TW201043620A - Isoxazolines as inhibitors of fatty acid amide hydrolase - Google Patents

Abstract

The present invention provides FAAH inhibitors of the formula (I), or subgenera thereof: or a pharmaceutically acceptable form thereof, wherein each of G, Ra, Rb, Rc, Rd, L, R15 and z are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable excipient. The present invention also provides methods for treating an FAAH-mediated condition comprising administering a therapeutically effective amount of a compound of formula (I) or pharmaceutically acceptable form thereof, to a subject in need thereof.

Description

201043620 VI. Description of the invention: [Make the technical name of the good name 3 Cross-reference of the relevant application. The case requests US Provisional Patent Application Nos. 61/179, 280, 61/179, 283 and 6U179, 285, the application date is May 18, 2009. The entire text of the 'Priority' is hereby incorporated by reference. FIELD OF THE INVENTION The present invention relates to the difference as a fatty acid guanamine hydrolase inhibitor. No. 〇 sit 0 forest. C prior art; 3 BACKGROUND OF THE INVENTION Fatty acid indoleamine hydrolase (FAAH), also known as oleoresin hydrolase and anandamide, is an intact membrane protein that decomposes fatty acids, first amines and ethanol. Amines include oleoresin and blisteramide. FAAH decomposes the neuromodulated fatty acid guanamine at its site of action and is closely involved in its regulation. It has been demonstrated that FAAH involves a variety of biological procedures and inhibition of FAAH has been shown to be effective for the treatment of a variety of conditions. For example, inhibition of FAAH has been shown to be useful in the treatment of chronic pain, acute pain, neuropathic pain, anxiety, depression, eating behavior, dyskinesia, glaucoma, neuroprotection, and cardiovascular disease. However, current FAAH inhibitors lack the target selectivity, biological activity and/or bioavailability required for in vivo studies and therapeutic use. Thus, the therapeutic potential of FAAH inhibitors has remained largely unexplored. 201043620 [Summary of the Invention] Summary of the Invention This study provides a formula for the treatment of (1) iso-type saliva FAAH inhibitor compounds:

Or a pharmaceutically acceptable form thereof, wherein: (1) Ra, Rb, and Rj are selected from H, respectively. Hey. Alkyl and Ci丨. a perhaloalkyl group, Rd is a -L-Z group, and z is selected from the group consisting of sc6_14 aryl groups; (8) Ra, Rb, and Re are each selected from _H, Ci, respectively. The alkyl group and the perfluoroalkyl group 'RtL-Z group' and the Z series are selected from the group consisting of a 3·14Μ heterocyclic group and a 5-14 member heteroaryl group; (in) Ra and Rd are bonded to form a Cwo carbocyclic group or 3_ a 4-membered heterocyclic fused ring, and Rb and Re are each selected from the group consisting of H, L, and &W; and (lv) Re and Rd are joined to form a % carbocyclic group or a 3-14 member. Heterocyclic snail-slightly ring, and _ from _H, Ci_' group and Cm alkyl group; L is a covalent bond or a monovalent 匸丨6 ketone group, wherein one, two or three of the L The base unit 70 is selectively and separately substituted with __ or more oxygen, sulfur or gas atoms; the G system is selected from the group consisting of -CN, -N02, -S(=〇)Re, _s〇2Re, _s〇2NRfRe, 201043620 -P02Re, -P〇2〇Re, -P〇2NRfRe, -(C=0)Re, -(C=0)0Re, -(C=0)NRfRe, -Br, -I, -F, - Cl, -ORe, -ONRfRe, -0NRf(C=0)Re, -0NRfS02Re, -0NRfP02Re, -0NRfP020Re, -SRe, -0S02Re, -NRfS02Re, -OP〇2Re, -〇P〇2〇Re, -NRfP02Re , -NRfP020Re, -〇p〇2NRfRe, _〇(〇0)Re, -0(C=0)0Re, -NRfRe, -NRf(C=0)Re, -NRf(C=0)0Re, -0 (C=0) NRfRe, -NRf(C=NRf)NRfRe, -〇(C=NRf)NRfRe,

-NRf(ONRf)〇Re, -[N(Rf)2Re]+X_ where x- is the counter ion; 廿ΊΙ2Ι XV 1 erjin - φ 1^3.1〇 carbocyclic group, c6.14 aryl group, 3_14M miscellaneous a ring group and a 5-14 M heteroaryl group; each V attached to the e nitrogen atom is selected from a valence group, or an amine protecting group; or a R1Rf bond is converted into a 3-14 membered heterocyclyl ring or a 5-14 membered heteroaryl ring. . The invention also provides a compound comprising formula (1), or a pharmaceutically acceptable formula thereof, and a pharmaceutically acceptable exclamation. The shape of this month also provides the faa method of the individual (four) treatment, including the condition of the disease

A ^ A traitor is an effective amount of a flW or a pharmaceutically acceptable form thereof. The formula (!) combines the detailed portions and examples of additional embodiments of the invention. Others:: The heart of the book is divided into sections and the patents are invited to _ more rides. And the advantages are thus defined in detail by specific functional groups and undergraduates. Chemical Yuan Du #. The details of the 说明 说明 说明 说明 说明 说明 说明 说明 I I I I I I I I I I I I I I 化学 化学 化学 化学 化学 化学 化学 化学 化学 化学 化学 化学 化学 化学 化学 化学In addition, the general principles of organic chemistry and specific functional and reactive aspects are described in Organic Chemistry, Thomas Sorrell, University Science Handbook,

Sausalito ' 1999 ; Smith and March, March's Advanced Organic Chemistry 5th Edition, John Wiley & Sons 'New York, 2001; Larock, Integrated Organic Conversion' VCH Publishing Company, New York 1989; and Carruthers, Several Modern Organic Synthesis Methods 3rd Edition, Cambridge University Press, Cambridge 1987. Several of the compounds of the invention contain one or more asymmetric centers, such that they can exist in a variety of isomeric forms, i.e., enantiomers and/or diastereomers. The compounds provided herein may be in the form of individual enantiomers, diastereomers or geometric isomers, or may be in the form of a mixture of stereoisomers, including racemic mixtures and one or more stereoisomers. a rich mixture. In several embodiments, the compounds of the invention are enantiomerically pure compounds. In several other compounds, a mixture of stereoisomers is provided. Moreover, unless otherwise indicated, several compounds as described herein have one or more double bonds which may exist as cis or trans, or E or z isomers. The invention additionally encompasses compounds which are substantially free of individual isomers of other isomers, and additionally encompasses mixtures of various isomers, such as racemic mixtures of E/z isomers or an E/Z isomeric A mixture of structures. The terms "enantiomerically rich", "enantiomerically pure" and "racemic" are used interchangeably herein to mean that the weight percent of one of the enantiomers is greater than the racemic composition. A composition of the amount of one enantiomer (e.g., greater than 1:1 by weight) in the control mixture. By way of example, the enantiomerically enriched formulation of the (s)-enantiomer means having greater than 50% by weight of the (s)-enantiomer relative to the (R)-enantiomer, more preferably A formulation of at least 75% by weight of 201043620 and more preferably at least 80% by weight of the compound. In some embodiments, the richness can be much greater than 80% by weight, providing "substantially enantiomerically rich", "substantially enantiomerically pure" or "substantially non-racemic" formulation. A formulation having a composition of at least 85% by weight, more preferably at least 9% by weight, and still more preferably at least 95% by weight of the enantiomer relative to the other isomer. In a preferred embodiment, the enantiomerically enriched composition has a higher strength compared to the racemic mixture of the composition per unit weight of therapeutic use. The enantiomers can be isolated from the mixture by methods known to those skilled in the art, including the formation and crystallization of palmitic high pressure liquid chromatography (HPLC) and palmate salts; or preferred enantiomers. Prepared by asymmetric synthesis. See, for example, jacques et al., Enantiomers, Racemates, and Optical Segmentation (Willie Technologies, New York, 1981); Wilen, SH et al., Tetrahedron 33: 2725 (1977); Eliel, E丄· Stereochemistry of Carbon Compounds (McRowell, New York, 1962); and Wilen, SH, Optical Segmentation and Optical Segmentation, page 268 (Editor E. Eliel, Notre Dame University Press, Notre Dame , Indiana 1972). When a range of numerical values is recited, it is intended to cover the various values and sub-ranges within the range. For example, "Ci_6 alkyl" is intended to cover Ci, c2, c3, c4, c5, C6.丨_6, c丨-5, C丨·4, c!_3, C “2, C2_6, C2_5, C2.4, C2-3, C3-6, C3.5, c3.4, c4 6, c4 5. And c5 6 burnt base. As used herein, "direct bond" or "covalent bond" refers to a single bond that joins two groups. As used herein, alone or as part of another group, halo" and "halogen" mean fluoro (fluorine atom, -F), gas (gas atom, -C1), 201043620 bromine (bromine atom, -Br). Or iodine (iodine atom, -I). As used herein, alone or as part of another group, "alkyl" refers to a monovalent or branched saturated hydrocarbon group containing from 1 to 1 carbon atoms ("CM 〇 alkyl"). In several embodiments the 'alkyl group contains from 1 to 9 carbon atoms ("C!-9 alkyl"). In some embodiments, the alkyl group contains from 1 to 8 carbon atoms ("Cm alkyl"). In several embodiments, the alkyl group contains from 1 to 7 carbon atoms ("CM alkyl"). In several embodiments, the alkyl group contains from 1 to 6 carbon atoms ("C.6 alkyl"). In several embodiments, the alkyl group contains from 1 to 5 carbon atoms ("Cn5 alkyl"). In several embodiments, the alkyl group contains from 1 to 4 carbon atoms ("Cw alkyl"). In several embodiments, the alkyl group contains from 1 to 3 carbon atoms ("Cw alkyl"). In some embodiments, the alkyl group contains from 1 to 2 carbon atoms ("CN2 alkyl"). In the examples, the alkyl group contains 1 carbon atom ("C, alkyl"). In several embodiments, the alkyl group contains from 2 to 6 carbon atoms ("C2.6 alkyl"). Examples of the Cw alkyl group include a mercapto group (C0, ethyl (C2), n-propyl (C3) 'isopropyl (C3), n-butyl (C4), a third butyl (CO, a second butyl ( C4), isobutyl (c4), n-pentyl (C5), 3-pentyl (C5), pentyl (c5), neopentyl (c5), 3-methyl-2-butyl (cs), Second pentyl (cs), and n-hexyl (C6). Additional examples of alkyl groups include n-heptyl (C7), n-octyl (C8), etc. Unless otherwise specified, the alkyl groups are each not Substituted ("unsubstituted alkyl") or substituted ("substituted alkyl") substituted by i, 2, 3, 4 or 5 substituents as described herein. The 'burning base' is the unsubstituted Cmo yard base (for example, -ch3). In some implementations, the base is replaced by Cl.: 炫基. Here, "全画烧基" means 1 Each of the hydrogen atoms of each of the 10 carbon atoms is replaced by a dentate such as a gas, a gas, a gas or a 201043620 iodine atom ("cMQ all-alkyl"). In several embodiments, the alkyl moiety comprises 1 to 8 carbon atoms ("Cw all-alkyl"). In several embodiments, the alkyl moiety contains 1 Up to 6 carbon atoms ("CN6 functional alkyl"). In several embodiments, the alkyl moiety contains from 1 to 4 carbon atoms ("Cm perhaloalkyl"). In several embodiments, the alkyl moiety Containing from 1 to 3 carbon atoms ("Cw perhaloalkyl"). In some embodiments, the alkyl moiety contains from 1 to 2 carbon atoms ("Cu perhaloalkyl"). In several embodiments, all Each of the hydrogen atoms is replaced by a fluorine atom. In some embodiments, all of the hydrogen atoms are each replaced with a chlorine atom. 实例 Examples of perhaloalkyl groups include -CF3, -CF2CF3, -CF2CF2CF3, -CC13, _-CFC12 , -CF2C1, etc. As used herein, alone or as part of another group, "alkenyl" refers to a straight or branched hydrocarbon group containing from 2 to 1 carbon atoms and one or more carbon-carbon double bonds. Monovalent group ("C2-10 alkenyl"). In several embodiments, an alkenyl group contains 2 to 9 carbon atoms ("C29 alkenyl"). In several embodiments, the alkenyl group contains 2 to 8 Carbon atom ("C2.8 alkenyl"). In several embodiments, the alkenyl group contains from 2 to 7 carbon atoms ("CM alkenyl"). In several embodiments Alkenyl contains 2 to 6 carbon atoms ("C2.6 alkenyl"). In several embodiments, alkenyl contains 2 to an anaerobic atom ("匚2·5"). In several embodiments , the dilute group contains 2 to 4 ^ anti-atom (C2_4 fluorenyl). In several embodiments, the dilute group contains 2 to 3 carbon atoms "sub ("CM alkenyl"). In several embodiments, alkenyl Containing one carbon (2 alkenyl). One or more carbon-carbon double bonds may be internal (such as 2_: base) or terminal (such as W-butenyl 4 alkenyl) including ethylene dimei ^ 1 - Propenyl (c3), 2-propenyl (C3), κbutenyl ((5), 2-butyl), butadienyl (C4), and the like. Examples of the C2.6 alkenyl group include the aforementioned c2_4 9 201043620 alkenyl group and pentenyl group (c5), pentadienyl group (c5), hexenyl group (c6) and the like. Additional examples of alkenyl groups include heptenyl (c7), octenyl (c8), octatrienyl (c8) and the like. Unless otherwise specified, each of the alkenyl groups is unsubstituted ("unsubstituted alkenyl") or substituted by 1, 2, 3, 4 or 5 substituents as described herein ("substituted Alkenyl";). In several embodiments, the alkenyl group is an unsubstituted C2_1G dilute group. In several embodiments, the dilute group is a substituted C2_] fluorene. As used herein, alone or as part of another group, "alkynyl" refers to a valence group of a straight or branched hydrocarbon group containing from 2 to 1 carbon atoms and one or more carbon-carbon hydrazone bonds ( "C2-10 alkynyl"). In several embodiments, an alkynyl group contains 2 to 9 carbon atoms ("c2-9 alkynyl"). In several embodiments, an alkynyl group contains 2 to 8 carbon atoms ("c2.8 alkynyl"). In some embodiments, an alkynyl group contains 2 to 7 carbon atoms ("c2-7 alkynyl"). In several embodiments, an alkynyl group contains from 2 to 6 carbon atoms ("c26 alkynyl"). In some embodiments, an alkynyl group contains 2 to 5 carbon atoms ("c2_5 alkynyl"). In several embodiments, an alkynyl group contains 2 to 4 carbon atoms ("C2_4 alkynyl"). In several embodiments, an alkynyl group contains 2 to 3 carbon atoms ("C2_3 alkynyl"). In some embodiments, an alkynyl group contains two carbon atoms ("C2 alkynyl"). One or more carbon-carbon bonds may be internal (such as 2-butynyl) or terminal (such as 1-butynyl). Examples of C2-4 alkynyl groups include, but are not limited to, ethynyl (C2) '1-propynyl (C3), 2-propynyl (CD, 丨-butynyl (C〇, 2-butynyl (c4) Examples of C2-6 alkynyl groups include the aforementioned C2_4 alkynyl and pentynyl groups (CD, pentadiynyl (C5), hexynyl (C6), etc. Additional examples of alkynyl groups include heptynyl (C7) , octynyl (C8), etc. Unless otherwise specified, each of the alkynyl groups is unsubstituted ("unsubstituted alkynyl") or via 2, 10 201043620 3, 4 or 5 as herein The substituent is substituted ("substituted alkynyl"). In several embodiments, the alkynyl group is an unsubstituted C21G alkynyl group. In several embodiments, the alkynyl group is a substituted c210 alkynyl group. The divalent (^_6 hydrocarbyl group) is a divalent Cl-6 alkyl group, a divalent Cw alkenyl group or a divalent Cw alkynyl group in which one, two or three fluorenylene units (_ch2_) of the hydrocarbon chain are selectively and respectively The ground is replaced by one or more oxygen, sulfur or nitrogen atoms. As used herein, alone or as part of another group, "alkoxy" refers to an alkyl group, as defined herein, substituted by an oxygen atom, Where the attachment point Oxygen atom. In several embodiments, the alkyl group contains hydrazine to 1 碳 carbon atoms - ("Cl_1G alkoxy"). In several embodiments, the alkyl group contains 1 to 8 carbon atoms. ("Cl_8 Oxygen In some embodiments, the alkyl group contains from 1 to 6 carbon atoms ("Cm alkoxy"). In several embodiments, the alkyl group contains from about 4 carbon atoms ("Cm alkoxy" Examples of the c, -4 alkoxy group include a decyloxy group (Ci), an ethoxy group (C2), a propoxy group (o, an isopropoxy group (anthracene, a butoxy group, a third butoxy group (Cs) And the like: ("" Examples of the hospitaloxy group include the aforementioned oxy group and pentyloxy fluorenyl group (C5), isopentyloxy group (C5), neopentyloxy group (6), hexyloxy group ((5), etc. Examples include heptyloxy (C7) and octyloxy (10). Unless otherwise specified, the alkyl groups of the oxo groups are each unsubstituted ("unsubstituted oxy") or m, 2, 3, 4, respectively. Or 5 substituents as described above ("substituted alkoxy"). In several embodiments, the methoxy group is an unsubstituted C2.10 alkoxy group (eg _ squeezing. In several implementations) In the example, the methoxy group is a Cw-forming oxy group ( A full-tooth alkoxy group as defined herein.) All ii alkoxy group is an oxygen-lowering group in which all of the gas atoms of the alkyl group 11 201043620 are each selected from the group consisting of fluorine, gas, bromine and iodine. Atomic substitution. In some embodiments, the alkyl moiety contains from 1 to 10 carbon atoms ("CMo perhalooxy"). In several embodiments, the alkyl moiety contains from 1 to 8 germanium atoms ("Cw all Haloalkoxy"). In several embodiments, the alkyl moiety contains hydrazine to one carbon atom ("C1·6 functional alkoxy"). In several embodiments, the alkyl moiety contains from 1 to 4 Carbon atom (rCl 4 perhaloalkoxy)). In some embodiments, the alkyl moiety contains from 1 to 3 carbon atoms ("Cl_3 perhaloalkoxy"). In some embodiments, the alkyl moiety contains hydrazine to 2 carbon atoms ("(^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ All hydrogen atoms are each replaced with chlorine. Examples of homodentate alkoxy include, but are not limited to, 〇CF3, -〇CF2CF3, -OCF2CF2CF3, -0CC13, -OCFCl2, -〇CF2Cl, etc. As used herein, alone or as another A group - "group" refers to a non-aromatic cyclic hydrocarbon group having from 3 to 10 ring carbon atoms ("c3 1 () carbocyclic group)) and a non-aromatic ring system having zero heteroatoms. In some embodiments, the carbocyclic group contains 3 to 8 ring carbon atoms ("Cw carbocyclic group"). In several embodiments, the carbocyclic group contains 3 to 6 ring carbon atoms ("〇36 carbocyclic group" In some embodiments, the carbocyclic group contains 5 to 1 ring carbon atoms ("q heptacarbocyclyl"). Examples of CM carbocyclic groups include, but are not limited to, cyclopropyl (cj, cyclobutyl) (CO, cyclopentyl (Co, cyclopentenyl (Co, cyclohexyl (C6), cyclohexenyl (C6), cyclohexanediyl (Q), etc. Examples of c3_8 carbocyclic groups include the aforementioned ^Cyclo and cycloheptyl (C7), cycloglycan ((:7), cycloheptatrienyl), cyclooctyl (C8), bicyclo[2.2.1]heptyl, bicyclo[2 2 2] octyl and the like. Examples of the c3(7) carbocyclic group include the aforementioned CM carbocyclic group and octahydro-1H-fluorenyl group, decahydroxene 12 201043620 group, spiro[4.5] fluorenyl group, etc., as exemplified in the foregoing examples, in several In the expanded example, the carbocyclic group is a monocyclic ring system ("monocyclic carbocyclic group" _^ (example = fused ring system, bridged ring system or spiro ring system such as bicyclic system s ^ bearing (a ring system carbon) a cyclic group") or a tricyclic system ("tricyclic carbocyclyl")) and may be saturated or may contain one or more carbon-carbon double bonds or a bond. "Carbocyclyl" also includes A defined carbocyclyl ring is a ring system in which one or more aryl or heteroaryl groups are attached to a carbocyclic ring. Unless otherwise specified, each of the carbocyclic groups is unsubstituted ( "Unsubstituted carbocyclic group") or substituted with ]^], 3, 4 or 5 substituents as described herein ("substituted carbocyclic"). In several embodiments, carbocyclyl In several embodiments of the unsubstituted C3_1Q carbon ring 2, The ring group is a substituted Cm carbocyclic group. • In some embodiments, a "carbocyclic group" is a saturated ring-containing group having 3 to 1 ring carbon atoms ("C3.1G cycloalkyl"). In some embodiments, the cycloalkyl group contains from 3 to 8 ring carbon atoms ("Cw cycloalkyl"). In several embodiments, the cycloalkyl group contains from 3 to 6 ring carbon atoms ("(:3_6 cycloalkyl) In some embodiments, the q cycloalkyl group contains 5 to 6 ring carbon atoms ("C5·6 cycloalkyl"). In several embodiments, the cycloalkyl group contains 5 to 10 ring carbon atoms ( "(^^cycloalkyl)". Examples of the Gy cycloalkyl group include a cyclopentyl group (C5) and a cyclohexyl group (c5). Examples of the c3_6 cycloalkyl group include the aforementioned C5-6 cycloalkyl group and a cyclopropyl group (C3) and a cyclobutyl group (CJ. The C3-8 cycloalkyl group includes the aforementioned C3·6 cycloalkyl group and cycloheptyl group (c7) and cyclooctane. Base (Cs). Unless otherwise specified by #, each of the cycloalkyl groups is unsubstituted ("unsubstituted % alkyl") or 1, 2, 3, 4 or 5 as described herein. Substituent substitution ("substituted cycloalkyl"). In several embodiments, the cycloalkyl group is an unsubstituted C3-i〇 cycloalkyl group. In several embodiments, the cycloalkyl group is replaced by 13 201043620 a cycloalkyl group. h蜀 or as a group of another group means a non-aromatic group of 3-14 members having a π heterocyclic ring group of a vermiculite mountain, a complex intermediate = 1 and 4 ring hetero atoms. Ring base"),. The μΓ atom is selected from the group consisting of nitrogen, oxygen and sulfur, respectively (“w when the number of w is allowed, the core: one or more heteroatoms of one or more gas atoms, when the valence system (“monoatomic or nitrogen atom. Heterocyclic group can be Monocyclic or spiro ring systems such as di(tetra)" or polycyclic systems (eg, fused ring systems, bridged ring system heterocyclic groups)), and V ("bicyclic heterocyclic") or tricyclic ( "Tricyclic or para-bonded. Heterocyclyl poly-I and or may contain one or more carbon-disc double bonds or a plurality of heteroatoms. "Miscellaneous: it may be included in one ring or two rings - one ring system Also included in the heterocyclic or heterocyclic ring as defined above, wherein the attachment point is attached to the carbocyclic ring, 'or ' or a heterocyclic ring thereof as defined above One or more aryl" groups are fused on a ring system. If the attachment point is in the heterocyclic ring to 4 ring heteroatoms =, the heterocyclic group has a ring A carbon atom and a heterocyclic group are used for carbon; a heterocyclic group; In some embodiments, the atom and one to four ring heteroatoms of the 5-8 member are non-aromatic to four ring heteroatoms in the %, wherein the heterocyclic group has a ring carbon atom and one is selected from the group - 5 '6 member non-aromatic ring system, wherein each hetero atom is 5_6^a!^ ("5·6 member heterocyclic group") ° In several embodiments, +眚1 ^ to 3 are selected from nitrogen, oxygen and Sulfur ring heteroatoms. In several embodiments, the 'W member heterocyclic group contains (1) a ring selected from nitrogen, oxygen, and sulfur. 201043620 = two =: '5, the ring group contains 1 terminal, __ group, and: hetero:: 2: ring group The truth: package 2 but not limited to μ base 'μ base and (4) base. Examples of the base and the two-membered atom include, but are not limited to, tetrachloromethane: a group, a tetrahydro-thenyl group, a chlorinyl group, and (d). Base,

And the base is a diketone. A 5-membered heterocyclic group containing 2 heteroatoms; ^ is limited to a dicosyl ruthenium (tetra)yl group and a diasteryl group. Examples of the 5-membered heterocyclic group containing 3 include, but are not limited to, a tribasic group of 2, 2, and a red group. An example group of a 6-membered heterocyclic group having 1 hetero atom, a tetrahydro group, and a dihydrogen group Examples of a 6-membered heterocyclic group of a fluorenyl group and two = 32 heteroatoms include, but are not limited to, hydrazine, imiline, ruthenium, and hexamethylene. 6-member heterocycles containing 2 heteroatoms: Examples include, but are not limited to, Thirty-six. Examples of a 7-membered heterocyclic group containing a hetero atom include, but are not limited to, d-pyryl, rugged, and cyclized. It is secretive but secretive to (iv) yl, yl and thiazide. Examples of bicyclic heterocyclic groups include, but are not limited to, porphyrinyl, isoindole, monolinyl, dihydrobenzo-following, and Hydrobenzobenzophenyl, tetrahydrobenzoxyl, thiophene, tetrachlorobenzopyranyl, tetrahydroindolyl, tetrahydroindenyl, tetrahydroisoindolyl, decahydrocarbyl, Decahydroisoyl, human hydrogen decyl, octahydroisodecyl, decahydroacridinyl, decahydro-indole-acridinyl, octahydropyrrolo[3,2-b]pyrrole, porphyrin , quinone imine, naphthoquinone imine, biting thiol, biting thiol, 1 Benzo[e][i,4]dioxinyl, 1,4,5,7-tetrahydropyrano[3,4-7]pyrrolyl, 5,6-dihydro-4H-furo[3 ,2-b]pyrrolyl, 6,7_ 15 201043620 dihydro-5H-trinop[3,2-b]bromopyranyl, 5,7-dihydro-4H-°cepheno[2,3- c] piperidyl, 2,3-dihydro-1H-pyrrole [2,3_b] ° ° base, 2,3~ dihydrofuro[2,3-b]pyridyl, 4,5,6 ,7-tetrahydro-1H-° ratio[2,3_bl·pyridinyl, 4,5,6,7-tetrahydrofuro[3,2-c]pyridyl, 4,5,6,7-tetra Hydrothieno[3,2-b]pyridyl, 1,2,3,4-tetrahydro-1,6-acridinyl, etc. Unless otherwise specified, each of the heterocyclic groups is unsubstituted ( The "unsubstituted heterocyclic group" is substituted by 1, 2, 3, 4 or 5 substituents as described herein ("substituted heterocyclic group"). In several embodiments, the heterocyclic group is an unsubstituted 3-14 membered heterocyclic group. In several embodiments, the heterocyclic group is a substituted 3-14 membered heterocyclic group. As used herein, alone or as part of another group, "aryl" refers to a monocyclic or polycyclic ring containing from 6 to 10 ring carbon atoms and containing no heteroatoms in the aromatic ring system (eg, bicyclic or tricyclic) An aromatic ring system (for example, a group having 6, 1 or 14 π electrons shared in a circular array) ("C6_14 aryl"). In several embodiments, the aryl group contains 6 ring carbon atoms ("C6 aryl", such as stupid). In some embodiments, the aryl group contains 10 ring carbon atoms ("ClG aryl"; for example, a naphthyl group such as 1-naphthyl and 2-naphthyl). In several embodiments, the aryl group contains 14 ring carbon atoms ("CM aryl"; for example, fluorenyl). "Aryl" also includes ring systems wherein the aryl ring system as defined above is fused to one or more carbocyclic or heterocyclic groups wherein the group or attachment point is attached to an aryl ring. Unless otherwise specified, each aryl group is unsubstituted ("unsubstituted aryl") or substituted with 2, 3, 4 or 5 substituents as described herein ("Substituted Aryl"). In her case, the 'aryl group is an unsubstituted % aryl group. In several embodiments, the aryl group is a substituted C6.丨4 aryl group. 16 201043620 Part as used herein, alone or as part of another group, "heteroaryl" means that the ring carbon atom and the _ ring hetero atom are provided in the aromatic ring system to be premature or polycyclic (eg bicyclic or a tricyclic) aromatic ring system (for example, in a ring = column having 6, 1 or 14 shared (four) sub) groups, each of which is heterozygous

... pores and sulfur ("5-14 member heteroaryl"). In a substrate containing -= or multiple pour atoms, the _ number is allowed, the attachment point may be a charcoal:, or the nitrogenogen + heteroaryl polycyclic system may be in one ring or two rings including one: or a eve Hetero atom. "Heteroaryl" also includes (10) wherein the heteroaryl 2% is a combination of one or more aryl groups, wherein the attachment point is on the aryl = or on the heterosis, or A heteroaryl ring system as defined above is a ring system of one or more carbocyclic or heterocyclic groups wherein the attachment point is on a clothing: clothing. For a polycyclic aryl group (ie, 3 wood, (4), (4), etc.) in which the ring contains no heteroatoms, the attachment point may be on any ring, and also the % of the hetero atom (eg 2 _ ah base or ring without heteroatoms (eg 'wood base'). In some embodiments, the heteroaryl group is a MG member (four) having a ring carbon atom and one to four are provided in the county of Aroma County, wherein each hetero atom is selected from the group consisting of nitrogen, oxygen, and sulfur ("5__ Aryl"). In a number of embodiments, the 'heteroaryl group is a 5-8 membered aromatic ring system having a ring carbon atom and a hetero atom provided to the aromatic ring system, wherein each hetero atom is selected from the group consisting of nitrogen, oxygen and sulfur (". ") in a number of real/hetero 1 bases having a ring carbon atom and a hetero atom providing an aromatic ring system 17 201043620 5-6 shell aromatic ring system, wherein each hetero atom is selected from nitrogen, oxygen and Dish (6 members of heteroaryl)). In several embodiments, the 5-6 membered heteroaryl contains from 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In several embodiments, the heteroaryl contains from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In several examples, the 5-6 membered heteroaryl contains 1 hetero atom selected from the group consisting of nitrogen, oxygen, and sulfur. Examples of 5M heteroaryl groups having one hetero atom include, but are not limited to, % sylylene, thiol and porphinyl. Examples of a 5-membered heteroaryl group containing 2 heteroatoms include, but are not limited to, a sulphonyl group, a thiophene group, a decyl group, a decyl group, and a stilbene group. Examples of the top heteroaryl group containing 3 hetero atoms include, but are not limited to, a triazolyl 'oxadiazolyl group, a thiadiazolyl group. Examples of 5-membered heteroaryl groups containing 4 heteroatoms include, but are not limited to, four filaments. Examples of 6-membered heteroaryl groups containing i heteroatoms include, but are not limited to, sulfhydryl groups. Examples of 6-membered heteroaryl groups containing 2 heteroatoms include, but are not limited to, taphthyl, fine and fluorenyl. Examples of 6M heteroaryl groups containing 垓 4 heteroatoms include, but are not limited to, trimorphyl and tetramorphyl, respectively. Examples of 7-membered heteroaryl groups containing one hetero atom include but not: ah ki's ah base and ° sehehki. Examples of the 5,6·bicycloheteroaryl group include, but are not limited to, a benzyl group, a filament, a (tetra) group, a benzotrizole, a benzononenyl group, an isobenzopyranyl group, a benzofluorenyl group, and a stupid Diterpene π-Nanyl, benzoxazolyl, benzoxanthyl, benzoiso-indenyl, benzopyrene, etc. Diterpenoids, benzoxanthyl, benzoisoindolyl, stupid and thiazepine Salivary + towel base, and sulfhydryl. Examples of 6,6-bicyclic heteroaryl groups include, but are not limited to, acridinyl, acridinyl, fluorenyl, isoindolyl, phylhenyl, and mercapto. Examples of tricyclic heteroaryl groups include, but are not limited to, phenanthryl, dibenzofuranyl, fluorene, fluorenyl, morphyl, cyano, and cyano. 201043620 Unless otherwise specified, each of the heteroaryl groups is unsubstituted ("unsubstituted heteroaryl") or substituted with a substituent as described herein ("Substitution Miscellaneous shirt"). In the case of rape, the heteroaryl is an unsubstituted 5_14 base. In a number of implementations, the heteroaryl group is a substituted 5-14 membered heteroaryl group. A subset of the "aromatic base" A "burning base" and refers to

The genus of the genus is so ambiguous that its garnish is attached to the alkyl moiety. As used herein, the term "partially unsaturated" means a ring portion that includes at least one double bond or a key bond. "Partially unsaturated" - the word is intended to encompass a ring having multiple unsaturations' but is not intended to include an aromatic group (e.g., an aryl or heteroaryl moiety) as defined herein. The alkyl, alkenyl, alkynyl, alkyl, heterocyclyl, aryl and heteroaryl groups as defined herein may be substituted as desired (eg, "substituted" or "unsubstituted", "Substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" hindered cyclic, "substituted" Or "unsubstituted" heterocyclic group, "substituted" or "unsubstituted" aryl or "substituted" or "unsubstituted" heteroalkyl). In general, the term "substituted", whether or not it is required in the front, means that at least one hydrogen present on a group (for example, a carbon atom or a nitrogen atom, etc.) is tolerable. Substituent substitutions, for example, when substituted, may result in substituents that stabilize the compound, such as compounds that do not spontaneously undergo conversion, such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a "substituted" group has 19 201043620 substituents at one or more substitutable positions of the group, and when more than one position in any given formula is substituted, This substitution is the same or different based on each location. Examples of carbon atom substituents include, but are not limited to, halogen (i.e., fluorine (-F), bromine (-Br), gas (-C1), and iodine (-1), -CN, -N02, -N3, - S02H, -S03H, -OH, -ORaa, -ON(Rbb)2, -N(Rbb)2, -N(Rbb)3+X, -N(ORec)Rbb, -SH, -SRaa, -SSRCC, -C(=0)Raa, -C02H, -CHO, -C(ORcc)2, -C02Raa, -0C(=0)Raa, -0C02Raa, -C(=0)N(Rbb)2, -0C( =0) N(Rbb)2, -NRbbC(=0)Raa, -NRbbC02Raa, NRbbC(=0)N(Rbb)2, -C(=NRbb)Raa, -C(=NRbb)ORaa, -OC( =NRbb)Raa ' -OC(=NRbb)ORaa ^ -C(=NRbb)N(Rbb)2 ' -OC(=NRbb)N(Rbb)2 , -NRbbC(=NRbb)N(Rbb)2 , - C(=0)NRbbS02Raa, -NRbbS02Raa, -S02N(Rbb)2, -S02Raa, -S020Raa, -OS02Raa, -S(=0)Ra, _〇S(=0)Raa, _Si(Raa)3, - OSi(Raa)3, -C(=S)N(Rbb)2, -C(=〇)SRaa, -C(=S)SRaa, -SC(=S)SRaa, -P(=0)2Raa, -〇P(=〇)2Raa, _P(=0)(R-)2, -0P(=0)(Raa)2, -OP(=0)(ORcc)2, -P(=〇)2N( Rbb)2, -0P(=0)2N(Rbb)2, -P(=0)(NRbb)2, -0P(=0)(NRbb)2, -NRbbP(=0)(ORcc)2, - NRbbP(=〇)(NRbb)2, _P(Rec)2, -P(R")3, -OP(Rec)2, -OP(Rcc)3, _B(ORce)2, _BR, 〇ReC), Ci i〇alkyl , CM〇 all i alkyl, C2_1G alkenyl, C2-1G alkynyl, (33.14 carbocyclyl, 3-14 heterocyclyl, (6-fluorene, 5-14 membered heteroaryl), wherein each alkyl group, The dilute, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are each substituted with 〇, 1, 2, 3, 4 or 5 Rdd groups; 20 201043620 or on a carbon atom Two geminal hydrogens are grouped by 0, = S, = NN(Rbb)2, =NNRbbC(=0)Raa, =NNRbbC(=0)〇Raa, =NNRbbS(=〇)2Raa , =NRbb, =N〇Rcc replacement;

Each of Ra is selected from C丨-10 炫, CM0 perhaloalkyl, C2_decenyl, C2_1G alkynyl, C3-io carbocyclyl, 3-14 membered heterocyclic, c6.14 An aryl group, and a 5-14 membered heteroaryl group, wherein each of the alkyl group, the dilute group, the fast group, the carbocyclic group, the heterocyclic group, the aryl group, and the heteroaryl group are respectively 〇, 1, 2, 3, 4 or 5 Rdd group substitutions; each of bb - R is selected from the group consisting of hydrogen, -OH, -ORaa, _N(Rce)2, _CN, -C(=0)Raa. -C(=〇)N( Rcc)2 > -C02Raa . -S02Raa > _c(=NRCC)0Raa, -c(,Rcc)n(Rcc)2, -so2n(r-)2, _S〇2r' s〇2〇Rec, _S0Raa , _c(=s)n(r«)2, _C(=0)SR", _C(=S)SRCC, -P( 0)2R > -P(=〇)(Raa)2 > -P (=〇) 2N(Rcc)2 . -P(=〇)(NRcc)2 ^ CMQ alkyl, alkyl, c2_iq alkenyl, C21G alkynyl, Cw❶ carbocyclic fluorenyl, 3-14 heterocyclyl, C6. a 14-aryl group, and a 5-14 membered heteroaryl group, or two R« groups attached to a milk atom to form a 3-14 membered heterocyclic ring or a 5-14 membered heterocyclic group, wherein each of the alkyl groups and the dilute group , a block group, a carbocyclic group, a heterocyclic group, an aryl group, and a heteroaryl group are respectively substituted with hydrazine, b, 2, 3, 4 or 5 Rdd groups; Rcc Each of the examples is selected from the group consisting of hydrogen, cM, alkyl, Cm, all (tetra), and then alkenyl, alkenyl, alkynyl, C3_1〇carbocyclyl, 3-14 heterocyclyl, Q丨* aryl And a 5 14-shell heteroaryl group, or two Ree groups attached to a nitrogen atom, to form a 3-14 membered heterocyclyl ring or a 5-14 membered heteroaryl ring, wherein each alkyl group, a dilute group, an alkynyl group, or a carbon group a cyclic group, a heterocyclic group, an aryl group, and a heteroaryl group are substituted by 0, 1, 2, 3, 4 or 5 Rdd groups by 21 201043620;

Each of Rdd is selected from the group consisting of hydrogen, -CN, -N〇2, -N3, -S02H, -S03H, -OH, -ORee, -ON(Rff)2, -N(Rff)2, -N( Rff)2+X-, -N(ORee)Rff ' -SH ' -SRee > -SSRee ' -C(=0)Ree ' -C02H ' -C02Ree, -0C(=0)Ree, -〇C02Ree, -C(=0)N(Rff)2 ' -OC(=0)N(Rff)2 , -NRffC(=0)Ree, -NRffC02Ree, -NRffC(=0)N(Rff)2, _C(= NRff)ORee, -OC(=NRff)Ree, -OC(=NRff)ORee, -C(=NRff)N(Rff)2, -〇C(=NRff)N(Rff)2, -NRffC(=NRff N(Rff)2, -NRffS02Ree, S02N(Rff)2, -S02Ree, -S020Ree, -〇S02Ree, -S(=0)Ree, -Si(Ree)3, -〇Si(Ree)3, - C(-S)N(Rff)2, -C(=〇)SRee, -C(=S)SRee, -SC(=S)SRee, -P(=〇)2Ree,·Ρ(=0)( γ)2, _〇p(=〇)(Ree)2, _〇p(=〇)(〇Ree)2, q-6 alkyl, (^ all-alkyl, c2 6 alkenyl, c2 6 alkyne a carbocyclyl group, a 3-10 membered heterocyclic group, an aryl group, and a 5_1 member heteroaryl group, wherein each alkyl group, alkenyl group, alkynyl group, carbocyclic group, heterocyclic group, aryl group, and hetero The aryl group is substituted with 0' 1, 2, 3, 4 or 5 core groups, respectively, or the two 偕Rdd substituents can be joined to form =0 or = s; : The knife is selected from C1_6 Base, C1_6 all-group, .26 dilute 2-6 block, C(tetra)carbocyclyl, C(tetra)filament, 3_3·10 membered heteroaryl, wherein each alkyl group, dilute base, block group, indeed =, and ring group 'Aryl, and heteroaryl are divided by 2, hetero group; 2, 3, 4 or 5 11

Each of the Rff examples is selected from the group consisting of hydrogen, Ci 6 alkyl, C3-i〇 carbocyclyl, 3-10 membered heteroalkenyl 'c2_6 alkynyl, ci-6, decylene, C2, CM0 aryl, 22 201043620 And a 5-10 membered heteroaryl group, or two Rff groups attached to a nitrogen atom, are joined to form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl ring, wherein each alkyl group, a dilute group, an alkynyl group, a cycline, a heterocyclyl, an aryl, and a heteroaryl are substituted with 〇, i, 2, 3, 4 or 5 Rgg groups, respectively;

