiment, in Formula (Ill.a.), R2 is heteroalkyl. In a particular embodiment, in Formula (IILa.), R2 is aryl. In a particular embodiment, in Formula (Ill.a.), R2 is a heteroaryl group. In a particular embodiment, in Formula (Ill.a.), R2 is cycloalkyl. In a particular embodiment, in Formula (Ill.a.), R2 is cycloalkenyl. In a particular embodiment, in Formula (111.a.), R2 is heterocycloalkyl. In a particular embodiment, in Formula (Ill.a.), R2 is heterocycloalkenyl. In a specific embodiment, in the formula (Ill.a.), Z is (=0). 135177 -128- 200922559 ^ Z is (=s). , 2 is (= wind 1113)). 'Z is (=N(CN)). , Z is (=N(OR14)). Z is (=N(R)5)(R16)) Z is (=c(r17)(r18))

In the formula (m.a.), R2 is -C(Z)R7, and Z

(d) for a group substituted by - or a plurality of substituents which may be the same or different substituents, each substituent being independently selected from the group consisting of a ketone group, a hydroxyl group, a (tetra) group, a ", a can, a ", an anthracene, an aryl group,

In a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment The middle (= 0) 0 is in a specific embodiment in a specific embodiment in a specific embodiment in a specific embodiment in the formula (IILa.) in the formula (Ill.a·) In the formula (Ill.a.), in the formula (Ill.a.), in the formula (Ill.a.), a heteroaryl group, a bad alkyl group, a cycloalkenyl group in the formula (Ill.a.) Cycloalkyl, heterocycloalkenyl, azido-OR19 '-〇C(0)〇R2〇, -NR2 1R2 2 , _NR2 3S〇2R24 ^ .NR2 3C(〇)〇R2 0 -NR23C(〇)R24 , _Sq2Nr25r26, (Which 24,, (10)., View] 9, -S(〇)R*9 . _S〇2R19 . _〇C(〇)r24 , .C(〇)NR25r26 χ _NR2 3C(N.CN: NR2 5 R2 6 ^ _NR2 3 C(〇)NR2 5 R2 6 0 ^ - In the specific embodiment, in the formula (III.a.), r2^c(〇)r7, where J is - to two a base which may be substituted with the same or different substituents, each substituent being unique The column is selected from the group consisting of _0R1 9, _NR2, R22 and naphthene. In the case of the specific item, in the ^_·) towel, r2^c(q)r7, wherein] 35177 -129- 200922559 the R7 is an alkane a group wherein the alkyl group is substituted with an alkyl group and _〇H. In a specific embodiment t, in the formula (Ill.a.), R2 is -C(0)R7, wherein the R7 is one to three An alkyl group which may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of 〇H, -NH2 and cyclopropyl. In a particular embodiment, in the formula (Ill.a.) , Rule 2 is _c(〇)R7, wherein R7 is an alkyl group substituted by one or two substituents which may be the same or different, each substituent being independently selected from the group consisting of _NH2 and a cyclopropyl group. In a specific embodiment 'in the formula (Ill.a.), r2 is _c(〇)R7, wherein the R7 is an alkyl group substituted by _〇H. In a specific embodiment, in the formula (IILa. Wherein R2 is _C(0)R7, wherein R7 is unsubstituted heterocycloalkyl. In a particular embodiment, in formula (Ill.a.), r2 is _c(〇) R7, wherein R7 is substituted heterocycloalkyl. In a particular embodiment 'in formula (ll.a.), R2 is _C(0)R7, wherein R7 is a heterocycloalkyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, _Cn, -N〇2 House base, miscellaneous base, halogenated base, dilute base, _ dilute base, alkynyl group,! g alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -OC(0)OR20, -NR21R22, _nr2 3s〇2r2 4, -nr23c(o)or20, -NR23C(0)R24, _S〇2NR2 5R26, _c(〇)r24, -C(0)0R20, -SR19, -SCCOR1 9, -S02RB, _〇c(〇) R24, c(〇)nr25r26, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 R2 6. In a specific embodiment 'in the formula (Ill.a.), r2 is _c(〇)R7, wherein § 玄R7 is selected from the group consisting of substituted six gas p-bite, substituted hexahydroquinone p well, 135177-130- 200922559 substituted morphine, substituted tetrahydropyrrole and substituted one nitrogen tetraindole. In a specific embodiment, in the formula (m.a.), the R2 is selected from the group consisting of:

In a specific embodiment, in the formula (Ill.a.), R2 is -CCCONR9!^0. In a specific embodiment, in the formula (Ill.a.), R2 is -C(0)NH2. In a specific embodiment, in the formula (Ill.a.), R2 is ((CONI^R1 〇, wherein R9 and Rio may be the same or different, each independently selected from an alkyl group). In one embodiment In the formula (Ill.a.), R2 is _c(〇)NR9Rl 〇, wherein R9 is an unsubstituted heterocycloalkyl group, and R10 is selected from the group consisting of ruthenium and alkyl. EXAMPLES Α, scoop where R9 is a substituted heterocyclic alkyl group, and R10 is selected from the group consisting of hydrazine and hydrazine based on the specific embodiment, in the formula (III.a.), 2" 兀 potatoes in R9 A, 士为-C(0)NR9 R1 (Eight 〒K is one or three of the same or different, alkyl groups, each substituent is independently selected from the group of silk, and the substituent is substituted. Selected from the group consisting of a heterohaloalkyl group in the formula (ΠΙ.a.), a group in the specific embodiment, a dentate alkyl group, a heteroalkyl-C(0)NR9 R1 〇. 'R2 is selected from the group consisting of : alkane C(0)R7, -C(0)0R8 and in a particular embodiment, in formula (IIIa)

' R2 is selected from CHF2 including

135177 -131 - 200922559 ί.

In a specific embodiment, in the formula (IILa.), R2 is

In a specific embodiment, in the formula (Ill.a.), R2 is

135177 > 132- 200922559

In a specific embodiment, in a specific embodiment of the formula (ni.a.), in the formula (Ill.a.), in a specific embodiment, in the formula (ni.a.) In a specific embodiment, in the formula (III.a,)

p is 0 ' and R3 is not present in a particular embodiment, in formula (III.a.), & 2 is / in a particular embodiment, in formula (III.a.) . P is 1. ’ P is 2. ’ P is 3. , P is 4. 'P system ^ 2, and at least two in a specific embodiment, in a specific embodiment in the formula (III.a), in a specific embodiment, in the formula (III.a.) In a specific embodiment of formula (m, a.), in a particular embodiment, in formula (in.a.), a group R3 is attached in formula (Ill.a.) To the same ring atom. In a specific example, in the formula (Ill.a.), p is 1, and R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl , aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halogen, -CN, -N02, -OR1 9, -0C(0)0R20, _NR2 1 R22, _NR23S 〇2r24, -nr23c(o)or20, -nr23c(o)r24, _s〇2Nr25r26, _c(〇)r24, -C(0)0R2°, -SR19, -SCCOR1 9, -S02R19, -〇c(〇 R24, _c(〇)nr25r26, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 . In a specific embodiment, in the formula (iiu.), 1) is 2, 3 or 4' and each of 135177-133 - 200922559 R3 is independently selected from the group consisting of alkyl, miscible, dilute, and heterogeneous Base, block, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocyclo, heterocycloalkenyl, halogen, -CN, -N02, -OR19, -〇C(0 )OR20, _NR21R22, -NR23S02R24, _NR23C(0)OR20, -NR23C(0)R24, -S〇2NR25R26, -C(〇)R2 4, _c(〇)〇r20, SRl9, s(〇)Rl9, _s 〇2RI9, 〇c(〇)r24, -C(0)NR2 5 R2 6 , _NR2 3 C(N_CN)NR2 5 R2 6 and _NR2 3 C(〇)Nr2 5 R2 6. In a particular embodiment, in Formula (Ill.a.), p is 2, 3 or 4, and at least two groups R3 are bonded to the same ring carbon atom, wherein each R3, which may be the same Or different 'separations are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl' cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero Cycloalkenyl, halogen, -CN, _n〇2, _〇Rl 9, , -NR2 1R2 2, _NR23s〇2R24 ' _nr23c(〇)〇r2〇, _nr23c(〇)r24, -S〇2NR25R2 6, _C( 〇)R2 4, _c(〇)〇r20, SRj9, s(〇)r19, s〇2Rl9, -〇C(0)R24 ^ -C(0)NR25R2 6 , -NR23C(N-CN)NR25R26^- NR23C(0)-NR25R26 0 In a particular embodiment, in formula (IILa.), hydrazine is a hydrazine or a hopper, and at least two groups R3 are bonded to the same ring carbon atom, wherein two feet 3 groups 'which may be the same or different, together with the carbon atoms to which they are attached form a cycloalkyl group, a ring-dense group, a heterocyclic alkyl ring, and one to three are selected from the group consisting of inclusion, enthalpy and S. The primary or heterocyclic dilute ring contains - to three heteroatoms selected from the group consisting of N, 0 and S. In a specific embodiment, in formula (III.a), p is 1 or 2, and each R3 is independently selected from the group consisting of alkyl, heteroalkyl, dilute, hetero, _cn, _n〇2 , -〇R19 > -〇C(0)〇R2〇. .NR2.R2 2 , _NR2 3s〇2R24 ^ _nr23C(〇)〇r2〇. 135]77 •134- 200922559 -NR23C(0)R2 4. _S〇2NR2 5R26, _c(〇)r24, _c(5)r24, _c(〇)〇r20, -SR19, -S(〇)R19, -S〇2R19, -〇Q〇)R2 4, _C(〇)nr25r2 6. -NR23 C(N-CN)NR25 R26, -NR23C(0)NR25R26 and -NR2 3 -C(NH)-NR26R26, wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group and each of the heteroolefins The base system is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a dentate, -CN, -N〇2, an alkyl group, Heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, azide , _〇R19, _〇c(〇)〇r2〇, -NR21R22, -NR23S〇2R2 4, _NR2 3C(〇)〇R2〇, nr23c((7)r24, -S02NR25R26, -C(0)R2 4, _c( 〇)〇r2 Groups of 0, _SRl9, s(〇)Rl9, -S02R19, -0C(0)R24, -C(0)NR2 5R2 6, _nr23c(n cn)nr25r26 and -NR2 3 C(0)NR2 5 R2 6 In a specific embodiment, in the formula (III.a.), the oxime is selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, and a heteroalkenyl group, wherein each of the alkyl groups and each The heteroalkyl group, each of the alkenyl group and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from a keto group, Halogen, -CN, -N02, alkyl, miscible, anthracenyl, county, south base, fast radical, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkane , heterocyclenyl, azide, _〇R]9, _〇c(〇)〇r2(), -NR21R22, -NR23S02R2 4, _nr23c(〇)〇r2, nr23c(〇)r24, - S〇2NRUR26, -C(0)R24, _C(0)0R2Q, -SR19, _s(〇)Ri9 ' -S02R19 ' -0C(0)R24 x -C(〇)NR25R2 6 , -NR23C(N-CN ) NR25R2 6 135177 -135 - 200922559 and -NR2 3 C(0)NR2 5 R2 6 group. In one embodiment, the group P is 2 in formula (m.a.) and is employed together with any two R3 groups of the same ring A atom. In a specific embodiment, in the formula (m.a.), P is 2 and is taken together by any two R3 groups of the same ring A atom. σ main ^ is used to form a spiroheterocyclic base. There are 1 to 3 independent choices including _ΝΗ-, _Ν 6·, US, S(Q) f

And a ring hetero atom of S(O)2, or a spiroheterocyclic group, having from 3 to 3 independently selected from the group consisting of -NH-, -NR6-, 〇, S, S(O) and S(0)2 Ring heteroatoms. In a particular embodiment, in the formula (Ill.a.), R3 is an alkyl group. In a specific embodiment, in the formula (Hl.a.), R3 is a heterocyclic group. In a specific embodiment, in the formula (in.a.), R3 is an alkenyl group. In a particular embodiment, in Formula (III.a.), R3 is a heteroalkenyl group. In a specific embodiment, 'R3' is a block group in the formula (m.a.). In a specific embodiment, in the formula (ni.a.), R3 is a heteroalkynyl group. In a specific embodiment, in the formula (ni.a.), R3 is an aryl group. In one embodiment, 'in the formula (m.a.)' r3 is a heteroaryl group. In a specific embodiment, in Formula (IILa), R3 is a ring-based base. In a particular embodiment, in Formula (IILa), R3 is cycloalkenyl. In a particular embodiment, in Formula (III.a.), R3 is heterocycloalkyl. In a particular embodiment, in the formula (III.a.), R3 is a heterocycloalkenyl group. In a specific embodiment, in Formula (III.a.), R3 is halogen. In a specific embodiment, in the formula (Ill.a.), R3 is -CN. In a specific embodiment, in formula (III.a.), 妒 is 〇2. 135177 -136- 200922559, in the formula (IILa.) ' R3 4 _QRl 9 ^ , in the formula (Ill.a.) ' R3 is _〇c(〇)〇r20. In the formula (IILa.), hydrazine is -NR21R22. In the formula (IILa·), R3 is -nr23so2r24. In the formula (Ill.a.), R3 is _nr23c(9)〇r2〇. In a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment In a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment In an embodiment, NR25R26 is used in an embodiment. 'In the formula (IILa.)' R3 is -nr23c(o)r24. In the formula (m.a.) 'R3 is the mother NR25R26. In the formula (m.a.), r, _c(〇)r24. 'In the formula (Ill.a.)' R3 is _c(〇)〇r20. In the formula (Ill.a.), R3 is _SRl 9. , in the formula (Ill.a.) ' is _s_Rl 9. 'In the formula (Ill.a.)' R3 is _s〇2Ri 9. In the formula (IILa·), R3 is -0C(0)R24. In the formula (In, a.), R3 is -C(0)NR2 5 R2 6 . In the formula (Ill.a.), R3 is _nr2 3 C(N CN)_ In a specific embodiment, in the formula (Ill.a.), R3 is _nr23c(〇)_NR25R26. In a specific embodiment 'in formula (ll.a.), r3 is selected from the group consisting of: fluorenyl, ethyl, propyl (straight or branched), butyl (straight or branched) ), pentyl (straight or branched), stupid,

H2n, 135177 -137- 200922559

In a specific embodiment, in the formula (Ill.a.), when E is -NR6-, R3 is absent. In a specific embodiment, the formula (Ill.a.) has the general structure (III.a.l):

(lll.a.1) wherein R1, R2, R3, R27, R28, p, E and ring B are independently selected from each other, and wherein: E is selected from the group consisting of -0-, -S-, -S ( O)-, -S(0)2-, -C(R4)(R5)-, -N(R6)-, -N(C(Y)R7)-, -N(C(Y)OR8)- And -N(C(Y)N(R9)(R10))-; and p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R27, 135177 -138- 200922559 R28, Y and ring B are selected as defined in the specific examples. In a specific embodiment, the general structure: a substituent 任何 as described in the above formula (Ill.a.), wherein the formula (Iii.a.1) has the formula (m.a.u)

("l.a.1.1). In one embodiment, the formula aiI.a,) has the general structure m.a.2:

(lll.a.2) wherein R1, R2, R3, R27, R28, p, E and ring B are independently selected from each other, and wherein: E is 'includes -0-, -S-, -S( O)-, -S(〇)2 -, _c(R4)(R5)-, _n(r6)_ '-N(C(Y)R7)_, -n(c(y)〇R8)_&_N(c(y)n(r9)(r10))_; and selection of P, Ri, R2, R3, R4, R5, R6, r7, R8, R9, R10, r27, R28, Y and ring B The substituents are all as defined in any of the specific acoustic embodiments described in the above formula (Ill.a.). 135177 - 139- 200922559 In one embodiment, the formula (III.a.2) has the general structure shown in formula (III.a.2.1):

In one embodiment, the formula (III.a.2) has the general structure shown in formula (III.a.2.2):

In a specific embodiment, formula (III.a.2) has the general structure shown in formula (III.a.2.3):

135177 - 140- 200922559 In one embodiment, the formula (III.a.2) has the general structure shown in formula (III.a.2.4):

/2 N--R /

R

E (lll.a.2.4). In some embodiments, in the various formulae (III.a.1), (III.a.1.1), (III.a.2), (III.a.2.1), (III.a.2.2), In (III.a.2.3) and (III.a.2.4), p is 〇. In some embodiments, in the formula (III.al), (IIl.aU) ' (IILa.2), (III.a.2.1), (III.a.2.2), (III.a.2.3 And (III.a.2.4), pgi. In some embodiments, in the various formulae (III.a.1), (m, aU), (III a.2), (III.a.2.1), (III.a.2.2), (III. In a.2.3) and (III.a.2.4), p is 2. In some embodiments, 'in the various formulas (III.a.1), (III.au), (IILa.2), (III.a.2.1), (III.a.2.2), (111 children 2.3 And (lll.a.2.4), E is -C(R4)(R5)-. In some embodiments, 'in each of (III.a.1), (III_a.u), (m, a 2), (III.a.2.1), (III.a.2.2), (III. In a.2.3) and (III.a.2.4), e is selected from the group consisting of -〇-, -S-, -S(O)-, -S(0)2-, and -N(R6)-. In some specific examples, 'in the various formulas (III.a.1), (ni.a.1.1), (ni.a.2), (III.a.2.1), (III.a.2.2) (III.a.2.3) and (ma2.4), the E system is selected from the group consisting of _〇_, -S-, -S(O)-, -S(0)2-, and -N(R6)-, Wherein R6 is selected from the group consisting of H, alkyl, -C(0)R24 and -C(S)R24. In some specific examples, 'in the various formulas (III.a.1), (ni.a.1.1), (HI.a.2), 135177-141 · 200922559 (III.a.2.1), (III .a.2.2), (III.a.2.3) and (III.a.2.4) with -N(R6)-, wherein R6 is selected from the group consisting of H, alkyl, and in some embodiments In various formulas (III.a, l), (III.a.2.1), (III.a.2.2), (III.a.2.3) and (III.a.2.4), in some embodiments, In the specific formulas (Ili.al), (III.a.2.1), (III.a.2.2), (III.a.2.3) and (III.a.2.4), in various embodiments (mu), (III.a.2.1), (III.a.2.2), (III.a.2.3) and (III.a.2.4) in some embodiments, in each formula (mu), (III.a.2.1), (III.a.2.2), (III.a.2.3) and (III.a.2.4) in some specific examples, in the various formulae (III.al), (III In .a.2.1), (III.a.2.2), (III.a.2.3) and (lll.a.2.4) in some specific examples, in the various formulae (III al), (III.a. In 2.1), (III.a.2.2), (III.a.2.3) and (in.a.2.4), in some specific embodiments, in the various formulae (III al), (III.a.2.1), (III.a.2.2) ' (II In some specific examples, Ia2.3) and (ni.a.2.4) 'in each formula (III al), (III.a.2.1), (III.a.2.2), (III.a.2.3) And (in.a.2.4) in some specific examples, in the formulas (ma l), (III.a.2_l), (III.a.2.2), (III.a.2.3) and (III) In .a.2.4), E is in some specific examples, in the formulas (ni al), (III.a.2.1), (in.a.2.2), (in.a.2.3), and (ni) .a, 2, 4) In some embodiments, in the formulas (nLa l), (III.a.2.1), (III.a.2.2), (in.a.2,3) and Ni.a.2.4) 135177, E is selected from the group consisting of -O--C(0)R24 and -C(S)R24. (III.a.1.1), (III.a.2), and £ is -0. (III.a.1.1), (III.a.2), and E are -S-. (III.a.1.1), (III.a.2), and E are -S(O)-. (III.a.1.1) '(III.a.2) ' , Eg-S(0)2-. (III.a.1.1), (III.a.2), and E are -C(R4)(R5)-. (III.a.1.1), (III.a.2), and E are -N(R6)-. (III.a.1.1), (III.a.2), ,Eg-N(C(Y)R7)-. (III.a.1.1) > (III.a.2) ' , £ is - ie (丫辉8)-. (III.a.1.1), (III.a.2), -N(C(Y)N(R9)(R10))-= (III.a.1.1), (III.a.2), , Y is (=0). (III.a.1.1) > (III.a.2) > ’ Y is (=s). -142· 200922559 In some embodiments, in the formula (IILa丨), (ΙΠ al丨), (HI.a.2), (III.a.2.1), (III.a.2.2), ( In III.a.2.3) and (in.a.2.4), γ is (=N(R13)). In some embodiments, in the formula (IILa丨), (ΠΙ a"1), (III a.2), (III.a.2.1), (III.a.2.2), (III.a. In 2.3) and (in.a.2.4), γ is (=N(CN)). In some embodiments, 'in each formula (ΙΠ a丨), a丨丨), a 2) ' (III.a.2.1), (III.a.2.2), (III.a.2.3), and In ma2.4), γ is (=N(OR14)). In some embodiments, in the formulae (III a 1}, (nLa ll), (In.a.2), (III.a.2.1), (III.a.2.2), (III.a. In 2_3) and (IIl.a.2.4), γ is (=N(Ri 5 )(Ri 6)). In some embodiments, in each formula (III.al), (ΐπ.ιυ), ( Ni a 2), (III.a.2.1), (III.a.2.2), (III.a.2.3) and (Ill.a.2.4), 丫 is (=C(Ri7)(Ri8)) In some embodiments, in the formulae (IILaj), (IILa U), (ni a 2) (III.a.2.1), (III.a.2.2), (Ill.a.2.3), and (III) In .a.2.4), r] is a phenyl group substituted by one to four substituents which may be the same or different, each substituent excluding a halogen group, -OH, -CN, -N02, -NR21R22 and _ Burning and standing

In a specific embodiment, in formula (I), R! is: 135177 ‘143· 200922559

In some embodiments, 'in each formula (III.a.1), (iILa, u), (ΙΠ a 2), (III.a.2.1), (III.a.2.2), (III.a In .2.3) and (III.a.2.4), Ri is a phenyl group substituted with three fluoro groups. In some embodiments, in each of the formulas, (III.aU), (ma 2), and (ma), (ma2.2), (III.a.2.3), and (ma2.4), R1 is Fluoro substituted phenyl. In some embodiments, in the various formulae (III.a.1), (III.au), (ma 2), (UUZl), (III.a.2.2), (III.a.2.3), and In III.a.2.4), R1 is a phenyl group substituted by a fluorine group. "" In some specific embodiments, 'in various formulas (iii.a.1), (ih.h.d, (nLa2),

In (III.a.2.1), (ma2.2), (III.a.2.3) and (ma2.4), Ri is: In some specific examples, in each formula (III.a.1), ( In ni.au), (ma 2), (III.a.2.1), (ni.a.2.2), (III.a.2.3) and (ma2.4), r27 and R28 are each independently selected from the group consisting of H and alkyl. In some embodiments, 'in the various formulas (III.a.1), (Ill.au), (III.a.2), (III.a.2.1), (III.a.2.2), (III In .a.2.3) and (ma2.4), lanthanides are selected from the group consisting of: alkyl, ketone, miscible, heterohaloalkyl, _C(〇)R7, _C(〇)〇R8 and ~C( 〇) NR9Ri〇. In some embodiments, 'in each of (III.a.1), (In.a.U), (IILa 2), 135177-144-200922559

(III.a.2.1), (III.a.2.2), (III.a.2.3) and (III.a.2.4), R2 is selected from the group consisting of:

In some embodiments, in the various formulae (III.al), (III.a.1.1), (III.a.2), (III.a.2.1), (III.a.2.2), (III) In .a.2.3) and (III.a.2.4), p is 1 or 2, and each 135177 -145 - 200922559 R3 is independently selected from the group consisting of a yard, a compound, an alkenyl, a heteroalkenyl, a _CN, -N02, -OR19, -〇QO) OR20, -NR21R22, -NR23S02R24, -NR23C(0)OR2〇, -NR23C(0)R24, -S02NR25R26, -C(0)R24, -C(S)R24, -C(〇)〇R2〇, -SR19, -S(0)R19, -S02R19, -〇C(0)R24, -C(0)NR25R26, -NR2 3 C(N-CN)NR25R26, -NR23C (0) NR25R26 and -NR2 3 -C(NH)-NR2 6R2 6 wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heterogeneous groups is unsubstituted or optionally Substituted by one or more substituents which may be the same or different 'each substituent is independently selected from keto, halo, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, halo Alkenyl, alkynyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocyclic, azide, -OR1 9, 〇C (〇)〇 R2 〇, -NR2] R22, -NR23S〇2R24, -NR2 3c (〇)〇r2 0, _nr2 3c(〇)r2 4, -S02NR25R26, -C(0)R24, -C(0)0R20, -SR19, _s(〇)r19, -S02R19 ' -0C(0)R24 a group of '-C(0)NR25R26 % -NR2 3 C(N-CN)NR2 5 R2 6 and -nr23c(o)nr25r26. In some embodiments, 'in each of (III.al), (III.a, U), (III a 2), (III.a.2.1) ' (III.a.2.2), (III.a In .2.3) and (III.a.2.4), p is 1, and r3 is selected from the group consisting of alkyl, heteroalkyl, alkenyl and heteroalkenyl, each of which is The dilute group and each of the heterogeneous groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different. Each substituent is independently selected from the group consisting of a keto group, a γ group, a -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, aryl, haloalkynyl, yl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, Heterocyclenyl, azido, -OR19, 〇R20, 135177 * 146- 200922559 -NR21R22, -NR2 3S〇2r2 4, _NR2 3C(〇)〇r2〇, nr23c(〇)r24, -S02NR25R2 6, _C (〇) R2 4, _C(〇)〇R2 0, Guan 19, s(〇)Rl9, -S02R19, -〇c(〇)R24, -C(0)NR25R26, -NR23C(N-CN)NR25R2 6 And a group of -NR2 3 C(0)NR2 5 R2 6 . In some embodiments, in the various formulae (III.al), (ni.aU), (ma2), (III.a.2.1), (III.a.2.2), (III.a.2.3) And (III.a.2.4), p is 2, and is employed together with any two R3 groups bonded to the same ring A atom to form a group. ί In some embodiments, in the various formulae (III.a.1), (III a丨1}, (ΙΠ a 2), (III.a.2.1), (III.a.2.2), (III In .a.2.3) and (III, a24), ? is 2, and is employed together with any two R3 groups bonded to the same ring A atom to form a spiroheterocycloalkyl group having 1 to 3 independent Selected from ring heteroatoms including _NH_, _NR6_, 〇, s, S(〇) and S(O)2, or spiroheterocycloalkenyl, having 丨 to 3 independently selected from the group consisting of -cis-, pendulum 6- '0, 8, Liu) and Liu) 2 ring heteroatoms. In a particular embodiment, the compound of the invention has the structure shown in formula (IV), and I comprises a pharmaceutically acceptable salt, solvate of the compound: ester, prodrug or isomer: σ '

Wherein R1, R2, R3, R27, R28, ring A and ring B are independent of each other 135177 • 147- 200922559, and wherein: ring A (containing E and the unsaturation shown) is a 5-membered cycloolefin. Or a heterocyclic alkenyl ring; E is selected from the group consisting of -0-, -S-, -S(O)-, -S(0)2-, -C(R4)(R5)_, _n(r6) _, -N(C(Y)R7)-, -N(C(Y)OR8)-, -N(C(Y)N(R9)(R)0))-, _C(〇)_N(Rll )_, -N(R]1 )-C(0)-, -S(0)2-N(R]1)-, -N(Rn )-S(0)2-, -C(〇K )_, seven_c(〇)_, -0-N(R6)-, -N(R6)-0-, -N(R6)-N(R12)-, -N=N- and -C( R7)=N . Ring B is a substituted or unsubstituted heteroaromatic ring; 昱p, Rl, R2, R3, R4, R5, R6, R7, R8, r9, Rl〇, R1 2, R27, R28 The optional substituents on Y, and Ring B are as defined in any of the specific examples described above in Formula 1. In one embodiment, the formula (IILb) has the following general structure:

In a specific embodiment, the formula (m.b) has the following general structure

In a particular embodiment, in Formula (Ill.b.), p is 〇, i or 2 135177 -148- 200922559 环环 is a cycloalkenyl ring, in one embodiment, in Formula (Ill) In .b.) and E is -C(R4)(R5)-. In a specific embodiment, in the formula _), the ring VIII is a heterocyclic ring, and the lanthanide is selected from the group consisting of -C(0)-N(Rii)_, _N(Ri))_( :(〇)_, _s(〇)2_n_, -N^'-SCO)〗-, -C(0)-0-, _0_C(0)_, _〇_N(R6)_, n(r6) 〇, -N(R6)-N(R12)-, -N=N-, and -C(R7)=n_. By way of non-limiting illustration, wherein E is a compound of the formula (m.a.) of -QCO-^KR11)-

Examples are included in a specific embodiment, in Formula (IILb.), Ring A is a heterocycloalkenyl ring, and E is selected from the group consisting of -〇-, -S-, _s(0)_, -S (0) 2- and -N(R6)-. In a specific embodiment, in the formula (Ill.b.), the E system is selected from the group consisting of _〇_, -S-, -S(O)-, -S(0)2-, and -N (R6). And wherein r6 is selected from the group consisting of η, alkyl, -C(0)R24 and -C(S)R24. In a specific embodiment, in the formula (mb), the 'E system is selected from the group consisting of _〇_ and -N(R6)-' wherein R6 is selected from the group consisting of η, alkyl, _(:(〇)尺24 And _C(S)R24. In a specific embodiment, in the formula (IH.b.), E is -〇-. In a specific embodiment, in the formula (ni.b.), E is -S-. In one embodiment, in the formula (ni.b.), E is -S(0)-. In one embodiment, in the formula (IH.b.) And E is -S(0)2-. In a specific embodiment, in the formula (III.b.), E is _C(R4)(R5)-. In a specific embodiment, In the formula (IH.b.), E is -N(R6)-. In a specific embodiment, in the formula (mb), E is -N(C(Y)R7)-. 135177 -149· 200922559 In a specific embodiment, in the formula (IILb.), E is -N(C(Y)OR8)-. In a specific embodiment, in the formula (IIIb), E is _N (C(Y)N(R9)(R)〇)). In one embodiment, in the formula above, e is -C(0)-N(Rn)-. In a specific embodiment, in the formula (IILb.), E is -NCR11)-C(0)-. In a specific embodiment, in the formula (III.b.;), E is -SCOh-I^R11)-. In the specific embodiment, in the formula (111.), e is -n(r! y-scov. In the specific embodiment, in the formula (ni.b.), E is -C (0)-0-. In the specific embodiment, in the formula above, e is -〇-c(o)-. In the specific embodiment, in the formula (in.b.), E is -〇-N(R6)-. In a specific embodiment, in the formula (Ill.b.), E is -N(R6)-0-. In the specific embodiment, in the formula (Ill.b.), E is -Ν(Κ6)-Ν(Ι^ 2)-. In the specific embodiment, in the formula (Ill.b.), Ε is -Ν=Ν-. In the specific embodiment, in the formula (Ill.b.), Ε is -C(R7)=N-. In the specific embodiment, 'in the formula (IILb.), γ is (=〇). In the specific embodiment, in the formula (Ill.b.), Y is (=s).

In the specific embodiment, 'in the formula (Ill.b.), Y is (=N(Ri3)). In the specific embodiment, in the formula (Ill.b.), Y is (=N(CN)). In a specific embodiment, 'in the formula (Ill.b.), γ is (^(ORi4)). In the specific embodiment, in the formula (Ill.b.), γ is. In the specific embodiment, in the formula (Ill.b.), γ is (=C(R17)(R?8)). In the specific embodiment, 'in the formula (III.b.), B is an unsubstituted heteroaryl ring. . In the specific embodiment, 'in the formula (Ill.b.), B is an unsubstituted 5-6-besinfish aspect ring' has 1-3 ring heteroatoms which may be the same or different, each Miscellaneous 135177 -150- 200922559 The ring atomic system is independently selected from the group consisting of N, s, o, s(0) and s(0)2. In a specific embodiment, the name - mT u, i ^ ^ JT is in the formula (IILb·), and the Β is a heteroaromatic ring, and the one or more may be the same or not ', think η... "Substituent substitution of 'J", each substituent is _, -CN, _N〇2, fluorenyl, heteroalkyl, ketone, alkenyl, haloalkenyl, alkynyl, alkynyl, Aryl, heteroaryl, aryl-shallow base, heteroaryl-alkyl-, sulfonyl, heterocyclic, heterocyclic;::, f, fluorene, -ORB ... 〇C ( 〇)〇R20, nr21r22, post, heart, -NR^3C(〇)〇R2〇, _NR23C(〇)r24 ^ _s〇2Nr25r26 ^ _W4 ' -C(〇)〇R2., visual 丨9, _驿1 9. _s〇2Rl 9, _qc(〇)r24, c(〇)nr25r26, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 c(〇)nr2 5 R2 6. In the example, 'in a pottery, __member heteroaromatic soil' has 1-3 ring heteroatoms which may be the same or different, and each hetero atom atom is independently selected from the group consisting of N, S, 〇, S (〇ms). (〇) 2, the heteroaromatic ring system is substituted by one or more substituents which may be the same or different, and each substituent is independently selected from the group consisting of halogen, ., _N〇2, fluorenyl, and hetero Base, core group, dilute group, (tetra) group, alkynyl group, alkynyl group, aryl group, heteroaryl group, aryl group, alkyl group, heteroaryl group, alkyl group, cyclodyl group, ring group, heterocyclic ring Base, heterocyclic dilute group, azide group, -OR19, _OC(O)〇R20, _nr21r22, nr23s〇2R24, -NR23C(〇)〇R2G, _nr23c(〇)r24, s〇2Nr25r26, _c(〇2) R24 ' -C(0)〇R2〇, _SR1 9 , _S(〇)Rl 9 . _s〇2Rl 9. _〇C(〇)r24 ^ _C(〇)nr25r26 ^ -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In a specific embodiment, in the formula _), the unsubstituted &amperer/aromatic ring has a simple 3 (4) same or The different ring heteroatoms, each heterocyclic 5 atomic system are independently selected from the group consisting of N, S and 0. 135177 - 151 - 200922559 = In a specific embodiment, 'in the formula, B is a 6-membered heteroaromatic ring, Having 1-3 ring heteroatoms which may be the same or different, each hetero atom atom is independently selected from the group consisting of N, S and 0'. The heteroaromatic ring system is substituted by one or more substituents which may be the same or different. Each substituent is independently selected from the group consisting of a package (four), winter

- ship 2, base, miscellaneous, dentate, ortho, alkenyl, fast radical, alkynyl, aryl, heteroaryl, aryl fluorenyl, heteroaryl alkyl...cycloalkane Base, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, collar 19, _〇c(〇)〇r2〇, -NR21R2 2, _nr23s〇2r24, nr23c(〇)〇r2. , see 23. Team 24, -so2nr25r26, _C(0)r24, ,C(〇)〇r20 ^ sr19 ^ s(〇)R]9 ^ s〇2Rj9 ^ —〇cx_4, _(10)nr25r26, view 23c (Nc job 25R26 and view nr25r26 ο In a specific embodiment, in Formula (IILb.), B is an unsubstituted 6-membered heteroaromatic ring having 2 ring heteroatoms, each ring heteroatom independently selected from N, S, and In a specific embodiment, in the formula (III-b.), the 6-membered heteroaromatic ring has 2 ring heteroatoms, and each ring hetero atom is independently selected from N, s and oxime. The aromatic ring system is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a pixel, _CN, _N〇2, alkyl, heteroalkyl, decyl, and -OR. , pendulum 2lR22, _c(〇)r24, c(〇)〇r2, observation 19, -S(〇)R19, _s〇2Rl9, _〇c(〇)r24 and _c(〇)nr25r26. In a specific embodiment, in the formula (Ill.b.), B is an unsubstituted 5_beta heteroaromatic ring having 1-2 ring heteroatoms which may be the same or different, and each hetero atom is independently selected. Self-contained N, S, and Ο. In the specific embodiment, 'in the formula (Ill.b.), B is 5-member hetero Ring, 135177 -152- 200922559 has 1-2 heteroatoms which may be the same or selected from the spoon, each heteroatomic atom is independently covered by N, S and Ο, 砵碰# & , each mouth is the same or N 〇 甘 取代 取代 substituents are independently selected from the group consisting of ghrelin, _CN, 〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, ialkenyl, and thus, alkyne Base, aryl, heterozygous a, #w π 诀 诀, i 杂 暴 · · 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 榼Ά Alkenyl, heterocycloalkyl, heterocyclic ring np21d22 and fluorenyl, -OR19, -〇C(0)〇R2 〇, -Nm -NR23s〇2R24, _NR23c_2Q, (iv)(9)R24 -s〇2nr25r26. _C(0)R24. _C (〇)〇r2〇^ SR19 ^ s(〇)Ri9^ 9 ^ -〇C(0)R24 > -C(0)NR25R26 \to2 3^

UU'JNK K , _NR2 3 c(n_cn)nr2 5 R NR2 5R26. R C(〇)'. In the specific embodiment, in the formula _, B is an unsubstituted 5-membered heteroaromatic ring' having i ring heteroatoms selected from N, 8 and 0. In the specific embodiment, in the formula (movement.), 3 is a 5-membered heteroaromatic ring, and eight has a ring hetero atom of N, s, and fluorene, and the heteroaromatic ring system is- Or a plurality of substituents which may be substituted with the same or different substituents each independently selected from the group consisting of dentate, CN, _N〇2, alkyl, miscible, halogen-based, collar 19, -NR2lR22, -C ( 0) R24, -C_R2. ...SRl9, _s(〇)Rl9, _s〇2Rl9, -0C(0)R2 4 and _c(〇)NR2 5 R2 6. In a specific embodiment, in Formula (mb), B is a 5-membered heteroaromatic ring having S as a ring heteroatom, and the heteroaromatic ring system may be substituted by one or more of the same or different Substituent, each substituent is independently selected from the group consisting of halogen, _CN, _N02, alkyl, heteroalkyl, haloalkyl, -OR1 9, -NR2 1 R22, _c(〇)R24, -C(0)0R2 〇 , _SRl 9, _s(〇) Rl 9, _s〇2 Rl 9, 〇c(〇)r2 4 and c(〇)NR2 5 γ 6. In a specific embodiment, in the formula (III.b.), β is unsubstituted. 5-135177-153-200922559 b is selected from the group consisting of a heteroarylene ring having s as a ring hetero atom. In a specific embodiment, in the formula (m.b.)

In a specific embodiment, in the formula (IILb.) '... is an unsubstituted aryl group. In a specific embodiment, in the formula (m.b), R1 is an unsubstituted stupid group. And in a specific embodiment, in the formula (III.b.), ... is an unsubstituted phenyl group. In a specific embodiment 'in the formula (m.b.), R! is a substituted aryl group. In a particular embodiment, in Formula (m.b.), R1 is substituted phenyl. In a specific embodiment, in the formula (m.b.), R1 is a substituted fluorenyl group. In a specific embodiment, in Formula (mb), R1 is an aryl group substituted by one or more substituents which may be the same or different. Each substituent is independently selected from the group consisting of halogen, -cn'-N. 〇2, alkyl, heteroalkyl, _alkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl, ring Anthracenyl, cycloaliphatic, heterocycloalkyl, heterocycloalkenyl, azide, -〇R]9, -〇C(O)〇R2 0, _NR2 1R2 2, ·ΝΚ2 35〇2Κ2 4, nr23c( 〇)〇r2〇, -NR2 3C(〇)R24, _s〇2Nr25r26, _c(〇)r24, _c(〇)〇r2(), n -S(0)R*9 , -S02R!9 . -〇 C(〇)R24 > -C(0)NR25R2 6 n -NR2 3C(n.CN) NR2 5 R2 6 and _NR2 3 c(〇)NR2 5 R2 6. In a particular embodiment, in Formula (Iii.b.), Ri is phenyl substituted by one or more substituents which may be the same or different, each substituent being independently selected from 135177 • 154-200922559 Including halogen, -cn, -N〇2, alkyl-alkylene, "radical, dilute, alkenyl, alkynyl, alkynyl, aryl, heteroaryl, aryl.alkyl", hetero Aryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19 > -0C(0)0R2° > -NR21R2 2 , -NR2 3S〇2R2 4 n _NR2 3C(〇)〇R2 0 , -NR23C(0)R24, _S〇2Nr25r26, c(〇)r24, c(〇)〇r2〇, JR”, -S(0)R19 ^ -S02R^ &gt ; -0C(0)R2 4 . .C(〇)NR25R26 ^ _NR2 3C(N.CN). NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. /

In a specific embodiment, in the formula (ni.b.), ... is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of a halogen group, -OH , -CN, -N02, -NR21R22 and haloalkyl. In a specific embodiment, in the formula (Ill.b.), the Ri is selected from the group consisting of

In the formula (Ill.b.) R1 is: in a specific embodiment

In a specific embodiment, in the formula (Ill.b.), R1 is a phenyl group substituted by one to three gas groups. In a specific embodiment, in the formula (Iii.b.), R1 is a phenyl group substituted by two fluorine groups. 135177 - 155- 200922559 In a specific embodiment, in the formula (III.b.), Ri is a phenyl group substituted by a fluorine group.

In a specific embodiment, in Formula (IILb.), R1 is: In a specific embodiment, in #_·), R27 and R28 are each independently selected from the group consisting of ruthenium and alkyl. In a specific embodiment, in the formula (III.b.), R2 is _C(Z)R7. In the specific embodiment, in the formula (IILb.), R2 is _c(z)nr9r1 〇. In a specific embodiment, in the formula (III.b.), R2 is _c(z)〇R8. In the specific embodiment, in the formula (IILb.), R2 is _s〇2NR9r1 〇. In a specific embodiment, in the formula (IILb), R2 is an alkyl group. In a specific embodiment, in the formula (m.b), R2 is a heteroalkyl group. In a specific embodiment, in the formula (m b ), R 2 is an aryl group. In a specific embodiment, in the formula (m b ), R 2 is a heteroaryl group. In a specific embodiment, in the formula (m b ), R 2 is a cycloalkyl group. In a particular embodiment, in Formula (m.b), R2 is cycloalkenyl. In a specific embodiment, in the formula (m.b), R2 is a heterocycloalkyl group. In a particular embodiment, in the formula (m b ), R 2 is a heterocycloalkenyl group. In a specific embodiment, in the formula (III.b.), Z is (=〇). In a specific embodiment, in the formula (in.b.), Z is (=s). In a specific embodiment, 'in the formula (IILb.), Z is (=N(R) 3)). In a specific embodiment, in the formula (Ill.b.), Z is (=N(CN)). 135177 -156- 200922559 In a specific embodiment, in the formula (III b.), Z is (=Ν(ΟΙ^ 4)). In a specific embodiment, in the formula (m.b), Z is (=N(R15)(R16)). In a specific embodiment, 'Z is (=c(Ri 7)(ri 8) in the formula (nLb). In a specific embodiment, in the formula (III b.), r2 is _C (Z) R7, and Z is (=〇). In one embodiment, in Formula (III b ), R 2 is _C(〇)H. In one embodiment, in Formula (IILb) Wherein R2 is _C(〇)alkyl. In a particular embodiment, in formula (mb), r2 is -c(〇)CH3.

C In a specific embodiment, in the formula (IILb), R2 is _C(〇)R7, wherein the R7 is an alkyl group substituted by one or more substituents which may be the same or different, each substituent Independently selected from the group consisting of keto, halogen, _CN, _N 〇 2, alkyl, heteroalkyl, i alkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, naphthenic , cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -OR19, -0C(0)0R20, _NR21R22, -NR23S02R24, -NR23C(0)OR2〇, -NR2 3C(0)R2 4, _s〇2Nr25r26, c(〇)r24, c(〇)〇R2(), SR19, ^ -S(0)R19 ' -S02R19 . -0C(0)R24 ^ -C(0)NR25R2 6 . NR2 3 C(N-CN)- NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 R2 6. In a specific embodiment, 'in the formula (III.b.), 圮 is seven (wherein 5 R R is an alkyl group substituted by one or two substituents which may be the same or different, each substituent) Is independently selected from the group consisting of 〇R1, NR2, R22 and cycloalkyl. In a specific embodiment 'in s(III.b.), r2^c(0)r7, wherein R7 is alkyl Wherein the alkyl group is substituted with an alkyl group and _〇H. In a specific embodiment, in the formula (mb), r2K(q)r7, wherein the R7 is - to three may be the same or different Substituent substituted alkyl, 135177 -157- 200922559 each substituent is independently selected from the group consisting of _〇H, _NH2 and cyclopropyl. In the formula (mb), r2 is the elevation r7, wherein忒11 is an alkyl group substituted by one to two substituents which may be the same or different, each substituent being independently selected from the group consisting of _NH2 and a cyclopropyl group. In a specific embodiment, in the formula (IILb), the rule 2 is _C(0)R7, wherein the R7 is an alkyl group substituted by -OH. In a specific embodiment, in the formula (III.b.), it is protected by _c(〇)R7, wherein the R7 is an unsubstituted heterocycloalkyl group. In a particular embodiment, in the formula (III.b.), 'R2 is -c(o)R7, wherein the R7 is a substituted heterocycloalkyl. In a specific embodiment, in the formula (Ill.b.), R2 is -C(〇)R7, wherein the R7 is a heterocyclic alkyl group substituted by one or more substituents which may be the same or different substituents. 'Each substituent is independently selected from the group consisting of keto, halogen, _CN, -N02 'alkyl, heptyl, haloalkyl, fine, halo, fast, halo, aryl, heteroaryl , cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR] 9, -〇C(0)〇R20, -NR21R22, -NR23S02R24, -NR23C(O)〇R2 0, -NR2 3C(〇)R2 4, _s〇2nR2 5R2 6, -C(〇)r24, -C(0)OR20, -SR19, -S(0)R19, -S〇2R19, -0C(0 R24, -C(0)NR25R26, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 . In a specific embodiment 'in the formula (Ill.b.) 'R2 is -C(0)R7, wherein the R7 is selected from the group consisting of substituted hexahydropyridine' substituted hexahydropyrazole, Substituted for the phloem, substituted tetrahydropyrrole and substituted one of the nitrogen tetraindoles. In one embodiment, 'in the formula (Ill.b.)' R2 is selected from the group consisting of: 135177 -158- 200922559 0II -c- Ο4 〇 II -c- Η3σ , H3c 〆 and η3. In a specific embodiment, in the formula (Ill.b.), in a specific embodiment, in the formula (IILb.), in the specific embodiment, in the formula (Ill.b. In the case, 〆R2 is -c(o)nr9r10. R2 is -c(o)nh2. ^ ^. R2 is -c(o)nr9r10, /, and R and (4). They may be the same or different and each independently selected from a burn group. In the nine specific embodiments, in the formula _, R^_w)nr9r1. , wherein R9 is unsubstituted heterocycloalkyl' and R1. Is selected from the group consisting of η and alkyl D = in the specific embodiment, in the formula _), R 2 is _Q 〇) Nr9r1 〇, Ί is a substituted heterocyclic compound ' and RlG is selected from the group consisting of ruthenium and Court base. In the specific f example, in the formula (moving.), r24 _c(q)nr9r1. , =R9 is a heterocyclic ring which is substituted with three substituents which may be the same or different substituents. Each substituent is independently selected from the group consisting of an alkyl group, and the R1Q system is selected from the group consisting of ruthenium and ruthenium. In the specific embodiment, 'in the formula (ni.b.), R2 is selected from the group consisting of: alkylhaloalkyl, heteroalkyl 'halohaloalkyl, -C(0)R7, -C( 〇) NR9R10. In the two specific. For example t, in the formula (m.b.), the R2 is selected from the group consisting of V' and 'human CF3, 'CHF" into '"V^'.卜 . , Τ 〇, χΑ.0

ο,Α^οη i , 0 ^ HO and

135177 -159- 200922559

ο In a specific embodiment, in the formula (Ill.b.), R2 is Άει=3 0

In a specific embodiment, in a specific embodiment of the formula (Ill.b.), in the formula (Ill.b.)

