TW200823202A - Certain chemical entities, compositions, and methods - Google Patents

Abstract

Chemical entities that modulate smooth muscle myosin and/or non-muscle myosin, pharmaceutical compositions and methods of treatment of diseases and conditions associated with smooth muscle myosin and/or non-muscle myosin are described.

Description

200823202 IX. INSTRUCTIONS: This application claims priority from the following US provisional patent applications: 60/835 251 of August 2, 2006 and 6G/835,249 of 2 August 2, 2, They are all citing this article for reference. 5TECHNICAL FIELD OF THE INVENTION The present invention provides specific chemicals, pharmaceutical compositions, and related to smooth muscle myosin and/or non-muscle myosin, which regulate smooth muscle myosin and/or non-muscle myosin. Treatment of diseases and symptoms. [Prior Art] 10 15 Myosin is present in all muscle and non-muscle cells. In human fine, ten kinds of myosin, myosin_π is considered to be responsible for the form of contraction of the collateral muscle, myocardium and smooth muscle. Myosin-II is also present in the presence of f-muscle myosin; it is also called cytoplasmic myoglobin. Non-muscle myosin is ubiquitous in eukaryotic cells. Myosin is usually present in smooth muscle cells. Moon muscle myosin II is significantly different from the other nine different classes of myosin in terms of t-formation and overall structure. Myosin_π consists of two spherical head functional parts (called: -1 or S1) that are connected together by a coil. Depending on the hydrolysis conditions of the protein, the muscle egg is often produced / S1 or heavy enzymatic myosin _M, with a truncated tail part = two ATPase and the combination of the molecule actin can be 兮:, : The actin filament was moved inside the test tube, so this was reported as the motor region of the molecule (mot〇rd〇main). 5 20 200823202 The isoforms of myosin-π from different tissues, although some biological properties are different, they share the same basic molecular structure of two heavy chains (about 200 kDa), which are non-covalent. Sexually combined with two pairs of light chains (approximately 20 and 17 kDa). The di-globular amine-based end is tethered together by a carboxy-terminal 5α-helical coil of the tail. It is generally believed that the tails are involved in the aggregation of filaments of myosin molecules; these heads are believed to have actin-activated Mg2+-ATPase activity. Each myosin head can be divided into approximately 25, 50, and 20 kDa peptides based on three protease sensitive regions. The 25 kDa _ 50 kDa junction near the amino terminus is close to the ATP binding region, while the actin 10 protein binding function site is close to the 50 kDa - 20 kDa junction. S1 consists of a so-called catalytic actinal globular actin binding and a nucleotide binding region. This function is located at its carboxy terminus and is connected to an alpha-helical structure wound by a light chain of about 20 kDa. The light chain coupling function of S1 is a so-called lever arm. During the transition from the pre-pump state to the post-shock state, it is generally believed that the lever arm swings approximately 90 degrees near the fulcrum in the catalytic functional portion near the nucleotide acid binding site. This "powerful hit" is driven by helium hydrolysis. The other end of the myosin molecule is the α-helical coiled tail that involves the myosin molecule self-aggregating into a bipolar thick myofilament. These thick muscle filaments are interdigitated between the 20 thin actin filaments, and the two filaments slide against each other during muscle contraction. This myofilamental sliding mechanism is thought to involve a structural change in the myosin head that is driven by the sputum hydrolysis, along the thin actin filaments. Although non-muscle myosin acts in the same manner, it is known to slide at a slower rate than smooth muscle myosin. 6 200823202

The complete cDNA of human smooth muscle myosin has been described. The sequence of human smooth muscle myosin is 52% identical to human cardiac myosin in the catalytic S1 region. See, for example, PCT Bulletin No. WO 03/14323 〇 5 [Summary of the Invention] The present invention provides at least one chemical selected from the following formula X and a pharmaceutically acceptable salt thereof:

Wherein U is selected from the group consisting of an optionally substituted aryl group, an optionally substituted cycloalkyl group, an optionally substituted heterocycloalkyl group, an optionally substituted heteroaryl group, and twiow2 (wherein The junction with Z1); W1 and W2 are independently selected from CRnR12, NR13, and Ο; but at least one of W1 15 and W2 is NR13; W3 is selected from CR12, NR14 and Ο; Z1 is aryl; Z2 is Aryl; R8 is selected from the group consisting of argon, optionally substituted alkyl, optionally substituted 20 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted Heterocycloalkyl; 200823202 R1, R2, R11, and R12 are independently selected from the group consisting of hydrogen, hydroxy, carboxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, If desired, substituted alkynyl groups, optionally substituted alkoxy groups, optionally substituted aryloxy groups, optionally substituted heteroaryloxy groups, 5 optionally substituted heterocycloalkyloxy groups, A substituted aminocarbonyloxy group, an optionally substituted alkoxy group, an optionally substituted alkoxycarbonyloxy group, Optionally substituted alkoxycarbonyl, optionally substituted amine, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine a carbonyl group, optionally substituted with an amine fluorenyl sulfonyl group; or R1 and R2, together with any intervening atom to which they are attached, form a cycloalkyl group selected from optionally substituted and optionally substituted a group of a heterocycloalkyl group; R and R14 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, 15 substituted cycloalkyl, optionally substituted aryl, optionally substituted An aryl group, optionally substituted heterocycloalkyl; in each case, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, hydroxy, optionally substituted alkyl, optionally substituted ring. Alkyl, optionally, left substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally A substituted heterocycloalkyloxy group, optionally substituted aminocarbonyloxy group, A substituted methoxy group, optionally substituted alkoxycarbonyloxy group, optionally substituted fluorenyl group, optionally substituted alkoxycarbonyl group, optionally substituted amine group, optionally substituted aromatic group And, if necessary, take 8 200823202 ί heteroaryl, optionally substituted heterocyclic thiol, optionally substituted amine group, and optionally substituted amino group thiol; or R1 and existing A R5 may optionally be combined with any intervening atoms to form a group selected to be substituted with a cycloalkyl group and optionally substituted 5-heterocycloalkyl; one or the opposite of 14 and the presence of one of R5 may be required Combines with any intervening atoms to form an optionally substituted heterocycloalkyl ring; if the pot or right wl is NRl3, then R13 and R1 may be combined with any atom between them to form an optionally substituted Heterocycloalkyl ring; 1〇 or if hip! For NrU, then Rl3 and one of the R5 groups may be combined with any intervening atoms to form a heterocyclic ring which is optionally substituted; R7 and R10 are independently selected from the group consisting of hydrogen, cyano, and hydroxy groups. , carboxyl group, azido group, schlossyl group, fluorenyl group, sulfhydryl group, thiol group, 15 groups of alkoxy groups, optionally substituted aryloxy groups, optionally substituted heteroaryloxy groups The base q is a heterocyclic methyloxy group which is substituted, an optionally substituted alkoxycarbonyl group, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, optionally, if necessary Substituted block, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclic 20 alkyl, optionally substituted amine, optionally substituted thiol, Substituted amine carbonyl, optionally substituted aminosulfonyl, optionally substituted formazan; W is selected from 0, 1, 2 and 3; w is selected from 〇, 1, 2 3, and 4; 9 200823202 The household is selected from 1, 2, and 3; and "selected from 0, 1, 2, 3, and 4. The invention also provides a pharmaceutical composition comprising at least one chemical described herein, and at least one pharmaceutically acceptable carrier selected from the group consisting of a carrier, an adjuvant, and an excipient. The invention also provides a method of treating a smooth muscle myosin or a non-muscle type myosin or a plurality of conditions; the cardiac therapy method comprising administering a therapeutically effective amount of at least one of the chemicals described herein, or comprising At least one chemical, and a pharmaceutical composition selected from the group consisting of a carrier, an adjuvant, and an excipient, at least one pharmaceutically acceptable carrier. Other aspects and specific examples will be apparent from the following description for those skilled in the art.

The following words and touches used in this manual t are otherwise indicated, otherwise they are usually intended to have the meanings described below. - If any of the variables used in this article appear more than once in the chemical formula, then the boundary of each occurrence of 0^ is independent of the definition of each other occurrence.

PIPES ATP The following abbreviations and terms have the meaning indicated in the full text. 1,4-pipelined diethanesulfonic acid adenosine 5'-triphosphate

DTT BSA DL-dithiothreitol bovine serum albumin

NADH PEP EGTA final test indoleamine adenine dinucleotide acid olefinic propanol-acid glycol-bis(2-aminoethyl ether)-N,N,N,,N,·tetrazine 200823202

Ac = APCI = atm = Boc = c- = CBZ = CDI = DCM = DIAD = DIBAL-H = DIEA = DMAP = DMF = DMSO = (DPPF)PdCl2 = Et = EtOAc = EtOH = g = GC = H or hr = HATU = acid ethyl ketone atmospheric pressure chemical free method atmospheric third butoxycarbonyl cyclobenzyl oxycarbonyl carbonyl diimidazole dichloromethane = CH2C12 azodicarboxylic acid diisopropyl vine argon diisobutyl aluminum DIPEA = N, N- Diisopropylethylamine 4-(dimethylamino)pyridine N,N-didecylguanamine disulfoxide [1, fluorene-bis(diphenylphosphino)ferrocene]dichloropalladium (II Ethyl ethyl acetate, ethanol, gas chromatography, hourly hexafluorophosphate, 0-(7-azabenzotriazol-1-yl)tetradecyl fluorene 11 200823202 HBTU = bismuth hexafluorophosphate-(benzotrim) Zin-1-yl) Tetramethylhydrazine HOBT = 1-hydroxybenzotriazole HPLC = High pressure liquid chromatography i- = iso kg or Kg = kg L or 1 = liter LC/MS = LCMS = liquid layer Analytical-mass spectrometry LDA = lithium diisopropylamide LRMS = low resolution mass spectrometry m/z = mass-to-charge ratio Me = methyl NMP = N-methyl_2_σ ratio Lodinate NMR = nuclear magnetic resonance MPLC = medium pressure liquid phase Chromatography min = min mL = ml MW = microwave N- = positive Ph = phenyl (Ph3P) 4Pd = 肆 (triphenylphosphine) palladium (0) (Ph3P) 2PdCl2 = dichlorobis(triphenylphosphine) palladium (II) RP-HPLC = reverse phase - south pressure fluid Phase chromatography rt or RT = room temperature 12 200823202 s_ = sec-= second t- = tert-= third TBAF = tetrabutylammonium fluoride TBS = TBDMS = third butyl decyl fluorenyl TES = three Ethyl decyl or triethyl decane TMS = trimethyl decyl decyl or tridecyl decane TFA = trifluoroacetic acid THF = tetrazinc yt TLC = thin layer chromatography UV = UV

Volume = equivalent to the volume of ML/g or liter/kg limited reagent (unless otherwise stated) The dash "_" between two letters or symbols is used to indicate the point of attachment of the substituent. For example, -conh2 is linked via a carbon atom. "As needed" means that the subsequently described event or condition may or may not occur, and the statement includes the occurrence or non-occurrence of the event or condition. Example 5 For example, "alkyl as appropriate" encompasses both "alkyl" and "substituted alkyl" as defined below. Those skilled in the art will appreciate that with respect to any group containing one or more substituents, the group is not intended to introduce any substitution or substitution pattern that is impractical, unsynthetic, and/or inherently unstable. 10 The term "ATPase" as used herein refers to an enzyme capable of hydrolyzing ATP; ATPase includes a protein containing a molecular motor (eg, myosin) "alkyl" encompassing the number of carbon atoms shown (usually 1 to 20) Carbon 13 200823202 A straight chain and a branched chain of an atom, for example, 1 to 8 carbon atoms, for example, up to 6 carbon atoms. For example, the Cl_C6 alkyl group encompasses straight-chain and branched-chain alkyl groups having from 1 to 6 carbon atoms, and examples thereof include methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, and Tributyl, pentyl, 2-5 10 15 pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, 3-methylpentyl, and the like. An alkylene group is another subgroup of alkyl groups and refers to the same residue as the alkyl group, but has two points of attachment. The alkylene group usually has 2 to 2 carbon atoms, for example, '2 to 8 carbon atoms', for example, '2 to 6 carbon atoms. For example, h狎alkyl means a covalent bond and (alkyl) is a methyl group. When an alkyl residue having a specific carbon number is stated, all geometric isomers having that carbon number are intended to be encompassed. Therefore, "butyl" is intended to include n-butyl, t-butyl, isobutyl and tert-butyl; "propyl" includes n-propyl and isopropyl. "low-city" brain a "lower alkyl group" having - to four carbons. - "alkenyl group" means an unsaturated branched chain having at least one carbon-carbon double bond derived from a parent chain-removed carbon atom. Or a straight group; the base may be in a cis or trans configuration at a double bond. A typical group includes, but is not limited to, a vinyl group; a propylene group such as a propyl group, a yl group, a group, a propyl group 1_yl (dilyl), propyl, cyclopropyl; cyclopropane-2-diamine; butyl group such as butylene-diyl, small f, butyl-..., butyl-u - dilute a • base, dilute 4 base, succinyl-l-yl, cyclobutane _3_yl, cyclobutene < % of the two ritt body, the alkenyl group has 2 to 2. Carbon atom: in his specific case, with 2 to 6 Carbon atom. 20 200823202 Derivatives of the methane chain of the methane system - carbon atom removal - a chlorine atom group ϋ bond unsaturated branch chain or direct bond smoldering, type alkynyl group, but not limited to , an alkyl group such as prop-1-yne-!-yl, propan-2-alkynyl, steroidal J-based group such as but-1-alkyn-1-yl, but-1-yn-3-yl, __3_ alkynyl, etc. .Hl aa ® θ ^ . In the specific example, the fluorenyl group has 2 to 2 carbon atoms and in other specific examples, 3 to 6 carbon atoms. 10 15 carbon production. A non-aromatic second coat usually having 3 to 7 ring carbon atoms, which may be saturated or have - or multiple carbon-carbon double bonds. The ring-based group of ^iS2. A pentenyl group, a cyclohexyl group, a decyl group, and a bridged group with a caged saturated ring group such as a hydrazine. "Alkoxy group" means a hospital having an indication of the number of carbon atoms connected via an oxygen bridge. Oxyl, ethoxy, propoxy, isopropoxy, n-butoxy, second butoxy, second butyl butyl butyl, pentyl, 2-pentyloxy, Isoprenyl, neodecyloxy, hexyloxy, 2-hexyloxy 3 hexyloxy, 3-methyl, pentyloxy, etc. The alkoxy group usually has an alkyl group bonded via an oxygen bridge to 7 = atomic 16-group decyloxy group means a group having one to four carbon atoms. 1 20 i mono- and dinonyl decylamine encompasses a group of -(C=〇)NRaRb, wherein: 1 and 1 are independently selected from hydrogen and an alkyl group containing the indicated number of carbon atoms' However, Ra and Rb are not hydrogen at the same time. "Alkyl" means (alkyl) (0)-; (cycloalkyl)-C(O)-; (aryl)_c(o)_; (heteroaryl) a group such as _c(0)_; and (heterocycloalkyl)hepta(9); wherein the group m is bonded to the parent structure by a carboxyl group, and the group thereof is burned 15 200823202, 5 sulphur, aryl, hetero Both aryl and heterocycloalkyl are as described herein. The thiol group has an indication of the number of carbon atoms, wherein the carbon group of the ketone group is included in the carbon number counted. For example, the 'C2 fluorenyl group is an acetamino group having the formula ch3(c=o)-. "Methyl group" refers to the _C(0)H group. 5 "Amine-based" refers to the group (amino)-c(o)-o-. "Substituted aminemethanyl" refers to a group (substituted amino group) -c(o)-o-. "Carboxyl" means a _C(0)0H group. The "oxygenated alkoxy group" means a group of the formula (alkoxy) (〇0)- which is bonded via a carbonyl carbon, wherein the alkoxy group has an indication of the number of carbon atoms. Thus the 10 Ci-c:6 alkoxy group is an alkoxy group having from 1 to 6 carbon atoms attached to the carbonyl linkage via its oxygen. "Amine" means a -NH2 group. "Mono- and di-(alkyl)amino" embraces both secondary and tertiary alkylamino groups wherein alkyl is as defined above and has the indicated number of carbon atoms. The point of attachment of the alkane 15 -amino group is on the nitrogen. Examples of the mono- and di-alkylamino groups include an ethylamine group, a diammonium group, and a mercapto-propyl-amino group. The term "amine carbonyl" refers to the group _C〇NRbRc, wherein Rb is selected from hydrogen, optionally substituted CrC6 alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, If desired, substituted aryl, and optionally substituted heteroaryl; and selected from hydrogen and optionally substituted Cl_c4 alkyl, or R and Re, and nitrogen bonded thereto, formed as needed Substituted 5 to 7 membered nitrogen-containing heterocycloalkyl groups optionally containing one or two additional heteroatoms selected from the group consisting of hydrazine, N, and S in the heterocycloalkyl ring; 200823202 wherein each substituted group The group is independently substituted with one or more substituents independently selected from the group consisting of CVCU alkyl, aryl, heteroaryl, arylalkyl, heteroaryl-CrCU alkyl, Ci-CU halide , -OCVC4 alkyl, -OC1-C4 alkylphenyl, -C1-C4 alkyl-OH, -OC1-C4 alkyl, halo-5, -OH, _NH2, -Ci-Q alkyl-ΝΗ2 Ν((ν(:4 alkyl XCkCU), ΝΗ(〇ν(:4 alkyl), -NA-CU alkyl) (Ci-C4 alkylphenyl), -NHCCrC4 alkylphenyl ), cyano, nitro, keto (cycloalkyl, heterocycloalkyl) Or a substituent of a heteroaryl group), _C02H, -(:(0)0(^-04alkyl, -CONA-CU alkyl XCVQ alkyl), -CONHCCVC4 alkyl), 10 -CONH2, -NHC (0 (CVC4 alkyl), -NHC(0)(phenyl), -N(Cl-c4 alkyl)c(o)(cvc4 alkyl), -N(Ci-c4 alkyl)c(0)( Phenyl), -QOKvq alkyl, _c(0)Cl_c4 alkylphenyl, _c(〇)Ci_C4 haloalkyl, -〇C(〇) (VC4 alkyl, _s〇2 (Cl_c4 alkyl), _s〇 2 (stupid), -scmcvcu haloalkyl), _s〇2Nh2, _s〇2NH (Ci C4 alkyl b 15 -S02NH(phenyl), _nhs〇2 (Ci_c4 alkyl), _NHs〇2 (phenyl plate) -NHS02 (CVC4 _ burnt base). ', square base" covers: 6-shell carbocyclic steroid ring, for example, benzene; double bad system, at least one of which is a carbocyclic ring and an aromatic ring, for example, laughter, 20 and naphthalene And a tricyclic ring system in which at least one ring is a carbocyclic ring and an aromatic ring, for example, fluorene. For example, an aryl group is fused to a hetero atom containing hydrazine or a plurality of S and 5 to 7 Chang, 〇, 贝, 贝 5 衣 衣 衣 衣 5 5 5 5 5 5 5 5 此 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠 稠In the case of a family ring, its linkage 17 200823202 may be located in the carbocyclic aromatic ring or the heterocycloalkyl ring. The divalent group having a free valence at the substituted awkward atom is designated as a &quot;shouben group. A bivalent 2 group obtained by removing a hydrogen atom from a carbon atom having a free valence of a monovalent polycyclic ring whose name is terminated by "_base", the name of which is "sub" before the name of the corresponding monovalent group. 7 column 2, a naphthyl group having two points of attachment is referred to as a naphthylene group. However, the aryl group is never covered or overlapped with a heteroaryl group as defined hereinafter. Thus, if a "or" ring is fused to a heterocyclic alkyl aromatic ring, the resulting ring system is a heterocyclyl' rather than an aryl group as defined herein. The term ίο 15 aryloxy means _〇_aryl group. The term "aryl" refers to a -alkyl-aryl group. "Mercapto" refers to a -C(=NH)-NH2 group. e substituted methiol refers to the group -C(=NRe)_NRfRg, wherein R, is from: hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, A substituted aryl group, optionally substituted heteroaryl, and optionally substituted heterocycloalkyl; &quot; and! ^ is independently selected from the group consisting of: hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted a cycloalkyl group; wherein at least one of Re, Rf, and Rg is not hydrogen and the alkyl group substituted with I, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl are respectively alkyl, cycloalkyl And one or more (e.g., up to 5, for example, up to 3) hydrogen atoms of the aryl, heterocycloalkyl, and heteroaryl groups are replaced by substituents independently selected from the group consisting of:

Ra, -ORb, optionally substituted amino group (including ·ΝΙ^〇ιι1), 20 200823202 _NRcC02Ra, -NRcCONRbRc, _NRbC(NRc)NRbRc, _NRbC(NCN)NRbRe, and -NReS02Ra), halo, cyano , nitro, keto (which is a cycloalkyl, heterocycloalkyl, and heteroaryl substituent), optionally substituted thiol (eg, -CORb), optionally substituted alkoxycarbonyl (Example 5 Such as -C02Rb), amine carbonyl (such as -CONRbRe), -OCORb, -0C02Ra, -OCONRbRc, -0P(0)(0Rb)0Rc, sulfur alkyl (such as SRb), sulfinyl (such as -SORa), And a sulfonyl group (for example, -S02Ra and -S02NRbRc); wherein Ra is selected from a Cr9 alkyl group which is optionally substituted, an optionally substituted aryl group, and optionally substituted heteroaryl group; 10 Rb is selected from a CVC6 alkyl group, optionally substituted aryl group, and optionally substituted heteroaryl group, as desired;

Re is selected from the group consisting of hydrazine and an optionally substituted CrQ alkyl group; or 1^ and R°, together with the nitrogen to which it is bonded, forms a heterocycloalkyl group optionally substituted; and 15 each of which is optionally substituted The group is unsubstituted or independently substituted with one or more, for example one, two, or three, substituents independently selected from the group consisting of Ci-CU alkyl, aryl, heteroaryl, aromatic Alkyl, heteroaryl-CVC4 alkyl, CVC4 haloalkyl, ·OCrQ alkyl, -OCVC4 alkylphenyl, -CVC4 alkyl-OH, -OCrQ haloalkyl, halo, -OH, 20 _NH2 , -CVC4 alkyl-NH2, -NCCi-q alkyl KCVCU alkyl), -NI^CVCU alkyl), alkyl) (〇ν(:4 alkylphenyl), -ΝΗ((ν〇:4 Alkylphenyl), cyano, nitro, keto (which is a substituent of a cycloalkyl, heterocycloalkyl or heteroaryl), -C02H, -CfCOOCi-CU alkyl, -CONCCVC^alkyl KCVCU Alkyl), -CONH^CVC^alkyl), 200823202 -CONH2, -NHC^OKCi-CU alkyl), -NHC(0)(phenyl), -NCCkQ alkyl)(:(0)((^ -(:4 alkyl), _Ν((ν(:4 alkyl)C(0)(phenyl), -cccoc^-cu alkyl, -c^coc^-cu alkyl Base, -(:(0)(^-(:4 haloalkyl, -0(:(0)(^-(:4 alkyl, -SOdCVC^ alkyl), -S02(phenyl), 5 - SOdCi-CU haloalkyl), -S02NH2, -SC^NI^CVC^ alkyl), -S02NH(phenyl), -NHSOKCVC^alkyl), _NHS02(phenyl), and -NHSO^C^CU halogen The term "halo" includes a fluoro group, a gas group, a bromo group, and an iodine group; the term "rhosin" includes fluorine, chlorine, molybdenum, and hydrazine. 10 15 20 "halogen group" means 1 Examples of alkyldidentate alkyl groups as defined above having a specific number of carbon atoms substituted by a plurality of halogen atoms (generally up to the maximum number of halogen atoms allowed), but not limited to 'trifluoromethyl, difluoromethyl Base, 2-fluoroethyl, and pentafluoroethyl. Heteroaryl" encompasses: 5 to 7 membered aromatic, monocyclic, containing one or more, or, in a specific embodiment, 1 to 3 a hetero atom selected from the group consisting of a hetero atom, the remaining ring atoms being carbon; for example, 1 to 4 N, hydrazine, and s bicyclic heterocycloalkyl ring, and containing a right octagonal μ or a specific 罝...V or more 'for example , 1 to 4, will be 疋 specific examples, 〗 〖 to 3, the remaining ring atoms are magnetic moon In the miscellaneous materials of 士, 〇, and 8; and "Atom is a stone anaerobic and at least one of the heteroatoms thereof is present in the aromatic cyclodiazepine heterocycloalkyl ring, which contains the right one: in a specific specific example, 1 to 4:, V is from '...I, the rest is carbon and at least:; hetero atoms from /, di and S appear in the aromatic ring 20 200823202. - for example, a heteroaryl group is fused to a 5- to 7-membered cycloalkyl or heterocyclic" to a 7-membered heterocycloalkyl, an aromatic ring. These fused, bicyclic heteroaryl are only one of the rings When one or more heteroatoms are present, the point of attachment may be in the ring-ring. When the total number of S and deuterium atoms in the heteroaryl group exceeds μ, the heteroatoms are not adjacent to each other. In a specific embodiment, the heteroaryl group Group: The total number of S and deuterium atoms is not more than 2. In a specific embodiment, the total number of S and deuterium atoms in the aromatic heteropoly is not more than i. Examples of heteroaryl groups include, ίο 15 20 but not limited to 24唆 base, 3′′ than bite base, 4′′ than bite base, 2, 3′′ than tillage, 3]4_吼π well base, 2′ pyrimidinyl, 3,5-pyrimidinyl, pyrazolinyl, 2 , imidazolinyl, isoxazolinyl, oxazoline, thiazolinyl, thiadiazolyl, tetrazolyl, thienyl, benzothienyl'furanyl, benzofuranyl, benzimidazoline Base, porphyrinyl, hydrazine, triazolyl, quinolyl, pyridyl and 5,6,7,8-tetrahydroisoquinoline. Early price by its name "_base" ^ Aromatic oxime removal at the free radical Hydrogen atoms are obtained, a monovalent group, named based on the added alkylene "derived" For example, there are two points of attachment referred to as alkylene pyridinyl pyridinyl before the name of the corresponding univalent radical. A heteroaryl group does not encompass, or overlap with, an aryl, cycloalkyl, or heterocycloalkyl group, as defined herein. The substituted heteroaryl group also includes a ring system substituted with one or more oxygen ion (-〇-) substituents. "Heterocyclic alkyl" means a single, non-aromatic ring which generally has, in addition to being independently selected from the group consisting of oxygen, sulfur, and nitrogen, and containing at least one of the foregoing heteroatoms, and from 1 to 3 heteroatoms of S, 3 to 7 rings 21 containing at least 2 carbon atoms 200823202 2 . The % can be saturated or have one or more carbon-carbon double bonds. Suitable heterocycloalkyl groups &amp; include, but are not limited to, for example, piroxicam, 2, heart sputum 2, 3 than salivation, 2-0 chin, thiol, 'Bucking base And 2'5 piperage base (the bond position is preferentially designated as 1 to be numbered). Also included are morpholine 5 groups/including oxamorpholinyl and 3-morpholinyl (where oxygen is designated as 1 and numbered). The substituted heterocycloalkyl group also includes a ring system substituted with one or more keto (= oxime) or oxygen ion (0) substituents, such as phenanthrenyl oxime, morphine oxime-oxide, ; μ keto-; u thiomorpholinyl and diketopyl 丨 硫 thiophenanthyl. 1 〇 "Heterocycloalkyl" also includes a bicyclic ring system in which one ring is a non-aromatic ring, which typically has a heterogeneous combination of, independently selected from the group consisting of oxygen, sulfur, and nitrogen, and at least one hetero atom. Outside the atom, 3 to 7 ring atoms containing at least 2 carbon atoms; the other ring usually has 3 to 7 ring atoms, optionally containing -3 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and 15 Non-aromatic. As used herein, "modulation" refers to the change in activity in the presence of the chemical, either directly or indirectly, relative to the chemical described herein. This change may be an increase in activity or a decrease in activity, either because the compound interacts directly with the target 20 or because the compound interacts with one or more other factors, thereby affecting the activity of the target. For example, the presence of a chemical may increase or decrease the activity of the target, or increase (or directly or indirectly) by, for example, directly binding to the target, by (directly or indirectly) causing another factor to increase or decrease the activity of the target. The amount of the target in the cell or organism increases the activity of the target. _ 22 200823202 The term "sulfanyl" embraces the following groups: _s_ (Ci-C (j alkyl) as appropriate, (optionally substituted aryl), -S- (optionally substituted) Heteroaryl), and _8. (heterocycloalkyl optionally substituted). Here, the sulfanyl group contains a Ci-Ce alkylsulfanyl group. 5 The term "sulfinyl" includes the following Group: -S(0)-(CrC6 alkyl optionally substituted), -S(0)-(optionally substituted aryl), _s(〇)_(heteroaryl optionally substituted) , -S(0)-(heterocyclic cyclyl optionally substituted); and -S(0)-(amino group optionally substituted). The term "sulfonyl" includes the following groups: -S(〇2)-(Ci-C6 alkyl group substituted by 10), _S(〇2)-(optionally substituted aryl group), -S(〇2)_ (replaced as needed Heteroaryl), -S(〇2)-(heterocycloalkyl optionally substituted), -s(〇2)-(optionally substituted alkoxy), 4(〇2)- Relating aryloxy), _S(〇2)-(optionally substituted heteroaryloxy), -s(〇2)-(optionally substituted heterocyclyloxy); and 4( 0)-(Replaced as needed by 15 Amine) The term "substituted" as used herein means that any one or more of the hydrogens on the indicated atom or group are replaced by a selected group, but not beyond the normal valence of the indicated atom. When the substituent is a keto group (ie, =0), then 2 hydrogens on the atom are replaced. The combination of substituents and/or variables is 20, and the combination is stable. A compound or a useful synthetic intermediate stabilizing compound or stabilizing structure means that a compound is sufficiently robust to be isolated from the reaction mixture and then formulated into a formulation having at least one practical use. Unless otherwise stated, the substituents are Named in the core structure. For example, when a (cycloalkyl) fluorenyl group is listed as a possible substituent, then 23 200823202 will generally understand that the point of attachment of this substituent to the core structure is in the alkyl moiety. Unless otherwise defined, The term "substituted" alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl refers to alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, respectively. One or more (for example, up to 5 5, for example, up to 3) hydrogen atoms are replaced by substituents independently selected from the group consisting of: -Ra, -ORb, optionally substituted amine groups (including _NReCORb, NRcC02Ra, -NRcCONRbRc, -NRbC(NRc)NRbRc &gt; -NRbC(NCN)NRbRe, and -NReS02Ra), halo, cyano, nitro, 10 keto (which is a cycloalkyl, heterocycloalkyl, heteroaryl substituent) a substituted thiol group (e.g., -CORb), an optionally substituted alkoxycarbonyl group (e.g., -C02Rb), an amine carbonyl group (e.g., -CONRbRc), -OCORb, -0C02Ra, -OCONRbRc, -0P (0) (0Rb)0Rc, a sulfanyl group (for example, SRb), a sulfinyl group (for example, -S0Ra), and a sulfonyl group (for example, -S02Ra and _S02NRbRc); 15 wherein Ra is selected from a Cr9 alkane which is optionally substituted Substituted, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, and optionally substituted a heteroaryl group; 1^ is selected from the group consisting of hydrazine, an alkyl group which is optionally substituted, a cycloalkyl group which may be substituted as desired, a heterocycloalkyl group optionally substituted, and optionally Substituted aryl, and optionally substituted heteroaryl; and Re is selected from the group consisting of hydrogen and optionally substituted C^CU alkyl; or / and R°, together with the nitrogen to which it is combined, forms Substituted heterocycloalkyl; and 24 200823202 wherein each optionally substituted group is unsubstituted or independently one or more, such as one, two, or three, independently selected from the group consisting of Substituent substitution: CrCU alkyl, aryl, heteroaryl, arylalkyl, heteroaryl-cvc4 alkyl, cvc4 haloalkyl, -OCi-C^alkyl, alk-5 phenyl, -CVC4 alkane -OH, -OCi-CU haloalkyl, dentate, -OH, -NH2, -(VC4 alkyl_ΝΗ2, _Ν((ν(:4 alkylalkyl)), -Nl^Ci-CU alkyl ), _N(CVC4 alkyl) (〇ν&lt;:4 alkylphenyl), -NH(C 1-C4 alkyl), chaotic, nitro, fluorenyl (cycloalkyl, heterocycloalkyl) Or a substituent of a heteroaryl group), -C02H, -CCC^OCi-CU alkyl, 10 CONiCVq alkylalkyl), -CONHA-CU alkyl), C0NH2, -NHC^OKCVCU alkyl), -NHC (0) (phenyl), _N (CVC4 alkyl) C(0) (CVC4 alkyl), -NiCi-CU alkyl) C(0) (benzene ), /(0)0^0:4 alkyl, -0(0)(^-(:4 alkylphenyl, -qcocvcu haloalkyl, ·OQCOCVCU alkyl, -SOdCVC^ alkyl), -so2 (phenyl), 15 -SCMCrCU haloalkyl), -S02NH2, -SC^NH^CVCU alkyl), -so2nh(phenyl), -NHS〇2(Cl_c4 alkyl), _NhS〇2 (phenyl) With -NHSOWCkC^ haloalkyl). The term "substituted thiol" refers to the following group: · HC(o)·, (substituted alkyl)-C(〇)-, (substituted cycloalkyl)-C(O) -, (substituted 20 aryl) -C(O)-, (substituted heteroaryl bc(0)_, and (substituted heterocycloalkyl)-c(o)_; a group is attached to the parent structure via a carbonyl functional group, and wherein the substituted alkyl, cycloalkyl, aryl, heteroaryl, and heterocycloalkyl are respectively alkyl, cycloalkyl, aryl, Heteroaryl, and heterocycloalkyl, wherein one or more (eg, up to 5, for example, up to 3) 25 200823202 Hydrogen atoms are replaced by substituents independently selected from the group consisting of: - Ra, -ORb, optionally substituted amine groups (including -NReCORb, -NRcC02Ra, -NRcCONRbRc, -NRbC(NRc)NRbRc, -NRbC(NCN)NRbRe, and -NReS02Ra), halo, cyano, nitro a 5-keto group (which is a cycloalkyl group, a heterocycloalkyl group, a substituent with a heteroaryl group), an optionally substituted group (for example, -CORb), an optionally substituted azide group (for example, -C02Rb) ), amine carbonyl (eg -CONRbRc), -OCORb, -0C02Ra, -OCONRbRc, -0P(0)(0Rb)0Rc, a sulfur group (for example, SRb), a sulfinyl group (for example, -SORa), and a sulfonyl group (for example, -S02Ra and -S02NRbRe); 10 wherein Ra is selected from a substituted CrG alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, and optionally a substituted heteroaryl group, if necessary;

Rb is selected from H, optionally substituted iCi-Q alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl-15, and optionally substituted Heteroaryl; and

The Re is independently selected from the group consisting of hydrogen and optionally substituted (:Gyroalkyl; or Rb and Re, together with the nitrogen to which it is bonded, forms a heterocycloalkyl group optionally substituted; and each of them is optionally substituted The group is unsubstituted or independently substituted by one or more, for example one, two, or three, substituents independently selected from the group consisting of C1-C4 alkyl, aryl, heteroaryl , aryl-C1-C4 alkyl, heteroaryl-C1-C4 alkyl, C1-C4 halogen, -OC1-C4 alkyl, -OC1-C4 alkylphenyl, -Ci-CU alkyl _OH, haloalkyl, halo, -OH, -NH2, -CVCU alkyl-NH2, alkyl) (Ci-C4 alkyl), 26 200823202 alkyl), · Ν (〇ν〇: 4 alkyl (CVC4 alkylphenyl), -NHCCrC*alkylphenyl), cyano, nitro, keto (which is a substituent of a cycloalkyl, heterocycloalkyl or heteroaryl), -C02H, - (:(0)0(^(:4 alkyl, -COi^Ci-C^alkylalkyl), -CONI^CVC^alkyl), 5-C0NH2, -NHC^OKCrCU alkyl), -NHC (0) (phenyl), _Ν (〇ν(:4 alkyl)qoxcvcu alkyl), -NiCi-CU alkyl)C(0)(phenyl), -(:(0)(^-(: 4 alkyl, -0:(0)(^( : 4 alkylphenyl, -(:(0)〇ν〇:4 haloalkyl, -oqcocvcu alkyl, -SOdCrC^ alkyl), -so2(phenyl), -S〇2(CVC4 haloalkyl ), -S02NH2, -SC^N^Ci-C^ alkyl), 10 _S02NH(phenyl), -NHS02CCVC4 alkyl), _nhso2 (stupyl), and -NHSOdCVCU haloalkyl). The term "oxy" refers to an alkoxy group wherein the alkyl group is substituted (ie, -0-(substituted alkyl)); wherein "substituted alkyl" refers to alkyl, one or A plurality (for example up to 5, for example, up to 15 up to 3) of hydrogen atoms are replaced by substituents independently selected from the group consisting of: -Ra, _ORb, optionally substituted amine groups (including _ NReCORb, -NRcC02Ra, -NRcCONRbRc, -NRbC(NRc)NRbRc, -NRbC(NCN)NRbRe, and -NReS02Ra), halo, cyano, nitro, keto (cycloalkyl, heterocycloalkyl, and a substituent of a heteroaryl group, optionally a substituted fluorenyl group (e.g., _C0Rb), an optionally substituted alkoxycarbonyl group (e.g., -C02Rb), an amine carbonyl group (e.g., -C0NRbRc), -OCORb, -0C02Ra, -OCONRbRc, -0P(0)(0Rb)0Rc, sulfur burning (e.g., SRb), sulfinyl (e.g., -SORa), and sulfonyl (e.g., -S02Ra and -S02NRbRe); wherein Ra is selected from the group consisting of an optionally substituted CrCe alkyl group, optionally substituted 27 200823202 a substituted alkynyl group, optionally substituted aryl group, and optionally substituted heteroaryl group;

Rb is selected from H, optionally substituted iCrC6 alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclic alkyl, optionally substituted aryl 5, and optionally substituted. Base; and

Re is independently selected from the group consisting of hydrazine and optionally substituted CrCU alkyl; or

Rb and Re, together with the nitrogen to which they are combined, form a heterocycloalkyl group optionally substituted; and each of the optionally substituted groups is unsubstituted or independently substituted by one or more, for example, one or two Or three substituents independently selected from the group consisting of: Ci-CU alkyl, aryl, heteroaryl, aryl-C^C^alkyl, heteroaryl-Ci_C4 alkyl, C1 -C4 _ alkyl, _Ci_C4 alkyl, _OCi-C4 alkyl, -C1-C4 alkyl-OH, -OC1-C4 self-alkyl, dentate, -OH, -nh2, _CVC4 alkyl-NH2 , (Ci-CU alkyl XCi-CU alkyl), 15 alkyl), -Nfi-CU alkyl) (cvc4 alkylphenyl), alkylphenyl), cyano, &gt;6 succinyl, Keto group (which is a cycloalkyl, heterocycloalkyl or heteroaryl substituent), -C02H, alkyl, -CONCCrQ alkyl KCVC4 alkyl), -CONHCCVC^ alkyl), -CONH2, -NHC^ OKCVC^alkyl), -NHC(0)(phenyl), -Ν(〇ν(:4 20 alkyl)alkyl), alkyl)C(0)(phenyl), -(:(0) (^(: 4 alkyl, alkylphenyl, -(:(0)(^-(:4 haloalkyl, -OC^COCVCU alkyl, -SOdCrC^ alkyl), -S02(phenyl), SOKCVCU halogen Alkyl), -S02NH2, -SOsNKKC^-CU alkyl), -S02NH(phenyl), -NHSOdCi-C^alkyl), -NHS02(phenyl), and 28 200823202 -NHSOdCrQ haloalkyl) In some embodiments, the substituted alkoxy group is a "polyalkoxy" or -〇-(optionally substituted alkyl)-optionally substituted alkoxy group, and includes, for example, -〇ch2ch2och3, etc. The group, a residue with a glycol ether such as polyethylene glycol, and -o(ch2ch2o)xch3, 5 wherein X is 2 to 20, for example 2 to 10, for example, an integer of 2 to 5. The other substituted alkoxy group is a hydroxyalkoxy group or -〇CH2(CH2)yOH, wherein y is from 1 to 10, for example, an integer from 1 to 4. The term "substituted alkoxycarbonyl" means a (substituted alkyl)-〇-C(0)- group in which the group is bonded to the parent 10 structure via a carbonyl functional group, and the substituted system thereof Refers to an alkyl group in which one or more (eg, up to 5, for example, up to 3) hydrogen atoms are replaced by substituents independently selected from the group consisting of:

Ra, -ORb, optionally substituted amine groups (including -NReCORb, -NRcC02Ra, -NRcCONRbRc, -NRbC(NRc)NRbRc, 15 _NRbC(NCN)NRbRe, and -NReS02Ra), halo, cyano, nitro a keto group (which is a cycloalkyl group, a heterocycloalkyl group, a substituent with a heteroaryl group), an optionally substituted thiol group (for example, -CORb), an optionally substituted alkoxycarbonyl group (for example, -C02Rb), Amine carbonyl (e.g., -CONRbRe), -OCORb, _0C02Ra, OCONRbRc, -0P(0)(0Rb)0Rc, thioalkyl (e.g., SRb), sulfinyl 20 thiol (e.g., -SORa), and sulfonyl (e.g., _S02Ra and -S02NRbRc); wherein Ra is selected from an optionally substituted CrCe alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, and optionally substituted Heteroaryl

Rb is selected from the group consisting of H, an optionally substituted iCrQ alkyl group, a cycloalkyl group which is optionally substituted 29 200823202, a heterocyclic alkyl group to be substituted, an optionally substituted aryl group, and optionally substituted. a heteroaryl group, and R is independently selected from the group consisting of hydrogen and optionally substituted Ci_C4 alkyl; or R and R, together with the nitrogen to which it is bonded, form an optionally substituted heterocyclic 5-alkyl group; If desired, the substituted group is unsubstituted or independently substituted by one or more, for example one, two, or three, substituents independently selected from the group consisting of CVC4 alkyl, aryl, Heteroaryl, aryl-Ci-C4 alkyl, heteroaryl-CVC4 alkyl, Ci-CU halo, -OCVC4 alkyl, -OCj-CU 10 alkyl, -C1-C4 alkyl-OH , _0Ci_C4 haloalkyl, halo, -OH, -NH2, -Ci-CU alkyl-NH2, _N(CVC4 alkylalkyl), -NHCCVC^alkyl), -alkylene) (〇ν&lt;: 4-alkylphenyl), -NI^C^_C4 alkylphenyl), cyano, nitro, keto (which is a cycloalkyl, heterocycloalkyl or heteroaryl substituent), -C02H, -(:(0)0(^-04 alkyl, 15-CONCCVCU alkyl XCVC4 Base), {ΟΝΗΑΑ alkyl), -C0NH2, -NHCCOKCrC^ alkyl), -NHC(0)(phenyl), -Ν(〇ν&lt;:4 alkyl)CCOXCi-CU alkyl), -NCCVC^ Alkyl)c(o)(phenyl), -C(0)Ci-C4 alkyl, -C(0)Ci-C4 alkylphenyl, -C(0)Ci-C4 halogen alkyl, -OCCCOCi -CU alkyl, -SOdCi-CU alkyl), -so2(phenyl), 20 ·8〇2 (〇ν&lt;:4 decyl), -S02NH2, -SC^NHCCi-CU alkyl), - S02NH (phenyl), -NHSOdCi-CU alkyl), _NHS02 (phenyl), and -NHSCMCVCU haloalkyl). The term "substituted amino group" refers to a -NHRd or -NRdRe group, wherein Rd is selected from the group consisting of: a hydroxy group, an optionally substituted alkoxy group, an alkyl group as required in 200823202, optionally substituted a cycloalkyl group, optionally substituted fluorenyl group, optionally substituted fluorenyl group, amine carbonyl group, optionally substituted aryl group, optionally substituted heteroaryl group, optionally substituted heterocycloalkane Substituted, optionally substituted alkoxycarbonyl, sulfinyl and sulfonyl, and wherein Re is selected from: optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted An aryl group, optionally substituted heteroaryl, and optionally substituted heterocycloalkyl; wherein substituted alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl are respectively referred to as an alkane One or more (e.g., up to 5, for example, up to 3) 10 hydrogen atoms of the group, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl are independently selected from the group consisting of Substituent substitution of the group: -Ra, -ORb, optionally substituted amino groups (including -NReCORb, NRcC02Ra, -NRcCONRbRc, _NRbC ( NRc) NRbRc, • NRbC(NCN)NRbRe, and -NReS02Ra), halo, cyano, nitro, keto (which is a cycloalkyl, heterocycloalkyl, and heteroaryl substituent), if necessary 15 Substituted indenyl (eg _CORb), optionally substituted alkoxycarbonyl (eg -C02Rb), amine carbonyl (eg -CONRbRe), -OCORb, -0C02Ra, -OCONRbRc, -0P(0)(0Rb) 0Rc, a sulfanyl group (for example, SRb), a sulfinyl group (for example, -SORa), and a sulfonyl group (for example, -S02Ra and -S02NRbRc); wherein the Ra is selected from a CVQ alkyl group which is optionally substituted, if necessary Substituting an alkenyl group of 20, an alkynyl group optionally substituted, an optionally substituted aryl group, and optionally substituted heteroaryl groups;

