TW200804280A - Phospho-indoles as HIV inhibitors - Google Patents

Abstract

3-phosphoindole compounds for the treatment of retroviral infections, and particularly for HIV, are described. Also included are compositions comprising the 3-phosphoindole derivatives alone or in combination with one or more other anti-retroviral agents, processes for their preparation, and methods of manufacturing a medicament incorporating these compounds.

Description

200804280 IX. Invention Description: The cross-references of relevant applications refer to US Provisional Application No. 60/611,061, and the application is September 16, 2005, No. 60/711,445, and the application date is August 25, 2005.曰' and No. 60/711,565, the application was August 26, 2005, the priority of which was “phosphorus-indole as an HIV inhibitor”. TECHNICAL FIELD OF THE INVENTION The present invention provides novel human immunodeficiency virus (HIV) reverse transcriptase inhibitory compounds and pharmaceutically acceptable salts, prodrugs, analogs and derivatives thereof. Also included are methods of using such compounds to prevent or treat HI V infection and AIDS, and pharmaceutical compositions containing such compounds. [Prior Art] Since the discovery of human immunodeficiency virus (HIV) in 1983 as a cause of acquired immunodeficiency (AIDS), many compounds have been synthesized to combat the virus. The focus of AIDS research has been and continues to be the development of inhibitors of human-immune-deficient virus (HI V-1) reverse transcriptase, which is the reverse transcription of DNA that reverse-transcribes retroviral RNA into latent viruses. Role (WC Greene, New England Journal of Medicine (l99"' 324: 308-17; Mitsuya et al., Science H990). 249: 1533〆44 'EJ· DeClercq, Retrovirusil 992), 8: 119-34). Inhibitors Including a non-nucleoside reverse transcriptase inhibitor or NNRTI that binds to a specific ectopic site of the HIV reverse transcription near the polymerase position and interferes with reverse transcription by altering the reverse transcriptional configuration or mobility, thus The game that leads to this enzyme # 5 93533 200804280 Content inhibition (Kohlstaedt et al., Science H992), 256: 1783-90) Several classes of compounds have been identified as NNRTIs of HIV. These examples include: 1) M(2) -hydroxyethoxy)indenyl]-6-(phenylthio)thymine (HEPT) (Tanaka et al, J. Med. Chem. n99n. 34: 349-57; Pontikis et al., J. Med. Chem .n997^ 40 : 1845-54 ; Danel et al., J. Med. Chem.n996^ 39 : 2427-31 Baba et al., Antiviral Res. n992)· 17 : 245-264); 2) Bis(heteroaryl) piperculosis (BHAP) (Romero et al., J. Med. Chem. n993), 36: 1505-8 3) Dihydroalkoxybenzyl ketopyrimidine (DABO) (Danel et al, Acta Chemica Scandinavica H 997). 51: 426-30; Mai et al, J. Med. Chem, (1997) 40: 1447 -54); 4) 2,-5'·bis-0-(t-butyldidecyldecylalkyl)-3,-spiro-5"-(4"-amino oxathiole-2 ", 2''-Dioxide) Pyrimidine (TSAO) (Balzarini et al., PNAS USAH992). 89: 4392-96); 5) Phenylethylthiazolylthiourea (PETT) derivatives (Bell et al., J · Med· Oiem, (1995)? 38: 4929-36; Cantrell et al, J. Med. ChenL. (1996)? 39: 4261-74); 6) Tetrahydro-imidazo[4,5,l- Jk][l,4]-benzodiazepine-2(1H)-one and -thione (TIB0) derivatives (Pauwels et al, Nature (1990), 343 · 470-4); 7) Phosphorus-substituted sorrel derivative (Gilead Science, Inc. PCT Publication 6 93533 200804280 WO 03/091264 A2) 8) α-anilinophenethylamine (α_ΑΡΑ) derivative (Pauwels et al., PNAS US) A (1993) 5 90: 1711-15); and 9) anthracene derivatives (US Patent No. 5,527,819 to Merck & Co. and its corresponding PCT Publication WO 94/19321). The anthracene derivatives described in U.S. Patent No. 5,527,819 to Merck & Co. have been shown to be inhibitors of HIV reverse transcriptase. Some of these compounds exhibit a quinone for HIV reverse transcriptase IC5 at concentrations ranging from 3 to 35 ηΜ. Merck & Co. also developed a method for synthesizing optionally substituted sigma by palladium-catalyzed formation of a ring between a ketone and an iodoaniline (Chen et al., J. Org. Chem. n997V 62 (9) ) : 2676-77). The compounds disclosed in the '819 patent are generally represented by the following general formula (III):

The variables X, Y, Z, R and R6 are broadly defined.

U.S. Patent No. 5,124,327 to Merck & Co. discloses a class of sulfonylphenyl hydrazine compounds which are optionally substituted. This patent teaches that the compound has the activity of a reverse transcriptase inhibitor and is useful for the treatment of HIV infection and AIDS.

U.S. Patent No. 6,710,068 to Idenix Pharmaceutical, Ltd. discloses a class of phenyl hydrazines which are substituted on one or both rings with at least two 7 93533 200804280 moieties other than hydrogen. See also pCT publication WO 02/083126.

Another class of phenyl hydrazines exhibiting enhanced anti-Hi V activity is disclosed in PCT Publication No. 2004/014364 to Idenix Pharmaceutical. These compounds are also substituted on one or both of the rings with at least two moieties other than hydrogen. Further, these compounds contain a plurality of different substituents having a methine functional group at position _2 of the anthracene ring, and the position is "Ζ" in the above formula (η). Typical substitutions are at the 3, and 5" positions of the phenyl ring, as well as the 4, and 5, 5, and 6, or 5' and 7' positions of the benzo ring of the oxime moiety.

Bristol Myers Squibb discloses a variety of steroids, azaindoles, piperazines, and pyrrolidines that are optionally substituted for use in the treatment of HIV and/or AIDS in several US patent cases, as well as in the US and PCT publications. . See U.S. Publication No. 2004/0006090; 2004/0063746; 2003/0096825; 2003/0236277; and WO 03/068221.

WO 01/02388 to Smith Kline Beecham SPA discloses an optionally substituted phenyl hydrazine having an amine carbhydryl substituent which is claimed to have therapeutic use for the treatment of HIV, AIDS, osteoporosis, cancer, and Alzheimer's disease. .

Warner-Lambert, U.S. Patent No. 5,424,329; U.S. Patent No. 5,565,446; U.S. Patent No. 5,703,069; and WO 96/29077, the disclosure of which are incorporated herein by reference. Oxazolone, diazepinone, benzophenone, benzofuran, and σ-to-no-methyl 8 93533 200804280 guanamine for the treatment of HI V .

An on-demand substituted indole derivative, which is a viral integrase inhibitor, can be used as an anti-HI V drug, as disclosed in U.S. Patent Publication No. 2002/0019,434, and U.S. Patent Nos. 6,716,605 and 6,506,787.

U.S. Patent No. 5,945,440 to Kleinschroth et al. discloses a class of oxazolamides for the treatment of various diseases including cancer, viral diseases (including HI V), heart and vascular diseases, bronchial diseases, inflammatory diseases, central Degenerative diseases of the nervous system, as well as other diseases.

No. 4,866,084 to Gunasekera et al. teaches a specific biguanide bioassay having antiviral and antitumor activity, the virus comprising HSV (herotherapy virus). U.S. Patent No. 5,935,982 to Dykstra et al. teaches a different type of double π scorpion which has anti-reverse virus infection, particularly HIV infection.

U.S. Patent No. 5,852,011 to Matsunaga et al. discloses a type of anthracene derivative substituted with a heteroaryl function and a guanamine function. The compound claims to have anti-tumor, anti-viral and anti-microbial properties.

U.S. Patent No. 5,935,982 to Dykstra et al. discloses a class of diterpenoids and specifically for use in the treatment of retroviral infections, particularly HIV infection.

U.S. Patent No. 5,929,114 to the disclosure of U.S. Pat.

No. 5,830,894 to Pevear et al. discloses a third class of cultivating derivatives which are reported to have anti-prion activity, 9 93533 200804280. The activity against bovine viral diarrhea-mucosal disease virus (BVDV) is most pronounced. . Terpenes have been used to treat diseases other than HIV. F. U.S. Patent No. 5 discloses a series of two treatments for osteoporosis based on the ability of mites to inhibit H-ATPase of osteoblasts and thereby reduce bone resorption. Another group of anthraquinone derivatives, also known as heteroaromatic pentadienoic acid derivatives, is also taught in the U.S. Patent No. 6, 〇 25, 39, to Farma et al., and is also used in the treatment of osteoporosis. No. 5,489,685 to Houpis et al. discloses a series of compounds of fluoro(2,3-b)pyridinecarboxylates which are claimed to be useful in the treatment of HIV. 'Antiviral agents known to have anti-HIV activity are induced to mutate in the virus over a period of time to reduce the efficacy of the drug. The steroidal compounds of Merk are clearly shown in U.S. Patent No. 5,527,819 (Williams et al., L Med. Chem, 1993, 36(9), 1291-94). Drug resistance is most typically caused by mutations in the gene encoding the enzyme used for viral replication, the most typical examples being mv, reverse transcriptase, protease or DNA integrase. It has been demonstrated that the efficacy of drugs that prolong, enhance or restore anti-HIV infection can be extended, enhanced or restored by binding or alternation with a second or a third antiviral compound which causes a mutation other than that caused by the main drug. Musical dynamics, biodistribution, or other parameters of the drug may be altered by such combinations or alternate treatments. In general, combination therapy is more effective than parental therapy because the combination therapy will simultaneously stress the virus. However, it is impossible to predict which mutations will be caused by the drug in the vq gene, regardless of whether the mutation is permanent or transient. 93533 10 200804280 It is also impossible to predict the infected cell pair with the HIV_1 sequence with mutation. What kind of reaction will occur with the medicinal agent used by the sputum or the sputum. This is exacerbated by the lack of kinetic data on the resistance of the anti-retroviral agents to long-term treatment of cell culture strains. Therefore, there is a need to provide novel compounds and methods for the treatment of HIV. The purpose of this month is to provide novel compounds, compositions, methods, and uses for treating HIV-infected patients. Still another object of the present invention is to provide novel compositions and methods for treating a patient infected with HIV which exhibits activity against a virus in a drug-resistant form. SUMMARY OF THE INVENTION The 3_phosphonium compound exhibits antiviral activity against HIV, particularly for mv virus strains which have developed cross-resistance to other anti-HIV drugs. The present invention discloses a compound, a composition and a method for treating HIV infection, which comprise a phosphazenium compound. The 3_phosphonium can be in a wide variety of forms, including, but not limited to, phosphate, decyl ester, thiophosphate (ph〇Sph〇rthi〇ate), including phosphorothioate, thiophosphine Acid esters, phosphate esters, and phosphonium esters (ph〇sph〇ramidate), comprising an imido phosphate and an imidophosphonate. In one embodiment, the compound having anti-HIV activity is a compound of formula (A) below. These compounds contain a phosphorus-bonded substituent at position 吲哚3 and a specific substituent at position-2, and a single substitution at position R5' at the position of benzo ring or at position R4, and R5,,R5 And R6, or r5, and R7' have a double substitution. 93533 11

X 200804280

In a particular embodiment, the substituent "X" represents a phenyl ring which is unsubstituted or substituted with one or more halogens or a lower alkyl group such as methyl or ethyl. Particular substituents at position 2 of the oxime moiety include, for example, hydrogen, hydroxy, halogen, alkyl, aryl, heteroaryl, and especially substituents having a methamine or formamide moiety, in formula (A) ) is displayed as "z". Substituents on the benzo ring of the oxime moiety include, but are not limited to, chlorine, fluorine, bromine, iodine, CF3, CN, N02, and methoxy. The active compound can be a salt or a prodrug which, after administration, provides the desired activity either directly or indirectly to the parent compound or itself. Another specific real name, in which the compound of formula A contains a charged impurity? And in certain specific embodiments, the compound comprises a 1 oxide group. Also included herein are the ambiguous effects of the biological activity of the compound of the invention, such as any change in activity that would result in an increase in the delta species. [Embodiment] The composition and method of use (details of the present invention). The following features are included in the present invention: w, and as described herein, 3-phosphonium, which is a commercially available salt, and 93533 12 200804280 prodrugs, substantially free of other chemistry as needed Entity; ^ 3 of the formulae A to C described herein - squamosa and their pharmaceutically acceptable salts and prodrugs, substantially free of other chemical entities as needed; Phosphonium and its pharmaceutical prodrugs, which are effective against HIV in the host; and 3_phosphonium as described herein and its pharmaceutically acceptable prodrugs, A drug-resistant strain that is effective against HIV in a host, in: in a specific embodiment, a drug-resistant strain of HIV is produced by a reverse transcriptase mutation = 'e.g., from an amine n-aspartate (a agine) and / or salic acid 1 8 1 4 cysteine; • 3·_(4) and its medicine as described herein: for: treating or preventing HIV infection in a host, and preventing the infection of 主5 main HIV-infected drugs' In particular, it is used for individuals who are diagnosed as having a feeling of convulsion or who are at risk of such infections. Two copies ==! called the genus and its pharmaceutically acceptable salts and = using cardiotherapy or preventing HIV infection, or for the manufacture of a substance for the treatment of eucalyptus, wherein the HIV is resistant to the serotonin reverse transcriptase inhibitor in the host; 3_ 醯 醯 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 及其 m m m m m m m m m m m m m m m For individuals with HIV infection or individuals at risk of this infection; times • 3_Phosphorus as described herein, π-category and its pharmaceutically acceptable salts and 93533 13 200804280 == i?: For the treatment or prevention of HIV infection in a host, or for the manufacture of a drug for infecting HIV, which is due to resistance to a reverse 2' ' or multiple reverse transcriptase inhibitors, 103~ aspartame and/or lysine 181~>cysteamine=and nine special for individuals diagnosed as having an infection or having a risk of such sensation; The preparation method is substantially separate from other 3's containing the effective anti-talking therapeutic amount, or the salt of the & A drug, a pharmaceutically acceptable carrier or a thin pharmaceutical composition, 1 Η a pharmaceutically acceptable amount of a combination of 3 or a combination of D, or a combination of agents, as needed:: or a variety of other anti-HIV Medicine for the treatment or prevention of a host: two doses; for one or more reverse transcriptase inhibitors (the mv has been effectively resistant to one of the selected ones), the pharmaceutical composition comprises a prodrug, if desired: or A pharmaceutically acceptable salt or a pharmaceutically acceptable carrier or a combination of a harsh agent, and if desired, a set of 3 plates for the treatment or prevention of a pharmaceutically acceptable salt or sputum of the host infection h 1 v =! = 3 刺 朵 or its medicine he anti-mL, 'and = music composition as needed with at least one of its diluents; now need to have a pharmaceutically acceptable carrier or 93533 14 200804280 • for the treatment or prevention of the host Salty on one or more of the knots! a pharmaceutical composition (the Ηίν has been recorded by mutations in the enzyme, the:::: two: resistance, the resistance is reversed by n + lysine 103 - winter Amine and /

The amount of the treatment is 3# The composition of the medicine includes effective anti-XV: (4) Rewarding its pharmaceutically acceptable salt or pre-Huahua, depending on at least one type of 苴 _ _, 孤 3, depending on the number of 1 V Combination of agents, and if necessary and right to kill radish acceptable carrier or diluent; wish to have Xi Le Shang • used to treat or prevent the host minus one or more reverse transcriptase inhibition methods, wherein the Qing can be administered Effective anti-HIV treatment =,::, the method includes the host salt or prodrug, which may optionally be used in a tray or a pharmaceutically acceptable alternate thereof, and if desired, , / /, I have a acceptable carrier or diluted to 丨 · • in the form of rescue treatment for treatment, tablets, including (4) "the main method of HIV infection, Park Ge A and effective anti-HIV treatment The amount of 3-phosphonium 殹 1 殹 上 acceptable salt or prodrug, Li Ciqi Xixi West HIV sputum group human form six, depending on at least one other anti-#, 05 and 曰Use, and if necessary, pharmaceutically acceptable carrier or diluent; mourn: for treatment or rib The main money wins the square m = transcription; the inhibitor is resistant, and the resistance is formed by the heart & the mutation is, for example, 1 〇3 of the lysine, including the day of administration to the host == to or its medicinal Acceptable salts or prodrugs' can be used as a combination or alternate use. The domain needs to have a carrier or diluent that can be used in the West; a 93533 15 200804280 • 3-phosphonium Or its medicine can be # at least one recorded WP rrT to be salt or 刖乐 (it needs to

Other HI V 荦 丨έ 丨έ 丨έ 丄 丄 丄 丄 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 For the treatment or prevention of • 3_phosphorus or its medicinal heart 5 / h —,, the salt or prodrug (which is as needed and the other anti-HI V Huanan u Japanese 4> 4 I, u ^ ^ ” I, and a or the parent for use, and if necessary, have a carrier acceptable for Xile or dilute ^ ^ 怦 ^), used to treat or prevent injury HIV 'or for manufacturing purposes

^ ^ L / 衣 ^ used to treat or prevent host infection with HIV, the HIV is resistant to one or more reverse transcriptions per inhibitor due to a backhoe 俾 俾 仏 夂 transcriptase mutation, the mutation, Add 1 μ of the plate, and the text is, for example, the acid-free 103-aspartate and/or the lysine 181-^. This use may be in the form of a rescue treatment; and • any or all of the aforementioned hosts are human. I. Active Compounds of the Invention In a general embodiment of the present invention, lithosic acid is provided. The sputum or its may be connected to the salt, the moon ij, the oxide, the quaternary amine, the stereochemical isomer or the mutual isomer. The 34 acid yttrium may be in the form of an acid anhydride, a phosphonic acid vinegar, a phosphorothioate, a thiophosphonate, an imido acid vinegar or an imidophosphonate. In a first embodiment of the invention, the compound is generally represented by the following chemical formula (Α)·· 16 93533

X 200804280

Or a pharmaceutically acceptable salt, prodrug, hydrazine oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein: each X and Y are independently a) oxime; b) halogen (F, CBr, or I), typically F; c) R3; d) CF3; e) Cw alkyl; f) C2_6 alkenyl; g) C2-6 fast radical; h) alkyl heterocycle; i) 3 to 14 membered carbocyclic, aryl, heterocyclic ring, any of which may include a monocyclic, bicyclic, tricyclic or spiro structure; j) OH; k) OR2; l) Ο-alkyl; m) fluorene-ene η) Ο-fast radical, ο) Ο-alkylaryl; 17 93533 200804280 P) 0-aryl; q) Ο-heterocyclic; r) Ο-aralkyl; s) 〇-carbon 哀, t) SH ; u) SR2 ; v) S-alkyl; w) S-alkenyl; x) S-alkynyl; y) S-alkylaryl; z) S-aryl; aa) S-heterocyclic Bb) S-aralkyl; cc) S-fluorene ring; dd) NH2; ee) NHR2; ff) NR2R2; gg) NH-alkyl; hh) N-dialkyl; ii) NH-aryl; Jj) N-alkylaryl; kk) N-aralkyl; 11) NH-heterocyclic ring; mm) N-alkyl-heterocyclic ring; 18 93533 200804280 nn) N-alkenyl-heterocyclic ring; oo) N- Alkynyl-heterocyclic ring; or alternatively, X and Y may form together as needed A bicyclic or tricyclic phosphorylated heterocyclic ring, wherein each ring includes 3 to 7 ring members; is: a) Η; b) CN; c) N〇2; d) Ck alkyl; e) C2-6 D6; a) alkoxy; h) an aryl group n) SR2 ; 〇) S(0)nR2 ; p) S(0)nNR2R3 ; q) N(R2)(R3); r) formamidine; s) guanamine; 19 93533 200804280 t) sulfhydryl u) C(-W)-R3 ; v) C(two W) NH-C(R3)(R3)-C(W)-N(R2)(R2); w) C(=W)NH_P( =W)(R3)-A-R3 ; X) C(=W)NH-AS(0)n-NR2 ; y) C(=W)NH-CR3R3-S(0)n_NR2R2 ; z) C(二W)-NH-AC(=W)-N(R2)(R2); aa) C(-W)-N(R2)(R2); bb) C(=W)_NH-A-R3 ; cc) C(=W)-NH-NH-R3 ; dd)C(=W)_NH_C(R3)(R3), C(=W)NH_C(R3)(R3)C(=W)_N( R2)(R2 ); ee) C(=W)-NH_R2 ; ff) C(=W)-NH_A-C(=W)-NH-AC(=W)-NH2 ; gg) C(R2)(R3)(R3) ; hh) C(R2)(R3)-NH-R2 ; ii) AS(0)n-R3 ; jj) C(=W)-AC(-W)-AC(=W)R3 ; kk) A- R3; 11) C(=W)-(0)R2; mm) C(=W)-AC(=W)_NH2 ; nn) Amino acid residue; oo) C(=W)-NR2_A-(amine Base acid residue); pp) C(=W)-NR2-A-(amino acid Base)-C(=W)_R3; 20 93533 200804280 qq) C(=W)-amino acid residue; rr) C(=W)-N(R2)_A-(amino acid residue)-AC (2) -R3; ss) C(=W)-OR2; tt) C(=W)-SR2; im) C(=W>NH-NH-R2; vv) C(=W)-NH- N(R2)-AC(-W)R3; ww) C(=W)_N(R2)_C(=W)-R3; xx) C(di W)-A-NH-C(=W)R3 ; Yy) C(=W)_A-NH-C(=W)OR2 ; zz) C(=W)-A-R3 ; aaa) C(=W)-NH-NH-CH2-C(=W)R3 ; bbb) P(=W)(R3)(R3); or ccc) AP(=W)(R3)(R3). Ddd) C Bu WVNH-Cwo alkyl-heteroaryl eee) alkyl-heteroaryl fff) C(=W)-NH-CH2-heteroaryl

Ggg) wherein in the specific examples (ddd), (eee) and (fff), the heteroaryl group may optionally comprise a charged hetero atom, in particular may comprise an N-oxide wherein each of X, Y and Z may independently Is unsubstituted or substituted by one or more; alkoxy; 0H; keto; halo (F, Cl, Br, or I); NR2R2; optionally substituted aryl; substituted as needed Heterocycle; 21 93533 200804280 0-C(=W)-alkyl; C(=W)-OR2 ; CN ; N02 ; NH-C(=W) facet alkyl; NH-S(0)n-alkyl NH-S(0)n_NR2R2; or C3_6 cycloalkyl substituted; each W is independently: j)0; j) S ; j) NH ; j) NN(R2)(R2); j) N(R2) j) N-OH; j) NO-alkyl; or j) N_0-R2; R1 is a) H; b) -R2; c) C(=W)_R3; d) C(=W)-0 (R2); e) C(-W)-S(R2); f) C(=W)-NH-R2; g) C(=W)_N(R2)(R2); h) C(=W&gt NH-A-(amino acid residue); i) A-(amino acid residue)-R3; j) S(0)n-R3; or k) S(0)2-N(R2) (R2); 22 93533 200804280 Any one of which may optionally be substituted by one or more Ci_6 alkyl; OH; alkoxy; aryl; halo; CN; N02; or N(R2)(R2); Independently: a) Η; b) CF3; c) CN; d) optionally substituted, branched or unbranched alkyl, such as Cw alkyl; e) optionally substituted, branched or unbranched alkenyl, such as C2_6 alkenyl; f) substituted as needed a branched or unbranched alkynyl group, for example a C2-6 alkynyl group; g) 3 to 14 shells of carbon, h) an optionally substituted aryl group; i) an optionally substituted aralkyl group; j) a substituted alkaryl group as desired; k) a substituted heterocyclic ring as desired; l) an optionally substituted alkyl heterocyclic ring; m) optionally substituted heterocyclic-alkyl group; η) A-heterocyclic ring ; 〇) fluorenyl; Ρ) alkoxy; q) CH2-S(0)nR3; r) C(alkyl)2-S(0)n alkyl; s) CH(alkyl)-S(0 n) alkyl; t) CH2NH2; u) CH2NH(alkyl); 23 93533 200804280 v) CH2N(alkyl)2; w) CH(alkyl)-NH2; x) CH(alkyl)-NH(alkane) y) CH(alkyl)-N(alkyl)2; z) C(alkyl)2-NH2; aa) C(alkyl)2-NH(alkyl); bb) C(alkyl 2-N(alkyl)2; cc) CH2-C(=W)H; dd) CH2-C(=W)alkyl; ee) A_alkyl; ff) C(alkyl)2-C (=W)alkyl; gg) CH2-C(-W)H; hh) CH2-C(=W)alkenyl; ii) CH(alkenyl)-C(=W)H ; jj) A_S(〇)alkyl; kk) CH(NH)-S(0)n alkyl; or 11) Α·Ν(ΝΗ)alkyl; mm) C(R3)(R3)-S(0)nNH2 ; Nn) C(R3)(R3)-S(0)nCF3; oo) C(R3)(R3)-NH2; each R3 is independently: a) H; b) OH; c) halogen (F, Cl, Br, or I); 24 93533 200804280 d) CF3; e) CN; f) optionally substituted, branched or unbranched alkyl, such as alkyl; g) optionally substituted, branched or unbranched Alkenyl of the chain, for example C2_6 alkenyl; h) substituted, branched or unbranched alkynyl, optionally C2_6 alkynyl; i) 3 to 14 membered carbocycle; j) optionally substituted aryl k) an optionally substituted aralkyl group; l) an optionally substituted alkaryl group; m) an optionally substituted heterocyclic ring; η) an optionally substituted alkyl heterocyclic ring; Substituted heterocyclic-alkyl; p) A-hetero, q) aryl; r) formamidine; s) aminomethyl thiol; t) alkoxy; u) OH; v) OR2; Ο-alkyl; X) 0-dilth; y) 0-alkynyl; z) 0-alkylaryl; aa) 0-aralkyl; 25 93533 200804280 bb) Ο-carbocycle; cc) 0- Heterocycle; dd) Ο-aryl; ee) SH ; ff) SR2; gg) S-alkyl; hh) S-alkenyl; ii) S-alkynyl; jj) S-alkylaryl; kk) S-aralkyl; 11) S-carbon ring; mm) S- Heterocycle; nn) S-aryl; oo) S(0)n_R2; PP) amine; qq) NH2; rr) NHR2; ss) N(R2)(R2); tt) NH-S(0)n -R2; uu) NHC, W)-aryl; vv) NHC(=W)-alkyl; ww) NH_C(=W)_heterocycle; XX) CH2-S(0)nR2; yy) C(= W)R2 ; 26 93533 200804280 zz) C(=W)-N(R2)-R2 ; aaa) C(alkyl)2-S(0)nR2 ; bbb) CH(alkyl)-S(0)nR2 ; ccc) C(alkyl)2_NH2; ddd) CH(alkyl)-N(alkyl)R2; eee) C(R2)(R2)-NR2R2; fff) CH2N(alkyl)R2; ggg) CH( Alkyl)-NHR2; hhh) C(alkyl)2_NHR2; iii) C(alkyl)2-N(alkyl)R2; jjj) CH2-C(=W)H ; kkk) CH2-C(=W ) alkyl; 111) CR2R2-C(=W)R2 ; mmm) A_R2 ; nnn) C(R2)2-C(=W)R2 ; ooo) CH2-C(-W)H ; ppp) CH2_C(= W) alkenyl; qqq) CH(alkenyl)-C(=W)H; rrr) AS(0)R2; sss) CH(NH)-S(0)nR2; or ttt) AN(NH)R2; Uuu) C(R2)(R2)-S(0)nNH2 ; vvv) C(R2)(R2)-S(0)nCF3 ; www) C(R2)(R2)_NH2 ; 27 93533 200804280 where this is needed Alternative substitution One or more of the following: a) a substituted or unsubstituted heterocyclic ring; b) C(=W)0-aryl; c) C(=W)0-alkyl; d) C(two W NH2; e) C(=W)NH-alkyl; f) C(=W)NH-aryl; g) C(=W)N-di-alkyl; h) C(=W)N( Alkyl)-aryl; i) α-amino acid; j) α-amino ester; k) α-amino-decylamine; l) β-amino acid; m) β-amino ester; Or η) β-amino-decylamine; wherein, when the optional substitution includes a substituted heterocyclic ring, the substitution of the heterocyclic ring is selected from the group consisting of the following, alone or in any combination. a) C(=W)0-aryl; b) C(=W)0-alkyl; c) C(-W)NH2; d) C(=W)NH-aryl; e) C(= W) NH-alkyl; 28 93533 200804280 f) C(=W)N-di-alkyl; g) C(=W)N(alkyl)-aryl; h) α-amino acid; i) 〇!-amino ester; j) α-amino-carbamamine; k) β-amino acid; l) β-amino ester; or m) β-amino-carbamamine; n) halogen; Or 〇) cyano, η is independently 〇, 1 or 2; each Α is independently a disubstituted spacer selected from the group consisting of: a) Gw alkyl, branched or non- Branching, and optionally having one or a hetero atom, an aryl group, a cycloalkyl group or a heterocyclic group, may be present in the chain or attached to the chain; b) Cm extended alkenyl, branched or unbranched And optionally having one or a hetero atom, an aryl group, a cycloalkyl or a heterocyclic group functional group present in the bond or attached to the chain; c) a C2-12 alkynyl group, a branched or unbranched group, And optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached to the bond; d) optionally substituted arylene; e) 0 a stretch or a non-branched group, and optionally one or more 93533 29 200804280 heteroatoms, aryl, cycloalkyl or heterocyclyl functional groups present at the bond or attached to the chain; An aralkyl group, branched or unbranched, and optionally one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present at the bond or attached to the chain; g) as needed a substituted cycloalkyl group; and h) a heterocyclic ring which may be optionally substituted; wherein "A" may be linked by any desired linkage (Unkage), for example, an ether Thioether, amine, formamidine, ester or carbon-carbon linkage, or any combination thereof; ^ each 114', 115', 116' and inverse 7' are independently: a) Η; b) halogen (F, Cl, Br, ι); c) N02; d) CN; e) CF3; f) OH; g) OR2; h) SH; i) SR2; j) nr2r2; k) NHS(0)nR2; l) NHCOCu alkyl; m) S(0)nR2; 93533 30 200804280 η) aryl; 〇) heterocyclic; Ρ) Ci_6 alkyl; q) C2-6 roast; r) C2-6 fast radical, s C(2)-S(0)nR2; t) C(=W)-S(0)nNR2R2; u) C(=W)-aryl; v) C(=W)-alkyl; w C(=W)-heterocyclic ring; or x) C(=W)-NR2R2; each of which may be substituted by one or more of the following groups: a) OR2; b) S(0)nR2; c C(2)-S(0)nR2; d) C(=W)-S(0)n-NR2R2; e) C(=W)-aryl; f) C(=W)_alkyl g) C(=W)-heterocyclic ring; h) C(=W)NR2R2; i) N02; j) CN; k) CF3; l) halogen (F, Cb Br, I); 31 93533 200804280 m NHS(0)nR2; n) NHCO-Cu alkyl; 〇) aryl; p) heterozygous, q) Cw alkyl; r) C2-6 dilute; S) C2-6 alkynyl; or t) NR2R2 is in a specific embodiment of formula (A), X is as needed The substituted phenyl group; Y defined in any one of its one; R1, R4 ', to 6, and R7, are all hydrogen; R is halo, Z is a carboxylic acid and an amine moiety (m〇iety). In another embodiment, R1 is a fluorenyl, alkyl, aryl, alkaryl, or aralkyl group. In yet another embodiment, R4 is fluoro, nitro or cyano, W is oxygen, and Y is fluorenyl-alkyl. In a second embodiment of formula (A), X is optionally substituted phenyl; Y is any of its definitions; R1, R4', R6' and r7 are all hydrogen; R5 is chlorine And z is a decylamine or formamido-heterocyclyl moiety. In still another embodiment of formula (A), X is tolyl, oxime or 0-alkyl; R1, R4', R6' and R7, oxime is an amine group, g blue group, burned Base _ sulphate or pyridinyl; Y is η, OH, both are hydrogen; R 5 is halogen; and indigo or acid derivative. Further, in the above specific examples, R7 and R5 are as defined above, and in the formulae, X, Y, Ri, R4, r6, and ϊZ are a formazanyl-alkylene group-heterocyclic ring, 93533 32 200804280: 3L is also 曱^-amino-alkyl-hydrazine. A thiolamino group, a pyridine group, which is substituted by a quinone group, or a hydrazine H' 〇Me or a lower alkyl group; an imido-nitrile; or a hospital; δ-xanthyl-aryl. In yet another embodiment, z is a formamidine-alkylene-heterocycle, and the thief comprises at least one N-oxide group (N_Qxide gr〇up). In a specific embodiment of the second embodiment, the present invention provides a phenyl hydrazine for treating mv by the following (B): Fly R4"

Or a pharmaceutically acceptable salt thereof, a pro-antimony, a N ^ 永 永 虱, a quaternary amine, a stereochemical isomer or a tautomer, wherein: A, n, R 4 ', R 5 ', r 6 , and each W, Y, Z, R1, r2, r3 r7' are as defined by the above formula (A); and R6 is independently R2,, R3,,, R4,, R5,,, a) Η; b Halogen; c) N〇2; d) CN; e) OR2; 93533 33 200804280 f) SR2; g) nh2; h) NR2R3; i) alkyl; j) NCR^-SOrCw alkyl; k) Ci_6 l) C2-6 dilute; m) C2_6 alkynyl; n) aryl; o) CF3; p) CR2R2_S(0)nR3; q) CR2R2NR2R3; r) C-OH; s) CR2R2-C(- W) R2; t) sulfhydryl; u) C(=W)R2; v) C(=W)OR2; w) C(-W)SR2; x) C(=W)-NR2R3 ; y) C( =W) NH(CH2)p-(amino acid residue); z) an amine residue; or aa) A-(amino acid residue); wherein any of the above may be substituted as needed; or alternatively, R2" or R6'' may be bonded to Y to form an optionally substituted double 34 93533 200804280 cyclic or tricyclic phosphorylated heterocyclic ring, wherein each ring _ _r . to 14 环昌. The following is formula (B) Non-_ of the specific embodiment Examples: a) Y is an alkyl group; W is 〇, S(0)n, or NH; Rl, r4,, R7, ^'奵', 115', and anti 6' are all hydrogen; 115, is halogen; and Z is a brewing amine; b) Y is an aryl group; W is 〇, S(0)n, or NH; R1, r4,, R7', R2'', R3", R4' ', R5', and r6' are all hydrogen; r5' is an amino-k group, a thioamino-alkyl group, or an aminocarbonyl-alkyl group; and z is a formamide; C) Y is -OH or -SR2 ; W is Ο, S(〇)n, or N-NH2; R1, R4, R6', R7', R2,, R4", and R6, all are hydrogen; r5, halogen; R3 And R5" are fluorenyl; and Z is decylamine; d) Y is -OH; W is 0, S(0)n, or NH; R1, R6, R7, R2,,, R4", And R6" are all oxime; R4' and R5' are halogen; R3" and R5" are methyl; and Z is decylamine; e) Y is -OH; W is Ο, S(0)n, or N -NR2R2 ; R1, R4, R6, R7, R2", R3", R4'', R5", and R6" are all hydrogen; r5' is halogen; and Z is a decylamine; f) Y is an alkene Base; W is 0, S(0)n, or NH; R1, R4', R6', R7', R2", R3 ', R4", R5", and R6" are all hydrogen; R5 is halogen; and Z is a formamide or a guanamine-heterocycle; g) Y is a fast group or _nr2r3, and W is 〇, s ( 0) n, or N-0-alkyl; R1, R4', R6', R7', R2'', R3", R4", R5", and R6" are all hydrogen; R5 is halogen; Brewing amine; 93533 35 200804280 h) Y is an alkenyl group; W is Ο, s(Ch, χτ ...)n, or Wi; R1, R4, R6,

R7, R2,,, R3,,, R4,,, R5,, K6 are hydrogen; R5 is halogen· and z is formazan; π is ethyl; wg0, s(0)n, or R7, m, R5''iR6"t"H,"R, „7 . ^ is hydrogen; R5 is chlorine; and Z is decylamine; j) Y is -0-methyl; W is 0, S (Ch , χ ϋ7,...3" 4,, (〇)η, or oil;...,!^,,!^,, R7, R2, R3, R4,,, R5,, 6 and R white are hydrogen; R5' Is halogen; and Z is formamidine; uu fruit, k) Y is ethyl; W is 〇, Sfπ, ★ 6, 7, 9,, (〇)n, or N-NH2; R1, R4, R6, R7, R2", R3", r4,, ,, ,..^^^, R, and R6, all are hydrogen; R5, halogen, and Z is a keto-heterocycle·l) Y is -0_ ethyl; W is 〇, SiCh, χτ νυ) η, or NH; Rl, R4, R6, R7, R2, R3,,, R4,, R5,,, p6,, ratio, and R White is hydrogen; R5 is chlorine; and Z is formazan; m) Y tO-H; W is Ο, s(9)n, or NH; Rl, r4, R6, R7, 'R2^R3,, 'R4% R5,,^^t4A;R^i^; and z is a methotrexate' which is unsubstituted or One or more -N〇2, -NH-C(=0)-alkyl, or _NH_s(〇)n_alkyl substituted; η) Y is -0-H; W is Ο, S(0)n Or N-NH2; ri, r4, r6, R7, R2", R3", R4", R5"mnR5, ^t and Z are a formazanyl-alkylene-heterocyclyl group, wherein the hetero The ring is a scorpion, a sigh, a biting or a sulphur, and wherein the heterocyclic ring is unsubstituted or further passed through one or more halogens, ketone groups, _〇H, _NC>2, 93533 36 200804280 - MeOH , -NH-C(=〇)-alkyl, or -NH-S(〇)n-alkyl substituted; 〇)Y is -OH; W is Ο, S(0)n, or NH; R1, R4 ', R6', R7', R2", R3", R4", R5, ', and R6'' are all hydrogen; R5' is halogen; and Z is a guanamine-cyclopropyl or formamide-ring Butyl; p) Y is _〇_methyl; W is Ο, S(0)n, or NH; R1, R4', R6', R7', R2", R3", R4", R5", and R6" is hydrogen; R5' is halogen; and Z is formazan-ethyl, decylamine-ethanol, or decylamine-ethyl-methoxy; q) Y is -OH or _NR2R3; Is 〇, S(0)n, or N-0-alkyl; R1, R4', R6 ', R7', R2", R3'', R4'', R5,, and R6" are all oxime; R5' is halogen; and Z is a methionine-phenyl group, wherein the phenyl group is further One or more halogens, g-isodentyl, -N〇2, -MeOH, or -NH-C(=0)-alkyl substituted; r) Y is -OH or -SR2; W is 〇, s(〇 n, or N-NR2R2; R1, R54, ', r6', r7', r2'', r3'', R4'', r5'', a r6" are all nitrogen; R is halogen; and z is The isopropanol formate moiety; and s) Y is -OH; W is Ο, S(0)n, or N-OH; R1, R4, R6, R7', R2", R3", R4", R5'', and R6, are all hydrogen; R5 is halogen; and z is thioethylamino. In the third embodiment, the present invention is used for the treatment of mv (IV) ^ month is not the following formula (c):,, the two-substituted 9 to 11 member double-ring 3-phosphorus 93533 37 200804280 R4”

Or a pharmaceutically acceptable salt, prodrug, hydrazine oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein: each of W, Z, R1, R2, R3, A, n, R4, , R5, 6, and R7, as defined by the above formula (A); R3, R4, 5'', and 6'' are each defined by the above formula (; 6); There are single or double bonds, wherein: When two 1ZZ represents the presence of a double bond, each γ and τ are independently: (a) CR3; (b) N; or (c) S(=W); and Y and T At least one of them is CR3; and when two 2 represents the presence of a single bond, each of ¥ and τ is independently: (a) CHR3; (b) C(R3)(R3); (c) 〇; d) S ; or (e) NR2 ; 38 93533 200804280 and at least one of Y and T is C(R3)(R3); and m is 1 or 2, but when T or Y=CR2, m can only 2. The following are non-limiting examples of specific embodiments of formula (C): a) W is Ο, Y is CR2, T is (CH2)2, R1, R4', R6', R7', R3", R4'' R5", and R6'' are all Η; R5' is halogen, and Z is formazan; 13)^/ is 8, 丫 is 0,1[for (:112,111,114', ruler 6' , 117', 113'', R4", R5", and R6" are all hydrazine; R5' is halogen, and hydrazine is a hydrazino-heterocyclic ring, wherein the heterocyclic ring is an optionally substituted furan, imidazole , σ 嗤 , or σ ratio tr fixed; c) W is S, Y is NR2, T is CH2, R1, R4', R6', R7', R3", R4", R5", and R6" are Η ; R5 'is halogen, and Z is formamidine; d) W is Ο, Υ is SR2, Τ is CH2, R1, R4', R6', R7', R3", R4", R5'', and R6" is Η; R5' is halogen, and Z is alkyl-formamide; e) W is S, Υ is SR2, Τ is CH2, R1, R4', R6', R7', R3", R4 ", R5'', and R6" are all H; R5' is halogen, and Z is formamidine; f) W is Ο, Υ is CR2, Τ is CC(=W)R3, R1, R4 ', R6', R7', R2", R3", R4", R5", and R6" are all Η; R5' is halogen, and Ζ is 曱oxymethyl-carbamamine; g) W is S , Y is 0, D is CC(=W)R3, R1, R4', R6', R7', R3", R4'', R5", and R6" are all Η; R5' is halogen, and Z is Indole-cyclobutyl; 39 93533 200804280 h) W is Ο, Y is SR2, T is CC(=W)R3, R4', R6', Rr, R3", R4", R5'', and R6 "all are H; R5' is chloro, and Z is alkyl decylamine, wherein the alkyl group is optionally subjected to one or more halo, keto, -OH, -N02, -MeOH, -NH_C (=0) ) alkyl, or -NH-S(0)n-alkyl substituted; i) W is S, Y is NR2, T is CC(=W)R3, R4, R6', R7', R3", R4 ", R5'', and R6'' are all Η; R5, is chlorine, and z is decylamine; 』) ^¥ is 8, 丫 is >!, 1: is (:-(:(=^) 113,111,;^4,,1^6,,;^7,, R, R4, R5, and R6 are all H; R5' is fluorine, and z is decylamine; k) W is NH, Y is CR2, τ is NR2, R1, R4, R6, r7, R, R, R5, and R 6 is H; r5' is an amino-alkyl group, and Z is a decylamine; l) ^ is NR2, Y is 〇, τ is (CH2)2, Rl, r4, r6, r7, R , R4, R5, and R6, all are H; R5, is gas, and z is decylamine; m) W^N_OH, ^〇, ^cH2, Rl, R4, R6, R7, R3, R4, R5', and r6, the ratio is H; R5 is a thioamino-alkyl group, and Z is an alkyl formamide; light is S, Y is SR2, T is, r4, r6, r

R4", R5''m6>Au v R % ^ ', , H ' R is a halogen, and z is a carbamide 1 隹 bad group, wherein the heterocyclic hair styling requires a substituted pyridine, thiazolidine Or furan; soil & 93533 40 200804280 〇) W is NO-alkyl, Y is nr2, T is CH2, R1, R4', R6, R7', R3", R4'', R5", and R6" All are H; R5' is halogen, and Z is a formamide-alkyl group, wherein the alkyl group is optionally subjected to one or more -N02, -NH2, _NH_C(=W)alkyl, or _NH_S(0) N-alkyl substituted; P) W is NH, Y is SR2, T is (CH2)2, R1, R4, R6', R7', R3", R4", R5'', and R6" are all Η R5' is halogen, and Z is a amide-alkyl group phenyl wherein the phenyl group is optionally subjected to one or more halogens, ketone groups, OH, N02, MeOH, or _NH-C (=0) Substituted or _NH-S(0)n-alkyl substituted; q) w is NR2, Y is (CH2)2, τ is NR2, R1, R4, R6', R7', R3, R4'', R5", and R6" are all η; R5 is halogen, and z is formazan-cyclopropyl; r) W is N-OH, Y is CH, T is Ο, R1, R4, R6', R7 ', R3, R4, R5", and R6'' are all Η; R5, which is a sulphate, and hydrazine is a carbamide-cyclopropyl;

- a base, Y is 〇, T is (CH2)2, R1, R4', R6', R4', R5'', and R6'' are all Η; R5' is chlorine, and Z s) W is Ν -0

R R7 is a decylamine _methoxyethyl group; the force is ο'γ is Ν, Τ is ch2, R1, R4, R6, R7, R3,,, R, and R6" are Η ; R5' is halogen, and Z is decylamine, ethanol; U) w is n-NR2R2 R7, R:

Y is NR2, T is CH2, Ri, R4', R6', R5", and R6" are all H; R5' is halogen, and 41 93533 200804280 z is methotrexate; and v) W is 〇, Y is CR2, τ is CH2, R1, R4, R6, R7, R3'', R4'', R5", and R6" are all H; r5 is an aminocarbonyl-alkyl group, and Z is 曱醯amine. In a particular embodiment of the set of formulas A, B or c, z is C(=W)_R3; C(=W)-NH-AC(=W)-N(R2)(R2) . C(=W )-NH-A-R3; C(=W)-NH-R2; or C(=W)_a_r3. In a specific embodiment of Formula A, B or C, the compound contains a hetero atom of a charge. Youdou, "Lei from * " N'A ^5 C (〇) NH_ alkyl, or body two i, sub-, for example, via - ring: also "by. (. 靡 而 位于 附 附 附 附 附=0);: In a specific embodiment of R 2 β or C, 2 is II is an optionally substituted alkylidene heterocycle, wherein the heterocyclic ring has the following formula: In a specific embodiment, Medium/medium... is ^, or c two: XJ is specifically methylene or

Stretch ethyl. In a particular embodiment, R2 is Formula 1 wherein _n is 0, 1, or 2. In a specific embodiment of formula A, Br, the compound is: 93533 42 200804280

C B;

G; 43 93533 200804280

Other examples of specific examples of N-oxides of compounds of formula A, B or C are: 44 93533 200804280

V Each substituent on the phenyl ring may be substituted by CN, Me, halogen, alkyl, alkenyl, alkynyl, alkyl-CN or alkenyl-CN, such as the most commonly synthesized and tested N-oxidation to date Series of things. 11. Specific Sub-Embodiment of the Invention In a first embodiment of the invention, the compound is generally as shown in formula (A):

X

45 93533 200804280 or a pharmaceutically acceptable salt, prodrug, oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein: X and γ are each independently: a) 3 to 14 members Carbocyclic, aryl, heterocyclic, any of which may include a monocyclic, bicyclic, tricyclic or spiro structure, or optionally substituted; b) Η; c) OH; d) C][, Br, I, F; e) CF3; f) Cw alkyl; g) C2-6 dilute; h) C2.6 alkynyl; i) alkyl heterocycle; j) NH2; k) NH·alkyl; N-dialkyl; m) NH-aryl; η) N-alkylaryl; 〇) N-aralkyl; p) NH-heterocyclic; q) N-alkyl-heterocyclic; r) N- Alkenyl-heterocyclic ring; s) N-alkynyl-heterocyclic ring; t) O-alkyl group, 46 93533 200804280 u) 0-thin group; ν) Ο-fast group; w) Ο-alkylaryl group; Ο-aryl, y) Ο-heterocyclic; ζ) Ο-aralkyl; aa) Ο-carbon, bb) SR2; or cc) NR2R3; or, X and Y may be linked to form a substituted double ring as desired Or a tricyclic phosphorylated heterocycle wherein each ring comprises from 3 to 7 ring members; Z is a) a); b) alkoxy; C) N〇2; d) N(R2)(R3); ) OR2 ; f) amidino g) guanamine; h) fluorenyl; i) S(0)nR2; j) S(0)nNR2R3; k) Cw alkyl; l) C2_6 alkenyl; 47 93533 200804280 m) C2-6 fast radical, n) alkaryl; 〇) aralkyl; Ρ) heterocyclic; q) alkyl-heterocyclic; r) aryl; s) CN; t) C(=W)-R2; u) C(=W NH-C(R2)(R2)-C(=W)-N(R2)(R2); v) C(=W)NH-P(two W)(R2)-A-R2 ; w) C (=W) NH-AS(0)n-NR2 ; x) C(=W)NH-CR2R3-S(0)n-NR2R3 ; y) C(=W)-NH-AC(=W)-N (R2)(R3); z) C(=W)_N(R2)(R3); aa) C(=W)-NH-A_R2; bb) C(two W)-NH-NH-R2 ; cc) C(二w)-nh-c(r2)(r2)-c(=w)nh-c(r2)(r3)c(=w)-n(r2) (R3); dd) C(two W ) _NH_R2 ; ee) C(two W)-NH-AC(two W)_NH-AC(=W)_NH2 ; ff) C(R2)(R2)(R3); gg) C(R2)(R2)- NH-R2 ; hh) A_S(0)n-R2 ; ii) C(two W)-A_C(two W)-AC(=W)R3 ; 48 93533 200804280 jj) a,r2 ; kk) C(=W )-(0)R2 ; 11) C(=W)-AC(=W)-NH2 ; mm) amino acid residue; nn) C(=W)-N(R2)-A·(amino acid Residue); oo) C(=W)_N(R2)-A-(amino acid residue)_C(=W)-R2; pp) C(=W)-amino acid residue; qq) C (=W)-N(R2)-A-(amino acid residue)-A_C(=W)-R2 ; rr) C(=W)-OR3 ; ss) C(=W)-S(R2) ; tt) C(=W)-NH-NH-R2 ; uu) C( Two W>NH-N(R2)-AC(=W)R2; vv) C(=W)-N(R2)-C(-W)-R3; ww) C(=W)-A-NH- C(=W)R2 ; xx) C(=W)-A-NH-C(=W)OR3 ; yy) C(=W)-A-R3 ; zz) C(=W)-NH-NH- CH2-C(=W)R2; aaa) P(=W)(R2)(R2); or bbb) AP(=W)(R2)(R2); wherein each of the foregoing X, Y and z can be independently Substituted or substituted with one or more of the following groups: a) H; WCw alkyl; c) alkoxy; 49 93533 200804280 d) OH; e) keto; f) halo; g) NR2R2; An optionally substituted aryl; i) a heterocyclic group which is optionally substituted; j) 0-C(=W)-alkyl; k) C(=W)-OR2 ; l) CN ; m) N 〇2; n) NH-C(=W)-alkyl; o) NH_S(0)n-alkyl; p) NH-S(0)n-NR2R2; or an alkyl group; W is: a) hydrazine; b) S; c) NH; d) NN(R2)(R2); e) N(R2); f) N_OH; or g) NO-alkyl, R1 is a) H; 50 93533 200804280 b) R2; c) C(=W)-R2 ; d) C(=W)-0(R2); e) C(=W)-S(R2); f) C(-W)-NH-R2 ; g) C(=W)_N(R2)(R2); h) C(=W>NH-A-(amino acid residue); i) A-(amino acid residue)-R2; j) S( 0) n-R3; or k) S(0)2-N(R2)(R2); any of which may be substituted by one or more of the following groups as needed: Alkyl; b) OH; c) alkoxy; d) aryl; e) halo; f) CN; g) N02; or h) N(R2)(R2); R2: a) Η; b OH ; c) halogen; d) optionally substituted, branched or unbranched alkyl; 51 93533 200804280 e) optionally substituted, branched or unbranched alkenyl; f) substituted as needed , branched or unbranched fast radicals; g) 3 to 14 membered carbocyclic rings; h) alkylheterocyclic rings; i) fluorenyl groups; j) formamidine; k) amine fluorenyl; Alkoxy; m) optionally substituted aryl; η) optionally substituted arylalkyl; 〇) optionally substituted alkaryl; Ρ) 0-alkyl, q) 0-fine, r 0-fast group, s) 0-calcinyl; t) 0-aralkyl; u) 0-carbon bad, v) 0-heterocyclic; w) 0-aryl; X) CF3; y) CN z) S(0)n_R3 ; aa) N(R3)(R3); bb) NH-S(0)n-R3 ; 52 93533 200804280 cc) NHC(=W)-aryl; dd) NHC(= W>alkyl; ee) NHC(=W)-heterocyclic ring; ff) CH2-S(0)nR3; gg) C(=W)R3; hh) C(=W)NR3R3; ii) C(alkyl ) 2-S(0)nR3 ; jj) CH(alkyl)-S(0)nR3 ; kk) C(alkyl)2-NH2 ; 11) CH(alkyl)-N(alkyl)R3 ; mm ) CR3R3_N R3r3; nn) CH2N(alkyl)R3; oo) CH(alkyl)-NHR3; pp) C(alkyl)2_NHR3; qq) C(alkyl)2-N(alkyl)R3; rr) CH2- C(=W)H ; ss) CH2-C(=W)alkyl; tt) CR3R3_C(=W)R3 ; uu) A-R3 ; vv) C(R3)2-C(-W)R3 ; ww CH2-C(=W)H ; XX) CH2-C(=W)alkenyl; yy) CH(alkenyl)-C(=W)H ; zz) AS(0)R3 ; 53 93533 200804280 aaa) CH(NH)-S(0)nR3; or bbb) AN(NH)R3; wherein the optional substitution includes one or more of the following: a) a substituted or unsubstituted heterocyclic ring; b) C (=W)0-aryl; c) C(=W)0-alkyl; d) C(=W)NH2; e) C(=W)NH-alkyl; f) C(=W)NH -aryl; g) C(=W)N-di-alkyl; h) C(=W)N(alkyl)-aryl; i) α-amino acid; j) α-amino ester; k) α-amino-carbamamine; l) β-amino acid; m) β-amino group S, or n) β-amino-decylamine; R3 is: a) hydrazine;

b) OH C) Ci_6 alkyl; d) C2_6 alkenyl; e) C2-6 fast radical; f) alkoxy 54 93533 200804280 g) cf3 ; h) CN ; i) amine; j) NR2R2 ; k) O-alkyl; l) O-alkenyl; m) 0-alkynyl; n) C(R2)(R2)-S(0)nNH2; ο) C(R2)(R2)-S(0)nCF3 ; ρ) C(R2)(R2)-NH2 ; q) Α-heterocyclic ring; r) C(R2)(R2)-NR2R2 ; s) CR2R3-C(=W)R2 ; t) aryl; u) Carbocyclic ring; V) heterocyclic ring; W) cycloalkyl group; X) pyrrolyl group; y) alkylidene heterocyclic ring; Z) arylalkyl group; or aa) heterocyclic-alkyl group; any of which may be unsubstituted Or substituted by one or more of the following groups in any combination: a) dentate, 55 93533 200804280 b) OH; c) OR2; d) SR2; e) COOH; f) carboxylic acid ester; g) C (=W)R2 ; h) C(=W)OR2 ; i) C(=W)OR3 ; j) C(=W)SR2 ; k) AC(=W)NH2 ; l) C(=W)NR2R3 m) NR2R2; g) NR2R3; 〇) NR2-S(0)nR3; p) NR^CtWhCw alkyl; q) s(〇)nR3; r) Cw alkoxy; s) Cle6 thioether; a base acid residue; u) an NH-A-(amino acid residue); v) a C(=W)NH_A-(amino acid residue); and wherein, when the optional substitution includes a substitution Heterocyclic Then, the substitution effect is selected from the group or group of the following groups, alone or in any combination: 93, 35, 56, 04, 2008, a, a, C (= W) 0-aryl; b) c (= w) o · alkane c) C(=W)NH2; d) C(=W)NH-aryl; e) C(=W)NH·alkyl; f) C(=W)N-di-alkyl; g C(=W)N(alkyl)-aryl; h) α-amino acid; i) α-amino ester; j) α-amino group decylamine; k) β-amino acid; l) β-amino ester; or m) β-amino-decylamine; η) halo; or 〇) murine 5 η is independently 〇, 1 or 2; each Α is independently selected from the following a double-substituted separator of the group a) Ck extended, branched or unbranched, and optionally one or more heteroatoms, aryl, cycloalkyl or heterocyclic functional groups present in the Chain or attached to the chain; b) Cm is alkenyl, branched or unbranched, and optionally has one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or Attached to the chain; OC2·〗 2 an alkynyl group, branched or unbranched, and optionally one or 93353 57 200804280 multiple heteroatoms, aryl, cycloalkyl or heterocyclic groups Can be present in the chain or attached to the bond; d) an optionally substituted aryl group; e) a fluorene-alkyl group, a branched or unbranched group, and optionally one or more heteroatoms, a base, cycloalkyl or heterocyclyl functional group present in the chain or attached to the chain; aralkylene, branched or unbranched, and optionally one or more heteroatoms, aryl, cyclized a cyclyl or heterocyclyl functional group is present at the bond or attached to the chain; g) optionally substituted cycloalkyl; and h) optionally substituted heterocycle; wherein "A" can be bonded by any desired Linked to, for example, mystery, thioether, amine, amidino, hydrazine or carbon-carbon linkage, or any combination thereof; 'each R4, R5, R6 and R' are independently: a) hydrazine; b) halogen; c) N〇2; d) CN; e) CF3; f) OR2; g) NR2R2; h) NHS(0)nR2; i) NHCO-Cb3 alkyl; 93533 58 200804280 j) S (0) nR2; k) aryl; l) heterocyclic ring; m) Cp6 alkyl; n) C2_6 alkenyl; 〇) C2-6 fast radical, p) C(-W)-S(0)nR2 ; q C(二W>S(0)nNR2R2; r) C(=W)-aryl; s) C(=W)-alkyl; t) C(=W)- Ring; or u) C(=W)-NR2R2; each of which may be substituted by one or more of the following groups: a) OR2; b) S(0)nR2; c) C(=W)-S( 0) nR2; d) C(di W)-S(0)n-NR2R2; e) C(=W)-aryl; f) C(=W)-alkyl; g) C(=W)- Heterocycle; h) C (two W) NR2R2;