OH In a specific embodiment, in the formula (Ill.b.), R2 is in \135177-160-200922559, in the formula (mb), in the formula (Ill.b.), In the formula (Ill.b.),

a specific embodiment in a specific embodiment in a specific embodiment

P is 0 ' and R3 is not present in a specific embodiment. In the formula (Ill.b.), R2 is in a specific embodiment, in the formula (Ill.b.)

in. In a specific embodiment, in the formula (Ill.b.), p is i. In a specific embodiment, in the formula (Ill.b.), p is 2. In a specific embodiment, in the formula (Ill.b.), p is 3. In a specific embodiment, in the formula (Ill.b.), p is 4. In a particular embodiment, in the formula (Ill.b.), p is > 9 n s , p is S 2 , and at least two groups R3 are attached to the same ring atom. In a specific embodiment, in the formula (III.b.), p is 1, and the r3 is independently selected from the group consisting of an alkyl group, a heteroalkyl group, a fluorenyl group, a heterocyclic group, a block group, and a hetero block. Aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, halogen, -CN, -N02, -OR1 9, -0C(0)0R20, -NR2 1 R22, _Nr23s 〇2r24, -nr23c(o)or20, -nr23c(o)r24, -so2nr25r26, _c(〇)r24, -C(0)0R20, -SR1 9, -S^R1 9, and -SC^R1 9,- 0C(0)R2 4 ' _c(〇)nr25r26, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In a particular embodiment 'in formula (III, b.), p is 2, 3 or 4, and each R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, block , heteroblock, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, hetero 135177 -161 - 200922559 cycloalkenyl, halogen, _CN, _n〇2, -OR19, _〇C ( 〇)〇R20, _nr21r22, -NR23s〇2r24, -NR23C(0)OR20, -NR23C(0)R24, -S02NR25R26, -C(〇)R24, -C(〇)〇R20, _SR19, _s(〇) Rl9, _S〇2r19, _〇c(〇)r24, -C(0)NR2 5 R2 6 , _NR2 3 C(N_CN)NR2 5 R2 6 and _NR2 3 C(〇)NR2 5 R2 ό 一项In a particular embodiment, in formula (mb), {) is 2, 3 or 4, and at least two groups R3 are bonded to the same ring carbon atom, wherein each R3, which may be the same or different 'system independent Selected from alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halogen , _CN, _N 〇 2, _ 〇 Rl9, _ 〇 c (〇) 〇 r2 〇, _nr21r22, _Nr23s 〇 2R24, -nr23c (o) or 2. , -NR2 3C(〇)r24, -S〇2NR25R2 6 . _C(〇)R2 4 x _C(〇)〇R2 0 , _sr19 , _S(〇)R19 , _s〇2Rl9 λ -0C(0)R24 . C(〇)NR25r2 6 , -NR23C(N-CN)NR25r2 6^_NR2 3C(〇)_ nr25r26. In a specific embodiment, in the formula (IILb), the mouth is a pipe or a pipe, and at least two groups R3 are bonded to the same ring carbon atom, wherein two groups are

Groups, which may be the same or different, together with the carbon atoms to which they are attached, form a cycloalkyl group, a cycloaliphatic group, a heterocyclic alkyl ring, and contain up to three heterogenes selected from the group consisting of (4), 0 and S. Or a heterocycloalkenyl ring containing one to three heteroatoms selected from N, 0 and s. ... K M i 5 and Z, and Valley! Independently selected from the group consisting of alkyl, hydrazine and its *v

Miscellaneous, alkenyl, heteroalkenyl, -CN, -NO -〇R19, -〇C(0)0r2〇, _nr21r22, 2 S02R^4 , -NR2 3c(〇)〇R2 0 -nr2^C( 〇)R24 . _s〇2Nr25r26 ^ _C(〇)r24 ^ C(S)R24 ^ c^〇R2 1919, -S(W9, _S〇2Ri9, '〇c(〇)r24, c_25R26 135177 -162- 200922559 -NR: 3 C(N-CN)NR25R26, Na 3 c(〇)nr25r26 and 2 3 (__nr26r26, each of which is a Xuan Xuan base, each of the miscible groups, each of the dilute bases and each of the heterogeneous groups Is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a ke group, a peptidene, a -CN 'alkyl group, a miscible group, a fluorenyl group , alkyl, dentate, alkynyl, lS alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, hetero-alkyl, heterocycloalkenyl, azido, _0R1 9, 〇c (〇)〇r2 〇, -NR2]R22, _NR2 3S〇2R2 4, _NR2 3C(9)〇r20, nr23c(〇)r24, -so2nr25r26, _C(0)R2 4, _c(〇)〇r20, SRl9, disaster )r19,

-S02R19 > -0C(0)R24 x -C(0)NR25R26 > -NR23C(N-CN)NR25R26 and -nr23c(o)nr25r26 Group D is in a specific embodiment 'in the formula (mb Wherein p is 1, and R3 is selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, and a heteroalkenyl group, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heteroalkenyl groups Unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of keto, halogen, -CN, -N〇2, alkyl, heteroalkyl Haloalkyl, alkenyl, haloalkenyl 'alkynyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, 〇 R 〖9, _〇C(〇)〇R20, -NR21R2 2, _NR2 3S〇2R2 4, _NR2 3C(〇)〇R2 0, _NR2 3C(〇)R2 4, -S〇2NR25R2 6, _C(〇) R2 4, _C(〇)〇R2 0, _SR19, _S(〇)Rl9, -S02R19, -〇C(〇)R2 4 , _C(〇)NR25R26 ' -NR23C(N-CN)NR25R2 6 and -NR23C( 0) Group of NR25R26. In a particular embodiment, in formula (m.b.), p is 2 and is employed in combination with two R3 groups of the same % A atom bonded to 135177-163-200922559 to form a group. (υ) - based on a specific example in 'in the formula _.), ρ is 2, and any two R3 groups of the same ring-shaped atom of the girl gentleman are used together, := 炫 base, with 丄Up to 3 independently selected from the group consisting of _nh_, _nr6_, 〇, s^^-NR6-, in a specific embodiment in a specific embodiment in a specific embodiment in a specific embodiment In a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment In a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, and in the ring (four) sub- or snail Heterocyclic dilute group, having 1 to 3 independent 2 including -NH... vein, 〇, s, s (〇ms(〇)2 ring hetero atom. 込f in formula (Ill.b.) 'R3 is an alkane In the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b.) Ill.b.) in the formula (Ill.b.) In the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b.) in the formula (Ill.b) In the formula (Ill.b.), in the formula (Ill.b.), R3 in the formula (Ill.b.) is a heteroalkyl group. R3 is an alkenyl group. R3 is a heteroalkenyl group. R3 is an alkyne. R3 is a heteroalkynyl group. R3 is an aryl group. R is a heteroaryl group. R3 is a cycloalkyl group. R3 is a cycloalkenyl group. R3 is a heterocycloalkyl group. R3 is a heterocycloalkenyl group. R is a 13⁄4 element. Is ~CN. R is ~n〇2. R3 is -OR1 9. R3 is -OC(0)OR20 135177 164- 200922559 In a specific embodiment, in the formula (Ill.b.), R3 is _ NR2 1 R2 2 ° In a specific embodiment, in the formula (Ill.b.), R3 is _NR23 s 〇 2r24. In a specific embodiment 'in the formula (ni.b.), R3 is _nr23c(0)OR20. In a specific embodiment 'in the formula (Ill.b.), R3 is _NR23C(〇)R24. In a specific embodiment, in the formula (Ill. In b.), R3 is _s〇2NR25r26. In a specific embodiment, in the formula (Ill.b.), R3 is _c(〇)R24. In one embodiment, 'in the formula (Ill.b.), R3 is _C(〇)〇R2〇. Body embodiment, in Formula (Ill.b.), R3 is _SRi9. In one particular embodiment, in Formula (Ill.b.), R3 is _s (square) Ri 9. In a specific embodiment, in the formula (Ill.b.), R3 is -s〇2Ri9. In a specific embodiment, in the formula (Ill.b.), R3 is _〇c(〇)R24. In a specific embodiment, in Formula (Ill.b.), R3 is _C(0)NR25R26. In a specific embodiment, in Formula (Ill.b.), R3 is _nr2 3 C(N-CN)-NR25R26. In a specific embodiment, 'in the formula (Ill.b.), R3 is _NR23c(〇)_

Nr25r26. In a specific embodiment, in the formula (Ill.b.), R3 is selected from the group consisting of methyl, ethyl, propyl (straight or branched), butyl (straight or branched) ),

135177 -165- 200922559

OH and H2N. In a specific embodiment, in Formula (Ill.b.), when E is -NR6-, R3 is absent. In a specific embodiment, the formula (Ill.b.) has the general structure (III.b.1):

(lll.b.1) wherein R1, R2, R3, R27, R28, p, E and ring B are independently selected from each other, and wherein: E is selected from the group consisting of -〇-, -S-, -S ( 〇)-, -S(0)2-, -C(R4)(R5)-, -N(R6)-, _N(C(Y)R7)-, _N(C(Y)0R8)- and The optional substituents on P, R1, R2, R3, R4, R5, R6, R7, RS, r9, Rio, r2, R28, Y and ring B are all as described in the above formula (mb). The definition in . In a specific embodiment, the formula (III.b) has one of the formulas (m.b 2) 135177 -166- 200922559

(ll.b.2) In one embodiment, the formula (Ill.b) has one of the structures shown in the formula (III.b.2.1).

(lll.b.2.1). In a specific embodiment, the formula (Ill.b) has one of the structures shown in the formula (III.b.2.2).

In a specific embodiment, the formula (Ill.b) has one of the structures shown in the formula (III.b.2.3) 135177 -167- 200922559

(lll.b.2.3). In a specific embodiment, the formula (Ill.b) has one of the structures shown in the formula (m.b.2.4).

(Ill.b.2.4). In some embodiments, 'in the various formulae (III.b.1), (III.b.2), (III, b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b, 2.4), p is 0. In some embodiments, 'in the various formulas (III.b.1), (ll.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), p is 1. In some embodiments, 'in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III_b.2.4), p is 2. In some embodiments, 'in each of the formulas (in.bl), (III.b.2), (m_b.2.1), (III.b.2.2), (III.b.2.3), and (III.b) In .2.4), E*_C(R4)(R5)·. In some embodiments, in the formulas (III bl), (III b 2), (III.b.2.1), 135177-168-200922559 (III.b.2.2), (III.b.2.3) and In (III.b.2.4), E is selected from the group consisting of -〇-, -s-, -S(O)-, -S(0)2-, and -N(R6)-. In some embodiments, in the various formulae (III.b.1), (Iil.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and (III.b.2.4), wherein E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2-, and -N(R6)-'. wherein r6 is selected from Including η, alkyl, _c(〇)R24 and -C(S)R24. In some embodiments, 'in the various formulas (III.b.1), (in.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and (III.b.2.4), wherein E is selected from the group consisting of -〇- and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(〇)R2 4 and -c(S)R2 4. In some embodiments, in the formulas (Ill.bl), (mb2), (III.b.2.1), (III.b.2.2), (III.b.2.3), and (III.b. In 2, 4), E is -Ο-. In some embodiments, 'in the various formulas (III.b.1), (mb2), (III.b.2.1), (III.b_2.2), (III.b.2.3), and (III. In b.2.4), E is -S-. In some embodiments, 'in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), E is -S(O)-. In some embodiments, in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), E is -S(0)2 -. In some embodiments, 'in the various formulas (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (mb2.3), and (mb2.4 In the formula, E is -C(R4)(R5)-. In some embodiments, 'in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), E is -N(R6)-. In some embodiments, in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (mb2.3), and (III. In b.2.4), E is -N(CXY)R7)-. In some embodiments, 'in the various formulas (III.b.1), (III.b.2), (III.b.2.1), 135177-169^200922559 (III.b.2.2), (III. In b.2.3) and (III.b.2.4), E is -N(C(Y)OR8)-. In some embodiments, 'in the various formulas (IILb.l), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3), and (III) In .b.2.4), E is -N(C(Y)N(R9)(R10))-. In some embodiments, 'in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), γ is (z = 〇). In some embodiments, in the various formulae (III.b.1), (III.b.2), (in.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), γ is (=s). In some embodiments, 'in the various formulas (III.b.1), (mb2), (III.b.2.1), (III.b.2.2), (III.b.2.3), and (III. In b.2.4), γ is 3)). In some embodiments, 'in the various formulas (III.b.1), (mb2), (III.b.2.1), (III.b.2.2), (III.b.2.3), and (III. In b.2.4), γ is (=n(CN)). In some embodiments, in the various formulae (III.b.1), (III.b.2), (III.b.2,1), (III.b.2.2), (III.b.2.3 And (III.b.2.4), γ is (two guide paws 14)). In some embodiments, 'in various formulas (ΠΙ.Μ), (III, b.2), (mb21), (IILb.2.2), (III.b.2.3), and (III.b.2.4) In the middle, γ is (=ν(Κ^ 5 )(Ri 6)). In some embodiments, in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), γ is (=c(r1 7 )(r1 8)). In some embodiments, in the formulas (ni.bl), (III.b.2), (in.b.2.1), (III_b.2.2), (IILb.2.3), and (III.b.2.4) Wherein Ri is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, -OH, -CN, -N〇2, -NR21R22, and a halogen-based group. . In some embodiments, in the formulas (ni bl), b 2), (mb 2丨), (III.b_2.2), (III.b.2.3), and (III.b.2.4), Ri is selected from the group consisting of: 135177 -170· 200922559

In formula (I), R1 is: in a specific embodiment

In some embodiments, in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), Ri is a phenyl group substituted by one to three ι groups. In some embodiments, 'in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), Ri is a phenyl group substituted by two ι groups. In some embodiments, 'in the various formulae (III.b.1), (III.b.2), (III.b.2.1), 1' (III.b.2.2), (III.b.2.3 And (III.b.2.4), Ri is a stupid base substituted by a gas group. In some embodiments, in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and In (III.b.2.4), Ri is:

In some embodiments, 'in the various formulas (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2_3) and (III.b.2.4), R2 7 and r28 are each independently selected from the group consisting of 1_1 135177 • ]71 - 200922559 and an alkyl group. In some embodiments, in the various formulas (IILb.l), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3), and (III) In .b.2.4), R2 is selected from the group consisting of alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, -C(0)R7, -C(0)0R8 and -CCCONi^R1 0. f

In some embodiments, in the various formulae (III.b.1), (III.b.2), (III.b.2.1), (III.b.2.2), (III.b.2.3) and (III.b.2.4), R2 is selected from the group consisting of:

135177 -172- 200922559

In some embodiments, in the formulas (mbi), (mb2), (mb2.i), (III.b.2.2), (III.b.2.3), and (III.b.2.4) , p is 1 or 2, and each R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, -CN, -N02, -OR19, -OC(0)OR20, -NR21R22, -NR23S02R24 , -nr23c(o)or2〇, -NR23C(0)R24 ' -S02NR25R26 λ -C(0)R24 ' -C(S)R24 ' -C(0)OR20 > f -SR19, -S(0) R19, -S02R19, _0C(0)R2 4, _c(〇)nr25r26, -NR23 c(n-cn)nr25r26, -nr23c(0)nr25r26 and -NR23-C(NH)-NR26R26, wherein each of the alkyl groups Each of the heterozygous 'j: a group, each of the dilute groups, and each of the heterogeneous groups are unsubstituted' or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independent Selected from keto, halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl , cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, 〇Rl9, -〇C(〇)〇R20, i-NR21R22, -NR23S02R24, _NR2 3C(〇)〇R2 0, _NR2 3C (〇)R2 4, -S02NR25R26, -C (0) R24, _c(0)OR20, -SR丨9, -S(〇)R]9, -S02R19 ' -0C(0)R24 > -C(〇)NR25R26 ' -NR2 3 C(N- CN) NR2 5 Group of R2 6 and -nr23c(o)nr25r26. In some embodiments, in each of the formulas (III b, (III b 2), (mb 2J), (III.b.2.2), (mb2.3), and (III.b.2.4), p is i And r3 is selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, and a heteroalkenyl group, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heteroalkenyl groups 135177 '173-200922559 is Unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, a -CN, a -N02, a decyl group, a hetero-substrate, a tooth-burning Base, bake, (tetra), alkynyl, halo, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocycloalkenyl, azido, _〇r19, 〇 c(〇)〇r2(), -NR2lR22, _NR23S〇2R24, fly 23c(c))〇r2G, _NR23c(〇)R24,

\

-S02NR25R26, -C(Q)R24, _c(〇)〇r2G, _SRl9, delete Ri9, -so2r- ^ -0C(0)R- ^ -C(〇)NR25r26 . .NR23C(N.CN)NR25R26 and a group D of -nr23c(o)nr25r26 in the specific embodiments, in the formulas (HLb.D, (III b 2), (mov.21), (mb2'2), _.2.3) In (mb2.4), p is 2 and is employed together with any two R3 groups bonded to the same ring A atom to form a _c(〇)- group. In some embodiments, in each of the equations (movement), (movement·2), (four) 21), (mb2.2), (mb23), and (III.b.2.4), ρ is 2, and Any two R3 groups bonded to the same ring enthalpy atom are employed together to form a spiroheterocycloalkyl group having from 1 to 3 independently selected from the group consisting of _NH..._NR6 _, 〇, s, _, and s(〇) 2 ring heterocyclogen + ' or a spiroheterocyclic group having U 3 independently selected from ring heteroatoms including 2 -NH-, -NR6-, hydrazine, S, s(0) and s(0)2. In a specific embodiment, the compound of the invention has the structure shown in formula (ιν) and includes a pharmaceutically acceptable salt, solvate, ester, prodrug or isomer of the compound: 135177 -174 - 200922559

R 3 ί \ wherein R1, R2, R3, r27, R28, ρ, Ε, ring α and the ring Β and the remote group attached to the ring are each independently selected, and wherein: -C(R4)(R5)_, _〇..._heart, _qing 2 and -n(r6)_ ; % B is an unsubstituted or substituted aromatic ring, or unsubstituted or substituted Each of the heteroaromatic rings has w ring heteroatoms, which may be the same or different, and each ring hetero atom is independently selected from the group consisting of N, s, 〇, s(〇) and s(o)2. The substituent on the aromatic ring or the heteroaromatic ring, when present, is independently selected from the group consisting of _, -CN, _N02, alkyl, heteroalkyl, -alkyl, alkenyl halide Alkyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-homo-based, heteroarylalkyl-lactyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide Base, -OR19, _〇c(〇)〇r20, _nr21r22, R24, -NR23C_R2Q, _NR23C(0)R24, Nr25r26 'c(〇)R24, (O)OR, -SR 9, _s( 〇) Rl 9, s 〇 2 Rl 9, 〇 c (〇) R2 4, c (〇辉2 5 r2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and _nr2 3 c(9) nr2 5 r2 6 ; R] is a substituted aryl group, or an aryl group substituted by one or more substituents which may be the same or different substituents, each substituent being independently selected from the group consisting of a tetrazine, a CN, a N2, a ketone group An alkyl group, an alkenyl group, a benzyl group, a fast group, a halogen n mm 'aryl-alkyl group, a heteroaryl group, a cycloalkyl group, a 135177-175-200922559 cycloalkenyl group, a heterocycloalkyl group, a heterocyclic group Cycloalkenyl, azide, -OR1 9, _OC(0)〇R2〇, _NR2 1R2 2 , -NR23S02R24 ^ -NR23C(0)0R2° ' -NR23C(0)R24 ' -S02NR25R26, _C(0)R2 4, _c (〇) 〇 r20, _SRl9, _s (〇) R] 9, _s 〇 2Rl9, - 〇 C (0) R24, _C (〇) NR2 5R2 6, _NR2 3C (N-CN) NR2 5R2 6 & _NR2 3C(〇)· cis 2 5R26 ; R2 is selected from the group consisting of -c(o)R7, -c(o)NR9R10 and -c(o)or8; P is 0, 1 or 2; and each R3 (when present Independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, -CN, -N02, -OR19, 〇(:(〇)〇Ι120, _NR21R22, _c(〇)R24, -C (S) R24, -C(〇)〇R20 and _c(0)NR25R26, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups and each of the heteroalkenyl groups is unsubstituted or The situation is independent of one or more can be the same Substituted by different substituents, each substituent is independently selected from the group consisting of a keto group, a hydroxyl group, a _CN, a -N 〇 2, an alkyl group, a heteroalkyl group, a haloalkyl group, an alkenyl group, a haloalkenyl group, an alkynyl group, a haloalkyne group. , aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -〇q〇)〇R2〇, -NR2 1R2 2 3s 〇 2R24, nr23c (〇) 〇 r2. , NR23c Na 24, -S02NR25R26, -C(0)R2 4, _c(0)0r2g, _SRl9, part) R19, _s〇2Ri9,_0C(0)R24, -c(〇)nr25r26, -nr23c(n- Cn) a group of nr25r26 and -nr23c(o)nr25r26; and all remaining variables are as defined in the specific examples described above in formula (I). In one such specific embodiment, in formula (iv): E is from the group consisting of -0- and -N(r6)_; 135177-176-200922559 ring B is an unsubstituted or substituted moiety a group selected from the group consisting of benzo, furyl, thiophenyl, pyrrolyl, oxazolyl, pyrazolyl, imidazolyl, pyrazolyl, oxazolyl, isothiazolyl, triazolyl, thiadiazole a pyridyl group, a pyridyl group, a hydrazine group, a pyrimidinyl group, a pyridinyl group, and a tri-farming group; R is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of a halogen group , 〇H, _CN, Ν〇2, _nr2丨r2 2 and haloalkyl; r27 and R28 are each independently selected from the group consisting of ruthenium and alkyl; R2 is selected from the group consisting of -c(o)R7, c(0) 0r8; P is 0 or 1; and each R3 (when present) is independently selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, and a heterocyclic group, wherein each of the alkyl groups, each of the heteroalkyl groups, and the respective alkene And each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a pharmaceutically element, -CN, -N 〇2, alkyl, heteroalkyl, haloalkyl, , haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, 〇Rl9, 〇〇c 〇)〇r2(), -NR21R22, _NR23S〇2R2 4, NR2 3C(〇)〇R20, nr23c(〇)r24, -S02NR25R26, -C(〇)R2 4, _c(〇)〇R2 0, SR] 9. _s(〇)Rl9, -S02R19 > -0C(0)R24. -C(〇)NR25R26 > -NR23C(N-CN)NR25R26 and -nr23c(0)nr25r26. In one such embodiment, in formula (IV): R1 is: 135177 177- 200922559

R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, _c(〇)〇r2〇, and _c(s)r2 4 . In one embodiment, the compound of the invention has the formula (Iv.a) The structure of the present invention, and includes pharmaceutically acceptable salts, solvates, prodrugs or isomers of the compound:

The ground is selected, and wherein: ring A (comprising E and the unsaturation shown) is a 6-membered cycloalkenyl or heterocyclic ring; E is selected from the group consisting of -0-, -S-, -S ( O)-, -S(0)2-, -C(R4)(R5)- '-N(R6)-, -N(C(Y)R7)-, -N(C(Y)OR8)- , -N(C(Y)N(R9)(R10))-, -C(0)-N(Rn)-, -N(Rn)-C(0)-, -S(0)2-N (Rn)-, -N(Rn)-S(0)2-, -C(0)-0-, -0-C(0)-, -0-N(R6)-, -N(R6) -0-, -N(R6)-N(R12)-, -N=N-, -C(R7)=N-, -C(0)-C(R7)=N-, -C(0) -N=N-, -O-CXYVN^11)-, -^R11)-C(Y)-0-, -N(Rn)-C(Y)-N(R12)-, -C(Y) -N(Rn)-〇-, -C(Y)-N(Rn)-N(R12)-, -0-Ν(Ι^ 1 )-C(Y)- and -N(R) 2)- Ν(Ι^ 1 )-C(Y)-, ring B is a substituted or unsubstituted aromatic ring; 135177 -178- 200922559 and p, R1, R2, R3, R4, R5, R6, R7, R8 The selected substituents on R9, R10, R11, R1, R27, R28, Y and ring B are all as defined in the specific examples described in the above formula (I). In a specific embodiment, the formula (IV.a) has a general structure as shown in the formula (IV.a.l).

(IV.a.1). In a specific embodiment, formula (IV.a) has one of the structures shown in formula (IV.a.2):

(IV.a.2). In a specific embodiment, formula (IV.a) has one of the structures shown in formula (IV.a.3): 135177 -179- 200922559

(IV.a.3), where p is 0, 1, 2 or 3. In a specific embodiment, formula (IV.a) has one of the structures shown in formula (IV.a.4).

(IV.a.4) ' where p is 0, 1, 2 or 3.

In a specific embodiment, formula (IV.a) has one of the structures shown in formula (IV.a.5):

(IV.a.5), where p is 0, 1, 2 or 3. In a specific embodiment, formula (IV.a) has one of the structures shown in formula (IV.a.6) 135177-180-200922559.

(IV.a.6), where p is 〇, 1, 2 or 3. In some embodiments, in the various formulae (IV.a), (in), (IVa 2), (IV.a.3), (IV.a.4), (IV.a.5), and In 'IV.a.6), 'ring A is a cycloalkenyl ring and E is -C(R4)(R5)-. In some embodiments, 'in the various formulae (IV.a), (iv.al), (Iv.a 2), (IV.a.3), (IV, a.4), (IV.a. 5) and (IV.a.6), ring A is a heterocyclic ring, and the group E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2- and -N(R6)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a_5 And (IV.a.6), ring A is a heterocycloalkenyl ring, and E is selected from the group consisting of -〇-, -S-, -S(O)-, -S(0)2- and - N(R6)-, wherein the lanthanide is selected from the group consisting of ruthenium, alkyl, -C(0)R24 and -C(S)R24. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV,a In .5) and (IV.a.6), ring A is a heterocycloalkenyl ring, and E is selected from the group consisting of -〇- and -N(R6)-, wherein R6 is selected from the group consisting of anthracene, alkyl, -C(0)R24 and -C(S)R24. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -Ο-. In some embodiments, 'in the various formulae (IV.a), (IV.al), (IV.a.2), 135177-181 - 200922559 (IV.a.3), (IV.a.4) , (IV.a.5) and (IV.a.6), E is -S-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -S(O)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -S(0)2-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -C(R4)(R5)-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a_4), (IV.a.5) And (IV.a.6), E is -N(R6)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -N(C(Y)R7)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -N(C(Y)OR8)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -N(C(Y)N(R9)(R10))-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -C(0)-N(R]1)-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV, a.6), E is -NCR11)-C(0)-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV_a.6), E is -S(0)2 -Ν^11)-. In some embodiments, 'in the various formulae (IV.a), (IV.al), (IV.a.2), aV.a.3), (IV.a.4), (IV.a. In 5) and (IV.a.6), E is -N(Rn)-S(0)2-. In some embodiments, in the formula (IV.a) '(IV.al), (IV.a.2), 135177-182. 200922559 (IV.a.3), (IV.a.4) , (IV.a.5) and (IV.a.6), E is -C(0)-0-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -OC(O)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -0-N(R6)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -N(R6)-0-. In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a, 6), E is -NCR6)-:^^1 2)-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV_a.4) ' (IV.a.5 And (IV.a.6), E is -N=N-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a_4), (IV.a.5) And (IV.a.6), E is -C(R7)=N-. In some embodiments, 'in each of formulas (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), E is -C(0)-C(R7)=N-. In some embodiments, 'in each formula (IV.a), (IV.al), (IV.a.2) ' (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -C(0)-N=N-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a .5) and (IV, a.6), E is -O-CXY^N^11)-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -Ν(Ι^ 1 )-C(Y)-0-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a .5) and (IV.a.6), E is -NKRHKX^-N^12)-. In some embodiments, 'in the various formulae (IV.a), (IV.al), (IV.a.2), 135177-183-200922559 (IV.a.3), (IV.a.4) In (IV.a.5) and (IV.a.6), E is -Cm-NCR1 1 )-0-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a, 6), E is -C(Y)-N(Rn)-N(R12)-. In some embodiments, 'in each of formulas (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), E is -O-NCR11)-C(Y)-. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), E is -N(Ri2 VNCR11 )-C(Y)-. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), Y is (two). In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), Y is (=S). In some embodiments, 'in each of formulas (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), Y is (=Ν(Ι^3)). In some embodiments, 'in each of formulas (IVa), (IVa l), (IVa 2), (IV.a.3), (IV.a.4), (IV.a.5), and (IV) In .a.6), Y is (=N(CN)). In some embodiments, in the various formulae (IV.a), (IV_a.l), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), Y is (^NCOR14)). In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), Y is (^NCR15 XR1 6)). In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), Y is OCXR17 XR18)). In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), B is an unsubstituted aromatic ring. In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), 135177 184.200922559 (IV.a.3), (IV, a.4) And (IV.a.5) and (IV_a.6), B is an unsubstituted benzo ring and formula (IV.a.) has the following general structure:

f

In some embodiments, 'in the various formulae (IV.a), av, a.: 〇, (IV.a.3), (IV_a.4), (IV.a_5), and (IV.a.6) Wherein B is an aromatic ring which is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, heteroalkyl , haloalkyl, alkenyl, *alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, hetero Cycloalkyl, heterocycloalkenyl, azide, -OR19, _〇C(〇)〇R20, _nr21r22, nr23s〇2R24 : -NR23C(〇)〇R2〇, _Nr23C(〇)r24, 妈服25尺26, c Na 24, -C(0)0R20 ^ -SR1 9 x -S^R19 > -SO2R1 9 ' -0C(0)R24 -C(0)NR25R2 6, -NR2 3 C(N-CN) NR2 5 R2 6 and -NR2 3 C(0)NR2 5 r2 6. In some embodiments, in the various formulae (IV: a), (IVa l), (iva. 2) (IV.a.3), (IV.a.4), (version 5), and (IVa 6) Wherein B is a benzo ring, which is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a sulphate, a _CN, a _N 〇 2, a fluorenyl group, a heteroalkyl group, Distillyl, dilute, (tetra), block, halo, aryl, heteroaryl, arylgo group, heteroaryl-fluorenyl, tetrakis Mercapyl, stack 135] 77 -185- 200922559 Nitrogen group, -OR19, -〇C(〇)〇R20, -NR21R22, -NR23S02R24, -NR23C(0)OR20, -NR23C(0)R24, -S02NR25r2 6. -C(0)R24, -C(0)OR20, -SR]9, -SCC^R1 9, -S02R1 9,-0C(0)R24, -C(0)NR25R26, -NR2 3 C(N- CN) NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R1 is an unsubstituted aryl group. In some embodiments, in the various formulae (IV.a), (iV.ai), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R1 is an unsubstituted phenyl group. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R1 is an unsubstituted sulfhydryl group. In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R1 is a substituted aryl group. In some embodiments, 'in the various formulae (IV.a), (IVa l), (IVa 2), (IV.a.3), (IV.a.4), (IV.a.5) and In (IV.a.6), R is a substituted phenyl group. In some embodiments, 'in each of formulas (IV.a), (IVa l), (IVa.2), (IV.a.3), (IV.a.4), (IV.a.5) And (IV.a.6), Ri is a substituted thiol group. In some embodiments, 'in the various formulae (IV.a), (IVaj), (IVa 2), (IV.a.3), (IV.a.4), (IV.a.5), and In IV.a.6), Ri is an aryl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N02, alkyl, and , haloalkyl, dilute, difunctional, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocyclic Alkyl, heterocycloalkenyl, azide, _0R19, -oc(o)or2〇, -NR2, R2 2, _nr23s〇2R24, nr23c(9)〇r20, -NR23C(0)R24, _S〇2Nr25r26, _c(〇 ) R24, _c(〇)〇R20, SR19, 135177 186- 200922559 ()R S02R 9 . -0C(0)R24 ^ -C(〇)NR2 5R6 , -NR23C(N-CN)-Nr2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the formulas (Iv.a), _"), (IVa2), (version 3), (IV.a.4) ' (iv.a.5) and _.6) Wherein R1 is a phenyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of dentin-CN, -N02, alkyl, sulfhydryl, south yard, and rare Base, dentate, ^ group, alkynyl, aryl, heteroaryl, aryl-alkyl...heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl , azide group, _〇r1 9, -0C(0)0R2. , _Nr2] R2 2, depending on 23s 〇 2R24, nr23c (9) 〇 R2. -NR23C(0)R24, -S02NR25R26 ^ -C(0)R2 4 , _C(〇)〇R2 0 λ _SR19 , -S(0)R19, -S02R19, _〇C(〇)R2 4'00) ^2 5^6, _nr23c(n cn) NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some specific examples, 'in the various formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV. In a.5) and (IV.a.6), R1 is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, -OH, _CN, - N02, -NR2iR22 and haloalkyl. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R1 is selected from the group consisting of:

In some embodiments, 'in various formulas (IV.a), (IV.a.l), (IV.a.2), 135177-187-200922559

In (IV.a.4), (IV.a.5) and (IV.a.6), R1 is:

In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R1 is a phenyl group substituted by one to three fluoro groups. In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), R1 is a phenyl group substituted by two fluorine groups. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R1 is a phenyl group substituted by a fluorine group. In some embodiments, 'in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4) ' (IV.a_5 And (IV.a.6), R1 is:

In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV, a, 6), R2 7 and R2 8 are each independently selected from the group consisting of H and an alkyl group. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a_5 And (IV.a.6), R2 is -C(Z)R7. In some embodiments, 'in each of formulas (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), R2 is -C(Z)NR9 R]0. 135177 -188- 200922559 In some embodiments 'in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4) In (IV.a.5) and (IV.a.6), R2 is _c(Z)OR8. In some embodiments, 'in each of formulas (IV.a), (jy.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R2 is _S〇2NR9Ri〇. In some embodiments, 'in each formula (IV_a), (p/.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a. In 5) and (IV.a.6), R2 is an alkyl group.

In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a_6), R2 is heteroalkyl D. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV. In a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is an aryl group. In some embodiments, 'in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a_4), (IV.a.5) And (IV.a.6), R2 is a heteroaryl group. In some embodiments, 'in various formulas (IV.a), (p/.ai), (iv.a.2), (IV.a.3), (IV.a.4), (IV. In a.5) and (IV.a.6), R2 is a cycloalkyl group. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R2 is a cycloaliphatic group. In some embodiments, 'in each of formulas (IV.a), (iv.aD, (IV.a.2), (IV.a.3), (IV.a.4), (IV.a. 5) and (IV.a.6), R2 is heterocycloalkyl. In some embodiments, 'in each of formulas (IV.a), (iv.aj), (IV.a.2), In IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is a heterocycloalkenyl group. In some embodiments, 'in each formula ( IV.a), (p/.aj), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6) Where Z is (=〇). In some embodiments, 'in each formula (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV) In .a.4), (IV.a.5) and (IV.a.6), Z is (=s). 135177 -189- 200922559 In some embodiments, in each formula (IV.a) , (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), Z is (=N(R)3)). In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a, 2), (IV.a.3), (IV) In .a.4), (IV.a.5) and (IV.a.6), Z is (=N(CN)). In some embodiments, in each formula (IV.a), IV.al), (IV.a.2), (IV.a 3), (IV.a.4), (IV.a.5) and (IV.a.6), Z is (sNCOR1 4)). In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV'a.4), (IV.a In .5) and (IV.a.6), Z is (=N(R]5 XR16)). In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), Z is (=(:(1117 XR18)). In some embodiments, 'in each formula (IV.a), (IV.al), (IV. In a.2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is -C(Z)R7 and Z is (=0). In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a. 4), (IV.a.5) and (IV.a.6), 妒 is _C(0)H. In some embodiments, 'in each formula (IV.a), (m), In Iv.a.2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is _c(0)alkyl. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R2 is _c(0)CH3. In some embodiments, 'in each of formulas (IVa), (IVa), (IVa2), (IV.a. 3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is _c(0)R7, wherein the R7 is one or more may be the same or Alkyl substituted with different substituents The base is independently selected from the group consisting of keto, halogen, _CN, _N 〇 2, alkyl, heteroalkyl, dentyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, fluorene Alkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _〇Rl 9, 135177 -190- 200922559 -0C(0)0R20 . -nr21r22 > -NR2 3S〇2R2 4 . _nr23c (〇)〇r20 ' -NR23C(〇)R24, _S〇2NR2 5R2 6, c(〇)r24, c(〇)〇r2, sr19, -S(0)R, -S〇2R〗 9, _ 〇C(〇)R2 4, c(〇)Nr25r26, nr23c(n cn)_NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 R2 6. In some embodiments, 'in each formula (Iva) , (Iv.al), (Iv.a.2), (IV'a.3), (IV.a.4), (rv.a.5), and (iv.a.6), R2 is _c(0)R7, wherein R7 is an alkyl group substituted by one or two substituents which may be the same or different, each substituent being independently selected from the group consisting of -OR1 9, NR 2 1 R 2 2 and a ring-based group. In some embodiments, in the formula (Iva), (Iv.al), (Iv.a 2), (IV.a.3) '(IV.a.4) ' (iv.a.5) And (IV.a.6), R2 is _c(〇)R7, wherein the R7 is an alkyl group wherein the alkyl group is substituted with an alkyl group and -〇H. In some embodiments, 'in the various formulae (IVa), (IVa l), (IVa2), (IV.a.3) ' (IV.a.4), (IV.a.5), and (IV. In a.6), R2 is _c(0)R7, wherein the R7 is an alkyl group substituted by one to three substituents which may be the same or different, each substituent being independently selected from the group consisting of -OH, -NH2 and Cyclopropyl. In some embodiments, in the various formulae (IVa), (IVa l), (IVa 2), (IV.a.3), (IV.a.4), (IV.a.5), and (IV) In .a.6), R2 is _c(〇)R7, wherein the r? is an alkyl group substituted by one or two substituents which may be the same or different, each substituent being independently selected from the group consisting of -NH2 and a ring. Propyl. In some embodiments, in the various formulae (IV.a), dV.a"), (IVa 2), (IV.a.3), (IV.a.4), (IV.a.5) And (IV.a.6), R2 is -C(〇)R7, wherein the r7 is an alkyl group substituted by -OH. In some embodiments, 'in each of (IV.a), dV.aj), (IVa2), (IV.a.3), (iv.a.4), (IV.a.5), and In IV.a.6), R2 is -C(0)R7, wherein the r7 135177-191 - 200922559 is an unsubstituted heterocycloalkyl group. In some embodiments, 'in each of formulas (IVa), (IVa1), (IVa2), (IV.a.3), (IV.a.4), (iv, a, 5), and (iv. In a.6), R2 is -C(0)R7, wherein R7 is substituted heterocycloalkyl. In some embodiments, 'in each of formulas (IVa), (IVa υ, (IVa 2), (IV.a.3), (IV.a.4), (iv_a.5), and (IV.a. 6), R2 is -C(0)R7, wherein R7 is a heterocycloalkyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a ketone group, a halogen, -CN, _N〇2, alkyl, heteroalkyl, haloalkyl 'alkenyl'haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkane , heterocyclenyl, azide, -OR19, -0C(0)0R20, -NR21R22, -NR23S02R24, -NR23C(0)OR2〇, -NR23C(0)R24 ' -S02NR25R26 ' -C(0) R24 ' -C(0)OR20 > -SR19 ' -S(0)R19, -S02R19, -0C(0)R24, -C(0)NR25R26, -NR23C(N-CN)-NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2),

(IV.a.3) ' (IV.a.4), (IV.a.5) and (IV.a.6), R2 is C(0)R7, wherein the R7 is selected from the group consisting of Substituted hexahydropyridine, substituted hexahydropyridinium, substituted oxaflune, substituted tetrahydropyrrole, and substituted one nitrogen tetraindole. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R2 is selected from:

In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV_a.3), (IV.a.4), (IV.a.5) And (IV.a.6), R2 is -C(0)NR9R10. 135177 -192- 200922559 In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4) In (IV.a.5) and (IV.a.6), R2 is _C(0)NH2. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a,2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R2 is -C(〇)NR9R10, wherein R9 and RIG may be the same or different and each independently selected from an alkyl group. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R2 is -C(0)NR9R1 0 ' wherein R9 is an unsubstituted heterocycloalkyl group, and R1 0 is selected from the group consisting of H and an alkyl group. In some embodiments, 'in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a_3), (IV.a.4), (IV.a.5) And (IV.a.6), R2 is -C(0)NR9R10, wherein R is a substituted heterocycloalkyl group, and R10 is selected from the group consisting of H and an alkyl group. In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), R2 is -C(O)NR9R]0, wherein R9 is a heterocycloalkyl group substituted by one to three substituents which may be the same or different, each substitution The base is independently selected from the group consisting of alkyl groups, and the R1G is selected from the group consisting of ruthenium and alkyl groups In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IVa.3), (IV.a.4), (iv.a.5) And (IV.a.6), R2 is selected from the group consisting of alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, -C(0)R7, -C(0)0R8, and -C ( 0) NR9 R10. In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (iv In .a.5) and (IV.a.6), R2 is selected from the group consisting of

135177 -193- 200922559 V.

In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2) χλ (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R2 is cf3. In some embodiments, in the various formulas (IV.a), (IV.al), (IV.a.2)

(IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is in some embodiments, in each formula (IV.a) , (IV.al), (IV.a.2), 135177-194- 200922559 ο

(IV.a.3), (IV.a.4), (IV.a.5), and av.a.6), R2 is in some embodiments, in each formula (IV.a), (iv.al), (IV.a.2) (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is χΐ' In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2) (IV.a.3), (IV.a.4), (IV. In a.5) and (IV.a.6), R2 is Ί0'. In some embodiments, 'in each formula (IV.a), (iv.al), (IV.a.2),

In the meanings (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is . In some embodiments, 'in various formulas (IV.a), (iv.a.1), (lV.a.2),

(IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is in some embodiments, in each formula (IV.a) , (iv.a.1), (iv.a.2)

(IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R2 is in some embodiments, in each formula (IV.a) , (iv.a.1), (IV.a.2) (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), p For 〇, and R3 does not exist. In some embodiments, 'in each formula (IV.a), (rv.al), (rV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), p is i. In some embodiments, in the various formulae (IV.a), (iV.a.1;), (IV.a.2), (IV.a.3), (IV.a.4), In IV.a.5) and (IV.a.6), p is 2. In some embodiments, in the various formulae (IV.a), (iv.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), p is 3. In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), 135177-195, 200922559 (IV.a.3), (IV.a.4) , (IV.a.5) and (IV.a.6), p is 4. In some embodiments, in the various formulae (IV.a), (iv.a.1), (iv.a.2), (IV.a.3), (IV.a.4), (IV) In 'a.5) and (IV.a.6) 'p is g 2 and at least two groups R3 are attached to the same ring atom. In some embodiments, 'in the various formulae (IV.a), (IV.a.1), (IV.a.3), (IV.a.4), (IV.a.5), and In IV.a.6), 'p is 1, and r3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl < base, heteroaryl, ring Alkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, _, -CN, -N〇2, -OR19, -〇C(〇)〇R2. , _NR21r2 2, _nr2 3s 〇 2r2 4, -nr23c(o)or20, -NR23C(0)R2 4, _S〇2Nr25r26, c(〇)r24, -C(0)0R2. , -SR1 9, -SO^R1 9, -S02R19, _〇c(〇)R2 4, _c(〇)nr25r26, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0) NR2 5 R2 6. In some embodiments, 'in the various formulae (IV.a), (IVa l), (IVa 2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), p is 2, 3 or 4, and each R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkyne (yl, aryl, Heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halogen, -CN, -N02, -〇R]9, _〇c(〇)〇r20, _nr2ir22, -NR23S02R24, -NR23C(0)0R2G, _NR2 3C(〇)r24, _s〇2Nr25r26, -C(0)R24, -C(0)〇R2〇, _SRi9, _s(〇)Rl9, s〇2Rl9, 〇c(〇 R24, -c(o)nr25r26, _NR2 3C(n_cn)nr25r26&_nr23c(〇)nr25r26. In some embodiments, in the formulae (Iv.a), (lva l), (lva2), (IV) .a, 3), (IV.a.4) ' (IV.a.5) and (IV.a.6), p is 2, 3 or 4, and at least two groups R3 are bonded to The same ring carbon atom, wherein each r3, which may be the same or different, is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, 135177-196-200922559 alkynyl, heteroalkynyl, aryl, Heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl Heterocyclenyl, halogen, _CN, -N02, -OR] 9, -〇c(〇)〇r2〇, NR2〗R22, -NR23S〇2R24, -NR23C(0)OR20, -NR23C(0)R24, _S〇2NR25R26, -C(〇)R2 4, _C(〇)〇R2 0, _SR19, _s(〇)R19, s〇2Rl9, _OC(0)R24, -C(〇)NR25R26, -NR23C(N- CN)NR25R26&-NR2 3c(〇)-NR25R26. In some embodiments, in the various formulae (IV.a), (IVa l), (IVa2), '·3), _.4), (version) 5) and _.6), 1) is 2, 3 or 4, and at least two groups R3 are bonded to the same ring carbon atom, wherein two oxime groups, which may be the same or different, and And the attached carbon atoms together form a cycloalkyl, cycloalkenyl, heterocycloalkyl ring, containing one to three heteroatoms selected from N, fluorene and S, or a heterocycloalkenyl ring, containing one to three Since the inclusion of n, 〇 and s heteroatoms. In a specific embodiment, in the formula (iv.a), p is 丨, 2, 3 or 4, and each R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl 'seven N, (-N02 ' -OR19 ' -0C(0)0R20 > -NR21R2 2 . -NR23S02R24 -nr23c(〇)〇r2 0, _NR2 3C(0)r24, s〇2Nr25r26, c((7)r24, -C(5)R24, _C(〇)〇R2G, _SR19, but) Rl9, s〇2Rl9, 〇c(〇)R24, -C(0)NR2 5R2 6, _NR2 3C(n_cn)Nr25r26, _nr23c((7) nr25r26&-NR23-C( NH)-NR26R26, wherein each of the alkyl groups, each of the heterogeneous groups, each of the dilute groups, and each of the heterozygous bases are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different Substituted, each substituent is independently selected from the group consisting of a keto group, a halogen, a -CN, a -N02' phenotype, a brothel group, a halogen-based group, a dilute base, a dentate group, 135177 197-200922559 an alkynyl group, a haloalkyne group, an aromatic group. Base, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -ORM, _〇C(〇)〇R20, -NR21R22, -NR23S〇2R24, _NR2 3C (〇)〇R2 0, _NR2 3C(〇)R24, -S02NR25R26 ' -C(0)R2 4, _c(〇)〇R2 0, _SRl9, s(〇)Rl9, -S02 A group of R1 9, -0C(0)R2 4, -C(〇)NR2 5 R2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 . In a specific embodiment, in the formula (IV.a), p is 1, and r3 is selected from the group consisting of alkyl, hetero, alkenyl and heteroalkenyl groups, wherein each of the alkyl groups The alkyl group, each of the alkenyl groups and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different. Each substituent is independently selected from the group consisting of a keto group and a _ group. , -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, i-alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, hetero Cycloalkyl, heterocycloalkenyl, azide, 〇Ri9, _〇C(〇)〇R2〇, -NR2 丨妒2 ', NR2 3S〇2R24, _nr23c(〇)〇r2〇, nr23c_4, - S02NR25R26, -C(〇)R2 4, -C(〇)〇R2 0, _SR]9, _s(〇)r19, -so2r19 > -0C(0)R24 ^ -C(0)NR25R26 > -NR23C (N-CN) NR25R26 and -nr23c(o)nr25r26 group. In a particular embodiment, in Formula (IV.a), p is 2, 3 or 4 and is employed together with any two R3 groups bonded to the same ring Α atom to form -C(O) )- group. In a particular embodiment, in Formula (IV.a), p is 2, 3 or 4 and is employed together with any two R3 groups bonded to the same ring Α atom to form a spiro-heterocycloalkane. The base 'having from 1 to 3 independently selected from the group consisting of _NH_, _nr6_, 〇, 135177-198- 200922559 S, S(O) and (0) 2 ring heteroatoms, or spiroheterocycloalkenyl groups, having 1 to 3 The rings are independently selected from the group consisting of -NH-, -NR6-, Ο, s, S(O) and S(0)2. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is a burnt group. In some embodiments, 'in each of formulas (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is a mixed yard. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is a dilute base. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is a heteroalkenyl group. In some embodiments, 'in each formula (IV.a) ' (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is an alkynyl group. In some embodiments, 'in each of formulas (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is a heteroalkynyl group. In some embodiments, 'in each formula (IV.a), (iv.al), (IV.a.2;), (IV.a.3) ' (IV.a.4), (IV. In a.5) and (IV.a.6), R3 is an aryl group. In some embodiments, 'in each formula (IV.a), (by), (iv.a.2), (IV.a.3), (IV.a.4), (IV.a. 5) and (IV.a.6), R3 is a heteroaryl group. In some embodiments, 'in the various formulae (IV.a)', gv.a.2), (IV.a.3), (IV.a.4), (IV.a.5), and (IV) In .a.6), R3 is a cyclosyl group. In some embodiments, 'in the various formulae (IV.a), (jY.a.2), (IV.a.3), (IV.a.4), (IV.a.5), and In IV.a.6), R3 is a cycloaliphatic group. In some embodiments, 'in each of formulas (IV.a), (IVa: 〇, jVa, (IV.a.3), (IV.a.4), (IV.a.5), and (IV. In a.6), R3 is a heterocyclic alkyl group 135177-199- 200922559. In some embodiments, 'in each formula (IV.a), (Ιν.&.υ, Q; Va2:), ( In IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R3 is a heterocycloalkenyl group. In some embodiments, 'in each formula ( In IV_a), (IVa l), (IVa.2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R3 is halogen In some embodiments, 'in the various formulae (IV.a), (p/.d), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), R3 is _CN. In some embodiments, 'in each formula (IV.a), (iv.al;), (IV.a.2) , (IV.a.3), (IV.a, 4), (IV.a.5), and (IV.a.6), R3 is _N〇2. In some embodiments, 'in each Formula (IV.a), (iv.al), (JV.a.2), (IV.a.3), (IV_a.4), (IV.a.5) and (IV.a.6) Where R3 is _0Ri 9000 in some embodiments 'in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a. 3), (IV.a.4), (IV.a.5), and (IV.a.6), R3 is _0C(0)0R2 〇. In some embodiments, in each formula (IV) .a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6) , R3 is _NR2 1 R2 2. In some embodiments, in the various formulae (IV.a), (iv.a.1), (IV.a.2), (IV.a.3), In IV.a.4), (IV.a.5) and (IV.a.6), R3 is _NR2 3 s 〇 2r2 4. In some embodiments, 'in each formula (IV.a), (iv.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a.5) and (IV.a.6), R3 Is _nr2 3 C(0)OR20. In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV) In .a.4), (IV.a.5) and (IV.a.6), R3 is _NR2 3 C(0)R2 4 . In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is _S〇2NR2 5 R2 6. In some embodiments, in the various formulae (IV.a), (by), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a. 5) and (IV.a.6), R3 is _c(〇)R2 4. 135177 -200- 200922559 In some embodiments 'in the various formulae (IV.a), (rv.al), (IV.a.2), (IV.a.3), (IV.a.4) , (IV.a.5) and (IV.a.6), R3._c(〇)〇r2〇. In some embodiments, 'in each of formulas (IV.a), (iv.a_i), (iv_a.2), (IV.a.3), (IV.a.4), (IV.a.5) And (IV.a.6), R3 is _SRi 9. In some embodiments, 'in each formula (IV.a), dv.aj), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a. 5) and (IV.a.6), R3 is _s(〇)Ri 9. In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), (IV, a.3), (IV.a.4), (IV.a .5) and (IV.a.6), R3g_S〇2Ri9. In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is _〇c(〇)R2 4. In some embodiments, in the various formulae (IV.a), (iv.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is _c(0)NR25R26. In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), 圮 is _Nr2 3 C(N_CN)_ NR2 5R2 6. In some embodiments, in the various formulae (IV.a), (IV.a.1), (IV.a.2), (IV.a.3), (IV.a.4), (IV) In .a.5) and (IV.a.6), R3 is -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the various formulae (IV.a), (IV.al), (IV.a.2), (IV.a.3), (IV.a.4), (IV.a In .5) and (IV.a.6), R3 is selected from the group consisting of fluorenyl, ethyl, propyl (straight or branched), butyl (straight or branched), fluorenyl ( straight

135177 -201 - 200922559 〆

H2N. In some embodiments, 'in the various formulas (Iv.a)' (Iv.al), (Iva2), (IV.a.3), (IV.a.4), (Iv.a.5) and (IV.a.6) When 'e is -NR6-, the R3 system does not exist. In a particular embodiment, the compound of the invention has the structure shown in formula (IVb) and includes a pharmaceutically acceptable salt, solvate, brew, prodrug or isomer of the compound R1 R2V -\

(IV.b.) Ring B is independent of each other wherein R1, R2, R3' R27, r28, p, E, ring VIII and ground are selected, and wherein: heterocyclic ring %A (containing E and the indicated unsaturated () is a member of the cycloalkenyl group or 135177-202-200922559 base ring; E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(〇)2-, -C(R4) (R5)-, -N(R6)-^-N(C(Y)R7)- ^ -N(C(Y)OR8)- . -N(C(Y)N(R9)(R10))- ^ -C(0)-N(R11)-, -N(Rn)-C(0)-, -S(0)2-N(R11)-, -N(R11)-S(0)2- , -C(0)-0-, -OC(O)-, -〇-N(R6)-, -N(R6)-0-, -N(R6)-N(R12)-, -N= N-, -C(R7)=N-, -C(0)-C(R7)=N-, -C(0)-N=N- ' -0-C(Y)-N(R] 1 )- ' -N(R] 1 )-C(Y)-0- ' -N(R! 1 )-C(Y)- N(R12)- ' -CXY)-N(R")-〇- , -C(7)-N(Rn)-N(R12)-, -〇-N(Ru)-C(Y)- and -N(R] 2)-N(Rn )-C(Y)-; ring B Is a substituted or unsubstituted heteroaromatic ring; and ρ, R, R2, R3, R4, R5, R6, R7, R8, R9, R10, R1 1, R1 2, R27, R28, Y and ring The substituents selected on B are as defined in any of the specific examples described in the above formula (I). In one embodiment, Formula (Iv.b) has one of the structures shown in Formula (lvb l)*

R2 (IV.b.1). In one embodiment, the formula (IVb) has one of the structures shown in the formula (IVb 2): 135177 - 203 - 200922559

R3 In a specific embodiment, the formula (IV.b) has the structure shown in the formula (IV.b.3):

f In a specific embodiment, formula (IV.b) has the structure shown in formula (IV.b.4).

R3 (IV.b.4), where p is 0, 1, 2 or 3. In a specific embodiment, the formula (IV.b) has the structure shown in the formula (IV.b.5). 135177 -204- 200922559

R3 (IV.b.5), where p is 0, 1, 2 or 3. In a specific embodiment, the formula (IV.b) has a general structure as shown in the formula (IV.b.6).