Rb is selected from H, optionally substituted C!-C6 alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted Heteroaryl; and 31 200823202

Re is independently selected from the group consisting of hydrogen and optionally substituted alkyl; or, together with Re, and the nitrogen to which it is bonded, forms an optionally substituted heterocycloalkyl; and each of the optionally substituted groups Unsubstituted or independently substituted by one or more substituents, such as one, two, or three, independently selected from the group consisting of Ci-C4 alkyl, aryl, heteroaryl, aryl -Ci&gt;eC4 alkyl, heteroaryl-C1-C4 alkyl, C1-C4 halogen, 〇Ci-C4 alkyl, -OCi-C4 alkylphenyl, alkyl-OH, -OCVC4 halogen , halo, -oh, _NH2, -Ci-CU alkyl-NH2, -NCCrq alkyl XCVCU alkyl), 10 -NEKCVC^ alkyl), -NA-q alkylalkylphenyl), -Nf ^CVC: 4-alkylphenyl), cyano, &gt;6 succinyl, keto (which is a cycloalkyl, heterocycloalkyl or heteroaryl substituent), -C02H, -(:(0) 0 (^-04 alkyl, -CONAA alkyl XCVCU alkyl), -CONHA-q alkyl), -CONH2, -Li (10) muscle. Alkyl), -NHC(0)(phenyl), _N(Cl_C4 15 alkyl)alkyl), _Ν(〇ν(:4 alkyl)C(〇)(phenyl), -C(0)CVC4 Alkyl, alkylphenyl, -C(0)Cl_C4 haloalkyl, -〇C(〇)Ci-C4 alkyl, -S〇2 (Ci-C4 alkyl), -S〇2 (phenyl) , -SOdCVC^dental alkyl), -S02NH2, -SC^NH^CVCU alkyl), -S02NH(phenyl), -NHSCMCi-CU alkyl), _nhso2(phenyl), and 20-NHSO^CrCU halogen An alkoxycarbonyl group, an anthracene group and a sulfonyl group which are substituted as needed, and which are optionally substituted, are as defined herein. The term "substituted amino group" also refers to the N-oxide of each of the -NHRd, and NR R-specific groups as described above. The ruthenium oxides can be prepared by treating the corresponding amine groups with hydrogen peroxide or m-chloroperoxybenzoic acid as described in Example 32 200823202. Those skilled in the art are familiar with the reaction conditions for carrying out the oxidation. Compounds of formula X include, but are not limited to, optical isomers of the compound of formula x, racemates thereof, and other mixtures. In such cases, a single mirrored 5 isomer or a non-image isomer, i.e., an optically active form, can be prepared by asymmetric synthesis or by racemate resolution. The resolution of the racemate can be achieved by a conventional method such as a crystallization method in the presence of a resolving agent, or using, for example, a palm high pressure liquid chromatography (HPLC) column or the like. Further, the hydrazine compound contains a compound having a carbon-carbon double bond of Z_ and E_ (or cis and trans). When a compound of formula 10X is present in a variety of tautomers, the chemicals described herein comprise all tautomeric forms of the compound. 15 20 The chemicals described herein contain, but are not limited to, all of the pharmaceutically acceptable forms of the hydrazine compound and the pot. The chemical of the chemical detailed herein; in addition, the formula includes the pharmaceutically acceptable salt, solvate, crystalline form, the type (4), the compound (1), the s complex, and the non-covalent complex It is a mixture of 3. In the specific example of Zhao, the time described herein is in the form of a therapeutically acceptable salt. Therefore, "Mouth 1 also covers its pharmaceutically acceptable salt cognac", a complex, a pre-Olympic drug, and its Pan He:: 丨...integration, non-covalent "pharmaceutically acceptable salt" Containing, salt, such as hydrochloride, acid salt, in: with inorganic acid acid salt, sulfite, nitrate, etc.: sulphur such as malate, maleate, fumaric acid 16: sulphate, -w shot acid, butyl T, buy salt, 2 · hydroxyethyl 33 200823202 acid salt, benzoate, salicylate, hard (tetra) salt, and Acetate, salt such as H00C_(CH2)n_C00H (where nu_4), and pharmaceutically acceptable cations are included, but not limited to Cui Lu, Zhong, and Qian. 5 10 In addition, if a compound of the formula X which is an acid addition salt is prepared, a free test can be obtained by using a solution which tests the acid salt. On the other hand, if the product is a free test, it can be used according to the conventional procedure for preparing an acid additional salt by using the compound, and then using an appropriate organic solvent to dissolve the solution, and then treating the solution with an acid to prepare an additional salt, especially in medicine. Accept the additional salt. A pharmaceutically acceptable synthetic method that is non-toxic is prepared by the skilled artisan. As noted above, prodrugs, such as vinegar or guanamine derivatives of the compound of formula X, are also within the scope of the chemical. The term "precursor drug" is included in the administration of a patient, for example, after any metabolic procedure of the prodrug, it becomes any product of the compound of formula X15. Examples of prodrugs include, but are not limited to, derivatives of acetates, formates, phosphates, and benzoates of functional groups (e.g., alcohols or amine groups) of the formula X. The term "solvate" means a solvate which is prepared by the interaction of a solvent with a compound, and which is a pharmaceutically acceptable solvate, for example, a hydrate, including a monohydrate and a hemihydrate. . The term "chelate" refers to a chemical formed by the coordination of a compound to two (or more) points of a metal ion. The term "non-co-defective complex" refers to a chemical formed by the interaction of a compound with another molecule in which no bond is formed between the compound and the molecule. For example, mismatches can occur via van der Waals interactions, hydrogen bonding, and electrostatic interactions (also known as ionic bonding). The term "active agent" is used to mean a biologically active chemical. In a specific embodiment, an "active agent" is a compound having a pharmaceutical use. In five cases, the active agent can be an anti-cancer therapeutic. "Significant" means any statistically significant change in a standard parameter test of statistical significance, such as in Student's T-test, p &lt; 0. Q5. The term "effective therapeutic amount" of a chemical described herein means 'effectively providing a therapeutic advantage when administered to a human or non-human patient (eg, improving symptoms, slowing disease progression, or preventing disease) The amount. "Treatment" means any treatment of a disease in a patient, including: a) preventing the occurrence of the disease, that is, causing no clinical symptoms of the disease; 15 b) inhibiting the disease; c) slowing or stopping clinical symptoms Forming; and/or d) relieving the disease, that is, causing the clinical symptoms to recover. "Patient" means an animal, such as a mammal, that has or will be a subject of treatment, observation or experimentation. The methods described herein can be used for both human therapy and 20 Western applications. In some embodiments, the patient is a mammal; in some embodiments, the patient is a human; and in some specific instances A, the condition is selected from the group consisting of a cat and a dog. The present invention provides at least one chemical selected from the group consisting of the following formulas and pharmaceutically acceptable salts thereof: 35 200823202

Wherein U is selected from the group consisting of an aryl group as required, a ring-based ring of 5 as needed, and a heterocyclic group which is optionally substituted, and if necessary, (where "*,, and 21" a junction point); the hetero-groups W1 and W2 are independently selected from the group consisting of CR11R12, NRl3, and 〇··wl and W2 are at least one of NR13; W3 is selected from CRiR2, NR14 and 〇; 10 Z1 is an aryl group; Is an aryl group; r 8 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted Heterocycloalkyl; 15 R1, R2, Rl1, and R12 are independently selected from the group consisting of hydrogen, hydroxy, carboxy, alkyl substituted by hydrazine, optionally substituted cycloalkyl, optionally substituted olefin a substituted alkynyl group, optionally substituted alkoxy group, optionally substituted aryloxy group, optionally substituted heteroaryloxy group, optionally substituted heterocycloalkyloxy group , if desired, substituted aminocarbonyloxy, optionally substituted methoxy, substituted alkoxycarbonyloxy, optionally substituted Alkenyloxycarbonyl, optionally substituted amino group, optionally 36 200823202 substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine carbonyl, And optionally substituted aminoalkylsulfonyl; or R1 and R2 may be bonded to any of the atoms interposed therebetween, forming a cycloalkyl group optionally substituted with a cycloalkyl optionally substituted a group of an alkyl group; R13 and R14 are independently selected from the group consisting of anthracene, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, And optionally substituted heterocycloalkyl; 10 In each case, R3, R4, R5, and R6 are independently selected from hydrogen, hydroxy, optionally substituted alkyl, optionally substituted cycloalkyl. Alkenyl substituted, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted Heterocycloalkyloxy, optionally substituted amino 15 carbonyloxy, as needed a substituted alkoxy group, an optionally substituted alkoxycarbonyloxy group, an optionally substituted fluorenyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted amino group, an optionally substituted aryl group, Optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine carbonyl, and optionally substituted aminosulfonyl; 20 or R1 and one of R5 may optionally be Any intervening atoms are joined together to form a group selected from optionally substituted cycloalkyl and optionally substituted heterocycloalkyl; or R14 and one of R5 may be optionally taken with any intervening atom Combining to form a heterocycloalkyl ring which may be optionally substituted; 37 200823202 or if it is 3, Riq Rl may optionally be bonded to any atom between the eight groups to form a heterocycloalkyl ring which may be optionally substituted; or ^ is NRU, then Rl3 and one of the R5 may be combined with any atom in between to form an optionally substituted heterocyclic ring 5 base ring; the R7 and R10 systems are independently selected from hydrogen, cyano, Halogen, hydroxyl, carboxyl, azide , nitro, sulfonyl, sulfinyl, sulfanyl, if necessary, by alkoxylation, optionally taking an aryloxy group, depending on the heteroaryloxy group to be substituted, if necessary A heterocycloalkyloxy group, optionally substituted 10 alkoxycarbonyl group, optionally substituted alkyl group, optionally substituted cycloalkyl group, optionally substituted alkenyl group, optionally substituted alkynyl group Substituted substituents are considered to be substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine, optionally substituted thiol, optionally substituted amine a carbonyl group, an optionally substituted aminosulfonyl group, optionally a substituted mercapto group; W is selected from the group consisting of ruthenium, 1, 2 and 3; and « is selected from the group consisting of 0, 1, 2, 3, and 4; Is selected from 1, 2, and 3; and "selected from 0, 1, 2, 3, and 4. In some embodiments, U is selected from the group consisting of an optionally substituted aryl group, an optionally substituted cycloalkyl group, an optionally substituted heterocycloalkyl group, and optionally a substituted heteroaryl group. In some embodiments, U is, wkow2 (where "*," represents the point of attachment to Z1). 38 200823202 at least one chemical and its medicinal invention The present invention provides a salt selected from the group consisting of:

Wherein W1 and W2 are independently selected from the group consisting of CR11R12, NRl3, and hydrazine; wherein at least one of w] and W2 is nr13; W is selected from CR^R2, nr14 and hydrazine; Z1 is aryl; 10 Z2 Is an aryl group; R is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted. a heterocycloalkyl group; R, R2, R11, and R12 are independently selected from the group consisting of hydrogen, hydroxy, carboxy, 15 optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted, a substituted alkyl group, optionally substituted alkoxy group, optionally substituted aryloxy group, optionally substituted heteroaryloxy group, or optionally substituted heterocyclic alkyloxy group, A substituted amino oxy group, optionally substituted methoxy group, optionally substituted alkoxycarbonyloxy group, 20 optionally substituted alkoxycarbonyl group, optionally substituted amino group, optionally substituted amino group, if desired Substituted aryl, optionally substituted heteroaryl, optionally substituted 39 200823202 heterocycloalkyl, optionally substituted a carbonyl group, optionally substituted amino sulfonyl group; or R1 and R2 together with any atom interposed therebetween, forming a cycloalkyl group selected from the group which may be optionally substituted and optionally substituted 5 a group of a cycloalkyl group; R13 and R14 are independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl And optionally substituted heterocycloalkyl; in each case, R3, R4, R5, and R6 are independently selected from hydrogen, hydroxy 10, optionally substituted alkyl, optionally substituted ring Alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally Substituted heterocycloalkyloxy, optionally substituted aminocarbonyloxy, optionally substituted methoxy, optionally substituted alkoxycarbonyl 15 oxy, optionally substituted thiol, optionally A substituted alkoxycarbonyl group, an optionally substituted amino group, and optionally substituted Substituted, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine carbonyl, optionally substituted aminosulfonyl; or R1 and optionally present, R5 Combining with any intervening atom 20 to form a group selected from optionally substituted cycloalkyl and optionally substituted heterocycloalkyl; or R14 and one of R5 may be optionally present with any intervening The atoms are bonded together to form an optionally substituted heterocycloalkyl ring; or if W1 is NR13, then R13 and R1 may be combined with any atom between 200823202 to form an optionally substituted heterocycloalkyl ring; If W1 is NNi3' then Rn and one of R5 may be combined with any 'half atom' to form a heterocyclic cyclyl ring which is optionally substituted; 5 ft and ulnar are independently selected from hydrogen and cyano , halo, hydroxy, carboxy, azide: a sulfhydryl group, a fluorenyl group, a subunit, a thiol group, an optionally substituted alkoxy group, an optionally substituted aryloxy group, optionally substituted Heteroaryloxy, optionally substituted heterocycloalkane Alkoxy group, optionally substituted alkoxycarbonyl group, optionally substituted alkyl group, optionally substituted cycloalkyl group, 10 optionally substituted alkenyl group, optionally substituted alkynyl group, optionally Substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine, optionally substituted thiol, optionally substituted amine carbonyl, optionally Substituted aminosulfonyl, optionally substituted formazan; 15 w is selected from 0, 1, 2 and 3; « is selected from 〇, 1, 2, 3, and 4; From 1, 2, and 3; and "from 〇, 1, 2, 3, and 4. In some embodiments of the compound of Formula I, zl is phenyl. In some specific examples of compounds of formula I, z2 is phenyl. In some embodiments of the compound of Formula I, W1 is cRnRl2. In some embodiments of the compound of Formula I, W1 is NRn. In some embodiments of the compound of Formula I, W1 is deuterium. In some embodiments of the compound of Formula I, w2 is cr11r12. In some specific examples of compounds of formula I, W2 is NR13. In some embodiments of the compound of Formula I, W2 is deuterium. In some embodiments of the compound of Formula I, W3 is CWR2. In some embodiments of the compound of Formula I, W3 is NR14. 5 In some embodiments of the compound of formula I, R8 is selected from the group consisting of hydrazine and lower alkyl such as may be substituted. In some embodiments of the compound of formula I, R8 is selected from the group consisting of hydrazine and lower alkyl. In some embodiments of the compound of Formula I, R8 is selected from the group consisting of fluorenyl and fluorenyl. In some specific examples of compounds of formula I, R8 is deuterium. In some embodiments of the compound of formula I, R11 and R12 are independently selected from the group consisting of hydrogen and optionally substituted lower alkyl. In some embodiments of the compound of formula I, R11 and R12 are independently selected from the group consisting of hydrogen and lower alkyl. In some embodiments of the compound of formula I, R11 and R12 are independently selected from the group consisting of hydrogen and sulfhydryl. In some embodiments of the compound of formula I, R11 is hydrogen and R12 is thiol. In some embodiments of the compound of formula I, R13 is selected from the group consisting of hydrazine and lower alkyl which are optionally substituted. In some embodiments of the compound of formula I, R13 is selected from the group consisting of hydrazine and lower alkyl. In some embodiments of the compound of formula I, R13 is selected from the group consisting of hydrazine and hydrazine 42 200823202. In some embodiments of the compound of formula I, R13 is fluorenyl. In some specific examples of compounds of formula I, q is 2. In some specific examples of compounds of formula I, i. In some specific examples of compounds of formula I, g is deuterium. 5 In some embodiments of the compound of formula I, each R5 and R6 are independently selected from the group consisting of hydrazine, optionally substituted lower alkyl, and lower alkoxycarbonyl. In some embodiments of the compounds of formula I, each R5 and R6 are independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, hydroxymethyl, and oxiranylcarbonyl. In some embodiments of the compound of Formula I, each R5 and R6 is hydrogen. In some specific examples of compounds of formula I, m is selected from the group consisting of 1 and 2. In some embodiments of the compound of formula I, R7 is selected from the group consisting of halo, lower alkyl, and optionally substituted lower alkyl. In some embodiments of the compound of formula I, R7 is selected from the group consisting of chloro, fluoro, methyl, and trifluoromethyl. In some specific examples of compounds of formula I, R7 is a gas group. In some embodiments of the compounds of formula I, R7 is at position 2 or 3 relative to the point of attachment of the phenyl ring. In some embodiments of the compound of Formula I, w is selected from the group consisting of 1 and 2. In some specific examples of the compound of formula I, "is 1. In some embodiments of the compound of formula I, each R3 and R4 are independently selected from the group consisting of hydrogen, optionally substituted lower alkyl, and lower alkoxycarbonyl. In some embodiments of the compounds of formula I, each R3 and R4 are independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, hydroxymethyl, and methoxycarbonyl. In some embodiments of the compound of Formula I, each R3 and R4 are hydrogen. 43 200823202 In some embodiments of the compounds of formula I, p is selected from the group consisting of 1 and 2. In some embodiments of the compound of Formula I, P is 1. In some embodiments of the compound of Formula I, each Rio is independently selected from the group consisting of cyano, chloro, bromo, methyl, ethyl, isopropyl, tert-butyl, 5 methyl, trifluoromethyl , oxime, phenoxy, phenyl, trifluoromethoxy, methoxy, N,N-diamine, and oxime-imidazolyl. In some embodiments of the compounds of Formula I, each Rio is selected from the group consisting of decyl, ethyl, isopropyl, and trifluoromethyl. In some embodiments of the compound of formula I, p is 1 and Rio is selected from the group consisting of 10 ethyl and isopropyl. In some embodiments of the compound of formula I, R14 is selected from the group consisting of argon and a lower alkyl group which is optionally substituted. In some embodiments of the compound of formula I, R14 is selected from the group consisting of hydrogen and lower alkyl. In some specific examples of the compound of formula 1, R14 is hydrogen. In some embodiments of the compounds of formula I, each of Ri and R2 is independently selected from the group consisting of hydrogen, lower alkyl, and substituted alkyl. In some embodiments of the compounds of formula I, each of R1 and R2 is independently selected from the group consisting of hydrogen and methyl. In some embodiments of the compound of Formula 1, R1 and R2 are hydrogen. In some embodiments of the compound of Formula I, Ri and R2 are methyl. In some embodiments of the compound of Formula I, Ri is hydrogen and R2 is sulfhydryl. In some embodiments of the compounds of formula I, Ri and R2, together with the carbon to which they are attached, form a group selected from the group consisting of optionally substituted cycloalkyl groups and, if desired, the heterocycloalkyl group of the group 20082008202. In some embodiments of the compound of formula I, r2, and the fused carbon-formation are selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentyl, 5 piperidinyl, and 211-3,4 The beauty of 5,6_tetrahydropyranyl needs to be substituted. In the concrete examples of the group of the bauxite, in which the respective groups are regarded as the L-form, R1 and r2' together with the carbon to which they are attached form a group selected from the group consisting of pentyl, cyclohexyl, piperidinyl, The invention with 2H-3,4,5,6-tetramethylene is also provided selected from the group consisting of lower/τ' wherein each group is optionally substituted. 10 pharmaceutically acceptable salts: at least one chemical of a and its doctor

The invention also provides a salt selected from the group consisting of: a pharmaceutically acceptable salt: at least one chemical of formula 1b and a physician thereof

Formula lb 45 200823202 wherein Ri, R2, η, R3, R4, q, m, R7, R8, p, and R10 are as defined in the compound of formula I. The invention also provides at least one chemical selected from the group consisting of the following formula Ic and a pharmaceutically acceptable salt thereof:

Wherein Ri, R2, η, R3, R4, q, m, R7, R8, p, and R10 are as defined in the compound of formula I. The present invention also provides at least one chemical selected from the group consisting of Id and a pharmaceutically acceptable salt thereof:

All are as defined in the compounds of formula I. The present invention provides at least one chemical selected from the group consisting of the following formula II and a pharmaceutically acceptable salt thereof: 46 200823202

(R10)P

Formula II

Wherein W1 is an optionally substituted aryl group, optionally substituted cycloalkyl group, optionally substituted heterocycloalkyl or optionally substituted heteroaryl ring; W2 is selected from CWR2, NR14 and hydrazine Z1 is an aryl group; Z2 is an aryl group; R1 and R2 are independently selected from the group consisting of hydrogen, a hydroxyl group, a carboxyl group, an alkyl group which may be substituted 10 times, an optionally substituted cycloalkyl group, and an optionally substituted alkene; a substituted alkynyl group, optionally substituted alkoxy group, optionally substituted aryloxy group, optionally substituted heteroaryloxy group, optionally substituted heterocycloalkyloxy group, An aminocarbonyloxy group to be substituted, an optionally substituted methoxy group, an optionally substituted alkoxy oxo group, an alkyl alkoxycarbonyl group optionally substituted, an optionally substituted amino group, An optionally substituted aryl group, optionally substituted heteroaryl group, optionally substituted heterocycloalkyl group, optionally substituted amine carbonyl group, and optionally substituted amino sulfonyl group; or R1 and R2 may be bonded to the carbon atom to which it is bonded, to form a cycloalkane selected from the group which is optionally substituted a group of a hetero 20 cycloalkyl group substituted as desired; in each case, R 3 , R 4 , R 5 and R 6 are independently selected from the group consisting of an anthracene, a hydroxyl group, a carboxyl group, an alkyl group optionally substituted, and optionally Substituted cycloalkyl, 200823202 optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy a substituted heterocycloalkyloxy group, optionally substituted aminocarbonyloxy group, optionally substituted anthraceneoxy group, optionally substituted alkane 5 oxycarbonyloxy group, optionally substituted Anthracenyl, optionally substituted alkoxycarbonyl, optionally substituted amine, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally Substituted amine carbonyl, and optionally substituted aminosulfonyl; each R7 and R1G are independently selected from the group consisting of hydrogen, cyano, halo, hydroxy, carboxy 1 fluorenyl, azide, nitro, sulfonium sulfonate a sulfinyl group, a thio group, an alkoxy group optionally substituted, an optionally substituted aryloxy group, a heteroaryloxy group to be substituted, an optionally substituted heterocycloalkyloxy group, an optionally substituted oxygenated Ik group, an alkyl group to be substituted, an optionally substituted cyclodyl group, and optionally A substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted heterocycloalkyl group, an optionally substituted amino group, if necessary , optionally substituted thiol, optionally substituted amine carbonyl, optionally substituted aminosulfonyl, optionally substituted formazan; ^ R and R are independently selected from hydrogen, optionally Substituted S. sylvestris, 20 which requires a substituted cycloalkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, and optionally a substituted heterocycloalkyl group; w is selected from the group consisting of hydrazine 1, 2, and 3; «separated from 0, 1, 2, and 3; households are selected from 1, 2, and 3; and 48 200823202 "Selected from 〇, 1, 2, and 3. In a particular embodiment of the compound of formula II, Z1 is a stupid group. In a particular embodiment of the compound of formula II, Z2 is a stupid group.

In a particular embodiment of the compound of formula II, w is 5 wherein Wla, Wlb, and Wlc&amp; are independently selected from -CH and N. In a particular embodiment of the compound of Formula II, at least one of Wla, Wlb, and Wlc is N. In a particular embodiment of the compound of Formula II, at least two of Wla, Wlb, and Wlc are N. In a specific embodiment of the compound of formula 11, wla, wlb, and wlc are N. In a particular embodiment of the compound of formula II, w is selected from the group consisting of 1 and 2. In a specific specific example of the compound of Formula 11, "1. In a particular embodiment of the compound of formula 11, each R3 and R4 are independently selected from the group consisting of hydrogen, optionally substituted lower alkyl and lower alkoxycarbonyl. In a particular embodiment of the compound of formula 11, each R3 and R4 are independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, hydroxydecyl, and methoxycarbonyl. In a particular embodiment of the compound of formula II, each "and R4 is hydrogen. In a particular embodiment of the compound of formula II, the p-line is selected from the group consisting of hydrazine and 2.6. In a particular embodiment of the compound of formula 11, the household is i. In a particular embodiment of the compound of formula II, the 9 is selected from the group consisting of i and 2. In a particular embodiment of the compound of formula 11, 9 is 1. 49 200823202 In a particular embodiment of the compound of formula II, gr is 〇. In a specific embodiment of the compound II, each Rio is independently selected from the group consisting of a cyano group, a chloro group, a bromo group, a methyl group, an ethyl group, an isopropyl group, a butyl group, a hydroxymethyl group, a trifluoromethyl group, and a methoxy group. Carbonyl, phenoxy, trifluoromethoxy: methyl 5-oxo, hydrazine, hydrazine-dimethylamino, and 1-indolyl. 1 In a specific embodiment of the compound of formula II, each Ri is selected from the group consisting of Base, ethyl, isopropyl, and CF 3. In a specific embodiment of the compound of formula II, the formula 1 and R10 are ethyl or isopropyl. 10 In a specific embodiment of the compound of formula 11, an R10 group Is located at position 4 of the phenyl group. In a specific embodiment of the compound of formula II, the Ri and R2 systems are independently selected from the group consisting of hydrogen and lower In a particular embodiment of the compound of formula II, R1 and R2 are independently 15 selected from the group consisting of hydrogen and methyl. In a particular embodiment of the compound of formula II, Ri and R2 are gases. Specific to the compound of formula II In the examples, Ri and R2 are methyl. In a specific embodiment of the compound of formula II, R1 is hydrogen and R2^methyl. 20 In a specific embodiment of the compound of formula II, R1 and R2 are joined together to form a moiety selected from the group consisting of a group of a pyridyl group and a heterocyclic group. In a specific embodiment of the compound of formula II, R1 and R2 are bonded together to form a group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, and a group of 2H-3,4,5,6-tetrahydroxanthyl, wherein each group is taken as 50 200823202 as needed. In a specific embodiment of the compound of formula II, R1 and R2 are joined together to form a group selected from Substituted cyclopropyl, optionally substituted cyclopentyl, optionally substituted cyclohexyl, optionally substituted piperidinyl, and optionally substituted 2H_3, 4, 5, 6- a group of a tetrahydropyranyl group. In a specific embodiment of the compound of formula II, each R5 and R6 are independently selected from the group consisting of hydrogen, A substituted lower alkyl group and a lower alkoxycarbonyl group are required. In a specific embodiment of the compound of formula II, each R5 and R6 is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, methyl, and Oxidyl. In a specific embodiment of the compound of the formula, each of R5 and R6 is hydrogen. In a specific embodiment of the compound of formula II, it is 1 or 2. In a specific embodiment of the compound of formula II, w is 1 And R7 is C1, F, methyl, or CF3. In a specific embodiment of the compound of formula II, w is 1 and R7 is C. In a specific embodiment of the compound of formula 11, w is 2 and each R7 is C1. . In a particular embodiment of the compound of formula II, the chloro groups are located at positions 2 and 3 of the phenyl ring. In a specific embodiment of the compound of formula 11, m is 2 and each R7 is C1 or F. 51 4 200823202 In a specific embodiment, the compound of formula X is selected from the group consisting of: chemical name

N-[(2-chlorophenyl)methyl]-3-{[(4-ethylphenyl)amino]carbonylamino}-2,2-dimethylpropanamide (4-{[N -(4-Ethylphenyl)amine-methylcarbonyloxy]methyl}(211-3,4,5,6-tetrahydrotetram-4-yl))-;^-[(2-chloro Phenyl) indenyl] formamide

V

〇 〇

(4-{[N-(2-Chlorophenyl)aminecarbamyloxy]methyl}(211-3,4,5,6-tetrahydropentan-4-yl))-&gt;1- [(2-chlorophenyl)methyl]carbamamine

N-[(2-Chlorophenyl)methyl](4-{[N-(3-methoxyphenyl)amine-carbenyloxy]methyl}(2-3,4,5,6- Tebufen-4·yl))carbamide

2·(Ethylamino)-N-[(2-phenylphenyl)methyl]-3-[N-(4-ethylphenyl)amine-methanoloxy]propanol 52 200823202

4-{[(4-{Ν·[(2-chlorophenyl)methyl]amine fluorenyl}-211-3,4,5,6-tetrahydrooxa-4-yl)methoxy] Carbonyl}}ethyl benzoate Ν·[(2-chlorophenyl)methyl](4-{[N-(4-methylphenyl)aminecarboxylideneoxy]fluorenyl}(211-3 ,4,5,6-tetrahydrofuran-4-yl))carbachamide

N-[(2-Chlorophenyl)methyl][4-({N-[4-(trifluoromethyl)phenyl]amine decyloxy}methyl)(211-3,4,5 ,6-tetra-argon "pyran-4-yl"]carbenamide

N-[(2-chlorophenyl)methyl](4-{[N-(2-cyanophenyl)aminecarboxylideneoxy]methyl}(2Η-3,4,5,6·tetrahydro) Η-pyran-4-yl))carboxamide

Ν-[(2-Chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)-fluorenyl-methylamine-mercaptooxy]methyl}(211-3,4, 5,6_tetrahydro σ than odor-4 -yl)) anthraquinone

4-{[(4-{Ν-[(2-chlorophenyl)indolyl]amine-carbamoyl}-211-3,4,5,6-tetrahydro-11-pyan-4-yl)nonyloxy Aminoamino}benzoic acid methyl ester 53 200823202

N-[(2-chlorophenyl)indolyl][4-({N-[4-(2-indolyl(1,3-thiazol-4-yl))phenyl]amine decyloxy} Methyl)(2H-3,4,5,6-tetrahydrofuran-4-yl)]decylamine

N-[(2-chlorophenyl)indenyl](4-{[N-(3-fluoro-4-indolylphenyl)amine decyloxy]fluorenyl}(2H-3,4,5 ,6-tetrahydrofuran-4-yl))decylamine N-[(2-chlorophenyl)indolyl]{4-[(N-hydroindol-5-ylaminodecyloxy)anthracene (211-3,4,5,6-tetrahydrofuran-4-yl)}carbenamide N-[(2-chlorophenyl)indolyl](4-{[N-(6-fluoro) 2-nonylphenyl)amine fluorenyloxy]fluorenyl}(2Η·3,4,5,6-tetrahydropyran-4-yl))guanamine

(4-{[Ν-(3-chloro-2-indolylphenyl)amine fluorenyloxy]fluorenyl}(2Η·3,4,5,6-tetrahydrofuran-4-yl)) -Ν-[(2-chlorophenyl)indolyl]guanamine

Ο CI Ν-[(2-chlorophenyl)indolyl][4-({Ν-[4-mercapto-3-(trifluoromethyl)phenyl]amine decyloxy}fluorenyl) ( 2H-3,4,5,6-tetrahydrofuran-4-yl)]decylamine 54 200823202 )ατ

ο α (4-{[Ν-(3,4·Dimethylphenyl)aminecarboxylideneoxy]methyl}(2H-3,4,5,6-tetrahydron-pyran-4-yl ))-N-[(2-chlorobenzene)

Methyl]carbamamine (4-{[Ν-(3-gas-4-methylphenyl)amine fluorenyloxy]fluorenyl} (2 士 3,4,5,6-tetrahydro) Indole-4-yl))-[[2-chlorophenyl)methyl]carbamamine-[(2-chlorophenyl)methyl][4-({Ν-[4-(methyl) Ethyl)phenyl]amine-mercaptooxy}methyl)(211-3,4,5,6-tetradecano-4-yl)]carbenamide (4_{[Ν-(3,5 -dichlorophenyl)amine-mercaptooxy]methyl}(211-3,4,5,6-tetrahydrooxa-4-yl))-:^-[(2-chlorophenyl)fluorene Amidoxime (4-{[Ν-(2,4-dimethylphenyl)amine decyloxy]methyl}(211-3,4,5,6-tetrahydrofuran-4 -yl))-:^-[(2-chlorophenyl)methyl]carbamamine 3-{Ν-[(2-chlorophenyl)indolyl]amine sulfhydryl}-3-{[(4 -ethylphenyl)amino]carbonylamino}pyrrolidinecarboxylic acid methyl ester 55 200823202

N-[(2-Chlorophenyl)methyl][4-({Ν·[4-(hydroxyethyl)phenyl]aminemethanyloxy}indenyl) (2 ± 3, 4, 5, 6-tetrahydrofuran-4-pyryl-4-yl)]carbenamide N-[(2-chlorophenyl)indolyl]{4-[(N-phenylaminoindenyloxy)methyl](211 -3,4,5,6-tetrahydrofuran-4-yl)}carbenamide

4-{[(4-{N-[(2-chlorophenyl)methyl]aminemethanyl}-211-3,4,5,6-tetrahydropyran-4-yl)decyloxy] Carbonylamino}benzamide N-[(2-chlorophenyl)indenyl][4-({[(4-ethylphenyl)amino]carbonylamino}methyl)(4-piperidine) Benthylamine N-[(2-phenylphenyl)indolyl][4-({[(4-ethylphenyl)amino)carbonylamino]methyl)-1-(2-hydroxyl) Ethyl)(4-piperidinyl)]carboxamide N-[(2-chlorophenyl)methyl][4-({[(4-ethylphenyl)amino]- fluorenyl) Carbonylamino}methyl)-1-(2-hydroxyethyl)(4-piperidinyl)]carbamamine 56 200823202

2-(Ethylamino)-N-[(2-chlorophenyl)methyl]_3-[N-(4-ethylphenyl)amine decyloxy]-2-methylpropionate amine

N-[(2-Chlorophenyl)methyl]-3-[N-(4-ethylphenyl)aminecarbamidooxy]-2-(methoxycarbonylamino)-2-methylpropane Guanamine

N-[(2-Chlorophenyl)methyl]-3-[N-(4-ethylphenyl)amine decyloxy]-2-(2-3⁄4ylethylamino)-2 -methyl propyl

Indole 2-{2-[(Tertibutoxy)carbonylamino]ethinylamine S}-N-[(2-chlorophenyl)methyl]-3-[N-(4-ethyl Phenyl) amidinoyloxy]-2-methylpropanamide

2-(2-Aminoethyl decylamino)-N-[(2-chlorophenyl)methyl]-3-[N-(4-ethylphenyl)amine-mercaptooxy]-2 -methylpropanamide

2-((2S)-2-amino-3-hydroxypropionylamino)-N-[(2-chlorophenyl)methyl]-3-[N-(4-ethylphenyl)amine Mercaptooxy]-2-mercaptopropionamide 57 200823202

{[1-(2-Aminoethyl)-4-({[(2-chlorophenyl)methyl)amino}methyl)(4-piperidinyl)]methoxy}-N- (4-ethylphenyl)carhamamine

N-[(l-(2-Aminoethyl)-4-{N-[(2-chlorophenyl)methyl]aminemethanyl}(4-piperidinyl))methyl][( 4-ethylphenyl)amino]-N-(3-methoxypropyl)carhamamine

N-[(l-(2-Aminoethyl)-4-{N-[(2-chlorophenyl)methyl]aminemethanyl}(4-piperidinyl))methyl]-^ [-(2-aminoethyl)[(4-ethylphenyl)amino]carbamamine

(Third butoxy)-Ν·(2-{Ν-[(1-{2-[(Tertidinoxy)carbonylamino]ethinyl}-4-{Ν-[(2·Chlorine) Phenyl)methyl]aminomethane}}(4-piperidinyl))methyl][(4-ethylphenyl)amino]carbonylamino}ethyl)carboxamide

3-(1-(2-Aminoethyl)-4-{]^-[(2-methylphenyl)methyl]aminecarbazide}(4-piperidinyl))-Ν-( 4-ethylphenyl) propylamine

N-{(lS)-2-[N-(4-ethylphenyl)amine-mercaptooxy]-isopropyl}{[(2-chlorophenyl)methyl]amino}methanamine 58 200823202

2-(N-{(lS)-2-[N-(4-ethylphenyl)amine decyloxy]-isopropyl}{[(2-chlorophenyl)methyl]amino} Carboxyamino)acetic acid tert-butyl ester 2-(N-{(lS)-2-[N-(4-ethylphenyl)aminecarboxylideneoxy]-isopropyl}{[(2-chloro Phenyl)methyl]amino}carbonylamino)acetic acid N-{(lS)-2-[N-(4-ethylphenyl)amine decyloxy]-isopropyl}{[(2 -Chlorophenyl)methyl]amino}-N-methylformamide [(2R)-2-({[(2-chlorophenyl)methyl]amino}-N-methylcarbonylamino) )propoxy]-fluorenyl-(4-phenylphenyl)carbenamide N-{(lS)-3-[N-(4-ethylphenyl)aminecarboxylideneoxy]-1-fluorenyl Propyl}{[(2-chlorophenyl)methyl]amino}-^methylformamide {[(2-chlorophenyl)indolyl]amino}-N-{4-[N-( 4-ethylphenyl)amine-mercaptooxy]butyl}-N-methylnonylamine 59 200823202

{[(2-Chlorophenyl)methyl]amino}·Ν-{3-[Ν-(4-ethylphenyl)amine decyloxy]propyl}-oxime-methylformamide

(Third butoxy)-indole-[2-({[(2-chlorophenyl)methyl]amino}}-:^-{2-[1^(4-ethylphenyl)amine-carbamidine Hydroxy]ethyl}carbonylamino)ethyl]-indole-methylformamide, α

{[(2-Chlorophenyl)methyl]amino}-Ν-{2-[Ν-(4-ethylphenyl)aminecarakioxy]ethyl}-Ν-[2-(A Amino)ethyl]carbamamine

2-Amino-indole-[2-({[(2-chlorophenyl)methyl]amino}}-&gt;^-{2-[14-(4-ethylphenyl)aminecarboxamoxy Ethyl]ethyl}carbonylamino)ethyl]-indole-methylacetamide

〇2-Amino-Ν-{2-[{[(2-chlorophenyl)indolyl]amine*}-Ν-(2-{Ν-[4-(trifluoromethyl)phenyl]amine A Mercaptooxy}ethyl)carbonylamino]ethyl}-indole-methylacetamide

[2-({[(2-Chlorophenyl)methyl]amino}-indole-methylcarbonylamino)-isopropoxy]-indole-(4-ethylphenyl)carbenamide 60 200823202

{[(2-Phenylphenyl)methyl]amino}-N-methyl-N-{2-[N-(4-phenylphenyl)amine-methylcarbonyl]ethyl}carbamidine {[(2-Phenylphenyl)indenyl]amino}-Ν·methyl-indole-[2-(indolyl-(2-naphthyl)aminecarboxylideneoxy)ethyl]carboxamide

3-(2-chlorophenyl)-indole-{2-[Ν-(4-ethylphenyl)amine decyloxy]ethyl}-indole-methylpropanamine Ν-{2-[ Ν-(4-ethylphenyl)amine-mercaptooxy]ethyl}-2-hydroxy-indole-methyl-3-[2-(trifluoromethyl)phenyl]propanamine Ν-{ 2-[Ν-(4-ethylphenyl)amine-mercaptooxy]ethylindole-N•methyl-3-[2-(trifluoromethyl)phenyl]propanamine {[(2 -Chlorophenyl)indenyl]methylamino}-indole-{2-[indolyl-(4-ethylphenyl)amine-mercaptooxy]ethyl}-indole-methylformamide 61 200823202

(2-{N-[(2-Chlorophenyl)indenyl]amine-methylcarbonyloxy}ethoxy)-N-(4-ethylphenyl)carboxamide Ν·[(2-chlorobenzene) Methyl]-4-{[N-(4-ethylphenyl)amine-methylmethyl]amino}-2,2-dimethylbutyramine

N-[(2-chlorophenyl)methyl]-2-{[(4-ethylphenyl)amino]carbonylamino}-2-methylpropanoxime oxime-[(2-chlorophenyl) )methyl]-3-[Ν-(4-ethylphenyl)amine-mercaptooxy]-2,2-dimercaptopropylamine Ν-[({Ν-[(2-chlorophenyl) )methyl]aminocarbazinyl}cyclopropyl) fluorenyl][(4-ethylphenyl)amino]carbamimidoxime-[({Ν-[(2-chlorophenyl)indolyl]amine Mercapto}cyclopropyl) fluorenyl]-2-(4-ethylphenyl)acetamide 62 200823202

[({N-[(2-Chlorophenyl)methyl]amine-carbamoyl}cyclobutyl)methoxy]_N-(4-ethylphenyl)decylamine

N-[(2-Chlorophenyl)indenyl]({[N-(4-ethylphenyl)aminemethyleneoxy]methyl}cyclohexyl)carboxamide

4-{N-[(2-Chlorophenyl)methyl]aminemethanyl}-4-{[\-(4-ethylphenyl)aminecarboxylideneoxy]methyl}piperidinecarboxylic acid Tributyl ester

N-[(2-Chlorophenyl)methyl](4-{[Ν·(4-ethylphenyl)amine)methylcarbonyloxy]indolyl}(4-piperidinyl))decylamine

(4-{[Ν-(4-chlorophenyl)amine fluorenyloxy]methyl}(211-3,4,5,6-tetrahydro)pyran-4-yl))-;^- [(2-Phenylphenyl)methyl]carbamamine

Ν-[(2-Chlorophenyl)methyl](1·{[Ν-(4-ethylphenyl)amine decyloxy]methyl}cyclopent-3-enyl)carbamamine 63 200823202

N-[(2-Chlorophenyl)methyl](1-{[Ν-(4-ethylphenyl)aminemethanemethoxy]methyl}-3,4-dihydroxycyclopentyl) A Guanamine

4-{N-[(2-Phenylphenyl)methyl]amine-carbamidine*}-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}piperidinecarboxylic acid Ester ((lS,2S)-2-{[(4-ethylphenyl)amino]carbonylamino}cyclohexyl)-N-[(2-chlorophenyl)methyl]carboxamide

V

(1-Ethylmethyl-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl) Methyl]carbamamine N-[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(methyl) Sulfhydryl)(4_piperidinyl))carboxamide

N-[(2-Phenylphenyl)methyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}·1_(2-hydroxyethyl)-(4) -piperidinyl))carbamamine 64 200823202

(Third butoxy)·Ν-[2-(4-{Ν-[(2-chlorophenyl)methyl]aminemethanyl}-4-{[&gt;1-(4-ethylbenzene) Aminomethyloxy]methyl}piperidinyl-2-oneethyl]carboxamide (t-butoxy)-N-[4-(4-{N-[(2-chloro) Phenyl) fluorenyl] amide methyl hydrazide *} -4-{[Ν-(4·ethylphenyl)amine methionyloxy]methyl}piperidinyl)-4- ketobutyl]carbamamine

(1-(2-Aminoethyl)-4-{[N-(4-ethylphenyl)aminemethyl decyloxy]methyl}(4-piperidinyl))-N-[( 2-chlorophenyl)methyl]carbamamine

(1-(4-Aminobutylidene)-4-{[N-(4-ethylphenyl)aminecarbomethoxy]methyl}(4-piperidinyl))-N-[(2- Phenyl phenyl) methyl] formamide

N-[(lS)-2-(4-{N-[(2-Chlorophenyl)methyl]amine-carbamidine*}-4-{[N-(4-ethylphenyl)aminecarboxamide Oxy]methyl}p-mentyl)-1-mercapto-2-indenyl](t-butoxy) formamide

(l-((2S)-2-Aminopropionyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl))- N-[(2-chlorophenyl)methyl]carbamamine 65 200823202

4-(4-{N_[(2-chlorophenyl)indolyl]amine-methylmercapto 4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}piperidinyl Methyl 4-ketobutyrate

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminemethylmercaptooxy]indolyl}-1-(4-hydroxybutanyl)(4- Piperidinyl))carbamide