i) H j) N02 ; k) CN ; 59 93533 200804280 i) cf3 ; m) halogen; n) NHS(0) nR2 ; cONHCO-Cy alkyl; p) aryl; q) heterocyclic; 〇Ci_6 alkyl ; S) C2-6 dilute; 〇. 2-6 block, or u) NR2R2 〇 In / (A) of the specific example, χ is the thiol group of the two I enemy; γ is the definition of the χ In Feng. VR, R1, R4, R6' and R7 are all hydrogen; R is halogen, and z is a form of a carbamide. In another specific embodiment, the RU is a base, a base, or an aralkyl group. The square base is another oxygen in another embodiment, and Y is a 〇-alkyl group. R is a fluoro group, a nitro group or a cyano group, w is a second embodiment of the formula (A), χ is a phenyl group which is optionally substituted; and 2 is one of its definitions; Ri, r4, R6' and r7 are both hydrogen, R5 is chloro'. and Z is a formamide or a formyl-heterocyclyl moiety. All of them are nitrogen; R5' is halogen; and z is an alkalyl group, a stilbene group, a leuco- zealine, and in another specific embodiment of the formula (A), the oxime is a tolyl group, a thiazolyl group or a pyridyl group. , Υ is Η, ΟΗ, or 〇-alkyl; RI, R4, r6, and R7, 3 helmet or a few acid derivatives. 93533 60 200804280 7, in another example of the specific embodiment of the month, χ, γ, r1, r4, han &, and R white are as defined above, and z is a carbamide-alkylene group _ Heterocycles ^1, medium-duo-heterocyclic rings are typically mwa, sigma, sigma, bite, or.乂 乂 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视 视Or an alkane fluorenyl-aryl group. A first series of sub-embodiments of the present invention is presented, wherein Formula (A) is as provided above, and W, X and Y are defined as ... a) W is 〇, X is alkyl, and γ Is _〇_alkyl; b) W is 〇, X is _〇_aryl, and γ is alkyl; C) W is 0, Χ is _〇-aryl, and Υ is _NR2R3; d) w Is 〇, X is an alkyl group, and γ is an alkyl group; e) W is 0 'x is a-0-alkyl group, and Y is a halogen group; f) w is 0, x is _〇_heterocyclic ring, and γ Is an alkyl group; g) w is 〇, χ is aryl, and γ is _〇_alkyl; h) W is 〇, X is a heterocyclic group, and γ is _〇_aryl; 0W is 〇, X Is an alkyl group, and γ is a _〇_heterocyclic group; j) W is _NR2R2, X is a heterocyclic group, and γ is _〇_aryl; k) W is -NR2R2, X is an alkyl group, and γ Is a halogen group; s, X is an alkyl group, and γ is a -〇-alkyl group; m) W is S, X is an alkyl group, and Y is -NR2R3; n) W is s 'X is -〇_芳a group, and Y is a burnt group; 〇) W is s' X is a -〇-aryl group, and Y is a C-dentate group; P) W is s, X is a -〇-alkyl group, and Y is an alkyl group; 61 93533 200804280 q) w is s, χ is _〇_heterocyclic, and γ is r) W is S'X is an aryl group, and γ is an alkyl group; S) W is s, X is a heterocyclic group, and γ is _〇_aryl; t) W is s, and X is an alkyl group. And γ is _〇_heterocyclic group; U) W is 〇, X is aryl, and γ is aryl; v) W is -NR2, X is _〇_alkyl, and γ is _NR2R3; W is 〇, x is _〇-aryl, and γ is -〇-aryl; x) w is 〇'x is alkyl, and γ is alkyl; and y) w is -nr2, X is 〇-alkyl, and γ is an alkyl group. A second series of sub-embodiments of the present invention is proposed, wherein formula (A) is as provided above, R1 is fluorene, alkyl, decyl, aryl, aralkyl or aryl; and lanthanide is defined as : a) _C(=W)NR2R3, R2 is Η, and R3 is NR2R2; b) _C(=W)NR2R3, R2 is Η, and R3 is NR2R2, or R2 is a Cu alkyl optionally substituted by OH and R3 is _NH2; e) _C(=W)NR2R3, R2 is Η, and R3 is (CH2)mC(=W)NR2R2; d) -C(=W)NR2R3, R2 is Η, and R3 is 经a substituted aryl or heterocyclic alkyl group; e) -C(=W)R3, R3 is an amino acid residue or -NH(CH2)p-(amino acid residue); f) ^ C(-W)NHNHC2H5〇H ; g) -C(-W)NHCH2C(=W)NH2 ; h) -C(-W)NHCH2CONHNH2 ; i) -C〇W)NHCH2CH2(2-N02,5-曱62 imidazole); 62 93533 200804280 j) -C(=W)NHCH2NHCH(CH3)C(=W)OH; k) -C(two W)NHCH=CHC(=W)NH2 ; l) -C(two W NR2R5NR2R3, R5 is (diO), R2 and R3 are as defined above, m) -C(=W)NR2NR2-C(=W)R3, R2 is H or alkyl, and R3 is aryl; -C(=W)N(-NR2R3)-N(-NR2R3)R3, R2 is Η, R3 is R2 or alkoxy; C) -C(=W)NHR2C(=W)-Q, Q is a heterocyclic ring, and R2 is as defined above; p) -C(=W)NR2R3, R2 is as defined above, and R3 is - ΌΗ ; q) -COR2R3, R2 is an amine group and R3 is a heterocyclic ring; r) -C(=W)NHNHC(=W)R2 and R2 are NH2; s) -C(=W)-R2-CH-AC (=W) NH2 and R2 are NH; t) -C(=W)-R2-CH-AC(=W)H, and R2 is NH; u) -C(=W)-R2-CH-AC( =W)OH, and R2 is NH; v) -C(di W)-R2-CH-A_R3, R2 is NH, and R3 is CH3; w) -C(=W)NHR2C(=W)NH2, and R2 is a branched alkyl group which is optionally substituted; X) -C(=W)R2R3, R2 is NH or alkyl, and R3 is NH2; y) -C(di W)R2-C(=W)OR3 And R2 and R3 are as defined above; z) alkoxy, and R2 are as defined above; aa) -C (dialkoxy, and R2 are as defined above 63 93533 200804280; bb) _C (2) R2, and R2 is NH2; cc) -C(=W)R2-NH-C(=W)OR3, and R2 and R3 are as defined above; dd) -C(=W)R2- C(=W)R2, and R2 are as defined above; ee)-C(=W)NHR2 where R2 is optionally substituted aryl, cycloalkyl or heterocyclyl ring; ff) -C( =W)R2-W_R3 Wherein R2 and R3 are as defined above; gg)_C(=W)-NH-CH(R2)-C(=W)-NH2, and R2 is as defined above; hh) -C(=(W _NH-NH2; ii) -C(gas W)-NH-NH(R2), and R2 is as defined above; jj) -c(=w)-nh-ch(c[=w]nh2)( Ch2-c[=w]-o-aryl); kk)-C(-W)-NH-CH(-[CH2]4-NH-C[-W]-t-BuO)(-C[- W]-NH2); 11) ·<3(=λ\〇-ΝΗ-αΗ(-αί2-Οί2Τ[二W]-t-BuO)(C[=W]-NH2); mm)-C( =W)-NH-CH(R3)(,C[=W]_NH2), and R3 is as defined above; nn)-C(=W)-NH-CH(-CH2-R3)(-C[ Two W]-NH2), and R3 are as defined above; 00) -C(=W)-NH-CH(-CH2OH)(-C[=W]-NH2); pp) -C(=W) -NH_CH(C[di W]-NH2)(C[di W]_NH2); qq) -C(=W)_NHR2-C[=W]NH2, and R2 is as defined above; rr)_C (two W)-NH-CH(-[CH2]4-NH-C[=W]_0-CH2-R3)(-C[=W] face NH2), as defined in R), 64 93533 200804280 ss) -C(=W)-NH-CH(-CH2-C[=W]-NH2)(-C[=W]-NH2); tt) -C(=W)-NH-CH(-CH2-R3 (-C[di W]-NH2), wherein R3 is as defined above; uu) -C(di W)-NH-CH(-[CH2]4-NH2)(-C[di W>NH2) ; vv)-C(=W)-NH-CH(face CH[R2][OH])(-C[=W]-NH2), and R2 is as above Defined; ww) -C(=W)-NH-CH(-R2)(-C[=W>NH2), and R2 is as defined above; XX) -C(di W)-NH-CH( _R2-C[=W]-NH2)(-C[di W]-NH2), and R2 is as defined above; yy) -C(=W)-NH-CH〇R2-SCH3)(-C[ =W]-NH2), and R2 is as defined above; zz) -C(=W)-NH-CH(-C[=N]-NH2)(-C[=W]-NH2); aaa) -C(=W)_NH_CH(-R3)(_C[=W]-NH2), and R3 is as defined above; bbb) -C(=W)-NH,CH(_CH2-R3)(_C[two W ]_NH2), and R3 is as defined above; ccc) _C(=W)_NH-CH(_R2)(_C[=W]-NH2), and R2 is as defined above; ddd) -C(two W )_NH-R2_C[di W]R3, and R2 is an alkylene group and R3 is an aryl or heteroaryl group; eee) -C(=W)-NH-R2-R3-C[di W]-NH2, wherein R2 is an alkylene group and R3 is an aryl or heteroaryl group; fff) -C(di W)-NH-NH-R2-R3-C(di W)NH2, wherein R2 is an alkylene group 65 93533 200804280 and R3 Is an aryl or heteroaryl; ggg) -c(:w)-nh-nh-ch(r3)_c(=w)R2, and 2 is nh: and R3 is an optionally substituted aryl or hetero An aryl group; hhh) wherein r2 is an alkylene group and R3 is an alkyl, aryl or heteroaryl group optionally substituted - ld) -C(=W)NHR2(-R3)-C(=W)NH-R2-C(=W)OH, where R2 is an alkylene group and R3 is an alkyl group which is optionally substituted, Aryl or heteroaryl; jjj) -c(=w)nhr2(-r3)-C(=w)nh_r2_NH2, wherein r2 is an alkylene group and R3 is an optionally substituted alkyl, aryl or heteroaryl (kkk) <(') leg #)-(:(,)·#, where R2 is an alkylene group and R3 is an alkyl, aryl or heteroaryl group optionally substituted; 111) -C (=W)-R2-(CH2VA-C(=W)-NH2, wherein R2 is a weight, p is 0 to 10, and A is a divalent linker or an optionally substituted aryl or heteroaryl group, and W is 〇 or s ; mmm)-C(=W)NH-R3, wherein R3 is a heterocyclic ring which is optionally substituted; mrn) -C(=W)-NH-R2-R5-r3, wherein w is 〇 Or s, r2 is a stretching group, an alkenyl group or an alkynyl group, R5 is -S〇2, and R3 is -NH2; 〇〇〇) -C(=w)-NH-NH-R2(R3)- R5-NH2, wherein w is hydrazine or S, R2 is a stretching group, an alkenyl group or an alkynyl group, R3 is an aryl group, an aryl group, or a heteroaryl group, and R5 is -S02; PPP) _c(= w)-nh-r3(r5-nh2), wherein W is 0 or 8, &3 is aryl, aryl, or heteroaryl, and R5 is S〇2 ; qqq) -C(di W)-NH-R2-R3(R5-NH2), wherein W is hydrazine or s, r2 93533 66 200804280 is an alkylene group, a dilute or an alkynyl group, and R3 is an aryl group. An aryl or heteroaryl group, and R5 is S〇2; rrr)-C(=W)-NH-R3(R2R5_NH2), wherein hydrazine is hydrazine or SR, alkylene, alkenyl or alkynyl , R3 is aryl, aryl, or heteroaryl, and R5 is S02; sss)-c(=w)-Nhr2(_r3)_c(=w)NH-R2_c(=w)〇h, where r2 An alkyl, an alkenyl or an alkynyl group which is optionally substituted, and R3 is any of the above definitions; ttt) -c(=w)-nhr2(-r3)-C(=w) nh_R2-c(=w)NH2, wherein R2 is an optionally substituted alkyl, alkenyl or alkynyl group, and R3 is any of the above definitions; uuu) -C(=W)- NHR2_C(=W)NH_R2-C(=W)OH, wherein R2 is an optionally substituted alkyl, alkenyl or alkynyl group, and R3 is any of the above definitions; or vvv) - C(=W)-NHR2-C(=W)NH-R2-C(=W)NH2, wherein R2 is an optionally substituted alkyl, alkenyl or alkynyl group, and R3 is as defined above Any of them; and where R, R3, and A are As defined above. The sixth series of the sub-embodiments of the present invention of the above-mentioned provided formula (A) is proposed herein, wherein the rule 4, the ruler 5, the meaning 6 and the 7 are defined as: a) R6 and R7 are氲, and 尺 4' and r5, independently halo; _n〇2; -N; -OR2; -NR2R2; -NH-R5-CW alkyl b NHC...Ci 3 alkyl, oxime; i;-iKSOdCu alkyl; -NH-O-Cu alkyl; -NHOH; or one or more _〇H...SR, 93533 67 200804280 -C(=W)H, -C(=W) as needed OH, _, -NR2R2, Cu alkoxy, or C _3 thioether substituted Cw alkyl or alkenyl; b) R4' and R7' are both hydrogen, and R5' and R6' are independently halo ;_n〇2 ; -N ; -OR2 ; -NR2R2 ; -NHSC^-Cu alkyl; -NHCO-Cu alkyl; hydrazine; hydrazine; -HO-Cu alkyl; -NH-OH; Or a plurality of -OH, -SR, -C(=W)H, halogen, -NR2R2, Cu alkoxy, or Cu sulfide substituted Cu alkyl or alkenyl; c) R4' and Rf are both hydrogen And R5' and R7' are independently halo; _N〇2; -N; -OR2; -NR2R2; -NHSCVCu alkyl; -NHCO-Cu alkyl; hydrazine; hydrazine; -HO-Cw alkyl; NH-OH; or as needed -OH, -SR, -C(=W)H, -(=W)OH, halogen, -NR2R2, C.3 alkoxy, or Cu thioether substituted Cu alkyl or a dilute group; d) R4' and R7' are both deuterium, and R5' and R6' are independently halo; ·Ν〇2; -Ν; -OR2; -NR2R2; -NH-O-Cu alkyl; -ΝΗΟΗ; or as needed An alkyl or alkenyl group substituted by one or more -OH, _SR, -C(=W)H, -C(=W)OH, halogen, or _NH2; e) R4' and R6' are both hydrogen, And R5' and R7' are independently halo; _n〇2; -N; -OR2; -NR2R2; -NH-O-Ch alkyl; -NHOH; or optionally one or more -OH, _SR, -C(=W)H, _C(=W)OH, halogen or -NH2 substituted c _6 alkyl or alkenyl; f) R6' and R7' are all hydrogen, and R4' and R5' are independently Halogen; (^-6 alkyl, alkenyl or alkynyl substituted by one or more halo groups as appropriate; 68 93533 200804280 g) R4' and R7' are all hydrogen, and R5 and r6 are independently halo; C _6 alkyl, alkenyl or block substituted by one or more halo groups as desired; h) R 4 'and R 6 ' are both hydrogen, and R 5 'and independently halo, optionally one or more Replaced by a 13⁄4 base C1 _6 alkyl, dilute or alkynyl, i) R6' and R7' are all hydrogen, and R4' and R5' are independently α, F, Br, I, thiol, ethyl or CF3; j) R4' and R7' are both hydrogen, and R5' and R6' are independently α, F, Br, I, thiol, ethyl or CF3; k) R4' and R6' are both hydrogen, and R5' and R7 'Independently, α, F, Br, I, decyl, ethyl or CF3; and wherein A is as defined above. The fourth series of sub-embodiments of the formula (A) is defined as where w, X and Y are as defined in the first series of sub-specific embodiments, and z is as defined in the second series of sub-specific embodiments. The fifth series of the specific embodiments of the formula (A) is defined as wherein " and γ are as defined in the first series of sub-embodiments, and Μ, r5, R6 and R7 are as in the sub-embodiment The three series are defined. The sub-fourth material of the formula (4) is defined as the second series of sub-specific embodiments and R4, 'R7' is defined as the third series of the sub-embodiments. The first and above defined by the above formula (A) are as follows: The unconstrained species of the one-piece example is 1) Z is -C(=W)NHNHC2H5〇H, r Cl, X is Η, and γ is Η; R6' and R7 are Η R5, which is 93533 69 200804280 2) Z is -C(=W)NHCH2C(=W)NH2, R4' is F or Cl, R6' and R7' are H, and R5' is F or Cl, X is H, and Y is OH; 3) Z is -C(=W)NHCH2CONHNH2, R4' is F or Cl, R6' and R7' are H, R5' is F or Cl, X is H, and Y is -O-alkyl; 4) Z is -C(=W)NHCH2CH2-(2-N02,5-Me-imidazole), R4' is F or Cl, R6' and R7' are oxime, and R5' is F or Cl, X is Η, and Y is -O-fine; 5) Z is -C(=W)NHCH2NHCH(CH3)C(di W)OH, R4' is F or Cl, R6' and R7' R ' R R R R R R R R R R R R R R R R 'And R7' is Η, R5' is F or C1, X is H, and Y is -0-alkylaryl; 7) Z is ·<:(=λν)ΝΗΝΗ(:Η2€:(=Ψ) ΝΗ2, R4' is F or Cn, R6' and R7' are Η, R5' is F or CBu X is Η, and Y is aryl; 8) Ζ is -C(=W)NHCH2C(= W) R2, wherein R2 is NH2, R4' is F or Cb R6, and R7' is Η, R5' is F or α, X is Η, and Υ is -0-heterocyclic; 9) Ζ is -C (=W) NHCH2-A_C(=W)NH2, where Α is a divalent separator, Rt is F or Cl, R6' and R7' are Η, R5' is F or Cl, X is Η, and Υ is Ci_6 10) Z is -C(=W)R2CH-AC(=W)H, where A is a divalent separator, R2 is NH, R4' is F or Cl, R6' and R7' are Η, R5 'is F or Cl, X is Η, and Υ is C2_6 alkynyl;

11) Z is _C(=W)R2CH_A-C(two W)OH, where A is a divalent separator, R2 is NH, R4' is F or CBu R6' and R7' is Η, R5' is F Or C Bu X 70 93533 200804280 is Η, and Y is C2-6 block; 12) Ζ is -C(=W)R2-CH-A-R3, where Α is a divalent separator, r2 is NH, R3 Is CH3, R4' is F or Cl, R6' and R7' are η, Rule 5, F or (:1, again 11, and ¥ is aryl; 13) Z is -C(two W)NHR2- C(=W)R2, wherein R2 is a bond which is optionally substituted or NH'R is F or Cl, R6 and R7' are η, R5' is F or Cl, X is Η, and Υ is Heterocycle; 14) Ζ is -C(=W)R2, where R2 is ΝΗ, R4' is F or Cl, R6, and R7 are Η, R5' is F or Cl, X is 〇H, and Y is η 15) Ζ is -C(=:W)R2R3_heterocyclic ring, wherein meaning 2 is oxime, anaphylide 3 is CH2, heterocyclic ring is morpholine, imidazole or pyrrole which is optionally substituted, rule 4, is F or C1 , R6' and R7' are Η, R5 is F or C1, X is Ci 6 alkyl, and γ is H; i 6) Z is _c(=w)r2c(=w)_〇_r3, The towel r2 is an alkyl group which is optionally substituted, R3 is a benzoquinoneoxy group, R4' is F or α, r6, and R7, and is & r5, F Or C Bu X is _〇_alkyl, and γ is H; 垸oxy, wherein R2 is as needed

, = substituted yard, R4 is F or α, R6, and r7, is H, r5, is F 3 , X is _〇 dilute, and Y is Η; =n_c(=w)R3_c(——W R2, wherein r2 is an alkyl group to which the oxy 'r3 is to be substituted, MC1, RmH, R5, ..., or C Bu X is 0_alkynyl, and γ AH · lg\ 7 , 4 ϋ ' J B is _C(=W)R2R3, where R2 is the same as *, which is the alkyl group that needs to be substituted as required, R3 ~ excellent to replace the molybdenum, r4, a is F ^ Or C, R6, and R7, which are η, R5, sub-Cl, X is _〇_alkylaryl, and γ is Η · 93533 71 200804280 is regarded as Η, 20) Ζ is -C(= W) R2-NH-C(=W)-0-R3, wherein r2 is alkyl, R3 is benzyl, R4' is F or α' VIII and R7, R5' is F or C is X - 0-Aralkyl, and γ is Ή · 2υ ζ is -C(=w)r2C(=w)_NH2, wherein y is a fine alkyl group as needed, R4' is F or Cl, and R6' and R7' are Η , R5, is F or < -〇_aryl, and γ is Η; Ζ is _C:('R2_W_R3 ' where & R3 is an alkyl group which is optionally substituted, and R4 is F or a, R6, And R7' is Η, R5, 幺π R is F or Cl, X is -O-hetero, and γ is Η; 23) Ζ -C(=W)r2c(=w)_〇_r3, where R2 is a substituted base as needed. R3 is a stupid methoxy group, r4, F or C1, r6

Is F or C1, X is _C2_6_ dilute, and MH; H'R = Z is -C(,)_nh_ch(r2)_c(=w) Na 2, where r2 is dish 2, R is F or ! ^, and r7, is Η, R5, is F or α, χ is % 6_alkynyl, and γ is H; 25) is -C(,)_NH_NH2 'where r4, ρ or α, r6, and r7, Is 1^115? Or (::1, again aryl, and 丫 as]9;; 26) ~ is,. (, depending on the milk, where R2 is dish 2, R4, is F or Cl 'R6' and R7' is H'r5, F or α, χ is heterocyclic, and γ is η; 27) Ζ is -C( =W)_nh_Ch(C[=W]Nh2)(Ch2-C[=w]-0-CH2-aryl), wherein the feet 4' and R5' are independently f or c, and R6' and R7' are Η , X is a carbocyclic ring, and γ is Η; 28) Ζ is -C〇w)-NH-CH(-[CH2]4-NH-C[=W]-t-BuO)(-C[two W]

-NH2), wherein anatomical 4' and r5' are independently F or C1, ulnar 6, and r7' are H, X 72 93533 200804280 is - hydrazine - aryl aryl and Y is C 1 -6 burning; Z is -C(=W)-NH-CH(-CH2-CH2-C[=W>t-BuO)(-C[=W] -NH2), wherein R4' and R5 are independently F or Cl , R6' and R7' are Η, X is -Ο-aryl' and Υ is -0-alkyl; 30) Ζ is -C(=W>NH-CH(-CH2R3)(-C[=W] -NH2), wherein R3 is CF3, R4' and R5' are independently F or C, R6' and r7' are Η, X is <2 6 alkenyl, and Υ is -ΟΗ; 31) Ζ is -C (=W)-NH-CH(-CH2R3)(-C[=W]-NH2), wherein R3 is as defined in the first embodiment, and R4' and R5' are independently F or ci, R6, and R7' is Η, X is -C2_6 alkynyl, and Y is Η; 32) Ζ is -C(=W)-NH-CH(-CH2OH)〇C|-W]-NH2), where r4, and R5 Independently F or a, R6, and R7 are η, X is -Ο-alkylene, and Υ is -〇-alkyl; 33) Ζ is _〇(=%)-1^11-€: 11(-0: 卜界)-:^112)(-€:卜~]-1«12), where R4 and R5' are independently F or CBu R6, and R7, Η, X is _ miscellaneous Ring, and Υ-ΟΗ; 34) ζ is -C(=W)-NH-CH(-R3)(-C[=W]-NH2), Wherein r4> r5, independently F or cn, R6' and R7, η, X is -Ο-alkenyl, and γ is a burnt group; 35) Ζ is -C(=w)_Nh_Chg[CH2]4_nh_c[ =w]-〇-ch2-r3)gc %W]_NH2), wherein R3 is as defined in the first embodiment, r4, and R are independently F or c, R6, and R7, Η, X is -OH, and γ-plated alkyl; horse 36) ζ is -CBub W]_NH2)(-CBuw]_nh2), 73 93533 200804280 where R4' and R5' are independently F or C1, R6' And R7' is H, X is · Carboniferous ring, and Y is -〇_alkyl; Length 37) Z is π(=ψ)-ΝΗ{Η({Η2-Κ3)(·ί:[=^μΝΗ2) Wherein R3 is as defined in the first embodiment, R4, and R5 are independently F or α, R and R are deuterium, X is an alkyl group, and γ is a heterocyclic ring; 38) Ζ is -C( =W)-NH-CH(-[CH2]4-NH2)(-C1-W]-NH2), wherein R4 and R5' are independently F or cn, R6, and R7 are Η, and X is _〇 _ dilute base, and Υ is -OH; 39) Ζ is _c(=W)-NH-CH(-CH[R2][OH])(-C[=W]-NH2), where R4' and R5 'Independently F or C, R6, and R7, are Η, X is a block group, and Υ is _〇_alkyl; 40) Ζ is _c(=W)-NH-CH(R2)(-C [=W]-NH2), where the ruler 4, and R5, The site is F or a, R6' and R7 are Η, X is -OH, and Y is the extension base; 41) Z is -CBu w)-NH-CH(-R2-C[=W]-NH2 (-C[=W]-NH2), wherein R2 is NH2, R4' and R5' are independently F or CU, R6, and R7 are Η, X is -C2, 6 alkyl, and γ is _〇η ; 42) Ζ is <(=ψ>νΗ-0Η((:[=ΝΗ]-ΝΗ2)(-(:Bu W>NH2), where R4' and R5' are independently F or a, R6' and R7' are deuterium, X is a carbocyclic ring, and deuterium is a hepta-alkyl group; 43) Ζ is _c(=W)-NH-CH(-CbNH]-NH2)(-C[= W]-NH2), wherein R4' and R5' are independently F or CL·R6' and R7' is Η, X is _OH, and Y is -0-stretching group; 44) Z is _c(= w) -NH-CH(-R3)(-C[di W]-NH2), wherein R3 is as defined in the first general embodiment, R4' and R5' are independently F or α, R6 'And R7' is Η, X is aryl, and γ is _Ci-6 alkyl; 45) Z is <(=^)-ΝΗ·0:Η(-(:Η2-Ι13)(〇Ψ] _Νη2), wherein r3 is as defined in the first general embodiment, feet 4' and R5' are independently F or a, R6' and R7' are H, x is _0H, and 丫 is _〇_desane Base; 〆46) Z is {(Which)_丽-^(-«[=外胆2), where r2 is NH2, R4' and R5' are independently F or α, r6' and r7' are η, and X is (alkynyl, And Υ is 〇 〇 aryl; 16 47) Ζ is -C(,)_NH marriage_ch(r3)_c[=w] r2, which is a two-substituted aryl or heterocyclic ring, r4' :... is alkyl, aryl R2 ^ , R3 ^i^): C(=W)NH'R2'C(=W^ ? + ^ F ^ c; , R:^ ^ ^ ^ ^ m ^ R- and Y are -o-alkyl; H, X is -O-alkenyl,

pHSEr;H:S 51) Z is -c(=w)-NHR2 (R2 is an alkylene group, R3 is an as needed R3)-C(^W)NH-R3-C(=W)〇H > Substituted alkyl, aryl or heterocyclic ring wherein R4, 93533 75 200804280 and R5' are independently F or Cl, 116' and Rr are η, x is _〇11, and γ is -Ο-alkylene 52) Ζ is -C(=W)-R2(CH2)pIC(=W)-NH2, where R2 is the title, Ρ is 〇 to 10, Α is divalent, optionally substituted aryl or hetero Ring, R3 is an optionally substituted theater group, aryl or heterocyclic ring, Rule 4, and R5, independently F or Cl 'R6 and R7 are Η 'X is -Cu alkyl group, and γ is _〇_ Alkenyl 2: 53) B is _(:(=\\〇->111-113, wherein R3 is a heterocyclic ring which is optionally substituted, R4' and R5' are independently F or cn, and 6, and R7 , Η, X is _〇_alkyl, and Υ is _〇Η; 54) Ζ is -C(=W)_NH_R2_R5_R3, wherein R2 is an alkyl, an alkenyl or an alkynyl group, and R5 is -S02 , R3 is -NH2, Han 4' and R5, independently F or Cl, R6' and R7, H, X is _〇_aryl, and 丫 is 〇 烧 烧; 〆 55) Z is - C(=W)_nh_NH_r2(R3)_r5_NH2, wherein the rule 2 soil is an alkyl group, an alkenyl group or an alkynyl group. R3 is aryl, R, _s〇2, 奵 and R5, ^ is F or Cl'R6, and R7 is H, X is _〇-alkynyl, and γ is ... out 56) Ζ is -C( =W) Nh_r3(r5_NH2), wherein r3 is aryl, aryl, heterocyclic, R, _s〇2, with 'and r5, independently F or c b r6, ^ r7 is η, X is - a heterocyclic group, and γ is _〇_alkyl; 57) Ζ is -C(=W)nh_r2r3(r5_NH2) ' wherein 2 is an alkylene group, an extended alkene group or an alkynyl group, and R3 is an aryl group. Aryl or heterocyclic group, r5 is na, R and R5' are independently cl, R6jR7' is fluorene, fluorene is -aryl, and fluorene is -〇·fine; %) z g_c(=w)NH_R3 (R2R5_NH2), wherein Han 2 is an alkylene group, an alkenyl group or an alkynyl group, R3 is an aryl group, an aryl group or a heterocyclic group, R5 is _so, 93533 76 200804280 R and R5 are independently F or Cl , R6, and R7' are η, X is -〇H, and Y is an alkaryl group; 59) Z g_c(=w)NiiR2(_R3)_c(=w)NH_R2_c(=w)〇H, where r2 is Optionally substituted alkyl, alkenyl or alkynyl, R3 is defined as any of the first general embodiments, feet 4' and R5, independently F or Cl'R6 and Η , χ is _C2_6 alkynyl, and γ _〇_妇基; 60) Ζ is -C(=W)NHR2(-R3)-C(=W)NH-R2-C(=W)NH2, where R is a substantially substituted alkyl group , an alkenyl group or a stretching group, r3 is any of the definitions provided in the first general embodiment, the feet 4' and R5, independently F or C1, R and r are Η, and χ is _c2_6 And γ is; 61) Z is -C(=W)NHR2_c(=w)nh_r2_c(=w)〇h, where r2 is an alkyl, alkenyl or alkynyl group which is optionally substituted, han 4 And r5, which is F or Ci, r6> R7, is "also...", and γ is _h; 62) Z is -C(=W)NHR2_c(=w)mi_R2_c(=w NH2, wherein y is an alkyl, alkenyl or alkynyl group substituted as desired, R4, and 'y: the ground is F or C1, R6, R7' are ^, 丫, and 丫 is 〇平某. Call Z is -C (, muscle R3, where w is 〇, and r3 is a heterocyclic ring which is a sulfhydryl group, a thiol group or a (tetra) group, which may optionally contain one or more fluorenyl groups, fluorenyl groups, and alkane. Substituted by alkenyl, alkenyl, alkynyl, or cyanoalkyl; Μ, I independently H, F or C1, R6, and R7' are deuterium, deuterium is optionally phenyl, and deuterium is -〇-alkyl ; and , and two replace the W system Α) defined. In a second embodiment, the invention provides a phenyl hydrazine for the treatment of mv as shown by (Β), Formula 93533 77 200804280 R4,

Or a pharmaceutically acceptable salt, prodrug, oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein: each of W, Y, Z, Ri, R2, R3, A, η, R4', R5', R6' and R7' are as defined by the above formula (Α); and each R2", R3", R4", R5'', and R6'' are independently: a) Η; b) Halogen; c) N〇2; d) CN; e) OR2; f) SR2; g) NH2; h) NR2R3; i) alkyl; j) NiRS-SCVCw alkyl; alkyl; 1) C2_6 alkenyl; 78 93533 200804280 m) C2_6 alkynyl; n) aryl; o) CF3; p) CR2R2-S(0)nR3; q) CR2R2NR2R3; r) C-OH; s) CR2R2_C(=W)R2; t) 醯u) C(two W)R2 ; v) C(=W)OR2 ; w) C(=W)SR2 ; x) C(=W)-NR2R3 ; y) c(=W)NH(CH2V( Amino acid residue); Z) amine residue; or aa) A-(amino acid residue); bb) cyanoalkyl; cc) cyanide group; or dd) cyanynyl group, wherein any of the above It may be replaced as needed; or alternatively, R2'' or R6" may be linked to γ to 14 ring members, and may be replaced by 4, 衣, or a core. Phosphorylation Ring. The first embodiment of the sub-system (8) contains all of the sub-specific embodiments. The second series of specific embodiments of the present invention relating to the specific embodiment of the formula (8) provided above, wherein R2'', R3", R4", R5 and R6" are It is defined as: a) R2", R4", and R6'' are oxime, and R3'' and R5" are each independently halogen; -N02; -CN; -OR2; alkyl; -NHCO-Cu alkyl;肟;肼;-Ν(〇Η)(^_6 alkyl; Cw alkoxy; -〇H; -NR2R2; or optionally one or more -〇h, -SR, -CN, -halo, -C(di W)H, -C(=W)OH, halogen, NR2R2, -Cw sulfur-, or -Cu alkoxy substituted c1-6 alkyl, alkenyl or alkynyl; b) R2, R4 And R6" are hydrogen, and &3, and r5" are each independently halo, or optionally substituted by one or more halogens, ci 6 alkyl, alkenyl or alkynyl; c)

KR and R6 are hydrogen; d) R2, e) R2, R f) R2,,, R4,, g) R2,,, R4,, h) R2,,, r4" i) R2,,, R4, And R6" are 氲 and R6 is hydrogen and R6" is hydrogen and R6" is hydrogen and R6 is hydrogen and R is chloro 4, and R3, and R5 are sulfhydryl; and R3, and R5, , which is chlorine; and R3" and R5, which are fluorine; R is ruthenium and r5" is bromine; r3 is methyl and R5" is chlorine; and .. 'R3 is chlorine and R5" is methyl. Here & the specific embodiment of the first embodiment of the invention described above is defined as: column, where W, Y, R2'R3' a) W is 〇' γ The bases are only independently and each independently is _R/R6 is hydrogen, and 2 and the marriage is ^6; _Nh^ ' ^ ; thiol; 肟; 肼; 93533 80 200804280 NCOI^Cu alkyl; Cw alkoxy ; OH; _NR2R2; or optionally one or more -OH, -SR, -C(=W)H, -C(=W)OH, halogen, NR2R2, -Cu sulfide, or _Ci_6 alkoxy Substituted Cw alkyl, ruthenium or fast radical, b) W is S, Y is OH, R2'', R4", and R6'' are hydrogen, and R3" and R5'' are each independently halogen, or a Cu alkyl group, a dilute group or an alkynyl group substituted with one or more halogens as desired; c) W is Ο, Y is a Cw alkyl group, and R 2", R 3", R 4 '', R 5" and R 6 " are hydrogen; d) W is S, Y is Cw alkyl, R2", R4'', and R6" are hydrogen, and R3'' and R5" are fluorenyl; e) W is NH, Y is -0-alkyl, R2'', R4", and R6" are hydrogen, and R3 and f) R5" are chlorine; g) W is S, Y is -0-alkenyl, R2", R4' And R6'' is hydrogen, and R3" and h) R5'' is fluorine; i) W is Ο, Y is aryl, R2", R4", and R6" are hydrogen, and R3" and R5" are Fluorine; j) W is NH, Y is -0-alkynyl, R2", R4", and R6'' are hydrogen, and R3" and R5" are fluorine; k) W is S, Y is S, R2" , R4", and R6" are hydrogen, and R3" and R5" are fluorine; l) W is Ο, Y is -0-alkyl, R2", R4", and R6'' are hydrogen, and R3" is 81. 93533 200804280 Iodine and R5" are bromine; m) W is Ο, Y is _〇-burning aryl, r2", ana 3", and R4, is -OH; and R6'' is hydrogen, n) W S, Y is -NR2R3, R2,,, r3", anodic 5, and R4, is _NH2; and R6 is hydrogen, 〇) W is oxygen, R4" is -N02; and P) W Y, Y is -0-aralkyl, r2", K, and p6" from a v,

It is chlorine and R5 is a sulfhydryl group. For gas, the fourth series of R sub-specific examples is defined as follows: γ in the second series of the specific embodiment of (A), "the middle 2 is as defined, and R2", R3", R4,, Rule 5, and R6, are as defined in the second series of the examples in the series ~. The sub-series of the formula (B) The fifth series of the specific embodiment is defined as follows, as in (A) In the first series of the specific embodiment, where the households of W and Y (A) are defined in the second series of specific embodiments, the Z system is as in the formula R5', R6 > R1 is embodied as a sub-form of the formula (A) 'R4', 定, and R2", R3", R4,,, 5, and r6 are all defined in the third series of the examples in the 罘-糸 column. The sixth series of sub-specific embodiments is defined as follows, any one of the second series of the specific embodiments of (A), wherein Z is of the formula R'R6, and R7, is a sub-embodiment of the formula (A) :者所-defined, 奵, 定, and W, Y, R2,,, R3,, 4" The K, R and the graves of the Ang II series are the sons of the (Β) 93533 82 200804280 The third embodiment of the series as defined. The non-limiting type of the second embodiment proposed by the second formula (8) is defined as follows: From the basis of w) NHNHC2H5〇H, r4, r6, and r7, η, r5, c is Y is Η, R2 ", r6" is H, and traits ' and R5' are sulfhydryl groups; B) Z is _C(==w)NHCH2C(=w)NH2, r4' is f or Q, "and r7, is H, R5 'F or Cl, γ is 0H, r2', ft 4, and r6, is h, and R3 and H5' are sulfhydryl groups; C) Z is -C(=w)NHCH2C〇NHNH2, rule 4 'For F or Q, Rule 6, and & 7, for H' R5 is F or C. Y is -CM complete, r2,,, ruler 4, and r6" are h, and R3'' and R5 , is 曱 ;; D) Z is -C(=W)NHCH2CH2-(2-N〇2,5-Me-mouth π sitting), r4' is f or Cl ' R and R7 is h, R5 is F or Cl, Y is -〇-alkenyl, r2", r4" and R6 are H, and R3" and R5" are methyl; E) Z is ·C(=w)NHCH2NHC(=w)〇H, R4' is F or α, r6, and R7' are H, R5' is F or c, Y is -0-alkynyl, r2,,, R4" and R6" are H, and R3" and R5" are 曱Base; F) z is ·ς:(=:ψ)(:Η=€Η(:(=λ\〇ΝΗ2, R4, is F or Cl R6, and R7, are H, R5' is F or ci, Y is -Oalkylaryl, R2", R4" and R6" are H, and R3" and R5" are methyl; G) z is -c (=W)NHNHCH2C(=W)NH2, R4' is F or CBuR6' and R7' is H, R5' is F or ci, Y is aryl, R2", R4" and R6" are H, and R3" and r5" are methyl groups;

Η) Z is _C(=w)nHCH2C(=W)R2, where R2 is NH2, R4' is F 83 93533 200804280 or Cl, R6' and R7' are Η, R5' is F or Cl, and Y is - Ο-heterocyclic ring, R2", R4" and R6" are fluorene, and R3" and R5" are methyl; I) Z is _C(=W)NHCH2_A-C(=W)NH2, wherein A is divalent Separator, R4' is F or CL·R6' and R7' is Η, R5' is F or Cl, Y is Cw alkyl, R2", R3", R5'' and R6" are Η, and R4'' Is -NH2; J) Z is _C(=W)R2CH-AC(=W)H, where A is a divalent separator, R2 is NH, R4' is F or CU, and R6' and R7' are Η, R5' is F or CBu Y is C2_6 alkynyl, R2", R4" and R6" are deuterium, and R3" and R5'' are methyl; Κ) Ζ is -C(=W)R2CH-AC(= W) OH, wherein Α is a divalent partition, R2 is NH, R4' is F or CU, R6' and R7' are Η, R5' is F or Cl, Y is C2_6 alkynyl, R2", R3", R5" and R6" are Η, and R4" is -Ν02; L) Ζ is -C(=W)R2-CH-A-R3, wherein Α is a divalent separator, R2 is NH, and R3 is CH3, R4 'For F or Cl, R6' and R7' are Η, R5' is F α, Υ is aryl, R 2 ′′, R 4 ′′ and R 6 ′′ are Η, and R 3 ′′ and R 5 ′′ are fluorenyl; Μ) Ζ is —C(=W)NHR2-C(=W)R 2 , wherein R2 is a branched alkyl or NH which is optionally substituted, R4' is F or Cl, R6' and R7' are oxime, R5' is F or CL. Υ is heterocyclic, R2", R4'' and R6 '' is Η, and R3" and R5'' are sulfhydryl groups; Ν) Ζ is -C(=W)R2, where R2 is NH, R4' is F or Cl, R6' and R7' are Η, R5' Is F or CL·Y is Η, R2'', R3", R5" and R6" are Η, and R4'' is -OH; Ο) Z is -C(=W)R2R3-heterocycle, wherein R2 is NH, R3 is CH2, heterocyclic ring is substituted as desired, sputum or sigma ratio, R4' is F or C1, R6' and R7' are Η, R5' is F or Cl:, Υ is Η , R2", R4" and R6'' are Η, 84 93533 200804280 and R3" and R5'' are sulfhydryl groups; P) Z is -C(=W)R2NH-C(=W)-0-R3, wherein R2 is an alkyl group which is optionally substituted, R3 is a benzoquinoneoxy group, R4' is F or Cl, R6' and R7' are oxime, R5' is F or CL? Υ is Η, R2'', R4" and R6" is Η, and R3'' and R 5'' is a methyl group; Q) Ζ is a -CpWjR^NH-CpWhCw alkoxy group, wherein R2 is an alkyl group which is optionally substituted, R4' is F or CP R6' and R7' is Η, and R5' is F Or C is Η, R2'', R4" and R6'' are Η, and R3" and R5" are 曱; R) Ζ is _C(=W)R3-C(=W)R2, where R2 is Cw alkoxy, R3 is an optionally substituted alkyl group, R4' is F or Cl, R6' and R7' are oxime, R5' is F or Cl, Υ is Η, R2", R4" and R6 "为Η, and R3" and R5" are methyl, S) Ζ is -C(=W)R2R3, wherein R2 is an alkyl group which is optionally substituted, R3 is a phenyl group which is optionally substituted, and R4' is F or CL· R6' and R7' are Η, R5' is F or Cl, Υ is Η, R2'', R4" and R6" are Η, and R3" and R5'' are sulfhydryl; Τ) Ζ _C(=W)R2-NH-C(di W)-0-R3, wherein R2 is an alkyl group which is optionally substituted, R3 is a phenylhydrazine group, R4' is F or Cl, and R6' and R7' are Η, R5' is F or Cl, Υ is Η, R2'', R4" and R6" are Η, and R3'' and R5" are methyl; U) Ζ is -C(=W)R2C(二W )-NH2, where R2 is taken as needed Alkali, R4' is F or Cl, R6' and R7' are H, R5' is F or Cl, Y is Η, R2", R4" and R6" are Η, and R3" and R5'' are曱基;

V) Ζ is -C(=W)-A-R3, wherein R3 is an optionally substituted alkyl group, A 85 93533 200804280 and R7 are oxime, and R3, and R5 are alkylene linkages ( Linker), R4' is F or Cl, R(R5' is F or α, Y is η, R2", R4'' and R6" are H, which is methyl; X) Ζ is -C(=W)R2c (=w)-0-R3, where R2 is the view * p. ^ 1?3 V, ^ 4, the brother is replaced by a burnt group, R is a stupid methoxy group, R4 is F or c b r7 5, Is F or Cl, γ is Η, R2", R4" and R6" are Η, and: 3H 'R5" is methyl; 乂 and R3 and R5 Y) Z is -C〇w)-NH-CH(R2 )-C(=W)-NH2,J: φ From 丄八甲 R is 丽2, R is F or C1, R7' is H, R5' is F or cBu γ is Η, r2”, R4 and R6 Is Η, and R3" and R5" are methyl; Z) Z is -0(=Μ^νη·ΝΗ2, where R4 is F or Cl, R6j is 7, and H is, R5' is F or Cl, γ For η, R2,, R4, and R6, Η, and 尺3,, and r5" are fluorenyl; AA) Z is, where r2 is Nh2, R4 is f or a, R6 and R7, For Η, R5, is F or C, and Y is η, R2,,, R4" and r6" are H, And R3" and R5, are sulfhydryl groups; BB) Z is -C(=W)-NH_CH(C, wherein R4' and R5' are independently F or Cl, R6, and R7 are η, and R2 is Alkyl or aryl, Y is Η, R2, ', R3,,, R5, and R6, is Η, and 尺4, is _Nh2; CC) Z is -cBu w)-NH-CH (-[CH2]4-NH-C[=W]-t-BuO)(-C[=W] -NH2), wherein R4' and R5' are independently F or α, R6, and R7, which are Η , γ is Cw alkyl, R2, ,, 4, and r6" are η, and R3j R5, is fluorenyl; DD) Z is -Cd)_NH_CH(-CH2-CH2-C[=W]- t-BuO)(-C[=W] -NH2) 'where ana 4' and R5' are independently F or Cl, R6, and R7' are Η, γ 86 93533 200804280 is -〇-alkyl, R2" , R4" and 6" are H, and feet 3" and r5, are methyl · EE) Z is _C(=W)-NH-CH(-CH2R3)(-C[=W]-NH2) Wherein r3 is CF3, R4 and R5' are independently F or cl, R6j is 7, is Η, γ is _, R2, R4 and R6'' are Η, and R3" and R5" are fluorenyl; FF Z is -C(=W)-NH-CH(-CH2R3)(-C[=W]-NH2), wherein r3 is as defined in the first embodiment, ruler 4, and R5, independently f Or C Bu R6 and R7 are Η, Y is Η R2", R3,,, 5, and 6, are H, and R4" is -Ν〇2; GG) Ζ is -C(=W)-NH-CH(-fluorenyl)(-C [=W]-NH2), wherein R4, and R5, 'independently F or α, ..., and R7, are H, γ is _(7) alkyl, r2", R4" and R6'' are Η, and R3,, and R5, are fluorenyl; H,)z is -C(=W)-NH-CH〇C[=W]-NH2)(-C[=W>NH2), where R and R5 are independent The ground is F or Cl, R6, and R7 are Η, Y is -OH, R2,, R3, R5" and R6" are Η, and R4" is -ΟΗ; Η) Ζ is, where r4, and r5 , independently F or Cl, R6' and R7, η, Y is -0-alkyl, R2,,, r4, and R6 are fluorene, and R3" and r5" are fluorenyl; JJ) z is Wherein R3 is as defined in the first embodiment, R4' and R5' are independently F or C1, R6' and R7' are deuterium, Y is a heterocycle, R2", r4" and r6" are η, R3" and r5'' are methyl; KK) Z is _c(=W>NH-CH(-[CH2]4NH2)(-C[=W]-NH2), wherein R4 and R5' are independently F Or a, R6' and R7' are Η, Y is ΟΗ, R2", R4 and R6" are Η, and R3'' and R5, are sulfhydryl; 87 93533 200804280 LL·) Z is -C(=W)-NH-CH(-CR2R2)(-C[=W]-NH2), wherein r4, and R5' are independently F or Cn, R6, and R7, Η, Y is -cualkyl, r2,,, R4" and R6" are H, and R3'' and R5" are methyl; MM) Z is -C(=W)-NH-CH(R2)( -C[=W]-NH2), wherein Han 4, and R are independently F or ci, R6' and R7 are Η, Y is -0_alkyl, R2,,, R4 and R6" are H And R3" and R5, are methyl; NN) z is -cBu W)-NH-CH(-R3)(-C[=W]-NH2), wherein R3 is as in the first general embodiment As defined, R4, and R5 are independently F or C1, R6 and R7' are Η, Y is -Cw alkyl, R2,,, R4, and R6" are Η, and R3'' and R5" are Methyl; 〇〇) Z tC(,)-NH-CH(-CH2-R3)(-CBu W]-NH2), wherein R3 is as defined in the first general embodiment, R4, and R5, independently The ground is F or R and R is Η, Y is -〇-extension base, r2", r4" and r6" are Η, and R3" and R5, are methyl; pP) Z , where r2 is 2 R And R is independently F or α, & 6, and r7' is Η, γ is _〇_ = base, r2, ', r3', r5, R6, h^: ^r4, _NH2; _ U) Z,-C(=w)_n H_nh_ch(r3)_c卜w]r2, wherein r2 is 2 R is an optionally substituted aryl or heterocyclic ring, R4' and R5, independently ❹=C1 R and R7 are H 'Y is -0H, R2, , , Han 4,, and r6" are H, and R3 and R5, are methyl; :V) Z3 丨c(,)_nhr2(_r3)_c[=w]nh2, where & : The ground requires a substituted alkyl, aryl or heterocyclic ring, r4, and r5' are either f or a, R6' and r7 are Η, γ is ...h, r2", r4, r6" 93533 88 200804280 H, and R3" and R5" are methyl; WW) Z is ·ς:(=^ν)ΝΗΙ12(-Κ3)-(:(=\ν)ΝΗ-:ΚΛ(:〇\ν)〇Η R2 Is an alkyl group, R3 is an optionally substituted alkyl, aryl or heterocyclic ring |, R4, and R5, independently F or a, R6, and R7' are H, and Y is _〇_alkyl R4'' and R6" are Η, and 尺 3'' and r5" are f groups; XX) Z is -C(=w)NHR2(-R3)-C(=W)NH-R2-NH2, wherein R2 is a stretching group, R3 is an optionally substituted alkyl group, an aryl group or a heterocyclic ring j is independently F or cb R6, and R7' is η, Y is a hepta-alkyl group, r2", a ruler 4" And R6" is Η, and R3" and R5" are ψ base; 凡土,, YY) Z ^-C(=W)NHR2(-R3)-C(=W)NH-R3-C(=W)〇h 5 Α Φ is a silk-based group or a heterocyclic ring of 4, =, :: _, R6, and R7, H, u_0, alkyl, R and R are η, and 3, 'and R5' are fluorenyl. ZZ^Z^c(^^ is regarded as the second price Depending on the aryl or heterocyclic ring to be substituted, R3 is the peak of the peak, r F or C b R6, 7 and K are independently

Η, Υ is alkenyl, R2,,, R3,,, R5,jR6,, is η, and r4, is _n〇2; and R AAA) Z is _c(=w)_nh_r3, ring' R4' and R5 are independently F or c: R6, and the mouth is required, the substituted heterocycles R2, R4, and V" are η, and r3" is, γ is -〇H, and RRm 7 is inferior. The long rule is methyl; the face) Z is -c(=w)NH-A_s(0)n_R2, the base or the alkynyl group, and R, _NH2, R4 are still the extension base, the extension and R7, which are H, YA, p2, independently F or C, R6, is -〇-虎基, RHH, with 93533 89 200804280 and R5" as methyl; ccc) Z is -c, w)nh_nh_r2(r3)_a_c(= w) nH2, wherein r2 is alkyl, A is alkyl, alkenyl or alkynyl, R3 is aryl, aryl or heterocyclic, and R4' and R5' are independently F or α, 1 ^, and r7, are H, i is -OH, R2", Miao' and r6" are H, and feet 3', and R5' are methyl groups;

Brain) Z is now w) NH_A[s(〇)2_NH2], where A is a stretching group, an alkenyl group or an alkynyl group, and the feet 4' and r5' are independently F ..., a group, ... and a... ^ )Z is any definition in which R2 and R3 are provided as a general embodiment, r4, and r5, independently 6 is F or a, R6jR7 is Η, γ is _〇_ dilute, r2, , r4 ” and R6 are Η, and &3,, and R5” are methyl; F ′)Z is <(,)νηκ2(_κ3)<(,)ΝΗ42<Bu w)NH2 , where ^ R3 is the first to be substituted alkyl, alkenyl or alkynyl

: Routinely defined in the six embodiments, R4' and R5, independently F or R and R7 are H, γ is -H, R2'', R4, and R6, are Η, and R And R5'' is a methyl group; ) Z is -c(=W)NHR2-C(=W)NH-R2-C(=W)OH, wherein R2 is an alkylene group or an alkylene which is optionally substituted Or an alkynyl group, R4, and R5, independently F or a, r6, and r7, Η, γ is ·H, r2", r4, and r6, are H, and Han 3" and R5 , is a thiol group; is _C(=W)NHR2-C(=W)NH-R2-C(=W)NH2, wherein R2 is an alkylene group, an alkenyl group or an alkyne which is optionally substituted Base, R4, and R5, independently F or C1, ", and r7, H, γ is _0_alkyl, r2 ”, r4, and 93533 90 200804280 f is & and r3, r5” Is a methyl group; and wherein the W system is as defined in formula (4). In the second embodiment, the (j) Μ咏 Μ咏 Μ咏 本 本 本 本 本 藉 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、吲哚: Ί 9 to 11 members double ring R4”

Or a pharmaceutically acceptable A chemical isomer or a mutual compound, each of W, z, Rl, R, A, n, R, R5', R6' and R7' is as defined by the above formula (Α) Each R3,,, R4,,, r5" ^ -1, and R is as defined by the above formula (B); represents the presence of a single or double bond, wherein: Tian 77~= when there is a double bond in the table, each ¥ and τ is independently: (a) CR2; (b) N; or (c) SR2; only Y and T. One of the ones must be CR2; one for the presence of a single bond, then γ and T is independently: 91 93533 200804280 (a) CR2; (b) 〇; (c) NR2; or (d) SR2; only one of Y and T must be cr2; and m is 1 or 2, only when The first series of the specific examples of the formula (c) includes all of the sub-specific examples provided by the above formula (a), wherein the substituent "χ" is an aryl group or a heterocyclic ring. A group, a 0-aryl group, and a fluorene-heterocyclic group. The second series of specific embodiments of the present invention relating to the specific embodiment of the formula (C) provided above is proposed herein, wherein γ and τ are defined as: (j) Τ is _CH2 and Υ is -〇 - (k) T is -CC(=0)-0CH3 and γ is (1) τ is -0 and γ is -CR2; (m) T is (_CH2)2 and Y is -NR2; (n) T is _〇 112 and Y are -SR2; (〇) Τ is -〇 and γ is -c-aryl; (Ρ) D is -NR2 and Υ is C-halogen; (q) τ is -sr2 and υ is _ C_heterocyclic ring; (r) T is -c-cw alkyl and Y is -〇-; (s) T is -C_C(di-S)CH2 and Y is -Ch2_; (1) τ is -CH-OCH3 and Y is -SR2 ; (u) T is _〇ΟΗ and Y is _CH2·; (ν) τ is -C-OCu alkyl and Y is -CH2-; 93533 92 200804280 (w) T is -C-NH2 and Y Is -CH2-; (X) T is -C-NH-Cu alkyl and Y is -CH2-; and (y) T is -(CH2)2 and Y is -(CH2)2. A third series of sub-embodiments of the present invention relating to the specific embodiment of formula (c) provided above is set forth herein, wherein R3", R4,, R5, and R6" are defined as: a) R4" And R6" is 氲, and R3'' and r5" are each independently halogen; -N02; -CN; _〇R2; _NH_R5-Ci_6 alkyl; -NHCO-Cu alkyl; hydrazine; alkyl; CU6 oxygenated Base; _〇H; _NR2R2; or one or more -〇H, -SR, -C(two W)H, -C(=W)〇H, Nansu, NR R2, -Cu sulfur puzzles as needed Or a -C alkoxy substituted C1-6 alkyl, alkenyl or alkynyl; b) R4'' and R6" are hydrogen, and R3" and r5" are each independently halogen or, if desired, one or a plurality of halogen-substituted Cw alkyl, alkenyl, alkynyl groups; c) R3", R4", r5, and r6" are hydrogen; d) R4 and R6" are hydrogen, and R3" and R5" are methyl e) R4 and R6" are hydrogen, and R3" and R5" are chlorine; f) R4 and R6" are hydrogen, and R3" and R5" are fluorine; g) R4" and R6" are 氲, R3" is Iodine and R5" are bromine; h) r3, R4'' and R6" are hydrogen, and R5'' is chlorine; i) R4 and R6'' are hydrogen, R3" is chloro, and R5" is fluorenyl; Ο R3, R5 and R6" are hydrogen, and R4" is halogen; _cn; -OR; -NH-R5_Ci_6 烧基卜NHC〇-C"炫基;n(〇h)Ci_6文基基;Cl_6垸oxy;-OH;-NR2R2; or as many as 93 93533 200804280 _OH, -SR, _C(=W)H, _C(=W) 0H, Cl_6 alkyl, alkenyl or alkynyl substituted by a cyclin, Nr2r2, thioether or -Cw alkoxy. • i) R3'', R5" and R6'' are hydrogen, and the ruler 4" is _ N〇2 ; k) R3'', R5" and R6" are hydrogen, and R4" is _〇R2; !) R, R5'' and R6" are hydrogen, and R4'' is halogen; and m) R3 '', R5' and R6, are hydrogen, and R4, _NH2.