(IV.b.6), where p is 0, 1, 2 or 3. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and av.b.6), ring A is a cycloalkenyl ring and E is -C(R4)(R5)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b, 2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), the E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2-, and -N(R6)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2- and -N(R6)-, of which R6 It is selected from the group consisting of hydrazine, alkyl, -C(0)R24 and -C(S)R24. 35177 - 205 - 200922559 In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4) And (IV.b.5) and (IV.b.6), wherein E is selected from the group consisting of -Ο- and -N(R6)-, wherein R6 is selected from the group consisting of ruthenium, alkyl, and -C(0). ) R24 and -C(S)R24. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -Ο-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -S-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -S(O)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -S(0)2-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(R4)(R5)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N(R6)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N(C(Y)R7)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N(C(Y)OR8)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N(C(Y)N(R9)(R10))-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(0)-N(Rn)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), 135177-206-200922559 (IV.b.3), (IV.b.4) , (IV.b.5) and (IV.b.6), E is -NCR11)-C(0)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -S(0)2-N(Ru)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N(Rn)-S(0)2-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(0)-0-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -OC(O)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -0-N(R6)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N(R6)-0-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -NCF^-NCR1 2)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N=N-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(R7)=N-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(0)-C(R7)=N-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(0)-N=N-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), 135177-207-200922559 (IV.b.3), (IV.b.4) , (IV.b.5) and (IV.b.6), E is -O-CXY^NCR11)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -Ν(Ι^ 1 )-C(Y)-0-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -N^11 yQD-NCR1 2)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(Y)-N(RU )-0-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -C(Y)-N(Rn)-N(R12)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -O-NCR11)-C(Y)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), E is -NXR1 2 )-Ν(Ι^ 1 )-C(Y)-. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Y is (=0). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Y is (=S). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b_6), Y is (=Ν(Ι^ 3)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Y is (=N(CN)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Y is (=Ν(0ί^ 4)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), 135177-208*200922559 (IV.b.3), (iv.b.4) In (IV.b.5) and (IV.b.6), Y is (=N(R! 5 )(R) 6)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (iv.b.4), (IV.b) In .5) and (IV.b.6), Y is (=C(R17)(R18)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (iv.b.4), (IV.b) In .5) and (IV.b.6), B is an unsubstituted heteroaromatic ring. In some embodiments, 'in each formula (IV.b), (IV.bl), (IV.b.2), , (IV.b.3) ' (p/.b.4), (IV In .b.5) and (IV.b.6), B is an unsubstituted 5-6-membered heteroaromatic ring' having 1 to 3 ring heteroatoms which may be the same or different, each heteroatomic atomic system being independent It is selected from the group consisting of N, S, 〇, S(O) and S(0)2. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (iv.b.4), (IV_b.5) And (IV.b.6) 'B is a heteroaromatic ring substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N 〇2, alkyl, heteroalkyl 'haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, hetero(aryl-alkyl_ , cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido '-OR19, -〇C(0)OR20, -NR21R22, _NR2 3S〇2R24, -NR23C(0)OR2〇. -NR23C(0)R24 . -S02NR25R2 6 , .C(〇)R2 4 -C(0)0R2 〇, -SRl 9, _S(〇)Rl 9, _S〇2 r1 9, 〇〇C(〇)r2 4. c(〇)nr2 5 r2 6 , —NR 2 3 C(N-CN)NR 2 5 R 2 6 and —NR 2 3 C(0)NR 2 5 R 2 6 . In some embodiments, in each formula (IV. b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b.5) and (IV.b.6), B is a 5-6-membered heteroaromatic ring having 1-3 ring heteroatoms which may be the same or different, and each hetero atom atom is independently selected from the group consisting of N, S, Ο, S(O) and S(O). 2, the heteroaromatic ring system is - or more than 135177 -209 - 200922559 may be substituted by the same or different substituents 'each substituent is independently selected from the group consisting of halogen, -CN, -Ν〇2, alkyl, Miscellaneous, haloalkyl, dilute, haloalkenyl, alkynyl, haloalkynylaryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl , heterocycloalkyl, heterocycloalkenyl, azide, -OR19, -0C(0)0R2, -NR2 1R2 2, -NR2 3S〇2R24, nr23c(〇)〇r2〇, -NR23C(〇 ) R2 4, _s〇2NR25r26, _c(〇)r24, c(〇)〇r2(), JR", -S(0)R〗 9, _S〇2Rl9, -〇C(〇)R2 4, _c( 〇)Nr25r26, _nr23c(n cn)-r

NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, 'in the various formulas (m), (ιν.κι, GVb2), (IV.b.3), (IV.b.4), (IV.b.5), and (IV. In b.6), B is an unsubstituted 6-membered heteroaromatic ring having 1-3 ring heteroatoms which may be the same or different, and each hetero atom atom is independently selected from the group consisting of N, S and oxime. In some embodiments, in the various formulae (IV.b), (Iv.bl), (IVb.2), (exciting .3), _.4), (IV.b.5), and (6) Wherein B is a 6-membered heteroaromatic ring having 1-3 ring heteroatoms which may be the same or different, each hetero atom atom is independently selected from the group consisting of N, S and fluorene, and the heteroaromatic ring system is Or a plurality of substituents may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of a functional element, _CN, -N02, a decyl group, a heteroalkyl group, a dentate group, a dilute group, a functional group, a block group, Halo, aryl, heteroaryl, aryl-alkyl, heteroaryl-fluorenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, 〇 R19, ^_r2〇, -NR21R22 > -NR23S〇2R2 4 , _NR2 3C(〇)〇R2 0 λ _NR2 3C(〇)r24 , -S〇2NW6, —C(Q)R24, .C_R2Q, view 19,柳)r", SO#, -0C(0)R2 4, -C(0)NR2 5 R2 6 , _nr2 3 C(N c_r2 5 R2 6 kiln. nr25r26 〇135177 -210- 200922559 in some embodiments In the various formulas (IV.b), (IV.bl), (iv.b.2), (IV.b.3), (IV.b.4), (IV.b.5) and In IV.b.6), B is an unsubstituted 6 heteroaromatic ring. Having two ring heteroatoms, each ring heteroatom is independently selected from the group consisting of N, s and oxime. In some embodiments, in the various formulae (IV.b), (iv.bl), (iv.b.2) , (IV.b.3), (IV.b.4), (IV.b.5), and (IVb.6), the heterocyclic ring of the ^ member has two ring heteroatoms. The atomic system is independently selected from the group consisting of N, s and hydrazine, and the heterocyclic, aromatic ring system is substituted by one or more substituents which may be the same or different, and each substituent is independently selected from the group consisting of _, _CN, _ Ν〇 2 Alkyl, heteroalkyl, alkenyl, -OR1 9, _NR2 ] R22 ' _c(〇)r24, c(〇)〇r2〇, _SR1 9, o-failure 9, -S02 Rl 9, ·〇(:( 〇) Κ 2 4 and _c(〇) nr2 5 r2 6. In some embodiments, in the various formulae (IV.b), (IVb l), (IV b 2), (IV.b.3) , (IV.b.4), (IV.b.5), and (IVb6) where 'B is an unsubstituted &an heterocyclic ring' having L2 ring heteroatoms which may be the same or different, each The hetero atomic atoms are independently selected from the group consisting of N, S and 〇. In some embodiments, in the formulae (IV_b), (IVb.l), (lVb.2), (IV.b.3), _ .4), _.5) and ((4)6), B is a 5-member heterosexual The ring has 1-2 ring heteroatoms which may be the same or different, each hetero atom is independently selected from the group consisting of N, S and ◦', the heteroaromatic ring system is - or a plurality of substituents which may be the same or different Substituting 'each substituent is independently selected from the group consisting of halogen '-CN, N〇2, alkyl, heteroalkyl, alkyl, alkenyl, dentate, fast radical, texyl, aryl, heteroaryl, Aryl-alkyl-, heteroaryl-alkyl-, cycloalkyl, % alkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _0R] 9, _OC_R20, -NR2 1R22, _NR23SQ2R24, _nr23(10) 〇R2G, _NR23c(〇)R24, 135177-211 · 200922559 -S02NR25R2 6. _C(〇)R2 4, _c(〇)〇r20, _SRl9, s(〇)r19, called r19, -0C(0)R24, _C(0)NR2 5R2 6, _nr23c(n_cn)nr25r26&_nr23c(〇) nr25r26 In some embodiments, 'in each formula (iv.b), (iv.bD, (IVb2), (iv_b.3) , (IV_b.4), (IV.b.5), and (IV.b.6), B is an unsubstituted 5-membered heteroaromatic ring having one ring selected from N, S, and O. Hetero atom.

In some embodiments, in the various formulae (IV.b), (IVb l), (iv.b knives, (IV.b.3), (IV.b.4), (IV.b.5) And (IV.b.6), having a 5-membered heteroaromatic ring having one ring hetero atom selected from N, S and fluorene, the heteroaromatic ring system being a < or = Substituted by the same or different substituents, each substituent is independently selected from the group consisting of halogen, -CN, -N02, alkyl, heteroalkyl, haloalkyl, 〇R1, _nr21r2 di-C(〇)R2 4, _C(〇)〇r2G, _sr19, _s(〇)r19, s〇2R19 〇c(〇)r24 and -C(0)NR25r2 6. In some embodiments, 'in various formulas (Ivb), (lvb υ , (Iv.b2), _3), (IV.b.4), (Iv.b.5), and (Iv.b6), ^5_membered heteroaromatic ring, having S as a ring heteroatom The heteroaromatic ring system is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of _, -, -N02, alkyl, heteroalkyl, haloalkyl ' _ 〇 Rl 9, _nr2 i r22, seven (9) r24, -C(O) 〇 R2 0, _SR19, _s(〇)r19, s〇2Rl9 -C(0)NR25R2 6. -〇C(〇)R2 4 and some specific In the examples, 纟. (rv.b), (iv.bD, (IVb2) , _·3), (Excitation 4), (Iv.b.5), and (IVb6), the unsubstituted 5-membered heteroaromatic ring 'has S as a ring hetero atom. In some embodiments t 'In the various formulas (Ivb), (lvb l), (lvb2), 135177-212- 200922559 (IV.b.3), (IV.b.4), (IV.b.5) and (IV.b) .6), B is selected from the group consisting of

In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is an unsubstituted aryl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is an unsubstituted phenyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is an unsubstituted thiol group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R] is a substituted aryl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV_b.3), (IV.b.4), (IV.b.5) And (IV.b.6), R1 is a substituted phenyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is a substituted phenyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is an aryl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N02, alkane , heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl, cycloalkyl, ring Alkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -0C(0)0R2. , -NR21R22, -NR23S02R24, -NR23C(0)OR20, -NR23C(0)R24, -S02NR25R26, -C(0)R24, -C(0)OR20, -SR19, -S(0)Ri9, -S02R19 -0C(0)R24, -C(0)NR25R26, -NR23C(N-CN)-135177-213- 200922559 NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, 'in each of formulas (IV.b), (iv.bl:), (IV.b.2), (IV.b.3), (IV.b.4), (IV. In b.5) and (IV.b.6), Ri is a phenyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N〇 2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, yl, heteroaryl, aryl-homo-based, heteroaryl-alkyl, ring Alkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, -OR19, -OC(0)OR20, -NR21R22, -NR2 3S02R2 4, _NR2 3C(〇)〇r20,

-NR23C(0)R24, -S02NR25R26, _C(0)R2 4, c(〇)〇r20, SRl9, -S(0)R1 9 ' -S02R19 ' -0C(0)R24 ' -C(0)NR25r2 6 - -NR2 3 C(N-CN)- NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the various formulae (IV.b), (IV.b.}, (Ivb.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Ri is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, -OH, -CN, - N02, -NR21R22 and haloalkyl.

In some embodiments, 'in each of formulas (IV.b), (jv.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is selected from the group consisting of:

In some embodiments, in the various formulae (IV.b), (iv.bl), (IV.b.2), (IV.b_3), (IV.b.4), (IV.b.5) And (IV.b.6), R1 is: 135177 -214- 200922559

In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is a phenyl group substituted by one to three fluorine groups. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is substituted by two fluoro groups (phenyl. In some embodiments, in each of formulas (IV.b), (IV.bl), (IV) In .b.2), (IV.b.3), (IV.b.4), (IV.b.5) and (rV.b.6), R1 is a phenyl group substituted by a fluorine group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R1 is:

In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R27 and R28 are each independently selected from the group consisting of H and alkyl. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(Z)R7. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(Z)NR9R10. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), 135177-215-200922559 (IV.b.3), (IV.b.4) In (IV.b.5) and (IV.b.6), R2 is -C(Z)OR8. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -S02 NR9 R10. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is an alkyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is a miscible group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is an aryl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is a heteroaryl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is a cycloalkyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b_4), (IV.b.5) And (IV.b.6), R2 is a cycloaliphatic group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is a heterocyclic group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is a heterocycloalkenyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Z is (=0). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Z is (=S). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), 135177-216-200922559 (IV.b.3), (IV.b.4) In (IV.b.5) and (IV.b.6), Z is (=N(R13)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Z is (=N(CN)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Z is (=Ν(ΟΙ^ 4)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Z is (=N(R)5 XR16)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), Z is hCXR17)(R]8)). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(Z)R7, and Z is (=0). In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)H. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(O)alkyl. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)CH3. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is an alkyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected Including keto, halogen, -CN, -N02, alkyl, heteroalkyl, haloalkyl, dilute, halo, fast, halo, aryl, heteroaryl, cycloalkyl, ring Alkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -0C(0)0R2G, -nr21r22, -nr23so2r24, -nr23c(o)or20, 135177 -217- 200922559 -NR23C(0) R24, -S02NR25R26, -C(0)R24, -C(0)OR20, -SR19, -S(0)R19, -S02R19, -0C(0)R24, -C(0)NR25R26, -NR23C(N -CN)-NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (rV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is an alkyl group substituted by one to three substituents which may be the same or different, each substituent being independently selected from Including -OR19, -NR21R22 and cycloalkyl. In some embodiments, in the various formulae (IV.b), (IV.bl) ' (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is alkyl, wherein the alkyl group is substituted with an alkyl group and -OH. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is an alkyl group substituted by one to three substituents which may be the same or different, each substituent being independently selected from Including -OH, -NH2 and cyclopropyl. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is an alkyl group substituted by one to two substituents which may be the same or different, each substituent being independently selected from Includes -NH2 and cyclopropyl. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is an alkyl group substituted by -OH. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is an unsubstituted heterocycloalkyl group. 135177 - 218- 200922559 In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4) And (IV.b.5) and (IV.b.6), R2 is -C(0)R7, wherein the R7 is a substituted heterocycloalkyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein R7 is a heterocycloalkyl group substituted by one or more substituents which may be the same or different, each substituent Independently selected from the group consisting of keto, halogen, -CN, -N02, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl , cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -OC(0)OR20, -NR21R22, -NR23S02R24, -NR23C(0)OR20, -NR23C(0)R24 ' - S02NR25R26 ' -C(0)R24 ' -C(0)0R2° ' -SR19 ' -S(0)R19, -S02R19, -0C(0)R24, -C(0)NR25R26, -NR23C(N-CN )-NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)R7, wherein the R7 is selected from the group consisting of substituted hexahydropyridine, substituted hexahydropyridinium, substituted phloem, The substituted tetrahydro-p isomer and the substituted one of the nitrogen tetraindoles. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b_6), R2 is selected from:

In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)NR9R10. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), 135177-219-200922559 (IV.b.3), (IV.b.4) In (IV.b.5) and (IV.b.6), R2 is -C(0)NH2. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)NR9R10, wherein R9 and R1G may be the same or different and each independently selected from an alkyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)NR9R10, wherein R9 is an unsubstituted heterocycloalkyl group, and R1G is selected from the group consisting of H and an alkyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)NR9R1(), wherein R9 is a substituted heterocycloalkyl group, and R1 G is selected from the group consisting of H and an alkyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is -C(0)NR9R10, wherein R9 is a heterocycloalkyl group substituted by one to three substituents which may be the same or different, each substituent being independently selected From the alkyl group, and R1 Q is selected from the group consisting of ruthenium and alkyl. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is selected from the group consisting of alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, -C(0)R7, -C(0)0R8 and - C(0)NR9 R10. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is selected from the group consisting of

135177 - 220 - 200922559

In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2) Λ (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R2 is cf3. In some embodiments, in each of formulas (IV.b), (IV.bl), (IV.b.2)

(IV.b.3), (IV.b.4), (IV.b.5) and (IV.b.6), R2 is in some embodiments, in each formula (IV.b) , (IV.bl), (IV.b.2), 135177 -221 - 200922559 (IV.b.3), (IV.b.4), (IV.b.5) and (IV.b.6) Wherein R2 is in some embodiments, in each formula (IV.b) ο

(IV.bl), (IV.b.2) Ο , ΟΗ (IV.b.3), (IV.b.4), (IV.b.5) and (IV.b.6), In some embodiments, in each of the formulas (IV.b) (IV.b.3), (IV.b.4), (IV.b.5), and (IV.b.6), in some specific embodiments In the examples, in the various formulas (IV.b) (IV, b.3), (IV, b.4), (IV.b.5) and (IV.b.6), in some specific embodiments In the formulas (IV.b), (IV.b.3), (IV.b.4), (IV.b.5) and (IV.b.6), R2 is (IV.bl) ) ' (IV.b.2) ΟΊο, (IV.bl) ' (IV.b.2) Ο NH2. (IV.b.l) > (IV.b.2) In some embodiments, in the various formulae (IV.b), (IV.b.l), (IV.b.2)

In N—(IV.b.3), (IV.b.4), (IV.b.5) and (IV,b.6), R2 is

In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2) (IV.b.3), (IV.b.4), (IV.b. 5) and (IV.b.6), p is 0, and R3 is not present in some specific examples, in each of formulas (IV.b), (IV.bl), (IV.b.2) , (IV.b.3), (IV.b.4), (IV.b.5), and (IV.b.6), p is 1. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), p is 2. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), p is 3. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), 135177-222-200922559 (IV.b.3), (IV.b.4) , (IV.b.5) and (IV.b.6), p is 4. In some embodiments, 'in the various formulae (IV.b), (jv.bl), (IV.b.3), (IV.b.4), (IV.b.5), and (IV. In b.6), p is g 2 and at least two groups R 3 are attached to the same ring atom. In some embodiments, 'in each formula (iv.b), (ιν.κυ, (IVb 2), (IV.b.3), (IV.b.4), (IV.b.5) and (IV.b.6), p is [, and R3 is independently selected from the group consisting of an alkyl group, a heteroalkyl group, a dilute group, a heterocyclo group, a block group, a heteroalkynyl group, an aryl group, a heteroaryl group, and a ring. Alkyl, cycloalkenyl, heterocycloalkyl, heterocyclic, dentate, -CN, -N02, -OR19, -OC(0)OR20, -NR21R22, _NR2 3S〇2R2 4, -nr23c(o) Or20, -NR23C(0)R24, -S02NR25R2 6, _c(〇)R2 4, -C(0)0R2 0, -SR1 9, -S^R1 9, -S02 R19, -0C(0)R2 4, _C(0)NR2 5 r2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, 'in each formula (IV.b) , (iv.bl), (iv.b.2), (IV.b.3), av.b.4), (IV.b.5) and (IV.b.6), p is 2 , 3 or 4, and each of 113 is independently selected from the group consisting of an alkyl group, a hetero (yl, alkenyl, hetero, alkynyl, hetero alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl group). ,heterocycloalkyl,heterocyclenyl,halogen, -CN, -N02, _〇R19, -〇C(0)OR2〇, _NR21R22, -NR23S02R24, -NR23C(0)0R2Q, -NR23C(0)R24 , -S02 NR25R26, -C(0)R24, -C(0)OR20, -SR19, -S(0)R19, -S02R19, _〇c(〇)R2 4, -C(0)NR25R26, -NR23C(N- CN) NR25R26A-NR23C(0)NR25R26. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV) In .b.4), (IV.b.5) and (IV.b.6), p is 2, 3 or 4, and at least two groups R3 are bonded to the same ring carbon atom, wherein each r3 , which may be the same or different ', independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, 135177 - 223 - 200922559 alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, Cycloalkenyl, heterocycloalkyl, heterocyclic, halogen, -CN, -N02, -ORl 9, _〇c(〇)QR2 〇, -NR2, R2 2 , -nr23so2r24 ' -NR23C(0)〇 R2〇. -NR23C(0)R2 4 λ -S02NR2 5R2 6. _c(〇)r24, _c(〇)〇r20, _sr19, s(〇)r19, _s〇2R19, -0C(0)R2 4, _c (〇) nr2 5 r2 6 , nr2 3 C(N cn)nr2 5 r2 6 and _nr2 3 c(〇) NR25R26. In some embodiments, 'in each of formulas (IV.b), (iv.bl), (IV.b.2), plant (ivb.3), (m.4), (IVb.5), and In Chinese b.6), p is 2, 3 or 4, and at least two groups R are bonded to the same ring carbon atom, wherein two R3 groups, which may be the same or different, are linked to each other The carbon atoms together form a cycloalkyl, cycloalkenyl, heterocycloalkyl ring containing one to three heteroatoms selected from N, 0 and S, or a heterocycloalkenyl ring containing from one to three selected from the group consisting of N , 〇 and S heteroatoms. In a specific embodiment, in the formula (lvb), 卩 is ^ 2, 3 or 4, and each R 3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, _CN, ( N02, -0R19, _〇C(〇)〇r20, nr21r22, nr23s〇2R24, -NR2 3C(〇)〇R2 0, _nr23c(〇)r24, s〇2nr25r26, c(〇)r24, -S02R19,- 〇C(〇)R24, -nr23c(o)nr25r26 and -C(5)R24, -C(O)〇R20, _SRl9, _s(〇)Rl9, -C(0)NR25R26, -NR23C(N-CN)NR25R2 6, -NR23-C(NH)-NR26R26, wherein each of the & base, oxime & base, each of the alkenyl group and each of the heterogeneous groups is unsubstituted or, as the case may be, independently one or more Substituting the same or different substituents' each substituent is independently selected from the group consisting of a keto group, a lignin,

Halogen group, fine base, dentate base, 135177 •224- 200922559 alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide Base ' _0Rl9, _〇c(〇)〇R20, _NR2 1R2 2, _NR2 3S〇2r2 4, nr23c(〇)〇r2〇, nr23c(〇)r24, -S02NR25R26, -C(0)R24, -C( 0) 〇R20, -SR19, -S(〇)R19, -S02R19 ' -0C(0)R24 ' -C(〇)NR25R26 > -NR2 3 C(N-CN)NR2 5 R2 6 and -nr23c( o) Group of nr25r26. In a specific embodiment, in the formula (IV.b), P is 1, and R3 is selected from the group consisting of alkyl, heteroalkyl, alkenyl and heteroalkenyl groups, wherein each of the alkyl groups The alkyl group, each of the alkenyl groups and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group and a dentate , -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, i-alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, hetero Cycloalkyl, heterocyclic, azide, 〇Rl9, -〇c(〇)〇r20, _NR2]R22, -NR2 3S02R24, _NR2 3C(〇)〇R2 0, nr23c(〇)r24, - So2nr25r26, -C(0)R2 4, _C(〇)〇R2 0, _SR]9, s(〇)Rl9, -S02R19, -〇C(〇)R24, _C(〇)NR2 5R2 6, _nr2 3c( A group of N cn)nr25r2 6 and -nr2 3 C(0)NR2 5 R2 6 . In the specific example, in the formula (IV.b), p is 2, 3 or 4, and is employed together with any two R3 groups bonded to the same ring A atom to form -C(0). )_ group. In a particular embodiment, in formula (IV, b), p is 2 2 and is employed together with any two R 3 groups bonded to the same ring A atom to form a spiro-heteroalkyl group, having } to 3 independently selected from ring heteroatoms including _NH_, _nr6_, 〇, S, 135177 • 225 - 200922559 S(O) and S(0)2, or spiroheterocycloalkenyl, having 1 to 3 independent It is selected from ring heteroatoms including -NH-, -NR6-, hydrazine, S, S(O) and S(0)2. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a burnt group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a miscible group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a dilute base. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a miscellaneous base. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a fast radical. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a heteroalkynyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is an aryl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a heteroaryl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a cycloalkyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a cyclodecyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a heterocycloalkyl group. 135177 - 226 - 200922559 In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4) And (IV.b.5) and (IV.b.6), R3 is a heterocycloalkenyl group. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is a halogen. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -CN. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -N02. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -OR1 9. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -OC(0)OR20. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3) ' (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -NR21 R2 2. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -NR2 3 S02R2 4. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -NR2 3 C(0)OR20. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -NR2 3 C(0)R2 4 . In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -S02 NR2 5 R2 6. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -C(0)R2 4. 135177 - 227 - 200922559 In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4) In (IV.b.5) and (IV.b.6), R3 is -C(0)OR20. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV, b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -SR1 9. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV_b.3), (IV.b.4), (IV.b.5) And aV.b.6), R3 is -S(0)R] 9. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -SC^R19. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -0C(0)R2 4. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is -C(0)NR2 5 R2 6. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), R3 is, 1123 (: (the team is called -NR25R26. In some embodiments, in the various formulas (IV.b), (IV.bl), (IV) In .b.2), (IV.b.3), (IV.b.4), (IV.b.5) and (IV.b.6), R3 is -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), In IV.b.5) and (IV.b.6), R3 is selected from the group consisting of fluorenyl, ethyl, propyl (straight or branched), butyl (straight or branched), Pentyl (straight S^\ chain or branched), phenyl Η νη2, Η2Ν, Η2Ν 135177 '228· 200922559

In some embodiments, in the various formulae (IV.b), (IV.bl), (IV.b.2), (IV.b.3), (IV.b.4), (IV.b) In .5) and (IV.b.6), when E is -NR6-, R3 does not exist. In a particular embodiment, the compound of the invention has the structure shown in formula (V.a) and includes a pharmaceutically acceptable salt, solvate, ester, prodrug or isomer of the compound:

Wherein R1, R2, R3, R27, R28, p, E, ring A and ring B are independently selected from each other, and wherein: ring A (containing E and the unsaturation shown) is 7- to 8-member Cycloalkenyl or heterocycloalkenyl 135177 - 229 - 200922559 base ring; E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2-, -C(R4) (R5) )-, -N(R6)-, -N(C(Y)R7)- '-N(C(Y)OR8)- '-N(C(Y)N(R9)(R10))- ' - C(0)-N(Rn )- ' -N(Rn)-C(0)-, -S(0)2-N(R")-, -N(Rn)-S(0)2-, -C(O)-0-, -OC(O)-, -0-N(R6)-, -N(R6)-〇-, -N(R6)-N(R12)-, -N=N -, -C(R7)=N-' -C(0)-C(R7)=N- > -C(0)-N=N- ' -0-C(Y)-N(R11)- ' -NCR11 )-C(Y)-〇- > -ΝΟΙ^-α^-Ν^12)-, -C(Y)-N(Rn)-0-, -C(Y)-N(Rn )-N(R12)-, -〇-N(Ri1)-C(Y)- and -N(R] 2)-N(Rn )-C(Y)-; Ring B is substituted or unsubstituted An aromatic ring; and the selected substituents on P, Ri, R2, R3, R4, R5, R6, R7, R8, R9, R10, 1, R1 2, R27, R28, Y and ring B are as defined above The definitions in the specific embodiments described in (i). In a specific embodiment, the formula (V.a) has the general structure shown in the formula (V.a.l).

(V.a.1). In a specific embodiment, the formula (V.a) has the general structure shown in the formula (V, a. 2). 135177 - 230 - 200922559

(V.a.2). In a specific embodiment, formula (V.a) has the general structure shown in formula (V.a.3):

R' 〆 (V.a.3), where p is 0, 1, 2 or 3. In a specific embodiment, formula (V.a) has the general structure shown in formula (V.a.4):

FT (V.a.4), where p is 0, 1, 2 or 3. In a specific embodiment, the formula (V.a) has the general structure shown in the formula (V.a.5): 135177 -231 - 200922559

(V.a.5) ' where p is 〇, u or 3. In one embodiment, the formula (V.a) has the general structure shown in formula (V.a.6):

(V.a.6) ' where p is 〇, i, 2 or 3. In some embodiments, 'in a variety of (Va), (VU), (Va 2), (Va 3), [(Va.4), (Va.5), and (Va.6) 'ring a Is a cycloalkenyl ring, and e is -C(R4)(R5)-. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va.3), (Va4), (Va5), and (Va6), the ring A is hetero a cycloalkenyl ring, and the E is selected from the group consisting of -Ο-, -S-, -S(O)-, -S(0)2-, and _n(R6)-. In some embodiments, in each of the formulas (Va), (Va l), (va 2), (Va.3), (Va4), (V_a_5), and (Va6), the 'E system is selected from the group consisting of _〇_, _s_, _s(〇)_, _s(〇)2_ and -N(R6)- 'wherein R6 is selected from the group consisting of H, alkyl, 匸(〇) 尺 24 and _C(5)R24. In some embodiments, in the formulas (Va), (Va l), (va 2), (va3), • 232- 135177 200922559 (Va4), (Va5), and (Va6) The E is selected from the group consisting of _〇_ and _n(r6)_, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(〇)R24&_c(5)R24. In some embodiments, 'in each of (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), E is -〇- . In some embodiments, 'in each of the formulas (Va)' (val), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -S- 〇 In some embodiments, 'in each of (Va), (Va l), (Va.2), (Va.3), (V, a.4), (Va5), and (Va6), E is -S(〇)-. In some embodiments, in each of the formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -S (〇 )2-. In some embodiments, 'in each of (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -C (R4) )(R5)-. In some embodiments, in each of the formulas (Va), (ViD, (Va2), (Va3), (Va4), (Va5), and (Va6), E is -N(R6) In some embodiments, 'in each of (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -N (C(7)R7)-. In some embodiments, in each of the formulae (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), E Is -N(C(Y)OR8)-. In some embodiments, in the formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), In (Va6), E is -N(C(Y)N(R9 XR1 0))-. In some embodiments, 'in each formula (Va), (Val), (Va2), (Va3) In (Va4), (Va5), and (Va6), E is -C(0)-N(Rn)-. In some embodiments, 'in each formula (Va), (Val), In (Va2), (Va3), (V_a.4), (Va5), and (Va6), E is -NCR11)-C(0)-. 135177 - 233 - 200922559 In some embodiments, in the formulae (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), E Is -S(0)2-N(Rn)-. In some embodiments, 'E is -Ν in each of the equations (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6) Ι^ 1 )-S(0)2-. In some embodiments, 'E is -C(0) in each of the equations (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6). )-0-. In some embodiments, 'E is -〇-C in each of the formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6) (0)-. In some embodiments, 'in each of (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -〇 -N(R6)-. In some embodiments, 'in each of (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -N ( R6)-〇-. In some embodiments, 'in each of (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -N (R6) )-N(R]2)-. In some embodiments, 'in each of formulas (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -N. =N-. i In some embodiments 'in each of formulas (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -C (R7) = N-. In some embodiments, 'E is -C in each of (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6). 0) -C(R7)=N-. In some embodiments, 'in each of (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -C(0) ) -N=N-. In some embodiments, 'in each of (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), E is -O- CWNCR11)-. • 234- 135177 200922559 In some embodiments 'in the various formulas (Va), (Va l), (Va.2), (va 3), (Va4), (Va5) and (Va, 6) Medium, £ is _N(Ri 1 )_c(y)_〇_. In some embodiments, in the formulas (Va), (Va l), (va2), (Va 3), (Va4), (Va5), and (Va6), e is -NCR11) -C(7)-Is^R1 2)-. In some embodiments, 'e is -C(7)- in each of the equations (Va), (Va1), (Va 2), (va3), (Va4), (Va5), and (Va6). N(R)1)-0-. In some embodiments, 'in each of formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), e is -C(7) -N(R] 1 )-N(Ri2 ). In some embodiments, 'in each of formulas (Va), (VaU, (Va, 2), (va3), (Va4), (Va5), and (Va6), e is -O-NfR11 )-C(Y)-. In some embodiments, 'E is -N(Ri) in each of the equations (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6) 2 yNCR11 )-C(Y)-. In some embodiments, in each of the formulas (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), γ is (=〇 ). In some embodiments, 'in each of (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), Y is (=s) . In some embodiments, in each of the equations (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), Y is (=n( R13)). In some embodiments, 'in each of (Va), (Va 1), (Va2), (Va3), (Va4) ' (Va5), and (Va6), Y is (=n (CN)). In some embodiments, 'in each of (Va), (Val), (Va2), (Va3), (V, a_4), (Va5), and (Va6), Y is (=n) (〇R14)). In some embodiments, in each of the formulas (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), Y is (the second wind) Rule 15) (1116)). 135177 • 235 - 200922559 In some embodiments, 'Y is in each of the equations (Va), (Val), (Va2), (Va 3), (Va4), (Va5), and (Va6) . In some specific examples, 'B is unsubstituted in each of the formulas (Va), (Val), (va2), (Va3), (Va4), (Va5), and (Va6). The aromatic ring. In some specific examples, in the various formulas (Va), (Val), (va2), (va3), (Va4), (Va5), and (Va6), B is unsubstituted. Stupid and ring, and formula (IVa.) has the following general structure:

In some specific examples, in the various formulas (Va), (val), (Va2), (Va3), (V_a.4), (Va5), and (Va6), B is aromatic. a ring which is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen (., -CN, _N〇2, alkyl, miscible, halogen, Dilute, halogeno, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero Cycloalkenyl, azide, 〇Rl 9, -OC(0)OR20, _NR2]R22, _NR2 3S〇2R24, nr23c(〇)〇r20, -NR23C(0)R24, -S02NR25R2 6, _c(〇 )r24, _c(〇)〇r2(), _sr19, -S(0)R19 ' -S02R19 ' -0C(0)R24 ^ -C(〇)NR2 5R2 6 n -NR2 3 C(N-CN)- Nr25r26&-nr23c(o)nr25r26. In some embodiments, in the formulas (va), (Va l), (v.a2), (va3), (Va4), (Va5), and (Va) In 6), B is a stupid ring which is substituted by the same or different substituents by one or 135177 -236-200922559, and each substituent is independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, Heteroalkyl, Haloalkyl, fluorenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl group, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocyclic Alkyl, heterocycloalkenyl, azide, 〇Ri 9, -OC(0)OR20, -NR21R22, _NR2 3s〇2R24, _nr23c(〇)〇r20, -nr23c(o)r24, -S02NR25R2 6, _c(0)r24, _c(〇)〇r20, SRl9, -S(0)R19, -S02R丨9, -〇C(〇)R24, _C(〇)NR2 5R2 6, _NR2 3C(N_CN)_ NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 0 In some embodiments, in the formulas (va), (vd), (va 2), (Va 3), (Va4), In Va5) and (Va6), R is an unsubstituted aryl group. In some embodiments, in the formulae (Va), (Va l), (Va. 2), (va 3), In (Va4), (Va5) and (Va6), R1 is an unsubstituted phenyl group. In some embodiments, in the formulae (Va), (va l), (Va 2), In Va 3), (Va4), (Va5) and (Va6), Ri is an unsubstituted fluorenyl group. In some embodiments, in each of the formulas (Va), (Va!), (Va 2), (Va 3), (Va4), (Va5), and (Va6), R1 is substituted. Aryl. In some embodiments, ' Ri is a substituted benzene in each of the formulae (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6) base. In some embodiments, in each of the formulas (Va), (VU), (Va 2), (Va. 3), (V'a.4), (Va5), and (Va6), Ri is Substituted thiol. In some embodiments, among the various formulas (Va), (V.aj), (Va 2), (va3), (Va4), (Va5), and (Va6), One or more aryl groups which may be substituted with the same or different substituents are each independently selected from the group consisting of _-, -CN, -N 〇 2, alkyl, heteroalkyl, haloalkyl, alkenyl, Haloalkenyl, alkynyl, 135177 > 237 . 200922559 Haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl ,heterocyclenyl, azide, _〇Rl9, -OC(0)OR20 '-NR21R22 '-NR23S02R24 > -NR2 3 C(0)0R2 0 > -NR2 3 C(0)R2 4,- S〇2 NR2 5 R2 6, _c(0)R2 4, -C(〇)〇r2 o, _sr1 9, -S(0)R1 9 ' -S02R19 ' -0C(0)R24 s -C(0) NR25R26 n -NR2 3 C(N-CN)- NR2 5 R2 6 and _NR2 3 C(0)NR2 5 R2 6. In some embodiments, in each of the formulas (Va), (Val), (va2), (Va3), (Va4), (Va5), and (Va6), R1 is one or more The phenyl' substituents which may be substituted with the same or different substituents are independently selected from the group consisting of dentate, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl , alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide ,_0R19, -OC(0)OR20, -NR2] R22, -NR23s〇2R24, nr23c(〇)〇r20, _NR23C(0)R24, -S02NR25R2 6, _c(0)r24, C(〇)〇R20, Sr19, -S(0)R19, -S〇2rB, -0C(0)R2 4, _c(〇)nr25r26, nr23c(n cn) NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 . In some specific examples, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), Ri is one to four. The phenyl group may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of halo, -OH, -CN, -N02, -NR21R22, and a halogen group. In some specific embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), Ri is selected from the group consisting of Includes: 135177 '238- 200922559

In some embodiments, 'in each of formulas (v.a), (V.a.l), (V.a.2), (V.a.3), (V.a.4), (V.a.5), and (V.a.6), R] is:

f In some embodiments 'in the various equations (Va), (Val), (Va2), (Va3), (Va4), (Va5) and (Va6) 'Ri is one to three a fluoro group substituted phenyl group. In some embodiments, 'in each of (Va), (Va l), (Va.2), (va3), (Va4), (Va5), and (Va6), ri is two a fluoro group substituted phenyl group. In some embodiments, in each of the formulas (va), (Va l), (va2), (va 3), (Va4), (Va5), and (Va6), R1 is a fluorine. Substituted phenyl. κ

In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), Ri is . In specific embodiments, in each of the formulas (Va), (va2), (v.a_3), (Va4), (Va5), and (Va6), R27 and R28 are each independently selected from the group consisting of H. With the base. In the case of t yubei & in various equations (10), 135177 - 239. 200922559 (Va4), (Va5) and (Va6) in some embodiments (Va4), (Va 5) and (Va6) are in some embodiments (Va4), (Va5) and (Va6) in some embodiments (Va4), (Va5) and (Va6) In some embodiments f (Va4), (Va-5), and (Va6) are in some embodiments (Va4), (Va5), and (Va6) in some embodiments. Medium (Va4), (Va5) and (Va6) in some embodiments (Va4), (Va5) and (Va6) in some embodiments #.. (Va4) (Va5) and (Va6) in some embodiments (Va4), (Va5) and (Va6) in some embodiments (Va4), (Va5) and (Va) 6) In some embodiments (Va4), (Va5), and (Va6), in some specific embodiments, 'R2 is -C(Z)R7. In each of the formulas (V.a), (V.a.l), (V.a.2), (V.a.3), and R2 is -C(Z)NR9R10. In the formulas (V.a), (V.a.l), (V.a.2), (V, a.3), and 'R2' is -C(Z)OR8. In each of the formulas (V.a), (V.a.l), (V.a.2), (V.a.3), and R2, it is -S02NR9R10. 1 In each of the formulae (V.a), (V.a.l), (V.a.2), (V.a.3), and R2 is an alkyl group. 1 In each of the formulae (V.a), (V.a.1), (V.a.2), (V.a.3), and R2 are heteroalkyl groups. 1 In each of the formulae (V.a), (V.a.1), (V.a.2), (V.a.3), and R2, it is an aryl group. 'In each formula (V.a), (V.a.1), (V.a.2), (V.a.3), and 'R2 are heteroaryl groups. 1 In each of the formulae (V.a), (V.a.l), (V.a.2), (V.a.3), and 'R2' is a cycloalkyl group. In the formulae (V.a), (V_a.l), (V.a.2), (V.a.3), and R2 are a cycloalkenyl group. In the formulae (V.a), (V.a.l), (V.a.2), (V.a.3), and R2 are heterocycloalkyl groups. In each of the formulae (V.a), (V.a.1), (V.a.2), (V.a.3), and R2 are heterocycloalkenyl groups. 'In each of the equations (Va), (Va 1), (Va2), (Va3), 135177-240-200922559 (Va4), (Va5), and (Va6), z is (=0) . In some specific embodiments, in the equations (Va), (Val), (Va 2), (Va.3), (Va4), (Va5), and (Va6), z is (= S). In some specific embodiments, 'in each of formulas (Va), (Va l), (Va 2), (Va 3), (V.a.4), (V.a.5), and (V.a.6), z is . In some embodiments, in the equations (va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), z is (=n) (cn)). In some specific embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), z is (r) ^OR14)). In some embodiments, in the formulae (Va), (Va l), (Va 2), (Va 3), (V.a.4), (V.a.5), and (V.a.6), z is. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), z is "(R17) XR18)). In some embodiments, in each of the equations (Va), (va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), R2 is _c ( z) r7, and z is (=〇). In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va.3), (Va4), (Va5), and (Va6), R2 is _c. (〇) H. In some embodiments, in each of the formulas (Va), (Va l), (va 2), (va 3), (Va4), (Va5), and (Va6), 圮 is -C ( 〇) alkyl. In some embodiments, in each of the formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), R2 is _c (〇) )ch3. In some embodiments, in each of the equations (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), 'R2 is _c (〇) And r7, wherein the r7 is an alkyl group substituted by one or more substituents which may be the same or different, each substituent being independently 135177-241 · 200922559 selected from the group consisting of a ketone group, a halogen, -CN, -N02, Alkyl, heteroalkyl, haloalkyl, alkenyl, ilalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, Azido group, _〇Ri9, -OC(0)〇R20 '-NR21R22 ' -NR23S02R24 ' -NR23C(0)0R2° ' -NR23C(0)R24, -S02NR25R26, _C(〇)r2 4, _Q〇) 〇R2 0, _SR19, -S(0)R19, -S02R19, -0C(0)R2 4, -C(〇)NR2 5R2 6, _NR2 3C(N_CN)_ NR2 5 R2 6 and -NR2 3 C(0 ) NR2 5 R2 6. In some embodiments, 'in the various equations (Va), (Val), (Va2), (Va3), f (Va4), (Va5), and (Va6), 'R2 is _C ( 0) R7, wherein R7 is an alkyl group substituted by one to three substituents which may be the same or different, each substituent being independently selected from the group consisting of -OR19, -NR21R22 and cycloalkyl. In some embodiments, 'R2 is _c in each of the equations (Va), (Va 1), (Va2), (Va3), (Va4), (va5), and (Va6). R), wherein R7 is an alkyl group, wherein the alkyl group is substituted with a -OH group. In some embodiments, 'in the various equations (Va), (Val), (Va2), (Va3), (.(Va·4), (va5), and (Va,6), 'R2 is _c(〇)R7, wherein R7 is an alkyl group substituted by one or two substituents which may be the same or different, each substituent being independently selected from the group consisting of 〇H, -NH2 and cyclopropyl. In the specific embodiment, 'in each of the formulas (Va), (Val), (Va2), (Va3), (Va, 4), (va5), and (v, a.6), r2 is _c (〇)r7, wherein the r7 is an alkyl group substituted by one to two substituents which may be the same or different, each substituent being independently selected from the group consisting of -NH2 and a cyclopropyl group.

In some embodiments, 'R2' in each of the formulae (Va), (Val), (Va2), (Va3), (V, a.4), (va5), and (va·6) Is -C(0)R7, wherein R7 is an alkyl group substituted by -〇H 135177 -242- 200922559. In some specific embodiments, 'in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), R2 is _c (〇)r7, wherein R7 is an unsubstituted heterocycloalkyl group. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (va3), (Va4), (Va5), and (Va6), R2 is _c ( R), wherein R7 is a substituted heterocycloalkyl. f: In some embodiments, in each of the formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), R2 is _c (〇)r7, wherein the r7 is a heterocycloalkyl group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, a _CN, a _N〇2, an alkyl group ,heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide Base, _〇R19, -〇C(0)〇R2G, -NR21R22, -NR23S02R24, -nr23c(o)or20, -NR23C(〇)R24, -S02NR25R26 ' _c(0)R24, -C(0)OR20 , -SR] 9, -S(〇)R19, -S〇2R19, -0C(0)R24, -C(〇)NR25R26, -NR23C(N-CN)-NR25R26&_NR2 3C(〇)NR2 5R2 6 . In some embodiments, in each of the formulas (Va), (va 1), (Va2), (Va3), (Va4), (Va5), and (Va6), R2 is _c ( 0) R7, wherein the R7 is selected from the group consisting of substituted hexahydropyridine, substituted hexahydropyridinium, substituted morpholine, substituted tetrahydropyrrole, and substituted one nitrogen tetraindole. In some embodiments, 'in each of formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), R2 is selected from the group consisting of: 135177 - 243 - 200922559

〇h3〇ο In some embodiments, in the equations (va), (Va l), (Va2), (Va3), (Va4), (Va5), and (Va6), R2 is _ c (〇) nr9r10. In some embodiments, 'in each of (Va), (Va l), (Va 2), (va 3), (Va4), (Va5), and (Va6), R2 is . ο)·?. In some specific embodiments, in each of the formulas (Va), (Val), (Va2), (Va.3), (Va4) ' (Va5), and (Va6), R2 is _c( 〇)nr9 Rl 0, wherein r9 and Rl 0 may be the same or different, each independently selected from a burnt group. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (va5), and (va6), wherein r9 is not Substituted heterocycloalkyl, and R1 Q is selected from the group consisting of H and alkyl. In these specific λ examples, in the equations (va), (vai), (va2), (va3), (V.a_4), (va5), and (va6), R2 is _c. (〇) nr9r1 0, wherein r 9 is a substituted heterocyclic alkyl group, and R 1 0 is selected from the group consisting of H and an alkyl group. In some embodiments, 'in the various equations (Va), (Val), (Va2), (Va3), (Va4), (va5), and (Va6), 'R2 is ', where R9 is One or two heterocycloalkyl groups which may be substituted by the same or different substituents, each substituent being independently selected from an alkyl group, and R1 G being selected from the group consisting of hydrazine and alkyl. In some embodiments, 'in the various formulas (Va), (ν.α.υ, (Va2), (va3), (Va4), (Va5), and (Va6), the 'R2 system is selected Including: alkyl, haloalkyl, heteroalkyl, heterodentate, -C(0)R7, -C(〇)〇R8 and _c(〇)NR9 R1 0. In some embodiments 'In each of the formulas (Va), (Va 1), (Va2), (Va3), (Va4), (Va5), and (va6), the R2 is selected from the group consisting of 135177-244-200922559

In some embodiments, in the various formulas (V.a), (V.a.l), (V.a.2), (V.a.3),

In CF3 〇(Va4), (Va5) and (Va6), R2 is in some embodiments, in the formulas (va), (Val), (Va2), (Va3), 135177 - 245 - 200922559 ο (Va4), (Va5) and (Va6), R2 is in some specific embodiments, in each:

In the various formulas (V.a), (V.a.l), (V.a.2), (V.a.3),

(V.a.4), (V.a.5) and (V.a.6)

In some embodiments, in the formulae (Va), (Va l), (Va 2), (Va 3), (Vi in some embodiments, in each: , (Va5), and (Va6) Among them, (Va4), (Va5), and (Va6), R2 is

In some specific embodiments, in the various formulas (Va), (V a l), (Va 2), (Va 3),

In (V.a.4), (V.a.5) and (V.a.6), R2 is in some embodiments, in the formulae (Va), (Va l), (Va 2), (v.a 3),

In (V.a.4), (V.a.5) and (V.a.6), R2 is in some embodiments, in the formulae (Va), (Va l), (Va 2), (v.a 3)

In (Va4), (Va5) and (Va6), R2 is in each of the specific examples 'in each of the formulas (Va), (Va l), (Va 2), (Va.3), (Va 4), (Va5) and (Va6), p is 〇, and r3 does not exist. In some embodiments, 'in each of formulas (Va), (Va l), (Va 2), (Va 3), (V.a.4), (V.a.5), and (V.a.6), p is 1. In some embodiments, in each of the formulae (Va), (v.a l), (Va.2), (Va 3), (V.a.4), (V.a.5), and (V.a.6), p is 2. In some embodiments, 'in each of formulas (Va)' (Va l), (Va 2), (Va.3), 135177-246-200922559 (Va4), (Va5), and (Va6) , p is 3. In some embodiments, p is 4 in the formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6) . In some embodiments, in the various formulas (Va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), 0仫, 0 ^, P is g 2 ' and at least two groups r3 are attached to the same ring atom. In some embodiments, in each of (Va), (Va l), (Va 2), (Va.3), f (va4)' (va·5), and (va6), P is And R3 are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, Heterocyclenyl, halogen, _CN, _N02, -OR19, -OC(0)OR20, -NR2]R22, _nr23s〇2r24, _nr23c(^〇r2〇, -NR2 3C(0)R2 4, _S〇2NR25r26, c(〇)r24, _c(〇)〇r20, sRl9, -S(0)R19 > -S02R19 ' -0C(0)R24 , -C(〇)NR25R26 >-NR23C(N-CN> NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the formulae (Va), (H), (va2), (Va 3), ((Va4), ( In Va5) and (Va6), p is 2, 3 or 4, and each R3 is independently selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, a heterocyclic group, a fast group, a heteroalkynyl group, an aryl group, Heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halogen, -CN, -N〇2, -OR19, -0C(0)0R20, -NR21R22, -NR23S02R24, -nr23c (o)or20, -NR23C(0)R24 ' -S02NR25R26, -C(0)R2 4, -C (0) OR20, -SR19, 3(0)111 9, 9, S02R19, -0C(0)R24, -C(0)NR25R2 6, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In some embodiments, in the formulae (Va), (Val), (Va2), 〇/.a.3), (Va4), (Va5) and In (Va6), p is 2, 3 or 4, and at least two groups r3 135177 -247- 200922559 are bonded to the same ring carbon atom 'where each R3, which may be the same or different, is independently selected from Including alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halogen, - CN, -N02, -019, _〇c(〇)〇r2〇, -NR21R22, -NR2 3S〇2R2 4, _nr23c(〇)〇r20, _nr23c(〇)r24, _s〇2Nr25r26, -C(0) R2 4, 0, SRl9, s(〇)Rl9, s〇2Rl 9, _〇C(〇)R2 4, •C(〇)NR2 5 R2 6, NR 2 3 C(n_cn)nr2 5 r2 6 and _nr2 3 c(〇)nr2 5 r2 6. (In some embodiments, in each of (Va), (Va l), (Va 2), 3 (Va4), (va5), and (va6), p is 2, 3, or 4. And at least two groups R3 are bonded to the same ring carbon atom, wherein two 3 groups, which may be the same or different, together with the carbon atoms to which they are attached form a cycloalkyl, cycloalkenyl, hetero a cycloalkyl ring containing from one to three heteroatoms selected from N, fluorene and 5, or a heterocycloalkenyl ring containing from one to three heteroatoms selected from the group consisting of N, hydrazine and s. In the formula (va), the mouth is a one or a bucket, and each R3 is independently selected from the group consisting of alkyl 'heteroalkyl, alkenyl, heteroalkenyl, _cn, _n〇2, -0R19, _0C (〇) ) 0R2G, -NR21R22, -nrhs〇2R24, _nr23c(〇)〇r20, -NR C(〇)R24, -S02NR25R2 6 , _C(〇)R2 4 λ _C(S)R2 4 λ _C(〇)〇R2 0 , SR -S(0)R] 9 ' -S02R>9 , -〇C(〇)R24 . -C(0)NR25R26 ^ 2 2 c(n.cn)nr25r26, view 23c(0)nr25r26iNr2 3 -C(nh)_nr2 6 r2 6 wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently Or a plurality of substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, a -CN, a -N02, a decyl group, a hetero group, a halogen group, a dilute group, a dentate group, an alkyne , haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, hetero 135177 -248 - 200922559 cycloalkyl, heterocyclic, azide, -OR19, -〇C (; C) R20, -NR21R22, -NR23S02R24, -NR23C(〇)〇R20, -NR23C(0)R24, -S02NR25R26, -C(0)R24, -C(0)〇R2〇, _SR19, _s(〇 Rl9, -so2r19 ' -0C(0)R24 ' -C(0)NR25R2 6 - -NR23C(N-CN)NR25R26 and -NR2 3 C(0)NR2 5 R2 6 group. In one embodiment, 'in formula (Va), p is i, and r3 is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and heteroalkenyl, wherein each of the alkyl, each of the heteroalkyl Each of the alkenyl group and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, -CN , -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl , heterocyclenyl, azide, _0Rl9, _〇C(〇)〇r20, -NR2IRU ' _NR23s〇2R24, _nr23c(〇)〇r2. , nr23c (〇) r24, -S02NR2 5R26 ' _c (0) r24, paste (10). , 19, _驿]9, -S〇2R19 ^ -0C(0)R24 , -C(〇)NR25R26 , .NR2 3C(N-CN)NR^R2 6 and -nr23c(0)nr25r26 .