N-[(2-Chlorophenyl)methyl]{3-[N-(4-ethylphenyl)amine-methylcarbonyloxy]piperidinyl}carboxamide

{3-[N-(4-ethylphenyl)amine-carbenyloxy]piperidinyl}-~[(2-methylphenyl)methyl]carboxamide

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1_(Ν-mercaptoaminecarbamyl) (4-piperidinyl))carhamamine

(Third butoxy)-Ν-[2-(4-{Ν·[(2-chlorophenyl)indolyl]amine-methylhydrazine*}-4-{[Ν-(4-ethylphenyl) Aminomethyl methoxy]methyl}piperidinyl-1-(hydroxymethyl)-2-oneethyl]carbamamine 66 200823202

(1 -(2-Amino-3-presylpropyl)-4-{[N-(4-ethylphenyl)aminemethylmercaptooxy]indolyl}(4-piperidinyl)) -N-[(2-chlorophenyl)methyl]carbamamine N-[(lR)-2-(4-{N-[(2-chlorophenyl)methyl]amine 曱醯S}-4 -{[N-(4-ethylphenyl)amine-mercaptooxy]methyl}piperidinyl)-1-methyl-2-oneethyl](t-butoxy)carbamidine Aminomethyl methoxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carbenamide (1-(2-amino-3-methylbutanyl) )-4-{[N-(4-ethylphenyl)amine-methyleneoxy]indolyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]formamidine Amine 4-[(4.{Ν-[(2-chlorophenyl)methyl]amine oxime ethylphenyl)amine methyl methoxy]methyl}piperidinyl)carbonyl]piperidinecarboxylic acid third Butyl phthalate-[(2·chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)aminemethyl methoxy)methyl}-1-(4-piperidinylcarbonyl) )(4-piperidinyl))carbamamine 67 200823202

3·[(4-{Ν-[(2-Chlorophenyl)indolyl]amine-methylhydrazine*}-4-{[N-(4-ethylphenyl)amine-methylcarbonyl]methyl} Piperidinyl)carbonyl]morpholine-4-carboxylic acid tert-butyl ester

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(morpholin-3-ylcarbonyl) (4-piperidinyl)) guanamine

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-benzyl (4-piperidinyl) Methotrexate

N-[(2-Chlorophenyl)methyl](1-ethyl-4-{[N-(4-ethylphenyl)aminecarbinyloxy]methyl}(4-pyridinyl) Methotrexate 2-(4-{N-[(2-phenylphenyl)methyl]amine 曱醯*}-4-{[N-(4-ethylphenyl)aminemethanyloxy] Methyl}methylpiperidinyl)acetate

N-[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}-1-[3-hydroxy-2-(hydroxyl) Methyl)-2-mercaptopropyl](4-piperidinyl)) decylamine 68 200823202

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-(2-hydroxyethyl)(4 -piperidinyl)) formamide (1-(2.amino-2-methylpropenyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl }(4-piperidinyl))-N-[(2-phenylphenyl)methyl]decylamine

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminemethylmercaptooxy]indolyl}-1-[2-(methylamino)B Mercapto](4-piperidinyl))carhamamine

N-[(2-Chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-methyl(4-piperidinyl) Methotrexate

}}_4-{[&gt; 1-(4-ethylphenyl)amine decyloxy]indolyl}piperidinyl)-1-(hydroxymethyl)-2-oneethyl] (third Butoxy)carbamamine

(1-((211)-2-Amino-3-hydroxypropionyl)-4-{[1^(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidine) Base))-N-[(2-chlorophenyl)methyl]carbamamine 69 200823202

*}·4-{[Ν·(4-ethylphenyl)aminemethanyloxy]fluorenyl}pyryl)-1-(methyl)-2-indolyl]

Oxy)carbamamine (l-((2S)-2-amino-3-hydroxypropanyl)-4-{[N-(4-ethylphenyl)amine decyloxy]methyl }(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carboxamide

(1-(2-Aminoethyl)-4-{[N-(4-ethylphenyl)aminemetholyloxy]methyl}(4-piperidinyl))-N-[(2- Chlorophenyl) fluorenyl] guanamine

(1-(2-Amino-3-cyanopropionyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl)) -N-[(2-chlorophenyl)methyl]formamide N-[(2-chlorophenyl)methyl][4·({Ν-[4·(trifluoromethyl)phenyl]amine Mercaptooxy}methyl)(4-piperidinyl)]carboxamide

(1-[(2-Aminoethyl)sulfonyl]-4-{[N-(4-ethylphenyl)aminemethylmercaptooxy]methyl}(4-piperidinyl))·Ν -[(2-phenylphenyl)methyl]carbamamine 70 200823202

(l-(2,3-Diaminopropionyl)-4-{[N-(4-ethylphenyl)aminemethylmercaptooxy]methyl}(4-piperidinyl))-N -[(2-chlorophenyl)methyl]decylamine γ^νη2

(1-(2,4-Diaminobutyrylsyl)-4-{[indolyl-(4-ethylphenyl)aminemethylmercaptooxy]methyl}(4-piperidinyl))-indole-[ (2-chlorophenyl)methyl]carbamamine

Ν-[(2-Chlorophenyl)methyl][1-(2-hydroxyethyl)-4-({N-[4-(trifluoromethyl)phenyl]aminemethanyloxy} Methyl)(4-piperidinyl)]carbamamine

[1-(2-Aminoethyl fluorenyl)-4-({N-[4-(trifluoromethyl)phenyl]amine-methylmethyloxy}methyl)(4-piperidinyl)]- N-[(2-chlorophenyl)methyl]carbamamine [l-((2S)-2-amino-3-hydroxypropanyl)-4-({N-[4-(trifluoromethyl) Phenyl]amine-methylmercaptooxy}methyl)(4-piperidinyl)]-N-[(2-chlorophenyl)indolyl]carboxamide

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminemethanyloxy)indolyl}-1-(2-methoxyethenyl) (4-piperidinyl))carhamamine 71 200823202

2-[(4-{N-[(2-Chlorophenyl)methyl]aminecarboxamidine S}-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl} Piperidinyl)carbonyl]azetidinecarboxylic acid tert-butyl ester (1-(azetidin-2-ylcarbonyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]indole (4-(piperidinyl))-N-[(2-chlorophenyl)methyl]carbenamide N-[(2-chlorophenyl)methyl](4-{[N-(4- Ethylphenyl)amine-mercaptooxy]methyl}-1-(3-methoxypropenyl)(4-piperidinyl))decylamine (1-(2,5-diaminopentyl) Mercapto)-4-{[N-(4-ethylphenyl)amine fluorenyloxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl] Formamidine {(3R)-3-[N-(4-ethylphenyl)amine decyloxy]piperidinyl}-N-[(2-chlorophenyl)methyl]carboxamide N -[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}-1-(phenylcarbonyl)(4-piperidine) Base)) methotrexate 72 200823202

N-[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}-l-(3-n-pyridylcarbonyl) (4-piperidinyl))carzamide (t-butoxy)-N-[2-(4_{N-[(2-chlorophenyl)methyl]aminecarboxamidine*}-4-{[ N-(4-ethylphenyl)amine-mercaptooxy]methyl}Benyl)-1_methyl-2-ketoethyl]-N-methylformamide N-[(2- Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)amine-carbenyloxy]methyl}-1-[2-(methylamino)propanyl](4- Piperidinyl))carzamide N-[(2-chlorophenyl)methyl]-N'-(4-ethylphenyl)-2,2-dimethylpentane-1,5-diindole Amine (3S)-3-amino-4-(4-{Ν·[(2-chlorophenyl)methyl]aminecarbamyl}-4-{[Ν-(4-ethylphenyl)amine Methyl decyloxy]methyl}piperidinyl-4-ketobutanoate (1-(3-Amino-2-hydroxypropionyl)-4-{[N-(4-ethyl) Phenyl)amine-mercaptooxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carbamamine 73 200823202

ο α

(1-(4-Amino-2-3⁄4ylbutyryl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl)) -N-[(2-chlorophenyl)methyl]decylamine (1-(2,3-dihydroxypropyl)-4-{[N-(4-ethylphenyl)aminecarboxamide Oxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carbenamide {(3S)-3-[N-(4-ethylphenyl)amine Methyl methoxy]piperidinyl}-N-[(2-chlorophenyl)methyl]carbamamine 3-amino-4-(4-{N-[(2-chlorophenyl)fluorenyl) Amine 曱醯*}-4-{[N-(4-ethylphenyl)amine-mercaptooxy]methyl}piperidinyl)-4-ketobutanoic acid N-[(2-chlorobenzene) Methyl](1-(cyclopropylcarbonyl)-4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}(4-piperidinyl))carboxamide N-[(2-chlorophenyl)methyl](1-(cyclohexylcarbonyl)-4-{[N-(4-ethylphenyl)amine decyloxy]methyl}(4-piperidyl) Pyridyl))carbamamine 74 200823202

N-[(2-chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}-1-(2-«pyridylcarbonyl) (4-piperidinyl))carhamamine

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]indolyl}-1-(imidazol-2-ylcarbonyl)( 4-piperidinyl)) guanamine

(Third-butoxy)-N-[2-(3-{N-[(2-chlorophenyl)methyl]amine-methylmercapto 3-{[N-(4-ethylphenyl)amine Methyl methoxy]methyl}piperidinyl)-2-oneethyl]carbamamine

N-[(lS)-2-(3-{N-[(2-chlorophenyl)methyl]aminoindolyl}-3-{[&gt;1-(4·ethylphenyl)amine A Mercaptooxy]methyl}piperidinyl-1-(hydroxyindole)-2-oneethyl](t-butoxy)carbamamine

(1-(2-Aminoethyl)-3-{[N-(4-ethylphenyl)aminemethyl decyloxy]methyl}(3-piperidinyl))-N-[( 2-chlorophenyl)methyl]carbamamine

N-[(2-Chlorophenyl)indenyl](3-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-(2-hydroxyethyl) 3-pyridyl))carbamamine 75 200823202

(l-((2S)-2-Amino-3-ylpropyl)-3-{[Ν-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(3-piperidine) Base))-Ν-[(2-chlorophenyl)methyl]carbamamine

4-{Ν-[(2·Chlorophenyl)methyl]aminecarbazide}-4-{[^^-(4-ethylphenyl)amine decyloxy]methyl}piperidinium Acid 2-aminoethyl hydrazine

Ν-(2-Aminoethyl)(4-{Ν-[(2-chlorophenyl)methyl]aminemethanyl}-4-{[Ν-(4-ethylphenyl)aminecarboxamide Oxy]methyl}piperidinyl)carhamamine

3-{N-[(2-Chlorophenyl)methyl]amine-carbamoyl}-3-{[1(4-ethylphenyl)amine-carbamoyloxy]methyl}piperidinecarboxylic acid methyl ester

(1-(2-Aminoethyl)-{{N-(4-ethylphenyl)amine-methylcarbonyl]methyl"pyrrolidin-3-yl)-indole-[( 2·Chlorophenyl)methyl]carbamamine (1-((28)-2,5-diaminopentenyl)-4-{[?^-(4-ethylphenyl)amine formazan氧基oxy]methyl}(4-piperidinyl))-indole-[(2-chlorophenyl)methyl]carbamamine 76 200823202

(1·(2·Aminoethyl)-4-{2-[N-(4-ethylphenyl)aminecarboxylideneoxy]ethyl}(4-piperidinyl))-N_[ (2-Chlorophenyl)methyl]decylamine [1-(2.Aminoethyl fluorenyl)-4-({N-[2-chloro-4-(trifluoromethyl)phenyl]amine A Mercaptooxy}indenyl)(4-piperidinyl)]-indole-[(2-chlorophenyl)indolyl]carbamamine [1-(2-aminoethyl)-(4) Ν-[4-indolyl-3-(trifluoromethyl)phenyl]amine decyloxy}fluorenyl)(4-piperidinyl)]-N-[(2-chlorophenyl)methyl Methionamine (1-(2-aminoethenyl)-4-{[N-(2-chloro-4-mercaptophenyl)amine decyloxy]fluorenyl}(4·piperidine) Base))_N-[(2-phenylphenyl)indolyl]guanamine

{1-(2-Aminoethyl fluorenyl)-4-[(N-hydroquinol-5-ylaminocarbamoyloxy)methyl](4-piperidinyl)}-N-[(2- Chlorophenyl)indenyl]decylamine (1-(2-aminoethenyl)-4-{[N-(4-chlorophenyl)amine decyloxy]methyl} (4-piperidyl) Pyridyl))-N-[(2-chlorophenyl)indenyl]decylamine 77 200823202

4-{[(1-(2-Aminoethyl)methyl]{{^[(2-chlorophenyl)methyl]amine-carbamoyl}-4-piperidyl)methoxy]carbonyl Methyl benzyl benzoate

(1-(2-Aminoethyl fluorenyl)-4-{[N-(3-fluoro-4-indolylphenyl)amine decyloxy]methyl}(4-piperidinyl))- N-[(2-chlorophenyl)indolyl]carboxamide

N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methylphenylcarbonyl)phenyl]carbonyl](4-piperidyl) Pyridyl) carbenamide

(1-(2-Aminoethyl fluorenyl)-4-{[N-(4-phenylphenyl)amine-carbenyloxy]methyl}(4-piperidinyl))-N-[( 2-chlorophenyl)methyl]carbamamine

{1-(2-Aminoethyl fluorenyl)-4-[(N-(2-naphthyl)aminecarbinyloxy)indenyl](4-piperidinyl)}-N-[(2- Chlorophenyl)methyl]carbamamine

ο α Ν-[(2-Chlorophenyl)methyl]-4-[indolyl-(4-ethylphenyl)amine-mercaptooxy]butanamine 78 200823202 2-Amino-indole-[( 2-chlorophenyl)methyl]-4-[indolyl-(4-ethylphenoyl)ylcarbamoyloxy]butanamine

2-(2·Aminoethylhydrazino)-indole-[(2-chlorophenyl)methyl]-4-[indolyl-(4-ethylphenyl)aminecarboxylideneoxy]butanamine

2-(1-(2-Aminoethyl fluorenyl)-4-{[indolyl-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl))-oxime- [(2-chlorophenyl)methyl]acetamide

Ν-[(2-Chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)aminemethanyloxy]methyl}(211-3,4,5,6-four Hydrogen "pyran-4-yl") formamide

1-(2-Aminoethyl fluorenyl)-4-{[indolyl-(4-ethylphenyl)amine-carbamoyloxy]methyl}piperidine-4-carboxylic acid methyl ester (third butoxy group) )-Ν-[2·(4-{[Ν-(4-ethylphenyl)amine-carbenyloxy]fluorenyl}-4-{Ν-[(2-mercaptophenyl)methyl] Aminomethylmercapto}piperidinyl)-2-oneethyl]carbamamine 79 200823202

(Third butoxy)-N-[2-(4-{[N-(4-ethylphenyl)amine-carbenyloxy]methyl}-4-[N-benzylaminecarbamyl ] piperidinyl)-2-ketoethyl]carbendazim (tert-butoxy)-N-[2-(4-{ [N-(4-ethylphenyl)aminemethanyloxy] Methyl}-4-{N-[(2-fluorophenyl)methyl]aminemethanyl}piperidinyl)-2-oneethyl]carboxamide (1-(2-aminoethyl) )-4-{[N-(4-ethylphenyl)amine-mercaptooxy]indolyl}(4-piperidinyl))-N-[(2-methylphenyl)methyl]- Indoleamine (1-(2-aminoethenyl)·4-{[indole-(4-ethylphenyl)aminecarbomethoxy]methyl}(4-piperidinyl))-oxime- Benzylcarbamide (1.(2.Aminoethyl fluorenyl)-4-{[indole-(4-ethylphenyl)amine decyloxy]methyl}(4-piperidinyl)) -Ν-[(2-fluorophenyl)methyl]carbamamine (1-{2-[(t-butoxy)carbonylamino] acetamidine*}-4-{[Ν-(4·B Phenyl)aminomethane oxy] decyl}(4-piperidinyl))-indole-[(2-methoxyphenyl)methyl]carbamamine 80 200823202

[(1-{2-[(Tertidinoxy)carbonylamino)]ethinyl}-4-{&gt;1-[(4-chlorophenyl)methyl]aminecarboxylidene}(4- Piperidinyl)) decyloxy]-indole-(4-ethylphenyl)carboxamide [(4-{Ν-[(2,3-dichlorophenyl)methyl]aminecarbamyl}- 1-{2-[(Tertibutoxy)carbonylamino]ethenyl}(4-piperidinyl))methoxy]-indole-(4-ethylphenyl)carboxamide (1- (2-Aminoethyl fluorenyl)-4-{[indolyl-(4-ethylphenyl)amine-mercaptooxy]methyl}(4-piperidinyl))-indole-[(2-A) Oxyphenyl)methyl]carbamamine {[1-(2-aminoethenyl)-4-(anthracene-{[2-(trifluoromethyl)phenyl]fluorenyl)amine) (4-piperidinyl)]decyloxy}-&gt;^-(4-ethylphenyl)carboxamide [(1-(2-aminoethyl)]-{{--[(4 -Chlorophenyl)indenyl]amine-carbamoyl}(4.piperidinyl))methoxy]-N-(4-ethylphenyl)carboxamide [(1-(2-aminoethyl hydrazide) -4-(N-[(2,3-dichlorophenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy]-N-(4-ethylphenyl) Formamide 81 200823202

[(1-(2-Aminoethyl)methyl]{{^-[(3-methyl(2^pyridyl))methyl]aminoindolyl}(4-piperidinyl)) Methoxy]-N-(4-ethylphenyl)formamide

[(1-(2-Aminoethyl)-4-{N-[(2-bromophenyl)methyl]amine)methyl}}(4-piperidinyl))methoxy]-N- (4-ethylphenyl)carhamamine

[(1-(2-Aminoethyl)methyl]{{--((3-chlorophenyl)indenyl]aminoindenyl}(4-piperidinyl))methoxy]-N- (4-ethylphenyl)methaneamine [(4-{N-[(2,3-difluorophenyl)methyl]aminemethanyl}-1-{2-[(t-butoxy) )carbonylamino]ethinyl}(4-piperidinyl))decyloxy]-N-(4-ethylphenyl)carboxamide

[(1-(2-Aminoethyl)methyl]{{-((2,3-difluorophenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy] -N_(4-ethylphenyl)formamide

[(1-(2-Aminoethyl)methyl]{{--((3-chloro-2-fluorophenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy ]-N-(4-ethylphenyl)carbamamine 82 200823202

[(1-(2-Aminoethyl)methyl]{{--((3-fluoro-2-indolylphenyl)methyl]aminemethylmercapto}(4-piperidinyl))methoxy [-]-N-(4-ethylphenyl)carbamamine [(1-(2-aminoethyl)methyl]-4-{N-[(3-chloro-2-methylphenyl)methyl Aminomethyl}(4-piperidinyl))methoxy]_N-(4-ethylphenyl)carboxamide [(1-{2-[(Tertidinoxy)carbonylamino]] Ethyl }*}-4·{Ν-[(3-fluorophenyl)methyl]aminemethanyl}(4-piperidinyl))methoxy]-indole-(4-ethylphenyl)- Indoleamine [(1-{2-[(Tertidinoxy)carbonylamino]]]indolyl}_4-{&amp;[(4-fluorophenyl)methyl]aminoindolyl}(4-piperidyl) Pyridyl)) methoxy]-indole-(4-ethylphenyl)carboxamide [(1-(2-aminoethyl) -4-)-[(3-fluorophenyl)fluorene] Aminomethyl}(4-piperidinyl))methoxy]-indole-(4-ethylphenyl)carboxamide [(1-(2-aminoethyl)]-4-{ Ν-[(4-Fluorophenyl)indenyl]aminoguanidino}(4-piperidinyl))methoxy]-indole-(4·ethylphenyl)carbamamine 83 200823202

({1-(2-Aminoethyl)-4-[N-(2-decyridylmethyl)aminecarboxyl](4-piperidinyl)}methoxy)-N-(4 -ethylphenyl)carbenamide [(1-{2-[(tatabutoxy)carbonylamino]ethinyl}-4-[yimidazolyl-2-ylmethyl)aminecarboxamide (4-piperidinyl))methoxy]-N-(4-ethylphenyl)carboxamide [(1-{2-[(t-butoxy)carbonylamino] acetamidine*} 4-{N-[(3-fluoro-2-indolylphenyl)indolyl]aminoindenyl}(4-piperidinyl))methoxy]-N-[4-(trifluoromethyl) Phenyl]decylamine [(1-{2-[(Tertibutoxy)carbonylamino]acetamidine*}-4-{N-[(3-chloro-2-fluorophenyl)methyl) Aminomethyl}(4-piperidinyl))methoxy]-N-[4-(trifluoromethyl)phenyl]decylamine [(4-{N-[(2,3-) Chlorophenyl)methyl]aminemethanyl}-1-{2-[(tatabutoxy)carbonylamino]ethenyl}(4-piperidinyl))methoxy]-N-[ 4-(Trifluoromethyl)phenyl]carboxamide ({1-(2-aminoethenyl)-4-[N-(imidazol-2-ylmethyl)aminemethanyl) (4· Piperidinyl)}methoxy)-N-(4-ethylphenyl)carbamamine 84 200823202

(1-{2-[(Tertidinoxy)carbonylamino]ethyl hydrazide*}-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4- Piperidinyl))-N-[(2-cyanophenyl)methyl]carboxamide

[(1-(2-Aminopropyl)-4-{N-[(3- gas-2-methylphenyl)indolyl]aminoindenyl}(4-piperidinyl))methoxy -N-[4-(trifluoromethyl)phenyl]carboxamide

[(1-(2·Aminoethyl)-4-{N-[(3-chloro-2-fluorophenyl)methyl]aminemethylmercapto}(4-piperidinyl))methoxy ]-N-[4-(trifluoromethyl)phenyl]decylamine 〇^Y^sTMH2

[(1-(2-Aminoethyl)methyl]{{2-((2,3-dichlorophenyl)methyl]amino]amino}(4-piperidinyl))methoxy ]-N-[4-(trifluoromethyl)phenyl]decylamine [(1-{2-[(Tertidinoxy)carbonylamino]acetamidine*}-4-{N-[( 3-chloro-2-methylphenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy]-N-[4-(trifluoromethyl)phenyl]carboxamide

(1-(2-Aminoethyl)-4-{[N-(4-ethylphenyl)amine decyloxy]fluorenyl}(4-piperidinyl))-N-[( 2-cyanophenyl) decyl] decylamine 85 200823202

[1-(2-Aminoethyl fluorenyl)-4-({N-[4-(trifluoromethyl)phenyl]amine-carbenyloxy}methyl)(4-piperidinyl)]· Ν-[(2-cyanophenyl)methyl]carbamamine [(1-(2-aminoethyl)methyl]-4-{Ν-[(3-chloro-2-methylphenyl)methyl Aminomethyl}(4-piperidinyl))methoxy]-indole-[4-(trifluoromethyl)phenyl]carboxamide 2-({[1·(2-aminoethyl)) 4-({Ν-[4-(Trifluoromethyl)phenyl]amine-carbamoyloxy}methyl)-4-piperidinyl]carbonylamino}methyl)benzoic acid methyl ester ({1 -(2-Aminoethyl fluorenyl)-4-[N-(naphthylmethyl)aminecarboxylidene](4-piperidinyl)}methoxy)-N-(4-ethylphenyl) Methionamine [(1-{2-[(Tertibutoxy)carbonylamino]acetamidine-4-fluorophenyl)methyl]aminecarbenyl}(4-acridinyl))methoxy [-]-N-(4-ethylphenyl)carboxamide [(1-(2-aminoethyl) phenyl)-4-{N-[(2-chloro-4-fluorophenyl)methyl] Aminomethyl}}(4-piperidinyl))decyloxy]-N-(4-ethylphenyl)carbenamide 86 200823202

{[1-(2-Aminoethyl)-(N-{[2-fluoro-4-(trifluoromethyl)phenyl]methyl}aminemethyl)-(4-piperidinyl) )]Methoxy

[(1-(2-Aminoethyl)]-{Ν-[(4-chloro-2-fluorophenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy ]-Ν·(4-ethylphenyl)formamide

[(1-(2-Aminoethyl)-4-(indolyl-[(2,4-dimethylphenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy ]-Ν-(4-ethylphenyl)formamide

[(1-(2-Aminoethyl)methyl]{{Ν-[(4-chloro-2-indolylphenyl)indenyl]amine-carbamoyl}(4-piperidinyl))methoxy Base]-Ν-(4-ethylphenyl) anthraquinone

[(1-(2-Aminoethyl)-4-{Ν-[(2,4-dichlorophenyl)methyl]aminoindolyl}(4-piperidinyl))methoxy] ·Ν-(4-ethylphenyl)formamide

[(1-(2-Aminoethyl)-4-{Ν-[(2-indolyl(3-η-pyridyl))methyl]aminemethanyl}(4-piperidinyl)) Methoxy]-indole-(4-ethylphenyl)formamide 87 200823202

(1-(2-Aminoethyl fluorenyl)-4-{[N-(4-ethylphenyl)amine-mercaptooxy]methyl}(4-piperidinyl))-N-{[ 2-(hydroxymethyl)phenyl]methyl}carbamidine

[(1-(2-Aminoethyl)]4-{Ν-[(2-ethylphenyl)methyl]aminemethylmercapto}(4-piperidinyl))methoxy]-oxime -(4-ethylphenyl)carhamamine

(4-(2-Aminoethyl)-3-{Ν-[(2-chlorophenyl)indenyl]amine-methylmethyl}piperidinyl 1)-indole-(4-ethylphenyl) Formamide

Ν-[(2-Chlorophenyl)methyl][2-({[(4-ethylphenyl)amino]carbonylamino}methyl))pyrrolidyl]carboxamide

(4-(2-Aminoethyl fluorenyl)-2-{[indolyl-(4-ethylphenyl)amine-mercaptooxy]methyl}piperidinyl 1)-indole-[(2-chloro Phenyl)methyl]carbamamine

((2S)-2-{[N-(4-ethylphenyl)amine-mercaptooxy]methyl"pyrrolidyl)-indole[(2-chlorophenyl)methyl]formamidine Amine 88 200823202

Methyl]carbamamine

N-[(l-(2-Aminoethyl)-4-{N-[(2-chlorophenyl)methyl]amine-carbamoyl}(4-piperidinyl))methyl]-2 -(4-ethylphenyl)acetamidine (1-(2-aminoethenyl)-4_{[N-(4-cyanophenyl)aminecarboxylideneoxy]methyl}(4- Piperidinyl))-N-[(2-chlorophenyl)methyl]carbenamide (1-(2.Aminoethyl fluorenyl)-4-{[N-(4-mercaptophenyl)amine A Mercaptooxy]fluorenyl}(4-piperidinyl))-N-[(2-chlorophenyl)(1-(2-aminoethenyl)-4-{[Ν·(4-fluoro Phenyl)amine-mercaptooxy]methyl}(4-bristidyl)-N-[(2-chlorophenyl)methyl]carbenamide {1-(2-aminoethenyl) 4-[(Ν-Phenylaminocarbamoyloxy)methyl](4-piperidinyl)}-indole-[(2-chlorophenyl)methyl]carbamamine (4-{[Ν -(4-Ethylphenyl)amine-methylcarbonyloxy]indolyl}-1-(2-aminoethenyl)(4-piperidinyl))-indole-[(2-chlorophenyl) )methyl]carbamamine 89 200823202

((5S,3R)-3-Amino-5-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}lahydropyridyl)-N-[(2-chlorobenzene) Methyl]carbamamine

N-((5S,3R)-l-{N-[(2-Chlorophenyl)methyl]amine-formamidine*}-5-{[N-(4-ethylphenyl)amine-mercaptooxyl Methyl}methyl} πpyrrolidine-3-yl)-2-aminoamine

N-((5S,3R)-l-{N-[(2-chlorophenyl)methyl]amine-carbamoyl} - 5-{[N-(4-ethylphenyl)amine-branched oxygen Methyl]pyrrolidin-3-yl)acetamide {[(2-chlorophenyl)indolyl]amino}-indole-{2-[Ν-(4-ethylphenyl)aminecarboxamide Hydroxy]ethyl}-indole-mercaptomethylamine

{[(2,3-Dichlorophenyl)indolyl]amino}-;^-{2-[&gt;1-(4-ethylphenyl)aminecarboxylideneoxy]ethyl}-oxime - mercaptocarbamide ο α

[2-({[(2-Chlorophenyl)methyl]amino}-Ν·(2-hydroxyethyl)carbonylamino)ethoxy]-indole-(4-ethylphenyl)formamidine Amine 90 200823202

N-[2-({[(2-Chlorophenyl)methyl]amino)-N-methylcarbonylamino)ethyl][(4-ethylphenyl)amino]carbamamine [(4 -{N-[(2-chlorophenyl)methyl]amine-carbamoyl}morpholin-2-yl)methoxy]-N-(4-ethylphenyl)carbenamide N-(3- Aminopropyl){[(2-phenylphenyl)methyl]amine*}-Ν-{2-[Ν-(4·ethylphenyl)aminecarboxylideneoxy]ethyl}carboxamide 2-[(Tertibutoxy)carbonylamino]-indole-[3·({[(2-chlorophenyl)methyl]amino}-Ν-{2-[Ν-(4-ethyl) Phenyl)amine,mercaptooxy]ethyl}carbonylamino)propyl]acetamide 2-amino-indole-[3-({[(2-chlorophenyl)methyl]amine) N-{2-[N-(4-ethylphenyl)amine-mercaptooxy]ethyl}carbonylamino)propyl]acetamide N-(2-aminoethyl){[(2- Phenyl phenyl)methyl]amino}-1^-{2---(4-ethylphenyl)amine-mercaptooxy]ethyl}carbenamide 91 200823202

2-Amino-N-[2-({[(2-chlorophenyl)methyl]amine)}}-N-{2-[N-(4-ethylphenyl)amine-methylcarbonyloxy] Ethyl}carbonylamino)ethyl]acetamide

[2-(N-(4-Aminobutyl){[(2-chlorophenyl)methyl]amino}carbonylamino)ethoxy]-N-(4-ethylphenyl)formamidine amine

2-Amino-indole-[4-({[(2)chlorophenyl)methyl]amine S}-N-{2-[N-(4-ethylphenyl)amine-methylcarbonyl)] Ethyl}carbonylamino)butyl]acetamide

N-{2-[N-(4-ethylphenyl)amine decyloxy]ethyl} acetamidine

{[(2-Chlorophenyl)methyl]amino}-N-methyl-N-[2-(N-(6-quinolinyl)amine decyloxy)ethyl]methaneamine

N-(5-Aminepentyl){[(2-chlorophenyl)indenyl]amine*}-N-{2-[N-(4-ethylphenyl)aminecarboxylideneoxy]ethyl }Metamine 92 200823202

{[(2-Chlorophenyl)methyl]amino}-Ν-{2-[Ν·(4-ethylphenyl)amine-mercaptooxy]ethyl}-Ν-(4-hydroxybutyrate) Methylamine (t-butoxy)-indole-[2-(4-{Ν-[(2-bromophenyl)methyl]aminecarboxamidine S}-4-{[N-(4- Ethylphenyl)amine,carboxylideneoxy]methyl}piperidinyl)-2-oneethyl]-N-methylformamide [(4-{N-[(2-bromophenyl)) Aminomethylamino}-1-[2-(decylamino)ethenyl](4-piperidinyl))decyloxy]-N-(4-ethylphenyl)carbenamide N- [(2-Chlorophenyl)indenyl]({[N-(4-ethylphenyl)aminemethyleneoxy]methyl}cyclopropyl)carboxamide 4-(ethenylamino) -N-[(2-chlorophenyl)methyl]-2-{[N-(4-ethylphenyl)amine-methylmethyloxy]methyl}-2-methylbutylamine

4-{2-[(Tertibutoxy)carbonylamino]ethynylamino}-[[2-chlorophenyl]indenyl]-2-{[N-(4-ethylphenyl) Aminomethyl methoxy]methyl}-2-methylbutanamine 93 200823202

4-Amino-N-[(2-chlorophenyl)methyl]-2-{[N-(4-ethylphenyl)aminemethyleneoxy]methyl}-2-methylbutanindole amine

4-(2-Aminoethyl decylamino)-N-[(2-chlorophenyl)methyl]-2-{[N-(4-ethylphenyl)aminemethyl decyloxy]- -2--methylbutyridinium

Ν-[(2-Chlorophenyl)methyl]-4-[indolyl-(4-ethylphenyl)amine-methylcarbonyl]-2,2-dimethylbutyramine

{[(2-Chlorophenyl)methyl]amino}-Ν-{2-[Ν-(4-ethylphenyl)aminecarbamyloxy]-t-butyl}-...methyl A Indoleamine (2S)-2-({[(4-ethylphenyl)amino)]carbonylamino}indenyl) ηpyrrolidinecarboxylic acid (2-chlorophenyl)methyl ester

Ν-[(2-Chlorophenyl)indolyl]-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanoid Amine 94 200823202

2.2-Dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}-&gt; 1-benzylpropionamide 2.2-Dimethyl-3-{5-[4-(indolyl)phenyl](1,2,3,4-tetrazol-2-yl)}-&gt;^-(2-« ratio Acridine-based N-[(2-fluorophenyl)methyl]-2,2-dimethyl-3·{5-[4-(methylethyl)phenyl](1, 2,3,4-tetrazol-2-yl)}propanamine 2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4 -tetrazol-2-yl)}-indole-[(2-methylphenyl)methyl]propanoxime oxime-[(3-fluorophenyl)methyl]-2,2-dimethyl-3 -{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanamine-[2-(2-chlorophenyl)ethyl ]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanamine 95 200823202

2,2-Dimethyl-3-{5-[4.(fluorenylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}-indole-(3-thienyl) Methyl) propylamine

2,2-Dimethyl-3-{5-[4-(indolylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}-&gt; 1-(1, 3-oxazol-2-ylmethyl)propanamide

Ν-[(2-chlorophenyl)methyl]-3-[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]-2,2-di Methyl propyl amide

Ν-[(2-Chlorophenyl)methyl]_2,2-dimethyl-3-{5_[4-(trifluoromethoxy)phenyl](1,2,3,4-tetrazole- 2-yl)}propanamine Ν[[(2-chlorophenyl)methyl]-2,2-dimethyl-3-[5-(4-phenoxyphenyl)(1,2,3,4- Tetrazol-2-yl)]propanamide

Ν-[(2-chloro-4-fluorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3, 4-tetrazol-2-yl)}propanamide 96 200823202

N-[(2,4-dichlorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4 -tetrazol-2-yl)}propanamide

N-[(6-chloro-2-fluorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3, 4-tetrazol-2-yl)}propanamide

4-[(2,2-Dimercapto-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanylamine 3-methyl]benzoic acid 3-[5·(4-bromophenyl)(l,2,3,4-tetrazol-2-yl)]-N-[(2-phenylphenyl)methyl l·2,2-dimethylpropanamide

Ν-[(2,3-Dichlorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4 -tetrazol-2-yl)}propanamide

Ν-[(2-Chlorophenyl)methyl]-3-[5-(4-cyanophenyl)(1,2,3,4-tetrazol-2-yl)]-2,2-diindole Propionamide 97 200823202

3-{5-[4-(dimethylamino)phenyl](1,2,3,4-tetrazol-2-yl)}-N-[(2-chlorophenyl)methyl]-2 ,2-dimethylpropionamide 4-[2-(2-{N-[(2-chlorophenyl)indolyl]aminemethanyl}-2-methylpropyl)-1,2,3 , 4-tetrazol-5-yl] benzoic acid oxime ester N-[(2-chlorophenyl)methyl]-3-{5-[4-(hydroxymethyl)phenyl](1,2,3 , 4-tetrazol-2-yl)}-2,2-dimethylpropanamide

N-[(2-chlorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazole -2-yl)}propanamine N-[(2-chlorophenyl)indolyl]-2,2-dimercapto-3-(2-[4-(methylethyl)phenyl](1) ,2,3,4-tetrazol-5-yl)}propanoxime-[(2-chlorophenyl)methyl]-2-methyl-3-{2-[4-(methylethyl) Phenyl](1,2,3,4-tetrazol-5-yl)}propanamine 98 200823202

N-[(2-chlorophenyl)methyl]-3-{3-[4-(methylethyl)phenyl](1,2,4-oxadiazol-5-yl)}propanamide

2-(2,2-Dimethyl-3-{5-[4-(indolylethyl)phenyl](l,2,3,4-tetrazol-2-yl)}propanylamino Methyl-2-(2-chlorophenyl)acetate

^|1-[1-(2-Phenylphenyl)-2-ethyl}-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1, 2,3,4-tetrazol-2-yl)}propanamide

N-[(2-chlorophenyl)methyl]({[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]methyl}cyclopropyl) Formamide

N-[(2-chlorophenyl)methyl]({[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]indolyl}cyclobutyl) Formamide

N-[(2-Phenylphenyl)methyl](4-{[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]methyl} (211 -3,4,5,6-tetrahydroindolepyran-4-yl))carbamamine 99 200823202

N-[(2-chlorophenyl)methyl](l-{[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]methyl}cyclopentyl -3-alkenyl) meglumine

N-[(2-chlorophenyl)indenyl](1-{[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]methyl}-3 , 4_dihydroxycyclopentyl)carhamamine

3_[5-(4-chlorophenyl)(1,2,3,4-tetrazol-2-yl)]-^[-[(2-chlorophenyl)methyl]-2,2-dimethyl Propylamine

N-[(2-chlorophenyl)methyl]-3-[5-(4-methoxyphenyl)(1,2,3,4-tetrazol-2-yl)]-2,2-dimethyl Propylamine

3-{5-[4-(t-butyl)phenyl](1,2,3,4-tetrazol-2-yl)}-N-[(2-chlorophenyl)methyl]-2 2-dimethylpropanamide

N-[(2-chlorophenyl)methyl]-2,2-dimethyl-3-[5-(4-methylphenyl)(1,2,3,4-tetrazol-2-yl )] propylamine 100 200823202

3-[5-(3-chlorophenyl)(l,2,3,4-tetrazol-2-yl)]-N-[(2-chlorophenyl)methyl]-2,2-dimethyl Propylamine

Ν-[(2·Chlorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(trifluoromethyl)phenyl](1,2,3,4-tetrazole -2-yl)}propanamide

N-[(2-Phenylphenyl)methyl]-2,2-dimethyl-3-[5-(3-methylphenyl)(1,2,3,4-tetrazol-2-yl )] propylamine

N-[(2-Phenylphenyl)methyl]-3-[5-(4-imidazolylphenyl)(1,2,3,4-tetrazol-2-yl)]-2,2-di Mercaptopropylamine

(2S)-N-[(2-chlorophenyl)methyl]-2-methyl-3-[5-(4-mercaptophenyl)(1,2,3,4-tetrazole-2- Propionamide

{[(2-Chlorophenyl)methyl]amino}-N-{2-[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]B Base}-N-methylformamide 101 200823202 The compounds described herein can be named and numbered as described below (eg, using NamExpertTM from Cheminnovation Software, Inc. or from CambridgeSoft Corporation).

Structure of ChemDraw Utlra version 10.0 &lt;=&gt; Named Feature). For example 5, the following compounds: 〇 people. That is, according to the compound of formula I, R1G is ethyl, W2 is NR13, R13 is hydrogen, W1 is hydrazine, R5 is hydrogen, R6 is hydrogen, W3 is CRk2, and R1 and R2 and the carbon atom bonded thereto form a cyclobutyl group. , R8 is hydrogen, R3 is hydrogen, R4 is hydrogen, and R7 is a chlorine group, and 10 can be named [({N-[(2-chlorophenyl)methyl)aminemethanyl}cyclobutyl) Methoxy]-indole-(4-ethylphenyl)decylamine or 'ethylphenylaminecarboxylic acid (1-(2-chlorobenzylaminecarbamimidyl)cyclobutyl)methyl ester. Moreover, chemical names generated by structures drawn by certain software environments do not necessarily result in the same structural formula when the chemical name is converted from a different soft environment to a structural form. Many of the starting compounds and other reactants which are optionally substituted are commercially available, for example, from Aldrich Chemical Company (Milwaukee, WI) or can be readily prepared by conventional methods of synthesis by those skilled in the art. The chemicals described herein can be synthesized using 20 commercially available starting materials and reagents using techniques well known in the art. For example, the chemicals described herein can be prepared as described below with reference to the examples and reaction schemes. 102 200823202 Reaction pattern

Referring to Reaction Scheme 1 'Step 1, an excess (e.g., about 1. 5 equivalents) of tri-aluminum is added to a solution of a compound of formula 101 in an excess (e.g., about 1.2 equivalents) of a compound of formula 102 in a non-polar solvent (e.g., toluene). (For example, 2M Sankenjiming's hexane solution). The reaction mixture is stirred at about room temperature to 15 ° C for about 1 hour to 24 hours. The product (compound of formula 1〇3) is isolated and purified if necessary. 10 Referring to Reaction Scheme 1, Step 2, in a solution of a compound of formula 103 in a non-polar solvent (eg, dichlorohydrazine), a catalytic amount of 4-dimethylamine pyridine and an excess of (for example, about 1.5 equivalents) are added. 1〇4 compound. The reaction mixture is stirred for about 1 hour to 24 hours. The product (compound of formula 105) is isolated and purified if necessary. 103

200823202 Reaction Pattern II

205 5 10 Refer to Reaction Scheme II, Step 1, approximately _78. ^ /» C to a room temperature, such as the polarity of a diisopropylamine, aprotic dissolved 丨

In a solution of 4 (e.g., tetrahydrofuran), an antimony (e.g., about 1.2 equivalents) of an organometallic reagent such as n-butyllithium (e.g., 2M n-butyl hexane) is added. The reaction mixture is allowed to be mixed for about 5 hours to 24 hours. The polar, aprotic solvent (e.g., tetrahydrocry) solution of the compound of formula 201 is then added dropwise at about _78 ° C to room temperature. The reaction mixture is stirred for about 1 hour to 24 hours, followed by the addition of an excess (e.g., about i eq) of methyl chloroformate. The product (compound of formula 2〇2) is isolated and purified if necessary. Referring to Reaction Scheme II, Step 2, an excess (e.g., about 1.1 equivalents) of a base such as an aqueous lithium hydroxide solution is added to a solution of the compound of Formula 2 2, which is a polar solution of 15 (e.g., a 1:1 mixture of tetrahydrofuran and methanol). For example, 2N lithium hydroxide aqueous solution). The reaction mixture was stirred at about room temperature to 15 ° C for about an hour to 24 hours. The product (compound of formula 2〇3) is isolated and purified as needed 104 200823202. Referring to Reaction Scheme II, Step 3, an excess (eg, about 1.2 equivalents) of a peptide coupling reagent such as hexafluoroacid n is added to a polar, aprotic solvent (eg, dimethylformamide) solution of the compound of Formula 203. N,N',N'·Tetramethyl 5-indole-(7-azabenzotriazol-1-yl)1 urine, excess (for example, about 1.2 equivalents) of the formula 1〇2 compound, and about 〇· Equivalent base (eg diisopropylethylamine). The reaction mixture is stirred for about 1 hour to 24 hours. The product (compound of formula 204) is isolated and purified as needed. Referring to Reaction Scheme II, Step 4, a solution of a polar solvent (e.g., a 1:1 mixture of tetrahydrofuran and methanol) of a compound of formula 204 is added with a reducing agent (e.g., lithium borohydride). The reaction mixture is scrambled for about 1 hour to 24 hours. The product (compound of formula 205) is isolated and purified if necessary.