Each of Rgg is halogen, -CN, -N〇2, -N3, -S02H, -S03H, -OH, -OCw alkyl, -OlSKCk, 2, -ΝΑβ alkyl)2, -Νβκ alkane 3), -NH(Ci_6 alkyl) 2X, -NHXCw alkyl) Χ, -ΝΗ3Χ, -I^OCkalkyl XCw alkyl), -NCOHXCw alkyl), -NH(OH), -SH, - SCu alkyl group, -SSCCu alkyl group, -CPOXCk alkyl group, -co2h, -ccmCw alkyl group, -ocpoxck alkyl group), -OCO/Cw alkyl group, -C(=0)NH2, -(: (=0)1^((:,.6 alkyl)2, -0(:(=0)1^((^.6 alkyl), -NHCtOXCw alkyl), -Nfw alkyl)CPOXCw alkyl ), -NHCOXCk alkyl), -NHCPCONCC^ alkyl)2, -NHCpCON^Cu alkyl), -NHC(=0)NH2, -(:(=1^)0((^.6 alkyl), -OCNI^Cw alkyl), -0(:(=1^)0(^-6 alkyl, alkyl)2, alkyl), -C(=NH)NH2, -OC(=NH)N( Ci_6 alkyl) 2, -OCXNI^NHew alkyl), -OC(NH)NH2, -NHCXNI^NCCk alkyl)2, -NHC(=NH)NH2, -NHSO^Cualkyl), -SCWCCk alkyl 2, SC^NI^Cu burnt base), -S〇2NH2, -S02Ci.6 dazzle, -SO2OC1-6 yard, -OSO2C1-6 burnt base, _SOCi-6 dazzle, _Si (Cl-6 burn) Base) 3, -〇Si(Ci-6 alkyl)3, -CpSMC^ alkane 2, -CPS^HCCm alkyl), -C(=S)NH2, -(:(=0)8((^.6 alkyl), -C(=S)SCV6 alkyl, -scpspcw alkyl , -PpoMCw), -p(=〇)(Cn6 alkyl) 2, 23 201043620 -OPhOXCw alkyl 2, -OPpOXOCw alkyl) 2, Cw alkyl, c"6 perhalogenated, C2- 6 dilute group, C 2-6 fast group, C 3 -10 carbon bad group, C 6-10 square group, 3-10 member heterocyclic group, 5-10 member heteroaryl group; or two 偕Rgg substituents can be joined to form =0 or two S; where X_ is a counterion. As used herein, a "counterion" is a negatively charged group that maintains electron neutrality in combination with a positively charged fourth amine. Examples of counterions include halide anions (eg, F-, Cl-, Br, Γ), N〇3·, C1CV, OH-, H2PO4', HSCV, sulfonate ions (eg, mesylate, trifluorosulfonate) , p-toluenesulfonate, benzenesulfonate, 10-camphorsulfonate, naphthalene-2-sulfonate, naphthalene-1-sulfonate-5-sulfonate, ethyl-1-sulfonate-2-sulfonate, etc.) and carboxy An acid anion (eg, acetate, ethyl ketoate, propionate, benzoate, glycerate, lactate, tartarate, glycolate, etc.). When the valence permits, the nitrogen atom may be substituted or unsubstituted, and include the first, second, third and fourth nitrogen atoms. Examples of nitrogen atom substituents include, but are not limited to, hydrogen, -OH, -ORaa, -N(RCC)2'-CN'-C(=0)Raa, -C(=〇)N(Rce)2, _C〇 2Raa, _S〇2Raa, _C(=NRbb)Raa, -C(=NRce)0R' -C(=Nir)N(R")2, _s〇2N(Ree)2, _s〇2RCC, -so2〇rcc , _S0Raa, _c(=s)n(r")2, _c(=〇)SRee, _c(=s)srCC, -P(=0)2Raa, _P(=〇)(Raa)2, _p(= 〇) 2N (Ree) 2, p (= 〇) (NRCC) 2

Cmg alkyl, C1 丨❹ all-alkyl, C2-1. Alkenyl, C2"Q alkynyl, c3.1Q carbocyclyl, 3-14 membered heterocyclyl, c^4 aryl, and 5-14 membered heteroaryl, or two RCC groups attached to 5 atoms Forming a 3-14 membered heterocyclyl ring or a 5-14 membered heteroaryl group wherein each of the alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, 24 201043620 aryl, and heteroaryl groups are respectively 〇, 1, 2, 3, 4 or 5 Rdd group substitutions, and wherein Raa, Rbb, Rcc and Rdd are as defined above. In several embodiments, the substituent present in the nitrogen atom is an amine protecting group. Amino protecting groups include, but are not limited to, -OH, -ORaa, -N(Rec)2, •c(=0)Raa, -C(=〇)N(RcV -C02Raa, -S02Raa, -C(=NRcc) Raa, _C(=NRCC)〇Raa, -C(=NRec)N(Rcc)2, S02N(Rcc)2, -S02Rcc, _S〇2〇Rcc, -SORaa, -C(=S)N(Rcc 2, _C (=0) SRcc, _C (= S) SRcc, ¢) Cl-10 alkyl (such as aralkyl), c2_1 () alkenyl, c2_1 () alkynyl, c3.1 () carbon ring a 3-14 membered heterocyclic group, a c614 aryl group, and a 5-14 membered heteroaryl group, wherein each alkyl group, an alkenyl group, an alkynyl group, a carbocyclic group, a heterocyclic group, an aryl group, and a heteroaryl group are respectively Substituted by 〇, 1, 2, 3, 4 or 5 Rdd groups, and Raa, Rbb, RCC and

Rdd is as defined above. Amino protecting groups are well known in the art and include those detailed in organic synthetic protecting groups, T_W. Greene and PGM· Wuts, 3rd edition, about the group of the Willie Wiley & Sons, 1999, incorporated by reference. Here. Examples of, for example, an amine protecting group such as a guanamine group (e.g., -C(=0)Raa) package, but not limited to guanamine, acetamide, gas acetamide, triethylene acetamide, trifluoroacetamidine Amine, phenylacetamide, 3-phenylpropionamide, pyridine carbenamide, 3_β butyl lysine, _N benzoyl propylamine amide derivative, nodal amine, p-phenyl Brewing base, o-nitrophenyl acetamide, o-succinyl ethoxylated amine, acetamidine, sul-disulfide oxyalkylamine, ethylamine, 3 thio-phenyl Propionamide, HUM xiao phenyl) propyl hydrazide ' 2 曱 冬 冬 ( ( 硎 硎 ) ) 丙 丙 丙 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 Butylamine, 1 methyl ~ xiaobuturamine, o 4 cinnabarin amine ' _ Ν _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Guanamine. Amino protecting groups such as urethane groups (e.g., _C(=0)0Raa) include, but are not limited to, methyl carbamate, ethyl amine decanoate, 9-fluorenyl methyl formate (Fmoc), amine formic acid 9 -(2-sulfonyl) decyl methyl ester, 9-(2,7-dibromo)decyl methyl carbamate, 2,7-di-tert-butyl amide [9-(l0, l0_) Diketone _l0,10,10,10_tetrahydrothioxanthyl)]methyl ester (DBD-Tmoc), 4-methoxybenzoic acid methyl ester (Phenoc), aminic acid 2,2,2 - trioxoethyl ester (Troc), aminicyl 2-trimethyldecylethyl ester (Teoc), aminic acid 2-phenylethyl ester (hZ), uric acid 1-(1-adaring)- 1-methylethyl ester (Adpoc), 1,1-didecyl-2-haloethyl carbamate, 1,1-dimercapto-2,2-dibromoethylamine (DB-t-BOC ), 1,1-dimethyl-2,2,2-trimethyl urethane (butyl sulphate, 1-methyl-1-(4-biphenyl) urethane) (Bpoc), 1-(3,5-di-t-butylphenyl)-1-decylethylamine (t-Bumeoc), 2-(2'- and 4,-pyridyl)ethylcarbamate (pyoc ), 2-(N,N-dicyclohexylcarboxamine) urethane, tert-butylamine citrate (BOC), carboxylic acid 1-Aluminum vinegar (Adoc), urethane Rare vinegar (Voc), allyl carbamate (Alloc), 1-isopropylallyl amide (Ipa〇c), cinnamate citrate (Coc), 4-carbobenzoic acid (Noc) , 8-carbene carbamate, N-hydroxypiperidine carbamate, alkyl dithiocarbamate, benzyl carbamate (Cbz) 'p-methoxybenzyl carbamate (M〇z), uric acid p-N-benzyl ester, p-bromobenzylamine amide, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinyl benzyl carbamate (Msz), 9-mercaptomethyl carbamate, diphenyl methyl carbamate, 2-methyl thioethyl carbamate, 2-methylsulfonyl ethane acetate, 2-(p-toluene sulfonyl) carbamic acid Ethyl ester, carboxylic acid [ίο,, dithiaxyl) methyl ester (Dmoc), 4-methylthiophenyl carbamate (Mtpc), uric acid 2,4- 26 201043620 dimercaptothiophenyl ester ( Bmpc), 2-phosphoethylamine phthalate (Peoc), aminic acid 2_triphenylphosphinopropyl isopropyl ester (Ppoc), amide carboxylic acid 1,1 -didecyl-2- cyanoacetic acid, amine hydrazine Acid-m-p-p-decyloxybenzyl ester, carboxylic acid to _(dihydroxypeptidyl) vinegar, carbamic acid 5-benzoiso-pyridyl decyl phthalate, uric acid 2 _ ( Fluoromethyl)_6-chromonyl methyl ester (Tcroc), m-triphenyl carbamic acid ester, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, aminic acid 3 , 4-Dimethoxy-6-recognition, Months formic acid base (o-nitrophenyl) vinegar, aminic acid third acetal, thiocarbamic acid S-benzyl ester, uric acid p-cyano Benzyl ester, cyclobutyl carbamic acid, cyclohexyl carbazate, valeric acid, valeric acid, cyclopropyl hydrazine acetate, carbamic acid carboxylic acid, methic acid 2, 2-dimethyl amide Oxycarbonyl carbonyl ester, o-(n,N-dimercaptocarboxamide) benzyl carbamate, 1,1-didecyl _3_(N,N-dimercaptocarboxamide) propyl carbamate, 1,1-dimethylpropynylamine amide, bis(2-pyridyl) decylamine phthalate, 2-furylmethyl carbamic acid methyl ester, 2- hydrazine methyl carbamate, isobornyl carbamate, Isobutyl carbamide, isonicotinic acid amine amide, p_(p, 曱 曱 oxyphenyl azo) benzyl formate, 1-mercaptobutyl butyl phthalate, 1 - decyl cyclohexylamine , 1-methyl-1-cyclopropyl methyl carbamate, 1-methyl-1_(3,5-dimethoxyphenyl)ethylamine phthalate, 1-mercapto-1- hydride P-phenyl N-phenyl)ethyl ester, 1-methyl-1-phenylethylamine phthalate, 1-methyl-1-(4-pyridyl)ethyl amide, phenyl carbamide, carboxylic acid Benzyl azo) benzyl ester, 2,4,6-tri-tert-butylphenyl carbamate, 4-(trimethylammonium) benzyl carbamate, and 2,4,6-trimethylbenzyl carbamate vinegar. Amino protecting groups such as sulfonamide groups (eg, -S(=〇)2Raa) include, but are not limited to, p-nonylbenzenesulfonamide (Ts), sulfoxamide, 2,3,6-trimethyl-4 -Methoxy stupin (Mtr), 2,4,6-trioxabenzenesulfonamide (Mtb), 2,6-dimethyl-4-methyl 27 201043620 Oxybenzamine (Pme) , 2,3,5,6-tetradecyl-4-oxooxybenzenesulfonamide _e), 4-methoxyphthalide xanthine (Mbs), 2,4,6-trimethylbenzene Amine (Mts), 2,6-dimethoxy-4-mercaptobenzenesulfonamide (iMds), 2,2,5,7,8-pentacenyl acridine-6-sulfonamide (Pmc), hydrazine Sulfonamide (Ms), β-trimethyldecyl sulfonamide (SES), 9-enxanthin, 4-(4',8'-dimethoxynaphthylmethyl)benzene Amine (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and benzamidine methylamine. Other amine-based protecting groups include, but are not limited to, the phenanthrene-based derivative, the -Ν'-p-toluenesulfonylamine carbonyl derivative, and the _N'_phenylamine thiol derivative. , -N-phenylmercaptophenylpropylamine decyl derivative, _n_ethyl methionine derivative '4,5-diphenyl-3-hydrazinyl-2-ketone, blown imine -N-di-butadiene-diimine (Dts), -N-2,3-diphenyl-p-butane-imine, and -N-2,5-diindenyl. Pyrrole, -Nl,l,4,4-tetradecyldioxanylcyclopentane adduct (STABASE), 5-substituted 1,3-dimethyl-i, 3,5-triterpene Cyclohexyl-2-y, 5-substituted 1,3-indolyl-1,3,5-tri.丫cyclohexan-2-indole, 1-substituted 3,5-dinitro-4-ratio. _,-Ν-methylamine, -Ν-dilylamine, -Ν-[2-(trimethyldecyl)ethoxy]methylamine (SEM), -N-3-acetyloxypropane Amine, isopropyl-4-diazepine-2-one-3-brown (pyro〇iin)-3-3-)amine, tetrabasic salt, -N-benzylamine '-N-di (4 -nonyloxyphenyl)decylamine, -N-5-dibenzocycloheptylamine, -N_triphenylmethylamine (Tr), -N-[(4-anthoxyphenyl)diphenyl Methyl]amine (MMTr), -N-9-styl mercaptoamine (PhF), _ν·2,7-dichloro-9-mercaptomethyleneamine, -N-ferrocenyl Base amine (Fcm), -N-2-. 〇 曱 曱 胺 胺 - - '-oxide, dimethyl sulfoximine, benzylidene, -N-p-methoxybenzylideneamine, _N-diphenylaryleneamine, -N -[(2-pyridine 28 201043620 ❹

Methyl)methyleneamine, -n-(n',n'-dimethylaminomethylene)amine, -oxime, Ν'-isopropylidenediamine, -N-p. Benzylamine, -N-ylideneamine, -Ν-5-chlorosalicylideneamine, -Ν-(5-gas-2-hydroxyphenyl)phenylmethyleneamine, _Ν_cyclohexylene Amine, -Ν-(5,5-dimethyl-3-keto-1-cyclohexyl)amine, Ν-borane derivative, -Ν-diphenyldihydroxyboronic acid derivative, -Ν - [Phenyl (pentacarbonyl chromium- or tungsten) carbonyl]amine, -Ν-copper chelate, -Ν-zinc chelate, -Ν-nitrosamine, Ν-nitrosamine, amine ruthenium-oxide, Diphenylphosphine decylamine (Dpp), dimethyl sulfinylphosphine decylamine (Mpt), diphenyl sulfathioni rutheniumamine (Ppt), linalic acid diacetate, dibenzyl phosphonium citrate , diphenyl phosphonium citrate, sulfinamide, o-nitrobenzoin (Nps), 2,4-dinitrobenzenesulfinamide, pentachlorophenyl hydrazine, 2-nitrate -4-oxophthalene sulfoximine, triptypicylmethylsulfinamide and 3_nitropyridine sulphate (Npys). As used herein, "leaving group" is a term known to the artisan to refer to a molecular fragment with a -electron departure in a non-sequential bond cleavage, wherein the molecular fragment is an anion or a (tetra) molecule, as described in Smhh, Order Organic Chemistry, 6th Edition (pp. 501-502). The details of these and other examples of substituents are set forth in the detailed description, examples and claims. The present invention is by no means limited to the exemplary forms described above. As used herein, "the pharmaceutically acceptable form thereof" includes pharmaceutically acceptable salts, waters, solvates, prodrugs, and mutual compounds of the compounds of the invention as defined hereinafter and herein. Isomers, isomers, and/or polycrystals:. As used herein, the term "medicalally acceptable salt" refers to such dark classes, which are suitable for use in intensive medical judgments. 固周〇 is used to contact humans and lower animals 29 201043620 Toxicity, irritation, allergic reactions, etc., and can be matched with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., in Pharmaceutical Sciences Journals 1977, 66, 1-19, detail pharmaceutically acceptable salts. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are with inorganic acids such as hydrochloric acid, hydrogen acid, linonic acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, and lemon The acid, succinic acid or malonic acid or a salt of an amine group formed by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, besylate, benzoate, hydrogen sulfate, borate, butyrate, camphorate , camphor sulfonate, citrate, cyclopentyl propionate, digluconate, dodecyl sulfate, ethionate, formate, fumarate, glucose heptanoate , glycerol phosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactose diketonate, lactate, laurate, lauryl Sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinic acid, nitrate, oleate, oxalate, palmitate , bamoate, pectate, persulphate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinic acid Salt, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, orthovalerate, and the like. Salts derived from appropriate bases include metal salts, soil metal salts, ammonium salts and strontium + ((^_4) base salts. Representative metal salts or soil test metals including sodium, chain, potassium, # 5. Towns, etc. 30 201043620 Other pharmaceutically acceptable salts include, where appropriate, the use of counterions such as anion, hydroxide anion, carboxylate, sulfonate, phosphate 'nitrate, lower alkyl sulfonate and aryl a non-toxic cation, a fourth ammonium cation, and an amine cation formed by the sulfonate. In some embodiments, the pharmaceutically acceptable form is an isomer. As used herein, the term "isomer" includes any and All geometric isomers and stereoisomers. For example, "isomers" include cis- and trans-isomers, e_0 and oxime isomers, ruthenium- and 8-enantiomers, diastereoisomers Constructs, isomers, (L)-isomers, racemic mixtures, and other mixtures falling within the scope of the invention. ' In several embodiments, the pharmaceutically acceptable form is tautomeric The term "tautomer" as used herein includes at least one of hydrogen atoms. Formal migration and at least one change in the valence (eg, a single bond becomes a double bond, a bond becomes a single bond) or vice versa) two or more compounds that can be exchanged interactively. The correct ratio of tautomers depends on the other Factors, 温度 include temperature, solvent, and pH. The tautomerization reaction (ie, providing a reaction to a pair of tautomers) can be catalyzed by acid or catalysis. Examples of tautomerization include keto-to-endo alcohol; Indoleamine-to-iminemine; indoleamine_to_indoline; enamine·to-imine· and enamine-to-(different) enamine tautomerization. Solvent: dry implementation In the present case, the pharmaceutically acceptable form thereof is a hydrate or a water. The term "hydrate" as used herein refers to a compound which is non-covalently bonded to one or more 〆T. Similarly, "solvent """ means a compound that is non-covalently associated with an organic molecule. In some embodiments, 'the pharmaceutically acceptable form thereof is a prodrug. For example, 31 201043620 "prodrug" is used herein - the word means A parental compound derivative that is converted to release a parent compound. In the case of money, the prodrug has better physical properties and/or delivery properties than the parent compound. Prodrugs are typically designed to enhance the pharmaceutical and/or pharmacodynamic properties associated with the parent compound. In terms of its physical properties, such as increased parental water when administered parenterally for parenteral administration, or increased absorption to the digestive tract, or improved drug stability for long-term storage. In several embodiments The pharmaceutically acceptable form thereof is in the form of a polymorph. As used herein, "polymorph" refers to a compound having more than one crystal structure, for example, due to differences in molecular packing and/or molecular configuration of a solid compound. No. SEQ ID NO: Homo sapiens FAAH amino acid sequence:

MVQYELWAALPGASGVA LACCFVAAAVALRWSGRRTARGAVVRARQRQRAGLENM draaqrfrlqnpdldseallalplpqlvqklhsrelapeavlftyvgkawevnkgtnc

VTSYLADCETQLSQAPRQGLLYGVPVSLKECFTYKGQDSTLGLSLNEGVPAECDSVVVH

VLKLQGAVPFVHTNVPQSMFSYDCSNPLFGQTVNPWKSSKSPGGSSGGEGALIGSGGSP

LGLGTDIGGSIRFPSSFCGICGLKPTGNRLSKSGLKGCVYGQF.AVRLSVGPMARDVESLA

LCLRALLCEDMFRLDPTVPPLPFREEVYTSSQPLRVGYYETDNYTMPSPAMRRAVLETK

QSLEAAGHTLVPFLPSNIPHALETLSTGGLFSDGGHTFLONFKGDFVDPCLGDLVSILKLP

QWLKGLLAFLVKPLLPRLSAFLSNMKSRSAGKLWELQHEIEVYRKTVIAQWRALDLDV

VLTPMLAPALDLNAPGRATGAVSYTIVILYNCLDFPAGVVPVTTVTAEDEAQMEHYRGY

FGDIWDKMLQKGMKKSVGLPVAVQCVALPWQEELCLRFMREVERLMTPEKQSS I: Embodiment 3 Detailed Description of Preferred Embodiments I. Compounds The present invention provides an isoxazole-lead FAAH inhibitor compound of formula (I): 32 201043620

Ra (I) or a pharmaceutically acceptable form thereof, wherein: () RR and R are each selected from the group consisting of h, Ch, and perhaloalkyl, Rd is -LZ based ' and 2 is selected from C6 i4 An aryl group; (9), and a self-selective group selected from the group consisting of hydrazine, a carboxylic acid group, and a CM0 perhalogen group, Rd is a -LZ group, and the z series is selected from a 3:14 member heterocyclic group and a 514 member heteroaryl group; (ill) R and 1 are joined to form a C3_10 carbocyclic group or a 3-14 membered heterocyclic fused ring, and Rb and Re are each selected from the group consisting of _H, Cmg alkyl and heart (1) functional alkyl; or (iv Re and Rd are joined to form a c3_1() carbocyclic group or a 3-14 membered heterocyclic snail-fused ring, and Ra&Rb are respectively selected from -H, Cmo alkyl and C^o perhalogenated groups; Is a covalent bond or a divalent Cu hydrocarbon group, wherein one, two or three methylene units of L are selectively and separately substituted with one or more oxygen, sulfur or nitrogen atoms; G is selected from -CN, -N02, -S(=0)Re, -S02Re, -S02NRfRe, -P02Re, -P020Re, -P02NRfRe, -(00)Re, -(C=0)0Re, -(C=0)NRfRe, -Br , -I, -F, -Cl, -ORe, -〇NRfRe, -0NRf(C=0)Re, -0NRfS02Re, -0NRfP02Re, -0NRfP020Re, 33 201043620 -SRe, -0S02Re, -NRfS02 Re, -0P02Re, -0P020Re, -NRfP02Re, -NRfP020Re, -0P02NRfRe, -0(C=0)Re, -0(C=0)0Re, -NRfRe, -NRf(C=0)Re, -NRf( C=0) ORe, -0 (C=0)NRfRe, -NRf(C=NRf)NRfRe, -0(C=NRf)NRfRe, -NRf(C=NRf)ORe, -[N(Rf)2Re] +X·where X- is a counter ion;

Each Re is selected from the group consisting of Cm alkyl group and C2.1 () alkenyl group. Alkynyl, C3.10 carbocyclyl, C6_14 aryl, 3-14 membered heterocyclic and 5-14 membered heteroaryl; each Rf attached to a nitrogen atom is selected from -H, CMG alkyl, or Amine protecting group; or Re and Rf are joined to form a 3-14 membered heterocyclyl ring or a 5-14 membered heteroaryl ring. Group G is as defined herein, and G is selected from the group consisting of -CN, -N〇2, -S(=0;) Re, -S02Re, -S02NRfRe, -P02Re, -P02〇Re, _p〇2NRfRe, _(〇〇 )Re, -(C=0)0Re, -(C=0)NRfRe, -Br, -I, -F, -CL· -ORe, -〇NRfRe, -0NRf(C=0)Re, -0NRfS02Re, _〇NRfP〇2Re, -〇NRfP〇2〇Re, -SRe ' -0S02Re ' -NRfS02Re > -〇P〇2Re > -OP〇2〇Re ' -NRfP02Re ' -NRfP020Re ^ -OP〇2NRfRe ' - 0(C=0)Re ' -0(C=0)0Re, -NRfRe, -NRf(〇〇)Re, -NRf(C=0)ORe, -〇(C=0)NRfRe, -NRf(C =NRf)NRfRe, -〇(C=NRf)NRfRe, -NRf(C=NRf)ORe, -[N(Rf)2r]+X- wherein x- is a counter ion; and wherein Re is selected from CM0 alkyl , Q 丨〇 alkenyl, C 2 i decynyl, C 3 fluorenyl, C 6 -M aryl, 3-14 membered heterocyclic and 5 14 membered heteroaryl; each R attached to a nitrogen atom Selected from a C^oalkyl group, or an amine protecting group; or R and R are joined to form a 3-14 membered heterocyclyl ring or a 5_i4 membered heteroaryl ring. In some embodiments, G is not a leaving group, for example, G is selected from the group consisting of _F, 34 201043620 -CN, -N〇2, -S(=0)Re, -S02Re, -S02NRfRe, -P02Re, -P02ORe -P02NRfRe, -(C=0)Re, _(C=0)0Re, and -(C=0)NRfRe. In several embodiments, the G system is selected from the group consisting of -CN and -N〇2. In several embodiments, G is -CN. In several embodiments, G is -N〇2. In several embodiments, G is selected from the group consisting of -S(=0)Re, -S02Re, and -S02NRfRe. In several embodiments, G is -S(=0)Re. In several embodiments, G is -S02Re. In several embodiments, G is -S02NRfRe. In some embodiments, G is selected from the group consisting of -P〇2Re, -P〇2〇Re, and -P02NRfRe. In several embodiments, G is -P〇2Re. In several embodiments, -P020Re. In several embodiments, G is -P02NRfRe. In several embodiments, G is selected from the group consisting of -(C=0)Re, -(C=0)0Re, and -(C=0)NRfRe. In several embodiments, G is -(C=0)Re. In several embodiments, -(C = 0) 0Re. In several embodiments, G is -(C=0)NRfRe. However, in several embodiments, g is a leaving group, for example g is selected from the group consisting of -cn, -Br, -I, -ORe, -ONRfRe, -0NRf(C=0)Re, -0NRfS02Re, -0NRfP02Re, -ONRfP02ORe , -SRe, -0S02Re, -NRfS02Re, -0P02Re, -0P020Re, -NRfP02Re, -NRfP020Re, -0P02NRfRe, -0(C=0)Re, -0(C=0)0Re, -NRfRe, -NRf(C =0) Re , -NRf(C=0)ORe , -0(C=0)NRfRe , -NRf(C=NRf)NRfRe, -0(C=NRf)NRfRe, -NRf(C=NRf)〇Re And -[N(Rf)2Re]+X·where X_ is a counter ion. In several embodiments, G is halogen; that is, selected from the group consisting of -F, -α, -Br, and -I. In several embodiments, G is -F. In several embodiments, G is -Br. 35 201043620 In several embodiments, G is -I. In several embodiments, G is -Cl. However, in several embodiments, G is not a halogen. For example, in several embodiments, G is not -Br. In several embodiments, G is not -I. In several embodiments, G is not -F. In several embodiments, G is not -C1. In some embodiments, G is selected from the group consisting of -ORe, -ONRfRe'-ONRf(C=0)Re, -ONRfS02Re, -ONRfP02Re, -ONRfP02ORe, -0S02Re, -0P02Re, -0P020Re, -OP02NRfRe, -0(C =0) Re, -0 (C=0) 0Re, -0 (C=0) NRfRe, and -0 (C=NRf) NRfRe. In several embodiments, G is selected from the group consisting of -ORe, -0 (C = 0) Re, -0 (C = 0) 0 Re, -0 (C = 0) NRfRe, and -0 (C = NRf) NRfRe. In some embodiments, G is selected from the group consisting of -ONRfRe, -0NRf(C=0)Re, -0NRfS02Re, -ONRfP02Re, -0NRfP020Re, -0P02NRfRe, -0(C=0)NRfRe, and -0(C=NRf). NRfRe. In several embodiments, G is -ORe. In several embodiments, G is -ONRfRe. In several embodiments, G is -ONRf (C = 0) Re. In several embodiments, G is -0NRfS02Re. In the examples, G is -0NRfP02Re. In several embodiments, G is 0NRfP020Re. In several embodiments, G is -OS02Re. In several embodiments, G is -0P02Re. In several embodiments, G is -0P020Re. In several embodiments, G is -0P02NRfRe. In several embodiments, G is -0 (C = 0) Re. In several embodiments, G is -0 (C = 0) ORe. In several embodiments, G is -0 (C = 0) NRfRe. In several embodiments, G is -0(ONRf)NRfRe. In several embodiments, the G system is selected from the group consisting of -ORe and -SRe. In several embodiments, the G system is selected from the group consisting of -ORe. In several embodiments, G is -SRe. 36 201043620 In several embodiments, G is selected from the group consisting of -NRfS02Re, _NRfP02Re, -NRfP020Re, -NRfRe, -NRf(〇0)Re, -NRf(00)ORe, -NRf(C=NRf)NRfRe, _NRf(C =NRf)ORe, and -[N(Rf)2Re]+x- wherein X- is a counter ion. In some embodiments, G is selected from the group consisting of _NRfS02Re, -NRfP02Re, -NRfP02〇Re, -NRfRe, -NRf(C=0)Re, and -NRf(C=0)0Re. In several embodiments, G is -NRfS02Re. In some embodiments 'G is -NR P〇2Re. In several embodiments, g is -NRfP020Re. In several embodiments, G is -NRfRe. In several embodiments, G is -NRf (C = 0) Re. In several embodiments, g is _NRf (C = 0) 〇 Re. In several embodiments, G is -NRf(C=NRf)NRfRe. In several embodiments, G is -NRf(C=NRf)ORe. In several embodiments, G is -[N(Rf)2Re]+X_ wherein X· is a counterion. Additional embodiments including the description of the clusters 6 and 1 and further exemplifying the G in the tables and examples are provided below and herein. The Re of the group G is as defined above in the 'in some embodiments, wherein the G is selected from the group consisting of -S(=0)Re, -S02Re, -S02NRfRe, -P〇2Re, _p〇2〇Re, -P02NRfRe, - (C=0) Re, -(C=0)0Re, -(C=0)NRfRe, -〇Re, -ONRfRe, -ONRf(C=0)Re, -0NRfS02Re, -〇NRfP02Re, -0NRfP020Re, _SRe , -0S02Re, _NRfS02Re, -〇P〇2Re, -0P020Re, -NRfP02Re, -NRfP020Re, -〇P〇2NRfRe, -0(C=0)Re, -0(C=0)0Re, -NRfRe, -NRf (C=0)Re, -NRf(C=0)0Re, -0(C=0)NRfRe, -NRf(C=NRf)NRfRe, -0(C=NRf)NRfRe, -NRf(C=NRf) ORe, and -[N(Rf)2Re]+X. wherein 37 201043620 χ· is a counter ion, Re is selected from Cl.1Q alkyl 'C2_iq alkenyl, C2, alkynyl, C3-10 carbocyclyl, c6_14 Aryl, 3-14 membered heterocyclic and 5-14 membered heteroaryl. In several embodiments, the 'Re is selected from the group consisting of C0 alkyl, c2-10 alkenyl c2 iq alkynyl, C3_1() carbocyclyl, C6_H aryl, 3-14 membered heterocyclyl, and 5-14 membered heteroaryl, Wherein alkyl, alkenyl, alkynyl, carbocyclyl 'aryl, heterocyclyl, and heteroaryl are 0, 1, 2, 3, 4 or 5 ph groups as defined hereinafter and herein Replaced. In some embodiments 'Re is a CM() alkyl group. In several embodiments, R is C!_6 alkyl. In several embodiments, Re is substituted with 2, Cl-6 alkyl with hydrazine, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, Re is substituted with 〇, 1, 2, 3, 4, or 5 Rh groups. In several embodiments, Re is 0, 1, 2, 3 or 4 Rh-substituted C]*alkyl groups. In several embodiments, 'Re is a Ci thiol group substituted with hydrazine, br. 2, or 3 Rh groups. In several embodiments, Re is 经, Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, t-butyl, pentyl, iso Each of the pentyl, neopentyl and hexyl groups is substituted with 0, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, '1^ is a Cm perhaloalkyl group. In the present example, ^ is a perhaloalkyl group. In several embodiments, ^ is a tetrahydrohaloalkyl group. In several embodiments, a RegCl 3 perhaloalkyl group. In several embodiments, R is C1 _2 Examples of R-halogenated groups include, but are not limited to, _cf3, -CF2CF3, _CF2CF2CF3, _ccl3, _CFCl2, and CF2a. In several embodiments, Re is a C2-10 alkynyl group. In several embodiments, 38 201043620 1^ is a 〇2_6 alkynyl group. In several embodiments, Re is a 6 alkynyl substituted with 〇, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, Re is 〇, 1 ' 2 ' 3, 4 or 5 Rh-substituted c2.5 blocks. In several embodiments, Re is c2_4 alkynyl substituted with 〇, i, 2, 3 or 4 Rh groups. In several embodiments, V is C, 1, 2 or 3 Rh-substituted C2_3 alkynyl groups. Examples of Re alkynyl groups include, but are not limited to, ethynyl, 丨-propynyl, 2-propynyl, ^butynyl, 2-butynyl And a pentynyl group, wherein the groups are substituted with 0, 1, 2, 3, 4 or 5 Rh groups via 0. In several embodiments, Re is a CVM aryl group. In several embodiments Wherein - R is a C6-10 aryl group. In several embodiments, Re is a C6-i aryl group substituted with hydrazine, 1, 2, 3, 4, or 5 ... groups. In several embodiments Re is an aryl group substituted with 〇, 1, 2, 3, 4 or 5 Rh groups (for example, phenyl. In several embodiments, Re is 〇, 1, 2, 3, 4 or 5 Substituted Ci. Aryl (e.g., naphthyl). In several embodiments, Re is a stupid group. In several embodiments, Bu 3 or transfected filamentous _Rh. To several embodiments,

Re is a phenyl group substituted with 0 small 2 or 3 Rh groups. In several embodiments, Re is a stupid group substituted with 0, 1 or 2 Rh groups. In several embodiments, ^ is phenyl substituted with a 0 or a t-h group. In several embodiments, Re is a disubstituted phenyl group (i.e., substituted with 2 Rh groups). In several embodiments, Re is a monosubstituted phenyl (ie, substituted with ##). In several embodiments t, Re is an unsubstituted phenyl group (i.e., substituted with a hydrazine Rh group). In several embodiments, Re is phenyl substituted with at least one ortho-Rh group. In several embodiments, Re is phenyl substituted by at least one meta-Rh group 39 201043620. In several embodiments, Re is phenyl substituted with at least one para-Rh group. For a number of implementations, Re is a phenyl group:

(Rh)x wherein X is 0, Bu 2, 3, 4 or 5, and Rh is as defined below and herein. In several embodiments, X is G'b2, 3 or 4. In several embodiments, x is fine, 1, 2 or 3. In several embodiments, X is 0, 丨 or 2. In some embodiments, 'X is G' or is in several embodiments, coffee. In several embodiments, 'r is a disubstituted phenyl group (i.e., 42 thereof). In some embodiments R is a left substituted phenyl group (i.e., wherein 乂 is ^. In several embodiments, Re is an unsubstituted phenyl group (i.e., wherein 〇 is). For example, in several embodiments, Re is A substituted or unsubstituted phenyl group of any of the following formulae:

Where Rh is as defined below and herein. 40 201043620 In several embodiments, Re is a naphthyl group. In some embodiments, Re is a naphthyl group of any of the following formula: %ΛΜΤ 丄 %/vw Λ ό〇 Λ or % (i-b) ^(R^x (i-c) Ο

Where X is 0, : 1, 2, 3, 4 or 5, and Rh is as defined below and herein. In several embodiments, X is 0, 1, 2, 3 or 4. In several embodiments, X is 0, 1, 2, or 3. In several embodiments, X is 0, 1, or 2. In some embodiments, X is 0 or 1. In several embodiments, Re is a trisubstituted naphthyl group (i.e., wherein X is 3). In several embodiments, Re is a disubstituted naphthyl group (i.e., wherein X is 2). In several embodiments, Re is a substituted naphthyl group (i.e., wherein X is 1). In several embodiments, Re is an unsubstituted naphthyl group (i.e., X is 0). For example, in several embodiments, Re is a substituted or unsubstituted 1-naphthyl group of any of the following formulae:

41 201043620 where Rh is as defined below and here. For example, in several embodiments, Re is a substituted or unsubstituted 2-naphthyl group of any of the following formulae:

Where Rh is as defined below and herein. In several embodiments, 1 is a 5-14 membered heteroaryl. In several embodiments, Re is a 5-10 membered heteroaryl substituted with 0, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, Re is a 5-8 membered heteroaryl substituted with 〇, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, Re is a 5-6 membered heteroaryl substituted with 0, 1, 2, 3 or 4 Rh groups. In several embodiments, Re is a 9-10 membered heteroaryl substituted with 0, 1, 2, 3, 4 or 5 Rh groups.

Examples of Re heteroaryl groups include, but are not limited to, pyrrolyl, furyl and thienyl, glutinous rice β, σ ratio σ, σ, U, sigma, U sigma, U sigma, Hetero-sigma 0 sitting, three α sitting, Saki two α sitting, ° plug disali, four β sitting, α than bite (eg 2-π & σ σ, 3-13⁄4 ° fixed, 4- 11 than β base), °荅 base (for example, 3-11 answer σ well base, 42 201043620 4-嗒 基 base), pyrimidinyl (eg 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), wealth Base, trimorphine, four. Well base,.丫呼基, 啊基"塞呼基" 引哚基,异基基, 丨丨峻基' stupid and trisyl, benzoindol, isobenzothienyl, benzofuranyl, stupid Isofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzisothiazolyl, benzothiadiazolyl, anthracene Base, fluorenyl, acridinyl, acridinyl, quinolyl, isoquinolinyl, porphyrinyl, quinoxalinyl, morphine, quinazolinyl, phenanthryl, dibenzofuranyl , carbazolyl, acridinyl, thioanthenyl, phenylidene, and phenylidene, wherein the groups are substituted with 0, i, - 2, 3, 4 or 5 Rh groups. In several embodiments, ^ is a 5-membered heteroaryl. In several embodiments,

Re is a 5-membered heteroaryl group substituted with 0' 1, 2 or 3 Rh groups. In several embodiments 'Re is selected from pyrrolyl, furyl, thienyl, imidazolyl, beta-pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazole a 5-membered heteroaryl group of a thiadiazole group, and a tetrazolyl group, wherein the oxime groups are substituted with 0, 1, 2 or 3 Rh groups. For example, in several embodiments, Re is a 5-membered heteroaryl group of the formula:

(id) wherein Ya, Yb, Ye, and Yd are respectively selected from CH, CRh, 〇, s, .N, or NRk, but the constraint is that at least one of Ya, Yb, Yc, and Yd is 〇, S, - Ν or NRk, and its Rh and # are as defined below and here. In some embodiments of the above formula (i-d), ya is 〇, s, _n, or NRk 43 201043620 and Yb, Ye, and Yd are selected from CH, CRh, and -NR1N, respectively. In several embodiments of the above formula (i-d), 'Y^O, s, -N, or NRk&Yb, Yc and 丫" are selected from CH or CRh, respectively. In several embodiments of the above formula (i-d), γ1〇, S, or NRk, Ye is Ν, and YlYd are selected from CH or CRh, respectively. In some embodiments of the above formula (i-d), Yb is 〇, S, or NRk and Ya, Yc, and Yd are each selected from CH, CRh, or N. In several embodiments of the above formula (i_d), Υ%0, S, or NRkYa, Yc, and yd are selected from CH4CRh, respectively. In some embodiments of the above formula (i_d), Yb is Ο, S, or NRk, Yd is N and Ya&Ye and are selected from CH or CRh, respectively. In some embodiments, Re is a substituted or unsubstituted 5 membered heteroaryl group of any of the following formulae:

Where X is 0' 1 or 2, and Rh and Rk are as defined below and herein. In several embodiments, Re is an unsubstituted 5 membered heteroaryl (i.e., wherein 乂 is 44 201043620 〇). For several shots, Re is a substituted #heteroaryl (eg, where X machine 2). In a number of implementations, "substituted 5-membered heteroaryl (ie, (4)). In several embodiments, Re is a disubstituted 5-membered heteroaryl (ie, wherein X is 2). In the embodiment, \ is 〇, .... In the embodiment, X is 〇 or 1. Right to several actual wipes, 6 aliquots. In several embodiments, R is 0, 2, 3 or 4 a substituted 6-membered heteroaryl group. In the examples, Re is selected from the group consisting of a bite group (eg, 2, specific, 3, butyl, 4-pyridyl), + well base (eg, well base , 4_tactinyl), 6-membered group of the group consisting of 2-♦-based, 4-hydroxyl, 5-(tetra)-bipyridyl, trimorphinyl and tetra-phenyl-phenyl An aryl group wherein the groups are substituted by 0, 1 '2, 3, or 4 Rh groups. For example, in several embodiments, Re is a 6-membered heteroaryl group: 丨a-y^ b (i-€> /where wa, Wb, we, Wd, and we are selected from CH, CRh, respectively, and the constraints are at least those of w, Wb, Wc, wd, and we: Definition: The person is Ν' for the war == Zhong Zheng bite base. In several embodiments, 1 case, base substitutionΜ · Π and in a number of solid-pyridinyl of the formula:

Wc R (Rh) x 45 201043620 wherein x is 〇, 1, 2, 3 or 4, and Rh is as defined below and Q is defined herein. In several embodiments, Re is an unsubstituted η ratio α base (also That is, where X is 〇). In several embodiments, Re is a substituted pyridyl group (eg, wherein X is 1, 2, 3, or 4). In several embodiments, Re is a monosubstituted pyridyl group (i.e., wherein X is 1). In several embodiments, Re is a disubstituted oxime base (i.e., wherein X is 2). R is a triple substituted hydrazine. Base (ie where X is 3). In some embodiments, X is 0, 1, 2 or 3. In several embodiments, X is 〇. In several embodiments, X is 0 or 1. In several embodiments, Re is 2-pyridyl, for example having the formula (i-e) wherein ^^ is >| and Wb, Wc, Wd and We are CH or CRh, respectively. In some embodiments, 'Re is 3-pyridyl', for example, has the formula (i-e) wherein Wb is N&wa, Wc, Wd and is CH or CRh, respectively. In some embodiments, ^ is a 咬 ° bite base', for example, having the formula (i_e) wherein wc is n and wa, Wb, W^We are CH or CRh, respectively. In some embodiments, Re is a substituted or unsubstituted 2-indenyl group of any of the following formulae:

Where Rh is as defined below and herein. In some implementations, Re is a substitute in the following formula or 46 201043620 Unsubstituted 3-pyridyl:

Where Rh is as defined below and herein. In some embodiments, Re is a substituted or unsubstituted 4-pyridyl group of any of the following formulae:

Where Rh is as defined below and herein.