-C(O)- group. a horse 2, 3 or 4, and used in combination to form a specific embodiment, in formula (v.a), to two R3 groups of the same ring A atom,

'p is 2, 3 or 4, and is used together by knots to form spiro I-, -NR6-, 〇, S, 'having 1 to 3 independent 135Π7 -249- 200922559 selected from -NH-, -NR6 -, 〇, s, 5 (〇) and disasters) 2 ring heteroatoms. In some embodiments, in each of the formulas (Va), (Va l), (Va.2), (Va.3), (Va4), (Va5), and (Va6), r3 is burned. base. In some embodiments, in each of the formulae (Va), (Va l), (Va.2), (va 3), (Va4), (Va5), and (Va6), R3 is a heteroalkane. base. In some embodiments, in each of the formulae (Va), (Va l), (v.a 2), (Va 3), (V.a.4), (V.a.5), and (V.a.6), R3 is a dilute group. In some embodiments, 'r3 is a heteroalkenyl group in each of the formulae (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6) . In some embodiments, in the formulas (va), (Va l), (Va 2), (Va 3), (V, a. 4), (Va5), and (V_a.6), R3 For fast base. In some embodiments, in the formulae (Va), (va l), (Va.2), (Va 3), (Va4), (Va5), and (Va6), it is a heteroalkynyl group. . In some embodiments, in the formulas (va), (Va l), (va 2), (Va.3), (Va4), (Va5), and (Va6), hydrazine is an aryl group. . In some embodiments, in each of the formulas (va), (Va l), (Va 2), (Va 3), (Va4) ' (Va5), and (Va6), R3 is a heteroaryl group. . In some embodiments, 'R3' is a cycloalkyl group in each of the formulae (V.a), (V.a.l), (V.a.2), (V.a.3), (V.a.4), (V.a.5), and (V.a.6). In some embodiments, 'R3 is a cycloalkenyl group in 'Va), (Val), (Va2), (Va3), (Va4), (V_a.5), and (Va6) .

In some embodiments, 'in each of (Va), (Va 1), (Va2), (Va3), (Va4), (V, a.5), and (Va6), 'R3 is Heterocycloalkyl D is in some embodiments, in the formulae (Va), (Va 1), (Va2), (Va3) ' 135177 -250 · 200922559 (Va4), (Va5) and In Va6), 'R3 is a heterocycloalkenyl group. In some embodiments, 'R3' is in the formulae (Va), (Va1), (Va 2), (Va 3), (V.a.4), (V.a.5), and (V.a.6). In some embodiments, in each of the formulas (Va), (V al), (Va 2), (Va.3), (Va4), (Va5), and (Va6), 'R3 is _CN. . In some embodiments, 'R3 is _N in each of the equations (Va), (Va l), (Va.2), (Va 3), (Va4), (Va5), and (Va6) 〇 2. In some embodiments, in each of the formulas, (Va l), (Va 2), (Va.3), (V.a.4), (V.a.5), and (V.a.6), R3 is _〇Rl 9. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), 'R3 is _〇c (〇)〇r2〇. In some embodiments, 'R3 is _nr2' in each of the equations (Va), (Va1), (Va 2), (Va 3), (Va4), (Va5), and (Va6). R22. In some embodiments, 'R3 is _nr23s' in each of the equations (va), (Va l), (va 2), (Va 3), (Va4), (Va5), and (Va6). 2r2 4. In some embodiments, 'r3j^_nr2 3' in each of the equations (Va), (Va l), (Va.2), (Va 3), (Va4), (Va5), and (Va6) 〇p)〇r2〇. In some embodiments, in the equations (va), (va l), (Va.2), (va3), (Va4), (Va5), and (Va6), r3 is _nr2 3c(〇)r2 4. In some embodiments, 'in each of (Va), (va l), (Va 2), (Va.3), (Va4), (Va5), and (Va6), 'R3 is _s 〇 2 nr2 5 r2 6. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), R3 is _c ( 〇) R2 4. In some specific embodiments, in the various formulas (Va), (Va l), (Va 2), (Va.3), 135177-251 - 200922559 (Va4), (Va5), and (Va6) Medium,; R3 is _c(〇)〇r2 〇. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), R3 is _SRl 9 . In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va 3), (Va4), (Va5), and (Va6), R3 is _^( 〇) Ruler 1 9. In some embodiments, in each of (Va), (Va l), (Va.2) ' (Va.3), (Va4), (Va5), and (Va6), R3 is _ s〇2Rl9. In some embodiments, in each of the formulas (Va), (Va l), (Va 2), (Va.3), (Va4), (Va5), and (Va6), R3 is _〇 c (〇) R2 4. In some embodiments, 'in the various formulas (Va), (Va l), (Va_2), (Va.3), (Va4), (Va5), and (Va6), the ruler 3 is (( 〇) serving 25 feet 26. In some embodiments, 'in the various formulas (Va), (Va l), (Va 2), (va3), (\^.4), (\^.5) and (\^.6) where '1^ is _; ^2 3(2(^_(^)]^2 5 ft 2 6 . In some embodiments, in the various formulas (va), (Val), (Va2), (Va3), (Va4), (Va5), and (Va6), R3g_NR23c(〇)NR25R26. In some embodiments, 'in each formula (Va), (Val), In (Va2), (Va3), (Va4), (Va5) and (Va6), R3 is selected from the group consisting of methyl, ethyl, propyl (straight or branched), and Base (straight or branched), amyl (straight or branched)

135177 - 252 - 200922559 HN, HN' HN,

HN \,

HN )τΝΗί 〇 / N, 'OH OH and H2N. In some embodiments, in the equations (va), (v.al), (va2), (Va3) (Va4), (Va5), and (Va,6), when '__nr6_, The r3 system does not exist. In a specific embodiment, the compound of the invention has the L structure of a in formula (V.b) and comprises a pharmaceutically acceptable salt, solvate, ester, prodrug or isomer of the compound 6:

R; R? R28

(V.b.) where RhR2, ^, ^^ R, P, E, ring A and ring B are independent of each other

The ground is selected, and wherein: @I (package 3 E and unsaturation) is 7.8. member cycloalkenyl or heterocyclic ring; E is selected from the group consisting of 0-, each, na, _s (〇 ) 2...c(r4)(r5)_, _n(r6), -n(C(Y)r7)- ^ _N(C(Y)or8)_ ^ _N(C(Y)N(r9)(r10 ))_ ^ _c(〇)_n(r]])_ ^ -N(R )-C(〇)_, _s(q)2_n(r11)', _n(rU)_s(〇)2, chat ·, 135177 -253 - 200922559 -0-C(0)-, -0-N(R6)-, -N(R6)-0-, -N(R6)_n(r12>, n=n_, _c( R7)=n_ ' -C(0)-C(R7 )=N- ' -C(0)-N=N- > -〇-C(Y)-N(Ri i)_ N -^(R11 )-C(Y)-〇-N(R]1)-C(Y)-N(R12)- ^ -C(Y)-N(R] ] )-〇. , -C(Y)-N (Ri i ).N(Ri 2, -0-N(RM )-C(Y)- and -N(R) qr^R11 )-C(Y)-; ring B is substituted or unsubstituted a heteroaromatic ring; and the selected substituents on p, Ri, R2, R3, R4, R5, R6' r7, R8, r9, R10, RU, R27, R28, Y and ring B are as in Formula 1 above. Definitions In a particular embodiment 'in the formula (vb), ring A is a cycloalkenyl ring. In a particular embodiment 'in formula (Vb), ring a is a heterocycloalkenyl ring. In a specific embodiment, in the formula (Vb), E is _C(R4)(R5)_. In a specific embodiment 'in formula (Vb), E is selected from the group consisting of _〇_, -S-, -S(O)-, -S(0)2-, -N(R6)-, -N(C(7)R7)-, _n(C(Y)OR8)-, -N(C(Y)N(R9)(R> °))- ^ -C^-NCR11)- ^ -N(R11 ). C(〇)- > -SCO^-NCR1 * )-, -N(R] ))4(0)2-, -C(0)-0-, -0-C(0)-, _aN( R6)_, _n(r6)_〇_, -N(R6)-N(R] 2)- ' -N=N- ' -C(R7 )=N- > -C(〇)-C( R7 )=N- ^ -C(0)-N=N- > -0-C(Y)-N(Rn )- ' -NCR11 )-C(Y)-0- , -N(R] 1 )-C(Y)-N(Rl 2)- ^ -C(Y)-N(Rn )-〇- , -C(Y)-N(Rn)-N(Ri2)-, -〇_N( Rll)_c(7)·and-wind ruler 12)-;^!^1:^:”)-. In a specific embodiment, in the formula (V.b.), the lanthanide is selected from the group consisting of -〇-, -S_, -S(0)-'-S(0)2- and -N(R6)-. In a specific embodiment 'in formula (Vb), E is selected from the group consisting of -〇-, -S-, -S(0)-, -S(0)2-, and -N(R6)-, Wherein R6 is selected from the group consisting of η, alkyl, -C(0)R24 and -C(S)R24 0 135177 -254- 200922559. In one embodiment, in the formula (v, b.) -N ( R6)- 'wherein R6 is selected from the group consisting of η, alkyl, in a particular embodiment, in formula (Vb) in formula (Vb) in formula (Vb) in formula (Vb) Vb) in the formula (Vb) in the formula (Vb) in a specific embodiment in a specific embodiment in a specific embodiment in a specific embodiment in a specific embodiment In a specific embodiment, in one embodiment, 1 E is selected from the group consisting of -〇- and -C(0)R24 and -C(S)R24. E is -Ο-. E is -S-. E is -S(O)-. E is -S(0)2-. E is -C(R4)(R5)-. E is -N(R6)-. E is -N(C(Y)R7)-. E is -N(C(Y)OR8)-. In a specific embodiment, in the formula (V.b.), e is -n(C(Y)N(R9 XR10 ))-

'In the formula (Vb), in the formula (Vb) 'in the formula (Vb), in the formula (Vb), in the formula (Vb) 'in the formula (Vb), in the formula (Vb), In the formula (Vb), in the formula (Vb), in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment In a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, In a specific embodiment, E is -CCCO-N^11)-. E is -Ν(ϊ^ 1 )-C(0)-. E is -S(0)2-N(Rn)-. E is -NCR1 ^4(0)2-. E is -C(0)-0-. E is -O-C(O)-. E is -0-N(R6)-. E is -N(R6)-0-. E is -N(R6)-N(R12)-. E is -N=N-. In the formula (V.b.), e is -C(R7)=N-. In the formula (V.b.), e is -C(0)-C(R7)=N-. In the formula (V.b.), E is -C(0)-N=N-. 135177 - 255 - 200922559 In a specific embodiment 'In the formula (V.b.), e is _〇_C(Y)_N(Ri 1)_. In a specific embodiment 'in the formula (Vb), e is _N(Rl丨ycco-o. In the specific embodiment, in the formula Wb.), E is -N(Rii>C(7)- N(R12)-. In the specific embodiment, in the formula (vb·), e is -(^(Υ)-Ν(ΙΙ11)-0-. In the specific embodiment, in the formula (Vb) Wherein, e is -C(7)-l^R11)_ In the specific embodiment, in the formula (Vb), E is _〇_N(Ri 1 )_C(Y)_. In the specific embodiment, In the formula (Vb), E is _N(Rl2)_N(Rl \ C(Y)- 〇, Y is (=0). , Y is (=s). , Y is (=N(R13)) ' Y is (=N(CN)). , Y is (=N(0R14)). , 丫 is (= is called ruler 15)(1^6》. , Y is "(foot 17)^1%. , B is unsubstituted in the specific embodiment, in the formula (vb) in the specific embodiment, in the formula (Vb) in a specific embodiment, in the formula (vb) In the specific embodiment, 'in the formula (Vb)

In the specific embodiment, in the formula (Vb) _ TS, in the specific embodiment, in the formula (Vb); in the specific embodiment, in the specific embodiment of the formula (vb), in the formula (vb) an aromatic ring. In the case of a T5 member, "in the formula (Vb), B is an unsubstituted 5-6-cyclonon having one or the same ring hetero atom which may be the same or different. N'S, 〇, s(〇)u(〇) 2. In a specific embodiment, the tow, a is - or _; the towel is in the formula (Vb_), and B is a heteroaromatic ring, which may be Substituted by the same or different substituents, each substituent is 35177-256-200922559 independently selected from the group consisting of i, ..., CN, -N〇2, alkyl, heteroalkyl, _alkylalkenyl, haloalkenyl, alkyne , haloalkynyl, aryl, heteroaryl, aryl-alkyl-heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl azide, -0R 9, _ 〇 C (〇) 〇 R20, _nr21r22, _nr23s 〇 2R24 - NR2 3C (〇) 〇 R2 0, nr23c (〇) r24, _s 〇 2Nr25r26, c (〇) r24 - C (0) 〇 R2 〇. -SR] 9 . _S(〇)Rl 9 . _S〇2Rl 9 . _〇C(〇)r24 , _C(〇)nr25r26 ^ -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C( 0) NR2 5 R2 6. f is specifically carried out in the formula, in the formula (Vb), b^_6_ bet heteroaromatic ring, having 1-3 ring heteroatoms which may be the same or different, each heterocyclic ring Atomic system Selected from the group consisting of N, S, 〇, S (〇ms(〇) 2, the heteroaromatic ring system is - or a plurality of substituents which may be the same or different substituents' each substituent is independently selected from the group consisting of CN, L (four) Ketone base, dilute base, (d) = block group, dentate group, aryl group, heteroaryl group, aryl di-, : alkyl group, cycloaliphatic group, fluorenyl group, heterocyclic group, azide group, -,娜)0R., -Qing, NR23S02R24, 'NR C(〇)R24 ' -S0^R25R26 ' ^ -c(0)OR2〇. sr19 ^ -W9, _sq2R19, Na)R24, paste nr25r26, Na 3c (Qing _ nr2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. Β is an unsubstituted 6_ ring hetero atom, each of which is miscellaneous in the specific embodiment 'in the formula (Vb), The family ring 'having μ3 may be the same or different ring atomic systems independently selected from the group consisting of Ν, s, and 〇. In the example, in the formula (Vb), 1-3 may be the same or different The ring precursor and the clothes are selected from the group consisting of N, S and oxime, and the hetero (4) U sub-system is substituted by one or more substituents which may be different as 77-257 - 200922559, and each substituent is independently selected. Including halogen, _CN, -N〇2, alkyl, heteroalkyl 'haloalkyl, alkenyl Alkenyl, alkynyl, _alkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl...cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, Azido group, _〇Rl9, _〇c(〇)〇r2〇, •NR2lR22 '-NR23S02R^ . -NR^C(〇)〇R20 , _NR23C(〇)R24 . -S〇2NR25R26' _c(〇) R24, _C_R2G, SR19, s(〇)Ri9, s〇2Ri9, -〇C(0)R^ . -C(0)NR^R26 . -NR23C(N-CN)NR25r26A.NR23C(〇). nr25r26. In a specific embodiment 'in the formula (Vb), B is an unsubstituted 6-membered heteroaromatic m having 2 ring heteroatoms. Each ring heteroatom is independently selected from N, S and In a specific embodiment, in the formula, the heteroaromatic ring has two ring heteroatoms, each ring hetero atom is independently selected from N, S and oxime, and the heteroaromatic ring system is one or more The substituents may be substituted with the same or different substituents, and each of the lines is independently selected from the group consisting of: 素, 指, 2, alkyl, miscellaneous, S-read 19 cm, _C_R2Q, SR19, -S(0)R, _s〇2Rl9. -OC(〇)R2 4^.C(〇)nr25r26 In the specific embodiment, in the formula (vb·), b is unsubstituted:: the family ring 'has i-2 may be the same or The different ring-mixed protoplast atoms are independently selected from the group consisting of N, S and oxime. In the specific embodiment, 'in the formula (Vb), B has a ring hetero atom which may be the same or different, each hetero; the heteroaromatic ring ' is selected from the group consisting of N, S and oxime, the heteroaromatic The singular and sub-individual Dingmen Gong is replaced by: - or a plurality of substituents which may be different from each other, each substituent is unique, or the target includes Nansu, CN, 135177 • 258· 200922559 2 yuan base , heteroalkyl, _alkyl, alkenyl, haloalkenyl, alkynyl, halo', aryl, heteroaryl 'aryl-alkyl-, heteroaryl-homo-, cycloalkyl, alkene , heterocycloalkyl 'heterocyclenyl, azide, -OR, 9,_0CX0)0R2 〇, _NR2 1 p2 2 -NR23S02R24 > -NR23C(0)0R20 . -NR23C(0)R24 λ -so2nr =r26, c(q)r24, c_R2G, sr19, S(〇)R19, code R19, -〇C(0)R2 4 s _C(〇)NR2 5R2 6 s -NR23C(N-CN)NR2 5R2 6^ _NR2 3a〇) NR25R26. , ; In the specific embodiment, 'in the formula (V.b.), B is an unsubstituted 5 member heteroaromatic ring' having i ring hetero atoms selected from N, 5 and fluorene. In a specific implementation, in the formula (Vb), the heteroaromatic ring has one ring hetero atom selected from N, s and fluorene, and the heteroaromatic ring system may have the same or different substitutions. Substituent, each substituent is independently selected from 5 -CN, -N02, alkyl group, miscellaneous group, dentate group, 9 -MR2 1 P22 , -C(〇)R24, -C(9)〇R2 0, _SRl9, _s(9)Rl9, 19 - 〇C(0)R2 4 and _c(〇)nr2 5 r2 6. 2 In the specific embodiment, in the formula (Vb.), the B45_member heteroaromatic has S as a ring heteroatom 'the heteroaromatic ring system is substituted by one or more: or different substituents, Each substituent is independently selected from the group consisting of: South=N=CN N02, alkyl group, miscellaneous group, dentate group, and -9, _2. '〇C(0)R24 and .C(〇)〇R2 0 . 1Q '-C(〇)R2 4^ , -SR , -S(0)R19, _s〇2r19 -C(0)NR25R2 6 0 In the specific embodiment, in the formula (vb), B is not A heterocyclic ring with s as a ring (four)+. In a specific embodiment, in the formula (V.b.), the B series is selected from the group consisting of 135177 -259 - 200922559

s

In a specific embodiment and in the formula (Vb), the radical R1 is unsubstituted, based on a specific embodiment, in the formula (Vb), in a specific embodiment, in the formula (Vb) Wherein R1 is unsubstituted stupid R1 is unsubstituted in one embodiment in a particular embodiment in a particular embodiment in a particular embodiment in formula (VbH, h(d) In the formula (Vb), 'R1 is a substituted phenyl group. In the formula (Vb), Ri is a substituted group. In the formula (Vb.), Ri is one or more An aryl group which may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of i-, -CN, -N〇2, an alkyl group, a heterodole group, a south alkyl group, a dilute group, a dentyl group, Fast radical, (tetra)yl, aryl, heteroaryl, aryl_county_, heteroaryl

Base-alkyl, ring-based, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, -OR19, -0C(0)0R2G, _NR2lR2 2, _nr23s〇2R24, nr23c(〇)〇r2 〇-NR23C(〇)R24, _s〇2Nr25r26, c(〇)r24, c(〇)〇r2(), sr19, -S(0)R]9 ^ -S02R19 ^ -0C(0)R2 4 > -C(0)NR25R2 6 , -NR2 3 C(N-CN). NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 In a specific embodiment, in the formula (Vb), Ri is a stupid group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkene , haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl 135177-260- 200922559 benzyl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkane 'Heterocyclenyl, azido, -GW, -OC(0)OR2〇, _nr21r22, _NR23s〇2R24, nr23c(〇)〇r2〇, -NR23C(Q)R24, -S02NR25R2 6, _c(0 )r24, c(〇)〇R2Q, SR19, -S(0)R19 > -S〇2Rl9 . .〇C(〇)R24 . .C(〇)NR25R26 , _NR2 3 C(N_CN)_ NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In a specific embodiment 'in the formula (Vb.), R) is a phenyl group substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, -OH, -CN and _alkyl.

In a specific embodiment, in the formula (V.b.), Ri is

In one embodiment, 'in formula (10).), is a stupid group substituted with three oxygen groups. In one embodiment, in the formula (v.b.), the pellets, sage, and stalks are phenyl substituted by two murine groups. In the formula (V, b.), R1 is a phenyl group substituted by a -(tetra) group. 135177 261 · 200922559 In a specific embodiment, in the formula (V.b.), R1 is:

In a particular embodiment, in Formula (V.b.), R27 and R28 are each independently selected from the group consisting of hydrazine and alkyl. In a specific embodiment, in Formula (V.b.), R2 is -C(Z)R7. In a specific embodiment, in Formula (V.b.), R2 is -C(Z)NR9R10. In a specific embodiment, in Formula (V.b.), R2 is -C(Z)OR8. In a specific embodiment, in Formula (V.b.), R2 is -S02NR9R10. In a particular embodiment, in Formula (V.b.), R2 is alkyl. In a particular embodiment, in Formula (V.b.), R2 is a heteroalkyl group. In a particular embodiment, in Formula (V.b.), R2 is aryl. In a particular embodiment, in Formula (V.b.), R2 is a heteroaryl group. In a particular embodiment, in Formula (V.b.), R2 is cycloalkyl. In a particular embodiment, in Formula (V.b.), R2 is cycloalkenyl. In a particular embodiment, in Formula (V.b.), R2 is heterocycloalkyl. In a particular embodiment, in Formula (V.b.), R2 is heterocycloalkenyl. In a specific embodiment, in the formula (V.b.), Z is (=0). In a specific embodiment, in the formula (V.b.), Z is (=S). In a specific embodiment, in the formula (V.b.), Z is (=N(R13)). In a specific embodiment, in the formula (V.b.), Z is (=N(CN)). In a specific embodiment, in the formula (V.b.), Z is (=N(OR14)). In a specific embodiment, in the formula (V.b.), Z is (=N(R) 5)(R16)). 135177-262-200922559 In the specific embodiment 'in the formula (v.b.), zjk=c(r17)(r18)). In the specific embodiment, in the formula (vb), you are, and 2 is (=0) 〇 in the specific embodiment, 'in the formula (vb), r, -c(0)h . In a specific embodiment, in the formula (v.b.), R, _c(〇) is burned. In the case of specific implementation, in the formula (v.b.), W (〇) cH3. In a specific embodiment, in the formula (vb), r2^c(q)r7, wherein the R7 is a group substituted by - or a plurality of substituents which may be substituted with (four) or different substituents, each substituent Independently selected from the group consisting of shouting, self-priming, ., supplementing 2, alkyl, alkenyl, alkenyl, alkenyl, aryl, aryl, 4 aryl, ί, ί Nilute, heterocyclic, I, heterocyclo, valence, -R19, -〇C(〇)〇R2. , _NR2lR22, Na 3s〇2R24, nr23c(〇)〇r2〇, -NR23C(0)R24, _S〇2NR25R26, _c(〇)R24, (10)〇r2〇, _sr19, -S(0)R! 9 NR25R2 6 S02R ' -0C(0)R24 > -C(〇)NR2 5R2 6 , -NR2 3 C(N-CN)-&-NR23C(0)NR25R26d In the case of K, in the formula (V b Wherein R 2 is _C(〇)r7, wherein R is an alkyl group substituted by one to three substituents which may be the same or different, each substituent being independently selected from the group consisting of _〇Rl9, _NR2]R22 and Cycloalkyl. In a specific implementation, in the formula (V.b,) towel HQq) R7, wherein R7 is an alkyl group, wherein the alkyl group is substituted with an alkyl group and 〇H. In the example of palladium, in the formula (vb), r2 is _c(〇)r7, wherein the R7 is a group of H groups which may be substituted with the same or different substituents, and each substituent is independently selected from the group consisting of Including _0H, _NH2 and cyclopropyl. In a specific embodiment, in the formula (vb), 圮 is _c(0)r7, wherein 135177 • 263 - 200922559 the R7 is ', ', and the two may be substituted by the same or different substituents. The alkyl group is independently selected from the group consisting of -nh2 and cyclopropyl. In a specific embodiment, in the formula (Vb), R2 is _c(〇)R7, wherein the R7 is an alkyl group substituted by _〇H. In a specific embodiment, in the formula (Vb), R2 is _c(〇)R7, wherein the R7 is an unsubstituted heterocycloalkyl group. f

In a specific embodiment, in the formula (v.b.), R2 is _C(0)R7, wherein §H7 is a substituted heterocycloalkyl group. In a specific embodiment, in the formula (Vb.), R 2 is -C(〇)R7, wherein 5 R is a heterocycloalkyl group substituted by one or more substituents which may be the same or different, Each substituent is independently selected from the group consisting of keto, halo, _CN, _n 〇 2, alkyl androalkyl, 4 alkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, arylheteroaryl, naphthenic Alkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide 〇R -〇C(0)〇R20 '-NR2,R22 '-NR23S02R24 '-NR23C(0)0R2. , _Nr23C(〇)r24, _s〇2nr25r26, c(〇)r24, -C(0)0R2 °, -SR]9, _s(〇)Rl 9, s〇2 Rl 9, 〇c(〇)r2 4. ((〇)nr2 5 r2 6 , -NR2 3 C(N-CN)NR2 5 r2 6 and nr2 3 c(〇)nr2 5 r2 6 . In a specific embodiment, in the formula (Vb) R2 is _c(〇)R7, wherein the R7 is selected from the group consisting of substituted hexahydropyridinium, substituted hexahydrop-pyrion, substituted morphine, substituted tetrahydropyrrole and Substituting one of the nitrogen tetraindoles in one embodiment. In the embodiment, in the formula (Vb), the R 2 is selected from the group consisting of:

, h3c--C- and h3c In the specific embodiment, in the formula (V.b.), R2 is -C(0)NR9 R10. 135177 -264- 200922559 In a specific embodiment, in the formula (v.b.), r2 is _c(〇)nh. In a specific embodiment, in the formula (vb), R24_e ((WR29Ri., wherein R9 and Ri〇 may be the same or different, each independently selected from the territory. In a specific embodiment, in the formula ( In vb.), R2 is -C(〇)NR9R1〇, wherein R9 is unsubstituted heterocycloalkyl, and ri 〇 ^ 哒 哒 哒 哒 Η 烷基 烷基 烷基 烷基 烷基 于 于 于 于 于 于 于 于 于 于In the formula (vb), nr9ri〇, Γ(4) is a substituted heterocyclic filament, and R1. (d) is self-contained. In the specific embodiment, in the formula (10). R2 is -C(0)nr9r1〇, 'R is a heterocycloalkyl group substituted by one or two substituents which may be the same or different substituents, each independently selected from the group consisting of an alkyl group, and the R10 group is selected from the group consisting of ruthenium and ruthenium In the specific embodiment, in the specific embodiment, in the specific embodiment, in the specific embodiment

In the formula (V.b.), R2 is in the formula (v.b.), and R2 is V^CF3.

In a specific embodiment, in the formula (Vb), in the specific embodiment, in the formula (V, b.) 135177 • 265· 200922559 in a specific embodiment, in the formula (vb) R2 is 'Ί*—V_/N—in the specific embodiment, in the formula (vb), it does not exist. In a specific embodiment, in the formula (V.b.), ρ is i. In a specific embodiment, in the formula (v.b,), p is 2. In a specific embodiment, in formula (V.b.), p is 3. In a specific embodiment, in formula (V.b.), p is 4. In a specific embodiment, in the formula (V.b.), the 'p-system, and at least two of the groups R3 are attached to the same ring atom. In a particular embodiment 'in formula (Vb.), P is 1 and R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl , heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl 'heterocyclenyl, halogen, -CN, -N02, -OR1 9,_0C(0)0R2 〇, nr2 ! r2 2, nr2 3 s 〇2R2 4, -NR2 3C(〇)〇R2 0 , -NR2 3C(〇)R2 4 . -S〇2NR^R2 6 , _C(〇)r24 ^ -C(0)OR20, -SR1 9, name (seven) Shell 1 9 , -S02R1 9, -〇C(0)R2 4, _c(〇)nr25r26, -NR2 3 C(N_CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 圮6. In a particular embodiment 'in formula (Vb), p is 2, 3 or 4, and each R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkyne Base, aryl, heteroaryl, cycloalkyl 'cycloalkenyl, heterocycloalkyl, heterocyclic, halogen, -CN, -N〇2, -OR19, -〇C(〇)〇R20, _NR21R22 -nr23so2r24, -nr23c(o)or2 ◦, -nr23C(0)R24, _s〇2Nr25r26, -C(0)R24, -C(0)OR2〇, —SR”, _S(0)Ri9, _s〇 2Rl9, _〇c(〇)r24, -C(0)NR2 5 R2 6 , _NR2 3 C(N-CN)NR2 5 R2 6 and _NR2 3 C(0)NR2 5 R2 6. 135177 -266- 200922559 In a specific embodiment, in formula (vb), p is 2, 3 or 4, and at least two groups R3 are bonded to the same ring carbon atom, wherein each r3, which may be the same or different, Individually selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic , halogen, _CN, -N02, -OR1 9, -〇C(〇)〇R2〇, -NR21R2 2 , -NR23S02R24 > -NR23C(0)〇r2〇. -NR23C(0)R24 . -so2nr25r26,- C(0)R2 4. _c(〇)〇r2., SRl9, s(〇)r19, s〇2Ri9, -〇C(〇)R24, _C(〇)NR2 5r26, _nr23c(Ncn)nr25r24 nr23c(〇)_ NR25R26. In a particular embodiment, in formula (vb), p is 2, 3 or 4 and at least two groups R3 are bonded to the same ring carbon atom, wherein two R3 groups, which may be the same or Differently, together with the carbon atom to which they are attached, form a cycloalkyl, cycloalkenyl, heterocycloalkyl ring, containing one to three heteroatoms selected from N, 0 and S, or a heterocycloalkenyl ring, containing One to three heteroatoms selected from the group consisting of N, 0 and s. In a particular embodiment, in formula (Vb), the mouth system, and each R3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl ,heteroalkenyl,_CN,_N02, -OR19^ -0C(0)0R^ ^ -NR21R22 , _NR23s〇2R24 ^ _Nr23C(〇)〇r2〇^ -NR23C(0)R24, _S〇2NR25R26, _c(〇) R24, _c(s)r24, _c(〇)〇r2〇, -SR19, -S(0)R19, -S〇2Ri9, _〇c(〇)r24, c(〇)nr25r26, -NR23C(N_CN) NR25r26, tearing 23c(〇)nr25r26^nr23_c(nh)_nr26r26, wherein each of the burning base, each of the mixed bases, each of the rare bases, and each of the rare ones Is unsubstituted or, as the case may be, independently substituted by one or more A groups which may be the same or different, each substituent being independently selected from the group consisting of _ base, dentate, 135177-267-200922559-CN, -N〇 2. Alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl Base, azide group, _〇Rl9, _〇C(〇)〇R20, -NR21R22 ' -NR23S02R24 > -NR2 3 C(0)0R2 0 ' -NR23C(0)R24 ' -so2nr25r26, -c(o )r2 4, _c(o)〇r20, _SRl9, _s(〇)r19, -S02R]9, -〇C(0)R24, -C(〇)NR25R26, _NR23C(N-CN)NR25R26 and -nr23c( o) Group of nr25r26. In a specific example, in the formula (Vb), ρ is 1, and R 3 is selected from the group consisting of a leuko group, a heteroalkyl group, a dilute group, and a heterobasic group, wherein each of the alkyl groups and each of the heteroalkanes And each of the alkenyl groups and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a dentate, -CN, -N02, alkyl, heteroalkyl, haloalkyl, benzyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, hetero

V cycloalkyl, heterocycloalkenyl, azide, _〇Rl9, _〇c(〇)〇r2〇, -NR21R22, _NR23S〇2R24, _nr23c(〇)〇r2〇, NR23c(〇)R24, - S02NR^R^ . -C(0)R- . -C(〇)〇R20 . _sr19 ^ s(〇)r19 ^ -so2r- . -〇C(〇)R- ^ -c(〇)nr25r26 . A group of Nr23C(N_CN)Nr25r26 and -nr23c(o)nr25r26. , P is 2, and is employed in combination to form _C(0)- in one embodiment, in the formula (vb) to any two R3 groups of the same ring A atom - group . 'and combined to form a snail in a specific embodiment, in the formula (Vb), the p-system > 2 to any two R3 groups of the same ring A atom are used, 135177 -268- 200922559 a cycloalkyl group having 1 to 3 ring heteroatoms independently selected from the group consisting of -NH_, _Nr6_, hydrazine, S(O), and S(0)2, or a spiroheterocyclic group having a pseudomorphic selected from the group consisting of -NH-, _NR6_, 〇, s, s(〇) AS (〇) 2 ring heteroatoms. In a particular embodiment, in Formula (Vb), R3 is alkyl. In a particular embodiment, in Formula (Vb), R3 is heteroalkyl. In a particular embodiment, in Formula (V.b.), R3 is alkenyl. Specifically, in the formula (V.b.), R3 is a heterogeneous group. In a specific embodiment, in the formula (V.b.), R3 is an alkynyl group. In a particular embodiment, in Formula (V.b.), R3 is a heteroalkynyl group. In a specific embodiment, in the formula (V.b.), R3 is aromatic. In a particular embodiment, in Formula (v.b.), R3 is heteroaryl. In a specific embodiment, in the formula (v.b.), 'R3 is a cycloalkyl group. In a specific embodiment, in Formula (V.b.), R3 is cyclomethine. In a specific embodiment, in the formula (V.b.), R3 is a heterocyclic group. In a specific embodiment, in the formula (v.b.), R3 is a heterocyclic group. In a specific embodiment, in Formula (V.b.), R3 is a quotient. In a specific embodiment, in the formula (V.b.), r3 is cn. In a specific embodiment, in the formula (V.b.), r3 is _N〇. In a specific embodiment, in the formula (V.b.), R3 is _〇Rl 9. In a specific embodiment, in the formula (V.b.), R3 is _〇C(〇)〇R2〇. In a specific embodiment, in the formula (v, b.), R3 is _NR2 i R22. In a specific embodiment, in the formula (V.b.), R3 is _nr23s〇2R24. In a specific example, in the formula (V.b.), r3 is _nr2 3 c(〇)〇r2 〇. In a specific embodiment 'in the formula (V.b.), r3 is _NR23c(〇)R24. 135177 - 269 - 200922559 In a specific embodiment, in Formula (V.b.), R3 is -S02NR25R26. In a specific embodiment, in Formula (V.b.), R3 is -C(0)R24. In a specific embodiment, in the formula (V.b.), R3 is -C(0)0R2(). In a specific embodiment, in the formula (V.b.), R3 is -SR1 9. In a specific embodiment, in Formula (V.b.), R3 is -SCCOR1 9. In a specific embodiment, in the formula (V.b.), R3 is -SC^R1 9. In a specific embodiment, in Formula (V.b.), R3 is -0C(0)R24. In a specific embodiment, in Formula (V.b.), R3 is -C(0)NR25R26. In a particular embodiment, in Formula (V.b.), R3 is -NR23C(N-CN)-NR25R26. In a specific embodiment, in Formula (V.b.), R3 is -NR23C(0)_nr25r26. In one embodiment, Formula (v.b) has the following general structure:

In a specific embodiment, formula (v.b) has the following general structure:

135177 - 270- 200922559 In a specific embodiment, the formula (v.b) has the following general structure

FT , where p is 0, 1, 2 or 3 In one embodiment, the formula (V.b) has the following general structure:

FT , where p is 0, 1, 2 or 3 In one embodiment, the formula (V.b) has the following general structure: 135177 271 - 200922559

In a specific embodiment, the compound of the present invention has the structure shown in formula (10) and includes a pharmaceutically acceptable M, solvate, prodrug or isomer of the compound:

Wherein Rl, R2, R3, R27, r28, p, E are selected, and wherein:

Ring A and Ring B are independent of each other (A (including E and the unsaturation shown) is a 4-8-membered cycloalkenyl or heterocycloalkenyl ring; E is selected from the group consisting of -〇-, _S_, _s(〇) _, _s(〇)2_, _C(R4)(R5)_, _n(r6)_, -N(C(Y)R7)- > -N(C(Y)〇R8)_ . -N( C(Y)N(R9)(R10))- ^ -C(0)-N(R] 1)-. -N(Ru)-C(0)-, -S(〇)2_N(rH)_ , _N(Rn)-S(0)2-, -C(〇)-〇-, -OC(O)-, -〇-N(R6)-, -N(R6)-〇-, -N( R6)-N(R12)-, -N=N-, -C(R7)=N- '-C(0)-C(R7)=N- > -C(〇)-N=N- ' -0-C(Y)-N(R] 1)- ' -N(R! 1 )-C(Y)-〇- > -NCi^KXYVNKR12)-,·(:(7)-N(Rn)- 0-, -C(7)-N(Rn)-N(R12)-, 135177 •272· 200922559 -0-N(R )-C(Y)__ and _N(R1 2 )_n(ri 1 )_QY)_ Ring B is unsubstituted or, as the case may be, part of the silk (4) and an alicyclic or partially unsaturated heterocyclic ring, and P, R1, R2, R3, r4, r5, r6, r7, R8, r9 The selected substituents on RiR, Rn, R]2, R27, R28, Y and Ring B are all as defined in Formula 1 above. In a particular embodiment, in Formula (VI), Ring A is a cycloalkyl ring. In the specific embodiment, 'in the formula (10)', ifA is a heterocyclic ring. In a specific embodiment, in the formula (VI), the ring VIII is a 4 member ring. In a specific embodiment, in Formula (VI), Ring A is a 5-membered ring. In a specific embodiment, in Formula (VI), Ring A is a 6-membered ring. In a specific embodiment, in Formula (VI), Ring a is a 7-membered ring. In a specific embodiment, in Formula (VI), Ring a is an 8-membered ring. In a specific embodiment 'in formula (VI), e is -QR4)^5)-. In a specific embodiment, in formula (VI), E is selected from the group consisting of _〇_, , S-, -S(O)-, -S(0)2-, -N(R6)-, -N(C(Y)r7)_, _n(c(Y)〇R8)-, -N(C(7)N(R9)(R] 〇))-, -C(0)-N(Ri1)-, - N(R1! )_c(〇)_, _s(〇)2_N(Rl μι -N(Rn)-S(0)2-, -C(0)-0-, -OC(O)-, _〇 _n(R6)_ , N(R6)_〇_ , -N(R6)-N(R12)-, -N=N-, -C(R7)=N-, -C(〇)_c(r7 )=n_,·〇(〇)_Ν=Ν_, -0-C(Y)-N(Rn)-, -N(Rn)-C(Y)-0-, _N(Rll)_c(Y)_N (Rl2)_, -C(Y)-N(Rn)-0-, -C(Y)-N(Ru)-N(Ri2y_, _〇_N(Rl))_c(Y) and -N( R12)-N(Rn)-C(Y)-. In a specific embodiment 'in formula (VI), e is selected from the group consisting of -0-, -s-, -s(o)-, - s(o)2- and -n(r6)- 0 135177 > 273 - 200922559 In a specific embodiment, in formula (VI), E is selected from the group consisting of -Ο-, -S-, -S (O)-, -S(0)2- and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24 and -C(S)R24. In the formula (VI), the E is selected from the group consisting of -0- and -N(R6)-, wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, and -C(S)R24. In a specific embodiment, at In (VI), E is -0-. In one embodiment, in formula (VI), E is -S-. In one embodiment, in formula (VI), E is - S(O)-. In a specific embodiment, in the formula (VI), E is -S(0)2-. In a specific embodiment, in the formula (VI), E is -C (R4)(R5)-. In a specific embodiment, in the formula (VI), E is -N(R6)-. In one embodiment, in the formula (VI), E is - N(C(Y)R7)-. In a particular embodiment, in Formula (VI), E is -N(C(Y)OR8)-. In one embodiment, in Formula (VI) In the formula, E is -N(C(Y)N(R9 XR1 0))-. In a specific embodiment, in the formula (VI) j, Eg-C(0)-N(Rn)-. In a particular embodiment, in Formula (VI), E is -NCR11)-C(0)-. In one embodiment, in Formula (VI), E is -SCOh-I^R11. In a specific embodiment, in Formula (VI), E is -NCR11)-S(0)2-. In a specific embodiment, in Formula (VI), E is -C(0)-0-. In a specific embodiment, in Formula (VI), E is-0-C(0)-. In a specific embodiment, in Formula (VI), E is-0-N(R6)-. In a specific embodiment, in Formula (VI), E is -N(R6)-0-. In a specific embodiment, in Formula (VI), E is -I^Ri-NKR1 2)-. In a specific embodiment, in Formula (VI), E is -N=N-. 135177 - 274 - 200922559 In a specific embodiment, in the specific embodiment, in the specific embodiment, in the concrete embodiment, E is -C (in the specific example) R7) = N-. E is -C(0)-C(R7)=N-E is -C(0)-N=N-. E is -O-QY^NKR11)-E is -N(R) 1 )-C(Y)-0- in formula (VI) in formula (VI) in formula (VI) t in formula (Vi) In a specific embodiment of formula (VI), 'E is -NCR11)-C(Y)-N(R12)- in $ & r 八(VI). In a specific embodiment, in the formula (ντ) 士 ^ ,, E is _C(Y)_N(Rl i )_〇_. In a specific embodiment, in the formula J, in the formula (VI), E is _C(7)_N(R11)_N(R12)-. In a specific embodiment, force -V Γ\/τ, A is in the formula (Vl), and E is -O-NCR11)-C(Y)-. In the specific case of the " item, A 4 i J A is in the formula (VI), and E is _N(Rl 2 )-N(Rl ! )_C(Y)_. Y is (=0). Y is (=s). Y is (=N(R13)). Y is (=N(CN)). Y is (=N(0R14)). Y is (=N(R15)(R16)). Y is (=C(R17)(R18)). , Ring A is a 4-membered ring, and E-C(R4)(R5)-, -N(R6)-, in one embodiment, in a particular embodiment in Formula (VI) In a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, in a specific embodiment, In the formula (VI), in the formula (VI), in the formula (VI), in the formula (VI), in the formula (VI), in the formula (VI), the formula (VI) is selected from the group consisting of -0-, -s -, -S(9)-, -S(9)2_-N(C(7)R7)-, -N(c(7)〇R8)_, _n(c(y)n(r9)(r1〇))_. In a specific embodiment, in Formula (VI), VIII is a 4 member ring, and e is selected from the group consisting of -CH2_, -CH(R4)-, -C(R4)(R5). 135177 - 275 - 200922559 In a specific embodiment 'in formula (VI), A is a 5-membered ring and E is selected from the group consisting of -0-, -S-, -S(O)-, -S (0)2-, -C(R4)(R5)-, _n(R6)-, -N(C(Y)R7)- > -N(C(Y)OR8)- '-N(C( Y)N(R9)(Ri〇)). -0(0)^11)- ^ -N(Rn )-C(0)-, -SCOh-NCR11)-, -I^R11 )-S( 〇)2-, -C(0)-〇-, -〇-C(0)-, -0-N(R6)-, -N(R6)-0-, -N(R6)-N(R12 )_, _n=N- and -C(R7)=N-. In a specific embodiment, -0- 于 in a particular embodiment, f ' -S-. In a specific embodiment, -s(o)-. In a specific embodiment, -s(o)2-. In a specific embodiment, -C(R4)(R5)-. In one embodiment, i, -N(R6)-. In a specific embodiment '-N(C(Y)R7)-. In a specific embodiment, _N(C(Y)0R8:l·. In a specific embodiment '-N(C(Y)N(R9)(R1()))). In the examples 'in the formula (VI), 'a is a 5-membered ring, and E is in the formula (VI), a is a 5-membered ring, and Eg is in the formula (VI), and A is a 5-membered ring. And e is in the formula (VI), a is a 5-membered ring, and £ is in the formula (VI), 'a is a 5-membered ring, and e is in the formula (VI), and A is a 5-member Ring, and e is in the formula (VI) 'a is a 5-membered ring, and e is I & (10) 'eight is a 5_member ring, and £ is in the formula (vi), A is 5_member a ring, and E is in the formula (W), A is a 5-membered ring, and e is 135177 276- 200922559 -C(0)-N(Rn)-., and ε is in a specific embodiment, In the formula (VI), eight is a 5-membered ring N(Rn)-C(0)-. In the specific embodiment, in the formula (VI), eight is 5 such as -S(0)2-N. (Rn)-. In the specific embodiment, 'in the formula (VI), eight is a 5-member ring-N(Rn)-S(0)2-. For f in a specific embodiment In the formula (10), A is a 5-membered ring -c(o)-o-. In a specific embodiment, in the formula (VI), -OC(O)-eight is a 5-membered ring, and E is for one item In the specific embodiment, in the formula (VI), eight is a 5_member ring·\ΤΠ?6, _0h is -0-N(R6)- in the specific embodiment, 'in the formula (10), eight Is a 5-member ring -N(R6)-N(R12)-. and E is -N(R6)-0-. and Eg is in a specific embodiment, in the formula (VI), A is 5- In the specific embodiment, in the formula (VI), eight is a 5_membered ring, -N=N- and E is in a specific embodiment, in the formula (VI), eight is 5 _ member ring -C(R7)=N- and ε is in a specific embodiment, in the formula (νι), eight is a 6_member ring selected from the group consisting of -0-'-S-, -s( o) -, -s(o)2-, _CiR4VR5, 1 XK )', -N(R6)... -N(C(Y)R7)-, -N(C(Y)0R8)-, -N( C(Y)N(R9)(Rl0))_, _c(〇) is called..., and £ is 135177 -277- 200922559 -N(Rn)-C(0)-, -S(0)2-N( Rn)-, -N(Rn)-S(0)2-, -C(0)-0-,-0-C(0)-, -0-N(R6)-, -N(R6)- 〇-, -N(R6)-N(Ri2)_, _n=N-, -C(R7)=N-, -C(0)-C(R7)=N- '-C(0)-N =N- ' -0-C(Y)-N(R11)- > -N(Rl 1 )-C(Y)-0- ' -N(Rn)-C(7)-N(R12)-, -C (Y)-N(Ru)-〇-, -C(7), -Oi^R11)-C(Y)- and -N(Rl 2 )-Ν(Ι^ 1 )-C(Y)-. In a specific embodiment 'in formula (VI), a is a 6-membered ring and E is -0- 〇 In one embodiment, 'in formula (VI), A is a 6-membered ring And E is -S- 〇 In a specific embodiment 'In the formula (VI), A is a 6-membered ring, and E is -S(0)-. In a specific embodiment, in the formula (VD, eight is a 6_member ring, and £ is, S(〇)2·. In the specific embodiment, 'in the formula (10), the 厶 is a (four), And £ is -C(R4)(R5)-. A is 6: member ring, and E is A is a 6-membered ring, and e is A is a 6-membered ring, and e is A is a 6-membered ring. And e is A is a 6-member ring, and E is