Reaction pattern III

Referring to Reaction Scheme III, Step 1 'In a solution of the polar, aprotic solvent (eg, tetrahydrofurfuryl) solution of the compound of Formula 3〇1, an excess (eg, about 1.1 equivalents) of a compound of Formula 102 and about 〇·5 equivalents of trioxane are added. Base aluminum (for example, 2m trimethylaluminum benzene solution). The reaction mixture was stirred for about i days to 7 days. The product (compound of formula 205) is isolated and purified as needed. ' 105 200823202 Reaction pattern ιν

Referring to Reaction Scheme iv, Step 1, in a polar, aprotic solvent (e.g., tetrahydrofuran) solution of the compound of Formula 103, an excess (e.g., about 5 i·5 equivalents) of the defeated imine (Formula 401) and excess are added. (e.g., about 1.5 equivalents) of a phosphine (e.g., triphenylphosphine). An excess (e.g., about 1.5 equivalents) of a dialkyl azocarboxylate such as (diisopropyl azodicarboxylate) is then added dropwise to the reaction mixture. The resulting mixture is allowed to be mixed for 1 hour to 48 hours. The product (compound of formula 402) is isolated and purified as needed. &quot; Referring to Reaction Scheme IV 'Step 2, an excess of hydrazine is added to a solution of the polarity of the compound of Formula 402, a solution of a shellfish solvent (e.g., methanol). The reaction mixture is stirred for 1 hour to 48 hours. The product (compound of formula 403) is isolated and purified as needed. Referring to Reaction Scheme IV, Step 3, 'adding excess (eg, about 20 equivalents) 2::iso:ethylamine) to excess (eg, about 1.5 equivalents) in the solution of Formula 4, eg, methylene chloride. The compound of formula 104 is forcibly reacted with the reaction mixture for about (U hours to 24 hours. The product is obtained (Formula 4〇4 106 15 , 200823202)

Compounds are isolated and purified as needed. Reaction pattern V

HVqNH R5 R6 +

R3 R4 502 NCO Step 2 501 +

104

The compound of formula 502 is added to the reaction of the formula V 'step 1 ' in an excess (e.g., about 1.00 equivalent) of a compound of the formula 5, in a solution of an aprotic solvent (e.g., tetrahydroanthracene II). The reaction mixture is stirred for about 1 hour to 24 hours. The product (compound of formula 503) is isolated and purified if necessary. Referring to Reaction Scheme V, Step 2, an excess (e.g., about 10 1.5 equivalents) of a compound of Formula 1〇4 is added to a solution of the compound of Formula 503 in a polar, aprotic solvent (e.g., tetrahydrofuran) solution. The reaction mixture is stirred for about 1 hour to 24 hours. The product (compound of formula 504) is isolated and purified as needed.

Reaction pattern VI

604 &lt;fQ4 605 107 200823202

608 Referring to Reaction Scheme VI'Step i, an excess (eg, about 11 equivalents) of a dialkyl protecting group reagent (eg, a third butyl group) is added to a solution of a compound of formula 6〇1 in a non-polar cold hydrazine (eg, dichloromethane). Dimethyl decyl chloride) is tested in excess (for example, about μ equivalent) (for example, diisopropylethylamine). The reaction was stirred for about 7 hours and simmered for 24 hours. The product (compound of formula 602) is isolated and purified as needed. Referring to Reaction Scheme VI, Step 2, in an excess (e.g., about 12 equivalents), for example, the polarity of the sodium hydride (e.g., 60% sodium chloride in mineral oil), an aprotic solvent (e.g., dimethylformamide) In the solution, a compound of the formula (9) 2 is added. The reaction mixture is scrambled for about 1 hour to 24 hours, followed by addition of (e.g., about 1.2 equivalents) of Ru, _x (wherein &quot;, as desired, the substituted alkane, X is a halo). The reaction mixture is then stirred for about 1 hour to 24 hours. The product (compound of formula 603) is isolated and purified if necessary. 15% with reference to Reaction Scheme VI, Step 3, in a solution of the polarity of the compound of Formula 6〇3, in a protic solvent (eg, tetrahydrofuran), an excess (eg, about 1.5) of a fluoride release reagent such as tetrabutylammonium fluoride (eg, , fluorinated tetra &quot;I ammonium tetrafurfuran solution). The reaction mixture was stirred for about 0.1 hour to 24 &gt; small %. The product (compound of formula 604) is isolated and purified as needed. -, Reaction Scheme VI, Step 4, the polarity of the compound of Formula 604, 108 200823202 Aprotic solvent (eg tetradecylpyridinium and equivalent). Stir the reaction mixture about compound) in a solution such as tetrahydrofuran) A catalytic amount of 4% excess (e.g., about 1.1 equivalents) of the formula 1 〇4 compound is added for about 0.1 hours to 24 hours. The product (formula 6〇5 is purified as needed. Referring to Reaction Scheme VI, Step 5 in a protic solvent (eg, sterol) solution: Step 5, in the polarity of the compound of Formula 605, I, add an excess (eg, about 3) 〇 equivalent)

The acid is, for example, hydrogen chloride (e.g., &lt; 4M argon chloride). The resulting material is reacted for about 1 hour to 24 hours. The product (compound of formula 006) is isolated and purified as needed. 10 Referring to Reaction Scheme VI, Step 5, adding about 1 equivalent of the compound of formula 607 to an excess (eg, about 2.5 equivalent) in a solution of the compound of formula 6〇6 in a polar, aprotic solvent (eg, tetrahydrofuran) (eg, two Isopropylethylamine). The reaction mixture is stirred for about 1 hour to 24 hours. The product (compound of formula 608) is isolated and purified if necessary. 15 Reaction Scheme VII

Referring to Reaction Scheme VII, Step 1, in a solution of the polarity of the compound of Formula 701, 109 200823202 protic solvent (eg, sterol), an excess (eg, about 3.0 equivalents) of an acid such as cesium chloride (eg, 4M hydrogen chloride) is added. Solution). The resulting reaction mixture is stirred for about 1 hour to 48 hours. The product (compound of formula 702) is isolated and purified if necessary. 5 Referring to Reaction Scheme VII, Step 2, in an excess (e.g., about 1.2 equivalents) of a compound of formula 703 (wherein Z is an optionally substituted alkyl group, optionally substituted alkenyl group, optionally substituted alkynyl group, a polar, aprotic solvent (eg, dimercaptomethyl), optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl) In the solution of guanamine), an excess (for example, about 1.2 equivalents) of hexafluoro acid N,N,N',N'-tetramethyl·0_(7-azabenzotriazol-1-yl)indole is added. 702 compound, an excess (e.g., about 2.0 equivalents) of a base such as diisopropylethylamine. The reaction mixture is stirred for about 1 hour to 24 hours. The product (formula 704) is isolated and purified as needed.

15 Reaction Scheme VIII

103

Step 1 (R10) P/C

106 (R1V&lt;= 101 Step 2 Excellent, 104

110 107 200823202 Referring to Reaction Scheme VIII, Step 1, an excess (e.g., about 1.4 equivalents) of NaCN and an excess (e.g., about 1.4 equivalents) of ΝΗβΙ are added to a solution of the hydrazine compound of formula 1 in an inert solvent (e.g., DMF). The reaction mixture was heated. The product (compound of formula 103) is isolated and purified as needed. 5 reference to the reaction scheme νπι, step 2, a compound of formula 〇3, an excess (eg, about 1.5 equivalents) of a compound of formula 104 with an excess (eg, about 15 equivalents) of a phosphine reagent such as triphenylphosphine (PPhO) (eg, In the THF) solution, a gas (for example, about 1.25 liters) of a gas carboxylic acid vinegar reagent such as monoazadicarboxylate (DEAD) is added, and the reaction mixture is stirred for about 1 hour to 24 hours. The compound of formula 105) is isolated and purified as needed. Referring to Reaction Scheme VIII, Step 2, an excess is added to the mixture of the compound of Formula 105 with an excess (e.g., about 1.4 equivalents) of an inert solvent (e.g., toluene) of the compound of Formula 106 ( For example, about 1.4 equivalents of A1Mes. Stirring reaction mixing: about 30 minutes, followed by about room temperature 150. (: stirring for about i hours to 24 hours'. 15 The product (compound of formula 107) is isolated and purified as needed.

Reaction pattern IX

Step 1

111 205 200823202

Step 3 (R10) p〇-€r 208 Referring to Reaction Scheme IX'Step 2, in the solution of Formula 2〇ι, such as Xiao), 'add excess (eg, about Μ equivalent) of the coupled phase such as hexafluoroantimonate- (7-azabenzotrisinyl)_n, n, n, n, , · 4: a guanidine (HATU) with an excess (eg, about 15 equivalents) of a compound of formula 2〇3. The reaction mixture is disturbed for about 1 hour to 24 hours. The product (compound of formula 205) is isolated and purified as needed. Referring to Reaction Scheme IX', step 2, an excess (e.g., about 2 equivalents) of a reducing agent such as ruthenium is added to a solution of the compound of formula 2〇5 and a solvent (e.g., methanol). The reaction mixture was spoiled for about 1 hour to 24 hours and the reaction was quenched with a dilute aqueous acid solution. The product (compound of formula 207) is isolated, if necessary, purely ruthenium reaction scheme IX, step 3, in an excess (for example, 2 equivalents) of a solution of the compound of formula 207 in an inert solvent (eg, THF), about equivalent phosphine is added. 15 doses (e.g., diphenylphosphine), about i equivalents of azadicarboxylate reagents such as aza-dimethyl hydrazine-ethylidene (DIAD), and a compound of formula 208. The reaction mixture is stirred for about 1 hour to 24 hours. The product (compound of formula 107) is isolated and purified if necessary. The isolation and purification of the compounds and intermediates described herein, if required, can be performed by any suitable separation or purification procedure, for example, filtration, extraction, crystallization, column chromatography, thin layer chromatography or thick The layer color analysis method, or the combination method of the steps 112 200823202, is achieved. This document provides specific instructions for proper separation and separation procedures; however, of course, other equivalent separation or separation procedures may be used. If desired, the (R) and (S) isomers can be resolved by methods known to those skilled in the art, for example, by the formation of separable non-image-area salts or complexes, for example, by crystallization. By selective formation of a non-mironomer derivative, for example by crystallization, gas-liquid phase or liquid chromatography; selective reaction of a mirror image isomer with a mirror image isomer specific reagent, such as enzymatic oxidation or Reduction, followed by separation of the modified and unmodified mirror image isomers; or in a palmitic environment [eg, on a palm support (eg, a gel with 10 binding to a palmitic ligand), or Gas-liquid phase or liquid phase chromatography is carried out in the presence of a palmitic solvent. It will generally be appreciated that when one of the above separation procedures is used to convert the desired mirror image isomer to another chemical, further steps may be required to liberate the desired mirror image isomer form. Alternatively, the specific mirror image isomer can be converted to another mirror isomer by asymmetric synthesis using an optically active reagent, matrix, catalyst or solvent 15 or by asymmetric transformation. Synthesize. The chemicals described herein are useful in a variety of applications involving smooth muscle cells and/or non-muscle cells. In a particular embodiment, the chemical is for inhibiting smooth muscle myosin; for binding, and/or inhibiting the activity of smooth muscle globules. In a particular embodiment, the smooth muscle myosin is a human, but the chemical can be used to bind or inhibit the activity of smooth muscle myosin from other organisms (e.g., other mammals). In a particular embodiment, the chemical can be used to inhibit non-muscle myosin; it can be used to bind, and/or inhibit the activity of non-muscle myosin 113 200823202. In a particular embodiment, the non-muscle myosin is a human, but the chemical can be used to bind or inhibit the activity of non-muscle myosin obtained from other organisms (e.g., other mammals). The chemicals described herein can be used to treat conditions associated with smooth muscle and/or non-muscle type 5 myosin. The disease conditions that can be treated with the chemicals described herein include, but are not limited to, hypertension, asthma, incontinence, chronic obstructive pulmonary disease, premature labor pain (pre_tem lab〇r), and the like. It will be known that in some cases, the cells may not be in an abnormal state and still require treatment. Thus, in a particular embodiment, the chemicals 10 described herein can be administered to cells or individuals that have suffered or are about to suffer from any of the diseases or conditions. In particular, the chemicals described herein can be used to treat diseases or symptoms associated with abnormally increased or excessive contraction of muscle tone, or blood 15 tube smooth muscle in the systemic, coronary, and pulmonary circulation, and microcirculatory smooth muscle. For example, systemic high blood &gt; 1, malignant hypertension, hypertension crisis, symptomatic hypertension, pulmonary hypertension, pulmonary infarction, angina pectoris, cardiovascular infarction, microcirculatory insufficiency under shock, and in human or animal body Infarction of other parts or organs. Other diseases or conditions that may be treated with the chemicals described herein include: 20 gastrointestinal smooth muscles (including sphincters), such as stomach cramps, pyloric fistula, and bile ducts caused by inflammation, stones or parasites, urethral fistulas; (eg uterus, fallopian tubes, etc.); tracheal-bronchial smooth muscle, diaphragmatic tendons, such as various types of asthma, snorkeling, difficulty breathing, diaphragmatic convulsions, etc.; and "114 200823202 gastrointestinal smooth muscle (including stomach, small intestine and Colon, bile duct and pancreatic duct, etc.; and urethral smooth muscle thinning. In addition, the chemicals described herein can be used to regulate, manage and manipulate the pain during the surviving period. The financial method can be used to suppress premature birth if not treated or Natural premature birth, and inhibition of the pain caused by surgery during fetal surgery in the uterus. This method can also be used to induce the pain of an overdue pregnancy without pain in the full pregnancy, and to induce induced pain to ensure normal production. Pain. 10 Furthermore, the chemicals described in this article can be used to treat "airway wall weight This is a condition associated with a disease or symptom characterized by thickening of the airway wall and obstruction of the air. For example, a small airway that may occur in a patient suffering from a specific respiratory disease condition, for example, chronic obstructive pulmonary disease (C) 〇pD). They may be treated with the chemicals, compositions and methods provided herein. 15 Disease conditions also include, but are not limited to, glaucoma and other signs of the eye. DETAILED DESCRIPTION The chemicals described herein can be used to treat diseases or conditions associated with glaucoma, including increased intraocular pressure, decreased intraocular water flow, and optic nerve damage. Other diseases or conditions which may utilize the chemicals, compositions, and methods described herein include high intraocular pressure. ° Myosin uses helium hydrolysis to generate force; increasing Ατρ hydrolysis is equivalent to increasing muscle contractility or speed. In the presence of actin, the chymase activity of myosin was stimulated more than 1 fold. Therefore, the measurement of Ατρ hydrolysis not only measures the activity of myosin enzyme, but also determines its interaction with actin filament. For the determination of such activity, smooth muscle muscle 115 200823202 globulin derived from human origin can be used, but myosin obtained from other organisms can also be used; it can also be used as a model for the regulation of calcium in myosin binding. . The in-tube rate of ATP hydrolysis is related to smooth muscle myosin enhancing activity, which can be determined by detecting ADP or phosphate production, for example, as described in U.S. Patent No. 6,410,254. ADP production can also be used to couple the ADP production to NADH oxidation (using, for example, enzymes such as pyruvate kinase and lactate dehydrogenase) and to monitor NADH levels, for example by absorbance or fluorescence (Greengard) , P. 178 (Part 4534): 632-634 (1956); Mol Pharmacol 1970 10 Jan; 6(l): 3 1-40). Phosphate production can be coupled to the cleavage of purine analogs using purine nucleoside phosphorylase, thus producing absorbance (Proc Natl Acad Sci USA 1992 Jun l; 89(ll): 4884-7) or fluorescent J 1990 Mar l; 266 (2): 611-4) detected and changed. Although a single assay can be used, it is usually possible to use multiple assays of the same sample at different times to determine the absolute ratio of protein activity; these assays are particularly similar to the absorbance or fluorescence properties of enzyme assays. In the presence of test compounds, it has a high specificity. The test compound can be tested in a highly parallel manner using a multi-tank tray, placing the compounds individually in the tanks or bringing them into a mixture. The components of the test 20 include a target protein complex, a coupled enzyme and a substrate, and then ATP is added to the troughs to measure the absorbance or fluorescence of each trough in the disc by a disk reader. One method uses a 384-well plate format with a 25 microliter reaction volume and is assayed using pyruvate kinase/lactate dehydrogenase couples (Huang TG and Hackney DD. (1994) J Biol Chem 269(23): 16493-16501). ATP hydrolysis rate of 116 200823202 in the tank. As will be appreciated by those skilled in the art, the components used in the assay are buffered and reagent added. Since the method outlined herein allows for kinetic measurements&apos;, the incubation time can therefore be optimized to obtain an appropriate detection signal relative to the background. The assay was performed simultaneously to obtain an ATP hydrolysis kinetics that increased the measured signal to noise ratio of 5. The selectivity to smooth muscle myosin can be replaced by other myosin in one or more of the above assays and the results obtained are compared to results obtained using cardiac equivalents. Identification by the methods described herein as smooth muscle myosin modulators can be further tested in a potency screening assay (e.g., using a screening method derived from osmotic smooth muscle sheets such as chicken gizzards). When preparing calcium-sensitive smooth muscle slices, the chicken gill tissue was first cut and then treated with 1% Triton X-100 to allow the muscle pieces to penetrate the foreign compound (Bars〇tti, RJ, a/., Am J Physiol. 1987 May; 252 (5 Pt l): C543-54). These muscle pieces can be stored in 5% glycerol at -20 ° C for several weeks, and multiple experiments are performed on each batch of muscle tablets. These experiments were performed using a solution of 20 mM imidazole pH 7.0, 5.5 mM ATP, 7 mM MgCl2, 55 mM KC1, 1 μΜ Calmodulin, and 10 mM EGTA. Free calcium is regulated by the addition of various amounts of CaCl2 according to the calculation of MAXChelator (Patton, et al. Cell Calcium 35/5 ρρ 20 427-431, 2004). Isometric tension was measured using an isometric muscle fiber device, such as an Aurora Scientific 400A transducer with a National Instruments PCI-MIO-16E-4, 16 channels, 12-bit A/D data capture plate. The chemically peeled chicken face fibers are slack when immersed in a low calcium (pCa 8) solution, but when the free calcium of the impregnation solution is increased to pCa, the shape 117 200823202 becomes an isometric tension. By converting high-calcium and low-calcium immersion liquids, their fibers can be shrunk and relaxed again and again. ^ The relaxed fiber is first pre-incubated with the compound and subsequently transferred to a South Calcium solution containing the compound to test the ability of the compound to prevent shrinkage of the bract. Then, 5 the ability of the compound to cause relaxation of the contracted fibers was tested by adding the compound to the fibers which had been grown in the high calcium solution. Rinse experiments are performed to ensure that the inhibitory effect is reversible, so that the compound does not cause deterioration of smooth muscle myosin or other irreparable damage. The chemical is administered at a therapeutically effective dose, e.g., a dose sufficient to provide a treatment for the disease states previously described. Generally, the daily dose is from about 〇5 to about 100 mg/kg body weight, for example from about 010 to about 1 mg/kg body weight or from about 0.15 to about 1 mg/kg body weight. Thus, when administered to a person weighing 7 kg, the dosage range is from about 3.5 to about 7000 mg per day, for example from about 7 to about 700 mg per day or from about 1 to about 1 mg per day. The dosage of the administered activity is, of course, dependent on the subject to be treated and the disease state, the severity of the disease, the mode of administration and the course of treatment, and the judgment of the prescribing physician; for example, the dosage range for oral administration is about 7 per day. The dose is about 7 mg, and the dose administered intravenously ranges from about 700 to about 7000 mg per day. The active agent can be selected for a longer or shorter half-life of the slurry, respectively. 2. Any accepted mode of administration of a chemical described herein that can be administered by a similar use includes, but is not limited to, oral, subcutaneous, intravenous, intranasal, topical, transdermal, sublingual, Intramucosal, intraperitoneal, intramuscular, intrapulmonary, intravaginal, rectal, and intraocular (including intraocular injection). Oral, topical, parenteral, and intraocular administration is a treatment for many of the symptoms listed in the present invention 118 200823202. The composition of the medically acceptable article comprises solid, semi-solid, liquid and aerosol dosage forms, for example, tablets, capsules, powders, liquids, suspensions, suppositories, aerosols and the like. Chemicals may also be administered in a sustained or controlled release dosage form, including long-acting injections, osmotic pumps, pills, skin (including electromigration) patches that are administered at a predetermined rate for long-term and/or timed, pulsed delivery. Wait. The composition may be in a unit dosage form suitable for single administration in precise dosages. The chemicals described herein may be administered alone or in combination with conventional pharmaceutical carriers (eg, mannitol, lactose, starch, magnesium stearate, sodium saccharin, talc, 10 cellulose, croscarmellose sodium) , glucose, gelatin, sucrose, magnesium carbonate, etc.) are administered in combination. If desired, the pharmaceutical composition may also contain minor amounts of non-toxic auxiliary substances such as wetting agents, emulsifying agents, solubilizing agents, pH buffering agents, etc. (for example, sodium acetate, sodium citrate, cyclodextrin derivatives, sorbitan) Early laurel s owes δ 曰, diethanolamine acetate vinegar, triethanolamine oleic acid vinegar). Generally, 15 means that the pharmaceutical composition may contain from about 5% by weight to about 95% by weight, for example, from about 5% by weight to about 50% by weight, of at least one of the descriptions herein. Chemicals. The exact methods of preparing such dosage forms are known or are apparent to those skilled in the art; for example, &lt;RTI ID=0.0&gt;&gt;&gt; Pharmaceutical compositions are also known as pharmaceutical formulations. Further, the chemical can be administered together with a pharmaceutical composition containing a pharmaceutical agent, a pharmaceutical agent, an adjuvant, and the like. In a particular embodiment, the composition is in the form of a pill or lozenge 'and thus contains, in addition to the active ingredient, one or more diluents such as 119 200823202 lactose, sucrose, phosphoric acid, etc.; lubricants such as magnesium stearate And; and binders such as starch, gum arabic, polyvinylpyrrolidone, 'gelatin, cellulose, cellulose derivatives and the like. In another solid dose, a powder, marume, solution or suspension is enclosed in Mingsheng Capsule (for example, in 5 propylene carbonate, vegetable oil or triglyceride). The liquid pharmaceutical composition can be, for example, used in a carrier (for example, water, a saline solution, an aqueous glucose solution, glycerin, a glycol-ethanol, etc.) to dissolve and disperse at least: a chemical and/or a plurality of pharmaceuticals as needed. The agent is used to form a solution or suspension. The injection may be in the form of a liquid solution or suspension, in the form of a conventional 10 emulsion, or in a solid form suitable for dissolution or suspension in a liquid prior to injection. The percentage of chemicals contained in such parenteral compositions depends on their specific nature, as well as the activity of the chemical and the needs of the patient. However, the percentage of active ingredient that can be used in the solution is from about 001% to about 10%, and if the composition is solid, it can be higher, and then it is diluted to the above-mentioned specific ratio in the specific example, the composition is in solution. It contains from about 2% to about 2% active ingredient. , a composition containing at least one chemical can be administered intraocularly (including intraocular, periocular, and post-ocular injection and perfusion). For intraocular administration, the sterile composition is usually aqueous, and a suitable buffer system may be added to prevent pH deviation under storage conditions. Administration during intraocular surgery, such as post-ocular or periocular injections and intraocular perfusion or injection, may require the use of a balanced salt rinse; in the case of multiple doses, a preservative may be required to prevent microbial contamination during use. . Compositions containing at least one chemical may also typically be administered as ophthalmic drops 120 200823202 d eye drops, eye creams, eye ointments, gels, and sprays. When administered as an ophthalmic drop or eye drop, the active ingredient is typically dissolved or suspended in a suitable carrier (typically a sterile aqueous solvent); a suitable buffer (4) pH deviation under storage conditions may be added. When used in multiple doses, 5 may require a preservative to prevent microbial contamination during use. The composition containing at least one chemical may also be administered as an aerosol or a solution for a nebulizer, or as a fine powder for blowing, alone or in combination with an inert carrier, such as lactose, to the respiratory tract; The granules have a particle size of less than % micron, for example, less than 10 microns. 10 Typically, when the chemicals described herein are used in a method of screening for binding to smooth muscle myosin, the smooth muscle myosin is bound to a support and then added to &gt; a chemical in the assay. Alternatively, the chemical can be bound to the support and then the smooth muscle myosin can be added. The class of compounds in which the novel lysing agent can be found includes specific antibodies, non-natural binding agents identified in chemical library screening, peptide analogs, and the like. Of particular interest are screening assays for candidates with low toxicity to human cells. A variety of assays that can be used for this purpose include labeled in-vitro protein-protein binding assays, electrophoretic displacement assays, protein binding immunoassays, functional acidification assays, and the like; see, for example, U.S. Patent No. ν, 6,495,337. 2 〇 [Embodiment] EXAMPLE The following examples are used to more fully describe the method of using the present invention. The examples are for illustrative purposes only and are in no way intended to limit the true scope of the invention. 0 121 200823202 Example i 4-(2-Chlorobenzylamino)-2,2-dimethyl Preparation of 3-ylpropyl propyl ester

4-ethylphenylaminecarboxylic acid 3-(2-chlorobenzylamino)-2,2-dimethyl-3-ketopropyl ester

Methyl hydroxy-2,2-dimethylpropanoate (1 g, 7 31 mmol) and 2 chlorobenzylamine (1 ml, 8.75 mmol, 12 equivalents) in toluene, 1) To the hydrazine solution, trimethylaluminum (2 hexane solution, 5.4 ml, 10·8 mmol, 1.5 eq.) was added. The reaction mixture was stirred at 8 ° C for 2 hours. The reaction mixture was quenched with saturated NaHC〇3. The resulting mixture was extracted with Et 〇Ac. The organic layer is dried over NaeO4 and concentrated to give bis(2-dichlorobenzyl)- 3-hydroxy-2,2-dimethylpropanamine (1.5 g, 85 〇/〇). purification. LRMS (M+H+) w/z 242·1. 〇Cl DMAP, CH2CI2 〇〇Cl in ch-C12 solution of #-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (30 mg, 〇·12 mmol) DMAP with 4-ethyl vinegar isocyanate (21 μl, 〇·ΐ 5 mmol, 1.5 equivalents). Stirring the reaction mixture 122 200823202 1 hour, the contraction reaction mixed private I. Yu Chuan α~.,..________

LRMS (M+H+) w/z 389.1 〇

Example II Preparation of 4-ethylphenylamine decanoic acid (1-(2-aminoethenyl)-4(2-chlorobenzylaminomethyl)piperidin-4-yl)methyl ester °τ&quot;νη2

-78 C under THF (20 liters of isopropylamine (3. 5 ml, 24.7 mmol) cold; in the east solution 'add n_BuLi (2) y [hexane solution, 14.8 house liters] 1· 2 equivalents). The reaction mixture was stirred for 1 hour. A solution of piperidine-1,4-dicarboxylic acid 1-t-butyl 4-methyl ester (5 g, 20·ό mmol) (1 eq.) in THF (15 mL) . The reaction mixture was stirred for 1 hour. Methyl formate (17 ml, 22.6 mmol, hi equivalent) was added to the above mixture _. The reaction mixture was allowed to slowly warm to room temperature with stirring. After 3 hours, the reaction mixture was quenched with EtOAc EtOAc (EtOAc)EtOAc. The organic layer was dried over NaJCU and concentrated to give 4, &lt;RTI ID=0.0&gt;&gt;&gt;&gt; LRMS (M+H'Boc) m/z 202.1 〇

5 THF (11 ml) and ci^OH (11 ml) of 4,4-dimethylpiperidine-1,4,4-tricarboxylic acid 1·t-butyl ester (6.2 g, 20.5 mmol) In solution, an aqueous solution of LiOH (2 N, 11 mL, 22 mmol, 1.1 eq.) was added. At 80. (The reaction mixture was stirred for 1 hour. The reaction mixture was concentrated to dryness with EtOAc (1 N). The residue was taken from ethyl acetate. )-4-(methoxy group) uchen bite _4· citric acid (4·7 g, 80%), used without further purification. lrMS (M+H+-Boc) w/z 188.0 〇

Add HATU (6 gram, in a solution of 1-(2,2-butoxy)-(-methoxy-yl)-branched formic acid (3.715 g, 13.2 mmol) in DMF (30 mL) 15.8 house moles, 1.2 equivalents), 2-chlorobenzylamine (1·9 ml, 15·8 mmol, 1.2 equivalents) and DIEA (228 μL, 1.31 mmol, 〇1 equivalent). The reaction mixture was stirred for 3 hours and purified on RP_HPLC using EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc , 52%). [RMS (M+H.-Boc;) 124 200823202 w/z 311.0.

Boc

UBH4

THF, CH3OH HO in 4-(2-chlorobenzylaminecarboxylidene) ruthenium _i,4_dicarboxylic acid 1_second butyrate 4-methyl ester (2.8 g, 6.8 mmol) of THF ( Add 20 ml) to the solution of 5 ml), add lithium borohydride (1.4 g, 68 mmol, 1 )). The reaction mixture was stirred for 3 hours and neutralized with HCl (1N). The residue was partitioned between EtOAc and He. The organic layer was dried over NaeO4, concentrated, and purified on RP-HPLC using acetonitrile and H.sub.2 mixture to give 4-(2-benzylbenzylcarbazinyl)-4-(methyl) n-n-bit-l-carboxylic acid Third vinegar (2 2 10 grams, 84%). LRMS (Μ_'Βιι+Η+) 327.0 〇

DMAP was added to a solution of 4-(2-chlorobenzylaminoindenyl) 4-(methyl)pyrene]-tert-butyl formate (1.8 g, 4.8 mmol) in THF at room temperature. (118 mg, 0·9 mmol, 0·ι equivalent) with isocyanatoethyl 15 benzene vinegar (1.1 ml, 7.3 mmol, 1.5 equivalent). The reaction mixture was stirred for 1 hour. The reaction mixture was concentrated to dryness. To the CH3OH solution of the above product was added '4M HCl, </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; The white solid was filtered and dried to give 4-ethylphenylaminecarboxylic acid (4-(2-dichlorobenzylamine fluorenyl)pyr-4-yl) hydrazine hydrochloride (1·7 g, 20 81%) ). LRMS (M_Boc+H+) w/z 430.1 〇 125 200823202

Ο Η〇Α^ΝΗΒ〇〇 ---- Η hatu, diea, dmf jj^&quot;Nvf0 〇丫, HBoc

Add HATU (120 mg, 0.31 mmol, 1.2 eq.) to a solution of Boc-Gly-OH (54 mg, EtOAc, EtOAc, EtOAc) Subsequently, 4_ethylphenylaminecarboxylic acid (4-(2- benzylbenzyl 5-aminoindolyl)piperidin-4-yl) decyl ester hydrochloride (120 mg, 〇·26 mmol, 1 equivalent) was added. With DIEA (89 μl, 〇·5ΐ millimoles, 2 equivalents). The reaction mixture was scrambled for 3 hours, and purified by RP-HPLC using a mixture of acetonitrile and η20 to give 4-ethylphenylamine decanoic acid (丨-(2-(t-butoxycarbonyl)aminoethyl)- 4 -(2_Chlorobenzylamine methyl thio) ruthenium-4-yl) methyl vinegar (127 10 mg, 84%). LRMS (M_Boc+H+) m/z 487.1.

4-ethylphenylamine decanoic acid (1_(2-(t-butoxycarbonyl)aminoethenyl)-4-(2-chlorobenzylaminecarbazyl)piperidinyl)methyl ester (87) Add HCl (4 Μ 崎 烷 15 15 solution, 100 μl, 〇·4 mmol, 2.6 eq.) in milligrams, 〇15 mM) in CHsOH (1 mL), stir for 2 hours. . The reaction mixture was concentrated to dryness by co-evaporation with toluene to give 4-ethylphenylaminecarboxylic acid (1-(2-aminoethyl)- 4-(2-chlorobenzylamine-carbazyl)piperidine. - base) vinegar (81 mg, quantitative). LRMS (M+H+) m/z 487.1. 126 200823202

Example III 4-(Difluoromethyl)phenylamine decanoic acid (s)_(1_(2_Amino-3_ mercaptopropyl)-4-(2-chlorobenzylamine) Preparation

°Y^nh2

Early OC

O CI 1) F3C-^^NCO 2) HCI, lite〇H~~

Add 4-(2-chlorophenyl) guanidino M (methylene) to hexane + formic acid (referred to as mg, i · 3 mmol) in THF, add Αρ (32 P耄Gram, 0.26 mmol, 〇 2 equivalents) with isocyanic acid 'trifluoromethyl benzene vinegar (〇 28 耄, 1.97 house Moule, ι·5 equivalent). Spoil the reaction mixture for hours. The reaction mixture was dried to dryness. To a solution of the crude mixture of CH3 〇h (3 ml), HCl(4)V [di-alpha-al-al-altane solution, j ml, 4 mM, 3 篁) was added. Over night, filter it to a white solid and dry to give 15 to 4-(difluoromethyl)phenylamine decanoic acid (4-(2-chlorobenzylamine fluorenyl)piperidine-4-yl) vinegar (615 mg) , 93%). LRMS (M_Boe+H, w/z 47〇). 127 200823202

^OH

Add HATU (300 mg, 0·79 mmol, 2 eq.) to a solution of Boc-Ser-OH (162 mg, 0·79 mmol, 2 eq.) in DMF (2 mL). (Trifluoromethyl)phenylaminecarboxylic acid (4-(2-chlorobenzylamine 5 -methylindolyl)piperidin-4-yl)methyl ester (200 mg, 0.39 mmol, 1 eq.) with DIEA (140 Microliter, 0. 79 millimoles, 2 equivalents). The reaction mixture was stirred overnight and purified on RP-HPLC using acetonitrile and hydrazine 20 to give bis((trifluoromethyl) phenylamine phthalic acid bismuth S)-(l-(2-(t-butoxycarbonyl)amine) Methyl-3-hydroxypropionyl)-4-(2-chlorobenzylaminecarbamimidino)piperidin-4-yl)methyl ester 10 (145 mg, 56%). LRMS (M+H+_Boc) w/z 557·1.

4-((Trifluoromethyl)phenylamine decanoic acid (5&gt;(1_(2-(t-butoxycarbonyl)amino-3-hydroxypropyl)-4-(2-chlorobenzylamine) Add a solution of 15 4M HCl in dioxane (200 μl, 0·8 mmol) in a solution of hydrazino)piperidin-4-yl)methyl ester (145 mg, 0.22 mmol) in CH3OH (1 mL) , 3·6 eq.), which was stirred for 2 hours. The reaction mixture was concentrated to dryness by co-evaporation with toluene to give 4-(trifluoromethyl)phenylamine decanoic acid (phantom-(1-(2-amino) -3-hydroxypropionyl)-4-(2-chlorobenzylaminoindolyl)piperidin-4-yl) decyl ester (130 mg, fixed at 128 200823202). LRMS (M+H+) m/z 557·1 〇

Example IV Preparation of 4-ethylphenylamine decanoic acid 4·(2-tribenzylamino)-3,3-diindol-4- butylbutyl ester

4-(2-chlorobenzylamino)-3,3-dimethyl-4-ketobutyl butyl 4-ethylphenylamine

Add 2-Chlorobenzylamine to a solution of 3,3-indolyl-dihydrocarbamate-2(3Η)-_(2.04 g, 17·9 mmol) in THF (15 mL) • 4 ml, 19.9 Γυ millimolar, 1.1 eq) with AlMe3 (2 Torr in toluene, 4.5 mL, 9 mM, 〇·5 eq). The reaction mixture was stirred for 3 days. The reaction mixture was quenched with EtOAc (EtOAc)EtOAc. The organic layer was washed with saturated NaHCO.sub.3, H.sub.sub.sub.sub.sub.sub.sub.ssssssssssssssssssssssssssssssssssssssssss 15 g, 83%), no further purification required. Lrms (M+H+) zw/z 256.0 ° 129 200823202

Add 4-C isocyanate to a solution of #-(2-chlorobenzyl) 4-hydroxy-2,2-dimercaptoamine (400 mg, 1.6 mmol) in THF (25 mL) Phenyl phenyl ester (276 μl, ι·92 mmol, 1.2 eq.) and DMAP (293 mg, 5 2·4 mmol, 1.5 eq.). The reaction mixture was stirred overnight and the reaction mixture was concentrated. The residue obtained was purified by RP-HPLC using acetonitrile and hydrazine 20 mixture and further purified by flash column chromatography using hexanes and EtOAc to afford 4-ethylphenylamine Benzylamino)-3,3-dimercapto-4-ketobutyl butylate (160 mg, 25%). LRMS 10 (M+H+) m/z 403.1 〇

Example V Preparation of ΛΚ2-chlorobenzyl)·3-(3·(4-ethylphenyl)ureido)·2,2·dimercaptopropionamide

ΛΓ-(2-chlorobenzyl)-3-(3-(4-ethylphenyl)glycosyl)-2,2-dimethylpropionamide

130 200823202 Oxyl 3-hydroxy-2,2-dimethylpropanoate (1·〇克, 7.57 mmol) and 2-chlorobenzylamine (1·09 ml, 9.08 mmol, 1.2 equivalents) ) Benzene (1 liter) solution ten, adding trimethylaluminum (2 Μ hexane solution, 5.6 ml, η·4 house Moer '1.5 equivalent). At 80. (The reaction mixture was stirred for 2 hr. The reaction mixture was evaporated, evaporated, mjjjjjjjjjjjjjjjjjjjjjj Purification was carried out using a mixture of ethyl acetate and hexane to give W(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamine (1.55 g, 84%). LRMS (M+H+ ) w/z 242.1. 〇

Add in a solution of #-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (〇·5〇g, 2·〇7耄莫) in THF (5 ml) Indoleamine (〇·457 g, 3.10 mmol, 1.5 eq) and pph3 (0.813 g, 3·10 mmol, 1.5 eq.). DIAD (600 μl, 3·10 mmol, ι·5 Ij equivalent) was added dropwise to the reaction mixture. The resulting mixture was stirred overnight. LC/MS showed no starting material was consumed. The reaction mixture was concentrated, and the obtained residue was purified eluting with EtOAc EtOAc EtOAc EtOAc 2,2-Dimercaptopropanamide (0.50 g, 65%). LRMS (M+H+) w/ζ 371·1 〇 20

Ηη2νη2 MeOH ο ο Cl

131 200823202

One step purification. LRMS (M+H+) m/z 241 · 1 〇

Add a diea (157 μl, in a solution of 3-amino-#-(2-chlorobenzyl)-2,2-dimethylpropanamide (〇·45 mmol) in DCM (5 mL) 〇·90 1〇耄mol, 2 equivalents) with 'ethylphenyl isocyanate (97.0 μl, 0.675 mmol, 1.5 equivalents). The reaction mixture was stirred for 3 minutes. The mixture was concentrated and purified by RP-HPLC using acetonitrile and η 2 hydrazine mixture to give #-(2-chlorobenzyl)-3-(3-(4-ethylphenyl)ureido)_2,2_2 Mercaptopropionamide (29.6 mg, 17% in two steps). LRMS (M+H+) w/z 388.1.

Example VI Preparation of 4-ethylphenylaminecarboxylic acid chlorobenzylaminecarboxamido)pyridinyl-2(yl)methyl ester

4-ethylphenylamine-formic acid benzylamine-methyl indenyl)pyrrolidine-2-yl)methyl ester 132 200823202

Add 2-chlorobenzyl isocyanate (167 mg, millimolar) to a solution of s-p-pyrrolidin-2-ylmethanol (no mg, millimolar) in thF (2.0 mL) . The reaction mixture was stirred for 1 hour, and concentrated under reduced pressure to give (yield (2-dichlorobenzyl)-2 (hydroxymethyl)-pyrrolidine _m-carbamide (277 mg) as an oil. No further purification is required. LRMS (Μ+Η+) m/z 269.0.

Addition of isocyanine to a solution of 〇S&gt;A^(2-chlorobenzyl)_2•(hydroxymethyl)pyrrolidinecarbamamine (268 10 mg, L〇 mmol) in THF (2.0 mL) 4-ethyl-phenyl ester (220 mg, 15 mmol). The reaction mixture was stirred for 1 hour. LC/MS showed the reaction was complete. The reaction was concentrated and the residue was purified using EtOAc EtOAc EtOAc (EtOAc) Base) A 15 ester (42 house grams, 10% in two steps). LRMS (M+H+) /w/z416.0 〇

Example VII Preparation of 4-ethylphenylaminecarboxylic acid (s&gt;2-(3 gas 2-chlorobenzyl)-1-methylureido)propyl ester 133 200823202

(S)-2-(3-(2-chlorobenzyl)-1-methylureido)propyl 4-ethylphenylamine decanoate

TBDMSCI HO^ShBoc

DIEA, DCM

V sr〇v^ NHBoc was added to a solution of 〇S)-tert-butyl 1-hydroxypropan-2-ylcarbamate (3.06 g, 17.46 mmol) in DCM (30 mL). 19.2 mmol, 1.1 eq.) and DIEA (4.3 mL, 26.2 mmol, 1.5 eq.), the reaction was stirred for 1 hour. LC/MS showed the reaction was complete. The reaction mixture was poured into hydrazine 20 and diluted with EtOAc. The organic layer was separated, washed with saturated NaH.sub.3 and brine, dried over Na? The filtrate was concentrated under reduced pressure to give 1-(t-butyl dimethyl </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; LRMS (M-Boc+H+) m/z 190·1. NHBoc 1)NaH, DMF 2) Mel J^sr〇x^NBoc in a solution of NaH (60% dispersion in mineral oil, 60 mg, 1.49 mmol, 15 1·15 equivalent) in DMF (2.0 mL) Add 1-(t-butyldidecyldecyloxy)propan-2-ylamine ruthenate 〇S)-t-butyl ester (360 mg, 1.3 mmol). The reaction mixture was stirred for 30 minutes, then decyl iodide (93 μL, 1.49 mmol, 1.15 eq.) was added and stirred for 1 hour. LC/MS showed the reaction was complete. The reaction mixture was quenched with EtOAc EtOAc EtOAc. The organic layer was separated, washed with brine, dried over Na 2 s 4 and filtered. The filtrate was concentrated under reduced pressure to give a crude oil (yield: &lt;RTI ID=0.0&gt;&gt;&gt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; Further purification was used directly in the next step. LRMS (M-Boc+HT) m/z 204.1 〇

THF solution of V in 1-(2,2-butyldidecyloxy)propan-2-yl(methyl)amine decanoic acid (S)·Third vinegar (301 mg, ι·mole) TBAF (1M in THF, 1 .5 mL, EtOAc (5 mL), EtOAc, EtOAc). The organic layer was separated, washed with brine, dried over Na 2 EtOAc and filtered. Reduce the filtrate by decompression, and add the crude oil to THJ? (2 毫升 ml). To this THF solution was added DMAP and 4-ethyl phenyl isocyanate to disturb the reaction mixture for 30 minutes. LC/MS showed the reaction was complete, the mixture was filtered, and the filtrate was purified on RP-HPLC using acetonitrile and H.sub.2 mixture 15 to give 4-ethylphenylamine decanoic acid (5)-2-(methyl (third Butoxycarbonyl)amino)propyl ester (118 mg, 30%). LRMS (M_Boc+H+) w/z 237.1.

Η ^ ? 1) HCI, MeOH 0^nb〇c _,

O 丨 2) DIEA or Nco in 4-ethylphenylamine carboxylic acid oxime S)-2-(methyl(t-butoxycarbonyl)amino) 135 200823202 propyl ester (105 mg, 0.27 mmol) in MeOH HCl (4 Μ dioxane solution, 0.2 ml, 0.81 mmol, 3 eq.) was added and the mixture was stirred for 2 hr. LC/MS showed the reaction was completed and the mixture was concentrated under reduced pressure to afford crude oil. To this THF solution was added 5 ethyl 4-ethylphenyl isocyanate (30 μL, 0.26 mmol) followed by DIEA (0.11 mL, 0·66 mmol, 2.5 eq.). The reaction mixture was stirred for 2 hours. LC/MS showed the reaction was complete. The mixture was filtered, and the filtrate was purified on RP-HPLC using acetonitrile and hydrazine 20 to give 4-ethylphenylamine carboxylic acid (S)-2 (3 - (2-chlorohexyl)-1-methyl) Propylene vinegar (88.6 house grams, 81% in two steps 10). LRMS (M+H+) w/z 404.1.

EXAMPLE VIII 4-Ethylphenylamine decanoic acid (1-(2-aminoethenyl)-4-(3-fluoro-2-indolylbenzylaminemethanyl)piperidin-4-yl)indole Preparation of ester °Y^nh2

4-ethylphenylaminecarboxylic acid (1-(2-aminoethenyl)-4-(3-fluoro-2-methylbenzylamine hydrazino)piperidin-4-yl) decyl ester

1-(T-butoxycarbonyl)-4-(methoxycarbonyl)piperidine-4-carboxylic acid (6 g, 21 mmol) with DIEA (7.3 mL, 42 mmol, 2.0) Methyl chloroformate (1·94 ml, 25 mmol, 1.2 eq.) was added to a solution of 136 (200823202) in THF (60 mL). The mixture was stirred at 0 ° C until the reaction was complete. NaBH4 (3.16 g, 84 mmol, 4.0 eq) was added at 0 ° C, followed by MeOH (10 mL). This mixture was stirred at 0QC for 90 minutes. 5 The reaction mixture was then quenched with saturated NaHC03 and concentrated to dry. The residue was dissolved in ethyl acetate, washed with saturated NaH.sub.3, water and brine, dried and evaporated. The residue obtained was purified by column chromatography to give 4-(hydroxymethyl)piperidine-1,4-dicarboxylic acid 1-t-butyl 4-methyl ester (2.6 g, 46%). LRMS (M_Boc+H+) m/z 174.1.