The fourth series of the specific embodiments of the formula (C) is defined as follows, which are defined in the second system 2, the middle Z column of the sub-embodiment of the formula (A), and the R3", R4", and the ruler 5 And R6, as defined in the third series of the two-body embodiment. The fifth series of the specific embodiment is defined as follows, which is defined in the second series of the sub-embodiments of the formula (A). Ren:: The boundaries R6' and R7' are as defined in the third series of the specific embodiment of the formula (4) and the Y and T systems are defined in the sub-form of the formula (C). The sixth series of the specific embodiments of the present invention is the next one of the second series of the specific embodiments of the present invention; : 2, R5 n R7' is the sub-embodiment of the embodiment of the formula (8): The boundaries mR3', R4, R, R5" and 2 are defined in the H. The type of the third embodiment proposed by the formula (8) is as follows: a) Z is _C(=W)N(R2R3)C(W2, where is NH and R3 93533 94 200804280 is an alkyl group; R1, R4', R6' and R7' are deuterium, R5' is halo or _N02; R4, and R6 are deuterium; R] and R5" are independently -〇H or _NR2R2; Y is 〇; and butyl is CH2; b) Z is _C(=W)-NH_CH(_C[=W]NH2(_CH2-C[=W]_0_CH3-aryl); R1, R4, R6 and R7' R5' is halo or -CN; R4" and R6, 'is H; R3 and R5 are independently -Cu alkoxy or -Cu alkyl substituted by -Cu methoxy group as desired; Y is SR2; and T is CH2; c) Z is -C(=W)Li NH2 '· R1, R4', ", and r7, η; r5, halo or -NR2R2; R4 and R6 are Η; R3 And R5 is independently _n〇2 or -CN; Y is CH2; and T-R2-R3 is ch2; d) Z is -c(two W)NH-CH2-C(=W)NHNH2; R1, R4 , R6, A R7, is H, R5 is halo or alkyl, wherein r5 is _〇(〇) or _s(0)n and η is 0, 1 or 2; R4" and R6" are Η; R3> r5" is independently _OR2 or -CN; Y is C_Ci_6 alkyl; and τ is N; e) Z R1, r4, r6, and r7 are H; R5 is halo or alkyl, wherein r5 is c(q) or -S(0)n and n is 0, 1 or 2; R4" and R6 "ηη; 厌3,, and r5" are independently _OR2 or -CN; Y is C-Cw alkyl; and τ is sr2 and r2 is as defined by formula (A); f) z is -C( , NH-CH (a C (, NH2, wherein R2 is a 2 or an alkyl group: a ruler "" eight to 'and ^: ^' is a halogen or -^^(7)^ alkyl; R4'' and R6'' is Η; R3'' and R5" are independently g_NHOH; γ % / 欲 · and T are (CH2) 2 ; g) Z is -C(=W)NR2-C(=W)R3, where R2 For the t to be replaced by the burned 93533 95 200804280 base, alkenyl or alkynyl; R3 is NH2; Rl, R4', rule 6, and r7, is H; r5, is a halogen H" and R- is H; Miao ' and r5" are independently h or -NH_R5_CV6 alkyl, wherein R5 is _c(0)4_s(〇)n and 11 is 〇, i or 2; Y is C, alkynyl; and T is _〇; h) Z is -C(=W)NH_R2_SR2, wherein r2 is an alkyldiene or alkynyl group which is optionally substituted, and a radical or a ruthenium of '^^'; R and R6 are oxime; R. And R5 is independently η or -NHCO-Cu alkyl; y is a c-carbocyclic ring; and butyl is NR2, wherein R2 is as defined by formula (A) or optionally via one or more -〇H, _SR , -C(=W)H, <Bu\〇011, halogen, -nr2r2, c!.3 alkoxy or Ci.3 thioether substituted Cl_6 alkyl or alkenyl, R4 and R6 are η; R3 and R5 are independently η or -CN; Y is C-aryl; and τ is Ν; i) Z is -C(=W)_NH_N(R3)(R2), wherein R2 is hydroxy or alkoxy, And R3 is H or a burnt group; Ri, R4, ft. 6, and r7 are η; r5 is a halogen group j) Ζ is; R1, R4, R6, and R are H; R5 is a halogen group or CF3 R4 and R6" are η; R3" and R5, independently Η or -NH-O-Cu alkyl; Υ is 〇; and τ is CH2;

k) Z is ·&lt;:(=π)-ΝΗ-Ν(ί12){Η(ί12)·€(=λν)Ι12, where: ^2 is H or NH2; R1, R4',...' and r7 'H; r5, halo or η; R4" and R are H, R3 and R5 are independently η or halogen; γ is -NR2 and τ is CR2, wherein R2 is as defined in the general embodiment l) Ζ is -C(=W)-N(R2)-C(=W)R3, where R2 is ΝΗ and R3 is CH3; R1, R4', R6j R7' is Η, R5' is halo or 114" and R6, are H, R3 and R5 are independently η or halogen; Y is -〇; and τ is (C-〇_ 96 93533 200804280 alkyl); m) Z is -C(=W -NH-CH=CH-C(=W)R2, wherein R2 is NH2; R1, R6' and R7' are H; R4' and R5' are halo or h; R4" and R6, are H; R3, and R5" are independently H or -OR2, wherein r2 is as defined in the first general embodiment; Y is _〇; and T is (C_CH2_CH3); η) Z is -C(=w)-NH -CH=CH-C(=W)R2, where R2 is _ leg 2; R], R and R are H; R4 and R5 are from the base or _n〇2; R4" and r6" are η. R3 and R5 is independently Η or -ΝΗΟΗ; Υ is -〇 and τ is c_CH3. ο) Z is, where r2 is bribe or Jane 23; R1, R6' and R7' are Η; R4' and R5, _ group or _〇r2, wherein r2^ is as defined in the first general embodiment; ruler 4, and R6" are H; ruler 3" and R5 , independently, or as desired - one or more _〇11, _SR, _c(=w) 〇h, halogen, or -NH2 substituted -C 〗 3 alkyl or alkenyl; γ is _SR2 And D is CH2; P) Z is _c(=w)-r2-ch2-ac(=w)r2, where R2 is as defined in the first general embodiment, and A is as in the first general implementation Example: The bivalent linker mR7' is mm: -CN; "and R6" is H; r3'&gt; R5" is independently H or ^ alkoxy, Y is -NR2' wherein R2 is 帛As defined by the general embodiment; τ is (ch2)2; q)z is -C(,_R2_CH2|C(=W)R2, its towel is a base or -=H2, and a is a divalent linker; RI, r6, and r7 are H; and R is i or -nr2r2, where R2 is ^^ Η; R3&gt; ^ ^ ^ ^ K is independently H or Η·, and Υ is -Ch2 93533 97 200804280 And T is ((:112)2; r) Ζ is -C(=W)-A-R2-C(=W)〇r3, where r2 is _νη and r3 is -H or alkyl; and R7, Is H; R4j r5, _ base or hr5-Ch alkyl, wherein R5 is as defined in the first general embodiment; R4, and r6, are Η; R3 and R5 are independently η or _nr2r2 wherein R2 is as in the first general embodiment界^; γ is "16 alkyl; and M CH2; s) Z is: C(=W)-NH-C(=W)0r3, where r3 is as defined by equation (8); R, R and R are PJ R4 and ]^5' gas a pots into the ^ and Κ are haloalkyl; R4'' and R6'' are Η; R3" and R5" independent secret gas a | bucket, lt long eight independently halogen Or Ή; γ is alkenyl; and T is 0; t) Z is -C(=W)R3_NH-C(=W)_R2, where r2 g_NH2 and r3 shoulder-NH; Rl, Rl R7, are Η; R4'a r5, which is a dentate group or a hydrazine; R4, and r6 are H; R3" and R5" are independently η or optionally substituted by one or more dentate-Q.3 alkyl or alkenyl groups γ is _C_alkynyl; and τ is ^^)2; 11) ζ is -c(=w)-n(oo)-n(r2)-r3 'where r^h or alkyl, R3 is :NH2, R1, R6j R7' is η; # and r5' are dentate or 肼&amp;4" and R6 is Η; R3 and R5" are independently Η; Y is -C% aryl; and τ is ( CH2)2 ; V) Z is _C(=W)-N(R2)-N(R2)-C(two W)R3, where the ruler 2 is H Alkyl, and R3 is NH2; R1, R6, and R7 are H; feet 4, and r5 are halo or -NHS(0)2_Cl_3 alkyl; R4j R6" is H; r3&gt; r5, independent ^ Η or -曱; γ is _c-heterocyclic; and τ is 〇; w) Ζ is -C(=W)_N(_n[r2][r3])_r3, where r, h or alkane, and R3 is NH2; Ri,..., and V are Η; and, and R5, is _ = ^ is 93533 98 200804280 requires 2 or 2 - 〇H, -SR, -C(=W)H , _C (== w) 〇 H, halogen t, -nr2r22, CiW oxy or Cw thioether substituted _Ci 6 alkyl or olefin, wherein R is as defined in the first general embodiment; R4" and R6, 'is H; R3 and R5' are independently Η or -NR2R2, wherein R2 is as defined in the first general embodiment; γ is &lt;_carbocyclic; and τ is NR2, wherein R2 is as described above Provided; x), Z is _C(=W)R2-C(=W)NH2, wherein R2 is alkyl; Rl, r6, and R7 are deuterium; 4' and R5 are halo or -H; "and r6,, is H; ruler 3, and r5" are independently helium or gas; γ is _SR2 and butyl is ch2; y) Z is -CBu W)R2-SR2, where R2 is _NH Or alkyl; Rl, r6, and R7' are oxime; feet 4' and R5, halo or _C F3; meanings 4, and r6, are h; han 3, and r5" are independently Η or fluorine; γ is -〇; and τ is (ch2)2; z) Z is -C Ψ)&lt;;Η(Κ2)-(:(=ΝΗ)Κ2, where r2 is Η or 丽2; R1, R4' and R7' are Η; ;^' and R6' are halo or Η; and 4, 'and R6,, is η; R3'' and R5" are independently η or -cf3; γ is _nr2; and τ is cr2; wherein R2 is as defined by formula (A); aa) Z is -C〇W) _NH_a-NH-C(=W)-AC(=W)-R2, wherein R2 is NH2 and A is a divalent linker; R1, 4, and r7 are H; R5, and r6 are -CN or ^^^' and "for ^^ and ^ are independently ^^ or -N02; Y4_CH2; and τ is NR2, where r2 is as defined by formula (A); bb) Z is R2 is Η, alkyl Or NH; A is a divalent partition as defined by formula (A), R, R4 and R7 are Η; R5 and R6 are Η or -NHCO-C! 6 alkyl; 93533 99 200804280 R4 and R6 are Η ; R3'' and R5" are independently η or 肼; γ is (CH2)2; and T is N; cc) Z is -C(=W)_NH-A(_cBuW]_NH2), wherein A is an alkyl or aryl monovalent separator linkage; R1, R4, and R7 are Η; R5, and 116 are H or -NH (S〇2)Cl_6 alkyl; &amp;4" and r6, are H; R3j r5 "is independently η or -ΝΗΟΗ; γ is _c_alkenyl; and τ is ν ; dd) Z is -C (=W&gt;NH-CH(-A-R3)(-C[=W]-NH2), where A is a stretching or an alkenyl spacer (Spacer); r3 is 〇H; Rl, R4' and R7, is Η; R5' and R6' are Η or CF3; R4'' and R6" are η; R3, and R5, are independently H or -NR2R2, where r2 is as defined by formula (A); Is a <_ carbon ring; and Τ is SR2; ee) Z is -C(=W)-NH-CH(R2)(R3), where r2 and r3 are each C(=W)NH2; R1, R6' And Η; &amp; 5' and R4' are H or halo; R4" and R6 are H; R3'' and R5" are independently h or -Cm alkoxy; Y is -〇; and Τ is ch2 ; ff) Z is -C(=W)-A-CH(R2-C[=W]-NH2)(-C[=W]-NH2), where A is a partition as defined by formula (A) Bonding; R2 is nh; R1, R6, and R7 are Η; R5 and R4' are Η or -N〇2; R4" and R6, are η; R3,, and R5, are independently Η or _ ΟΗ ; Υ is -Ν ; and Τ is CH2 ; gg) Z is -C(=W)-NH-CH(-CH-R2-0H)(-C[=W]-NH2), where R2 is NH or Alkyl; R1, R6' And R7' is Η; R5j R4' is Η or - halogen; R4" and R6" are Η; R3" and R5" are independently η or -halogen; γ is -SR2; and Τ is CH-OCH3; hh) Z is · ί:(=λ\〇-ΝΗ-0:Η(-Κ2)(-(:[=λν]-ΝΗ2), where R2 is burned 93533 100 200804280 base; R1, R6 and R7 are Η; 5, and R4, is η or -N02; R4, and R6, are H; R3 and R5 are independently h or -CN; Y is _C-aryl; and T is N;

R1, R6 and R7 are Η; 5, and R4 are η or -〇H; R4, and R6" are Η; R3 and R5 are independently η or -CN; Y is -C-heterocycle ; and T is (ch2)2; jj) Z is -C(=W)-NH-CH(-R2-C[=W]-NH2)(-C[=W]-NH2), where R2 is stretch Alkyl; R7' is H; sense 4, and rule 5, H or 〇2; R4 and R6 are Η; R3 and R5'' are independently H or -ΝΗ〇Η; γ is _〇; T is CH2 ; kk) Z is -C(=W)-NH-CH(-R2)(-C[=W]-NH2), wherein R2 is -S(0)R3 and R3 is as defined by formula (A) ; Rl, r6, and r7 are H; r4, and R5 are Η or -OR2; R4 and r6" are η; &3, and r5" are independently η or -Cw alkoxy; Υ is - NR2, wherein R2 is as defined in the general embodiment, and T is ch2; , 11) Z ^-C(=W)-NH-CH(-C[=NH].NH2)(-C[ =W]-NH2); R1, R6' and R7' are Η; R4' and R5 are Η or _nr2r2, where r2 is as defined in the first general embodiment; R4" and R6" are Η; 3,, and R5, which are Η or -〇H; Y is -SR2, and τ is (CH2)2; mm) Z is -C(=W)-Simplified-NH-CI^RYct,] #, where R2 is -NH2 and R3 is an optionally substituted aryl group Or a heteroaryl group; Ri, y/'' R7' is Η, R4' and R5' are Η or ·CN; R4\R6, W, 3, and independently Η or -NR2R2, wherein r2 is The first person is Η; R3 and r5" are as defined in the specific example 93533 101 200804280; Y is -C-Ci_6 alkyl; and T is]Si; nn) Z is -C(=W)-NHR2(-R3 -C[=W]-NH2, wherein R2 is a fluorenyl group, and R3 is an alkyl, aryl or heteroaryl group optionally substituted; R1, r6, and R7' are oxime; R4' and R5' are Η or -NH-R^Cw alkyl, wherein R5 is as defined in the first general embodiment; R4" and R6" are Η; R3, &gt; R5, independently Η or optionally via one or a plurality of _〇h, -SR, halogen, or NH2 substituted -Cw alkyl or alkenyl; γ is -c-alkenyl; and T is SR2 'where R2 is as defined by formula (A); 00) z is -c(=w)-nhr2(-r3)-C[diw]nh-r2-c(=w)oh, wherein R2 is an alkyl group, and R3 is an alkyl group or an aryl group which is optionally substituted Or a heteroaryl; R1, R6 and R7 are Η; R4' and R5' are H or -NHC〇_Ci 3 alkyl; R4 and R6 are Η; R3 and R5" are independently H or optionally Multiple halogen substituted _C1_6 alkane Or alkenyl; γ is &lt;-alkynyl; and τ is CH2; pp) z is -c(=w)-li 112(43)4bw]nh_r2 丽2, where r2 is alkyl, and R In the case of an alkyl group, an aryl group or a heteroaryl group which is optionally substituted, ? =,, R6 and R7' are η, · r4' and R5, H ^, hr6, h; R3 and R5'' are independently η Or _ self-prime; γ is &lt;η2; and τ is 屮r2 where R2 is as defined by formula (A); qq) z is 3 c( w)-nhr (-r3)-c(=w)nh- R3, wherein r2 is alkyl, and 7, R is an alkyl, aryl or heteroaryl group optionally substituted; Ri, R6, and R7 are Η; R4, and R5, H or - spell; r4, And R6, is H; &amp;3,, and r5" are independently H; Y is ·nr2, wherein R2 is as defined in the first general embodiment; and τ is (CH2)2; 93533 102 200804280

Rr) Z is -C(=W)-R2-AC(=W)NH2, wherein R2 is -NH, and A is a divalent partition bonded to an optionally substituted aryl or heteroaryl; r1 , r6 and r7' are η; r4' and sense 5 are H a-NH(s〇2)Ci 6 alkyl; R4 and R6 are Η; R3'' and R5'' are independently η or methyl; γ is -C_Cl_6 alkyl; and T is N; ss) Z is -C(=W)NH-R3, wherein R3 is an optionally heterocyclic ring; R1, r6, and R are Η; R4 and R5 are H or _Ci_6 alkyl or alkenyl substituted by one or more of _〇H, -SR, C(=W)H, C(=W)OH, halogen, NR2R2, Cu alkoxy, or Cw thioether, if desired The ruler 4, and r6, are H; r3" and R5 are independently ruthenium or chlorine; γ is _C_alkenyl; and τ is nr2, wherein R2 is as defined by formula (A); tt) Z Is _C(=W)NH_a_s(〇)2_r3, wherein a is a dialkyl group, an alkenyl group or an alkynyl divalent spacer linkage, R3 is -nh2, and R5 is _s〇2; 1^, , R6' and R7' are Η; R4, and R5 are H; 4, and r6, are Η; r3" and R5 are independently Η or fluorine; γ is -(Ch2)2; (CH2)2; 仙)2 is &lt;(二^¥爪沁1^^_(113)_8(〇)2屮112, where VIII is an alkyl, an alkenyl or an alkynyl divalent partition, R3 is an aryl, aryl or heteroaryl, and Μ is _S〇2; Ri, r6&gt; r7, is H; R4, and Rt, are Η or _CF3; R4 'and R6' are H; 3, and r5" are independently η or Cf3; Y is -〇; and T is CH2; vv) Z is -C( = W) Nh_r3 (S(VNH2), wherein r3 is aryl, aryl or hetero 6 aryl, R1, ugly 4, and r7 are H; and r6 is H or a stil group; &amp; And R6 are H; R3, R5" are independently Η or _Ν〇2; γ is -〇; and butyl is Cr2, wherein R2 is as defined by formula (Α); 93533 103 200804280 ww) Z is -C( =W)NH-Av\m,^ - A ^ 伸 烯 美 美 - 严 八 ^ 2, /, 中 A is an alkylene group, an alkenyl group or

An alkyne-pellet spacer linkage; R1, r4, and R7, which are H or ·Ν02, · R4, and 6, are Ή 3, and R is Η and Τ is a C-carbon ring; The ground is yttrium or -dentate; γ S i is bonded to aryl, aryl or heteroaromatic, H; R5 and R6 are Η or -CN; 114, and R6, are H; R3 "and R5" are independently H or a sr5 々3 alkyl group, the V system in the basin is as defined in the general embodiment of the mc_carbocyclic ring; and NR2, wherein R2 is as defined by formula (A); ... yy) z is -c(=w)nh-(-r3)-C(=w)nh_a_c(=w)〇h, where a is an extended or extended alkenyl group or a stretching group as desired a divalent separator bond such as R is as defined in the general embodiment; R1, ruler 4, and Rr are Η'·R5' and f is η or _or2, wherein r2 is as in the first general embodiment疋, R and R6 are Η, R3 and R5 are independently H or _cn; γ is -c-aryl; and T is CH2;

Zz) Z is -C(=W)NH(-R3)-C Bu W)NH-AC(=W)NH2, where A is a divalent spacer bond as defined by formula (A) y is as defined in the first general embodiment; R1, R4, and R7 are H; R5, and R6 are Η or -NR2R2, wherein R2 is as defined in the first general embodiment, R4 And R6 is Η; R and R5 are independently η or alkyl, wherein r5 is as defined in the general embodiment; γ is _c_ heterocycle; and T is SR2; aaa) z is _C(=W nhr2-C(=W)nh_R2_c(=w)〇h, where r2 is 93533 104 200804280 联; ; R4, T is as defined by formula (A) 'A is a divalent spacer bond R as needed , R and R are H'Rl R6, which is η or -NHS〇2_Ci6 alkyl and ^ is ^3" and 1^ is independently 11 or 肼; ¥ is _〇 and (CH2)2; and bbb) Z is -C(=W)NHR2«&gt;w)NH-R2-C(=W)NH2, wherein R2 is as defined by formula (A), and A is a divalent partition linkage which is optionally substituted;

R1, R4 and R7 are H; R5 and R6 are Η or -NHCO-Ch alkyl; R4, and R6 are Η, R3 and R5 are independently H or _〇H; γ is _nr2, wherein R2 is As defined by the first general embodiment, and D is Ch2; "where W is as defined in the first general embodiment of the above formula (A). In all embodiments, the sub-specific embodiments are defined as follows. 1) Z is -C(=w)-NH-R2; -cpwRHW; heart r2r3; -CR2-C(=W)R3; -R2.c(=W)R3 ; .r2.c(=W)R2 ; -R2r3 ; R3 . or C(-W)-NH-CR2R2-C(=W)-NH-CR2R3-C(=W)-NR2R3 ; 2) R4,, and R7' are H, and R5, i) halogen, and especially chlorine; ii) spelling out; Cl-6 alkyl, alkenyl, alkynyl, amine-based, thiol-alkyl, or amine-based, alkyl, each of which It may be substituted by one or more -OH, gram W)H, .C(:w) 〇H, _nr2r3, Ci 3 oxy, or ^ 3 thioether; or one of the following combinations: a) R5', R6' and R7' are hydrogen, and are considered to be halogen; 13)!14', 1^ and ]^ are oxime, and 1^ is halogen; c) R4, R and R6' are hydrogen, and R7' is Halogen; d) r5, R6 and R7' are hydrogen, and R4' CF3; e) R4, R5 and R7' are hydrogen, and R6' is CF "93533 105 200804280 ^^ and 'for hydrogen' and ruler". III. Definitions Unless otherwise indicated, the following definitions are used and Explanation of terms. The ranges, specific values, and values representing ί± of groups, substituents, and derivatives are for g-month use only, and do not exclude other definitions of groups, substituents, and organisms. Values or other values falling within the scope of the definition. Each range of the range includes the members of the range. For example, the case of the children, when enumerated Ci 6 alkyl, this list is independent The ground contains a group, a c2_alkyl group, a c3_alkyl group, a c4-shallow group, a c5_mercapto group, and a c" group. The base is "fluorine", bromine or broken. The k-based group, the "alkoxy group", the "mercapto group", the "alkynyl group" and the like mean that a linear or branched group is contained. However, the reference to an individual group such as "propyl" includes only a straight-chain group, and a branched isomer such as "isopropyl" is specifically indicated. The term "alkyl" as used herein, unless otherwise specifically indicated, such as a saturated direct bond, a bond, or a cyclic, primary, secondary or tertiary hydrocarbon of 'C1 to C1 Q, And specifically including mercapto, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, pentyl, cyclopentyl, isopentyl, neopentyl, hexyl, Isohexyl, cyclohexyl, cyclohexyldecyl, methylpentyl, 2,2-dimercaptobutyl, and 2,3-dimethylbutyl. When the alkyl group herein is substitutable, the moiety which can be used to replace the alkyl group includes, but is not limited to, a hydroxyl group, an amine group, an alkylamino group, an arylamino group, an alkoxy group, an aryloxy group, an aryl group, a hetero group. Cyclic, halo, carboxy, decyl, decyloxy, decylamino, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, sulphate, or phosphonate, 106 93533 200804280 It may be protected or Unprotected and known to those skilled in the art, for example, taught in Greene et al., Protective Groups in

Organic Synthesis, John Wiley and Sons, Third Edition, 1999. The term "low carbon number alkyl" as used herein, unless otherwise specifically indicated, includes a C-saturated linear, branched or, if appropriate, cyclic (eg, '% propyl) group. 'contains substituted and unsubstituted forms. Unless otherwise specified in this application, when the alkyl group is a suitable fraction, it is represented by a low carbon number. Similarly, when a base or a low number of alkyl groups is a suitable moiety, the unsubstituted alkyl or lower alkyl group is represented by the term "alkenyl" and "alkynyl" means an alkyl moiety, A substituted or unsubstituted form is included in which at least one saturated c_c bond is replaced by a double bond or a ^ bond. Thus, the Q_6 alkenyl group may be a vinyl group, an allyl group, a propylene group, a 2-propenyl group, a butenyl group, a 2-butenyl group, a 3-butenyl group, a fluorenyl-pentenyl group, a pentenyl group, and -pentenyl, 4-pentenyl, hexyl, 2-hexyl, 3-hexenyl '4-hexenyl' or 5-hexenyl. Similarly pentynyl '2-pentynyl, 3-e-pentyl, 4-pentenyl, hexyl, 2-hexal, 3-hexynyl, 4-hexyl, or Block base. '^1的伸丝" means a chemical formula of the sum of n_ and a linear one = where "n" may be any one of 1 to 10. Unless otherwise specified, the ": monocyclic, bicyclic or tricyclic carbon ring used in this article is the most in each ring; two:: at least one ring is (four) kel's 4n+2 two is 8 shells' The aromatic group defined. 93533 107 200804280 Examples of the base ring system include phenyl, naphthyl, tetrahydronaphthyl and biphenyl. The aryl group may be substituted by one or more moieties, Not limited to hydroxyl, amine, amphoteric, arylamino, alkoxy, aryloxy, alkyl, heterocyclic, halo, carboxy, decyl, decyloxy, decyl, nitro, cyanide Base, sulfonamide, sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate, which may or may not be protected as desired, and is known to those skilled in the art, for example, taught by Greene et al. Protective Groups in Organic Synthesis, John Wiley and Sons, Third Edition, 1999. The term "heterocycle" or "heterocyclic" as used herein, unless otherwise indicated, refers to a stable 5- to 7-membered single ring. Or a stable 8- to 11-membered bicyclic heterocyclic ring which is saturated or unsaturated, contains a heteroaryl group, and It consists of carbon atoms and one to four heteroatoms including but not limited to 0, S, N and P; wherein the nitrogen and sulfur heteroatoms can be oxidized as needed, and/or the nitrogen heteroatoms can be aminated by quaternary And any bicyclic group comprising a heterocyclic ring defined by any of the above, fused to a benzene ring. The heterocycle can be attached to any heteroatom or carbon atom resulting in a stable structure. The heteroaromatic ring may be partially hydrogenated or fully deuterated, as needed. For example, dihydro σ can be used instead of guanidine. The functional oxygen and nitrogen groups in the heteroaryl group can be protected as desired. Suitable protecting groups for oxygen or nitrogen include trimethyl decyl decyl, didecyl hexyl decyl, tert-butyl dimethyl methacrylate, tert-butyl diphenyl aryl, trityl, Substituted triphenyl fluorenyl, alkyl, decane sulfonyl, p-toluenesulfonyl, or fluorenyl such as ethyl hydrazino and propyl fluorenyl. Non-limiting examples of heteroaryl and heterocyclic groups include a thiol group, a 吼σ group, a sigma group, a takinyl group, a σ ratio cultivating group, a sigma group, a samarium group, a sigma group, a ratio of 108 93533 200804280 各 基, each 琳 基, σ 毕 σ 定 、, imilinyl, tetracalyl, trisal, tri-tough, thioxyl, oxazolyl, fluorenyl, carbazolyl, quinolyl, , than Junji, morphinyl, benzimidazolyl and the like. Any heteroaromatic and heterocyclic moiety may optionally be substituted as described above for an aryl group, including one or more of the following substituents: hydroxy, amine, alkylamino, arylamino, alkoxy, aryloxy , an alkyl group, a heterocyclic group, a yl group, a carboxyl group, a decyl group, a decyloxy group, a decylamino group, a nitro group, a cyano group, a sulfonic acid group, a sulfate group, a phosphonic acid group, a phosphate group, or a phosphine ruthenium root, which may be used as needed Protected or unprotected, and is well known to those skilled in the art, for example, as taught by Greene et al., Protective Groiij^j^ Organic Synthesis, John Wiley and Sons, Third Edition, 1999. The term "mercapto" refers to a compound of the formula ":(〇&gt;", wherein r is a substituted or unsubstituted alkyl or aryl group as defined herein. ^ The term "carboxy" refers to the formula " A compound of RC00H", wherein R is substituted or unsubstituted alkyl or aryl as defined herein. b Unless otherwise indicated, the term "aralkyl" as used herein is as defined above. The aryl group is attached to the molecule via an alkyl group as defined above. The term "calcined aryl" is used herein. The alkyl group as defined above is attached to the molecule via the aryl group as defined above. In addition, as used herein, the term "alkoxy" is used in the structure of the "alkoxy" group, wherein the alkyl group is as defined above. ', "^ otherwise specified outside the terminology used herein" The part represented by the structure of "amino group R2", and including a primary amine which is substituted by an alkyl group, 9 93533 109 200804280 aryl group, a heterocyclic group, and/or a sulfonyl group, and a secondary and tertiary female Therefore, R2 may represent two hydrogens, two alkyl moieties, or one hydrogen and The term "amine-amine" as used herein, unless otherwise indicated, refers to a moiety represented by the structure "-C(0)NR2", which is converted to H, alkyl, aryl, Anthracenyl, heterocyclyl and/or sulfonyl. "Amino acid" or "r-amino acid residue" as used herein is a natural amino acid of the formula d or L or some part thereof (also That is, Αΐ &amp;, Ag, Asn ' Asp ' Cys, Glu ' Gln, Gly, His ' Hyl, Hyp, Hua, Leu, Lys, Met, Phe, pr0, Ser, Thr, Trp, Tyr, and Vai), or Non-natural amino acids having one or more open valences, for example, second butyl glycine, ornithine, urushi, and threonine. Other non-natural amino acids are of the formula " And NH2(CH2)yc〇〇H", wherein y = 2 to 12, and an aminoalkanoic acid such as e-aminohexanoic acid (i^NJCH^-COOH). The term also includes, for example, a thiol group, The natural and non-natural amino acids of the amino group of the trifluoroethyl group and the benzyl group of the benzyloxy group, and the base group are protected by, for example, Ci 6 alkyl, phenyl or benzyl vinegar and the amine The base protects both natural and non-natural amino acids, and the protection is known to those skilled in the art. In all examples of natural and non-natural amino acids containing one or more palm centers, all possible stereo Modifications: The configuration 'comprising 'D' and 'L' types and mixtures thereof, including racemic mixtures, are included herein. The term "quaternary amine" as used herein includes quaternary ammonium with a positive gas. Salts. These are formed by the reaction of an inert nitrogen in a compound of interest with an appropriate quaternary aminating agent of 93533 110 200804280, for example, methyl iodide or phenylmethane iodide. Suitable counterions accompanying the quaternary amines include acetate, trifluoroacetate, chlorine, bromine and anion. As used herein, the term "oxide" refers to a state of the compound of the invention wherein one or more of the nitrogen atoms are oxidized by an oxygen atom. As used herein, "retrovirus" encompasses any virus that exhibits a reverse transcriptase. Examples of retroviruses include, but are not limited to, HI V_1,

HIV-2, HTLV-I, HTLV-II, FeLV, FIV, SIV, AMV, MMTV, and MoMuLV. As used herein, "reverse transcriptase" or "RT" refers to an enzyme having a non-nuclear inhibition binding site similar to HIV-1 RT, and a ligand thereof which is also bound to a compound binding pocket of the compound of the present invention. Enzyme. One method of measuring RT activity is to determine the ability of a virus to replicate. The method for determining the replication ability of Ηΐν·1 virus is an automated test using ΜΤΤ, as detailed in the specification as previously described. Another measurement is the ρ24 core antigen enzyme immunoassay, e.g., the analysis group is commercially available from Coulter Corpration/Immunetech, Inc.® (Westbrooke, Mich.). Another method for measuring RT activity utilizes analysis of the activity of recombinant HIV-1 reverse transcriptase, for example, by using the Quan_T-RTTM analytical system commercially available from Amersham® (Arlington Heights, IL), detailed in Bosworth et al. Natrue 1989, 341: 167-168 ° As used herein, a compound that "inhibits replication of human immunodeficiency virus (HIV)" means that when the compound is contacted with HI V-1 (eg, through cells infected with HI V) In the meantime, the compound was reduced by 111 93533 200804280 compared to the untreated control, and the assay was determined by the inhibition method known in the art. The action is as described in the above-mentioned p24 acid. The reagent indicated as "❿从" in the composite diagram is m-chloro-peroxybenzoic. The term "response to the treatment after the failure of the initial treatment of rescue treatment can be given in any therapy. As used herein, the term "host" is a multicellular or single cell organism. Therefore, "the host two It is a mammal, and preferably a human. Or the host can carry a cell strain, a gene body, and the replication or function of the HIV genome can be changed via the present invention. The term host specifically refers to Infected cells, two::, cells transfected with the adjacent HIV gene, and mammals, especially 1. In the main mammal application of the present invention, the first consideration is, for example, black seams. IV. Pharmaceutically Acceptable Salts, Prodrugs, Stereoisomers The active compounds can be administered in the form of a salt or a prodrug which, when administered, can provide, directly or indirectly, a parent compound. Pharmaceutically acceptable salt two fingers: salt that can be forked." In addition, for a compound ==, in some instances, the activity is increased and the second is obtained by preparing a salt or prodrug form of the compound, and hunting is performed by using the methods described herein or using Then m 93533 112 200804280 other methods known to the skilled artisan to test its antiviral activity. The term "pharmaceutically acceptable salt or prodrug" as used throughout this specification is used to describe any pharmaceutically acceptable form of the compound (eg, ester, amine, ester salt, guanamine salt or related group). The activator of the present invention is provided by administering a pharmaceutically acceptable salt or prodrug to a patient. The terms "stereoisomer" and "tautomer" as used herein encompass all possible stereoisomers and tautomeric forms of the compounds of the invention, as well as the quaternary amines, salts, solvates, prodrugs thereof. , derivatives, and, oxide forms. When the compounds of the formulae (1) and (9) contain one: two: the day ' contains all possible mirror image isomers and non-image mirroring terms "pharmaceutically acceptable salts Refers to the state of the compound in the pot: with a pharmaceutically acceptable relative ion, and the salt retains the sputum, recognizing the desired biological activity of the compound, while exhibiting the smallest non-household t 4 people The role of biology. These are not non-toxic, therapeutically useful forms of the compounds of the invention. This document contains any salts which retain the desired properties of the compound and which are intended to contain the silver barrier, + τ θW. The doctor does not have the undesired or toxicological knowledge to the right:: Benefits: κ acceptable salts include those derived from pharmaceutically acceptable transmitter acids or bases. Acids and bases are also used herein, for example, with a commercially available product. Therefore, this article intends to include all "salts". Non-limiting examples of suitable salts of the mouth include a. The inorganic acid is, for example, hydrogen acid, gas ' / heat machine salt, mountain, bismuth bromate, sulfuric acid, phosphoric acid, nitrate, sulphur acid, Carbonic acid, etc.; and 盐 酉夂〃 酉夂〃 酉夂〃 酉夂〃 酉夂〃 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 935 , citric acid, benzoic acid, tannic acid, palmitic acid, algae =, poly- faceted acid, p-toluenesulfonic acid, methanesulfonic acid, naphthalenesulfonic acid, naphthalene di-, alpha-ketopentanoic acid-glyceryl Dish acid and polygalacturonic acid. $When the salt contains ^self-tested metal, such as Li, _ and Na; soil test, such as calcium and magnesium; and other bases well known in the pharmaceutical industry. Other suitable salts include those derived from metal cations, for example, zinc, ruthenium, osmium, or aluminum, or cations formed from amines such as, for example, ammonia, hydrazine, hydrazine-dibenzylethylamine, D-glucosamine, Tetraethylammonium or ethylenediamine. Further, a suitable salt hydrazine is derived from a salt in combination with an acid and a base, for example, a tannic acid salt. A pharmaceutically acceptable prodrug is a compound which can be metabolized (i.e., hydrolyzed or oxidized, for example) to form a typical example of the present invention. The active compound is included in the active compound. The functional part has a compound that is biologically unprotected and protected. Prodrugs can be oxidized, reduced, aminated, deaminated, hydroxylated, dehydroxylated, hydrolyzed, dehydrolyzed, alkylated, dealkylated, deuterated, deuterated, phosphorylated, and/or Or a compound that is knocked down to produce the active compound. The compounds of the invention have antiviral activity against retroviruses, and in particular HIV, "metabolisms which are metabolized to exhibitable activity." Any of the keto-pyrimidine compounds described herein can be administered as prodrugs to increase activity, bioavailability, stability, or otherwise alter the properties of the keto-nextrin. Ligands of various prodrugs are also known. In general, the ketone treatment of the atomization, alkylation or other lipophilic modification enhances the stability of the compound. One or more hydrogens may be substituted on the heterocyclic ring: take 93533 114 200804280 Examples of algebra include, but are not limited to, the compound comprises a sugar to a disaccharide phosphate and an alcohol. This is the official month... The fat test of the dish is combined with the combination of one thing::: One of the fruits is exhausted. V. The treatment method is complete:: With =: In the case, it is provided in the host for treatment or prevention of guessing: : Law, including the administration of 3 substances to the host in need. In a specific embodiment, the compound is administered by: oral administration, enteral administration, intravenous Shanghai +, Ding Fei, intradermal administration, subcutaneous administration, transdermal administration, intranasal administration. Administration, topical administration or by inhalation therapy can be administered to a host diagnosed as HIV-infected by measuring == in the blood and tissues of the host. In other specific embodiments = can be measured by measuring the anti-mV antibody titer in the blood. In another embodiment, the compound is administered to the host to reduce AIDS (acquired immunodeficiency) Symptoms. In yet another specific embodiment, the compounds of the invention are administered to a host having the risk of infection (IV). In another specific embodiment, the active compound exhibits activity against the drug form, and thus the active compound exhibits lower cross-resistance to currently recognized antiviral therapies. The term "HIV-exhibiting activity against a pharmaceutical form" means that the compound (or a prodrug or pharmaceutically acceptable salt thereof) is active against a mutant strain of the virus, and has an EC5q of less than about 5, 25, , 0 or 1 micro. Molar concentration. In a specific embodiment, the non-nucleoside reverse transcriptase inhibitor (10) RTI) exhibits less than about / 93533 115 200804280 2.5, 1 or (E micromolar concentration of Ec called molar concentration in a non-mutant strain against mv In a specific embodiment, the mutant of the HIV mutant has a reverse transcriptase mutation of lysine 103 - aspartame and/or lysine 181 - hemi-amic acid. The ability of L to inhibit the activity of reverse transcriptase in vitro. The spectrum of activity exhibited by any particular compound is tested by the assays described herein or other known to those skilled in the art of anti-hiv compounds. The assay is evaluated by a validation assay and the assay typically exhibits less than 1 〇 to 5 μΜ 2 Ε €: 50. ° In one embodiment, the efficacy of the 3 - dish acid is via the foot _ "4 kinase link The immunosorbent assay was determined by Ρ24 ELISA. Τ = :ΓΧΗΐνΡ24 antigen is expressed in the example of the rapid and sensitive assay test body. The correlation can be used in the specificity test: the efficacy of the two dIV compounds Plaque reduction test Human,, ..., 1 is used in vitro to reduce the number of plaques in the virus, and the compound is inferior to 5 〇% of 4 baht on the 4th and 4th (also g &amp; more specific method proposed) , P, EC5〇 of the compound. In some embodiments, the chemical conversion = external appearance is less than -, or less than i. Micro-Mile VI. Combination or alternation therapy In various embodiments, the 3-scale brewing Ten compounds are combined with - or early, 轱 轱 病毒 viruses or anti-HIV agents, and/or alternately. The effects of only one agent per 仏 / 丨丄 are combined with L or alternately administered. Or a variety of such sputum; inhibiting the synergy of HIV replication. The effect of combining two or more of these agents in another, and also illusory, 93533 116 200804280 will produce an additive effect on inhibition of HIV replication. In combination therapy, an effective dose of two or more agents is administered together, and during the alternation therapy, the effective dose of each agent is administered sequentially according to the absorption and inactivation of the drug (maCtivation) And excretion rates and those known to those skilled in the art Factor. The value of the agent will also change with the severity of the condition to be alleviated. For any given individual, the dosage therapy and schedule should be adjusted over time to meet the needs of the individual and to give the composition or # The resistance of the person to the composition is most typically due to a negative mutation in the viral replication cycle, and the most typical example in the case is the anti-virtual: and the three antiviral compounds of the final brother (which are triggered by The mutational mutation can extend the effect of 'strengthening or restoring _ ^ 2. These combinations of drugs simultaneously reduce the likelihood of resistance to any single toxicity: = any associated toxic effects. Alternatively, VIII::: or parental therapy can be used to alter the pharmacokinetics and biologic parameters of the drug. For example, 'the combination of drugs can be used to feed material two:=; the substance: the amount of Π1 is lower than the use of the drug in the single-administration therapy, and the combination is for the various drugs of the different stages:: The possibility of drug action. Re-C:, 】 Use a combination of music to reduce or eliminate ::: still r therapy because combination therapy can make more money on the disease at the same time. 93533 117 200804280 A second antiviral agent for the treatment of HI V may be, for example, a protease inhibitor, an HIV-integrase inhibitor, a chemokine inhibitor, or a reverse transcriptase inhibitor ("RTI") The latter may be a synthetic nucleoside reverse transcriptase inhibitor ("NRTI") or a non-nucleoside reverse transcriptase inhibitor ("NNRTI"). In other specific embodiments, the second or third compound can be a pyrophosphate analog or a fusion-binding inhibitor. Drug resistance data collected from in vitro or in vivo by certain antiviral compounds were found in Mutations in retroviral genes associated with drug resistance, jW/vz·plant fl/TVews, 1997, 5 (3⁄4). The poor materials compiled. In certain embodiments, the guanidine compound is administered in combination with or alternately with FTC (2',3'-dideoxy-3'-thia-5-fluorocytidine); 141 W94 (amprenavir, Glaxo Wellcome, Inc.); Viramune (nevirapine), Rescriptor (delavirdine); DMP-266 (efavirenz), DDI (2',3'-dideoxyinosine); 3TC (3'-thia-2,3'-dideoxycytidine); DDC (2', 3'-dideoxycytidine, abacavir (1592U89), which is (lS,4R)-4-[(2-amino-6-cyclopropyl-amino)-9H-oxime -9-yl]-2-cyclopenten-1-nonanol succinate, Tenofovir DF (Viread), D4T or AZT. Other examples of antiviral agents that can be administered in combination or alternation with the compounds disclosed herein include, but are not limited to, foscarnet; carbovir; aziclovir; Interferon; fusion inhibitors such as enfuvirtide; and β-D-118 93533 200804280 Dioxane nucleosides such as β-D·didecylalkylguanine (DXG), β-D-II A decylalkyl-2,6-diaminopurine (DAPD), and /3-D-di-alkylalkyl-6-chloroindole (ACP). Interferons that can be used include Schering-Plough's interferon-2b products 'Intron® A and PEG-IntronTM; and Hoffmann La Roche's Co-Pegasus and PEGASYS (PEGylated interferon a-2a). Combinations that can be administered with 3-phosphonium include Epzicom (ABC+3TC), Trizivir (ABC+3TC+AZT), Truvada (FTC+Viread), and Combivir (AZT+3TC). Examples of protease inhibitors administered in combination and/or in an alternating manner include, but are not limited to, dinavir (4 to 1^¥b) ({1(1,8,211)55(8)}-253,5 -trideoxy-1^(2,3-dihydro-2-ylidyl-1Η-indol-1-yl)-5-[2-[[(1,1·didecylethyl)amino] Alkyl]_4-(3-acridinylindolyl)-1-pipedyl]-2-(phenylmethyl)erythro-pentacarbamide sulfate; Merck &amp; Co·, Inc); Navfinavir (Agouron); ritonavir (AbbottLabs); saquinavir (Roche); Amprenavir; Atazanavir; Fusanna Fosamprenavir; Kaletra; and 1&gt;]\4?-450{[4 feet-4 (Bu &amp;, 5-3, 6-13, 7-6)-Six-5-5,6 - bis(hydroxy)-1,3-bis(3-amino)phenyl]indolyl-4,7-bis(phenylmethyl)-2Η·1,3-diazepine-2-one} Trimethoate vinegar (Triangle Pharmaceuticals, Inc.) 〇 Others can be combined with phenyl hydrazine A compound which is administered in combination or in an alternating manner to enhance its anti-viral properties comprises (lS,4R)-4-[2-amino-6-cyclopropyl-amino-9H-indol-9-yl]-2 - cyclopentene-1 - sterol succinate (1592U89, 119 93533 200804280 card carburvir analog, available from GlaxoSmithKline); BILA 1906 (N_{lS-[[[3-[2S-{(l ,l-dimethylethyl)amino}carbonyl]-4R-]3-acridinyl fluorenyl]thio]-1-piperidinyl}-2R-hydroxy-IS-(phenylindenyl)propene Amino)carbonyl)-2-mercaptopropyl)-2-quinolininamine (Bi〇Mega/ Boehringer Ingelheim); BILA 2185(N-(1,1-dimethylethyl)-l -[2S-[[[2-2,6-Dimethylphenoxy]-1-oneethyl]amino]&gt;211_yl-4-phenylbutyl]4R-pyridylthio Benzyl-2-piperidine amide (Bi〇Mega/ Boehringer Ingelheim); BM+51.0836 (triazoloindole j derivative) and BMS 186,318 (amino diol derivative HRM protease inhibitor) (Bristol-Myers Squibb); d4API (9-[2,5-dihydro-5-(phosphinomethoxy)-2-furanyl]-adenine) (Gilead); HBY097 (S-4-isopropyl Oxymethane-6-methoxy-3-[indolyl-indenyl]-3,4- Hydroquinone-2(ι η)-# ketone); ΗΕΡΤ(1-[(2-hydroxy-ethoxy)indolyl]6-(phenylthio)_thymidine); KNI-272(( 2S,3S)-3-Amino-2 Hydroxy-4_phenylbutyric acid_containing tris(), L-697,593(5-ethyl-6-mercapto-3-(2-indenine) Base-ethyl)^ ratio. D-732 (R), L-732, 524 (hydroxy-aminopentane decylamine HIV-1 protease inhibitor) (Merck &amp;Co·); L_697, 661 (3_{[(_4,7_2 Chlorobenzopyrene bite -2_yl) fluorenyl]aminoethyl-6-mercaptopurine 唆-2 (1Η&gt; · L-FDDC((一)-/3 -L-5-fluoro-2',3 Di-deoxycytopenic; L-Fd〇C(()-/3-L-5-fluoro-dioxanthionine; PFA (phosphonium citrate; "foscarnet"; Astra ; PMEA (9-(2•phosphonium methoxyethyl) gland $ 呤) (Gilead); PMPA ((R)_9-(2_phosphonium hydroxypropyl) _ gland) (Gilead) Ro 31_8959 (hydroxyethylamine derivative HIV_1 protease inhibitor) (Roche); RPI_3121 (peptidyl protease inhibitor, i_^3s)_3_(正93533 120 200804280 - benzyloxy-based aspartame)- Amino-2-trans-yl-4-phenylbutyryl)-n-t-butyl-1-cholamine sulphate, 2720 (6-gas-3,3-monomethyl•4- (isopropyloxymethyl)-3,4-diaza-σ 奎 °若淋-2(1Η)-thiopurine), SC-52151 (hydroxyethyl urea protease inhibitor stereoisomer (isostere) (GD·Searle); SC-55389A (hydroxyethylurea-protease inhibitor isostere) (G. D· Searle) ; TIBO R82150((+)-(5S)-4,5,6,7-tetrahydro-5-mercapto-6-(3-methyl-2-butenyl)-imidazo[ 4,5,1^1&lt;:]-[1,4]-benzodiazepine-2(1H)-thione) (Janssen Pharmaceuticals); TIBO 82913 ((+)-(5S)-4, 5,6,7·4 rat-9-chloro-5-methyl-6-(3-methyl-2-butyl fine)-imidazo[4,5,l_jk:Kl,4]-benzo- Diazolidine-2(1Η)-thione) (Janssen Pharmaceuticals); TSAO-m3T ([2%5'·bis0-(t-butyldimethylmethylalkyl)-3'-spiroamine- Γ, 2'-oxathiazepine_2', 2, dioxide)]-β-Β-five carbon 喝 drinking sugar-based Ν3_methyl-thymus σ close bite; U90152 (l-[3 -[(l-methylethyl-amino)2-acridinyl]-4-[[5-[(fluorenylsulfonyl)-amino]-1Η-indol-2-yl]-carbonyl] Piperage]; UC (thiobenzidine derivative) (Uniroyal); UC_781 (N_[4_chloro-3-(3-methyl-2-butoxy)phenyl]_2_methyl-3 · furancarbothioamide); UC-82 (N-[4-chloro-3-(3-methyl-2-butoxy)phenyl]-2-mercapto-3- Thiophene thioguanamine); VB 11,328 (hydroxyethylsulfonamide inhibitor) (Vertex/ Glaxo Wellcome); XM 323 : cyclic urease inhibitor (Dupont Merck); and penciclovir. In yet another embodiment, the indole compound of the invention is administered in combination with a protease inhibitor LG 1350. The following drugs have been approved by the FDA or are currently or have been used in clinical trials 121 93533 200804280 to treat HI V infection, so in one embodiment, the following drugs may be combined and/or used interchangeably with the compounds of the invention. 1 Drug name meal 5 Manufacturer 3TC, commercially available drug name Epivir®·^^ lamivudine GlaxoSmithKline abacavir pan-shake to GlaxoSmithKline GlaxoSmithKline Ziagen®, ABC, or 1592U89 ABC, marketed drug Abrahammer, Ziagen®, or 1592U89 ABT-378/r, or lopinavir/ritonavir, commercially available under the name Kaletra®, Abbott Laboratories AG-1549, S- 1153, 鲞t 蚯魄{capravirine){C?N) Pfizer AGH61, commercially available drug name Remune® t H1V-1 immune antigen, or Salk vaccine Immune Response Corp. Quinnarvir (APV), 141W94, or VX_478 GlaxoSmithKline Aldesleukin is commonly referred to as Proleukin®, or Chiron Corporation Amdoxovir, or Gilead Sciences is known as Agenerase® , APV, 141W94, or VX-478 GlaxoSmithKline APV, commercially available drug name Agenerase®, annaweivir, 141W94, or VX-478 GlaxoSmithKline Azanaso is commonly known as RevatazTM, or BMS-232632 Brist ol-Myers Squibb AZT, commercially available under the name Drugvir® zidovudine (ZDV) GlaxoSmithKline BisCPOC) PMPA, commercially available drug name Viread® DF Gilead Sciences [^MS-232632, Or the commercial drug name is Bristol-Mvers Squibb | 122 93533 200804280

ReyatazTM's atazanavir BMS-56190, or JDPC-083 sarain Sl de A (caIanoIide A) Gallaviling (CPV), AG-1549, or S-1153 Commercially available drug name Combivir® Zidovudine + Lamivudine, or AZT+3TC CPV (Galaviline) has dGWWP or a commercial drug called Crixivan® i indinavir (IDV), or MK-639

d4T Fuding (st DAPD, commercially available drug name Zerit® tavudine), or BMY-27857 ^^H*MM*K, BSK==a^^B^^^^s^BSSS8SaSB8BSSSSSS^SSSSSS^BS :^^B8BSBSSSBSBS8SS^aS8SSSBS8BBSBSaBBSSBaSSBSaB8BSSSSSS or Amdoxovir B=a=!i=M^=^^8B==ai^^^^^a^^^^ssssBaassaa^^^sassasae^aa^sa^ a:^^^aaa—asasss^^^sgsaaB^sssBsassaasaaa, commercially available drug name hivid® zalcitabine MI, commercially available drug name Videx® didanosine, or BMY_40900 ................... -----

Delevirdine is commonly referred to as Rescriptor®, DLV, or U-90152S/T

Bristol-Myers Squibb

Sarawak Medichem

Pfizer 1 &quot;' —'· — &quot;' —r

GlaxoSmithKline

Pfizer

Merck &amp; Co.

Bristol-Myers Squibb

Gilead Sciences

Hoffmann-La Roche

Bristol-Myers Squibb sssssaoBsssas =E3s:=s=sssssassssss=sasKsaaBBEassBBSs^^asB=

Pfizer is known as Videx®, ddl, or BMY-40900 PLY, commercially available under the name Rescriptor® delavirdine, or U-90152S/T DEC-083, [BMS_56I90 commercially available drug name Droxia® hydroxyurea (HU) is legally known as fefavirenz), commonly known as Sustiva®, or EFV 1ZY, and commercially available ϋα is called Sustiva®.

Emtricitabine is commonly known as | five mirz’vaTM, or FTC

Bristol-Myers Squibb

Pfizer

Bristol-Myers Squibb

Bristol-Myers Squibb

Bristol-Myers Squibb Bristol-Myers Squibb Gilead Sciences 123 93533 200804280 Commercially available drug name is five w/Wva® for emtricitabine, or F7T forfuvirtide for trimeris and Hoffmann-La Roche GlaxoSmithKline FuzeonTM, Or Ding-20 commercially available drug name Epivir® lamivudine, or 3TC erythropoietin aiepoetin alfaVir erythropoietin) is commonly known as Procrit® 1 _ - ....... erythropoietin (red) Blood Bole Peaks ^ ) Genericly known as Procrit®, a commercially available drug called Fortovase®, saquinavir (soft gel capsule), or SQV (SGC), fosamprenavir, gas Ortho Biotech Ortho Biotech Hoffmann-La Roche GlaxoSmithKline Gilead Sciences Trimeris and Hoffmann-La Roche GW-433908, Fluorine VX-175 Z^TC 'or the commercially available drug name | the emboxabin commercially available drug name FuzeonTM Ground, or T-20 GW-433908, Wolf Shawana, or VX-175 | -- -------------- GlaxoSmithKline 77 5 2 (10) or α-Abby Burma (alpha) · epibromide) HollisEden Pharmaceuticals HJV-1 immune antigen ReRemune®, Shake Vaccine, A AG1161 ........... , ' ----- Immune Response Corp. Commercially available drug name is Hivid® zalcitabine, or ddC .. ........ · - 1 Hoffmann-La Roche HU, or the commercially available drug name Droxia® 基ί] ureide H Γ 11 ---- Bristol-Myers Squibb hydroxyurea is commonly known as Droxia®, or Ττπ IDV, commercially available as Crixivan® indinavir, or MK-639 111 in leukotriene-2, or commercially available drug called Proleukin®, Bristol-Myers Squibb Merck &amp Co. Chiron Corporation 124 93533 ---- 1 —__ 200804280

Indinavir is commonly referred to as Crixivan®, IDV or MK-639___ Interleukin - a generic term called Proleukin®

Merck &amp; Co. is marketed under the name of Invirase®, Saquinavir (hard gelatin capsule), SQV (HGC), or Ro-31-8959. The marketed drug is Kaletra®. Ritonavir, or ABT-378/r

Chiron Corporation

Abbott Laboratories lamivudine is commonly referred to as Epivir®, or 3TC lopinavir/ritonavir is commonly known as = Kaletra®, or ABT-378/r MK-639, and the commercial drug name is Crixivan® indinavir (IDV) nelfinavir is commonly referred to as Viracept®, NFV, or AG-1343. Nevirapine is commonly known as Viramune®, NVP, or BI-RG-587 NFV, and the commercial drug name is Viracept®. Navfinavir, or AG-1343, is marketed under the name of Norvir®, ritonavir (RTV), or ABT-538 NVP, and the commercial drug name is Viramune®2 Nevipine, or BI_RG-587_ PNU-140690 ' or tipranavir PRO-542 is a commercially available drug called Procrit® erythropoietin alpha (erythropoietin). The commercially available drug is called Proleukin®, or interleukin. -2 (IL-2)

GlaxoSmithKline Abbott Laboratories

Merck &amp; Co.