In a specific embodiment, in the formula (VI) -N(R6)-. In a specific embodiment, in the formula (VI) -N(C(Y)R7)-. In a specific embodiment, in formula (VI) -N(C(Y)0R8)- in one embodiment, in formula (VI) -N(C(Y)N(R9) (R1G))-. In a specific embodiment, 'in the formula (VI) 135177 -278 - 200922559 -(:(9)-浑11)-. In a specific embodiment, in formula (VI), a is a ring of members -N(R1))-C(0)-. In a specific embodiment, in the formula (VI), a is 6-member -S(0)2-N(Ru)-. In a specific embodiment, in the formula (VI), a is a 6-membered ring -N(RH)-S(0)2-. In a specific embodiment, in the formula (VI), A is 6-member net -c(o)-o-. In a specific embodiment, in the formula (VI), eight is a 6-membered ring -o-c(o)-. In a specific embodiment, in the formula (VI), A is a 6-membered ring -0-N(R6)-. In a specific embodiment, in Formula (VI), A is a 6-membered barrier -n(r6)-o-. In a specific embodiment, in the formula (VI), A is 6_member field -N(R6)-N(R12)-. In a specific embodiment 'in the formula (VI), A is a 6-membered ring-N=N- 〇 in a specific embodiment, in the formula (VI), A is a 6-membered ring-C (R7) = N-. In a specific embodiment 'in the formula (VI), a is a 6-membered ring-C(0)-C(R7)=N- 〇 in a specific embodiment 'in the formula (VI), a is a 6_membered ring, and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is, and E is, And E is 135177 -279 - 200922559 -C(0)-N=N-. In a particular embodiment, in Formula (VI), A is a 6-membered ring and E is -0-C(Y)-N(Rn)-. In a particular embodiment, in Formula (VI), A is a 6-membered ring and E is -N(Rn)-C(Y)-0-. In a specific embodiment, in the formula (VI), a is a 6-membered ring and E is -NKRHhCXYH^R12)-. In one embodiment, in Formula (VI), a is a 6-membered ring and E is -C(Y)-N(Rn)-0-. In one embodiment, 'in formula (VI)' a is a 6-membered ring and E is -C(Y)-N(Rn)-N(R12)-. In a particular embodiment, in Formula (Vl), A is a 6-membered ring and Eg-0-N(Rn)-C(Y)-. In a particular embodiment, in Formula (Vl), a is a 6-membered ring and E is -N(R12)-N(Rn)-C(Y)-. In a specific embodiment, in Formula (VI), A is a 7-membered ring, and E is selected from the group consisting of -0-, -S-, -S(O)-, -S(0)2- , -c(R4)(r5)_, _n(r6)-, -N(C(Y)R7)- ^ -N(C(Y)OR8)- ' -N(C(Y)N(R9) (ri〇)). . .C(0)-N(RU)- ^ -N(Rn)-C(0)-, -S(0)2_N(Rn)-, call (1^) other 0) 2-, _C(0)_0_, -OC(O)-, -0-N(R6)-, -N(R6)-0-, -Ν(Ι16)-Ν(Ι^ 2)-, _N= N-, _C(R7)=N_, -C(0)-C(R7)=N-, _C(0)-N=N-,-0-C(7)-NCR11)- ' _N(ri l )_c(7)- 〇_, -N(Rn)-C(7)-N(R12)-, -C(7)-N(Rn)-0-, -C(Y)-N(R")-N(R12)-, -0-N (Rn )-C(Y)· and -N(R] 2)-N(Rn )-C(Y)-. In a specific embodiment, in Formula (VI), A is a 7-membered ring, and E is 135177 - 280 - 200922559 - 〇 - 一项 In a specific embodiment, in Formula (VI), Α Is a 7-membered ring, and Ε is -S- 〇 In a specific embodiment, in the formula (VI), Α is a 7-membered ring and Ε is -S(O)-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and E is -S(0)2_. In a particular embodiment, in Formula (Vl), A is a 7-membered ring and E is -C(R4)(R5)-. In a specific embodiment, in Formula (Vl), A is a 7-membered ring and E is -N(R6)-. In a particular embodiment, in Formula (Vl), A is a 7-membered ring and E is -N(C(Y)R7)-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and E is -N(C(Y)OR8)-. In a particular embodiment, in Formula (Vl), A is a 7-membered ring and E is -N(C(Y)N(R9)(R1C}))-. In a specific embodiment, in Formula (Vl), A is a 7-membered ring and E is -C(0)-N(Rn)-. In a particular embodiment, in Formula (Vl), A is a 7-membered ring and E is -N(Rn)-C(0)-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and E is -S(0)2-N(Rn)-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and E is 135177 -281 - 200922559 -N(Rn)-S(0)2-. In a particular embodiment, in Formula (Vl), A is a 7-membered ring and Eg-C(0)-0-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and Eg-o-c(o)-. In a particular embodiment, in Formula (Vl), A is a 7-membered ring and Eg-0-N(R6)-. In a specific embodiment, in Formula (Vl), A is a 7-membered ring and Eg-n(r6)-〇-. In a specific embodiment, in Formula (Vl), A is a 7-membered ring and E is -N(R6)-N(R12)-. In a specific embodiment, in Formula (Vl), A is a 7-membered ring and E is -N=N-. In a specific embodiment, in Formula (Vl), A is a 7-membered ring and E is -C(R7)=N-. In a specific embodiment, in Formula (Vl), A is a 7-membered ring and E is -C(0)-C(R7)=N-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and E is -C(0)-N=N-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and E is -0-C(Y)-N(Rn)-. In a particular embodiment, in Formula (Vl), A is a 7-membered ring and E is -N(Rn)-C(Y)-0-. In a specific embodiment, in Formula (VI), A is a 7-membered ring and E is 135177 282- 200922559 -N(Rn)-C(Y)-N(R12)-. In a particular embodiment, in Formula (VI), a is a 7-membered ring and E is -C(Y)-N(Rn)-0-. In a specific embodiment, in Formula (VI), a is a 7-membered ring and E is -QYh^R11 2)-. In a specific embodiment, in formula (VI), a is a 7-membered ring and E is 0-N(Rn)-C(Y)-. In a specific embodiment 'in the formula (VI), A is a 7-membered ring, and E is in a specific embodiment. In the formula (VI), a is an 8_membered ring, and the ε is Selected from the group consisting of -0-, -S_, -S(O)-, -s(0)2-, _qR4xin5)_, _n(r6)_, -N(C(Y)R7)-, -N (C(Y)OR8)-, -N(C(Y)N(R9XRl0))_, <(〇)_Ν(κ11)_, -NCR11 )-C(0)- ^ -SCO^-^R11 ) - ^ -N(Rii).S(〇)2. . .C(〇).〇.. -OC(O)-,-0-N(R6)-, -N(R6)-0-- -N(R6)-N(Ri 2)_, _N=N_, _C(R7 )=N_ ' -C(0)-C(R7 )=N-, -C(0)-N=N-,- 0-C(Y)_N(Rn )_, _n(R^ 1 )-C(Y)-0-, -N(Rn)-C(Y)-N(Ri2)_, -C(Y)- N(R")-a, -C(Y)_N(Rll)_N(Rl2)_, -0-N(Rn)-C(Y)-, and -N(R] 2 )-Ν(ί^ 1 )-C(Y)-. In a specific embodiment, in the formula (VI), eight is an 8-member ring, and £ is -0- in one embodiment, in the formula (VI), eight is an 8-member ring. And £ is S- 〇 In a specific embodiment, in the formula (VI), eight is an 8-member ring, and £ is -s(o)-. In a specific embodiment, in formula (VI), eight is an 8_membered ring and £ is 135177 - 283 - 200922559 -s(o)2-. In a particular embodiment, in Formula (Vl), A is 8-membered ring -C(R4)(R5)-. In a specific embodiment, in Formula (VI), A is 8-membered ring -N(R6)-. In a particular embodiment, in Formula (Vl), A is 8-membered ring -N(C(Y)R7)-. In a specific embodiment, in Formula (VI), A is 8-membered ring / -N(C(Y)OR8)-. In a particular embodiment, in Formula (Vl), A is 8-membered ring -N(C(Y)N(R9)(R1G))-. In a specific embodiment, in Formula (Vl), A is 8-membered ring -C(0)-N(Ru)-. In a specific embodiment, in Formula (VI), A is 8-membered ring -N(Rn)-C(0)-. In a specific embodiment, in Formula (Vl), A is 8-membered ring -S(0)2-N(Rn)-. In a specific embodiment, in Formula (VI), A is 8-membered ring -N(Rn)-S(0)2-. In a specific embodiment, in Formula (VI), A is 8-membered ring -C(0)-0-. In a specific embodiment, in Formula (VI), A is 8-membered ring -O-C(O)-. In a specific embodiment, in Formula (VI), A is an 8-membered ring, and E is, and E is, and E is, and E is, and E is, and E is, and E is, And E is, and E is, and E is, and E is, and E is 135177 - 284 - 200922559 -0-N(R6)-. In a specific embodiment, in Formula (VI), A is 8-membered ring -N(R6)-0-. In a particular embodiment, in Formula (Vl), A is 8-membered ring -N(R6)-N(R12)-. In a specific embodiment, in Formula (VI), A is an 8-membered ring -N=N-. In a specific embodiment, in Formula (VI), A is 8-membered ring f, -C(R7)=N-. In a specific embodiment, in Formula (V), A is 8-membered ring -C(0)-C(R7)=N-. In a specific embodiment, in Formula (VI), A is an 8-membered ring -C(0)-N=N-. In a specific embodiment, in Formula (VI), A is 8-membered ring -0-C(Y)-N(Rn)-. In a specific embodiment, in Formula (VI), A is 8-membered ring \ -N(Rn)-C(Y)-0-. In a particular embodiment, in Formula (Vl), A is 8-membered ring -N(Rn)-C(Y)-N(R12)-. In a specific embodiment, in Formula (VI), A is 8-membered ring -C(Y)-N(Rn)-0-. In a particular embodiment, in Formula (Vl), A is 8-membered ring -C(Y)-N(Rn)-N(R12)-. In a specific embodiment, in Formula (VI), A is an 8-membered ring, and E is, and E is, and E is, and E is, and E is, and E is, and E is ' And E is, and E is, and E is, and E is, and E is 135177 - 285 - 200922559 -0-N(Rn)-C(Y)-. A is an 8-membered ring and E is in a particular embodiment, in the formula (VI) -N(R12)-N(RU)-C(Y)-. B is a partially unsaturated alicyclic ring. In one embodiment, a ring of formula (VI) is unsubstituted. B is a partially unsaturated alicyclic ring, in a particular embodiment, wherein the family ring is substituted with one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of dentate, _CN, _N02, phenotype, minus group, dentate group, county, halkenyl group, alkynyl group, halogen block group, aryl group, heteroaryl group, aryl group-alkyl group, heteroaryl group-alkyl group... ring 垸, cycloalkenyl, heterocycloalkyl, heterocyclic, azide, _0R19, _〇c(())〇r20, _nr21r22, -nr-s〇2r- . -NR-C(〇)〇 R2〇, -nr23C(〇)r24 ^ , s〇2Nr25r26 ^ -C(0)R24, _C(〇)〇R2G, _SR19, _s(〇)Rl9, R19, 浑24, -C(〇)NR^ R^. -NR23C(N-CN)NR^R26^, nr23c(〇)Nr25r26 o In a specific embodiment 'in formula (VI), B is a partially unsaturated heterocyclic ring' Replaced. In a specific embodiment, 'in formula (10), B is a partially unsaturated heterocyclic ring which is substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of alizarin, , ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, , cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocycloalkenyl, azido, _0Rl9, _〇C(〇)〇R20, Nr21r22, nr23s〇2R24, -NR^C(0)〇R2〇 _NR2 3C(〇)R2 4 , -S〇2NR2 5R26 , _C(〇)r24 . -c(9)(10). , ···9, _S_ 9, _S〇2Rl 9, 〇〇c(〇)R24 (10)nr25r26, 135177 -286- 200922559 -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In a particular embodiment, in formula (VI), hydrazine R is an unsubstituted aryl group. In a particular embodiment, in Formula (VI), A + κ is an unsubstituted phenyl group. In a particular embodiment, in Formula (Vl), R is an unsubstituted thiol group. In a specific embodiment, 'in the formula (VI), R is a substituted aryl group. In one embodiment, in the formula (VI), pl is inferior R R is a substituted phenyl group. In a specific embodiment, in the formula (VI), the formula r R is a substituted fluorenyl group. In a particular embodiment 'in formula (VI), pl*R is aryl substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N02, alkyl, heteroalkyl, its pendant, alkenyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-院, cycloalkyl, cycloalkenyl, hetero (tetra), heterocycloalkenyl, azide, -OR" ' -0C(_2., -Nr2ir22, .NR23s〇2R24, nr23c(_2〇, -NR23C(0 ) R24, -S02NR25R26, -C(CT)R2 4 (U)R , -C(〇)〇R2〇, _SR19, -S(0)R19, -S02R19, -0C(0)R2 4, _a〇, UU)NR2 5R2 6 , _NR2 3C(N.CN). NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In the specific embodiment, in the formula (VI), R1 is - Or a plurality of phenyl groups which may be substituted by the same or different substituents, each substituent being independently selected from the group consisting of a lignin, -CN, -N〇2, an alkyl group, a heteroalkyl group, a "base group, a dilute group, a tooth thinner" Alkyl, alkynyl, alkynyl, aryl, heteroaryl, aryl-alkyl, heteroaryl _ 炫, ring county, ring m group, heterocycloalkenyl, 4 nitrogen, -OR19 -0C(0)0R2(), -NR2 丨R22, _ΝΚ2 3ςη NK S〇2R24, -NR23C(0)OR20, -NRnC(〇)R24, -S〇2NR25R26, _c(〇)r24, paste r2◦ , i9, , _GC(〇)R24, —(10)Nr25r26, _NR23C (N volumes 135177 -287- 200922559 NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6 . In the specific embodiment, in the formula (T'R is a stupid A substituted by one to four substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, 〇H 'CN '-N02 and -NR2iR22 n and lS-fired In a specific embodiment, in the formula (VI), a halogen group,

Halogen

NC, haloalkylalkyl,

Halogen base

R1 is selected from the group consisting of 02N and a halogen group.

Halogen group and

In the formula (VI), in the formula (VI), R1 is a substituted phenyl group. In the formula (VI), R1 is a substituted phenyl group. In one embodiment, R in formula (VI) is a stupid base that is taken up by two fluoro groups. ~ In a specific embodiment, the stupid base in formula (VI). ' V is replaced by a fluorine group

In a specific embodiment, in the formula (VI), R1 is: In the specific embodiment, in the formula (VI), R27 and R28 are each independently 135177-288-200922559 comprising an anthracene and an alkyl group. In a specific embodiment, in a specific embodiment of Formula (VI), in Formula (VI), in a specific embodiment, in Formula (VI), in a specific embodiment, In a specific embodiment of Formula (VI), in Formula (VI), in a specific embodiment, in Formula (VI), in a specific embodiment, in Formula (VI) In a specific embodiment, in a specific embodiment of formula (VI), in formula (VI), in a specific embodiment, in formula (VI), in a specific embodiment, (VI) In a specific embodiment, in a specific embodiment of formula (VI), in formula (VI), in a specific embodiment, in formula (VI) In an embodiment, in a particular embodiment of formula (VI), in formula (VI), in a particular embodiment, in formula (VI), in a particular embodiment, in formula (VI) In a particular embodiment, in Formula (VI), in a particular embodiment, in Formula (VI) (=0). In a particular embodiment, in Formula (VI), in a particular embodiment, in Formula (VI), R2 is -C(Z)R7. , R2 is -C(Z)NR9 R1 0. , R2 is -C(Z)OR8. , R2 is -S02NR9R10. , R2 is a burnt base. R2 is a heteroalkyl group. R2 is an aryl group. R2 is a heteroaryl group. R2 is a cycloalkyl group. R2 is a cycloalkenyl group. R2 is a heterocycloalkyl group. R2 is a heterocycloalkenyl group. Z is (=0). Z is (=S). Z is (=N(Ri3)). , Z is (=N(CN)). , Z is (=N(OR14)). ' Z is (=N(R15)(R16)). ' Z is (=C(R17)(R18)). , R2 is -C(Z)R7, and Z is , and R2 is -C(0)H. R2 is -C(O)alkyl. 135177 289 - 200922559 In a specific embodiment, in formula (VI), r2^c(q)ch3. In a specific embodiment, in the formula (νι)*, r2^c(〇)r7, wherein the R7 is an alkyl group substituted by one or more substituents which may be the same or different, each substituent being independently Selected from the group consisting of keto groups, ketones, _CN, -N 〇 2, alkyl groups, heteroalkyl groups, functional groups, dilute groups, dilute groups, alkynyl groups, aryl groups, aryl groups, heteroaryl groups, cycloalkyl groups , cycloaliphatic, heterocycloalkyl, heterocyclic, azide, acrocardium-OC (_2., 21R22, Nors 3s2R24, nr23c(〇)〇r2〇, -NR"C(〇) I^, S〇2Nr25r26, _c(〇)R24, c(〇)〇R2, such as 9, -s(〇)R-^-so2r19 . _0C(0)R24 . _C(0)nr25r26 ^ _NR23C(N_CN NR25R26&-NR2 3C(〇)nr25r26. In the specific embodiment, in the formula (VI), r2 is _C(〇)r7, wherein the R=: to three may be the same or different a substituent-substituted alkyl group, each substituent being independently selected from the group consisting of (IV) R19, collar 21r22, and cycloalkyl. In one embodiment, and 彳rvT, 丄Rm...), R, -C(0) R7, wherein the ,, ', 兀·" /, the alkyl group is substituted by an alkyl group and -OH. : ΓΤ Embodiment 10, in the formula (VI), r2 is -_7, The same or different substituted one groups are each independently selected from the group consisting of -0Η, ·ΝΗ2 and cyclopropyl. R7 is - to: in two cases 'in formula (VI) 'R2 is -C(〇)R7' Wherein the substituents are independently the same or different substituents, and each k includes -NH2 and a cyclopropyl group. In the case of an I# every #R7 is taken by -OH, and in the case of VI) wherein 'R2 is -C(〇)R7, wherein the 'form' is base. In the specific embodiment, in the formula (VI), R2 is _c(〇)r7, wherein the 135177-290-200922559 R7 Is a non-substituted heterocycloalkyl group. In a particular embodiment, in formula (VI), wherein R.sup.7 is a substituted heterocycloalkyl group. Or in a particular embodiment, In VI), 圮 is seven (seven) saponin 7, wherein ▲ R7 is a heterozygous group substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a dentate, and a _CN. , _N long = i group, miscible group, dentate group, alkenyl group, alkenyl group, alkynyl group, dentate group, aryl group, heteroaryl group, cycloalkyl group, cycloaliphatic group, heterocyclic group, hetero Ring-like, azide, -〇Ri9, _OC(0)OR2〇, Na 1r22, service 23 # 4, -nr "c_r2. , _nr23c(〇)r24, is the mail heart, -c(9)^, -C_R2, SRI 9, _S(0)R], S〇2Rl 9, 〇c(〇)r24, C(_25R26, -NR2 3 C(N -CN) NR2 5 R2 6 and -NR2 3 C(O) General 2 5 r2 6.

In a specific embodiment, in the formula (VI;), ???, WT ' R2 is -C(0)R7, wherein the R7 is selected from the group consisting of substituted hexahydropyridine, hydrazine, hydrazine Substituted hexahydropyridinium, substituted velocin, substituted tetrahydro-p-combination, and substituted one. In the embodiment (1), the r2 is selected from the group consisting of: and η3〆 〇II • c- , H3c〆 οII -- and R2 is -C(0)NR9R10. ' R2 is -c(o)nh2. 'R2 is -c(o)nr9r1() selected from an alkyl group. 'R2 is -c(o)nr9r10, which is selected from the group consisting of ruthenium and alkyl. In a specific embodiment, in a specific embodiment in the formula (\q) 'in the formula (VI), in a specific embodiment, in the formula (\q), R9 and R1 0 may be Or the same or different, each independently of a particular embodiment, wherein R9 is unsubstituted heterocycloalkyl in formula (Vj), and R1 〇135177 -291 - 200922559 is in a particular embodiment, In the formula (VI), R2 is -CCC^NR9!^ G, wherein R9 is a substituted heterocycloalkyl group, and R1Q is selected from the group consisting of ruthenium and alkyl. In a specific embodiment, in formula (VI), R2 is selected from the group consisting of alkyl, haloalkyl, heteroalkyl, heterohaloalkyl, -C(0)R7, -C(0)0R8 And -CCCONR9!^ Q. In a specific embodiment, in formula (VI), R2 is selected from the group consisting of:

135177 - 292 - 200922559 f Λ O' , . UNHHUN-. In the specific embodiment, in the formula (VI), _c(〇)nr9r1. The heterocyclic burned hydrocarbons which may be substituted with the same or different substituents are each independently selected from the group consisting of a fluorene group and the R10 group is selected from the group consisting of a ruthenium group and a ruthenium group. In a specific embodiment, in the formula (VI), R2 is ο r\

In 135177, in the specific embodiment, in the formula (VI), R2 is in the specific embodiment, in the formula (VI), R2 is in the specific embodiment, in the formula (VI) , R2 is γΛ^ΟΗ In the specific embodiment, in the formula (VI), r2 is Ί〇, —-specific f, and is produced in the formula (VI) l '. In the specific embodiment, in the formula (VI), R2 is 0. In the specific embodiment, in the formula (VI), the ruler 2 is \^^-<^ a table- item implementation In the example, in the formula (VI) Φ. , 卩 is 〇, and R3 is not named in the specific embodiment, in the formula (VI), ΤΕ ΤΕ ρ is 1. In the specific embodiment, in the formula (VI), a ts Ρ is 2 0 , and in the specific embodiment, Φ _ _ _ Ρ is 3 in the formula (VI). In the specific embodiment, in the formula (VI), Ρ is 4 〇

• 293 - 200922559 and at least two in one embodiment where a group R3 is attached to the same ring atom in formula (VI). In a specific embodiment, 'in formula (VI), also, P is 1, and r3 is selected from the group consisting of an alkyl group, a heterocyclic group, a dilute group, a heterofluorenyl group, an alkynyl group, and a hetero group. Alkyne, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocyclic dilute, dentate, -CN, -N〇2, -ORi 9, -OC(O)OR20, Marriage 2 t ^, tear 23 commit ^ -NR23C(〇)〇R2 0, _Nr23C(〇)r24, _ 2 , 2 KR ' -C(0)R2 4, -C(0)0R2. , -SR19, -S(0)R19, -SO# 9, _〇c 2 UU: 0) R2 4, _c(〇)Nr25r26, -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 6. In the specific embodiment, 'in the formula (VI),? Is 2, 3 or 4, and each W is independently selected from the group consisting of minus, (tetra), dilutyl, (tetra), alkynyl 'heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycle Alkyl group, heterozene group, halogen, _CN, _N〇2, _〇Rl9, _〇c(〇K)r2〇, HU & -NR23S〇2R24 . _NR23C(〇)〇R20 . ^ .s〇2Nr25r26 ^ -c(〇)R24. -C(〇)〇r2〇. .Sri9 . _S(0)r19 ^ s〇2Rl9 ^ _〇C(〇)r24 ^ -C(0)NR2 5 R2 6、_nr2 3 c(n_cn)nr2 5 r2 6 and _nr2 3 c(9)NR2 5 R2 6. In a particular embodiment, in Formula (VI), p is 2, 3 or 4, and at least two of the bases R3 are bonded to the same ring carbon atom, wherein each R3, which may be the same or different' Individually selected from the group consisting of alkyl, heteroalkyl, alkenyl, hetero, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl , halogen, _CN, _N〇2,_0R19, _〇c(〇)〇r20, _nr2]r22, -NR23S02R24, -NR23C(0)0R2Q, -NR23C(0)R24, -S02NR25R2 6, _c(〇)r24 , c(〇)〇r20, SRl9, s(〇)Rl9 s〇2R19, -〇C(0)R24, -c(o)nr25r26, -NR23C(N-CN)NR25R26&-NR23C(0)- 135177 -294- 200922559 nr25r26 In a particular embodiment, in formula (VI), P is 2'3 or 4, and at least two groups are bonded to the same ring carbon atom, wherein two (four) groups, The same or different, and the carbon atom to which they are attached may form a cycloalkyl group, a cycloaliphatic group, a heterocycloalkyl ring, and contain - to three heteroatoms selected from the group consisting of S and a heterocycloalkenyl group. The ring contains - to three heteroatoms selected from the group consisting of N, oxime and S. In the specific embodiment, 'in the formula (VI),? System > 〇, and each r3 is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, heteroalkenyl, _CN, _N〇2, _〇R]9'-〇C(〇)〇r2〇. Nr-r22 . .nr23S〇2R24 ^ _nr23c(〇)〇r20 ^ -NR23C(0)R2 4, _S〇2Nr25r26, c(〇)r24, c(5)R24, ((9)(10) 〇, SR, -S(0)R,- S02R19, _〇c(〇)r24, c(〇)nr25r26, wherein each of the alkyl groups, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently Or a plurality of substituents may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of a keto group, a dentate, a -CN, a -N〇2, an alkyl group, a heteroalkyl group, a haloalkyl group, an alkenyl group, an alkylene group. Alkyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _〇r19, 〇〇c(〇)〇r2 0, -NR2 1 R2 2, -NR2 3 S02 R2 4, _NR2 3 C(〇)〇R2 0, -NR2 3 C(0)R2 4, -S02NR25R26, -C(0)R24, _C(〇)〇 R2〇, _sri9, _s(〇)Rl9,

-S02R19 ' -0C(0)R24 ' -C(〇)NR25R26 > -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 Group R of 6 R2 6 In a specific embodiment, in the formula (VI), p is i, and R3 is selected from the group consisting of 135177-295 - 200922559, including a pyridyl group, a heteroalkyl group, an alkenyl group, and a heterofluorenyl group, wherein each of the alkyl groups The base group, each of the alkenyl groups and each of the heterogeneous groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of _ group, _ , -CN, -N02, alkyl, miscellaneous, south, base, dilute, dentate, silk, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl , heterocyclic dilute group, azide group, _〇R] 9, goods (_2〇, —ΝΜ22, 礼23岣R24, 33C_R2G, _Nr23c(〇)r24, -S〇2nr25r26, _C(0)R24, _c (〇) groups of 〇r2Q, 察19, _s_9, -s〇2R-^-0C(0)R-, -C(0)NR25r26, -nr23C(n_CN)nr25r26 and -NR23C(0)nr25r26. In a specific embodiment, in the formula (VI), p is 2, 3 or 4' and is bonded to any two of the same 3 bases -C(〇)- groups of the same atom. form

In a specific embodiment, any two of the same ring A atoms are 2, 3 or 4' and are combined with the K group and the other to form a spiro ring. The alkane counter contains - to three independently selected from the group consisting of: a group: a ring heteroatom of a ring and a heterocyclic ring of a snail (〇m from including a blessing, a tearing 6-, a _^(〇) 3 having - Three ring heteroatoms independently selected from the group consisting of a ring of v (〇)2- and -〇-, and a heterobicycloalkyl ring of the formula, containing - to::: field-forming cycloalkyl, cycloalkenyl , and -:, =:, ·,, -, -乂%; % base ring, containing one to 135177 •296- ί

200922559 Two independently selected from the group consisting of -ΝΗ-, -NR6-, -S-, ring heteroatoms. In a specific embodiment, in the formula (VI), in a specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), In the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), In the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), In the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in the specific embodiment, in the formula (VI), in a specific embodiment, in the formula (VI) in the specific embodiment, in the formula (VI), - specific implementation , In formula (VI), at - of a particular embodiment, in Formula (VI), 135] 77 ~ S (°) '' -S (0) 2-A-0- R3 is alkyl. R3 is a heteroalkyl group. R3 is an alkenyl group. R3 is a heteroalkenyl group. R3 is an alkynyl group. R3 is a heteroalkynyl group. R3 is an aryl group. R3 is a heteroaryl group. It is a ring-burning base. R3 is a cycloalkenyl group. R3 is a heterocycloalkyl group. R3 is a heterocycloalkenyl group. K3 is halogen. R3 is -CN. R is -N02. R3 is -OR1 9. R3 is -OC(0)OR20. R3 is -NR21R22. R3 is -NR23S02R24. R3 is -nr23c(o)or20. R3 is -nr23c(o)r24. R3 is -so2nr25r26. - 297 - 200922559 /" in a specific embodiment in a specific embodiment in a specific embodiment in a specific embodiment in a specific embodiment In a specific embodiment, in a specific embodiment, NR25R26 0 is in formula (VI) in formula (VI) in formula (VI) in formula (VI) in formula (VI). In the formula (VI), in the formula (VI), R3 in the formula (VI) is -c(o)r24. R3 is -C(s)R24. R3 is -c(o)or20. R3 is -SR1 9. R3 is -SCCOR19. R3 is -so2r19. R3 is -0C(0)R24. R3 is -c(o)nr25r26. In the formula (VI), R3 is _NR2 3C(N_CN)_ in the specific embodiment. In the formula (Vi), r3 is _nr23c(〇)_ nr25r26. In the specific embodiment, 'in the formula (VI), r3 is selected from the group consisting of methyl, ethyl, propyl (straight or branched), τ (straight or branched), fluorenyl (straight

135177 -298 - 200922559

H2n. In a particular embodiment, in Formula (IV), when E is -NR6-, it is absent. In a specific embodiment, formula (VI) has the following general structure:

In a specific embodiment, formula (VI) has the following general structure:

In a specific embodiment, formula (VI) has the general structure: R1 R R3 , wherein p is 0, 1, 2 or 3. In one embodiment, Formula (VI) has the following general structure: 135177 - 299 - 200922559

R3 , where p is 0, 1, 2 or 3 Formula (VI) has the following general structure:

In a specific embodiment, 28.27 R

Where ρ is 0, 1, 2 or 3. In a particular embodiment, the compounds of the invention have the structure shown in the table below and include pharmaceutically acceptable salts, solvates, esters, prodrugs or isomers of the compounds.

135177 - 300- 200922559

301 - 135177 200922559

- In other specific embodiments t, the present invention provides methods for the manufacture of the compounds described in the various embodiments of the above limbs, compositions or compositions comprising one or more such deltas, and treatment or prevention One or more methods associated with symptoms or diseases associated with actin activity, as detailed below. As used above and throughout this patent specification, the following terms, unless otherwise indicated, are intended to have the following meanings: The subject includes both mouth-to-mouth and non-mammalian animals. "Mammal" includes humans and other mammals. 135177 -302· 200922559 Substituted '-the word means to be on a given atom' or - a plurality of gas systems are replaced by a group selected from the indicated, provided that Will exceed the normal valence bond of the specified atom in the presence of, and this substitution will result in a stable compound. The combination of substituents and / or variables 'only allow for 5 noon in this combination will result in a stable compound. So-called I' The stability compound "or, stability structure" means that the compound is sufficiently robust to survive from the reaction mixture, is isolated to a useful purity, and formulated into an effective therapeutic agent. f ’ is replaced as appropriate, and the word “four” is replaced by the selection of a specific group, atomic group or partial basis. It should be noted that in the text, drawings, examples and tables herein, any atomic system having an unsatisfied valence bond is assumed to have a gas atom to satisfy the valence bond. Whether a term is used alone or in combination with other terms, the following definitions apply unless otherwise indicated. Therefore, the definition of "burning base" applies to "hospital base", as well as "hydroxyalkyl", "haloalkyl, I," alkoxy, etc., alkyl "part." A radical, meaning an aliphatic hydrocarbon radical, which may be straight or branched, and contains from about 1 to about 10 carbon atoms in the chain. Preferably, the alkyl group contains from about 1 to about 12 carbon atoms in the chain. More preferably, the alkyl group contains from about i to about 6 carbon atoms in the chain. Branched means that one or more lower alkyl groups, such as methyl, ethyl or propyl, are attached to a linear alkyl chain. "Lower alkyl" means a group having from about 丨 to about 6 carbon atoms in the chain which may be straight or branched. The "alkyl group can be unsubstituted or, as the case may be, substituted by one or more substituents as described herein. Non-limiting examples of suitable alkyl groups include methyl, ethyl, n-propyl, isopropyl and tri-butyl. "Alkyl" includes "alkylidene," which refers to a difunctional 135177-303.200922559 group obtained by the removal of a ruthenium atom by an alkyl group as defined above. Illustrative examples include methylene (-ch2-), hypoethyl (-ch2ch2-) and propylene (_c3H6_); which may be linear or branched. "Heteroalkyl" means an alkane as defined above a radical moiety having - or a plurality of deuterium atoms, such as one, two or three carbonogens +, replaced by one or more heteroatoms which may be the same or different, wherein the attachment points of the remainder of the molecule It is a carbon atom that passes through a miscellaneous group. Suitable such heteroatoms include (and S(〇), 5(0)2, etc.). Non-limiting examples include shouts, sulphur, amines, 2-aminoethyl, 2-dimethylaminoethyl, and the like. "Alkenyl" means an aliphatic hydrocarbon group containing at least one carbon-carbon double bond, and which may be straight-chain or branched, and contains from about 2 to about 15 carbon atoms in the chain. Having from about 2 to about 12 carbon atoms in the bond; and more preferably from about 2 to about 6 carbon atoms in the chain. Branched means a radical, such as methyl, ethyl or propyl, Attachment to the line (tetra)ylalkenyl means that about 2 to about 6 carbon atoms are attached thereto, which may be straight or branched. "alkenyl" may be unsubstituted or optionally substituted with one or more substituents as described herein. Non-limiting examples of suitable alkenyl groups include vinyl, propenyl, n-butenyl, 3-mercaptobut-2-enyl, n-nonenyl, octenyl and decenyl. "alkynyl'' means an aliphatic hydrocarbon group containing at least one carbon-carbon porphyrin and which may be straight or branched and comprising from about 2 to about 15 carbon atoms in the chain. Preferred alkynyl groups have from about 2 to about 2 carbon atoms in the chain; and more preferably from about 2 to about 4 carbon atoms are in the chain. Branched means that one or more lower alkyl groups, such as decyl, ethyl or propyl, are attached to a linear alkynyl chain. "Low-carbon block system means that about 2 to about 6 carbon atoms of the stomach are in this chain, which may be a direct bond or a branch of 135177 '304-200922559. Non-limiting examples of suitable alkynyl groups are available. · Methylbutyl group.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, An aromatic monocyclic or polycyclic ring system having from about 14 to about 1 carbon atoms, preferably from about 6 to about 1 carbon atoms. Aro: 3,; Both are the same or listed in this article, 荇基. Non-limiting examples of Tian Fangji include phenyl and "heteroaryl" systems, meaning aromatic monocyclic or polycyclic rings, and 1 comprises from about 5 to about (iv) ring atoms, preferably from about 5 to About a ring atom, one or one of the atoms is an element other than carbon, such as nitrogen, oxygen or sulfur. Preferred heteroaryl groups contain from about 5 to about 6 ring atoms. "Heteroaryl" is used interchangeably with a plurality of "ring system substituents" which may be the same or different and are as defined herein. Miscellaneous; the radical nitrogen, oxygen or sulfur in front of the root of the base of the square, to >, a gas, oxygen or sparse atom exists as a ring atom. Heteroatoms can be oxidized to their corresponding ruthenium-oxides as appropriate. A non-limiting example of a base, including a base, a base, a base, a base, and a ketone (including N-substituted oxime, iso-oxazolyl, isoxazolyl, carbazole) "Sedazolyl, pyrazolyl, furazolyl, pyrrolyl: pyrazolyl, triazolyl, oxadiazole, pyridinyl, tower spray, quinine cisplatin, blown base" ; No. ♦ 来基"米唾和[1,2-咖比 bite base, taste wow and [2J ship base, benzene bite 咕 base" 嶋, nitrogen ♦ base, benzene open base, stupid and 4 Base, «yl, (4)yl 4 phenocardyl, ... porphyrinyl "1 phenocardiyl" bis oxetylene, miso base, 135177 - 305 - 200922559 isoquinolinyl, benzodiazepine Sulfhydryl, 1,2,4-tri-grain, benzothiazolyl, etc., "heteroaryl" also refers to a partially saturated heteroaryl moiety, such as tetrahydroisoquinolinyl, tetra Hydroquinolyl or the like. '•Aralkyl" or "arylalkyl" means an aryl-alkyl group, wherein aryl f and an alkyl group are as described above. Preferred aralkyl groups Containing a lower alkyl group. Non-limiting examples of suitable aralkyl groups include benzyl, 2-phenylethyl and The aryl group is bonded to the parent moiety. The alkyl aryl group means an alkyl-aryl group, wherein the alkyl group and the aryl group are as described in the above. The aryl group contains a lower alkyl group. A non-limiting example of a suitable alkyl aryl group is a tolyl group. The bond to the parent moiety is via an aryl group. "Cyclodyl" a mono- or polycyclic ring system comprising from about 3 to about 10 hinder atoms, preferably from about 5 to about 1 G post atoms. Preferred cycloalkyl groups containing from about 5 to about 7 ring atoms The cycloalkyl group may be optionally substituted with one or more ring system substituents, which may be the same or different, and are as defined above. When non-limiting examples of monocyclic lysyl groups include cyclopropyl, Cyclodecyl, cyclohexyl, cycloheptyl, etc. Non-limiting examples of suitable polycyclic cyclic alkyl groups include 1-decahydronaphthyl, n-retinyl, gold-steel alkyl, etc. "" means a ring-forming moiety as defined above, linked to the parent core via a ketone moiety (defined above). Examples include cyclohexylmethyl, diamond (tetra)methyl, and the like. "Cycloalkenyl" means a non-aromatic mono or polycyclic ring system comprising from about 3 to about 10 carbon atoms, preferably about 5 to About 1 () carbon atoms containing at least one carbon-carbon double bond. Preferably, the cycloaliphatic ring contains from about 5 to about 7 ring atoms. 135177 -306- 200922559 The cycloalkenyl group may be - or more Or not @, and all are as m system substituents, substituting 'which can be a qualitative example, including a cyclopentyl group, a suitable monocyclic ring, a non-limiting, an indomethacin, a cycloheptane-1 , 3-dienyl and the like. Non-limiting, "cycloalkenyl fluorenyl", meaning as ± sb. From the base of the alkyl group (defined above), the = moiety of the moiety, the non-pp of the decane A, ’w - , '° to the parent core. Suitable cycloalkenes and the like: , '', including cyclopentenylmethyl, cyclohexenylmethyl chloride, bromine. Preferably, it is fluorine, chlorine and the like. "衣衣" is meant to be a substituent attached to a ring, a saturated or partially unsaturated, such as a helium or a heterocyclic system, for example: A carbon atom or a hetero atom substituent may be referred to as such, or may be a conjugate or a plurality of variable or specific functional Α ', , , , , , , ###% system, such as 'cutting Where is the towel me team", and R is a substituted heterocycloalkyl group, which is a ring system substituent. If two substituents of the $/worker group are defined, the m core/ring system substituent is present in In particular, %, upper, then such multiple f & / Zuo Ganzhi r" (iv) algebra can be linked to the same or different available n slaves or heteroatoms. The ring system takes , and the soils may be the same or different and are as described herein. Ring system substituents, alkenyl groups, block groups, aryl groups, hetero-, non-limiting examples thereof include calcination, arylalkyl, alkylaryl, heteroarylalkyl, heteroarylalkenyl, hetero Guan I #方土杂经院基,院氧,芳J heteroaryl, aryloxy, arylalkoxy, fluorenyl, aryl fluorenyl, nitro, cyano, carboxy, P ～ Base group, aromatic two =, aryloxy group, aryloxy sulfhydryl, heteroaryl sulfonyl, alkane 135177 -307. 200922559 Forms the following partial groups: Λ~〇 \Arylthio,heteroarylthio, arylsulfanyl, thiolthio, decyl, heteropoly, _C(=N_CN)_NH2, ((4) 顺顺2, ((=丽)视视(烧) Υ, Υ2Ν-, Υιγ2Ν_烧基·, YiY2Nc(〇)_, 丫1丫2 ship 2_ and %ΝΥΐ Υ2 'where Y】 and Y2 may be the same or different, and are independently selected from the group consisting of ί = aryl, aryl, aryl, and fang., ring system substituent ', also σ 单 卩 卩 , , , , , , , , , , 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换 置换On each of the carbons - a Η). Examples are methylenedioxy, hypoethylenedioxy, (called ^ Λ> u \ , eight)

α 1 knives, ”, 〇/V and #潍方k基(or,heteroaryl-alkyl), meaning heterozygous as defined above: radical moiety 'via alkyl moiety Linked to the parent core (as defined above). Non-limiting examples of suitable heteroaryl groups include 2-pyridyl oxime, 4-linylmethyl, and the like. "Heterocyclyl", (or, heterocyclic, phenyl), (4) aromatic saturated: 亀, which contains from about 3 to about 1 ring atoms, preferably about 5: : one: atom ... in the ring system - or a plurality of atoms other than carbon, such as murine, milk or sulfur, individually. In this ring system, no = oxygen and / or sulfur atoms are present. Preferably, the heterocyclic group contains about 5 To the suffix of the first nitrogen, oxygen or sulfur in front of the name of the heterocyclic base, it means that the murine and sulfonium atoms exist as ring atoms individually. Heterocyclic group #团^ = _ΝΗ Τ ^ ^ Α (4) ' _N (CBZ), the -N(Tos) base in 'this protection is also considered to be part of the invention. Heterocyclyl 135177 > 308- 200922559 σ depends on the condition - or multiple 'ring system substituents' Substituents, which may be the same or different and are as defined herein. The nitrogen or sulfur atom of the heterocyclic group may be divisible to its corresponding N-oxide, s-oxide or s,s-dioxide. Non-limiting examples of suitable monocyclic heterocyclyl rings include hexa-H, tetrahydropyrrolyl, Ahydropyridinyl, morpholinyl, thiomorpholine-based oxazolidine-oxygen-based Four gas Thiopyranyl, phenyl tetrachloro thinning, stretch four parks group, lactam, lactone, and the like. The kiln base also includes a ring in which the lanthanide is substituted for two available gases on the same carbon atom (i.e., the heterocyclic group includes a ring having several groups in the ring). An example of such a moiety is tetrahydropyrrolidone:

Miscellaneous by the base of the base '' (or ''heterocyclic base, or, 'heterocyclic base - yard base".) = said (four) alkyl group (defined above) linked to the parent Core properties ° Non-limiting '^ /, hydropyridylmethyl, hexahydropyrrylmethyl and the like of a suitable heterocyclic group. The cyclic alkenyl '. (or "heterocycloalkenyl group") means a non-aromatic monocyclic or poly-=, which contains from about 3 to about hexa, preferably from about 5 to about - 'wherein the ring system - or a plurality of atoms other than carbon, such as nitrogen, oxygen or sulfur atoms, alone or in combination, and which contain a carbon double bond or a charcoal-nitrogen double bond. No adjacent oxygen species are present. Preferably, the heterocyclenyl ring contains from about 5 to about 6 ring atoms 135177 -309- 200922559. The first nitrogen in the prefix of the heterocyclenyl root name is less than one nitrogen, oxygen or sulfur. The existence of an atom alone is a genus of the genus 'as defined above. The nitrogen-substituted substituent of a heterocycloalkenyl group'. The corresponding N-oxide, S-oxide or S,S-dioxide = heart Non-limiting examples of the formation of the base, including the like dilute 1,4-dihydrop than the bite, (9 q ^ wind p than mouth sulfhydryl, soil U, 3,6-tetrapyridinium, u, 5,6 _ Base, 3-dichloromentyl, 2_dichloromycoid;: broad-she, second, two gas, saliva, one 2-surgery, two-dip T-soil, carbazole, 4-- Prepare piperane, dihydrofuranyl, gas-milk, one...-alkenyl, dihydrogen furnace - its soil a thiol group, a 7-oxobicycloheptan-/L-local, a fluorenyl-thiopyranyl group, etc. a heterocycloalkenyl group, or a moiety (for example, a few groups), which simultaneously replaces the phase of the ring system 1: Two of them are available for chlorine. An example of such a group is four gas.

^, decenealkyl (or "heterocycloalkenylalkyl," or "heterocycloalkenyl-alkyl-") means a heterocyclic moiety as defined above, via a burnt moiety The group (defined above) is attached to the parent core. It should be understood that in the ring system containing a hetero atom of the present invention, no hydroxyl soil is on the carbon atom adjacent to N, 〇 or 5' and there is no N or $ The group is on the carbon adjacent to another hetero atom. Therefore, for example, in the following ring: 135177 -310- 4 200922559

N Η No-ΟΗ is directly attached to the carbons labeled 2 and 5. Also to be noted are 'tautomeric forms, such as the following partial groups: α Η and ν Λ;) Η In some embodiments of the invention, they are considered to be equivalent. ( '' fast-base group'' means an alkynyl-alkyl group, wherein the alkynyl group and the alkyl group are as described above. Preferred alkynylalkyl groups contain a lower alkynyl group and a lower alkyl group. The bond to the parent moiety is via an alkyl group. Non-limiting examples of suitable alkynylalkyl groups include propargylmethyl. '• Heteroarylalkyl" means heteroaryl-alkyl- a group wherein the heteroaryl group and the alkyl group are as described above. Preferably, the heteroaralkyl group contains a lower alkyl group. Non-limiting examples of suitable aralkyl groups include pyridylmethyl and quinoline groups. The bond to the parent moiety is through an alkyl group. The hydroxyalkyl group means a fluorenyl-alkyl group, wherein the alkyl group is as defined above. Preferred hydroxyalkyl group contains a lower alkylene group. Non-limiting examples of suitable hydroxyalkyl groups include hydroxyindenyl and 2-hydroxyethyl. ''Indolyl" means HC(0)-, alkyl-C(0)- or cycloalkyl a _c(〇)_ group in which the various groups are as described above. The bond to the parent moiety is a carbonyl group. Preferably, the fluorenyl group contains a lower alkyl group. Sexual examples 'including formazan,醯基和丙醯基。 "芳醯基" means an aryl-C(0)- group in which the aryl group is as described above. The bond to the parent moiety is via a carbonyl group. Non-盱 135177 200922559 Examples of suitable groups, including phenyl fluorenyl and 1-naphthyl fluorenyl. "alkoxy" means an alkyl-hydrazine- group, wherein the alkyl group is as described above Non-limiting examples of suitable alkoxy groups include decyloxy, ethoxy, n-propoxy, isopropoxy and n-butoxy. The bond to the parent moiety is via a bond oxygen. An aryloxy group is intended to mean an aryl-0- group in which the aryl group is as previously described. Non-limiting examples of suitable aryloxy groups include phenoxy and naphthyloxy groups. The bond of the group is ether oxygen. The aralkyloxy group means an aralkyl-0- group in which the aralkyl group is as described above. Non-limiting examples of suitable aralkyloxy groups include benzyloxy groups. And 1- or 2-methoxymethoxy. The bond to the parent moiety is via ether oxygen. "alkylthio" means an alkyl-S- group, wherein the alkyl group is as described above. Suitable alkylthio group Non-limiting examples include methylthio and ethylthio. The bond to the parent moiety is via sulfur. The π arylthio group means an aryl-S- group, wherein the aryl group is as previously described Non-limiting examples of suitable arylthio groups include phenylthio and decylthio. The bond to the parent moiety is via sulfur. "Aralkylthio" means aralkyl An -S- group in which the aralkyl group is as previously described. A non-limiting example of a suitable aralkylthio group is benzylthio. The bond to the parent moiety is via sulfur. "Alkylalkyl "Delay" means an alkyl-Si- group wherein the alkyl group is as defined above and the point of attachment to the parent moiety is on Si. Preferably, the alkylalkyl group contains a lower carbon group. An example of a base stone base is trimethyl sulfonate (-Si(CH3)3). 135177 -312- 200922559 " Alkoxycarbonyl '' is an alkyl-o-co- group. Non-limiting examples of suitable alkoxycarbonyl groups include methoxycarbonyl and ethoxycarbonyl. The bond to the parent moiety is passed through several groups. The π aryloxycarbonyl '' line means an aryl-o-c(o)- group. Non-limiting examples of suitable aryloxycarbonyl groups include phenoxycarbonyl and decyloxycarbonyl. The bond to the parent moiety is through the carbonyl group. "Aralkyloxycarbonyl" means an aralkyl-OC(O)- group. A non-limiting example of a suitable aralkoxycarbonyl group is a benzyloxycarbonyl group. The bond to the parent moiety is Carbonyl. "Alkylsulfonyl" means an alkyl-s(o2)- group. Preferred groups are those wherein the alkyl group is a lower alkyl group. The bond to the parent moiety is sulfonated. Indenyl. "Arylsulfonyl π is an aryl-s(o2)- group. The bond to the parent moiety is followed by a S-blue group. The term "substituted" means that one or more hydrogen systems on a given atom are replaced by a group selected from the indicated group, provided that the normal valence bond of the specified atom is not exceeded. And this substitution will result in a stable compound. The combination of substituents and/or variables can only be tolerated if such a combination would result in a stable compound. The so-called "stabilizing compound'' or "stabilizing structure" A compound that is sufficiently robust to remain in the reaction mixture, separated from useful purity, and formulated into an effective therapeutic agent. The term "as appropriate" is used to mean a specific or intended group, radical or moiety. Substituting for the choice of a group. The term "purified" or "in a purified form" or "in a purified form" means that the compound is in a self-synthesis or natural source or its 135177-313 - 200922559 The physical state after the combination of the individual. Therefore, the term "purified", "in purified form" or "in isolated and purified form" means that the compound is obtained from purification. Or the method described herein or the rear skilled conventional method like the technician physically bad, which system was sufficiently pure, it can be by the conventional or described herein the skilled technician characterizable by standard analytical techniques. It should also be noted that in the text, drawings, examples and tables herein, any carbon having a non-satisfied valence bond and a hetero atom are assumed to have a sufficient number of hydrogen atoms to satisfy the valence bond. When a functional group in a compound is referred to as "protected", this means that the group is in a modified form' to exclude unwanted side reactions at the protected position when the compound is subjected to the reaction. The appropriate protection base will be clarified by those skilled in the art and by reference to standard textbooks, such as τ. w. Gree^ et al., which became the squad of the squad (1991), Wiley, New York. When any variable (eg, aryl 'heterocycle, r2, etc.) occurs more than - in any composition or in any of the present invention, its definition at each occurrence is defined in each of its other occurrences. Nothing. - The term "composition" as used herein is intended to encompass a product comprising a particular component in a particular quantity, and any product that is formed, either directly or indirectly, in a specific combination. The term "pharmaceutical composition" is also intended to cover both the overall composition and the individual dosage unit 'which contains more than one (eg, two) pharmaceutically active agents, eg, one inventive compound and another agent 1 as described herein. Other rate agents:: ... with any pharmaceutically inactive excipients, each dosage unit may contain a fixed amount of the above-mentioned "medicine two 135177 -314 · 200922559 agent". The overall composition is a substance that has not been made into individual dosage units. Illustrative dosage units are oral dosage units such as tablets, pills, and the like. Similarly, the methods described herein for treating a patient by administering a pharmaceutical composition of the invention are also intended to encompass the administration of the foregoing integral compositions with individual dosage units. Prodrugs and solvates of the compounds of the invention are also intended to be encompassed herein. The discussion of prodrugs is provided in ΊΓ Higuchi and V. Stella, ## # #作4 #广#肩. Key (1987) ACS series 14 of the series, and in # # 设# f立立曲T inverse 痧(1987) edited by Edward B. Roche, American Medical Association and Pergamon Press. The term "prodrug" means a compound which is converted in vivo to produce a compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate of such a compound (e.g., a drug precursor). This transformation can occur by various mechanisms, such as by metabolic or chemical processes, such as hydrolysis in the blood. Discussion of the use of prodrugs by T. Higuchi and W. Stella, "Prodrugs as Novel Delivery Systems", Volume 14 of the ACS Collection, and Bioreversible Carriers in Drug Design, Edward B. Roche Edited by the American Medical Association and Pergamon Press, 1987. For example, if a compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate of such a compound contains a carboxylic acid functional group, the prodrug may comprise a hydrogen atom formed by replacing the acid group with a group. An ester such as an A-C8) alkyl group, 2) an alkyloxycarbonyl group, a 1-(alkyloxy)ethyl group having 4 to 9 carbon atoms, having 5 to 10 carbon atoms. 1-mercapto-1-(alkyloxy)-ethyl, alkoxycarbonyloxyindenyl having 3 to 6 carbon atoms, 1-(alkoxycarbonyloxy) having 4 to 7 carbon atoms Ethyl, 1-methyl-1-(alkoxycarbonyloxy)ethyl having 5 to 8 carbon atoms 135177 -315- 200922559, n-decyloxycarbonyl)-amine having 3 to 9 carbon atoms Methyl, i_(N_(alkoxycarbonyl)amino)ethyl, 4-mercapto, 4-crotonolide, butyrolactone, di-N'NA - having 4 to 10 carbon atoms C2) an amine group (q-c; 3) alkyl group (such as diammonium ethyl), an amine aryl-(cKC2) alkyl group, N, Nc (Ci_C2) alkylamine methyl ketone group _ ( Ci_c2) alkyl, and hexahydropyrrole. Indole-, tetrahydropyrrolo- or morpholine (c)-c^alkyl, etc. Similarly, if the compound of formula (I) contains an alcohol functional group, the prodrug can be substituted with the alcohol by a group Formed by a hydrogen atom, such as (C-C6) alkoxymethyl, -C6) alkoxy)ethyl, methyl-l-CA-c: 6) Ethyl, (qQ) alkoxycarbonyloxyindenyl, N-CC!-C6) alkoxycarbonylaminomethyl, sulphonyl, _C6)alkylhydrazine, decylamine (q-C4) An alkyl group, an aryl fluorenyl group and an amidino group or an amidoxime group, wherein each α-amine fluorenyl group is independently selected from naturally occurring L-amino acids, P(0)(0H) 2, 4 (0) (0 ((^ - C: 6) alkyl h or a glycosyl group (due to the removal of a hydroxyl group in the form of a fatty acid hemiacetal), etc.. If the compound of formula (1) incorporates an amine function The base drug can be formed by replacing a hydrogen atom in the amine group with a group such as R_carbonyl, R0-carbonyl, NRR'-carbonyl, wherein R and R' are each independently (Ci_Ci 〇)alkyl, (CVCy)cycloalkyl, benzyl or R-group is a native amine sulfhydryl or a natural a-amine sulfhydryl group , -CCOHXXOPY1 'where Υ1 is Η, -C6) alkyl or benzyl, -c(oy2)y3, where Y2 is (c] -C4), and γ3 is (c)_C6) alkyl, carboxyl ( C] -C6) alkyl, amine (Ci-Q) alkyl or mono-N- or di-anthracene, Ν-%-C6) acrylamino, -C(Y4)Y5 'where Y4 is Η Or fluorenyl, and γ5 is mono- or di-N, N-(C-C6) amphetamine-based phenanthrene, hexahydropyrene is more than 1-1 _ group or tetrahydro ρ ratio σ__1 135177 • 316- 200922559 based. One or more compounds of the invention may exist in unsolvated as well as solvated forms, with pharmaceutically acceptable solvents such as water, ethanol, and the like, and the invention is intended to include both solvated and unsolvated forms. The π solvate '' means the physical association of a compound of the invention with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In some cases, the solvate can be isolated, for example, when one or more solvent molecules are incorporated into the crystal lattice of the crystalline solid. "Solvate" encompasses both the solution phase and the solvable solvate. Non-limiting examples of suitable solvates include ethanolates, methanolates, and the like. "Hydrate" is a solvate wherein the solvent molecule is η2. One or more compounds of the invention may optionally be converted to a solvate. The preparation of the solvate is generally known. Thus, for example, M. Caira et al. , /. corpse > Sd ·, 93 (3), 601-611 (2004) describes the preparation of antifungal agents, fluconazole in ethyl acetate and solvates from water. A similar preparation of hemisolvates, hydrates, etc., is by E. C. van Tonder et al., AAPS P/iarmSdrec/i., 5(1), paper 12 (2004); and AL Bingham et al., C/ Zem. Co., 603-604 (2001). A typical non-limiting method involves dissolving a compound of the invention in a desired amount (organic or water or a mixture thereof) at a temperature above ambient temperature. The solution is allowed to cool at a rate sufficient to form crystallization and then isolated by standard methods. Analytical techniques, such as IR spectroscopy, show that the solvent (or water) is present in the crystal as a solvate (or hydrate). The compounds can form salts which are also within the scope of the invention. 135177 -317- 200922559 The reference to the compounds of the present invention is intended to include reference to the prion: it is indicated. As used herein, the term "salt" means the acid salt formed by or with an organic acid, and / ^ ^ ^ The intellectual salt formed by the heat engine and/or the organic base. Further, when the present invention contains a basic moiety, the %, if not limited to the heart or the sitting, and the acidic part A moiety, such as, but not limited to, a carboxylic acid, can form a zwitterion ("internal salt"), and is included in the "salt" used herein as a salt. Salts which are non-toxic, physiologically acceptable are preferred, but other salts may also be employed. Salts of the compounds of the invention may be formed, for example, by reacting a compound of the invention with a quantity of an acid or a base, such as an equivalent amount, in a medium such as a salt, or in an aqueous medium f, followed by It is dry for cold. Examples of acid addition salts, including acetate, ascorbate, benzoate, sulfonate, acid sulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, Oleate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, methanesulfonate, sulfonate, nitrate, oxalate, phosphate, C Acid salts, salicylates, succinates, sulfates, tartrates, thiocyanates, toluenesulfonates (also known as tosylate), and the like. Further, it is generally considered that an acid suitable for use in the formation of a pharmaceutically usable salt for a self-initiating pharmaceutical compound is, for example, by R Stahl et al., Camille G. (ed.) 艋#, 摩摩和厉遗. (2002) Zurich : Wiley-VCH S. Berge et al., ## 存学游办 (1977) 66(1) 1-19; P. Gould, M mM Μ ΨΜ //(1986) 33 201-217 ; Anderson et al, ##/6 Xue Shi # (1996), University Press, New York; and 135177-318-200922559 discussed in 襦龙# (Food and Drug Administration, Washington, DC on its website). The disclosures are hereby incorporated by reference. Examples of basic salts, including ammonium salts, alkali metal ruthenium, such as sodium, lithium and potassium salts, 'soil test metals', such as words and magnesium salts, with organic salts (such as organic amines) such as dicyclohexylamine a class, a third-butylamine, and a salt with an amino acid such as arginine, lysine, or the like. The nitrogen-containing group can be tetracyclized, such as a lower alkyl block (such as methyl, ethyl and butyl chloride, bromide and iodide), a dialkyl sulfate (such as dimethyl / Base, monoethyl and dibutyl sulfate), long chain halides (eg sulfhydryl, lauryl and stearyl chloride, bromide and broken), aryl halides (eg sulfhydryl and stupid) Bromide) and others. All such acid salt and base salts are intended to be pharmaceutically acceptable salts within the scope of the present invention' and for the purposes of the present invention, all acid and salt tests are considered equivalent to the free form of the corresponding compound. The pharmaceutically acceptable esters of the compounds of the present invention include the following groups: (1) carboxylic acid esters obtained by esterification of a hydroxyl group, wherein the carboxyl group of the ester group (the non-carbonyl moiety group of the acid moiety) It is selected from a linear or branched alkyl group (for example, an ethylene group, a n-propyl group, a tri-butyl group or a n-butyl group), an alkoxyalkyl group (for example, a methoxymethyl group), or an aralkyl group ( For example, benzyl), aryloxyalkyl (eg, phenoxyindenyl), aryl (eg, phenyl, optionally substituted with, for example, an oxo, alkyl or C! a-4 alkoxy or amine group); 2) a fatty acid ester such as a aryl-alkyl sulfonyl group (for example, methanesulfonyl); (3) an amino acid ester (for example, L-isochlorin or a L-iso-amine thiol group) (4) phosphonates, and (3) mono-, di- or triphosphates. Phosphates may further be, for example, Ci 2 sterol or a reactive derivative thereof or 2,3_di (C6 24) Mercaptoglyceride. 135177 -319- 200922559, sulphate, and its salts, solvates, esters and prodrugs, may exist in tautomeric forms (eg as guanamine or imine ether) . The presence of such tautomeric forms is intended to be encompassed herein, in part. The compounds of the formula (!) may contain asymmetry or a center of the palm, and thus exist in different stereoisomeric forms. All stereoisomers of the compound of formula 1: and mixtures thereof 'including racemic mixtures, which constitute the bruises of the present invention. This invention contains all geometric and positional isomers. ^: Compound of formula (1) A bond or a fused ring, both cis and trans-form, and a mixture 'is included within the scope of the invention. Diastereomeric mixtures can be based on physicochemical differences, It is known that the essence is classified by heat and, for example, by chromatography and/or fractional crystallization, and is classified as "the individual diastereomer. The palmomer isomer can be converted into a non-object by the palm: An enantiomeric mixture is isolated by means of a disk suitable for the optically active compound (for example, for a palmitic adjuvant such as palmitic alcohol or