To a solution of 4-(hydroxymethyl)piperidine-1,4-didecanoate 1-t-butyl 4-decyl ester (470 mg, 1.72 mmol, 1.0 eq.) in MeOH (1 mL) HC1 (4 Μ dioxane solution, 1 ml). The mixture was stirred at room temperature for about 1 hour and concentrated to dryness to give &lt;RTI ID=0.0&gt;&gt; LRMS (Μ+Η+) m/z 174.0.

Add HBTU (718 mg, 137 200823202 1.89 mmol, 1.1 equivalents) to a solution of Boc-Gly-OH (331 mg, 1.89 mmol, 1.1 eq.) in DMF (1 mL). Methyl 4-(hydroxymethyl)piperidine-4- decanoate (1.72 mmol, 1 eq.) was then added with DIEA (749 μL, 4.30 mmol, 2.5 eq.). The reaction mixture was stirred for 1 hour. The mixture was partitioned between EtOAc and H20. The organic layer was washed with saturated NaHCO.sub.3, water and brine, and dried over Na? The residue obtained is purified by column chromatography to give methyl 1-(2-(t-butoxycarbonylamino)ethyl)-4-(hydroxymethyl)piperidine-4-carboxylate (560 mg) , 98%, two steps). LRMS (M-Boc+H+) w/z 231.1.

10 THF of 1-(2-(t-butoxycarbonylamino)ethenyl)-4-(hydroxyindenyl)piperidine-4-carboxylic acid methyl ester (2.5 g, 7.56 mmol, 1.0 eq.) A solution of LiOH (2N, 7.56 mL, 15.13 mmol, 2.0 eq.) was added to aq. The reaction mixture was stirred at 60 ° C for 1 hour. The reaction mixture was neutralized with HCl (1 N), and concentrated to dryness to give 15 1-(2-(t-butoxycarbonylamino)ethyl s-yl)-4-(hydroxymethyl)piperidine-4-furic acid (3.0 g), used without further purification. LRMS (M-Boc+H+) w/z 261.0.

Crude 1-(2-(t-butoxycarbonylamino)ethyl)-4-(hydroxymethyl)piperidine 138 200823202 -4·carboxylic acid (120 mg, ~0.379 mmol, 1.00 equivalents In a solution of DMF (30 ml), add HBTU (144 mg, 0.379 mmol, 1.0 eq.), 2-methyl-3-fluorobenzylamine (53 mg, 0.379 mmol, 1.0 eq.) with DIEA ( 132 microliters, 0.758 millimolar, 2.0 equivalents). The reaction mixture was stirred at room temperature overnight. The mixture was partitioned between EtOAc and H20. The organic layer was washed with 1 N HCl, sat. NaHC.sub.3, water and brine, dried over Na.sub.2SO.sub. (Methyl) Bent-1-yl)-2-indoleethylamine formic acid 2 butyl vinegar (185 mg) was used without further purification. 10 LRMS (M+H+) w/z 439.1.

Crude 2-(4-(3-carbo-2-indenyl) -4-yl-4-yl)-2-ketoethylaminecarboxylic acid tert-butyl ester (185 mg, ~0.422 mmol, 1.0 eq.) in THF (2 mL), DMAP (10 mg, 15 0.085 mmol, 0.2 eq.) and 4-ethylphenyl isocyanate (61 micron) l, 0.422 millimolar, 1. 0 equivalents). The reaction mixture was stirred overnight and then concentrated. The residue obtained was purified by RP-HPLC using a mixture of acetonitrile and hydrazine 20 to give 4-ethylphenylamine carboxylic acid (1-(2-(t-butoxycarbonylamino) ethinyl)-4-(3- Fluoro-2-indenyl amide-based ketone) BTS 4-yl) methyl ester (12 mil 20 g, 5% in three steps). LRMS (M-Boc+H+) w/z 485.2. 139 200823202

4-ethylphenylaminecarboxylic acid (1-(2-(t-butoxycarbonylamino)ethyl)-4-(3-fluoro-2-indylbenzylamine sulfhydryl) brigade bite_ To a solution of 4% decyl ester (12 g, 0.021 mmol, 1 〇 eq) in CH^Cl2 (1 mL), 5 4N HCl (1 mL). This mixture was stirred at room temperature for about 1 hour and concentrated to dryness. The residue obtained was purified by RP-HPLC using acetonitrile and HsO mixture to give 4-ethylphenylamine carboxylic acid (1-(2-aminoethyl fluorenyl) _ 4 _ ) Tourism _4_ base) methyl vinegar (8 mg, 79%). LRMS (M+H+) zw/z 485.1 〇

Example IX Preparation of naphthalene-2-ylamine phthalic acid 2-(3-(2-chlorobenzyl guanylureido)ethyl ester

2-(3-(2-chlorobenzyl)-1_methylureido)ethyl naphthalen-2-ylcarbamate

Add 2-chlorobenzyl isocyanate (〇·75 ml, 6.66 mmol) to a solution of 2_(methylamino)ethanol (600 mg, 7.99 mmol) in THF (5.0 L) ) The temperature is given to the reaction for 3 minutes. The mixture was concentrated, redissolved in MeOH, filtered and purified on EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc 1-decylurea (950 mg, 49%). LRMS (M+H+) w/z 243·0 〇

Add DMAP (3.0 mg) to a solution of 3_(2·chlorobenzyl)-1_(2-ethyl)-1-indolyl (120 mg '0.50 5 mmol) in THF (1.0 mL) , 0.02) with 2-isocyanatophthalene (100 mg, 0.60 mmol). The reaction mixture was stirred for 30 minutes. LC/MS showed the reaction was complete. The mixture was filtered, and the filtrate was purified on RP-HPLC using a mixture of acetonitrile and hydrazine 20 to give 2-(3-(2-chlorohexyl)-1-indolyl) ethyl acetate (165). House 10 grams, 80%). LRMS (M_Boc+H+) w/z 412·1.

Example X Preparation of 2-(3-(2,3-dichlorobenzyl)-1-indolyl)ethyl 4-ethylphenylamine phthalate

2-(3-(2,3-dichlorobenzyl)-1-methylureido)ethyl 4-ethylphenylaminecarboxylate

2,3-dichlorobenzylamine (100 mg, 0.59 mmol) in THF solution was added dropwise to a solution of triphosgene (89 mg, 0. 3 mmol) in THF, 141, 200823202. DIEA (209 μl, 1.2 μm). The reaction mixture was stirred at room temperature for 10 minutes and 2-(f-amino)ethanol (90 mg, 1.2 mmol) was added. The reaction mixture was stirred at room temperature for 15 minutes and purified on RP-HPLC using EtOAc EtOAc (EtOAc) (70 mg, 44%) 〇LRMS (M+H+) m/z 277.1〇HO, V 丫

Add DMAP and isocyanic acid to a solution of 3-(2,3-dichlorobenzyl)-1-(2-hydroxyethyl)-1-indenyl urea (7 mg, 0.27 mmol) in DMF 'Ethyl knows (80 house grams '0.54 house Moer). The reaction mixture was disturbed overnight. The 10 reaction mixture was concentrated, and the obtained residue was purified on RP-HPLC using acetonitrile and h20 mixture to give 4-ethylphenylamine phthalic acid 2-(3·(2,3-dichlorobenzyl)-1-methylurea Ethyl ester (7 mg, 6.5 %). LRMS (Μ+Η+) w/z 424·1 〇

Example XI 15 Preparation of 2-(3-(2-acetobenzyl)-1(2-hydroxyethyl)ureido)ethyl 4-ethylphenylaminecarboxylate

142 200823202

OH ho^nh

To a solution of 2,2'-iminodiethanol (1.58 g, 15 mmol) in DMF (5 mL) was added 2-chlorobenzyl isocyanate (1.26 g, 7.5 mmol). The reaction mixture was stirred at room temperature for 30 minutes. This mixture was purified on RP-HPLC using EtOAc EtOAc (EtOAc:EtOAc) LRMS (M+H+) w/z 272.1 〇

OH 0 ΗΟ—νΛν

DMAP, THF

OH O people h

Add DMAP and 4-ethyl isocyanate to a solution of 3-(2-chlorobenzyl)-l,l-bis(2-hydroxyethyl)urea (2.3 g, 8.46 mmol) in THF Phenyl ester (1.24 10 g, 8.46 mmol). The reaction mixture was stirred for 1 hour and concentrated. The residue obtained was purified by RP-HPLC using a mixture of acetonitrile and H20 to afford 4-(2-(2-chlorobenzyl)-1-(2-hydroxyethyl)ureido Ethyl ester (1.7 g, 48%). LRMS (M+H+) m/z 420.1.

EXAMPLE XII 15 4-Ethylphenylaminecarboxylic acid ((2&amp;4Λ)-4-(2-aminoethylguanidinyl)-1-(2-chlorobenzylaminecarboxamido)pyrrolidin-2-yl Preparation of oxime ester

4-ethylphenylamine decanoic acid ((2S,4i?)-4-(2·aminoethylguanidinyl)-1-(2-chlorobenzylaminemethanyl)pyrrolidin-2-yl) Methyl ester 143 200823202

4-(((9H_^_9-yl))oxy)carbonylamino)-2-(hydroxyindenyl)pyrrolidine-1-carboxylic acid (2&amp;4 and)-t-butyl ester (403 mg, To a solution of DMAP (134 mg, 1.1 mmol) in THF (10 mL), EtOAc (EtOAc) The reaction mixture was stirred at room temperature overnight and concentrated to give 4-((((9-9-)-9-yl) methoxy)carbonylamino)-2-((4-ethylphenylamine decyloxy) Indoleyl pyridinium-1-decanoic acid (2&amp;4 and)-t-butyl ester was used without further purification. LRMS (M+H+) w/z 585.1. 10

1) HCI, MeOH 2 &gt; OCM

Cl DIEA, THF 3) Pyridine, DCM

4-(((9H- -9-yl) methoxy)carbonylamino)-2-((4-ethylphenylaminodecyloxy)indolyl)pyrrolidine-1-pyrene To the MeOH solution of acid (2 &amp; 4i?)-t-butyl ester, HCl (4 N dioxane solution) was added. The reaction was stirred at room temperature for 1 hour and concentrated. The residue was dissolved in THF (10 mL). 15 DIEA (469 μl, 2.7 mmol) and 2-chlorobenzyl isocyanate were added to this solution. This mixture was stirred at room temperature for 1 hour and concentrated. The residue was dissolved in 10 mL of 20% piperidine in DCM. The reaction mixture was stirred at room temperature for 15 min, concentrated and purified with EtOAc EtOAc EtOAc EtOAc EtOAc (2-Chlorobenzylaminomethane)pyrrolidin-2-yl)methyl ester (210 mg, 53% in 4 steps). LRMS (M+H+) tw/z 431·1.

4-ethylphenylamine decanoic acid ((2&amp;4 and)-4-amino-1-(2-chlorobenzylamine 5-methylindenyl)pyrrolidin-2-yl)methyl ester (60 mg, Boc-Gly_OH (37 mg, 0.21 mmol) and HBTU (80 mg, 0.21 mmol) were added to a 0.14 mmol of DMF solution. The reaction mixture was stirred at room temperature overnight and purified EtOAc EtOAc EtOAc. The product-containing fractions were combined and concentrated. The residue was dissolved in MeOH and 4N EtOAc (EtOAc). The reaction mixture was stirred at room temperature for 1 hour and concentrated to give 4-ethylphenylamine carboxylic acid ((2S,4R)-4-(2-aminoethylamino)-1-(2-chlorobenzylamine) Mercapto) pyrrolidin-2-yl) decyl ester (37 mg, 51%). LRMS (M+H+) w/z 488.1.

EXAMPLE VIII 15 Additional Synthetic Compounds The compounds in the table below were synthesized and tested using procedures similar to those described herein. IC50 arithmetic mean ion m/z MW chemical name N-[(2-chlorophenyl)indenyl]-3-{[(4-ethylphenyl)amino] 8·821 M+H+ 388. 1 387·9 Carbamoyl}-2,2-dimethylpropanamide (4-{[N-(4-ethylmercaptophenyl)amine-mercaptooxy)] 273 M+H+ 445. 1 444·91 base} (2H-3,4,5,6-tetrahydropyran-4-yl))-Ν·[(2-chlorobenzene 145 200823202 IC50 arithmetic mean ion m/z MW chemical name 17 . 331 M+H+ 437. 0 437. 32-methyl) decylamine (4-{[N-(2-chlorophenyl)amine-methyl hydrazino)] ==3 A = four gas (four) 19. 039 M+H+ 433. 1 432. 9 Benzene, its t](4-{[N-(3-methoxyphenyl)amine decyloxy]methyl}(2H-3,4,5,6-tetrahydropyran-4- Base)) guanamine 13. 723 M+H+ 418. 1 417. 89 2-(Ethylamino) Ν-[(2-phenylphenyl)methyl]-3-[indole-(4-ethylphenyl)amine decyloxy]propanamide 6. 388 M+H+ 475. 1 474. 93 4-{[(4-{Ν-[(2-Phenylphenyl)indolyl]amine-carbamoyl}-211-3,4,5,6-tetrahydrofuran-4-yl)methoxy Amino} benzoic acid ethyl ester 0. 697 M+H+ 417. 0 416. 9 Ν-[(2-carbyl) fluorenyl](4-{[Ν-(4-mercaptophenyl)amine fluorenyloxy]fluorenyl}(2Η-3,4,5,6 - Tetrahydropyrene is more than 〇南-4_ base)). 135 M+H+ 471. 1 470. 87 Ν-[(2-;^phenyl)indolyl][4-({Ν-[4-(:蠹甲美,笑基]amine-methylmethyloxy}methyl)) (2Ηΐ·3,υ Methyl tetrahydrogen): -4--4-yl)] decylamine 17. 023 M+H+ 428. 1 427. 88 Ν·[(2-chlorophenyl)methyl](4-{[Ν-(2-cyanophenyl)amine 曱 基 氧基 oxy]methyl}(2Η·3,4,5,6-four Hydrogen. Ratio of α South _4_ base)) Formamide 7. 628 M+H+ 445. 2 444. 95 Ν-[(2_Chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)decylaminodecyloxy]fluorenyl}(2Η-3,4,5, 6-tetrahydropyran-4-yl)) decylamine 3. 555 M+H+ 461. 1 460. 91 4-{[(4-{Ν-[(2-chlorophenyl)indenyl]amine fluorenyl}-211-3,4,5,6-tetrahydron-pyran-4-yl) oxime Carboxylidene} benzoic acid oxime ester 3. 915 M+H+ 500. 0 500. 01 Ν-[(2-Chlorophenyl)indolyl][4-({Ν-[4-(2-methyl(1,3-thiazol-4-yl))phenyl])indolyloxy }methyl)(2Η-3,4,5,6-tetrahydropyran-4-yl)]decylamine 2. 215 M+H+ 435. 1 434. 89 Ν-[(2-chlorophenyl)methyl](4-{[Ν-(3-fluoro-4-indolylphenyl)amine decyloxy]fluorenyl}(2Η-3,4, 5,6-tetrahydro.pyran-4-yl))decylamine 0. 361 M+H+ 443. 1 442. 94 Ν-[(2-Chlorophenyl)indenyl]{4-[(Ν-hydroquinone-5-ylaminoindolyloxy)indenyl](2Η-3,4,5,6-tetrahydro)吼 -4--4-yl)} carbamide 14. 25 M+H+ 435. 1 434. 89 Ν·[(2-Phenylphenyl)methyl](4-{[Ν-(6-fluoro-2-indolylphenyl)amine decyloxy]methyl}(2Η-3,4, 5,6-tetrahydroanthracene 0 -4--4-)) 159 M+H+ 451. 0 451. 34(4-{[Ν-(3-chloro-2-methylphenyl)amine fluorenyloxy]fluorenyl}(211-3,4,5,6-tetrahydropyran-4-yl ))-&gt;^-[(2-Chlorobenzene 146 200823202 IC50 arithmetic mean ion m/z MW chemical name base) methyl] indoleamine N-[(2-chlorophenyl)methyl][4- ({N-[4-Methyl-3-(trifluoromethyl)phenyl]amine-methylmethyloxy}methyl)(2H-3,4,5,6- 12. 137 M+H+ 485. 0 484. 9 tetrahydro 0-butoxy-4-yl)]carbamamine (4-{[N-(3,4-dimethylphenyl)aminecarboxylideneoxy]methyl} (211-3,4, 5,6-tetrahydrogen|1-pyran-4-yl))-[[2-chlorobenzene. 335 M+H+ 431. 1 430. 92-)methyl]carbamamine (4-{[N-(3-chloro-4-methylphenyl)aminecarboxylideneoxy]methyl}(211-3,4,5,6-four Hydrogen ° 喃-4-yl))-1^-[(2-chlorobenzene 1. 961 M+H+ 451. 0 451. 34-Methyl]carbamamine N-[(2-chlorophenyl)methyl][4-({N-[4-(indolylethyl)phenyl]aminecarboxylideneoxy}methyl )(2H-3,4,5,6-tetrahydroanthracene^. 498 M+H+ 445. 1 444. 95 喃-4-yl)]carbamamine (4"{[N-(3,5-dichlorophenyl)amine decyloxy]methyl}(211-3,4,5,6-four Hydroquinone-4-yl))-1^[(2-chlorobenzene 18. 341 M+H+ 471. 0 471. 76-)methyl]carbamamine (4-{[N-(2,4-dimethylphenyl)amine-carbenyloxy]methyl}(211-3,4,5,6-tetra-argon Ola-4-yl))-&gt;^[(2- benzene benzene 1. 262 M+H+ 431. 1 430. 92 ))methyl]carbamamine 3-{N-[(2-chlorophenyl)methyl]amine-methyl hydrazino 3-{[(4-E 18. 559 M+H+ 459. 1 459. Methyl 92-phenyl)amino]carbonylamino}pyrrolidinecarboxylate N-[(2-chlorophenyl)methyl][4-({N-[4-(hydroxyethyl)phenyl]amine A Mercaptooxy}methyl)(211-3,4,5,6-tetrahydroanthracene 4 5. 229 M+H+ 447. 1 446. 92 喃-4-yl)]cartoamine N-[(2-chlorophenyl)indolyl]{4-[(N-phenylaminecarbamidooxy)methyl](211-3,4, 5,6-tetra argon||taste-4-based)} 244 M+H+ 403. 1 402. 87 Amine 4-{[(4-{N-[(2-Phenylphenyl)indolyl]aminemethanyl}-211-3,4,5,6-tetrahydro"pyran-4-yl) A Oxy]carbonylamine 101 M+H+ 446. 1 445. 9-yl}benzamide N-[(2-chlorophenyl)indenyl][4-({[(4-ethylphenyl))amine 18. 192 M+H+ 429. 1 428. 95-aminoamino}methyl)(4-Benbityl)]carbamamine-[(2·chlorophenyl)methyl][4-({[(4-ethylphenyl))) ]carbonylamino}methyl)-1-(2-aminoethyl)-(4-bite 1. 879 M+H+ 487. 1 486. 99 base)]carbamidine N-[(2-chlorophenyl)methyl][4·({[(4-ethylphenyl)amino]-fluorene-methylcarbonylamino} fluorenyl)- 1-(2-hydroxyethyl hydrazine 18. 738 M+H+ 501. 1 501. 02 base) (4-Big bite base)] an amine II-(ethylideneamino)-N-[(2-chlorophenyl)methyl]-3-[N-(4-ethylphenyl) Amine methyl ketone 2 - A 3. 138 M+H+ 432. 0 431. 91 propyl amide 4. 088 M+H+ 448. 1 447. 91 N-[(2-Chlorophenyl)methyl]-3-[N-(4-ethylphenyl)amine A 147 200823202 IC50 arithmetic mean ion m/z MW chemical name fluorenyloxy]-2 -(methoxycarbonylamino)-2-methylpropionamide N-[(2-chlorophenyl)methyl]-3-[N-(4-ethylphenyl)aminecarboxylideneoxy] -2-(2-hydroxyethylamino)-2-methylpropane 9. 184 M+H+ 448. 0 447. 91 indole 2-{2-[(tatabutoxy)carbonylamino]ethinylamino}-~[(2-chlorophenyl)methyl]-3-[N-(4-ethyl Phenyl) 19. 38 M+H+ 547. 1 547. 04 Aminomethyl methoxy]-2-methylpropanamide 2-(2-aminoethyl decylamino)-N-[(2-chlorophenyl)methyl]-3-[N-( 4-ethylphenyl)amine-mercaptooxy]-2-pin 3. 988 M+H+ 447. 1 446. 93-propionylamine 2-((2S)-2-amino-3-hydroxypropionylamino)-N-[(2-phenylphenyl)methyl]-3-[N-(4-B Phenyl phenyl) amine carbenyl group 11. 172 M+H+ 477. 1 476. 95 oxy]-2-methylpropionamide {[1-(2-aminoethenyl)-4-({[(2-)phenyl)methyl]amino}methyl)(4-) Piperidinyl]]methoxy}-N-(4-ethylbenzene 13. 086 M+H+ 473. 3 473. 01 base) formamide N-[(l-(2-aminoethenyl)-4-{N-[(2-chlorophenyl)methyl]aminemethanyl}(4-piperidinyl) ) methyl hydrazine (4-ethylbenzene 12. 353 M+H+ 558. 1 558. 11-amino)]-indole-(3-decyloxypropyl) decylamine N-[(l-(2-aminoethenyl)-4-{Ν-[(2-chlorophenyl)) Aminomethyl}(4-piperidinyl))methyl]-indole-(2-amine B. 385 529. 07 base)[(4-ethylphenyl)amino]carbamamine (t-butoxy)-fluorene-(2-{Ν-[(1-{2-[(t-butoxy))carbonyl) Amino]ethyl hydrazino}-4-{Ν-[(2-chlorophenyl)methyl]aminocarbamoyl}(4-piperidinyl))indenyl][(4-ethylphenyl)amine 19. 481 M+H+ 729. 3 729. 3-yl-carbonylamino}ethyl)carbamamine 3-(1-(2-aminoethyl)-4-{indole-[(2-mercaptophenyl)methyl]aminecarbamyl} (4-piperidinyl))-indole-(4-ethylphenyl) 15. 319 464. 6 propylamine N-{(lS)-2-[N-(4-ethylphenyl)amine-methylcarbonyloxy)· 1. 632 M+H+ 390. 1 389. 88 isopropyl}{[(2-chlorophenyl)methyl]amino}carbamamine 2-(N-{(lS)-2-[N-(4-ethylphenyl)aminecarbamyl) Oxygen M-'Bu-based]-isopropyl}{[(2-chlorophenyl)methyl]amino}carbonylamine 18. 521 +H+ 448. 1 504. 02 base) acetic acid tert-butyl ester 2-(N-{(lS)-2-[N-(4-ethylphenyl)aminemethanoyloxym-h2 group]-isopropyl}{[(2 -Chlorophenyl)methyl]amino}carbonylamine 1. 67 0+H+ 430. 1 447. N-{(lS)-2-[N-(4-ethylphenyl)amine-mercaptooxy]-isopropyl}{[(2-chlorophenyl)methyl]amino }-N-methylmethyl. 148 M+H+ 404. 1 403. 9 guanamine [(2R)-2-({[(2-chlorophenyl)methyl]amino}}Ν-methylcarbonyl 6. 814 M+H+ 404. 1 403. 9 Amino)propoxy]-indole-(4-ethylphenyl)formamide 148 200823202 IC50 arithmetic mean ion m/z MW &gt;ί匕 scientific name N-{(lS)-3-[N- (4-ethylphenyl)amine-mercaptooxy]-1-mercaptopropyl}{[(2-chlorophenyl)methyl]amino}-N- 0. 198 M+H+ 418. 1 417. 93 methylmethamine {[(2-chlorophenyl)methyl]amino}-N-{4-[N-(4-ethylbenzene 6. 071 M+H+ 418. 0 417. 93-aminoglycolyloxy]butyl}-N-methylformamide {[(2-chlorophenyl)indolyl]amino}-N-{3-[N-(4-ethyl Benzene 1. 669 M+H+ 404. 1 403. 9-)amine mercaptooxy]propyl}-N-methylformamide (t-butoxy)-N-[2-({[(2-chlorophenyl)methyl]amine)} -N-{2-[N-(4-ethylphenyl)amine-mercaptooxy]ethyl 18. 247 M+H+ 533. 1 533. 06 base}carbonylamino)ethyl]-N-methyldecylamine {[(2-chlorophenyl)methyl]aminopyr N-{2-[N-(4-ethylphenyl)amine Mercaptooxy]ethyl}-N-[2-(methylamino)ethyl 16. 325 M+H+ 433. 1 432. 94 merylamine 2-amino-N-[2-({[(2-chlorophenyl)methyl]amine)}}-Ν-{2-[Ν-(4·ethylphenyl)amine Methyl methoxy] b. 856 M+H+ 490. 1 489. 99-yl}carbonylamino)ethyl]methylacetamide 2-amino-indole-{2-[{[(2-chlorophenyl)methyl]amine*}-Ν-(2-{Ν- [4-(Trifluoromethyl)phenyl]aminecarbamyl 15. 008 M+H+ 530. 1 529. 94 oxy}ethyl)carbonylamino]ethyl}-indole-methylacetamide [2-({[(2-chlorophenyl)methyl)amino}-indole-methylcarbonylamine 8. 52 M+H+ 404. 3 403. 9-)isopropoxy]·Ν-(4-ethylphenyl)formamide {[(2-phenylphenyl)methyl]amino}-Ν-methyl-Ν-{2-[ Ν-(4-Phenylphenyl)amine-mercaptooxy]ethyl} 0. 248 M+H+ 438. 1 437. 92-Mercaptoamine {[(2-chlorophenyl)methyl]amino}-Ν-methyl-Ν-[2-(Ν-(2-naphthyl)aminemethylmercaptooxy)ethyl]anthracene醯0. 03 M+H+ 412. 1 411. 88 Amine 3-(2-chlorophenyl)-indole-{2-[Ν-(4-ethylphenyl)aminecarboxamide 0. 875 M+H+ 389. 1 388. 89-Alkyl]ethyl}-indole-methylpropanamine Ν-{2-[Ν-(4-ethylphenyl)amine-methylcarbonyl]ethyl}-2-hydroxy-indole-A Base-3-[2-(trifluoromethyl)phenyl]propene 17. 505 M+H + 439. 1 438. 44 Amidoxime Ν-{2-[Ν-(4-ethylphenyl)aminecarboxylideneoxy]B. 21 M+H+ 423. 1 422. 44 }}·Ν-methyl-3-[2-(trifluoromethyl)phenyl]propanamine {[(2-phenylphenyl)methyl]methylamino}-Ν-{2-[Ν -(4-ethyl 2. 075 M+H+ 404. 1 403. 9 phenyl)amine-based milk-based]ethyl}-indole-methylcartoamine (2-{Ν-[(2-chlorophenyl)methyl]amine-mercaptooxy}ethoxy) 69 M+H+ 377. 2 376. 83 base)·Ν-(4-ethylphenyl)cartoamine Ν-[(2-chlorophenyl)methyl]-4-{[Ν-(4-ethylphenyl)amine 4. 732 M+H+ 402. 2 401. 93-Mercapto]amino}-2,2-dimethylbutyramine Ν-[(2-chlorophenyl)methyl] winter {[(4-ethylphenyl)amino] 13. 629 M+H+ 374. 1 373. 88 amino-amino}-2-methylpropanol 149 200823202 IC50 arithmetic mean mean ion m/z MW 2. 515 M+H+ 389. 1 388. 89 5. 232 M+H+ 385. 1 385. 89 18. 156 M+H+ 385. 1 384. 9 1. 879 M+H+ 401. 2 400. 9 0. 238 M+H+ 429. 3 428. 95 3. 211 M+H+ 430. 2 530. 06 1. 663 M+H+ 430. 2 429. 94 2. 784 M+H+ 437. 0 437. 32 1. 362 M+H+ 413. 1 412. 91 5. 511 M+H + 447. 1 446. 92 0. 53 M+H+ 488. 1 487. 98 16. 807 M+H+ 414. 1 413. 94 0. 418 M+H+ 472. 1 471. 97 0. 496 M+H+ 508. 1 508. 03 0. 173 M+H+ 488. 1 487. 98 0. 919 M+H+ 487. 1 587. 11 0. 481 M+H+ 616. 2 615. 16 Chemical name N-[(2-Chlorophenyl)methyl]-3-[N-(4-ethylphenyl)amine-mercaptooxy]-2,2-dimethylpropanamine&gt; 1-[({]^-[(2-chlorophenyl)methyl]aminemethanyl}cyclopropyl)methylindole (4·ethylphenyl)amino]carbamamine 1^-[( {1^-[(2-Chlorophenyl)methyl]aminemethanyl}cyclopropyl)methyl]-2-(4-ethylphenyl)acetamidine [({N-[(2- Chlorophenyl)methyl]amine-methylmethyl}cyclobutyl)methoxy]-N-(4-ethylphenyl)carbenamide N-[(2-chlorophenyl)methyl]({[ N-(4-ethylphenyl)amine-mercaptooxy]methyl}cyclohexyl)carzamide 4-{N-[(2-chlorophenyl)methyl]amine-methylhydrazinyl 4_{[ N-(4-ethylphenyl)amine-methyleneoxy]methyl}Benidinecarboxylic acid tert-butyl ester N-[(2-chlorophenyl)methyl](4-{[N-(4-ethyl) Phenyl)amine-mercaptooxy]methyl}(4-piperidinyl))carbenamide (4-{[N-(4-chlorophenyl)aminecarboxylideneoxy]methyl} (211 -3,4,5,6-tetrahydro"pyran-4-yl))-:^-[(2-phenylphenyl)methyl]carbenamide N-[(2-chlorophenyl)methyl (l-{[N-(4-ethylphenyl)amine-carbamoyloxy]methyl}cyclopent-3-enyl)carbamamine N-[(2-chlorophenyl)methyl] (1-{[ν_(4·B) Phenyl)amine-mercaptooxy]methyl}-3,4-dihydroxycyclopentyl)carbenamide 4-{&gt;1-[(2-chlorophenyl)indenyl]amine fluorenyl} Methyl 4-([1^-(4-ethylphenyl)amine-carbamoyloxy]methyl}piperidinecarboxylate ((lS,2S)-2-{[(4-ethylphenyl)) Amino]carbonylamino}cyclohexyl)-N-[(2-chlorophenyl)indolyl]decylamine (1-ethylindolyl-4-{[N-(4-ethylphenyl)amine A) Mercaptooxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carbenamide N-[(2-chlorophenyl)methyl](4-{ [N-(4-ethylphenyl)amine-methylmethyloxy]methyl}-1-(methylsulfonyl)(4-piperidinyl))carbenamide N-[(2-chlorobenzene) (4-{[N-(4-ethylphenyl)aminemethylmercaptooxy]methyl}-1-(2-hydroxyethyl)(4-piperidinyl)) Indoleamine (t-butoxy)-indole-[2·(4-{Ν-[(2-chlorophenyl)methyl]amine 曱醯*}-4-{[Ν-(4-ethylbenzene) Aminomethylamino]methyl}piperidinyl-2-oneethyl]carboxamide (t-butoxy)-indole-[4-(4-{Ν·[(2-chloro) Phenyl)methyl]amine-methylhydrazine*}-4-{[Ν-(4-ethylphenyl)amine-carbamoyloxy]methyl}piperidinyl)-4-onebutyl]carboxamide 150 200823202 IC50 Surgery average value of the ion m / z MW Name 0 dagger. 175 M+H+ 487. 1 486. 99 (1-(2-Aminoethyl fluorenyl[n-(4-ethylphenyl)amine)-yloxy]methyl}(4-piperidinyl))-N-[(2-chlorobenzene) Base) methyl]carbamamine 0. 246 M+H+ 515. 2 515. 04 (1-(4·Aminobutylidene)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl))-N-[(2 - gas phenyl) fluorenyl] methotrexate 1. 511 M+H+ 501. 1 601. 13 N-[(lS)-2-(4-{N-[(2-Chlorophenyl)methyl]aminemethanyl 4-{[N-(4-ethylphenyl)amine) Oxy]methyl}piperidinyl)-1-methyl-2-oneethyl](t-butoxy)carbamamine 0. 724 M+H+ 501. 1 501. 02 (l-((2S)-2-Aminopropionyl)·4-{[Ν-(4-ethylphenyl)aminecarbamyloxy]methyl}(4-piperidinyl)) -N-[(2-chlorophenyl)methyl]carbamamine 0. 426 M+H+ 545. 1 544. 04 4-(4·{Ν-[(2-Phenylphenyl)methyl]aminemethanoyl 4-{[Ν-(4-ethylphenyl)aminemethanyloxy]fluorenyl) Mercapto)-4-methylbutyric acid methyl ester 0. 492 M+H+ 516. 2 516. 03 N-[(2-Chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)amine-mercaptooxy]methylcarbyl butyl) (4-Butrylyl) )) methotrexate 2. 261 M+H+ 416. 1 415. 91 N-[(2-Chlorophenyl)methyl]{3-[N-(4-ethylphenyl)aminemethyleneoxy]piperidinyl}carboxamide 5. 544 M+H+ 396. 2 395. 49 {3-[N-(4-ethylphenyl)amine-carbenyloxy]piperidinyl}-1^-[(2-methylphenyl)methyl]carboxamide 0. 302 M+H+ 487. 1 486. 99 Ν-[(2·Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(Ν-methylamine formazan) () 4-(piperidinyl))carhamamine 0. 661 M-Bo c+H+ 517. 2 617. 13 (Third-butoxy)-N-[2-(4-{N-[(2- phenyl)methyl]amine 曱醯S}-4-{[N-(4-ethylphenyl) Aminomethyl methoxy]methyl}piperidinyl-1-(hydroxymethyl)-2-oneethyl]carbamamine 0. 143 M+H+ 517. 1 517. 02 (1-(2-Amino-3-hydroxypropionyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl)) -N-[(2-Phenylphenyl)methyl]carbamamine 11. 978 M-Bo c+H+ 501. 2 601. 13 N-[(lR)-2-(4-{N-[(2-chlorophenyl)methyl]aminemethanyl}-4-{[N-(4-ethylphenyl)aminecarboxamide氧基 曱 曱 } } ) ) ) -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 255 M+H+ 501. 2 501. 02 (l-((2R)-2-Aminopropyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl)) -N-[(2-Phenylphenyl)methyl]carbamamine 0. 54 M+H+ 529. 2 529. (1-(2-Amino-3-methylbutylidene)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl))- N-[(2- 151 200823202 IC50 arithmetic mean ion m/z MW chemical name 3. 549 M-Bo c+H+ 541. 1 641. 2 chlorophenyl)methyl]carbamamine 4-[(4-{&gt;1-[(2-phenylphenyl)methyl]aminemethanyl}-4-{[&gt;1-(4- Ethylphenyl)amine methyl hydrazinyloxy]methyl}piperidinyl)carbonyl]piperidinecarboxylic acid tert-butyl ester 0. 808 M+H+ 541. 2 541. 08 N-[(2-Chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-(4-piperidinylcarbonyl) (4-piperidinyl))carhamamine 1. 679 M+H+ 643. 3 643. 17 3-[(4-{N-[(2-Chlorophenyl)methyl]aminemethanyl}-4-{[]^-(4-ethylphenyl)aminecarboxylideneoxy]- }}piperidinyl)carbonyl]morpholine-4-carboxylic acid tert-butyl ester 0. 515 M+H + 543. 2 543. 05 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(morpholin-3-ylcarbonyl) (4 · piperidinyl)) methotrexate 14. 41 M+H + 520. 2 520. 06 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}-1-benzyl (4-piperidinyl) )) Formamide 6. 276 M+H+ 458. 1 457. 99 N-[(2-Chlorophenyl)methyl](1-ethyl-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl) )) methotrexate 1. 52 M+H+ 503. 4 502 2-(4-{N-[(2-Phenylphenyl)methyl]aminecaramidine*}-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl }piperidinyl)methyl acetate 0. 275 M+H+ 546. 2 546. 05 N-[(2-Chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)aminemethanyloxy]methyl}-1-[3-hydroxy-2-( Hydroxymethyl)-2-methylpropenyl](4-piperidinyl))carbenamide 4. 036 M+H+ 474. 1 473. 99 N-[(2-Chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-(2-hydroxyethyl)( 4-piperidinyl)) formamide 0. 67 M+H+ 515. 2 515. 04 (1-(2-Amino-2-methylpropenyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl) )-N-[(2-chlorophenyl)methyl]carbamamine 0. 213 M+H+ 501. 2 501. 02 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-[2-(methylamino) Ethyl](4-piperidinyl))carboxamide 4. 928 M+H+ 444. 1 443. 97 Ν-[(2·Phenylphenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl b 1-methyl(4-piperidinyl) ) methotrexate 3. 502 M-Bo c+H+ 517. 1 617. 13 N-[(lR)-2-(4-{N-[(2-Chlorophenyl)methyl]amine-carboxamidine S}-4-{[N-(4-ethylphenyl)amine-formamidine氧基oxy]methyl}piperidinyl)-1-(hydroxymethyl)-2-oneethyl](t-butoxy)carbamamine 152 200823202 IC50 arithmetic mean ion m/z MW chemical name 0 . 164 M+H+ 517. 2 517. 02 (1-((2R)-2-Amino-3-ylpropenyl)-4-{[N-(4-ethylphenyl)amine decyloxy]methyl}(4- Piperidinyl))-N-[(2-chlorophenyl)methyl]carbamamine 0. 416 M-Bo c+H+ 517. 1 617. 13 N-[(lS)-2-(4-{N-[(2-Chlorophenyl)methyl]aminemethanyl}-4-{[1^-(4-ethylphenyl)amine A Mercaptooxy]methyl}piperidinyl)-1-(hydroxymethyl)-2-oneethyl](t-butoxy)carbamamine 0. 125 M+H+ 518. 2 517. 02 (l-((2S)-2-Amino-3-pyridyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4- Piperidinyl))-N-[(2-chlorophenyl)methyl Icarboxamide 1. 162 M+H+ 474. 1 473. 01 (1-(2-Aminoethyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4·piperidinyl))-N-[(2 -Chlorophenyl)methyl]carbamamine 0. 797 M+H+ 526. 1 526. 03 (1-(2-Amino-3-cyanopropyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl) )-Ν-[(2·Chlorophenyl)methyl]carbamamine 5. 936 M+H+ 470. 1 469. 88 Ν-[(2-Chlorophenyl)indenyl][4_({Ν-[4-(trifluoromethyl)phenyl]aminecarmeyloxy}methyl)(4-piperidinyl)] Formamide 0. 274 M+H+ 537. 1 537. (1-[(2-Aminoethyl)sulfonyl]-4·{[Ν-(4-ethylphenyl)amine fluorenyloxy]methyl}(4-piperidinyl))- Ν-[(2-Phenylphenyl)methyl]carbamamine 1. 023 M+H+ 516. 1 516. 03 (1-(2,3-Diaminopropionyl)·4-{[Ν-(4-ethylphenyl)amine fluorenyloxy]methyl}(4-piperidinyl))- Ν-[(2-Phenylphenyl)methyl]carbamamine 0. 585 M+H+ 530. 2 530. 06 (1-(2,4-Diaminobutanyl)-4-{[1^-(4-ethylphenyl)amine-methylmethyloxy]indolyl}(4·piperidinyl))-Ν_ [(2-Phenylphenyl)methyl]carbamamine 0. 456 M+H+ 528. 1 527. 92 Ν-[(2-Chlorophenyl)methyl][1-(2-hydroxyethyl)-4-({N-[4-(trifluoromethyl)phenyl]aminecarboxamidooxy) }methyl)(4-piperidinyl)]carbamamine 0. 285 M+H+ 527. 1 526. 94 2-·(2-Aminoethyl fluorenyl)-4-({N-[4-(trifluoromethyl)phenyl]amine-methylmethyloxy}methyl)(4-piperidinyl)]- Ν-[(2·Chlorophenyl)methyl]carbamamine 0. 138 M+H+ 557. 1 556. 96 [l-((2S)-2-Amino-3-hydroxypropanyl)-4-({N-[4-(trifluoromethyl)phenyl]aminecarmeyloxy}methyl) (4-piperidinyl)]-Ν·[(2-phenylphenyl)methyl]carbamamine 0. 486 M+H+ 502. 2 502 Ν-[(2-Chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)aminecarboxylideneoxy]methylmethoxyethyl)(4-piperidine) Base)) formazan 4. 829 M+H+ 513. 2 613. 14 2-[(4-{N-[(2-Chlorophenyl)methyl]amine-methyl phenylethyl)amine-methyl sulfonyloxy]-A 153 200823202 IC50 arithmetic mean ion m/z MW chemical name 0. 221 M+H+ 513. 2 513. 03 }}piperidinyl)carbonyl]azetidinecarboxylic acid tert-butyl ester (1-(azetidin-2-ylcarbonyl)-4-{[N-(4-ethylphenyl)aminemethantyloxy) Methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carboxamide 0. 606 M+H+ 517. 2 516. 03 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}-1-(3-methoxypropenyl) (4-piperidinyl))carhamamine 1. 495 M+H + 544. 1 544. 09 (1-(2,5-Diaminopentylidene)-4-{[1^-(4-ethylphenyl)aminemethylmercaptooxy]methyl}(4-piperidinyl)) -N-[(2-chlorophenyl)fyl]carbenamide 1. 564 M+H+ 416. 1 415. 91 {(3R)-3-[N-(4-ethylphenyl)amine decyloxy]piperidinyl}-N-[(2-chlorophenyl)methyl]carboxamide 0. 412 M+H+ 535. 2 534. 05 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)amine-carbenyloxy]indolyl}-1-(phenylcarbonyl)(4- Piperidinyl)) formamide 0. 695 M+H+ 536. 2 535. 03 N-[(2-Chlorophenyl)methyl](4·{[Ν-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1·(3-η-pyridylcarbonyl) (4-piperidinyl))carhamamine 6. 184 M-Bo c+H+ 515. 2 615. 16(Tertibutoxy)-indole-[2-(4.{Ν-[(2-chlorophenyl)methyl]aminemethanyl}-4-{[&gt;1-(4-ethyl Phenyl)amine-methyl hydrazinyloxy]fluorenyl} benzyl)-1 -methyl-2-indolyl]-indole-methylcarboxamide 1. 784 M+H+ 516. 1 515. 04 Ν-[(2-Chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-[2-(methylamino) Propionyl](4-piperidinyl))carhamamine 18. 544 M+H+ 387. 1 386. 91 Ν-[(2-Chlorophenyl)methyl]-Ν'-(4-ethylphenyl)-2,2·dimethylpentane·1,5-diamine. 119 M-Me +H+ 545. 2 559. 05 (3S)-3-Amino-4-(4-{Ν·[(2-chlorophenyl)methyl]aminemethanyl}-4-{[Ν-(4-ethylphenyl)amine Methyl methoxy]methyl}piperidinyl)-4. methyl butyl keate 0. 12 M+H+ 517. 2 517. 02 (1-(3-Amino-2-hydroxypropionyl)·4-{[Ν-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl)) -Ν-[(2-chlorophenyl)methyl]carbamamine 0. 187 M+H+ 532. 2 531. 04 (1-(4-Amino-2-hydroxybutanyl)-4-{[indolyl-(4-ethylphenyl)amine-methylcarbonyloxy]methyl}(4-piperidinyl))-oxime -[(2-Chlorophenyl)methyl]carbamamine 0. 123 M+H+ 518. 2 518 (1-(2,3-dihydroxypropyl)-4-{[indolyl-(4-ethylphenyl)aminemethylmercaptooxy]methyl}(4-piperidinyl))- Ν-[(2-Chlorophenyl)methyl]carbamamine 10. 197 M+H+ 416. 1 415. 91 {(3S)-3-[N-(4-ethylphenyl)aminecarboxylideneoxy]piperidinyl}-N-[(2-chlorophenyl)methyl]cartoamine 154 200823202 IC50 Arithmetic mean ion m/z MW chemical name 1. 526 M+H+ 545. 1 545. 03 3-Amino-4-(4-{N-[(2-chlorophenyl)methyl]aminemethanyl}-4-{[&gt;1-(4-ethylphenyl)amine oxime氧基oxy]methyl} slightly biti)-4-ketobutyric acid 0. 641 M+H+ 499. 3 498. 01 N-[(2-Chlorophenyl)methyl](1-(cyclopropylcarbonyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4 - piperidinyl)) formamide 2. 766 M+H+ 540. 2 540. 09 N-[(2-Chlorophenyl)methyl](1-(cyclohexylcarbonyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4- Piperidinyl))carhamamine 0. 757 M+H+ 535. 1 535. 03 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(2-«-pyridylcarbonyl) (4-piperidinyl))carhamamine 0. 394 M+H+ 524. 1 524. 01 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminemethionyloxy]methyl}-1-(imidazol-2-ylcarbonyl) (4-piperidinyl))carhamamine 1. 431 M-Bo c+H + 487. 2 587. 11 (tert-butoxy)-N-[2-(3-{N-[(2-chlorophenyl)methyl]aminemethanyl}-3-{[&gt;1-(4-ethyl Phenyl)amino-mercaptooxy]methyl}piperidinyl)-2-oneethyl]carbamamine 9. 088 M-Bo c+H+ 517. 3 617. 13 N-[(lS)-2-(3-{N-[(2-Chlorophenyl)methyl]amine-carbamidine*}-3-{[N-(4-ethylphenyl)amine oxime氧基oxy]methyl}piperidinyl)-1-(hydroxymethyl)-2-oneethyl](t-butoxy)carbamamine 0. 474 M+H+ 487. 1 486. 99 (1-(2-Aminoethyl)-3-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(3-piperidinyl))-N-[ (2-chlorophenyl)methyl]carbamamine 0. 399 M+H+ 488. 1 487. 98 N-[(2-Chlorophenyl)methyl](3-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(2-hydroxyethyl) (3-piperidinyl))carhamamine 1. 483 M+H+ 517. 3 517. 02 (l-((2S)-2-Amino-3-hydroxypropionyl)-3-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(3-piperidyl) Pyridyl))-N-[(2-phenylphenyl)methyl]carbamamine 0. 336 M+H+ 517. 1 517. 02 4-{N-[(2-Phenylphenyl)methyl]aminemethanyl}-4-{[1(4-ethylphenyl)aminecarboxylideneoxy]methyl}piperidinecarboxylic acid 2 -Aminoethyl ester 0. 159 M+H+ 516. 2 516. 03 N-(2-Aminoethyl)(4-{N-[(2-chlorophenyl)methyl]amine曱醯*}-4-{[N-(4-ethylphenyl)aminecarboxamide氧基oxy]methyl}piperidinyl)carboxamide 0. 474 M+H+ 488. 1 487. 98 3-{N-[(2-Chlorophenyl)methyl]aminemethanyl}-3-{[^-(4-ethylphenyl)aminecarboxylideneoxy]methyl}piperidinecarboxylic acid Methyl ester 0. 526 M+H+ 472. 1 472. 96 (1-(2-Aminoethyl)-3-{[N-(4-ethylphenyl)aminecarboxhydryloxy]methylpyrrolidin-3-yl)-indole-[( 2·chlorobenzene 155 200823202 IC50 arithmetic mean ion m/z MW chemical name 1. 323 M+H+ 558. 2 544. [12] hydrazinyl] guanamine (1-((2 5)-2,5-diaminopentenyl)-4-{[&gt; 1-(4-ethylphenyl)amine fluorenyl Oxy]mercapto}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]decylamine 2. 44 M+H+ 501. 2 501. 02 (1-(2-Aminoethyl)-4-{2-[Ν-(4-ethylphenyl)amine decyloxy]ethyl}(4-piperidinyl))-oxime -[(2-Chlorophenyl)indenyl]carbamamine 0. 44 M+H+ 561. 1 561. 38 Π-(2-Aminoethyl fluorenyl)-4-({Ν-[2-chloro-4-(trifluoromethyl)phenyl]amine decyloxy}fluorenyl)(4-piperidine) Base)]-Ν·[(2-chlorophenyl)indenyl]decylamine 1. 966 M+H+ 541. 1 540. 96 Π-(2·Aminoethyl fluorenyl)-4-({Ν-[4-methyl·3-(trifluoromethyl)phenyl]amine decyloxy}fluorenyl) (4-piperidyl) Pyridyl)]-Ν-[(2-phenylphenyl)indenyl]decylamine. 281 M+H+ 507. 1 507. 41 (1-(2-Aminoethyl)-4-{[Ν-(2-chloro-4-indolylphenyl)amine decyloxy]indolyl}(4-piperidinyl)) -Ν-[(2-Phenylphenyl)indolyl]carbamamine 0. 126 M+H+ 499. 2 499 {1-(2-Aminoethyl fluorenyl)-4-[(indole-hydroquinone-5-ylaminocarbamoyloxy)indenyl](4·piperidinyl)}-N-[( 2-chlorophenyl)indenyl]decylamine 0. 569 M+H+ 493. 1 493. 38 (1-(2-Aminoethyl)-4-{[N-(4-chlorophenyl)amine decyloxy]methyl}(4-piperidinyl))-N-[( 2-gas stupid) methyl] guanamine 1. 81 M+H + 517. 2 516. 97 4-{[(1-(2-Aminoethyl)methyl]{{-[(2-chlorophenyl)indenyl]amine hydrazinyl 4-piperidinyl) decyloxy]carbonyl Amino} benzoic acid oxime ester 0. 742 M+H+ 491. 1 490. 95 (1-(2-Aminoethyl decyl)-4-{[N-(3-fluoro-4-indolylphenyl)amine decyloxy]methyl}(4·piperidinyl)) -N-[(2-chlorophenyl)indenyl]decylamine 4. 948 M + H + 638. 1 638. 15 N-[(2-Phenylphenyl)indenyl](4-{[N-(4-ethylphenyl)amine 曱 基 氧基 氧基 氧基 }}}}{{4-(phenylcarbonyl) Phenyl] carbonyl}(4-piperidinyl))carhamamine 0. 277 M+H + 535. 1 535. 03 (1-(2-Aminoethyl fluorenyl)-4-{[Ν-(4·phenylphenyl)amine 曱 基 氧基 oxy] fluorenyl}(4-piperidinyl))-Ν·[ (2-phenylphenyl)methyl]decylamine 0. 083 M + H + 509. 2 509 U-(2-Aminoethyl fluorenyl)·4·[(Ν·(2-naphthyl)amine fluorenyloxy)indenyl](4-piperidinyl)}-Ν-[(2 - gas phenyl) fluorenyl] decylamine 3. 429 M+H+ 375. 1 374. 86 Ν·[(2-Phenylphenyl)indenyl]-4-[indolyl-(4-ethylphenyl)amine hydrazinyloxy]butanamine 6. 808 M+H+ 390. 1 389. 88 2·Amino-indole-[(2-chlorophenyl)indenyl]·4-[indole-(4-ethylphenyl)aminecarboxylideneoxy]butanamine 156 200823202 IC50 arithmetic mean ion m/z MW chemical name 4. 37 M+H+ 447. 0 446. 93 2-(2-Aminoethyl decylamino)-N_[(2-chlorophenyl)methyl]-4-[N-(4-ethylphenyl)aminecarakioxy]butane Amine 744 M+H+ 501. 1 501. 02 2-(1-(2-Aminoethyl)-4-{[N-(4-ethylphenyl)amine-methylcarbonyl]methyl}(4-piperidinyl))-N -[(2-Chlorophenyl)methyl]acetamide 0. 197 M+H+ 431. 2 430. 92 N-[(2-Chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(211-3,4,5,6- Tetrahydro 0-pyan-4-yl))carhamamine 17. 962 M+H+ 378. 1 377. 43 1-(2-Aminoethyl fluorenyl)-4-{[indole-(4.ethylphenyl)amine methyl hydrazinooxy]methyl}piperidine-4-carboxylic acid methyl ester 0. 975 M+H+ 567. 2 566. 69 (Third-butoxy)-indole-[2-(4-{[Ν-(4-ethylphenyl)amine-carbenyloxy]methyl}-4-{Ν-[(2·甲甲Phenyl)methyl]amine-methylmethyl}piperidinyl)-2-oneethyl]carbamamine 11. 102 M-Bo c+H+ 453. 2 552. 66 (Third-butoxy)-N-[2-(4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-4-[N-benzylaminecarbamidine Base] piperidine)-2-indolyl] 769 M+H+ 471. 2 570. 65(Tertidinoxy)·Ν-[2-(4-{[Ν-(4-ethylphenyl)amine fluorenyloxy]fluorenyl}-4-{Ν-[(2-fluoro Phenyl)methyl]aminomethylmercapto}piperidinyl)-2-oneethyl]carboxamide 0. 167 M+H+ 467. 2 466. 57 (1-(2-Aminoethyl)-yl-{{N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl))-N-[ (2-methylphenyl)methyl]carbamamine 8. 111 M+H+ 453. 1 452. 55 (1. (2-Aminoethyl)-[{N-(4-ethylphenyl)amine-methylcarbonyl]methyl}(4-piperidinyl))-N-benzyl Carbenamide 0. 307 M+H+ 471. 1 470. 54 (1-(2-Aminoethyl)-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]indolyl}(4-piperidinyl))-N-[ (2-fluorophenyl)methyl]carbamamine 11. 307 M-Bo c+H+ 483. 2 582. 69 (1-{2-[(Tertibutoxy)carbonylamino]acetamidine*}-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4 -piperidinyl))-N-[(2-methoxyphenyl)methyl]carbamamine 14. 457 M-Bo c+H+ 487. 1 587. 11 [(1-{2-[(Tertidinoxy)carbonylamino)]ethinyl}-4-{&gt;1-[(4-phenylphenyl)methyl]amine fluorenyl}([ Piperidinyl)) methoxy]-indole-(4-ethylphenyl)carbamamine 0. 313 M-Bo c+H+ 521. 1 621. 55[(4-{Ν-[(2,3-Dichlorophenyl)methyl]aminemethanyl}-1-{2-[(tatabutoxy)carbonylamino]ethenyl}( 4-piperidinyl)) methoxy]-indole-(4-ethylphenyl)carbamamine 2. 164 M+H+ 483. 2 482. 57 (1-(2-Aminoethyl fluorenyl)-4-{[indolyl-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4-piperidinyl))-indole-[ (2-methoxyphenyl)methyl]decylamine 157 200823202 IC50 arithmetic mean ion m/z MW chemical name {[1-(2-aminoethyl fluorenyl)-4-(N-{[2- (Trifluoromethyl)phenyl]methyl}amine-methyl hydrazino) (4-Benbityl)] methoxy 0. 086 M+H+ 521. 2 520. 54 }}-1^-(4-ethylphenyl)carboxamide [(1-(2-aminoethyl) phenyl)-4-{Ν-[(4-chlorophenyl)methyl]amine A Mercapto}(4-piperidinyl))methoxy]-indole-(4-ethylbenzene 1. 28 M+H+ 487. 1 486. 99-aminoglycolamine [(1-(2-aminoethylindenyl-{Ν-[(2,3-dichlorophenyl)methyl]aminecarbamyl} (4--fluorenyl)) Methoxyethyl 0. 088 M+H+ 521. 0 521. 44-phenyl)carbamamine [(1-(2-aminoethylhydrazino)-4-{Ν-[(3-methyl(2-piperidinyl)))]methyl) 4_piperidinyl)) oxime 2. 98 M+H+ 468. 2 467. 56 ]]-Ν-(4-ethylphenyl)carbamamine [(1-(2-aminoethyl) -4-)-[(2-bromophenyl)methyl]amine formazan }}(4-piperidinyl))methoxy]-indole-(4-ethylbenzene 0. 146 M+H+ 531. 1 531. 44-aminoglycolamine [(1-(2-aminoethyl) -4-(indole-[(3-chlorophenyl)methyl])aminomethyl]}-(4-piperidinyl)) Oxy]-Ν-(4-ethylbenzene 0. 729 M+H+ 487. 1 486. 99-aminoglycolamine [(4-{Ν-[(2,3-difluorophenyl)methyl]aminemethanyl}-1-{2-[(t-butoxy)carbonylamino]]乙醯基}(4_ 1. 593 M+H+ 589. 2 588. 64 piperidinyl)) methoxy]-indole-(4-ethylphenyl)carboxamide [(1-(2-aminoethyl) -4-)-[(2, 3-) Fluorophenyl)methyl]amine-mercapto}(4-piperidinyl))decyloxy]-indole-(4-ethyl. 164 M+H+ 489. 1 488. 53-phenyl)carbamamine [(1-(2-aminoethylhydrazino)-4-{Ν-[(3- gas-2-fluorophenyl)methyl]amine)] Piperidinyl)) methoxy]-Ν-(4- 0. 099 M+H+ 505. 2 504. 98 ethyl phenyl) formamide [(1-(2-aminoethyl) sulfonyl] 4-{indole-[(3-fluoro-2-methylphenyl)methyl]aminecarbenyl} ( 4-piperidinyl)) methoxy 0. 081 M+H+ 485. 2 484. 56 ]]-Ν-(4-ethylphenyl)carbamamine [(1-(2-aminoethyl aryl)-4-{Ν-[(3·chloro-2-methylphenyl)) Aminomethyl}(4-piperidinyl))methoxy 0. 083 M+H+ M-Bo 501. 1 501. 02 ]]-Ν-(4-ethylphenyl)carbamamine [(1-{2-[(Tertidinoxy)amino)]]**-4-{Ν-[(3- Fluorophenyl)methyl]amine sulfhydryl} (4_pipetaline 8. 238 c+H+ M-Bo 471. 1 570. 65 pyridine)) methoxy]-indole-(4-ethylphenyl)carbamamine [(1-{2-[(t-butoxy)carbonylamino]ethinyl}-4-{ &gt; 1-[(4-Fluorophenyl)methyl]aminecarboxylidene} 12 c+H+ 471. 1 570. 65 mercapto)) methoxy]-indole-(4-ethylphenyl) anthracene [(1-(2-aminoethyl) -4-)-[(3-fluorophenyl) Methyl]aminomethane}(4-piperidinyl))decyloxy]-indole-(4-ethylbenzene 1. 03 M+H+ 471. 1 470. 54 base) formamide 158 200823202 IC50 arithmetic mean mean ion 1. 098 M+H+ 7. 22 M+H+ 1. 769 M+H+ M-Bo 3. 176 c+H+ M-Bo 6. 558 c+H+ M-Bo 3. 718 c+H+ 18. 473 M+H+ M-Bo 7. 688 c+H+ 0. 412 M+H+ 0. 37 M+H+ 0. 284 M+H+ 5. 645 M+H+ 0. 904 M+H+ m/z 471. 1 454. 1 543. 2 525. 2 545. 1 560. 1 443. 0 478. 2 525. 1 545. 0 561. 0 541. 0 478. 2 MW chemical name [(1-(2-aminoethyl fluorenyl)-4-{^[-[(4-fluorophenyl)methyl]amine)carboxamide}(4-piperidinyl))methoxy Base]-N-(4-ethylbenzene 470. 54-) guanamine-aminoethyl -4-)[Ν-(2-β-butylidylmethyl)amine-carbamoyl](4-piperidinyl)}methoxy)-Ν-(4 -ethylbenzene 453. 53-amino)carbachamide [(1-{2-[(t-butoxy)carbonylamino]ethinyl) 4-[indole-(imidazol-2-ylmethyl)aminecarboxyl] (4 - piperidine 542.63 base)) methoxy]-indole-(4-ethylphenyl)carbamamine [0-(2-1:(t-butoxy)carbonylamino]ethenyl} -4-{[[3-fluoro-2-methylphenyl)methyl]amine-carbamoyl}(4·piperidinyl))methoxy]-N-[4-(trifluoromethyl) Benzene 624. 62-yl]carbamamine [(1-{2-[(t-butoxy)carbonylamino) I oxime &amp;}-4-{N-[(3-chloro-2-fluorophenyl)methyl Aminomethyl}(4-piperidinyl))methoxy]-N-[4-(trifluoromethyl)benzene 645. 04 base] formamide [(4-{N-[(2,3-dichlorophenyl)methyl]aminemethanyl}-1-{2-[(t-butoxy)carbonylamino]] Ethyl}}(4_piperidinyl))methoxy]-N-[4-(trifluoromethyl)phenyl]-. 5 decylamine ({1-(2-aminoethenyl)-4-[N-(sodium-2-ylmethyl)aminemethanyl](4-piperidinyl)}methoxy)- N-(4-ethylbenzene 442. Methyl decylamine (1-{2-[(t-butoxy)carbonylamino] acetamidine*}-4-{[N-(4-ethylphenyl)amine decyloxy] A 577. 67-based}(4-piperidinyl))-N-[(2-cyanophenyl)indenyl]cartoamine [(1-(2-aminoethyl)]-4-{N-[(3 -Fluoro-2-methylphenyl)indolyl]aminocarbazino}(4-piperidinyl))oxime 524. 51-[](Ν-[4-(trifluoromethyl)phenyl]carboxamide [(1-(2-aminoethyl)-yl]-4-{N-[(3-chloro-2-fluorobenzene) Methyl]amine carbenyl}(4-piperidinyl))methoxy 544. 93-]-N-[4-(trifluoromethyl)phenyl]carboxamide [(1·(2-aminoethenyl)-4-{N-[(2,3-diphenyl) )methyl]aminoindenyl}(4-piperidinyl))methoxy]-N-[4-(three 561. 38fluoromethyl)phenyl]carboxamide [(1-{2-[(Tertibutoxy)carbonylamino]ethinyl}-4-{&gt;1-[(3-chloro-2 - Methylphenyl)methyl]aminemethylmercapto}(4-piperidinyl))methoxy]-indole-[4.(trifluoromethyl)benzene 641·〇8-yl]carbamamine (1- (2-Aminoethyl fluorenyl)-4-{[Ν-(4-ethylphenyl)amine 曱477. 56醯-yloxy]methyl}(4-Benbityl))-Ν-[(2-cyanophenyl) 159 200823202 IC50 arithmetic mean mean ion 3. 238 M+H+ 0. 179 M+H+ 2. 288 M+H+ 0. 439 M+H+ 1. 081 M+H+ 0·158 M+H+ 11. 841 Μ+Η+ 0. 262 Μ+Η+ 0. 576 Μ+Η+ 0. 145 Μ+Η+ 0·197 Μ+Η+ 9. 436 Μ+Η+ 0. 949 Μ+Η+ m/z 518. 1 541. 1 551. 2 503. 2 606. 2 505. 2 539. 1 505. 1 481. 2 501. 1 521. 1 468. 1 483. 2 MW Chemical name methyl]carbamamine [1-(2-aminoethenyl)-4-({N-[4-(trifluoromethyl)phenyl]amine decyloxy} fluorenyl) )(4-piperidinyl)]-N-[(2-517. 5-cyanophenyl)methyl]carbamamine [(1-(2-aminoethyl)methyl]]{{--((3-methyl-2-methylphenyl)methyl]amine) }(4-piperidinyl))methoxy 540. 96-[]-N-[4-(trifluoromethyl)phenyl]carbamamine 2-({[1-(2-aminoethyl)-yl)-4-({N-[4-(trifluoro) Methyl) phenyl]amine-mercaptooxy}methyl)-4·piperidinyl]carbonylamine 550. Methyl 53-methyl}methyl)benzoate ({1-(2-aminoethenyl)-4-[N-(naphthylmethyl)aminemethanyl](4-piperidinyl)}oxime Base)-N-(4-ethylphenyl)-methyl 502. 6 decylamine [(1-{2-[(t-butoxy)carbonylamino]]indolyl}-4-{^[(2-chloro-4-fluorophenyl)methyl]aminecarboxamido }(4-(indolyl))methoxy]-N-(4-ethylphenyl)- 605. 1 decylamine [(1-(2-aminoethenyl)-4-{N-[(2-carb-4-fluorophenyl)methyl]aminemethanyl}(4-piperidinyl))曱oxy]-N-(4-5〇4·98 ethylphenyl)formamide {[1_(2_aminoethyl fluorenyl)_4-(Ν-{[2-fluoro-4-(three) Fluoromethyl)phenyl]methyl}amine-mercapto)(4-tele-based)]methoxy 53. 53 *}-N-(4-ethylphenyl)carbamamine [(1-(2-aminoethyl)-yl]-{{--((4-chloro-2-fluorophenyl) fluorenyl) Aminyl}(4_piperidinyl))methoxy]-indole-(4-5〇4·98 ethylphenyl)carbenamide [(1-(2-aminoethyl)] -4-{Ν-[(2,4-dimethylphenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy]-Ν_(4_ 480. 6-ethylphenyl)carboxamide [(1-(2-aminoethyl)methyl]-4-{Ν-[(4- gas-2-methylphenyl)methyl]amine-methylmercaptopurin-4- Brigade base)) methoxy 501. 02]-Ν-(4-ethylphenyl)carbamamine [(1-(2-aminoethyl) -4-)-[(2,4-dichlorophenyl)methyl] Aminomethyl sulfhydryl} (4-teletonyl)) methoxy]-indole-(4-ethyl 521. 44-phenyl)carbamamine [(1·(2-Aminoethyl)-4-{Ν-[(2-methyl(3-oxaridinyl))indolyl]amine-carbyl-decyl Base)) methoxy 467. 56-yl]-indole-(4-ethylphenyl)carbamamine (1-(2-aminoethyl) benzyl]{{Ν-(4-ethylphenyl)aminecarboxylideneoxy ]methyl}(4·piperidinyl))-Ν-{[2-(hydroxymethyl) 482. 57 phenyl]methyl}carbamamine 160 200823202 IC50 arithmetic mean mean ion m/z MW 0. 951 M+H+ 481. 2 480. 6 15. 191 M+H+ 458. 3 457. 95 2. 622 M+H+ 415. 1 414. 93 2. 38 M+H+ 488. 1 487. 98 0. 185 M+H+ 416. 0 415. 91 14. 906 M+H+ 485. 1 485. 02 7. 784 M+H+ 484. 1 483. 95 0. 191 M+H+ 473. 1 472. 96 14. 615 M+H+ 477. 1 476. 93 9. 212 M+H+ 459. 1 458. 94 1. 186 M+H+ 501. 1 500. 97 1. 443 M+H+ 431. 1 430. 93 0. 234 M+H+ 488. 1 487. 98 1. 857 M+H+ 473. 1 472. 96 0. 084 M+H+ 390. 1 389. 88 Chemical name [(1-(2-Aminoethyl)]-4-{N-[(2-ethylphenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy ]-N-(4-ethylphenyl)formamide (4-(2-aminoethyl)-3-{N-[(2-chlorophenyl)methyl]amine) Tillage 1)-Ν-(4-ethylphenyl)formamide N-[(2-chlorophenyl)methyl][2-({[(4-ethylphenyl)amino]carbonylamine) Methyl}methyl)3⁄4-pyridyl]carbendazim (4-(2-aminoethyl)-{{N-(4-ethylphenyl)amine-methylcarbonyl]methyl} Piperidin 1)-indole-[(2-chlorophenyl)methyl]carbamamine ((2S)-2-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl }°Byrridinyl)-N-[(2-chlorophenyl)methyl]carbenamide N-[(l-(2-aminoethyl)-[N-[(2-chloro)] Phenyl)methyl]aminomethane}}(4-piperidinyl))methyl]-2-(4-ethylphenyl)acetamidine (1-(2-aminoethyl)--4) -{[N-(4-cyanophenyl)amine decyloxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carboxamide (1- (2-Aminoethyl fluorenyl)-4-{[N-(4-methylphenyl)amine-mercaptooxy]methyl}(4-piperidinyl))-Ν·[(2-chloro Phenyl)methyl]carbamamine (1-(2-aminoethyl)--4-{ [Ν-(4-Fluorophenyl)amine-mercaptooxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carbenamide {1-(2 -aminoethenyl)-4-[(N-phenylaminodecyloxy)methyl](4-piperidinyl)}-oxime[(2-phenylphenyl)methyl]carbamidine Amine (4-{[Ν-(4-ethylmercaptophenyl)amine decyloxy]methyl}-1-(2-aminoethyl) (4-Benyl)-Ν- [(2-Phenylphenyl)indenyl]carbamamine ((5S,3R)-3-amino-5-{[Ν-(4-ethylphenyl)amine decyloxy]methyl} "Byrridinyl"-indole-[(2-phenylphenyl)methyl]carbenamide N-((5S,3R)-l-{N-[(2-phenylphenyl)methyl]amine A醯*}-5-{[N-(4-ethylphenyl)amine decyloxy]methyl}pyrrolidin-3-yl)-2-aminoacetamide N-((5S,3R) )-l-{N-[(2-Phenylphenyl)methyl]aminecarbamyl}-5-{[&gt;^(4-ethylphenyl)amine-methylcarbonyloxy]methyl P ratio (rhokidin-3-yl)acetamamine {[(2-chlorophenyl)indolyl]amino}-N-{2-[N-(4-ethylphenyl)amine decyloxy]B }}-N-mercaptomethylamine 161 200823202 IC50 arithmetic mean ion m/z MW chemical name {[(2,3-dichlorophenyl)methyl]amino}-Ν-{2·[Ν- (4-E0. 059 M+H+ 424. 1 424. 32-phenyl)amine-mercaptooxy]ethylmethylformamide [2-({[(2-chlorophenyl)methyl]amino}-Ν-(2-hydroxyethyl)). 21 M+H+ 420. 2 419. 9 carbonylamino)ethoxy]-indole-(4-ethylphenyl)carbamamine oxime-[2-({[(2-chlorophenyl)methyl]amino]- Ν-fluorenylcarbonyl) Amine 754 M+H+ 389. 1 388. 89-)ethyl][(4-ethylphenyl)amino]carbamamine [(4-{Ν-[(2·gasphenyl)methyl]aminemethano)morpholine-2- 11 . 668 M+H+ 432. 2 431. 91-yl)methoxy]-indole-(4-ethylphenyl)carbenamide-(3-aminopropyl){[(2-chlorophenyl)methyl]amine*}-Ν-{ 2-[Ν-(4-ethylphenyl)amine-mercaptooxy]ethyl 2. 543 M+H+ 433. 2 432. 94 base}carbamide 2-[(tatabutoxy)carbonylamino]-indole-[3-({[(2-)phenyl)methyl]amino}-Ν-{2-[Ν -(4-ethylphenyl)amine A. 087 M+H+ 590. 3 590. 11 mercaptooxy]ethyl}carbonylamino)propyl]acetamide 2-amino-indole-[3-({[(2-chlorophenyl)methyl]amine S}-N-{2 -[N-(4-ethylphenyl)aminemethanyloxy]ethyl 0. 188 M+H+ 490. 2 489. 99-yl}carbonylamino)propyl]acetamide N-(2-aminoethyl){[(2-chlorophenyl)indolyl]amine*}-N-{2-[N-(4-B Phenyl)amine methylmercaptooxy]ethyl 2. 83 M+H+ 419. 2 418. 92 base}carbalamine 2-amino-N-[2-({[(2-chlorophenyl)methyl]amine)}}-Ν-{2-[Ν·(4-ethylphenyl)amine Methyl methoxy] ethyl 0. 896 M+H+ 476. 2 475. 97 base}carbonylamino)ethyl]acetamide [2-(Ν-(4-aminobutyl){[(2-chlorophenyl)methyl]amino}}. 346 M+H+ 447. 2 446. 97 carbonylamino)ethoxy]-indole-(4-ethylphenyl)carbamamine 2-amino-indole-[4-({[(2-chlorophenyl)methyl]amino}-) &gt; 1-{2-old-(4-ethylphenyl)amine-mercaptooxy]ethyl 0. 223 M+H+ 504. 1 504. 02 base}carbonylamino)butyl]acetamide Ν-{2-[Ν-(4-ethylphenyl)amine-mercaptooxy]ethyl} 17. 394 M+H+ 251. 1 250. 29 acetamamine {[(2-chlorophenyl)methyl]amino}-indole-methyl-indole-[2-(indolyl-(6-quinolinyl)aminecarboxylideneoxy)ethyl] A 1. 413 M+H+ 413. 2 412. 87 amidoxime-(5-aminepentyl){[(2-phenylphenyl)methyl]amine*}-Ν-{2-[Ν-(4-ethylphenyl)amine decyloxy ] B 0. 487 M+H+ 461. 1 461 }}carbamamine {[(2·chlorophenyl)methyl]amino}-Ν-{2-[Ν-(4-ethylphenyl)aminecarboxylideneoxy]ethyl}- Ν-(4-hydroxybutyl)formamidine 0. 355 M+H+ 448. 2 447. 95 Amine (t-butoxy)-Ν·[2-(4-{Ν·[(2-bromophenyl)indolyl]amine-methylhydrazine*}-4-{[Ν-(4-ethylbenzene) Aminomethyl thiol oxide 865 M+H+ 646. 3 645. 基 嗣 甲基 嗣 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 162 168 M+H+ 545. 2 545. 47[(4-{N-[(2-Bromophenyl)methyl]aminemethanyl}-1-[2-(decylamino)ethenyl](4-piperidinyl))methoxy ]-Ν-(4·ethylphenyl)carbamamine 3. 052 M+H+ 387. 2 386. 87 Ν-[(2-Chlorophenyl)methyl]({[Ν-(4-ethylphenyl)aminemethyl methoxy)methyl}cyclopropyl)carboxamide 0. 742 M+H+ 460. 1 459. 97 4·(Ethylamino)-Ν-[(2·chlorophenyl)methyl]-2-{[Ν-(4·ethylphenyl)amine decyloxy]methyl b 2 -methylbutanamine 1. 297 M+H+ 575. 2 575. 1 4-{2-[(Tertidinoxy)carbonylamino]ethynylamino}-[(2-chlorophenyl)methyl]-2-{[Ν-(4-ethylbenzene) Aminomethyl hydrazide oxy] methyl b 2-methylbutanamine 1. 738 M+H+ 418. 1 417. 93 4-Amino-indole-[(2-chlorophenyl)methyl]-2-{[indolyl-(4-ethylphenyl)aminecarboxylideneoxy]indolyl}-2-methylbutene Guanamine 0. 283 M+H+ 475. 1 474. 98 4-(2-Aminoethylguanidino)-indole-[(2-chlorophenyl)methyl]-2-{[indole-(4-ethylphenyl)amine-methylcarbonyl] Methyl}-2-methylbutyramine 0. 235 M+H+ 403. 1 402. 91 Ν-[(2-Chlorophenyl)methyl]-4-[indole-(4-6-phenylphenyl)amine-methylcarbonyl]-2,2-dimethylbutanamine 0. 621 M+H+ 418. 2 417. 93 {[(2-Chlorophenyl)methyl]amino}-Ν-{2-[Ν-(4-ethylphenyl)amine decyloxy]-tert-butyl fluorene-N-A Base carbamide 526 M+H+ 416. 3 415. 91 (2S)-2-({[(4-ethylphenyl)amino)]carbonylamino}indenyl)pyrrolidinic acid (2-chlorophenyl)methyl ester Example ix chlorobenzyl)-3- Preparation of (5-(4-isopropylphenyl)·2Η-tetrazol-2-yl)_2,2-dimercaptopropionamide