Pfizer

Boehringer Ingelheim

Pfizer

Abbott Laboratories

Boehringer Ingelheim

Boehringer Inselheim Progenies Pharmaceuticals Ortho Biotech

Chiron Corporation's market name is Remune® HIV-1 \ Immune Response Corp 125 93533 200804280 Long thin and shoulder-resistant, or Shake thin -----

The commercially available drug name is Diliviridine (DLV) of Rescriptor®, or U-90152S/T is commercially available under the name of Retrovir® ZDV, or AZT_ is commercially available under the name ReyatazTM. ^^ Nawei, or BMS-232632 | Ritonavir Pan 13⁄4 Norvir®, Rf?! or ABT-538 RTV, commercially available drug name Norvir® ritonavir, or ABT-538 sand-free vaccine, city The drug is called HIV-1 immune antigen of Remune®, 氙AG1661 Saquinavir (hard gelatin capsule) is commonly known as Invirase®, SQV (HGC), or Ro-31-8959__ Saquinavir (soft gel capsule) ) i Fortovase®, SQV (SGC) SCH-C a Commercially available drug called Serostim® growth hormone (somatropin). Growth hormone is commonly called % Serostim® SQV (HGC), and the commercially available drug name is Invirase®. (hard gel capsule), or Ro_31_8959 SOV (SGC) or a commercially available drug name | Fortunas® (soft gel capsule), stavudine istaudine), commonly known as Zerit®, d4T, or BMY-27857 Commercially available drug name Suffiva® (EFV) T-1249

Pfizer

GlaxoSmithKline

Bristol-Myers Squibb

Abbott Laboratories

Abbott Laboratories

Immune Response Corp·

Hoffmann-La Roche

Hoffmann-La Roche

Scherins-Ploush Serono Laboratories

Serono Laboratories

Hoffmann-La Roche

Hoffmann-La Roche

Bristol-Myers Squibb

Bristol-Myers Squibb

Trimeris anti-Hoffmann-La Roche 126 93533 200804280 T-20, or commercially available drug name FuzeonTM enfuvirtide TDF, defovir DF generically called VireadTM, or Bis(POC) PMPA tenofo f ^~DF(TDF) is commonly referred to as Viread8, Bis(POC) PMPA_Tirranavir, or PNU-140690 TMC-114 TMC-125

Trimeris and Hoffmann-La _Roche_ Gilead Sciences

Gilead Sciences

Boehrinser Inselheim

Tibotec-Virco Group Tibotec-Virco Group is marketed under the name of Trizivir®, Abacamere + Zidovudine + Lamivudine GlaxoSmithKline (ABC+AZT+3TC). The drug is called Dextran in Videx®. , ddl, or BMY-40900 Bristol-Myers Squibb The drug sold under the name of Videx® EC is dystrophic (_ddl) ·• Sustained-release capsule Bristol-Myers Squibb. The drug is marketed under the name of Viracept® NFV (NFV). ), or AG-1343__ The commercially available drug name is Viramune® Niprate (NVP), or BI-RG_587 Pfizer Boehrinser Inselheim. The market name is Viread® for Tenofo DF, or Bis (POC) PMPA Gilead Sciences. VX-175, or sasanavir (fosamprenavir), or 卯S GlaxoSmithKline zalcitabine is commonly known as Hoffmann-La Roche GlaxoSmithKline Hivid®, or ddC ZDV, and the commercially available drug name is Retrov ir®. Or, AZT is marketed as a drug called Zerit®, stavudine, d4T, or BMY-27857. Bristol-Myers Squibb is marketed under the name of Ziaeen® Abbakamir (ABC), or 1592U89 GlaxoSmithKline Zidovudine. Pan shake for Retrovir®, ''~ 1 - ---- ,... - 1 GlaxoSmithKline 127 93533 200804280 1-------1-

AZT, or ZDV IL__-r- a---a-a II , , ===== ----------·ι=::_;丨:___:_ 's= Ss=s=s=s= Other drugs that can be combined with 3-phosphonium in clinical trials and/or alternately include: Phase I, Phase II, Phase III, GW5634 (GSK) MIV-150 (Medivir/ Chiron) Tipranavir (BI) RO033-4649 (Roche) TMC125 (Tibotec) GW640385 (GSK/Vertex) TMC114 (Tibotec) Eloxacinbine (Achillion Ph.) Alovudine (Achillion Ph.) Alovudine) (FLT) (BI) MIV-210 (GSK/Medivir) Racivir (Pharmasset) SPD754 (Shire Pharm.) Reverset (Incyte Corp.) FP21399 (Fuji Pharm.) AMD070 ( AnorMed) GW873140(GSK) BMS-488043(BMS) Schering C/D (417690) PR0542 (Progenies Pharm) TAK-220(Takeda) TNX-355(Tanox) UK-427,857(Pfizer) The drug has been approved by the FDA for use in the treatment of complications of HIV infection and AIDS, which may be combined with and/or alternated with the compounds of the invention. 128 93533 200804280 Commercially available drug name and name manufacturer Abelcet, Ambisome Amphotericin B, ABLC Antifungal agent for sputum disease Bactrim, Septra Sulfamethoxazole and Trimethoprim ( Trimethoprim) Antibiotics for the treatment and prevention of pneumocystis pneumonia A number of manufacturers Biaxin, Klacid clarithromycin Antibiotics for the prevention and treatment of Mycobacterium avium Abbott Laboratories Cytovene ganciclovir, DHPG Anti-viral agent for CMV retinitis Roche DaunoXome daunorubicin - chemotherapy for microlipid Kaposi's sarcoma Gilead Diflucan Fluconazole Candida rickets, cryptococcal meningitis antifungal agent Pfizer Doxil doxorubicin hydrochloride - chemotherapy for microlipid Kaposi's sarcoma Ortho Biotech Famvir famciclovir Herpes antiviral agent Novartis Foscarnet foscavir herpes, CMV retinitis Antiviral agent Astra Pharmaceuticals Gamimune N immunoglobulin, 7 globulin, IGIV immunopotentiator for the prevention of bacterial infection in children Bayer Biologicals Intron A interferon a-2b Kaposi's sarcoma, and hepatitis C Schering Marinol dronabinol treatment of loss of appetite Roxane Laboratories Megace acetic acid Megestrol acetate for appetite, weight loss, Bristol Myers-Squibb Mepron, Atox S with (atovaquone) for the treatment and prevention of pneumocystic pneumonia, antibiotics Glaxo SmithKline Mycobutin, Ansamycin rifabutin Adria Pharmaceuticals NebuPent for the prevention of Mycobacterium avium. Pentaidine Antibiotics for preventing lung cystic pneumonia 4: Prime Fujisawa Neutrexin Gemcitrate Trimetrexate Glucuronate) and leucovorin antibiotics for the treatment of pneumocystis pneumonia Medidmmune Panretin gel 9-cis retinoic acid gel 0.1% (alitretinoin) AIDS-related Kaposi's sarcoma Ligand Pharmaceuticals Procrit &gt; Epogen erythropoietin, EPO treatment is associated with AZT therapy Amgen 93533 129 200804280

Roferon A interferon a -2a Kaposi's sarcoma and hepatitis C Roche Serostim growth hormone rDNA treatment of Serono Sporanox itraconazole sclerotium, histoplasmosis, sclerotium, and candidiasis Antifungal agent Janssen Pharmaceuticals Taxol Pacific paclitaxel Kaposi's sarcoma Bristol Myers-Squibb Valcyte valganciclovir CMV retinitis antiviral agent Roche Vistide cidofovir, HPMPC "~CMV retinitis Antiviral agent Gilead Vitrasert implant ganciclovir implant CMV retinitis antiviral agent Bausch & Lomb Vitravenel intravitreal injection Fomivirsen sodium injection CMV retinitis antiviral agent Isis Pharmaceuticals Zithromax azithromycin | Mycobacterium avium Pfizer Several products have been approved by the FDA as a new drug (IND) for the treatment of complications of HIV infection and AID S. Therefore, the following The drug can be combined with and/or administered with a compound of the invention For use in AIDS patients who cannot tolerate standard forms of treatment, pneumocystis pneumonia can be treated with trimetxexate glucuronate. • Ganciclovir can be used to treat large cells of AIDS patients. Retinitis • Aerosolization can be used to prevent pneumocystic pneumonia in AIDS patients • Erythropoietin can be used to treat anemia associated with zidovudine • Attorikone can be used to treat lungs AIDS patients with cysticercosis, the patient can not withstand or respond to trimethoprim-sulfamethoxazole. 130 93533 200804280 • Can use rifabutin to prevent Mycobacterium avium complex bacteremia ° • Vistide's intravenous Hoffmann-La Roche can be used for HIV-infected individuals with recurrent macrophage virus (CMV) retinitis (although treated but still worsening) • Serostim is derived Recombinant human growth hormone from mammals for the treatment of AIDS-related weakness (Serono Laboratories). Typically, during alternation therapy, the effective dose of each agent is administered in divided doses.The effective dose of two or more agents is administered together during the combination therapy. The dosage to be administered depends on factors such as the absorption of the drug, the rate of biodistribution, the rate of metabolism, and the rate of excretion as well as other factors known to those skilled in the art. It should be noted that the dosage will vary with the severity of the condition, age, weight, and general physiological condition of the recipient of the drug. It will also be appreciated that for any particular subject, the particular dosage regimen and time schedule thereof will vary over time, depending on the subject's response to the drug, the needs of the subject, and the judgment of the compound or the person administering the compound. Anti-HIV compounds (including nucleoside derivatives such as D4T, DDI and 3TC, or protease inhibitors such as Navannavir and Indinavir) are suitable for inclusion in the scientific literature and in the Physicians' Desk Reference. Examples of dosage ranges. The suggested range of effective doses of the compounds of the invention is for reference only and is not intended to limit the scope or use of the invention. The disclosed combination and alternation therapy are used to treat and prevent retroviral infections and other related symptoms, such as AIDS-related syndrome (ARC), persistent systemic lymphadenopathy (PGL), AIDS-related nerves. Symptoms 131 93533 200804280 Symptomatic, positive anti-hIV antibodies and HIV-positive symptoms, Kaposi's sarcoma, thrombocytopenic purpura and opportunistic infections. In addition, these compounds or formulations can be used prophylactically to prevent or slow down the clinical resistance of a positive anti-Ηιν^ body: a positive HIV_ antigen or an individual who has been exposed to HIV. The compositions of the present invention can be administered to a subject in need thereof, in combination or alternation with other anti-HIV or anti-retroviral agents, and/or with pharmaceutically acceptable carriers, diluents or excipients - Starting from: In a specific embodiment, a subject infected with HIV can administer an effective amount to the subject in the presence of a pharmaceutically acceptable carrier or diluent == salt, prodrug, stereoisomer Or tautomers: As for the county with h heavy (four) sex, can be spurred by the singer + Dinghua: or with - or a variety of other anti-retroviral agents or anti-rules: two: to non-active; active substances can be Any suitable route of administration, for example: oral administration, enteral administration, intravenous administration, intradermal administration, skin administration by inhalation therapy, and pots can be solid, internal and local administration Or borrow m and it is in the form of solid, liquid or gas. - The lingual compound is contained in a medicinal excipient, and the therapeutic agent (5) is used as a diluent or is administered to the patient to inhibit the replication of the virus in vivo. Compound delivery two two: heavy toxicity. "Inhibition amount" means the measurement of the active ingredient in the 'S stop disease system. s its #'hunting by 'for example, this is for all the mentioned conditions ※ one of the compounds of the introduction of wood compounds dose 93033 132 200804280 perennial daily O.moOmg / kg body weight, or about daily UK mg / Kg body weight, and even more typically from about every 曰 to 2 〇 mail / weight. The effective dosage range of the acceptable derivative of the western medicine is calculated based on the weight of the parent compound to be delivered. If the derivative itself exhibits activity, the effective amount can be assessed as described above using the weight of the derivative, or other means known to those skilled in the art. The compound may conveniently be administered in any suitable unit dosage form including, but not limited to, from about 7 to 3 mg, or from about 1400 mg, and even more typically from about to 1400 mg per unit dosage form. 〇〇mg of active ingredient. For example, an oral dose of usually 5 〇 to 1 〇〇〇 mg is convenient. Desirably, the active ingredient is administered such that the peak concentration of the active compound in the plasma ranges from about 0. 02 to about 7 μΜ, and typically from about 5 to 10 μΜ. For example, the above concentration can be achieved by intravenous injection of a solution of 25% to the active ingredient (as needed in saline) or by administration of the active ingredient in a pill form. It should be understood that for any particular subject, the specific dosing regimen should be adjusted over time to meet the individual's needs. The foregoing ranges of concentrations are illustrative only and are not intended to limit the scope or implementation of the claimed compositions. The live generating knife can be administered all at once, or divided into small doses and administered at different time intervals. One mode of administration of the sputum active compound is oral. Oral compositions generally comprise an inert diluent or an edible carrier. The active compound can be enclosed in a gelatin, compressed into a tablet, or delivered in liquid form. For oral treatment, the active compound may be combined with an excipient or formulated into a solid dispersion or a solid solution, and used in the form of a tablet, lozenge or capsule. "Solidity 93533 133 200804280" refers to a solid state comprising at least or less dispersed and evenly distributed to another - into, / in, in a seed component or in a multi-body state comprising at least two components of which are characterized by a chemical vapor: a solid solution "refers to the product of Gubei. Generally, the solid solution system is superior to the solid base. When the liquid medium is in contact, it is easier to form a liquid solution, and the monthly factor and the appropriate material availability. A point of compatibility in medicine. Increasing the production of music is included as part of this composition. And/or the adjuvant substance may also be a compound of a similar nature such as a lozenge, a tablet, a capsule or a lozenge: a binder such as micro-intestines or a gelatin; an excipient such as powder or lactose; , scutellaria or gangolytic agent such as alginic acid, carboxymethyl

Sterotes, slip agents such as colloidal dioxygen, monosaccharide; and flavoring agents, and (4) such as saccharin, when the unit dosage form is a capsule, in addition to the sputum or the scented flavoring agent. Ancient, Guangzao #7 In addition to any type of substance, it may contain liquids such as lang oil. In addition, single (4) (3) may contain other substances in the physical form of the dosage unit σ "other casing agents. 丫 如 , 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 、 、 、 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮 悬浮', and into a shirt. In addition to the active compound, the sugar system, as well as containing preservatives, dyes, cockroaches and seasonings ^ I raw compounds or their pharmaceutically acceptable salts or prodrugs can work with The active substance is mixed 'or with a substance that can supplement the desired effect, such as an antibiotic, an antifungal, an anti-inflammatory agent, a protein coffee, or other nuclear or non-nucleoside antiviral agent. For non-oral, 93533 134 200804280 f, soluble, anhydrous, saline solution, di: alcohol, benzoic acid w · wide 1, synthetic solvent; antibacterial agent such as benzyl alcohol or Agents such as ethylenediamine such as ascorbic acid or sodium bisulfite; integrated acid salts, and for use in the detection of, for example, acetate, saponin or sputum production + eve, °. Positive Q reagents such as sodium chloride or glucose. Non-:::::: agents usually contain sterile water and are sealed in ampoules, disposable/shot: or glass or plastic multi-dose vials. In the case of intravenous administration, a typical carrier is a physiological =, a glucose solution, or a dose comprising glucose and a salt, for example, by using a patch or ointment, the relevant threshold enhances the penetrant and/or does not Suitable thirst for injuring the skin: if the inhalation or inhalation is the desired route of administration, the present invention; 2 == solution, suspension or dry powder delivered by the oral cavity and/or nasal cavity, U know </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; And the potential, = as described in U.S. Patent No. 4,522,811, all of which are incorporated herein by reference. For example, it can be dissolved in an inorganic solvent which is subsequently evaporated, by applying a suitable lipid, for example, a glyceryl group, a hard (tetra) basal, a ruthenium, and cholesterol. A dry lipid film is left on it. An aqueous solution of the active compound, or a salt or prodrug thereof, is then introduced into the container. The container was rotated to allow the lipid 93533 135 200804280 to leave the edge of the container and disperse the lipid agglomerate, thereby forming a liposome suspension. VIII. Process for preparing active compounds General reaction diagram 136 93533 200804280 Reaction diagram 1:

Method A

G/

20 methods

137 93533

δ 133⁄4 200804280 Reaction Figure 3 ··

Method p

Reaction Figure 4:

24 Reaction Diagram 5:

139 93533 200804280 Reaction Figure 6:

Reaction Diagram 7 &gt;

MethodΗ

29 Reaction Diagram 8 ··

140 93533

35 E or Z E or Z 200804280 Reaction Figure 9: 34

E+Z reaction diagram 10:

Ar/Het 141 93533 200804280 Specific reaction scheme Reaction Figure 11: N-branched heterocyclic ring

44 45 4B

Het-Br method k Reaction Figure 12: phosphinate heterocycle

HetJ-OEt - Bu OEt

OEt 0H 47 48 £法三 HetJ-OEt 6l 49 Not separated From the crude product

142 93533 200804280 Reaction Scheme 13: Alkyl/alkenyl/alkynylphosphinates Ο

Alk-Br

Alk-p-〇Me — method! - Alk-P-〇Me I OMe 53

Method C OH 54

Aik-P-OMe Cl 55 is not isolated. Use crude product.

Method G

OMe C02Et 56 S02Ph

Aik 〇'p, OMe method K

Reaction Figure 14: alkyl phosphinate

Aik-Bu OMe I Cl

Alk-P-CI ϋ.·_ Ci 1eq. MeOH 58 55 Reaction Figure 15: alkyl mercaptocarbamamines

method

143 93533 200804280

6 or 7

Method The following is a description of the methodology used in the aforementioned reaction chart. The number in bold corresponds to the number of the compound in Figures 1 to 16. Methods a, b, C, D, F, L, N, T, U and A A are known to those skilled in the art of making such general classes of compounds, but have been modified to prepare particular compounds of the invention. The same applies to the methods Η, I, J, Μ, P, Q, γ, z, AB and AC. The methods £, 0, 〖, 0, 尺, 3, ^^, ¥ and} are new methods for preparing the compounds of the present invention.

Method A: bromine benzene 1 (1 eq.) is pulverized with diethyl chlorate (deuterium) and diethylamine (1 · 1 when I) in a pressure tube, and the mixture is degassed with N 2 . 15 minutes. Then, the compound (paiia (iiU in tetrakis) was added and the mixture was stirred overnight under a pressure of about 85 ° C. ★ Field 9 morning, Ε Ο Ο and filtration were added to the reaction. The mixture is evaporated and the crude product is purified by chromatography on a hair gel (eluent • oil ether / EtOAc from 8/2 to 6/4). Alternatively, the reaction can be utilized under the same conditions 144 93533 200804280 10 volumes of 1,2-diethoxyethane were carried out.

Method B All reagents (1 equivalent of diethyl phosphonate 2 or di-decyl phosphonate 1 9 and 6 s sodium hydroxide and ethanol or methanol (3 mi / min 〇 1)) were stirred at room temperature About 5 hours. Then ethanol (or decyl alcohol) was evaporated in vacuo and the mixture was acidified to ρ Η = 1 with 2·5 ν HCl. The mixture was then saturated with NaCI and extracted with ethyl acetate. The combined organic layers were dried over Na 2 S 〇 4, filtered and concentrated to give the desired product 3 or 2 s.

Method C: Compound 2 or 3 (1.2 equivalents) and sulfoxide (3.6 §), dichloromethane (5 ml/mm 〇1) and a few drops of dimethyl hydrazine at A and room temperature The amine was stirred for about 5 hours. An aliquot was taken and placed in anhydrous methanol and ε^ν to monitor the reaction. When the reaction was completed, dichloromethane and sulfoxide were co-purged with benzene in a vacuum to obtain an oil which was stored under N2.

Method D To a solution of arylphosphine dichloride 21 (1 mL, 6·35 mm 〇1) in anhydrous dichloromethane (25 rnL), add ethanol or methanol (112 mL, 19 〇 4 mmol). Then diethylamine (2·65 m; L, 19.04 mmol) was added. The reaction mixture was stirred at room temperature for about 2 hours, then washed with 1N EtOAc (5 EtOAc). The aqueous layer was taken from methylene chloride. The combined organic layers were dried and concentrated under reduced pressure. The oil was purified by chromatography on silica gel (eluent: C^H^/EtOAc 6/4) to yield dimethyl arylphosphonate 19 or diethyl phenylphenylphosphonate.

Method E 93533 145 200804280 Diethyl arylphosphonate 2 (1 eq.) and methylene sulphate (10 eq.) and methylene chloride (5 ml/mmol) are interspersed at about 5 at room temperature. hour. Then, a bromine dimethyl dream was burned and a gas was burned to obtain a yellow oil. Next, grass chloro, dimethylformamide and dichloromethane were added under A and the mixture was stirred overnight at room temperature, followed by evaporation of chloroform and solvent. The methylene chloride solution containing the oil was stirred and allowed to cool to about, and ethanol or methanol (1.12 mL, 19.04 mmol) was added under N2, followed by dropwise addition of a three-month-old female. The mixture was then warmed to room temperature. This compound 14 was obtained by evaporating the solvent and purifying the product by chromatography on silica gel (eluent: ch2ci2 / EtOAc: 8/2).

Method F To a stirred solution of diethyl arylphosphonate 2 (1 eq.) in dichloromethane (5 ml / mmol) was added bromotrimethyl decane (5 eq.). After stirring at room temperature for about 3 hours, the solvent was evaporated and dichloromethane (5 ml/mm )l), a drop of dimercaptocarbamide and oxalyl chloride (2.5 equivalents) were added. The mixture was stirred overnight at room temperature, and the solvent was evaporated to give an oil. The solution containing the oil (1.2 equivalents) in diethyl ether (3 ml/mmol) was stirred and cooled to about -17 ° C, then anhydrous decyl alcohol (1.2 equivalents) was added dropwise to remove the double added component and diethylamine. . The resulting mixture was warmed to room temperature, spoiled for about 1 hour, and then filtered through a disposable filter cup (Aut〇CUp) to remove triethylamine salts. This compound 15 was obtained by evaporating a solvent.

Method GA, dropwise addition of 93533 146 200804280 n-BuLi in a solution containing bromine 吲哚 11 (1 eq.) of anhydrous thf (i 〇 / mmol) and cooling (cooling to about -9 〇. 〇) (2.5M in hexane, 1 ί2 equivalent). After the solution is about _9 Torr for about 5 minutes, the appropriate disc acid hydrate (Chl〇r〇Ph〇Sph〇rus) reagent 丨5, 4 or diphenylphosphine is added dropwise to the solution at the same temperature. Acid vapor (1) S). The reaction was gently warmed to about _40. [] (with TLC in the extract CH2cl2/Et0AC 9/1). Then add water. The extract is extracted with ethyl acetate, _ is dehydrated and the residue is prepared (4) (4), and the silk is oiled and purified by chromatography to obtain compound 16, 5 or 26. Method 饱和 The methanol containing the compound 5, 16, 26, 28 or 3 压力 in the pressure tube was stirred and cooled (cooled to about the next generation) and dissolved in methanol (tetra) ΝΗ 3 (tetra) for about 10 minutes. The mixture is then brought to about 50. After stirring overnight, the mixture was monitored by TLC, and excess ammonia and decyl alcohol were evaporated in vacuo and the crude product was purified by chromatography on silica gel to afford tonicamine 6, 7, 27 ' 29 or 31. Method I, lithium hydroxide (14 equivalents) was added to a stirred solution of tetrahydrofuran (20 ml/mmol) and water (2 〇 ml/mm 〇1) 2 containing compound 16 or 5. The mixture was then stirred at room temperature and monitored by TLC. If necessary, add an equal amount of lithium hydroxide until the reaction is completed. The THF was then evaporated and ttCl (1 N) was added to reach pH 1. The aqueous layer is extracted with ethyl acetate and the combined organic phases are dried, filtered and concentrated under reduced pressure to give compound 17 or 8 s. Compound 17 or 8 (1 eq.) with dichloromethane (2 〇ml/ Mm〇i) or DMF was used as a scrambler, and 1 _ benzopyranotrione (1 eq.) was added followed by 93533 147 200804280 plus EDCI (1 eq.) followed by additional amine (1 eq.). The mixture was stirred at room temperature overnight. The mixture was washed with water (to pH 5-6) the next morning, and the organic layer was dried, filtered and concentrated under reduced pressure. The obtained oil was purified by chromatography on silica gel (eluent: CH.sub.2Cl.sub.2/EtOAc) to yield powder 18 or 9.

Method K In a microwave tube, compound 5 or 6 (1 equivalent) was stirred with DMF (5 ml/mmol) and TMSBr (5 equivalents) was added. The tube was heated by microwave irradiation for about 50 minutes at a pressure of about 60 ° C (maximum output power 100 W, CEM Discover instrument). The DMF was evaporated in vacuo and the mixture was placed in a pressure tube. Tridecyl phosphite (4 ml/mmol) was added and the mixture was stirred and heated at about 90 °C overnight. The mixture was then cooled in an ice water bath and HCl (1 N) was added dropwise. The mixture was extracted with ethyl acetate and the combined organic layers were washed with &lt;RTI ID=0.0&gt;&gt; Then, it is dehydrated, filtered, and concentrated under reduced pressure to give an oil. The obtained oil is purified by chromatography on EtOAc.

Method L Under N2, NaH (60% in oil, 1.2 eq.) was added dropwise in a portion of DMF (2 ml/mmol) containing ethyl hydrazine-2-carboxylate 10 (1 eq.) and cooled (cooled) To a solution of about 0 ° C). When the gas ceased to be released, benzenesulfonium chloride (L2 equivalent) was added. The reaction mixture was stirred for about 1 hour (monitored by TLC, the extract was dichloromethane); then a small portion of water was carefully added and the DMF was evaporated. The crude residue was dissolved in ethyl acetate and washed with water and brine. After dehydration and evaporation of the solvent, the compound was chromatographed on silica gel (purging 148 93533 200804280: C6H12/EtOAc 9/1 to 7/3) to obtain 1-phenylsulfonylhydrazine- Ethyl 2-carboxylate. To a stirred solution of DMF (2.5 ml/mmol) containing ethyl 1-phenylsulfonylindole-2-carboxylate (1 eq.) was added DMF (0.5 ml) containing bromine (4 eq.). /mmol) solution. The reaction mixture was stirred at room temperature for about 4 hours, then water was added and the mixture was extracted with dichloromethane (x3). The organic layer was washed with a saturated solution of Na2S05, dehydrated and evaporated to give a crude yellow oil. Chromatography (eluent: C6H12 / EtOAc 9/1) was purified on silica gel to afford 3-bromide. MethodΜ

Degassing containing 5 or 16 (1 equivalent), acrylonitrile (10 equivalents), palladium acetate (20% molar), triethylamine (1 equivalent) and tri-o-nonylphenylphosphine (1 equivalent) The mixture of acetonitrile (30 mL/mmol) was heated in a pressure tube for about 45 minutes under microwave irradiation. Water was then added and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried and concentrated and purified on EtOAc (EtOAc:EtOAc:EtOAc Compound 32 of a mixture. Method N bromobenzene 1 (1 eq.), dimethyl decylamine (1 ml/mmol), triethylamine (3 eq.) and phenylammonium salt* (1.25 eq.) were placed in a pressure tube and degassed with N2 The palladium tetra compound was then added for about 15 minutes and the mixture was stirred overnight at 85 ° C, then the solvent was evaporated and water was added to bring the pH to about 5 to 6. The compound was basified with NaHC03 until pH 8 was obtained and then extracted with diethyl ether. The aqueous layer was acidified to pH = 1 with EtOAc (1 N) and extracted with ethyl acetate. The combined organic layers of 149 93533 200804280 were dehydrated, filtered and concentrated under reduced pressure to give compound 14. *The stupid ammonium salt is synthesized according to the method of Montchamp et al. (j Am c/?em 2001? 123, 510-511). The method is as follows: in the case of N2, in the toluene containing compound 14d · 2 equivalents (4 ml / mmol) To the stirred solution was added tetramethyl ortho-decanoate (1.2 equivalents). The mixture was heated under reflux for about 1.5 hours and then cooled to room temperature. This mixture was then degassed with N2 before addition of triethylamine (3.3 eq.), bromo oxime equivalent, and palladium tetra compound (5 eq.). The mixture was stirred at about 1 Torr: for a weekend (about 48 hours), after which the reaction was cooled to room temperature and water was added to reach a pH of about 8 to 9. Next, the mixture was extracted with ethyl acetate and the organic phase was washed with KHS 〇 4 (1N) saturated with NaCl. Then, it was subjected to dewater filtration and concentration under reduced pressure to give an oil which was purified by chromatography (eluent: CAVMeOH) to afford compound 12. Add a portion of trimethyldecyldiazide (13 mil) to a stirred solution of methanol (25 ml/mmol) containing compound 12 (equivalent toluene) under A and at room temperature overnight. Water was added and the decyl alcohol was evaporated under reduced pressure. Then NaHC® 3 was added to reach pH 8, and the mixture was extracted with ethyl acetate. The organic phase was dried, filtered and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (eluent: C6Hi2/EtOAc) to afford compound 16. Compound 18 is dissolved in chloroform (or CH2Cl2) at room temperature with stirring; 93533 150 200804280

The m-chloroperoxybenzoic acid was added and the reaction was allowed to stir overnight (about 15 hours). The mixture was then diluted with dichloromethane and extracted with a saturated K.sub.2CO.sub.3/H.sub.2 ( 1/3) mixture. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried with EtOAc (EtOAc)EtOAc. The crude product was purified by chromatography on silica gel to give compound 22. Method R

In a microwave sealed tube, compound 11 (1 equivalent) and 23 (1.1 equivalent) were added to toluene (8 ml/mmol) and triethylamine (3.3 equivalent) and degassed with N2 for about 10 minutes. The tube was then heated by microwave irradiation for about 30 minutes by the addition of Pd(PPh3)2 and at a pressure of about 120 ° C (maximum output power 200 W, CEM Discover instrument). The reaction was monitored by TLC and the tube was heated for about 30 minutes if necessary. The solvent was evaporated and the crude product was purified by chromatography (EtOAc EtOAc: EtOAc: Method S In a microwave sealed tube, compound 11 (1 equivalent) and 24 (2 equivalents) were added to toluene (8 ml/mmol) and then degassed with N2 for a period of about 10 minutes or longer. Next, about 20% of the Pd(OAc) 2 solution was added, and the tube was irradiated with microwave for about 45 minutes at a pressure of about 150 ° C (maximum output power 200 W, CEM Discover instrument). The reaction was monitored by TLC and if any starting material was present, the tube was reheated at about 170 ° C for about 45 minutes. Next, HCl (1 N) (8 ml/mmol) was added and the solution was extracted with ethyl acetate. The combined organic layers were dried, filtered and concentrated under reduced vacuum. The crude product was purified by chromatography on silica gel (eluent: petroleum ether /EtOAc: 1 /1) to afford compound 5 or 16. 151 93533 200804280 Or the δHel reaction is completed in about 1 hour at about 150 °C.

Method T Carefully add pyridine (1 eq.) to a vigorously stirred solution of the alkyl chloroformate (1 eq.) and arylphosphonic acid (1 eq.) in dichloromethane (2 ml/mmol). in. When the foaming was stopped, the solution was refluxed for about 15 minutes and then cooled to room temperature. This solution was poured into hydrazine·1M hydrochloric acid (1) and the organic layer was separated. After washing with water and dehydrating with NaJO4, the solvent was removed in vacuo to give the compound 23.

Method U An alkyl or aryl bromide (〇15 mol) was added dropwise to a mixture of magnesium (3.6 g) and anhydrous tetrahydrofuran (4 mL) in a N2 atmosphere at about 50 °C. After the addition, the reaction mixture was stirred at about 50 ° C for 1 to 2 hours to complete the reaction. The mixture is then added dropwise to a solution of triethyl phosphite (〇·; [mol) and THF (25 mL) in a N2 atmosphere at 40 ° C to 50 ° C and at about 50 ° C Stir for about 3 hours. After removing the solvent under reduced pressure,

This crude product was obtained by distilling the crude product from the semisolid residue in vacuo. Method V Compound 6 or 7 (1 eq.) and LaWesson reagent (4 eq.) were heated in a pressure tube at about 90 ° C in toluene (1 〇 my mmol) under N2. The reaction was monitored by Dc and continued heating until no starting material residue (about 5-5 hours). The crude solution was filtered and the filtrate was evaporated to yield and purified by chromatography on silica gel to afford compound 25 and compound 25'. 152 93533 200804280 Method w Under agitation and cooling (cooling to about _9 〇〇c) of bromine. An n-butyl group (1.2 equivalent) was added dropwise to the solution. After about 10 minutes, tetrahydrofuran (15 ml/mmol) containing phenylphosphine dichloride 21 (1.1 wt.) was added dropwise at a temperature of about 7 ° C, and then the temperature was lowered to about _9 Torr. And keep the minutes. Methylmagnesium bromide (11 equivalents) was then added, and the mixture was allowed to warm to about -40 ° C for about 1 hour, then quenched with water and extracted with ethyl acetate and then taken and taken. The organic layer was dried over Na.sub.4, filtered and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (eluent: CI^CVAcOEt: 9/1 to 7/3) to afford compound 28.

Method X is stirred and cooled (cooled to about _55. 〇Phenylphosphine 醯 dichloro 2 ΐ (ι当 i) in diethyl ether (15 ml / mm 〇i) solution was added dropwise dimethylamine (1 Then, triethylamine (1 equivalent) was added and the mixture was warmed to room temperature. The mixture was filtered and the filtrate was evaporated to give an oil/mixture. To remove the phenylphosphine in the oil/mixture Gas, the oil/mixture is washed twice with Et0AC, HCl pH 4 to 5, and the organic phase is dehydrated with Na2s〇4, filtered and concentrated under reduced pressure to give an oil. Stir 2 and add n-butyl lithium (1.2 eq.) dropwise to a solution of hydrogen hydride (5 ml/mmol) cooled to about -8 (rc) containing bromine oxime equivalent. At the time, the mixture was warmed to about -6 (rc and tetrahydrofuran (.2 g, 3 ml/mmol) was added dropwise to the oil. The mixture was then slowly warmed to, MC, The reaction was quenched with water (8 ml/mmol). Add HCl (1 N) to about 5 and evaporate the solvent in vacuo. The aqueous phase was extracted with ethyl acetate 93533 153 200804280 and combined The layer was washed with brine, dried over Na2 EtOAc, filtered and evaporated.. Compound 3〇. Method Y Suzuki cross coupling Under N2, Pd(PPh3)4(l〇% m〇l), Na2C03 (6 equivalents) of H2 bath (2M) and An EtOH solution (0.3M) containing an aryl group, a aryl group or a heteroaryl acid (2 equivalents) is added to a degassed toluene containing 5 or 16 (having a halo or trifluorosulfonate substituent) The solution was stirred and the mixture was heated to about 11 Torr under microwave irradiation until no starting material remained. Water was added and the reaction was extracted with EtOAc, dried and concentrated.

The residue was chromatographed on silica gel (PE/EtOAc 8/2) to afford 37. Method Z In a nitrogen atmosphere, a cuprous oxide (1 ()% mol), a ligand (20% mol), a nucleophile (1.5 equivalent), and a carbonic acid planer (2 dynasty) are built into the dry reaction tube. And a halogen halide 5 or 16 (having a halo or trifluorosulfonate residue) (1 equivalent), followed by the addition of anhydrous and degassed acetonitrile (addition of aryl halide per mm〇) .6mL). The tube was sealed and placed at approximately 8 Torr. 0 stirring until the reaction is completed. The reaction mixture was then cooled to room temperature, diluted with tributyl decyl ether and filtered through a pad of Celite, and the filter cake was rinsed with butyl methyl ether. The filtrate was concentrated in vacuo to remove B and then dissolved again in toluene. The organic layer was filtered, washed with water twice and washed once with brine, before dehydrated and filtered with Na2S04. The crude product was obtained by removing the solvent in vacuo, and the crude product was purified by chromatography on silica gel to afford compound 42. 154 93533 200804280

Method AA The alkyl halide was heated overnight at about 90 ° C in tridecyl phosphite (10 mL/mmol). The reaction medium was cooled to about 〇 ° C in an ice bath and the HCl (1N) solution was carefully added. The aqueous layer was extracted with EtOAc. The combined organic layer was washed with HCl (1N) and water, then dehydrated and concentrated to afford compound 53 as a colorless oil.

Method AB In a microwave sealed tube, compound 17 (1 equivalent), furfural (37% by weight in water, 1 equivalent), and morpholine (1 equivalent) were added to the third butyl alcohol (4 ml/mmol). in. The tube was heated by microwave irradiation for about 60 minutes at a pressure of about 170 ° C (maximum output power 200 W, CEM Discover instrument). The reaction was monitored by TLC and if any starting material remained, the tube was heated at about 170 ° C for an additional 45 minutes. The solvent was evaporated in vacuo and the crude residue was purified eluting eluting eluting eluting

Method AC In a microwave tube, compound 5 or 6 (1 equivalent) was stirred with DMF (5 mL/mmol) and TMSBr (5 equivalents) was added. The tube was heated by microwave irradiation for about 50 minutes at a pressure of about 60 ° C (maximum output power 100 W, CEM Discover instrument). After cooling, water was added and the compound 60 was collected by filtration. IX. Representative Examples of the Active Compounds Tables 1 and 2 contain a non-limiting list of representative compounds which can be prepared by this method and according to the reaction schemes provided above in Figures 1 to 16. 155 93533 200804280 Compound Structure Table 1 Description 2a

156 colorless oil, lH NMR (CDa3 &gt; 250 MHz) δ 1,33 (t, /-7.1 Hz, 6H), 4.05-4.25 (m, 4H), 7.46-7.57 (m, 3H), 7.78-7.87 (m , 2H) , 3IPNMR (CDa3, 10L256 MHz) δ 19.3. 93533 200804280 Description of compound structure 2c

Colorless oil, 屯: NMR (CDa3, 300MH2:) S 1.26 (t, /=7-5Hz, 3Η), 1.33 (t, 7.05 Hz, 6H), 2.1 (q, /= 7.5 Hz, 2H), 4.04- 4.19 (m, 4H), 737^7.4 (m, 2H), 7.58-7.69 (m, 2H), 31P NMR (COd3r 121.49 MHz) δ 19^3.

2d colorless oil, lH NMR (CDC13, 300 MHz &gt; δ 1.35 ft /= 7·05 taken 6H), 4.05-4.26 (in, 4H), 7.62 (td, J * 3.9 and 7.8 Hz, 1H), 7.8-7.83 (3⁄4 1H), 7.97-8.1 (m, 2B〇, 31P NMR (CDa3j 121.49 MHz) δ 164, 19F NMR (CDa3 &gt; 282.4 MHz) δ 9.27 (s, 3F), MS (ESI, Bl^) m/z - 283 (MH4). 2e

White solid, 1H NMR (GDC13, 300 MHz) δ 1·36 ft ·/= 7·05 Hz» 6H), 4.09-4.25 (m, 4H), 7.62 (td, 3.9 ^ nd 7.8 Hz, 1H), 7.83 -7.85 (m, 1H), 8.02-8.12 (m, 2H), 3lP NMR (0Σ&gt;σ3, 121.49 MHz) δ 15.13⁄4 MS (ESI, El4) ?w/z = 240 (NDt). 2f

Colorless oil, NMR (C〇a3, 300 MHz) δ 134 ft 7·0513⁄4 6H), 4.05-4.21 (m, 4H), 732-7.38 (m, 1H), 7.66-7.71 (m, 1H), 7.73 -7.78 (in, 1H), 7.92-7.97 (m, 1H), 31P NMR (CDC13, 121.49 MHz) δ 16.37, MS (ES4) τη/ζ - 292.9/294.8 (ΜΗ). 2g

Colorless oil, worm NMR (GDCI3, 300 MHz) S 1·35 ft ·/= 7·05 13⁄4 6H), 4.04-4.23 (m, 4H), 753 (t, 1.8 Hz, 1H), 7.65 (d, 1.8 Hz, 1H), 7.7 (d, J-1.8 Hz, 1H), 31P NMR (CDC13, 121.49 MHz) 6 14.74. 2h /=\ 9 colorless oil, 1H NMR (CDC13, 300 MHz) δ 1.34 (A &gt; 7·05 Take 6H), 4.0W.22 (m, 4H), 5.44 (d, /= 47.4 Hz, 2H), 7,51-7.6 (m, 2I?), 7.7S-7.85 (i^2H) ,19FNMR (CDa3,: 282.40MHz) e_ 209.67 (t, J= 47.4 Hz, IF), MS (ES4) m/z - 247 (MH). 157 93533 200804280 Compound Structure Description 2i

Colorless oil, h NMR (CDC13, 300MHz) 31.34^/=7.0513⁄4 6H), 4.044.2 (m, 8H), 5.86 (s, 1H), 7.48-7.54 (m, 1H), 7.68-7.7 (m, 1H), 7.8-7.87 (m, 1H), 7.93-7.98 (m, 1H), 31P NMR (CDC13, 121.49ΜΗζ) δ 18.45, MS (£8^^=287(ΜΗ). 2j

OEt colorless oil, lH NMR (CDC13, 300 MHz) δ 135 (t, 7%05 Hz, 6H), 2.39 (s, 3H), 4.054^1 (m, 4H), 734-736 (m, 1H), 7.5-7.6 (m, 2H)a 31P NMR (CDCI3, 121.49 MHz) δ 17.18, MS (ES4) m/z = 263.2 (MH). 2k

Colorless oil, ^ NMR (CDCU, 300 MHz) δ 1,37 (t, /= 7·05 Hz, 6H), 4.07^4.27 (m, 4H), 737-7.65 (m, 6H), 7.78-7.85 ( m, 2H), 8.04-8-09 1H), 3lP NMR (CDC13, 121, 4? MHz) δ 18.84, MS (ESt)^ = 291.17 (MH).

OEt colorless oil, 4 NMR (C〇a3, 300ΜΗζ) δ 1.33 (t, /=7.05Hz, 6H), 2.15 (s, 3H), 4.06-4.22 (m, 4H), 5*44 (s, 2H) , 738-7.60 (m, 3H), 7.95-8Ό3 (m, 1H), 3lP NMR (CDa5&gt; 121.49 MHz) δ 17^99, MS (ESI, El^ m/z = 287 2m

Yellow oil,! H NMR (CDC13, 300 MEfe) δ 1.32 (t,6·9 Hi, 3H), 1323 (t, 6.9 Hz, 3H), 3.84 (s, 3H), 4.034.16 (m, 4H), 7.06-7.1 (m, 1H), 73^7.4 (m, 3H), 31P NMR (CDa3, 121.49 MHz) δ 19.21, MS (ESI, El4) 245.13 2q

Light yellow oil, worm NMR (CDC13, 400MHz) δ 1·37~·7 =7.05 Hz, 6H), 4.11-4.28 (m, 4H), 8.046-8.048 (m, 1H), 8.237-8.24 (m, 1H ), 8.27-8.273 (m, 1H), 31P NMR (CDa3, 101256 MHz) β 14.36, MS (ESI, El4) w/z = 351 (MH4). 2r

F3C

Light yellow oil, worm NMR (CDC13 &gt; 400 MHz) δ 1·36 (ζ·7=7·07 Hz, 6H), 4.08^26 (ro, 4H), 7.49-7.52 (m, 1H), 7.67-7.73 (m, 1H), 7.85-7.89 (m, 1H), 31P NMR (C〇a3 &gt; 101256 MHz) 5 14.73 158 93533 200804280 Compound structure description (at 7·813⁄4 IP), MS (ESI, Ef) = 301 ( ΜΗ&quot;)· 2t

Colorless oil, ^ NMR (ArDMSO, 300 MHz) δ 124 (4 6.9 Hz, 6H), 1.25 (t, J = 7J2 Hz, 6H)3 3.07 (heptuplet, J = 6.9 Hz,, 1H), 4.02-4.11 ( m, 4H), 7.84-7.94 (m, 2H), 8.04 (brs, 1H), 31P NMR (cfe-DMSO, 121.49 MHz) δ 15.12, MS (ESI, El4) w/z = 282.3 (MH4). 2u

Light yellow oil, JH NMR (CDa3, 300 MHz) δ 1.35 (t, J = 7.05 Hz, 6H), 4.07-4.22 (m, 4H), 7.25-7.29 (tn, 1H), 7.37-7.45 (m, 1H ), 7.57-7.61 (m, 1H), 3lP NMR (C〇a3, 12L49 MHz) δ 14.82 (d, 9.1 Hz, IP), MS (ES4) tw/γ »267.11 (Μΐί). 2v

Colorless oil, NMR (CDCI3, 300 MIfe) δ 0·94 ft /= 7·5 Hz, 3H), 132 (t, 7.2 Hz, 6H)3 1.66 (sextuplet, 7.5 Hz, 2H), 2.63 (t, J = 7.5 Hz, 2H), 4-4.21 (m, 4H), 734-7.41 (m, 2H), 7.58-7.67 (m, 2H), 31P NMR (CDCI3, 121.49 MHz) δ 19.53, MS (ES4) w /z= 257.37 (MH4). 2w

Colorless oil, NMR (4 DMSO, 300 MHz) δ 0.67-0.73 (tn, 2H), 0.97-1.03 (m, 2H), U3 (t, /= 7.05 Hz, 6H), 1.97-2.06 (m, 1H) , 3.93-4.06 (m, 4H), 7.27-7.31 (m, 1H), 738-7^1 (m, 3H), 31P NMR (^DMSO, 121.49 MHz) δ 18.35, MS (ES4) m/z = 255.06 (Mlf). 2x

Colorless oil, seven NMR WrDMSO, 300 MHz) δ 123 (t 7.05 Hz, 6H), 2.37 (s, 3H), 3.97-4.09 (33⁄4 4H), 7.49-7.57 (3⁄4 2H), 7.69 (brs, 1H), 31P NMR (rfrDMSO, 121.49 MHz) δ 15.74, MS (ES4) 7w/z-309.24 (MH4). 2y

Colorless oil, H NMR (rfrDMSO, 300 MHz) S 1·23 (3⁄4/- 7·05 Hz, 6H), 2.34 (s, 3H), 2.63 (q, /= 7.05 Hz, 2H), 3.94-4.05 (m, 4H), 729-731 (m, 2H), 7.44-7.45 (m, 1H), 3lP NMR (^DMSO, 121.49 MHz) δ 18 Jl, MS (ES4) m/z = 257.4 (MH4).

Colorless oil, lH NMR (itrDMSO, 300 MHz) S 0,88 (t J = 7.2

Hz, 3H), 1.22 (t, /= 7.05 Hz, 6H), 1.54-1.62 (τη, 2H), 234 (s, 3H), 2.55-2.6 (m, 2H), 3.94-4.05 (m, 4H) , 7.27-736 (m, 3H), 31P NMR (rf^DMSO, 121.49 MHz) δ 1873, MS (ES4) = 271.36

159 93533 200804280 Description of the structure of the compound 2aa / colorless oil, 'H NMR (CDa3, 300 MHz) δ 1.28 (d, J- 7.0 Hz, Ο 6H), 134 (t, J = 7.2 Hz, 6H), 2.97 (m, 1H), 4.13 (m, 4H), 736-i 7.45 (m, 2H)3 7.58^7.75 (m, 2H), MS (ESI, Ef) m/z = 257 (MH4). N^( OEt 2ab

Brown oil, NMR ((VDMSO, 300 MHz) δ 1; 22 (t, /= 7213⁄4 6H), 2.37 (s, 3H), 3.92-4.05 (m, 4H), 733-737 (m, 2H), 7.57-7.64 (m, 2H), 31P NMR (d^-DMSO, 101^56 MHz) δ 18.62. 2ae

Prr yellow oil, 1H NMR (d^rDMSO, 400 MHz) δ 1,22 a 7.3 Hz, 6H), 2.2S (s, 6H), 353^.03 (m, 4H), 7.29-7.32 (xn, 1H ), 7.4-7.49 (m, 2H), 31P NMR (d«-DMSO, 101^56 MHz) δ 19.86, MS (ESI, Et) m/z = 2A3 (MH4). 2af

Yellow oil, MS (ESI, El4) m/z = 243 (MH4)· 2ag yellow oil, lE NMR (d&lt;rDMSO, 300 MHz) δ 1,24 (t, / « 7.05 unloading, 2.28 (s shoulder, 2·42 3H), 3.96^4.06 (iMH), 722 (td, «7 OEt - 9A2 and 7.5 Hz, 1H), 7.41 (d, /- 7.5 Hz, 1H), 7.62 (dd, 7.5 and 13.8 Hz, 1H), 3lP iMR (de-DMSO, 12L49 MHz) δ 20.29. 2ah

Oil, ^ NMR (CDC13, 300 MHz) δ 1.32 (t, «7 » 7·05 Hz, 6H), 4.04-4.19 (m, 4H), 7.12-7.19 (m, 2H), 7.7S-7.87 (m , 2H), ^ NMR (CDa3, 282.4 MHz) δ 409.1S, 31P NMR (CDa3 &gt; 101256 MHz) δ 18.33. 2ai

2ao

OEt light yellow oil, JHNMR (CDQs, 300 MHz) δ 1.36 (t, J = 6.9 Hz, 6H), 4.08-4^3 (m, 4H), 6.96^7.04 (m, 1H), 7.30-7.38 (m , 2H), 3lP NMR (CDa3, 101 MHz) δ 14.77-15.3 (m, 1P), 19F NMR (CDCl3 &gt; 235.36 MHz) δ -107.56 (m, 2F), MS (ESI, Ef) m/z = 251 (MH*). Yellow oil, 1H NMR WrDMSO, 300 MHz) δ 1·19 (t 7.5 Hz, 3H), 1.24 (t, J = 7.05 Hz, 6H), 2.89 (q, J- 7.5 Hz, 2H) , 3.97-4.07 (m, 4H), 7.29-7.41 (m, 2H), 7.53-7.58 (m, 1H), 7.74 (dd4 J= 12 and 7.5 and 13.8 Hz, 1H), 31P NMR (^DMSO, 121.49 MHz) δ 18.71, MS (ESI, Ef) /n/z = 243 (ΜΗ〇. 160 93533 200804280 Description of the structure of the compound 2ap

OEt yellow oil, lH NMR (drDMS0, 300 MHz) δ 1.23 (t, /- 7.05 Hz, 6H), 3.81 (s, 3H), 3.96-4.06 (m, 4H), 7.15-732 (m, 3E〇, 7.44-7.51 (m, 1H), 31P NMR (^DMSO, 121.49 MHz) δ 17.71; MS (ESI, Bt) m/z = 245 (MH^) 2aq OBn

P-OEt 2ar

P - OEt OEt 2as 2at

NC

2m

2aw said. Et 3a

-0Et N^f OH oil, 1H NMR ('DMSO, 300 MHz) δ 1·22 (t, «/= 7.05 Hz, 6H), 3.94^.07 (m, 4H), 4.56 (s, 2H), 4.61 (s, 2H), 7.28^7.37 (m, 5H), 7.5-7.72 (3⁄4 4H), 3lP NMR (^DMSO, 121.49 MHz) δ 17.97; MS (ES4) ^/:=335 (ΜΗ4) colorless oil , lH miK (itf-DMSO, 300 MHz) δ 1.22 (^/-7.2 Hz, 6H), 3.97-4.03 (m, 4H), 7.43^7.56 (m, 2H), 7.65-7.7 (m, 2H), 3lP NMR (^DMSO, 121.49 MHz) δ 18.6; MS (ES&quot;) - 271.2 (MH4) oil NMR WrDMSO, 300 MHz) δ 1·24 ft /= 7·05 Hz, 6H), 2.42 (s, 3H) , 3^99-4.1 (m, 4H), 7.82-7.94 (m, 3H), 3lP NMR (^ DMSO, 121.49 MHz) δ 15.09, MS (ES4) m/z = 254 (Mlf). Yellow oil, 1H NMR WrDMSO, 300 MHz) δ 1.25 (3⁄4 ·/= 7·213⁄4 6H), 4.01-4.13 (m, 4H), 7.49-7.57 (m, 1H), 7.65-7.7 (ίώ, 1H), 7.88-7.92 ( m, 1H), 31P NMR (rf^DMSO, 121.49 MHz) δ 13.5 (d, / = 8.7 Hz, IP), 19F NMR (irDMSO, 282.4 MHz) δ -108.43 (m, IF)· Orange oil, 1H NMR (4^1^0,3001^32:)51.25(1^=7.213⁄4 6H), 4.044.13 (m, 4H), 7.82-7.90 (m, 1H), 7.96-8.01 (m, 1ΕΓ), 8.15 -8.18 (m, 1H), 31P NMR (rf^DMSO, 121.49 MHz) δ 1 2.83 (d, 8.02 Hz, IP), I9FNMR (^DMSO, 282.4 MHz) - 108.7 (q, 8.2 Hz, IF),. MS (ES4) m/z « 258.2 oil, 1H NMR OirDMSO, 300 MHz) δ 1 ·25 (t, /= 7·05 Hz, 6H), 3.97-4.13 (m, 4H), 7.46-7.53 (m, 1H), 7.57-7.66 (m, 2H), 7.84-7.96 (m, 1H) </ RTI> </ RTI> <RTIgt; 4.08 (3⁄4 73 Hz, 2H)3 7.42^7.56 (m, 3H), 7J9-7.86 (m, 2H), 10.67 (brs, 1H), 31P NMR (CDC13, 101.256 MHz) δ 21·3· 161 93533 200804280 Compound structure 3b 3c

F3C 3d

OH 3e

NC &gt;^f OH 3f

3g

3h

Description Colorless oil, ^ NMR (CDC13, 300MHz) δ 1,31 7.05Hz, 3H), 2.32 (s, 6H), 4.03-4.15 (m, 2H), 7.15 (s, 1H)9 7.42 (d, J- 13.8 Hz, 2H), 9.64 (brs, 1H), 3lP NMR (CDCl^ 101.256 MHz) δ 2236, MS (ESI, El4) m/z - 215 (MH4). colorless oil, NMR (C〇a3, 300 MHz) δ 1 3H), 4.02-4.11 (m, 2H), 7.09-7.16 (m, 2H), 7.76-7.85 (m, 2H), 8.37 (brs, 1H), 19F NMR (00(3⁄4 282·4) δ 406 (3⁄4 IF), 31P NMR (CDC13 &gt; 101.256 MHz) δ 20, MS (ESI, El4) w/z « (Mlf). Colorless oil, 1H NMR (CDC13, 300MHz) δ 1.32 (1^= 7.0513⁄4 3H), 4·11 (quintuplet^ 7·05 13⁄4 2H), 7.55-7.61 (iv) 1H), 7.78- 7.8 (m, 1H), 7i&gt;5-8.13 (m, 3H), 31P NMR (CDC13, </ RTI> </ RTI> </ RTI> <RTIgt; 7'05Hz, 3H), 4.04 (quintuplet, 7.05 Hz, 2H), 7r27-8.09 (m, 5H), 31P NMR (CDC13, 101.256 MHz) δ 16.59, MS (ESI, E〇/wA· = 212 colorless oil , 4 NMR (CDC13, 300MHz) δ 1·33 (ζ/=7·05Ηζ, 3H), 4.1 (quintuplet, /= 7.05 Hz, 2H), 7.51 (t, 7 - 1.8 Hz, 1H), 7.62 (d, 1.8 Hz, 1H), 7.67 (d, 1.8 Hz, 1H), 11.63 (brs, 1H), 31P NMR (CDa3, 121, 49 MHz) δ 15.74, MS (ESI , E〇^ -255 (MEt). Colorless oil, NMR (CDC13, 300 MHz) S 1.26 (t, / = 7·5 Hz, 3H), 1.33 (t, J - 7.2 Hz, 3H), 2.69 ( q, J = 7.5 Hz, 2H), 4.1 (quintoplet, /= Hz, 2H), 736-7.39 (m, 2H), 7.61-7.69 (m, 2H), 10.83 (brs, 1H)? 31P NMR (CDOj , 121.49 MHz) δ 21.63, MS (ESI, El4) tw/z=215 (MH*) colorless oil, worm NMR (CDC13, 300 MHz) δ 1·25 bait 6·9 13⁄4 6Η), 131 (t, 7.05 Hz, 3H), 2.88-2.98 (m, 1H), 4.03-4.13 (m, 2H), 7.35-7.41 (m, 2H)5 7.60-7.69 (m, 2H), 11.26 (brs, 1H), 31P NMR (CT&gt;a3, 121.49 MHz) δ 21.85, MS (ESI, El4) ni/z = 229

162 93533 200804280 Description of the structure of the compound 3i \〇 colorless oil, ^1^111(00013, 300 1^1112)8 1.32(4/=7.013⁄4 ^ OEt 6H), 2.35 (s, 3H), 4.04^1.14 (m , 2H), 732 (s, 1H), 7.45-7^9 (m, 〇H 2H), 828 (brs, 1H), 31P NMR (C〇a3, 121.49 MHz) δ 19·16· 3j

Ph λf OH colorless oil, h NMR (CDCU, 300 MHz) δ 1·31 (4/= 7·0 Hz, 6H), 2.35 (s, 3H), 4.05^.17 (m, 2H), 7.32 (s, 1H), 7.36-7.83 (m, 8H), 8.03 (d, J = 14.3 Hz, 1H), 10.16 (brs, 1H), 31P mm. (CDa35 121.49 MHz) δ 21.13, MS (ESI, El&quot;) ^ -263 (MH&quot;). 3k

Colorless oil, seven: NMR (CDC13, 300MHz) δ 1.32^/=7.0112, 3H), 3.83 (s, 3H), 4.08 (quintuplet, J= 7.0 Hz, 2H), 7.05-7.09 (m, 1H), 7.3 -7.44 (m, 3H), 10.25 (brs, 1H), 31P NMR (CDa3, 121.49 MHz) 5 2036. 3n 3q

Light orange oil, NMR (CDCt, 300 MHz) S 1·36 (t, "/= 7.2 Hz, 3H), 4.16 (quintiqjlet, J = 7.2 Hz, 2H), 8.06 (brs, 1H), 8.22 (brs , 1H), 8.27 (brs, 1H), 10.95 (brs, lip, 3lP NMR (CDC13 &gt; 121.49 MHz) 5 15.19, MS (ESI, El4) t?i/z = 322.99 (ΜΗΓ*). 1H NMR (CDCI3, 300 MHz) S l_34(t, /= 7.05 Hz, 3H), 2.4 (s, 3H), 4.11 (qi±itiq)let, /= 7.05 Hz, 2H), 7.04-7.08 (m, 1H), 7.27-7.35 (m, 1H), 7.4-7.43 (m, 1H), 1137 (brs, 1H), 3lP NMR (CDC13, 121.49 MHz) g 19.37 (d, /= 9.6 Hz, IP), MS (ESI, El4) m/z - 219 (MH4), 3r

With yellow oil, 1H NMR (d^DMSO, 300 MHz) δ 1JL8 (W = 7.1 Hz, 3H), 3.87-3.97 (m, 2H), 7.55^7.67 (m, 3H), 7.98^8.18 (m, 3H ), 8.53 (d, J = 8.4 Hz, 1H), 3lP NMR (drDMSO, 300 MHz) ? 14.76, MS (ESI, El4) m/z = 237 (MH4).