Chlorination reaction, separation of diastereomers, and conversion of individual diastereomers (eg, k M ^ W _ into their corresponding pure palmomers. Some: 1 compound can also be An anisotropic isomer (for example, a substituted biaryl group) 'is considered to be one of the present inventions ^ ^ ^ ^ ^ Separation of the HPLC column. The dry isomer can also be used as a formula (I The compounds may also exist in different tautomeric forms, and all such: are included within the scope of the invention. Moreover, for example, all steel-based and di-(tetra)amine forms of the compound are included in the Compounds of the invention (including salts, solvates, vinegars of such compounds and 135177-320-200922559 prodrugs and salts, solvates and vinegars of prodrugs such as geometric isomers, optical isomerism (), etc., existed on the asymmetric carbon (IV) on the stereoisomer, H may exist in the absence of asymmetric carbon, or in the form of a rotating poison (the isomer and its diastereomeric form) Is intended to cover isomers in the home position (eg, a group and 3_咐: Within the dry perimeter, the compound is incorporated into a double bond or a conjugated ring, then cis is the right formula 1 and the imine is at t, and the (tetra) isomer of the compound may be, for example, in the form, or may be, for example, Mixing into a racemate, the selected stereoisomers are mixed. The invention is defined by his or other 1974 recommendations as defined by the terms vinegar &quot;, prodrugs&quot; </ br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br> The mode is the same as that described in the paper, except that it has an atomic mass, a tooth' or more atomic systems are atomically mass or mass number 2 miles different from what is usually found in nature. In the homo-octane, potted = sub-substitution. Can be incorporated into the isotope of the compounds of the present invention, such as a 35S, 18F and 36C1., , C, N, 18〇, 丨7〇, 3lp, 32p, 135177 021 200922559 Certain people identified by isotope

The identified one can be used in the formula = (for example, 3H and ! 4C ( (meaning 3h) and carbon _14 (in the sound and Ι or 组织 组织 tissue distribution detection. After preparation and detectable Isotope is particularly good, because it is easy to replace, can provide due to larger, isotope such as 氘 (meaning 2H) 乂 5 shot stability ^ t # (for example, increase in vivo half, into some treatment Benefits - in some cases may be preferred. / or reduce the amount of the agent), and therefore the compound of formula (1) can be used in a similar manner to the following formula and / or ^ - method is the appropriate isotope square - shell 1 kg of the procedure is not disclosed, the reagents for the identification thereof. ^ &quot;Reagents to replace the polymorphic form of the compound of the present invention which is not isotopically used, and the amount of the prodrug: the salt of the compound of the month Solvents [Embodiment] The formula "曰" is intended to be included in the present invention. Preparation Examples In general, the method of the invention of the γ 4 缂 method of the invention is based on various methods known to those skilled in the art. The method is as follows, for example, by the following figures and the methods outlined in the examples below. It should not be interpreted as limiting the scope of the disclosure. The alternative mechanism and similar structure Β ^ will be obvious to those skilled in the art. The exemplified ^ 化 σ 呈现 关于 EC EC EC EC EC EC EC EC EC EC EC EC EC It is expressed in terms of the following ranges:

A - ^ 500 nM

B - &gt; 500 nM

C - &gt; 500 nM to $ 1000 nM D - &gt; 1000 nM 1351^7 • 322- 200922559 The following abbreviations are used in the program and diagram ACN Acetonitrile AcOH Acetic acid Aq Aqueous solution BOC Third-butoxycarbonyl BOC-ON [2-(Third-butoxycarbonyloxyimino)-2-phenylacetonitrile] boc2o BOC anhydride C, Celsius, Cpd Compound CBZC1 Benzyl benzoate DCM Dichloromethane DEAD Azodicarboxylic acid diethyl Ester DIAD Diazodicarboxylate DIEA Diisopropylethylamine DMA Ν, Ν-dimercaptoacetamide DMAP il 4-Ν, Ν-diamidinopyridine DME Dimethoxyethane DMF Dimethyl decylamine DMSO Diterpenoid EDCI 1-(3-diodinopropyl)-3-ethylcarbodiimide hydrochloride El Electron ionization Eq Equivalent EtOAc Ethyl acetate EtOH Ethanol 135177 - 323 - 200922559 g 克h.hour]H proton HATU hexafluorophosphate, hydrazine, Ν', Ν'tetradecyl-0-(7-azabenzotriazol-1-yl)oxime Hex hexane HOBT 1 -Hydroxybenzotriazole HPLC High pressure liquid chromatography KSP transmission protein spindle protein LAH lithium aluminum hydride LDA lithium diisopropylamine LHMDS hexamethyl bismuth Amphoteric amine M molar concentration mmol millimole mCPBA m-gas peroxybenzoic acid Me thiol MeCN f i. MeOH acetonitrile sterol min min mg mg MHZ million hertz mL ml MPLC medium pressure liquid chromatography NMR NMR Resonance MS Mass Spectroscopy 135177 - 324- 200922559

NBS NIS NMM NMP ON PCC PTLC Pyr RT sgc tBOC TEA TFA THF TLC N-bromosuccinimide N-iodosuccinimide N-methylmorpholine 1-methyl-2-tetrahydrop ratio B Each of the helium chromic acid p-ingot preparation thin layer chromatography pyridine room temperature gel 60 chromatography third-butoxycarbonyl triethylamine trifluoroacetic acid tetrahydrofuran thin layer chromatography retention time example general figure 1:

135177 -325 200922559 r -i

Example 101: &amp;

Part A

Part B 101B

101C

101A

Part E

101 Part A: In a suspension of sodium hydride (800 mg, 20 mmol) in THF (3 mL), EtOAc (3 mL, EtOAc) Solution in (10 ml)' and the reaction mixture was stirred at room temperature for 1 hour. 1-Dihydrogen tea was added from a solution of 101A (2.92 g, 20 mmol) in THF (9 mL) and the reaction mixture was refluxed for 16 hr. The volatiles were removed in vacuo and the residue was redissolved in DCM and washed with water. Dehydrated and dried with magnesium sulfate, and purified by gradient elution (〇1%) to hexane/ethyl acetate to obtain the Z- and E-isomers of the compound (1.7 g '7.83 millimolar, 39%) eHPLC_MS tR=197 for 12 minutes (UV254 nm); for the mass of the formula C14H16〇2, calculated 2161, found LCMS 2171 (M+H). Part B: 135177 -326 - 200922559 isopropyl emulsified (2M, 6.94 ml, 13.9 mmol) was added dropwise to N,0-dimercaptohydroxylamine hydrochloride (677 mg, 6.94 mmol) at -20 C. The reaction mixture was incubated with compound 101B (1.0 g, 4.63 mmol) in THF (20 mL) over a period of 15 min, then allowed to react for 20 min. Quenched. Extracted with ethyl acetate, dehydrated and dried with sulfuric acid, concentrated, and purified by gradient chromatography (0 to 100%) with hexane/acetic acid to obtain Z- and E-forms of the compound. Structure (685 mg ' 2.96 mmol, 64%). HPLC-MS tR = 1.55-1.80 min (UV 254 mp); calcd for calc. C under the 'Ignition gasification town (2M '4.5 ml, 9.0 mmol) was added dropwise to 2,5-difluoro moth (1.1 ml, 9·〇 mmol) in THF (20 ml) In the stirred solution. The reaction mixture was cooked to _4 Torr. (:, and a solution of compound 101C (685 mg, 2.97 mmol) in THF (10 mL), warmed to room temperature and stirred for 16 hrs to afford compound 4 which was confirmed by LCMS analysis Adding a saturated ammonium chloride solution to quench the reaction mixture 'extracted with ethyl acetate vinegar', dehydrated and dried with sulfuric acid, concentrated, and subjected to flash chromatography (gradient elution (0 to 100%) hexane/acetic acid The ester was purified, and the mass of the Z- and E-isomer of the compound 101D (481 mg, 1.69 mmol, 57%) was determined by DHPLC-MStR=2.4-2Ph4 (UV254 i_)3HCi8Hi4F2 28284.1, found LCMS m/z 285.1 (M+H). Part D: 肼 肼 monohydrate (12 micrograms) in compound 101D (100 mg, 0.35 mmol) in 135177 • 327 · 200922559 solution in thF (2 ml) l, 〇 · 39 millimoles), and the reaction compound j in the microwave, heated under the boots for 2G minutes. Concentrate the reaction mixture 'and the sudden step of the stone layer of gelatin, the ladder is dissolved (0 to 1 〇 〇%) hexane/ethyl acetate purification to give compound 101E (45 mg, 〇15 mmol, 汜(6). HPLC-MS tR= 2.45 (UV25 4 nm); mass calculated for the formula c]8H]2f2N2 298.1, found value [CMS m/z 299.1 Part E: s s s s s s s s s s s s s s Beverage (14 μl, 0.2 mmol) and potassium carbonate 〇 4 mg, 〇ι mmol (in thf ml) = mix ^ ' at room temperature for 3 hours. The product formation was obtained by LCMS analysis. The reaction mixture was quenched by the addition of IN HCl, and then extracted with ethyl acetate. solid.

The IfL compound is synthesized using this program:

Compound ID Structure 0^· Correct Mass MS m/z (M++H) TR (minutes) EC50 (nM) 101 304.2 305.1 4.24 D 102 砸 '----- 340.1 341.1 4.33 D 135177 - 328 - 200922559

Example 201:

f

103 342.1 343.1 3.93 B 104 326.1 327.1 4.78 B 105 FN, N/ y 312.1 313.1 4.53 D 106 n^n Y~ 0 276.1 277.1 4.26 D 107 y 341.1 342.1 3.04 A Part A: Compound 101E (120 mg, 0.4 m) a mixture of 4-nitrophenyl chloroantimonate (242 mg, 1.2 mmol) and potassium carbonate (83 mg, 0.6 mmol) in THF (10 mL). hour. The product formation was analyzed by LCMS 135177 - 329 - 200922559 LCMS.益丄秘秘~ The reaction mixture is quenched by the addition of saturated NaHC〇3, dehydrated and dried with ethyl acetate, reduced by sorghum, and concentrated, Compound 201B, A Nian &amp;&amp; The crude was crude as an off-white solid. Zhengde (4) For the formula C24H17F2N3〇s, it has been estimated that Kabelli 4 has a value of 465·1 and found the value LCMS m/z 466.1 (M+H). Part B:

In a solution of the compound 2〇1B (18 mg, 〇. 〇 4 mmol) in DMF (1.5 mL), EtOAc (0.49 m), and the mixture minute. The reaction mixture was concentrated, and purified by preparative H. The following compounds were synthesized using this procedure:

Compound ID Structure correct mass MS m/z (M++H) TR (minutes) EC50 (nM) 201 HN 412.2 413.2 3.53 D 202 )=0 HN 414.2 415.2 3.11 D 203 &gt;=〇η2ν 343.1 344.1 3.48 D 135177 - 330- 200922559

204 )=0 ΗΝ ό \ 440.2 441.2 3.24 D 205 0 \ 454.2 455.2 3.27 D 206 '—·Ν \ 371.1 372.1 4.02 D 207 ί^8 h. ΗΝ \ 357.1 358.1 3.76 D 208 )=0 ΗΝ 0 456.2 457.2 3.12 D 209 )=0 ΗΝ B. 470.2 471.2 3.25 D 135177 -331 - 200922559

Part A: A mixture of compound 10 (〇·ΐ毫莫) 古—^) /5L DIEA (〇 2 莫耳) in police (2 ml), 16 small days at room temperature

Γ Formation system _ analysis confirmed. The reaction mixture was concentrated and purified by HPLC to give compound s as a white solid. Fine pre-column compound ^ is synthesized by this procedure: Compound ID &quot;^--- Structure correct mass MS m/z (M++H) TR (minutes) EC50 (_ 301 Μ 38U —-----1 — --- 135177 - 332- 200922559

v. 302 1 V/ΝΗϊ 385.2 303 i 384.2 304 365.1 305 Λί^ΝΗ! 369.2 306 c^rvP /^O^N 351.1 307 (^o&lt;P V ^ΝΗΐ 355.1 135177 333 · 200922559 Example 401:

Part A: 1-tetrahydrofurfurone (101A, 1.33 ml, 1 mmol), allyl alcohol (3.4 ml, 50 mmol), 2,2-dimethoxypropane (184) ML, 15 mmol, p-toluenesulfonic acid (345 mg, 2 mmol) and 3 molecular sieves (3 g) in toluene (15 liters), the reaction mixture that has been sealed in the schienk tube, Place in a 2〇〇C oil bath. The reaction mixture was stirred under 2 Torr for 15 hours and then cooled to room temperature. The reaction mixture was filtered through celite. The filtrate was concentrated. The residue was purified by column chromatography <RTI ID=0.0></RTI> to <RTI ID=0.0></RTI> </ RTI> </ RTI> </ RTI> <RTIgt; 1H NMR (400 MHz, CDC13) δ 8.04 (dd, J = 1.2, 7.6 Hz, 1H), 7.46 (dt, J = 1.6, 7.6 Hz, 1H), 7.30 (tt, J = 0.8, 7.6 Hz, 1H) , 7.23 (d, J = 8.0, 1H), 5.92-5.78 (m, 1H), 5.14-5.04 (m, 2H), 2.99 (dd, J = 4.8, 7.6 Hz, 2H), 2.80-2.72 (m, 1H), 2.60-2.50 (m, 1H), 2.32-2.20 (m, 2H), 1.92-1.80 (m, 1H). Part B: Compound 401B (46 mg '0.25 mmol), 2-acetylene The reaction mixture of 1,4-1,4-difluoro stupid (34 mg '0.25 mmol) and sodium tris-butoxide (38 mg, 〇 4 mmol) was stirred in tri-butanol (1 mL) . Column chromatography of the dissolving agent in hexane was used to obtain compound 401C (13 mg, 16% yield). HPLC-MS RT = 2.54 min, calc. for C2 </RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Add sulphuric acid (50 μl) to the solution in water (50 μl) while stirring. The reaction mixture was stirred in a microwave at 150 ° C for 15 minutes. The reaction mixture was concentrated. Column chromatography using 20% EtOAc in hexanes to afford compound 401D. HPLC-MS RT = 2.51 min, calcd for C2 </RTI> <RTI ID=0.0></RTI> </RTI> </RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; (0.1 ml) of the reaction mixture in acetic acid (0.5 ml) was stirred for 15 min. Purification using reverse phase HPLC, after lyophilization, gave compound 401 as the HCl salt. HPLC-MS RT = 6.54 min, calcd for </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; A solution of 9-BBN in THF (0.2 mL, 0.5 M) was added. The reaction mixture was stirred at room temperature for 2 hours. Then aqueous NaOH (1 mL, 1 M) and aqueous hydrogen peroxide (1 mL, 30%) were added. The reaction mixture was stirred at room temperature for 1 hour. Purification using reverse phase HPLC, after lyophilization, afforded compound 402 as the HCl salt. HPLC-MS RT= 5.66 min, 384.18 calcd for C23H24F2N202, found LCMS m/z 399.29 (M+H). 135177 - 335 - 200922559 Part F : Ancient = from Part E Compound 4〇2 Add 2 gas to the 2,6-dimethyl port and add 3 gas to the solution in DCM (〇5 ml) ((楗, 0.05 mmol). The reaction mixture was allowed to stand at room temperature for 2 hours: then the ammonia front in dioxane, 3 ml) was added. The reaction mixture was sealed in a schlenk tube and stirred at 58t: overnight. Purification by reverse phase HPLC was carried out, and after dried in the east, compound 4〇3 was obtained as a cation salt. Muscle c撼 RT - 3,89 knife clasp, pair ο: 23% 5? 2%. Mass calculated value 397 2〇, found Value LCMS m/z 398.23 (M+H). The following compounds were synthesized using this procedure:

Compound ID Structure Correct Mass MS m/z (M++H) TR (minutes) EC50 (nM) 401 ο human" 380.17 381.28 6.54 D 402 exhaust OH 398.18 399.29 5.66 D 403 νη2 397.20 398.23 3.89 D 135177 • 336- 200922559

2,3-Dihydro-1H-carboline-4-one (5〇iA, 1 g, 6.8 mmol) and DIEA (4 7 mL, 27 mmol) in DCM (3 mL) In the solution, chlorhexidine ia (2.8 ^: liter '20 mmol) was added. The reaction mixture was stirred at room temperature overnight then concentrated. The residue was purified by column chromatography. Dissolved with 20% EtOAc in hexanes to afford compound 5 EtOAc (1 585 g, 83% yield) as a yellow solid. 1H NMR (400 MHz, CDC13) 5 8.00 (dd, J = 1.2, 8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.54-7.48 (m, 1H), 7.44-7.32 (m, 5H), 7.21-7.16 (m, 1H), 5.29 (s, 2H), 4.23 (t, J = 6.4, 2H), 2.81-2.76 (m, 2H). Part B: 135177 - 337 - 200922559 501B (1.4 g, 5 mmol), allyl alcohol (L7 ml, 25 mmol), 2,2-methoxypropane (0.922 ml, 7,5 mmol), p-benzoquinone The reaction mixture of sulphate (172 mg, 1 mmol) and 3 molecular sieves (15 g) in xylene (5 ml) was charged into the schlenk tube. The scWenk tube was sealed and placed in a 200 C oil bath. The reaction mixture was mixed for 2 hours at 2, and then cooled to room temperature. The reaction mixture was filtered through celite. The filtrate was concentrated. The residue was purified by column chromatography. Dissolved in 12% EtOAc in hexanes to give compound 501 C as pale yellow oil (1 g, yield). iH NMR (400 MHz, CDC13) δ 8.04-7.98 (m, 1H), 7.84 (d, J = 8.8

Hz, 1H), 7.53-7.47 (m, 1H), 7.44-7.32 (m, 5H), 7.21-7.15 (m, 1H), 5.86-5.72 (m, 1H), 5.31 (d, J = 12 Hz, 1H), 5.26 (d, J = 12.4 Hz, 1H), 5.08 (d, J = 16.4 Hz, 1H), 5.07 (d, J = 10.8 Hz, 1H), 4.37 (dd, J = 4.0, 13.6 Hz, 1H), 3.85 (dd, J = 9.2, 13.6 Hz, 1H), 2.76-2.60 (m, 2H), 2.30-2.20 (m, 1H). Part C: Compound 501C (64.2 mg, 0.2 mmol) Add a solution of TBAF in THF with a solution of ((2,5-difluorophenyl)ethynyl)dimethyl decane (84 mg, 0.4 mmol) in THF (0.4 mL) (〇, 5 ml, 1 〇 M). The reaction mixture was stirred in a microwave <RTI ID=0.0></RTI> </RTI> <RTI ID=0.0></RTI> </RTI> MS RT = 2.10 min, mass calculated for C20H17F2 NO 325.1, found value LCMS 326 1 (M+H). Part D: Compound 501D in dioxane (0.5 ml) with water (1 〇〇 micro Sulfuric acid (100 μl) was added to the solution in liter while stirring. The reaction mixture was stirred in a wave of 135177 -338 · 200922559 for 30 minutes at 150 ° C. The reaction mixture was quenched with aqueous NaHCO 3 . The organic material was extracted with EtOAc (EtOAc). EtOAc (EtOAc) QoH! 7F2 NO mass calculated value 325.1, found LCMS m/z 326.1 (M+H). Part E: Compound 501E, DIEA (30 μL) and hydrazine monohydrochloride from Part D ( 10 mg) of the reaction mixture in EtOH (0.2 mL) in a microwave The mixture was stirred for 40 minutes at 140 ° C. The reaction mixture was quenched with EtOAc EtOAc EtOAc EtOAc. 9F2N3 mass calculated value 339.1, found LCMS m/z 340.1 (M+H). Part F: Gasified acetic acid (10 mg) was added to the solution of compound 501F in dioxane. Stir and then concentrate. Purify by reverse phase HPLC. After lyophilization, compound 501 is obtained as HCl salt. HPLC-MS RT = 3.62 </ br>, </ </ > Value 1^〇^ m/z 382.29 (M+H). Example 601:

Part A

Cbz Cbz 501B 601B

Cbz 601E 135177 339 - 200922559

Part A: Compound 501B (1.4 g, 5 mmol), allyl alcohol (1.7 ml, Molar), 2,2-dimethoxypropane (0.922 mL, 7.5 mmol) The reaction mixture of sulphuric acid (172 mg, 1 mmol) and 3A molecular sieve (1.5 g) in dioxane (5 ml) was loaded into the schlenk tube. The schlenk tube was sealed&apos; and placed in a 200 °C oil bath. The reaction mixture was taken off at 15 ° C for 15 °' and then cooled to room temperature. The reaction mixture was passed through diatomaceous earth. Concentrate the filtrate. The residue was purified by column chromatography. Compound 601B was obtained as a light yellow oil (10 g, 62% yield). 1 H NMR (400 MHz, CDC13) 5 8.04-7.98 (m, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.53-7.47 (m, 1H), 7.44-7.32 (m, 5H), 7.21-7.15 (m, 1H), 5,86-5.72 (m, 1H), 5.31 (d, J = 12 Hz, 1H), 5.26 (d, J = 12.4 Hz, 1H), 5.12-5.04 (m, 2H), 4.37 (dd, J = 4.0, 13.6 Hz, 1H), 3.85 (dd, J = 9.2, 13.6 Hz, 1H), 2.76-2.60 (m, 2H), 2.30-2.20 (m, 1H). Part B: At _78 C, the ozone was bubbled into a solution of compound 601B (94.5 mg, 〇 3 mmol) in DCM (5 mL) over 15 min. Then, diphenylphosphine (262 mg, 丨mmol) was added to the solution. The reaction mixture was allowed to warm to room temperature while stirring for 3 hours. The reaction mixture was concentrated. The residue 135177 - 340 · 200922559 was purified by flash chromatography eluting with 20% Et0Ac in hexane to afford compound 601 C (74 mg, 76% yield). 1 H NMR (400 MHz, CDC13) (5 9.80 (S, 1H), 7.99 (dd, J = 1.6, 7.6 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.55-7.49 (m, 1H), 7.44-7.32 (m, 5H), 7.19 (dt, J = 1.2, 7.6 Hz, 1H), 5.29 (s, 2H), 4.58 (dd, J = 4.8, 13.6 Hz, 1H), 3.74 (dd , J = 11.2, 13.2 Hz, 1H), 3.34-3.26 (m, 1H), 2.99 (ddd, J = 0.8, 5.2, 18.4 Hz, 1H), 2.66 (dd, J = 7.2, 18.4 Hz, 1H). Part C: In a mixture of compound 601C (780 mg, 2.4 mmol) and powdered 4A molecular sieve (2.77 g) in gas (11 ml) at 〇 ° C, add 芊月女 (553 Microliter ' 2.88 mmol.) The reaction mixture was mixed for 2 hours, then filtered to remove the molecular sieve. Add sodium triethoxysulfonate borohydride (61 在 in a filtrate solution in chloroform at room temperature) The reaction mixture was stirred at room temperature for 1 hour, then the reaction was quenched with aqueous solution of Ha (1 Torr). Then the mixture was purified by aqueous NaOH. The organic layer was combined and concentrated. The residue was purified by flash chromatography using 10% EtOAc. The lysing agent in the alkane was purified to give compound 601D (800 mg, 66% yield) as a yellow gel. 1H NMR (400 MHz, CDCI3) 5 7.97 (dd, J = 1.6, 8.0 Hz, 1H), 7.83 ( d, J = 8.4 Hz, 1H), 7-51-7.45 (m, 1H), 7.40-7.12 (m, 16H), 5.24 (d, J = 12 Hz, 1H), 5.18 (d, J = 12.4 Hz , 1H), 4.03 (dd, J = 4.0, 14 Hz, 1H), 3.65 (d, J = 13.2 Hz, 2H), 3.63 (dd, J = 8.4, 13.6 Hz, 1H), 3.42 (d, J = 13.2 Hz, 2H), 2.84-2.72 (m, 1H), 2-61-2.45 (m, 2H), 2.08-1.98 (m, 1H), 1.64-1.52 (m, 1H). Part D : 135177 - 341 · 200922559 Add Petasis Reagent in Toluene (5 wt% '3 mL, 0.75 Mauer) in a vial containing Compound 601D (75.6 mg, 0.15 mmol) under argon atmosphere. The reaction mixture was taken up in toluene in the dark at 7 Torr. Stir the underarms for 4 hours. The reaction mixture was quenched with a mixture of Et EtOAc and EtOAc (1) and then concentrated. The residue was purified by flash chromatography eluting elut elut elut elut elut elut elut lH NMR (4〇〇MHz, CDCl3) accounted for 7 66 (9)=8 〇Hz, iH), 7.50 (dd, J = ι·6, 8.4 Hz, 1H), 7.31-7.10 (m, 16H), 6.99-6.93 (m,1H), 5.38 (s, 1H), 5.12 (d, J = 12.4 Hz, 1H), 5.06 (d, J = 12.8 Hz, 1H), 4.60 (s, 1H), 3.82 (dd, J = 4.0, 13.2 Hz, 1H), 3.48 (d, J = 13.6 Hz, 2H), 3.36 (d, J = 13.6

Hz, 2H), 3.28 (dd, J = 3.2, 13.2 Hz, 1H), 2.72-2.64 (m, 1H), 2.45-2.32 (m, 2H), 1.54-1.46 (m, 2H). Part E: A mixture of geminyl monohydrochloride (0.8 g, 5 mmol) and sodium hydroxide (6 g, EtOAc) in THF (5 mL) was stirred at room temperature overnight. Transition reaction mixture. To the filtrate, 2,5-difluorobenzaldehyde (6 〇 ijr, 0.71 g '5 ^: mole) was added. The reaction mixture was stirred overnight at room temperature and then condensed to give compound 601G. HPLC-MS RT = 2.23 min, for

Mass calculated for Cl 4Hi 2p 2 N 2 246·1, found LCMS m/z 247.2 ( Μ + Η). Part F: in 601 EtOAc ( EtOAc EtOAc 'Addition of N-chlorosuccinimide (334 mg, 2.5 mmol). The reaction mixture was stirred at 60 ° C for 3 hours and then concentrated. The residue was purified by flash chromatography eluting elut elut elut elut elut elut elut elut 1 H NMR (400 MHz, CDC13) 5 7.40-7.28 (m, 6H), 7.10-6.95 (m, 2H), 6.31 (br s, 1H), 4.57 (s, 2H). Part G: in compound 601E (20 mg, 0.04 mmol) and 601H (11.2 mg, 0.04 mmol) in chloroform (1 mL), triethylamine (27.8 liters, 0.2 mmol). The reaction mixture was stirred at 6 CTC overnight then concentrated. The residue was purified by flash chromatography eluting with EtOAc EtOAc HPLC-MS RT = 2.37 min, calculated for mass C.sub.4H44F2N402, 746.3, found LCMS m/z 747.2 (M+H). Part Η : at 40 ° C and 40 bar Η 2 pressure, 0.4 A solution of compound 6011 (15 mg, 0.02 mmol) in MeOH / EtOAc (4 mL, 1 / 1) was passed through a pad of 10% palladium / carbon in H-cube. Purification by reverse phase HPLC, after lyophilization, gave compound 601 as the HCl salt. HPLC-MS RT = 4.60 min, calcd. for C26H26F2N4, 432.21. Found: LCMS m/z 433.22 (M+H). The following compounds were synthesized using this procedure:

135177 - 343 - 200922559 Example 701:

Part A: The Wittig salt (triphenylphosphonium bromide, 2.0 equivalents, 0.420 mmol, 150 mg) was weighed into a round bottom flask equipped with a stir bar. The flask was evacuated, f was scrubbed with N2 (gas) and sealed with a septum. Anhydrous THF (2 mL) was added and the solution was cooled to -78 &lt;RTI ID=0.0&gt;&gt;&gt; The ice bath was removed and the reaction was allowed to warm for 15 minutes (to about -25 °C). The reaction vessel was again cooled to -78 ° C and a commercially available 2-mercapto-2,3-dihydroisoquinoline-4(1H)-one solution (701A, 1.0 eq., 0.210 mmol) was added. Ear, 50 mg, in 2 ml of THF). The reaction was allowed to proceed for 15 hours and warmed. After a period of time, the reaction was quenched with EtOAc EtOAc EtOAc EtOAc EtOAc . HPLC-MS RT = 1.034 min (5 min), calc. calcd. </RTI> </RTI> </RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; 7.42-7.20 (6H, m), 6.96 (1H, m), 6.76 (1H, d), 5.56 (1H, s), 4.90 (1H, s), 3.68 (2H, s), 3.62 (2H, s) , 3.64 (2H, s). Part B: 2-Mercapto-4-indenyl-1,2,3,4-tetrahydroisoquinoline (Compound 701B, 1.0 eq, 0.076 mmol, 18 (m) and gasification (Z)-N'_Yuyl-2,5-difluorobenzil 135177-344- 200922559 肼醯 (601H, 43 mg, 0.153 mmol, 2.0 eq.) is reset to 20 In a small glass vial, dissolved in anhydrous CHC13 (1 mL). Triethylamine (5. 〇 equivalent, 0.380 mmol, 50 μl) was added, and the vial was degassed with N 2 (gas), sealed with a cap, and heated to 70 ° C for 18 hours. After this period of time, all volatiles were removed under reduced pressure and the residue was dissolved in DMS / acetonitrile (3: 1). The residue was purified using reverse phase HPLC to afford product 701. HPLC-MS RT = 5.801 min (10 min method), for C3, H2 7 F2 N3 calc. 479.2 s, found LCMS m/z 480.2 s (M+H). Pharmacological properties of the compounds of the invention, including The efficacy as an inhibitor of KSP activity can be confirmed by a number of pharmacological tests. The inhibitory activity of the compounds of the invention against KSP can be detected by methods known in the art, for example, using the methods described below and in the examples above. KSP Biochemical Detection KSP Biochemical Enzyme Detection was performed in a 384-well plate. Allow all reagents to melt on ice. The compound was diluted to the desired concentration in 100% DMS. 10 mg of microtubes (Cytoskeleton) in 10 ml of tubulin buffer (80 mM PIPES pH 6.8, 1 mM EGTA, 1 mM MgCl2, 0.005% sodium azide) plus 100 μl 2 mM Petri Rematched in paclitaxel (Cytoskeleton). Each reaction system contains 10 nM KSP delivery functional sites (amino acid 15-368), 20 paclitaxel (Cytoskeleton), 0.18 //M microtubes, 100 μM ATP (Roche) and teleporter Buffer (20 mM ACES pH 7.0, 1 mM EGTA, 1 mM MgCl2, 25 mM KC1, 1 mM DTT). For each reaction, a 19 microliter mixture containing the KSP delivery functional site, paclitaxel, microtubules, and a transporter buffer was combined with 1 microliter of the diluted compound. Reaction 135177 - 345 - 200922559 begins by adding 5 microliters of ATP. This reaction was allowed to proceed at room temperature for 1 hour. The reaction was stopped by the addition of 50 microliters of Biomol Green (Biomol International). After another 30 minutes, the absorbance at OD620 nm was measured using Envision. IC50 determination: The dose-response curve is an 8-point serial dilution of the self-inhibiting compound, plotted against inhibition data generated by each replicate. The concentration of the compound was plotted against kinase activity (OD reading). To generate IC50 values, the dose-response curve was then fitted to a standard sigmoidal curve and IC50 values were derived by nonlinear regression analysis. KSP cell assay: HCT116 colon cancer cell line was grown in DMEM·· F12 medium with 10% heat-inactivated FBS at 37° C. and 5% C02. Cells were plated in PDL coated 384-well tissue culture plates at 7,500 cells per well. After 6 hours, the medium was removed and a novel medium containing the drug was added. The cells were incubated with the drug for 16 hours. All other steps were carried out in the dark at room temperature. The cells were fixed with 25 μl/well of Prefer fixative plus 250 nM Hoechst dye and incubated for 30 minutes. The fixative solution was removed and the cells were washed with PBS. Then, the cells were permeabilized with 25 μl/well of 0.2% Triton-X in PBS, and cultured for 10 minutes. The cells were washed with PBS, followed by incubation with 25 μl/well PBS containing 3% FBS for 30 minutes. Cells were then stained overnight at 4 degrees with 25 microliters per well of antibody solution in PBS plus 3% FBS. The antibody used was a Phos-tissue protein H3 (serlO)-Alexa Flur 488 vehicle and Phos-MPM2 Texas Red. The cells were washed with PBS, and then immunofluorescence images were taken with an HT route microscope. Calculate the cell staining positive 135177 - 346 - 200922559 Knife ratio and test the EQ of the compound of the invention. Values were determined using (iv) XLfit. EC50 is set: the Qi1 quantity-response curve is the 8th point of the self-inhibiting compound. The dilution data is plotted against the inhibition data generated by each repetition. The concentration of the compound = one per activity (0D reading) was taken as _. To generate the EC% value, the dose-response curve is then fitted to the standard s-curve curve and the EC50 value is derived by nonlinear regression. r Examples of the above cell test The compounds of the present invention show EC50 values reported in the ranges in the above table. Method of Use As an inhibitor of coffee activity, the compound of the present invention (4) can be used to treat a wide variety of diseases, symptoms or conditions (&&quot;disease&quot;). In a specific embodiment, the invention provides a method of inhibiting KSP transmission activity in a subject (eg, a cell, an animal, or a human), comprising: administering to the patient at least one compound of the invention Or a composition, or a salt, an ester, an isomer, a tautomer or a prodrug. In a specific embodiment, the invention provides a method of selectively inhibiting just == in a sputum cell, animal or human) comprising administering to the patient at least one compound or composition of the invention, or A pharmaceutically acceptable salt, vinegar, isomer, tautomer or prodrug thereof. ,. In some embodiments, diseases that are susceptible to treatment include those that are susceptible to mitosis by inhibition of KSP activity. As is well known in the art 135177-347- 200922559, it is clear that mitosis can be altered in a number of ways, such as by the activity of a component in the mitotic pathway, or by scrambling: (for example by inhibiting or activating certain components). In the specific embodiment, the present invention provides a method for treating or preventing a disease associated with KSP activity in a need, wherein the patient administers at least one of a therapeutically effective amount Inventive Compound U A pharmaceutically acceptable salt or ester. The compounds of the present invention can be used to inhibit the formation of mitotic spindles, thus resulting in prolonged cell cycle in mitosis. , off (four), "inhibition" means to reduce (four) mitotic spinning: red formation, or cause mitotic spindle dysfunction. The "mitotic spindle formation" means that the microtubule II is composed of a mitotic transducer and constitutes a two-pole structure. "Wired, split-spinning dysfunction" means #mitosis suppression and monopolar spindle formation. In a particular embodiment, the compounds of the invention are useful for binding to and/or inhibiting the activity of KSP. In a specific embodiment, the Ksp is a human Ksp. In a particular embodiment, such KSP activity is inhibited in vitro, in vivo (e.g., in a patient in need thereof), or from a living organism. In other embodiments, the compounds of the invention may be used to bind to or inhibit the activity of KSP transmission from non-human organisms. In this regard, suppressing the π system means increasing or decreasing the pole separation of the spindle, resulting in a deformed pole of the mitotic spinning bell, meaning to expand outward or cause morphological disturbance of the mitotic spindle. For the purposes of the present invention, those also included within the definition of KSP are the 'cross-types and/or fragments of 135177-348 - 200922559 KSP (see, e.g., U.S. Patent 6,437,115). The hairy month can be used to treat diseases associated with or caused by cell proliferation. Such disease states include, but are not limited to, cancer (advancement: below), hyperplasia, cardiac hypertrophy, autoimmune disease, fungal disease, off-fire, graft rejection, inflammatory bowel disease, immune disease, inflammation, : course of treatment: cell proliferation caused by after, including but not limited to surgery, vascular w-shaped surgery. Treatment includes inhibition of cell proliferation. It should be understood that in this case, the cells may not be in an abnormally proliferative state and still require treatment. For example, during wound healing, cells may be in a "normal condition" hyperplasia, but may require inhibition of cell proliferation. Thus, in a particular embodiment, the invention herein includes administration to a cell or suffering from any of these A patient with a symptom, disorder, or condition, or a patient who is imminent with the condition, disorder, or condition. The term "treatment of cancer" and "the treatment of cancer" refers to the administration of a mammal that is suffering from cancer, and the county borrows It kills at least some cancer cells to alleviate the effects of cancer and causes inhibition of cancer growth and/or metastasis.

Due to their KSP inhibition, the compounds, compositions and methods provided herein are useful in the treatment of a wide variety of cancers. Non-limiting examples of such cancers include solid, 3⁄4 tumors and hematological cancers/symptoms such as skin, breast, brain, colon, gallbladder, thyroid gland, ? Cervical cancer, test pills and cancer of the blood. Other non-limiting examples of cancers suitable for use in therapy include: Heart: sarcoma (vascular aneurysm, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyomas, fibroids, lipoma, and teratogenesis; lungs: branches Endotracheal carcinoma (squamous cells, unidentified small cells, unidentified large cells, adenocarcinoma), lung cells (tuber tracheal) cancer, branch tracheal adenoma, sarcoma 'leaf 135177 • 349· 200922559 Baria, chondroma defects Tumor, mesothelioma; Tian gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma 'lymphoma), ® (cancer lymphoma, leiomyosarcoma), pancreas (tubal adenocarcinoma, yueji adenoma, Yidao Tumor pancreatic hypoglycemia, gastric pancreatic tumor 'light cancer tumor, snake tumor, small intestine (-adenocarcinoma, lymphoma, mild cancer, Karp〇si sarcoma, leiomyoma, hemangioma, lipoma, nerve fiber) Tumor, fibroid), large intestine (adenocarcinoma, tubular adenoma, villus adenoma, defective tumor, leiomyomas); [urinary genital tract: kidney (adenocarcinoma, m-cell tumor (neuroblastoma), lymphoma Leukemia), bladder and urethra Squamous cell carcinoma, metastatic cell carcinoma, adenocarcinoma), 4 glands (adenocarcinoma, sarcoma), testicular pills (sperm cell tumor, teratogenesis, embryonal cancer, teratocarcinoma, choriocarcinoma D, sarcoma, interstitial cells) Tumor, fibroid, fibroadenoma, adenoma, lipoma); Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatic blastoma, angiosarcoma, hepatocellular adenoma, hemangioma; bone: Osteosarcoma (osteosarcoma), fibrosarcoma, malignant fibrous group (lymoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (net cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondral Fibroids (cartilage exogenous osteophytes), benign chondromas, cartilage, chondral mucinous fibroids, osteoid osteoma and giant cell tumors; nervous system: skull (osteoma, hemangioma 'granuloma, yellow tumor, deformation Osteitis), meninges (meningioma, meningioma, glioma), brain (astrocytoma, blastocytoma, glioma, ependymoma, brain tumor (pine adenoma) Polymorphic nerve Maternal blastoma, dendritic glioma, schwannomas, retinoblastoma, congenital tumors, spinal nerve fibers 135177 - 350- 200922559 Tumor, meningioma, glioma, sarcoma; Gynecology: uterus (uterus) Endometrial cancer), cervix (cervical cancer, anterior cervical dysplasia), ovary (ovarian cancer (serosal adenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-envelope cell tumor , Sertoli_Leydig cell tumor, malignant embryonal tumor malignant teratogenesis, female genital (squamous cell carcinoma, intraepithelial neoplasia, adenocarcinoma, fibrosarcoma, melanoma), vaginal (clear cell carcinoma, squamous cell carcinoma, grape-like) Sarcoma (embryo rhabdomyosarcoma), fallopian tube (cancer); Hematology: blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, acute and chronic lymphocytic leukemia, myeloproliferative disease, multiple myeloma' spinal cord Dysplasia syndrome, Hodgkin's disease, Hodgkin's lymphoma (malignant lymphoma), &amp; cell lymphoma Τ-cell lymphoma, hairy cell lymphoma, Burkett's lymphoma, pre-myeloid cell white jk disease; skin. malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karp〇si (: sarcoma, dysplasia black *, lipoma, hemangioma, cutaneous fibroma, ovarian tumor, psoriasis; adrenal gland neuroblastoma; and other tumors: including skin coloration, horny acanthoma and squamous cell carcinoma. Tian Fang, as used herein, includes treatment of cancer cells, including cells that are ready to be in any of the above symptoms, conditions, or conditions. The compounds of the invention are also useful in the chemoprevention of cancer. Chemoprevention is defined as the inhibition of the development of invading cancer by either blocking the initiation of a contingency event or by blocking the progression of malignant progenitors that have been attacked. 135177 -351- 200922559 The compounds of the invention are also useful for inhibiting cancer recurrence.