Fluorinyl)-3-(5-(4-isopropylphenyl)-2Η_tetras-2-yl)_ 2,2-dimethylpropanamide ^

NaCN, NH4CI DMF / Addition of NaCN (2.6 g, 40.5 mmol, ΐ·4) in DMF (5 〇 163 200823202 house liter) solution of 4-isopropylbenzonitrile (4.2 g, 28.9 mmol) Equivalent) with ΝΗΑΙ (2.2 g, 4 〇 · 5 mmol, ι·4 equivalent). The reaction mixture was heated overnight with stirring. TLC showed the reaction was complete. The reaction mixture was filtered, and EtOAc was evaporated,jjjjjjjj LrmS (Μ+Η+) is /z 189.1. 〇

Crude 5-(4-isopropylphenyl)_2Η_tetrazole (1·〇g, ~5.3 mmol), 3-hydroxy-2,2-dimercaptopropionate (830 mg, 8 DEAD (1.35 mL, 8.0 mmol) was added dropwise to a solution of THF (5 mL) in THF (5 mL). The reaction mixture was stirred for 2 hours. LC/MS showed the reaction was complete. The reaction mixture was filtered and purified using EtOAc EtOAc (EtOAc) Methyl propyl propionate (480 mg, 32% in two oxime steps). LRMS (M+H+) m/z 303.2.

Methyl 3-(5-(4-isopropylphenyl)-2H-tetrazol-2-yl)-2,2-dimethylpropanoate (210 mg, 0.69 mmol) with 2-chloro To a mixture of benzylamine (π 7 mg, 0.97 vaole) in toluene (1 mL) was added dropwise EtOAc (2 EtOAc, &lt;RTIgt; The reaction mixture was stirred for 30 minutes, 164 20 200823202 and then stirred at 100 ° C for 1 hour. The reaction was cooled and the reaction was qu The organic layer was separated, washed with brine, dried over Na 2 EtOAc and filtered. The filtrate was concentrated under reduced pressure to give a crude oil. This crude mixture was purified by RP-HPLC using a mixture of acetonitrile and H20 to give 5 bis-(2-chlorobenzyl)-3-(5-(4-isopropylphenyl)-2H-tetrazole-2. Base 2,2-dimethylpropanamide (217 mg, 76%). LRMS (M+H+) w/z412.2 〇

Example X

Preparation of I gas benzyl)_:!_((-(4-ethylphenyl)-2Η·tetrazol-2-yl)methyl)cyclopropanoguanamine

#-(2-Azylbenzyl)-1-((5-(4-ethylphenyl)-2Η·tetrazol-2-yl)methyl)cyclopropanecarbamide 10

Add HATU (1.98 g, 5.2 mmol, 1.5 eq.) to 2-chlorobenzylamine in a solution of 15 μM (5 liters) of 1β(methoxycarbonyl)cyclopropanecarboxylic acid (500 mg, 3.5 mmol). (622 μl, 5.2 mmol, ι·5 equivalent). The reaction mixture was disrupted for 2 hours. The reaction mixture was purified twice with EtOAc (EtOAc m. LRMS (M+H+) m/z 268.0. 165 200823202 h3co

NaBH4 CH3OH, THF

Add borofluoride sodium to a solution of hydrazine 1-(2-chlorobenzylamine decyl)cyclopropanecarboxylate (330 mg, 1.2 mmol) in THF (5 mL) and CH3OH (5 mL) (93 mg, 2.4 mmol, 2 equivalents). The reaction mixture was stirred for 5 hours, and quenched with dilute AcOH. The reaction mixture was concentrated and taken up in EtOAc. The organic layer was washed with saturated NaHCO.sub.3, H.sub.2, and brine. The residue was purified on RP-HPLC using EtOAc EtOAc EtOAc (EtOAc) LRMS (M+H+) m/z 10 240 ·0.

N*NH PPh3, DIAD, THF

Add a solution of #-(2-chlorobenzyl)-1-(hydroxymethyl)cyclopropanecarbamide (164 mg, 〇·69 mmol, 2 eq.) in THF (2 mL) (180 mg, 0.69 mmol, 1 equivalent), DIAD (140 μl, 0.69 15 mmol, 1 equivalent) and 5-(4-ethylphenyl)-2Η-tetrazole (120 mg, 0.69 mM) Moore). The reaction mixture was stirred for 3 hours and concentrated. The residue obtained was purified by RP-HPLC using a mixture of acetonitrile and hydrazine 20 to give #-(2-chlorobenzyl)-1-((5-(4-ethylphenyl)-2-indole-tetrazol-2-yl) Methyl)cyclopropanecarbamide (95 mg, 74%). LRMS (Μ+Η+) m/z 396.1. 166 200823202

EXAMPLE XI ADDITIONAL SYNTHETIC COMPOUNDS The compounds in the table below were synthesized and tested using procedures similar to those described herein. IC50 median value ion m/z target substance _MW 4 匕 scientific name 17.72 M+H+ 384.1 383.87 N-[(2-chlorophenyl)methyl]-3-{5-[4-(methylethyl)benzene (1,2,3,4-tetrazol-2-yl)}propanamine 41.00 M+H+ 378.2 377.48 2,2-dimethyl-3-{5-[4-(mercaptoethyl) Phenyl](1,2,3,4-tetrazol-2-yl)}-:^-benzylpropanamide 48.08 M+H+ 379.3 378.47 2,2-dimethyl-3-{5-[4 -(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}-N-(2-pyridylmethyl)propanamine 10.37 M+H+ 396.2 395.47 N-[ (2-fluorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazole-2- Benzoamine 6.79 M+H+ 392.3 391.51 2,2-Dimethyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazole-2 -based)}-:^-[(2_methylphenyl)methyl]propanamine 44.20 M+H+ 396.2 395.47 Ν·[(3·fluorophenyl)methyl]-2,2·dimethyl -3-{5-[4-(methylethyl)phenyl](123,4-tetrazol-2-yl)}propanamine 52.73 M+H+ 426.2 425.95 Ν-[2-(2-chlorobenzene) Ethyl] 2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](123,4-tetrazol-2-yl)}propanamide 33.81 M+H+ 384.2 383.51 2,2-two 3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}-indole-(3-thienylmethyl)propanamide 75.92 M+H+ 369.3 368.43 2,2-Dimethyl-3-{5-[4·(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}-bei -(1,3-oxazol-2-ylmethyl)propanamide 1.99 M+H+ 398.2 397.9 (10)-Chlorophenyl^-^-yt-7-ethylphenyl) (1,2,3,4 -tetrazol-2-yl)]-2,2-dimethylpropanamide 7.44 M+H+ 454.1 453.85 ^-[(2-chlorophenyl)methyl]_2,2-dimethyl-3-{ 5-[4-(Trifluoromethoxy)phenyl](1 2 3 4-tetrazol-2-yl)}propanamine 15.58 M+H+ 462.2 461.94 Ν-[(2-chlorophenyl)methyl ]_2,2-Dimethyl-3-[5-(4-phenoxyphenyl)(1,2,3,4-tetrazol-2-yl)]propanamine 5.97 M+H+ 430.1 429.92 Ν- [(2_Chloro-4·fluorophenyl)methyl μ2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1 2 3 4tetrazol-2-yl) }Propylamine 200823202 IC50 The median value of the ion m/z _MW 4 匕 scientific name N-[(2,4-chlorophenyl) fluorenyl]-2,2-dimethyl--3-{5-[ 4-(methylethyl)phenyl](1,2,34^yl)}propanamine N-[(6-chloro-2-phenylene)methyl]-2,2-dimethylpyr 3-{5·[4·(A Ethyl ethyl) phenyl κ1,23 fluorenyl)}propanamine ^ 2' 4-[(2,2-dimethyl-3-{5-[4-(methylethyl)benzene 22.81 M+H+ 446.2 446.37 59.08 M + H+ 430.2 429.92 89.13 M+H+ 422.2 421.49 base](1,2,3,4-tetrazol-2-yl)}propanylamino)benzoic acid T 3·[5-(4 - (Phenylphenyl)(1,2,3,4-tetras-2-yl)]-indole-[(2-chlorophenyl)methyl]_2,2-dimethyl 3.92 M+H+ 448.1 448.74 Amine N- [(2,3-dichlorophenyl)methyl]·2,2-dimethyl 3-{5-[4-(methylethyl)phenyl](1,2,3,"tetrazole 3.42 M+H+ 446.2 446.37 base)}propanolamine-[(2-chlorophenyl)methyl]-3-[5_(4-cyanobenzene 58.92 M+H+ 395.1 394.86 base) (1,2,3,4 -tetras-2-yl)]-2,2-dimethylpropanol 3-{5-[4-(dimethylamino)phenyl](1,2,3 4-tetrazole·2_yl )}-Ν-[(2-chlorophenyl)methyl]_2,2-dimethylpropene 3.63 M+H+ 413.2 412.92 Amine 4-[2-(2-{Ν-[(2-phenylphenyl) )methyl]aminemethanyl 2_ 5.73 M+H+ 428.1 427.88 methylpropyl)-1,2,3,4-tetras-5-yl]benzoic acid methyl hydrazine-[(2-chlorobenzene) Methyl)-3-{5-[4-(methyl)phenyl](1,2,3,4-tetrazole-2-yl)}-2,2-dimethylpropyl ugly 6 4.49 M+H+ 400.1 399.87 Amidoxime-[(2-chlorophenyl)methyl]-2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](1,2 , 3,4-tetras-2. 2.63 M+H+ 412.1 411.93 base)}propanamine 1^-[(2-chlorophenyl)methyl]-2,2-dimethyl-3-{2-[ 4-(methylethyl)phenyl](ι,2,3,4-tetrasa_5- 35.77 M+H+ 412.1 411.93 base)}propanamine oxime-[(2-phenylphenyl)methyl] -2-methyl-3-{2-[4-(methyl 50.73 M+H+ 398.1 397.9 ethyl) benzyl](1,2,3,4-tetras-5-yl)} propylamine -[(2-chlorophenyl)methyl]-3-{3-[4-(mercaptoethyl)benzene 53.34 M+H+ 384.1 383.87 base](1,2,4-oxadiazol-5-yl )}propanamine 2-(2,2-dimethyl-3-{5-[4-(methylethyl)phenyl](l,2,3,4-tetrazol-2-yl)} Propionylamino)_2-(2- 15.25 M+H+ 470.1 469.96 chlorophenyl)acetic acid methyl ester]^-[1-(2-chlorophenyl)-2-ethyl]-2,2-di Methyl-3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetras-2-5.36 M+H+ 442.1 441.95 base)}propanamine Ν-[( 2-chlorophenyl)methyl]({[5-(4·ethylbenzene 0.48 M+H+ 396.1 395.89 base) (1,2,3,4-tetrazol-2-yl)]methyl}cyclopropane Base) Hyperthyroidism 168 200823202 IC50 Median Ion m/z target _MW 1.57 M+H+ 410.1 409.91 10.90 M+H+ 440.1 439.94 1.10 M+H+ 422.1 421.92 2.64 M+H+ 456.1 455.94 14.32 M+H+ 404.0 404.29 5.06 M+H+ 400.1 399.87 36.18 M+H+ 426.2 425.95 7.34 M+H+ 384.1 383.87 34.04 M+H+ 404.1 404.29 14.98 M+H+ 438.1 437.85 43.53 M+H+ 384.2 383.87 8.70 M+H+ 436.1 435.91 26.96 M+H+ 370.1 369.85 14.92 M+H+ 399.0 398.89 Chemical name amine N-[(2 -Chlorophenyl)methyl]({[5-(4-ethylphenyl)(1,2,3,4·tetrazol-2-yl)]methyl}cyclobutyl)carboxamide N- [(2-Chlorophenyl)methyl](4-{ [5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]indenyl}(2H_3,4 ,5,6-tetrahydrofuran-4-yl))carbenamide·[(2-chlorophenyl)methyl](1-{[5-(4-ethylphenyl)(1,2) ,3,4-tetrazol-2-yl)]methyl}cyclopent-3-enyl)carbamamine-[(2-chlorophenyl)methyl](1-{ [5-(4- Ethylphenyl)(1,2,3,4-tetrazol-2-yl)]methyl}-3,4-dihydroxycyclopentyl)carbenamide 3-[5-(4-chlorophenyl) (1,2,3,4-tetrazol-2-yl)]-indole-[(2-chlorophenyl)methyl]-2,2-dimethylpropionamide N-[(2-chloro Phenyl)methyl]-3_ [5-(4-methoxyphenyl)(1,2,3,4-tetrazol-2-yl)]-2,2-dimethylpropanamide 3-{5-[4-(third Butyl)phenyl](1,2,3,4·tetrazol-2-yl)}-N-[(2-chlorophenyl)methyl]-2,2-dimethylpropanamide N- [(2-Chlorophenyl)methyl]-2,2-dimercapto-3-[5-(4-methylphenyl)(1,2,3,4-tetrazol-2-yl)] Propionamide 3-[5-(3-chlorophenyl)(1,2,3,4-tetrazol-2-yl)]-indole-[(2-chlorophenyl)methyl]-2,2 - dimethylpropionamine N-[(2-chlorophenyl)methyl]-2,2-didecyl-3-{5-[4-(trifluoromethyl)phenyl](1,2 ,3,4-tetrazol-2-yl)}propanamine ^[-[(2-chlorophenyl)methyl]-2,2-dimethyl-3-[5-(3-methylbenzene (1,2,3,4-tetrazol-2-yl)]propanamine N-[(2-chlorophenyl)methyl]-3-[5-(4-miquidylphenyl) (1,2,3,4-tetrazol-2-yl)]-2,2-dimethylpropanamide (2S)_N-[(2·chlorophenyl)methyl]-2-methyl- 3-[5-(4-methylphenyl)(1,2,3,4-tetrazol-2-yl)]propanamine {[(2-chlorophenyl)methyl]amino}-N -{2-[5-(4-ethylphenyl)(1,2,3,4-tetrazol-2-yl)]ethyl}-1^methylcarbamide 169 200823202

Example XII Screening assay using an ATPase assay coupled with pyruvate kinase and lactate dehydrogenase containing the following reagents: Potassium PIPES (50 mM), MgCl2 (3 mM), KC1 (100 mM), ATP (0.15) mM), DTT (1 5 mM), BSA (0.1 mg/ml), NADH (0.5 mM), PEP (1.5 mM), pyruvate kinase (4 units/ml), lactate dehydrogenase (8 units / ml), with defoamer (50 ppm) (the concentration shown is the final test concentration). The pH was adjusted to 6.80 by the addition of potassium hydroxide at 22 °C. Lead optimization experiments using the more sensitive pyruvate kinase/horseradish peroxidase/pyruvate oxidase-conjugated 10 ATPase assay with the following reagents: potassiuin PIPES (12 mM), MgCl2 (2 mM), KC1 (100 mM), ATP (0·15 mM), BSA (0.05 housew/home liter), indeed: acid unloading (2 mM), amplex red (0·1 mM), PEP (0 · 1 mM), pyruvate kinase (4 units / ml), horseradish peroxidase (0.5 units / ml), pyruvate oxidase (〇 · 5 units / 15 liters), and defoamer (50 Ppm) (the concentration shown is the final test concentration). The pH was adjusted to 7.00 at 22 ° C by the addition of potassium hydroxide. The specific protein component of this test is the chemical cross-linking of the heart or bone with the excess of 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride and hydroxyammonia imine. Road actin chicken face smooth muscle myosin 20 fragment-1 (subfragment-l). In this test, the exact concentration of cross-linked smooth muscle myosin was determined experimentally: titration was used to achieve the desired rate of ATP hydrolysis. Since the fractions of the active molecules in the preparations are different, the concentrations differ between different protein preparations. In the compound dose response test, the 170 200823202 dilution series of test compounds are first prepared, each containing potassium PIPES, MgCl2, KCl, ATP, B SA, acid-filled clock, Anles red, PEP, cross-linked smooth muscle myodynamics. Globulin (secondary fragment-1), defoamer, and test mixture with water. The test was started by adding an isotonic solution containing potassium Pipes, MgCl2, KCl, BSA, potassium phosphate, 5 pyruvate kinase, horseradish peroxidase, pyruvate oxidase, antifoaming agent, and water. The ATP hydrolysis was detected by measuring the fluorescence of Anres red (excited at 480 nm and emitted at 615 nm). The resulting dose response curve is in accordance with the 4-parameter equation y: = lowest value + ((highest value - lowest value) / (i + ((iC5 〇 / xrmii)))). 1C5. Defined as ATP enzyme activity between the highest dose 10 curve Concentration intermediate to the lowest value. The specific chemical described herein has an IC5G value of less than 10 μΜ, for example, less than 1 μΜ. As discussed above, the specific example of the invention is the invention, and those skilled in the art should understand Various changes and substitutions of equivalents may be made without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, material composition, procedure, procedure, or procedure to the invention. Purpose, spirit and scope. All such modifications are intended to be included within the scope of the accompanying patent application.