With yellow oil, NMR (CDC13, 300 MHz) δ 1·25 (3⁄4 /= 6k9 Hz, 6H), 1.31 (t, J = 6.9 Hz, 3H), 2.70-3.00 (m, 1H), 4.00^4.20 (m, 2H), 7.89 (d, / - 5.4 Hz, 1H), 7.25-7.36 (m, 1H), 7.47 (d, J-13.5 Hz, 1H), 12.22 (brs, 1H) 31P NMR (003,121.49 MHz g 17.93,19F NMR (CDC13? 282.40 MHz) δ -11235 (m, IF). 163 93533 200804280 Compound Structure Description 3t

Colorless oil, NMR (CDC13, 300MHz) δ 1.27 (4/= 6·9 Hz, 6Η), 133. (1, 6.9 Hz, 3H), 2.94-3.03 (m, 1H), 4.07^4.16 (m, 2H), 5.15 (brs, 1H), 7.66 (bis, 1H), 7.83-7.95 (m, 2H), 31P NMR (CDC13, 12L49 MHz) δ 17.61, MS (ESI, Ef) w/r - 2543 (MH4) ). 3υ

Colorless oil, ^ NMR (CDC13, 300 MHz) δ 133 (W = 7.05 Hz, 3H), 41 (quintuplet, 7.05 Hz, 2H), 7,24-7.28 (id, 1H)3 735-7.44 (m, 1H ), 7.55-7.60 (m, 1H), 12.16 (s, 1H), 3lP NMR (CDC13, 121.49 ΜΗζ) δ 15.63 (d, J = 9.20 Hz, IP). 3y

3x

3z

3aa 3ad

Colorless oil, NMR ('DMSO, 300 MHz) S 1.17 (t^=X2 Hz, 3H), 1.17 (t, 7.5 Hz, 3H), 232 (s, 3H), 2.61 (3⁄4 J= 7.5 Hz, 2H) , 3.81-3.91 (m, 2H), 7^1 (bis, 1H), 7.29 (bis, 1H), 7.34 (fare, 1H), 31PMMR (^DMSO, 121.49 MHz) δ 15.62, MS (ES4) m/ Z-2293 (MH4). Yellow oil, NMR (de-DMSO, 300 MHz) δ l, 18 (t, /=6.913⁄4 3H), 2.36 (s, 3H), 3.87 (quintuplet, /= IJZHz, 2H ), 7.33-7.42 (m, 2H), 7.44-7.55 (m, 2H), 3lP NMR (de-DMSO, 101.256 MHz) δ 16.41. Light yellow oil, 咕&gt;0^((^0^130,300 1^) ) 5 1,19~/» 6.9Hz, 3E〇, 230 (brs, 33⁄4 2.45 (brs, 3ΕΓ), 3.87 (quintuplet, J ~ 7.5Hz, 2H), 7.18-7^7 (m, 2H), 7 </ RTI> <RTIgt; Hz, 3H), 227 (bxs3 6H), 3.85 (quintuplet, J = 7.2Hz, 2H), 7.23-7.27 (m, 1H), 7.37-7.47 (m, 2H), 31P NMR (d^-DMSO, 101 MHz) δ 16.92, MS (ESI, El4) ?«/z = 215 (MU'). Light yellow oil, iHNMRWrDMSO, 300 MHz) δ U7 (t, J^ 7.1 Hz, 6H), 3.84-3.94 (m, 2H), 7.51-7.69 (m, 3H), ^ NMR (d^ DMSO , 300 MHz) δ -141.87 (m, IF), -137.91 (m, IF), 3,P NMR (JrDMSO, 101.256 MHz) δ 12.80 (d, 6.5 Hz, IP), MS (ESI, 11^)^ = 223 (MH*)· 164 93533 200804280 Description of the structure of the compound 3ae

3af 3ag 3ai

NC

3aj

3ak

3al 0·!η〇Β

F oil, 1H NMR O^rDMSO, 300 MHz) δ 1.18 (t /= 7-5 Hz, 3H), 1.19 (t, / 7.05 Hz, 3H), 2.91 (q, J - 7.5 Hz, 2H), 3.89 (cprintuplet, /= 7.05 Hz, 2H), 7.24-736 (3⁄4 2H), 7.46-7.52 (m, 1H), 7.74 (ddd, J-1.2 and 7.5 and 13.8 Hz, 1H), 3lP NMR (rfr DMSO, δ 15.66, MS (ESI, El4) m/z^2l5 (MH4). Oil, 1H NMR (^DMSO, 300 MHz) δ U8 (t, /= 6·9 13⁄4 3H), 2.4 (s, 3H), 3.85-3.97 (m, 2H), 7.78-7.81 (m, 1H), 7.82-7.84 (m, 1H), 7.84-7.87 (m, 1H), 31P NMR (^DMSO, 12L49 MHz) δ 11.67 , MS (ES4) m/z = 2262 (MH*). Oil, 1HNMR (c^DMSO, 300 MHz) δ 1.17 .../ = 7,1 Hz, 3H), 13 (s, 9H), 3.82-3.91 ( m, 2H), 7.41-7.53 (in, 2H), 739-7.61 (m, 1H), 7.66-7.71 (m, 1H), MS (ES4) = 243 (MH4). Oil, 1H NMR (irDMSO, 300 MHz) δ 1.19 (W = 6·9 Hz, 3H), 3.87- 3.97 (m, 2H), 7.4-7.49 (m, 1H), 7.6^.64 (m, 1H), 7.78-7.82 (m, 1H) ), 19F NMR (^BMSO, 282.4 MHz) δ 4093 (q, 8.2 Hz, IF), MS (ES4) /k/z = 283/285 (MH4). Oil, NMR ('DMSO, 300 MHz) δ U9 (t /= 7·05 Hz, 3H), 3.87- 3.97 (m, 2H), 7.55-7.65 (m, 1H), 7.85 -7.91 (m, 1H), 8.03· 8.09 (iv) 1H), 31PNMR (/f^rDMSO, 121.49MHz) δ 11.94 (4/= 8.02 Hz3 IP), l9F NMR (drOMS09 282, 4 MHz) -112,04 ( m, IF), MS (ES*^ 2283 (MH4). Oil, 1H NMR (A-DMSO, 300 MHz) δ 1*20 generation /= 7.05 Hz, 3H), 3.87- 3,97 (m, 2H) , 7.4-7.47 (m, 1H), 7.51-7.59 (m, 2H)3 7.83-7*91 (m, 1H), 3lP NMR (rfrDMSO, 12L49 ΜΕΪζ) δ 11.26, MS (ESI, Ei&quot;) m/ z = 221.03 (MH4). Oil, 1H NMR (rfrDMSO, 300 MHz) δ 1.19 7.2 Hz, 3H), 3.9-4 (m, 2H), 7.31-7.53 (ib, 3H), 31P NMR (^DMSO, 101J256 MHz ) δ 8.05 (d, J = 5.5 Hz, IP), l9F NMR (^DMSO, 282.4 MHz) -110.71 (d, /= 19.4 Hz, IF), -11833 (diJ, /= 5.9 and 192 Hz, IF) , MS (ES4) 7?^=223.03 (MH4). 165 93533 200804280 Table 2 Compound Structure Description 5a

Colorless oil, worm NMR WrDMSO, 300 ΜΗζ) δ 1,27 (t, /= 7.1 Hz, 3H), 1,36 (t, J= 7.1 Hz, 3H), 4.03 (m, 2H), 4.38 (3⁄4 / = 7.1 Hz, 2H), 7.51-7.83 (m, 11H), S.05-8.11 (m, 3H), 31P NMR (dr DMSO, 101256 MHz) δ 23.3, MS (ESI, El4) w/z = 532 (MH4). 5b

Viscous yellow oil, NMR (CDCU, 300 MHz) δ 130 (t, /- Hz3H), 422-4.34 (3⁄4 2H), 5-5.12 (m, 2H), 7.26-7.33 (m, 6H), 7.42-7.54 (m, 5H), 7.60-7.66 (m, 1H), 7.77-7.78 (m, 1H), 7.85-7.92 (m, 3H), 8.07-8.10 (m, 2H), 31P NMR (CDa3, 101.256 MHz) δ 25.24, MS (ESI, Bt) m/z = 594

Light yellow solid, $ NMR (rfer DMSO, 300 MHz) δ 1,27 (t, /-7.1 Hz, 3H), 1,36 Hz, 3H), 230 (s, 6H), 3.94-4.06 (m, 2H) , 4.44 (q, /= 7.1 Hz, 2H), 7.25 (s, 1H), 7.39 (s, 1H), 7.42 (s, 1H), 7.53 (dd, J=2.1 and 9.0 Hz, 1H), 7.65- 7.71 (m, 2H), 7J7-7.82 (m, 2H), 8.05-8.11 (id, 3H), 31P NMR WrDMSO, 101.256 MHz) δ 23.6, MS (ESI, = 560 (MH4). 166 93533 200804280 Structure 5d

F

Viscous yellow oil, XH NMR (CDa3, 300 MHz) δ 1,37 (t, ·-- Hz, 3H), 1,44 (t, /- 7.2 Hz, 3H), 4.05-4.19 (m, 2H), 4.52 (q,7- 72 Hz, 2H), 7.11-7.17 (m, 2H), 7.32-736 (3⁄4 1H), 7.48-7.54 (m, 2H), 7.60-7.63 (to, 1H), 7.84-7.93 (m, 4H), 8.07-8.09 (m, 2H), 31P NMR (CDQ3, 101.256 MHz) δ 23.6, 19F NMR (CDCl3i 282.4 MEIz) δ -10536 (m, IF), MS (ESI, El^ m/ Z-550 (MH4). 5e

Viscous yellow oil, iHNMlUCDa^SOOMHz) S 1,38 (t, /*= 7.05 Hz, 3H)a 1,46 (t, Hz, 3H), 4.09^42 (m, 2H), 4.53 (q, ·/ - 7,2 Hz, 2H), 7.35 (dd, / = 2.1 and 9 Hz, 1H), 7.37-7.43 1H), 7.48^7.54 (m, 3H)9 7.6-7.95 (m, 5H), 8.07-8.1 (m, 2H), 31P NMR (00〇3, 101.256 MHz) δ 22.76, MS (ESI, Et) m/z = 566 (Mff). 5f 5g

Viscous yellow oil, also NMR (CDCls, 300 MHz) δ 03 ft /» 7.5 Hz, 3H), 1,37 (t, J=7.05 Hz, 3H), 1,44 (t, 7.2 Hz, 3H), 2.68 (q, 7.5 Hz, 2H), 4.06-4.18 (m, 2H), 4.5 (q, J = 7.2 Hz, 2H), 73-739 (m, 3H), 7.47-7.52 (m, 2H), 7.59- 7.76 (m, 3H), 7.87 (d, /= L8 Hz, 1H), 7.91 (dd, 1.5 and 9 Hz, 1H), 8.07-8.1 (m, 2H), 31P NMR (CDa3, 121.49 MHz) δ 21 , MS (ESI, El4) m/z « 560 (MB〇. Yellow solid, 1H NMR (GDd3, 400 MHz) δ 1.39 (t, / = 7 Hz, 3H), 1,44 (t, J - 7.2 Hz , 3H), 4.09-4^3 (m, 2H), 4.53 (qd, J -= 2 and 7.2 Hz, 2H), 735 (dd, J = 2 and 9.2 Hz, 1H)3 7.48-7.53 (m, 2H), 7.57-7.64 (m, 2H), 7.68-7.79 (id, 1H), 7.88 (d, J = 2 Hz, 1H), 7.94 (dd, L6 and 8.8 Hz, 1H), 8.04-8.1 (m , 3H), 8.16-8.2 (B3, 1H), 3lP NMR (CDCU, 101.256 MHz) δ 22.62, 19F NMR (CDC13, 235.36 MHz) δ -63*2, MS (ESI, El4) m/z 167 93533 200804280 Compound structure description

Sh

5i

= 600 (ΜΗ4)· Yellow solid, worm NMR (CDC133 300 MHz) S 1·4 (t, /= 7.05 Hz, 3H), 1,46 (t, J= Hz, 3H), 4.04-

4.24 (3⁄4 2H), 4.55 (q, 12 Hz, 2H), 7.37 (dd, J -2*1 and 9 Hz, 1H), 7.51-7.67 (m, 4H), 7.80 (dd, /= 1.5 and J = 7.8 Hz, 1H), 7.84 (d, /= 2.1 Hz, 1H), 7.95 (dd, 1.5 and 8.7 Hz, 1H), 8.07-8.17 (take 4H), 31P NMR (CDC13, 101.256 MHz) δ 2L64, MS (ESI, El4) m/z = 555 s. White solid, 1H NMR (CDC13, 300 MHz) δ 1.38 (t, J = 7,05 Hz, 3H), 1,46 (1, /= 7.35 Hz, 3H) , 4.10-4.19 (in, 2H), 4.53 (q, 7.2 Hz, 2H), 7.3- 7.37 (m, 2H), 7.49-7.55 (m, 2H), 7.6-7.67 (m, 2H), 7.77-7.84 (m, 1H), 7.87 (d, /= 2.1 Hz, 1H), 7.93 (dd, /= 1.8 and 9 Hz, 1H), 8-8.06 (m, 1H), 8.07-8.11 (3⁄4 2H), 3lP NMR (CDCl3 &gt; 121.49 MHz) δ 22.11, MS (ES^ /tj/z = 609.73/611.77

5j

168 viscous yellow oil, also NMR (cMDMSO, 300 MHz) δ U6 (d, / = 6.9 Hz, 3H), U7 (d, J = 6.9 Hz, 3H), 1^7 (t, /= 7.05 Hz, 3H ), 1,38 (t, 12 Hz, 3H), 2.88-2.97 (m, 1H), 4.03 (q, 7.2 Hz, 2H), 4.45 (3⁄4 / = 7.05 Hz, 2H), 7.45^7.69 (m, 7H), 7.75-7.79 (m, 2H), 8.05-8.1 (m, 3H), MS (ES4) wi/z ~ 573.8 (MBT^). Yellow solid; 1H NMR (rfrDMSO, 300 MHz) S 1.30 (t , / = 7.0 Hz, 3H), 1.35 (t, 7.0, Hz, 3H), 4.05-4.12 (m, 2H), 4.46 (q, 7.0 Hz, 2H), 5.56

(d, 12 Hz, 1H), 7.44-8.10 (m, 18H), 31P NMR (d^-DMSO, 121.49 MHz) δ 22.07, MS (ES4) = 608 (MH4). 93533 200804280 Compound Structure Description 51

Viscous yellow oil, 31P NMR (4DMSO, 121.49 MHz) δ 22.73, MS (ES^m/z = 580 (ΜΕΤ'). 5n

5p

White powder, NMR (C〇a3, 300 MHz) δ 1.37 (t, 12 Hz, 3H), L45 (t, /- 7.2 Hz, 3H), 3.81 (s, 3H), 4.05^.18 (m, 2H ), 4.53 (q, /- 7.2 Hz, 2H), 7.07 (dt, J * 1.2 Hz and 8.1 Hz, 1H), 7.28-7.63 (in, 7H), 7.87 (d, J *= 2.1,1H), 7.90 (dd, J = 1.5 Hz and 9 Hz, 1H), 8.08 (dd, J = 1.5 Hz and 7.5 Hz, 2H), 31P NMR (CDa3, 121.49 MHz) 524.00 yellow powder, $ NMR (CDCU, 300 MHz) δ 138 (t, /- 7.2 Hz, 3H), 1.47 (t, /= 12 Hz, 3H), 3.85 (s, 3H), 4.13 (q, J^72Ezy 2H), 4,53 (q, /= 7.2 Hz, 2H), 6.97 (dd, /= 2.7 Hz and 8.7 Hz, 2H), 734 (dd, /- 2.1 Hz and 93 Hz, 1H), 7.49-7.55 (m, 2H), 7.6-7.66 (m, 1H), 7.8-7.94 (m, 4H), 8·08_8·11 (3⁄4 2H), 31P NMR (CDC13, 121.49 MHz) δ 2436, MS (ESI, El4) miz « 562 (MH1). Yellow powder, 1H NMR (CDC13, 300 MHz) δ 1.36 (t, 7« 7.2 Hz, H), 138 (t, 7.05 Hz, 3H), 3.55 (s, 3H), 4.05-423 (m, 2H) , 4.42 (q, /=7-2 Hz, 2H), 6.82^6.87 (m, 1H), 7.05-7.11 (m, 1H), 7.35 (dd, /= 2.1 Hz and 9 Hz, 1H), 7.89- 7.53 (m, 3H), 7.6-7.66 (m, 1H), 7.9-7.98 (m, 2H), 8.03 (d, J = 2.1 Ηε, 1H), 8.09-8.12 (m, 2H), 3lP NMR (CDC13, 121.49 MHz) δ 21.9, MS (ESI, El4) 562 (MH4), 169 93533 200804280 Description Compound Structure

Sr

Yellow powder, 3lP NMR (CDCU,: 121.49 MHz) δ 20·6, 19F NMR (CDC13, 282.4 MHz) δ -633, MS (ESI, El4) m/z = 668 (ΜΕΪ4). 5s

Yellow powder, 3iP NMR (CDCk, 121.49 MHz) δ 20.86 (d, J - 7.8 Hz, IP), l^F NMR (CDCI3, 282.4 MHz) δ - 63.2 (s5 3F), 408.7 (q, J = 73 Hz, IF), MS (ESI, El&quot;) w/z- 618 (MH4). 5u

5v

Yellow powder, 1H NMR (CDa3, 300 ΜΗζ) δ 1.36 (quintuplet, / * 7.2 Hz, 6H), 4.09-4.3 (m, 2H), 4.42 (q, 6.9 Hz, 2H), 731 (dd, J= 2.1 Hz and 9 Hz, 1H), 7.47-7.64 (m, 6H), 7.71 (d, J-L8 Hz, 1H), 7.87-7.95 (m, 2H), 8.04-8.09 (3⁄4 3H), 8.16 (qd, I.2 Hz and Hz, 1H)S 8.69-8.72 (m, 1H), 31P NMR (CDClZ9121.49 MHz) δ 2431, MS (ESI, El4) w/r=582 (ME〇. yellow powder, 4 NMR (CDCfe, 300 MHz) δ 1,23 (d, J = 7.2 Hz, 6H), 138 (t, J = Hz, 3H), 1.46 (t, J- 7.2 Hz, 3H), 2.83-3.06 ( m, 1H), 4.05-4.25 (m, 2H), 4.55 (3⁄4 J = 7.0 Hz, 2H), 7.05-7.10 (m, 1H), 7.33 (dd, / = 2.1 Hz and 9.0 Hz, 1H), 7.31 -7.41 (m, 1H), 7.45-7.64 (m, 4H), 7.86 (d, /-1.8 Hz, 1H), 7.94 (dd, /= 8.7 Hz and 1.8 Hz, 1H), 8.06-8.11 (m, 2H), 31P NMR (CDC13, 121.49 MHz) δ 22.83 (d, J = 7.65 Hz), MS (ES4) mh * 592 (MH4). 170 93533 200804280 Compound Structure Description 5w

Yellow resin, 1H NMR (CDC13, 300MHz) δΐ.42 (t, 7.05 Hz, 3H), 1.49 (t, /- Hz, 3H), 4.11- 4.26 (m, 2H), 4.57 (q, 72 Hz, 2H ), 723-7.27 (m, 1H), 7.38 (dd, 1.8 and 9 Hz, 1H), 7.5-7.57 (m, 3H), 7.62-7.72 (m, 2H), 7.87-7.88 (m, 1H), 7.94-7.98 (m, 1H), 8.09-8.12 (m, 2H)S 31P NMR (CDCU, 121.49 MHz) δ 6.78, MS (ES4) τη/ζ = 584.26 (ΜΗ&quot;). 5x

Oil, 1H NMR (i^DMSO, 300 MHz) δ 1,27 (t /= 6.9 Hz, 3H), 1,37 (t, J = 7.2 Hz, 3H), 2.34 (s, 3H), 3.97-4.02 (m, 2H), 4.44 (q, /= 7.2 Hz, 2H), 734-7.38 (m, 2H), 7.51-7.55 (dd, / - 2.1 and 9 Hz, 1H), 7.65-7.72 (m, 4H ), 7.75-7.83 (m, 2H) 31P NMR (Je-DMSO, 101.256 MHz) δ 23.57, MS (ESI, El4)»^=546(MH+): 5aa

Oil, 1H NMR (do-DMSO, 300 MHz) δ 127 ft 7.05 Hz, 3H), 1,39 (t, 7.05 Hz, 3H), 2.25 (2s, 6H), 3.96-4.04 (m, 2H), 4.44 (q, 7.05 Hz, 2H), 73-7.34 (m, 1H)S 7.48-7.58 (m, 3H), 7.66-7.72 (m, 2H), 7J7-7.83 (m, 2H), 8.09-8.11 (m , 3H), 31P NMR (rfrDMSO, 10056 MHz) δ 23.64, MS (ESI, El4) w/z = 560 (MH4), 5ad

Dark yellow oil, NMR (4rDMSO, 300 MHz) S 1,29 (1, J- 6.9 Hz, 3H), 1,37 (t, J- 7.2 Hz, 3H), 4-03-4.13 (m, 2H ), 4.46 (q, /= 7.1 Hz, 2H), 7.44-7.63 (m, 4H), 7.65-7.71 (m, 2H), 7.78-7.83 (m, 1H), 7.88 (d, /= 2A Hz, IH), 8.06-8.11 (m, 3H), 19F NMR (JrDMSO) δ-109.98 (m, IF) + inq&gt;urete, 31P NMR (rfrDMSO, 101 MHz) δ 20.41 (t, J = 8.4 Hz, IP) , MS (ESI, El4) = 569 (M+2H4). 171 93533 200804280 Description of the structure of the compound 5ae 5ah 5ai 5aj

Yellow oil; 1H NMR (rfrDMSO, 300 MHz) δ 1^2-1.30 (m, 6H), 4.95-4.13 (m, 2ΕΓ), 4.31 (d, /= 7-2-Hz, 2H), 7.25-7.45 (m, 3H), 7.55 (dd, 9.3 and 2.0 Hz, 1H), 7.66-7.85 (m, 6H), 8.06-8.10 (m, 2H), 31P NMR (irDMS05 101 MHz) δ 13.91,19F NMR (^ DMSO) δ-107.59 (m, IF), MS (ESI, Bt) m/z 550 (MK 〇. Yellow powder, NMR NMR (form: r DMSO, 300 MHz) δ 0.77 (t, 7.5 Hz, 3H), 1 , 23 (t, /= 6.9 Hz, 3H), 1.26 (1, /= 7.2 Hz, 3H), 2.76 (q, J = 7.5 Hz, 2H), 3.83-4.13 (m, 2H), 4.24-4.35 ( m, 2H), 73-7.42 (m, 2H), 7.48-7.6 (3⁄4 3H), 7.65-7.8 (m, 4H), 8.06-8.1 (m, 3H), 31P NMR (^rDMSO, 101 MHz) δ 22,65, MS (ESI, Ef), m/z - 560 oil, 4 NMR WrDMSO, 300 MHz) δ 1.25 (s, 9H), 1.25 (t, 72 Hz, 3H), 1.39 (t, 7.2 Hz, 3H), 3.99 (m, 2H), 4.46 (q, /= Hz, 2H), 7.47-7.55 (m, 2H), 7.6-7.7 (m, 4H), 7.75-7.83 (m, 3H), 8.05- 8.1 (3⁄4 3H), 31P NMR (rfrDMSO, 12L49 MHz) 5 22.6, MS (ES4) = 588.17 (MH4). Oil, 1HNMR (C〇a3, 300 MHz) δ 1.4 a/= 7.05 Hz, 3H), L47 (t, /= 7.2 Hz, 3H), 2.44 (s, 3H), 4-4.25 (m, 2H), 4^5 (q, J^72Bz, 2H), 7.37 (d d, J = 2.1 and 9 Hz, 1H), 7.52-7, 65 (m, 4H), 7.85-7.97 (in, 4H), 8.08-8.11 (m, 2H), 31P NMR (^DMSO, 101.256 MHz) δ 21.58, MS (ES4) /?z/z = 571.4 172 93533 200804280 Compound structure description 5ak

Cl S02Ph 5al

6a 6b

Oil, 'HNMR O^pDMSO, 300 MHz) δ 1·21 ft/= 7.2 Hz, 3H), 126 (t, 6.9 Hz, 3H), 4.03 (q5 /= 7.2 Hz, 2H), 4.18-4.26 (m , 2H), 7.52-7.63 (m, 3H), 7.66-7.71 (m, 4H), 7.78-7.83 (m, 1H), 7.92-8 (m, 1H), 8.05-8.09 (in, 3H), 31P NMR (rf^DMSO, 121.49 MHz) δ 18.06, MS (ES4) w/r = 565.93 (MH^). Oil, 1H NMR OirDMSO, 300 MHz) δ 1.3 (t» / = 7.05 Hz, 3H), 137 ( t, /= 7.05 Hz, 3H), 4-4.16 (m, 2H), 4.46 (q, 7.05 Hz, 2H), 7.56 (dd, J« 2.1 and 9 Hz, 1H), 7.66-7.71 (m, 2H ), 7.79-7.84 (m, 1H), 7.91-7.99 (no, 2H), 8.08-8.18 (m, 5H), 19F NMR (^DMSO, 282.40 MHz) -112.68 (q, / = 8.2 Hz, IF) , MS (ES4) m/r « 575 (MH〇. White solid, 1H NMR WrDMSO, 300 MHz) δ 1,34 (t, /= 7.1 Hz, 3H)S 4.05 (m, 1H), 4J20 (m, 1H), 7.32 (dd, J-2.1 and 8.7Hz, 1H), 7.49-7.61 (m, 5H), 7.68-7.75 (m, 2H), 8.02 (brs, 1H), 10^7 (brs, 1H) , 12.77 (brs, 1H), 3XP NMR (rf^DMSO, 101.256 MHz) δ 31.1, MS (ESI, El4) m/z = 363 (Μΐί). White solid; 1H NMR (rfrDMSO, 300 MHz) δ 1.32 ( t, /- 7.0 Hz, 3H), 226 (s, 6H), 3.90-4.03 (m, 1H), 4.09-4 ^2 (m, 1H), 7.21 (s, 1H), 729- 7.33 (m, 3H), 7.57 (dd3 / = 1.8 and 9.0 Hz, 1H), 7.60 (d, 1.8 Hz, 1H), 7.99 (brs , 1H), 103 (brs, 1H), 12.7 (brs, 1H), 31P NMR (rfrDMSO, 101.256 MHz) δ 313, MS (ESI, El4) τη/ζ = 391 (ΜΗ4).

F

White solid, 1H NMR (rfr DMSO, 300 MHz) δ 1,34 (% J = 6.9 Hz, 3H) S 4-4.04 (m, 1H)S 4.18-4.21 K 1H), 7.31-7.4 (m, 3H), 7.57-7.62 (in, 2H), 7J4-7.83 (m, 2H), 8.02 (brs, 1H), 10.18 (brs, 1H), 12.79 (brs, 1H), 31P NMR (rfrDMSO, 121.49 MHz) δ 29.29, 19F NMR (rfrDMSO, 282.4 MHz) 173 93533 200804280 Compound Structure 6d 6e 6f

Description δ -106.3, MS (ESI, Ε〇w/z = 381 white solid, 1H NMR WrDMSO, 300 MHz) δ 1,35 (t, / = 7.05 Hz, 3H), 4-4.09 (m, 1H), 4.17-4.25 (m, 1H), 73-7.35 (m, 1H), 7.55-7.74 (m, 6H), 8.05 (brs, 1H), 10.07 (brs, 1H), 12.84 (brs, 1H),33P NMR WrDMSO, 121.49 MHz) δ 28.24, MS (ESI, El4) tw/z - 397 (MH1). White solid, 1H NMR (rfe-DMSO, 300 MHz) δ 1.13 (t, /= 7.5 Hz, 3H), 1 , ( ( ( ( ( ( ( ( ( ( ( -7.5 (m, 3H), 7.56-7.61 (m, 3H), 8 (bts, 1H), 10.31 (brs, 1H), 12.74 (brs, 1H)S MS (ESI, El4) /7z/z-391 (MH4). White solid, 31P NMR (CDp3, &lt;RTI ID=0.0&gt;&gt;&&&&&&&&&&&&&&&&& . 6g

White solid, 1H NMR (dir DMSO, 400 ΜΗζ) δ 136 (t, J = 7.05 Hz, 3H), 44.12 (m, 1H), 4.17-4^7 (m, 1H), 7.33 (dd, J - 2 and 8 J6 Hz, 1H), 739 (dd, J-1.56 and 8.78 Hz, 1H)5 7.66 ((!,/ = 1.99 Hz, 1H), 7.73 (td, /-33 and 7.78 Hz, 1H), 7.97- 8.08 (m, 3H), 8.17-8.21 (m, 1H), 9.98 (brs, 1H), 12.83 (bis, 1H), 3,P NMR (JrDMSOs 101J256 MHz) δ 28.62, MS (ESI, El4) m/ z * 388

6i

174 white solid, 1H NMR (d^ DMSO, 300 MHz) δ 1.16 (d, 6.9 Hz, 3H), 1.17 (d, 6.9 Hz, 3H), 134 (t, 7.05 Hz, 3H), 2.88-2.97 (m , 1H), 3.97-

4.06 (m, 1H), 4.15^23 (m, 1H), 731 (dd, J-1.8 and 8,7 Hz, 1H), 7.42-7.66 (m, 6H), 8.01 (brs, 1H), 1031 ( Brs, 1H), 12.74 (brs, 1H), 31P NMR 93533 200804280 Compound Structure

175 Description (drOUS03 121.49 MHz) δ 30.22, MS (ES*1) m/z -404.8 (MH4). White solid; 1H NMR (drDMSO, 300 MHz) δ 1.37 (t, /= 7.0 Hz, 3H), 3.99 ^.09 (m, 2H), 4^5 (q, /= 7.0 Hz, 2H), 556 (d, 12 Hz, 1H), 7.35- 8.04 (m, 14H), 10.20 (brs, 1H), 12.78 (brs, 1H), 3lP NMR (rfrDMSO, 121.49 3VIHz) δ 22.07, MS (ES+)Tn/z« 439 (MH4). Yellow solid; 1H NMR WrDMSO, 300 MHz) δ 1.35 (t, 7.0 Hz, 3H) , 4.01-4.12 (m, 2H), 4.17-

4.25 (m, 2H)5 7.35 (dd, J= 8.8 and 1.8 Hz), 7.50-7.71 (m, 4H), 7,83^7,87 (m, 1H), 8.04(brs, 1H), 9.87 ( Brs, 1H), 12.86 (brs, 1H), 3lP NMR DMSO, 121.49 MHz) δ 26.47 (4 7.4 Hz), 19F NMR (^DMSO, 282.4 MHz) δ -111,96 (q5 / = 7.9 Hz, MS ( ES&quot;) m/z = 459/460 (MH4). White solid; NMR WrDMSO, 121.49 MHz) δ 28.35, MS (ES*1) w/z = 411 (MH4). White powder, 1H NMR WrDMSO, 300 MHz ) δ 1,39 (t, 7.04 Hz, 3H), 3.77 (s, 3H), 425-3.95 (two m, 2H), 7.29-7.14 (m, 4H), 7.33 (dd, 8.8 and 1.98 Hz, 1H ), 7.49-7.42 (m, 1H), 7.59 (dd, /= 8.8 and J&lt; 1.5 Hz, 1H), 7.66 (d, J- 1.93 Hz, 1H), 8.00 (brs, IH), 10.20 (brs, </ RTI> </ RTI> <RTIgt; structure

Description White powder, 咕NMRWrDMSO, 300 ΜΗζ) δ 1.35 (1/=6.9112,310,4.054.14 (1^111), 4.18-4.26 (m, 1H), 7.33 (dd, /= 1.8 Hz and 8.7 Hz, 1H ), 7.59 (dd, J « L8 Hz and 8.7 Hz, 1H), 7.74 (4/= 1.8 Hz, 1H), 7.83-75 (m, 2H), 7.97-8.03 (m, 2H), 9.74 (brs, 1H), 12.87 (brs, 1H), 31P NMR (rfrDMSO, 300 MHz) δ 27.25 (4 J = 6'57 Hz, IP), MS (ESI, El4) = 449 (MH4) white powder; 300 MHz) δ 1.35 (t, /= 7.2 Hz, 3H), 4.08-4.29 (m, 2H), 7.35 (dd, J = 2.1 Hz and 8.7 Hz, 1H), 7.6 (dd, J= 1.5 Hz and 8.7 Hz, 1H), 7.8 (d, /= 1.8 Hz, 1H), 8.08 (bis, 1H), 831 (hrs, 1H), 8.36 (brs, 1H), 8.41 (brs, 1H), 9.6 (brs, 1H) ), 12.88 (brs, 1H), 31P NMR (^ DMSO, 121.48 MHz) δ 26.63, MS (ESI, El4) m/z = 499 (MH4). White solid, b NMR WrDMSO, 300 MHz) δ 135 (t , /= 6.9 Hz, 3B〇, 3.95-4*08 (3⁄4 1H), 426-4.37 (m, 1H), 7.27 (dd, 1.8 Hz and 8.7 Hz, 1H), 738 (d, 1.8 Hz, 1H) , 7.56-7.65 (m, 4H), 7.86-754 (m, 1H), 8.02-8.06 (m, 1H), 8.12 (brs, 1H), 8.19 (d, J== 8.1 Hz, 1H), 8.54- 8.57 (m, 1H), 10.45 (brs, 1H), 1 2.83 (brs, 1H), MS (ESI, El^ m/z = 413 (MH1). yellow powder, 31P NMR (CDC13, 121.49 MHz) δ 29^7 (d, 8.0 Hz, IP), MS ( ES^) m/z- 423

176 93533 200804280 Compound Structure Description 6v 6w 6z 6ab

Colorless oil, 1H NMR (CDCU, 300 MHz) δ 1·48 (t, 7.05 Hz, 3H), 4.05-4.18 (m, 1H), 4.28- 4.41 (3⁄4 1H), 6.18 Cbrs, 1H), 7.22-7.26 (m, 1H), 731-7.4 (m, 2H), 7.53-7.55 (m, 1H), 7.57-7.58 (m, 1H), 7.67-7.68 (m, 1H), 1050 (brs, 1H), 11.13 (brs, 1H), 31P NMR (CDC13? 121.49 MHz) δ 27.7 (d, 7.8 Hz, IP), MS (ES〇tw/z = 41528, off-white powder, h NMR (iW DMSO, 400 MHz) 5 1,31 ( t/=7Hz, 3H), 2.33(s,3H), 3.94·4.04 (m, 1H), 4.IW.22 (m, 1H), 7.30-734 (ra, 3H), 7,57-7.62 ( m, 4H), 7.98 (brs, 1H), 103 (brs, 1H), 12.72 (brs, 1H), 31P NMR (rf^DMSO, 101.256 MHz) δ 31.46, MS (ESI, Ef) m/z = 377

Yellow powder, 4 NMR (rfrDMSO, 300 MHz) δ 1,29 (t, 7.05 Hz, 3H)S 2.22 (s, 3H), 2.37 (s, 3H), 3.81-3.94 (m, 13⁄4 4.11-4.24 (m , 1H), 7.21« 7^6 (m,lH), 7.27 (dd, /= 2.1 and 8.7 Hz, 1H), 7.32 (d, J- L8 Hz, 1H), 7.4 (4/= 7.5 Hz, 1H ), 7.48-7.6 (m, 2H), 8.01 (brs, 1H), 10.42 (brs, 1H), 12.75 (brs, 1H), 3lP NMR (^BMSO, 101256 MHz) δ 3L55, MS (ESI, E〇 /?i/z = 391 (MH&quot;). Off-white powder; 咕 NMR WrDMSO, 300 MHz) δ 133 (t, J- 6.9 Hz, 3H), 2.32 (s, 3H), 3.95-4.04 (m, 1H) , 4.12-4.24 (m, 1H), 731 (dd, / =1.5 and 8.7 Hz, 1H), 7.41-7.61 (m, 6H), 8.00 (brs, 1H), 10.28 (brs, 1H), 12.74 (brs , 1H), 31P NMR (drDMSO, 101.256 MHz) δ 3128, MS {ESI, Ef) 7^=377(1^· 177 93533 200804280 Description Compound Structure 6ac 6ad 6ab

Light yellow powder, NMR (eg *DMSO, 300 MHz) δ 135 (t, 6.9 Hz, 3H), 3.99- 4.13 (m, 1H), 4.17-4^8 (m, 1H), 7.32-7.43 (m, 3H), 7.50-7.61 (m, 2H), 7.68 (d, 1.8 Hz, 1H), 8.04 (brs, 1H), 9.91 (brs, 1H), 12.9 (brs, 1H), 3lP NMR (άΓ DMSO, 101 MHz) δ 28.0 (t, 8·113⁄4 IP), 19F NMR (drDMSO) δ-106.92 (m, 2F), MS (ESI, £1^^^399 (MH4). pale yellow powder, NMR (dr*) DMSO, 300 MHz) δ 1,35 (t, 6.9 Hz, 3H), 3.97-4.11 (m, 1H), 4.16^.29 (m, 1H), 7.22-7.42 (m, 3H), 7.56-7.59 ( m, 2H), 7.61-7.75 (m, 1H), 7.77-7.88 (m, 1H), 8.01 (brs, 1H), 10.08 (brs, 1H), 12.78 (brs, 1H), 31P NA4R (rf^DMSO , 101 MHz) δ 252 (4 ^ =11.3 Hz, IP), 19F NMR (^DMSO) δ-104.85 (take IF), MS _ ΕΓ*) 381 (ΜΗ4)· yellow powder, 1H NMR WrDMSO, 300 MHz) δ 0.94 (t, /= 7.5 Hz, 3H), 13 (t, J = 7.05 Hz, 3H), 2.73-2.98 (m, 2H), 3.83^3.96 (m, 1H), 4.1-4.25 (in, 1H ), 728 (dd, J-2.1 and 8,7 Hz, 1H), 732-7.38 (m, 3H), 7.5-7.6 (m, 2H), 7.66-7.73 (m, 1H), 8.02 (brs, 1H) ), 10.42 (brs, 1H), 12.76 (brs, 1H), 31P NMR (cfrDMSO, 121.69 MHz) δ 29 .63, MS (ESI, £1^) 7^ = 391 (MH4). Off-white powder, 4 NMR (rfrDMSO, 30D MHz) δ 131 (t, /= 7.05 Hz, 3H), 3.92-4.05 (m, 1H ), 4.15-4.28 (m, 1H), 7.25 (dd, J - 1.95 and S.85 Hz, 1H), 7.35 (d, /= 2.1 Hz, 1H), 7.47-7.61 (m, 4H), 8- 8.1 (m, 2H), 10.17 (bis3 1H), 12.71 (brs, 1H), 3lP NMR (rf^OMSO, 101 MHz) δ 2531, MS (ESI, El4) ^ == 397 (ΜΗ4). 178 93533 200804280 Compound Structure Description 6aj

Orange oil, worm NMR (CDC13, 300 MHz) δ 1·48 (3⁄4 7·〇5 Hz, 3Η), 4·054·23 twist 1Η〇, 4·29·4·4 twist 1Η), 633 (bts, 1Η), 7.33 (dd, J-1.8 and 8.7 Hz, 1H), 7.4-7.52 (in, 1H), 7.57-7.62 (m, 2H), 7.64-7J2 (m, 1H), 7.81-7.85 (m, 1H), 10.81 (brs, 1H), 11.42 (brs, 1H), 3iP NMR (CDa3, 121.49 MHz) δ 26.56 (d, / = 3.1 Hz, IP), ^ NMR (CDC13 > 28240 MHz) -107 (3⁄4 734 Hz, IF), MS (ES4) wi/z — 406.3 (MH4). 6ak

7a

White solid, 1H NMR WrDMSO, 300 MHz) δ 1.35 (ζ 7.0 Hz, 3H), 4.02-4.25 (m, 2H), 734 (d, / - 8.5 Hz, 2H), 7.59 (d, 8.5 Hz, 1H) , 7.74 (d, /= 8.5Hz, 1H), 8.04 (m, 2H), 8.16 (m, 1H), 8.29 (fars, 1Η), 9.70 (brs, 1H), 14.73 (brs, 1H), 31P NMR (J^DMSO, 121.49 MHz) δ 26.87, MS (ES4) m/z = 575 (MH4), MS (ES&quot;) = 422 (MET&quot;) · pale yellow solid, h NMR OW DMSO, 300 MHz) δ 2Ji7 ( s, 6H), 3.73 (4/= 11J Hz, 3H), 7.23 (hrs, 1H), 7^9-7.33 (m, 3H), 7.56-7.59 (m, 2H), 8 (brs, 1H)3 10^7 (bra, 1H), 12.75 (brs, 1H), 3lP NMR (^DMSO, 101.256 MHz) δ 33.27, MS (ESI, Bf) m/z = 377 (MH4) White solid, 1H NMR , 300 MHz) δ 3.79 (d, 11.7 Hz, 3H), 7.35 (dd, L8 and 8.7 Hz, 1H), 7.6 (dd, J= 1.8 and 8.7 Hz, 1H), 7.67 (d, /-1.8 Hz, 1H), 7.7 (t, J-1.8 Hz, 2H), 7.89 (t, 7= L8 Hz, 1H), 8.06 (brs, 1H)? 9.78 (brs, 1H), 12·89 (brs, 1H), 31P NMR (drDMSO, 101250 MHz) δ 29.44, MS (ESI, El4) - 417 (ME〇. 179 93533 200804280

Description White solid, lH NMR (dd-DMSO, 300 MHz) δ 3.77 (d, / = 11.7 Hz, 3H), 733 (dd, /= 1.8 and 8.7 Hz, 1H), 7.54-7.74 (m, 6H), 8.05 (brs, 1H), 10.01 (brs, 1H), 12.84 (brs, 1H), 31P NMR DMSO, 121.49 MHz) δ 30.23, MS (ESI, El4) m/z = 383 (MH4). White solid, lH NMR (4rDMSO, 300 MHz) S 1.14 (t, 7.5 Hz, 3H), 2.63 (q, / * 7.5 Hz, 2H), 3.75 ((!,/= 11.4 Hz, 3H), 7.32 (dd, J= 1.95 And 8*85 Hz, 1H), 7.41-7.52 (m, 3H), 7.57^7.63 (m, 3H), 8.02 (brs, 1H), 1027 (brs, 1H), 12.78 (brs, 1H), 3IP NMR (CDCl39 121.49 MHz) δ 32.2; MS (ESI, Ef) m/z = 377 (MH4). White solids NMR Oir DMSO, 300 MHz) δ 3.g (d, 11.7 Hz, 3H), 7.34 (dd, /= 1.8 and 8.7 Hz, 1H), 7.6 (dd, /= 1.5 and 8.7 Hz, 1H), 7.64 (d, 1.8 Hz, 1H), 7.76 (td, J - 3.3 and 7.8 Hz, 1H), 7.94. 8.07 (m, 4H), 9.97 (brs, 1H), 12.7 (brs, 1H), 31P NMR (rfrDMSO, 121.49 MHz) δ 29.98,19F NMR (C〇a3, 282.4 MHz) δ 118.06 (s, 3F), MS (ESI, El&quot;) ik/z-417 (MH4). White solid, lR NMR (^ DMSO, 300 MHz) δ 3.79 (d, / = 11.7 Hz, 3H), 733 (dd, J = 1.95 and 8 J Hz, 1H), 7.59 (dd, J = 1.8 and 8.7 Hz, 1H), 7.65 (d, L8 Hz, 1H), 7.69-7 J5 (m, 1H), 7.96- 8.08 (m, 3H), 8.17-8.21 (m, 1H), 9.9 (brs, 1H), 12.88 (brs, 1H), 31P MMR (^DMSO, 121.49 ΜΉζ) δ 29.65, MS (ES^ w/z=373.86 (MH4). White solid , NMR WrDMSO, 300 MHz) δ 1.16 (d, J= 6.9 Hz, 3H), U7 (d, 6.9 Hz, 3H)5 2.88-2.98 (m, 1H), 3.76 (d, 7= 11.4 Hz, 3H ), 732 (dd, /= 1.95 and 8*85 Hz, 1H), 7.41-7.68 (m, 6H), 8.03 (brs, 1H), 1028 (brs, 1H), 12.77 (bis, 1H)9 31P NMR (rfrDMSO, 121.49 MHz) δ 32.16, MS 180 93533 200804280 Compound structure 7h 7i 7j 7k

Description (£^^=390.9 (ΜΗ&quot;). White solid, also NMR (wood-DMSO, 300 MHz) δ 3.77 (d, J-1L7 Hz, 3H), 5.47 (d, /- 47.4 Hz, 2H)a 7.33 (dd, 2.1 and 8.7 Hz, 1H), 7.55-7.81 (m, 6H), 8.04 (brs, 1H), 10.19 (brs, 1H), 12.78 (hrs, 1H), 3IP NMR (^DMSO, 121.49 MHz δ 31.62, 19F NMR (de-DMSO, 282.40 MHz) δ -207.99 (tyJ^ 47.4 Hz, IF), MS (ES4) w/z = 380.83 (MH4). White solid; ^ NMR (i^DMSO, 300 MHz) δ 3.81 (d, 11.7 Hz, 3H), 733 (dd, 8.7 and 2.1 Hz, 1H), 7.41-7.72 (m, 9H), 7.87-8.01 (in, 2H), 8.05 (brs, 1H), 10.21 (hrs, 1H), 12.79 (brs, 1H), 3lP NMR (^-DMSO, 121.49 MHz) δ 31.74, MS (ES, 425 (MET). White solid; NMR (&amp; DMSO, 300 MHz) δ 3,79 (d, /= 11.7 Hz, 3H), 7.35 (dd, J= 8.7 and 2.1 Hz, 1H), 7.51-7.72 (m, 9H), 7.83-7.87 (m, 2H), 8.06 (bis, 1H), 9.83 (brs, 1H), 12.88 (brs, 1H), 31P NMR (JrDMSO, 121.49 MHz) 8 28.46 (d, /= 7.2 Hz), 19F NMR (drDMSO? 282.4 MHz) δ -110.60 (m) a MS (ES4) ζτι/r « 445/447 (MH4). White solid; NMR (J^DMSO, 300 MHz) δ 2.32 (s, 3H), 3.77 (d, 11.4 Hz, 3H), 7.34 (dd, J = 9.0 and 2.1 Hz, 1H), 7.47-7.59 (m, 5H), 8.04 (brs, 1H), 10.04 (brs, 1H), 12.88 (brs, 1H), 31P NMR ( </ RTI> </ RTI> <RTIgt; Hz, 3H), 6.02 (brs, 1H), 7.06-7.08 (m, 1H), 7.28-737 (m, 4H); 7.49-7.52 (m, 1H), 7.73 (brs, 1H), 10.67 (brs, 1H), 11.01 (brs, 1H);, 3lP NMR (CDa3, 121.49 MHz) δ 32.67, MS (ESI, El4) 7?i/z * 379 (MH4). 181 93533 71 200804280

White powder, also NMR (CDC13, 300 ΜΗζ) δ 3.92 (d, /- 1L7 Hz, 3H), 6.12 (brs, 1H), 7.36 (dd, /= 1.8 Hz and 8.7 Hz, 1H), 7.48-7.51 ( m, 1H), 7.55-7.65 (m, 3H), (d, 12.9 Hz, 1H), 10.81 (brs, 1H), 10.97 (bis, 1H), 3lP NMR (CDC13, 121.49 MHz) δ 29.27 (d, / = 6.8 Hz, IP), 19F NMR (CX &gt; C13, 282.40 MHz) δ -62.89 (s, 3F), -107.86 (q, / = 7.6 Hz, IF), MS (ESI, El&quot;) tti/z -435 white powder, NMR (0)3⁄4 300 MHz) δ 3.94 (d, /-11.7 Hz, 3H), 6.12 (brs, 1H), 737 (dd, /= 2.1 Hz and 9 Hz, 1H), 7.57 (dd, /= 1.8 Hz and 8.7 Hz, 1H), 7.63-7.637 (m, 1H), 8.04 (brs, 1H), 8.21 (brs, 1H), 8.26 (hrs, lB〇, 10.81 (brs, 1H) , 10.94 (brs, 1H), 19F NMR (CDa3 &gt; 282.40 MHz) δ ^62.96 , MS (ESI, Et) m/z = 485 (MH4), white powder, NMR (C〇a3, 300 MHz) δ 3.92 (d, /- 11.7 Hz, 3B〇, 6.04 (brs, 1H), 7.3 (dd, 2.1 Hz and 9 Hz, 1H), 7.42-7.65 (m, 5H), 7 J7 (qd, 12 Hz and 7.2 Hz , 1H), 7.9-7.93 (m, 1H), 8,03-8.06 (m, 1H), 8.68 (d, 8.4 Hz, 1H), 10.58 (hrs, 1H), 11.19 (brs, 1H), 31P NMR (CDa3, 121.49 MHz) δ 34.98, MS (ESI, Ef) m/z « 399 (MIT). Gray-white powder, worm NMR (CDC13, 300MHz) δ L24 (d, / = 6.9 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 2.96 (hept, J = 6.9 Hz, 1H), 3.83 (d, /= 11.7 Hz „ 3H), 5.99 (brs, 1H), 7.07-7.13 (m, 1H), 7.20-7.29 (m, 1H) ), 7.34 (dd, / = 2.1 Hz and 9 Hz, 1H), 7.49-7.53 (m, 2H), 7.68 (d, 2.1 Hz, 1H), 7.95 (dd, / = 9.6 Hz and 1.8 Hz, 1H) , 8.08-8.14 (m, 2H), 10.54 (brs, 1H), 10.95 (brs, 1H), 3IP NMR (CDC13, 121.49 MHz) δ 31.35 (d, 8.4 Hz, IP), MS (ES^ m/z =409 (MB〇. 182 93533 200804280 Compound Structure Description 7v 7w 7x 7y

Off-white solid, lH NMR (CDC13, 300 MHz) δ 3.9 (d, 11.7 Hz, 3H), 6.09 (fars, 1H), 724-728 (m, 1H), 7.32-7.40 (m, 2H), 7.53-7.59 (m, 2H), 7.65-7.66 (m, 1H), 10.81 (brs, 1H), 10.87 (bis, 1H), 31P NMR (CDC13, 121.49 MHz) δ 29.77 (d, J ^ 7.78 Hz, IP), 19F NMR (CDa3, 282.40 MHz) δ -111·22 (4) 1F), MS (ES, m/z = 401J29 (ΜΗ4)· white solid, 1H NMR ('DMSO, 300 MHz) δ 1.12 (t, J = 7.5 Hz, 3H)3 2J28 (s, 3H)? 2.58 (q, J-7.5 Hz, 2H), 3.74 (d, /- 1L4 Hzs 3H), 7.26 (brs, 1H), 7.31 (dd, 1.8 and 8.7 Hz , 1H), 734-7.40 (in, 2H), 7.56-7.60 (m, 2H), 8 (brs, 1H), 1029 (brs, 1H), 12.75 (brs, 1H), 3lP NMR (JrDMSO, 121· 49 MHz) δ 3221, MS (ES) m/z = 391.3

White solid, 1H; NMR (4 DMSO, 300 MHz) δ 0.83 (t, 7.2 Hz, 3H), 1.54 (sext^let, / = .7.2 Hz, 2H), 2.58 (t, / = 7.2 Hz, 2H), 3.75 (d, /= 11.4 Hz, 3H), 7.31 (dd, /= 2.1 and 8.7 Hz, 1H), 7.4-7.51 (m, 3H), 7.55-7.60 (m, 3H), 8 (brs, 1H) , 10.25 (brs, 1H), 12.75 (brs, 1H), 31P NMR DMSO, 121.49 MHz) δ 32.17, MS (ES^) m/z = 391.26 (ΜΗ〇. White solid, hNMR (CDa3, 300 MHz) 52.40 (s, 3H), 3.88 (d, /= 117 Hz, 3H), 5.89 (d, /-16.5 Hz, 1H), 5.97 (hrs, 1H), 733-7.67 (3⁄4 7H), 10.46 (s, 1H ), 10.89 (bis, 1H), 31P NMR (CDa3, 121.49 MHz) δ 31.54, MS (ES^ w/r « 414

183 93533 200804280 Compound Structure Description 7z 7aa 7ab

Off-white solid, NMR (dtf-DMSO, 300 MHz) δ 226 (sa 6H), 3.69 (d, 11.4 Hz, 3H), 7.20 (brs, 1H), 7.25 (brs, 1H), 7.29 (brs, 1H) , 738 (dd, 6.3 and 8.4 Hz, 1H), 7.44 (dd, 7-1.5 and 8.7 Hz, 1H) 8.02 (brs, 1H), 10.77 (brs, 1H), 12.96 (hrs, 1H), 31P NMR ( Rf^DMSO, 121.49 MHz) δ 31.74, MS (ES4) m/z^ 394.9 (Mit). </ RTI> , 2H), 1.85-L95 (3⁄4 1H), 3.86 (d, 11.7 Hz, 3H), 5.98 (brs, 1H), 7J2-7.22 (m, 1H), 7.28 -7.35 (m, 3H), 7.47-7.58 (Ma 3H), 7·71-7·72 Twist 1H), 10.50 (brs, 1H), 1L04 (brs, 1H), 3lP NMR (CDa3> 121.49 MHz) δ 33.04, MS (ES^) m/z « 389.08 (MH4). Yellow powder, NMR (&amp;DMSO, 300MHz) S 2.33 (s, 3H), 3.74 (d, J = 11.7Hz, 3H), 731-733 (m, 3H), 7.57-7.60 ( m, 4H), 8 (brs, 1H), 10.26 (brs, 1H)3 12.76 (brs, 1H), 31P NMR (rfrDMSO, 121.49 MHz) δ 32.48, MS (ESI, El4) m/z - 363 7ae

Light yellow powder, ^INMR OirDMSO, 300 MHz) δ 2·23 (3⁄4 6H), 3.73 (4/=11.4 Hz, 3H), 7.25-733 (m, 2H), 7.36-7.43 (m, 1H-), 7.49 (d, J = 12.9 Hz, 1H), 7.56-7.60 (m, 2H), 7.99 (brs, 1H), 10.28 (brs, 1H), 12.74 (brs, 1H), 31P NMR (^ DMSO, 101.256 MHz ) δ 33.45, MS (ESI, El4) ^/2^377(1^1114). 7ah

Light yellow powder, eat [NMR (CDC13, 300 MHz) δ 3.85 (d, /= 11.4 Hz, 3H), 6.08 (brs, 1H), 730 (dd, /= 2.0 and 9,0 Hz, 1H), 736 -7.56 (m, 4H), 7.68 (d, /- 1.813⁄4 1H), 7.73-7.81 (m, 2H), 10.78 (brs, 1H), 10.03 (brs, 1H), 3lP NMR (CDa3&gt; l〇l MHz) δ 33.3, MS (ESI, El4) = 349 (MH4). 184 93533 200804280 Description of the structure of the compound 7ai

7aj 7ak 7an 7ao

Light orange powder, also NMR (CDC13, 300 MHz;) δ 3.84 (d, 7 = 11.4 Hz, 3H), 5.97 (brs, 1H), 7.18-7.23 (m, 1H), 7.32-7.56 (na, 5H) , 7.69-7.83 (m, 3H), 10.44 (bra, 1H), 11.04 (brs, 1H), 3lP NMR (C3DC13,1〇1ΜΗζ)δ33.8 5 MS (ESI, Ef) m/r = 315 (MH4 )· Orange powder, 1H miR OirDMSO, 300MHz&gt; δ 3.79 (d, /= 11.4 Hz, 3H), 7.32-7.44 (m, 3H), 7.51- 7.61 (m, 2H), 7.67 (d, 1.8 Hz, 1H ), 8.05 (brs, 1H), 9.86 (brs, 1H), 12.86 (bis, 1H)3 3IP NMR (rf^DMSO, 101 MHz) δ 29.99 (t, J- 83 Hz, IP), l9F NMR (dtf -DMSO, 300MHz) 5-106.93 (m, 2F), MS (ESI, El**) = 385 (MH4). pale yellow powder, b NMR (&amp;DMSO, 300 MHz) δ 3,75 (d, 11.4 Hz, 3H), 7.31-7.38 (m, 3H), 7,54^7.62 (id, 2H), 7.71-7.83 (m, 2H), 8.01 (brs, 1H), 10.10 (brs, 1H), 12.76 ( Brs, 1H), 31P NMR (rfrDMSO, 101 MHz) δ 32.30, 19F NMR (ier DMSO) δ -106.35 (m, IF), MS (ESI, El4) = 367 (MH+). 300 MHz) δ 0.92 (t, 7.5 Hz, 3H), 2.78-2.92 (3⁄4 2H), 3.7 (d, J* 11.7 Hz, 3H), 7.25-738 (m, 4H), 7.52- 7.59 (m, 2H) ), 7.67- 7.75 (m, 1H), 8.02 (brs, 1H), 1036 (bis, 1H), 12.78 (brs, 1H), 3lP NMR (i^DMSO, 101 MHz) δ 32.41, MS (ESI, Bf) m/z = 377 (ΜΗ^. white powder, 1H NMR OVDMSO, 300 MHz) δ 3.75 (d, /= 1L7 Hz, 3H), 7^7 (dd, Z1 and 8.7 Hz, 1H), 7.34 (d, 7= 1.5 Hz, 1H), 7.49-7.65 (m, 4H), 8.04-8.11 (m, 2H), 10.15 (brs, 1H), 12.8 (brs, 1H), NMR (rf^DMSO, 101 MHz) δ 27.33, MS (ESI, El4) m/z^3S3 (MH&quot;). 185 93533 200804280 Compound Structure Description 7ap 7aq 7ar 7as