The compounds of the invention may also be used in &amp; I, x to inhibit tumor angiogenesis and spine shoots. The compounds of the present invention are also useful as antifungal agents, and the fungal member activity of the di-C transmission subgroup is 疋 modulation 6,284,480. The invention is described in the above-mentioned specific examples, and the amount administered is preferably an effective amount for the purpose of the present invention to mean the use of the present invention. The wording "effective amount" is known as the beta-chemical substance and other amounts described herein, which will induce the drug to be administered to the drug (the "tissue of tissue, cells, and cells" ("life or veterinary" is seeking L疋 clusters (eg, a group of sputum-proliferating octocytes or psoriasis cells, a biological or medical response to cancer, its animal or human), and the prevention, mitigation or suspension of symptoms or diseases Effective progression of cell proliferative diseases." Department of the heart, which includes the effective amount of human or non-human patients in the treatment of V. :::. This hair...:: Second-class two = treatment; Administration in any suitable manner, which will be in contact with the site of action in the body of the body. &amp; And depending on the intended use, the appropriate dosage range is about 5. 〇mg/kg body weight/day of the compound of the invention: a salt of acceptable salt, _ or a prodrug (etc.). A suitable heart system covers a range from about _ to about 25 mg/kg body weight/day. For administration of a pharmaceutically acceptable salt of the compound, the weight indicated above is 135177 • 352 - 200922559 which refers to the weight of the acid equivalent or base equivalent of the therapeutic compound derived from the salt. KSP transportin inhibitors, which specifically inhibit KSP transport activity at low concentrations, for example, at 5 〇 or less, or 乂 or 乂 ^ or 50 nM or less The administration of such a compound of the present invention means a different specific embodiment of the present invention. The composition 'in some specific implementations, at least one of the compounds of the present invention is pure In other specific embodiments, the compounds of the invention are administered in a composition of 4, and therefore, a pharmaceutical composition comprising at least the compound of the invention is within the scope of the invention. Pharmaceutical Composition 匕3 At least one compound of the invention (e.g., a dose of the invention, a second, a compound of the same), accompanied by - or a plurality of acceptable carriers I, 1 = other therapeutic agents. For example, the meaning of adjuvant is The other ingredients of the composition are compatible, and the purpose of the two is, or in the case of treatment, the patient being treated. In the other embodiments, the present invention also provides a pharmaceutical composition, two: a seed A compound of the invention, or a pharmaceutically acceptable -, chilled oxime, ester, prodrug or hetero-accepting carrier. &amp; at least - (iv) academically acceptable pharmaceutical composition, inert solid or liquid. Forms, capsules, cachets and suppositories. For the pharmaceutically acceptable carrier from the compounds of the present invention, it may be powder, tablet, dispersible granules 135177-353 · 200922559 powder and sword It may contain from about 5 to about 95 percent of the active ingredient. Suitable solid carriers are known in the art, for example, magnesium carbonate, stearic acid, stearyl or lactose. Tablets, powders, sacs, and sacs can be used as solid dosage forms suitable for sputum. Examples of pharmaceutically acceptable carriers and various groups: For the preparation of the substance, see A. Ge_ (eds.), __戌梦•笋 18th edition (1990), Mack Publishing Company, E_n, pennsylvania. , Pharmaceutical Composition - The word is also intended to encompass both the entire conjugate and the individual dosage unit 'which contains more than one (eg, two) pharmaceutically active agents, eg, one compound of the invention and another agent' selected from the description herein The list of other agents is accompanied by any pharmaceutically inactive excipients. The individual composition dosage unit may contain a fixed amount of the above-mentioned "one or more pharmaceutical active tablets J genuine composition is a substance that has not been made into individual dosage units. The illustrative dosage unit is an oral dosage unit, such as a tablet. Pills, etc. Similarly, by administering the pharmaceutical composition of the present invention to treat patients, the administration of the whole composition and individual dosage units is described herein. The substance may be formulated in a sustained release form to provide controlled release of any one or more of the components or active ingredients to maximize therapeutic benefit. Suitable dosage forms for sustained release include laminated tablets. , ^II homophilic rate layer, or controlled release of the polymer matrix, to act as a tablet or in the form of a tablet or a capsule containing such a matrix of impregnated or coated porous polymer. Preparations are white, six, including ☆ liquid, suspension and emulsion. The following examples can be used to extract water or water. Propylene glycol solution for parenteral injection, or add 135177 -354- 200922559 sweetener An opacifying agent for oral solutions, suspensions and emulsions. Liquid form preparations may also include solutions for intranasal administration. Aerosol formulations suitable for inhalation may include solutions and solids in powder form which may be used in combination with pharmaceutically acceptable Accepted carriers such as inert compressed gases, such as nitrogen. Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations, whether for oral or parenteral (eg subcutaneous, intramuscular, sputum). Administration in the inner, intracapsular, intraspinal, sternal, intravenous, etc. This liquid form includes solutions, suspensions and emulsions. a. The compounds of the invention may also be delivered transdermally. In the form of a lotion, aerosol, and/or emulsion, and may be included in a transdermal patch of a base lambda or reservoir type as in the art of this J. In a specific embodiment, at least one compound or composition of the present invention is formulated for subcutaneous administration. In a specific embodiment, at least one compound or group of the present invention The compound is formulated for oral administration. In the specific embodiment, the at least one compound or combination of the present invention is in the form of a compound or a combination of 5 In a specific embodiment, the present invention is in the form of a compound or a combination of sputum, and is formulated for intravenous administration. In the specific embodiment, the medical treatment is 丨# , Xile preparation is provided in a unit dosage form. In the form of the preparation, the preparation is subdivided into the appropriate amount of the appropriate amount, the tongue # &amp; field size unit dose, containing the active ingredients, such as the effective amount to achieve the desired purpose Ϊ35177 - 355 . 200922559 As described elsewhere herein, the amount of the active compound in the early dosage formulation has been altered or adjusted to the deliberate purpose of the human being. Other non-limiting examples of such dosages range from about 10,000 ounces to about 100 grams 'or, about i 亳. to about 50 milligrams, or, from τ 京 A A 耄 to a range of about 25 grams, Depending on the specific application. The actual dosage employed can vary depending on the severity of the s. It is within the technical scope of this f-article to determine the appropriate dosage regimen for the strictness of the symptoms to be treated. Rabbit 彳 s soil, for convenience, can be divided into total sputum doses, and divided in one day, as needed. The dosage and frequency of the present compound and/or its pharmaceutically acceptable salt or ester are adjusted according to the judgment of the responsible clinician, and the factors such as the age, symptoms and size of the patient and the treatment are treated. The severity of the symptoms. Typical recommendations for oral administration can be in the range of from about 1 mg/day to about 500 mg/day, and the rate is from i mg/day to mg/day, in two to four divided doses. . C' In another embodiment, the invention provides a kit comprising a therapeutically effective amount of at least one compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt, and at least one pharmaceutically acceptable The carrier, adjuvant or vehicle 'and illustrations and/or labels as appropriate, including instructions for use. In another embodiment, the invention provides a kit comprising at least one compound of the invention, or a pharmaceutically acceptable salt thereof, or at least one of the above-exemplified Another therapeutic agent, the amount of the two or more components will cause the desired therapeutic effect. In another embodiment, the invention provides the use of at least one compound of the invention, or a pharmaceutically acceptable salt, solvate, vinegar or precursor thereof, for use in the manufacture of An agent for inhibiting the activity of ksp actin in a patient. In another embodiment, the invention provides the use of at least one compound of the invention, or a pharmaceutically acceptable salt, solvate, vinegar or prodrug thereof, for the manufacture of a medicament, in need thereof One or more diseases are treated by inhibiting ksp actin activity. f In another embodiment, the invention provides that at least one acceptable salt, solvate, vinegar or prodrug is used to produce a treatment for any of the symptoms, diseases or conditions described herein. Pharmacy. In another embodiment, the invention provides: a combination comprising (i) at least one compound of the invention, or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof; And (8) at least one second active ingredient described herein. Combination Therapy The compound of the present invention (in combination with at least one compound of the present invention may be used in combination with the compound of the present invention or a plurality of therapeutic agents. Such treatment is selected according to the intended purpose. The non-limiting real effect of such a medicament is effective. Treating the disease or symptom to which it belongs, and/or making the therapeutic agent one of the following::::1: use, to the lowest, and/or enhance or change the agent to which the therapeutic agent is administered. Other anti-cancer or combination of chemotherapeutic agents are included in this dry circumference. Non-limiting examples of such agents can be found in the waste 135177.357 '200922559 Cancer and Physic-Free Purple, ν·τ· Devita and s · Hellman (editor), 6th edition (February 15, 2001), Lippincott Williams &amp; Wilkins Press. - A person familiar with this artist can use the specific characteristics of the drug and the cancer involved (or other indications) Based on this, it is possible to identify which combination of agents can be used. The following description provides other non-limiting examples of such combination agents. Those skilled in the art are immediately able to determine other suitable agents. An anticancer agent combined with at least one compound of the present invention (or a composition comprising at least one compound of the present invention), including but not limited to the following: an estrogen receptor modulator, an androgen receptor modulator, a retinoid Modulators, cytotoxic agents, microf inhibitors/stabilizers, topoisomerases: preparations, antisense RNA and DNA oligosporic acid, antimetabolites, antibodies or radioactive isoforms coupled to cytotoxic agents, na 〇A reductase: preparation, prenyltransferase inhibitor, farnesyl protein transferase inhibitor, angiogenesis inhibitor, kinase inhibitor, which 2 inhibitor, integrin blocker 'PPAR mobilizer and job Inhibitors.# His anticancer agents also include hypoxia-activating W] a babe degrading inhibitor, ubiquitin inhibitor, hdm2 inhibitor, TNF activator, bUB_r inhibitor, CENp_E inhibitor, and interferon (eg Such an anti-cancer agent may be a small molecule or a biological agent (for example, an rna anti-significant agent and an antibody). The compound of the present invention can also be used when co-administered with radiation therapy. - Female/producible X body Modulator Refers to the compounding mechanism of a compound that interferes with or inhibits the binding of estrogen to a receptor. Examples of estrogen receptor modulators include, but are not limited to, tam〇xifen, rosinose (ϋ色耶), Id〇Xifene, LY353381, Xiao, Tori Mito (9) No. (4), 135177 -358· 200922559 Fulvests (fulvestrant), propionic acid 4-[7-(2,2-dioxin) Keto-1-ketopropoxy-4-methyl-2-[4-[2-(l-hexahydropyridinyl)ethoxy]phenyl]-2H-1-benzopipene-3- Base]-phenyl-2,2-dimethyl ester, 4,4'-dihydroxybenzophenone-2,4-dinitrophenyl-gland and SH646. Other examples include Anas. Sitting (anastrozole) and columno 0 (letrazole). "Androgen receptor modulator" refers to a compound that interferes with or inhibits the binding of androgen to a receptor, regardless of mechanism. Examples of androgen receptor modulators include finasteride and other 5 α-reductase inhibitors, nilutamide, flutamide, and bicalutamide. ), Lilo. Sit (liarozole) and abiraterone acetate. "Retinoid receptor modulator" refers to a compound that interferes with or inhibits the binding of a retinoid to a receptor, regardless of the mechanism. Examples of this class of retinoid receptor modulators include bexarotene, cui Tretinoin, 13-cis-retinoic acid, 9-cis-retinoic acid, difluorodecanoguanine, ILX23-7553, trans-N-(4'-light phenyl) Xanthine and N-4-sulfoyl-based stearylamine. Examples of cytotoxic agents include, but are not limited to, sertenef, cachexia toxin, ifosfamide, tasporin ( Tasonermin), lonidamine, carboplatin, altretamine, prednimustine, diclofenac, ranimustine, flubens (fotemustine), nedaplatin, oxaliplatin, temozolomide (TEMODARTM, available from Schering-Plough, Kenilworth, New Jersey), cyclophosphamide, heptapiatin , estramustine, improsulfan tosylate, cyclohexylphosphonium, Nimustine, dibrospidium 135177 - 359 - 200922559 chloride, pumitepa, lobaplatin, satraplatin, Pycnogenol Profiromycin, cis chloramine #, erythromycin, irofulven, dexifosfamide, cis-amine di-(2-methyl-pyridine) platinum , fluorenylguanine, glufosfamide, GPX100, tetrachlorinated (trans, trans, trans)-bis-//-(hexane-1,6-diamine)-//- [Diamine-Ming (II)] bis [diamine (Chloryl) Ming (II)], diazizidinylspermine, dioxane trioxide, 1-(11-dodecylamido-10 -via Ί--based)-3,7-dimercaptopurine, zombicin, idadamycin, daunorubicin, bisantrene, flavonoids (mitoxantrone), pirarubicin, pinafide, valvidin, amrubicin, antineoplaston, 31-dean new (deansino)-3'_fofinyl-13-deketone -10-via erythromycin, annamycin, galarubicin, elinafide, MEN10755, 4-deoxyoxy-3-deamino- 3-Aziridine-4-methylsulfonyl-danomycin (see WO 00/50032), amidoxime, gemcitabine and mixtures thereof. Examples of microtubule inhibitor/microtubule stabilizers include paclitaxel, vinca sulphate, 3 Ά didehydro-4'-deoxy-8'- vinorelbine, thank you Docetaxel, Changchun new test, Changchun test, vinorelobine, rhizoxin, dorazyme, mivobulin via ethanesulfonate, orimycin (auristatin), cemaadotin (cemadotin), RPR109881, BMS184476, vinflunine, cryptophyll, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4 -nonyloxyphenyl)benzamide,hydrovinblastine,indole,indole-dimercapto-L-isochlorinyl-L-isochlorinyl-N-曱135177 - 360- 200922559 --L-isochlorinated sulfhydryl decyl phthalocyanine-tert-butyl decylamine, TDX258 epothilone (see, for example, U.S. Patents 6,284,781 and 6,288,237) and BMS 188797. Topologically isomerase inhibitors - examples are t-tecan, hycaptamine, ilin〇tecan, mbitecan, 6- Ethoxypropyl hydrazino _3', 4' _ 〇 _ exo _ benzylidene _ borschin, 9 methoxy-N, N-methyl _5 nitropyrazolo[3, 4,5-k]]P acridine-2-(6H)propylamine, f, 1_aminoethyl-5'fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H, 12H-benzo[de]pyrano[3,4':b7]-indole and [i,2b]4 porphyrin-i〇, i3(9H,15H)dione, lurototecan, '7-[2-(N-Isopropylamino)ethyl]-(2(6)camptothecin, BNP1350, BNPI1100, genus 0915, BN8〇942, etodoside (et〇p〇side) 4酉 sense salt , teniposide, sobuzoxane, 2'-diamino- 2'-deoxy-etoposide, team 331, group [2-(dimethylamino) Ethyl]-9-carbyl-5,6-dimethyl-6H-pyrido[4,3-b]pyrazole-1-carboxamide, asuracrine, (5 mad, 53 Ugly plus 3,%)-9-[2-[]^-[2-(didecylamino)ethyl]- 曱I amino]ethyl]-5_[4-hydroxy-3,5-di Alkoxy Phenyl]-5,5a,6,8,8a,9-hexahydrofuran (3',4':6,7)indole (2,3-d)-l,3-dioxolanes -6-keto, 2,3-(indenylenedioxy)-5-methyl-7-hydroxy-8-decyloxybenzo[c]-morphine, 6,9-bis[(2-amine) Benzyl)amino]benzo[g]isoindoline-5,10-dione, 5-(3-aminopropylamino)-7,10-dihydroxy-2-(2-hydroxyethylamine曱H)-6H-pyrazolo[4,5,1-de]acridin-6-one, N-[l-[2-(diethylamino)ethylamino]-7-methoxy -9-keto-9H-pyrimidin-4-ylindenyl]decylamine, N-(2-(dimethylamino)ethyl)oxaridin-4-carboxyguanamine, 6-[[ 2-(Diammonium)ethyl]amino]-3-hydroxy-7Η-indolo[2,1-C]porphyrin-7-one, dimesna and charcoal Putta (camptostar) -361 · 135177 200922559 Examples of antisense RNA and DNA oligonucleotides include: G3139, ODN698, RVASKRAS, GEM231 and INX3001 〇 gene therapy can be used to transmit any tumor suppressor gene. Examples of such genes include but not Limited to p53, which can be transferred by recombinant virus-mediated gene transfer (see, e.g., U.S. Patent 6,069,134), uPA/uPAR antagonist ("uPA/uPAR antagonist adenovirus" The transmission of the media suppresses angiogenesis-dependent tumor growth and spread in mice&quot;, Poor #法, August 1998; 5(8): 1105-13) and interferon T gene therapy (//muscle雠(10)/ 2000 ; 164 : 217-222) transmission. For an overview of genetic strategies for the treatment of cancer, see Hall et al. (Am «7 //«m G(9) deduction 61: 785-789, 1997) and Kufe et al. (Cancer Doctor #, 5th edition, pp. 876-889) , BC Decker, Hamilton 2000). Examples of antimetabolites include: 5-fluorouracil, enocitabine, carmofur, tegafur, pentostatin, doxifluridine , trimetrexate, fludarabine, capecitabine, galocitabine, acfosfate, fotiabine (fosteabine) sodium hydrate, raltitrexed, paltitrexid, emitefur, tiazofurin, decitabine, novo拉提西得_ (nolatrexed), pemetrexed, nelzarabine, 2^deoxy-2'-arylene cytosine, 2'-fluoro-indenyl -2'-deoxycytidine, N-[5-(2,3-dihydro-benzofuranyl)sulfonyl]-NH3,4-dichlorophenyl)urea, N6-[4-deoxy-4 -[N2-[2(E),4(E)-tetradecadienyl]glycine]-L-glyceryl-BL-mannose-heptylpyranosyl] adenine, A Aplidine, ecteinascidin, 卓沙西塔135177 -362- 200922559 (troxacitabine), 4-[2-amino-4-3⁄4yl-4,6,7,8-tetrahydro-3H-°Bite and [5,4-b][l,4 Thiacin-6-yl-(S)-ethyl]-2,5-pyrimidinyl-L-glutamic acid, aminoguanidine, 5-fluorouracil, nitrosohydroxyalanine, 11-B Mercapto-8-(amine-mercaptooxymethyl)-4-mercapto-6-methoxy-14-oxo-1,11-diazatetracyclo(7.4.1.0.0)-fourteen -2,4,6-trien-9-yl acetate, swainsonine, lometrexol, dexrazoxane, methionin, 2'-cyano -2'-deoxy-N4-palmitino arabinofuranosylcytosine and 3-aminopyridine-2-carboxaldehyde urethiourea. The monoclonal antibody is an example of a target therapeutic agent, and includes a therapeutic agent having a cytotoxic agent or a radioisotope linked to a cell-specific monoclonal antibody specific to a cancer cell. Examples include Bexxar. The nHMG-CoA reductase inhibitor &quot; refers to an inhibitor of 3-hydroxy-3-mercapto quinone-CoA reductase. Examples of HMG-CoA reductase inhibitors can be used including, but not limited to, lovastatin (MEVACOR®; see U.S. Patents 4,231,938, 4,294,926 and 4,319,039), simvastatin (ZOCOR) ®; see U.S. Patents 4,444,784, 4,820,850 and 4,916,239), pravastatin (PRAVACHOL®; see U.S. Patents 4,346,227, 4,537,859, 4,410,629, 5,030,447 and 5,180,589), fluvastatin (fluvastatin) LESCOL®; see U.S. Patents 5,354,772, 4,911,165, 4,929,437, 5,189,164, 5,118,853, 5,290,946 and 5,356,896) and atorvastatin (LIPITOR®; see U.S. Patents 5,273,995, 4,681,893, 5,489,691 and 5,342,952). The structural formulae of these and other HMG-CoA reductase inhibitors that can be used in the methods of the present invention are described in M. Yalpani, 'Pfr Low Cholesterol Drugs' Yun Sung Industrial, pp. 85-89 (19%) Page 2 135177 • 363 - 200922559, 5th), page 87' and US Patents 4,782,084 and 4,885,314. The term HMG-CoA reductase inhibitor as used herein, includes all pharmaceutically acceptable lactone and open-chain acid forms (ie, wherein the lactone ring system is opened to form a free acid) and has The HMG-CoA reductase inhibits the salt and ester forms of the active compound. Therefore, the use of such salts, esters, open acids and lactone forms is included in the scope of the present invention. "Prenyl-protein transferase inhibitor" means a compound which inhibits any one or any combination of isoamyl-protein transferases, including farnesyl protein transferase (FPTase), geranyl Geranyl-protein transferase type I (GGPTase-I) and geranyl-based geranyl-protein transferase type-II (GGPTase-II, also known as Rab GGPTase).

Examples of isopentenyl-protein transferase inhibitors can be found in the following publications and patents: WO 96/30343, WO 97/18813, WO 97/21701, WO 97/23478, WO 97/38665, WO 98/28980, WO 98/29119, WO 95/32987, U.S. Patent Nos. 5,420,245, 5, 523, 430, 5, 532, 359, 5, 510, 510, 5, 589, 485, 5, 602, 098, European Patent Publication 0 618 221, European Patent Publication 〇 675 112, European Patent Publication 0 604 181, European Patent Publication 0 696 593 , WO 94/19357, WO 95/08542, WO 95/11917, WO 95/12612, WO 95/12572, WO 95/10514, US Patent 5,661,152, WO 95/10515, WO 95/10516, WO 95/24612, WO 95/34535, WO 95/25086, WO 96/05529, WO 96/06138, WO 96/06193, WO 96/16443, WO 96/21701, WO 96/21456, WO 96/22278, WO 96/24611, WO 96/24612, WO 96/05168, WO 96/05169, WO 96/00736, US Patent 5,571,792, WO 96/17861, WO 96/33159, WO 96/34850, WO 135177-364-200922559 96/34851 WO 96/30017, WO 96/30018, WO 96/30362, WO 96/30363, WO 96/31111, WO 96/31477, WO 96/31478, WO 96/31501, WO 97/00252, WO 97/03047 , WO A/C. Patent No. 5,532,359. For examples of the role of isopentenyl-protein transferase inhibitors in angiogenesis, see Chin Tao Pain, Vol. 35, No. 9, pp. 1394-1401 (1999). Examples of farnesyl protein transferase inhibitors include SARASARtm (4-[2-[4-[(llR)-3,10-dibromo-8-yl-6,11-dihydro-5H-benzo) [5,6]cyclohepta[l,2-b]p is more specific than oxo-l-yl-]-1-hexahydro-n-butyl]-2-indole-ylethyl]-1-hexahydroport 0 temperamine, available from Schering-Plough, Kenilworth, New Jersey), tipifarnib (Zamestra® or R115777 from Janssen Medicine), L778, 123 (farnesyl protein transferase inhibition) Agent, available from Merck, Whitehouse Station, New Jersey, BMS 214662 (Farnesyl Protein Transferase Inhibitor, available from Bristol-Myers Squibb Pharmaceuticals, Princeton, New Jersey). ''Angiogenesis inhibitors' are compounds that inhibit the formation of new blood vessels, regardless of mechanism. Examples of angiogenesis inhibitors include, but are not limited to, tyrosine kinase inhibitors such as the tyrosine kinase receptor Flt-1 (VEGFR1) Inhibitors of Flk-1/KDR (VEGFR2), epidermal-derived, fibroblast-derived or platelet-derived growth factor inhibitors, MMP (interstitial metalloproteinase) inhibitors, integrin blockers, Leukocourtin-12, pentasaccharide polysulfate, cyclooxygenase inhibitors, including non-steroidal anti-inflammatory agents (NSAIDs), such as aspirin and ibuprofen, and selective cyclooxygenase-2 Inhibition of 135177 365 * 200922559 agents, such as celecoxib and rofecosibis (rofecoxib X/WAS, vol. 89, p. 7384 (1992); «7ΛΟ, vol. 69, p. 475 (1982) ; Arc/i. Vol. 108, p. 573 (1990); Αηαί. T^c·, Vol. 238, p. 68 (1994); F, melon L, ers, vol. 372, p. 83 ( 1995); C7 plus. Οί/ίορ. Vol. 313, p. 76 (1995) ', J, Mol. Endocri Nol., Vol. 16, p. 107 (1996); //w. /. P/zflmMco/·, Vol. 75, p. 105 (1997); Cancer Vol. 57, p. 1625 (1997); Ce //, Vol. 93, p. 705 (1998); Μ/. /. Μσ/. Μβ., Volume 2, page 715 (1998); σ/. C/im., Volume 274, 9116 (1999)), steroid anti-inflammatory agents (such as corticosteroids, mineral corticosteroids, dexamethasone, prednisone, prednisolone, methylprednisone, /5 - methadone), carboxy guanamine Triazole, windmill bacteriocin A-4, squalamine, 6-0-glycolyl-aryl)-fumagillol, @太胺11 bottom ketone, angiogenin , hemoprotein-1, angiotensin II antagonist (see Fernandez et al, Lah C7k. Md. 105: 141-145 (1985)), and antibodies against VEGF (see Nature Biotechnology, Vol. 17, No. Pp. 963-968 (October 1999); Kim et al., Mzm% 362, 841-844 (1993); WO 00/44777; and WO 00/61186). Other examples of angiogenesis inhibitors include, but are not limited to, endostatin, krarain, ranpirnase, IM862, 5-methoxy-442-methyl-3-(3) -Methyl-2-butenyl)oxiranyl]-1-oxo[2,5]oct-6-yl(chloroethenyl)S, dinanaline, 5-amino-l-[[3,5-dioxa-4-(4-chlorophenylphenyl)phenyl]indolyl]-1H-1,2,3-triazole-4-carboxyindole Amine, CM101, squalamine, windmill bacteriocin, RPI4610, NX31838, sulfated mannose pentose phosphate, 7,7-(carbonyl-bis[imino-N-mercapto-4,2-pyrrole 135177 •366· 200922559 carbonylimino [N-fluorenyl-4,2-pyrrole]-carbonylimino]-bis-(1,3-naphthalene disulfonate) and 3-[(2,4- Dimethylpyrrole-5-yl)methylene]-2-indanone (SU5416). Other therapeutic agents that modulate or inhibit angiogenesis and may also be used in combination with the compounds of the invention, including modulation or inhibition of coagulation An agent with a system of plasmin action (see review in CZiVi. 1«. 38: 679-692 (2000)) which modulates or inhibits coagulation and plasmin Examples of such agents of the route include, but are not limited to, heparin (see TTzwmh 80: 10-23 (1998)), low molecular weight heparin and carboxypeptidase U inhibitors (also known as active thrombin-activated plasmin An inhibitor of the action inhibitor [TAFIa] (see Office 101: 329-354 (2001)). Examples of TAFIa inhibitors have been described in PCT Publication WO 03/013, 526. Examples of kinase inhibitors include: inhibition A cell surface receptor that reacts with a latent signal transduction cascade of these surface receptors. This agent inhibits cell proliferation and survival. It includes inhibitors of EGFR (eg, gefitinib and ah roti). Erlotinib), antibodies against EGFR (eg C225), inhibitors of ERB-2 (eg trastuzumab), inhibitors of IGFR, inhibitors of cytokine receptors, MET Inhibitors, inhibitors of PI3K (eg LY294002), serine/threonine kinases (including but not limited to inhibitors of Akt, such as at W0 02/083064, W0 02/083139, W0 02/083140 and W0 02 /083138), inhibitor of Raf kinase (eg BAY-4 3-9006), inhibitors of MEK (eg CI-1040 and PD-098059), inhibitors of mTOR (eg Wyeth CCI-779) and inhibitors of C-abl kinase (eg GLEEVEC®, Novartis Pharmaceuticals). Other kinase inhibitors include those that inhibit proteins involved in 135177-367-200922559 and cell cycle. These include aurora kinase inhibitors, CDK inhibitors (e.g., flavonol, CYC202, BMS387032, and polar kinase inhibitors). These also include agents that interfere with the cell cycle checkpoint and thereby sensitize the cancer cells to DNA nociceptors. Such agents include, for example, inhibitors of ART, ATM, Chkl, and Chk2. The invention also encompasses combinations with NSAIDs, which are selective COX-2 inhibitors. For the purposes of this patent specification, NSAID, which is a selective inhibitor of COX-2, is defined as having a specificity for inhibiting COX-2 that is at least 100 times greater than COX-1, when by cell or particle Body assays were assessed by dividing the IC50 of COX-2 by the ratio of IC50 to COX-1. A COX-2 inhibitor particularly useful in the treatment of the present invention is: 3-phenyl-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone; and 5-chloro- 3-(4-oxasulfonyl)phenyl-2-(2-methyl-5pyridinyl)pyridinyl; or a pharmaceutically acceptable salt thereof. It has been described as a specific inhibitor of COX-2 and Compounds which are therefore useful in the present invention include, but are not limited to, parecoxib, CELIEBREX® and BEXTRA® or a pharmaceutically acceptable salt thereof. "Integrin blocker" means selective antagonism a compound that inhibits or neutralizes a physiological ligand that binds to av /3⁄4 integrin, selectively antagonizes, inhibits, or neutralizes a compound that binds to a physiological ligand to αν A integrin, antagonizing, inhibiting, or a compound that binds to a physiological ligand to both 6KV/3⁄4 integrin and av/3⁄4 integrin, and a compound that antagonizes, inhibits, or neutralizes specific integrin activity expressed on microvascular endothelial cells. Refers to antagonists of α ν /36, αν /3⁄4, α]怂, α2 /3], α5怂, Α and Α integrin. This term also refers to αν yS3, y55, Q:v /3⁄4, /3⁄4, 卬, (3⁄4 A, 135177 - 368 - 200922559 A, an antagonist of any combination of α6 A and % /3⁄4 integrin. Combinations of compounds other than anticancer compounds are also encompassed by the present invention In a method, for example, a combination of a compound of the present invention with a PPAR-7 (ie ppAR-gamma) catalyst and a PPAR-5 (meaning PPAR-delta) catalyzer (collectively referred to as "ppar priming agent") is available For the treatment of certain malignant conditions. PPAR-r and ppAR_ 5 are individual nuclear peroxisome proliferator-activated receptors 7 and 5. The expression of PPAR-γ on endothelial cells and its involvement in angiogenesis has been reported in In the literature (see ··· CaWoviwc. Corpse &quot;a Jan. 1998; 31: 909-913; &gt;/. by c/iem. 1999; 274 · 9116-9121; Invest. Ophthalmol Vis. Sci. 2000 ; 41 : 2309-2317). Recently, PPAR-R mobilizers have been shown to inhibit angiogenic responses to VEGF in vitro; troglitazone and rosiglitazone maleate It inhibits the development of retinal neovascularization in mice (Arc/z. OpMmm?/. 2001; 119: 709-717). PPAR-r Examples of kinetic agents and PPAR-χ/α agonists include, but are not limited to, ρ-serazole dandione (such as DRF2725, CS-011, troglitazone, rosiglitazone, and pico Pioglitazone), fenofibrate, gemfibrozil, clofibrate, GW2570, SB219994, Ar-H039242, JTT-501, MCC-555, GW2331, GW409544, NN2344, KRP297, NP0110, DRF4158, NN622, GI262570, PNU182716, DRF552926, 2-[(5,7-dipropyl-3-trifluoromethyl-1,2-benzisoxazole-6 -yl)oxy]-2-mercaptopropionic acid and 2(R)-7-(3-(2-carbyl-4-(4-fluorophenyloxy)phenoxy)propoxy)- 2-ethylindole-2-carboxylic acid. The compounds of the invention may also be administered in combination with one or more inhibitors of intrinsic multidrug resistance (MDR), particularly those associated with high levels of transporter protein expression 135177-369-200922559. Such MDR inhibitors include inhibitors of ρ-glycoprotein (P-gp) such as LY335979, XR9576, OC144-093, R101922, VX853 and PSC833 (valspodar). Other anticancer agents also include hypoxic activators (such as tirapazamine), protein degrading inhibitors (such as lactacysamine and bortezomib), ubiquitin inhibitors, and HDM2 inhibitors. , TNF activator, BUB-R inhibitor, CENP-E inhibitor and interferon alpha. The compounds of the invention may also be employed in combination with one or more antiemetic agents to treat nausea or vomiting, including acute, delayed, advanced, and expected vomiting, which may result from the use of the compounds of the invention, either alone or with the use of radiation therapy. In order to prevent or treat sputum sputum, the compound of the present invention can be used together with one or more other antiemetic agents, especially a neurokinin-1 receptor antagonist, a 5ΗΤ3 receptor antagonist, such as ondansetron, From granisetron, tropisetron and zetisetron, GABAB receptor agonists, such as clofenac, corticosteroids, such as decadon (Decadron) ) (Dexamesone), Kenalog, Aristocort, Nasalide, preferid, Benecorten, or as In the U.S. Patent Nos. 2,789,118, 2,990,401, 3,048,581, 3,126,375, 3,929,768, 3,996,359, 3,928,326, and 3,749,712, anti-dopamines, such as phenol sulfonate (eg, prochlorperazine, fluphenazine) Fluphenazine), bismuth sulphate and mesoridazine, metoclopramide or dronabinol. In a specific embodiment, the antiemetic agent selected from the group consisting of neurokinin _; [receptor antagonists, 5HT3 receptor antagonists, and corticosteroids is administered as an adjuvant to 135177-370-200922559 for treatment or Prevention of vomiting that may occur when the compound of the invention is administered. Examples of neurokinin d receptor antagonists that can be used in conjunction with the compounds of the invention are described in U.S. Patents 5,162,339, 5,232,929, 5,242,930, 5,373,003, 5,387,595, 5,459,270, 5,494,926 &gt; 5,496,833 &gt; 5,637,699 and 5,719,147 And for reference in this article. In a specific embodiment, the neurokinin_!! receptor antagonist used in conjunction with a compound of the invention is selected from the group consisting of: 2-(8)-(l-(R)-(3,5-bis(trifluoro indole) ()phenyl)ethoxy)(5)-(4-fluorophenyl)-4-(3-(5-keto-1H,4H-1,2,4-triazolo)indolyl)morphine Or a pharmaceutically acceptable salt thereof, which is described in U.S. Patent 5,719,147. The compounds of the invention may also be administered with one or more enhanced immunopharmaceuticals, such as levamisole, isoprote, and Zadaxin. As described above, the invention includes a combination comprising an amount of at least one compound of the invention (or a composition comprising the compound), or a pharmaceutically acceptable &quot;T-acceptable salt or Or a plurality of other therapeutic agents listed above (administered together or sequentially), wherein the amount of the compound/therapeutic agent causes the desired therapeutic effect. When a combination therapy is administered to a patient in need of such administration, the therapeutic agent in combination, or one or more pharmaceutical compositions comprising the therapeutic agent, can be administered in any order 'eg, sequentially, collectively', Wait at the same time. The amount of the various active substances in such combination therapy may be different amounts (different doses) or the same amount (same dose). Therefore, for the purpose of illustration, the compound of the present invention and another therapeutic agent may be present in a fixed amount (dose). In a single dosage unit (eg capsule, tablet, etc.). A commercially available example of such a single dosage unit containing a fixed amount of two different active compounds 135177-371 - 200922559 is VYTORIN® (available from Merck Schering-Plough Pharmaceuticals, Kenilworth, New Jersey). If formulated as a fixed dose, such combination products will employ the compositions of the invention within the dosage ranges set forth herein, and other pharmaceutically active agents or treatments are within the dosage range. When the combination formulation is not suitable, the compounds of the invention may also be administered sequentially with known therapeutic agents. The invention is not limited by the order of administration; the compounds of the invention may be administered prior to or after administration of a known therapeutic agent. This technique is within the skill of the artist and the physician. It will be apparent to those skilled in the art that changes may be made to the specific embodiments described above without departing from the broad inventive concept. Therefore, it is understood that the invention is not limited to the specific embodiments disclosed, and the invention is intended to cover the modifications and the scope of the invention as defined by the appended claims. K &quot; 135177 - 372 ·

Claims (1)