Claims (1)

200823202, the scope of application for patents: a salt of at least one chemical from the compound of formula X, acceptable salt, on Shangle (R?)m wherein 10 15 u is selected from an optionally substituted aryl group, optionally substituted cycloalkyl group, optionally substituted heterocycloalkyl group, optionally substituted hetero group, and IM^COW2 (where "*,, indicates a point of attachment to ζι); ', the squares W1 and W2 are independently selected from CRnR12, NR13, and 〇; but at least one of W1 and W2 is NR13; W3 is selected from cWR2 , NR14 and 0; Z1 is aryl; Z is aryl; R8 is selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted a heteroaryl group, optionally substituted heterocycloalkyl; R1, R2, R11, and Ri2 are independently selected from the group consisting of hydrogen, hydroxy, carboxy, optionally substituted alkyl, optionally substituted naphthenic Alkenyl group, optionally substituted alkenyl group, optionally substituted alkynyl group, optionally substituted alkoxy group, optionally substituted aryloxy group, optionally substituted 172 20 200823202 heteroaryloxy, visual A substituted heterocycloalkyloxy group, an optionally substituted aminocarbonyloxy group, an optionally substituted methoxy group, A substituted alkoxycarbonyloxy group, optionally substituted alkoxycarbonyl group, optionally substituted amine group, optionally substituted aryl group, optionally substituted hetero 5 aryl group, optionally substituted a heterocycloalkyl group, optionally substituted amine carbonyl, and optionally substituted amino sulfonyl; or R1 and R2, together with any intervening atom to which they are attached, may be formed, optionally substituted a group of a cycloalkyl group and optionally a substituted heterocycloalkyl group; 10 R13 and R14 are independently selected from the group consisting of an anthracene, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, optionally substituted. An aryl group, optionally substituted heteroaryl, and optionally substituted heterocycloalkyl; in each case, R3, R4, R5, and R6 are independently selected from hydrogen, hydroxy, and optionally substituted Alkyl, optionally substituted cycloalkyl, 15 optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally Substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, A substituted aminocarbonyloxy group, an optionally substituted alkoxy group, an optionally substituted alkoxycarbonyloxy group, an optionally substituted thiol group, and optionally a 20-alkyl alkoxycarbonyl group, A substituted amino group, optionally substituted aryl group, optionally substituted heteroaryl group, optionally substituted heterocycloalkyl group, optionally substituted amine carbonyl group, and optionally substituted amino group are required. a sulfonyl group; or R1 and one of the R5 groups may be combined with any intervening 173 200823202 to form a group selected from optionally substituted cycloalkyl groups and optionally substituted heterocycloalkyl groups; Or R14 and one of the R5 groups may be combined with any intervening atom to form an optionally substituted heterocycloalkyl ring; 5 or if W1 is NR13, then R13 and R1 may be optionally combined with any atom in between. Combining together to form an optionally substituted heterocycloalkyl ring; or if W1 is NR13, R13 and one of R5 may be bonded together with any intervening atom to form a heterocycloalkyl ring optionally substituted 10 ; R7 and R 1G is independently selected from the group consisting of hydrogen, cyano, halo, hydroxy, carboxy, azide, fluorenyl, fluorenyl, fluorenyl, thiol, optionally substituted alkoxy, optionally Substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally Substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted A substituted amine group, an optionally substituted thiol group, an optionally substituted amine carbonyl group, an optionally substituted aminosulfonyl group, and optionally a substituted fluorenyl group are required; m is selected from 0 1, 2, and 3; w is selected from 0, 1, 2, 3, and 4; the line is selected from 1, 2, and 3; and the line is selected from the group consisting of 〇, 1, 2, 3, and 4. 174 200823202 2. At least one of the chemicals of claim 1 wherein the compound of formula X is selected from the group consisting of compounds of formula I Wherein W and W2 are independently selected from the group consisting of CRUR12, NR13, and Ο; but at least one of W1 and W2 is nr13; ^ W3 is selected from cWr2, NR14 and 〇; Z1 is aryl; 10 Z2 is aryl R8 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted heterocyclic ring. Alkyl; R1, R2, R11, and R12 are independently selected from the group consisting of hydrogen, hydroxy, carboxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally Substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted Aminocarbonyloxy, optionally substituted methoxy, optionally substituted alkoxycarbonyloxy, 20-substituted alkoxycarbonyl, optionally substituted amine, optionally substituted Aryl, optionally substituted 175 200823202 aryl, optionally substituted heterocycloalkyl, as needed Substituted amine carbonyl, optionally substituted aminosulfonyl; or R1 and R2 together with any intervening atom attached thereto, forming a cycloalkyl group optionally substituted with and optionally substituted a group of 5 heterocycloalkyl; R13 and R14 are independently selected from the group consisting of hydrazine, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted a heteroaryl group, optionally substituted heterocycloalkyl; in each case, R3, R4, R5, and R6 are independently selected from the group consisting of hydrazine, 10 hydroxy, optionally substituted alkyl, optionally substituted a cycloalkyl group, optionally substituted alkenyl group, optionally substituted alkynyl group, optionally substituted alkoxy group, optionally substituted aryloxy group, optionally substituted heteroaryloxy group, A substituted heterocycloalkyloxy group, optionally substituted aminocarbonyloxy group, optionally substituted anthraceneoxy group, optionally substituted 15 alkoxycarbonyloxy group, optionally substituted fluorenyl group , if desired, substituted alkoxycarbonyl, optionally substituted amino group, as needed Substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine carbonyl, optionally substituted aminosulfonyl; 20 or R1 and present One of R5 may optionally be combined with any intervening atoms to form a group selected from optionally substituted cycloalkyl and optionally substituted heterocycloalkyl; or R14 and one of R5 may be present as desired The intervening atoms are joined together to form an optionally substituted heterocycloalkyl ring; 176 200823202 or if W1 is NR13, then R13 and R1 may be combined with any intervening atom to form an optionally substituted heterocyclic ring. Or an alkyl group; or if W1 is NR13, R13 and one of R5 may be combined with any atom in between to form an optionally substituted heterocycloalkyl ring; R7 and R10 are independently selected from Hydrogen, cyano, halo, hydroxy, carboxy, azide, prosthetic, fluorenyl, fluorenyl, thiol, optionally substituted alkoxy, optionally substituted aryloxy, Replace 10 as needed An oxy group, optionally substituted heterocycloalkyloxy group, optionally substituted alkoxycarbonyl group, optionally substituted alkyl group, optionally substituted cycloalkyl group, optionally substituted alkenyl group, A substituted alkynyl group, optionally substituted aryl group, optionally substituted heteroaryl group, optionally substituted heterocycloalkyl group, optionally substituted amino group, optionally substituted 15 Substituted, optionally substituted amine carbonyl, optionally substituted aminosulfonyl, optionally substituted formazan; W is selected from 0, 1, 2 and 3; w is selected from 〇, 1, 2, 3, and 4; 夕 is selected from 1, 2, and 3; and 20 is selected from 0, 1, 2, 3, and 4. 3. For example, at least one chemical of claim 2, wherein W1 is NR13. 4. The at least one chemical of claim 3, wherein R13 is selected from the group consisting of hydrogen and optionally substituted lower alkyl. 177 200823202 5. At least one chemical as claimed in claim 4, wherein R 3 is selected from the group consisting of hydrogen and lower leuco. 6. At least one of the chemicals of claim 5, wherein rU is hydrogen. 7. At least one of the chemicals of claim 3, wherein w1 is CRnR12. And at least one chemical of claim 8 wherein R: and 10 R are each independently selected from the group consisting of hydrogen and optionally substituted lower alkyl 9 · at least one chemical as claimed in claim 9 Wherein rU and Rl2 are each independently selected from the group consisting of hydrogen and lower alkyl. 10. A chemical according to claim 9 wherein at least one of R11 and R12 is hydrogen. </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; 13. The at least one chemical of claim 12, wherein Rn η /, R are each independently selected from the group consisting of hydrogen and optionally substituted lower alkyl. The at least one chemical of claim 13 wherein R11 1 is each independently selected from the group consisting of hydrogen and lower alkyl. 5. If at least one of the chemicals of claim 14 is claimed, both Rn and R12 in the bean are hydrogen. VIII 6 · If you apply for the patent range 2 to the school, where W2 is NR13. At least one of the 11 items 178 200823202 17. The at least one chemical of claim 16 wherein y3 is selected from the group consisting of hydrogen and optionally substituted lower alkyl. 18. The at least one chemical of claim 17, wherein r1s is selected from the group consisting of hydrogen and lower alkyl. And at least one chemical as claimed in claim 18, wherein Ri3 is hydrogen. The at least one chemical of any one of claims 2 to 6, wherein W2 is hydrazine. Worker 21. At least one chemical product of any one of claims 2 to 20 wherein W3 is CR1r2. 22. The at least one chemical of claim 21, wherein R1 and R2 are independently selected from the group consisting of hydrogen and optionally substituted alkyl. 23. The at least one chemical of claim 22, wherein R1 Μ 2 and & are independently selected from the group consisting of hydrogen and optionally substituted lower alkyl. 4. The at least one chemical of claim 23, wherein R1 and R2 are independently selected from the group consisting of hydrogen and lower alkyl. 25. The at least one chemical of claim 24, wherein Ri and R2 are independently selected from the group consisting of hydrogen and methyl. 20% wind, at least one of any one of claims 2 to 21, wherein R1 and R2, together with the carbon to which they are attached, form a cycloalkyl group selected from the group which is optionally substituted and optionally a group of a substituted heterocycloalkyl group. 7. The at least one chemical of claim 26, wherein Ri-R, together with the carbon to which it is attached, is selected from the group consisting of cyclopropyl, cyclobutyl, 179 200823202 cyclopentyl, cyclohexyl, chiral a group with tetrahydroanthracene, wherein each group is substituted as needed. 28. The at least one chemical of claim 27, wherein R and R2, together with the carbon to which they are attached, form a group selected from the group consisting of piperidine and tetrahydropyran 5, wherein each group is optionally 2_Aminoethyl hydrazino or 2-gas tert-butoxycarbonylamino) ethinyl substituted. 29. The at least one chemical of claim 28, wherein r1 and R2, together with the carbon to which they are attached, form a tetrahydropyran, 1-(2-(t-butoxycarbonylamino) acetamidine. a group of a piperidinyl group and an amino group 10 acetyl group). 3. A chemical product according to any one of claims 2 to 20, wherein W3 is NR14. 31. The at least one chemical of claim 30, wherein Ri4 is selected from the group consisting of hydrogen and optionally substituted lower alkyl. 15 32. The at least one chemical of claim 31, wherein Ri4 is selected from the group consisting of hydrogen, lower alkyl, and alkoxy selected from the group consisting of hydroxyl groups, optionally substituted amine groups, and optionally substituted alkoxy groups A lower alkyl group substituted with one or two groups. 33. At least one chemical according to claim 32, wherein R14 2 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and isopropyl, wherein methyl, ethyl, propyl, and iso are The propyl group is optionally substituted with one or two groups selected from the group consisting of a hydroxyl group, an optionally substituted amino group, and an optionally substituted alkoxy group. 34. At least one chemical according to claim 33, wherein ri4 180 200823202 is selected from the group consisting of hydrogen, mercapto, ethyl, propyl, and isopropyl, wherein methyl, ethylpropyl, and isopropyl The base view needs to be replaced by one or two warp groups. 35. / at least one of the chemicals of claim 34, wherein y4 is selected from the group consisting of methyl, ethyl, hydroxymethyl, 2-hydroxyethyl, and isopropyl. 5 36. The at least one chemical of claim 35, wherein Ri4 is selected from the group consisting of methyl and hexyl. And at least one of the chemical mouths of any one of claims 2 to 36 wherein R is selected from the group consisting of hydrogen and optionally substituted lower alkyl. 38' At least one chemical as claimed in claim 37, wherein R8 10 is selected from the group consisting of hydrogen and lower alkyl. 39. For example, at least one chemical of claim 38, wherein y is selected from the group consisting of hydrogen and methyl. 4〇·,, at least one chemical of claim 39, wherein rS is iron^. At least one chemical according to any one of claims 2 to 40, wherein 9 is 2. 42. At least one of the chemicals of any one of claims 2 to 4, wherein g is 1. 43. At least one chemical as claimed in claim 42 and wherein the 5G is selected from the group consisting of hydrogen and a lower-grade hospital base that is optionally replaced. 44. The at least one chemical of claim 43, wherein R5 is selected from the group consisting of hydrogen, lower alkyl, and alkoxy optionally substituted, optionally substituted alkoxy, Substituted alkoxycarbonyl, hydroxy, optionally substituted amine, optionally substituted amine carbonyl 181 200823202, fluorenyl, substituted with one, two or three groups of azide Burning base. 45. At least one chemical according to claim 44, wherein R5 is selected from the group consisting of hydrogen, lower alkyl, and selected from 4-(lower alkyl) piperazine; μ5-based, keto-based piperene 1_yl, morpholinyl, benzyloxy, benzyloxycarbonyl, methoxycarbonyl, hydroxy, amine, diammonium, anthracenyl, fluorenyl, ethyl fluorenyl Lower alkyl substituted with one, two, or three groups of an azide group. 46. At least one chemical according to claim 45, wherein R5 10 is selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, isobutyl, n-propyl, n-butyl, n-pentyl, iso Amyl, and 4-methylpentyl, wherein methyl, ethyl, isopropyl, isobutyl, n-propyl, n-butyl, n-pentyl, isopentyl, and 4-decylpentyl Is selected from the group consisting of 4-methyl hydrazine, 3-ketopiperidin-1, morpholinyl, benzyloxy, benzyloxycarbonyl, methoxycarbonyl, 15 hydroxy, amine, dimethylamino, A methoxy(methyl)amine, a decyl group, an acetamino group, an ethyl fluorenyl group, and one, two, or three groups of an azide group are substituted. 47. At least one chemical as claimed in claim 46, wherein R5 is selected from the group consisting of hydrogen, ethyl, 2-(benzyloxy)-2-oneethyl, benzyloxymethyl, isobutyl, iso Propyl, methyl, 2-hydroxyethyl, 2-methoxy-2-ketoethyl, 20 3 _(benzyloxyketonepropyl, 3-hydroxypropyl, 3-methoxy-3-one Propyl, 4-aminobutyl, 4-azidobutyl, 4-dibutyl, 4-methoxy-4-ketobutyl, light methyl, 2-cysyl-2-methylpropane 4-, 4-yl-based 4-methylpentyl, 3-aminopropyl, (4-methylpiperidin-1-yl)methyl, 2 gas ketone ketone + ethyl), TV - morphinylethyl, morphinylmethyl, (3_keto-based koukou 182 200823202 -1·yl) methyl, (methyl-methyl-peptid-1)-ethyl, (diamine Base, fluorenyl, (R)&gt;&quot;2-hydroxypropyl, (S)·2·hydroxypropyl, 2—(oxiranyl (fluorenyl)amino)_2-_ethyl, 3-(methoxy (Methyl)amino)-3-ketopropyl, 3•hydroxy-3-indolylbutyl, 3-hydroxybutyl, 'acetamidobutyl, 4-hydroxypentyl, and '5-based. The invention is the at least one chemical of claim 42, wherein R6 is selected from the group consisting of hydrogen and a lower alkyl group which is optionally substituted. 49. The at least one chemical of claim 48, wherein R6 is selected from the group consisting of hydrogen and lower alkyl. For example, at least one chemical of claim 49, wherein r6 is hydrogen. 51. According to at least one chemical of claim 2, wherein w2 is NH' W1 is 〇, and W3 is cr1r2. 52. If at least one of the chemicals in the second paragraph of the patent application is applied, 15 is Cong' W1 is CH2, and W3 is NR14. • For example, at least one of the chemicals in the second paragraph of the patent application, where w2 is bribe, Wi is 〇, and W3 is 14. 54. At least one chemical product according to any one of claims 2 to 53 wherein w is 〇. 20 Hurricane u is at least one of any one of claims 2 to 53: the mouth is selected from the group consisting of i and 2, and each R7 is selected from the group consisting of a halogen group and an alkyl group to be substituted. base. 6.7 The at least one chemical of claim 55, wherein each R is selected from the group consisting of a dentate group and a lower leuco group which is optionally substituted. 183 200823202 57.  The at least one chemical of claim 56, wherein each R7 is selected from the group consisting of a halogen group and a lower alkyl group. 58.  For example, at least one chemical of claim 57, wherein each R7 is selected from the group consisting of a chlorine group, a fluorine group, and a methyl group. 5 59. At least one chemical of claim 55, wherein _(R)m', together with the phenyl ring to which it is attached, is selected from the group consisting of 2-chlorophenyl, 2-methylphenyl, 2- Chloro-4-fluorophenyl, 2-chloro-3-fluorophenyl, 2,3-dichlorophenyl, 2,3-difluorophenyl, 2,4-dichlorophenyl, 2,4_2 a group of a fluorophenyl group and a 3-chloro-2-fluorophenyl group. At least one chemical of any one of claims 2 to 59, wherein W is selected from the group consisting of 1 and 2. 61. For example, at least one chemical of claim 60, where &quot; is 1 〇 15 20 62. And at least one of the two or two types of the patent application range of any one of claims 2 to 4 is independently selected from the group consisting of hydrogen and at least one of the chemicals which are required to be substituted by the 'Π* request patent range 62, Each methyl group is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, and at least one of the chemicals of the 'dt range 63, each of which is 65. Γ Γ Λ Λ Λ Λ Λ 第 第 第 第 第 第 第 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 if if if if if if if if if if if if if if if if if if if if If necessary, replace the diluted base, and if necessary, 184 200823202 by 66, substituted aryl 5 10 15 20 71 as claimed in the third paragraph of the patent scope. At least one chemical, 67. If you apply for the patent scope, item 5, 5, you are selected, And each Rl〇,  ^ kinds of chemicals, Where Ρ replaces p A φ ^ , , Independently selected from #基, Aryl group, as needed Depending on the county to be At least one of the chemicals in the scope of item 67, as required, Each of them is independently selected from the record, Low-grade base, as needed Substituted lower alkenyl, A phenyl group substituted as needed.  69 such as at least one chemical of claim 68, Wherein each R is independently selected from a chlorine group, Fluorine-based, Moji, Tri-gas methyl, methyl,  Ethyl, Vinyl, With phenyl.  7〇· ι, Applying at least one chemical of Article 65 of the patent scope, Where (R )p, Together with the phenyl ring to which it is attached, Forming a selected from 6-methylphenyl group, 5-ethylphenyl, 4-methylphenyl, 5_methylphenyl, 5, 6-dichlorophenyl, 5, 6·difluorophenyl, 5, 6-dimercaptophenyl, 5_bromophenyl, % phenyl base, 5-vinylphenyl, 6·fluorophenyl, 5-fluorophenyl, With a 6-trifluoromethylphenyl group.  • At least one chemical as claimed in item 2 of the patent scope, Wherein the compound of formula I is selected from the group consisting of {[(2-chlorophenyl)methyl]amino}-N-indolyl-indole-[2·(Ν-(2-naphthyl)amine fluorenyloxy) Ethyl]carbamamine {[(2, 3-Dichlorophenyl)methyl]amino}-Ν-{2-[Ν-(4-ethylphenyl)amine A is P 185 200823202 acid oxy]ethyl}-N_methyl A Indoleamine [(l-(2-fe-ethylidene)-4·{Ν-[(3-fluoro-2-indenylphenyl)methyl]amine)](4-piperidinylmethoxy) Base&gt;; ^-(4_Ethylphenyl)formamidine [(1-(2-aminoethyl)-)-[indole-[(3-chloro-2-methylphenyl)methyl]amine formazan ((4-piperidinyl))methoxy]_Ν_(4-ethylphenyl)formamide {1-(2-aminoethenyl)-4-[(Ν-(2-naphthyl) Aminomethyl methoxy)methyl](4-bryridinyl)}-v_[(2-chlorophenyl)methyl]carbenamide {[(2-chlorophenyl)methyl]amino} _Ν_{2_[Ν_(Heartylethylphenyl)amine 曱 ethoxy]ethyl}methylmethamine {[1-(2-aminoethyl fluorenyl)-4-(Ν_{[2 gas three Fluorofluorenyl)phenyl]indolyl}aminocarboxamido) (hydroxypiperidinyl)]methoxy}-indole-(4-ethylphenyl)carboxamide [(1_(2_Aminoethyl hydrazide) Base)_4-{Ν-[(2, 3-dichlorophenyl)indenyl]amine-carbamoyl}(4-piperidinyl))methoxy]-indole-(4-ethylphenyl)decylamine [(1-(2-amino) Ethyl)-4-{Ν-[(3-chloro-2-fluorophenyl)indolyl]aminoindenyl}(4-bromodinyl))methoxy]-indole-(4-ethyl Phenyl) decylamine (1-(3-amino-2-hydroxypropionyl)_4_{[Ν-(4-ethylphenyl)amine decyloxy]fluorenyl}(4_piperidine) Base))-Ν-[(2-chlorophenyl)indolyl]carbamamine (1-(2, 3-dihydroxypropionyl)-4-{[indolyl-(4-ethylphenyl)amine decyloxy]methyl}(4-piperidinyl))-indole_[(2-chlorophenyl)曱 曱醯]] guanamine (l-((2S)-2-amino-3-hydroxypropanyl)_4_{[Ν_(4_ethylphenyl)aminecarboxylideneoxy]methyl}( 4-piperidinyl))-Ν^(2-chlorophenyl)methyl]methaneamine {1-(2-aminoethenyl)_4-[(indole-hydroquinone-5-ylamine fluorenyl) Oxy)methyl](4-piperidinyl)}-oxime [(2-chlorophenyl)methyl]decylamine [l_((2S)-2-amino-3-hydroxypropyl) _4-({Νβ_[4_(Trifluoromethyl)benzene 186 200823202 yl]amine carbamoyloxy}methyl)(4-piperidinyl)]-N-[(2-chlorophenyl)methyl] Methionamine (1-(2-amino)-3-{[N-(4-ethylphenyl)aminecarboxylideneoxy]indolyl}(4-piperidine) Base))_Ν·[(2·chlorophenyl)indolyl]decylamine [(1-(2-aminoethyl)methyl]-4-{Ν-[(4·chloro-2-methylphenyl) )methyl]aminocarbazino}(4_piperidinyl))methoxy]-indole-(4-ethylphenyl)decylamine [(1-(2-aminoethyl)]4 -{Ν-[(2-bromophenyl)methyl]aminoindolyl}(4-piperidinyl))methoxy]-indole-(4-ethylphenyl)carbenamide N-{(lS )-2-[N-(4-B Phenyl phenyl)amine fluorenyloxy]-isopropyl}{[(2- chlorophenyl)methyl]amino phenyl N-mercaptocarboxamide [(1-(2-aminoethyl)] -4-{N_[(2-Ga-4-ylfluorophenyl)methyl]amine-carbamoyl}(4-Butryridyl)-decyloxy]ethylphenyl)carbenamide N-(2- Amineethyl)(4_{N-[(2-chlorophenyl)methyl]amine sulfhydryl 4-{[]^_(4-ethylphenyl)amine-methylcarbonyloxy]methylhydrazine Piperidinyl) decylamine (l-((2R)-2-amino-3-cyanopropyl)-4-{[N-(4-ethylphenyl)amine decyloxy] Mercapto}(4-piperidinyl))-N-[(2-chlorophenyl)indolyl]carbamamine [(1-(2-aminoethyl)]-4_{N-[(2, 3-difluorophenyl)methyl]amine fluorenyl}(4-piperidinyl))decyloxyphenyl)decylamine (1-(2-aminoethyl) benzyl) [N-(4-ethylphenyl)amine-mercaptooxy]methyl}(4-acridinyl))-N-[(2-mercaptophenyl)methyl]carboxamide [(4- {N-[(2-bromophenyl)indolyl]amine sulfhydryl 1-[2 decylamino)ethenyl](4-tridinyl))methoxy]|(4_ethyl Phenyl)carbamamine-[(2-chlorophenyl)indenyl](4-{[n-(4-ethylphenyl)amine decyloxy] 187 200823202 methyl}-1·(2 -carboxyethyl fluorenyl) (4-pyrimidinyl)) mercaptoamine (1-(2-aminoethyl fluorenyl) 4-{[Ν-(4-ethylphenyl)amine carbamoyloxy) ](yl)(4-piperidinyl))-indole-[(2-chlorophenyl)methyl]carboxamide [(1-(2-aminoethyl)]- 4·{Ν-[(3- Chloro-2-mercaptophenyl)indolyl]aminocarbazino}(4-piperidinyl))decyloxy]-indole-[4-(trifluoromethyl)phenyl]decylamine ((2S) -2-{[N-(4-ethylphenyl)amine decyloxy]nonylpyrrolidyl)_&gt; 1-[(2-chlorophenyl)indenyl]decylamine (1-(4-amino-2-hydroxybutanyl)-4-{[Ν-(4-ethylphenyl)amine fluorenyloxy) (4-piperidinyl))-indole-[(2-chlorophenyl)methyl]carbamamine 2_amino-indole_[3-({[(2-chlorophenyl))) Amino]-amino}-Ν_{2·[Ν-(4-ethylphenyl)amine-methylcarbonyloxy]ethyl}carbonylamino)propyl]acetamide (1-(2-amino)醯4)_4_{[N-(4_f-phenyl)amine carbaryloxy]fluorenyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carboxamide N -[(2-chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}(2H_3, 4, 5, 6-tetrahydrofuran-4-yl))carbenamide [(1-(2-aminoethyl)]-4-{N-[(2, 4c chlorophenyl) fluorenyl]aminoguanidino}(4-piperidinyl))methoxy]ethylphenyl)carbenamide N-{(lS)-3-[N-(4·ethyl Phenyl)amine-mercaptooxy]_1-methylpropyl}{[(2-chlorophenyl)methyl]amino}-N-methylformamide [2_({[(2-chlorobenzene) Alkyl]amino}_N_(2-hydroxyethyl)amino)ethoxy]-N-(4-ethylphenyl)carbenamide N-[(2-chlorophenyl)methyl ](4-{[N-(4-ethylphenyl)aminemethylmercaptooxy]methyl}-1-[2-(nonylamino)ethenyl](4-piperidinyl))indole Indoleamine (1-(azetidin-2-ylcarbonyl)_4-{[N-(4-ethylphenyl)amine fluorenyloxy 188 200823202 yl]methyl}(4-piperidinyl))- N-[(2-chlorophenyl)indolyl]carbamamine 2-amino-indole_[4_({[(2)chlorophenyl)methyl]amino)b-N-{2-[N_(4- Ethylphenyl)amine-mercaptooxy]ethyl}carbonylamino)butyl]acetamide N-((5S, 3R)-l-{N-[(2-chlorophenyl)indenyl]amine sulfhydryl}-5-{[((ethyl)ethyl) carbamoyloxy] fluorenyl} Pyridin-3-yl)-2-aminoacetamide N-[(2-chlorophenyl)indolyl]-4-[N-(4-ethylphenyl)amine-mercaptooxy]_2, 2-Dimercaptoamine N-[(2-chlorophenyl)indenyl]({[Ν-(4.ethylphenyl)amine decyloxy]fluorenyl}cyclohexyl)carboxamide (1-(4-Aminobutylidene)-4-{[Ν-(4-ethylphenyl)amine decyloxy]fluorenyl}('piperidinyl))-Ν-[(2-gas Phenyl) fluorenyl] decylamine {[(2-chlorophenyl)indolyl]aminodipyridyl-methyl-indole-{2-[Ν-(4_phenylphenyl)amine fluorenyloxy Ethyl]ethyl}decylamine (l-((2R)-2-aminopropionyl)-4-{[indole-(4.ethylphenyl)aminecarboxylideneoxy]methyl}( 4-piperidinyl))-indole-[(2-chlorophenyl)methyl]decylamine [(1·(2·aminoethyl fluorenyl)-4-{N-[(4i_2-fluorophenyl)曱 ] ] 胺 胺 胺 胺 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 H H H H H H H H H H H H H H H H H [N_(4)ethylphenyl)amine decyloxy]methyl}(4-piperidinyl))-N-[(2-phenylphenyl)methyl]carbamamine N_[(2-chlorophenyl) )methyl](4_{[N-(4-ethylphenyl)aminemethanyloxy) decyl 1-[3-hydroxy-2-(hydroxymethyl)_2-mercaptopropyl] (4-piperidinyl)) formamide (H2-aminoethenyl)_4_{[N-(4-phenylphenyl)amine-methylcarbonyl]- 189 2008 23202 基}(4_旅咬基))-N_[d-phenylphenyl)methyl]decylamine (1-(2-aminoethyl)-4-{[N-(2-chloro·4- Methylphenyl)aminemethylmercaptooxy]methyl}(4-piperidylchlorophenyl)indolyl]carbamamine 4-(2-aminoethylamine)*-N_[(2_ Chlorophenyl)methyl]_2_{[N-(4-ethylphenyl)amine-mercaptooxy]methyl}_2-mercaptobutylamine [(1_(2-aminoethyl)]-4 -{&gt; 1-[(2, 3-dichlorophenyl)indenyl]amine-carbamoyl}(4-Butryl))methoxy]·Ν_[4_(trifluoromethyl)phenyl]decylamine [1-(2-amine)基乙醯基)-4_({Ν_|; 4-(Trifluoromethyl)phenyl]amine-mercaptooxy}indolyl)(4-piperidinyl)]-indole-[(2-chlorophenyl)indolyl]decylamine-[( 2-chlorophenyl)indenyl](4-{[Ν-(4-ethylphenyl)aminecarboxylideneoxy] fluorenyl}_1-(Ν-methylaminoindolyl) (4-piperidyl) Pyridyl)) decylamine (1-(2-aminoethyl)- 4_{[N-(4-ethylphenyl)aminecarboxylic acid oxy]indolyl}(4_piperidinyl))-N -[(2_fluorophenyl)indolyl]decylamine [(4-{N-[(2, 3_: Phenyl phenyl) fluorenyl] hydrazinyl} small {2_[(t-butoxy) amide] ethyl aryl} (4. 唆 ))) 曱 oxy]-N_(4-ethyl Phenyl)carzamide 4-{N-[(2-chlorophenyl)indenyl]amine 曱醯*}-4-{[N-(4-ethylphenyl)amine decyloxy]indole 2-Aminoethyl [piperidinyl] 2-[N-(4-aminobutyl){[(2-chlorophenyl)methyl]amino}carbonylamino)ethoxy]- N-(4-ethylphenyl)decylamine {[(2·chlorophenyl)indolyl]amino}-N-{2-[N-(4-ethylphenyl)amine fluorenyloxy Ethyl]ethyl}-N-(4-hydroxybutyl)formamide N-[(2-chlorophenyl)indolyl]{4-[(N-hydroquinone-5-ylaminodecyloxy) )曱基](2H_3, 4, 5, 6_ra氲σpyran-4-yl)} guanamine 190 200823202 [(1-(2-Aminoethyl fluorenyl)-4-{N-[(3-chloro-2-fluorophenyl)methyl]] Aminomethyl}(4-piperidinyl))methoxy]_n_[4-(trifluoromethyl)phenyl]decylamine N-[(2-chlorophenyl)methyl](4-{ [N-(4-ethylphenyl)amine-carbenyloxy]methyl}-1-(imidazol-2-ylcarbonyl)(4.piperidinyl))carbenamide N-[(2-chloro) Phenyl)methyl](3-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(2-hydroxyethyl)(3-piperidinyl)) Methionamine N-[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarbamidooxy]methyl}-1-(phenylcarbonyl)( 4-Benyl group)) Methionamine [(1-(2-aminoethyl)-yl]-4-{Ν·[(3-fluoro-2-methylphenyl)methyl]amine fluorenyl} (4-piperidinyl))nonyloxy]-indole-[4-(trifluoromethyl)phenyl]decylamine N_[(lS)_2-(4-{N-[(2-chlorophenyl) )methyl]aminocarbazinyl}_4-{[yi(4-ethylphenyl)aminecarboxylideneoxy]indolyl}piperidinyl)-1-(hydroxymethyl)_2-one ethyl] (t-butoxy)carbamamine (1-ethylindenyl-4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}(4_piperidinyl))-N -[(2-chlorophenyl) Methotrexate 4-(4-{N-[(2-chlorophenyl)methyl]aminecaramidine*}-4-{[Ν·(4-ethylphenyl)aminecarboxylideneoxy Methyl]piperidinyl)-4-ketobutanoic acid methyl ester ({1-(2-aminoethyl fluorenyl) 4-[N-(naphthylmethyl)aminemethyl hydrazino] (4_piper Iridyl)}methoxy)-N-(4-ethylphenyl)carboxamide [1-(2-aminoethyl)-({N-[2-chloro-4.(trifluoro) Methyl)phenyl]amine-based milk base}methyl)(4_pyrylyl)]-N-[(2-chlorophenyl)methyl]anthracene Ν-[(2·chlorophenyl) )methyl][1-(2-hydroxyethyl)-4-({N-[4-(trifluoromethyl)phenyl]aminecarboxylidene}methyl)(4-brazinyl) )]methanosylaminoethyl)-3-{[Ν-(4.ethylphenyl)amine-mercaptooxy]oxime 191 200823202 }}(3-piperidinyl))_N-[( 2-chlorophenyl)methyl]carbamamine 3-{N-[(2-chlorophenyl)methyl]amine sulfhydryl 3-{[N-(4-ethylphenyl)aminecarboxamide Methoxy]methyl} sentic acid methyl vinegar (t-butoxy)·Ν_[4_(4-{Ν_[(2_chlorophenyl)methyl]aminemethano]*-4-[[Ν -(4.ethylphenyl)aminecarboxylideneoxy]methyl}piperidinyl)-4. ketobutyl]carbamamine-[(2-chlorophenyl)methyl](4- {[Ν-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(2-oxoethoxyethyl)(4-succinyl))nonylamine N-(5- Amine amyl){[(2-chlorophenyl)methyl]aminobenzyl N-{2_[N_(4-ethylphenyl)aminecarboxylideneoxy]ethyl}carbenamide N-[( 2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]indolyl}-1-(4-pyridinyl)-(4-Bucking base) )) indoleamine N_[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-1-(mercaptosulfonate) (4-piperidinyl))carboxamide N_[(2-chlorophenyl)methyl][4-({N-[4-(methylethyl)phenyl]aminecarboxamidooxy) }methyl)(2H-3, 4, 5, 6-tetrahydropyran-4-yl)]carbamamine N-[(2-chlorophenyl)methyl]ethylphenyl)amine decyloxy]methyl}-1-(morpholine- 3-(ylcarbonyl)(4-piperidinyl))carboxamide (1-(2-aminoethyl)-3-{[N-(4-ethylphenyl)aminecarboxylideneoxy] Methyl}pyridin-3-yl)_N_[(2_phenylphenyl)indolyl]decylamine 4_{N_[(2-chlorophenyl)methyl]aminecarbenyl}-4-{[ Ethyl 1(4-ethylphenyl)amine,carboxylideneoxy]methyl}piperidinecarboxylate (1.