7au

White powder, 1H NMR (rfrDMSO, 300 MHz) δ 3.75 (4/= Π.7 Hz, 3H), 4.47 (s, 2H), 4.54 (s, 2H), 7.23-7.37 (m, 6H), 7.5- 7.73 (m, 6H), 8.01 (brs, 1H), 10.21 (hrs, 1H), 12.8 (brs, 1H), 31P NMR (rfrDMSO, 121.49 MHz) δ 32.13, MS (ES4) m/z ~ 468.86 (MH4 Light yellow powder, seven MMR (CDCU, 300 MHz) δ 3.88 (d, 11.7 Hz, 3H), 4.73 (s, 2H), 5.98 (brs, 1H), 73-735 (m, 1H)3 7.42- 7.49 (m, 2H), 7.56-7,59 (m, 1H), 7.66-7.73 (m, 2H), 7.8-7.85 (m, 1H), 10.34 (brs, 1H), 10.99 (brs, 1H), <RTIgt; </ RTI> <RTIgt; 4 Hz, 3H), 73-7.34 (3⁄4 1H), 7.4-7.65 (m, 5H), 7.76-7.81 (m, 1H), 8.02 (brs, 1H), 1027 (brs, 1H), 12.75 (brs, 1H), 31P NMR (itf-DMSO, 121.49 MHz) δ 32.29, MS (BS^fn/z-=40SAl(Mit). White powder, lH NMR (CDd3, 300 MHz) S 2.4 (s, 3H), 3.9 (d, J = 11.7 Hz, 3H), 6.1 (brs, 1H), 7.34 (dd, 7 = L8 and 8.7 Hz, 1H), 7^3-7.6 (m, 3H), 7.76-7.85 (m, 2H) ), 10.84 (brs, 1H), 10.92 (brs, 1H), 31P NMR (C〇ah 101.256 MHz) δ 7.27, MS (ES') m/z « 388.3 (MH4). White powder, 1H NMR (d^DMSO, 300 MHz) δ 3 J8 (d, ^ = Π.4 Hz, 3H), 6.60 (d, J = 8.4 Hz, 1H), 734 (d, /= 1.8 Hz, 1H), 7.74 (dd, U and 8.4 Hz, 1H), 8.03-8,18 (m, 3H), 829 (brs, 1H)9 9.67 (bis, 1H), 12.89 (brs, 1H), 3lP NMR (d&lt;rDMSO, 121.49 MHz) δ 27.88, MS (ES〇m/z = 406 (MH4). 186 93533 200804280 Compound Structure Description 7av

White powder, NMR (de-DMSO, 300 MHz) δ 3.78 (d, / = 11.4 Hz, 3H), 7.34 (dd, 7 = 1.8 and 8.4 Hz, IH), 7.42-7.56 (m, 1H), 7.58 -7.73 (m, 3H), 7.80-7.89 (m, 2H), 8.05 (brs, 1H), 10.01 (brs, 1H), 12.86 (brs, 1H), 31P NMR (d^DMSO, 121.49 MHz) δ 30.0 , MS (ES〇τη/ζ = 427/429 7aw

7ax

7ay 7az

187 93533 200804280 Compound Structure Description 7aaa 7aab 7aac 7aad 7aae

188 93533 200804280 Compound Structure Description 7aaf

8a

Grayish white solid; iH NMR (00013, 2501^) 51, 43 (1^= 7.0 Hz, 3H), 2.33 (ε, 6Η), 4.03-4.10 (m, 1Η), 4.28-4.35 (m, 1H), 7.20 (s, 1H), 735 (dd, 2.0 and 8.7 Hz, 1H), 7.41(s, 1H), 7.46 (s, 1H), 7.56-7.60 (m, 1H), 10.7 (brs, 1H), 3tP NMR (CDa3, 101J256 MHz) δ 33.9, MS (ESI, El&quot;) 9a

Light yellow solid, also NMR (CDC13, 300 MHz) δ 1,45 ft·/ -7.2 Hz, 3H), 2.29 (s, 6H), 4^.13 (in, 1H), 4.22-433 (m, 1H ), 4.65 (dd, J = 5.6 and 16.1 Hz, 1H), 4.80 (dd, J-6.1 and 16.1 Hz, 1H), 7.15 (brs, IH), 7.24-7.34 (m, 6H), 7.75 (d, 2.1 Hz, 1H), 8.54-8.56 (m, 2H), 10.60 (brs, 1H), 11.81 (t, J = 5.7 Hz, IH), 31P NMR (CDa3, 101.256 MHz) δ 32.8, MS (ESI, Ef ) /«/z = 482 (MH4). 11a lib

Off-white solid, NMR ('DMSO) δ l, 37 (tJ = 7.2

Hz, 3H), 4.48 (q, /= 7Λ Hz, 2H), 7.59-7.68 (πι, 4H), 7.77 (m, 1H)? 7.96-8.09 (m, 3H), MS (ESI, Et) m/ z « 442^44

Off-white solid, also NMR O^DMSO, 300 MHz) 3 4 (s, 3H), 7.66-7.72 (m, 3H), 7.78-7.83 (m, 1H), 7.93 (c3, J = 9 Hz, 1H), 7.99-8.02 (m, 2H), MS (ES〇m/z = 468.18/470.15 (MH4). 189 93533 200804280 Description of the structure of the compound 11c 14a

Br

Yellow powder, 1H NMR (GDC13, 300MHz) δ 1.46^·/= 72 Hz, 3H), 4.53 (q, /= 7.1 Hz, 2H), 731-7.36 (m, 1H), 7.42-7.59 (m, 5H ), 7.95-8.04 (m, 3H), MS (ESI, El 4); n/z «= 408 (MH4). Colorless oil, 1H NMR (kDMSO, 300 MHz) δ 2·37 (s, 3H), 7.45 (d, /- 544 Hz, 1H), 735 (dd, 2.85 and 7.95 Hz, 2H), 7.57 (d, 13J2 Hz, 1H), 7.6 (d, /- 13.5 Hz, 1H), 31P NMR (CDa3, 101.256 MHz) δ 23.8. 16a

Yellow solid, 1H NMR WrDMSO, 300 MHz) δ 1,37 ft J =72 Hz, 3H), 3.75 (d, 1L7 Hz, 3H), 4.46 (q, 7.2 Hz, 2H), 7.54-7.58 (33⁄4 1H) , 7.67-7.9 (m, 5H), 8.07-8.24 (m, 6H), 3,P NMR (dfi-DMSO, 101.256 MHz) δ 22.98, MS (ES4) m/z = 542.7 (Μΐί). 16b

Viscous yellow oil; also NMR (CDC13, 300MHz) 81.46 (1·/ =7.05 Hz, 3H), 3.8 (d, J = 11.7 Hz, 3H)? 4.54 (q, /= 7.05 Hz, 2H), 732-738 (m, 2H), 7.5-8.1 (m, 10H), 3lP NMR (CDDj, 101^56 MHz) δ 24.54, MS (ES4) m/z = 595.74/597.72 (MEI4). 16c

S02Ph 16d

S02Ph viscous yellow oil, also NMR 0WDMSO, 300 MHz) δ 1.36 (t, /= 7.2 Hz, 3H), 3.7 (d, 11J Hz, 3H), 4.44 (q, /= Hz, 2H), 5.49 (1 , /-47.4 Hz, 2H), 7.54 (dd, 2.1 and 9 Hz, 1H), 7.6-7.B8 (m, 8H), 8.05-8,11 (m, 3H), 3lP NMR (drDMSO, 121.49 MHz δ 23.82, MS (ES&quot;) mJz = 550 (MB〇. Yellow powder, 1H NMR (CDCI3, 300 MHz) δ 1.26 (4 / = 6.9 Hz, 6H), 128 (t, J- 6.9 Hz, 3H), 1.48 (t, J= 6.9 Hz, 3H), 2^6 (quint, ^ = 6.9 Hz, 1H), 3.83 (d, / = 11.4 Hz,, 3H), 4.56 (q, /= 6.9 Hz , 2H), 7.07-7.13 (m, 1H), 7.37 (d4 J = 2.1 Hz and 9.0 Hz, 1H), 7.31-7.40 (m, 1H), 7.49-7.68 (m, 4H), 7.85 (d, J = 1.8 Hz, 1H), 7.95 (dd, J = 9.6 Hz and 1.8 Hz, 1H), 8.08-8.14 (m, 2H), MS (ES4) « 190 93533 200804280 Description Compound Structure 16e

578 (ΜΗ4). Yellow resin, 1H NMR WrDMSO, 300 MHz) δ 0.83 ft J =7.5 Hz, 3H), 138 (t, 7.2 Hz, 3H), 1^5 (sextuplet, 7.5 Hz, 2H), 2.59 ( t, /- 7.5 Hz, 2H), 3.69 (d, 11.7 Hz, 3H), 4.45 (3⁄4 7.2 Hz, 2H), 7.44-7.8 (m, 9H), 8Λ5-8.12 (3⁄4 3H), 31P NMR WrDMSO, 121.49 MHz) δ 24.36, MS (ES4) mlz =3 56038 (MH4). 16f

Viscous yellow oil, also NMR WrDMSO, 300 MHz) δ 2_29 (s, 6H)3 3.64 (d, / == 11.7 Hz, 3H), 4.04 (s, 3H), 7.25-734 (m, 3H), 7.6- 7J5 (m, 3H), 7.81-7.84 (m, 1H), 7.9^7.94 (4) 1H), 8.12-8.16 (4) 2H), MS (4) 550 16g

Gray-white solid, NMR (CDC13, 300 MHz) δ 0.6WJ.71 (m, 2H), 0.91-0.99 (3⁄4 2H), L81-1.94 (m, 1H), 3.69 (s, 3H), 3.79 (d, 11.4 Hz, 3H), 7.13-7.17 (m, 1H), 7.28- 7.4 (m, 3H), 7.51-7.64 (m, 2H), 8.39-8.4 (m, 1H), 9.96 (bis, 1H), 31P NMR (CDa3, 121.49 MHz) δ 31.29. 16h

Viscous yellow oil, NMR WrDMSO, 300 MHz) δ 1.15 (t, 7.5 Hz, 3H), 139 (t, 7 = Hz, 3H) 2.32 (s, 3H), 3.69 (d, / - 11.7 Hz, 3H) , 4.46 (q, /= 7.5 Hz, 2H), 7.29 (brs, 1H), 7.4-7.46 (m, 2H), 7.53-7.56 (m, 1H), 7.63-7.81 (3⁄4 4H), 8.03-8.12 ( m, 3H), 31P NMR (rfrDMSO, 121.49 MHz) δ 24.57, MS (ES^m/z- 560.5 (MH*). 191 93533 200804280 Compound Structure Description 16i 16j 16k 16m

Yellow resin, worm NMR ('DMSO, 300 MHz) S 1·39 ft J = 7.2 Hz, 3H)a 2.35 (s, 3H), 138 (t, 7.2 Hz, 3H), 3.71 (d, J = 11.5 Hz , 3H), 4.46 (q, J= 7.2 Hz, 2H), 7.53-7.85 (m, 8H), 8.05-8.12 (m, 3H), 31P NlviR (^DMSO, 121.49 MHz) δ 22.40, MS (ES&quot; m/x - 610/612 (MH4). Colorless oil, NMR (CDC13, 300 MHz) δ 1.45 ft J = 72 Hz, 3H), 3.80 (d, J = 11.4 Hz, 3H), 4.54 (q, Hz, 2H), 736 (dd3 J = 2.1 and 9.0 Hz, 1H), 7.47-7.67 (m, 6H), 7.84-7.96 (m, 4H), 8.09-E.12 (m, 2H), 31P NMR ( CDa3? 101 MHz) δ 26.7, MS (ESI, El4) == 518 (MH*). Light yellow oil, 1H NMR WrDMSO, 300 MHz) S 1,36^ 7.5 Hz, 3H), 3.69 (d, 11.7 Hz , 3H), 4.45 (q, J= 7.1 Hz, 2H), 7.41 (td, 8.9 and 2.5 Hz, 2H), 7. 54 (dd, / = 9.0 and 2.1 Hz, 1H), 7.66-7.71 (m, 2H), 7.78-7.90 (ro, 4H), 8.05-8.11 (m, 3H), l9F NMR (drOMSO) δ -105.46 (m, IF), 31P NMR (J^DMSO, 101 MHz) δ 24.32, MS ( ESI, Ef) m/z - 558 (M+Na4). oil, 1H NMR (t/r DMSO, 300 MHz) δ 1·38 (t J = 7·05 Hz, 3H), 3.7 (d, 11.7 Hz, 3H), 3.78 (s, 3H), 4.46 (q, J -7.05 Hz, 2H), 7.19-7.4 (m, 3H), 7.47-7.56 (3⁄4 2H), 7.66-7.71 (m, 2H), 7.79-7.81 (m, 2H), 8.06-8.12 (m, 3H), 3lP NMR (rfrDMSO, 101256 MHz) δ 24.91. 192 93533 200804280 Description of compound structure 16η

lR NMR (d^DMSO, 300 MHz) δ 1^7 (t, 7.1 Hz, 3H), 2.29 (s, 6H), 3.66 (d, / = 11.4 Hz, 3H), 4.44 (q, / = 7.1 Hz , 2H), 7.25 (s, 1H), 7.37 (s, 1H), 7.42 (s, 1H), 7.53 (dd, /=2.1 and 9.0 Hz, 1H), 7.65-7.71 (m, 2H), 7.78- 7.83 (m, 2H), 8.05-8.11 (m, 3H), MS (ESI, El^ m/z - 546 16ρ

Brown oil, 1111 &lt;11^11 (heart 0^150, 3001^) 5 1.33 / / 7.05 Hz, 3H), 3.69 (d, /= 11.4 Hz, 3H), 4.42 (q, /= 7.05 Hz, 2H )S 4.52 (s, 2H), 4.57 (s, 2H), 728-7.37 (m, 6H), 7.52-7J8 (m, 9H), 8.05-8.1 (m, 2H), 31P NMR {d^ DMSO, 101.256 MHz) δ 24.18, MS (ES4) m/z = 638(mt). 16q

Yellow oil, worm NMR (rfrDMSO, 300 MHz) 8 7.2 Hz, 3H), 2.4 (s, 3H), 3.73 (d, /= 11.4 Hz, 3H), 4.45 (q, 7.2 Hz, 2H), 7.55 (dd , 1.8 and 8.7 Hz, 1H), 7.66-7.71 (m, 2H), 7.78-7.82 (m, 1H), 7.89-7.9 (m, 2H), 7.94-8.12 (πχ 5H), 31P NMR (^DMSO, 121.49 MHz) δ 22.16, MS (ES4) m/z = 557.4 (MH4).

193 193 white solid, 屯 NMR O^DMSO, 300 MHz) δ 2·33 (s, 3H), 3.73 (d, J-11.7 Hz, 3H), 736-7.43 (m, 3H), 7.57-7.66 (m , 3H), 7.81-7.82 (m, 1H), 13.01 (brs, 1H), 31P NMR (^DMSO, 121.49 MHz) δ 32.55, MS (ES4) m/z« 362 (M-H4). 93533 200804280 Compound structure 17b

</ RTI> <RTIgt; (brs, 1H), 7.36-7.40 (m, 1H), 7.39-7.5 (m, 2H), 7.57-7.61 (take 1H), 7.78 (brs, 1H), 13·01 (brs, 1H), 14.82 ( Brs, s, 1H), 31P: NMR (rf^DMSO, 12149 MHz) δ 32.89, MS (ES4) m/z = 392 (MB4). 17c

Off-white solid, NMROirDMSO, 300 MHz) δ 2.29 3.78 (4 7- 11.7 Hz, 3H), 7^8 (brs, 1H), 7.37 (brs, 1H), 7.42 (brs, 1H), 7.46-7.48 (m , 2H), 13.35 (s3 1H), 31P NMR (drDMSO, 121.49 MHz) 635.15, 19F NMR (drDMSO, 282.40 MHz) δ-115.84 (s, IF) + MS (ES4) m/z - 395.9 (MH4). 17d

Yellow powder, 1H NMR (CDa3, 300 MHz) δ 3.88 (d, /= 12.0 taken 3H), 7.37 (paper 2.0 and 9·0 taken 1H), 7.47-7.63 (?5H), 7.81-7.89 (in, 2H ), 1033 (brs3 1H), MS &lt;ESI, El4) m/z - 350

17e 17f

Oil, 1H NMR (cVDMSO, 300 MHz) δ 3/71 (d3 11.7 taken 3H), 3J6 (s, 3H), 7.13-7J6 (m, 1H), 729-7.45 (m, 4H)3 7.56 (dd, J^ L8 and 9.0 Hz, 1H), 7.91 (d, 1.8 Hz, 1H), 12.86 (brs, 1H), 14.51 (brs, 1H), 31P NMR (d^DMSO, 121.49 MHz) δ 31.68, MS (ESI , El4) m/z = 380 0^114). Light brown oil, 1H NMR ('DMSO, 300 MHz) δ 3.72 (4/ = 11.7 Hz, 3H), 7.25-7.64 (m, 6H), 8.06 (d , 2.1 Hz, 1H), 12.99 (brs, 1H), 31P NMR (i^DMSO, 121.49 MHz) δ 29.23 (d, /= 73 Hz, IP), 19F NMR (^DMSO, 300 MHz) δ -112.01 ( m, IF), MS (ESl9Ef) m/z^36i (MH4). 194 93533 200804280 Description Compound Structure 17g

Oil, 1H NMR WrDMSO, 300 MHz) δ 2·28 (s, 6H), 3·71 (4 11.7 Hz, 3Η), 7.2-7.24 (m, 1Η), 7.36-7.45 (m, 3Η), 7.57- (7.6, m) z = 378 (MH4). 17h

Off-white solid, MS (ES4) 389 (1^1〇· 18a

Pink solid, worm NMR (t^DMSO, 300 MHz) δ 2·3 (s, 3H), 3.76 (d, 11.7 Hz, 3H)? 4.57-4.75 (m, 2H)5 731-7.61 (m, 9H ), 8.52-8.54 (m, 2H), 1137 (t, J « 5.7 Hz, 1H), 12.87 (brs, 1H), 31P NMR (J^DMSO, 121.49 MHz) δ 32.81, MS (ES&quot;) i? z/z - 4535 (MU4). 18b

White solid, 1H NMR (^J DMSO, 300 MHz) δ 2.3 (s, 3H), 3.74 (d, 11.4 Hz, 3H)5 4.56-4.65 (m, 2H), 6.38-6.45 (m, 2H), 7.31- 7.65 (m, 8H), 11.23-1L27 (m, 1H), 12.84 (brs, 1H), 31P NMR (^Dl^SO, 121.49 MHz) δ 32.72, MS (£8^^ = 442.9 (Mif). 18c

White solid, also NMR WrDMSO, 300 MHz) δ 3·78 (4 · / ^ 11.7 Hz, 3H), 4.58-4.74 (m, 2H), 5.46 (d, / - 47.4 Hz, 2H), 7.32-7.38 ( m, 3H), 7-55-7.82 (m, 6H), 8.5U8.53 (m, 2H), 113 (t, J= 5.7 Hz, 1H), 12.92 (d, 7 = 2.1 Hz, 1H), 19F NMR (cirDMSO, 282.40 MHz) δ -211.09 (t, / = 47.4 Hz, IF), MS (ES4) m/z = 472 (MH4). 195 93533 200804280 Compound Structure Description 18d

F

18e

18f

Off-white powder, lH NMR (C〇a3, 300 MHz) δ 2.35 (s, 3H), 3.88 (4/= 11.7 Hz, 3H)a 4.77 (qd, 6 Hz and 15.9 Hz, 2H), 7.04-7.35 (m , 7H), 7.68 (hrs, 1H), 8.59-9.61 (in, 2H), 11.22 (brs, 1H), 11,.71 (t, 5.7 Hz, 1H), 31P NMR (CDa3, 121.49 MHz) δ 32.55 (d, /= 8.2 Hz, IP), ^ NMR (CDC13 &gt; 282.40 MHz) δ -111.55 (q, 82 Hz, IF), MS (ES4) m/z = 471.92 (MH^. pale yellow powder, worm NMR (CDC13, 300 MHz) δ 3.88 (d, J = 1L7 Hz, 3H), 4.7-4.77 (m, 2H), 6.97 (tt, 2.4 Hz and 8.7 Hz, 1H), 7.2-7.33 (m, 6H), 7.64 (brs, 1H), 8.52-8.6 (m, 2H), 11.55-11.58 (m, 2H), 31P NMR (CDC13, 121.49 MHz) 5 31.11 (t, J = 8.5 Hz, IP), 19F NMR (CDC13 , 282.40 MHz) δ -106.21 (m, 2F), MS (ES**) »z/z = 476.17 (MH4). White powder, NMR (CDCI3, 300 MHz) δ 228 (s, 6H), 3.82 ( d, 7= 11.7 Hz, 3H), 4.69 (d4 6 Hz and 15 Hz, 1H), 4.78 (dd, 6 Hz and 15 Hz, 1H), 7.13 (brs, 1H), 7^4-7.28 (m, 5H), 7.29-731 (m, 1H), 738-7.39 (m, 1H), 7.68-7.69 (m, 1H), 7.76-7.8 (m, 1H), 8.56 (dd, /-L5 Hz and Hz, 1H), 8.7 (d, 2.1 Hz, 1H), 31P NMR (CDCI3, 121,49 MHz) δ 34.18, MS (ES4) m/z = 468.33

X8g

White powder, 1H NMR (CDCls, 300 MHz) δ 23 (s, 6H), 3.03 (t, / = 7.2 Hz, 2H), 3.76-3.88 (m, 2H), 3.79 (d, / = 11.7 Hz, 3H ), 7.16-7.3 (m, 6H), 7.47-7.5 (m, 1H), 7.62-7.63 (m, 1H), 8.43-8.45 (m, 2H), 10.83 (brs, 1H), 1136-11.38 (m , 1H), 31P NMR (CDa3, 121.49 MHz) δ 34.38, MS (ES*1) w/z=482.38 (MH4). 196 93533 200804280 Description Compound Structure 18h

White solid, 1H NMR (m DMSO, 300 MHz) δ 226 (s, 6H), 3.75 (d, / - 11.4 Hz, 3H), 4.66 (dd, 5.4 and 15.9 Hz, 1H), 4.78 (dd, /= 5.7 and 15.9 Hz, 1H), 12A (hrs, 1H), 73-7.35 (m, 3H), 7.45-7.49 (m, 1H), 7.6 (dd, J= lg and 9 Hz, 1H), 7.62 (d , 1.8 Hz, 1H), 8.4 (dd, J- 12 and 4.8 Hz, 1H), 8.58 (d, /- 1.5 Hz, 1H)} 1L41 (t, 5.4 Hz, 1H), 12.86 (brs, 1H), 3lP NMR (rfrDMSO, 121.49 MHz) δ 32.81, l9F NMR (rf^DMSO, 282.40 MHz) δ -132.93 (d, 5.9 Hz, IF), MS (ES*1) m/z ^ 4863 (MH4).

White solid, 1H NMR WrDMSO, 300 MHz) δ 2.26 (s, 6H)5 3.75 (d, J = 11.4 Hz, 3H), 4.7 (dd, 5.1 and 15.9 Hz, 1H), 4.84 (dd, 6 and 15.9 Hz , 1H), 7.22 (brs, 1H), 7.33 (dd, 2.1 and 8.7 Hz, 1H), 7.32-736 (m, 2H), 7.59 (dd, 1.8 and 8.7 Hz, 1H); 7.63 (d, /- 1.5 Hz, 1H), 8.6 (dd, 2.55 and 14.4 Hz, 1H)5 8.62 (d, 7- 2.4 Hz, 1H), 8.72 (4 /= 1.5 Hz, 1H), .11.46 (t, /= 5.7 Hz , 1H), 12.87 (brs, 1H), 31P NMR (i^DMSO, 121.49 MHz) δ 32.69, MS = 469.4 (MH4). 18k

White solid, 1H NMR (rfrDMSO, 300 MHz) δ 2.24 (s, 6H), 3.74 (d, 1L7 Hz, 3H), 4.51 (dd, /= 5.25 and 15 Hz, 1H), 4.67 (dd, /- 6.0 And 15 Hz, 1H), 7.22-738 (m, 6H), 7.53-7.64 (m, 4H), 1134 (t, J = 5.7 Hz, 1H), 12.66 (brs, 1H), 31P NMR (^-DMSO , 121.49 MHz) δ 32.79, MS (ES&quot;) = 545.33/54731 (MH*). 181

Gray-white solid, also NMR (drDMSO, 300 MHz) δ 128 (s, 6H), 3.77 (d, /= 11.4 Hz, 3H), 4.64^.82 (m, 2H), 7^4 (brs, 1H), 734 (dd, J = L8 and 8.7 Hz, 1H), 7.36 (fars, 1H), 7.4 (brs, 1H), 7.52 (dd, /= 1.5 and 5.4 Hz, 1H), 151-7.63 (m, 2H) , 8.76 (d, /- 5.1 Hz, 1H), 9.14 (d, 1.5 Hz, 1H), 11.48 (t, 6.0 Hz, 1H), 12.85 (brs, 1H), 31P NMR (d^DMSO, 121.49 MHz) δ 32.68, MS (ES4) m/z - 469.4 197 93533 200804280 Description Compound structure 18m

Grayish white solid, 1珏1&gt;^11(00(33&gt;3001^!1£2;)81.19((^-7.6 Hz, 3H), 2.60 (q, /= 7.6 Hz, 2H), 2.31 (s, 3H) ), 3.84 (4" face 11·7Ηζ» 3H), 4·76 (13⁄42Η), 7.18-7·43 (called 6H), 7·70 (m, ΙΗ), 7.81 (m, 1Η), 8.57 (d , 4.8 Hz, 1H), 8.72 (s, 1H), 10.62 (brs, 1H), 11.78 (t, 7.6 Hz, 1BQ, 31P NMR (CDC13, 121.49 MHz) δ 34.08. 18n

Gray-white solid «, NMR (drDMSO, 300 MHz) δ 224 (s, 6E 〇, 3.74 (d, J = 11^ Hz, 3H), 439 (dd, /*=5.7 and 15.6 Hz, 1H), 4.53 ( Dd* / = 5.7 and 15.6 Hz, 1H), 5.62 (te, 2H), 6.52 (t, /- 7.2 Hz, 1H), 6.63-6.70 (3⁄4 1H), 6.97-7.35 (m, 6H), 7.58- 7.65 (m, 2H)5 1134( t, ^ * 5.7 Ηζ, ΙΗ), 12.66 (bis, 1H), 31P NMR (d^DMSO, 121.49 MHz) δ 851, MS (ES4) τη^-482 (ΜΗ4) . 18p

Off-white powder, also NMR (drDMSO, 300MHz) δ 1.12 (t, 7.5 Hz, 3H), 228 (s, 3H), 2.58 (q, 7.5 Hz, 23⁄4 3.77 (d, 11.7 Hz, 3H), 4.68 (dd, 5.4 and 17.1 Hz, lH)a 4.78 (dd, 5.7 and 16.8 Hz, 1H), 7.27 (brs, 1H), 733 (dd, 2.1 and 8.7 Hz, 1H), 7.36-7.46 (m, 2H), 7.52 ( D4 1*2 and 5.1 Hz; 1H), 7.60 ((13⁄41" and 8.7 Hz; 1H), 7.63 (d, J-L5 Hz, 1H), 8.76 (d, 5.4 Bz, 1H), 9.14 (d, / = 12 Hz, 1H), 11.47 (t, 5.4 Hz, 1H), 12.82 (te, 1H), 3lP NMR (&lt;frI&gt;MSO, 121.49 MHz) δ 32.62, MS (ES^m/s^AZS (MET ). 18q

Gray-white solid, also NMR (&lt;i&lt;rDMSO, 300 MHz) δ 3.78 (d, 11.7 Hz, 3H)t 4.6 W.78 (m, 2H), 735 (dd, 2.1 and 8.7 Hz, 2H), 738 -7.41 (m, !H), 7.5-7.55 (13⁄4 1H), 7.57-7.6 (m, 3H), 7.73 (d, J* 2.1 Hz, 1H), 7.82-7.85 (m, 2H), 10.87-10.91 (m, 1H), 1256 (te, 13⁄4 MS (ES4) w/r = 49835 (MH4). 198 93533 200804280 Compound Structure Description 18r

Gray-white solid, also NMR (4rDMSO, 300 MHz) δ 2.27 (s, 6H), 3.72 (d, 11.7 Hz, 3H), 4.65-4.68 (m, 2H), 7.22 (brs, 1H), 7.29 (brs, 1H ), 7.33 (brs, 1H), 738-7.48 (m, 4H), 8.53-8.55 (m, 2H), 11.86 (t, /- 5.4 Hz, 1H), 13.08 (brs, 1H), 31P NMR (i ^DMSO, 121.49 MHz) δ 32.16, MS (£5^)/^ = 485.9 (MH4). ISs

18t

18u

199 93533 200804280 Description Compound Structure 18v 18w 18x 18y

Cl

Cl

P^OMeN^° N HN

200 93533 200804280 Compound Structure Description 18z

18aa

18ab

N 18ac

201 93533 200804280 Description Compound Structure

N

N 18ad 18ae 18af 18ag

OMe

Cl

£

N

202 93533 200804280 Description Compound Structure

18ah 18ai 18aj ISak

Bu OMe C!

HN_V/F-〇

203 93533 200804280 Description Compound Structure

204 93533 200804280 Compound Structure Description 18ap 18aq 18ar 18as

Light yellow powder, worm NMR (drDMSO, 300 MHz) δ 1.12 (ΐ, 7.5 Hz, 3H), 2.61 (qt /= 7.5 Hz, 2H), 3.77 (d, /- 11.7 Hz, 3H), 4.61 (dd, 5.4 and 15,9 Hz, 1H), 4.72 (dd, J = 6.0 and 15.9 Hz, 1H), 731-7.61 (m, 9H), 8.51-8.53 (m, 2H), 11.4 ft 5.4 Hz, 1H), 12.87 (brs, 1H), 3lP NMR (tf6-DMSO, 121.49 MHz) δ 32.74, MS (BS4) tw/z = 467.89 pale yellow powder, iHNMR (4-DMSO, 300 MHz) δ 1.15 (d, 6.9 Hz, 6H), 2.9 (quintuplet, J-6.9 Hz, 1H), 3.77 (d, /- 11.4 Hz, 3H), 4.61 (dd, 5.4 and 16.5 Hz, 1H), 4.72 (dd, J = 6 and 16.2 Hz, 1H), 733 (dd, J - 2.1 and S.7 Hz, 1H), 737^7.39 (m, 2H), 7.41-7.54 (in, 3H), 7.58-7,66 (m, 3H), 8.52^ 8.54 (m, 2H), 11.42 (t, /= 5.7 Hz, 1H), 12.87 (bis, 1H), 3IP NMR (rf6-DMSO, 121.49 MHz) δ 33.64, MS (ES4) m/z - 481.94 Solid, ^ NMR (CDC13, 400 MHz) S 3.86 (4 11.8, 3H), 4.67 (dd, 5.7 and 15.9 Hz, 1H), 4.79 (dd, /= 6.0 and 15.9 Hz, 1H), 7.25-7.28 (dd , 1.9 and 8.4 Hz, 1H), 7.30-7.34 (m, 3H), 7.41-7.45 (m, 2H), 7.52-7.56 (m, 1H), 7.69-7.75 (m, 3H), 8.55-8.57 (in , 2H), 10.7 6 (s, 1H), 11.72 (t, /= 5.8 Hz, 1H), 31P NMR (CDa3, 101 MHz) δ 34.2, MS (ESI, ΕΙ&quot;*) m/z « 440 (Μΐί). White powder, 1H NMR WrDMSO, 300 MHz) δ 3.62 (s, 3H)5 3.74 (d, / = 11.7 Hz, 3H), 4.53-4.67 (m, 2H), 6.9 (brs, 1H), 7.32 (dd, 1.8 and 8.7 Hz, 1H), 7.46-7.65 (m, 8H), 11.09 (t, 7 = 5.1 Hz, 1H), 12.85 (hrs, 1H), 3lP NMR (JrDMSO, 10U56 MHz) δ 33.71, MS (ESI, El4) w/z = 443 (MH4). 205 93533 200804280 Description of compound structure 18at

Off-white powder, NMR WrDMSO, 300 ΜΗζ) δ 3.76 (d, 11.4 Hz, 3H), 4.56 (dd, /= 4.8 and 15.6 Hz, 1H), 4.66 (dd, J- 5.7 and 15.6 Hz, 1H), 6.38 -6.45 (m, 2H), 7.33 (dd, 2.1 and 8.7 Hz, 1H), 7.48-7.7 (m, 8H), 11.21 (t, J « 5.25 Hz, 1H), 12.86 (brs, 1H), 31P NMR DMSO, 101.256 MEIz) δ 33.59, MS (ESI, El4) iw/z = 429

Yellow powder, 1H NMR (CDC13, 300 MHz) δ 3.76 (s, 3H)5 3.84 (d, J = 1L4 Hz, 3H), 4.7 (dd, = 5-1 and 15.6 Hz, 1H), 4.83 (dd, J = 5.5 and 15.75 Hz, 1H), 6.33-6.36 (m, 2H), 7-7.04 (m, 1H), 7.23-7.32 (m, 4H), 7.38-7.4 (m, 1H), 7.48 (dd, /= 1.5 and 8.7 Hz, 1H), 7.7 (d, 2.1 Hz, 1H), 11.61-11.64 (m, 2H), 31P NMR (CDa3, 12L49 MHz) δ 33.64, MS (ESI, E〇tw/z = 459 (MH4). 18av

Light yellow powder, NMR (C〇a3, 300 MHz) δ 3.76 (s, 3H), 3.86 (d, /*= 11.7 Hz, 3H), 4.69 (dd, /= 5.7 and 15.9 Hz, 1H), 4.83 (dd, /= 5.7 and 15.9 Hz, 1H), 7.03-7.07 (m, 1H), 7.2-7.37 (m, 7H), 7.71 (hrs, 1H), 8.55-8.58 (m, 2H), 11.48 (brs , 1H), 11.8 (t, 5.7 Hz, 1H)3 31P NMR (σ)α3,121.49 MHz) δ 33·93, MS (ESI, El4) wi/r = 470 (MHT&quot;). 18aw

Light yellow solid, lH NMR (&amp;DMSO, 300 MHz) δ 3.78 (d, J « 11.7 Hz, 3H), 4.65 (m, 2H), 7.33-7.65 (m, 9H), 8.52 (d, J = 6 Hz, 2H), 1L13 (t, / = 5.5 Hz, 1H), 12.94 (brs, 1H), 3lP NMR (rfrDMSO, 121.49 MHz) δ 3076 (d, 7.4 Hz, IP), 19F NMR (rfrDMSO, 300 MHz δ -111.0 (m, IF), MS (ESI, El4) m/z = 458 (MH4). 206 93533 200804280 Description Compound Structure 18ax

Yellow powder, worm NMR WrDMSO, 300 MHz) δ 2.25(s, 6H), 3.75 (d, 11.4 Hz, 3H), 4.6 (dd, J = 5.4 and 16.2 Hz, 1H), 4.72 (dd, /= 5.7 and 16.2 Hz, 1H), 7^4-7, 39 (m, 6H)&gt; 7.59-7.63 (m, 2H), 8.52-8.54 (m, 2H), 11,41 (t, J-5.7 Hz, 1H ), 12.86 (brs, 1H), 31P NMR (^DMSO, 121.49 MHz) δ 32.88, MS (ES4) mJz = 467.9 (MH4). 18ay

White powder, worm NMR (CDC13, 300 MHz) δ 2,3 (s, 6H), 2J-2.75 (m, 4H), 3.73-3J7 (m, 4H), 3.86 (d, /= 11J Hz, 3H) , 4.43 (dd, / - 5.7 and 12.9 Hz, 1H), 4.52 (dd, J = 6 and 12.9 Hz, 1H), 7.17 (brs, 1H), 7.32 (dd, J-2.1 and 8.7 Hz, 1H), 736 (bis, 1H), 7.41 (brs, 1H), 7.49 (dd, /= 2.1 and 8.7 Hz, 1H), 7.71-7.72 (m, 1H), 10.5 (bxs, 1H), 11.46 (t, /= 5.7 Hz, 1H), 31P NMR (CDC13, 101.256 MHz) δ 34.52, MS (ES4) mh = 475.87 (MH4). 18az

Light yellow powder, also NMR (&amp;DMSO, 300 MHz) δ 2.24 (s, 6H), 3.73 (d, 11.7 Hz, 3H), 4.56 (dd, 5.4 and 15.3 Hz, 1H), 4J3 (dd, /= 5.4 and 15.3 Hz, 1H), 7-15-7.4 (m, 7H), 7.47 (td, 1.8 and 7.5 Hz, 1H), 7.59 (dd, /= 1.8 and 8,1 Hz, 1H), 7.63 (d , 2.1 Hz, 1H), 1132 (t, 54 Hz, 1H), 12.83 (brs, 1H), 31P NMR (dr DMSO, 121.49 MHz) S 32.76, 19F NMR (^DMSO, 2E2.40 MHz) δ -118.4 (m, IF), MS (ES4) * 485

18aaa

N 207 white powder, 1H NMR O^rDMSO, 300 MHz) δ 2·25 (s, 6H), 3.66 (s, 3H), 3.72 (d, 11.7 Hz, 3H), 4.52-4.7 (m, 2H), 6.9 (brs, 1H), 7.22 (brs, 2H), 7.26 (brs, 1H), 7.33 (dd, /= 2.1 and 9.3 Hz, 1H), 7.59-7.61 (m, 3H), 1L17 (t, /= 5.1 Hz, 1H), 12.83 (bra, 1H), 3lP NMR (^DMSO, 121.49 MHz) δ 32.93, MS (ES〇m/z=47136 (MlT). 93533 200804280 Description Compound Structure 18aab

Off-white powder, NMR (&amp;DMSO, 300 MHz) δ 3.75 (d, / = 11.7 Hz, 3H), 4J8 (dd, 5.1 and 15.3 Hz, 1H), 4.7 (dd, J « 5.7 and 15.3 Hz, 1H ), 7.17-7.28 (m, 2H), Ί32-1.52 (m, 5H), 7.57-7.7 (m, 5H), 11J24 (t, J= 5.4 Hz, 1H), 12.87 (brs, 1H), 3lP NMR (rf^DMSO, 121.49 MHz) δ 32.64, NMR (^DMSO, 282.40 MHz) δ -118.41 (m, IF), MS (BS^) m/z = 456*8 18aac

Off-white powder, 1 ugly 1^111 (〇1 &gt; 013, 30〇]\1112;) 52.67-2.72 (m, 4H), 3.71^3.75 (m, 4H), 3.86 (d, J - 11.7 Hz, 3H) , 4.39-4.5 (m, 2H), 7.3 (dd, J*= 1.8 and 8.7 Hz, 1H), 7.41-7.54 (m, 4H), 7.66-7.67 (m, 1H), 7.73-7.81 (m, 2H ), 10.49 (brs, 1H), 11.42 (t, / = 5.7 Hz, 1H), 31P NMR (CDQ3, 121.49 MHz) δ 33.56, MS (ES4) m/z = 447.92 18aad

Light yellow powder, h NMR (rfrDMSO, 300 MHz) δ 3.78 (d, Π.7 Hz, 3H), 4.54-Φ.74 (m, 2H), 7.16-7.28 (m, 2H), 7^8-7.65 (m, 7H), 7 J4-7.75 (m, 1H), 10.84 (bis, 1H), 12.95 (brs, 1H), 3lP NMR (d, -DMSO, 12L49 MHz) δ 2936, 19F NMR (^DMSO, 282.40 MHz) δ -138 (m, IF), -126.5 (m, 2P), MS (ES4) m/z = 493 (MS1). 18aae

White powder, 1H NMR (drDMSO, 300 MHz) δ 3·64 (s, 3H), 3.77 (d, 7- 11.4 Hz, 3H), 4.54^.67 (in, 2H), 6.91 (brs, 1H), 7.33-739 (m, 3H), 7.5-7.62 (m, 3H), 7.67-7.68 (m, 1H), 10.68-10.72 (m, 1H), 12.95 (brs, 1H), 3,P NMR (rfr- DMSO, 121.49 MHz) δ 30.92 (ζ J= 8.5 Hz, IP), 19F NMR O^DMSO, 282.40 MHz) δ -106.77 (4) 2F), MS (£8^7^ = 479(1^). 208 93533 200804280 Compound Structure Description 18aaf

Light yellow powder, ^ NMR (CDa3, 300 MHz) δ 239 (s, 3 Η), 3.88 (d, J - 11.7 Hz, 3H), 4.76 (d, · / = 5.4 Hz, 2H), 7 J5-7.33 ( m, 4H), 7.57-7.61 (m, 2H), 7.71-7.8 (m, 2H), 8.58-8.6 (m, 2H), 11JZ7 (brs, 1H), 11.59 (1, 5.4 Hz, 1H), 31P NMR (CDC13, 121.49 MHz) δ 31.35, MS (ES&quot;)/^ = 479.35 (MH4). 18aag

N pale yellow powder, NMR (CDC13, 300 MHz) δ 2.39 (s, 3H), 3.72 (s, 3H), 3.84 (d, J = 1L4 Hz, 3H), 4.71 (d, J = 5.4 Hz, 2H) , 7.12 (s, 1H), 7.32 (dd, 7 = 1.5 and 8.7 Hz, 1H), 7.47-7.59 (m, 4H), 7.66-7J4 (m, 2H), 1121 (brs, 1H), 11.38 (t , J = 5.4 Hz, 1H), 31P NMR (C〇as, 121.49 MHz) δ 31.21, MS (ES〇w/z-482.38 (MH4). 18aaj

Off-white solid, also NMR (d^DMSO, 300 MHz) δ 224 (s, 6H), 3.72 (d, ·-- 11J Hz, 3H), 4.53 (dd, 5.1 and 153 Hz, 1H)S 4.68 (dd, /= 5.4 and 15 Hz, 1H), 7.06-7.12 (m, 1H), 721-7.34 (m, 5H), 7.48-7.53 (3⁄4 1H), 7.58 (dd, 7= 1.8 and 8.7 Hz, 1H), 7.63 (d, 1.8 Hz, 1H), 1129 (t, J = 5.1 Hz, 1H), 12.82 (hrs, 1H), 31P NMR (de-DMSO, 121.49 MHz) δ 32.79, MS (ES4) tw/z = 503 (MB〇. 18aak

Off-white solid, NMR (d^DMSO, 300 MHz) δ 2.26 (s, 6H), 3.74 (d, 11.4 Hz, 3H), 4.60 (dd, 5.4 and 15.3 Hz, 1H), 4.77 (dd, J « 5.4 and 153 Hz, 1H), 7.22 (brs, 1H), 729 (brs, 1H), 731-738 (m, 4H), 7.49-7.52 (m, 2H), 7.6 (dd, J= 1.5 and 9 Hz, 1H ), 7.64 (d, J= L8 Hz, 1H), 11.35 (t, /= 5.4 Hz, 1H), 12.84 (brs, 1H), 3lP NMR (d^ DMSO, 121.49 MHz) δ 3272, MS (ES4) 7«/z = 501 (MH4) 209 93533 200804280 Description Compound structure ISaal

Light yellow solid, NMR (d^DMSO, 300 MHz) δ 2.24 (s, 6H), 3.73 (d, / = 11.7 Hz, 3H), 4.71 (dd, J = 4.8 and 15.3 Hz, 1H), 4.85 ( Dd, / = 4,8 and 153 Hz, 1H), 7.22-731 (3⁄4 3H), 7.32 (dd, 21 and 8.7 Hz, 1H), 7.5-7.56 (m, 1H), 7.6 (dd, 1.8 and 9 Hz, 1H), 7.64 (dd, 1.8 and 10.5 Hz, 1H), 7.67 (d, /= 1J2 Hz, 1H), 7J6-7.79 (m, 1H), 1138 (t, /= 5.4 Hz, 1H), 12.86 (brs, 1H), 31P NMR (cVDMSO, 121.49 MHz) δ 32.74, MS (ES4) m/z - 535 18aam

White powder, 1H NMR (d^DMSO, 300 MHz) δ 2.26 (s, 6H), 3.75 (d, 11.7 Hz, 3H)5 4.64 (dd, /- 5.4 and 15.9 Hz, 1H), 4.78 (dd, 6 And 15.9 Hz, 1H), 7.23 (brs, 1H), 7.29-7.42 (m, 5H), 7.6 (dd, 7= 1.5 and 8.7 Hz, 1H), 7.65 (d, 7 = L8 Hz, 1H), 7.78 (td, J = 1.8 and 7.5 Hz, 1H), 8.54-8.57 (m, 1H), 1139 (t, /= 5.7 Hz, 1H), 12.82 (bre, 1H), 31P NMR (dfi-DMSO, 121.49- MHz) δ 32.70, MS (ES4) m/z - 468 (MET1) 18aan

White powder, NMR (d&lt;rDMSO, 300 MHz) δ 2.26(s, 6H)? 3.69 (d, /- 11.7 Hz, 3H), 4.65 (ddd, J-5.7 and 15.3 and 21.6 Hz, 2H), 7.21 (brs, 1H), 7.25 (brs, 1H), 73 (brs, 1H), 7.37-7.45 (m, 2H), 7.46 (dd, 1.5 and 8.7 Hz, 1H), 7.82 (td, /= 1.8 and 7.8 Hz, 1H), 8.49 (dd, 1.95 and 4.65 Hz, 1H), 8.64 (d, J - 1.8 Hz, 1H), 11.81 (t, 5.7 Hz, 1H), 13.06 (brs, 1H), 31P NMR (de -DMSO, 121.49 MHz) δ 32.10, MS (ES4) m/z-4S6 (MH〇18aao

Light yellow solid, 4 NMR ('DMSO, 300 MHz) δ 3.75 (d, J- 11.4 Hz, 3H), 5,67 (d, 7.5 Hz, 1H), (brs, 1H), 7.85 (dd, /= 1.8 and 8.7 Hz, 1H), 7.85-7.95 (m, 3H), 8.02-8.16 (m, 6H), 8.22 (d, J - 1.8 Hz, 1H), 8.28 (brs, 1H), 8.46-8.53 (m , 2H), 11.47 (d, 7.5 Hz, 1H), 12.76 (bis, 1H), 31P NMR (d«-DMSO, 121.49 MHz) δ 31.79, MS (ES4) ^4 = 482 (1^ 210 93533 200804280 Description Compound Structure 18&amp;ap

Off-white solid, lH NMR (d^-DMSO, 300 ΜΗζ) δ 3.80 (4 / - 11.4 Hz, 3 Η), 5.63 (d, 7.5 Hz, 1H), 7.2 (hrs, 1H), 7.33 (dd, 2.1 and 8.7 Hz, 1H), 7.33-7.45 (m, 5H), 7^2-7.61 (m, 6H), 7.69 (d, ^ - 2.1 Hz, 1H), 7.77 (bis, 1H), 1132 (d, 7= 7.5 Hz, 1H), 12.8 (brs, 1H), 31P NMR (&lt;VDMSO, 121.49 MHz) δ 32.12. ISaaq

White solid, NMR (drDMSO, 300 MHz) δ 3.77 (Jiang-11.4 Hz, 3H), 5.34 (d, 1L1 Hz, 1H), 5.86 (d, /- 17 J Hz, 1H), 6.79 (dd, 11.1 And 17.7 Hz, 1H), 7.32 (dd, 7= 2.1 and 8.7 Hz, 1H), 7.48-7.61 (m, 4H), 7.73 (dd, 1.5 and 7.8 Hz, 1H), 7.78-7.83 (m, 1H) , 8.03 (brs, 1H), 10.2 (brs, 1H), 12.8 (brs, 1H), 31P NMR (d^DMSO, 121.49 MHz) δ 3L86, MS (ES4) wfe = 374.83 (MH4) 18aar

Viscous off-white solid, $^411(0003,300^1112:)53.84 (4/= 11.4 Hz, 3B〇, 4.70 (dd, ^=r 5.4 and 15 Hz, 1H), 485 (dd, /- 6 and 15 Hz, 1H), 7.16 (dd, /= 1.8 and 8.7 Hz, 1H), 7.22-7.51 (m, 9H), 7.65-7 J3 (m, 3H), 11.63 (brs, 1H), 11.68 ( t, 7= 5.4 Hz, IH), 31P NMR {CDCi3p 121.49 MHz) δ 33.98, MS (ES**) tm/z = 438.87 (MET) 18a

18aat

211 93533 200804280 Compound 19a 19b 19c 19d 19e 19f 19g 19h Structure Description

Colorless oil, NMR (CDC13, 300 MHz) δ 3·76 [4«/= 11.1 Hz, 3H), 7.44-7^8 (m, 3H), 7.76-7.84 (m, 2H), 31P NMR (CDa3j 101.256 MIL·;) δ 22.2. Colorless oil, 4 NMR (CDC13, 300 MHz) δ 3 1 (4·/= 1U Hz, 6H), 7.59-7.66 (m, 1H), 7,84-7.87 (m , 1H), 8-8.1 (m, 2H), 31P NMR (CDC13, 121.49 MHz) δ 17.94, MS (ES4) s-212 (MH). colorless oil, NMR (C〇a3, 300 MHz) S 1 ·27 = 7.5 Hz, 3H), 2.72 (q, /= 7.5 Hz, 2H), 3.78 (d, /- 11.1 6H), 7.4-7.43 (3⁄4 2H), 7.59-7.69 (m, 2H), MS ( ES*1) m/r«215(MH). Oil, NMR (C〇a3, 300 MHz) δ 3.77 (d, 11·1 taken 6H), .7.28-7.39 (m, 2H), 7.57-7.66 (m, 2H), MS (ES4) w^ = 201 (MH). , h—P-OMe ΟΜθ F x~f OMe

Colorless oil, 1H NMR (CDC13, 300 MHz) δ 3/78 (4/ = 11.4 Hz, 6H), 733-7.4 (m, 1H), 7.69-7.77 (m, 2H), 7.91-7.96 (m, 1H 31P NMR (CT>a3i 121.49 MHz) δ 19.2, MS (ES^m/z^ 265/267 (MH). Colorless oil, 1H NMR (CDCU, 300 MHz) δ 3.79 (4/= 1L1 Hz, 6H ), 5.44 (d, /- 47.4 Hz, 2H), 7.5-7.63 (m, 2H), 7.78-7.85 (m, 2H), 31P NMR (CDCfe, 121.49 MHz) δ 22, , 9F NMR (CDC13) 282.40 MHz) δ -209.94 (t, 47.4 Hz, IF), MS (ES&quot;) /w/z « 219 (MH). Yellow oil, lH NMR (CDC13, 300 MHz) δ 2.41 (s, 3H), 3.77 (d, /« 1L1 Hz, 6H), 7.06-7.1 (m, 1H), 724-7.32 (m, 1H), 7.4-7.44 (m, 1H), 31P NMR (C〇a3, 121.49 MHz) δ 20.13 (&lt;!, /= 9.7 Hz, IP), l9F NMR (CDa3, 282.40 MHz) δ 12.5 (m, IF). colorless oil, NMR WrDMSO, 300 MHz) δ 0.89 (t, J = 7.5 Hz, 3H), 1.6 (sextuplet, J=7.5Hz, 2H), 2.63 (t, J= 7.5 Hz, 2H), 3.65 (d, J- 11.4 Hz, 3H), 3.654 (d, /- 1L1 Hz, 3H) , 7.47-7.50 (3⁄4 3H), 7.54-7.55 (m, 1H), 31P NMR (4-DMSO, 121.49 MHz) δ 21.04, MS (ES4) w/z - 2293 212 93533 200804280 Compound Structure Description 19

Ρ-ΌΜθ OMe 13⁄4 19k 191 19m

F 19n

p-OMe colorless oil, NMR WrDMSO, 300 MHz) δ 1,18 ft / =7.5 Hz, 3H), 235 (s, 3H), 2.63 (q, /= 7.5 Hz, 2H), 3.64 (d, 11.1 Hz, 3H), 3.65 (d, /= 1L1 Hz, 3H), 7.31 (bis, 2H), 7.45-7.48 (m, 1H), 3lP NMR (rfrDMSO, 121.49 MHz) δ 21.40, MS (ES*1) m/z = 229.3 (Μΐί). colorless oil, NMR WrDMSO, 300 MHz) δ 0.68-0.74 (m, 2H), 0.97-1.03 (m, 2H), 2-2.07 (m, 1H), 3.65 (d , J = 11.1 Hz, 3H), 7.29-7.33 (m, 1H), 7.4-7.49 (m, 3H), 31P NMR (^DMSO, 121.49 MHz) δ 21.05, MS (ES4) m/z = 227 (MH4) Colorless oil, NMR OWOMSO, 300 MHz) δ 2.37 (s, 3H), 3.67 (d, /= 11.1 Hz, 3H), 7.51-7.72 (m, 3H), 3IP NMR (d^DMSO, 121.49 MHz ) δ 18.44, MS (ES4) m/z = 279/281 (MH4). 'Yellow oil, ^NMR (0003,3001^)3127 bait/=6.9 Hz, 6H), 2.95 (quintuplet, 6.9 Hz, 1H) , 3.77 (d, /* 1U Hz, 6H), 7.39-7.46 (m, 2H), 7.56-7.7 (m, 2H), 31P NMR (CDa3, 121.49 MHz) δ 22.41. Colorless oil, NMR (C〇 A3, 300 MHz) δ 3.8 (4/ = 11.1 Hz, 6Η), 6.98-7.05 (m, 1H)? 7.27-7.36 (m, 2H), 3lP NMR (CDa33 121.49 MHz) δ 17.87 (3⁄4 /= 9.96 Hz , IP), I9F NMR (CDa3, 282.40 MHz) δ -107.27 (m, 2F). Yellow oil, NMR (rfr DMSO, 300MHz) δ 3·65 (He 1U Hz, 6H), 3.8 (s, 3H), 7.1Φ-7.31 ( m, 3H), 7.45-7.52 (m, 1H), 31P NMR (rfrDMSO, 121.49 MHz) δ 20.45, MS (ESI, Ef) m/z-= 217 2 (Mit) 19p \-^ 〇1H NMR (^ DMSO, 300 MHz) δ 233 (s, 6H), 3.63 P-OMe (d, J= 11.1 Hz, 6H), 7^8-7.29 (m, 2H), 7.32-7.34 (m, )~^ OMe 1H ), 3lP NMR (rfrDMSO, 121.49 MHz) δ 21.34, MS Qing El, = 213 93533 200804280 Compound Structure Description 19q

19r DBn

OMe 20a 20b

20c 20d

)=\ M - OMe λ^f OH )=\ π 4 P—ΟΜθ N^f OH 20e F 〈\ /)-P - 〇Me 20f

Oil, worm NMR (CDC13, 300 MHz) δ 3.79 (3⁄4 1U Hz, 6H), 7.25-7.3 (m, 1H), 7.43-7.64 (m, 3H), 31P NMR (C〇a3, 101.256 MEs) δ 20 (4 J β 8·66 Hz» IP), 19F NMR (CDa3 &gt; 282.4 MHz) δ -130.9 (m, IF), MS (ESI, Ε〇ι«/ζ&quot;205 (ΜΗ4). Oil, 1HNMR WrDMSO, 300 MHz) δ 3·65 (4 11.1 Hz, 6E〇, 4.56 (s, 2H), 4.61 (s, 2H), 7.28-7.41 (m, 4H), 7.51-7.71 (m, 5H), 31P NMR ( ^DMSO, 121.49 MHz) δ 20.68; MS (ES4) mk = 307 (MH4) colorless oil; 1H NMR (CDCI3, 300 MHz) δ 3.71 and 3J4 (2s, 3H), 7.41-7.54 (m, 3H)5 7.77 -7.84 (m, 2H), 10.70 (brs, 1H); 31P NMR (CDa3, 101 MHz) δ 22.3. colorless oil, NMR (CDC13, 300 MHz) δ 3.76 (4J = 11.4 Hz, 3H), .7.57 -7.64 (m, 1H), 7.82-7.85 (m, 1H), 7.99-8.1 (m, 2H)a 8.9 (brs, 1H), 31ί&gt; NMR (CDa3, 121.49 MHz) δ 18 J3, MS (ES4) m/z = 197.9 (MH). colorless oil; 1H NMR (CDC13, 300 MHz) S 2.37 (s,3H)3 3.71 (d,J= 11.4 Hz, 3H), 732-7.35 (m, 2H), 7.58 -7.64 (m, 2H), 10.73 (brs, 1H), (ES4) m/fe -187 (MH). Colorless oil, NMR (〇&gt;a3, 300 MHz) S 3.71 (4·/= 11.1 Hz , 3H), 7.2 6-7.32 (m, 1H), 7.65-7.95 (m, 4H), 3lP NMR (C〇a3, 121.49 MHz) δ 19.07, MS (ES4) = 251/253 (MB〇. Colorless oil, ^ NMR (CDCls , 300 MHz) δ 375 (4·/ = 11.4 Hz, 3H), 5.42 (d, /= 47.4 Hz, 2H), 7.4-7.6 (m, 3H), 7.8-7.85 (m, 2H), 31P NMR ( </ RTI> </ RTI> <RTIgt; 〇13,300]^) 5 0.93 ··/» 7.5 take 3H),1·64 (scxtipK ·/ = 7.5 Hz, 2H), 2.6 ft / = 7.5 Hz, 2H)5 3.71 (d, /-11.4 Hz , 3H), 7.34-737 (m, 2H), 7.59-7.66 (m, 2H), 9.78 (brs, 1H), 31P NMR (CDa3, 121.49MHz) δ 22.76, MS (ES4^ m/z- 215.2 ( MH4). 214 93533 200804280 Compound Structure Description 20g