In several embodiments, Re is a syllabary. In several embodiments, Re is a ruthenium base substituted with 0, 1, 2, or 3 Rh groups. For example, in several embodiments, Re is of the formula: (Rh)x wherein X is 0, 1, 2, or 3, and Rh is as defined below and herein. In the examples, Re is an unsubstituted oxime (i.e., where X is 0). In the examples, Re is a substituted argon (e.g., where X is 1, 2 or 3). In several embodiments, Re is a substituted turf (i.e., where X is 1). In several embodiments, Re is a disubstituted oxime (ie, wherein X is 2). Re is a three-substituted syllabary (that is, where X is 3). In several embodiments, 47 201043620 X is 0, 1, 2, or 3. In some embodiments, 乂 is 〇. In some embodiments, X is 0 or 1. In a number of embodiments, R is 3-嗒 耕, for example having the formula (丨_6) where Wa&Wb is N and W, W and you 6 are respectively (:^ or (:1111.) in several embodiments Wherein Re is a 4-» combination, for example having the formula (i_e) wherein wb and wC are N and Wa, and Wd & We are respectively CH or CRh. In several embodiments, R is any of the following Substituted or unsubstituted 3-嗒 耕 :

Where Rh is as defined below and herein. In several embodiments, Re is an unsubstituted 4-indolyl in the formula:

Where Rh is as defined below and herein. In several embodiments, Re is pyrimidinyl. In several embodiments, the mouth is bitten by a mouth substituted with 0, 1, 2, or 3 Rh groups. For example, in several embodiments, 'Re is a pyrimidinyl group:

Wherein X is 0, 1, 2 or 3, and Rh is as defined hereinafter and as defined herein. In the examples, Re is an unsubstituted pyrimidinyl group (i.e., wherein X is 0). In the dry embodiment of the invention, Re is a substituted pyrimidinyl group (for example, wherein χ is 1, 2 or 3). In several embodiments, Re is a monosubstituted pyrimidinyl group (ie, wherein X is 1). In several embodiments, Re is a disubstituted 嗒4 group (ie, wherein χ is 2). Re is a trisubstituted pyrimidinyl group (i.e., wherein χ is 3). In several embodiments, χ is 0, 1, 2, or 3. In several embodiments, χ is 0, 1, or 2. In some embodiments, χ is 0 or 1. In some embodiments, Re is a 2-pyrimidinyl group, for example, having the formula (i-e) wherein Wa and We are N and Wb, We, and Wd are CH or CRh, respectively. In several embodiments, Re is a 4-pyrimidinyl group, for example having the formula (i-e) wherein Wa& We are N. and Wb, Wd and We are CH or CRh, respectively. In several embodiments, Re is 5-pyrimidinyl, for example having the formula (i-e) wherein Wb & Wd is N and Wa, We and We are CH or CRh, respectively. In some embodiments, Re is a substituted or unsubstituted 2-pyrimidinyl group of any of the following formulae:

Where Rh is as defined below and herein. In some embodiments, Re is a substituted or unsubstituted 4-pyrimidinyl group of any of the following formulae:

Where Rh is as defined below and herein. In several embodiments, Re is substituted or any of the following formulas: 49 201043620 Unsubstituted 5-pyrimidinyl:

Where Rh is as defined below and herein. In several embodiments, Re is a pyr" well. In several embodiments, Re is pyridinyl substituted with 0, 1, 2, or 3 Rh groups. For example, in several embodiments, Re is the following formula:

Where X is 0, 1, 2 or 3, and Rh is as defined below and herein. In the examples, Re is an unsubstituted pyridinyl group (i.e., wherein X is oxime). In the examples, Re is a substituted pyridinyl group (e.g., wherein X is 1, 2 or 3). In several embodiments, Re is a substituted pyridinyl (ie, wherein X is 1). In several embodiments, Re is a disubstituted pyridene (i.e., wherein X is 2). Re is a three-substituted ratio of cultivating base (that is, where X is 3). In several embodiments, X is 0, 1, 2, or 3. In several embodiments, X is 0, 1, or 2. In some embodiments, X is 0 or 1. In some embodiments, Re is a substituted or unsubstituted ratio of any of the following formulae:

Where Rh is as defined below and herein. 50 201043620 In several embodiments, Re is a three-speaking base. In several embodiments, Re is a three tillage group substituted with 0, 1 or 2 substituents. For example, in several embodiments, Re is the following three π well base: , Ν^Ν 丨Ί

Where X is 0, 1 or 2, and Rh is as defined below and herein. In several embodiments, Re is an unsubstituted pyrenyl group (i.e., wherein X is 0). In several embodiments, Re is a substituted pyridinyl group (e.g., wherein X is 1 or 2). In the examples, Re is a substituted pyridinyl group (i.e., wherein X is 1). In the examples, Re is disubstituted. Than the base (that is, where X is 2). In some embodiments, X is 0, 1, or 2. In several embodiments, X is 0 or 1. In some embodiments, Re is a substituted or unsubstituted tri-farming base of any of the following formulae:

WVW •丄 hK N ΛΛΑ/·N丄

N

Where Rh is as defined below and herein. In several embodiments, Re is a four tillage. In several embodiments, Re is a four tillage group substituted with 0 or 1 Rh group. For example, in several embodiments,

Re is the following four bases: 'Ν^Ν (Rh)x where x is 0 or 1, and Rh is as defined below and here. In several embodiments, Re is an unsubstituted pyridinyl group (i.e., wherein X is 0). In a number of implementations 51 201043620, in the case of the replaced county (ie, where χ is υ. In several embodiments, X is 〇 or 1. - In several embodiments, Re is any of the following) Substituted or unsubstituted four π pingji: ιΛΑΛ/ νΑ.

丄 fN where Rh is as defined below and here. In a number of implementations, Re is a 9-membered heteroaryl (e.g., 5,6·bicycloheteroaryl). In several embodiments, Re is a 5-red cycloheteroaryl group substituted by the epoch. In a number of real _, Re is selected from the group consisting of 引 = 基 基 基 异 异 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 、 、 、 、 、 、 、 、 、 、夫 喃 基 、, Benzene, “milyl, benzoyl, benzo-hetero-m-salt, thiol, benzoheptyl, benzene, lining, base, and base A group of 5,6-bicyclic heteroaryl groups wherein the groups are substituted with hydrazine, b, 2, 3, 4 or 5 Rh groups. For example, in several embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula:

Wherein Ye, Yf, Yg, Yi, Yj, YkM, ^c, CH, CRh, Ο, S, _N, or NRk and r are C or N, but the constraints are ye, Yf, Yg Select from Q, S, and Dun, as defined in the following paragraph 52 201043620 and here. In some embodiments, Re is a 5,6-bicyclic heteroaryl group of formula (i-f), wherein Ye is selected from Ο, S, or NRk, γη is C, and Yf, Yg, V, γί, Yk and Υ are C, CH, or CRh respectively. For example, in several embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula:

<Rh)x-

(Rh)x or

Where X is 0, 1, 2, 3, 4 or 5 and Rh and Rk are as defined below and herein. In several embodiments, Re is an unsubstituted 5,6-bicyclic heteroaryl (i.e., wherein X is 0). In several embodiments, Re is substituted 5,6-bicyclic

Aryl (ie, where X is 1, 2, 3, 4 or 5). In several embodiments, Re is a monosubstituted 5,6-bicyclic heteroaryl (ie, wherein hydrazine is hydrazine). In several embodiments, Re is a disubstituted 5,6-bicyclic heteroaryl (i.e., wherein 乂 is 2). In several embodiments, Re is a trisubstituted 5,6-bicyclic heteroaryl (i.e., wherein χ is 3). In several embodiments, 乂 is 0, 1 χ 243. In several embodiments, X is 〇, 1 or 2. In several embodiments, In several embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula wherein ye is selected from the group consisting of Ο, S, or NRk; yg is N; Ynge; Yf is e, eH, geRh or N' and γ , YJ, Yk and Ym are respectively c, or cRh. For example, in the examples, 'Re is a 5,6-bicyclic heteroaryl group of the formula:

53 201043620 Where χ, 、, 2, q h . Z 3, 4 or 5 and Rh and Rk are as defined below and here. In several embodiments φ butyl ' R is an unsubstituted 5,6-bicyclic heteroaryl (i.e., wherein X is 0). In the case of Yu Ruo; Yu, the Re is a substituted 5,6-bicyclic heteroaryl (ie, where X is 1)

2, 3, 4 or 5). In several embodiments, Re is a substituted, substituted 5-, 6--------------------------------- In several embodiments, Re is a disubstituted octagonal <5,6-bicyclic heteroaryl (i.e., wherein χ is 2). to

In the right-hand embodiment, 'R is a trisubstituted 5,6-bicyclic heteroaryl (i.e., wherein X is 3). In several embodiments, 4 is less than 2 or 3. In several embodiments, X is 〇, 1 or 2. In several embodiments, X is 〇 or 卜 in several embodiments, Re is a 56-bicyclic heteroaryl group, wherein ye is NRk, S or Ο; Ym is Μ; Ylc; and Yf, yg, yi , Yj, and Yk are C, CH, or CRh, respectively. For example, in several embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula:

Where X is 0, Bu 2, 3, 4 or 5 and Rh and Rk are as defined below and herein. In several embodiments, Re is an unsubstituted 5,6-bicyclic heteroaryl (i.e., wherein X is 0). In several embodiments, Re is a substituted 5,6-bicyclic heteroaryl (i.e., wherein X is 1, 2, 3, 4 or 5). In several embodiments, Re is a monosubstituted 5,6-bicyclic heteroaryl (ie, wherein X is 1). In several embodiments, 'Re is a disubstituted 5,6-bicyclic heteroaryl (i.e., wherein the parent is 2). In several embodiments, Re is a trisubstituted 5,6-bicyclic heteroaryl (i.e., wherein χ is 3). In some embodiments 'X is 0, 1, 2 or 3. In several embodiments, 54 201043620 x is 〇, 1 or 2. In several embodiments, this is the case. In some embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula wherein Yg is 〇, S, or NRk; ΥΐΝ; γη is c; and Ye, Yf, γί, γϊ, and Yk are respectively C. CH, or CRh. For example, in several embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula:

Righteousness. In several real forms, Re is an unsubstituted 5,6_U aryl group (i.e., where X is G). In several embodiments, Re is a substituted 5,6-bicycloheteroaryl (i.e., wherein x is 1, 2, 3, 4 or 5). In several embodiments, Re is a 5,6-acyclic heteroaryl substituted with λ! (ie, wherein X is). In several embodiments, Re is a disubstituted 5,6-bicyclic heteroaryl (i.e., wherein X is 2). In some embodiments, 'Re is a trisubstituted 5,6-bicyclic heteroaryl (i.e., wherein X is 3). In several embodiments, X is G, Bu 2 or 3. In some embodiments, X is 0, 1 or 2° in several shots, X is 0 or in several embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula wherein Ye is selected from N Y" is N; and 6 Yi, Yj, γ1^γΠ1 are C, CH, or CR, respectively. For example, in several embodiments, Re is a 5,6-bicyclic heteroaryl group of the formula: wherein X is G, 丨, 2 '3, and "#" is as defined below and herein. In several embodiments Re is an unsubstituted 5,6-bicyclic heteroaryl (also 55 201043620 wherein X is deuterium). In several embodiments, Re is a substituted 5,6 bicyclic heteroaryl (ie, wherein乂 is 1, 2, 3, 4 or 5). In several embodiments, Re is a substituted 5,6-bicyclic heteroaryl (ie, wherein X is 1). In several embodiments, R is a disubstituted 5,6-bicyclic heteroaryl (ie, wherein X is 2). In several embodiments, Re is a trisubstituted 5,6-bicyclic heteroaryl (ie, wherein χ 3) In some embodiments, χ is 〇, 1, 2 or 3. In several embodiments, X is 〇, 1 or 2. In several embodiments, 乂 is ❶ or 。. In the example, R is 1 member heteroaryl (e.g., 6,6-bicyclic heteroaryl). In several embodiments, 'Re is substituted by 〇, 12, 3, 4, or ##, 6-Bicyclic heteroaryl. In several embodiments, Re is selected from the group consisting of acridinyl, acridinyl, quinolinyl, isoquinolinyl, porphyrin a 6,6-bicyclic heteroaryl group of a quinolinyl group, a hydrazine group, and a quinazolinyl group, wherein the groups are substituted with hydrazine, 1, 2, 3, 4 or 5 Rh groups. For example, in several embodiments, Re is a 6,6-bicyclic heteroaryl group of the formula: (*-g) wherein W, Wg, wh, w1, WJ, wk, WmA wn are selected from C, CH, respectively. CRh or N, but with the constraint that at least _ of Wf, wg, <, wi, wj, W, W, and Wn is N, and wherein # is as defined below and herein. In some embodiments, Re is a quinolyl group; for example, having the formula (i-g) wherein N and ^, Wf, wj, wk, and ψη are c, ch, and CR, respectively. For example, in several embodiments, Re is a quinolinyl group: 56 201043620

Where x is 0, 1, 2, 3, 4 or 5 and Rh is as defined below and herein. In several embodiments, Re is an unsubstituted quinolyl group (ie, wherein X is 0). In several embodiments, Re is a substituted quinolyl group (ie, wherein X is 1, 2, 3, 4, or 5). In several embodiments, Re is a monosubstituted quinolyl group (i.e., wherein X is 1). In several embodiments, Re is a disubstituted quinolinyl group (i.e., wherein X is 2). In several embodiments, Re is a trisubstituted quinolyl group (i.e., wherein X is 3). In several embodiments, X is 0, 1, 2, or 3. In some embodiments, X is 0, 1, or 2. In several embodiments, X is 0 or 1. In some embodiments, Re is an isoquinolyl group; for example, having the formula (i-g) wherein Wh is N and Wf, Wg, Wj, Wk, Wm and Wn are C, CH, CRh, respectively. For example, in several embodiments, Re is an isoquinolinyl group of the formula:

Where X is 0, 1, 2, 3, 4 or 5 and Rh is as defined below and herein. In several embodiments, Re is an unsubstituted isoquinolyl group (i.e., wherein X is 0). In some embodiments, Re is a substituted isoquinolyl group (ie, wherein X is 1, 2, 3, 4, or 5) in several embodiments, and Re is a monosubstituted isoquinolyl group (also That is, where X is 1). In several embodiments, Re is a disubstituted isoquinolyl group (i.e., wherein X is 2). In several embodiments, Re is a trisubstituted isoquinolyl group (i.e., wherein X is 3). In several embodiments, X is 0, 1, 2, or 3. In several embodiments, X is 0, 1, or 2. In several embodiments, X is 0 or 1. 57 201043620 In some embodiments, 'Re is a quinoxaline group; for example, having formula (i_g) wherein # and # are >^ and Wg, Wh, such as, wk, W*^Wn are C, CH, CRh, respectively. For example, in several embodiments, Re is a quinacridine of the formula:

Where X is 0, 1, 2, 3, 4 or 5&Rh is as defined below and herein. In several embodiments, 'R is an unsubstituted 喧0 lyophilized group (i.e., wherein the parent is 〇). In some embodiments 'Re is a substituted quinoxaline group (i.e., wherein χ is 1, 2, 3, 4 or 5). In several embodiments, ^ is a substituted quinolin (i.e., wherein X is 1). In several embodiments, Re is a disubstituted Chelenski (i.e., towel 42). In a number of implementations, "three-substituted quinolin-based (ie, where x is 3). In several embodiments, X is 0, 1, 2

X or 3 In several embodiments, 乂 is 〇, 1 or 2. In some embodiments it is 0 or 1. In 5 dry _, R, 3_14 ring groups. In some embodiments, R is a 3,14-membered hetero-subunit substituted with 1 '2, 3, 4, or 5'. In several embodiments, λ 1 is a 5-10 membered heterocyclic group substituted with hydrazine, b, 2, 3, 4 or 5 hydrazine. In the example of the right-hand drying, Re is s 2 , ^ 弋 8 杂环 heterocyclyl substituted with 0, 1, 2 3, 4 or 5 Rh groups. In several embodiments, Re~ is substituted with a 56-membered heterocyclic group substituted with 〇, 1, 2, 3, 4 or 5. Examples of the heterocyclic group Re which are substituted by G 2, 3, 4 or 5 4 include, but are not limited to.丫口元基 T兀卷, °塞崎土,. Zuji, argyl, base, tetrahydro π(tetra)yl, dihydrocarbyl, 58 201043620 tetrahydroquinolyl, = hydrogen. A thiophene group, a scaly dentate group, a dihydro π-pyrrolyl group, an alpha-l-butyryl-2,5-dione, a diindolyl group, a nonylthiol group, a dithiazinyl group, a triazolyl group, and a g-di. Pure H♦ fluorenyl, tetrahydro", dioxaridinyl, thioxanthene, piperylene, porphyrinyl, dithianyl, diterpenoid, trimorphinyl, anthracene Base, mercapto, thioxyl, fluorenyl, fluorenyl, thiophenyl, porphyrin, isoindolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, tetrahydrobenzene And thienyl, tetrahydrobenzofuranyl, tetrahydroindenyl, tetrahydroquinolyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrofluorenyl, eight Hydrogen isoindole, decahydroacridinyl, decahydro-1,8-acridinyl, octahydroindolo[3,2-b]pyrrole, porphyrinyl, quinone imine, naphthalene Imino group, bite α complete, bite ° Hickey, 1H-benzo[e][l,4] bis. oxime, 1,4,5,7-tetrahydro 11 decano[3,4 -b]. π each, 5,6 diaza _4H_ benzo[3,2-b]pyrrolyl, 6,7-dihydro-5H-furo[3,2-7]piperidyl , 5,7-dihydro-4H-.seceno[2,3-c]D-drinking base, 2,3-dihydro-ih_u, biluo[2,3-b] 0 than biting base, 2 , 3-Bista β-pyrano[2,3-b]n is more than fluorenyl, 4,5,6,7-tetrahydro-1H·pyrrolo[2,3-b]pyridinyl, 4,5, 6,7·four Furando[3,2-c]pyridinyl, and 4,5,6,7-tetrahydrothieno[3,2-b]° pyridine, 1,2,3,4-tetrahydro-1, 6-°neptidyl, wherein these groups are substituted with 0' 1, 2, 3, 4 or 5 Rh groups. In the embodiment, Re is 〇, 1, 2, 3, 4 or 5 Rh-substituted 6-membered heterocyclic groups. In several embodiments, Re is selected from the group consisting of piperidinyl, tetrahydropyranyl, dihydropyridinyl, thia-beta, and well a 6-membered heterocyclic group of a phenyl group, a porphyrin group, a dithiazide group, a bismuth group, and a ruthenium group, wherein the groups are 0, 1, 2, 3, 4 or 5 Substituent substitution. For example, in several embodiments, K is a heterocyclic group of the formula 6: 59 201043620

W°—WP I—w* w*» ^ \ / ws—wr (i-h) where W. , Wp, Wq, WrAWs are respectively selected from (: Ιί2, CHRh, -C(Rh)2, -NRk, O or S, and Wl is N, CH, CRh, but the restrictions are W°, Wp, Wq, At least one of W and Ws is selected from N, -NRk, Ο or S, and wherein Rh and Rk are as defined below and herein. In several embodiments, Re is piperidinyl. In several embodiments Wherein Re is a piperidinyl group substituted with 0, 1, 2, 3, 4 or 5 Rh groups, for example, having the formula:

Where X is 0, 1, 2, 3, 4 or 5 and Rh&Rk is as defined below and herein. In several embodiments, Re is unsubstituted piperidinyl (ie, wherein X is 0). In several embodiments, Re is substituted piperidinyl (ie, wherein X is 1, 2, 3, 4, or 5). In several embodiments, R1 is substituted with a piperidinyl group (i.e., wherein X is 1). In several embodiments, Re is a disubstituted 0-alkyl group (i.e., wherein X is 2). In several embodiments, Re is a trisubstituted piperidinyl group (i.e., wherein X is 3). In several embodiments, X is 0, 1, 2, or 3. In several embodiments, X is 0, 1, or 2. In several embodiments, X is 0 or 1. In some embodiments, Re is 1-piperidinyl, for example, having the formula (ih) wherein \¥1 is > 4 and W°, Wp, Wq, W1" and Ws are selected from CH2, CHRh, respectively. C(Rh)2. In some embodiments, Re is 2-piperidinyl, for example having the formula (ih) wherein W° is NRk; Wp, Wq, and \¥5 are CHRh, -C(Rh)2 or 60 201043620 CH2, respectively; W1 is CH or CRh. In several embodiments, Re is 3-piperidinyl, for example having the formula (ih) wherein Wp is NRk; W° 'Wq, Wf & Ws are CHRh, -C(Rh)2 or CH2, respectively; and 妒 is CH Or CRh. In several embodiments, Re is 4-piperidinyl, for example having the formula (i-h) wherein; W[deg.], Wp, and Ws are CHRh, _C(Rh)2 or CH2, respectively; and W>CH or CRh. In several embodiments, Re is piperidinyl. In several embodiments, Re is a piperene substituted with 0, 2, 3 or 4 Rh groups, for example having the formula:

Where X is 0, 1, 2, 3, 4 or 5 and Rh&Rk is as defined below and herein. In several embodiments, Re is an unsubstituted piperidinyl (ie, wherein X is 0). In several embodiments, Re is a substituted piperage (i.e., wherein X is 1, 2, 3, 4, or 5). In several embodiments, Re is a monosubstituted beta-thiophene group (i.e., wherein X is 1). In several embodiments, Re is a disubstituted piperage (i.e., wherein X is 2). In several embodiments, Re is a trisubstituted piperidinyl (i.e., wherein X is 3). In several embodiments, X is 〇, 1, 2, or 3. In several embodiments, X is 0, 1, or 2. In several embodiments, X is 0 or 1. In some embodiments, 1 is a 1-piperage group, for example, having the formula (ih), wherein W1 is N, Wq is NRk & W°, Wp, λΤ, and Ws are selected from CH2, CHRh, and -C, respectively. Rh) 2. In some embodiments, Rl2-piperidinyl, for example, has the formula (ih) wherein W° & Wf are NR1^Wp, Wq, and Ws are respectively CHRh, -C(Rh)2 or CH2; and W1 is CH or CRh. In several embodiments, Re is 咮琳基. In several embodiments, Re is a porphyrin group substituted with 0, 2, 3 or 4 Rh groups, for example having the formula: 61 201043620 k -HR' wherein x is 0, 1, 2, 3, 4 Or 5 and Rh and Rk are as defined below and herein. In several embodiments, Re is an unsubstituted porphyrin group (ie, wherein X is 0). In several embodiments, Re is a substituted porphyrin group (ie, wherein X is 1, 2, 3, 4, or 5). In several embodiments, Re is a monosubstituted porphyrin group (i.e., wherein X is 1). In several embodiments, Re is a disubstituted porphyrin group (i.e., wherein X is 2). In several embodiments, Re is a trisubstituted porphyrin group (i.e., wherein X is 3). In several embodiments, X is 0, 1, 2, or 3. In several embodiments, X is 〇, 1 or 2. In several embodiments, X is 0 or 1. In some embodiments, Re is a formula (i-h) porphyrin group wherein Wt is N, Wq is Ο and W°, Wp, Wr and Ws are selected from the group consisting of CH2, CHRh, and -C(Rh)2, respectively. In several embodiments, Re is a diyama. In several embodiments, Re is a fluorenyl group substituted with 0, 1, 2, 3 or 4 Rh groups, for example having the formula:

Or ό"Λ where X is 0, Bu 2, 4 or 5 and Rh&Rk is as defined below and here. In several embodiments, Re is an unsubstituted diterpene sigma base (i.e., wherein X is 0). In several embodiments, Re is a substituted π-mountain (i.e., wherein X is 1, 2, 3, 4, or 5). In several embodiments, Re is a substituted one. No. σ Shanji (that is, where X is 1). In several embodiments, Re is the second substituted. number. Shanji (that is, where X is 2). In several embodiments, Re is a trisubstituted sulfhydryl group (i.e., wherein X is 3). In several embodiments, X is 0, 1, 2 62 201043620 or 3. In several embodiments, χ is 〇, 1 or 2. In several embodiments, χ is 0 or 1. In some embodiments, Re is a diterpenoid, for example having the formula (i_h), wherein W° and Wr are 0 and Wp, Wr and Ws are CHRh, -C(Rh)2 or CH2, respectively; and W>;CH or CRh. Other 6-membered heterocyclyl Re groups encompassed by formula (ih) include monosaccharide saccharides, for example selected from the group consisting of ribose, arabinose, xylose, lyxose, allose, arzoose, glucose, mannose, Gourose, iodose, galactose and talose. - In several embodiments, Re is a C3-10 carbocyclic group. In several embodiments, 'Re is a C3-10 carbocyclic group substituted with 0, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, Re is a C5-8 carbocyclic group substituted with 〇, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, Re is a C5-6 carbocyclyl substituted with 〇, 1, 2, 3 or 4 Rh groups. In several embodiments, Re is a C9-10 carbocyclic group substituted with hydrazine, bromo 2, 3, 4 or 5 Rh groups. Examples of Q Re2C3-1{) carbocyclic groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, And cycloheptadienyl, wherein the groups are substituted with hydrazine, 1, 2, 3, 4 or 5 Rh groups. The group G2Rf is as defined above, in several embodiments, wherein the G system is selected from the group consisting of -S02NRfRe, _p〇2NRfRe, -(C=0)NRfRe, -〇NRfRe, -ONRf(〇〇)Re, -〇NRfS02Re, -0NRfP02Re, -0NRfP020Re, -NRfS02Re, _NRfP〇2Re, _NRfP〇2〇Re, -〇p〇2NRfRe, 63 201043620 -NRfRe ' -NRf(C=〇)Re ^ _NRf(c=〇)〇Re ^ -0 (C-0)NRfRe > -NRf(C=NRf)NRfRe, _〇(c=NRf)NRfRe, _NRf(c=NRf)〇Re, and -[N(Rf)2Re]+X_where χ- As a counter ion, each Rf attached to a nitrogen atom is selected from -Η or Cmg alkyl, or an amine protecting group, or Re&Rf is joined to form a 3-14 membered heterocyclic ring or a 5-14 membered heteroaryl group. ring. In several embodiments, 1 is 11 or CM0 alkyl. In several embodiments, Rf is Η. In several embodiments, it is considered to be an alkyl group. In several embodiments, Rf is a Cmo alkyl group substituted with 0, 1, 2, 3, 4 or 5 groups. Examples of Rf alkyl groups include, but are not limited to, decyl, ethyl, propyl, allyl, and benzyl. In several embodiments, Rf is an unsubstituted thiol group, ie, -CH3. In the examples, 'Rf is an unsubstituted ethyl group, i.e., _CH2CH3. In several embodiments, Rf is an amine protecting group. For example, in several embodiments, Rf is selected from the group consisting of _〇H, -ORi, _N(Rk)2, _c(=〇)Ri, C(=0)N(Rk)2, -CC^Ri, -s〇 2Ri, _c(=NRk)Ri, _cb NRk)〇Rj, _C(=NRk)N(Rk)2, -S02N(Rk)2, _S02Ri, _S020Ri, -SORi, -C(=S)N(Rk 2, -C(=〇)SRi, _c(=s)SRi, Ci i◦alkyl (for example aralkyl), C2_1G alkenyl, c2 lQ alkynyl, c3_1G carbocyclyl, 3-14 heterocyclyl, a C6-u aryl group, and a 5-14 membered heteroaryl group, wherein each of an alkyl group, an alkenyl group, an alkynyl group, a carbocyclic group, a heterocyclic group, an arylalkyl group, an aryl group, and a heteroaryl group 1, 2, 3, 4 or 5 thiol substitutions, wherein Ri, Rk, Rm are as defined below and herein. Additionally, in several embodiments, Re is joined to Rf to form a 3-14 membered heterocyclyl ring or a 5-14 membered heteroaryl ring; for example, when 〇 is _§〇2; ^/1^, _p〇2NRfRe, 64 201043620 - (C=0) NRfRe, -〇NRfRe, -OP02NRfRe, -NRfRe, -〇(C=〇)NRfRe, -NRf(C=NRf)NRfRe ' -〇(C=NRf)NRfRe, and _[N(Rf ) 2Re]+x·where X_ is a counter ion. In several embodiments, wherein ^^ and 1^ are joined to form a 3-14 membered heterocyclyl ring or a 5-14 membered heteroaryl ring, the heterocyclyl or heteroaryl ring system is 〇, 1, 2 3, 4 or 5 Rh group substitutions, as defined below and herein. In several embodiments, G is -NRfRe, and Re is joined to Rf to form a 3-14 hexacyclyl ring. In several embodiments, G is -NRfRe, and 1^ is bonded to a 3-14 membered heterocyclyl ring substituted with 0, 1, 2, 3, 4 or 5 Rh groups. • In several embodiments, G is -NRfRe, and 11 is bonded to 1^ to form a 5-10 membered heterocyclyl ring substituted with 〇, ι, 2, 3, 4 or 5 Rh groups. In several embodiments, 'G is -NRfRe, and R%Rf is joined to form a 5-8 membered heterocyclyl ring substituted with hydrazine, 1, 2, 3, 4 or 5 Rh groups. In several embodiments, g is -NRfRe, and Re is joined to Rf to form a 5-6 membered heterocyclyl ring substituted with 2 or 3 Rh groups. In several embodiments, G is -NRfRe, and 1^ is bonded to Q to form a 9-10 membered heterocyclyl ring substituted with hydrazine, 1, 2, 3, 4 or 5 Rh groups. In some embodiments, G is -NRfRe, and 1^ and 1^ are joined to form a moiety selected from 0. Elemental basis, σ丫11 danyl, 吼11 each bite group, dihydro-β ratio π group, β ratio _2,5-diketone, triazoline group, oxadiazolyl group, thiadiazolyl group , piperidinyl, dihydropyridyl, thioxyl, cyano, porphyrin, tricotyl, sulfhydryl, alpha thiol, tiophanyl, fluorenyl, porphyrin, iso Porphyrin, tetrahydrobenzothiophenyl, tetrahydroindenyl, tetrahydroquinolyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, porphyrinyl and anthracene A heterocyclic group in the quinone imine group, wherein the groups are taken as 0, 1, 2, 3, 4 or 5 Rh groups, 65 201043620 generation. For example, in several embodiments, GVNRfRe, and R^Rf are joined to form a 5-membered heterocyclyl ring selected from the group consisting of: τ τ ^ 〇 ύ where x is ο, 1'2 or 3' wherein Rh and The system is as defined below and here. For example, in several embodiments, G is an apparent fRe, and R^Rf is joined to form a 6-membered heterocyclyl ring selected from the group consisting of:

Where X is 0 1, 2 or 3' as defined below and herein. . In several embodiments, G is NRfRe and the chelating is formed to form a fluorene heteroaryl ring. In a number of real _, G is _NRfRe, and Re and Rf are bonded to each other to form a 5-14 aryl aryl ring substituted with G 2, 3, 4 or 5 Rh groups. In several embodiments, the G4_NRfRe, (4) junction forms a 5_1 member heteroaryl ring substituted with a reduced 34 or 5 R groups. In a number of embodiments, h is NR R ' and R$Rf is joined to form a 5.8 membered heteroaryl ring which is taken from 〇, 1, 2, 3 or 4 R groups. In several embodiments, G is _NRfRe and the bond is formed to form a 5-6 membered heteroaryl group substituted with a G small 2, a torn (tetra) group. In the right-hand embodiment, G is -NRfRe' and the 5-14 membered heteroaryl ring substituted with hydrazine, 1, , , 3, 4 or 5 groups. In several embodiments, 66 G is _NRfRe, and Rf is joined to form a 91() heteroaryl ring substituted with a 2, 3, 4 or 5 Rh group. For example, in several embodiments, Gg_NRfRe, and R%Rf are joined to form a 5-membered heteroaryl ring selected from the group consisting of:

Ding Ding ^ , , ( 气, where X is 〇, 1 or 2 ' where Rh and 0 are as defined below and herein. In some embodiments, G is -NRfRe, and is formed by bonding with !^ 9-membered heteroaryl (r 5,6-bicycloheteroaryl) ring from the following group:

Where X is 0, Bu 2 or 3, and Rh and Rk are as defined below and herein. Substituent for group G

The implementation of Rh is as hereinbefore described and used herein, and each of Rh is selected from the group consisting of halogen (fluorine Q (-F), bromine (-Br), gas (-C1), and iodine (-1), -CN, -N〇2, -N3, -S02H, _S03H, -OH, _ORi, -〇N(Rk)2, _N(Rk)2, -N(Rk)3+X., -N(ORj)Rk, - SH, -SR^, -SSRj, -C(=0)Ri, -C02H, -CHO, -COjR1 ' -OCC^O)^ ' -OCOzR1 ' -C(=0)N(Rk)2 - -OC (=0)N(Rk)2, -NRkC(=0)Ri, -^RkC02Rl, _NRkC(=0)N(Rk)2, -C(=NRk)Ri, -C(=NRk)ORi, - OC(=NRk)Ri, -OC(=NRk)ORi, -C(=NRk)N(Rk)2, -OC(=NRk)N(Rk)2, _NRkC(=NRk)N(Rk)2 -C(=0)NRkS02Ri, -NRkS02Ri, -S02N(Rk)2, -SC^Ri, -SC^ORJ, -OSO#, 67 201043620 -8(=0)111, -08(=0)111, -S'r%, _(^(11丨)3, -C(=S)N(Rk)2, -CpC^SR1, -CC^SR1, -SC(S)SRi, -P(=0) 2Ri, -〇Ρ(=0)2Ι^, -P(=0)(R')2 ^ -〇p(=〇)(Ri;>2 N .〇p(=〇)(〇Rj)2 -P(=〇)2N(Rk)2 ^ -0P(=0)2N(Rk)2 ^ -P(=0)N(Rk)2 ^ -0P(=0)N(Rk)2 . - NRkP(=0)(0R")2, _NRkp(=〇)(NRk)2, _p(Rj)2, _p(10)3, -OP(Rj)2, -OP(Rj)3, _B(〇Rj)2 _BRi(〇Rj), Ci, alkyl, Ci (7) perhalogenated, C2_1G alkenyl C2_i. alkynyl, (: 3.14 carbocyclyl, 3-14 membered heterocyclic, C6-14 aryl and 5-14 membered heteroaryl, wherein alkyl, dilute, fast radical, carbocyclic, heterocyclic The base, the aryl group, and the heteroaryl group are each substituted with hydrazine, hydrazine, 2, 3, 4 or 5 Rm groups;

Ri is selected from cM at each occurrence. An alkyl group, a Cl.a-alkyl group, a C2-1G alkenyl group, a C2-1G fast group, a (: 3-14 carbocyclic group, a 3-14 membered heterocyclic group, a % aryl group, and a 5·14 anthracene green, wherein the alkyl group, the alkene The base, the fast group, the hindering ring group, the heterocyclic group, the aryl group, and the heterogeneous group are each difficult to be substituted with G 2, 3, 4 or 5 Rm groups;

Rk is selected from hydrogen, _〇H, _〇Ri, _N(Rj)2, CN_C(_0)R, _C(=0)N(RJ)2, _c〇2Ri, s〇 at each occurrence. 2Ri, C(=NRj)ORi, _C(=NRj)N(Rj)2, s〇2N(Rj)2 s〇2Rj S020R, -SOR, -C(=s)N(Rj)2, _c(= 〇) SRj, c(=s)SRj, P( 〇)2R ' -P(-0)(R)2, -P(=0)2N(Rj)2 ^ _p(=〇)(NRj)2, Ci i oxime, CM°M alkyl, c(tetra)alkenyl, 'alkynyl, % carbocyclyl, 3-M member heterocyclic, Q 4 aryl and 5-14 heteroaryl, or attached to nitrogen The two counties of the atom are joined to form a m14M heterocyclic group or a 5-14 membered heteroaryl ring, wherein the alkyl group, the alkenyl group, the alkynyl group, the carbocyclic group, the heterocyclic group, the aryl group, 68 201043620 and the heteroaryl group are respectively After the embarrassment,! , 2, 3, 5槪, base substitution; each occurrence is selected from hydrogen, Ci• 灭基 'Q”. All (4) yl 'C2_1D alkenyl' C2 1 decynyl, (^ carbocyclyl a 3_14 membered heterocyclic group, a C6_14 moiety group, and a 5.14 membered heteroaryl group, or two Rj groups attached to a nitrogen atom are bonded to form a 3]4 membered heterocyclic group or a 5·14 membered heteroaryl ring, Wherein the alkyl group, the dilute group, the fast group, the nucleus group, the heterocyclic group, the aryl group, and the heteroaryl group are each substituted with 〇, 丨, 2, 3, 4 or 5 尺"1 groups; Each occurrence is selected from the group consisting of fluorine (_F), bromine Br), gas (_C1), and angstrom (-1), -CN, -N〇2, -N3, -S02H, -S03H, -OH, -OR., -〇N(Rn)2, _N(Rn)2, _N(Rn)3+x., _N(〇R〇)Rn, _SH, _SR., -SSR., -C(=〇) R., -C02H, -C02R°, -〇C(=0)R°, -〇C02R°, -C(=0)N(Rn)2, -〇C(=〇)N(Rn)2 ' -NRnC(=0)R.' -NRnCO2R0, -NR C(=〇)N(Rn)2, -C(=NRn)〇R., -〇c(=NRn)R°, OC(=NRn) 〇R., _c(=NRn)N(Rn)2, -〇c(=NRn)N(Rn)2, -NRnC(=NRn)N(Rn)2 ' -NRnS02R° > -S02N(Rn) 2 ' -S02R° ' -S〇2〇R°, _〇s〇2R., _s(=〇)R°, _si(R 3, -〇Si(R°)3, _C(=S)N(Rn)2, -C(=O)SR0, -C(=S)SR〇, -SC(=S)SR0, -P (=0)2R° x -P(=〇)(R°)2 λ -0P(=0)(R°)2 . -〇P(=〇)(〇r°)2 x Q-6 , Cw all-dentate alkyl, C2_6 alkenyl, C2_6 alkynyl, C3_14 carbocyclyl, 3-14 membered heterocyclic, C^4 aryl and 5-14 heteroaryl, wherein alkyl, alkenyl, alkynyl, Carbocyclyl, heterocyclyl, aryl, and heteroaryl are each substituted with hydrazine, 1 '2, 3, 4, or 5 Rp groups, or two fluorene substituents may be joined to form =0 or = S; R〇 is selected from Cw alkyl, Cl_6 functional alkyl, 69 201043620 c2-6 alkenyl, c2_6 alkynyl, r ^ ^ group, C6.1 aryl, 3-10, respectively. Heterocyclic

a group, and a 3-10 member of the heterocyclic group I, wherein the alkyl group, the alkenyl group, the alkynyl group, the carbocyclic group, the heterocyclic group, the aryl group, and the long heterocyclic group are respectively 〇, 1, 2 3, 4 or 5 Rp group substitutions;

Rn is selected from hydrogen, Q 6 alkyl, ^perhaloalkyl, C2·6 alkenyl, C2_6 block, C3-ig carbocyclic, 3-10 membered heterocyclic, C6-, respectively. a 10 aryl group and a 5 1G member heteroaryl group, or two Rn groups attached to a nitrogen atom, are bonded to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring, wherein the alkyl group, the dilute group, the fast group, Each of the hydroxy group, the heterocyclic group, the aryl group, and the heteroaryl group is substituted with 〇, i, 2, 3, 4 or 5 Rp groups, respectively; and RP is respectively fluorine (_F), bromine at each occurrence (_Br), gas (_cl), and iodine (-1), -CN, -N02, _n3 '-S02H, -S03H, -OH, -OCk alkyl, -ONiCw alkyl) 2, _N (Cl 6 alkane 2) _n(Ci_6 alkyl)3χ ' _nh(Ci 6 alkyl) 2X, -NHKCw alkyl)X, -NH3X, alkyl XCw alkyl), -NCOHXCw alkyl), -NH(OH), -SH, -SCy alkyl, -SSfu alkyl), -c(=o)(c丨-6 alkyl), -C02H, -co2(c丨-6 alkyl), -OCtOXCwalkyl)' - OCCMCw alkyl), -C(=0)NH2, -(:(=0^((^.6 alkyl)2, -OCtCONHde alkyl), -NHCpOXCw alkyl), -Νγκ alkyl) (:( =0) ((:, .6 alkyl), -NHCOJCw alkyl), -NHChCO^Cw alkyl) 2, -NHCPCONI^Ck alkane ), -NHC(=0)NH2 ' -C(=NH)0(Ci.6^1.) '-OC(=NH)(Ci.6^ base), -OCPNHPCk alkyl, -CbN^NCCK alkane Base) 2, alkyl), -C(=NH)NH2, -OC(=NH)N(C丨_6 alkyl)2, -OCXNI^N^Cw alkyl), -OC(NH)NH2 70 201043620 -NHC^NI^NCCk alkyl)2, -NHC(=NH)NH2, -NHSOZCk alkyl), -SOaNCCw alkyl)2, -SOzNHCCw alkyl), -S02NH2, -SOsCm alkyl, -S 〇2〇CN6 alkyl, -OSC^Cw alkyl, -SOCw alkyl, -SKCw alkyl)3, -OSKCw alkyl)3,alkyl)2, alkyl), -C(=S)NH2 -(:(=0)8((:,.6 alkyl), -CPSPCkalkyl, -scpspcwalkyl, -PPOMCmalkyl), -PtOXCw alkyl)2, -OPPOXCk alkyl)2, -OPtOXOCw Alkyl) 2, Ci_6 alkyl, C!-6 perhalogenated group, C2-6 thin group, C2-6 block group, C3_i〇ο carbocyclic group, C6_l4 aryl group, 3-14 membered heterocyclic group, 5 -14 member heteroaryl; or two hydrazine Rp substituents may be joined to form =0 or =S; wherein X_ is a counterion. In some embodiments, the Rh is selected from the group consisting of fluorine (-F), bromine (-Br), chlorine (-C1), and broken (-1), _CN, -N〇2, -OH, -ORi, -SR1 , -S02H, -S03H, -N(Rk)2, -N(Rk)3+X, -0(=0)111, -CO2H, -CO2R1, -00(=0)1^1, -OCOzRi, -C(=0)N(Rk)2, -0C(=0)N(Rk)2, -NRkC(=0)Ri, Q -NMcoA, -NRkC(=0)N(Rk)2, -C (=NRk) Ri, -C(=NRk)ORi, -OC(=NRk)Ri, -OC(=NRk)ORi, -C(=NRk)N(Rk)2, -OC(=NRk)N( Rk)2 ' -NRkC(=NRk)N(Rk)2 ^ -C(=0)NRkS02Ri > -NI^SC^, -S02N(Rk)2, -S02Ri, -S020Ri, -〇S02Ri, -SpCOR1 , -OS(=0)R丨, -C(=S)N(Rk)2, -C(=0)SRi, -(:(四)娜, -SC(S)SRl ' ^(=0)2^ ' -0?(=0)2^ ' -?(=0)(^)2 ' -0Ρ(=0)(Ϊ02 , -0P(=0)(0Rj)2 , -P(=〇)2N( Rk)2, -0P(=0)2N(Rk)2, -P(=0)(NRk)2, -OP(=〇)(NRk)2, -NRkP(=0)(0RJ)2, - NRkP(=〇)(NRk)2, -B(ORj)2, -BRi(ORj), 71 201043620 "Ci-|G 全_炫基,匚3_|4 carbocyclic group, 3_i4 member heterocyclic group, a C6_14 aryl group and a 5-14 membered heteroaryl group, wherein each of the alkyl group, the ring-inhibiting group, the heterocyclic group, the aryl group, and the heteroaryl group are each substituted with 2, 3, 4 or 5 Rm groups; Which χ-for resistance In the right-right embodiment, Rh is selected from the group consisting of fluorine (_F), bromine (_Br), gas (C1), and cerium (-1), -CN, -NO, -OH, -OR1, -SR1 , -N(Rk)2, -N(Rk)3+X., C(-C^R1, _c〇2Rl 'c〇2h, 〇c(=〇)Ri, 〇c〇2Ri, -C(- 0) N(Rk)2 ' _〇c(=〇)N(Rk)2, _NRkc(=〇)Ri, _NRkc〇2Ri, -NR C(=〇)N(Rk)2 , -C(=〇 NRkS02Ri '-NRkS02R' > _S02N(Rk)2, _s〇2Ri, Ci i〇alkyl, C6 aryl and 5.6-membered heteroaryl, wherein each of the alkyl, aryl, and heteroaryl groups is respectively Substituted with 0, 1, 2, 3 or 4 Rm groups; and its χ- is a counter ion. In several embodiments, R1-OR1, for example selected from the group consisting of -OCH3, -OCF3, -OCH2CH3, -〇CH2CF3, -OiPr, and -OnBu. In several embodiments, Rh is -SR1, for example selected from -SCH3. In several embodiments, Rh is _N(Rk)2 or -N(Rk)3+X-, for example, selected from -NH2, -ΝΗ3+Χ·. In several embodiments, Rh is, for example, selected from -C(=0)CH3. In several embodiments, Rh is -CO#, for example selected from -C02CH3. In several embodiments, Rh is -C(=0)N(Rk)2, for example selected from the group consisting of -C(=〇)NHOH, -C(=0)NH2, -C(=0)NHCH3, -c( =o)n(ch3)2, -C(=0)NHCH2CH3, -C(=0)NHCH2CF3, -C(=〇)NH(CH2)i.6NH3+X, -C(=0)NHCH2C(= 0) 0CH3, -c(=o)nhch2c(=o)oh, and -c(=o)nhch2ch2oh. 72 201043620 In several embodiments, Rh is -0C(=0)Ri, for example selected from -oc(=o)ch3. In several embodiments, Rh is -002Ri, for example selected from -0C02CH3. In several embodiments, Rh is -0C(=0)N(Rk)2, for example selected from -oc(=o)nh2. In several embodiments, Rh is -NRkC(=0)Ri, for example selected from -nhc(=o)ch3. In several embodiments, Rh is -NRkC02Ri, for example selected from the group consisting of -NHC(=0)0CH3 and -NHC(=0)0tBu. In several embodiments, Rh is -NRkC(=0)N(Rk)2, for example selected from the group consisting of -nhc(=o)nh2. In several embodiments, Rh is -C(=0)NRkS02Ri, for example selected from the group consisting of -C(=0)NHS02CH3, -C(=0)NHS02CH2CH3, -C(=0)NHS02C5H9, and -C(=0)NHS02iBu . In several embodiments, -NHS02CH3. In several embodiments, _S02NH2, -S02N(CH3)2.