(2-amino-3-mercaptobutyl)-4-{[Ν·(4 -ethylphenyl)amine-mercaptooxy]indolyl}(4-piperidinyl))-indole-[(2-chlorophenyl)methyl]methaneamine 192 200823202 (1-(2-amine) Ethyl ethyl)-4-{[N-(4-chlorophenyl)amine decyloxy]fluorenyl}(4-piperidinyl))-N-[(2-chlorophenyl)fluorenyl ]Metamine [(1-(2-aminoethyl)]-4-{N-[(2, 4-dimercaptophenyl)indenyl]amine oxime fluorenyl}(4-piperidinyl))methoxy]-N-(4-ethylphenyl)carboxamide (1-(2, 4-Diaminobutyryl)-4·{[N-(4-ethylphenyl)amine oximeoxy]indenyl}(4-piperidinyl))-N-[(2-chloro Phenyl)methyl]decylamine N-[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy]indolyl 1-( 3-methoxypropenyl)(4-piperidinyl))carboxamide {[(2-chlorophenyl)indolyl]amino-based N-{2-[N-(4-ethylphenyl) Aminomethyl methoxy]-t-butyl}-&gt; 1-methylammonium N-[(2-chlorophenyl)indenyl](1-(cyclopropylcarbonyl)-4-{[N-(4-ethylphenyl)aminecarboxamidooxy ]methyl}(4-piperidinyl))carboxamide (t-butoxy)-indole-[2-(4-{Ν-[(2·chlorophenyl)methyl]aminecaramidine*} -4-{[Ν-(4-ethylphenyl)amine decyloxy]methyl}piperidinyl-1-(hydroxymethyl)-2-oneethyl]carboxamide (1- (2-Amino-2-mercaptopropyl)-4-{[N-(4-ethylphenyl)amine decyloxy]methyl}(4-piperidinyl))-N- [(2-Chlorophenyl)indenyl]carbamamine N-[(2-chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl Pyridylcarbonyl)(4-piperidinyl))decylamine N-[(2-chlorophenyl)methyl](4-{[N-(4-methylphenyl)aminemethanyloxy] Methyl}(2H_3, 4, 5, 6-tetradecano-4-yl)) decylamine (l-((2S)-2-aminopropionyl)-4-{[N-(4-ethylphenyl)amine fluorenyl) Oxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)indolyl]decylamine [(1-(2-aminoethyl)]-4-{N- [(3-Chlorophenyl)indenyl]aminoindenyl}(4- 193 200823202), methoxy]-N-(4-ethylphenyl) anthracene 4-(ethenyl) Amino)-N-[(2-chlorophenyl)methyl]-2-{[N-(4-ethylphenyl)aminecarakimethoxy]methyl}-2-methylbutanamine ( 1-(2-Aminoethyl fluorenyl)-4-{[N-(3-fluoro-4-methylphenyl)amine decyloxy]methyl}(4-piperidinyl))-N -[(2-chlorophenyl)methyl]carbamamine N-[(2-chlorophenyl)methyl](4-{[N-(4-ethylphenyl)aminecarboxylideneoxy] Methyl group (i.e., 4-branched base)), urethane (1-(2-amino-3-cyanopropionyl)-4-{[N-(4-ethylphenyl) Aminomethyl methoxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carbenamide N-[(2-chlorophenyl)methyl]( 4-{[N-(4-ethylphenyl)amine-mercaptooxy]methyl}-1-(4-piperidinylcarbonyl)(4-piperidinyl))carboxamide 3-(2 -milk phenyl)-N - {2-[N-(4 - Yl) amine stuffed Yue-yloxy] propionic acid methyl N- Jibu Amides amine 2_ -N_ [2 _ ({[(2- chlorophenyl) methyl] amino} - &gt; ^{2_[]^(4_Ethylphenyl)amine-mercaptooxy]ethyl}carbonylamino)ethyl]acetamidamine (1-(2-aminoethenyl)-4-{ [N-(4-ethylphenyl)amine-methyleneoxy]methyl}(4-piperidinyl))-indole[(2-cyanophenyl)indolyl]carbamamine (third butyl) Oxy)-indole-[2-(4_{Ν-[(2-chlorophenyl)methyl]aminoindolyl}-4-{[Ν-(4-ethylphenyl)aminecarboxamidooxy Methyl} dimethyl ketone ethyl] decylamine (1-(2-aminoethyl fluorenyl)-4-{[indole-(4-ethylphenyl)amine decyloxy]methyl }(4-piperidinyl))-indole-{[2-(hydroxyindolyl)phenyl]indolyl}decylamine [(1-(2-aminoethylhydrazinyl)-4-{Ν-[ (2-ethylphenyl)methyl]aminoindenyl}(4-piperidinyl))nonyloxy]-indole-(4-ethylphenyl)decylamine 194 200823202 (Third butoxy )_N_[2-(4-{[N-(4_6-ylphenyl)amine fluorenyloxy]methyl}-4_{N-[(2-fluorenylphenyl)fluorenyl]amine fluorenyl} Piperidinyl)-2-oneethyl]carbamamine (1-(2, 3-diaminopropyl fluorenyl) 4-{[N-(4-ethylphenyl)amine-methylcarbonyloxy]methyl}(4-piperidylchlorophenyl)indolyl]carboxamide [ (1-(2-Aminoethyl)-4-{N-[(3-fluorophenyl)methyl]aminecarbamyl}(4_piperidinyl))methoxy]-N-(4 -ethylphenyl)decylamine [(1-{2-[(t-butoxy)carbonylamino]ethinyl) 4_{ν·[(2_chloro-4-ylfluorophenyl)methyl Aminyl}(4_piperidinyl))methoxine 4-ethylphenyl)carboxamide [(1-(2-aminoethyl)]-4-{Ν_[(4-fluorobenzene) Methyl]aminomethane}}(4_piperidinyl))decyloxy]-indole-(4-ethylphenyl)carbenamide (3S)-3-amino-4-(4_{Ν -[(2-Chlorophenyl)indenyl]amine-carbamoyl}-4-{[Ν·(4_6-phenylphenyl)amine-carbenyloxy]methylpyridinyl)_4_ ketobutanoate Ester oxime-[(2-chlorophenyl)methyl][4-({Ν-[4_(trifluoromethyl)phenyl]aminecarboxylideneoxy}methyl)(2Η-3, 4, 5, 6_tetrahydroindole than _4_yl)] an amine (1-(2-aminoethyl)-4_{[Ν-(4·ethylphenyl)amine decyloxy]methyl} (4-piperidinyl))-indole-[(2-chlorophenyl)methyl]decylamine (4-{[Ν-(4-ethylhydrazinophenyl)amine decyloxy]fluorenyl) Ιι_(2_Aminoethyl)-(4-piperidinyl))-indole-[(2-chlorophenyl)methyl]carbenamide N-{2_[N-(4-ethylphenyl) Aminyloxy]ethyl bv-methyl-3-[2-(trifluoromethyl)phenyl]propanamine (4-{[Ν-(2, 4-dimethylphenyl)amine decyloxy]methyl 195 200823202 base} (2H-3, 4, 5, 6-tetrahydroanthracene-2-yl))-N-[(2-chlorophenyl)indolyl]decylamine [(1-(2-aminoethyl)]-4-{N-[ (4-chlorophenyl)methyl]aminoindenyl}(4·piperidinyl))methoxy]-indole-(4-ethylphenyl)carbenamide 4-{2-[(third Butoxy)aminoamino]ethinylaminodipyridyl-[(2-chlorophenyl)methyl]-2-{[indole-(4-ethylphenyl)amine decyloxy]indole Keb 2-methylbutymidine (l-((2S)-2, 5. Diaminopentydenyl)-4-{[indolyl-(4-ethylphenyl)amine-mercaptooxy]methyl}(4-piperidinyl))-indole-[(2-chloro) Phenyl)methyl]carbamamine oxime-[(2-chlorophenyl)methyl](1-{[Ν-(4-ethylphenyl)aminecarboxylideneoxy]methyl}cyclopentane- 3-alkenyl)carbamamine {[(2-chlorophenyl)methyl]amino}-indole-methyl-indole-[2-(indolyl-(6-quinolinyl))indolyloxy Ethyl]decylamine (t-butoxy)_Ν-[2-(3-{Ν_[(2-chlorophenyl)methyl]amine曱醯*}-3_{[Ν_(4-ethyl Phenyl)amine-mercaptooxy]methyl}piperidinyl)-2-ketoethyl]carbenamide ((5S, 3R)-3-Amino-5-{[Ν-(4-ethylphenyl)amine-carbenyloxy]fluorenyl} 0-rhododecyl)-Ν-[(2_phenylphenyl)fluorenyl Medramine (l-((2S)-2-amino-3-carbyl)-{{Ν-(4-ethylphenyl)aminecarboxylideneoxy]methyl} (3-piperidinyl))-indole-[(2-chlorophenyl)methyl]carbenamide (1-(2, 5-diaminopentylidene)-4_{[Ν-(4_6-phenylphenyl)aminecarboxylideneoxy]methyl}(4_派唆基))_Ν-[(2-chlorophenyl) A ]]N-mercaptoamine N-[(lS)_2-(4-{N-[(2-chlorophenyl)methyl]aminemethanyl) {{Ν-(4-ethylphenyl)amine oxime Mercaptooxy]methyl}piperidinyl)-1-methylketone B 196 200823202 base](t-butoxy)carbamamine 2-(4-{N-[(2-chlorophenyl)) Methylaminocarbazide}_4-{[]^-(4-ethylphenyl)amine-methylmethyloxy]methyl}piperidinyl)acetate methyl 3-amino-4-(4-{ &gt; 1-[(2-Chlorophenyl)methyl]aminoindenyl}-4-{[]^-(4-ethylphenyl)aminecarboxylideneoxy]methyl}pyrene)-4 -ketobutyric acid {(3R)_3-[N-(4-ethylphenyl)amine-carbenyloxy]piperidinyl}-oxime [(2-chlorophenyl)methyl]carbamamine oxime -[2-(Ν-benzothiazol-6-ylaminocarbamoyloxy)ethyl]{[(2-chlorophenyl)methyl]amino}_Ν-methylformamide [(4- {Ν-[(2, 3-difluorophenyl)methyl]aminemethanyl}-1-{2_[(t-butoxy)carbonylamino]ethenyl}(4-piperidinyl))methoxy]-oxime -(4-ethylphenyl)formamidine N_{(1S)_2-[N_(4-ethylphenyl)amine-mercaptooxy]-isopropyl}{[(2- chlorophenyl) A Amino]carbamamine N-[(2-chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)amine decyloxy]methyl}(4-piperidyl) Pyridyl))carbamide {[(2-chlorophenyl)methyl]amino}-ν·{3-[Ν-(4-ethylphenyl)amine decyloxy]propyl}- N_mercaptoamine 2·(Ν- {(1S)-2-[N·(4-ethylphenyl)amine oximeoxy]-isopropyl}{[(2_气phenyl) Methyl]amino}carbonylamino)acetic acid 3_[(4_{Ν-[(2-chlorophenyl)indolyl]aminecarbenyl}-4-{[Ν-(4-ethylphenyl) Aminomethyl methoxy]methyl}piperidinyl)carbonyl]morpholine-4-carboxylic acid tert-butyl ester 4-amino-indole-[(2·glyphenyl)indenyl]-2-{[Ν -(4-ethylphenyl)amine 曱醢197 200823202 oxy]methyl b 2-mercaptobutylamine [(1-{2-[(t-butoxy)carbonylamino]ethenyl) }_4-[N彳imidazole-2-ylmethyl)amine hydrazino](4-piperidinyl))decyloxy]-N-(4-ethylphenyl) N-[N-[(2-chlorophenyl)methyl](4_{[N_(4-ethylphenyl)amine-carbenyloxy]methyl}-1-[2-(methylamino)propene (醯-[4-piperidinyl))carboxamide 4-{[(1-(2-aminoethyl)methyl]-4-{N-[(2-chlorophenyl)methyl]amine oxime } _ _ ^ 啶 曱 曱 曱 ] ] ] ] ] ] ] ] ] ] ] ] 甲酯 甲酯 甲酯 甲酯 3R)-1-{N_[(2-chlorophenyl)methyl]amine fluorenyl}-5_{|&gt; [-(4-Ethylphenyl)amine-mercaptooxy]methyl}pyridin-3-yl)acetamide [({N-[(2-chlorophenyl)methyl]amine) }{cyclobutyl)methoxy]-N-(4-ethylphenyl)carbenamide N-[(2-chlorophenyl)methyl][4-({[(4-ethylphenyl) Amino]carbonylamino}methyl)-1-(2-hydroxyethyl)(4-piperidinyl)]carboxamide (4-{[N-(3_chloro-4-methylbenzene) Aminomethylamino]methyl}(2H-3, 4, 5, 6-four winds τl ratio tI south-4_base))_N-[(2-chlorophenyl)methyl]methyl,  Indoleamine [1-(2.Aminoethyl fluorenyl)- 4-({N-[4-indolyl-3-(trifluoromethyl)phenyl]aminecarboxylideneoxy}methyl) (4- Piperidinyl]]-N-[(2-chlorophenyl)methyl]carbenamide {[(2-chlorophenyl)methyl]methylamino}-N-{2-[N_(4-B Phenyl phenyl)amine mercaptooxy]ethyl b N-mercaptocarboxamide (1-(2-aminoethyl aryl)-4- {[N-(4-ethylphenyl)) Alkyloxy]methyl}(4-piperidinyl))-N-[(2-f-oxyphenyl)methyl]carbamimid 198 200823202 Ν·[(2-chlorophenyl)methyl](4_{ [N_(3_Fluoro-4-methylphenyl)amine decyloxy]methyl}(2Η-3, 4, 5, 6-tetrahydropyran-4-yl))carnitine-[(2-chlorophenyl)methyl]{3_[Ν_(4_ethylphenyl)aminecarboxylideneoxy]piperidinyl }Metformin 2-({[Η2-aminoethenyl)_4-({) 4-(trifluoromethyl)phenyl]amine decyloxy}methyl)-4-piperidinyl] Carbonylamino}methyl)benzoic acid methyl ester (4-{[N-(3, 4-dimethylphenyl)amine-mercaptooxy]methyl}(211-3, 4, 5, 6-tetrahydrofuran-4-yl))·Ν-[(2-chlorophenyl)methyl]carboxamide (4_(2-aminoethenyl)_2-{[ν_(4-ethyl) Phenyl)amine-mercaptooxy]methyl}branched base 1)-indole-[(2-chlorophenyl)methyl]carbamamine (1-(2-aminoethyl)--4-) {2_[Ν-(4-ethylphenyl)amine-mercaptooxy]ethyl}(4-piperidinyl))-indole-[(2-chlorophenyl)methyl]carbamamine-[ (2-Chlorophenyl)methyl]-3-[indolyl-(4.ethylphenyl)aminemethylmercaptooxy]-2, 2_Dimethylpropanolamine (3-aminopropyl){[(2-chlorophenyl)indolyl]amino}_Ν_{2-[Ν-(4•ethylphenyl)aminecarboxamide Hydroxy]ethyl}carbamidamine-[(2-chlorophenyl)methyl][2-({[(4-ethylphenyl)amino)]carbonylamino}methyl)pyrrolidinyl ]carbendazim-[(2-chlorophenyl)indenyl](1_(cyclohexylcarbonyl)-ethylphenyl)amine-methylcarbonyl]indolyl}(4-piperidinyl))carboxamidine Amine (Μ[Ν·(4-chlorophenyl)amine decyloxy]methyl}(2η-3, 4, 5, 6-tetrahydropyran-4-yl))-indole-[(2-chlorophenyl)methyl]decylamine-(2-aminoethyl){[(2-chlorophenyl)methyl] Amine-based ν-{2-[Ν-(4-ethyl199 200823202 phenyl)amine-mercaptooxy]ethyl}carbenamide (t-butoxy)-N_[2-(4_{N -[(2-bromophenyl)methyl]amine fluorenyl}-'{[Ν-(4-ethylphenyl)amine carbamoyloxy]fluorenyl}piperidinyl)-2 ketoethyl Methylcarhamamine [(1-(2-aminoethyl)-yl]- 4-{Ν-[(3-methyl(2-acridinyl))methyl]aminecarbenyl}(4-piperidine) Base)) methoxy]-indole-(4-ethylphenyl) amidoxime [[[2-chlorophenyl)methyl]({[Ν-(4-ethylphenyl)amine fluorenyl) Oxy]mercapto}cyclopropyl)carbamamine 2-(ethionylamino)-indole-[(2-chlorophenyl)methyl]-3-[indolyl-(4-ethylphenyl) Amine-based oxy]-2-methylpropanol [(1-{2-[(t-butoxy)carbonylamino]ethenyl}_4_{]^-[(3-fluoro-2) -methylphenyl)indolyl]aminoindenyl}(4-piperidinyl))decyloxy]-indole-[4-(trifluoromethyl)phenyl]carbenamide 4-{Ν-[ (2-Chlorophenyl)methyl]aminecarboxylidene}_4_{[]^-(4-ethylphenyl)aminecarboxylideneoxy]methyl}piperidinecarboxylic acid Butyl ester [1-(2-aminoethenyl)-4-( {Ν-[4-(trifluoromethyl)phenyl]amine decyloxy}methyl)(4-piperidinyl) ]-Ν-[(2-cyanophenyl)methyl]carbamimidoxime-[(2-chlorophenyl)methyl]-4-[indole-(4.ethylphenyl)aminecarboxyloxy Butylamine N-[(lR)-2_(4-{N-[(2-chlorophenyl)indolyl]amine sulfhydryl 4_{[Ν_(4-ethylphenyl)aminecarboxamide Hydroxy]methyl}piperidinyl-1-(hydroxyindole)-2-ketoethyl](t-butoxy)carbamamine (2S)-2-({[(4-ethyl) Phenyl)amino]carbonylamino}methyl)upyrrolidinecarboxylic acid (2-chlorophenyl)methyl ester 200 200823202 4-[(4-{N-[(2-Chlorophenyl)indenyl]amine Formazan*}_4-{[N-(4-ethylphenyl)amine-mercaptooxy]methyl}piperidinyl)carbonyl]piperidinecarboxylic acid tert-butyl ester 4-{[(4-{N -[(2-chlorophenyl)methyl]aminemethanyl}-2H-3, 4, 5, 6_tetrahydrofuranyl-4(yl)methoxy]carbonylamino}benzoic acid oxime [(4·{Ν-[(2, 3-dichlorophenyl)methyl]amine oxime}small {2-[(tatabutoxy)carbonylamino]ethenyl}(4-piperidinyl))decyloxy]-oxime- [4-(Trifluoromethyl)phenyl]carbamamine 2-(1_(2-aminoethyl fluorenyl)-4_{[Ν-(4-ethylphenyl)aminecarboxylideneoxy] A ((4-piperidinyl))-indole-[(2-chlorophenyl)methyl]acetamide (t-butoxy)_Ν-[2-(4-{[Ν-(4-B Phenyl phenyl)amine methyl hydrazino oxy] methyl}-4-{Ν-[(2-fluorophenyl)methyl]amine carbaryl}piperidinyl)-2-oneethyl]carboxamide N-[(2-chlorophenyl)indolyl][4-({N-[4-(2-methyl(1, 3-thiazole-4.yl))phenyl]aminecarboxyamino}indenyl) (2H-3, 4, 5, 6-tetrahydrofuran-4-yl)]decylamine 2-(2-aminoethenylamino)-N-[(2-chlorophenyl)methyl]-3-[Ν-(4 ·Ethyl phenyl)amine oxime oxy]-2-methylpropionamide Ν[[2-chlorophenyl)methyl](4-{[Ν-(4-ethylphenyl)amine oxime] Mercaptooxy] methyl b- 1-(2-ethyl) (4-. Basement))carbamide 2-[(tatabutoxy)carbonylamino]-indole-[3·({[(2-chlorophenyl)methyl)amino) {2-[1 ^(4-ethylphenyl)amine decyloxy]ethyl}carbonylamino)propyl]acetamidoxime_[(2-chlorophenyl)methyl]-3-[Ν-(4- Ethylphenyl)amine-mercaptooxy]_2-(oxacarbonylamino)-2-methylpropionamide 201 200823202 (4-{[N-(4-Ethylphenyl)amine)氧基oxy]methyl}(2H_3, 4, 5, 6-tetrahydrofuran-4-yl))-N-[(2-chlorophenyl)methyl]decylamine 2-(2-aminoethenylamino)-N-[(2-gas Phenyl)methyl]-4_[N-(4-ethylphenyl)amine-mercaptooxy]butanamine N_[(2-chlorophenyl)indolyl]_4_{[N-(4-B Phenyl)aminomethane]amino}-2, 2-Dimercaptobutylamine 2_[(4_{N-[(2-chlorophenyl)methyl]aminemethanyl}_4_{[yi(4_ethylphenyl)aminemethanyloxy] Tert-butyl}piperidinyl)carbonyl]azetidinic acid tert-butyl ester N-[(2-chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)aminecarbamyl) Oxy]methyl}-1-methyl (4-pyro))N-[(2-chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)) Aminomethyl methoxy]methylphenylcarbonyl)phenyl]carbonyl}(4-piperidinyl))carboxamide N-[(2-chlorophenyl)indenyl][4-({N_[4 -(hydroxyethyl)phenyl]amine-mercaptooxy}indenyl) (2H_3, 4, 5, 6-tetrahydropyran-4-yl)]carbamamine N_[({N_[(2-chlorophenyl)methyl]aminemethanyl}cyclopropyl)methyl][(4-ethylbenzene) Amino]carbamamine N-[(2-chlorophenyl)indenyl](l-{[N-(4-ethylphenyl)aminecarboxylideneoxy]methyl}-3, 4-Dihydroxycyclopentyl)guanamine {3-[N-(4-ethylphenyl)amine decyloxy]piperidinylmethylphenyl)indolyl]carbamamine [(1- {2-[(Tertidinoxy)carbonylamino]ethinyl-4-{N-[(3-Chloro-2-methylphenyl)methyl]aminoindolyl}(4-piperidine) Base)) methoxy]-N-[4-(trifluoromethyl)phenyl]formamide 202 200823202 2-Amino-Ν-[2·({[(2-chlorophenyl)methyl]] Amino}_N-{2-[N_(4-ethylphenyl)amine-carbamoyloxy]ethyl}carbonylamino)ethyl]_N-methylacetamide N-[(2-chlorobenzene) (曱)][4_({N-[4-(trifluoromethyl)phenyl]amine-carbenyloxy}fluorenyl)(4-piperidinyl)]decylamine {[(2-chloro) Phenyl)methyl]amino-based N-{4-[N-(4-ethylphenyl)amine-methylcarbonyloxy]butyl}·Ν-mercaptocarboxamide (t-butoxy) ·Ν-[2-(4-{Ν-[(2-Chlorophenyl)methyl]amine-formamidine*}-4-{[Ν-(4-ethylphenyl)amine decyloxy] Mercapto}piperidinyl)-1_methyl-2-ketoethyl]methylmethamine Ν-[(2-chlorophenyl)methyl](1-ethyl-4-{[Ν-(4 -ethylphenyl)amine-mercaptooxy]methyl}(4-piperidinyl))carbenamide 4_{[(4-{Ν-[(2-chlorophenyl)methyl]aminecarboxamide base }-211-3, 4, 5, Ethyl 6-tetrahydropyran-4-yl)methoxy]carbonylamino}benzoate [(1-{2-[(Tertidinoxy)carbonylamino]ethinyl}_4·{ Ν_[(3-Gas-2-fluorophenyl)methyl]amine-carbamoyl}(4-piperidinyl))methoxy]-indole-[4-(trifluoromethyl)phenyl]indole Amidoxime-[2-({[(2-chlorophenyl)methyl]amino}-indole-mercaptocarbonyl)ethyl][(4·ethylphenyl)amino]guanamine 2 -amino-indole-[(2-chlorophenyl)methyl]-4-[indolyl-(4-ethylphenyl)amine-mercaptooxy]butanamine [(2R)-2-({ [(2-Chlorophenyl)methyl]aminopyridinium-methylcarbonylamino)propoxy]·Ν-(4-ethylphenyl)decylamine ({1-(2-Amino B) Mercapto)-4-[indolyl-(2-acridinylmethyl)amine-carbamoyl](4-piperidinyl)}nonyloxy)-indole-(4-ethylphenyl)carbamamine 203 200823202 N-[(2-Chlorophenyl)indenyl](4-{[N-(4-ethylphenyl)methylamine-mercaptooxy]indolyl}(2H_3, 4, 5, 6-tetrahydrofuran-4-yl))carbenamide (1-{2-[(t-butoxy)carbonylamino]ethenyl}-4-{[N-(4-ethylbenzene) Aminomethyl hydrazinyloxy] decyl}(4-piperidinyl))-N-[(2-cyanophenyl)methyl]carbamidine (1-(2-aminoethyl)-) 4-{[N-(4-cyanophenyl)amine-mercaptooxy]methyl}(4-piperidinyl))-N-[(2-chlorophenyl)methyl]carboxamide (1 -(2-aminoethenyl)-4-{[N-(4-ethylphenyl)amine decyloxy]fluorenyl}(4-piperidinyl))-N-benzyl hydrazine Amine [(1-{2-[(Tertidinoxy)carbonylamino)]ethinyl}-4-{N-[(3-fluorophenyl)methyl]aminecarboxyl} (4-piperidyl) Pyridyl)) methoxy]-N-(4-ethylphenyl)carboxamide [2-({[(2.chlorophenyl)indolyl]amino)-N-methylcarbonylamino)- Isopropoxy]-N-(4-ethylphenyl)cartoamine N-[(2-chlorophenyl)methyl]_3-{[(4-ethylphenyl)amino]carbonylamino }_2, 2_ Dimethylpropionamide N-[(lS)-2-(3-{N-[(2-chlorophenyl)methyl]aminemethanyl-3-{[N-(4-ethylbenzene) Aminomethyl hydrazinyloxy] hydrazinyl yl) l-(hydroxymethyl)-2-oneethyl](t-butoxy)carbamamine N-[(2-chlorophenyl) )methyl]-3-[N-(4-ethylphenyl)amine decyloxy]-2-(2-hydroxyethylamino)-2-mercaptopropylamine {1-( 2-aminoethenyl)-4-[(N-phenylamine-mercaptooxy)methyl](4-piperidinyl)}-N-[(2-chlorophenyl)methyl]indole Indoleamine [(1-(2-aminoethenyl)-4-{Ν-[(2.methyl(3-heptidyl)))]]]]]]] Base)) methoxy]-N-(4-ethylphenyl)carbamamine [0-(2-1: (Tertibutoxy)carbonylamino]ethinyl}-4-{N-[(4-fluorophenyl)indolyl]aminocarbazino}(4-piperidinyl))decyloxy]B Phenyl phenyl) decylamine {(3S)_3_[N-(4_6-phenylphenyl)amine-carbenyloxy]pyridinyl N-[(2-chlorophenyl)methyl]decylamine Tributoxy)-N-[2-(4_{[N-(4-ethylphenyl)aminecarboxylideneoxy] fluorenyl}-4-[N-pyrylamine fluorenyl] brigade bite 2-ketoethyl]carbamamine 2-((2S)-2-amino-3-hydroxypropionylamino)-N-[(2-chlorophenyl)methyl]-3- [N-(4-ethylphenyl)amine-mercaptooxy]-2-methylpropanoxime (1-{2·[(t-butoxy)carbonylamino]ethinyl) 4- {[N-(4-ethylphenyl)amine-mercaptooxy]indolyl}(4-Benbityl)-N-[(2«•methoxyphenyl)methyl]carboxamide [ (4_{N-[(2-chlorophenyl)indolyl]amine-carbamoyl}morpholin-2-yl)methoxy]-N-(4-ethylphenyl)cartoamine {[1- (2-Aminoethyl fluorenyl)-4-(N-{[2-fluoro-4-(trifluoromethyl)phenyl]methyl}amine carbhydryl)(4-piperidinyl)]methoxy }---(4-ethylphenyl)decylamine N-[(lR)-2-(4-{N-[(2-chlorophenyl)indolyl]amine-methylpyridylethylphenyl) Amidoxime Base}Benyl)-1-methyl-2-ketoethyl](t-butoxy)carbamamine N-[(2-chlorophenyl)indolyl][4-({N_[4 - Methyl-3-(trifluoromethyl)phenyl]amine-based milk base} thiol) (2H-3, 4, 5, 6-tetraziniumpyran-4-yl)]carbamamine N-[(l-(2-aminoethenyl)-4-{N-[(2-chlorophenyl)methyl]amine oxime醯205 200823202 base}(4-piperidinyl))methyl][(4-ethylphenyl)amino]-N-(3-methoxypropyl)carbenamide {[1-(2-amine) Ethyl benzyl)-4-({[(2-chlorophenyl)methyl]amino}methyl)(4-piperidinyl)]methoxy}-N-(4-ethylphenyl) Methionamine^-[(2-carbyl)methyl]_2-{[(4-ethylphenyl)amino]]]]]]]]]]] )-Ν-[(2·Chlorophenyl)methyl]-3-[N-(4-ethylphenyl)amine-mercaptooxy]propanamine N_[(2-chlorophenyl)fluorenyl ](4-{[仏(6-fluoro-2-methylphenyl)amine decyloxy]methyl}(2Η-3, 4, 5, 6·tetrahydrofuran_4_yl))carbenamide-[(2-chlorophenyl)methylΚ4_{[Ν-(4-ethylphenyl)amine decyloxy]methyl b 1 -benzyl (4-piperidinyl))carboxamide [GPK tert-butoxy)carbonylamino]ethynyl chlorophenyl)methyl]aminemethanyl}(4-piperidinyl)) Oxy]_ν-(4-ethylphenyl)carbamamine (1-(2-aminoethyl fluorenyl)_4_{[helium fluorophenyl)amine mercaptooxy]methyl}(4 -piperidinyl))-indole-[(2-chlorophenyl)methyl]carbamamine Ν[[(1_(2_aminoethyl hydrazide)&gt; 4-{Ν-[(2-chlorophenyl)methyl]amine fluorenyl (4-piperidinyl)) fluorenyl]-2-(4·ethylphenyl)acetamidamine 2-amino -Ν-{2-[{[(2-Chlorophenyl)methyl]amino) ν·(2-{Ν·[4-(trifluoromethyl)phenyl]amine-methylcarbonyl]} Carboxyamino]ethylmethylethylamine (4-(2-aminoethyl)-3_{ν_[(2-chlorophenyl)methyl]aminemethanyl}piperidine 1) - Ν-(4-ethylphenyl)carbamamine 206 200823202 N-[(2-Chlorophenyl)methyl]{4-[(N-phenylaminecarbamidooxy)methyl](2H_3 , 4, 5, 6-tetrahydropyran-4-yl)}carbamimid-3-(1-(2-aminoethyl)-4-{Ν-[(2·methylphenyl)methyl]aminecarboxamide }(4-Butyl))·Ν-(4-ethylphenyl)propanol 4-{[(4-{Ν-[(2-chlorophenyl)methyl]amine fluorenyl} -211-3, 4, 5, 6_tetrahydrofuran-4-yl)methoxy]carbonylamino}benzamide (4-{[Ν-(3-chloro-2-methylphenyl)aminecarboxylideneoxy]- Base} (2H-3, 4, 5, 6-tetrahydrofuran_4_yl))_Ν-[(2-chlorophenyl)indolyl]decylamine {[(2-chlorophenyl)methyl]aminophenyl]-{2-[Ν -(4-ethylphenyl)amine decyloxy]ethyldip-[2-(methylamino)ethyl]carbenamide N-[(l-(2-aminoethenyl)) -4-{Ν-[(2-chlorophenyl)indolyl]aminoindenyl}(4-piperidinyl))indenyl]-indole-(2-aminoethyl)[(4-ethylbenzene) Amino] meglumine ((lS, 2S)-2-{[(4-ethylphenyl)amino]carbonylamino}cyclohexyl)-indole-[(2-chlorophenyl)methyl]decylamine-[(2-chlorobenzene) Methyl](4-{[Ν-(2-cyanophenyl)amine-carbenyloxy]fluorenyl} (211-3, 4, 5, 6-tetragerpyridin-4-yl))ylamine (4-{[Ν-(2-chlorophenyl)aminecarboxylideneoxy]methyl} (211-3, 4, 5, 6-tetramethane-4_yl))-Ν_[(2-chlorophenyl)methyl]carbamamine-{2-[Ν-(4-ethylphenyl)aminecarboxamidooxy Ethyl}acetamidamine-{2-[Ν-(4-ethylphenyl)amine decyloxy]ethyl}-2-hydroxy-indole-yl-3-[2-(three Fluorofluorenyl)phenyl]propanamine 1-(2-aminoethenyl)-4-{[indolyl-(4-ethylphenyl)amine decyloxy]indole 207 200823202 -4-methyl formate N-[({N-[(2-chlorophenyl)indenyl]amine fluorenyl}cyclopropyl)indolyl]-2-(4-ethylphenyl)acetamidamine N- [(2-Chlorophenyl)methyl][4-({[(4-ethylphenyl)amino]carbonylamino}indolyl)(4-piperidinyl)]carboxamide (third butyl) Oxy)-N-[2-({[(2-chlorophenyl)methyl]amine) S}-N-{2-[N-(4-ethylphenyl)amine-methylcarbonyloxy]B Ethyl}carbonylamino)ethyl]-indole-mercaptocarboxamide (4-{[Ν-(3, 5-dichlorophenyl)amine-mercaptooxy]indolyl}(2Η-3, 4, 5, 6· tetrahydrofuran _4, Base))_Ν_[(2·chlorophenyl)indolyl]carbamamine ({1-(2•aminoethylhydrazinyl)-4-[indolyl-(imidazol-2-ylmethyl)amine) (4-piperidinyl)}nonyloxy)-indole-(4-ethylphenyl)carbenamide 2-(N-{(lS)-2_[N-(4-ethylphenyl)amine Tert-butyloxy]-isopropyl}{[(2-chlorophenyl)indenyl]amino}carbonylamino)acetic acid tert-butyl ester N-[(2-ranylphenyl)methyl]_Ν^ ·(4-ethylphenyl)-2, 2-dimercaptopurine -1, 5-diguanamine 3-{Ν-[(2-chlorophenyl)methyl]amine-methylmethyl}-3-{[(4-ethylphenyl)amino]carbonylamino}pyrrolidinecarboxylate Ethyl chlorophenyl)methyl][4-({[(4-ethylphenyl)amino]-indole-methylcarbonylamino}indolyl)-1-(2-hydroxyethyl)-(4) -piperidinyl)]nonylamine N-[(2-chlorophenyl)methyl](4-{[N-(3-indolylphenyl)amine decyloxy] fluorenyl} (2H- 3, 4, 5, 6_tetranitrogen ratio - 4_ base)) mercaptoamine 2_{2-[(t-butoxy)carbonylamino]ethinylamine-based N-[(2-chlorophenyl)methyl ]_3-[N-(4-ethylphenyl)amine-carbenyloxy]-2-mercaptopropanamide 208 200823202 with (t-butoxy)-N_(2_{N-[(l- {2-[(Tertidinoxy)carbonylamino]ethinyl bromide 4_{N_[(2-chlorophenyl)methyl]aminoindolyl}(4-piperidylmethyl)[(4 _Ethylphenyl)amino]carbonylamino}ethyl)carbenamide.   72. If at least one of the chemicals of claim 1 is applied, Wherein the compound of formula x is selected from the group consisting of a compound of formula II Wherein Wi is a substituted aryl group, an optionally substituted cycloalkyl group, an optionally substituted heterocycloalkyl group or an optionally substituted heteroaryl ring; W2 is selected from the group consisting of cWR2 and NR14 10 Z1 is an aryl group; Z2 is an aryl group; R and R are independently selected from the group consisting of hydrogen, a carboxyl group, a thiol group, an optionally substituted alkyl group, an optionally substituted ring alkyl group, and optionally Substituted dilute group, optionally substituted alkynyl group, optionally substituted alkoxy group, 15 optionally substituted aryloxy group, optionally substituted heteroaryloxy group, optionally substituted heterocyclic ring Alkoxy, optionally substituted aminoxyoxy, optionally substituted methoxy, optionally substituted alkoxycarbonyloxy, optionally substituted alkoxycarbonyl, optionally substituted amine Base, 209 200823202 optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amine carbonyl, optionally substituted amino sulfonyl Or R1 and R2 may be bonded to a carbon atom in a combination of 5 and a group selected from a cycloalkyl group optionally substituted with a heterocycloalkyl group optionally substituted; in each case, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, hydroxy, carboxy, and optionally Substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, Optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted aminocarbonyloxy, optionally substituted decyloxy, optionally substituted alkoxycarbonyl An oxy group, optionally substituted fluorenyl group, optionally substituted alkoxycarbonyl group, optionally substituted amine group, optionally substituted 15 aryl group, optionally substituted heteroaryl group, optionally substituted a heterocycloalkyl group, optionally substituted amine carbonyl, and optionally substituted aminosulfonyl; each R7 and R1G is independently selected from the group consisting of hydrogen, cyano, halo, hydroxy, decyl, azide Base, Jingji, D., sulfhydryl, thiol, as desired An optionally substituted aryloxy group, optionally substituted heteroaryloxy group, optionally substituted heterocycloalkyloxy group, optionally substituted alkoxycarbonyl group, optionally substituted alkyl group, optionally A substituted cycloalkyl group, optionally substituted alkenyl group, optionally substituted alkynyl group, optionally substituted aryl group, optionally substituted heteroaryl group, 210 200823202 optionally substituted heterocyclic ring are required. An alkyl group, an optionally substituted amino group, an optionally substituted thiol group, an optionally substituted amine group, an optionally substituted amino sulfonyl group, optionally substituted formazan group; R and R is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted heterocyclic ring. The base is selected from the group consisting of 〇, 1, 2, and 3; the line is selected from 0, 1, 2, and 3; is selected from 1, 2, and 3; and the 10 points are selected from 0, 1, 2, and 3. . 73. At least one of the chemicals of claim 72, wherein From -CH and N 〇, Wla, Wlb, and Wlc are independently selected as at least one chemical of claim 73, and at least one of wla, wn, and wlc is Ν. 75. At least one of W, Wlb, and _ at least two of the scope of patent application 帛 73 is Ν. , 76. h such as the application of at least one of the 73 patents, including W a, Wlb, and W, N. </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; 78. The at least one chemical of claim 78, wherein: 211 20 200823202 79. at least one chemical according to any one of claims 72 to 79, wherein each ... is independently from the rule 4 a lower alkyl group and a lower calcination carbonyl group selected from the group consisting of hydrazine, optionally substituted. 5 80 · $At least one chemical according to claim 79, wherein each of r3 and R4 is independently selected from hydrogen, methyl, Ethyl, isopropyl, hydroxymethyl, and methoxycarbonyl. II 81 · At least one of the chemicals of claim 80, wherein each of R3 and R4 is hydrogen. 10 82. The at least one chemical to any one of the items 81, wherein /7 is selected from the group consisting of 1 and 2. 83. At least one chemical as claimed in claim 82, wherein 1 〇 84. η is as claimed in the patent scope At least one chemical of item 82, wherein each 15 R1° is independently selected from the group consisting of cyano, chloro, bromo, methyl, ethyl, isopropyl-second butyl, hydroxymethyl, trifluoromethyl , methoxycarbonyl, phenoxy, trifluoromethoxy, methoxy, N, N. dimethylamino, and m-唾················································ And at least one chemical of any one of clauses 72 to 86, wherein R1 and R2 are independently selected from the group consisting of at least one of the compounds, wherein R1 and R2 are independently selected from the group consisting of: Hydrogen and lower alkyl. 212.200823202 88. The at least one chemical of claim 87, wherein r1 and R2 are independently selected from hydrogen and methyl. 89. At least one of claim 88 a chemical, wherein R1 and R2 are hydrogen. 5 90. At least one of the chemicals of claim 88, wherein r1 and R2 are methyl. ', 91· at least one chemical as claimed in claim 88 And wherein R 2 is a methyl group. 92. At least one of 10 to 91, wherein R1 and R2 are bonded together to form a cycloalkyl group and a heterocyclic ring. A group of an alkyl group. 15 20 93 · At least one of the 92nd paragraph of the patent application And r1 and R are joined together to form a group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, decyl, piperidinyl, and 2H-3,4,5,6-tetrahydropyranyl Groups wherein each group is substituted as needed. 94. At least one chemical of claim 93, wherein Ri and R2 are joined together to form a cyclopropyl group, optionally substituted, optionally substituted A cyclopentyl group, optionally substituted cyclohexyl group, optionally substituted piperidinyl group, and optionally substituted 2H-3,4,5,6-tetrahydropyranyl group. 95. At least one chemical according to any one of claims 72 to 94 wherein each of R5 and R is independently selected from the group consisting of hydrogen, optionally substituted lower alkyl and lower alkoxycarbonyl. 96. At least one of the chemicals of claim 95, wherein each of 213 200823202 r#r6 is independently selected from the group consisting of a pot, an anthracene, a methyl group, an ethyl group, an isopropyl group, a hydroxymethyl group, and a T-oxide. Carbonyl. For example, at least one chemical of claim 96, wherein each of R and R6 is hydrogen. At least one chemical of any one of clauses 72 to 97, wherein R7 is C1, F, methyl, or CF3. 99. At least one chemical as claimed in claim 98, wherein R7 is C1. VIII100. The at least one chemical item of any one of claims pursuant to claim 99, wherein w is 1 or 2 〇 101, and at least one chemical as claimed in claim 1 wherein R7 Is located at position 2 or 3. 102. The at least one chemical of claim 73, wherein the hydrazine compound is selected from the group consisting of N-[(2-chlorophenyl)methyl] (several 5_(4_ethylphenyltetrazole_2) Base]]methyl}cyclopropyl)carhamamine N-[(2-chlorophenyl)methyl](1_{[5_(4_ethylphenyl)(1,2,3,4_tetrazole) -2-yl)]methyl}cyclopent-3-enyl) decylamine N-[(2-chlorophenyl)methyl]({[5-(4-ethylphenyl))(1,2 ,3,4_tetrazole_2_yl)]methyl}cyclobutyl)carbenamide·[(2-chlorophenyl)methyl]-3-[5-(4-ethylphenyl)( ι,2,3,4-Tetras-2-yl)]_2,2-dimercaptopropylamine-[(2,3_-disorganophenyl)indenyl]-2,2-dimethyl] 3-{5-[4 _(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanamine 214 200823202 N-[(2-carbene) A 2,2-dimethyl-3-{5-[4-(methylethylamino)phenyl](1,2,3,4-tetraindole-2-yl)} propylamine 3-{ 5-[4_(Dimethylamino)phenyl](1,2,3,4-tetrazole-2-phenyl)methyl]_2,2·dimethylpropionamide [(^ 3- [5- (4-bromophenyl)(1,2,3,4-tetrazol-2-yl)]-N-[(2-chlorophenyl)indolyl]-2,2-dimercaptopropenamine N -[(2-chlorophenyl)methyl]_3_ [5_(4_methoxyphenyl)anthracene, 2,3,4 tetrazole·2_yl)]-2,2-dimercaptopropanamide 4- [2-(2·{Ν-|χ2-chloride Phenyl) fluorenyl]amine carbazyl methyl propyl)_1,2,3,4-tetrazole _5-yl]methyl benzoate _[[2-chloro-4-fluorophenyl)methyl Methylmercaptoethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanamine 2,2-dimethyl-3-(5-[4-(methylethyl) Phenyl](1,2,3,4-tetrazol-2-yl)}-indole-[(2-methylphenyl)indolyl]propanamine oxime [(2-chlorobenzyl)methyl] _2,2-Dimethyl_3_[5-(4-methylphenyl)(1,2,3,4-tetrazol-2-yl)]propanamine di-[(2-chlorophenyl) Methyl]·2,2-dimethyl|{5 Park (tri-methoxy)phenyl](1,2,3,4-tetrazol-2-yl)}propanamine-[o-chloro Styyl)methyl]_3_[5_(4_imidazolylphenyl)(1,2,3,4-tetrazol-2-yl)]-2,2-dimethylpropionamide [[2- Fluorophenyl)methyl].2,2-dimethyl]{5 Park (methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanamine [(2_Chlorophenyl)methylΚ4_{[5_(4-ethylphenyl)(1,2,3,4-tetrazole•2_yl)]methyl}(2Η_3,4,5,6 -tetrahydropyranyl)) formamide 215 200823202 N-[(2_chlorophenyl) (1_{[5_(4_ethylphenyl)(1,2,3,4-tetrazol-2-yl)]methyl b 3,4-dihydroxycyclopentyl)decylamine N_[ L-(2-Chlorophenyl)-2-hydroxypropyl]_2,2_dimethyl_3-{5-[4-(methylethyl)phenyl](1,2,3,4-tetra Salin-2-yl)}propanamine 3·[5-(4-chlorophenyl)(1,2,3,4-tetrazol-2-yl)]-anthracene-[(2-chlorophenyl) Methyl]-2,2-dimethylpropanosamine {[(2-chlorophenyl)methyl]aminophenyl]_{2-[5 gas 'ethylphenyl) (1,2,3,4 Tetrazolium-2-yl)]ethylidene-methylformamide,,,Ν-[(2-chlorophenyl)methyl]_2,2-dimethyl_3-{5-[4- (trifluoromethyl)phenyl](1,2,3,4_tetras-2-yl)}propanamine-[(2-chlorophenyl)methyl]_2,2-dimethyl_ 3-[5-(4-phenoxyphenyl)(1,2,3,4-tetrazol-2-yl)]propanoxime-[(2-chlorophenyl)methyl]_3_{5- [4-(Methylethyl)phenyl](1,2,3,4_tetras-2-yl)}propanamine Ν-[(2,4-dichlorophenyl)methyl]_2,2 -Dimethyl·3-{5_[4-(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanamine (2S)-N-[(2 _Chlorophenyl)methyl]methyl_3_[5-(4-methylphenyl)(1,2,3,4-tetrazol-2-yl)]propanamide 3-[5-(3 - Phenyl)(ι,2,3,4_tetrazol-2-yl)]-N-[(2-chlorophenyl)methyl]_2,2-dimethylpropanamide 3_{5-[4_ (t-butyl)phenyl]g,2,3,4-tetrazol-2-yl)}_:^_[(2-chlorophenyl)methyl]_2,2·dimethylpropanamide N-[(2-chlorophenyl)methyl]-2,2-dimethyl_3·{2_[4_(methylethyl)phenyl](1,2,3,4_tetrasa_5 _ base)} propylamine 216 200823202 2.2- Dimercapto-3-{5-[4-(mercaptoethyl)phenyl](l,2,3,4-tetrazole·2-yl)}_Ν -benzylpropionamine chlorophenyl)methyl]_2,2-dimethylmethylphenyl)(1,2,3,4-tetrazol-2-yl)]propanoxime Ν[[3_ Fluorophenyl)methyl]_2,2-dimercapto-3-{5-[4 gas methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanoid Amine 2,2-dimethyl-3·{5-[4-(mercaptoethyl)phenyl](ι,2,3,4-tetrazol-2-yl)}-Ν-(2-吼Pyridylmethyl)propanamine Ν[[2-(2-chlorophenyl)ethyl]_2,2-dimethyl_3-{5_[4-(methylethyl)phenyl](1,2, 3,4_tetrazol-2-yl)}propanamine Ν[[(2-chlorophenyl)indenyl]_3_{3_[4-(methylethyl)phenyl](1,2,4_啐一峻-5_基)} propylamine Ν[[2_chlorophenyl)indenyl]_3_{5-[4-(hydroxyl Phenyl](ι,2,3,4-tetradent-2-yl)}-2,2-dimethylpropanamine-[(2-chlorophenyl)methyl]-2-methyl _3-{2_[4-(methylethyl)phenyl](1,2,3,4-tetrazol-5-yl)}propanamine-[(2-chlorophenyl)methyl] _3_[5 gas 'cyanophenyl) (1,2,3,4-tetrazolyl)]-2,2-dimethylpropionamide 2.2-dimethyl_3-{5-[4_(methyl Ethyl)phenyl](1 2 3 4tetrazolyl)}-indole-(3-thienylmethyl)propanoxime oxime-[(6-chloro-2-fluorophenyl)methyl]·2, 2_Dimethyl_3_{5_[4_(methylethyl)phenyl](1,2,3,4-tetrazol-2-yl)}propanamide 2.2-dimethyl-3-{5 -[4·(decylethyl)phenyl](12 3,4-tetrazol-2-yl)}-indole-(1,3-oxazol-2-ylindenyl)propanamine and 217 200823202 4 -[(2,2_Dimethyl_3-{5_[4_(methylethyl)phenyl](1,2,3,decapyridin-2-yl)}propanylamino) fluorenyl Benzoic acid. A pharmaceutically acceptable composition comprising a pharmaceutically acceptable carrier and at least one chemical according to any one of claims 1 to 102. The pharmaceutical composition of claim 103, wherein the composition is formulated in the form of a tablet, a capsule, a powder, a liquid, a suspension, a suppository, and an aerosol. • A coated pharmaceutical composition comprising a pharmaceutical composition as claimed in claim 103 or 104 and the use of the composition for treating a condition associated with a smooth muscle myosin or a non-muscle myosin-related disease 10 . 106. The pharmaceutical composition of the package of claim 105, wherein the disease associated with smooth muscle myosin is selected from the group consisting of hypertension, asthma, chronic obstructive pulmonary disease (COPD), asthma, bronchoconstriction, glaucoma, and Other eye symptoms, incontinence and other bladder dysfunction, large 15 intestinal irritation syndrome, premature labor pain, abnormal esophageal motility, stroke, subarachnoid hemorrhage, anterior hernia, erectile dysfunction and smooth muscle myosin and / Or other non-muscle myosin-related acute illnesses and difficult makeup. A method for treating or ameliorating a mammalian muscle myosin-related disease associated with a smooth muscle myoglobin, the method comprising administering a therapeutically effective amount of a mammal having a pot need At least one chemical of any one of the ranges of ^^103. 218 20 200823202 108·If you apply for the method of ι 〇 相关 , , , , , , , , , , , , , , — — — — — — — — — — — — — — — — — — — — — — — — — — — — — Disease, glaucoma and other eye diseases 5 groups, early η ban and other bladder dysfunction, irritable bowel syndrome, esophageal abnormalities, stroke, subarachnoid hemorrhage, (10) sputum, erectile dysfunction and smooth muscle ball Other acute and chronic diseases and symptoms associated with protein and/or non-muscle myosin. 10 219 200823202 VII. Designated representative map: (1) The designated representative figure in this case is · (No) map. (2) A brief description of the symbol of the representative figure: None 5 10 15 VIII. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: 20 4 25