20h

20i

Colorless oil, NMR WrDMSO, 300 MHz) δ 2.36 (s, 3H), 3.53 (d, / = 10.0 Hz, 3H), 7.47-7.64 (m, 3H), 31P NMR (i^DMSO, 121.49 MHz) δ 14.79, MS (ES^) m/z - 263/265 (MH4). Light yellow oil, NMR (CDC13, 300MHz) δ 125 ((1,7 =63 Hz, 6H), 2.89-2.98 (m, 1H) 3.72 (d, 11.4 Hz, 3H), 6.59 (brs, 1H), 7.34-7.43 (m, 2H), 7.59-7.69 (m, 2H), 31P NMR (CDa3, 121.49 MHz) δ 23.21. Oil, 1H NMR (CDC13, 300 MHz) S 1.24 (ζ·/ -75 Hz, 3H), 2.67 (q, /- 7.5 Hz, 2H), 3.72 (d, J- 11.4 Hz, 3H), 7.35-739 (m, 2H), 7.59-7.67 (m, 3H), 31P NMR (CI) a3, 121.49 MHz) δ 23.07, MS (ES4) m/z - 201 20j

P-OMe OH yellow oil, NMR (C〇a3, 300 MHz) δ 3·66 (4 J = 11.4 Hz; 3H), 6.92-6.98 (m, 1H), 724-731 (m, 2H), 7.64 ( Brs, 1H), 31P NMR (CT>C13, 121.49 MHz) δ 16.92. 20k 201 20m

Oil, 1H NMR (CDCU, 300 MHz) δ 2.37 (s, 313⁄4 3·Ή (at J = 11.4 Hz, 3H), 7.02-7.05 (m, 1H), 7.24-732 (3⁄4 1H), 736-7.41 ( m, 1H), 3lP NMR (CDa3, 121.49 MHz) δ 19.66 (d, 9.6 Hz, IP), 15F NMR (CDC13, 282.40 MHz) δ-112.7 (3⁄4 «7=9.32 Hz, IF). Yellow oil, 咕NMR (4DMSO, 300 MHz) δ 3.51 (4/ =11.1 Hz, 3H), 3.79 (s, 3H), 7.12-7.28 (m, 3H), 739-7.46 twisted 1H), 31P NMR (cfrDMSO, 101.256 MHz) S 17.03, MS (ESI, El4) m/z « 203.2 (MH4). Light pink oil, lH NMR (&amp;DMSO, 300 MHz 〇δ 3.53 03⁄4 / =11.1 Hz, 3H), 737-7.62 (π) , 4H), 31P NMR (^DMSO, 101.256MHz) δ 15.11 (d?J-8.77Hz, IP), 19FNMR (^ DMSO, 23536 MHz) δ -111.8 (m, IF), MS (ESI, El4) w /z=191 (MH4). 215 93533 200804280 Description of the structure of the compound \—^ eucalyptus oil, 1H NMR (rfrDMSO, 300 MHz) δ 2·31 (s, 6H), 3.50 20n p-〇H (d, J - 11.1 Hz, 3H), 7.20 (s, 1H), 7.26 (s, 1H), 731 (s, /^ OMe 1H), 12.03 (brss 1H), MS (ESI, El4) w/z = 201 (MH4) oil , worm NMR WrDMSO, 300 MHz) δ 3.51 (4 11·4 20p OBn

Hz, 3H), 4.56 (s, 2H), 4.59 (s, 2H), 7.3-7.71 (3⁄4 9H), 31P NMR (^5-DMSO, 121.49 MHz) δ 16.22, MS (ES4) m/z = 293 (MH1). Compound Structure Description 22a

F

White powder, 4 NMR (CDC13, 300 MHz) δ 3.87 (d, / = 11.7 Hz, 3H), 4.55-4.74 (m, 2H), 6.97 (tt, /- 2.4 Hz and 8.7 Hz, 1H), 7.18- 7.26 (m, 2H), 728-73 (m, 1H), 7.32-7.35 (m, 2H), 7.57 (dd, /= 1.8 Hz and 8.7 Hz, 1H), 7.61 (d, /= 2.1 Hz, 1H ), 8.33 (d, / = 65 Hz, 2H), 11.51 (t, J - 5.7 Hz, 1H), 12.15 (brs, 1H), 31P NMR (CDC139 121.49 MHz) δ 31.42 (t, /= 8.5 Hz, IP), 19F NMR (CDa3, 282.40 MHz) δ POSITIF, MS (ES4) = 492^8 (ΜΗΓ*). 22b

Light orange powder, NMR (CDC13, 300 MHz) δ 2.31 (s, 6H), 3.83 (d, 1L7 Hz, 3H), 4.6-4J7 (m, 2H), 7.16-737 (m, 6H), 7.46- 7.49 (m, 1H), 7.66-7.67 (m, 1H), 8.16^8.18 (m, 1H), 8.48 (brs, 1H), 1131 (brs, 1H), 31P NMR (CDa3, 121.49 MHz) δ 34.5, MS (ES4) m/z = 484.43 (MH4). 22c

White powder, 1H NMR (CDC13, 300 MHz) δ 2.33 (s, 6H), 3·02 ft /= 7·2 Ηζ» 2H), 3J7-3.82 (3⁄4 2H), 3.81 (d, /- 11.7 Hz, 3H), 7.19-7.21 (m, 3H), 7.26-7.33 (m, 3H), 7.47-7.51 (m, 1H), 7.63-7.64 (m, 1H), 8.04^8.07 (πϊ, 2H), 10.59 ( Bis, 1H), 11.32-1135 (m, 1H), 31P NMR (CDa3, 121.49 MHz) δ 34.58, MS (ES4) m/z = 498.42 (MH4). 216 93533 200804280 Description Compound Structure 22d

White solid, worm: NMR (heart-DMSO, 300 MHz) δ 2.26 (s, 6H), 3.74 (d, J = 11.7 Hz, 3H), 4.57 (dd, 5.1 and 15.6 Hz, 1H), 4.67 (dd, 5.7 and 15.6 Hz, 1H), 722-7.34 (m, 4H), 7.44-7.49 (m, 1H), 7.57-7.60 (m, 2H), 8.11-8.14 (m, 1H), 8.55-8.57 (m, 1H), 11.37 (t, 5.4 Hz, 1H), 12.86 (brs, 1H), 31P NMR (^DMSO, 121.49 MHz) δ 32.78, 19F NMR (dr DMSO, 2S2.40 MHz) δ -126.51 (take IF) , MS (ES&quot;) m/z = 502.4 (MH4). 22e

White solid, lH: NMR (CDCI3, 300MHz) 5 2.34 (s, 6H), 3.86 (d, 11.4 Hz, 3H), 4.82-4.85 (m, 2H), 7.18 (hrs, 1H), 7.33 (dd, / = 1.95 and 8.85 Hz, 1H), 7.36 (brs, 1H), 7.41. (brs, 1H), 7.47 (dd, 1.8 and 8.85 Hz, 1H)? 7.7 (d, 1.8 Hz, 1H), 8^8.01 ( m, 1H), 8.23 (brs, 1H), 8.41-8.42 (m, 1H), 10.45 (brs, 1H), 11.89-1153 (m, 1H), 31PNMR (CDa3, 121.49 MHz) δ 34.03, MS (ES4 ) m/z - 485.4 (Μίί). 22f

White solid, 1H NMR (CDC13 &lt; 300 MHz) δ 2.33 (s, 6H), 3.87 (d, 7 = 11.4 Hz, 3H), 4.92 (d, / - 5.4 Hz, 1H), 7.18 (brs, 1H), 732 (dd, /= 1.8 and 9 Hz, 1H), 7.38 (brs, 1H), 7.43. (brs, 1H), 7.45 (dd, /- 2.1 and 8.4 Hz, 1H), 7.74 (d, J= 1.8 Hz, 1H), 8.17 (d, J = 3.9 Hz, 1H), 8.4 (d, J- 35 Hz, 1H), 8.62 (brs, IB), 10.39 (brs, 1H), 11.85 (t, /- 5.7 Hz, 1H), MS (ES4) =485.4 (MH4). 22g

White solid, NMR (form: rDMSO, 300 MHz) 3 2.26 (s, 6H), 3.74 (d, /= 11.4 Hz, 3H), 4.59 (dd, /= 5.1 and 15.9 Hz, 1H), 4.69 (dd, / - 5.40 and 15.9 Hz, 1H), 7.22 (brs, 1H), 731-734 (m, 3H), 7.59 (dd, 1.8 and 9 Hz, 2H), 8.34 (d, J-1.8 Hz, 1H), 8.64 (t, / =1.8 Hz, 1H), 9.01 (d, J = 2.1 Hz, 1H), 11.34 (t, 5.7 Hz, 1H), 12.87 (brs, 1H), 3,P NMR (rfrDMSO, 121.49 MHz) δ 32.70, MS (ES&quot;) m/z = 4853 (MH1). 217 93533 200804280 Compound Structure Description 22h

221

22j

22k

White solid, worm NMR (GDa3, 300MHz) 5i.20ft / -7.5 Hz, 3H), 2.33 (s, 3H), 2.62 (q, /- 7.5 Hz, 2H), 3.84 (d, 11.7 Hz, 3H), 4.65 (dd, /= 5.7 and 15.5 Hz, 1H), 4.73 (dd, ·/- 5.7 and 15.6 Hz, 1H), 7.19-7.49 (m, 6H), 7.68 (m, 1H), 7.81 (m, 1H) ), 8.15 (d, J = 6.6 Hz, 1H), 8.42 (s, 1H), 10.70 (brs, 1H), 11.86 (t, 5.7 Hz, 1H), 31P NMR (003⁄4 121.49 MHz) 8 34.10, MS ( ES4) m/z = 498 (MH4). off-white solid, $ NMR Oir DMSO, 300 MHz) δ 2.27 (s, 6H), 3.76 (d, 11.7 Hz, 3H), 4.59*4.74 (m, 2H), 7^ 4 (brs, 1H), 734 (dd, J = 2.1 and 8.7 Hz, 1H), 7.33 (brs, 1H), 7.37 (brs, 1H), 7.53-7.55 (m, 1H), 7.58-7.62 (m, 2H), 8.56 (dd, 2.1 and 6.9 Hz, 1H), 9.03-9.04 (m, IH), 11.45 (t, 5.4 Hz, 1H), 12.86 (hrs, 1H), 31P NMR (^DMSO, 12L49 MHz) δ 32.67, MS (ES, m/z = 485.35 (MH). MH, NMR (. DMSO, 300 MHz) δ 2.27 (s, 6H), 3.70 (d, / = 11.7 Hz, 3H), 4.59- 4,60 (m, 2H), 7.22 (hrs, 1H), 728 (brs, 1H), 7.33 (brs, 1H), 735-7.47 (m, 4H), 8.14 (d, /= 5.1 Hz, 1H) , 8·29 (brs, lH)a 11.73 (t,/= 5.1 Hz, 1H), 13.07 (brs, 1 H), MP NMR (irDMSO, 121.49 MHz) δ 32.03, MS (ES4) 502-45 (ΜΕ〇·gray white solid, NMR (ODCl3, 300 MHz) δ 2.19 (s, 6H), 3.88 (d, 11.4 Hz , 3H), 4.96 (m, 2H), 7.24 (brs, 1H), 7^0-749(m, 6H), 7.75 (m, 1H), 8.15 (d, J -5.1 Hz, 1H), 9.40 ( s, 1H), 10.23 (fars, 1H), 11.79 (brs, 1H)? 31P NMR (CDC13, 121.49 MHz) δ 342, MS (ES4) 7n/z=485.35 218 93533 200804280 Compound Structure Description 221

22m

22η

22ρ

Off-white solid, NMR WrDMSO, 300 MHz) δ 229 (s, 6H), 3.64 (d, ^ - 12 Hz, 3H), 4.32 (s, 3H), 4.95 (d, 5.4 Hz, 2H), 7.26 (bis , 1H), 735 (dd, /= 2.1 and 9 Hz, 1H), 738 (brs, 1H), 7.42 (brs, 1H), 7.57 (d, J-1.8 Hz, 1H), 7.62 (d4 /= 1.8 And 9 Hz, 1H), 8.08 (d, 7 - 6.6 Hz, 2H), 8.93 (d, J - 6.6 Hz, 2H), 11.6 (t, /= 5.4 Hz, 1H), 12.88 (d, 1H), 31P NMR (rfrDMSO, 121.49 MHz) δ 32.64, MS (ES4) mk - 482.43 (M4). White solid, NMR (CDC13, 300MHz) S2.32 (s, 6H), 3.84 (d, / - 12 Hz, 3H), 4.68 (t, /- 5.1 Hz, 2H), 7.17 (brs, 1H), 7.28-738 (m, 6H), 8.26-8.28 (m, 2H), 1139 (brs, 1H), 12.44 (t , 5.1 Hz, 1H), 31P NMR (CDC13, 121.49 MHz) δ 33.73, MS (ES, tm/z = 502, off-white solid, s NMR (form: r DMSO, 300 MHz) δ 2.25 (s, 6H), 3.74 (d , /= 11.7 Hz, 3H), 455 (dd, /-5.4 and 15.9 Hz, 1H), 4.65 (dd, /- 5.4 and 15.9 Hz, 1H), 723 (bis, 1H), 7.28 (brs, 1H) , 7.31-7.35 (m, 2H), 7.38-7.4 (m, 2H), 7.59 (dd, 1-8 and 6.9 Hz, 2H)? 8.19 (d, /= 6.9 Hz, XH)5 11.36 (t, / -5.4 Hz, 1H), 12.86 (brs, 1H), 31P NMR (dr DMSO, 121,49 MHz) δ 32.83, MS (ES4) tm/z = 484.19 (MH*). off-white solid, hNMR (rfr DMSO, 300 ΜΗζ) δ 2.28 (s, 6H), 3.77 (d, / = 11.7 Hz , 3H), 4.64-4.74 (m, 2H), 7.24-7.47 (m, 7H), 7.57-7.64 (m, 2H), 834-8.36 (m, 1H), 11.32-11.37 (m, 1H), 12.86 (brs, 1H), 31P NMR (rfrDMSO, 121.49 MHz) 532.67, MS (ES4) m/z = 484.5 (MH&quot;). 219 93533 200804280 Compound Structure Description 22q

22r

22s

N+=N m6 22t

220 93533 200804280 Compound Structure Description 22u 22y

22w

22x

221 93533 200804280 Compound Structure Description 22y 22z 22aa 22ab

222 93533 200804280 Description Compound Structure 22ad 22ae 22af

223 93533 200804280 Description Compound Structure

22aj

224 93533 200804280 Compound Structure

Description Yellow powder, also NMR (CDC13, 300 ΜΗζ) δ 2.4 (s, 3H), 3.86 (d, /= 12 Hz, 3H), 4.58 (dd, J^5A and 15.6 Hz, 1H), 4.73 (dd, J « 5.4 and 15.6 Hz, 1H), 7.33-7.35 (m, 3H), 7.53-7.60 (m, 3H), 7J-7.8 (m, 2H), 8.27-83 (m, 2H), 11.55 (t, 5.4 Hz, 1H), 11.61 (fars, 1H), 31P NMR (GDCTs, 121.49 MHz) δ 31.62, MS (ES^) ^ = 495.4 (MH4). 22al

22am 23a

Colorless oil, also 1^01(0)013,300 1^112)3 5.03-5.2 (m, 2H), 7.3-7.47 (m, 5H), 7.48-7.63 (m, 3H), 7.64 (d, /= 565.8 Hz, 1H), 7.75-7.83 (3⁄4 2H), 31P NMR (CDa3, 101.256 MHz) δ 25.55, MS (ESI, E〇m/z-233 (MH4). 23b

Q-fotBu λ^f H colorless oil, 4; NMR (GDC13, 250MHz) δ 1.59(s, 9H), 7.76 (d, J= 552 Hz, 1H), 7.5-7.82 (m, 5H), 3lP NMR ( CDCiZ9 121.49 MHz) δ 15.27, MS (ESI, El4) m/z^l9S (MH4). 225 93533 200804280 Compound Structure 23c ~o Ο &gt;P_OMe 化合物 Compound Structure Description Colorless Oil, Insect NMR (de-DMSO, 300 MHz ) δ 2.38 (s, 3Η), 3.68 (d, 12 Hz, 3H), 7.49 (d, 7= 566 Hz, 1H), 7.4 (dd, 3 and 7.8 Hz, 2H), 7.62 (d, 13.8 13⁄4 1H) ), 7·64 13·5 Hz, 1H) Description 25a

White oil, 丨H NMR (CDC13, 300 MHz) δ 1·46 ··/ = 7.2 Hz, 3H), 3 J4 (4 /= 14,4 Hz, 3H), 4.46-4.57 (m, 2H), 7.33 (dd, /= L95 Hz and 8.7 Hz, 1H), 7.43-7.56 (m, 5H), 7.62-7.67 (m, 1H), 7.93-8.01 (m, 4H), 8.09-8.13 (m, 2H), 3IP NMR (CDa3, 121.49 MHz) 5 73.28, MS (ESI, El4) i«/z = 534 (MH4). 25b

White powder, 1H NMR (C〇a3, 300 MHz) 5 3.80 (4/= 14.4 Hz, 3H), 5.92 (brs, 1H), 732 (dd, 1.95 Hz and 9 Hz, 1H), 7.42-7^8 (m, 4H), 7.8-7.9 (m, 3H), 9^4 (brs, 1H), 10.15 (bis, 1H), 31P NMR (CT&gt;a3, 121.49 MHz) δ 80.48, MS (ESI, El4) ^ = 365 (MH4). 25,a

Yellow powder, 1H NMR (CDC13, 400 MHz) δ 3·86 (d, / 11.6 Hz, 3H), 7.31 (dd, /= 1.95 Hz and 8.8 Hz, 1H), 7.42-7,47 (m, 3H) , 7.52-7.56 (m, 1H), 7.69-7.78 (id, 3H), 8.05 (brs, 1H), 10.63 (brs, 1H), 12.5 (brs, 1H), 31P NMR (CDa3, 101.256 MHz) δ 34.54 , MS (ESI, ΒΫ) m/z - 365 25,b

Yellow powder, lH NMR (CDC13, 300MHz) δ 1,45 ((«/:= 7.2 Hz, 3H), 4.03-4.13 (m, 1H), 4.25-436 (m, 1H), 7.3 (dd, /= 1.95 Hz and 8.85 Hz, 1H), 7.41-7.47 (ed, 3H), 7.51-7.56 (m, 1H), 7.72-7.79 (m, 3H), 8.01 (brs, 1H), 10.59 (brs, 1H), 12.59 (brs, 1H), 31P NMR (CDa3, 12L49 MHz) δ 32.32, MS (ESI, Ef) »z/z«379 (MH4). 226 93533 200804280 Compound Structure Description 26a

White solid, NMR (CDCU) 300 MHz) δ U8 ft / = 7·2 Hz, 3H), 3.78 (q, J = 7.2 Hz, 2H), 733 (dd, J « 2.1 and 9 Hz, 1H), 7.45-7.75 (m, 14H), 7^3-7.97 (m, 1H), 8-8.04 (m, 2H), 3lP NMR (CDCl39 10L256 MHz) δ 22.23, MS (ESI, El1*} tn/z = »564 (MH4). 27a

White®, NMR O^rDMSO, 300 MHz) δ 6.13 (4 ·/ = L8 Hz, 1H), 722 (dd, /= 2J and 8.7 Hz, 1H), 7.53-7.72 (m, 11H), 7.92 ( Brs, 1H), 10.37 (bis, 1H), 12.84 (bisa 1H), 3IP NMR (JrDMSO, 101.256 MHz) δ 26.61, MS (ESI, Ε1, ιη/ζ»395(ΜΗ*). 28a

Yellow viscous oil, worm NMR (000^ 3001^) 51:36 jiang /= 72 Hz, 3H), 42-4.41 (m, 2H), 732-735 (dd, J = 2.1 Hz and 9 Hz, 1H), 7.47-7.65 (m, 6H), 7.74-7.81 (m, 2H), 7.88-7.93 (m, 2H), 8-8.03 (m, 2H), 3IP NMR (CDa3 &gt; 10U56 MHz) δ 25.04, MS (ESI , El4) « 502 (MH4). 29a

White solid, 1H NMR (rfr DMSO, 300 MHz) δ 2·24 (4 13.5 Hz, 3H), 7.1 (m, 1H), 7.25 (dd, /= 1.2 and 8.7 Hz, 1H), 7.51-7.64 (m, 4H), 7.74-7.8 (m, 2H), 7.83-7,86 (m, 1H), 10.53 (brs, 1H), 12.62 (fars, 1H), 3lPNMR (rf^MSO, 101256 MHz) δ 30.62, MS (ESI, El4) m/r - 333 (MH4). 30a

Yellow oil,! H NMR (CDC13, 300 MHz) δ 1.44 (t/= 6.5

Hz, 3H), 2.66 (d, / = 11.1 Hz, 6H), 4.48 (q, J = 6.7 Hz, 2H), 7-34 (d, J - 9.9 Hz, 1H), 7.45-7.52 (m, 5H ), 7.60 (m, 1H), 7.85-7.95 (m, 4H), 8.07-8.09 (m, 2H), 3lP NMR (CDa3j 101 MHz) 525.11, MS (ESI, Ef) ??i/z = 531

227 93533 200804280 Description Compound Structure 31a

淡 light orange powder, NMR (d^JOMSO, 300 ΜΗζ) δ 2.64 (d, J = 11.7 Hz, 6H), 732 (dd, /- 2.1 and 8.7 Hz, 1H), 7.5-7.59 (m, 4H) , 7 J2-7.79 (m, 3H), 7.86 (bis, 1H), 10.85 (brs, 1H), 12.61 (hrs, 1H), MS (ESI, El4) ^/z * 384 (M+Na). 32a

Light yellow solid; ^NMRiCDC^SOOMH^SUS-1.49 (in, 6H), 4.M24 (m, 2H), 4.55 (q, J= Hz, 2H), 5.97 (d, /- 16.8 Hz, 1H), 7.16-7.68 (m, 7H), 7.86-8.12 (m, 6H), 31P NMR (CDC13, 12L49 MHz) δ 22.83⁄4 MS (ES4) wi/z « 582.88 (MH4). 32b 33a

Light yellow solid; ^1^1^(0)0^ 300 1^)5 1.38-1.49 (m, 6H), 4.1-4.24 (3⁄4 2H), 4.55 (q, /= 72 Hz, 2H), 5.56 ( d, /= 12 Hz, 1H), 7.16-7.68 (m, 7H), 7.86-8.12 (m, 6H), 31P NMR (C3)a3, 121.49 MHz) δ 22.82, MS (ES4) m/ze 582.88 ( MH4). White solid, 4 NMR (CDC13, 300 MHz) δ 3.90 (4 11.7 Hz, 3H), 5.80 (brs, 1H), 5^3 (d, /= 16.5 Hz, 1H), 7.39-7.92 (m , 5.93, 8H), 10.16 (brs, 1H), 10.85 (brs, 1H), 31P NMR (C©a3, 121.49 MHz) δ 31.53, MS (ES4) m/z == 400 (MH4). 38a

228 93533 200804280 Compound Structure Description 38b 38c

38e

38i

229 200804280 Description Compound Structure

230 93533 200804280 Compound Structure Description 43a

43b

43c 47a

Yellow oil, 4 NMR (CDa3, 300 MHz) δ 1·32 (t 6.9 Hz, 6Η), 4.20-4.10 (ro, 4H), 9.01 (d, /= 6.6 Hz, 2B〇, 9.31 (cl, J * 3.3 Hz, 1H), 31P NMR (CDCI3, 121.49 MEIz) ? 12.37, MS (ESI, El4) ?w/z=217 (MH〇. 47b

Yellow oil, ^ NMR (CDCU, 300 MHz) δ 1·2 (3⁄4 · / = 7·2 Hz, 6H), 3.95-4.1 (m, 4H), 7.25-73 (m, 1H), 7.93-8 ( m, 1H), 8.62-8.64 (m, 1H), 8.83-8.85 (3⁄4 1H) 31P NMR (CDCl3 &gt; 121.49 MHz) δ 15.72. 47c

Yellow oil, worm NMR (CDCU, 300 MHz) δ 1·36 (t 7·2

Hz, 6H), 4.16^31 (in, 4H), 7.41-7.46 (m, 1H), 7.77-7.85 (m, 1H), 7.96-8.01 (m, 1H), 8.8-8.82 (m, lB〇31P NMR (CDCI3, 121.49 MHz) 9 7.16, MS (ESI, El4) m/z » 216

47d o

OEt

Brown oil,! H NMR (CDCl3i 300 MHz) δ 1J27 (t 6.9 Hz, 6H), 4.01-4.16 (m, 4H), 7.56-7.62 (m, 2H)5 8.67-8.71 (m, 2H), 31P NMR (CDC13, 121.49 MHz) δ 14.63, MS 231 93533 200804280 Compound structure description 47e ^&gt;L〇Et 47f 0~L〇Et 48a

|^VP-〇Et 0H (ESI, El4) m/z = 216 (MH〇. , !H NMR (CDa3, 300 MHz) δ 1,33 (t, 72 Hz, 6H), 4.04-4.19 (m, 4H), 7.32-735 (3⁄4 1H), 7.41-7.45 (m, 1H), 7.97-8.01 (m, 1H), 31P NMR (CDa3i 121.49 MHz) δ 13.35, MS (ESI, E〇m/z = 221.11 (ME!4). Light yellow oil, NMR (CDC13, 300 MHz) δ l, 34a/« 7.05 Hz, 6H), 4.06^22 (m, 4H), 7.16-7.20 (m, 1H), 7.65- 7.72 (m, 2H), 31P NMR (C〇a3, 121.49 MHz) δ 12.05, MS (ESI, Ef) m/z - 22L11 (MH&quot;). Yellow oil, 1H NMR (CDC13, 3001^)31^27 (^=7.05 Hz, 3H), 4.01-4.07 (m, 2H), 7.31-7.4 (m, 2H), 7.91-7.95 (3⁄4 1H), 12.73 (s, 1H), 31P NMR (CDC13, 101.256 MHz) δ 14.67. 48b yellow oil, NMR (CDC13, 300 MHz) S ljl (t7·05 Hz, 3H), 4.04^.14 (m, 2H), 7.12-7.16 (m, 1H), 7.61-7.68 (m , 2H), 9.12 (brs, 1H), 31P NMR (CDa3, 121.49 MHz) δ 14.7· 50a

50b

Yellow powder, NMR (CDC13, 300MHz) δ 1.41 ft· / =7.05 Hz, 3H), 1.49 (t, /= 7-05 Hz, 3H), 4.13-4.28 (m, 2H), 4.57 (qd , /= 1.8 Hz and 7.05 Hz, 2H), 7.16^7.19 (m, 1H), 7.36 (dd, J - 2.4 Hz and 9 Hz, 1H), 7.50-7.56 (m, 2H), 7.61-7.73 (m , 3H), 7.9-7.96 (m, 2H), 8.1-8.14 (m, 2H), MS (ESI, El4) w/z = 537 (MH4). Yellow powder, NMR (GDC13, 300MHz) δ 1.38 Ft / =7.05 Hz, 3H), 1.42 (t, /- 7.05 Hz, 3H), 4.08-4J26 (m, 2H), 4.52 (3⁄4 /= 7.05 Hz, 2H), 7.34 (dd, J- 2.1 Hz and 9 Hz, 1H), 735-7.41 (m, 1H), 7.47-7.53 (m, 2H), 7.58-7.64 (m, 1H), 7.77-7.84 (m, 1H), 7.88-7.92 (m, 1H) , 8.03-8.15 (m, 4H), 8.72-8.74 (m, 1H), 3,P NMR (CDC13, 121,49 MHz) δ 19.72. 232 93533 200804280 Compound Structure Description 50c

51

52a

52b

)=\ π / V-p«〇Me 53a OMe

Oil, worm NMR (CDCU, 300 MHz) δ L37 (t, 7·05 Hz, 3H), 1.45 (t, 72 Hz, 3H), 4.05-4.22 (3⁄4 2H), 4.52 (q, J = 12 Hz, 2H), 734 (dd, 2.1 and 8.7 Hz, 1H), 739 (dd, /= 2.1 and 3.3 Hz, 2H), 7.48-7.54 (m, 2H), 7.6-7.65 (m, 1H), 7.88 (d , /= 1.8 Hz, 1H), 7.92 (dd, J-1.8 and 9 Hz, 1H), 8.02-8.1 (m, 3H), 31P NMR (CDCli7 121.49 MHz) δ 18.36. White powder, also NMR (rfrDMSO, 300ΜΗζ)δ1.33(ί^ =7.05 Hz, 3H), 4.034.09 (m, 1H), 4.15-4.24 (m, 1H), 7.21-7.23 (m, 1H), 7.34 (dd, /= 2.1 and 8J Hz, 1H), 7.55-7.61 (m, 2H), 7.7 (d, J = 2.1 Hz, 1H), 8-8.03 (m, 2H), 10.12 (brs, 1H), 12.76 (brs, 1H), 31P NMR (rf^MSO, 121.49 MHz) δ 23.46, MS (ES4) = 368.8 (MET). beige powder, NMR (CDC13, 300 MHz) δ 3.83 (4 / = 12 Hz, 3H), 5.93 (brs, 1H), 7.3-734 (m, 2H), 7.39-7.42 (m, 1H), 7.47 (dd, /= 1.8 Hz and 8.7 Hz, 1H), 7.7 (d, J-1.8 Hz, 1H), 7.91 ( Ddd, U Hz and 2.7 Hz and 8.1 Hz, 1H), 10.44 (bra, 1H), 10.95 (brs, 1H), MS (ES〇/n/z = 353.06 (MH〇. White powder, fear of NMR (rfrDMSO) , 300 MHz) δ 3.77 (3⁄4乂=12 Hz , 3H), 722-7^4 (m, IE), 734 (dd, 1.8 and 8.7 Hz, 1H), 7.56-7.61 (m, 2H), 7.66 (d, /= 1.8 Hz, 1H), 8.0l · 8.05 (m, 2H), 10.1 (brs, 1H), 12.81 (brs, 1H), MS (ES4) m/z = 354.7 (Mlf). Colorless oil, insect 1^11(〇)(:13, 3001 ^)5 1.66(4·/&quot; 3.9 Hz, 3H), 1.76 (d, J » 5.4 Hz, 3H), 2.57 (dd, J = 7.65 and 21.75 Hz, 2H), 3.74 (d, /= 10.5 Hz , 6H), 5Λ2-521 (m, 1H), 31P NMR (C〇a3, 121.49 MHz) δ 7.32, MS (ESI, E〇m/z-179 (MH*). 233 93533 200804280 Compound Structure Description 56a

57a

57b 59a

Viscous yellow oil, NMR (CDC13, 300 MHz) δ U4 (4 / =3.9 Hz, 3H), 1,5 (t, /= 12 Hz, 3H), 1.54 (d, 6 Hz, 3H), 2.78 ( Dd, 8.1 and 19.5 Hz, 2ΒΓ), 3.7 (d, 11.1 Hz, 3H), 4.57 (q, J- 72 Hz, 2H), 5.07-5.1 (m, 1H), 7.37 (dd, J= 2.1 and 8.7 Hz, 1H), 7.5-7.55 (m, 2H), 7.63-7.67 (m, 1H), 7.87 (d, /= 1.8 Hz, 1H), 7.96 (dd, / = 12 and 9 Hz, 1H), 8.1 -8.13 (m, 2H), 31PNMR (CDa3, 121.49 MHz) δ 8.68, MS (ESI, Ef) m/z* 511 White solid, NMR ('DMSO, 300 MHz) δ 1.03138 (m, 4H), 1.49 -1.75 (m, 4H), 1.87-1.98 (m, 2H), 3.59 (d, /-1U Hz, 3H), 733 (dd, 1.95 and 8.7 Hz, 1H), 759 (d, J =8.7 Hz, 1H), 7.67 (brs, 1H), 7.87 (brs, 1H), 10.23 (brs, 1H), 12.69 (fers, 1H), 31P NMR (rf^DMSO, 101.256 MHz) δ 48.93, MS (ESI, El4) Tw/z = 355 (MH4). Light yellow solid, NMR (^ DMSO, 300 MHz) δ 1. Π (d, / = 3.6 Hz, 3H), L55 (d, J = 5.7, Hz, 3H), 2.81 (m, 2H), 3.62 ((3,/= 11.1 Hz, 3H), 5.0 (m, 1H), 733 (dd, J-2.0 and 8.7 Hz, 1H), 7.57 (d, /= 8.7 Hz, 1H), 7.68 (d, J-2.0 Hz, 1H), 7.85 (brs, 1H), 7.87 (brs, 1H), 10.10 (brs, 1H), 12.64 (brs, 1H), MS (ESI, El4) tw/z = 341 (MH4). Yellow powder, NMR (CDd3, 300 MHz) δ 3.88 (4 ·/= 12 Hz, 3H), 44 ( d, 5.4 Hz, 2H), 6.98 (tt, /= 2.4 Hz and 8.7 Hza 1H), 7.26-731 (m, 2H), 7.3S (dd, 7« 1.8 Hz and 8.7 Hz, 1H), 7.59 (d , 1.5 Hz, 1H), 7.46 (dd, 1.8 Hz and 8.7 Hz, 1H), 11.24 (brs, 1H), 11.79 (t, 5.4 Hz, 1H), 3lP NMR (CDa3, 121.49 MHz) δ 30.82 (t, 7« 8.6 Hz, IP), 19F NMR (CDCI3, 282.40 MHz) δ -106.02 (m, 2F), MS (ES*) (MH4). 234 93533 200804280 Compound Structure Description 59b

Yellow powder, NMR (CDCU, 300 MHz) δ 2·8 = 6.9 Hz, 2Η), 3.79-3.85 (m, 2Η), 3.87 (ά, 11.7 Hz, 3H), 6.96 (tt, / « 2.4 Hz and 8.7 Hz, 1H), 7-25-7.33 (m, 2H), 7.36 (d, /- 1.8 Hz, 1H), 7.53 (dd, /= 1.8 Hz and 8.7 Hz, 1H), 7.60 (d, J- Hz -106.25 (m, 2F), MS (ES4) m/z = 437.96 60a

White solid, worm NMR WrDMSO, 300 MHz) δ m7-17 (m, 1H), 7.32-7.73 (3⁄4 7H), 8.16 (brs, 1H), 11.78 (brs, lH)a 12 (brs, 1H)5 MS (ESI, Ef) m/z 335 (MB〇. 60b

White powder, 1H NMR WrDMSO, 300 MHz) δ 3.72 (s, 3H), 6.9-6.93 (m, 2H), 7.19 (dd, J- 1.5 Hz and 8.7 Hz, 1H), 7.43-7.46 (m, 1H) , δ 31.44, MS (ESI, ???, El4) w/z = 365 (MH4). 60d

Off-white powder, lH NMR WrDMSO, 400 MHz) S 2.3 (s, 3H), 7.26 (dd, / = 2 and 8.8 Hza 1H), 7.3-737 (m, 2H), 7.46-7.54 (m, 3H), 7.82 (brs, 1H), 7.88 (brs, 1H), 10.69 (bis, 1H)5 12.49 (brs, 1H), 31P NMR (JrDMSO, 101.256 MHz) δ 23.81, MS (ESI, El4) w/z * 349 ( MH4). 60f

Off-white powder, b NMR (drDMSO, 300 MHz) δ 2.21 (s, 6H), 7.2-7.28 (m, 2H), 7.37-7.53 (m, 3H), 7.79 (brs, 1H), 7.87 (brs, 1H) , 10.68 (brs, 1H), 12.47 (brs, 1H), MS (ESI, = 363 (MH4). 235 93533 200804280 Description of compound structure

60g orange powder, 咕 NMR (ώ-DMSO, 300 ΜΗζ) δ 7.27 (dd, 1.95 and 8.87 Hz, 1H), 7.48-7.54 (do, 3H), 7.61-7.71 (m, 1H), 7.85 (d, / - 1.8 Hz, 1H), 7.9 (brs, 1H), 10.54 (brs, 1H), 12.53 (bis, 1H), 3lP NMR (^DMSO, 101 MHz) δ 2039 ,19F NMR (derDMSO, 282.4 MHz) δ - 133.8 (m, IF), -1373 (m, IF), MS (ESI, El4) m/z - 371 (MH4). The following examples are provided to illustrate the invention, and are not intended to limit the scope of the invention . EXAMPLE X·Compound Synthesis General Synthetic Method Compound FW Equivalent CHC13 (or CH2C12) 75 ml/mmol mCPBA (70% in water) 172.57 2.5

Experimental: The pyridine precursor was dissolved in chloroform (or CH2Cl2) at room temperature with stirring; the m-benzoic acid was added to the mixture and the reaction was allowed to stand overnight (~15 hours). The mixture was diluted with dichloromethane and extracted with a saturated mixture of 236 93533 200804280 K2C03/H20 (l/3). The aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and evaporatedEtOAc. The crude product was then purified by chromatography. Compounds synthesized by the family·· 237 93533 200804280

238 93533 200804280

239 93533 200804280 Example 1· 3-淳: Synthesis of 5-chloro-1-(phenylsulfonyl) by two 5-U-(stupyl) ) _lj?^ 吲哚 carboxylic acid ethyl ester as a starting material (according to Silvestri R., De Martino G·, La Regina G·, Artico M·, Massa S·, Vargiu L·, Mura M·, Loi A.- G·,

Marceddu T.9 La Colla P. J. Med. Chem. 2003, 46 : Operation of 2482-2493):

Add NaH in portions under stirring in a cooled (〇°C) DMF solution (25 mL) containing ethyl-5-chloroindole-2-carboxylate (1·〇52 g, 4.70 mmol). (60% in oil, 230 mg, 5.64 mmol). When the gas ceased to be released, benzene was continuously added (0.72 mL, 5.64 mmol). The reaction mixture was turbulently immersed in a small day (detected by TLC as a dichlorohydrazine). Carefully add a small amount of water and evaporate the DMF. The crude residue was dissolved in EtOAc and washed water and brine. After dehydration and evaporation of the solvent, the compound was chromatographed on an extract (ion extract·cyclohexane/EtOAc 9/1 to 7/3) to obtain a protected hydrazine (1· 547 g, 90% yield). Off-white solid; !H NMR (^DMSO) δ 1?3〇(t, 7.2 Hz, 3H)5 435 (q5 /- 7.2 Hz, 2H), 7.37 (s, 1H), 7.53 (dd, 2J2 and 9.1 Hz ), 7.62-7.77 (m, 3H), 7.S0 (d, 2.2Hz, 1H), 7.99 2ΚΓ), 8.06 (d, J- 9.1 Hz); MS (ESI, ΒΫ) mfz = 364 (MH^) b) Synthesis of 3-chloro-5-chloro-1-(phenyl fluorescene)-1//-. π 朵 _2 - ethyl citrate intermediate: 240 93533 200804280

Add bromine (1.3 mL, 26.54) to a stirred DMF solution containing chloro-hydrazine-(phenylsulfonyl)-m-decanoate (4.83 g, 13.27 mm Gl) at %. A solution of MMF (10 mL) was stirred at room temperature for 4 hrs, water (15 mL) and dichloromethane (3×lOmL) was washed. The organic layer was washed with Naj. The crude product was obtained by dehydration and evaporation. The crude product was purified by chromatography (eluent: cyclohexane / EtOAc 9/1) to afford 3-bromide (5.548 g, 93% yield ) grayish white solid; hNMR (and -DMS0) δ 1,37 (〇7·2 Hz, 3H), 4·48 (q, &gt; 7·2 Hz, 2H), 7·59-7·68 (m , 4H), 7:77 (m, 1H), 7.96-8.09 (m, 3H); MS (ESI ΒΫ) m/z = 442^44 友龙二A: Synthesis of 5-argon-3-(dialkyl Alkylphosphonium group (containing a sulfhydryl group on the 吲哚2_carboxylic acid ethyl ester and 5-indene-3-decane gas base (mum)) thiol group UjlC phenyl sulfonyl ugly-吲哚-2 - Ethyl carboxylate is generally present under N2 in ethyl 3-bromo-5.chloro-1-(phenylsulfonyl)-1/7-indole-2-carboxylate (0·50 mmol ) stirred and cooled (-90. To a solution of THF (2.5 mL) was added dropwise BuCl (2.5 M in hexanes, 0.24 mL, 0.60 mmol). After </ RTI> </ RTI> Chlorophosphus) Reagent (0.60 mmol). The reaction was warmed to rt over EtOAc (EtOAc (EtOAc) EtOAc. Ethyl acetate extraction 241 93533 200804280 (3x20 mL), dehydration and evaporation to obtain a crude oil, which was purified by chromatography on the gum. Example 2. 5-indole-3- Gas-based ruthenium base)-1-(stupyl sulfonyl group VI and -吲pto-2-retensive vinegar

Method A: Purification on silica gel (eluent: dichloromethane / EtOAc 9/1 to 8/2) afforded the desired product (176 mg, 71% yield). White solid; ]H NMR (rf^DMSO, 300 MHz) δ 1,19 (t, J=7.1 Ηζ,6Η), l,39(t,/=7J Ηζ,3Η), 3.99-4.09 (m, 4H ), 4.46 (q? 7.1 Hz, 2H), 7.77 (dd, /= 2.1 and 8 J Hz, 1H), 7.67-7.82 (m, 4H), 8.07^8.12 (m, 2H); 31P NMR (^DMSO , 101 MHz) δ 9 J; MS (ESI, E〇-500 (ΜΗ&quot;). Example 3. 5-氲-3-丨Ethyl (meth)phosphonium- 1 - (stupyl) A VI ugly-indole-2-carboxylic acid ethyl ester a) according to Smith Α·Β· III, Ducry L., Corbett, RM Hirschmann R. (9 plant g· Ze/t· 2000, 2: 3887-3890 synthesis Hydrogen phenylphosphonochloridate t: i) Synthesis of diethyl phenylphosphonate: 242 93533 200804280 〇4, &gt;f OHt colorless oil; 1H NMR (C〇a3, 250 MHz) δ 1,33 (t 7·1 Hz, 6H), 4·054·25 (m, 4H), 7.46-7.57 (m, 3H), 7.78-7.87 (m, 2H); 31P NMR (CDC13 , 101 MHz) δ 193. ii) ethyl hydrogen phenyl phosphonate:

Oir colorless oil; 1H NMR (CDC13, 300 MHz) δ 1) 2^/=7,311^311), 4.08 ((^/=7.313⁄4 2H), 7·42-7·56 (4) 3H), 7·79- 7·86 (4) 2H), 10·67 (brs9 1H); 31P NMR (CDC13, 101 MHz) δ 21.3; iii) Synthesis of ethyl hydroxyphenylphosphonate λ~f Cl 31PNMR (CDC13) having the following physical properties , 101MHz) (5 10.20 and 10.24. b) Synthesis of the final product 5-chloro-3-[ethoxy(phenyl)phosphonium]1-(phenyl fluorescene)_ 1 ϋ多-2 - Ethyl citrate

Method A: Purification on silica gel (extraction: dichloromethane/EtOAc 9/1) to give debrominated (318 mg), then 243 93533 200804280吲哚 (326 mg, 41% yield). Colorless oil; !H NMR (4-DMS0, 300 MHz) δ 1,27 (t, J= 7.1 Hz, 3H)? 1,36 (t, J- 7.1 Hz, 3H), 4.03 (m, 2H), 4.38 (q5 /= 7.1 Hz, 2H), 7·5μ7·83 (m, 11H), 8.05-8.11 (m, 3H); 31P NMR (do-DMSO, 101 MHz) δ 23·3; MS (ESl· Ef) m/z « 532 Example 4· 5-Benzene-3-indolyl (3,5-dimethyl tomphenyl) phosphonium M. (stupid base)-1 ugly 12 嗓-2- slow acid vinegar

Hirao T.5 Masunaga T. 5 Agawa T. Synthesis 1981, Method 56-57 to synthesize diethyl 3,5-dimercaptophenylphosphonate intermediate.

0 f-OEt OEt was chromatographed on EtOAc (EtOAc: EtOAc/EtOAc/EtOAc) 300 MHz) δ 1,33 (t, 7.0 Hz, 6H), 235 (s, 6H), 4.02-4-18 (m, 4H), 7·18 (s, 1H), 7·40 (s51H), 7·45 (s, 1H); 31P NMR (CDC13, 101 MHz) δ 20·3· Other intermediates were synthesized according to Example 3 (i, ii and iii). b) Synthesis of 5-chloro-3-[ethoxy(3,5-dimercaptophenyl)phosphonium]-1-(phenyl fluorescene)-1 0 丨ϋ 丨ϋ _ 2 - citric acid B. Purpose:

244 93533 200804280 Method A: Purification on EtOAc (EtOAc:EtOAc:EtOAc: lE NMR (^-DMSO, 300ΜΕΙζ) δ 1,27 (t, 2.30 (s,6Η), 3.944·06 (4) 2Η), 4·44 (q,7·1 Ηζ, 2Η), 7·25 (s, 1Η),7·39 (s,1Η), 7.42 (3⁄4 1H), 7.53 (dd, ·/= 2.1 and 9Ό Hz, 1H), 7.65-7-71 (m, 2H), 7-77-7.82 ( m, 2H), 8Ό5-8.11 (m? 3H); 31P NMR (^-DMSO, 101 MHz) δ 23.6; MS (ESI, Et) m/z = 560 (M£t). Example 5· Synthesis of diphenyl ester of phenylphosphonate: a) alkyl-3-carbomethoxy (methyl)phosphonium bromide 1-(molylsulfonyl)-1 and -indole-2-carboxylic acid ethyl ester a)

Ethanol (1.12 mL, 19.04 mmol) was added dropwise to a solution of phenylphosphonium dichloride (1 mL, 6.35 mmol) in anhydrous dichloromethane (25 mL). ). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with a solution of HCl (50 mL). The aqueous layer was extracted with dichloromethane. The combined organic layers were dehydrated and concentrated under reduced pressure. The crude oil was purified on EtOAc (EtOAc:EtOAc:EtOAc lB NMR (CDC13s 300 MHz) δ 3.76 (d, 11.1 Hz, 3H), 7.44-7.58 (m5 3H), 7.76-7.84 (m, 2H); 31P NMR (CDC13, 101 MHz) δ 22.2. Other intermediates Synthesized according to Example 3 (i, ii and iii). b) Synthesis of the final product 5-chloro-3-[decyloxy(phenyl)phosphonium]-1-(phenyl fluorescene)-177-σ 丨 丨 ^ -2 - acetoic acid vinegar: 245 93533 200804280

Method A: colorless oil; 1H NMR (CDC13, 300 MHz) 51.45 (t, / = 7.2 Hz, 3H), 3·80 (d, 1 L4 Hz? 3H), 4.54 (q, / = 12 Hz, 2H) 5 736 ( Dd, J = 2.1 and 9.0 Hz, 1H), 7.47- 7.67 (m, 6H), 7.84-7.96 (m, 4H), 8.09-8.12 (m, 2H); 31P HMR (C3DC13? 101 MHz) δ 26.7; MS (ESI, El4) m/z = 518 (MH4). Example 6. 2-(aminocarbonyl)-5-chloro-1 and -indol-3-yl-(phenyl) phosphinate

5-Chloro-3-[ethoxy(phenyl)phosphonium]-1-(phenyl sulphate)-1//- was placed in a pressure tube. Bow. Toluene-2-oleic acid ethyl ester (268 mg, 0.50 mmol) was dissolved in a saturated solution of methanol (5 mL) containing ammonia. The tube was heated by microwave irradiation for about 2 hours at a pressure of 65 ° C (maximum output power 100 W, CEM Discover instrument). After evaporating the solvent, chromatography on silica gel (eluent: dichloromethane / MeOH 95/5 to 9/1) afforded the desired amidamine (107 mg, 81% yield) . White solid; 246 93533 200804280 ^ NMR (do-DMSO, 300 MHz) δ 1,34 (t, "7 = 7·1 Hz, 3H), 4·05 (m5 1H), 4·20 (called 1Η)5 7.32 (dd, 2.1 and 8.7Hz, 1H), 7.49-7.61 (m, 5H)3 7.68-7 J5 (m, 2H)? 8.02 (brs, 1E)910,27 (brs, 1H), 12.77 (brs? 1H); 31P NMR (^-DMSO, 101 MHz) δ 3L1; MS (ESI, ESI, ESI, 356 (MH4). Example 7· 2-(aminocarbonyl)-5- Ethyl-3-methyl-(3,5-dimethylmethyl)phosphonate

This was carried out in accordance with the same procedure as described in Example 5. White solid; 4 NMR (do-DMSO, 300 ΜΗζ) δ 1,32 (t, J 27.0 Hz, 3H), 2.26 (s, 6H), 3.90-4.03 (m, 1H), 4.09-4.22 ( m, 1H), 7.21 (s? 1H), 7.29-733 (m, 3H), 7.57 (dd, J= 1.8 and 9.0 Hz, 1H)? 7.60 (dd, J= L8 Hz, 1H), 7.99 (brs , 1H), 103 (brs, 1H) 512.7 (brs, 1H); 31P NMR (do-DMSO, 101 MHz) δ 31.3; MS (ESI; E 〇m/z = 391 (ΜΗ4^· Example 8·2 -(Aminocarbonyl)-5-gas-1 and 吲哚-3-yl-(phenyl)phosphinic acid methyl ester

This was carried out in accordance with the same procedure as described in Example 5. Light yellow powder; 247 93533 200804280 lE NMR (CDC13, 300 MHz) δ 3.85 (d9 /- 11A Hz, 3H), 6.08 (broad s, 1H), 730 (dd, J=2.0 and 9.0 Hz? 1H), 736 -7.56 (m, 4H), 7.68 (d, 1.8 Hz, 1H), 773^7.81 (m, 2H)5 10,78 (broad s51H)5 10.03 (broad s, IE); 3lP NMR (CDC13, l〇 l MHz) δ 333; MS (ESI, El4) m/z = 349 (MH&quot;). Example 9: Biological activity against drug-resistant HIV strains In one embodiment, the efficacy of anti-HI V compounds is in vitro It is measured by a rapid, sensitive, and automated test involving the reduction of 3-(4,5-dimercaptothiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The HI V-transformed cell line is highly licensed and selected for HIV infection. For example, the T-4 cell line (MT-4) is selected as the target cell line (Koyanagi et al., / J. Ca/7cer, 1985) , 36 : 445_451). In situ reduction of 3-(4,5-dimercaptothiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) evaluated spectrophotometrically by standard The standard measures the viability of both pseudo-infected cells and HIV-infected cells. The inhibition of the HIV-induced cytopathic effect is the end point. A 50% cytotoxic concentration (CC5G unit is μΜ) is defined as the concentration of the compound that reduces the absorbance of the pseudo-infected control sample by 50%. The percentage of efficacy of the anti-HIV compound is calculated by the following formula (in %): (0DHIV test compound X〇D control group) / (0D pseudo-infected cell X〇D control group) Here, (ODHIV test compound) is The optical maleity and degree measured in the treatment of HIV-sensitive cells with a specific amount of the test compound, (0 D s Xiao Xiao·β·) is the untreated HIV-infected cells, ie, the control cells. The measured optical density; and (0D pseudo-infected cells) are the optical densities measured in the control group, and the pseudo-infected cell lines are untreated. Optical density values are typically measured at 540 nm into the 248 93533 200804280 line. The dose of the anti-HIV test compound which provides 50% protection according to the above formula is defined as a 50% inhibitory concentration (IC5G unit is μΜ). The selectivity index (SI) is defined as the ratio of CC5G to IC5G. In another embodiment, the p24 ELISA assay is used to determine the efficacy of an anti-HIV compound. This viral replication immunoassay assay measures the antigen presentation of the p24 viral shell (nucleus) and is available from, for example, Coulter Corporation/Immunotech, Inc. (Westbrook, MI). Still other embodiments comprise a reverse transcriptase assay wherein the viral replication is measured by a homopolymer poly rA·oligo dT template, which is by scintillation counting (Southern Research Institute) , University of Alabama, Birmingham, AL) quantification of the deuterated thymidine monophosphate incorporated into the cells; fusion cell (syncytial) inhibition assay using CEM with immunofluorescence, chemiluminescence, or colorimetric ends -SS, HeLa_CD4, or HeLa_CD4-LTR_b_galactosidase cells; and attachment-and fusion-inhibition assays using indicator cell lines and by chemiluminescence, colorimetric or microscopic evaluation (Southern Research Institute, University) Quantification by of Alabama, Birmingham, AL). In one embodiment, the indole compound of the present invention exhibits no cross-resistance with other non-nucleoside reverse transcriptase inhibitors (NNRTIs), wherein the compounds of the invention exhibit less than about 50' in the mutated HIV strain. EC5G (mole concentration) at 25 '10 or 1 μΜ concentration. In a typical embodiment, 249 93533 200804280 the NNRTI exhibits an EC5 小于 concentration of less than about 5, 2.5, 1 or 0.1 μM in the mutated HIV strain. The degree of cross-resistance against a drug-resistant HIV strain can be measured by assessing the EC5G of the desired keto-pyrimidine compound in the target mutant (i.e., drug resistant) virus. Accordingly, in another important embodiment of the present invention, there is provided a method of treating a patient having cross-resistant HIV comprising administering an effective HIV-therapeutic amount of a bismuth compound, a salt thereof, and a prodrug A construct or tautomer. Biological activity against a drug-resistant HIV strain In a specific embodiment, the phenylhydrazine of the present invention exhibits no cross-resistance with other non-nucleoside reverse transcriptase inhibitors (NNRTI), wherein the phenylhydrazine of the present invention Anthraquinone exhibits EC5G (mole concentration) in a mutant HIV strain of less than about 50, 25, 10 or 1 micromolar. In a typical embodiment, the non-nucleoside reverse transcriptase inhibitor (NNRTI) exhibits a titer of less than about 5, 2.5, 1 or 0.1 micromolar in the mutated HIV strain (: 50 (mole concentration) By assessing the EC50 of the desired drug in the target mutant (ie, drug resistance) virus, the degree of cross-resistance to the drug-resistant HIV strain can be easily measured. Therefore, another important aspect of the present invention. In a specific embodiment, there is provided a method of treating a patient having cross-resistant HIV comprising administering a potent HIV-therapeutic amount of phenylhydrazine or a prodrug or salt thereof. 250 93533 200804280

L IC5〇K103N/ Y181C _ 6.75 1.662 IC5〇K103N _ 0.389 L634 2.607 0.93 IC5〇Y181C 0.349 1.968 4.311 0.489 | J IC5〇WT (μΜ) 1_ 0,309 CM Ο 1,641 § S 吲哚 Substituent position XXXX \〇XXXX δ ο ο X inch XXXX ΓΟ P(0)(Ph)0Me P(Q)(Phj〇Et P(0)(Ph:3,5-two-Me)Oet P(0)(Ph)OMe CONH2 CONH2 CONH2 CONHCH2( 4-pyridine) τ-Η XXXX Compound No. 7ah (0 (Ο s 18ar 251 93533 200804280