Rh is -NRkSC^Ri, for example selected from

Rh is _S02N(Rk)2, for example selected from several embodiments, and Rh is -SO#1, for example selected from the group consisting of -S02CH3, -S02CH2CH3, -S02C5H9, and -S02iBu.

In several embodiments, Rh is Cmo alkyl, for example selected from the group consisting of -CH3, -CH2CH3, -iPr, -nBu, -CF3, -CH2CH2C02Me, -CH2CH2C02H, and -ch2ch2co2nh2. In some embodiments, Rh is selected from the group consisting of -(:(=0)1^, -C02H, and 73 201043620 -S02Ri. In several embodiments, Rh is -C(=0)Ri. In several embodiments, Rh is -C02H or -S02CH3. In several embodiments, Rh is -C02H. In several embodiments, Rh is -S02CH3. In several embodiments, each instance of Rh is selected from the group consisting of fluorine (-F), Bromine (-Br), chlorine (-C1), and (-1), -NH2, -NH3+X, -CN, -N〇2, -S02CH3, -S02CH2CH3, -S02C5H9, S02iBu, _S02NH2, -so2n (ch3)2, -c(=o)nhso2ch3, -c(=o)nhso2ch2ch3, -C(=0)NHS02C5H9, -C(=0)NHS02iBu, -C(=0)CH3, -C02H, -C02CH , -OC(=0)CH3, -0C02CH3, -C(2)NH0H, -C(=0)NH2, -C(=0)NHCH3, -C(=0)N(CH3)2, -c (=o)nhch2ch3, -c(=o)nhch2cf3, -C(=0)NH(CH2)1.6NH3+X ' -0C(0)NH2 ' -NHC(=0)CH3 ' -NHC(=0) OCH3, -NHC(=0)0tBu, -NHC(=0)NH2, -NHSO2CH3, -CH3, -CH2CH3, -iPr, -nBu, -CF3, -OH, -OCH3, -SCH3, -OCF3, -〇 CH2CH3, -OCH2CF3, -OiPr, -OnBu, -CH2CH2C02Me, -CH2CH2C02H, -CH2CH2C02NH2, -C(=0)NHCH2C(=0)0CH3, -c(=o)nhch2c(=o)〇h, -C( =0) NHCH2CH2〇H a 5-6 membered heteroaryl group substituted with 0, 1 or 2 Rm groups and substituted with 0, 1 or 2 1 groups; and a ruthenium in the middle is a counter ion. In the examples, Rh is an aryl group (eg, phenyl) substituted with hydrazine, 1 or 2 Rm groups. In several embodiments, Rh is a c6 aryl group substituted with a 尺 !!! !!! group (eg, Phenyl)' and Rm are _c〇2h, -C〇2CH3, -C02CH2CH3, and -c(=o)nh2. 74 201043620

In the right-hand implementation of the financial 'R is (four) Q, domain m shirt m-substituted Μ hetero-aryl. In a number of implementations, Rh is a four-member heterobasic group replaced by (4) Q and 丨朗·基. Examples of 5-membered heteroaryl groups include, but are not limited to, pyrrolyl, fluorenyl, flg phenyl, imipenyl, (tetra) κ-based, iso-s-s-yl, s- s- s, s, s. Dimercapto, ^ tetrasyl, wherein these bases are substituted by one or one of the base groups. In a few % of the cases, the 'Rh5 member heteroaryl system, selected from the group consisting of (4) groups and $2, wherein the groups are substituted with 0 or 1 Rm group. ^Examples In the right-hand embodiment, Ri is selected from the group consisting of singly-based, 'dilute, C2'. alkynyl, carbyl, 3-14, heterocyclyl, c6. a 14-aryl, and a 5-14 membered carbaryl, 4-membered heteroaryl, wherein each alkyl, q, heterocyclyl, aryl, and heteroaryl is unsubstituted. In several embodiments, Ri is unsubstituted In the examples, "unsubstituted Ci, mM°. In a few, instead of Cl-〗 〇 all-tooth alkyl. In several examples K is an unsubstituted C2_1Q thin group. r In the right-handed example, R1 is not a 2-1 〇 block group. In some implementations of the carbocyclic group. In the case of ruo., 纟 纟 in some real ", Ο R1 is unsubstituted 3-H-membered heterocyclic group. In the case of 卞 %, RI is an unexpressed 〇6-丨4 square group. In some embodiments, R is a non-peak Μ#heteroaryl group. (9) Case + '~ examples are selected from _-Meng Qing, ο·2 Rhyme „—·. 2, cans) 2, Na η) 3+χ' N (〇R, n sh, 75 201043620 -SR° ' -SSR° ' -C(=〇)R° . _c〇2H > -C02R° ' -0C(=0)R° ' -0C02R., -C(=0)N(Rn)2 _〇c(=〇)N(Rn)2, -NRnC(=0)R0, -NRnCO2R0, -NRnC(=〇)N(Rn)2, -C(=NRn)OR0, -〇C(=NRn R〇, _〇C(=NRn)〇R〇, _C(=NRn)N(Rn)2, -OC(=NRn)N(Rn)2 . -NRnC(=NRn)N(Rn)2 ' -NRnS02R° ' -S02N(Rn)2, -S02R0, _s〇2〇R0, -〇S02R0, -S(=0)R0, -C(=S)N(Rn)2, -C(=〇) SR°, -C(=S)SR〇, -SC(=S)SR0, -P(=0)2R° ' -P(=0)(R°)2 . .〇p(=〇)(R 〇)2 . -〇P(=〇)(〇r°)2 . CN6 alkyl, Cw all i alkyl, C3_1G carbocyclic group, 3·14 membered heterocyclic group, c6 14 aryl group and 5-14 member a heteroaryl group wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl group is substituted with hydrazine, 1, 2, 3, 4 or 5 Rp groups, respectively. In some embodiments, each of Rm is selected from the group consisting of fluorine (_F), bromine (-Br), gas (-C1), and iodine (-1), -CN, -N〇2, -S02H, -S03H, -OH, -OR., -ON(Rn)2, -N(Rn)2, -N(Rn)3+X_, -N(OR°)Rn, -SH, -SR°, -SSR°, - C (=0) R. , -C02H, -C02R. -0C(=0)R°, -OC02R0, -C(=0)N(Rn)2, -0C(=0)N(Rn)2, -NRnC(=0)R°, -NRnC02R. NRnC(=0)N(Rn)2, -C(=NRn)OR. , -OC(=NRn)R. , -OC(=NRn)OR. , -C(=NRn)N(Rn)2, -〇C(=NRn)N(Rn)2, -NRnC(=NRn)N(Rn)2, -NRn02R°, -S02N(Rn)2, _S02R 〇, -S020R0, -OS02R0, -S(=0)R0, -C(=S)N(Rn)2, -C(=0)SR〇, -C(=S)SR〇, -SC(= S) SR0, -P(=〇)2R0, -〇P(=〇)(R0)2, -0P(=0)(0R0)2, CBu6 alkyl, Ci_6 perhalogen, C3-10 Carbocyclyl, 3-14 membered heterocyclic, C6_14 aryl, 5-14 membered heteroaryl. 76 201043620 In several embodiments, the Rm is selected from the group consisting of fluorine (-F), bromine (-Br), chlorine (-C1), and iodine (-1), -nh2, -nh3+x-, _cn, -no2 , -S02CH3, -SO2CH2CH3' -SO2C5H9' S02iBu ' -S02NH2 > -S02N(CH3)2 > -C(=0)NHS02CH3, -C(=0)NHS02CH2CH3, -C(=0)NHS02C5H9, -C (=0) NHS02iBu, -C(=0)CH3, -C02H, -C02CH, -0C(=0)CH3, -0C02CH3, -C(=0)NH0H, -C(=0)NH2, -C( =0) NHCH3, -c(=o)n(ch3)2, -C(=0)NHCH2CH3, -c(=o)nhch2cf3, -C(=0)NH(CH2)1.6NH3+X ' -0C (0) NH2 '-NHC(=0)CH3 '-NHC(=0)OCH3, -NHC(=0)0tBu, -NHC(=0)NH2, -NHS02CH3, -CH3, -CH2CH3, -iPr, - nBu, -CF3, -OH, -OCH3 ' -OCF3 ' -OCH2CH3 ' -OCH2CF3 ' -OiPr > -OnBu > -CH2CH2C02Me, -CH2CH2C02H, -CH2CH2C02NH2, -c(=o)nhch2c(=o)och3, -C(=0)NHCH2C(=0)0H, and -c(=o)nhch2ch2oh.

The implementation of Rk, for example, the foregoing examples of Rk used herein are selected from _H, _〇H, -OR1, -N(Rk)2, {(=0)1^, -C(=0)N, respectively. Rk)2, -CO#, _S〇2Ri, -C(=NRk)Ri, -C(=NRk)〇Rj ^ -C(=NRk)N(Rk)2 > -S〇2N(Rk)2 >-SO#1, -S020Ri, -SORi, -C(=S)N(Rk)2, _C(=〇)SRi, -CdSRi, Cl.1 〇alkyl (eg aralkyl), c2_1 ( Alkenyl, Cm alkynyl, Cm carbocyclyl, 3-membered 4-membered heterocyclic, 丨4 aryl, and 5-14 aryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, The heterocyclic group, the aralkyl group, the aryl group, and the heteroaryl group are each substituted with 0, 1, 2, 3, 4 or 5 feet 1", respectively, 77 201043620 wherein Rj, Rk, Rm are as previously described herein. Defined. In several embodiments, each of Rk is selected from the group consisting of -Η, -(:(=0)111, -(3(=0)01^, -SO2R1, or (^-6 alkyl). In the examples, each of Rk is selected from -H or Cw alkyl, respectively. In some embodiments, each of Rk is selected from -H and -CH3, respectively. In some embodiments, each of Rk is separately Selected from -H. In several embodiments, each of Rk is selected from -CH3. The groups Ra, RlRc are as defined above, wherein Rd is a group -LZ, and Ra, Rb and Rc are each selected from - Η, CM0 alkyl and CM0 perhaloalkyl. In several embodiments, Ra, Rb, and Rc are each selected from -H, C -6 alkyl, and Cw perhaloalkyl, respectively. In several embodiments , Ra, Rb, and Rc are each selected from the group consisting of -Η, Cw alkyl, and CN3 perhaloalkyl. In some embodiments, 'Ra, Rb, and Rc are each selected from Η, _CH3, -CH2CH3, and -CF3. In several embodiments, Ra, Rb, and Rc are each selected from the group consisting of -Η, -CH3, and -CF3. In some embodiments, Ra and Rb are ruthenium and Re is selected from CN3 alkyl and C,-3 perhaloalkyl. In several embodiments, Ra and Rb are H& Rc is selected from -CH3 -CF3. In several embodiments, Ra and Rb are deuterium and Re is selected from -CH3. In several embodiments, Ra& Rb is deuterium and Rc is selected from -CF3. In several embodiments, Rb and Re The oxime and Ra are selected from the group consisting of C!_3 alkyl and Cw perhaloalkyl. In some embodiments, Rb and Rc are ruthenium and Ra is selected from -CH3 and -CF3. In several embodiments, "and! ^ In some embodiments, Rb and Rc are H&Ra is selected from -CF3. In several embodiments, Ra, Rb, and RCS are selected from H, - respectively. CH3 78 201043620 and -CF3. In several embodiments, each of Ra, Rb, and Re is selected from Η or -CH3, respectively. In some embodiments, Ra, Rb, and Re are Η. The group Rd is substantially as As defined above, in several embodiments, Rd is a group -LZ, wherein L is a covalent bond or a divalent Cy hydrocarbon group, wherein one, two or three methylene units of L are selectively and individually passed through one or Multiple oxygen, sulfur or nitrogen atom substitutions, and

The Z series is selected from a C6-10 aryl group, a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl group. The group L of Rd is substantially as defined above, and L is a covalent bond or a divalent Cw hydrocarbon group, wherein one, two or three of the fluorene groups of L are selectively and separately passed through one or more of oxygen and sulfur. Or nitrogen atom replacement. In several embodiments, L is a covalent bond. In several embodiments, L is a divalent Cw hydrocarbyl group wherein one, two or three methylene groups of L are selectively and separately passed through one or more oxygen (-〇-), sulfur (-S-) Or a nitrogen (eg -NR1-) atomic substitution. In several embodiments, L is a divalent Ci-6 hydrocarbon group wherein one, two or three methylene groups of L are selectively and separately substituted with one or more oxygen (-0-) atoms. In several embodiments of L, the divalent Ci-6 hydrocarbon group is an unsubstituted divalent Cu hydrocarbon group. In several embodiments, L is a divalent Cw hydrocarbyl group wherein one of the methylene units of L is selectively and separately substituted with an oxygen, sulfur or nitrogen atom. In several embodiments, L is a divalent (^-6 hydrocarbyl group wherein one methylene unit of L is selectively and separately substituted with one oxygen atom. In several embodiments 79 201043620 'L is divalent ¢^6 The hydrocarbyl group wherein the L-methylene unit is selectively and separately substituted with a sulfur atom. In several embodiments, L is a divalent A 6 hydrocarbyl group wherein L-methylene is mono-selective And in each of the embodiments, L is a divalent Q hydrocarbon group, wherein one of the fluorene groups of L is replaced by an oxygen, sulfur or nitrogen atom, for example [selected from oxygen (_ 〇_), sulfur (-S-) or nitrogen (eg -NR1-). In several embodiments, L is oxygen (_〇_). In several embodiments, L is sulfur (-S-). In several embodiments, L is oxygen (_〇_). In several embodiments, L is nitrogen (eg, -NR1-). In several embodiments, L is selected from _(c(R1〇Dm_, -( C(R%)m-0-(C(Ri2)2)n-, _(C(Rn)2)m-s_(c(Rl2)2)n-, or -((^(RUDm-NR^ -i^R12)2;^- The group consisting of m&n is 〇, 1, 2, 3, 4, 5 or 6 ' and R1., R"ARi2 From hydrazine, halogen or Ci.6 alkyl. In several embodiments, L is -(C(R10)2)m-. In several embodiments, L is selected from -CH2-, -CH2CH2-'-CH2CH2CH2 -ch2ch2ch2ch2-, -ch2ch2ch2ch2ch2_ and -CH2CH2CH2CH2CH2CH2-. In several embodiments, L is -(C(Rn)2)m-〇-(C(R12)2)n-. In several embodiments' L is selected from the group consisting of -〇_, -ch2o-, -OCH2-, -OCH2CH2-, -OCH2CH2-, -OCH2CH2CH2-, -ch2ch2ch2o-'-CH2OCH2CH2-, and -CH2CH2OCH2-. In several embodiments, 'L is - (C(Rn)2)mS-(C(R12)2)n-. In several embodiments, L is selected from the group consisting of -S-, -CH2S-, -SCH2-, -SCH2CH2-, 80 201043620-ch2ch2s- - sch2ch2ch2-, -ch2ch2ch2s-, -CH2SCH2CH2-, and -CH2CH2SCH2-. In several embodiments, L is -(CXRUDm-NRkCCXR12)^-. In several embodiments, L is selected from -NR1-, - CHzNR1-, -NI^CHz-, -NR^HjCHz- '-CH2CH2NR1- > -NR'CHaC^CHi- '-CH2CH2CH2NR1-, -CH2NR1CH2CH2-, and -CHzC^NR^CHr ' where R1 is selected from h , Cw alkyl or amine protecting group. In several embodiments, R1 is selected from H or Cm alkyl. In several embodiments, R1 is hydrogen. In several embodiments, R1 is _CH3. Examples in which the group Z of Rd is an aryl group are substantially as defined above, and in several embodiments, B is an octadecylaryl group. In several embodiments, Z is c6.14 aryl. In several embodiments, z is a C6_14 aryl group. In several embodiments, Z is a C6_!4 aryl group substituted with 0, 1, 2, 3, 4 or 5 R groups. In several embodiments, z is a C6 aryl (eg, phenyl) substituted with hydrazine, 1, 2, 3, 4, or 5 R groups. In several embodiments, Z is a C丨〇 aryl group (e.g., naphthyl) substituted with 0, 2, 3, 4, or 5 R15 groups. In several embodiments, Z is a stupid base. In several embodiments, z is phenyl substituted with 0, 2, 3 or 4 R15 groups. In several embodiments, z is phenyl substituted with 0, 1, 2 or 3 R15 groups. In some embodiments 'Z' is a phenyl group substituted with 0, 1 or 2 R15 groups. In several embodiments, z is phenyl substituted with 0 or 1 R15 group. In several embodiments, z is a disubstituted phenyl (i.e., substituted with 2 RM groups). In several embodiments, Z is a monosubstituted phenyl (ie, substituted with 1 R15 group). In several embodiments 81 201043620, Z is an unsubstituted phenyl group (i.e., substituted with one R15 group). In several embodiments, z is phenyl substituted with at least one ortho-R15 group. In the embodiment, Z is a phenyl group substituted with at least one meta-R15 group. In several embodiments, Z is phenyl substituted with at least one para-R15 group. In several embodiments, '2' is a substituted phenyl group substituted with an ortho-R15 group. In several embodiments, z is a substituted phenyl group substituted with a meta-R15 group. In several embodiments, z is a substituted phenyl group substituted with a para-R15 group. In several embodiments, 2 is a disubstituted phenyl group substituted with an ortho-R15 group and a meta-R15 group. In several embodiments, Z is a disubstituted phenyl group substituted with / ortho-R15 groups and one para-R15 group. In the embodiment, 2 is a disubstituted phenyl group substituted with a meta-R15 group and a para-R15 group. In several embodiments, Z is a disubstituted phenyl group substituted with two meta positions r5. In several embodiments, Z is a phenyl group of the formula:

(ii-a) wherein z is 〇, 1, 2, 3, 4 or 5, and R15 is as defined below and herein. In some embodiments 'z is 〇, 1, 2, 3 or 4. In several embodiments, z is 0, 1, 2 or 3. In some embodiments 'z is 〇, 1 or 2. In the embodiment, z is 〇 or 1. In several embodiments, z is 3. In some embodiments 'Z is a disubstituted phenyl group (i.e., wherein z is 2). In several embodiments 82 201043620, Z is a substituted phenyl group (i.e., wherein z is 1). In some embodiments, Z is an unsubstituted phenyl group (i.e., wherein z is 0). For example, in several embodiments, Z is a substituted or unsubstituted phenyl of any of the formula:

Wherein R15 is as defined below and herein. In several embodiments, Z is naphthyl. In some embodiments, Z is a naphthyl group of any of the formula:

(R15)z or

Where z is 0, 1, 2, 3, 4 or 5, and R15 is as defined below and herein. In several embodiments, z is 0, 1, 2, 3 or 4. In several embodiments, z is 0, 1, 2 or 3. In several embodiments, z is 0, 1, or 2. In some embodiments, z is 0 or 1. In several embodiments, Z is a trisubstituted naphthyl group (i.e., wherein z is 3). In several embodiments, Z is a disubstituted naphthyl group (i.e., wherein z is 2). In several embodiments, Z is a monosubstituted naphthyl group 83 201043620 (i.e., where z is 1). In several embodiments, Z is an unsubstituted naphthyl group (i.e., wherein Z is 0). For example, in several embodiments, Z is a substituted or unsubstituted 1-naphthyl group of any of the formula:

In some embodiments, Z is a substituted or unsubstituted 2-naphthyl group of any of the formula:

^rR15 R15^^ , where R15 is as defined below and here. 84 201043620 Examples wherein the base of Rd® or heteroaryl is substantially as defined above, and is heterocyclyl and 5-14 membered heteroaryl. U ' Ζ is selected from 3-14 members in several embodiments, 2 is 5 〈, and ζ is substituted by (^, ", heterozygous: base ^ several examples. 4 or 5 R15 groups substituted 5 - 10 member heteroaryl. In the right-hand embodiment, 'ζ is a 5.8-membered heteroaryl group substituted by m3. In the case of 4 R-based Ο ...... ... In the right-drying example, Ζ is the 经, 2, 3 or 4 R groups substituted by 5-6 member hetero and soil. In several embodiments, hydrazine is a (four) member heteroaryl substituted with 1, 2, 3, 4 or 5 槪 15 groups. Examples include, but are not limited to, squama, thiol and singular: salivary "more than saliva, ten-sitting, hetero-sitting, sputum, sigh, earth, three money H-based, red silk, four Silk, (4) group (eg, W-based, 3-fluorenyl, 4-fluorenyl), base (eg, 3-cyanoyl 4+ fluorenyl), Qianki (eg, 2_keki, heart-based, 5_) Shooting base), ^ well base, three ploughing base, four silk, ahji, ahji, 嗟 pingji&quot; 引木基, 啊基, 异0引县, 〇 卜 坐 benzotrisyl, benzene And phenyl, isophenyl (tetra) phenyl, W-based, benzo-hetero-based, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzopyrene Azyl, benzothiazolyl, benzisothiazolyl, benzothiadiazolyl, fluorenyl, fluorenyl, acridinyl, acridinyl, quinolyl, isoquinolinyl, porphyrin, quin Porphyrin, morphine, quinazolinyl, phenanthryl, dibenzofuranyl, oxazolyl, acridinyl, thiophenyl, phenylidene, and morphyl, of which The group is substituted with 〇, 1, 2, 3, 4 or 5 R15 groups. In several embodiments, Ζ is substituted by 〇, 1, 2 or 3 R,5 groups. 5 85 201043620 In the right-drying embodiment, z is selected from the group consisting of 吼 基, 吱 嗟, 嗟 基 味 味 味 味 ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° ° 唾 唾 唾 唾 唾 唾a di-salt, a <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; For the following formula 5 heteroaryl:

(»-d) wherein γ, γ2, γ3 and Y4 are respectively selected from CH, CR15, 〇, s, -N, or NR18, but at least one of the constraints γ1, γ2 'γ3 and γ4 is selected from Ο, S, -Ν or NR18, and the intermediate and Rl8 are as defined below and herein. In some embodiments of the above formula (11-d), Y1 is Ο, S, or NR18 and Y2, Y and Y are selected from CH, CR15 or N. In some embodiments of the above formula (ii_d), 'Y1 is 0, S, or NR} 8 and Y2, γ3, and Y4 are each selected from (3) or CR15. In some embodiments of the above formula (ii-d), γι is 〇, s, or cis, Υ3 is Ν and Υ2 and γ4 are selected from CH4CRi5, respectively. In some embodiments of the above formula (ii d), Y1 is S, Y3 is N and Y2 and Y4 is Ch or CR15. In some embodiments of the above formula (ii_d), Y丨 is S, Y3 is N, Y2 is CRM, and Υ4 is CH. In some embodiments of the above formula (ιι-d), γΐ is s and γ2, γ3 and γ4 are CH or CR15. In some embodiments of the above formula (ii-d), Υ2 is 〇, S, 4NR18 and γΐ, Υ3 and Υ4 are respectively selected from CH, CR15 or Ν. In some embodiments of the above formula (ii-d), Y2 is Ο, S, or NR18 and Y1, Y3, and Y4 are each selected from (^ or CR15. In several embodiments of the above formula (ϋ-d) , γ2 is 〇, s, or nr18, 86 201043620 Υ4 is Ν and Υ1 and γ3 are respectively selected from CH or CR15. In several embodiments, 'Z is any of the following formulas.

Ο where R15 and R18 are as defined below and herein, and 2 is 〇, 丨 or 2. z is 0, 1 or 2 and R15 and R18 are as defined below and herein. In a few realities

In the example, 'z is an unsubstituted 5 membered heteroaryl (i.e., 2 of which is hydrazine). In several embodiments, 'Z is a substituted 5-membered heteroaryl (e.g., wherein z is deuterium or 2). In some of the facts, Z is a 5-membered silk (also known as). In the right dry embodiment towel, Z is a two-substituted five-membered silk (i.e., two of them). In several embodiments, the lion, 1 or 2. In several embodiments, 2 is 〇 or 1. In several embodiments, 'z is a 6-membered heteroaryl group substituted with hydrazine, 1, 2, 3 or 4 Rh groups. In several embodiments, z is selected from the group consisting of ruthenium. Determining (for example, 2 is more specific than thiol 3 than 4, 比 比 荅 ( ( ( ( ( ( ( ( ( ( 例如 例如 例如 例如 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 a 6-membered heteroaryl group of a group consisting of 4-α-tense base, 5-σ dense base, cultivating base, three tillage, and four tillage, wherein the groups are 0, 1, 2, 3 or 4 R15 group substitutions. For example, in several embodiments, Re is a 6-membered heteroaryl group: w1-w2

Wherein W1, W2, W3, W4 and W5 are respectively selected from CH, CR15 or N, but the constraint condition is that at least one of W1, W2, W3, W4 and W5 is N, and wherein R15 is as follows Defined. In several embodiments, Z is pyridyl. In several embodiments, Z is pyridyl substituted with 0, 1, 2, 3 or 4 R15 groups. For example, in several embodiments, Z is a pyridyl group of the formula:

Where z is 0, 1, 2, 3 or 4, and R15 is as defined below and herein. In several embodiments, Z is an unsubstituted pyridyl group (ie, wherein z is 0). In several embodiments, Z is a substituted pyridyl group (eg, wherein z is 1, 2, 3, or 4). In several embodiments, Z is a monosubstituted pyridyl group (i.e., wherein z is 1). In several embodiments, Z is a disubstituted pyridyl group (ie, wherein z is 2). In several embodiments, Z is a trisubstituted pyridyl group (ie, wherein z is 3). In several embodiments, z is 0, 1, 2, or 3. In several embodiments, z is 0, 1, or 2. In several embodiments, z is 0 or 1. 88 201043620 In several embodiments, hydrazine is 2-pyridyl, for example having the formula (ii-e) wherein W1 is N and W2, W3, W4 and W5 are CH or CR15, respectively. In some embodiments, Z is 3-pyridyl, for example having the formula (ii-e) wherein W3 'W4 and W5 are CH or CRb, respectively. In some embodiments, 2 is a 4_pyridyl group, for example, having the formula (ii-e) wherein W3 is N and W, and w2, w4, and w5 are CH or CR15, respectively. In some embodiments, Re is a substituted or unsubstituted 2-pyridyl group of any of the formula:

N

R15 Ν· 'R15 R15 R15

N

R15 N

R15 R15. R15 r15

R15

R15 R15.

Or R15, where R15 is as defined below and herein. In some embodiments, Z is a substituted 3-substituted 3- in the formula below.唆基基: one

Wherein R15 is as defined below and herein. Substituted or not in some embodiments, z is any of the following substituted 4-pyridyl groups: 201043620

Wherein R15 is as defined below and herein. In several embodiments, Z is a sorghum base. In several embodiments, z is a morphine group substituted with 0, 1, 2 or 3 R15 groups. For example, in several embodiments, Z is of the formula 嗒. Well base:

Where z is 0, 1, 2 or 3, and R15 is as defined below and herein. In some embodiments, Z is an unsubstituted morphine (i.e., wherein z is 〇). In several embodiments, Z is a substituted mashing base (e.g., wherein z is 1, 2 or 3). In some embodiments, Z is a monosubstituted morphine group (ie, wherein 2 is hydrazine. In several embodiments, Z is a disubstituted hydrazine cultivating group (ie, wherein 2 is 2). In the example, Z is a trisubstituted argon (i.e., where 2 is 3). In several embodiments, z is 0, 1, 2, or 3. In several embodiments, 'z is 0, 1, or 2. In some embodiments, z is 〇 or 1. In some embodiments, Z is a 3-merry group, for example, having the formula (11_e) wherein W1 and W2 and N and W3, W4 and W5 are CH or CR15, respectively. In some embodiments, Z is a 4-plowing base, for example having the formula (Ue) wherein trade 2 and arm 3 are N and W1, W4 and W5 are CH or CRh, respectively. In several embodiments, Z is lower Substituted or unsubstituted 3-嗒 speaking group of any of the formula: 90 201043620

N % where R15 is as defined below and herein. In some embodiments, Z is a substituted or unsubstituted 4-indolescent base of any of the formula:

Wherein R15 is as defined below and herein. In several embodiments, Z is pyrimidinyl. In several embodiments, Z is pyrimidinyl substituted with 0, 1, 2 or 3 R15 groups. For example, in several embodiments, Z is a pyrimidinyl group of the formula:

〇 where Z is 0, 1, 2 or 3, and R15 is as defined below and herein. In several embodiments, Z is an unsubstituted pyrimidinyl group (i.e., wherein z is 0). In several embodiments, Z is a substituted pyrimidinyl (e.g., wherein z is 2 or 3). In several embodiments, Z is a monosubstituted pyrimidinyl group (ie, wherein z is 1). In several embodiments, Z is a disubstituted oxime (i.e., wherein z is 2). In several embodiments, Z is a trisubstituted pyrimidinyl group (ie, wherein z is 3). In several embodiments, z is 0, 1, 2, or 3. In several embodiments, z is 0, 1, or 2. In several embodiments, z is 0 or 1. In several embodiments, Z is a 2-pyrimidinyl group, for example, having the formula (ii-e) wherein 91 201043620

Wi# is, and WjW4 is (3) or ^^ respectively. In several embodiments, 2 is 4_° dense. The base group has, for example, the formula (ii-e) wherein W1 and W3 are N and w, w and W are CH or CR15, respectively. In several embodiments, 2 is a 5-pyrimidinyl group, for example, having the formula (ii-e) wherein W2 and w4 are N&amp;wl, w3&amp;w5 are CH or CR15, respectively. In several embodiments, 'Z' is a 2-pyrimidinyl group of any of the formula:

Wherein R15 is as defined below and herein. In several embodiments, 'Re is the formula of the formula in the following formula:

Wherein R15 is as defined below and herein. In some embodiments, Z is a lower-style towel.

Wherein R15 is as defined below and herein. In the right-hand embodiment, Z is a pyridinyl group. In several embodiments, 2 is a 吼B well base substituted with 0, 1, 2, or 3 R15 groups. For example, in several embodiments, 'Z is a formula η than a base: C] (R15)z 92 201043620 wherein Z is 0, 1, 2 or 3, and R15 is as defined below and herein. In some embodiments, Z is an unsubstituted oxime (i.e., where z is 0). In several embodiments, Z is a substituted pyridinyl group (e.g., wherein z is 1, 2 or 3). In several embodiments, Z is a substituted pyridinyl (ie, wherein z is 1). In several embodiments, Z is a disubstituted pyridinyl (ie, wherein z is 2). In several embodiments, Z is a three-substituted "roughing base (ie, where z is 3). In several embodiments, z is 0, 1, 2, or 3. In several embodiments, z is 0, 1, or 2. In several embodiments, z is 0 or 1. In several embodiments, Z is pyridyl of any of the formula:

Wherein R15 is as defined below and herein. In several embodiments, Z is a three tillage base. In several embodiments, Z is a triplet substituted with 0, 1 or 2 R15 groups. For example, in several embodiments, Z is a three-sigma well base of the following formula:

Where ζ is 0, 1 or 2, and κ 1 shows: “〇佼文 and definition here. In some embodiments, Ζ is an unsubstituted ratio (i.e., where ζ is 0). In some embodiments, hydrazine is substituted. A morphine group (for example, wherein ζ is 1 or 2). In some embodiments, Ζ is a substituted base (i.e., wherein ζ is 1). In some embodiments, Ζ is a disubstituted ratio (i.e., wherein ζ is 2). In several embodiments, ζ is 0, 1, or 2. In several embodiments, ζ is 0 or 1. 93 201043620 In several embodiments, z is a substituted or unsubstituted three tillage base of any of the formula:

Wherein R15 is as defined below and herein. In several embodiments, Z is a four tillage. In several embodiments, Z is a four-speaking group substituted with 0 or 1 R15 group. For example, in several embodiments, Z is a four-sigma well base of the following formula.

Where ζ is 0 or 1, and R15 is as defined below and herein. In some embodiments, hydrazine is an unsubstituted pyridinyl group (i.e., wherein ζ is 0). In some embodiments, the oxime is a substituted pyridinyl group (e.g., wherein ζ is 1). In several embodiments, ζ is 0 or 1. In some embodiments, Ζ is the fourth plough of any of the following formulas: Ν I Ν

Wherein R15 is as defined below and herein. In several embodiments, the oxime is a 9 membered heteroaryl (e.g., 5,6-bicyclic heteroaryl). In several embodiments, hydrazine is a 5,6-bicyclic heteroaryl substituted with 0, 1, 2, 3, 4 or 5 R15 groups. In several embodiments, the oxime is selected from the group consisting of fluorenyl, isodecyl, oxazolyl, benzotriazolyl, benzothienyl, isobenzothiophene 94 201043620 pheno, benzofuranyl, benzo Isofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzoisoindole, benzoxyl And a 5,6-bicyclic heteroaryl group of the sulfhydryl group, wherein the group is substituted with hydrazine, 1, 2, 3, 4 or 5 R15 groups. For example, in several embodiments, Z is a 5,6-bicyclic heteroaryl group of the formula:

Wherein Y5, Y6, γ7, γ9, γ10, γ11 and γ12 are c, CH, CR15, Ο, S, -Ν or NR18, respectively, and Υ13 is C or Ν, but the limitation is at least Υ5, Υ6, Υ7 One is selected from the group consisting of hydrazine, S, -Ν, or NR18, and wherein R15 and R18 are as defined herein. In some embodiments, Z is a 5,6-bicyclic heteroaryl group of formula (ii-f), wherein Y5 is selected from the group consisting of ruthenium, S, or NR18, Y13 is C, and Υ6, Υ7, Υ9, Y10, Υ11 and Υ12 are C, CH, or CR15, respectively. For example, in several embodiments, Z is a 5,6-bicyclic heteroaryl group of the formula: (R1sk (R15)z

(R15)z

Where z is 0, 1, 2, 3, 4 or 5 and R15 and R18 are as defined below and herein. In several embodiments, Z is an unsubstituted 5,6-bicyclic heteroaryl (i.e., wherein z is 0). In several embodiments, Z is a substituted 5,6-bicyclic heteroaryl (e.g., wherein z is 1, 2, 3, 4 or 5). In several embodiments, Z is a 5,6-bicyclic heteroaryl which is substituted by 95 201043620 (ie, wherein 2 is fluorene. In several embodiments, Z is a substituted 1-6-cycloheteroaryl ( That is, where z is 2) ^ In several embodiments, Z is a trisubstituted 5,6•bicyclic heteroaryl (ie, wherein B is 3). In several embodiments, 'z is 0, 2 Or 3. In several embodiments, z is 0, 1 or 2. In several embodiments, 2 is 〇 or in several embodiments, Z is 5,6·bicyclic heteroaryl, wherein γ5 is selected Ο, S, or NR18; Y7 is N; Y&quot; is c; γ6 is c, (3) or (3), or N, and γ9, Y1G, Y11, and Y12 are respectively C, CH, or CRl5. For example, in several implementations In the example, 'z is a 5,6-bicyclic heteroaryl group of the formula:

Where z is 0, 1, 2, 3, 4 or 5 and R15 and R18 are as defined below and herein. In several embodiments, Z is an unsubstituted 5,6-bicyclic heteroaryl (i.e., wherein z is 0). In several embodiments, z is a substituted 5,6-bicyclic heteroaryl (e.g., wherein z is 1, 2, 3, 4, or 5). In several embodiments, z is a substituted 5,6-bicyclic heteroaryl (i.e., wherein z is 1). In several embodiments, Z is a disubstituted 5,6-bicyclic heteroaryl (i.e., wherein 2 is 2). In the examples, Z is a trisubstituted 5,6-bicyclic heteroaryl (i.e., wherein z is 3). In some embodiments 'z is 〇, 1, 2 or 3. In several embodiments, z is 0, 1, or 2. In several embodiments, z is 0 or 1. In some embodiments, Z is a 5,6-bicyclic heteroaryl group, wherein Y5 is NRk, S or Ο; Y12 is N; Y13 is c; and Y6, γ7 'Y9, γ10, and γ11 are C, CH, respectively. , or CR15. For example, in several embodiments, z is the following formula: 6 6-bicyclic heteroaryl: 96 201043620

(R15)z

Where 2 is 〇, 1, 2, 3, 4 or mRi^Ri8 is as defined below and herein. In several embodiments, 'Z' is an unsubstituted 5,6-bicyclic heteroaryl (i.e., wherein z is deuterium). In the 'dry' embodiment, Z is a substituted 5,6-bicyclic heteroaryl (e.g., wherein z is 1 '2, 3, 4 or 5). In several embodiments, z is a monosubstituted 5,6-bicyclic heteroaryl (ie, wherein 2 is 1}. In several embodiments, Z is a disubstituted 5,6-bicyclic heteroaryl. The base (i.e., wherein z is 2). In several embodiments, Z is a trisubstituted 5,6-bicyclic heteroaryl (i.e., wherein the redundancy is 3). In several embodiments, 'z is O' I'2 or 3. In several embodiments, z is 0, 1 or 2. In several embodiments, redundancy occurs. In several embodiments, Z is a 5,6-bicyclic heteroaryl, wherein γ7 Is 〇, s or NRk; Υ丨2 is Ν; Υ丨3 is c; and 丫5, γ6, γ9, and γπ are respectively C, CH, or CR15. For example, in the work pull, 丄1 夕 J For example, in the right-hand embodiment, ζ is the following formula 5,6-bicyclic heteroaryl:

Ding Yushuang; U. , "^^ and ruler and ^ are as defined hereinafter and herein. In several embodiments, ζ is unsubstituted 5, ie, wherein, in some embodiments, ζ is substituted 5,6_ Bicyclic hetero (aryl__^'2, 3, 4 or 5). In several embodiments, the 5,6-% heteroaryl (ie, hydrazine) of the second plant is taken. In several embodiments 97 201043620 Wherein Z is a disubstituted 5,6-bicyclic heteroaryl (ie, wherein z is 2). In several embodiments, Z is a trisubstituted 5,6-bicyclic heteroaryl (ie, Wherein 2 is 3). In several embodiments, 2 is 〇, 1, 2 or 3. In several embodiments, z is 0, 1 or 2. In several embodiments, z is 0 or 1. In the examples, 'Z is a 5,6-bicyclic heteroaryl group, wherein γ5 is selected from Ο, S or NRk; Y13 is N; and Y6, Y7, Y8, γ9 and γΐα are respectively 〇, CH, or CR15. For example, 'in several embodiments, Z is a 5,6-bicyclic heteroaryl group of the formula:

Where z is 0, 1, 2, 3, 4 or 5 and R15 and R18 are as defined below and herein. In some embodiments 'Z is an unsubstituted 5,6-bicyclic heteroaryl (i.e., wherein z is 0). In several embodiments, Z is a substituted 5,6-bicyclic heteroaryl (e.g., wherein z is 1, 2, 3, 4 or 5). In several embodiments, z is a monosubstituted 5,6-bicyclic heteroaryl (ie, wherein 2 is 1}. In several embodiments, Z is a disubstituted 5,6-bicyclic heteroaryl. The base (i.e., where 2 is 2). In several embodiments, Z is a trisubstituted 5,6-bicyclic heteroaryl (i.e., wherein the redundancy is 3). In several embodiments, z is 〇, }, 2 or 3. In several embodiments, z is 0, 1 or 2. In several embodiments, in several embodiments, Z is a 10-membered heteroaryl (eg, 6,6-bicycloheteroaryl) In some embodiments, Z is a 6,6-bicyclic heteroaryl substituted with hydrazine, br. 2, 3, 4 or 5 r15 groups. In several embodiments, 2 is selected from acridine. Base, bite base, material base, heterogeneous base, material base, cut storage, blowing base

98 201043620 2, 3, 4 or 5 R15 base substitutions. For example, in several embodiments, Z is a 6,6-bicyclic heteroaryl group of the formula:

(ii-g)

Wherein W6, W7, W8, W9, W10, W11, W12 and W13 are respectively selected from C, CH, CR15 or N, but the restrictions are at least W6, W7, W8, W9, W1G, W11, W12 and W13 One is N, and the R15 thereof is as defined below and herein. In some embodiments, Z is a quinolinyl group; for example, having the formula (ii-g) wherein W9 is N and W6, W7, W8, W9, W1G, W11, W12, and W13 are C, CH, or CR15, respectively. In some embodiments, Z is a quinolinyl group of the formula: ^(Ri5)"吖s&gt;

1 V where z is 0, 1, 2, 3, 4 or 5 and R15 is as defined below and herein. In several embodiments, Z is an unsubstituted quinolyl group (ie, wherein z is 0). In several embodiments, Z is a substituted quinolyl group (eg, wherein z is 1, 2, 3, 4, or 5). In several embodiments, Z is a monosubstituted quinolyl group (i.e., wherein z is 1). In several embodiments, Z is a disubstituted quinolinyl group (i.e., wherein z is 2). In several embodiments, Z is a trisubstituted quinolinyl group (i.e., wherein z is 3). In several embodiments, z is 0, 1, 2, or 3. In several embodiments, z is 0, 1, or 2. In several embodiments, z is 0 or 1. In some embodiments, Z is an isoquinolyl group; for example, having the formula (ii-g) wherein W8 is N and W6, W7, W9, W10, W11, W12, and W13 are respectively C, CH '99 201043620 or CR15 〇 For example, in several embodiments, Z is an isoquinolinyl group of the formula:

r^&gt;(Rl5)z or wherein Z is 0, 1, 2, 3, 4 or 5 and R15 is as defined below and herein. In several embodiments, Z is an unsubstituted isoquinolinyl group (i.e., wherein z is hydrazine). In some embodiments, Z is a substituted isoquinolyl group (eg, wherein z is a b, 2, 3, 4, or 5). In several embodiments, Z is a monosubstituted isoquinolyl group (ie, wherein z is 1). In several embodiments, Z is a disubstituted isoquinolinyl group (i.e., wherein z is 2). In several embodiments, Z is a trisubstituted isoquinolyl group (i.e., wherein z is 3). In several embodiments, z is 0, 1, 2, or 3. In several embodiments, z is 0, 1, or 2. In several embodiments, z is 0 or 1. In some embodiments, Z is a quinoxaline group; for example, having the formula (ii-g) wherein W6 and W9 are N and W7, W8, W1G, W11, W12 and W13 are C, CH, or CR15, respectively. For example, in several embodiments, Z is a quinoxaline group of the formula:

Where z is 0, 1, 2, 3, 4 or 5 and R15 is as defined below and herein. In several embodiments, Z is an unsubstituted quinoxaline group (i.e., wherein z is 0). In some embodiments, Z is a substituted quinoxalinyl group (eg, wherein z is 1, 2, 3, 4, or 5). In several embodiments, Z is a monosubstituted quinoxaline group (also That is, where z is 1). In several embodiments, Z is a disubstituted quinoxaline group (i.e., wherein z is 2). In several embodiments, Z is a trisubstituted quinoxaline group (i.e., wherein z is 3). In several embodiments, z is 0, 1, 2, or 3. In several embodiments, z is 0, 1, or 2. In several embodiments, z is 0 or 1. 100 201043620 In several embodiments, Z is a 3-14 membered heterocyclyl. In several embodiments, Z is a 3-14 member heterocyclic ring substituted with 0, 2, 3, 4 or 5 Rl5 groups. In several embodiments, Z is 5 oxacyclic heterocyclic groups substituted by hydrazine, i, 2, 3, 4 or 5 thereof. In several embodiments, z is a 5-8 membered heterocyclyl substituted with i3, 4 or 5 gamma groups. In several embodiments, z is a 5-6 membered heterocyclyl substituted with hydrazine, bromo 2, 3, 4 or 5 R15 groups. In the examples, Z is a 9_1〇 heterocyclic group substituted with 〇, 2', 3, 4 or 5 Rl5 groups. Examples of heterocyclic group Z include, but are not limited to, fluorenyl, fluorenyl, thioxyl, decyl, thiol, thiol, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophene , pyrrolidinyl, dihydropyrrolyl, pyrrolyl. _2,5-dione, didecyl, fluorenyl, dithianyl, triazolinyl, 0-oxazolyl, thiazepine Oxazolinyl, piperidinyl, tetrahydropyranyl, dihydropyridyl, thio&quot; sulphate, piperidinyl, porphyrinyl, dithia. Sylylene, diterpene beta sulphate, dimorphyl beta sulphate, fluorenyl, fluorenyl, thiophenyl, fluorenyl, fluorenyl, fluorinyl, porphyrin, isoindolyl , dihydrobenzofuranyl, dihydrobenzothiophenyl, tetrahydrobenzothiophenyl, tetrahydrobenzofuranyl, tetrahydroindenyl, tetrahydroquinolyl, tetrahydroisoquinolinyl, decahydro Quinolinyl, decahydroisoquinolinyl, octahydroguanidine, octahydroisophthalic acid, decahydroacridinyl, decahydro-indole-acridinyl, octahydropyrrolo[3,2_b]pyrrole, Porphyrin, quinone, naphthoquinone, guanidinium, sulfhydryl, 1H_benzo[^,4]dioxin, 1,4,5,7-tetrahydroper M-[3,4-sec-r-yl, 5,6-dihydro-4H-indolo[3,2-b]pyrrolyl, 6,7-dihydro-5H-furo[3,2-b , n-butyl, 5,7-dihydro-4H-thieno[2,3-c]piperidyl, 2,3-dihydro-1H-pyrrolo[2,3-b] 101 201043620 pyridyl, 2,3-dihydrofuro[2,3_b]pyridyl, 4,5,6,7 tetrahydropyrrolo[2,3-b]pyridinyl, 4,5,6,7-tetrahydrofuran [3, 2-c]pyridyl, and 4,5,6,7-tetrahydrothieno P,2-b]pyridyl, 1,2,3,4-tetrahydroindole, 6• aridinyl, Wherein such groups are substituted with hydrazine, i, 2, 3, or "solid scale" 5 groups. In several embodiments, Z is a 6 membered heterocyclic group. In several embodiments, z is 0, 2, 3, 4 or 5 R15-substituted 6-membered heterocyclic groups. In several embodiments, Z is selected from the group consisting of piperidinyl, tetrahydropyranyl, dihydropyridyl, thio; a 6-membered heterocyclic group of piperidinyl, porphyrinyl, dithiazinyl, dioxin, and trimorphinyl wherein the groups are 〇, 1, 2, 3, 4 Or 5 feet] 5 base substitution. For example, in several embodiments, hydrazine is a heterocyclic group of the formula 6: a|-W19 W16 w^-w17 (ii-h) wherein w14, w15, w16, W17 and W18 are respectively selected from Ch2, CHR15, - C(R15)2 ' -NR18, 〇 or s, and W19 are N, CH, CR15, but the constraints are w14, w丨5, w, 6, W17, W, 8 and w丨9 to the first one N, -NR18, o or s, and R5 and r18 thereof are as defined below and herein. In several embodiments, z is piperidinyl. In several embodiments, z is a piperidinyl group substituted with 0, 1, 2, 3, 4 or 5 R15 groups, for example having the formula:

102 201043620 where Z is 0, 1, 2, 3, 4 or 5 and R15 and R18 are as defined below and herein. In several embodiments, Z is an unsubstituted piperidinyl group (ie, wherein z is 0). In several embodiments, Z is substituted piperidinyl (i.e., wherein z is 2, 3, 4 or 5). In several embodiments, Z is a substituted π base (i.e., wherein ζ is 1). In several embodiments, Ζ is a disubstituted piperidinyl group (i.e., wherein ζ is 2). In several embodiments, hydrazine is a trisubstituted piperidinyl group (i.e., wherein hydrazine is 3). In several embodiments, ζ is 0, 1, 2, or 3. In the examples, ζ is 0, 1, or 2. In some embodiments, 'ζ is 〇 or 1 °. In several embodiments, Ζ is 1-°辰咬基', for example, has the formula (ii_h) 'where W19 is N and W14, W15, W16, W17, and W18 are respectively Selected from CH2, CHR15, -C(R15)2. In certain embodiments, Z is 2-piperidinyl', for example, having the formula (ii-h) wherein W14 is NR18; W15, W16, W17, and W18 are CHR15, -C(R15)2 or CH2, respectively; and W19 is CH or CR15. In some embodiments, Z is 3-piperidinyl, for example having the formula (ii-h) wherein W15 is NR18; W14, W16, W17 and W18 are CHR15, -C(R15)2 or CH2, respectively; and W19 is CH or CR15. In certain embodiments, Z is 4-piperidinyl, for example, having the formula (ii-h) wherein W16 is NR18; W14, W15, W17, and W18 are CHR15, -C(R15)2 or CH2, respectively; and W19 is CH or CR15. In several embodiments, Z is a piperene. In several embodiments, Z is a piperidinyl substituted with 0, 1, 2, 3 or 4 R15 groups, for example having the formula:

, R1\ or where x is 〇, 1, 2, 3, 4 or 5 and R15 and R18 are as defined below and here 103 201043620. In several embodiments, Z is an unsubstituted alpha swell (i.e., where z is zero). In some embodiments, Z is a substituted 11 bottom a well base (ie, wherein z is a b, 2, 3, 4 or 5). In some embodiments, the oxime is a substituted thiophene thiol (also That is, ζ is 1). In several embodiments, hydrazine is a disubstituted piperidinyl (i.e., wherein ζ is 2). In several embodiments, the oxime is a trisubstituted piperage (i.e., wherein ζ is 3). In some embodiments 'ζ is 0, 1, 2 or 3. In the examples, ζ is 0, 1, or 2. In several embodiments, ζ is 〇 or 1. In some embodiments, Ζ is a π bottom D well base, for example, having the formula (ii-h), wherein W19 is N, W16 is NR18, and W14, W15, W16, W17, and W18 are CHR15, -C(R15), respectively. 2, or CH2. In some embodiments, Z is a piperene group, wherein W19 is CH or CR15, W14 and W17 are NR18 and W15, W16, and W18 are CHR15, -C(R15)2 or CH2, respectively. In several embodiments, 'Z' is a sulphate substituted with 0, 1, 2, 3 or 4 R15 groups, for example having the formula:

Where ζ is 0, 1, 2, 3, 4 or 5 and R15 and R18 are as defined below and herein. In several embodiments, Z is an unsubstituted morpholinyl group (i.e., wherein ζ is 0). In several embodiments, Z is a substituted morpholinyl group (i.e., wherein hydrazine is 1, 2, 3, 4 or 5). In some embodiments, Z is a substituted aryl group (i.e., wherein ζ is 1). In several embodiments, Z is a disubstituted morpholinyl group (i.e., wherein ζ is 2). In some embodiments, Z is a trisubstituted morpholinyl group (ie, wherein ζ is 3^ in several embodiments, 2 is 〇, 1, 2, or 3. In some embodiments, ζ is 0, 1 Or 2. In some embodiments '2 is 〇 or 1. 104 201043620 In several embodiments, Z is a formula (ii-h) porphyrin group wherein W19 is N, W16 is Ο and W14, W15, W16 and W17 Each is selected from the group consisting of CH2, CHR15, and -C(R15) 2. In some embodiments, Z is a porphyrin group wherein W19 is CH or CR15, and W14 and W17 are selected from ruthenium and NR18, respectively, and W15, W16, and W18. Respectively CHR15, -C(R15)2 or CH2. In several embodiments, Z is a diterpene alpha mountain. In several embodiments, z is replaced by 0, 1, 2, 3 or 4 R15 groups. The second alpha base, for example

Where ζ is 0, 1, 2, 3, 4 or 5 and R15 is as defined below and herein. In some embodiments, Ζ is an unsubstituted 噚〇 mountain base (ie, where ζ is 0). In some embodiments, hydrazine is a substituted fluorenyl group (i.e., wherein hydrazine is 1, 2, 3, 4 or 5). In some embodiments, 'Ζ is a substituted 〇咢0 mountain base (i.e., where ζ is 1). In some embodiments, hydrazine is a disubstituted fluorenyl group (i.e., wherein Ζ is 2). In several embodiments, hydrazine is a trisubstituted diterpene. Mountain base (that is, where the ζ is 3). In several embodiments, ζ is 0, 1, 2, or 3. In some embodiments, ζ is 0, 1, or 2. In several embodiments, ζ is 0 or 1. In some embodiments, Ζ is a fluorenyl group, for example, having the formula (ii-h), wherein W14 and W17 are Ο and W15, W16 and W18 are CHR15, -C(R15)2 or CH2, respectively; and W19 is CH or CR15. In some embodiments, Z is a Erqikoushan base, wherein W19 is CH or CR15, W14 and W16 are respectively selected from ruthenium, and W15, W17 and W18 are respectively CHR15, -(:(1115)2 or 012. In some embodiments, Z is a 噚 mountain base wherein W19 is CH or CR15, and W15 and W17 are respectively selected from 105 201043620 〇 'and w' is CHR 丨 5, Na, 5) 2 or called. In several embodiments, Z is a C3_IQ carbocyclic group. In several embodiments, z is C31 substituted with 0, i, 2, 3, 4 or 5 Rl5 groups. Carbocyclic group. In several embodiments, Z is a carbocyclic group substituted with 5, 3, 4 or 5, 5 substituents. In several embodiments, z is a c5.6 carbocyclic group substituted with a small 2, 3 or R15 group. In some cases, z is a (1, 9, 4 or 5) substituted with a :115 group (: 9_1() carbocyclic group. In the embodiment, 1^ and 1^ are bonded (fused) substantially as In some embodiments, Ra&amp;Rd is joined to form c3]. Carbocyclyl or 3-14 membered heterocyclic fused ring, and RbARe are selected from _H, CM0 alkyl &amp; Cm〇, respectively. All of the alkenyl groups. In some embodiments, Rb and Re are each selected from the group consisting of _H, cardinyl, and C^6 perhaloalkyl. In several embodiments, each Rb&amp;RC is selected from - H, Cw alkyl, and Ci 3 all-alkyl. In some embodiments, each of Rb and R is selected from the group consisting of _H, Ci, and a hospital base. In some embodiments, 'Rb and RC are respectively Is selected from the group consisting of _H, _CH3, and _CF3. In some embodiments, each of Rb and Re is selected from the group consisting of "in some embodiments" Rb and r are each selected from the group consisting of HlCF3. In several embodiments, Rb and Rc are both -H. In several embodiments, r#Rd is bonded to form a heterocarbyl group or a 5-7 membered heterocyclic group. In some solid wipes, R%Rd is combined to form C5 of the following formula. 7 carbocyclic or 5-7 membered heterocyclic fused ring: 106 20104362 0

! I

Sc ^22 (»-j) where w20, w21, w22 and W23 are respectively ch2, chr15, _c(r15)2 or service 18, Rl, Rl8 are as defined below and 8 is 0 'W2, and The dotted line indicates that the ring is fused. In some embodiments, ^ is joined to form a c5.7 carbocyclic fused ring. For example, in several embodiments of the formula (ιι-j), w2〇, w2, w22, and W23, respectively, are CH2. Examples of CHR or C(R15)2:: and "c5 7 carbocyclic ring which can be joined to form include, but are not limited to, cyclopentyl, cyclohexyl and cycloheptyl, wherein the group such as ' 0 ' 1, 2, 3, 4 or 5 R15 groups are substituted. In several embodiments, Ra is bonded to Rd to form a 5-7 membered heterocyclyl fused ring. For example, in some embodiments of the formula (ii-j), w2 (^NRi8, and W22 and W23 are respectively (Ή!, CHRi5 or c(Ri5)2. In some embodiments of the formula (called) , W, NRl8, and w20, W22, and W23 are CH2, CHR15, or C(R15)2, respectively. In some embodiments of formula (ii_j), W22 is NR18, and W20, W21, and W23 are CH2, CHR15, or Examples of C(R15)2. Ra&amp;Rd can be joined to form a 5-7 membered heterocyclic group including, but not limited to, pyrrolidinyl, pyrazolidinyl 'imidazolidinyl, piperidinyl, piperidinyl and hydrazine a group wherein the groups are substituted with 0, 1, 2, 3, 4 or 5 R15 groups. In several embodiments, wherein 8 is 0, Ra is bonded to Rd to form a cs carbocyclic group of the formula Or a 5-membered heterocyclic fused ring: 107 201043620

Wherein W20, W21 and W22 are respectively CH2, CHR15, -C(R15)2 or NR18, R15 and R18 are as defined hereinafter and herein, and the dotted line indicates ring fused. In several embodiments of formula (ii-k), Ra is "joined to form a C5 carbocyclic fused ring (ie, cyclopentyl) wherein, for example, W2Q, W21, and W22 are CH2, CHR15, -C(R15), respectively. 2. In several embodiments of formula (ii-k), Ra is bonded to Rd to form a 5-membered heterocyclic fused ring (eg, pyrrolidinyl), wherein W21 is NR18, and W2G, W22, and W23 are respectively CH2. CHR15, -C(R15)2. In several embodiments of formula (ii-k), ^ and !^ are joined to form a 5-membered heterocyclic fused ring (e.g., pyrrolidinyl), wherein W20 is NR18, and W21 , W22 and W23 are CH2, CHR15, -C(R15)2, respectively. In several embodiments, wherein S is 1, Ra is "fused to form a C6 carbocyclic group or a 6-membered heterocyclic ring fused ring of the formula: :

Wherein W20, W21, W22 and W23 are respectively CH2, CHR15, -C(R15)2 or NR18, R15 and R18 are as defined hereinafter and herein, and the dotted line indicates that the ring is fused. In several embodiments of formula (ii-m), Ra is fused with a fused ring (i.e., cyclohexyl) formed by bonding to form a C6 carbocyclic group 108 201043620, for example. , w21, w22 and w23 are CH2, CHR15 and -C(R15)2, respectively. In the right-handed embodiment of formula (11 m), the combination of Ra and 6 forms a 6-membered heterocyclic fused ring (for example, a base), wherein f is, and ff and W are CH2, CHR And c(Rl5)2 in some embodiments of formula (1)-m) wherein R and R are 幵7 into a 6-membered heterocyclic fused ring (eg, a tether base), wherein W, NR' and W' w22 and W23 are Remuneration, CHR15, _c(Ri5)2.

In the case of the right scallop, where 8 is 2, Ra and the combination form a C7 carbocyclic group or a 7-membered heterocyclic group in the following formula:

W22

W23

Wherein W, W1, W22 and W23 are respectively ch2, CHR15, _C(R15)2 or NR18, R15 and R8 are as defined hereinafter and herein, and the dotted line indicates ring fused. In several embodiments of the formula (11_n), Ra is bonded to Rd to form a (:7 carbocyclic fused ring (i.e., cycloheptyl) wherein, for example, w2〇, w2i, w22, and w23 are CH2, CHR丨5, respectively. -C(R丨5) 2. In the hard drying example of formula (11_n), Ra is bonded to Rd to form a 7-membered heterocyclic fused ring (eg, fluorenyl), wherein W21 is NR18, and W20, W22 and W23 are CH2, CHR15, _C(R15)2, respectively. In several embodiments of formula (ii n), Ra and Rd are joined to form a 7-membered heterocyclic fused ring (e.g., fluorenyl), wherein w22 is NR18 ' and W2°, W21 and W23 are respectively Ch2, CHR15, c(Ri5)2. 109 201043620 Embodiments wherein 1^ and 1^ are joined (spiro-fused) substantially as defined above, in several embodiments, : and "joining to form a C3_1G carbocyclic group or a 3-14 membered heterocyclyl spiro-fused ring, and Ra &amp; Rb are selected from the group consisting of -H, CM0 alkyl and Cmo perhaloalkyl, respectively. In some embodiments , Ra and # are each selected from the group consisting of -H, Cw alkyl, and Cm perhaloalkyl. In some embodiments, Ra and Rb are each selected from -H, Cw alkyl, and Cm perhaloalkyl, respectively. In several embodiments, Ra and ... are each selected from - Η, q alkyl, and (^ perhaloalkyl. In some embodiments, Ra and Rb are each selected from -H, -CH3, and -CF3. In several embodiments, Ra&amp;Rb are each Selected from -H and -CH3. In several embodiments, Ra and "each are selected from -H and -CF3, respectively. In several embodiments, Ra&amp; Rb are both -H. In several embodiments,: ^ And "forming a C5.7 carbocyclic group, a 5-7 membered heterocyclic group, a 5,6-bicyclic carbocyclyl group, a 6,6-bicyclic carbocyclyl group, a 5,6-bicyclic heterocyclic group or 6 a 6-bicyclic heterocyclyl spiro-fused ring. For example, in several embodiments, 1 is bonded to Rd to form (5-7 carbocyclyl, 5-7 membered heterocyclyl, 5,6-bicyclic ring) a base, or a 5,6-bicyclic heterocyclyl-spiro-fused ring, having the formula:

(iii-a) wherein W24, W25, W26, W27, W28 and W29 are respectively CH2, 110 201043620 CHR, -C(Ri5)2 or NRw', wherein W25&w26 is fused with a C6 aryl ring Or a fused 6-membered heteroaryl ring; respectively, hydrazine or hydrazine; and R15 and R18 are as defined below and herein. In several embodiments, 〇 and v are 〇. In several embodiments, t is 〇 and 乂 is 丨. In several embodiments, the death is 1 and the ¥ is 〇. In several embodiments, t is 1 and v is 1. In several embodiments, r and Rd are joined to form a red 5. cycline-based fused-fused ring. For example, in some embodiments of the formula, W24, w25, w26, 〇 W27, Boundary 28, and Cao 29 are classified into TM2, CHR15, or C(R15)2. Examples of C5-7 carbon ring groups which R&lt;Rd can join to form include, but are not limited to, cyclopentyl, cyclohexyl and cycloheptyl' wherein such groups are 〇, 丨, 2, 3, 4 or Substituted. </ RTI> In several embodiments, Re is bonded to Rd to form a 5-7 membered heterocyclic group, a spiro fused ring. For example, in some embodiments of formula (iii-a), W25 is NRls and W26, W27, W28, and W29 are CH2, CHR15, -C(R15)2, respectively. In some embodiments of the formula (m-a), w26 is NR18 and W24, W25, W27, W28 ❹ and W29 are CH2, CHR15, -C(R15)2, respectively. In some embodiments of formula (iii-a), W27 is NR18 and w24, W25, W26, W28 and W29 are CH2, CHR15, -C(R15)2, respectively. Examples of Re and "5-7 member heterocyclic groups which can be joined to form include, but are not limited to, tons, bases, sputum bases, mother bites, squares, and sulfhydryl groups, wherein such bases The group is substituted with 0, 1, 2, 3, 4 or 5 R15 groups. In several embodiments, wherein t is 0 and ν is 0, RC is bonded to Rd to form a C5 carbocyclic group of the formula or 5 members. Heterocyclic snail _ fused ring: 111 201043620

Or NR18, and R15 and R18 are as defined below and herein. In several embodiments, the formation of a C5 carbocyclic snail-fused ring (eg, a cyclopentyl group); for example, having the formula (iii-b) wherein W25 is NR18 and W26, W27, and W28 are respectively CH2. CHR15 or C(R15)2. In several embodiments, 1^ and 1^ are joined to form a 5-membered heterocyclic snail-fused ring; for example, having the formula (iii-b) wherein W26 is NR18 and W25, W27 and W28 are CH2, CHR15 or C, respectively ( R15) 2. In several embodiments, wherein t is 0 and v is 1, :^ is combined with !^ to form a ring of 6 or 6 membered heterocyclic snail-fused rings:

(iii-c) wherein W25, W26, W27, W28 and W29 are CH2, CHR15, -C(R15)2 or NR18, respectively, and R15 and R18 are as defined below and herein. In several embodiments,: &quot;joining to form a C6 carbocyclic snail-fused ring (e.g., cyclohexyl); for example, having the formula (iii-c) wherein W25, W26, W27, W28, and W29 are CH2, CHR15, respectively Or C(R15)2. In several embodiments, :^ is joined to the ruler 11 to form a 5-membered heterocyclyl spiro-fused 112 201043620. The ring ' has, for example, the formula (iii-c) wherein W26 is NR18 and w25, W27, W28 and are respectively CH:, CHR15 or C(R15)2. In several embodiments, rc and ^ are joined to form a 5-membered heterocyclic snail-fused ring having the formula (iii-c) wherein W27 is 18 and %25, W26, W28 and W29 are respectively CH2, CHR15 or C(R15)2. In several embodiments, where t is 1 and ▽ is 1, RC is bonded to Rd to form a C7 carbocyclic group or 7 members of the formula Heterocyclic snail _ fused ring:

CHR, _C(R·]2 or NR·' and are as defined hereinafter and herein. In several embodiments, Re is bonded to Rd to form (^7 carbocyclyl spiro-fused ring (eg, cycloheptyl) For example, having the formula (iii-d) wherein W24, W25, W26, W27, W28 and W29 are respectively CH2, CHR15 or C(R15)2. In several embodiments, : a snail-fused ring; for example having the formula (iii-d) wherein W25 is NR18 and W24, w26, W27, W28 and W29 are respectively CH2, CHR15 or C(R15)2. In several embodiments, Joining forms a 7-membered heterocyclyl spiro-fused ring wherein W26 is NNi8 and W24, W25, W27, W28 and W29 are respectively CH2, CHR15 or C(Ri5)2. In several embodiments, Re is formed by bonding. a heterocyclic snail-fused ring wherein W27 is NR18 and W24, W25, W26, W28 and W29 are respectively Ch2, CHR15 or C(R15)2. 113 201043620 In several embodiments, Re and Rd are joined to form 5 , 6-bicyclic carbocyclyl spiro-fused ring or 5,6-bicyclic heterocyclyl spiro-fused ring. For example, in some embodiments of formula (iii-a), both t and v are 0, W25 and W26 are substituted with a fused C6 aryl ring or a fused 6 membered heteroaryl ring, and W27 CH2, CHR15, -C(R15)2 and NR18, and W28 are CH2, CHR15 or C(R15)2. In several embodiments of formula (iii-a), 1^ and 11 (1 join form 5,6 a bicyclic carbocyclic spiro-fused ring, for example wherein both 1 and v are 〇'W25 and W26 are substituted with a fused C6 aryl ring or a fused 6 membered heteroaryl ring, and W27 and W28 are respectively CH2, CHR15 or C(R15)2. In several embodiments, W25 and W26 are substituted with a fused aryl ring. For example, in several embodiments, '1 and ¥ are both 0 and w25 and W26 are Substitution with a fused C6 aryl ring to "join to form a 5,6-bicyclic carbocyclic spiro-fused ring of the formula:

/W27 (R1\

〇 ii-d) where W27 and W28 are CH2, CHRl5 and c(r15)2 ′ Z are Ο, 1, 2, 3 or 4; and R15 is as defined below and herein. In some embodiments, both W27 and W28 are CH2 groups. In some embodiments 'z is 0, 1, 2, 3 or 4. In several embodiments, z is 〇, 1, 2, or 3. In several embodiments, z is 0, 1, or 2. 'z is 2 in several embodiments. In several embodiments, z is one. In several embodiments, '2 is 〇° 114 201043620

In several embodiments, a 6,6-bicyclic carbocyclic spiro-fused ring or a 6,6-bicyclic heterocyclyl spiro-fused ring is formed by bonding. For example, in several embodiments of the formula (e.g., 3), t is 〇 and v is 1, and w25 and w26 are fused. An aryl ring or a fused 6-membered heteroaryl ring is substituted, and w27 and w28 are CH2, CHR15, -C(R15)2&amp;NRi8, respectively, and |29 is (:^2, (:111115 or (:(1115) 2) In the formula (except in some embodiments of the hook): :^ and ... are joined to form a 6,6-bicyclic carbocyclic snail-fused % ', for example, where t is 〇 and ^^ is 1, W25 and w26 are Substituted by a fused c6 aryl ring or a copper 6 membered heteroaryl ring, and W27, W28 and W29 are respectively CH2, CHR or C(R)2°. In several embodiments, w25 and w26 are fused. C6 aryl ring substitution. For example, 'in some embodiments, wherein t is 0 and V is 1 and W25 and W26 are substituted with a fused C6 aryl ring, and are bonded to Rd to form a 6 6-bicyclic carbon of the formula Ring-based snail-fused ring:

〇 1 2 3 or 4' and R are as defined below and here. In a few examples, greedy, z is 0, 1, 2 or 3. In (4) and &lt;, such as 2 base. In several embodiments, z is 0, 1, 2, 3 or 4. In several embodiments, z is 〇, 1 or in several embodiments, z is 1. In several embodiments, z is 2. In the embodiment, z is zero. 115 201043620 In another phase, Re is bonded to Rd to form a bridged carbocyclic group of the formula or a bridged heterocyclic snail-fused ring:

W30, W31, W32, W33 and W36 are CH2, CHR15, -C(R15)2 or NR18 respectively; and W34 and W35 are CH or CR15 respectively, and R15 and R18 are as defined below and here. In some embodiments of formula (iii-f), W30, W31, W32, W33 are CH2, CHR15 or C(R15)2, respectively; W36 is NR18; and W34 and W35 are CH or CR15, respectively. In some embodiments of formula (iii-f), 1W30, W31, W32, W33, and W36 are CH2, CHR15, or C(R15)2, respectively; and W34 and W35 are CH or CR15, respectively. In several embodiments of formula (iii-f), W34 and W35 are CH. The R15 group is as used herein, and each of R15 is selected from the group consisting of halogen (i.e., fluorine (-F), bromine (-Br), gas (-C1), and iodine (-1), -CN, -N02, - N3, -S02H, -S03H, -OH, -OR16, -ON(R18)2, -N(R18)2, -N(R18)3+X·, -N(OR17)R18, -SH, -SR16 , -SSR17, -C(=〇)R16, -C02H, -CHO, -C02R16, -0C(=0)R16, -0C02R16, -C(=0)N(R18)2, -0C(=0) N(R18)2, -NR18C(=0)R16, -NR18C02R16, -NR18C(=0)N(R18)2, -C(=NR18)R16, -C(=NR18)OR16, -OC(=NR18 R16, -OC(=NR18)OR16, -C(=NR18)N(R18)2, 116 201043620 -OC(=NR18)N(R18)2, -NR18C(=NR18)N(R18)2 , - C(=0)NR18S02R16, -NR18S02R16, -S02N(R18)2, _S02R16, -S020R16, -0S02R16, -S(=〇)Rl6, -0S(=0)R16, -Si(R16)3, -OSi (R16)3, -C(=S)N(R18)2, -C(=0)SR16, -C(=S)SR16, -SC(=S)SR16, -P(=0)2R16,- 0P(=0)2R16, -P(=0)(R16)2, -OP(=〇)(R16)2, -0P(=0)(0R17)2, -P(=0)2N(R18) 2 ...OP(=〇)2N(R18)2, -P(=〇)(NR18)2, -0P(=0)(NR18)2, -NR18P(=〇)(〇R17)2, -NR18P( =0)(NR18)2, -P(R17)2, -P(R17)3, -OP(R17)2, -OP(R17)3, -B(OR17)2, -BR16(OR17) , Chq alkyl, CM0 perhaloalkyl, C2_10 alkenyl, C2_10 alkynyl, (: 3-14 carbocyclyl, 3-14 membered heterocyclyl, C6-h aryl, and 5-14 membered heteroaryl, wherein The alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are each substituted with 〇, 1, 2, 3, 4 or 5 R19 groups; or two 偕R15 groups. Substituting _〇(c(r2)2)i 2〇_yl wherein R2 is Η, Cl_6 alkyl or halogen; each of R16 is selected from the group consisting of Cl l. decyl, 〇 11 () all-alkyl, C2 i〇, Cw alkynyl, C3_M carbocyclyl, 3-14 membered heterocyclyl, c6_14 aryl, and 5-14 membered heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl, The heterocyclic group, the aryl group and the heteroaryl group are each substituted with 〇, 1, 2, 3, 4 or 5 R19 groups; each of the examples of r18 is selected from the group consisting of hydrogen, -〇H, -〇Ri6, - N(R17)2, -CN, -C(=0)R16, -C(=0)N(R17)2, -C02R16, -S02R16, -C(=NR17)〇Rl6, -C(=NR17) N(R17)2, -S02N(R17)2, -S02R17, -S〇2〇R17, _s〇Rl6, _C(=S)N(R17)2, 117 201043620 -C(=0)SR17, _C( =s)SR17 P(-O) NiRl7, P(~〇)2Rl6 ^ -P(=〇)(Ri6)2 &gt; -P(-(J)2N(R17)2, _P r A ) 2, Cl-decyl, Ct_丨〇perhaloalkyl, C2-decenyl, c2.10 alkynyl, Γ „ Α . , . .D 3_丨0 a 3-14 membered heterocyclic group, a c6-14 group, and a 5-14 membered heteroaryl group, which are attached to the two R17 groups of the ruthenium atom to form a 3-14-shell heterocyclic group or a 5-14 hemene heterocyclic group. a base group in which each of an alkyl group, an alkenyl group, a fast group, a carbocyclic group, a heterocyclic ring, a pentanyl group, and a heteroaryl group are respectively 〇, 1, 2, 3, 4 or 5 r19 Base substitution

Each of Rl7 is selected from the group consisting of hydrogen and Cm. Alkyl, Cl-〗. All-tooth alkyl, C2-H) dilute, C2.1G alkynyl 'C31G carbocyclyl, 3-14 membered heterocyclyl, aryl and 5 14 membered heteroaryl' or two bases attached to the atom And forming a 3·1 collared heterocyclic group or a 5-Hf-based ring, and each of the saponin, alkenyl, alkynyl, sulphonyl, heterocyclyl, aryl, and heteroaryl groups thereof is respectively subjected to hydrazine, 1, 2, 3, 4 or 5 R19 group substitutions; each of R is selected from the group consisting of hydrogen, -CN, _no2, -N3, _so2h, -S03H, -OH, -OR20, -〇N(R21)2, _N (R21)2, -N(R21)3+X-, -N(OR20)R21, -SH, -SR20, -SSR20, -C(=0)R20, -CO2H, -CO2R20, -OC(=0 ) R20, -〇C02R20, -C(=0)N(R21)2, -0C(=0)N(R21)2, -NR2IC(=0)R20, -NR21C02R20, -nr21c(=o)n( R21)2, -C(=NR21)OR20, -OC(=NR21)R20, -OC(=NR21)OR20, -C(=NR21)N(R21)2, -OC(=NR21)N(R21) 2. -nr21c(=nr21)n(r21)2, -nr21so2r20, so2n(r21)2, -so2r20, -S〇2〇R20, -OS02R20, -S(=0)R20, -Si(R20)3 -OSi(R20)3, -C(=S)N(R21)2, -C(=0)SR20, -C(=S)SR20, -SC(=S)SR20, -P(=0) 2R2°' -P(=〇)(R20)2' -OP(=〇)(R20)2' -OP(=〇)(〇R20)2 ' 118 201043620

Cl-6 alkyl fluorenyl (tetra)yl, C26 alkenyl 3 忉 杂环 heterocyclyl, c c 3 _1 Q % %, alkenyl, fluorene, /, aryl, and 5-10 membered heteroaryl, wherein each alkyl group 0, 1, W ring group, heterocyclic group, aryl group, and heteroaryl group are respectively formed by bonding; = R22 group substituted 'or two or one, r J knife is selected from Cl · 6 alkyl, C |-6 full dentate base, c2.6 olefin

3 2:::, CLf group, C6·10 aryl group, 3-10 membered heterocyclic group, and heterocyclic group, wherein each cyclyl, alkenyl group, block group, carbocyclic group, miscible aryl group, and heteroaryl group The base system is substituted by G, Bu, 2, 3, 4 or 5 R22 groups respectively; each of R21 is difficult to be selected from hydrogen, Cl▲ base, Ci 6 whole sister base, C26 base group C2.6 alkynyl group, C31G Carbocyclyl, 31G membered heterocyclyl, aryl, and 5-10 membered heteroaryl' or two R21 groups attached to a nitrogen atom are joined to form a 3-14 membered heterocyclic or M4M heteroaryl ring, wherein Each of the silk, the dilute group, the block group, the carbocyclic group, the heterocyclic group, the aryl group, and the heteroaryl group are each substituted with 0, 2, 3, 4 or 5 R22 groups; and each of R22 is a halogen , _CN, _n 〇 2, _n3, -S02H, -S03H, -OH, -〇Cl_6 alkyl, _0N (Cl 6 alkyl) 2, _N (Ci 6 alkyl) 2, -NCCu alkyl) 3X, (C^ alkyl) 2χ, -NHXCw alkyl) χ, -ΝΗ3Χ, -NCOCw alkyl XCk alkyl), -NCOHXCw alkyl), -NH(OH), -SH, -SC,.6 alkyl, -SSfw alkyl), -CbOXCw alkyl), -C02H, -COXCw alkyl), -OC^OXCm alkyl, -OCO/Cm alkyl)' _c(=〇)NH2, -CeCONCCw alkyl)2 , -OCpCONHCCw alkyl), -NHCpoXCa alkyl), -N (CU6 alkane 119 201043620 base) (: (=0) ((^-6 alkyl), -NHCCMCw), -NHCtOWCw alkyl) 2, - NHCpC^NI^Cw alkyl), -NHC(=0)NH2, -(:(=^)0((^.6 alkyl), -OCPNHXCw alkyl), -OCPNI^OCm alkyl, alkyl) 2, -CpNI^NHCCw alkyl), -C(=NH)NH2, -OCpNi^NCCK alkyl)2, -OQNP^NHCCw alkyl), -OC(NH)NH2, -NHC^N^NCCk alkyl 2, -NHC(=NH)NH2, -NHSCMCk alkyl), -SOzNCCk said base 2, -SC^NI^Cw alkyl), -S02NH2, -SOzCw alkyl, -SC^OCw alkyl, - OSC^Cw alkyl, -SOCw alkyl, -Si(Ci_6 alkyl)3, -OSKCm alkyl)3,alkyl)2,alkyl), -C(=S)NH2, -COO^Cw alkyl ), -cpspc!—6 alkyl, -sc(=s)sc〗.6 alkyl group -p(=0)2(Cl 6 alkyl), _P(=0) (Cl 6 yard) 2 -OPbOXCK base) 2, _〇p (=〇) (〇Ci 6 alkyl) 2, Ci-6 alkyl, Ci-6 king 13⁄4 alkyl C2-6 base, 〇2·6 fast base, C3 -I0 charcoal bad base 'C6-10 aryl, 3-10 membered heterocyclic group, 5-10 membered heteroaryl; or two 偕R22 substituents may be joined to form =〇 or =s; wherein X is a counter ion . In some embodiments, each of R15 is selected from the group consisting of fluorine (_F), bromine (-Br), chlorine (-C1), and iodine (4), 〇Ri6, _c(=〇)n(ri8). 2, _S〇2N(R)2, Cl_1Q 炫基, Cwo 全密基, c2. 丨〇 基, c2.10 alkynyl, CVh aryl, and 5-14 member heteroaryl, each alkyl, alkenyl, The fastylaryl and heteroaryl groups are each substituted with G, 1, 2, 3, 4 or 5 R19 groups. In the right-handed embodiment, 'Rl5 is selected from the group consisting of fluorine (-F), desert (-Br), chlorine 120 201043620 (-C1), and touch (-1), -OR16 and cM0 perhaloalkyl. In some embodiments, R15 is selected from the group consisting of fluorine (-F), bromine (-Br), chlorine (-C1), and iodine (9) and 〇Ri6, respectively. In some embodiments, R15 is selected from the group consisting of fluorine (_F), bromine (-Br), gas (C1), and moth (-1) and (^_10) perhalogen. In several embodiments, R15 is selected. From _ORi6&amp;Ci i 〇perhaloalkyl. In several embodiments, R15 is -OR!6. In several embodiments, R16 is selected from C!. 丨0 alkyl, CM0 per-heptyl, C210 An alkenyl group, a c2 decynyl group, a 0 C6-1Q aryl group, and a 5-6 membered heteroaryl group, wherein each of the alkyl group, the dilute group, the alkynyl group, the aryl group, and the heteroaryl group is substituted with 0, i, 2, 3, 4 or 5 丨 9 yl substitutions. ' In some embodiments, R 15 is -OR16, and R 16 is selected from C mo alkyl. In several embodiments, R 15 is -〇R16, and R16 is Selected from c"6 alkyl. In several embodiments, Rl5 is -〇Rl6, and R16 is selected from c,.4 alkyl. In several embodiments, and R16 is selected from Ci2 alkyl. In some embodiments, R is -OR, and R16 is . (^, ^必必打如-正-pentyl. In some embodiments, R15 is in several embodiments, Rl5 is -OR16 and R16 is selected from Cl.10 perhalogenated. In several embodiments, R15 is a 16 and a 16 is selected from a Ci6 functional alkyl. In several embodiments Wherein, Rl5 is _〇R, and Rl6 is selected from the group consisting of a cardiac 4 all-tooth alkyl group. In the right-hand embodiment, R15 is a group of 16 and R16 is selected from a Cm perhalogen group. In several embodiments, R15 is - OR16 and R16 are -CF3, -CF2CF3, CF2CF2CF3, -CC13, -CFC12, or _CF2a. In some embodiments, R15 is -OR16 and R?6 is an even. In several embodiments, R15 is -or10 and R10 is selected from a C2-10 alkenyl group. In several embodiments, R15 is a collar 16 and R16 is selected from a C2-6 alkenyl group. In several 121 201043620 embodiments, Rl5 is _QRl6 and R16 is selected from the group consisting of c2.4. In several embodiments, 'R is -OR16 and Ri6 is selected from _CH2CHCH2 (ie, a dilute propyl group). In several embodiments, _ORi6&amp;Ri6 is selected from a C2 alkynyl group. (10) 6-form 16 ray from a wire. In several embodiments, ... is a 6-form 16-series selected from C2 4 alkynyl. In several embodiments, 'R15 is -OR16 and R16 is selected from _CH2CCH (ie, C). In some embodiments, R丨5 is _〇R丨6, and R16 is selected from aryl (e.g., phenyl) substituted with oq, 3 or 4 R groups. In several embodiments, R 5 is -OR16, and R16 is 〇, 丨 or Solid foot! 9 substituent of phenyl group. To several embodiments, Ri5 is _0Rl6, ... 6 and is substituted at the Shu a "9 phenyl groups. In several embodiments, Ri5 is _〇Ri6, and Ri6 is phenyl substituted with one 丨9 group (ie, -C6H5). In several embodiments, R15 is _ORi6, and R!6 is selected from the group consisting of 5-6 membered heteroaryl groups substituted with hydrazine, i, 2, 3 or 4 R19 groups. In several embodiments, Rls is -OR16, and R16 is selected from the group consisting of 〇, ! , 2, 3 or 4 r19-substituted 6-membered heteroaryl. In several embodiments, R15 is _ORi6, and Ri6 is selected from pyridyl groups substituted with hydrazine, 1, 2, 3 or 4 R19 groups (eg, 2-azino, 3-pyridine, 4-pyridyl) ). In several embodiments, R!5 is _〇Ri6, and 尺!6 is selected from pyrimidinyl groups substituted with 0, 1, 2, or 3 R19 groups (eg, 2-pyrimidinyl, 4-pyrimidinyl, 5 -pyrimidinyl). In several embodiments, 'R15 is -C(=0)N(R18)2. In several embodiments, R15 is -S02N(R18)2. In several embodiments, R15 is C^oalkyl. In several embodiments, ^^ is 匚!·6 alkyl. In several embodiments 'R15 is Cm alkyl. In several 122 201043620 embodiments, R15 is (^2 alkyl. In several embodiments, R15 is selected from the group consisting of -CF3, -CF2CF3, -CF2CF2CF3, -CC13, -CFC12, and -CF2C in several embodiments. R15 is selected from -CF3. In several embodiments, R15 is CMG alkyl substituted with ο, 1, 2, 3, 4 or 5 R19 groups. In several embodiments, R15 is 0, 1, 2, 3, 4 or 5 R19-substituted C-alkyl groups. In several embodiments, R15 is substituted with 0, 1, 2, 3, 4 or 5 R19 groups (^-4 alkyl) In several embodiments, the R15 alkyl group is unsubstituted (0 R19 groups). In several embodiments, ◎ R15 is -CH3, -Et, -iPr, -nBu, -n-pentyl. In several embodiments, R15 is C2_1()alkenyl substituted with Ο, 1, 2, 3, 4 or 5 R19 groups. In several embodiments, R15 is 0, 1, 2, 3 or 4 And a C.sub.1-6 alkenyl group substituted by R.sub.19. In several embodiments, R.sup.15 is C.sub.4 alkenyl substituted with 0, 1, 2 or 3 R19 groups. In several embodiments, R15 alkenyl is unsubstituted (0). R19 is a group. In several embodiments, R15 is -CH2CCH (ie, allyl). In several embodiments, R15 is C2_1() alkynyl substituted with 0, 1, 2, 3, 4 or 5 R19 groups. In several embodiments, R15 is 0, 1, 2, 3 or Four R19-substituted C2_6 alkynyl groups. In several embodiments, R15 is C2_4 alkynyl substituted with 0, 1, 2 or 3 R19 groups. In several embodiments, the R15 alkynyl group is unsubstituted ( 0 R19基). In several embodiments, R15 is -CH2CCH (ie, propynyl). In several embodiments, 1115 is (6-14 aryl. In several embodiments, R15 is selected from a C6 aryl group (e.g., phenyl) substituted with 0, 1, 2, 3 or 4 R19 groups. In several embodiments, R15 is an unsubstituted phenyl group. In several embodiments 123 201043620, R is a substituted phenyl group (i.e., substituted with 1 R19 group). In several embodiments, 'R15 is a 5-14 member substituted with 〇, 1, 2, 3'4 or 5 尺19 groups. Aryl. In several embodiments, R.sup.5 is a 5-6 membered heteroaryl substituted with 2'3 or 4 of R19 groups. In several embodiments, the formula is 2, 3 or 4 R19-substituted 6-membered heteroaryl. In several embodiments, R15 is In a small square, three or four substituents Rl9 instigate roar group (Example