200922559 X. Patent Application Range: 1. A compound having the general structure shown in formula (I) or a pharmaceutically acceptable salt, solvate, hydrazine, prodrug or isomer thereof: R3 (I) wherein R, R, R3, p, r27, r28, E, ring a and ring B are independently selected from each other, and wherein: p is 0, 1, 2, 3 or 4; E and the unsaturation shown) are 48-membered cycloalkenyl or heterocyclic ring; ie, selected from -a, s_, _s(〇)_, _s(〇)2_, _c(r4) (r5) )_, Na)... -N(C(Y)R )-, _N(C(Y)0R8)_, _N(C(7)n(r9)(r1G))_, _c(〇)_n(rU)_, - NCR11 )-C(0)- . , .N(Rii)-S(0)2- &gt; -C(0)-〇-, -OC(O)- ' -0-N(R6). , , -N(R6)-N(R12)- . _N=N. -C(R7)=N-, -C(〇)-c(R7)=N_, _c(〇)_N=N_, _〇_qY )_N(R&quot;)_, -N(R] 1 )-C(Y)-〇- &gt; -NCRU^qy^rII). , -C(Y)-N(RH ).〇. ^ ((7) -师1〗)-N(Ri 2)...七谭丨〗 and _n(r1 2 )_卿丨)((7)... Where each Y system is independently selected from (=〇), (=s), (= N(Rl3)), (=N(CN)) ^ (=Ν(〇κΐ4)} ^ (=N(R15)(R16)) ^(=0(^7)(^8)). % B is a tricyclic or heteroaromatic ring, or a partially unsaturated alicyclic ring, or a partially 135177 200922559 unsaturated heterocyclic ring, wherein the % is unsubstituted, or the 胄Λ ia η ^ is broken - or more Can be different or different The substituents of the red group are substituted independently, including halogen, -CN, -N02, alkyl, miscellaneous, °...sodium, _alkyl, fused, haloalkenyl, alkynyl ,haloalkynyl, aryl, oxa-glycanyl, aryl-alkyl-, aryl-alkyl, cycloalkenyl, heterocyclic, chiral, nitrogen, -OR19, _ 〇C(〇)〇R20, 22 土土挪3Γ_ρ20 ” R '-NR23S〇2R24 , c_P, _nr23c(0)r24, initial 2Nr25r26 -C(〇)〇R2〇, _sr]9, r19 厶U2R y , _〇c(〇)r24 ' -C(0)NR2 5 R2 6 , _nr2 3 C(N-CN)NR2 5 R2 6 « md2 3 and ·NR c(〇) 顺25r26'· k from aryl group And a heterocyclic alkyl group, a cycloalkenyl group, a heterocycloalkyl group, and a heterocycloalkenyl group, wherein each of the aryl group and each of the heteroaryl groups is a fluorene, each of the alkyl groups, and each of the cycloolefins The earth, each of the heterocyclic alkyl groups and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, independently taken by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of (4) Prime, -CN, -N02, burnt base, Yiyuan base, South base, base, tooth base, block 'i alkynyl, aryl 4, aryl-, heteroaryl-, cyclyl, cycloalkyl, heterocycloalkenyl, azide, -oy 9, OC(0)〇R20, R_NRS02R24, -NR23C(0)0R2°, -NR23C(0)R24, S02NR R, _c(〇)R2 4, c(〇)〇r2. , sr19, s(〇)r19, S02R -〇C(0)R2 4 , -C(〇)NR25r2 6 , -NR23C(N-CN)NR25R26 &amp;-NR23C(0)NR25r2 6; C(Z)R7,0,-〇:2:Χ)Ι^8,0,^5177 200922559 cycloalkenyl, heterocycloalkyl, heteroalkyl, aryl, heteroaryl, ring-based base and Heterocyclenyl, wherein each z is independently selected from the group consisting of (=〇), (=s), (=n(ri3)), (=N(CN)), ('OR14)), (=N(Rl5) (Rl6)) and (=c(r17)(ri, and each of the alkyl groups, each of the heteroalkyl groups, each of the aryl groups, each of the heteroaryl groups, each of the bad alkyl groups, and each of the cycloolefins Each of the heterocycloalkyl groups and each of the heterocycloalkenyl groups is unsubstituted or, as the case may be, independently substituted with one or more substituents which may be the same or different substituents. Each substituent is independently selected from the group consisting of: a group (with the proviso that the aryl group and the heteroaryl group are not substituted by a ketone group), halogen, -CN, -N02, alkyl, haloalkyl, alkenyl, azaalkylalkyl, block, Halo block, aryl 'heteroaryl, aryl.alkyl, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -OR19 -〇C(0)〇R2〇, tear 21r22, NR23sc)2R24, -NR23C(〇)〇R2〇s -NR23C(0)R24 &gt; -S02NR25R26 &gt; -C(0)R24 . -0C(0) R24, -C(0)〇R2〇, _srI9 -s(o)r19, _s〇2r19 -C(0)NR2 5 R2 6 , _NR2 3 c(n_cn)nr2 5 r2 6 and nr2 3 cNR2 5 R2 6 ; R (when not bonded to R28) are independently selected from the group consisting of H, alkyl, heteroalkyl , alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocycloalkenyl, halogen '-CN, -N02, -OR1 9, -〇C(O)〇R2 0, _NR2jR22, NR23s〇2R24, _nr23c(9)〇r20, -NR23C(0)R2 4 , _s〇2NR25R26 . -C(0)R24 &gt; -C(0)OR20 ' - SR19 ' -S(0)R19, ·δ〇2Κΐ9, _〇c(〇)r24, c(〇)nr25r26, _nr23c(n cn)_Nr25r26&amp;-NR23C(0)NR25R26, wherein each 5 Each of the heterodole, each of the alkenyl groups, each of the heterobasic groups, 135177 200922559, each: an alkynyl group, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, each of the 5 quinones, and each The cycloalkenyl group, each of the heterocycloalkyl groups and each of the heterocyclic ring groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from _ Base, dentate CN N02, sulfhydryl, heterodole, functional group, dilute base, dentate base: block group, halogen block group, aryl group, Aryl, cycloalkyl burned group, cycloalkyl group dilute 'heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -〇C (0) OR2. -NR2] R22, _NR2, R24, 33C(〇)〇R2G, 视23c(〇)R24, -so2nrur26, _c(〇)r24, _C(_2G, observation19, part)R19, -S02R&gt;^ &gt ; -0C(0)R24 , .C(0)NR^R26, .Nr23C(N.CN)nr25r26 and -nr23c(o)nr25r26 group; when not bonded to P) are independently selected from the group consisting of H, An alkyl group, a miscible group, a dilute group, a heterocyclic group, a aryl group, a heteroalkynyl group, a fluorenyl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, a heterocycloalkyl group, a heterocycloalkenyl group, a _ element, a _CN, _Ν02, 99, -0C_R2Q, -NR2lR22, _NR23s〇2R24, 掀23c(〇)〇r20, -nr"C(0)r24, _s〇2Nr25r26, _C(0)R24, c(〇)〇r2, brew 9, -S(0)R19, -S02R19, -〇C(〇)R2 4,_c (〇) nr25r26, nr23c(7)(3)) NR25R26&amp;-NR23C(0)NR25R2 6, wherein each of the mercapto group, each of the miscible groups, each of the dilute groups, each of the heterobasic groups, each of the alkynyl groups, and each of the alkynyl groups Each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, independently A plurality of substituents may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of fluorenyl 'Nansu, -CN, -N02, fluorenyl, hetero-homo-based, haloalkyl, roasting, and gibral 135177 200922559 , alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocycloalkenyl, azido, -OR19, -〇C(0)OR20, -NR2 'R2 2 . -NR2 3S〇2R2 4 , _NR2 3C(〇)〇r20 ^ _NR2 3C(〇)R2 4 . -S〇2NR2 5R2 6, _c(〇)r24, c(9)〇r2〇, such as 9 灾宁i9 , S02R 0C(0)R 4 . -C(〇)NR25r2 6 , -NR23C(N-CN)NR25R26 and -NR23C(0)NR25r26 group; or 'R27#R28 and their Linked carbon atoms - shaped "alkyl, cycloaliphatic, heterocyclic, containing - to three heteroatoms selected from N, 0AS, or heterocycloalkenyl, containing - to three selected from a hetero atom of N, 0 and S, wherein the heteroa-alkyl ring and the heterocycloalkenyl ring are each unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different Substituents are independently selected from the group consisting of keto, halogen, _CN, _N02 alkyl, heteromorphic, dentate, alkenyl, lienyl, fast radical, i-radyl, aryl, heteroaryl, aryl- Alkyl-, heteroaryl-alkyl-, cycloalkylcycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _〇Rl 9, 0C(0)0R, -NR2 1R2 2, _nr23s 〇2R24, NR2 3C(〇)〇R2 0, NR C(0)R &gt; -S〇2NR25R26 &gt; -C(〇)R2 4 , -C(〇)〇R20 ' -SR19 ' S(〇)R , -S〇2 Rl 9, 0C(0)R2 4, -C(0)NR2 5 R2 6 , -NR2 3 C(N-CN)-NR2 5 R2 6 and -NR2 3 c(〇)NR2 5 R2 6 ; each R 3 (when present) is independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, hetero, fast, hetero, aryl, heteroaryl, cycloalkyl, Alkenyl, fluorenyl, heterocycloalkenyl, halogen, _CN, _N〇2, _〇Rl 9, 〇〇c(〇)〇r20, nr R ' -NR23S〇2r2 4 , -NR23C(0) 0R2° ' -NR23C(0)R24 ' 135177 200922559 -s〇2Nr25r26, -c(〇)R24, _c(5)R24,,_, sr19, s(〇)Ri9, S02R, -OC(0)R, _C(〇) NR2 5R2 6 , Nr23c(n cn)nr25r26, -NR2 3 C(0)NR2 5 R2 6 and .NR2 3 _c(nh)_n(r2 6 , f wherein each of the alkyl groups, each of the heteroalkyl groups, each An alkenyl group, each of the heteroalkenyl groups, each (tetra) group, each of the heteroalkynyl groups, each of the aryl groups, and each of the heteroaryl groups. Each of the cycloalkenyl groups, each of the cycloalkenyl groups, each of the heterocyclic alkyl groups, and each of the heterocyclic ring groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each Substituents are independently selected from the group consisting of fluorenyl, dentate CN N02, alkyl, heteroalkyl, pyrenyl, divalent, dentate, alkynyl, aryl, heteroaryl, cycloalkyl, epoxide ,,,,, ) R2 4 x -s〇2nr25r26, _c(0)r24, _c(〇)〇r20, _SR19, __]9, -S〇2R19 ^ -0W4 , .C(〇)NR25R26 ^ _NR23C(N.CN)nr25r26 And a group of -NR23C(〇)Nr25r26, ft 'when p is 2, 3 or 4, the two R groups bonded to the same ring carbon atom are used together with their slaves and connected slave atoms To form a snail, a spirocycloalkenyl or a spiroheterocyclic ring, which comprises a ring comprising: sigma, sigma, succinyl, and sulphur heterocycle The base ring contains - to three ring heteroatoms independently selected from the group =/NR6...s_, -s(〇&gt;, money···◦. , two, R, and the series of atoms connected to the line, and the stone anion atoms connected to them _ twisted the field, produced 'to form a cycloalkyl, cycloalkenyl 'heterocyclic soil coat 3 one to three Independently selected from the group consisting of -NH-, -NR6-, -S-, 135177 -6-200922559 S(0), -s(0)2-, and _α - to three independently selected from the group consisting of Tear--〇-ring heteroatoms; -s(〇)-, -s(o)2- each when unconstrained) are independently selected from the group consisting of dilute bases, hetero-matrix bases, block bases, and heteroblock bases. , aryl, heteroaryl:, = ring dilute, 2 «alkyl, heterocyclic, dentate, rhyme, _; 〇 2: _ = 〇 C_, tear 21R22, NR23s 〇 2R24, N - NR23C (0 ) R^ , 〇 2NR25R26 ^.c(〇)R24 ^ ^ 'S〇2R19' _〇C(〇)R24' -C(〇)NR25R26' -NR-C(N-CN)-NR R26 and _NR23C (〇)NR25R2 6, wherein each of the alkyl groups is a heterologous group, each of the alkenyl groups, each of the heterobasic groups, each of the (tetra) groups, each of the heteroalkynyl groups, each of the aryl groups, and each of the heteroaryl groups, Each of the 3 mol% alkyl groups, each of the cycloalkenyl groups, each of the heterocyclic alkyl groups, and each of the heterocyclic ring groups are unsubstituted or, as the case may be, independently substituted by one or more of the same or different Substituent, each substituent is independently selected from the group consisting of fluorenyl, halogen CN N02, anthracenyl, heteroalkyl, dentate, alkenyl, alkenyl, alkynyl, dentate, aryl, heteroaryl, Cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _〇R] 9, 〇 〇 c (〇) 〇r2 〇, -NR21R2 2 . -NR23S02R2 4 , -NR23C(0 ) 0R2° ^ -NR23C(0)R2 4 . -S〇2NR25R2 6. _C(〇)R2 4, c(〇)〇r2g, _SRl9, _s(〇)r19, -S02 R]9, -〇c( 〇)r2 4, c(〇)nr2 5 r2 6 , nr2 3 C(N cn)nr2 5 r2 6 and -NR23C(0)NR25R26 group; each R5 (when not joined with R4) is independently selected from Including H, alkyl, heteroalkyl, alkenyl 'heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, 135177 200922559 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl , halogen ' _CN, _N 〇 2, _ 〇 r1 9, - 〇 C (〇) 〇 R2. , _NR2] r22, _NR23S 〇 2R24, _nr23c (9) (10). -NR23C(0)R2 4, _s〇2Nr25r26, _c(0)r24, c(9)〇R2〇, such as 9, -S(0)R19 ' _SQ2Rl9, _qC(q)r24, c(〇)Nr25r26 ' NR23c( N (3)) NR25R2 6^.NR2 3C(〇)NR2 5R2 6 , wherein each of the alkyl group, each of the miscible groups, each of the dilute groups, each of the heterobasic groups, each of the alkynyl groups, each of the heteroalkynyl groups, Each of the aryl group, each of the heteroaryl groups, each of the fluorene groups, each of the ring-like groups, each of the heterocyclic groups, and each of the heterocyclic groups are unsubstituted or, as the case may be, one or more The substituents may be substituted by the same or different substituents, each substituent being independently selected from the group consisting of a ketone group, a hydroxyl group CN, a _n 〇 2, a decyl group, a heteroalkyl group, a dentate group, a dilute base, a dentate f: a block group, a fast-acting group, an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkyl group, a heterocyclic group, a heterocyclic group, an azide group, 〇R1, 〇c(〇)〇r2〇, NR R22, -NR23S〇2R2 4, _nr23c(〇)〇r2. NR". (9) Ruler 24' is called nr25r26, _C(0)R24, c(〇)〇R2., View 19, _19, -0C(0)R24 &gt; -C(〇)NR2 5R2 6 , _NR23C(N-CN)NR25R26 and 'nr23c(〇)nr25r26 group; =R and R5 and their attached carbon atoms form The ring-shaped group, the ring W is a heterocyclic ring, containing three to three selected from the group consisting of N, hydrazine and S, or a heterocyclic ring containing - to three heteroatoms from _, ◦ and b. , wherein the heterocycloalkyl ring and the heterocyclic ring system are each unsubstituted, and the substituents are independently selected from one or more substituents which may be the same or different. Sulfhydryl, dentate, -CN, -N02, 135177 200922559 alkyl 'heteroalkyl, _alkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkane Base, heteroaryl-alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, 〇Rl 9, -0C(0)0R2. , -NR2 1R2 2, 235 〇 2 feet 24, nr23c (〇) 〇 r20, -NR2 3C (0) R2 4, _s 〇 2Nr25r26, c (〇) r24, cR2. , SR19, -SCCOR1 9, -S02 R1 9, -0C(0)R2 4, _c(〇)nr2 5 r2 6, _nr2 3 C(N CN)-NR2 5 R2 6 and -NR2 3 C(〇)NR2 5 R2 6 ; each R6 is independently selected from the group consisting of H, alkyl, _c(〇)r24, _c(〇)〇r2〇, -C(S)R24, heteroalkyl, dilute, heteroalkenyl, block , a heteroaryl group, an aryl group, a heteroaryl 'cycloalkyl group, a cycloalkenyl group, a heterocycloalkyl group, a heterocycloalkenyl group, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, each of the hetero An alkenyl group, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups Is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of keto, halogen, -CN, -N〇2, alkyl, heterocycloalkyl , haloalkyl, alkenyl, alkenyl, alkynyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _ 〇Rl9,·〇(:(〇)〇κ2(), _NR2lR22, -NR23S〇2R24, -NR23C(0)〇R20, -NR2 3C(0)R24, -S〇2NR25r26, -C(0)R24 -C(S)R24, -C(0)〇R2〇, _SR19, -s(0)Rl 9, -S02R19, -〇c(o)R24, -c(o)nr25r26, _NR2 3C(N cn) a group of nr25r26 and -nr23c(o)nr25r26; each R7 is independently selected from the group consisting of H, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl alkynyl, aryl, heteroaryl, ring An alkyl group, a cycloalkenyl group, a heterocyclic group 135177 200922559, a heterocycloalkenyl group, wherein each of the counties, each of the hetero (4), each of the dilute groups, each of the heterobasic groups, each: an alkynyl group, each of the alkynyl groups Each of the aryl groups, each of the heteroaryl groups = a hydroxy group, each of the cycloalkenyl groups, each of the heterocyclic groups, and each of the oxime groups are unsubstituted or, as the case may be, independently - or a plurality of may be phased or different Substituted by a substituent, each substituent is independently selected from the group consisting of fluorenyl 2 CN, -Ν02, fluorenyl, heterophenyl, dentate, dilute, _, alkynyl, alkynyl, aryl, heteroaryl Base, cycloalkane, heterocyclic, azide, -0R19, =, 2, R24, 23_R2G, collar 2, -s〇2Nr25r26, _c(〇)R24, _C(_2Q , SR19, -s〇2R- ^ -0C(0)R24 . .C(0)NR25R26 , -NR-C(N-CN)NR25r2'6 and tear 23C(〇)NR25R26 group; =8 is independently selected 'including H, alkyl, miscible, dilute, heterogeneous, ', alkynyl, aryl, heteroaryl, (tetra), cycloaliphatic, heterocycloalkenyl, , decane = each of the alkyl groups, each of the heteroalkyl groups, each of the thiol groups, each A heterobasic group, a hesenyl group, each of the heteroalkynyl groups, each of the aryl groups, and each of the heteroaryl groups are broad. The group of the ring, each of the ring, each of the heterocyclic groups and the groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be: dilute or different substituents, each substituent Independently selected from the group consisting of _ group, 1 ί η, Ν〇 2, alkyl, hydrazino, calcinyl, alkenyl, dentate, alkynyl, i-block, aryl, heteroaryl, cycloalkyl Μ, «, 叠, azide, 135177 • 10- 200922559 -NR2] R2 2, _NR23SQ2R24, nr23c(q)qr2() -W5r26, _c(〇)r24sri9 —, 'S〇2R19' '0C(0 R24'-C(〇)NR^R26. -NR23C(N-CN)NR25R26 and -NR2 3c(〇)nr25r26 group; each 未 when not bonded to the heart) is independently selected from the group consisting of (4) 2, a fine base, a heteroalkenyl group, a silk, a silk, an aryl group, a heteroaryl group, a ring-based group, a cycloalkenyl group, a heterocycloalkyl group, a heterocycloalkenyl group, and each of the alkyl groups An alkyl group, a ^ valenyl alkenyl group, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the δ^ φ δ 玄 玄, each of the heteroaryl groups, each of the cycloalkyl groups Each of the cycloalkenyl groups, the long-term valley D-Hertidecyl group, and each of the heterocyclic olefinic systems are not Generation 'or plug Wu, Fei Zhu brother ~ ask if conditions may be independently substituted with one or more of the same different substituents ΐ, each substituent is independently selected from keto, halo. , -CN, -N〇2, alkyl, miscellaneous, calcinyl, dilute, alkenyl, alkynyl, haloalkynyl, aryl'hetero]heterocyclyl, cycloalkyl, cycloalkenyl Base, heterocycloalkyl, heterocycloalkenyl, most nitrogen, -OR19, -0C(0)0R20, -NR2 1R22, _NR2 3S0 R24, N 23 KC(〇)〇R2 0, _nr23c(〇)r24 -S〇2NR25R2 6, _C(0)R2 4 L(〇)〇R2 0, _sr19, _s(〇)r19, -S02 Rl 9, _〇C(〇)R2 4, _c(〇2 K , - a group of nr23c(n-cn)nr25r26 and -nr23c(o)nr25r26; each RI 〇 (when not bonded to R9) is independently selected from w, self-contained H, alkyl, heteroalkyl, sulfhydryl, heteroolefin Alkynyl group, alkynyl group, heteroalkynyl group, a aryl group, a heteroaryl group, a cycloalkyl group, an alkenyl group, a heterocycloalkyl group, a heterocycloalkenyl group, wherein each of the alkyl groups, the various heterogeneous groups, An alkenyl group, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the fluorene-containing groups, each of the heteroaryl groups, each of the 135177 200922559, the ring-burning group, each of the rings, and the earth' σ the heterocycloalkyl group and each of the heterocycloalkylenes: ', : 35 substituted' or, as the case may be, independently - or multiple may be the same = no Substituent substituents 'each substituent is independently selected from the group consisting of — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — Aryl, heteroaryl, cyclodextrin, cycloaliphatic, heterocyclo, heterocycloalkenyl, azido, _〇r19, 〇〇c(〇)〇r2〇, NR R 2 ' -NR23S〇 2R2 4 x -NR2 3C(〇)〇r20 λ _NR2 3C(〇)r24 ^ f \ -s〇2nr25r26, _C(0)R24, c(〇)〇r2q, 视19, _i9, s〇2R, -0C (0) R24, _c(〇)Nr25r26, _nr23c (groups of nc R25R26 and -NR23C(0)NR25R26; or t'R9 and R1G and the N atoms to which they are attached form a heterocyclic group or a hetero a cycloalkenyl ring containing one to three heteroatoms selected from the group consisting of .0 and 5, wherein the heterocycloalkyl ring and the heterocyclic ring system are each unsubstituted, or independently from one or more The substituents may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of a keto group, a halogen, a —CN, —N02, an alkyl group, a heteroalkyl group, an alkyl group, an alkenyl group, a halogen group, an alkynyl group, and a halogen. Alkynyl, aryl, heteroaryl, aryl-homo-based, heteroaryl-alkyl group, ring , cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _0R19, -〇C(O)〇R2 0, 2]R22, _nr23s〇2r24, _nr23c(〇)〇r20, -NR23C (0) R24, _s〇2NR25R26, _C(0)R24, -C(0)OR20, -SR]9, -S(〇)R]9, -S02 Rl 9, -〇C(〇)R2 4, _c(〇)nr2 5 r2 6 , nr2 3 C(N CN) NR2 5 R2 6 and _NR2 3 c(〇)NR2 5 R2 6 ; each Rn is independently selected from the group consisting of H, alkyl 'heteroalkyl, alkene a base, a heteroalkenyl group, a fast group, a heteroalkynyl group, an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkenyl group, a heterocycloalkane 135177 12· 200922559, a heterocycloalkenyl group, wherein each of the alkyl groups a heteroalkyl group, each of the pendant alkenyl groups, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the heteroaryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, and each of the cycloolefins The base, each of the smocks and each of the heterocyclenyl groups are unsubstituted or, as the case may be, independently - or a plurality of substituents which may be the same or different, each substituent being independently selected from the group consisting of Halogen, -CN, -N〇2, alkyl, heteroalkane, '' Base, block group, haloalkynyl, aryl, heteroaryl 7丞, % alkyl, cycloalkenyl, heterocycloalkyl, heterocyclic county, Qianji, collar 19, cargo (〇)〇r2〇, - NR21R22, _NR23s〇2R24, NR23c_R2G, NR23c(〇)R24, -so2nr-r- &gt; -C(0)R24 . „C(O)〇r20 ^ sr19 ^ s(〇)Ri9 -S〇2R】9 a group of -0C(0)R24, _C(〇)nr25r26, nr23c(n cn)nr25r26 and -nr23c(o)nr25r26; each R12 is independently selected from the group consisting of an anthracene, an alkyl group, an alkynyl group, a heteroalkynyl group, An aryl group, a heteroaryl group, a group, a heterocycloalkenyl group, a heteroalkyl group, an alkenyl group, a heteroalkenyl group, a cycloalkyl group, a cycloalkenyl group, a heterocycloalkane, wherein each of the alkyl groups, each of the heteroalkyl groups, An alkenyl group, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloaliphatic groups, and each of the heterocycloalkyl groups and Each of the heterocyclic ring systems is unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different. Each substituent is independently selected from the group consisting of a keto group, a halogen, a -CN, a ruthenium 02, and a burn. Base, miscible, ketone, dilute, i-dilute, alkynyl, haloalkynyl, aryl, heteroaryl , cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocycloalkenyl, azido, _0R19, _oc(o)or20, 135177 -13- 200922559 _NR R22, _NR23S〇2r24, -NR23C(0)0R2. -NR23C(0)R24, -so2nr25r26, _c(0)r24, c(〇)〇r2, _sr19, _s(9)Ri9 26 S02R &gt; -0C(0)R2 4 n -C(〇)NR2 5R2 6 , NR23C(N-CN)NR25R: and a group of -nr23c(0)nR25R26; each R 3 is independently selected from the group consisting of anthracene, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, Aryl, ring, ring, heterocycloalkyl, heterocycloalkenyl, Each of the heteroalkyl groups in the decyl group, each of the alkenyl groups, each of the heteroalkenyl groups, each: an alkynyl group, each of the heteroblock groups, each of the aryl groups, each of the heteroaryl groups, and each β: The k-based L(tetra) group, each of the heterocyclic alkyl groups, and each of the heterocyclic rare earths are not! Substituting, or optionally, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a fluorenyl group, a letter, an NN 〇 2, a cyclization group, a aryl group, a halogen group; Dilute, haloalkenyl, block, ethynyl, aryl 'heteroaryl, cycloalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkenyl, azido, _or19, _oc(o)or20 -NR2 1R2 2, _NR23SQ2R24, _nr23c (◦辉2. NR23c Team 24, -S〇2NR2 5R26, _c(〇)r24, c(〇)〇r20, sr19, _s(〇)Ri9, -S〇2r19, _〇C(〇)R2 4 n _c(〇)NR25r2 6 n -NR2 3 C(N-CN)NR2 5 r2 6 and -NR2 3C(〇)NR25r26 group; each R] 4 series independently selected from H, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, each of which The alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, each of the heteroalkenyl groups, each of the alkynyl groups, each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, and each of the 135177 • 14-200922559 a cycloalkyl group, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted' or Optionally, independently, substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of fluorenyl, sulfhydryl, -CN, -N〇2, alkyl, heteroalkyl, alkyl, Alkenyl, haloalkenyl 'alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl 'cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, 〇R19, 〇( :(C))C)r2〇, -NR2 1R2 2, _NR2 3S〇2R24, nr23c(〇)〇r2〇, nr, (9), -S〇2NR25R2 6, _C(〇)R24, c(〇)〇r2 . , sr19, s(9)R 9 , -S02R!9 . .〇C(〇)R24 ^ -C(〇)NR25R2 6 , -NR23C(N-CN)NR25R2 6 and -NR2 3 C(0)NR2 5 R2 6 Each R15 (when not bonded to Ri6) is independently selected from the group consisting of hydrazine, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl a cycloalkenyl group, a heterocycloalkyl group or a heterocyclic fluorenyl group, wherein each of the alkyl group, each of the hetero aryl groups, each of the dilute groups, each t-bake group, each of the alkynyl groups, and each of the alkynyl groups Each of the aryl groups, each of the heteroaryl groups, each of the cycloalkyl groups, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted or, as the case may be, independently a plurality of substituents may be substituted with the same or different substituents, each substituent being independently selected from the group consisting of a keto group, a dentate, a -cn, a -no 2, a decyl group, a heteroalkyl group, a phenotypic group, a dilute group, a dilute group, an alkyne , haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -0R19, _0C(0) (DR=, -NR21R22, _NR23S 〇2R24, _nr23c(〇)〇r2(), nr23c(〇)r24, -s〇2Nr25r26, _C(0)RM, ((9)(10).,_SR19 s(〇)Ri9, -S〇2RHOC(0)R24, -C(0)nr25r26, 视23c(N cn)nr25r26 135177 15· 200922559 and -NR23C(0)NR2 5R26 group, ·W W And when bonded) are independently selected from the group consisting of a dilute group, a heterocyclic group, an alkynyl group, a heteroalkynyl group, an aryl group: a group, a ring group, a heterocyclic ring group, a heterocycloalkenyl group, The heterofluorenyl group, each of the dilute groups, the alkynyl group, each of the heteroacetylene groups, the heteroaryl group, the aryl group, each of the heteroaryl groups, each 忒% alkyl group, each of the cycloalkenyl groups, &amp; ^ ^ + each D-heteroalkyl and each of the heterocycloalkenyl groups are unsubstituted or, as appropriate, the brothers are independently substituted by one or more substituents which may be the same or different, each of which is substituted The base system is independently selected from the group consisting of a keto group, a dentate, a -CN, a _N02, an alkyl group, a heteroazaalkyl group, a south alkyl group, an alkenyl group, an olefinic group, a block group, a tooth alkynyl group, an aryl group, a heteroaryl group, Cycloalkyl, cycloaliphatic, heterocycloalkyl, heterocyclic, azide, 〇r19, _〇c(〇)〇r2〇, NR2 1R2 2 , _NR2 3S〇2R2 4 n _NR2 3 C( 〇)〇r2 〇^ .NR2 3C(〇)r24 . -s〇2Nr25r26, _C(0)R24, _c(〇)〇r2. sRi9, _i9, S〇2R'9 . .〇C(〇)R2 4 . -C(〇)NR2 5R2 6 . -NR2 3 C(N-CN)NR2 ^ R2 6 and -NR23C(0)NR25R26 a group of ^?' together with Rl6 and the N atom to which they are attached form a heterocyclic or heterocyclic fluorenyl ring containing - to three heteroatoms selected from n, 〇as, wherein the heterocycloalkyl The ring and the heterocycloalkenyl ring system are each unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of a keto group, a halogen, _CN, _N 〇2, ^, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, Cycloalkane U5177 -16- 200922559 yl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, 〇Rl9, -OC(0)OR20, -NR2, R22, -NR23S02R24, -NR23C(0 )OR2〇, -NR2 3 C(0)R2 4, -S02 NR2 5 R2 6, -C(〇)R2 4, _C(0)0R2. , -SR1 9, -S(0)R] 9, -S02R] 9, -〇C(0)R24, -C(〇)NR25R26, -NR23C(N-CN)-NR25R24-NR23C(0)NR25R26; Each R1 7 (when not bonded to R18) is independently selected from the group consisting of H, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, Cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, _CN, _〇c(〇)〇r2〇, 〇〇Rl 9, -NR21R22, -NR23S〇2R24, _NR23C(〇)〇r2 0, _NR2 3C( 〇) R24, -S02 NR2 5 R2 6, -C(0)R2 4, _C(0)0R2 o, _SRl 9, s(〇)Rl 9, s〇2 Rl 9, -〇C(0)R24, -C(0)NR25R26, _NR23c(N-CN)NR25R26&amp;_NR23C(0)-NR25R26 wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl groups, each of the heteroalkenyl groups, each of the alkynyl groups, Each of the heteroalkynyl groups, each of the aryl groups, each of the heteroaryl groups, the respective side of the bad alkyl group, each of the cycloalkenyl groups, each of the heterocycloalkyl groups, and each of the heterocycloalkenyl groups are unsubstituted or The conditions are independently substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of keto, halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl Haloalkenyl, alkyne , alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _0R1 9, _〇C(〇)〇R20, -NR21R22 . -NR23S 〇2r2 4 n -nr2 3 C(0)0R2 0 ' -NR23C(0)R24 . -S〇2NR25R26, -C(〇)R2 4, _c(〇)〇R2. , _SR19, _s(0)Rl9, -S02R19 &gt; -〇C(0)R24 ^ -C(〇)NR25R26 &gt; -NR2 3 C(N-CN)NR2 5 R2 6 and -NR23C(0)NR25R26 Groups; 135] 77 • ]7· 200922559 Each R18 (when not bonded to R17) is independently selected from the group consisting of hydrazine, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, aromatic , heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, _CN, _〇c(〇)〇R2G, 〇〇Rl 9, -NR21R2 2 &gt; -NR23S02R24 λ -nr2 3 C(0)0R2 0 &gt; -NR23C(0)R24 ' -S02NR2 5R2 6, _C(〇)r24, c(〇)〇r20, sr19, s((7)Ri9, _s〇2Rl9, -〇C(0) R24 . .C(〇)NR25R26 . -NR2 3C(N-CN)NR^R2^.NR2 3C(〇). NR25R2 6 , U&amp;, 谷边坤基柳丞 丞' each of the alkynyl groups, each of the alkynyl groups Each of the aryl groups, each of the heteroaryl groups, each of the heteroalkyl groups, each of the cycloalkenyl groups, each of the heterocyclic groups, and each of the heterocyclic groups are unsubstituted or, as the case may be, independently Or a plurality of may be the same; different substituents are substituted, each substituent is independently selected from the group consisting of a fluorenyl group, a CN N 〇 2 group thereof, a decyl group, a heterogeneous group, a functional group, an alkenyl group, a dentate::=, (4) Aryl, heteroaryl, sulfhydryl, _R22 ^ azide, 〇Rl9, -〇C(_2., , -NR so2R24, collar 23 r2G -S〇2NR2 5R2 6 C(〇)R - so2R^ &quot;?R ' — -S(0)R^ .NR23p ''C(〇)nr25r26-nr-c(n-cn)nr25r26 and -NR2 3 C(〇W 5 r2 6 group _ IN; JNR R or 'R' and Rl8 and their attached cycloalkenyl, heterocycloalkyl ring, human κ, e form a cycloalkyl group, a hetero atom, or a heterocyclic ring "with a - to - three One selected from the group consisting of N, 0 and S and s heteroatoms, and two selected from the group consisting of N, fluorene wherein the heterocycloalkyl ring 135177 _ ring system is unsubstituted, * J8. 200922559 or optionally Substituted by - or a plurality of substituents which may be the same or different, each substituent is independently selected from the group consisting of a BenQ, an anion, a _cn, a _n 〇 2, a decyl group, a heteroalkyl group, a functional group, a dilute group, and a dilute group. Base, block group, dentate group 'aryl, heteroaryl, aryl-alkyl (heteroaryl)-alkyl, cycloalkyl, cycloalkyl, heterocycloalkyl, heterocyclic, azide Base, _〇r]9, Na (four), view 2] R22, Na 3s〇2R24, Νι^_2〇, tear 23C (〇) R24, , NR25R26,, _c_2. , _SR]9, -S(0)R19, _S〇2R19, _〇c(〇)R24, c(〇)nr25r26' tear 2 coffee _ NR25R2 6^ _nr23c^nr25r26 . Each R〗 9 series is independently selected Including H, 护 I, 疋, 烧, 烧, 卤, aryl, heteroaryl, cycloalkyl, _cycloalkyl; each R20 is independently selected from the group consisting of Η, pt ^ 70 a base, a dentate alkyl group, a heteroalkyl group, a haloalkyl group, an aryl 'heteroaryl' cycloalkyl group, a naphthyl group; r (when not bonded to R22) are independently selected from the group consisting of ruthenium, dazzle, and teeth. The base of the (4)-yl-aryl, heteroaryl, cycloalkyl, and cyclization: R22 (when not bonded to R21) is independently selected from the group consisting of hydrazine, alkyl, and alkane. |Heterinyl, aryl, heteroaryl, cycloalkyl, cyclane, /, R, and the group to which they are attached, form a heterocyclic ring, a % dilute ring, containing - to three From the inclusion of N, 0 and S, :, independently* from H, alkyl, dentyl, heteroalkyl, pyridinium, aryl, heteroaryl, cycloalkyl, _cycloalkyl ; 135177 -19- 200922559 Diterpenes are independently selected from the group consisting of H, silk, i-based, miscellaneous, i miscellaneous earth, 25-membered, heteroaryl, cycloalkyl, halocycloalkyl; When selected from the group consisting of ruthenium, ruthenium, chitosan, dentate, aryl, heteroaryl, cycloalkyl, _cycloalkyl; and 圮6 (when not bonded to R25) ) are independently selected from the group consisting of hydrazine, alkyl, haloalkyl, and others! a heteroalkyl group, an aryl group, a heteroaryl group, a cycloalkyl group, a cycloalkyl group; ^ R and R together with the hydrazine atom to which they are attached form a heterocycloalkyl or heterocycloalkyl ring containing one to three It is selected from heteroatoms including N, hydrazine and S. 2. A compound of the formula wherein the ring a is a 4-7-membered cycloalkyl ring and e is -C(R4)(r5)_. 3. The compound of claim 1, wherein ring a is a 5-7-membered heterocycloalkyl ring, and E is adapted to include _〇_, _s_, _s(〇)_, _s(〇)2_, _n(r6 )_, _n(c(y)R7)_, _N(C(7)〇R8)...N(c(7)n(r9)(r10))...c(〇)_N(Rll)_, _N(Rn)_c(〇)_ , -S(〇)2-N(RH )-, -NCR11 )-S(0)2-, -C(0)-0-, -ac(O)-, -〇-N(R6)-, -N(R6)-〇-, -N(R6)-N(R12)-, -N=N-, -C(R7)=N-, -C(0)-C(R7)=N-, -C(0)-N=N-^ -O-CCYVNCR11)- '-NCR11 )-C(Y)-0- &gt; -NCR11 )-C(Y)-N(R12)-, -C(Y ) -N(Rn)-0-, -C(Y)-N(Rn)-N(R12)-, -〇-N(Rn)-C(Y)- and . 4. The compound of claim i, wherein ring a is a 5-6-membered heterocycloalkyl ring and the group E is selected from the group consisting of -〇-, -S-, -S(0)-, -S(0) ) 2-, -N(R6)-, _c(0)-N(Rn)-, and -N(Rn)-C(〇)_. 135177 20-200922559. The compound of claim 1, wherein ring A is a 5-6-membered heterocycloalkyl ring, and ', selected from the group consisting of _〇_, -S-, -S(O)- , -S(0)2_ and -N(r6)-. 6. The compound of claim 5 wherein R6 is selected from the group consisting of hydrazine, alkyl, -C(0)R24, -C(〇)〇R2 0 and _C(S)R2 4 . The compound of claim 1 wherein ring A is a 5-6-membered heterocycloalkyl ring and the group E is selected from the group consisting of _〇_ and _N(R6)_. 8. The compound of claim 7 wherein % is selected from the group consisting of η, alkyl, -C(〇)R24, -C(0)〇R2〇 and -C(S)R24. The compound of claim 8, wherein ring a is a 5-membered heterocycloalkyl ring. The compound of claim 8, wherein ring a is a 6-membered heterocycloalkyl ring. The compound of claim 1, wherein ring B is an unsubstituted aromatic ring or an aromatic ring substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogens, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl -alkyl-, cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero-5 alkenyl, azido, 〇R19, _〇c(〇)〇r20, _Nr21r22, -NR23S〇2R2 4 , _NR2 3C(〇)〇R2 0 , ,NR2 3C(〇)R2 4 , _S〇2NR2 5R2 6 . -C(〇)R24, -C(0)0r2. , —SRl9, _s(〇)Rl9, _s〇2Rl9, 〇c(9)r24, _C(〇)NR2 5 R2 6 , -NR2 3 C(N-CN)NR2 5 R2 6 and _NR2 3 c(〇)NR2 5 r2 6. 12. As requested! The compound 'wherein ring B is an unsubstituted stupid ring or a benzo ring substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halogen, -CN, -N 〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, Cycloalkyl, cycloalkenyl, heterocycloalkyl, 135177 -21 - 200922559 Heterocyclic sulfanyl, azide, -ORM, -〇c(9)〇R20, _nr21r22, -NR23S〇2R24, _服23c(〇)〇 R2. , tear 23c (〇) r24, nr25r26, _C (〇) 〇 R2. , view]9, part) r]9, _s〇2Ri9, _〇c浑", -C(0)NR25R26 . -NR^C(N-CN)NR25R26^_nr23C(〇)Nr25r26 〇f \ 13. a compound of the request, which is an unsubstituted or substituted heterocyclic ring, or a substituted heteroaromatic ring, which is substituted by one or more substituents which may be the same or different, each substituent being independent Selected from the group consisting of a single element, CN, -NQ2, affiliation, a heterofilament, a pyrolyl group, an alkenyl group, an alkenyl group, a block south block, an aryl group, a heteroaryl group, an aryl group, a aryl group, a heteroaryl group -alkyl-, arylalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _OR19, 〇c(0)0R2G, _nr21r22, NR23s〇2R24, NR23c(9)(10)〇, C(0)R 4. _S〇2NR2 5R2 6. c(〇)r24, c(〇)〇R2Q, (10) 9, -S(0)R'9 Λ _s〇2R]9 ^ , 〇C(〇)r24 n _C(〇 Nr25r26 ^ _NR23C(N_CN) R 5r26^-NR23C(0)NR25r2 6 0 and the compound of the formula 13 wherein the ring W5-6-membered heteroaromatic ring has the same or different ring heteroatoms, each The heterocyclic atom is independently selected from the group consisting of the snails N'S, 〇, s(0) and s(〇)2. ', the θ of the member 1, wherein the ring B is unsubstituted or taken The soil group is selected from the group consisting of benzo-'αα-based, thiophenyl group, tj-based group, azole, &lt;1/sedyl, °m-salt, &lt;°-sitting, iso-L, X4 Sit-base, three: 喧-salt base than bite base.荅11 well base 'mouth dense 唆 base, mouth than spray base and three ρ well base. Or the compound of item 1, wherein the rule 1 is an unsubstituted aryl group, or an aryl group substituted with the same or different substituent of -s, each substituent group 135177 -22-200922559 is independently selected from the group consisting of halogen, _CN, - N〇2, alkyl, heteroalkyl, naphthyl, alkenyl, ienyl, alkynyl, alkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl, Cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -OR19, -0C(0)0R20, -NR21R22, _NR23S〇2R2 4, -NR23C(0)〇R2〇, - Nr2 3c(〇)R2 4, _s〇2Nr25r26, c(〇)r24, -C(0)OR2〇, _SRl9, _s(〇)Rl9, -S〇2Rl9, 〇c(〇)r24, -C(0 NR2 5R26, _nr23c(N_cn)nr25r26&_nr23c(〇)nr25r26. The compound of claim 1, wherein R is a stupid group substituted by one to four substituents which may be the same or different substituents are independently selected from the group consisting of a dentate group, -OH, &lt;:N, -N 〇2, -NR2, 22 and _ alkyl. NC The combination of halogen groups is selected from the group consisting of the following 20. The compound of claim 1 wherein R] is And R27 and R28 are each independently selected from the group consisting of hydrazine and hydrazone 21. The compound of claim i, wherein r2 is selected from the group consisting of _c(〇)r7 135177 23· 200922559 -C(0)NR9R1. And _c(〇)〇R8. 22. The compound of claim 1, wherein p is ο and R3 is absent. 23. As requested! a compound wherein 卩 is ^" or 4, and each r3 is independently selected from the group consisting of fluorenyl, heptyl, alkenyl, hetero, _CN, _N〇2, _0R1 9, -〇C(〇)〇R2 0 Λ _NR21R22 ^ -C(〇)R2 4 , _C(S)R2 4 , -C(〇)〇R2〇^ -C(0)NR2 5R2 6 , Wherein each of the alkyl group, each of the heteroalkyl group, each of the alkenyl group, and each of the heteroalkenyl groups is unsubstituted or, as the case may be, independently substituted with one or more substituents which may be the same or different, each substituent Is independently selected from the group consisting of keto, halogen, CN, -no2, alkyl, heteroalkyl, mercapto, dilute, (tetra), alkynyl, halo, aryl, heteroaryl, cycloalkyl, ring Dilute, heteroalkyl, heterocycloalkenyl, azido, _or19, _oc(o)or20, - Ί-NR23S02R24, Na 3c_R2. , nr23c(0)r24, -s〇2nr25r26, _C(0)R24, _C(0)0R2. , -SR19, s(〇)Ri9, - is called Wqc(q)r24, ‘c_r25r26 ' nr23c(ncn)nr25r26 and -NR2 3C(〇)Nr25r26. 24. A compound according to claim i, a Tp horse 2, 3 or 4, and bonded to any two R3 groups of the same ring A atom, together with the carbon atoms to which they are attached A snail-based, a spirulina-based, a spiro-heterocyclic ring containing one to three rings independently selected from the group consisting of sylphy, spectroscopy, _s_, _s(g)_, _s(〇)2_, and -〇- Heteroatom, or spirulina. "Clothed alkenyl 5 garment, containing one to three independent telecontainers - including -ΝΗ-, -NR6_, each sub. (〇)-, part) 2- and _〇- The compound of claim 1 wherein R2 and R3 are together with the carbon atom 135J77-24-200922559 to form a cycloalkyl, cycloalkenyl, heterocycloalkyl ring, containing one to two Individually selected from ring heteroatoms including -NH-, -NR6 -, -S-, -S(〇)_, s(〇) and -Ο-, or heterocyclic ring, containing one to three independently selected From the ring heteroatoms including -ΝΗ-, -NR6-, -S-, -S(〇)-, -s(〇)2_ and -〇-^ 26. The compound of claim 1 or a pharmaceutically acceptable compound thereof Salt, solvate, 2 R (II) ” RR, R, R28, E and ring (4) are selected independently of each other, wherein E is selected from the group consisting of -a, each, m, machine...c(r4)(r5), Na%, Na) 〇R8)...n(c(7), r, _. 27. The compound of claim 26, wherein: E is selected from the group consisting of -a, _s_, na, _s(〇)2_, _c (r4 nano and ring B are not a substituted or substituted part of a group, a sulfanyl group, a thiophenyl group, a fluorenyl group, a fluorene group, a sulfonyl group, a pyridyl group, an isodecyl group, Iso-p-salt, three-seat, repeats, two-salt base: well-based... dense base" &quot; base and three, base; ... R is the benzene that can be replaced by the same or different substituents Substituents, each 135177 • 25- 200922559 substituents are independently selected from the group consisting of halo, -OH, -CN, -N〇2, -NR21R2 2 and 13⁄4 alkyl; and R2 is selected from -C(〇)R7, -C(0)NR9R10 and -C(〇)〇R8 28. The compound of claim 27, wherein R1 is: ☆^, and R27 and R28 are each independently selected from the group consisting of hydrazine and alkyl. a compound of 1, or a pharmaceutically acceptable salt, solvate, ester, prodrug thereof or Configuration thereof, having the general structure shown in formula (ΙΙΙ.1): Select, and wherein: ε is selected from the group consisting of -a, _s_, _s(0)...s(0)2...c(r4)(r5)·, Na, -N(C(Y)R7)-, -N (C(Y)OR8)- and -WC^NO^XRio)); and p is 0, 1 or 2. 30. The compound of claim 29, wherein: e is selected from the group consisting of coffee) (r5)_, _〇_, _s_, _s(〇)...s(〇v and Na^; ring b is unsubstituted or Substituted aromatic, or unsubstituted (d) substituted 5 member heteroaromatic rings having μ3 ring heteroatoms, which may be the same or different, 135177 -26- 200922559, each ring hetero atom is independently selected from The substituents (when present) of N, S, 〇, S(〇) and s(0) 2' on the (tetra) ring or the heteroaromatic ring are independently selected from the group consisting of: -CN, -N〇2, alkyl, heteroalkyl, dentyl, alkenyl, *alkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl tertyl aryl-alkyl _, cycloalkyl, cycloalkenyl, heterocycloalkyl, hetero-alkenyl, azide, 〇 Rl9, _〇c (9) 〇 R2 〇, - 妒 2 妒, NR S 〇 2R, Na busy (9) 01120, - NR23C(〇)R2 4, _S〇2NR2 5R2 6, i KC(0)RC(0)QR2G, SRl9, s(〇)Rl9, _s〇2Rl9, _qC(〇)r24, C(0)NRR, _NR23C( N-CN)NR25R26^NR2 3C(Q)NR2 5R2 6; R is an unsubstituted aryl group, or may be taken by one or more substituents which may be the same or different Substituted aryl 'each substituent is independently selected from the group consisting of dentate, _cn, -N02, alkyl, miscible, halogen-based, dilute, difunctional, alkynyl, alkynyl, aryl, hetero Aryl 'aryl-alkyl-' 'heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, _〇Rl 9, 〇C (〇) 〇R2 〇, -NR21R22, _NR23S〇2R24, -NR2 3C(〇)〇R2 0, _NR2 3C(〇)R2 4, -S02NR25R26, -(:(0)1^2 4, _c(〇)〇R2G, _SR1 9, _s(〇)R19, _S〇2Rl 9, -0C(0)R24 &gt; -C(0)NR25R2 6 , -NR23C(N-CN)NR25R26A-NR23C(0)- NR25R26 ; R2 is selected from Including -C(0)R7, -C(〇)NR9R10 and -C(0)0R8; p is 0 or 1; and each R3 (when present) is independently selected from the group consisting of an alkyl group, a heteroalkyl group, and a dilute group. , heteroalkenyl, -CN, -N02, -OR19, -〇c(0)OR20, -NR21R22, -C(0)R24 ' -C(S)R24, -C(0)OR20 and -C(〇 And NR25R26, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heteroalkenyl groups 135177 -27- 200922559 is unsubstituted or, as the case may be, independently - or a plurality of may be the same or different Substituent substitution - each substituent is independently selected _ base, dentate, -CN, -N02, alkyl, ketone, leucoyl, dilute, dentyl, alkynyl, haloalkynyl, aryl 'cycloalkyl, heterocycloalkenyl, - NR21R22 . -nr23so2r24 Heteroaryl, cycloalkyl, cycloalkenyl, heteroazepine, -OR19, -〇c(〇)〇r20, -NR2 3 C(〇)〇R2 0 Λ -NR23C(0)R24 ' &quot;S〇2NR25R26 ' -W4 ' -C(〇)〇R^〇. -SRi9 , .S(〇)ri9 . a group of -s〇2r19, -〇c(0)r24, _c(0)nr25r26, nr23c(n c_r25r26 and -nr23c(o)nr25r26. 31. A compound of the formula 3, wherein: ring B is The unsubstituted or substituted part of the group is selected from the group consisting of benzo, thiol, thiophene, ketone group, s-based group, s-based group, Salivary "plug two. Sitting base" than bite base, cultivating base 'pyrimidinyl, pyridinyl and three tillage; R is one to four, which may be the same or unsubstituted, independently selected from the group consisting of a halo group, and a haloalkyl group; a phenyl group substituted with a substituent, each -OH ' -CN &gt; -N〇2 ' -NR21R22 R2 is selected from the group consisting of: _c(q)nr9r1G and _c(〇)〇r8; P is 〇 or 1; and each R3 (when present) is independently selected from the group consisting of a hospital base, a miscellaneous base, an alkenyl group, and a hetero Fine base, each. The alkyl group, each of the heteroalkyl groups, each of the alkenyl groups and each of the heteroalkenyl groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different. Selected from ketone, halogen, 135177 -28- 200922559 -CN, -N〇2, alkyl, misalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl , cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azide, -OR19, _〇C(〇)〇R20, -NR2]R2 2, _NR2 3S〇2r2 4, _NR2 3C (〇)〇R2 0, nr23c(〇)r24, -S〇2NR2 5R2 6, _C(〇)R2 4, _c(〇)〇r20, view19, _s(〇)Rl9, _S〇2 R] 9, a group of -0C(0)R2 4, -C(0)NR2 5 R2 6, _nr2 3 c(N-CN)NR2 5 R2 6 and -NR2 3 c(〇)NR2 5 R2 6 . And the system domain includes Η, alkyl, -C(0)R24, -C(0)OR20 and -C(5)R24. 3 3. A compound of sirloin 1 or a pharmaceutically acceptable salt, solvate, steroidal drug or isomer thereof having the general structure shown in formula (III.2) : (III.2) The acoustic ruler 1, R2, R3, R2 7, R2 8, p' E and ring B are selected independently of each other, and wherein: E iS a , self-contained -〇_, -S-, -S(O)-, -S(0)2-, -C(R4)(R5)-, -N(R6)-, N(C(Y)R7)-, -N(C(Y)OR8 )- and -N(C(Y)N(R9)(R1(}))-; and 135177 -29- 200922559 P is 〇, 1 or 2. 34. The compound of claim 33, wherein: Self-contained ((10) nano...a, s ring B is not abbreviated to the secondary ten L-S(0)~, -S(〇)2- and -N(R6)-; eucalyptus, work-substituted or substituted An aromatic 5-6 Chang μ 〇, or an unsubstituted or substituted berberine ring having μ3 ring ia π heteroatoms, which may be 4 or different 'each ring hetero atom system' « Rn, Shishi blocked from the inclusion of N, S, 0, S(O) and s(〇)2, the substituent on the aromatic ring or the heteroaryl ^ ^ ^ . Independently including halogen, _c k gan Ν〇 2, alkyl, heteroalkyl, halo, dilute, haloalkenyl, fry, &amp; acetylene, phenyl-hospital Heteroaryl-homo-based, net e-suit pit, cycloalkenyl, heterocycloalkyl, Ring dilute, azide, _0R19, _〇c(〇)〇r20, _nr2ir22, -NR, #, 顿23c_R2Q 'Tear 23c(〇)r24, which pulse 25 feet 26, -C(〇)R24,- C(0)OR2Q, _SRi9, _s(〇)Rl9, s〇2r19, _〇c(〇)r24, -C(0)NR25R26 ' _Nr23c(n_cn)nr25r2^_nr23c(〇)nr25r26 ; R1 is unsubstituted An aryl group, or an aryl group substituted by one or more substituents which may be substituted or different, each substituent being independently selected from the group consisting of dentate, _CN, -N〇2, alkyl, heteroalkyl, halogen Alkyl, dilute, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, aryl-alkyl, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl ,heterocyclenyl, azide, _〇Rl 9, 〇〇C(〇)〇R2〇, _NR2 1R2 2 ' _NR2 3S〇2R2 4, nr23c(〇)〇r2〇, nr23c(〇)r24, - S02 NR2 5 R2 6, -C(0)R2 4, -c(〇)〇r2 〇, _SRi 9, _S(0)R19, _s〇2 R] 9, -〇C(0)R24, -C( 〇) NR25R26, _NR2 3C(N_CN)NR2 5R2 6&amp;_NR2 3C(〇)_ nr25r26 ; R2 is selected from the group consisting of -C(〇)R7, _c(0)NR9R10 and -C(0)0R8; 135177 *30· 200922559 p is 〇 or 1; and each R3 (when present) Independently selected from the group consisting of alkyl, heteroalkyl, dilute, heteroalkenyl, _CN, _N〇2, _0Rl 9, -〇C(0)〇R20, -NR2 1 R22, -C(〇)R24, -C (S) R24, _c(0)〇R2〇, and c(〇)Nr25r26, each of the sulfonyl groups in Y, each of the miscible groups, each of the fluorenyl groups, and each of the heteroalkenyl groups are unsubstituted or The conditions are independently substituted by one or more substituents which may be the same or different. Each substituent is independently selected from the group consisting of a keto group, a quinone, a CN NO:, a decyl group, a heteroalkyl group, a haloalkyl group, a decyl group, a halogenated alkene. , alkynyl, ynkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, 〇Rl9, -〇c(〇)〇r2 (), NR R &gt; -NR23s〇2r2 4 λ -NR2 3 C(0)OR2 0 ' -NR23C(0)R24 &gt; -S02NR2 5R2 6, _c(〇)r24, c(〇)〇r2g, sr19 , s(〇)Ri9, -S02R ' -〇C(〇)R2 4 λ -C(0)NR25R26 - -NR2 3 C(N-CN)NR2 5 R2 6 and -NR2 3 C(0)NR2 5 R2 Group of 6 groups. 35. The compound of claim 34, wherein: % B is an unsubstituted or substituted moiety selected from the group consisting of benzo, furanyl, thiophenyl, P. succinyl, carbazolyl, p-plug Salivary, mito, pyrazolyl, isoindole sigma, iso-p-plug. Sitrate, trisal, sulphate, occluded, argon, pyrimidinyl, pyridinyl and tri-farming; R] is benzene substituted by one to four substituents which may be the same or different The substituents are independently selected from the group consisting of halo, 〇h, _cn, -N02, -NR21R22 and halo; R2 is selected from the group consisting of -C(〇)R7, -C(0)NR9R10 and -C (〇) 〇r8 ; P is 0 or 1; and 135177 -31 · 200922559 The dilute base, the heterogeneous R (the field presence %) are independently selected from the group consisting of an alkyl group, a hetero group, an alkenyl group, and an alkyl group. The base, each of the alkenyl group and each of the heteroalkenyl groups are unsubstituted, substituted, or optionally substituted by one or more substituents which may be the same or different, each substituent being independently selected from a keto group' Halogen, (N〇2 alkyl, heteroalkyl, _alkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, hetero-alkyl ,heterocyclenyl, azide, 〇Rl9, _〇c(〇)〇r2〇, -NR2,R2 2 , -NR23S〇2R2 4 x -NR2 3 C(〇)〇R2 0 ^ _NR2 3 C (〇)R2 4 . -S〇2NRUr2 6, _c(〇)r24, _c(〇)〇r2〇, sr19, s(〇)Ri9, -S〇 2RW, _〇C(〇)R24, _c(〇)nr25r26, tearing 23c (n cn hui 25 feet 26 and -NR2 3 C(0)NR2 5 R2 6 group. 36' compound of claim 35 , where R1 is R2 7 and R2 8 are each independently selected from the group consisting of H and alkyl; and R is selected from the group consisting of H, alkyl, -C(0)R24, _C(〇)〇R20 and _C(5)R24. 37. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, prodrug or isomer thereof, having the general structure shown in formula (IV): 135177 -32· 200922559 E is selected from the group consisting of _c(r"(r5)_,...&amp; Ring B is an unsubstituted or substituted argon yarn, (=Pei-and cans~ 5-6-members)糁糁f. Long or unsubstituted or substituted by the same oxime, a hetero atom, the ring hetero atom can be different, each ring hetero atom is «, '&quot; 琏 琏 self includes N, s, 〇, S (Xy&gt;) 2, in the aromatic ring or the heterogeneous) system stands! 6 &amp; % The substituent on the % (when % is present) is independent of acne, _CN ^ ^ ^, alkane Base, heteroalkyl, haloalkyl, such as, alkenyl, alkenyl, alkynyl, enalkynyl, aryl, heteroaryl, aryl-alkyl-, heteroaryl-alkyl-, cyclic I 祗Alkenyl, heterocycloalkyl, heterocyclic, azide, _qr19, na) 〇r2q, Μηη, -NR23S〇2R24, .NR23c(〇)〇R2, nr23c(〇)r24, nr25r26, -C(0)R24 ^ -C(0)〇R2〇, _SRi9 , _S(〇)R,9 . _s〇2Rl9 ^ _〇C(〇)r24 ^ -C(0)NR2 5 R2 6、_NR2 3 C(N_CN)NR2 5 r2 6 and NR2 3 c(9)NR2 5 R2 6 ; R1 is an unsubstituted aryl group or may be one or more substituents which may be the same or different Substituted aryl, each substituent is independently selected from the group consisting of halogen, -CN, -N〇2, alkyl, heteroalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, Heteroaryl, aryl-alkyl-, heteroaryl-alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, azido, -0R] 9, _〇c (C0 〇R2 0, _NR2 1R2 2, _NR2 3S〇2r2 4, NR2 3C(〇)〇R2 0, NR2 3C(〇)R2 4, -S02NR25R26, -C(〇)R24, -C(0)OR20, -SR19 4(0)111 9 , -S02R1 9, -0C(0)R24, -C(0)NR25R26, -NR23C(N-CN)NR25R26&amp;-NR23C(0)-NR25R26 ; R2 is selected from the group consisting of -C (〇) R7, -c(o)nr9r10 and -C(0)0R8; P is 0, 1 or 2; and 135177 • 33- 200922559 when each heart is present) is independently selected from the group consisting of a yard base and a miscellaneous base , alkenyl, heteroalkenyl, -CN, -N02,_0R19, 〇c(〇)〇r20, _nr2]r22, c24, -C(S)R2 4, _C(O)OR2 0 and c(〇 And nr25r26, wherein each of the heteroalkyl groups, each of the alkenyl groups and each of the heterogeneous groups are unsubstituted or, as the case may be, independently substituted by one or more substituents which may be the same or different 'These substituents are independently selected County, halogen, -CN, -N02, alkyl, miscible, pyrolyzed, dilute, dentate, r-block _ fast-radical, aryl, heteroaryl, ring-based, ring-dense, Hetero 'cycloalkyl, heterocycloalkenyl, azido, _〇Rl9, _〇c(〇)〇r2〇, -NR^R22 . _NR23s〇2R24 ^ _nr23c(〇)〇r20 , _NR23C(〇)R24 -S02NR25R2 6. ((9)r24, _c_r2q, _sr19, part)r", -S〇2R'9, -〇C(〇)R2 4 , .C(〇)NR2 5R2 6 λ -NR2 3 C(N-CN a group of NR2 5 R2 6 and -NR23C(〇)NR25r26. 38. The compound of claim 37, wherein: E is selected from the group consisting of _N(R6)_; (cyclic B is an unsubstituted or substituted moiety selected from the group consisting of benzo, furanyl, sulfur Phenyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, pyridyl, 荅P well, pyrimidinyl, Pyridinyl and tri-cultivating; Rl is a stupid group substituted with four substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, 〇H, _Cn, -N02, -NR21 R2 2 and a halogen group; R2 is selected from the group consisting of ·((COR?, _c(0)NR9R10 and _c(〇)〇r8; p is 〇 or 1; and 135177 34· 200922559 each R3 (when present) Is independently selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, and a heterocyclic group, wherein each of the alkyl group, each of the heteroalkyl groups, each of the alkenyl groups, and each of the heteroalkenyl groups is unsubstituted, or Independently substituted by one or more substituents which may be the same or different 'each substituent is independently selected from the group consisting of a keto group, a halogen, a CN N 2 alkyl group, a heteromorphic group, a fluorene group, a dilute group, a dilute group, Alkynyl, haloalkynyl, aryl I, heteroaryl, cycloalkyl, cycloalkenyl, heterolacyl, heterocycloalkenyl, azido, 〇Rl9, 〇〇c(〇)〇r20, _NR2 1R2 2 . -NR23S02R2 4 n -NR23C(0)〇r2° x -NR23C(0)R24 ' -S02NR25R2 6. _C(〇)R24, _c(〇)〇r2. , SR19, s(〇)Ri9, -S02R1^ -0C(0)R2 4 , .C(0)NR2 5R2 6 λ -NR2 3C(N-CN)NR25R26 and -NR2 3 C(0)NR2 5 R2 6 Group of groups. 39. The compound of claim 38, wherein r] is And R27 and R28 are each independently selected from the group consisting of H and alkyl. The R6 is selected from the group consisting of hydrazine, alkyl, _C(0)R24, _c(〇)〇r2〇&amp;_c(s)r24. a compound of the class or a pharmaceutically acceptable salt, solvate, ester, prodrug or isomer thereof selected from the group consisting of: 135177 35· 200922559 135177 -36- 200922559 A compound of the formula (4), which is in the form of an isolated or purified form. A pharmaceutical composition comprising at least one compound of any one of claims 1 to 40, or a hydrazine, a commercially acceptable salt, a solvate or a hydrazine, which is therapeutically effective. The prodrug, the prodrug or the isomer, and the at least one pharmaceutically acceptable carrier comprise at least one additional treatment. 43. The pharmaceutical composition of claim 42 which is administered as an active agent. 44. If the pharmaceutical composition of the request item, the bean, and the medium δ 玄 at least one other therapeutic active agent is selected from the group consisting of: estrogen receptor modulation, 丨, Α ^ ^ η], androgen receptor modulation Preparation, retinoid receptor modulator, cytotoxicity, 丨, 舛 _ ν, ten &quot;~- mother d micro-inhibitor / stabilizer, topography 135177 -37- 200922559 isomerase inhibition over time, e + 立μ物用用dna recruitment of acid, anti-metabolism, f ^ / to cells (four) antibodies, radiation (four) type, HMG-COA == tube = trans: enzyme inhibitor, farnesyl protein transfer Effect, p-d, kinase inhibitor, COX2 inhibitor, bi-two blocker, PPAR motility agent, MDR inhibitor, hypoxia activator, sheller's inhibitor, ubiquitin inhibitor, HDM2 inhibition Agent, TNF 45 = trace R inhibitor, c-side bond ^ ... method for inhibiting the activity of Ksp-transferase in a patient in need thereof, and the X-patient of the X-ray is effective at least in the summer - as in any of the claims An anthraquinone compound' or a pharmaceutically acceptable salt, solvate, brew, precursor or isomer thereof. A method of treating a disease associated with or caused by a cell proliferation in a patient in need thereof, which comprises administering an effective amount to the patient to two of the claims 1-40 a compound, or a pharmaceutically acceptable salt, solvate, prodrug, ester or isomer thereof. I. The method of claim 46, wherein the disease is selected from the group consisting of cancer, hyperplasia, cardiac hypertrophy, autoimmune disease, bacteriological condition, arthritis, graft rejection, inflammatory bowel disease, immune disorder, inflammation, tumor Angiogenesis and cell proliferation caused by medical procedures. The method of claim 46, wherein the cell proliferative disorder is selected from the group consisting of solid tumor cancer and hematological cancer. The method of claim 46, wherein the disease is cancer, selected from the group consisting of skin cancer, breast cancer, brain cancer, colon cancer, gallbladder cancer, thyroid cancer, cervical cancer, testicular cancer, and blood cancer. 135177 -38- 200922559 50. The method of claim 46, wherein the disease is cancer, selected from the group consisting of: cardiac cancer, lung cancer, gastrointestinal cancer, urogenital cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, blood Learn cancer, skin cancer, adrenal cancer, skin coloration, keratoacanthoma and thyroid cell carcinoma. 51. The method of claim 46, wherein the cell proliferative disorder is selected from the group consisting of: adenocarcinoma, Wilm's tumor (neuroblastoma), lymphoma, leukemia, squamous cell carcinoma, metastatic cell carcinoma, adenocarcinoma, prostate cancer , testicular cancer, hepatocellular carcinoma (hepatocellular carcinoma), cholangiocarcinoma, hepatic blastoma, vascular muscles. - tumor, hepatocellular adenoma, hemangioma; osteosarcoma (osteosarcoma), fibrosarcoma, malignant Fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (net cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondromyma (cartilage exostose), benign chondroma , cartilage, chondral mucinous fibroids, osteoid osteoma and giant cell tumors; osteoma, hemangioma, granuloma, xanthoma, osteoarthritis, meningiomas, meningeal sarcoma, glioma, star Cell tumor, neural tube blastoma, god, glioma, ependymoma, brain tumor (pine pine adenoma), polymorphic glioblastoma, dendritic glioma, schwannomas, retinal embryo cell : congenital tumor, spinal cord neurofibromatosis, meningioma, glioma, sarcoma; &quot; sub-endoendothelioma, cervical cancer, anterior cervical dysplasia, cystic adenocarcinoma, mucinous cystadenocarcinoma, Unclassified carcinoma, granulosa, capsular cell tumor, Sert'Leydig cell tumor, malignant trace (4), squamous cell carcinoma, intraepithelial neoplasia, adenocarcinoma, fibrosarcoma, melanoma, 135177 -39· 200922559 , 'Field cell carcinoma, squamous cell carcinoma, grape sarcoma (embryo rhabdomyosarcoma), fallopian tube carcinoma; myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, acute and k-lymphocytic leukemia, myeloproliferative diseases , multiple myeloma, spinal dysplasia syndrome, Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma), B_cell lymphoma, D-cell lymphoma , hairy cell lymphoma, Burkett's lymphoma, pre-myeloid leukemia; malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karp〇si's sarcoma, dysplasia Nevi, lipoma, hemangioma, fibroma skin 'keloid, psoriasis, and neuroblastoma. 52. The method of claim 51, further comprising radiation therapy. 53. The method of claim 46, further comprising administering to the patient at least one additional therapeutically active agent selected from the group consisting of: an estrogen receptor modulator, an androgen receptor modulator, a retinoid receptor modulator, Cytotoxic agents, microtubule inhibitors/stabilizers, topoisomerase inhibitors, antisense RNA and DNA oligosporic acid, antimetabolites, antibodies coupled to cytotoxic agents, radioactive isoforms, hmg_c〇a reductase Inhibitors, prenyltransferase inhibitors, farnesyl protein transferase inhibitors, angiogenesis inhibitors, kinase inhibitors, c〇x2 inhibitors, integrin blockers, PPAR motivators, MDR#_ 4 Oxygen activators, protein degrading inhibitors, ubiquitin inhibitors, inhibitors, TNF activators, BUB_R inhibitors, CENp_E inhibitors, interferons and radiation. • 4CK 135177 200922559 54. Use of at least one compound according to any one of items 1 to 40, or a pharmaceutically acceptable salt thereof, a glutamic acid chelate, an ester or a prodrug for the manufacture of a medicament As described, the 5Hai agent inhibits KSP-transferase activity in patients in need thereof. 55. Use of at least one compound of any one of claims 1 to 40, or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof, for the manufacture of a medicament. The agent is used to treat one or more diseases by inhibiting KSP transmission activity in a patient in need thereof. And a pharmaceutically acceptable salt, solvate, vinegar or prodrug thereof, as claimed in any one of claims 1 to 40; And (9) at least one second compound selected from the group consisting of: an estrogen receptor modulator, an androgen receptor modulator, a retinoid receptor modulator, a cytotoxic agent, a microtubule inhibitor/stabilizer , 枯 异 ^ 酶 酶 酶 酶 酶 酶 酶 酶 酶 酶 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 募 # # # # # # # # # # # # Agent, farnesyl protein transferase inhibitor, angiogenesis inhibitor 'kinase inhibitor, (7) phantom inhibitor, integrin blocker, PPAR motivator, MDR inhibitor, sputum activator, protein degradation agent inhibition Agent, ubiquitin inhibitor, HDM2 inhibitor, TNF activator, BUB_R inhibitor, cenm inhibitor, interferon and radiation, which treats one or more diseases by inhibiting Ksp activin activity in a patient in need thereof disease. 135177 , 4】- 200922559 VII. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best display invention. Characteristic chemical formula·· 135177