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XX ο o 〇〇o 〇oooooo 〇o ϋ rc XXXXXXXXXXXXXXX φ Έ Ο LJL ιώ C0 a α ο GL Φ so IL CO i= o QL ω 銎i CO Jd 〇ST Φ sof CO g ΗΓ Έ Έ ou? l〇Ώ £ CL ( D 2 o 〇T 2 κΛ cp; g Q. &lt;1) § s ιΛ CO QL ❿ 0 2 1 CQ I CL ω 〇i ci £ I DL Φ s 0 &quot;oT 1 CO Jd 〇qT (D so it s ti CO if 〇qT CD Έ 〇&quot;αΓ Έ 1 cf £ qT ω 2 〇o ιό LL 00 αΓ CD S 0 oT 1 CO Cl φ 2 Ο i CO g ΒΓ Φ § '1 to CO if a O qT CM X Ο X ζ ο ο f 〇 £ wear oj: zooss OX zoo S z O o &quot;5Γ 5 T: in lean X o X 2: oo IL JZ a ri X 〇X zoo T-· 如· Ψ e 〇X zoo 〇CD fso X zoo ? 00 〇X zoo ? 竽s Si CM X 簦2 〇〇O ci X 〇X z 8 i (N ci X IO X zoo empty z Ο ο l CvT Ο X z Ο Ο CO CO 〇X zoo X 2 cil g CVJ X 〇X zoo XXXXXXXXXXXXXXXX CM CM s T- c CM CM Φ 00 r- (0 00 T- cd S 00 彐CN 00 T- σ&gt; 00 茗CM § cs 00 T- 7S &lt;β ο Λ s 259 93533 200804280 0,0504 0, 0416 σ&gt; CM ο ο&quot; 0,0087 00 ιο S 〇_ CD I 0,0011 Β ο § CM cT τ- Ο cT 00 T- so in 〇 _ Ο Ο) 5 〇' 0,0103 0,0022 CO &lt ;N 〇τ ο&quot; § o 〇00 I 00 C0 -τ— 〇_ ϊ § 〇· A σ&gt; ο ο % ο 〇· h: ο cT &lt;〇o cT 〇&gt; 〇· oo CD 〇cT Ο 〇· CO τ— Β Ο* ο ο* g ο 0,0393 CO r- s 〇&quot; inch τ- Ο S ο ΙΟ ια δ cT τ 0D τ- Ο 〇 _ ο ο σ gt δ ο* 卜 o δ s CO T~ &lt;D ο σ&gt; τ- Ο ο fe ο 〇' 卜χ — Ο Ο XIXXXXXXXXXXXXXXXXX ΙΕ X XXXIX XXXXX oo ο Ο ο ο Ο ϋ ο oou XXXXXXXXXXX UL UL XXI oso &quot;oT ώ CO if 〇ST os 0 1 CO dT φ Έ ο ο ι ό S CO £ αΓ φ 5 Ο £ C0 g αΓ α&gt; § I CO if 0. I CL φ 2 % 4 ςο: £ Ο □Γ φ 5 Ο 1 ο ιό α&gt; 2 φ· £ I Qu φ Έ Ο ί Ο ιά φ S ώ £ Ο οΓ φ 2 ο &quot;S' I Ο οΓ (D Έ o 2 III o ID of Έ CO έ 〇Cl CD 0 ^αΓ 1 CO JC s&gt; 〇αΓ Φ 5 〇^αΓ Έ in CO έ 1 Q. Φ 1 I CO; έ Ο αΓ 0) Έ % ώ C0 £ g Q. α&gt; 2 Ο f Ο LL LL C0 έ οΓ 0 S § i 9; έ S α. 1 o X 2 oo 1 ο X z ο ο Empty 2 Ο ο X ζ Ο Ο ο- s (Ν SZ to Ο X ζ Ο Ο 2 S Η to Ο X ζ: Ο α ^•ss CM X ο X z ο ο τ: ψ ώ οί X Ο ΙΕ ζ ο ο &lt;Dm CO c\T s 0 1 Z oo — s CM X o X zood X o X zoo Ψ 空 空 空 空 空 空 空 空 空 c c S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S XXX €0 T- ϊ 00 0) ι5 7? (Q οα WS τ- % (0 eo τ- wear S τ- ca &lt;N CM 73 s T&quot; ε ο (σ 00 τ- ?7 Μ α OJ CM 1S Ν- 00 260 93533 200804280 CM τ- Ο ο&quot;〇&gt; ο 〇· CD CO 8 〇- cn goo 0,0067 0,0018 O) R- | 0,003 0,0034 *T— 〇〇_ 0,0055 (Ν 00 Ο Ο* oo in o cT 5 t— Ο. 0,0015 00 CO δ o' 0,0051 I o 0,002 j 0,003 IS ο 0 ,0014 ί „__ 0,0016 0,0017 σ&gt; o 〇_ o 〇_ o' 0,0036 0,0021 S o 〇_ 00 τ- Ο 〇· XXXXXXXX Work XXXXXX Work XXXX ο ο o ϋ oo O oo 〇 Ί: XXIIXXXXXP(0)(Ph:3-Me,5-Et)0Me P(0)(Ph:3,5-di-Me)OMe P(0)(Ph:3-Me,5-Et)0Me P(0)(Ph:3,5-di-Me)OMe P(0)(Ph:3,5-di-Me)OMe P(0)(Ph:3,5-di-Me)OMe P (0)(Ph:3,5-di-Me)OMe P(0)(Ph:3,5·di-Me)0Me P(0)(Ph:3-CH=CHC5N&gt;0Me P(0)( Ph: 3-F, 5-Br) OMe CONH2 CONHCH2 (4. pyrimidine: 1-0) GONHCH2 (3 "pyridyl: 3-0" CONHGH2 (4-pyridinium: 3-F) CONHCH2 (4·pyridine: 3+,4-0) CONHCH2(2-pyrazine) CONHCH2(5-pyrimidine) C0NHCH2(&amp;pyrimidine:[0) CONH2 CONH2 XX r XZXXXXX 22h 18h 22d 3 ψ Ό&gt; CM OJ 33a | ΡΓ ο 荃99 inch inch Ό εΐΟΟΌ - 0U3 w^^t SSVN/Λ Inch ooI?uIooIASSS^SSVN/A inch 〇〇13^£02"^军-剞瀚钬^砘^葙荽^^ wtgj to qi3+#^客^w^^^^J'oaNu^Kyaas^^^- wZLr-oo^I^^^^^fl^Mf^#^ Φ Inc. 0102-凇&lt;&amp;3 driving J'w^^troM Gong Ming^^衾二曰/SILOOOKW II^Z/ONL Gong φ^ ¥J曰/wisz,^w ς·ΟΜ#φ^孤幸513⁄4尔?U009 a〇衾)^钕脔钕脔^)荽^^. ^〇翁甶^^:^卜瓣02:硪转_£ 261 93533 200804280 Toxicology 1. pH dependent type aqueous solubility The aqueous solubility of each compound is 1 mM by the conventional shake flask method. Determined at saturation concentration. The flask (vial) was shaken at ambient temperature for 3 hours and then centrifuged. The supernatant was analyzed by HPLC with UV detection to determine solubility. Generally, those with higher aqueous solubility are the preferred drug candidates. 2. Human plasma protein binding Human plasma protein binding lines were determined using the Equilibrium dialysis method. The dialysis system was carried out using pooled human blood plasma at a drug concentration of 1 μΜ at 37 ° C for about 6 hours. At the end of the dialysis, buffer samples were collected from the buffer-side of the dialysis cell and the free drug concentration was analyzed by LC/MS/MS. As for NNRTI, the lower the protein combination, the better. 3. Two-way CACO-2 permeability The purpose of this analytical test was to determine the two-way permeability classification of the test compounds in the Caco-2 cell monolayer system and the possibility of limited effluent uptake. Typically, this assay involves the measurement of the non-specific binding of the test compound to the Transwell instrument in pH 7.4 assay buffer. The test compound is evaluated by the bi-directional permeability of the Caco-2 cell monolayer, the apical-to - Basolateral transport assessment, base-to-top transport assessment, and single layer integrity. High permeability and no effluent indicate that the intestinal permeability is not expected to be a limiting factor for human oral absorption. 4. CYP450 Inhibition 262 93533 200804280 In vitro CYP450 inhibition screening can be used to predict possible drug-drug interactions. To determine if a test compound inhibits specific P450 enzyme activity, changes in P450-specific receptor metabolism by human liver microsomes are monitored at various concentrations of the test compound. The effectiveness and grade of this inhibition can be assessed by measuring the IC50 value of a particular isozyme. Regarding NNRTI, higher IC50 values showed less inhibition and thus showed a lower likelihood of drug-drug interaction in patients. CYP3A4 inhibition was screened using the CYP3A4/BFC Efficient Inhibitor Screening Kit (BD Biosciences), CYP2D6/AMMC Southern Effect Inhibitor Screening Kit (BD Biosciences) for Screening, and CYP2C9 Inhibition Using P450 The -G1〇TM test kit (Promega) was screened. 5. In vitro metabolic stability of liver microsomes This metabolic stability test is used to assess the stability of test compounds in biological matrices. This data helps to understand and predict the excretion mechanism of the test compound. The CYP450-dependent metabolism of drugs can also vary widely from species to species. The metabolism of the drug outside the body is assessed by liver microsomes from a variety of species, which allows for a comparison of animal and human metabolism. This helps identify the most relevant animal models for pharmacokinetic (PK) and toxicological studies. The metabolic stability of the test compounds was assessed in vitro by liver microsomes in rats, dogs, monkeys, and humans. 10 μΜ of the test compound and 1 mg/mL of liver microsomes were pre-incubated for 5 minutes in 0.1 Μ Tris buffer, ρ Η 7·4 containing 5 mM MgCl 2 and 0·1 mM EDTA at 37 °C. After the culture, NADPH (final concentration of 3 mM) was added to initiate the reaction and 263 93533 200804280 was sampled in culture sputum and 1 or 2 hours. After the reaction was terminated, the disappearance of the parent compound and the formation of metabolites in the supernatant were analyzed by muscle c_uv or LC/MS/MSA. The % of the residual parent compound is the ratio of the peak area of the sample of the 丨 or 2 hours to the peak area of the sample of time 0. Generally, the less metabolic action (higher parent compound % value) is better. 6. In vitro Metabolism of Liver Microparticles - Metabolic Pathway This test evaluates the first phase of biotransformation of test compounds. The metabolites of the samples from the metabolic stability test were analyzed by ^C/MS/MS. The structure of the metabolites is visualized according to multiple experiments such as a well-known scan, a scan of the scan, and a scan of the daughter ions. This metabolic pathway is then assumed based on the structure of the major metabolite. Regarding the compound derived from the cyanoic acid series, the terminal oxime epoxidation is the main route, followed by the oxidation of dimethyl-phenyl group, wherein the methyl group is subjected to crystallization, reoxidation to the more, and finally Oxidation to tick. 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—1003 嫦趣¢1213 嫦哒#-H0cos_ 哒^硪溆¥|· 丨0H3 嫦哒*'I0S3 嫦哒JJKy«)¥*&quot;:w^^rf-N α •Ν ζ g —NO Review φ ^#ι 0 丨N a. Attack φ^ψι 7· Pharmacokinetics (PK) in rats and dogs and oral bioavailability test compounds for pharmacokinetics in Sprague-Dawley rats and MiG Lu dog conducted an assessment. A typical PK study involved a single IV injection of 1 mg/kg for 2 to 3 animals and a single oral infusion of 5 mg/kg for 3 additional animals. Blood samples were collected at multiple time points during the 24-hour period. Plasma was isolated and tested for compounds and their metabolites by LC/MS/MS. PK parameters were calculated from the plasma concentration-time plot using the noncompartmental method. Oral bioavailability (F) is calculated from the dose-normalized AUC values obtained from oral and IV administration. The higher the value of oral bioavailability, the better. 266 93533 200804280

Average PK parameters (N=3 or 2) IL· p6.0% Ο z 2.9% 12.4% Vss (mUkg) 6368.6 l_______ 9587.9 ο z 4079.3 3715.7 Ο (mUk〇/hr) 5417.8 7992J2 ο z 1192.3 821.8 AUCInf / dose 188.3 302 I_ 125,9 ο z 070.1 I 27.7 1220,5 149.3 AUCinf 3 \ λ 188.3 tS0.9 J 125.9 ο 970.1 I 138.6 1220.5 740J •jg so 5 i €174.3 132.0 ! 108.3 ο ζ 923.5 I 116.4 1007.0 696.1 S! P s a&gt; d CN N. 〇&gt; o § CM to oi CM cc CP N Tmax 1 U&gt; d ο ζ • K dh OI Cmax (ngfinL) 166-7 45.0 I_ CO m ο ζ 407.0 60.9 429.7 116.2 Carrier PEG400 PEG400 PEG400 PEG400 I PEG400 PEQ400 PEG paste 0.5% MC dose (m_) qo iT&gt; q ο tfi c&gt; f- o id oo id pathway &gt; 〇CL Ο α. &gt; 0 tL &gt; 0 a. Rat I rat rat classification N-oxide|N-oxide I_ parent compound parent compound parent compound I parent compound N-oxide N-oxide compound QDZ ζ zz DD 267 93533 200804280 [Simplified illustration] 1st The figure shows that the general structures of the three inventions are of formula (A) and formula ( B), and formula (C). Figure 2 is a diagram showing the phosphorylated compounds (I) to (X) of the general formulae (A) and (B). Figure 3 illustrates the 9- and 10-membered double rings of the general formula (C). Phosphorylated compounds (XI) to (XX). 268 93533

Claims (1)

200804280 X. The scope of application for patents: 1. A compound of phosphine that has been replaced as needed. 2. The compound of claim 1, wherein the 3_scale is a phosphate, a phosphonate, a phosphorothioate, a thiophosphonate, an imidophosphate or an imido group. Phosphonate form. 3. A compound as claimed in claim 1, wherein the compound is a phosphate or a phosphonic acid vinegar. 4. A compound as claimed in claim 1, wherein the compound is further substituted at the 2-position. 5. The compound of claim 1, wherein the compound is substituted on the nitrogen of the 吲 u. 6. The compound of claim 1, wherein the compound is a compound of formula (A): X 3, commercially available salts, prodrugs, oxides, quaternary amines, stereochemical isomers or tautomers, wherein X and Y are each independently W 1 to 14 tetrapod carbon rings , aryl, heterocyclic, any of which may include a single f-fluorene- or spiro structure, or may be substituted as desired; 93533 269 200804280 dd) OH; ee) C b Br, I, F; ff) CF3; Gg) Cu alkyl; hh) c2_6 alkenyl; ii) C2_$ alkynyl; jj) alkyl heterocycle; kk) NH2; 11) NH-alkyl; mm) N-dialkyl; nn) NH-aryl ;) N-alkylaryl; pp) N-aralkyl; qq) NH-heterocyclic ring; rr) N-alkyl-heterocyclic ring; ss) N-alkenyl-heterocyclic ring; tt) N- Alkynyl-heterocyclic ring; uu) O-alkyl; νν) Ο-alkenyl; ww) Ο-alkynyl; χχ) Ο-alkyl aryl; yy) Ο-aryl; ζζ) Ο-heterocyclic; aaa 0_arylalkyl; 270 93533 200804280 bbb) 0-carbon, ccc) SR2; or ddd) NR2R3; alternatively, X and Y may combine to form a bicyclic or tricyclic phosphorylated heterocyclic ring which is optionally substituted, wherein Each ring includes 3 to 7 ring members; Z is: mm) Η; ηη) alcoxy; 00) Ν〇2; pp) N(R2)(R 3); qq) OR2; it) formamidine; ss) guanamine; tt) sulfhydryl; uu) S(0)nR2; vv) S(0)n-NR2R3; ww) Cu alkyl; XX ) thin base; yy). 2-6 alkynyl; ZZ) calcined aryl; aaa) arylalkyl; bbb) heterocyclic; CCC) alkyl-heterocyclic; ddd) aryl; 271 93533 200804280 eee) CN ; fff) C(=W) -R2 ; ggg) C(=W)NH-C(R2)(R2)-C(=W)-N(R2)(R2); hhh) C(=W)NH-P(=W)(R2 )-A-R2 ; iii) C(=W)NH-AS(0)n-NR2 ; jjj) C(=W)NH-CR2R3-S(0)n-NR2R3 ; kkk) C(-W)- NH-AC(=W)-N(R2)(R3); 111) C(=W)-N(R2)(R3); mmm) C(=W)-NH-A-R2 ; nnn) C( =W)-NH-NH-R2 ; ooo)C(-W)-NH-C(R2)(R2)-C(-W)NH-C(R2)(R3)C(= W)-N( R2)(R3); ppp) C(=W)-NH-R2 ; qqq) C(=W)-NH-AC(=W)-NH-AC(=W)-NH2 ; rrr) C(R2) (R2)(R3); sss) C(R2)(R2)-NH-R2; ttt) AS(0)n_R2; uuu) C(-W)-AC(=W)-AC(=W)R3 ; Vvv) A-R2 ; www) C(=W)-(0)R2 ; xxx) C(=W)-A_C(=W)-NH2 ; mm) Amino acid residue; aaa) C(=W) -N(R2)-A-(amino acid residue); bbb) C(=W)-N(R2)-A_(amino acid residue)_C(=W)-R2; 272 93533 200804280 ccc) C(=W)-amino acid residue; ddd) C(=W)-N(R2)-A-(amino acid residue)-AC(=W)-R2; eee) C(=W) _OR3 ; fff) C(=W)-S(R2); ggg) C(=W)-NH-NH-R2 ; hhh) C(=W)-NH-N(R2)_A-C(two W) R2 ; iii) C(=W)-N(R2)-C(-W)-R3 ; jjj) C(=W)-A-NH-C(=W)R2 ; kkk) C(=W&gt;A-NH_C(= W)OR3 ; 111) C(=W)-A-R3 ; mmm) C(=W)-NH-NH_CH2-C(=W)R2 ; aaa) P(=W)(R2)(R2); Bbb) AP(=W)(R2)(R2); hhh) AP(=W)(R3)(R3); iiDCtW^NH-Cwoalkyl-heteroaryl; jlDCtWhNH-C^alkyl-heteroaryl ; kkk) C(=W)-NH-CH2-heteroaryl; and Η &gt;=/ 111); wherein in the specific examples (ddd), (eee) and (fff), the heteroaryl group can be visually required Containing a charged heteroatom, and especially comprising an N-oxide wherein each of the foregoing X, Y and Z can be independently unsubstituted or substituted by a 273 93533 200804280 or more of the following groups: b) hydrazine; Ii) Cu alkyl; iii) alkoxy; iv) OH; v) keto; vi) halo; vii) NR2R2; viii) optionally substituted aryl; ix) optionally substituted heterocyclic X) 0-C(=W)_alkyl; xi) C(=W)-OR2 ; x) CN ; xi) N〇2 ; xii) NH_C(=W)_alkyl; xiii) NH-S (0) n-alkyl; xiv) NH_S(0)n-NR2R2; or xv) C3_6 cycloalkyl; W is: h) O; i) S; j) NH; k) NN(R2)(R2) ; l N(R2); 274 93533 200804280 m) N-OH; or n) NO-alkyl; R1 is: l) H; m) R2; n) C(=W)-R2; o) C(=W )-0(R2); p) C(=W)_S(R2); q) C(=W)-NH-R2 ; r) C(=W)-N(R2)(R2); s) C (=W)-NH-A-(amino acid residue); t) A-(amino acid residue)-R2, u) S(0)n-R3; or v) S(0)2_N( R2)(R2); any of which may be substituted by one or more of the following groups: i. Cu-based; ii. OH; iii. alkoxy; iv. aryl; V. halo; vi CN; vii. N02; or viii. N(R2)(R2); each R2 is independently selected from: 275 93533 200804280 aaa) Η; bbb) OH; ccc) halogen; ddd) substituted, branched as needed Or unbranched alkyl; eee) optionally substituted, branched or unbranched alkenyl; fff) substituted, branched or unbranched alkynyl as desired; ggg) 3 to 14 carbon rings ; hhh)alkylheterocycle; iii) fluorenyl; jjj) formamidine; kkk) aminomethanyl; 111) alkoxy; mmm) optionally substituted aryl; nnn) substituted as needed Aromatic base; 〇〇〇) substituted alkaryl; PPP) 0-alkyl; q Qq) 0-dilth; rrr) 0-alkynyl; sss) 0-burning group, ttt) 0_aralkyl; uuu) 0-carbocycle; vvv) 0-heterocycle; www) 0-aryl XXX) CF3; 276 93533 200804280 yyy) CN ; zzz) S(0)n-R3 ; aaaa) N(R3)(R3); bbbb) NH-S(0)n-R3 ; cccc) NHC(=W )-aryl; dddd) NHC(=W)-alkyl; eeee) NHC(=W&gt;heterocycle; ffff) CH2-S(0)nR3; gggg) C(=W)R3 ; hhhh) C(- W) NR3R3; iiii) C(alkyl)2-S(0)nR3; jjjj) CH(alkyl)-S(0)nR3; kkkk) C(alkyl)2-NH2; 1111) CH(alkyl )_N(alkyl)R3 ; mmmm) CR3R2-NR3R3 ; nnnn) CH2N(alkyl)R3 ; oooo) CH(alkyl)_NHR3 ; pppp) C(alkyl)2-NHR3 ; qqqq) c(alkyl) 2-n(alkyl)r3 ; rrrr) CH2-C(-W)H ; ssss) CH2_C(=W)alkyl; tttt) CR3R3-C(-W)R3 ; uuuu) A-R3 ; vvvv) C (R3)2-C(-W)R3; 277 93533 200804280 wwww) CH2-C(=W)H ; xxxx) CH2-C(=W) dilute base; yyyy) CH(alkenyl)-C(=W H; zzzz) AS(0)R3; aaa) CH(NH)-S(0)nR3; or bbb) AN(NH)R3; wherein the optional substitution includes one or more of the following: A) Substituted or unsubstituted heterocyclic ring; B) C(=W)0-aryl; c c(=w)o_alkyl; D) C(=W)NH2; E) C(=W)NH-alkyl; F) C(=W)NH_aryl; G) C(=W N-di-alkyl; H) C(=W)N(alkyl)-aryl; Ι)α-amino acid; J) a-amino ester; K) a-amino-decylamine L) P-amino acid; Μ) β-amino ester; or Ν) β-aminocarbamide; each R3 is: bb) Η; cc) OH; 278 93533 200804280 dd) Cle6 alkyl; ee C2-6 fine base, ff) C2_6 alkynyl; gg) alkoxy; hh) CF3; ii) CN; jj) amine group, kk) NR2R2; 11) 0-alkyl; mm) O-fluorenyl; Nn) O-alkynyl; oo) C(R2)(R2), S(0)nNH2; pp) C(R2)(R2)-S(0)nCF3 ; qq) C(R2)(R2)-NH2 ; rr) A-heterocyclic ring; ss) C(R2)(R2)-NR2R2; tt) C(R2)(R2)-C(=W)R2; uu) aryl; VV) hindered ring; ww) Ring; xx) cycloalkyl; yy)alkylaryl; zz)alkylidene; aaa) arylalkyl; or 279 93533 200804280 bbb)heterocyclic-alkyl; either of which may be unsubstituted or Or substituted by any of the following groups in any combination: i. halo, xxiv. OH; xxv. OR2; xxvi. SR2; xxvii. COOH; xxviii. oxoester; xxix·C(=W)R2 ; xxx· C(=W)OR2 ; xxxi· C(=W)OR3 ; xxxii. C(=W)SR2 ; xxxiii. AC(=W)NH2 ; xxxiv. C(=W)NR2R3 ; xxxv. NR2R2 ; Xxxvi. NR2R3; xxxvii. NR2-S(0)nR3; xxxviii· NR^CpWhCu alkyl; xxxix. S(0)nR3; xl. Ci_6 alkoxy; xli. Cu thioether; xlii. Amino acid residue Xliii·NH-A-(amino acid residue); 280 93533 200804280 xliv·C(=W)NH-A-(amino acid residue); and xlv·wherein the optional substitution includes In the case of a substituted heterocyclic ring, the substitution is selected from the group consisting of: b·C(=W)0-aryl; c·C(=W)0-alkyl; d. C(=W)NH2; e·C(=W)NH-aryl; f·C(=W)NH_alkyl; g·C(=W)N-di-alkyl; h· C(= W) N(alkyl)-aryl; i. amino acid; j·α·amino ester; k· α-amino-decylamine; k·β-amino acid; 1·β-amino group Or an ester; or m·β-amino-decylamine; η·halo; or 〇·money; η is independently 0, 1 or 2; Α is a double-substituted separator selected from the group consisting of : j· C!-6 alkyl, branched or unbranched, and It is desirable to have one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the bond or attached to the chain; 93533 281 200804280 k. (: 2-12 alkenyl, branched or unbranched a chain, and optionally one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions are present at the bond or attached to the chain; l. Cm an alkynyl group, branched or unbranched, And optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached to the chain; m. optionally substituted aryl; η·0-alkylene a group, a branched or an unbranched group, and optionally one or more heteroatoms, aryl groups, cycloalkyl groups or heterocyclic group functions present in the chain or attached to the chain; Chain or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached to the chain; Ρ· optionally substituted cycloalkyl; And q. optionally substituted heterocyclic ring; wherein "A" can be linked by any desired bond or any combination of desired linkages Each of R4', R5, R6, and R7, independently: a· Η; b·halogen; c·N〇2; d·CN; e·CF3; f. OR2; 282 93533 200804280 g. nr2r2 h. NHS(0)nR2; i·NHCO-C&quot;alkyl; j. S(0)nR2; k. aryl; 1 · heteropolar, m·Cu alkyl; n. C2-6 dilute; 0· C2-6 fast radical; p. C(=W)-S(0)nR2 ; q. C(=W)-S(0)n-NR2R2 ; r. C(=W)-aryl; s C(=W)-alkyl; t. C(=W)-heterocyclic; or u.C(=W)_NR2R2; each of which may be substituted by one or more of the following groups: r.OR2 Ii. S(0)nR2 ; iii· C(=W)-S(0)nR2 ; iv· C(=W)_S(0)n-NR2R2 ; xxi. C(=W)-aryl; xxii C(=W)-alkyl; xxiii·C(=W)-heterocycle; xxiv. C(-W)NR2R2; 283 93533 200804280 χχν. Η ; xxvi· Ν〇2 ; xxvii. CN ; xxviii. CF3 Xxix. Halogen; xxx. NHS(0)nR2; xxxi·NHCO-Cu alkyl; xxxii·aryl; xxxiii·heterocycle; xxxiv. Cu alkyl; xxxv·C2_6 alkenyl; xxxvi·C2_6 alkynyl; Xxxvii· NR2R2 ° 7. For the compound of claim 6, wherein R5' is halogen, CH3, CN CF3 or N02. 8. The compound of claim 7, wherein R5' is Cl. 9. A compound as claimed in claim 6 wherein W is deuterium or S. 10. A compound as claimed in claim 6 wherein Z is an optionally substituted guanamine or formamide. 11. A compound according to claim 6 wherein X is a substituted or unsubstituted phenyl group. 12. A compound according to claim 6 wherein Y is -O-Cw alkyl. 13. A compound as claimed in claim 6 wherein the compound is selected from the group consisting of: 284 93533 200804280 285 93533 200804280 286 93533 200804280 22ad Cl 22af 22ah Cl 22aj F^OMe C! 々fsOMe TCN i Vo- OMe Cl HN V ·0 〇C?-〇Me N ΗΝ-λ, , 22ae '-OMe Cl HN- &quot;V·. · , 22ag , 22ai \+·〇- , 22ak Cl H m 〇 know Cl HN- \+·0· -CN ,22al Cl And 22am HN—^ F F-f Ν+·0· 14. The compound of claim 1, wherein the compound is a compound of formula (B): 287 93533 200804280 R4" Or a pharmaceutically acceptable salt, prodrug, oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein: Y is: a. 3 to 14 membered carbocyclic, aryl, heterocyclic Any of which may comprise a monocyclic, bicyclic, tricyclic or spiro structure, or any of which may be substituted as desired; b. Η; c. OH; d. 13⁄4, c. CF3 j f. g. C2-6 dilute; h. C2_6 alkynyl; i. alkyl heterocycle; j. NH2; k. NH-alkyl; l. N-dialkyl; m·NH_aryl; 288 93533 200804280 η. N-alkylaryl; 〇·N-aralkyl; ρ·NH-heterocyclic; q·N-alkyl-heterocyclic; r. N-dilyl-heterocyclic; s · N-blockyl - mixed soil, t. 0-alkyl, u. 0-fluorenyl; v. 0-alkynyl; w. 0-alkyl aryl; X. 0-aryl; y. 0-heterocyclic; - arylalkyl; aa. 0-carbocycle; bb. SR2; or cc. NR2R3; H y bbb) alkoxy; CCC) N〇2 ; ddd) N(R2)(R3); eee) OR2 ;醯 醯 醯 ;; 289 93533 200804280 hhh) fluorenyl; iii) S(0)nR2; jjj) S(0)n-NR2R3; kkl^Cw alkyl; 111) C2_6 alkenyl; Mmm) C2_ 6 alkynyl; nnn) calcined aryl; 000) arylalkyl; ppp) heterocyclic; qqq) alkyl-heterocyclic; rrr) aryl; sss) CN; ttt) C(=W)-R2; uuu) C(=W)NH-C(R2)(R2)-C(=W)-N(R2)(R2); vvv) C(=W)NH-P(=W)(R2)-A-R2 ; www) C(=W)NH-AS(0)n-NR2 ; xxx) C(=W)NH-CR2R3-S(0)n-NR2R3 ; yyy) C(=W)-NH-AC(= W)-N(R2)(R3); zzz) C(=W)_N(R2)(R3); aaaa) C(=W&gt;NH-A-R2; bbbb) C(=W)-NH-NH -R2 ; cccc)C(=W)_NH_C(R2)(R2)_C(=W)NH_C(R2)(R3)C( W)-N(R2)(R3); dddd) C(=W)- NH-R2 ; 290 93533 200804280 eeee) C(=W)-NH-AC(=W)-NH-AC(=W)-NH2 ; ffff) C(R2)(R2)(R3); gggg) C( R2)(R2)-NH-R2 ; hhhh) AS(0)n-R2 ; iiii) C(=W)_A-C(=W)-A_C(=W)R3 ; jjjj) a-r2 ; kkkk) C(=W)-(0)R2; 1111) C(=W)_A_C(=W)-NH2 ; mmmm) Amino acid residue; nnnn) C(=W)-N(R2)-A-( Amino acid residue); oooo) C(=W)-N(R2)_A-(amino acid residue)-C(=W)_R2; pppp) C(=W)-amino acid residue; Qqqq) C(=W&gt;N(R2)-A-(amino acid residue)-AC(=W)_R2 ; rrrr) C(-W)-OR3 ; ssss) C(-W)-S(R2 ); tttt) C(=W)-NH_NH-R2 ; uuuu) C(=W)-NH-N(R2)-AC(=W)R2 ; vvvv) C (=W)-N(R2)-C(=W)-R3 ; wwww) C(=W)-A-NH-C(=W)R2 ; xxxx) C(=W)-A_NH_C(=W) OR3 ; yyyy) c(=w)-a-r3 ; zzzz) C(=W)-NH-NH_CH2-C(=W)R2 ; aaa) P(=W)(R2)(R2); or bbb) Α·Ρ(二W)(R2)(R2); 291 93533 200804280 wherein each of the aforementioned γ and z may be independently unsubstituted or substituted by one or more of the following groups: r. Η; s. Cle6 烧t; alkoxy; u. OH; v. keto; w. halo; χ· NR2R2; y. optionally substituted aryl; ζ · optionally substituted heterocyclic; aa· 0 -C(=W)-alkyl; bb·C(=W)-OR2 ; cc. CN ; dd. N02 ; ee· NH-C(=W)-alkyl; ff· NH-S(0)n -alkyl; gg. NH-S(0)n-NR2R2; or hh. C3_6 cycloalkyl; W is: h) Ο; i) S; j) NH ; k) NN(R2)(R2); 292 93533 200804280 l) N(R2); m) N_OH ; or η) NO-alkyl; R1 is: cc) H ; dd) R2 ; ee) C(=W)_R2 ; ff) C(=W)-0 (R2); gg) C(=W)-S(R2); hh) C(=W)-NH-R2 ; ii) C(=W)-N(R2)(R2); jj) C(= W)_NH-A_(amino acid residue); kk) A-(amino acid residue)-R2; 11) S(0)n-R3; or mm) S(0)2-N(R2) (R2); If necessary, it may be substituted by one or more of the following groups: i. alkyl; ix. OH; χ·alkoxy; xi. aryl; xii. halo; xiii. CN; xiv·N〇2; Or xv. N(R2)(R2); 293 93533 200804280 each R2 is: a) Η; b) OH; c) halogen; ccc) optionally substituted, branched or unbranched alkyl; ddd) Requiring a substituted, branched or unbranched alkenyl group; eee) a substituted, branched or unbranched alkynyl group as desired; fff) 3 to 14 membered carbocyclic ring; ggg) alkylidene heterocycle; hhh) ; iii) formamidine; jjj) amino fluorenyl; kkk) alkoxy; 111) optionally substituted aryl; mmm) optionally substituted aryl; nnn) substituted as needed Calcined aryl; 〇〇〇) 0-hospital; ppp) 0-alkenyl; qqq) 0-alkynyl; rrr) 0-calcinyl; sss) 0-arylalkyl; ttt) 0-carbocycle ; uuu) 0_heterocyclic; vvv) 0-aryl; 294 93533 200804280 www) CF3 ; xxx) CN ; yyy) S(0)n-R3 ; zzz) N(R3)(R3); aaaa) NH- S(0)n_R3; bbbb) NHC(=W)-aryl; cccc) NHC(=W)-alkyl; dddd) NHC(=W)-heterocycle; eeee) CH2-S(0)nR3 ; ffff) C(=W)R3 ; gggg) C(=W)NR3R3 ; hhhh) C(alkyl)2_S(0)nR3 ; iiii) CH(alkyl)-S(0)nR3 ; jjjj) C( Alkyl) 2-NH2; kkkk) CH(alkyl)·Ν(alkyl)R3; ini) cr3r2-nr3r3; mmmm) CH2N(alkyl)R3; nnnn) CH(alkyl)_NHR3; oooo) C( Alkyl) 2-NHR3; pppp) c(alkyl)2-N(alkyl)R3; qqqq) CH2-C(=W)H; rrrr) CH2-C(=W)alkyl; ssss) CR3R3- C(=W)r3 ; tttt) A-R3 ; 295 93533 200804280 uuuu ) C(R3)2-C(=W)R3 ; yvvv) CH2-C(=W)H ; wwww) CH2-C(=W ) (zxxx) CH(NH)-S(0)nR3; or aaaaa) AN(NH)R3; Substituting such substitutions include one or more of the following: I. substituted or unsubstituted heterocyclic ring; II. C(=W)0.aryl; iii.c(=w)o-alkyl; IV .C(=W)NH2; V·C(=W)NH-alkyl; VI. C(=W)NH-aryl; VII. C(=W)N-di-alkyl; VIII. C( =W) N(alkyl)-aryl; IX. cx-amino acid, 〇1-amino vinegar, XI. α-amino-carbamamine; XII. β-amino acid; XIII. --amino ester; or χιν.β-amino-decylamine; XV. halogen; or XVI Cyano, 296 93533 200804280 Each R3 is: bb) Η; cc) OH; dd) Cw alkyl; ee) C2_6 fluorenyl; ff) C2_6 alkynyl; gg) alkoxy; hh) CF3; ii) CN ; jj) amine; kk) NR2R2; 11) O-alkyl; mm) O-alkenyl; nn) O-fast radical, oo) C(R2)(R2)-S(0)nNH2; pp) C (R2)(R2)-S(0)nCF3; qq) C(R2)(R2)_NH2 ; rr) A-heterocyclic ring; ss) C(R2)(R2)_NR2R2 ; tt) C(R2)(R2 )-C(-W)R2; uu) aryl; vv) carbocyclic ring; ww) heterocyclic ring; xx) cycloalkyl; 297 93533 200804280 yy) aryl group; zz) alkyl group; aaa) Or bbb)heterocyclic-alkyl; any of which may be unsubstituted or substituted by one or more of the following groups in any combination: I. halo, ILOH; III. OR2; IV. V. COOH ; VI. Carboxylic ester; VII. C(=W)R2 ; VIII. C(=W)OR2 ; IX. C(=W)OR3 ; X. C(=W)SR2 ; XLA-C (=W)NH2; XII.C(=W)NR2R3; xiii.nr2r2; xiv.nr2r3; XV. NR2-S(0)nR3; XVI. NRtCpWyCK alkyl; XVII. S(0)nR3; XVIII. Cw Alkoxy; 298 93533 200804280 XIX. Cu thioether; XX. Amino acid Residue; XXI. NH-A-(amino acid residue); XXII. C(=W)NH-A_(amino acid residue); and XXIII. wherein when the optional substitution includes substitution In the case of a heterocyclic ring, the substitution is selected from the group consisting of, i.e., C(=W)0-aryl; ii. C(=W)0-alkyl; iii. C(=W)NH2; iv·C(=W)NH-aryl; v. C(=W)NH-alkyl; vi. C(=W)N-di-alkyl; vii·C(= W) N(alkyl)aryl; viii· α-amino acid; ix. α-amino ester; χ. α-amino-decylamine; xi. β-amino acid; xii. β-amine a base ester; or xiii·β-amino-carbamamine; η is independently 0, 1 or 2; Α is a disubstituted partition selected from the group consisting of: i) Cw alkyl, branched Or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain 299 93533 200804280 or attached to the bond; j) Ci12 stretching, branching Or unbranched, and optionally having an aryl or aryl, cycloalkyl or heterocyclyl functional group present in the chain or attached to the chain; k) C2_u alkynyl, branched or unbranched, and optionally one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached to the chain; , l) A substituted aryl group is required; m) a hydrazine-alkyl group, a branched or unbranched group, and optionally one or more heteroatoms, aryl groups, cycloalkyl groups or heterocyclic groups are present in the chain or Attached to the chain; n) an aralkyl group, branched or unbranched, and optionally one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached to The chain; 〇) optionally substituted cycloalkyl; and P) optionally substituted heterocyclic ring; wherein "A" may be linked by any desired linkage or any combination of desired linkages; each R4' , R5', R6' and R7' are independently: a. Η; b·halogen; c. N02; d. CN; e. CF3; 93533 300 200804280 f. OR2 ; g. nr2r2 ; h. NHS(0) nR2; i·NHCO-Cu alkyl; j· S(0)nR2 ; k. aryl; l. heteropolar, m. Ci_6 alkyl; n. C2-6 dilute; 〇· C2-6 fast radical;· C(=W)-S(0)nR2 ; q· C(=W)-S(0)n-NR2R2 ; r. C(=W)-aryl; s. C(=W&gt;alkyl; t. C(=W)-heterocyclic ring; or u·C(=W)_NR2R2; each of which may be substituted by one or more of the following groups: I. OR2; II· S(0)nR2 ; III · C(=W)-S(0)nR2; IV·C(=W)_S(0)n-NR2R2; V. c(=w)-aryl; VI. c(=w)-alkyl; VII. c(=w)-heterocyclic ring; 301 93533 200804280 VIII·C(=W)NR2R2 ; IX. Η ; x. no2 ; XI· CN ; XII. cf3 ; XIII. halogen; XIV. NHS(0)nR2 XV·NHCO-Cu alkyl; XVI·aryl; XVII. heterocyclic; XVIII·Cu alkyl; XIX. C2-6 alkenyl; XX. c2,6 alkynyl; or XXI·NR2R2 ; ', R3', R4'', R5", and R6'' are independently: bb) Η; cc) halogen; dd) N〇2; ee) CN; ff) OR2; gg) SR2; hh) NH2; Ii) NR2R3; jj) n(r2)-c (two wyCw alkyl; 302 93533 200804280 кк) NCRq-SOyCw alkyl; 11) Cu alkyl; mm) C2-6 alkenyl; nn) C2-6 fast radical , 〇〇) aryl; PP) CFs ; qq) CR2R2-S(0)nR3 ; rr) CR2R2NR2R3 ; ss) C_OH ; tt) CR2R2-C(= W) R2 ; uu) acid group; vv) C(=W)R2 ; ww) C(=W)OR2 ; xx) C(=W)SR2 ; yy) C(=W)_NR2R3 ; zz) C(= W) NH(CH2)P_(amino acid residue); ааа) amine residue; or bbb) A-(amino acid residue); wherein any of the above may be substituted as needed; or alternatively, R2 or R6" may be bonded to γ to form a bicyclic or tricyclic phosphorylated heterocyclic ring having 4 to 14 ring members which may be optionally substituted. 15. A compound of claim 14, wherein γ, CH3, CN, CF3 or N〇, 16 is a compound of claim 15 wherein r5 is ci. 93533 303 200804280 17. The compound of claim </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; w, , 2, 19, such as the unsubstituted phenyl compound of claim 14 of the patent application. among them Or 20. The compound of claim 12, wherein γ is a compound of ', &lt;1-6, ,, 21, and the compound of the patent scope: wherein the compound is a formula (c) R4 ” Or a salt, prodrug, oxide, tetramer chemical isomer or tautomer thereof, wherein: ·, female, and Υ are: ', may include a to 14 carbon a ring, an aryl group, a heterocyclic ring, any one of a single ring, a double ring, a tricyclic ring or a spiro structure; b· Η ; c. ΟΗ ; d. halogen; 93533 304 200804280 e. CF3 ; f. Cw alkyl; g C2-6 dilute; h. C2-6 fast radical, i. alkyl heterocycle; j. NH2; k. NH-alkyl; l. N-dialkyl; m. NH-aryl; N-alkylaryl; 〇·N-aralkyl; p. NH-heterocyclic; q. N-alkyl-heterocyclic; r. N-alkenyl-heterocyclic; s. N-alkynyl-heterocyclic ; t· O-alkyl, u. O-fluorenyl; ν· Ο-fast radical, w· 0_calcinyl; χ. Ο-aryl; y. Ο-heterocycle; ζ·Ο-aralkyl Aa. , bb. SR2 ; or 305 93533 200804280 cc. NR2R3 ; z is: aaa) H ; bbb) alkoxy; CCC) N〇2 ; ddd) N(R2)(R3); eee) OR2 ; f ff) formamidine; ggg) guanamine; hhh) fluorenyl; iii) S(0)nR2; jjj) S(0)n-NR2R3; kkk) Cu alkyl; 111) c2_6 alkenyl; mmm C2_6 alkynyl; Nnn) aryl aryl; 〇〇〇) aralkyl; ppp) heterocyclic; qqq) alkyl-heterocyclic; rrr) aryl; sss) CN; ttt) C(=W)-R2; uuu) C( =W) NH_C(R2)(R2)_C(=W)-N(R2)(R2); vvv) C(=W)NH-P(=W)(R2)-A-R2 ; 306 93533 200804280 WWW C(=W)NH-AS(0)n_NR2 ; xxx) C(=W)NH-CR2R3-S(0)n-NR2R3 ; yyy) C(=W)-NH-AC(=W)-N (R2)(R3); zzz) C(=W)-N(R2)(R3); aaaa) C(=W&gt;NH-A_R2; bbbb) C(=W&gt;NH-NH-R2 ; cccc)C (=W)-NH-C(R2)(R2)-C(=W)NH-C(R2)(R3)C(= w)_n(r2)(r3); dddd) C(=W)- NH-R2 ; eeee) C(=W)-NH-AC(=W)-NH-AC(=W)-NH2 ; ffff) C(R2)(R2)(R3); gggg) C(R2)( R2)-NH-R2 ; hhhh) AS(0)n-R2 ; iiii) C(=W)_A_C(=W)-AC(=W)R3 ; jjjj) A-R2 ; kkkk) C(=W) -(0)R2; 1111) C(=W)-AC(=W)-NH2 ; mmmm) amino acid residue; nnnn) C(=W)-N(R2)-A-(amino acid residue ()) oooo) C(=W)_N(R2)-A_(amino acid residue)-C(=W)-R2; pppp) C(=W)_amino acid residue; qqqq) C( =W)-N(R2)-A_(amino acid residue)-AC(=W)-R2; rrrr) C(=W)-OR3 ; ssss) C(=W)-S(R2); 307 93533 200804280 tttt) C(=W)-NH-NH-R2 ; uuuu) C(=W)-NH-N(R2)-AC(=W)R2 Vvvv) C(=W)-N(R2)-C(=W)-R3 ; wwww) C(=W)-A-NH-C(=W)R2 ; xxxx) C(=W)-A- NH-C(=W)OR3 ; yyyy) C(=W)_A-R3 ; zzzz) C(=W)-NH_NH-CH2_C(=W)R2 ; aaa) P(=W)(R2)(R2) Or bbb) A_P(=W)(R2)(R2); wherein each of the foregoing Y and z may be independently unsubstituted or substituted by one or more of the following groups: ηη) Η ; 〇〇) Cu Alkoxy; qq) OH; rr) keto; ss) halo; tt) nr2r2; uu) optionally substituted aryl; vv) optionally substituted heterocyclic; ww) 0_C (=W)_alkyl; XX) C(=W)_OR2 ; yy) CN ; ZZ) N〇2 ; 308 93533 200804280 aaa) NH-C(=W)-alkyl; bbb) NH_S(0)n -alkyl; ccc) NH-S(0)n_NR2R2; or ddd) C34 cycloalkyl; W is: h) O; i) S; j) NH; k) NN(R2)(R2); l) N (R2); m) N-OH; or η) NO-alkyl; R1 is: l) H; m) R2; n) C(=W)-R2; o) C(=W)-0(R2 p) C(=W)-S(R2); q) C(=W)_NH-R2 ; r) C(=W)-N(R2)(R2); s) C(=W)- NH-A-(amino acid residue); t) A-(amino acid residue)-R2; u) S(0)n-R3; or v) S(0)2-N(R2)( R2); 309 93533 200804280 One may be substituted by one or more of the following groups: i. Ci_6 alkyl; ii. OH; iii. alkoxy; iv. aryl; v. halo, vi. CN; vii· N〇2 Or viii. N(R2)(R2); each R2 is: ccc) Η; ddd) OH; eee) halogen; fff) optionally substituted, branched or unbranched alkyl; ggg) a substituted, branched or unbranched alkenyl group; hhh) an optionally substituted, branched or unbranched alkynyl group; iii) a 3 to 14 membered carbocyclic ring; jjj) an alkylheterocyclic ring; kkk) an acid group; 111) amidino group; mmm) aminyl fluorenyl; ηηη) alkoxy; 〇〇〇) an optionally substituted aryl group; ΡΡΡ) an optionally substituted aryl group; 310 93533 200804280 qqq) A substituted aryl group is required; rrr) 0-alkyl group; sss) &gt; ttt) Ο-alkynyl; uuu) Ο-burning aryl; ννν) Ο-arylalkyl; www) 0_carbon ring; XXX 0-heterocyclic ring; yyy) 〇_aryl; zzz) CF3; aaaa) CN ; bbbb) S(0)n-R3 ; cccc) N(R3)(R3); dddd) NH-S(0)n -R3 ; eeee) NHC(=W)-aryl; ffff) NHC(=W)-alkyl; gggg) NHC(=W)-heterocycle; hhhh) CH2-S(0)nR3 Iiii) C(=W)R3 ; jjjj) C(-W)NR3R3 ; kkkk) C(alkyl)2_S(0)nR3 ; 1111) CH(alkyl)-S(0)nR3 ; mmmm) C(burning Base) 2-NH2; nnnn) CH(alkyl)-N(alkyl)R3; 311 93533 200804280 〇〇〇〇) CR3R2-NR3R3; pppp) CH2N(alkyl)R3; qqqq) CH(alkyl)- NHR3 ; rrrr) C(alkyl)2-NHR3 ; ssss) C(alkyl) 2-N(alkyl)R3 ; tttt) CH2-C(-W)H ; uuim) CH2-C(=W) (vvvv) CR3R3-C(=W)R3 ; wwww) A-R3 ; xxxx) C(R3)2-C(=W)R3 ; yyyy) ch2-c(=w)h ; zzzz) ch2_c(= w) alkenyl; aaaaa) CH(alkenyl)-C(=W)H; bbbbb) AS(0)R3; ccccc) CH(NH)-S(0)nR3; or ddddd) AN(NH)R3; Wherein the optional substitution includes one or more of the following: i. a substituted or unsubstituted heterocyclic ring; ii. C(=W)0-aryl; iii. C(=W)0-alkyl; V. C(=W)NH-alkyl; vi. C(=W)NH-aryl; vii. C(=W)N_di-alkyl; 312 93533 200804280 viii C(=W)N(alkyl)-aryl; ix. a-amino acid; x. a-amino ester; X i · a-amino-cartoamine, χϋ.β-amino acid ; χίϋ.β-amino ester; or χίν.β-amino-曱Amine; each R3 is: bb) Η; cc) OH; dd) Cw alkyl; ee) C2-6 dilute; ff) C2_6 alkynyl; gg) alkoxy; hh) CF3; ii) CN; jj) Amine; kk) NR2R2; 11) 0-alkyl; mm) 0_fluorenyl; nn) O-alkynyl; oo) C(R2)(R2)-S(0)nNH2; pp) C(R2) (R2)-S(0)nCF3; qq) C(R2)(R2)-NH2; 313 93533 200804280 rr) A-heterocyclic ring; ss) C(R2)(R2)-NR2R2; tt) C(R2) (R2)_C(di W)R2; uu) aryl; vv) hindering ring; ww) heterocyclic ring; XX) cycloalkyl; yy) alkylaryl; zz) alkylidene; aaa) aryl; Or bbb) a hetero-and a leuco group, either of which may be unsubstituted or substituted by one or more of the following groups in any combination: i) halo; ii) OH; iii) OR2; iv) SR2 v) COOH ; vi) Wei acid ester; vii) C(=W)R2 ; viii) C(=W)OR2 ; ix) C(=W)OR3 ; x) C(=W)SR2 ; xi) AC (=W)NH2 ; 314 93533 200804280 xii) C(=W)NR2R3 ; xiii) NR2R2 ; xiv) NR2R3 ; xv) NR2_S(0)nR3 ; xvONR^CpWhCu alkyl; xvii)S(0)nR3 ; xviiQCu Oxy; xix) Ci_6 thioether; xx) amino acid residue; xxi) NH-A_ (amine Acid residue); xxii) C(=W)NH-A-(amino acid residue); and xxiii) wherein when the optional substitution includes a substituted heterocyclic ring, the substitution is carried out alone or in Any combination selected from the group consisting of: I. c(=w)o-aryl; II. c(=w)o-alkyl; III·C(=W)NH2; IV·C( =W)NH-aryl; V·C(=W)NH-alkyl; VI. C(=W)N-dialkyl; VII·C(=W)N(alkyl)-aryl; VIII. α-amino acid; IX. οι-amino vinegar, X. α-amino-decylamine; 315 93533 200804280 χι·β-amino acid; χιι·β-amino group; or XIII· Β-amino-formic acid amine; η is independently 〇;; or 2; Α is a disubstituted partition selected from the group consisting of: a. Cu alkyl, branched or unbranched, And optionally having one or more heteroatoms, aryl, cyclofilament or heterocyclyl functions present in the bond or attached to the chain; b, C2_u alkenyl, branched or unbranched, and optionally Having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached to the chain; c·C 2_n alkynyl, branched or unbranched, and optionally one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached to the chain; d. Substituted aryl; e· 〇-alkyl, branched or unbranched, and optionally one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached Attached to the chain; f. extended aralkyl, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions present in the chain or attached thereto a chain; g. optionally substituted cycloalkyl; and h. optionally substituted heterocyclic ring; wherein "A" may be linked by any desired linkage or linkage of any group 316 93533 200804280; Each R4', R5', R6' and R7' is independently: a. Η; b. halogen; C · N〇2, d. CN; e. CF3; f. OR2; g. nr2r2; h. 0) nR2; i·NHCO-Cu alkyl; j. S(0)nR2; k. aryl; l. heterocyclic ring; Π1·Cu alkyl group; n. C]-6 thin group; 〇·C2-6 Fast base; p C(=W)-S(0)nR2 ; q· C(=W)-S(0)nNR2R2 ; r. C(=W)-aryl; s. C(=W)-alkyl; t C(=W)_heterocyclic ring; or u.C(=W)-NR2R2; each of which may be substituted by one or more of the following groups: 317 93533 200804280 i. OR2 ; ii. S(0) n(r); iii. C(=W)-S(0)nR2; iv·C(=W)-S(0)n_NR2R2; v. C(=W)-aryl; vi. C(=W&gt;alkyl ; vii. C(=W)_heterocycle; viii· C(=W)NR2R2 ; ix. H ; X. N〇2 ; xi. CN ; xii. CF3 ; xiii·halogen; xiv. NHS(0)nR2 Xv. NHCO-Cu alkyl; xvi. aryl; xvii·heterocyclic; xviii· Cu alkyl; xix. C2-6 dilute; xx. C2_6 alkynyl; or xxi. NR2R2; each R3”, R4” , R5", and R6'' are independently: a. H; b. halogen; 318 93533 200804280 C. N〇2; d. CN; e. OR2; f. SR2; g. nh2; h. NR2R3; Alkyl; j. alkyl; k. Ck alkyl; l. C2-6 dilute; m. C2-6 fast radical, n. aryl; o. CF3; ρ·CR2R2-S(0)n- R3 ; q. CR2R2NR2R3 ; r. C-OH ; s · CR2R2-C(=W)R2 ; t. acid group; u. C(=W)R2 ; v· C(=W)OR2 ; w. C(-W)SR2 ; x. C(=W)-NR2R3 ; y. C(=W)NH(CH2)p-(amino acid residue); z. amine residue; or 319 93533 200804280 aa· A-(amino acid residue); wherein any of the above may be substituted as needed; and ^2 represents the presence of a single or double bond, where: when the two represents the presence of a double bond, each Y and T Independently: j. CR3 ; k. N ; or l. SR2 ; only one of Y and T shall be CR2; when two or two represent a single bond, then each γ and T are independently: m. CR2 n. O ; o. NR2 ; or p. SR2 ; but one of Y and T must be CR2 ; and m is 1 or 2, but m can only be 2 when τ or Y = CR2. 22. A compound according to claim 21, wherein the 5' is halogen, CH3, CN, CF3 or N02. A compound of claim 22, wherein R5 is cl. 24. A compound according to claim 21, wherein z is an optionally substituted amidino or guanamine. 25. A compound as claimed in claim 21, wherein ... is 〇 or S. 26. A compound as claimed in claim 1 wherein gamma is 6 alkyl. ", 27, a composition of medical music, including HI V - therapeutically effective amount of 3 - squamous sputum 320 93533 200804280 吲哚 compound or its pharmaceutically acceptable salts, prodrugs, stereoisomers, tautomers An oxide or a quaternary amine, and a pharmaceutically acceptable carrier or diluent. 28. The composition of claim 27, wherein the 3-phosphonium head is a primary phorate or a phosphonic acid A form of sulphuric acid, sulphur sulphuric acid, or a phosphoric acid sulphate. The composition of claim 27, wherein the compound is a phosphate or a phosphonate. The composition of claim 27, wherein the compound is further substituted at position 2. 31. The composition of claim 27, wherein the compound is substituted on the nitrogen of the hydrazine. For example, the composition of claim 27 of the patent scope includes the effective anti-HIV therapeutic amount: the compound of the patent application scope 6, 14, or 21 or its acceptable salt, prodrug, and stereo Structure, tautomerism: oxide or quaternary amine, A pharmaceutically acceptable carrier or dilution 33. A composition of at least n of the patent application, wherein the compound is in combination with a species, an anti-HIV agent, and a carrier or diluent as claimed. * Bengbu City has 4': Shenzhi Pharmaceutical Composition, which is the other horse reverse transcription S# inhibitor. 3 5 · If Shenqi Patent Fanzhan anti-mv agent is a two-component pharmaceutical composition, which Other anti-I-enzyme inhibitors. 93533 321 200804280 36. The pharmaceutical composition of claim 35, wherein the reverse transcriptase inhibitor elicits lysine 1 〇 3 - aspartate in HIV reverse transcriptase And/or tyrosine 181-&gt; mutation of cysteine. 37·&quot; an effective amount of a 3_phosphonium compound having a pharmaceutically acceptable carrier or diluent or a pharmaceutically acceptable amount thereof The use of a salt, a prodrug, a stereoisomer, a tautomer, a ruthenium osmium compound or a quaternary amine for the manufacture of a medicament for the treatment or prevention of HIV infection in a host. The use of 37 items, wherein the 3-phosphonium is a phosphate or a phosphonic acid The use of thiophosphate or guanamine phosphate. 39. The use of claim 37, wherein the compound is a phosphate or a phosphonate. 40. The use of claim 37, wherein The compound is further substituted at position 2. 41. The use of claim 37, wherein the compound is substituted on the nitrogen of the hydrazine. 42. The use of the compound according to claim 37, wherein the compound A compound of any one of claims 1, 9, or 16 or a pharmaceutically acceptable salt, prodrug, stereoisomer, tautomer, cerium oxide or quaternary amine thereof, as needed It has a pharmaceutically acceptable carrier or diluent. 43. The use of claim 37, wherein the host is a human. 44. The use of claim 37, wherein the compound is administered in combination with at least one other anti-HIV agent and/or alternately, optionally with a pharmaceutically acceptable carrier or diluent. 45. The use of the anti-HIV 322 93533 200804280 agent is a reverse transcriptase inhibitor, as claimed in claim 44. 46. For example, the fourth dose of the patent scope of the invention induces mv anti-Korean collateral + COSCO reverse transcriptase inhibition. Amino acid 181 Λ Aspartame and/or road makeup fee 18 cysteine mutation. 4=Apply for a patent (4) 37-ride, which has a mutation in the amino acid 1〇3-'cysteine in the Qingqing reverse transcriptase. And 4 or/or alkalamine H, the use of claim 37, wherein the mv is resistant to an anti-transcriptase inhibitor. 〆 49== Use of the item of item %, wherein the compound is administered in combination with and/or alternately with a drug-i::anti-drug agent, optionally having a commercially acceptable carrier or diluent. 5〇.-A compound of 3_phosphonium (IV) compound or a salt thereof, a prodrug, a stereoisomer, a tautomer thereof, which is required to have a therapeutically effective carrier or diluent The substance, strontium oxide or tetra-, and amine rides are used to manufacture a rescue treatment for the treatment or prevention of HIV. In the case of wood, the application of the scope of claim 50, wherein the compound of the compound is in the scope of any of the formulas 9 or 16; or the compound of the invention, or the salt, the drug, the stereoisomer, and the mutual Isomers, &quot;-oxides or quaternary amines. For the use of the patent application No. 5G, wherein the compound is administered in combination with a other anti-HIV agent and/or administered as a therapeutically acceptable carrier or diluent. 93533 323