Such as 2-pyridyl, 3-pyridyl, 4-pyridyl). In several embodiments, r1S is pyrimidinyl (eg, 2-pyrimidinyl, 4-indolyl, 5-indyl) substituted with 0' 1, 2, or 3 R19 groups. In several embodiments, the RlS heteroaryl group is unsubstituted (0 R19 groups). R18 is based on several embodiments, each of Ri8 is selected from the group consisting of _H, _〇H, -OR16, -ON(R17)2, _c(=〇)R16-S02R16, -C(=NR,7)r16 , -c(=o)n(r17)2, _c〇2R16, , -C(=NR17)〇Ri6, -C(=NR17)N(R,7)2 &gt; -S02N(R,7)2 -so2r16 &gt; -so2〇R16 . -SOR16, -C(=S)N(R17)2, _C(=0)SR16 ' _c(=s)sr16, c alkyl (eg aralkyl), C2 -1G alkenyl 'c2 lQ alkynyl, C31Q carbocyclyl, 3-14 heterocyclyl, C^4 aryl, and 5-14 heteroaryl, wherein each alkyl, alkenyl 'alkynyl, carbocyclyl, hetero The cyclo, aralkyl, aryl, and heteroaryl groups are each substituted with 0, 1, 2, 3, 4 or 5 R19 groups, wherein R16, R17, R19 are as defined above and herein. In several embodiments, the respective instances of R 7 are selected from the group consisting of _H, _C(=〇)Rl6, _C(=0)0Rl6, _s〇2Rl6, or ^6 alkyl. In some embodiments, each of R17 is selected from the group consisting of _H or Ci6 alkyl. In several embodiments 124 201043620, each of R17 is selected from the group consisting of -Η and -CH3. In some embodiments, each of R17 is selected from the group consisting of -H. In some embodiments, each of R17 is selected from the group consisting of -CH3. Additional Examples of Compounds of Formula (I) As broadly defined above, the present invention provides compounds of formula (I):

m or a pharmaceutically acceptable form thereof, wherein G, Ra, Rb, Re and Rd are as defined herein. In one phase, wherein Ra, Rb, Re are each H, and Rd is a Z group, the present invention provides a compound of formula (II):

(10) or a pharmaceutically acceptable form thereof, wherein G and Z are as defined herein. In several embodiments, L is a covalent bond. In several embodiments, G is -ORe. In several embodiments, G is -Br. However, in several embodiments, G is not a halogen (e.g., -Br). For example, in several embodiments, wherein L is a covalent bond, Ra, Rb, Re are each deuterium, and G is a -ORe group, the invention provides a compound of formula (ΙΙ-a): 125 201043620

Rtt.

Z (II-3) or a pharmaceutically acceptable form thereof, wherein ReAZ is as defined herein b) in the right-hand embodiment, wherein Z is a phenyl ring, and the present invention provides a compound of formula (11_:

Or a pharmaceutically acceptable form thereof, wherein G, L, Ra, Rb, Rc, and 2 are as defined herein. For example, in several embodiments, 2 is 1 and the R15 is in the ortho position. In several implementations &lt;columns, Z is 1 and the R15 is in the meta position. In the examples, B is 1 and Rl5 is in the para position. In several embodiments, z is 2 and the R15 is in the meta and para position. In several embodiments, l is a covalent bond. In several embodiments, G is a view e. In several embodiments, G is .Br. In the case of the right-handed palladium, G is not a halogen (for example, _Br). In several embodiments, R15 is selected from the group consisting of -OR16 and CMo perhaloalkyl. For example, in several implementations, the coffee and R15 provide the compound of formula (II_C) for (iv): 126 201043620

Or a pharmaceutically acceptable form thereof, wherein G, L, Ra, Rb, Re, R15 and z are as defined herein. In several embodiments, L is a covalent bond. In the examples, G is -ORe. In several embodiments, G is -Br. In the examples, G is not a halogen (e.g., -Br). In several embodiments, R15 is selected from the group consisting of -OR16 and C^o perhaloalkyl. For example, in several embodiments, z is 2 and R15 is meta and para to provide a compound of formula (II-c):

R1S

Or a pharmaceutically acceptable form thereof, wherein G, L, Ra, Rb, Re, R15 and z are as defined herein. In several embodiments, L is a covalent bond. In the examples, G is -ORe. In several embodiments, G is -Br. In the examples, G is not a halogen (e.g., -Br). In several embodiments, R15 is selected from the group consisting of -OR16 and C^o perhaloalkyl. For example, in several embodiments, wherein Z is a phenyl ring, and G is a -ORe 127 201043620 group, the invention provides a compound of formula (ΙΙ-d):

Or a pharmaceutically acceptable form thereof, wherein L, Ra, Rb, RC, Rl5, R and 2 are as defined herein. For example, in several embodiments, z is 1 and the R15 is in the ortho position. In several embodiments, z is 1 and the R15 is in the meta position. In several embodiments, z is 1 and the R15 is in the para position. In several embodiments, [is a covalent bond. In several embodiments, Ris is selected from the group consisting of _〇r16&amp;Ci i〇perhaloalkyl. In some embodiments, wherein Z is a phenyl ring, G is a -ORe group, and Re is a phenyl ring, the invention provides a compound of formula (II-e):

Or a pharmaceutically acceptable form thereof, wherein L, Ra, Rb, Rc, R15, R, x and z are as defined herein. For example, in several embodiments, z is 1 and the R15 is in the ortho position. In several embodiments, the coffee and r15 are in the meta position. In several embodiments, 'Z is 1 and the R15 is in the para position. In several embodiments, L is a covalent bond. In several embodiments, r15 is selected from the group consisting of _128 201043620. In several embodiments, wherein Z is a phenyl ring, G is -ORe*, and Re is a 5-membered heteroaryl ring, the invention provides a compound of formula (ΙΙ-ί):

(IW) or a pharmaceutically acceptable form thereof, wherein Ya, Yb, Ye, Yd, L, Ra, Rb, Re, R15 and z are as defined herein. For example, in several embodiments, z is 1 and the R15 is in the ortho position. In several embodiments, z is 1 and the R15 is in the meta position. In several embodiments, z is 1 and the R15 is in the para position. In several embodiments, L is a covalent bond. In several embodiments, R15 is selected from the group consisting of -OR16 and ¢^.10.

In several embodiments, wherein Z is a phenyl ring, G is a -ORe group, and Re is a 6 membered heteroaryl ring, the invention provides a compound of formula (Π-g):

(H-g)

Or a pharmaceutically acceptable form thereof, wherein wa, wb, we, wd, 129 201043620

We, L, Ra, Rb, Rc ' R15 and z are as defined herein. For example, in several embodiments, z is 1 and the R15 is in the ortho position. In several embodiments, 2 is 1 and the R15 is in the meta position. In several embodiments, z is 1 and the R15 is in the para position. In several embodiments, R15 is selected from the group consisting of -OR16 and CM0 perhaloalkyl. In several embodiments, L is a covalent bond. In several embodiments, Wb is N and Wa, We, Wd, &amp; We are selected from CH or CRh. In some embodiments, in several embodiments, Wc is CRh and Wa, Wc, Wd, and \\^ are each CH. In some embodiments, wb and Wd are N and Wa, Wc, Wd &amp; We are selected from CH or CRh. In several embodiments, wherein Z is a phenyl ring, G is a -〇Re group, and Re is a 9 membered heteroaryl ring, the invention provides a compound of formula (II-h):

And a pharmaceutically acceptable form thereof, wherein Ye, Yf, yg, Yi, Yj, Y, π, L, E, Rb, Re, Rl5 and z are as defined herein. For example, in the two right-handed embodiments, ... and Rl5 are in the ortho position. In several embodiments Z is 1 and the R system is in the meta position. In several embodiments, z is 1 and the system is in the para position. In some real _ towel, r15 face from Wei 16 shape 11 burning base. In a number of implementations, L is a covalent bond. In a number of implementations where Z is a phenyl ring, G is a t-group, and Re 130 201043620 is a 10-membered heteroaryl ring, the invention provides a compound of formula (Π-i):

Or a pharmaceutically acceptable form thereof, wherein Wf, Wg, Wh, W1, Wj, Wk, Wm, Wn, L, Ra,

Rb, Re, R15 and z are as defined herein. For example, in several embodiments, z is 1 and the R15 is in the ortho position. In several embodiments, z is 1 and the R15 is in the meta position. In several embodiments, z is 1 and the R15 is in the para position. In several embodiments, R15 is selected from the group consisting of -OR16 and Cun) perhaloalkyl. In several embodiments, L is a covalent bond. In several embodiments, wherein Z is a phenyl ring and G is -NReR^i, the invention provides a compound of formula (Π-j):

Or a pharmaceutically acceptable form thereof, wherein L, Ra, Rb, Re, Re, Rf, R15 and z are as defined herein. For example, in several embodiments, z is 1 and 131 201043620

The Rl5 line is in the ortho position. In several embodiments, she is in the meta position and is in the right position in the right _ middle _ and RL5. In R if, R] 5 is selected from -OW^C into the real M歹丨 丨0 king haloalkyl. In several embodiments, the = covalent bond. In several embodiments, R and Rf are joined to form (4) a member of the county. In the Xuxuan example, &quot;Rf joins to form a (4) heteroaryl ring. The present invention is provided in a number of actual closures, the towel 2 of which is a 5 贞 heteroaryl ring compound of formula (II-1):

Or a pharmaceutically acceptable form thereof, wherein γι, γ2, γ3, γ4, G,

L, Ra, Rb &amp; R, as defined herein. In several embodiments, l is a covalent bond. In several embodiments, G is _0Re. In some embodiments, ¥1 is 8, Y2 is CR15, Y3 is N, and γ4 is Cj^cr15, wherein Rl5 is as defined above and herein. In several embodiments, Y4 is CH. In several embodiments, the substituent present on Y2 is a c6 aryl (eg, stupid). In several embodiments, wherein z is a 6 membered heteroaryl ring, the invention provides a compound of the formula (ΙΙ-m): 132 201043620

Or a pharmaceutically acceptable form thereof, wherein W^W'W'W'G, L, Ra, Rb and Re are as defined herein. In several embodiments, L is a covalent _ bond. In several embodiments, G is -ORe. In several embodiments, the 6 membered doped aryl ring is pyridinyl (eg, 2-pyridyl, 3-pyridyl, 4-pyridyl) or alpha dense a-based (eg, 2-sigma-based, 4- ^π定基, 5-^σ定基). In several embodiments, wherein the oxime is a 9 membered heteroaryl ring, the invention provides a compound of the formula (ΙΙ-η):

Or a pharmaceutically acceptable form thereof, wherein Y5, Y6, Y7, Y9, Y1Q, γΐι, γΐ2, γΐ3, G, L, Ra, Rb and Re are as defined herein. In several embodiments, L is a covalent bond. In several embodiments, G is -ORe. In several embodiments, wherein Z is a 10-membered heteroaryl ring, the invention provides a compound of formula (11-〇): 133 201043620

G

(II*©) or a pharmaceutically acceptable form thereof wherein w6, w7, w8, w9, w10, W11, w12, W13 b G, L, R, Rb and RC are as defined herein. In several embodiments, L is a ϋ栌M ^ + horse conjugate. In several embodiments, G is f -ORe - : in several embodiments, wherein 2 is a 6 membered heterocyclic group, the invention provides a compound of formula (II-P):

Or a pharmaceutically acceptable form thereof, wherein w14, W15, w16, W17,

Τϊτ 18 τ-τ Τ19 , W , (}, [, ruler '1^ and 1^ are as defined herein. In several embodiments, '[is a covalent bond. In several embodiments, G is -〇Re. In another aspect, wherein the bond forms a Gw carbocyclic group or a 3-14 membered heterocyclic group, the present invention provides a compound of formula (III): 134 201043620

Or a pharmaceutically acceptable form thereof, wherein s is 0, 1 or 2 and W2G, W21, W22, W23, G, Re, Rd, R15 and R18 are as defined above and herein. In several embodiments, G is -ORe. In several embodiments, wherein s is 0, the invention provides a compound of formula (ΙΙΙ-a):

(IH-a) or a pharmaceutically acceptable form thereof, wherein G, Rb, Re, W2Q, W21 and W22 are as defined above and herein. In several embodiments, G is -ORe. In some embodiments, wherein s is 0, W21 is NR18, and W2G, W22, and W23 are CH2, CHR15, or C(R15)2, respectively, the invention provides a compound of formula (III-b):

Illb 135 201043620 or a pharmaceutically acceptable form thereof, wherein G, Rb, Re, R18 and R15 are as defined above and herein. In several embodiments, G is -ORe. In several embodiments, wherein s is 1, the invention provides a compound of formula (III-c):

Or a pharmaceutically acceptable form thereof, wherein G, Rb, Re, W2G, W21, W22 and W23 are as defined above and herein. In several embodiments, G is -ORe. In some embodiments, wherein s is 1, W21 is NR18, and W2G, W22, and W23 are CH2, CHR15, or C(R15)2, respectively, the invention provides a compound of formula (III-d):

(ffl-d) or a pharmaceutically acceptable form thereof, wherein G, Rb, Re, R18 and R15 are as defined above and herein. In several embodiments, G is -ORe. In some embodiments, wherein s is 1, W22 is NR18, and W2G, W21, and W23 are CH2, CHR15, or C(R15)2, respectively, the invention provides Formula (III-e) 136 201043620 Compound:

Re

(ΠΙ-e) or a pharmaceutically acceptable form thereof, wherein G, Rb, Re, R18 and R15 are as defined above and herein. In several embodiments, G is -ORe. In several embodiments, wherein S is 2, the invention provides a compound of formula (m-f):

(Iii-f) or a pharmaceutically acceptable form thereof, wherein G, Rb, Re, W2G, W21, W22 and W23 are as defined above and herein. In several embodiments, G is -ORe. In some embodiments, wherein s is 2, W22 is NR18, and W2Q, W21, and W23 are CH2, CHR15, or C(R15)2, respectively, the invention provides a compound of formula (III-g): 137 201043620

(ΐπ-g) or a pharmaceutically acceptable form thereof, wherein G, Rb, Re, R18 and R15 are as defined above and herein. In several embodiments, G is -ORe. In yet another aspect, wherein Re is bonded to Rd to form a C3_1() carbocyclic group or a 3-14 membered heterocyclyl ring, the present invention provides a compound of formula (IV):

Or a pharmaceutically acceptable form thereof, wherein W24, W26, W27, W28 and W30 are respectively CH2, CHR15, -C(R15)2 or NR18, optionally wherein W25 and W26 are fused to a C6 aryl group Ring or a 6-membered heteroaryl ring is substituted; t and v are each 0 or 1; wherein G, Ra, Rb, R15 and R18 are as defined above and herein. In several embodiments, G is -ORe. In several embodiments, t is 0 and v is zero. In some embodiments, t is 0 and v is 1. In several embodiments, t is 1 and v is 0. In the examples, t is 1 and v is 1. In several embodiments, wherein t is 0 and v is 0, the invention provides a compound of formula (IV-a): 138 201043620

Or a pharmaceutically acceptable form thereof, wherein G'R'Rb, w25, W26, W and W are as defined herein and herein. In several embodiments, 〇 is -ORe. In several embodiments, 'W27 is NR18, and W25, W26, and W28 are CH2, CHR15, or C(R)5, respectively. In several embodiments, w25, w26, W27, and W28 are CH2, CHR15, or C(R15)2, respectively. In certain embodiments, wherein t is 〇, v is 〇, W27 is NR18, and W25, W26, and W28 are CH2, CHR%c(Ri5)2, respectively, and the present invention provides a compound of formula (IV-b):

Or a pharmaceutically acceptable form thereof, wherein G, Ra, Rb, R!5 and Ris are as defined above and herein. In several embodiments, 〇 is _〇11£; In several embodiments, where t is OhW, the invention provides a compound of the formula (Work V_c):

139 201043620 or a pharmaceutically acceptable form thereof, wherein 〇, 113, 111), \\^5, '\^26, W27, W28 and W29 are as defined above and herein. In several embodiments, G is -ORe. In some embodiments, W26 is NR18 and W25, W27, W28 and W29 are CH2, CHR15 or c(R15)2, respectively. In some embodiments, W27 is NR18 and W25, W26, W28, and w29 are CH2, CHR15, or C(R15)2, respectively. In some embodiments, W25, W26, W27, W28, and W29 are CH2, CHR15, or C(R15)2, respectively. In some embodiments, wherein t*0, V is i, W27 is NR1S, and W25, W26, W28 and W29 are respectively Ch2, CHRi5 or c(Ri5)2, the invention provides a compound of formula (IV-d):

Or a pharmaceutically acceptable form thereof, wherein G, Ra, Rb, Ri5^i8 are as defined herein and herein. In the embodiment of the work &amp; right and right, G is -〇Re. And v is 1 '. The invention provides formula (IV_e) in several embodiments, wherein t is 1 compound:

Wherein G, Ra, Rb, w24, W25, or a pharmaceutically acceptable form thereof 201043620 W26, W27, w28 and W29 are as defined above and herein. In several embodiments, G is -〇Re. In some embodiments, W25 is NR18 and W24, W26, W27, W28, and W29 are CH2, CHR15, or C(R15)2, respectively. In some embodiments, W26 is NR18 and W24, W25, W27, W28 and W29 are CH2, CHR15 or C(R15)2, respectively. In some embodiments, W27 is NR18 and W24, W25, W26, W28, and W29 are CH2, CHR15, or C(R15)2, respectively. In several embodiments, W24, W25, W26, W27, W28, and W29 are CH2, CHR15, or C(R15)2, respectively. In some embodiments, wherein t is 1, v is 1, W27 is NR18, and W24, W25, W26, W28, and W29 are CH2, CHR15, or C(R15)2, respectively, and the present invention provides Formula (IV-f) Compound:

Or a pharmaceutically acceptable form thereof, wherein (}, 1^, 111), trans 15 and &amp; 18 are as defined above and herein. In some embodiments, 〇 is _〇]^. In several embodiments, wherein £ is 〇, ¥ is 〇, W27 &amp; w28 are (3⁄4, CHR15 and C(R15)2' and f and w26 are respectively substituted by fused aryl ring 'Re and R' Formation of a 5,6-bicyclic carbocyclyl group of the formula (Iv_g): 141 201043620

Αν-g) or a pharmaceutically acceptable form thereof, wherein G, Ra, Rb and R15 are as defined above and herein. In several embodiments, Ra and Rb are -Η. In several embodiments, ζ is 1. In several embodiments, G is -ORe. In several embodiments, R15 is selected from the group consisting of -OR16 and C^o perhaloalkyl. Examples of Compounds of the Invention Examples of the compounds of Formula (I), (II) and subclasses thereof are set forth below in the following la-lm, and Examples 1-253 are provided herein in further detail. The compound was assayed as a human FAAH inhibitor using the method detailed in Example 3 51. In some embodiments, the compound is any one of the compounds provided in Table la or a pharmaceutically acceptable form thereof: Table la· Compound G Ra Rc 1-10 -Br -Η -Η 1-17 -Cl -Η - Η 1-23 α0χ -Η -Η 1-24 ρχχ0λ -Η -Η 142 201043620 Table la. 1-25 Input -Η -Η 1-26 ,Λχ -Η -Η 1-27 NCXX0x -Η -Η 1- 28 CN -Η -Η 1-29 -Η -Η 1-30 Me.//° -Η -Η 1-31 :XX〇x -Η -Η 1-32 0-νΛ Η -Η -Η 1-33 όΛ -Η -Η 1-34 -Η -Η 1-35 &lt;αΛ -Η -Η 1-36 α〇Λ -Η -Η 1-37 Ci.入 -Η -Η 1-39 .Ν -Η -Η 1-40 Me./Ν. XI.入-Η -Η 143 201043620

Table la· 1-41 Cl0A -H -H 1-42 ca0x -H -H 1-43 fA. '-H -H 1-44 Me n^n cCx. /, -H -H 1-45 -OMe -H -H 1-47 .N. 0 -H -H 1-56 -H -H 1-57 aX, H -H -H 1-58 CN -H - H 1-59 ςν' F -H -H 1-60 f3 -H -H 1-61 C02Me 0L0x -H -H 1-62 Me〇2CXl0A -H -H 1-63 Me 0=S=0 ά. , -H -H 144 201043620

Table la. 1-64 nh2 0=S=0 0L〇A -H -H 1-65 .N MeO人』'0In-H -H 1-66 MeO, /N, XX' -H -H 1- 67 Μθ〇2〇^.Ν. XX)/' -H -H 1-68 Η .. ca0A -H -H 1-69 αΧ, -H -H 1-90 Η2Ν /? a. -H -H 1-92 BocHN^N. -H -H 1-93 h2nvn, -H -H 1-94 MelKtX〇A -H -H 1-98 Me〇A^Ci〇A -H -H 1 -99 Η〇λ^α0Λ -H -H 1-100 -H -H 1-110 H〇2Ctl〇A -H -H 145 201043620

Table la· im Me -H -H 1-146 c〇2h 6l0&gt; -H -H 1-147 XX' -H -H 1-155 Me -H -H 1-159 Me b〇-H -H 1- 160 Me α〇Λ -H -H 1-197 Μ%〇λ -H -H 1-243 H -H -H 1-244 H0^rf 〇Me -H -H 1-245 〇Vmx OH -H -H 1-256 ox -H -H 1-257 Me N, n, -H -H 146 201043620 Table la. 1-260 -Η -H Me into 1-78 (cis) -Br -ch3 -H 1-82 (trans) -Br -ch3 -H 1-91 (trans) 0-〇Λ -ch3 -H 1-76 -Br -H -ch3 1-89 -H -ch3 1-130 -Br -H -cf3 1-131 γΛ -H -cf3 1-95 -Br -H -CH2CH3

In some embodiments, the compound is any of the compounds provided in Table lb or a pharmaceutically acceptable form thereof:

Table lb. ga^O^0CF3 Ra Compound G Ra Rc 1-14 -Br -H -H 1-46 Me02C^^^〇&gt; -H -H 1-53 .N. h2Ny^JL〇A 0 -H -H 1-54 Μθ^γΛ〇Α 0 -H -H 147 201043620 Table lb. 1-55 -Η -Η 1-70 a0&gt; -Η -Η 1-71 -Η -Η 1-72 .Ν 〇r ^〇A -Η -Η 1-73 -Η -Η 1-83 -Η -Η 1-84 -Η -Η 1-85 -Η -Η 1-86 -Η -Η 1-96 μΛχ, -Η - Η 1-97 h〇X〇l0a -Η -Η 1-105 -Η -Η

148 201043620

Table lb· 1-106 -Η -Η 1-107 0 H 入入-Η -Η 1-108 -Η -Η 1-109 0 HU^〇&gt; -Η -Η 1-112 n〇l〇a - Η -Η 1-118 H2 丫-Η -Η 1-128 Η〇λ/Χλ0χ -Η -Η 1-132 xXa -Η -Η 1-133 Me,&quot;0 ^XX0A -Η -Η 1-134 MeStl0A -Η -Η 1-135 Me. //° ^Χλ0Λ -Η -Η 1-136 Μ:Λ0λ -Η -Η 1-151 _XX入-Η -Η 149 201043620

Table lb. 1-152 h〇2CXX〇&gt; -H -H 1-157 Me -H -H 1-161 BrtX0x -H -H 1-162 ^0Λ -H -H 1-163 -H -H 1- 165 -H -H 1-173 ^Cl0A -H -H 1-174 N=N NyNH ά0Λ -H -H 1-175 N'NH -H -H 1-176 co2h -H -H 1-177 H〇2CXX0x -H -H 1-178 NCtl0x -H -H

150 201043620

Table lb. 1-182 Et^X〇A -Η -Η 1-183 -Η -Η 1-184 Merfa〇x -Η -Η 1-186 ^α〇Λ -Η -Η 1-187 -Η -Η 1-188 H〇2C^tx0x -Η -Η 1-189 Ir^CioA -Η -Η 1-190 Me -Η -Η 1-191 f3c Me T^JLqA -Η -Η 1-192 Ν^α〇Λ -Η -Η 1-193 -Η -Η 151 201043620 Table lb. 1-194 -Η -Η 1-195 Ί -Η -Η 1-199 Me ¥ ά0Λ -Η -Η 1-200 N = N -Η - Η 1-201 Ί -Η -Η 1-218 Me -Η -Η 1-220 -Η -Η 1-221 Ν-Ν V ά0χ -Η -Η 1-223 Me 03⁄4 0.0Λ -Η -Η

152 201043620

Table lb. 1-224 Me Μ °γΝ A, -Η -Η 1-225 Λ, -Η -Η 1-226 〇CTn Λ0λ -Η -Η 1-230 -Η -Η 1-236 ,Ν'ΝΗ Ν ^0λ -Η -Η 1-246 Cw δΗ Η -Η -Η 1-248 asA -Η -Η 1-249 aSA w 0 -Η -Η 1-250 cT〇-Η -Η 1-251 -Η -Η 1-253 αΝΛ -Η -Η 153 201043620 Table lb. 1-255 Me -H -H 1-258 °7n 0l0a -H -H 1-75 -Br -H -ch3 1-88 -H -ch3 1-113 Ho2c_n XX〇A -H -ch3 1-114 0 Ί -H -ch3 1-115 -H -ch3 1-116 F3C^k1Ci0a -H -ch3 1-117 -H -ch3 1-129 n〇L〇A - H -ch3 1-154 -H -ch3 1-156 Me y〇-H -ch3

154 201043620

Table lb. 1-158 Me -Η -ch3 1-164 %0Λ -Η -ch3 1-167 Me./ -Η -ch3 1-171 -Η -ch3 1-172 %0Λ -Η -ch3 1-185 &lt ;Γ1 NN w -Η -ch3 1-196 Et, / N ^ΧΧ〇Λ -Η -ch3 1-198 广 N -Η -ch3 1-222 Me 03⁄4 -Η -ch3 1-227 A. /, -Η -ch3 155 201043620 Table lb. 1-228 〇7N ά0Λ -Η -ch3 1-229 Me )=1 〇γΝ -Η -ch3 1-231 〇'Vnh ΟγΝ ά0Λ -Η -ch3 1-232 ά0Λ -Η -ch3 1-233 Me, /Me Ν 0=S=0 -Η -ch3 1-234 Me./Ρ -Η -ch3 1-235 Me 々〇Ί -Η -ch3 1-240 Me -Η -ch3

156 201043620 Table lb. 1-241 ^Λ〇λ -Η -ch3 1-242 -Η -ch3 1-261 MeS. .Ν. Χλ〇Λ -Η -ch3

In some embodiments, the compound is any of the compounds provided in Table lc or a pharmaceutically acceptable form thereof:

Table lc. ga^〇-cF3 Ra Compound G Ra Rc 1-168 α0Λ -H -H 1-169 Me, sucking A -H -H 1-170 H〇2CtX〇A -H -H 1-216 Brti0x -H -H 1-217 0L0x -H -H 1-218 Me , N1 -H -H 157 201043620

Lc. Form: Table Id.

R15 g^^0~0CF3

Ra compound G Ra Rc R1S = halogen atom __Μ20 -Βγ -H -H -F - -1-121 r~-~~- &amp;〇χ -H -H -F 1-122 k circle-.-__ Me02C ^N. -H -H -F 1-123 _____Μ24 H02C^N. .Rr -H -H -F 1-125 1----- -H -H -H -H -Cl -Cl

In some embodiments, the compound is any one of the compounds provided in Table 16, or a pharmaceutically acceptable form thereof:

158 201043620

Table le· Compound G Ra Rc R16 = unsubstituted alkyl group 'fast group 1-142 -Br -H -H 1-143 N^X indole-H -H 1-144 Me〇2CXl〇A -H - H 1-145 H02C N -H -H 1-140 H02C N A -H -H Me |Me 1-141 -H -H Me ,Me 1-15 -Br -H -H Me , Corpse Me 1- 137 MeO〇C^ .N. XX, -H -H n-n-butyl 1-138 H02C N -H -H n-n-butyl 1-139 α0χ -H -H n-n-butyl 1-6 - Br -H -H -ch3 1-38 &amp; -H -H -ch3 1-77 (trans) -Br -ch3 -H -ch3 In several embodiments, the compound is provided by the table if a compound or a pharmaceutically acceptable form thereof:

159 201043620 Table If. Compound G Ra Rc R15 = alkyl, aryl 1-20 -Br -H -H n-butyl 1-180 A' -H -H η-butyl 1-181 Μθ^Χ〇Λ -H -H η-butyl 1-179 -Br -H -H η-pentyl 1-102 -Br -H -ch3 -c6h5 1-104 Ο. /' -H -ch3 -c6h5 1-9 -Br -H -H -c6h5 1-101 a0A -H -H -C6Hs 1-103 -H -H -c6h5 In several embodiments, the compound is in the form ig Provided as any one of the compounds or a pharmaceutically acceptable form thereof: Table ig. Gx^〇-R15 Ra Compound G R15 = halogen atom 1-3 -Br -Cl 1-153 nO-〇A -Cl 1-148 -Br -Br 1-149 Μθ〇2〇, -Br 1-150 H02C N \X〇&gt; -Br 160 201043620

Table lg. 1-237 Me, 々〇-Br _ -Br -F In some embodiments, the compound is any of the compounds provided in Table lh or a pharmaceutically acceptable form thereof: Table lh.

Ο

* In the context of the example, the compound is any of the compounds provided by Table li or its pharmaceutically acceptable form:

161 201043620 In some embodiments, the compound is any of the compounds provided in Table ij, or a pharmaceutically acceptable form thereof:

Compound G Ra Rc R2 = H, halogen atom 1-126 -Br -H -H -F, -F 1-127 γΛ -H -H -F, -F νΛ^ 1-16 -Br -H -H -H Table lj. In several embodiments, the compound is any one of the compounds provided in Table lk or a pharmaceutically acceptable form thereof: Table lk. Ra R18 Compound G Ra Rc R18 1-22 -Br -H -HH, - CH2Ph 1-214 Me, /In-H-HH, -CH2Ph 1-215 H02C N -H -HH, -CH2Ph 1-203 -Br -H -H -ch3, -ch3 1-212 Me, / N -H -H -ch3, -ch3 1-202 -Br -H -H 10 162 201043620 Table lk· 1-204 -Br -Η -Η -Η, -CH3 1-208 -Br /-Λ 1-209 -Br - Η -Η In several embodiments, the compound is any one of the compounds provided in Table η or a pharmaceutically acceptable form thereof:

Table 11· Ra R18 Compound G Ra Rc R18 1-205 -Br -H -H 1-207 -Br -H -H -H, -CH3 1-206 -Br -H -H -ch3, -ch3 1-210 -Br -H -H /-Λ o 1-211 -Br -H -H 1-213 Me /PN Paper A -H -H -ch3, -ch3 In several embodiments, the compound is provided by the table lm Any compound or a pharmaceutically acceptable form thereof: Table lm. Corpse Cl ΝΓ°νν\ Br'^ 1-4 1-5 163 201043620

Examples of compounds of formula (1), (III) and subclasses thereof are set forth in Tables 2a-2e below, and Examples 254-284 provided herein are also described in further detail. The compound was assayed as a human faAH inhibitor using the method detailed in Example 351. In certain embodiments, the compound is any one of the compounds provided in Table 2a or a pharmaceutically acceptable form thereof: 164 201043620 Table 2a. Compound G Ra Rc R15 R19 II-6 -Br -H -H -H -H 11-21 α〇Α -H -H -H -H 11-28 Μ%〇λ -H -H -H -H 11-18 -Br -H -ch3 -H -H 11-22 d0A -H -ch3 -H -H 11-23 .Ν. -H -ch3 -H -H 11-29 Me, /Ρ ^〇Λ -H -ch3 -H -H 11-19 (cis) -Br -ch3 -H - H -H 11-20 (trans) -Br ch3 -H -H -H 11-17 -Br -H -H -H -Cl

In some embodiments, the compound is any one of the compounds provided in Table 2b or a pharmaceutically acceptable form thereof:

Table 2b. Compound G Ra Rc 11-25 -Br -H -H 11-26 CXInclusion -H -H 11-27 h〇2c^n. In-H -H 165 201043620 In several embodiments, the compound Any of the compounds provided in Table 2c or a pharmaceutically acceptable form thereof:

Table 2c. Compound G Ra Rc II-8 -Br -H -H 11-31 OH -H -H 11-30 CW 6h H -H -H

In some embodiments, the compound is any of the compounds provided in Table 2d, or a pharmaceutically acceptable form thereof:

Table 2d. Ra Compound G R18 Ra Rc II-15 -Br -H -H Ί 3 11-16 -Br I /P -H -H

In some embodiments, the compound is any of the compounds provided in Table 2e or a pharmaceutically acceptable form thereof: 166 201043620 Table 2e·

Br

Br

III II-2

II-3 II-4

11-12

11-14

11-24 1117 Examples of compounds of formula (I), (IV) and subclasses thereof are set forth in Tables 3a through 3d below, and Examples 285-350 are provided herein in further detail. The compound was assayed as a human FAAH inhibitor using the method detailed in Example 3 51. 167 201043620 In several embodiments, the compound is any of the compounds provided in Table 3a, or a pharmaceutically acceptable form thereof:

168 201043620

Table 3a. III-58 ΙΙΙ-49 -Br \ ΙΙΙ-50 CXa \ ΙΙΙ-9 -Br K° o- ΙΙΙ-47 -Cl K° 〇一ΙΙΙ-53 cx KK° o- ΙΙΙ-14 -Br -H ΙΙΙ-15 -Br M° Me ΙΙΙ-17 -Br 0 /= ΙΙΙ-19 -Br ΙΙΙ-20 -Br Cl ΙΙΙ-21 -Br OMe 169 201043620 Table 3a· III-22 -Br ΙΙΙ-23 -Br ΙΙΙ-24 -Br Me ΙΙΙ-25 -Br Cl ΙΙΙ-26 -Br cf3 ΙΙΙ-28 -Br ΙΙΙ-29 -Br ΙΙΙ-30 -Br ΙΙΙ-31 -Br ΙΙΙ-32 -Br ΙΙΙ-33 -Br ΙΙΙ- 34 -Br ΙΙΙ-35 -Br H° OMe

170 201043620

171 201043620 In several embodiments, the compound is any one of the compounds provided in Table 3b or a pharmaceutically acceptable form thereof: Table 3b (cis-ring fused) 8 Compound G R18 III-43 -Br Vx 0 / \ III-44 -Br /y〇J〇〇III-45 -Br /^σα In some embodiments, the compound is any one of the compounds provided in Table 3c or a pharmaceutically acceptable form thereof: Table 3c· Compound G R15 III-63 -Br III-64 Y〇O III-66 -Br -ocf3 III-67 MeS^N. Recognized -ocf3 III-68 Me, / -ocf3 172 201043620 Table 3c· III-70 Me -ocf3 III-71 Me into -ocf3 III-73 nOL〇X -OCF3 III-74 Η〇λα〇Λ -OCF3

In some embodiments, the compound is any one of the compounds provided in Table 3d or a pharmaceutically acceptable form thereof: Table 3d. JOO Br III-l Br III-2 βγλΧ&gt;^ III-3 IH-4 III- 8 r&gt;〇hV 0 &lt; III-IO 0 / III-ll 0 III-12 173 201043620

However, in several embodiments of formulas (I) and (II), the following compounds are specifically excluded:

However, in several embodiments of formulas (I) and (III), the following compounds are specifically excluded:

However, in several embodiments of formula (I) and (IV), the following compounds are specifically excluded:

174 201043620 II. Pharmaceutical Compositions In several embodiments, the invention provides a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient. Pharmaceutically acceptable excipients include any and all solvents, diluents or other liquid vehicles, dispersing or suspending aids, surfactants, isotonic agents, thickening agents suitable for the particular dosage form desired. Agent or emulsifier, preservative, solid binder, lubricant, etc. For general considerations in the formulation and/or manufacture of pharmaceutical compositions, see, for example, Remington, s. Pharmaceutical Sciences 16th Edition, EW Martin (Mack Publishing, Co., Pennsylvania) 'Easton' 1980) 'and Remington: Pharmaceutical Science and Practice, 21st ed. (Lippincott Williams &amp; Wilkins, 2005). The pharmaceutical compositions described herein can be prepared by any of the methods known to the pharmaceutical industry. In general, such methods of preparation comprise the steps of combining the active ingredient with a carrier and/or one or more additional auxiliary ingredients, and then shaping and/or packaging the product if required and/or desired. In the desired unit dosage form or multi-dose unit. The pharmaceutical compositions can be prepared, packaged, and/or sold in bulk, in a single unit dosage form, and/or in a plurality of unit dosage forms. As used herein, "unit dosage form" is a divided amount comprising a predetermined amount of active ingredient and a pharmaceutical composition. The amount of active ingredient will generally be equivalent to the dosage of the active ingredient administered to the individual and/or the convenient amount of such dosage, such as one-half or one-third of such dosage. The active ingredient, pharmaceutically acceptable carrier, and/or any additional ingredients and relative amounts in the pharmaceutical compositions of the present invention may vary depending on the 175 201043620 妓, body and/or condition of the individual being treated. The location of the composition is different. For example, the composition may comprise from 0.1% to 100%. /. (w/w) active ingredient. The pharmaceutically acceptable excipients used in the manufacture of the provided pharmaceutical compositions include inert diluents, dispersing agents and/or granulating agents, surfactants and/or emulsifiers, disintegrating agents, binders, and _' Buffer, lubricant, and / or _. For example, cocoa butter and a smear, a coloring agent, a coating agent, a sweetener, a bridging agent, and a fragrance may also be present in the composition. Examples of diluents include carbonic acid dance, sodium sulphate, acid-suppressing mom, acid-filled two-mother, sulfuric acid dance, hydrogen phosphate dance, sodium sulphate 'lactose', cellulose, microcrystalline cellulose, kaolin, mannitol, Sorbitol, inositol, sodium chloride, anhydrous starch, corn starch 'powdered sugar, and the like, and combinations thereof. Examples of granulating agents and/or dispersing agents include potato starch S, corn starch, cassava powder, sodium glycolate powder, clay, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose and wood products, Natural sponge, cation exchange resin, calcium carbonate, strontium salt, sodium carbonate, cross-linked poly(ethylene bismuth bite _) (Cr〇Sp〇vid〇ne), methyl starch Na (sodium starch glycolate), carboxymethyl cellulose, croscarmellose sodium (croscarmellose), methyl cellulose, pregelatinized starch (starch 1500), microcrystalline starch, Water-insoluble starch, calcium carboxymethylcellulose, magnesium aluminum silicate (Veegum), sodium lauryl sulfate, a fourth ammonium compound, and the like, and a composition thereof. Examples of surfactants and/or emulsifiers include natural emulsifiers (eg, acacia, loam, alginic acid, sodium alginate, tragacanth, carrageen, 176 201043620 cholesterol, yellow gum, pectin, gelatin, Egg yolk, casein, lanolin, cholesterol, butterfly, and egg fat), colloidal clay (such as bentonite [石夕酸铭] and vitamin [magnesium aluminum citrate]), long-chain amino acid derivatives, high molecular weight Alcohols (such as stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol ), carbomer (eg carboxypolymethylene, polyacrylic acid, acrylic acid polymers, and eschar polymers), carrageenan, cellulose derivatives (eg sodium carboxymethylcellulose, powder) Cellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose), sorbitan fatty acid esters (eg polyoxyethylene sorbitan monolaurate) [Tween 20], polyoxyethylene ethyl sorbitan [Tween 60], polyoxyethylene Pomelan-oleic acid ester [Tween 80], sorbitan monopalmitate [Span 40], sorbitan monostearate [Shibang 60], sorbitan tristearate Ester [Shibang 65], oleic acid glyceride, sorbitan monooleate [Shibang 80], polyoxyethylene ethyl ester (such as polyoxyethylene ethyl stearate [Myrj] 45], polyoxyethylene ethyl hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol, sucrose fatty acid esters, polyethylene glycol fatty acid vinegar ( For example, Cremophor, polyoxyethylene ether (such as polyoxylauryl ether [Brij 3〇]), poly(vinyl-pyrrolidone), diethylene glycol, laurel Acid ester, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic F68, Poloxamer 188. Cetrimonium, cetylpyridinium chloride, vaporized benzathine rust, sodium docusate, and the like and/or combinations thereof 177 201043620 Examples of cements include starch (eg, corn) starch And starch paste), gelatin, sugars (such as sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol, etc.), natural and synthetic gums (such as acacia, browning Alternaria extract, panwar gum, ghatti gum, oxabago 叩〇1) shell viscous, carboxymethyl cellulose, thiol cellulose, ethyl cellulose, Hydroxyethyl cellulose, hydroxypropyl cellulose, propyl methyl cellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl piroxicam), strontium magnesium aluminum (dimensional rubber), and Larch arabinose galactan), alginate, polyethylene oxide, polyethylene glycol, inorganic calcium salts, phthalic acid 'polymethacrylates', waxes, water, alcohol Classes, etc., and/or combinations thereof. Examples of the preservative include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcohol preservatives, acidic preservatives, and other preservatives. Examples of antioxidants include alpha tocopherol, ascorbic acid, palmitic acid ascorbic acid, butylated fennel, butylated toluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl cholate, ascorbic acid Sodium, sodium bisulfite, sodium sulfoxide, and sodium sulfite. Examples of the meal mixture include ethylenediaminetetraacetic acid (EDTA) and salts and hydrates thereof (for example, sodium EDTA, disodium EDTA, trisodium EDTA, calcium EDTA, EDTA, etc.), citric acid and salts thereof. And hydrates (such as citric acid monohydrate), fumaric acid and its salts and hydrates, malic acid and its salts and hydrates, phosphoric acid and its salts and hydrates, and tartaric acid and its salts Classes and hydrates. Examples of antimicrobial preservatives include benzal chloride rust, gasification 178 201043620 benzyl rust, benzyl alcohol, bronopol, cetrimide, gasified whale base, biting, Chlorhexidine, oxybutanol, chlorhexidine, chloroxylenol, cresol, ethanol, glycerol, hexetidine, imidurea, phenoxyethanol, phenylethyl alcohol, nitric acid Phenylmercury, propylene glycol, and thimerosal. Examples of antifungal preservatives include benzoic acid butyl phthalate, p-benzoic acid benzoate, ethyl p-hydroxybenzoate, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, sorbus Potassium acid 'sodium benzoate, sodium propionate, and sorbic acid. Examples of the alcohol preservative include ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenols, oxybutanol, hydroxybenzoate, and phenylethyl alcohol. Examples of the acidic preservative include vitamin A, vitamin C, vitamin E, /5 carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid. Other preservatives include tocopherol, tocopherol acetate, deteroxime mesylate, meglumine, butylated anisole (BHA), butylated hydroxytoluene (BHT), ethyl Diamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium hydrogen sulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, Glydant Plus 'Phenonip, p-benzoate, Germall 15, Gemaben II, Neolone, Kathon, and Euxyl. In several embodiments, the preservative is an antioxidant. In other embodiments, the preservative is a chelating agent. Examples of the buffer include citrate buffer, acetate buffer, 179 201043620 phosphate buffer, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium gluconate, calcium heptanoate, gluconic acid. Calcium, D-gluconic acid, calcium glycerophosphate, calcium lactate, propionic acid, calcium acetylacetonate, pantothenic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium phosphate phosphate, potassium acetate, potassium carbonate , potassium gluconate, potassium mixture, two test traits, potassium phosphate, potassium phosphate mixture, sodium acetate, sodium hydrogencarbonate, sodium chloride, sodium citrate, sodium lactate, sodium dibasic phosphate, a base Sodium phosphite, sodium phosphate mixture, tromethamine, magnesium hydroxide, hydrogen hydride, alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethanol, and the like, and combinations thereof. Examples of the lubricant include magnesium stearate, calcium stearate, stearic acid, sulphur dioxide, talc, malt, glyceryl sulphate, deuterated vegetable oil, polyethylene glycol, sodium benzoate, acetic acid Sodium, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, and the like, and combinations thereof. Examples of oils include bitter almond oil, almond oil, cool pear oil, Brazilian plucked fruit oil, orange oil, black currant seed oil, borage oil, juniper oil, golden chrysanthemum oil, rapeseed oil, and geranium Seed oil, Brazilian butterfly oil, castor oil, cinnamon oil, cocoa butter, coconut oil, cod liver oil, coffee D non-oil, corn oil, cotton oil, and seedling oil, oyster sauce, evening primrose oil, fish oil, flaxseed Oil, geranium oil, gourd oil, grape seed oil, hazelnut oil, sage oil, isopropyl myristate, jojoba oil, kukui stone oil, lavandin Lavender, lemon oil, mountain pepper oil, Australian walnut oil, mallow oil, mango seed oil, ranch seed oil, oil, nutmeg oil, olive oil, willow oil, Atlantic spine Oil, building net oil, brown paste kernel 180 201043620 oil, peach kernel oil, peanut oil, poppy seed oil, pumpkin seed oil, rapeseed oil, rice bran oil, rosemary oil, safflower oil, sandalwood oil, saguana (sasquana) Oil, peppermint oil, sea air plum oil, sesame oil, shea oil, poly stone oil, Soybean oil, sunflower oil, tea tree oil, Li oil, camellia oil, vetiver oil, walnut oil, wheat germ oil. Examples of oils include, but are not limited to, butyl stearate, caprylic acid triglyceride, capric acid triglyceride, cyclomethicone, azelaic acid diacetate, and deximecin ( Dimethicone) 360, myristic acid isopropyl S, mineral oil, octyldodecanol, oleyl alcohol, polyoxanol, and combinations thereof. Liquid dosage forms for oral and parenteral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and granules. In addition to the active ingredient, the liquid dosage form may contain inert diluents such as water or other solvents, solubilizers and emulsifiers such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, which are commonly used in the art. Propylene glycol, 1,3-butanediol, dimethylformamide, oils (such as cottonseed oil, peanut oil, corn Q oil, germ oil, olive oil, castor oil, and sesame oil), glycerin, tetradecyl alcohol, Fatty acid esters of polyethylene glycols and sorbitans and mixtures thereof. Besides the inert diluent, the oral compositions may include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. In several embodiments for parenteral administration, the conjugate of the present invention is mixed with a solubilizing agent such as Cremophor, alcohols, oils, modified oils, glycols, polysorbates, cyclods. Refined, polymeric, and combinations thereof. Formulations for injection, for example, sterile aqueous or oily suspensions, can be formulated according to known techniques using suitable dissolving or wetting agents and suspending agents. Sterility 181 201043620 Formulation for injection may be a sterile injectable solution, suspension or emulsion in the form of a non-toxic parenterally acceptable diluent or solvent, for example, a solution in 1,3-butanediol. Useful acceptable vehicles and solvents are water, Ringer's solution U.S.P. and isotonic sodium chloride solution. In addition, sterile fixed oils are conventionally employed as a solvent or suspending medium. For this item, any brand of fixed oil may be used, including synthetic monoglyceride or diglyceride. Further, a fatty acid such as oleic acid is used for the preparation of an injection. The injectable preparation may be sterilized by filtration, for example, by filtration through a bacteria-retaining filter, or by sterilizing in a sterile solid composition, which may be dissolved or dispersed in sterile water or other sterile prior to use. Injection medium. In order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be achieved using a crystalline material having a poor solubility in water or a liquid suspension of an amorphous material. The rate of absorption of the drug is then determined by its rate of dissolution, which in turn is determined by crystal size and crystalline form. In addition, delayed absorption of the parenteral dosage form can be achieved by dissolving or suspending the drug in an oil vehicle. Compositions for rectal or vaginal administration are typically suppositories, which are prepared by admixing the conjugates of the invention with a suitable non-irritating excipient or carrier, such as cocoa butter, Polyethylene glycol or suppository wax is solid at ambient temperature, but is liquid at body temperature, so it dissolves in the rectum or in the vaginal cavity to release the active ingredient. Solid dosage forms for oral administration include capsules, troches, pills, powders, and granules. In such solid dosage forms, the active ingredient is mixed with at least one inert 182 201043620 pharmaceutically acceptable excipient or planting agent such as sodium citrate or soy sauce and/or a) filler or enhancer such as powder Class, lactose, Yan sugar, glucose, gamma alcohol' and Shixi Sit 'b) binders such as (tetra) cellulose, brown vinegar, gelatin 'polyvinyl-pyrene ketone, curtain sugar and gold Acacia gum; c) a humectant such as glycerin; d) a disintegrating agent such as agar, calcium carbonate, macadamia or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarder such as petrolatum ; f) absorption accelerators such as tetraammine compounds; g) humectants such as cetyl alcohol and glyceryl monostearate; h) absorbents such as kaolin and bentonite; and i) lubricants such as talc, calcium stearate, Magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, conjugates, and pills, the dosage form may contain a buffer. A solid composition of a similar type can be used as a filler for soft-filling and hard-filling gelatin capsules. The capsules employ the following excipients such as lactose or milk sugar, high molecular weight polyethylene glycols and the like. Solid dosage forms of lozenges, dragees, capsules, pills and granules can be prepared using coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulation industry. Optionally, an opaque agent may also be included and may have a composition that only releases the active ingredient, or selectively released in a delayed manner over a portion of the intestinal tract. Examples of the buried composition that can be used include polymeric substances and waxes. A solid composition of a similar type can be used as a filler in soft and hard-filled gelatin capsules using excipients such as lactose or lactose and high molecular weight polyethylene glycol. The active ingredient may be in the form of a microencapsulation using one or more of the foregoing excipients. The solid dosage forms of lozenges, dragees, capsules, pills, and granules can be prepared by coating and shell preparation, such as enteric coatings, release control coatings, and other formulations known in the art. In such solid dosage forms, the active ingredient may be mixed with at least one inert diluent such as sucrose, lactose or starch. As in the general practice, such dosage forms may contain additional materials other than inert diluents, such as a keying lubricant and other swirling aids such as magnesium stearate and microcrystalline cellulose. In the case of capsules, binders and pills, the dosage form may comprise a buffer. The opaque agent may optionally be included and may be selectively released in a delayed manner only or preferentially over a portion of the intestinal tract. Examples of the buried composition that can be used include polymeric substances and butterflies. Topical administrations and 7 or transdermal administration forms of the compounds of the invention include ointments, pastes, creams, lotions, sizing agents, powders, solutions, sprays, inhalants and/or patches. Typically, the active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier and/or any desired preservative and/or buffer as appropriate. Further, the present invention encompasses the use of transdermal patches, and often has the additional advantage of providing controlled delivery of the active ingredient into the body. Such dosage forms can be prepared, for example, by dissolving and/or dispersing the active ingredient in a suitable medium. Additionally or additionally, the rate of release can be controlled by providing a rate controlling membrane and/or by dispersing the active ingredient in a polymer matrix and/or gel. Suitable devices for the delivery of the intradermal pharmaceutical compositions described herein include short needle devices such as those described in U.S. Patent Nos. 4,886,499, 5,190,521, 5,328,483, 5,527,288, 4,270,537, 5,015,235, 5,141,496, and 5,417,662. The intradermal composition can be administered by a device that limits the effective penetration length of the needle into the skin, as described in PCT Publication WO 99/34850 and its equivalents. It is also suitable to use a liquid jet injector or to pierce the stratum corneum. 184 201043620 A jet injection device that produces a jet to reach the dermis to deliver a liquid vaccine to the dermis is also suitable. The ejector injection device is described, for example, in U.S. Patent Nos. 5,480,381; 5,599,302; 5,334,144; 5,993,412; 5,649,912; 5,569,189; 5,704,911; 5,383,851; 5,893,397; 5,466,220; 5,339,163; 5,312,335; 5,503,627; 5,064,413; 5,520,639; 4,596,556; 4,790,824; 4,941,880; 4,940,460; WO 97/37705 and WO 97/13537. A bullet-type powder/particle delivery device is also suitable for use in a compressed gas form to accelerate the passage of a vaccine in powder form through the outer layer of the skin to the dermis layer. Additionally or alternatively, conventional syringes which are conventionally used in the conventional intracellular administration of the tuberculin test method are also suitable. Formulations suitable for topical administration include, but are not limited to, liquid preparations and/or semi-liquid preparations such as plasters, lotions, oil-in-water emulsions and/or water-in-oil emulsions such as creams, ointments and / or paste, and / or solutions and / or suspensions. Formulations which can be administered topically, for example, comprise from about 丨% to about 10% (w/w) of the active ingredient, but the concentration of the active ingredient can be as high as the solubility limit of the active ingredient in the glutinous gluten. The topical pharmaceutical formulation can further comprise one or more of the additional ingredients described herein. The pharmaceutically acceptable agents of the present invention may be prepared, packaged, and/or sold in a formulation suitable for transpulmonary administration via the nasal cavity. Such formulations may comprise anhydrous particles comprising the active ingredient and having a diameter in the range of from about 0.5 nanometers to about 7 nanometers, or from about 6 meters to about 6 nanometers. Such compositions are conventionally used in dry powder form for administration using a packet of 3 dry powder receptacles which can be directed towards the powder container to disperse the powder and/or use self-propelling solvent/powder dispersion capacity such as 〇3 Ingredients dissolved in and/or (4) Low 185 201043620 boiling propellant device floating in a sealed container. Such powders comprise particles wherein at least 98% by weight of the particles have a diameter greater than 0.5 nanometers, and by number, at least 95% of the particles have a diameter less than 7 nanometers. Additionally, at least 95% by weight of the particles have a diameter greater than 1 nanometer, and by number, at least 90% of the particles have a diameter of less than 6 nanometers. The dry powder composition can include a solid fine powder diluent such as sugar and is conveniently provided in unit dosage form. Low boiling propellants typically include a liquid propellant having a boiling point below 65 °F at atmospheric pressure. Typically, the propellant will comprise from 50% to 99.9% (w/w) of the composition, and the active ingredient will comprise from 0.1% to 20% (w/w) of the composition. The propellant may further comprise additional ingredients such as liquid nonionic and/or solid anionic surfactants and/or solid diluents having the same grade of particle size as the particles that make up the active ingredient. Formulation of the pharmaceutical composition for pulmonary delivery provides the active ingredient in the form of solutions and/or suspension droplets. Such formulations may be prepared, packaged, and/or sold as aqueous and/or diluted alcoholic solutions and/or suspensions, optionally sterile and containing active ingredients, and conveniently nebulized and conveniently used. / or spray device. Such formulations may further comprise one or more additional ingredients including, but not limited to, bridge odorants such as sodium saccharin, volatile oils, buffers, surfactants, and/or preservatives such as hydroxybenzoate. The droplets administered by this route may have an average diameter ranging from about 0.1 nm to about 200 nm. Formulations for pulmonary delivery as described herein can be used for intranasal delivery of the pharmaceutical compositions of the present invention. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle 186 201043620 from about 0.2 microns to about 500 microns. Such a formulation is administered by rapid inhalation through a nasal passage by a powder container held close to the nostrils. Formulations suitable for nasal administration include, for example, low (w/w) and up to 100% (w/w) active ingredients, and may include one or more additional ingredients as described herein. The pharmaceutical compositions of this invention may be prepared, packaged, and/or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of a binder and/or lozenge, prepared using conventional methods, and containing, for example, from 1% to 2% (w/w) of the active ingredient, the difference comprising the mouth soluble and/or The decomposed composition, and optionally one or more additional ingredients as described herein. Additionally, formulations suitable for buccal administration may comprise a powder and/or an aerosolized and/or nebulized solution and/or suspension containing the active ingredient. Such pulverized, aerosolized, and/or aerosolized formulations, when dispersed, may have an average particle size and/or droplet diameter ranging from about 1 nanometer to about 200 nanometers. And may further comprise one or more additional ingredients as described herein. The pharmaceutical compositions of this invention may be prepared, packaged, and/or sold in a formulation suitable for ocular administration. Such formulations may, for example, be in the form of ophthalmic drops, for example, solutions and/or suspensions containing from 0.1% to 1.0% (w/w) of the active ingredient in an aqueous or oily liquid carrier. Such drops may further comprise buffers, salts and/or one or more other additional ingredients as described herein. Other useful ocularly administrable formulations include active ingredients in the form of microcrystalline and/or oligosaccharide formulations. Ear drops and/or ophthalmic drops are intended to be encompassed within the scope of the invention. While the description of the pharmaceutical compositions provided herein is primarily directed to pharmaceutical compositions suitable for administration to humans, those skilled in the art are aware of such compositions. 187 201043620 is generally suitable for administration to a variety of animals. It is well known that pharmaceutically acceptable compositions suitable for administration to humans are suitable for administration to a variety of animals. Pharmacists who are skilled in the art of animal use may use conventional experimental design and/or perform such modifications. General considerations for the formulation and/or manufacture of pharmaceutical compositions can be found in Remington: Pharmaceutical Science and Practice, 21st Edition, Lippincott Williams &amp;

Wilkins, 2005 The present invention further encompasses pharmaceutical packs and/or kits. The kits and kits or kits provided may comprise the provided compositions and containers (eg, vials, ampoules, bottles, syringes, and/or dispensers). Packaging or other suitable container). In some embodiments, the kit set can optionally further comprise a second container comprising an aqueous carrier for proper dilution and or suspension for the formulation of the formulation to be administered to the individual. In some embodiments, the contents of the provided formulation container and solvent container are combined to form at least one unit dosage form. In several embodiments, the compositions provided herein can be used in conjunction with a self-controlled analgesic device (PCA) wherein an individual can administer, for example, an opioid analgesic for pain management as desired. Alternatively, a single container may contain one or more chambers for containing the provided composition and/or a suitable fresh or dilute aqueous carrier. In a preferred embodiment, the &apos;single container is adapted to be modified so that the container can accept physical modifications permitting a combination of chambers and/or individual chamber components. For example, a foil pouch or plastic pouch may contain two chambers separated by a perforated seal that can be broken to allow the contents of the two individual chambers to be combined when the signal is broken. The pharmaceutical pack or kit set thus comprises such a plurality of 188 201043620 chambers including the provided compositions and suitable solvents and/or aqueous carriers suitable for suspension. Alternatively, a guide to use may be additionally provided in the kit of the present invention. These guidelines usually provide instructions on usage and dosage. In other embodiments, the guidelines further provide relevant details regarding specialized instructions for a particular container and/or system for administration. Again, the guide provides special instructions for combining and/or combining additional treatments. In one non-limiting example, the modulating formulation of the present invention can be used in conjunction with an opioid analgesic, optionally comprising the use of a self-controlled analgesic (PC A) device. Thus, the use of the provided formulations - the guidelines may include guidelines for use in conjunction with PCA dosing devices. IH. Use and Treatment Methods The present invention provides a method of treating a condition of a FAAH vehicle comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (1) or a pharmaceutically acceptable form thereof. The invention also provides a method of inhibiting FAAH in an individual comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable form thereof. The invention also provides a method of inhibiting activation of the Faah pathway in vitro or in vitro, comprising allowing the FAAH protein to contact a compound of formula (1) in an amount sufficient to reduce FAAH pathway activation. The invention also provides the use of a compound of formula (I) for use in the treatment of a condition of a FAAH vehicle by an individual. The invention also provides the use of a compound of formula (I) for the manufacture of a medicament. In the right-hand embodiment, the drug is used to treat conditions of the FAAH vehicle. 189 201043620 Expected administration + 个体 Individuals include, but are not limited to, humans (ie males of any age group or +&lt;1&gt;4_ sex, such as pediatric individuals (eg infants, children, adolescents) or adult individuals (you 丨i ± &gt (eg young adults, middle-aged adults or elderly adults) and/or other primates (eg '&amp;

Apes, rhesus monkeys; mammals include commercially relevant mammals such as A cattle, pigs, horses, sheep, goats, cats, and/or dogs; and/or birds include two. Birds related to the dish such as chicken, duck, crane and/or turkey. As used herein and unless otherwise specified, "treatment", "treatment and treatment i, ', / (2) are used to reduce the severity of the disease, sinus disease or condition when the individual has a particular disease, condition or condition or Delaying or slowing down the progression of a disease or condition. "Used here, unless otherwise specified, "preventing," "preventing, and preventing" encompasses the use of an individual to prevent or reduce a disease before it begins to have a particular disease, condition, or condition. The action of the severity of the illness or condition. :: used herein, unless otherwise specified, "administration", "administration", "reporting", etc., and individuals who have already suffered from the disease, disorder or condition to prevent recurrence, and/or prolongation of the condition or condition The term _ 1 and other terms that have already been relieved by the individual, the disease, and the stipulations of the disease, the threshold, the development and/or duration of the disease or condition, or the individual's response to the disease, The way the condition or condition is. As used herein, unless otherwise specified, a "therapeutically effective amount of a compound is sufficient to provide a therapeutic effect in the treatment or management of a disease, disorder or condition, or to delay or reduce one or more of the diseases, conditions or conditions associated with the disease, condition or condition. The number of symptoms. A therapeutically effective amount of a compound means treatment or management of a disease, disorder or condition, alone or in combination, 190 201043620

The number of therapeutic agents for therapeutic effects. "Therapeutic effective amount -:: body =:! Less or avoid disease or condition 2:: The quantitative word for the therapeutic effect of another therapeutic agent may cover the cause of change, or increase as used here, unless... Otherwise, the "preventively effective amount of the compound is sufficient to prevent the disease, condition or condition or condition associated with one or more symptoms: Pre = compound means that the use of the agent alone or in combination with other agents can be effective in preventing the prevention. #Prevention &amp; η 卜 n The condition or the right to treat the number of therapeutic agents for the prevention of rose fruit covers the number that can improve the overall pre-treatment. u stomach" - _ preventive effect disease, illness as used herein, "inhibition", "inhibition", "inhibition" and "inhibitor" are terms that the compound can be reduced compared to the carrier, The ability to suspend or prevent the activity (eg, activity) of specific biological processes within a cell.

"FAAH Media Money" is a disease, condition or condition that inhibits the activity of f. The disease, condition or condition is used interchangeably herein. Conditions of FAAH media include, but are not limited to, pain conditions, inflammatory conditions, immune disorders, central nervous system disorders, neoplasia, depression, anxiety disorders, anxiety related conditions, sleep disorders, eating behavior disorders, dyskinesias, glaucoma, neuroprotection, Nausea and vomiting, sputum and cardiovascular disease. In several supplements, the condition of the FAAH media is a painful condition. As used herein, "pain conditions" include, but are not limited to, neuropathic pain (eg, peripheral neuropathic pain), central nervous system pain, removal of afferent neuralgia, chronic pain (eg, chronic nociceptive pain, and other forms of chronic pain such as post-operative pain). For example, pain after hip, knee or other replacement surgery 191 201043620 pain), surgery pain, noxious receptor stimulation, new pain such as phantom limb pain and temporary acute ") non-inflammatory pain, inflammation Sexual dependence, cancer-related pain, traumatic pain, burn pain, postoperative pain, pain associated with medical procedures, pain associated with premenstrual irritability and/or secrets, pain associated with chronic fatigue syndrome, and Premature-related pain, pain associated with substance abuse and/or addiction (eg withdrawal symptoms), joint pain, arthritic pain (eg pain associated with rheumatoid arthritis, osteoarthritis), lumbar pain Musculoskeletal pain, headache, migraine, muscle pain, lower back pain, neck pain, toothache and tooth #/ and pain, visceral pain, etc. ▲ In several embodiments. The pain condition is neuropathic pain. "Neuropathic pain" - the term refers to pain caused by a nerve injury. Neuropathy Degenerative pain and injury to the charm of the latter is the skin of the skin and connective tissue of the small skin gods, the exact pain of the injury (4). Neuropathic pain typically lasts long or chronic and often develops days or months after the initial acute tissue injury. Neuropathic pain can be I# and persistent spontaneous pain and analgesia, which is a painful response to normal, painless stimuli. Neuropathic pain also has: see s, hyperalgesia is aggravating the usually unimportant pain stimuli such as dental picks. Neuropathic; pain conditions may be in God! The bruises are exhibited, and the resulting pain may last for months or years; == the first damage has healed. Neuronal damage may occur. ^疚^ Back root arsenic, notochord or certain areas of the brain. Nerve; , urinary neuropathy (eg peripheral diabetes, 1; "(4)"; non-specific low back pain; multiple sclerosis d 192 201043620 pain, carpal tunnel syndrome, fibromyalgia; HIV-related neuropathy; Pain such as post-hybrid neuralgia and trigeminal neuralgia; and due to physical trauma, amputation of cancer, chemotherapy-induced pain (such as chemotherapy-induced peripheral neuropathy), chemotherapy, surgery, invasive medical procedures, toxins, burns or infections or Pain caused by chronic inflammatory conditions. Neuropathic pain may be caused by peripheral neuropathy, such as God _; nerve compression; nerve crush, god recording or incomplete God's face; single neuropathy or multiple gods _Change. Neuropathic pain can also be caused by sub-constraints such as square root ganglion compression; spinal cord inflammation; spinal cord contusion, tumor or hemisection, brain stem, hypothalamic or cerebral cortical tumor; or brain stem, hypothalamus or Cerebral cortical trauma. Neuropathic pain syndrome &amp; for diversity is often described as spontaneous emission and tearing pain' or painful money. In addition, this is Pain associated with positive 4 painless feelings such as "pins and needles" (feeling and feeling dull), increased sensitivity to touch (sensation), pain after innocuous stimulation (dynamic, static or hot) Pain abnormalities), increased sensitivity to noxious stimuli (heat, cold, mechanical hyperalgesia), persistent pain (hyperalgesia) after stimuli removal, or absence or defect of selective sensory pathway (hyperalgesia). In some embodiments, the pain condition is non-inflammatory pain and/or inflammatory pain. The categories of non-inflammatory pain include, but are not limited to, peripheral neuropathic pain (eg, pain caused by focal or functional abnormalities of the peripheral nervous system), central nervous system Pain (eg pain due to focal or functional abnormalities of the central nervous system), removal of afferent neuralgia (eg due to sensory nerve input to the central 193 201043620)

In the case of a pain condition (e.g., inflammatory pain or non-inflammatory, sacral nervous system loss of 5 bursts of pain), chronic type of cancer pain, and repeated changes in the injury mass). In some cases, non-inflammatory pain is associated with inflammatory conditions and/or immune conditions. In several embodiments, the condition of the FAAH vehicle is an inflammatory condition. The term "inflammatory condition" means the disease, condition or condition characterized by the following symptoms: pain (dolor, from the production of harmful substances and nerve stimulation), fever (calor), from In vasodilatation), redness (mor, from vasodilation and increased blood flow), swelling (tumor 'from excessive or influx of body fluids), and/or loss of function (function) Function laesa, which may be partial or total, temporary or permanent. Inflammation presents a variety of forms including, but not limited to, acute, adhesive, atrophic, catarrhic, chronic, hard degeneration, diffuse, diffuse, exudative, fibrinous, fibrotic, focal, and swollen. Sexual, hyperplastic, hypertrophic, interstitial, metastatic, necrotizing, occlusive, substantial, plastic, productive, proliferative, pseudomembranous, suppurative, sclerosing, serous, Serous, simple, specific, subacute, vaginal, toxic, traumatic, and/or ulcerative inflammation. Examples of inflammatory conditions include, but are not limited to, inflammation associated with: acne, anemia (eg, dysplastic anemia, gold-soluble autoimmune 194 201043620 anemia), asthma, arteritis (eg, polyarteritis, Transient arteritis, multiple arterial nodules, aortic arch syndrome (high-angstrom arteritis), arthritis (eg, crystalline arthritis, osteoarthritis, dry arthritis, gouty arthritis, reactive arthritis, Rheumatoid arthritis, Wright's joints ^ &amp; straight spine, myositis (or amyl〇SiS), amyotrophic lateral sclerosis, autoimmune disease, allergy or Allergic reactions, atherosclerosis, bronchitis, bursitis, chronic mastitis, gingivitis, Chagas disease (Chagas disease h chronic obstructive pulmonary disease, dermatomyositis, diverticulitis, Diabetes (eg, type 1 diabetes, type 2 diabetes), dermatitis, eosinophilic gastrointestinal disorders (eg, eosinophilic esophagus: inflammation, eosinophilic gastritis, eosinophilic Enteritis, eosinophilia • Crohn's colitis, endometritis, gastrointestinal bleeding, gastritis, gastroesophageal reflux disease (GORD, or its synonym GERD), Qilan-Barr's syndrome, infection, deficiency Bloody heart disease, Kawasaki disease, glomerulonephritis, gingivitis, hypersensitivity, headache (eg, migraine headache, tension headache), choking (eg, postoperative intestinal obstruction and intestinal obstruction during septicemia) ), idiopathic thrombocytopenic purpura, interstitial cystitis, inflammatory bowel disease (IBd) (eg, Crohn's disease, ulcerative colitis, collagenous colitis, lymphocytic colitis, ischemic Colitis 'steering colitis, Bechert's syndrome, non-deterministic colitis), inflammatory bowel syndrome (B s), lupus, multiple sclerosis, hard spot, myasthenia gravis, myocardial ischemia, nephropathy Syndrome, pemphigus vulgaris, pernicious anemia, digestive ulceration, dryness, polymyositis, primary biliary cirrhosis, and brain disorders (eg, Pain, Dudington's disease, and Aziz) Neuritis associated with Herm's disease, Chronic inflammation associated with intracranial radiation injury 195 201043620, pelvic inflammatory disease, reperfusion injury, regional enteritis, wind dysfunction, linear lupus erythematosus, scleroderma 'scather〇d°ma', Sarcoidosis, spondyloarthropathy, Shering's syndrome, thyroiditis 'transplant rejection, tendonitis, trauma or injury (eg, east injury, chemical irritant 'poison m, seam wound, physical injury), blood vessels Inflammation, leukoplakia, and Wegener's granulomatosis. In several embodiments, the inflammatory condition is an acute inflammatory condition (eg, inflammation due to infection). In several embodiments, the inflammatory condition is a chronic inflammatory condition (eg, Inflammation due to asthma, arthritis, and inflammatory bowel disease. The compound can also be used to treat inflammation associated with trauma and non-inflammatory myalgia. These compounds are also useful in the treatment of inflammation associated with cancer. In several embodiments, the condition of the FAAH vehicle is an immune condition. Immune diseases = such as autoimmune diseases including but not limited to arthritis (including rheumatoid arthritis, spondyloarthropathy, gouty arthritis, degenerative joint diseases such as osteoarthritis, systemic lupus erythematosus, sedative syndrome) , ankylosing spondylitis, undifferentiated spondylitis, Becher's disease, hemolytic autoimmune anemia, multiple sclerosis, amyotrophic lateral sclerosis, myositis (or sputum-like degeneration) Amyl〇sis)), acute shoulder pain, dry arthritis, and juvenile = type arthritis) 'asthma, atherosclerosis, osteoporosis, bronchial muscle spasm, skin irritation (eg, dryness, eczema, Burns, skin rashes, ituria, eosinophils, gastrointestinal disorders (for example, inflammatory bowel disease (IBD), &gt; sinusitis, regional enteritis, ventricular inflammation, gastrointestinal bleeding, hum Diseases, gastritis, diarrhea, intestinal cramps, and ulcerative colitis), and Uchida I peristaltic enhancers can improve conditions (eg, intestinal obstruction, postoperative intestinal obstruction 196 201043620 plugs) and intestinal obstruction during septicemia Gastroesophageal reflux disease (Go Rd, or its synonym GERD), eosinophilic esophagitis, gastroparesis such as diabetic gastroparesis; food mismatch and food allergy and other functional bowel diseases, such as non-ulcerative dyspepsia (NUD) and Non-cardiac chest pain (NCCp, including rib cartilage)). In several embodiments, the immune disorder is a gastrointestinal disorder. In other embodiments, the immune disorder is inflammatory bowel disease (eg, Crohn's disease and/or ulcerative colitis), peptic ulcer, regional enteritis, diverticulitis, gastrointestinal bleeding, Crohn's disease, gastritis, Diarrhea, intestinal cramps, and ulcerative colitis. In its embodiment, the immune disorder is inflammatory bowel disease (IBD). In several embodiments, the condition of the FAAH vehicle is a skin condition. In some embodiments, the skin condition is aching (itching), dryness, moist treatment, burns, or dermatitis. In several embodiments, the skin condition is dryness. In several embodiments, the skin condition is itching. In several embodiments, the condition of the FAAH vehicle is anxiety. The term "anxiety Q" is used here, including but not limited to anxiety disorders and anxiety-related conditions, such as bed anxiety, fear, square phobia, generalized anxiety disorder, specific phobia, social phobia , obsessive-compulsive disorder, acute stress syndrome, post-traumatic stress syndrome, adjustment disorder with anxiety characteristics, anxiety disorder associated with depression, anxiety disorder due to systemic condition, substance-induced anxiety disorder, and substance Abuse and/or addiction-related anxiety disorders (eg, withdrawal symptoms, dependence, recovery). The treatment may also induce or promote sleep in an individual (e.g., a cold, an individual). In several embodiments, the condition of the FAAH vehicle is a sleep condition. "Sleep 197 201043620 sleep condition" includes but is not limited to insomnia, sleeplessness, sleep apnea syndrome, restless leg syndrome (RLS), sleep cycle delay syndrome (DSpS), periodic limb movement (PLMD) 'hypopnea syndrome, Rapid eye movement disorder (RBD), working sleep disorder (SWSD), and sleep problems (eg, parasomnia) such as nightmares, night terrors, dreams, head slamming, slamming, and closing tightness and/or Or molars (night bruxism). In several embodiments, the condition of the FAAH media is depression. The term "depression" is used herein to include, but is not limited to, depression or conditions such as severe depression (monopolar depression). ), affective disorder (chronic mild depression), bipolar disorder (bipolar disorder), and seasonal affective disorder, depression associated with substance abuse and/or addiction (eg, withdrawal). Depression can be clinical depression or subclinical depression. Depression can be associated with premenstrual syndrome and/or premenstrual irritability. In several embodiments, the condition of the FAAH vehicle is schizophrenia. In several embodiments, the condition of the FAAH vehicle is dietary behavior. The term "dietary behavior" is used herein to include, but is not limited to, eating disorders (eg, various types of anorexia and cachexia, overeating leading to obesity), cancer-related weight loss, weight loss associated with other systemic diseases, and not Can be associated with weight loss, and other wasting conditions. The compounds disclosed herein are also useful for reducing body fat and treating or preventing obesity in an individual. The compounds disclosed herein are also useful for the prevention or treatment of diseases associated with such health conditions. In several embodiments, the treatment of eating behavior involves a reduction in the weight of the individual. In certain embodiments, the treatment of 'dietary behavior' involves the control of the individual's appetite. In several embodiments, the condition of the FAAH vehicle is a metabolic disorder and/or a lipid disorder. 198 201043620 In several embodiments, the condition of the FAAH vehicle is dyskinesia. In several embodiments, the condition of the FAAH vehicle is cognitive promotion (e.g., 'learning enhancement and memory promotion'). In certain embodiments, the compounds disclosed herein are useful in the treatment of attention deficit disorder. In other embodiments, the condition of the FAAH vehicle is glaucoma. Ο

In a few real hoods, FAAH age money rides are degraded. In still other embodiments, the condition of the FAAH vehicle is neuroprotection. In addition to other embodiments, the money of the FAAH medium is heart disease. The compounds provided can be administered using any of the dosages and routes of administration which are effective for the treatment. The exact amount will vary from individual to individual, depending on individual * j, age and general condition, severity of infection, specific composition, mode of administration, and pattern of activity. The compound provided by j is typically a dosage form of Weicheng. It is convenient to administer the drug. However, it should be understood that the total daily dosage of the composition of the present invention is determined by the clinician in the form of intensive care. (4) Specific individuals or organisms The particular therapeutically effective dose will be determined based on a number of factors, including the disease, condition, or condition of the slave therapy, the severity of the condition, the activity of the particular active ingredient employed, the specific ingredients, and the age and weight of the individual: - general health status, sex and diet; time of administration, route of administration and rate of excretion of the particular active compound employed; duration of treatment; drug in combination or concurrent use with the particular active ingredient employed; and factors well known in the medical industry. The compounds and compositions provided herein can be administered by any route, 199 201043620 including oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, intradermal, transrectal , intravaginal, intra-abdominal, topical (eg, dispersion, ointment, cream, and / or drop dosage form) 'transmucosal, nasal Transvaginal, enteral, sublingual; intratracheal instillation, bronchial instillation and/or inhalation; and/or administration as an oral spray, nasal spray and/or aerosol. The intended route is systemic intravenous, transdermal and/or lymphatic supply to the affected area and/or direct administration to the affected area. Usually the most appropriate route of administration is determined by a number of factors, including the nature of the agent (in the gastrointestinal environment) ), the condition of the individual (eg, whether the individual can tolerate oral administration), etc. The exact amount of the compound required to achieve a therapeutically effective amount will vary from individual to individual 'eg according to the race, age and general condition, side effect or condition of the individual Severity, identity of specific compounds, mode of administration, etc. Expected doses can be administered 3 times a day, 2 times a day, once daily, every other day, every 3 weeks, every week, every 2 weeks, every 3 weeks, or every 4 weeks. In several embodiments, the desired dose can be delivered using multiple administrations (eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 More or more administrations). In several embodiments, daily The treatment of a compound administered 7 or more kilograms in a single or multiple doses is effective | contains a parental dosage form of about 1 mg to about 3000 mg, about 0.0001 mg to about 2000 mg, about 1 mg. To about 1000 mg, about 0.001 mg to about 1000 mg, about 0 01 mg to about 1000 mg, about 0.1 mg to about 1 mg, about 丨 mg to about 1 mg, about 1 mg to About 100 mg, from about 10 mg to about 1 mg, or from about 1 mg to about 1000 mg of the compound of the invention. It is to be understood that the dosage 200 as described herein provides for the administration of the provided pharmaceutical composition to an adult. A guide to administration of a drug, for example, a dose administered to a child or adolescent may be determined by a physician or a skilled practitioner and may be less than or equal to the dose administered to an adult. It will also be appreciated that the compounds or compositions so described may be administered in combination with one or more additional therapeutically active agents. The compound or composition may be used in one or more additional treatments (4), before or after. Each of the active agents will be administered with a dose and/or _ to the mosquito. Step-by-step understanding Ο

Additional therapeutically active agents for use in the present compositions can be administered together in a single composition or separately in separate compositions. The particular compositions used in the present invention will take into account the compatibility of the compounds of the invention with the additional therapeutically active agent and/or the desired therapeutic effect to be achieved. The level of the therapeutic agent used in the usual occupational group is not higher than the level of the side. In the Yu Xuan example, the level of combined use is lower than the level of individual use. The compound or composition can be combined to improve its bioavailability, reduce and/or modify its metabolism, inhibit its excretion, and/or modify the distribution of its body in the air. It is also necessary to understand the effect of the treatment of the disease on the disease (for example, the compound can be combined with anti-inflammatory agents, anti-domains, etc., etc. can achieve different effects (for example, bad by-products = examples of antiviral active agents include but not Limited to anticancer agents, antibiotics, anti-op auxiliaries, anesthetics, anticoagulants, enzyme inhibitors, __ 1 inflammatory or non-steroidal anti-inflammatory agents, anti-M-methylamine, immunization: alcohol anti-tumor agents, antigens, vaccines, Antibody, decongestant, tranquilizer, agent, pain relieving agent, analgesic, antipyretic, hormone, prostaglandin: 201 201043620 Pregnancy, anti-glaucoma agent, ophthalmic agent, anticholinergic agent, antidepressant, Antipsychotics, hypnotics, tranquilizers, anticonvulsants/anti-epileptics (eg, Neurontin, Lyrica, vaipr〇ates (eg, Pascal) epacon) ), and other neuroleptics), muscle relaxants, anticonvulsants, muscle contractions, channel blockers, miotic agents, antisecretory agents, anti-A agents, anticoagulants, anticholinergic agents , β-adrenergic blockers, diuretics, blood Tube active agents, vasoactive agents, vasodilators, antihypertensive agents, angiogenic agents, cell-extracellular matrix interaction regulators (such as cytostatics and anti-adhesive molecules) or DNA, RNA, protein-protein interactions Inhibitor/intercalator for action, protein-receptor interaction. Active agents include small organic molecules such as pharmaceutical compounds (eg, approved by the US Food and Drug Administration (FDA), such as compounds provided in federal regulations (CFR), peptides, proteins, carbohydrates, monosaccharides, sugar collection , nuclear proteins, mucins, lipoproteins, synthetic peptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNA, RNA, nucleotides, nucleosides, Nucleotides, anti-information nucleotides, lipids, hormones, vitamins, and cells. In some embodiments, the additional therapeutically active agent is a pain relieving agent. Examples of pain relieving agents include, but are not limited to, analgesics Such as non-narcotic analgesics [such as salicylates such as aspirin, ibuprofen (MOTRIN, ADVIL), ketoprofen (ketoprofen) ) (ORUDIS), naproxen (NAPROSYN), acetaminophen, indomethacin, or narcotic analgesics [eg Opium analgesics such as 202 2 01043620 Tramadol, fentenyl, sufentanil, morphine, hydromorphone, codeine, oxycodone, and pupp Buprenorphine]; non-steroidal anti-inflammatory agents (NSAIDs) [eg aspirin, etampamine, c〇x_2 inhibitors]; steroids or antirheumatic agents; migraine preparations such as beta adrenergic resistance Broken agent, ergot derivative; tricyclic antidepressant (such as amitryptyline, desipramine, imipramine); antiepileptic (such as clone Naxi half (ci〇) Naxepam), valproic acid, phenobarbital, phenytoin, tiagaine, gabapentin, carbamazepine, topiramide (topiramate), sodium valproate); (3⁄42 agonist; selective serotonin reuptake inhibitor (SSRI), selective norepinephrine absorption inhibitor; benzodiazepine; mexiletine (mexiletine) MEXITIL); Flecainide (TAMBOCOR); N MDA receptor antagonists [eg ketamine, detromethorphan, methadone]; and topical agents [eg capsaicin (Zostrix), EMLA creams, Lidocaine, prilocaine] ° In other embodiments, the additional therapeutically active agent is an anti-inflammatory agent. Examples of anti-inflammatory agents include, but are not limited to, aspirin; ibuprofen; captopril; naproxen; etodolac (LODINE); COX-2 inhibitors such as Celecoxib (CELEBREX), rofecoxib (VIOXX), valdecoxib (Bei 203 201043620 BEXTRA), Pa Parecoxib, etoricoxib (MK663), deracoxib, 2-(4-ethoxy-phenyl)-3~(4_曱石黄-基-phenyl Than sit and [l,5_b] 哄, 4_(2 ketone _3_ 基 · 2,3-dihydro D lip. sit-4-yl) benzoate, darbufelone ), flosulide, 4-(4-cyclohexyl-2-mercapto-5-P, etc., oxazolyl), meloxicam, nimesu Nimesulide, 1-methylsulfonyl-4-(l,l-dimethyl-4-(4-fluorophenyl)cyclopenta-2,4-dien-3-yl)benzene, 4 -(1,5-dihydro-6-fluoro-7-methoxy-3-(trifluoromethyl)-(2)-benzothiopyrano(4,3-c)oxazol-1-yl Benzenesulfonyl, 4,4-dimethyl-2-phenyl-3-(4-mercapto sulphate) base) 3⁄4-butyl quinone, 4- -N-(4-(2- gas-5-dioxyl)-supplementyl-2-yl)-phenylphosphine, 1-(7-t-butyl-2,3-dichloride -3,3-dimethyl-5-benzoquinone-α-fumyl)-4-cyclopropylbutan-1-one, or a physiologically acceptable salt thereof, a hydrazine or a solvate thereof; Sulindac (CUNORIL); diclofenac (VOLTAREN); piroxicam (FELDENE); diflunisal ) (DOLOBID), nabumetone (RELAFEN), oxaprozin (DAYPRO), and dexamethasone INDOCIN)); or steroids such as PEDIAPED prednisolone sodium sulphate oral solution, sedum (SOLU-MEDROL) 曱jipnisolone sodium succinate injection, pree PRELONE brand punisosol syrup. Additional examples of anti-inflammatory agents include Naproxen, commercially available EC-Naprosin (NAPROSYN) delayed release tablets, Naprosin, Anaprox (ANAPROX) and Anaproz DS tablets and Anap Lo Su Suspending Agents, etc. 204 201043620 Formulations are available from Roche Labs, the Xilex brand of Xilex, Loficxi of the Weikeshi brand, and the CELESTONE brand. Betamethasone, penicillamine capsules of the CUPRAMINE brand, titratable penicillamine lozenges of the brand, and methyl esters of the long-lasting Metso brand (DEPO-MEDROL) Sustained release ingots for nislon acetate injection, lavarian leflunomide lozenges, AZULFIDINE EN lozenges brand, sulfasalazine Reed's brand of Pelopixang Capsule, CATAFLAM brand of Coloprofen unloading agent, Futalin brand of cocaine sodium delayed release lozenge, Futalin-XR brand generation Copeprofen sodium extended release lozenge, or ENBREL Race (etanerecept) products. V. Methods of Assaying Biological Activity The assays for the activity of the compounds provided herein for a variety of therapeutic uses are known in the art. These include, but are not limited to, high throughput screening to identify compounds that bind to and/or modulate isolated FA AH activity, as well as in vitro and in vivo therapeutic models. A assay that can be used to screen for the compounds provided herein can detect the reaction product of the inhibitor binding to FAAH or via hydrolysis of an enzyme substrate such as ethanol-brown amine or oleamide (ananadamide). Release of (eg fatty acid amine or ethanolamine). The enzyme substrate can be labeled to assist in the detection of the released reaction product. U.S. Patent No. 5,559,410, the disclosure of which is incorporated herein by reference. Methods for screening the anti-allodynic effects of FA AH inhibitors are disclosed in the art. For example, compounds can be tested in a mouse hot plate assay and a mouse formalin test to measure the pain response to tissue damage caused by heat or chemistry (see, for example, U.S. Patent No. 6,326,156 for an explanation of anti-pain activity screening methods; also reference to Cravatt Etc., Proc. Natl. Acad. Sci. USA (2001) 98:9371-9376) Two experimental models of pharmacologically effective anxiety disorders are elevated zero-maze trials and isolation-induced ultrasound emission assays. The zero labyrinth contains an elevated circular platform with two open quadrants and two closed quadrants based on animal instincts to explore the contradiction between the environment and the animal's fear of open space (see, for example, Bickerdike, MJ et al., Eur. J. Pharmacol. (994) 271, 403-411; Shepherd, J_K. et al., Psychopharmacology, (1994) 116, 56-64). Clinically used anxiolytics such as benzodiazepines increase the proportion of time spent in open compartments and the number of times they enter the open compartment. The second test for anxiolytic compounds is the ultrasonic vocalization model, which measures the number of times the rat's larvae leave a nest to induce a tone-induced sound (see, for example, Insel, T.R_ et al.' Pharmacol. Biochem· Behav., 24, 1263- 1267 (1986); Miczek, K_A. et al., Psychopharmacology, 121, 38-56 (1995); Winslow, JT et al., Biopsychiatry, i5, 745-757 (1991)). The effects of the compounds provided herein for the treatment of depression can be tested in a rat model of chronic mild stress-induced loss of interest. This study model is based on the observation that chronic mild stress causes a gradual decrease in sensitivity to reward rewards. For example, sucrose consumption is reduced, and this reduction can be reversed by dose dependence by long-term use of antidepressant treatment. See, for example, Willner, Paul, Psychopharmacology, 1997, 134, 319-329. Another test for antidepressant activity is the forced swimming test (Nature 266, 730-732 '1977). In this test, the animals were dosed for 3 minutes or 60 minutes before the animals were placed in the water container to record the time during which they remained inactive. The shortening of mouse inactivity time is indicative of anti-depressant activity. A similar test for anti-depressant activity is the mouse tail suspension test (Psychopharmacology, 85, 367-370, 1985). In this test, animals were dosed 30 minutes or 60 minutes before the tail was suspended and recorded for periods of inactivity. The shortening of mouse inactivity time is indicative of anti-agent activity. Animal research models can be used to assess the anti-convulsive activity of test compounds (see, e.g., U.S. Patent Nos. 6,309,406 and 6,326,156). Inhibition of FA AH has been reported to induce sleep in test animals (see, for example, U.S. Patent No. 6,096,784). Methods of inducing sleep compounds are known in the art (for example, see U.S. Patent Nos. 6,096,784 and 6,271,015). The compound can be administered to a test animal (e.g., a rat or mouse) or human and subsequently monitored for time spent on sleep (e.g., closed eyes, motor silence) (e.g., starting point, duration). See also WO 98/24396. Screening methods for FAAH inhibitors that induce tonic fainting are also well known in the art (see, for example, Quistand et al., Toxicology and Applied Pharmacology 173:48-55 (2001); Cravatt et al., Proc. Natl. Acad. Sci. USA 98:9371-9376 (2001)) ° Methods for assessing appetite behavior are well known in the art world (see, for example, US Pat. No. 207, 2010, 436, PCT Patent No. 6,344, 474). - (10) Estimate the effect of appetite redness on the effect of the law on the feeding of large sugars (see, for example, w.c. Lynch et al., Physi〇1, 1993, 54, 877-880). Two pharmacologically effective animal research models for neuropathic pain are the rat spinal nerve junction model (Chung model) and a rat chemotherapeutic induced neuropathic pain model. After these models were used to determine neuropathy, as a measure of mechanical allodynia, the threshold of paw withdrawal was measured using v〇n Frey fibril stimulation (eg, reference to Kim SH&amp;Chung JM, Pain (1992). 50, 355-63; Nozaki-Taguchi N et al., Pain (2001) 93 '69-76). Neuropathic pain medications used on bed 6a, such as Gabapentin (Neuromin), increase the critical value of paw withdrawal when using Feveris fibrils. Two animal models of pharmacologically effective inflammatory pain and mechanical pain were used to treat rat joint compression studies using adjuvants or chemical agents that produce joint degeneration. The use of clinically used anti-inflammatory agents such as naproxen can increase the critical value of behavioral responses to joint compression (see, for example, Wilson AW et al., European Journal of Pain (2006) 10, 537-49; Ivanavicius SA Et al., Pain (2007) 128, 272-282). The pharmacologically effective animal research model for cancer pain is a mouse model in which the root bone is implanted with fibrosarcoma cells to produce hyperalgesia of the foot. Treatment with clinically used analgesics such as D# can increase the critical value of behavioral responses to mechanical pain (see, for example, Khasabova et al., Neuroscience (2008) 28, 11141-52). 208 201043620 The present invention is generally described with reference to the following examples, which are to be construed as illustrative and not restrictive. General Synthetic Method Method 1

General conditions for the preparation of 3-bromo-isoxazolines: olefin (1.2 equivalents) and hydrogencarbonate (2.5 equivalents) suspended in ethyl acetate (relative to olefin 4 〇 M). Add N, N_ two indigo (1.0 eq.) and allow the reaction to stir at 23 ° C for 14 to 28 hours. When the analysis was completed by thin layer chromatography, the reaction was partitioned between water and dibutyl methyl ether. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. Degraded reaction mixture by rapid sulphur dioxide

G chromatography (ethyl acetate/hexanes) purification affords the desired 3-bromo-isoxazoline. Method 2

General conditions for the preparation of the 3-bromo-iso-decane conversion: acetic acid-hydrate (1.0 eq.) and amine hydrochloride (11 eq.) were fed into the flask. The mixture was dissolved in water (2 〇 M relative to glyoxylic acid monohydrate) and stirred at 23 ° C for 24 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was dehydrated with sodium sulfate 209 201043620 and concentrated to give the desired crude product, which was used directly in the subsequent cyclization addition. The hydrazine (equivalent equivalent) obtained from the first step was suspended in dioxane: a 3:1 mixture of water (v/v) (15 M relative to hydrazine) and cooled to 〇t:. N-Bromobutaneamine (NBS) (2.0 eq.) was added and the reaction allowed at 23t: stirred for 2 Torr. The resulting mixture was then added to a solution of an alkene (1 eq. equivalent) and potassium hydrogencarbonate (25 eq.) in dimethoxyethane (15 〇M relative to hydrazine) and the reaction was allowed to stir at 23 C for 2 hr. When the analysis was completed by thin layer chromatography, the reaction was dissolved in water and tributyl decyl ether. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The concentrated reaction mixture was purified by rapid phosgene gel chromatography (ethyl acetate / hexanes) to give the desired 3 bromo s. Method 3

H〇Re NaOH

General conditions for the preparation of 3-aryloxy-isoxazolines or 3-_heteroaryloxy-isooxazolines: Microwave reaction vials for feeding a given 3_bromo-iso. (1_0 equivalent) and alcohol (such as phenol or hydroxypyridinium 3 〇 equivalent) and dissolved in Ν·曱基吼洛 bite (〇5〇Μ relative to isoxazoline). Add crushed sodium hydroxide (2.0 The equivalents and the mixture were sealed and heated in a microwave for 3 Torr at 15 ° ° then the reaction was partitioned between water and tributylmethyl ether, and the organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The concentrated reaction mixture was purified by rapid phosgene gel chromatography (ethyl acetate/hexanes) to afford the desired isoxazoline. 210 201043620 Method 4

Rb ORe -{

N for 3-aryl oxygen _

The preparation of Rdlc is based on the oxygen of the base oxygen and the different ten sittings. #醇J, the internal feeding of the given 3-bromo-iso-octaline (1.0), the butterfly (four) Yang t (four) equivalent) and dissolved in NN Methionine (relative to the different ten sittings for 〇·4, one soil) added sodium nitride (2.0 equivalents): Allow: the reaction was stirred for 10 minutes until the escape of gas ceased. The reaction was then heated to CM1 for 5 hours. After the analysis of the reaction by thin layer chromatography, the solution should be dissolved in water and the third keel, and the organic layer should be i N Na〇H and Weishi, with Wei water and decompression. Concentration of τ. The concentrated reaction w Kun 5 was purified by rapid silica dioxide chromatography (acetic acid ethyl acetate / hexane) to obtain the desired different B. Method 5

H0Re CS2CO3

General conditions for the preparation of 3-aryloxy·iso-n-oxazolines: feeding a given bromine-isoxazoline (1. 〇 equivalent) and an alcohol (eg phenol or hydroxypyrene) in a flask (2. 〇 equivalent) and dissolved in the group ~ dimethylformamide or N-methyl η pirone (relative to oxazoline 〇 15 Μ). Carbonate planer (1.2 to 3 equivalents) was added and the reaction was heated to 12 Torr in an oil bath. It takes 1 hour. The reaction was then dissolved in water and tributylmethyl. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure 211 201043620. The concentrated reaction mixture was purified by rapid phosgene gel chromatography (methanol / di-methane) to afford the desired isoxazoline. Method 6

NaHMDS

〇P(Ph)3MeBr General conditions for the preparation of olefins: under a nitrogen atmosphere, 〇·25 甲基 methyltriphenyl bromine scale (1.1 eq.) is dissolved in tetrahydrofuran and cooled to 0 ° C, then the mixture is six Sodium methotrexate (NaHMDS) was treated dropwise in tetrahydrofuran (1.0 Torr, 1.2 equivalents). After stirring for another 30 minutes at 0 ° C, a given aldehyde or ketone was added and the reaction was allowed to warm slowly to 23 ° C overnight. The mixture was quenched with saturated chlorination and concentrated to remove tetrahydrofuran. The mixture was then diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate sulfate The concentrated reaction mixture was purified by rapid phosgene gel chromatography (ethyl acetate/hexanes) to give the desired dilute. Method 7 nBuLi 〇 P(Ph)3MeBr Ra&gt;. Rb

General conditions for the preparation of olefins: under a nitrogen atmosphere, 〇15 M methyltriphenyl bromide scale (1 _5 eq.) is dissolved in tetrahydrofuran and cooled to -78 C ' and the mixture is then butyl Class (2.5 Μ, 1.5 eq.) is processed dropwise. After stirring at -78 ° C for an additional hour, a given aldehyde or ketone was added and the reaction allowed to warm slowly to 23 ° C overnight. The mixture was quenched with saturated ammonium sulfate 212 201043620 and concentrated to remove tetrahydrofuran. The mixture was then diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate The concentrated reaction mixture was purified by rapid phosgene gel chromatography (acetic acid acetonitrile / hexanes) to give the desired olefin. Method 8 KOtBu 〇 P(Ph)3MeBr Ra, ^Rb

U -π~~ |T

Rd Rc II Rd People Rc

Ra^Rb 〇

General conditions for the preparation of the olefins: 0.12 M methyltriphenylphosphonium bromide (2.5 eq.) was dissolved in tetrahydrofuran under a nitrogen atmosphere, followed by the addition of potassium tributoxide (4.0 eq.) in six portions. After further stirring at 23 ° C for 1 hour, a given aldehyde or ketone was added and the reaction was heated to 55 ° C for 2 hours. The mixture was quenched with saturated ammonium chloride and concentrated to remove tetrahydrofuran. The mixture was then acidified to pH 5-6 with 1 NHC1 and extracted with dichloromethane. The organic layer was washed with brine and dried over sodium sulfate and evaporated. The concentrated reaction mixture was purified by rapid phosgene gel chromatography (ethyl acetate/hexanes) to give the desired oxime. Method 9

General conditions for the preparation of styrene: aryl bromide (1_0 equivalent), potassium trifluoroborate (1.2 equivalents), 1,1"-indole (diphenylphosphine) in an anhydrous flask under an argon atmosphere )-Palladium dichloropalladium (II) dichloromethane adduct (0.02 equivalents) 213 201043620 and triethylamine (1.0 equivalents) and the mixture suspended in isopropanol (0.25 M relative to aryl bromide) and at 80 After heating for 2 to 24 hours, the mixture was diluted with water and extracted with diethyl ether. The organic layer was washed with brine and then dried over magnesium sulfate and concentrated under reduced pressure. Purification (ethyl acetate/hexanes) affords the desired styrene.

General conditions for the preparation of styrene: aryl bromide (1.0 eq.), tributylvinyltin (1.1 eq.) and dissolved in toluene (0.3 M relative to bromide) were fed in an anhydrous flask under a nitrogen atmosphere. ). The resulting mixture was further purged with nitrogen for 10 minutes, then hydrazine (triphenylphosphine)palladium (0.1 eq.) was added and the reaction was refluxed for 1.5 hr. After the completion of the reaction by TLC analysis, it was allowed to cool and immediately loaded onto the cerium oxide gel column, where it was purified by rapid phosgene gel chromatography (ethyl acetate/hexane). Expected phenelzine. Method 11

General conditions for the hydrolysis of pyridyl and pyrimidinyl dihydroborate to their corresponding phenols: a given diboric acid or its ester (1.0 equivalents) is fed in a flask 214 201043620

Concentration under pressure until all tetrahydrofuran was removed. :temperature. After 40 minutes, the reaction was carried out. The obtained solid was collected by vacuum filtration, washed with excess water and dried in a vacuum oven at 4 Torr for 3 days to obtain the desired phenol, 80% yield. For palm-wise HPLC methods • Enantiomeric or diastereomeric mixtures of compounds can be prepared using known methods including palm oil high pressure liquid chromatography (HPLC). Examples of palm-shaped HPLC columns that can be used to isolate mixtures of such compounds of the invention include, but are not limited to, Chiral Pak AD-H, Cairo Pike OD-H, Cairo Pike AY, Regis Pack, and ss. LUX and LUX cellulose 2 HpLC column. One or more of such columns are used to separate the enantiomeric mixture of the compounds of the invention to obtain substantially enantiomerically pure compounds. EXAMPLES Synthesis of Compounds of Formula I The synthesis of the exemplified compounds is set forth below. The compounds were assayed as human FAAH inhibitors using the method described in detail in Example 351. The activity is indicated by "A" indicating a compound having less than or equal to 1 〇〇 nM Ki, "B" indicating a compound having ΙΟΟηΜ to 1 μΜΚ; and "C" indicating a compound having greater than or equal to 1 μΜΚί. 215 201043620 Example 1

M a Mb (Ι-Ϊ) 3- Desert-4,5-dihydroisoxazole I-1a and Mb were prepared from styrene in a one-step procedure using Method 2. These compounds are isolated using the HPLC method known to the art. For example, refer to the palmar hPLc method disclosed herein. [M-H]-=225.〇m/z. Activity: b example 2

1-2 笾 _-2b (1-2) 3-bromo-4,5-dihydroisoxazole^ and j_2b were prepared in a one-step procedure from 4-fluorostyrene. These compounds are known to the skilled artisan

Separated by military HPLC method. For example, refer to the palm hplc method disclosed herein. Activity: B Example 3

3_Bromo-4,5-dihydroisoxazole and I-3b were prepared in a one-step procedure from 4-chlorostyrene. These compounds are isolated using a palmitic HPLC method known in the art. For example, refer to the article to read the HpLc* method. [Μ-Η]-=259·〇 m/z. Activity: a 216 201043620 Example 4

3-Bromo-4,5-dihydroisoxazoles I-4a and I-4b were prepared in a one-step procedure from 3-styrene styrene. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=258.9 m/z. Activity: B. Example 5

(1-5)

3-Bromo-4,5-dihydroisoxazole 1-5 &amp; and 1-51) were prepared in a one-step procedure from 3-styrene styrene. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=258.9 m/z. Activity: B. Example 6

3-Bromo-4,5-dihydroisoxazoles I-6a and I-6b were prepared in a one-step procedure from 4-methoxystyrene using Method 2. These compounds are isolated by the palm HPLC method using 217 201043620 known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=255.0 m/z. Activity: A. Example 7

OMe OMe

3-Bromo-4,5-dihydroisoxazoles I-7a and I-7b were prepared in a one-step procedure from 3-methoxystyrene. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=255_0 m/z. Activity: B. Example 8

MeO

\-$b (1*8) 3-Bromo-4,5-dihydroisoxazole 1-8&amp; and 1-81) were prepared in a one-step procedure from 2-methoxystyrene. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=255.0 m/z. Activity: C. Example 9

L-da l-9b (1-9) 218 201043620 3-bromo-4,5-diisoisoxazole 1-9&amp; and 1-91) using method 2 in a one-step process from 4-vinylbiphenyl preparation. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=301_6 m/z. Activity: A. Example 10

M Oa 1-1 Ob 〇 (hm 3-bromo-4,5-dihydroisoxazole I-10a and I-1 Ob are prepared in a step by step from 4-phenyloxystyrene. These are prepared. Compounds are isolated using the HPLC method known to those skilled in the art. For example, refer to the palmarity HPLC method disclosed herein. [MH]-=317_0 m/z. Activity: A. Example 11

3-Bromo-4,5-dihydroisoxazole 1-11&amp; and 1-1113 are prepared in two steps starting from the formation of 3-phenyloxybenzaldehyde using Method 8 followed by cyclization using Method 2. addition. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=317.0 m/z. Activity: A. Example 12 219 201043620

M 2a H2b (M2) 3-bromo-4,5-dihydroisoxazole 1-123 and 1-1213 were prepared in two steps starting from the use of Method 8 from 4-(pyridin-3-yloxy)benzaldehyde. The formation of the alkene is followed by the cyclization addition using Method 2. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ-Η]-=318·0 m/z. Activity: A. Example 13

N3a M 3b (1-13) 3-bromo-4,5-dihydroisoxazole I-13a and I-13b are prepared in two steps starting with the use of Method 8 from 4-(pyrimidin-2-yloxy) The formation of benzalkenes is followed by the cyclization addition using Method 2. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=319.0 m/z. Activity: A. Example 14

M 4a l-14b (1-14) 220 201043620 3-Dist-4,5-dihydroiso----------------------------------------------------------------- Then, for the use of the method of cyclization addition. These compounds are isolated using the palmitic HpLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=309.6 m/z. Activity: A. Example 15

Ο 3-Bromo-4,5-dihydroisoxazole I-15a and I-15b are prepared in two steps starting from the formation of 4-isopropoxybenzaldehyde using Method 8 followed by the use of Ring 2 Addition. These compounds are isolated using the palmitic HpLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=238.0 m/z. Activity: A. Example 16

221 201043620 Example 17

3-Gas-4,5-dihydroisoxazole i_i7a and I-17b were prepared using a similar procedure to that of Example 1 except that N-gasbutylidene was used instead of N-bromobutylamine. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=273.1 m/z. Activity: A 〇 Example 18

3_Bromo-4,5·dihydroisoxazole is prepared in two steps, starting with the use of Method 9 from the formation of 3-(4-indifferent oxygen)_6_曱心荅荅, followed by the use of Ring 2 Addition. These compounds are isolated using the palmitic HPIX method known in the art. Example (6) refers to the palm sail method disclosed herein. [M-H]-=333.0 m/z. Activity: b. Example 19

222 201043620 3-Bromo-4,5-diisoisoxazole 1-19&amp; and 1-1% were prepared in two steps starting from the use of Method 9 from 2-(4-bromophenyl)-5-phenyl The formation of -1,3.4-oxadiazole is followed by the cyclization addition using Method 2. These compounds are isolated using the HPLC method known to those skilled in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M-H]-=369.0 m/z. Activity: A. Example 20

I-2〇b 3-bromo-4,5-diisoisoxazole I-20a and I-20b are prepared in two steps, starting with the formation of 4-butoxybenzaldehyde using method 8 followed by the method of use. 1 cyclization bonus. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=297.0 m/z. Activity: A. Example 21

3-Bromo-4,5-dihydroisoxazole 1-213 and 1-211) were prepared in two steps starting with the coupling of 4-vinylbenzoic acid with benzyl alcohol as follows: 4-vinylbenzoic acid ( 1.0 equivalent) was dissolved in N,N-dimercaptocarbamide (0.20 M relative to the acid). Benzyl alcohol (2.0 equivalents) was added followed by EDC (1.05 equivalents) and a catalytic amount of DMAP (0.05 equivalents). The reaction was allowed to stir at 23 ° C for 14 hours, then the reaction 223 201043620 was dissolved in water and tert-butyl decyl ether, and the organic layer was washed with 0.5 Μ citric acid solution (2 times) and washed with saturated sodium bicarbonate solution ( 1 time), dehydrated with magnesium sulfate and concentrated under reduced pressure. The concentrated reaction mixture was purified by rapid phosgene gel chromatography (ethyl acetate/hexanes) to afford the desired ester. This compound is then converted to the desired 3-bromo-4,5-dihydroiso Dfazole using Method 1. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=359.8 m/z. Activity: A 〇 Example 22

The α-22) 3-bromo-4,5-dihydroiso 11-azoles 1-223 and 1-2213 were prepared using a similar procedure to that of Example 21 except that benzylamine was used instead of benzyl alcohol. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=358.9 m/z. Activity: Β. Example 23

3-Phenoxy-4,5-dihydroiso[1 azole 1-23&amp; and 1-2313 were prepared in a one-step procedure using Method 3, Compounds 1-10 and phenol. These compounds are isolated using the HPLC method known to those skilled in the art. For example, reference is made to the palm 224 201043620 HPLC method disclosed herein. [M-H]-=331.10 m/z. Activity: C. Example 24

α*24) 3-Phenoxy-4,5-dihydroisoxazole I-24a and I-24b were prepared in a one-step procedure using Method 4 from Compounds M0 and 4-fluorophenol. These compounds are isolated using the palmitic HP L C method known in the artisan community. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+=350.3 m/z. Activity: C. , example 25

(1-25) 3-Phenoxy-4,5-dihydroisoxazole 1-25a and I-25b were prepared in a one-step process using Method 4, 1-10 and 3-fluorophenol. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+=349.3 m/z. Activity: B. Example 26

3-Phenoxy-4,5-dihydroisoxazole 1_26&amp; and 1-2613 were prepared in a one-step procedure using Method 4 from Compounds 1-10 and 3-trifluoromethylphenol. These compounds are isolated by the 225 201043620 method known to the art for palm chromatography. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=400.3 m/z. Activity: C. Example 27

NC

3-Phenoxy-4,5-dihydroisoxazole 1-273 and 1-2713 were prepared in a one-step procedure using Method 3, Compounds 1-10 and 4-cyanophenol. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [Μ-Η]-=356·1 m/z. Activity: A. Example 28

L-28b

3-Phenoxy-4,5-diisoisoxazole I-28a and I-28b were prepared in a one-step procedure using Method 4, Compounds 1-10 and 2-cyanophenol. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+=357.3 m/z. Activity: C. Example 29

1-291) 0*29) 226 201043620 3-Phenoxy-4,5-dihydroiso. number. The i-29a and I-29b systems were prepared in a one-step process using Method 4 and Compounds 1-10 and 4-nitrophenol. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+=376.8 m/z. Activity: B. Example 30

··3〇) 3-Oxygen_4,5_Dihydroisoindole 〇I_3〇a and I-30b are used in a one-step process from compound 1-10 and 4-methylsulfonylphenol. preparation. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M_H]_=409.0 m/z. Activity: a. Example 31

(1-31) 3_phenoxy-4,5-dihydroisoxazole^ and the ratio are prepared by the method 4 using the compound I-1G and the 4-methyl_3_fluoro_-step. These compounds are isolated by the t'ft HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=364.4 m/z. Activity: c. Example 32 227 201043620

Racemic compounds 1-10 (1.0 eq.) and aniline (4.0 eq.) were fed in a microwave reaction vial. The mixture was sealed and heated in a microwave reactor at 150 °C for 2 hours. The reaction mixture was dissolved in water and EtOAc (EtOAc m. The concentrated reaction mixture was purified by rapid silica dioxide chromatography (ethyl acetate/hexane) to give the desired 3-amine-4,5-dihydroisoxazole 1-323 and 1-321) . These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=330.1 m/z. Activity: c. Example 33

L-33a μ331ι

1-(4,5-Dihydroisoxazolyl)pyridine_2_(1H)__I_33a&amp;I_33b is used in a one-step preparation of these compounds using the method 3 It is known in the branch art to separate palmar ^pLC methods. For example, refer to the palm muscle C method disclosed herein [M-H]-=332.1 m/z. Activity: c. Example 34 228 201043620

(1-34) The racemic compound 1-10 (1.0 equivalent) and the sodium salt of 1,2,4-triazole (2.0 equivalent) were fed in a microwave reaction vial. These reactants were dissolved in N-methylpyrrolidine (0.18 M relative to Compound 1-10). The mixture was sealed and heated in a microwave reactor at 10 ° C for 30 minutes. Excess water and brown solid were added to precipitate, and the desired 3-(1Η-1,2,4-triazol-1-yl)-4,5-dihydroisoxazole _34a and I were obtained by vacuum filtration and drying. -34b. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=306.1 m/z. Activity: C. Example 35

(1-35) Q pyrazole (3. decyl) is dissolved in N,N-dimethylformamide (0.60 Μ vs. pyrazole) and NaH (60% in mineral oil dispersion, 3.0 eq.) and The reaction was allowed to stir under nitrogen for 5 minutes. The racemic compound (M〇) is then added. The reaction was then heated to 90 ° C for 14 hours and then cooled and quenched with methanol (〇·3〇 μ vs. pyrazole). The crude product mixture was directly purified by cotton filtration and by semi-preparative reverse phase chromatography to give the desired 3-(1 -pyridazole small group) -4,5-diazepine I-35a and 1-3%. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm hplc method disclosed herein. [Μ+Η]+=306·4 m/z 〇 Activity: C 0 229 201043620 Example 36

3-(Pyridin-4-yloxy)-4,5-dihydroisoindole I-36a and I-36b were prepared in a one-step procedure using Compound 3 from Compound 1-10 and 4-hydroxypyridine. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=332.1 m/z. Activity: C. Example 37

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-37a and I-37b are used in a one step from racemic compounds 1-10 and 3-hydroxypyridine using method 3 or method 5. Preparation. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=332.1 m/z. Activity: A. Example 38

230 201043620 (° ratio D, 3-yloxy)_4,5-dihydroisoxazole I-38a and I-38b were prepared in a one-step process from #旋旋化合物16 and 3. These aliquots are separated using the HPLC method known to the art. For example, reference is made herein to &gt; I &amp;&lt;&lt;&gt;&gt; [M-H]-=270.1 m/z. Activity: B. Example 39

Ο (1-39) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-39a and I-39b are used from racemic compound 1-1 using method 3 or method 5 Methyl 5-hydroxynicotinate was prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=392.2 m/z. Activity: A. Example 40

❹ 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-40a and I-40b using Method 4 from racemic compounds 1-10 and 5-hydroxy-2-methylpyridine Prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=346·1 m/z. Activity: Α. Example 41 231 201043620

3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole 1-41 &amp; and 1-411) using method 3 from racemic compounds 1-10 and 5-hydroxypyrimidine in one step preparation. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=333.1 m/z. Activity: A 〇 Example 42

3-(quinolin-3-yloxy)-4,5-dihydroisoxazole I-42a and I-42b are used in a one-step process using racemic compounds 1-10 and 3-hydroxyquinoline preparation. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=382.1 m/z. Activity: A. Example 43

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-43a and I-43b are used in a method 3 from racemic compounds 1-10 and 5-fluoro-3-hydroxypyridine. Prepared in steps. These compounds are isolated using a palmitic HPLC method known in the art. Example 232 201043620 See the palmar HpLC method as described herein. [M H ho" m/z. Activity: A. Example 44

〇3-(1-Methyl-1H-pyrrolo[2,3_b]pyridine-5-yloxy)_4,5-dihydroisoindolyl I-44a and I-44b using method 3 from racemic compound 1_1 hydrazine and 1 methyl '-1H-pyrrolo[2,3_b]pyridine-5-phenol were prepared in a one-step procedure. These compounds are isolated using the HPLC method known to the art. For example, refer to here • Uncover the palmitic HPLC method. [M-H]-=385.1 m/z. Activity: B. Example 45

(1*45) The racemic compound M〇 (1 〇 equivalent) was fed in a vial and dissolved in decyl alcohol (0.05 Μ relative to isoxazole). Add potassium carbonate (5 〇 equivalent) and the reaction is sealed and heated to 50 (: 24 hours. Then the reaction is dissolved in water and acetic acid, and the organic layer is washed with brine, dehydrated with sodium sulfate and under reduced pressure. The concentrated reaction mixture was purified by rapid flash chromatography (acetic acid ethyl acetate / hexane) to obtain the desired methoxy-4,5-dihydroisoxazole and I-45b. Such compounds can be prepared by the art, and the HpLC method is divided into 233 201043620. For example, refer to the palmitic HPLC method disclosed herein. [Μ-Η]-=269·1 m/z. Activity: c. Example 46

(1*46) 3 octyl -3-yloxy)-4,5-dihydroisoxazole I-46a and I-46b using method 5 from racemic compounds 1-14 and 5-hydroxynicotine The acid esters are prepared in a one-step process using a palmitic HPLC method known in the art, for example, with reference to the palmitic HPLC method disclosed herein. [M+H]+= 384.0 m/z. Activity: B. Example 47

The racemic compound 1-39 was dissolved in ammonia in methanol (7·〇 in methanol, 0.02 Μ relative to isoxazole). The reaction was sealed and allowed to stir at 23 ° C for 24 hours, then the solvent and excess ammonia were removed under a nitrogen stream to afford a pale brown solid. The solid was dried using hexanes to afford the desired amides I-47a and I-47b as white solid. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=374.0 m/z. Activity: b. Example 48 234 201043620

3-Bromo-4,5-dihydroisoxazole 1-48&amp; and 1-481? were prepared in one step from 3-phenyl-1-propene using Method 2. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M-H]-=239.0 m/z. Activity: C.

Example 49

3-Bromo-4,5-dihydroisoxazole 1-49&amp; and 1-4% were prepared in one step from 4-phenyl-1-butene using Method 2. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M-H]-=253.0 m/z. Activity: B. Example 50

I tear (I-S0) phenol (1.0 eq.) was dissolved in ethanol (0.5 Torr vs. phenol) and sodium hydroxide (1.0 eq.) was added followed by 4-bromo-1-butene. The mixture was heated under reflux for 1 hour, then most of the solvent was removed under reduced pressure. The reaction is then dissolved in water and the third butyl methyl ether, and the organic layer is washed with brine, dried over sodium sulfate and concentrated under reduced pressure 235 201043620 to give the crude product olefin, which is directly converted into the desired 3 in one step. -Bromo-4,5-dihydroisoxazole 1-5 (^ and 1-5013. These compounds are isolated using the PLC method known to the artisan. For example, refer to the palmar HPLC method disclosed herein. [MH]; 269.0 m/z. Activity: Β. Example 51

Br

i-S1a l«S1b (1-51)

Phenol (1.2 eq.) was dissolved in N,N-dimercaptocarbamide (0.4 M vs. phenol) and carbonated (1.3 eq.) was added followed by 5 bromo-1-pentene (1.0 eq.) and tetrabutyl iodide Base (0.10 equivalent). The mixture was heated to 50 ° C for 16 hours. The reaction mixture was dissolved in water and EtOAc (EtOAc) eluted The crude product alkene is directly converted to the desired 3-bromo-4,5-dihydroisoxazole I-51a and I-51b in a single step using Method 2. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=283.0 m/z. Activity: A. Example 52

L*52a (1-52) 2-Phenylethanol (1.0 eq.) is dissolved in hydrazine, hydrazine-dimethylformamide (〇·8 Μ vs. alcohol) and added crushed sodium hydroxide (2.0 eq.) Allyl bromide (1.0 eq.) and tetrabutylammonium iodide (0.10 eq.) were added. The mixture was stirred at room temperature for 48 236 201043620 hours. The reaction was partitioned between water and tributylmethyl ether, and the organic layer was washed with dilute Na.sub.2SO.sub.3 and brine, dried over sodium sulfate and concentrated under reduced pressure. The concentrated reaction mixture is purified by rapid phosgene gel chromatography (ethyl acetate/hexanes) to obtain the desired alkene which is directly converted to the desired 3-bromo-4,5- using one step. Dihydroisoxazole 1-523 and 1-5213. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=285.6 m/z. Activity: B.

Example 53

Racemic compound 1-46 was dissolved in ammonia in methanol (7.0 Μ in methanol, 0,02 Μ relative to isoxazole was sealed and allowed to stir at 23 for 72 hours, then solvent and excess ammonia were removed under a stream of nitrogen. Light brown solid, solid

The desired brewed amines I-53a and I-53b were obtained as a white solid using a hexane-type wet milling. These compounds are isolated using the palmar HPLc method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=366.0 m/z. Activity: b. Example 54

The ocf3 racemic compound 1-46 was dissolved in ammonia to methylamine (2 () tetrazolium 237 201043620 ran, 0.02 Μ relative to isoxazole). The reaction was sealed and allowed to stir at 23 &lt;0&gt;C for 72 hours, then solvent and excess ammonia was removed under a nitrogen stream to afford a light brown solid, and solid solids using hexanes to afford the desired amines I-54a and I-54b as a white solid. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=380.0 m/z. Activity: Α. Example 55

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-55a and I-55b were used in the method 5 from racemic compounds I - 4 and methyl 5-hydroxynicotinate It was prepared in one step and separated as a by-product from the reaction during rapid cerium oxide gel chromatography. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=367.0 m/z. Activity: C. Example 56

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-56a and I-56b are used in the method 5 from the racemic compounds 1-10 and 5-hydroxy-2-trifluoromethyl Pyridine is prepared in a one step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=401·5 238 201043620 m/z. Activity: A. Example 57

3-(1Η-pyrrolo[3,2-b]pyridin-6-yloxy)-4,5-dihydroisoxazole 1-57&amp; and I-57b using method 5 from racemic compound 1- 10 and 1H-pyrrolo[3,2-b]pyridine-6-phenol were prepared in a one-step procedure. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M-H]-=370.0 m/z. Activity: A. Example 58

CN CN

3-Phenoxy-4,5-dihydroisoxazole 1-58&amp; and 1-5813 were prepared in one step from the racemic compounds 1-10 and 3-cyanophenol using Method 5. These compounds are isolated by the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=356.8 m/z. Activity: B. Example 59

239 201043620 3-Phenoxy-4,5-dihydroisoxazole i-59a and I-59b were prepared in one step from the racemic compounds 1-10 and 2-fluorophenol using Method 4. These compounds are isolated by the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=350.3 m/z. Activity: B. Example 60

3-Phenoxy-4,5-dihydroisoxazole i_6〇a and I-60b are used in one step from racemic compounds 1-10 and 4-fluoro-3-(trifluorodecyl)phenol. Preparation. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. Activity: C. Example 61

(1-61) 3-Phenoxy-4,5-dihydroisoxazole l-61a and I-61b are used in a one-step process using racemic compound I-10 and methyl 3-hydroxybenzoate. preparation. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=390.5 m/z. Activity: A. Example 62 240 201043620

(1-62) 3-Phenoxy-4,5-dihydroisoxazole I-63a and I-63b were used in a one-step procedure using racemic compound I-10 and methyl 4-hydroxybenzoate. preparation. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=389.7 m/z. Activity: Α.

Example 63

3-Phenoxy-4,5-diisoisoxazole I-63a and I-63b were prepared in one step from the racemic compound 1-10 and 3-(methylsulfonyl)phenol using Method 4. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=409.0 m/z. Activity: C. Example 64 NH2 nh2 0=8=0 0=8=0

3-Phenoxy-4,5-dihydroisoxazole 1-64&amp; and 1-6 flue using method 5 from external 241 201043620 racemic compound 1-10 and 3-hydroxybenzenesulfonamide are prepared in one step . These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=409.0 m/z. Activity: C. Example 65

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-65a and I-65b are used in the method 5 from racemic compounds 1-10 and 5-methoxypyridin-3-ol. Prepared in one step. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=363.2 m/z. Activity: A. Example 66

3-(Pyrimidine-5-yloxy)-4,5-dihydroisoxazole I-66a and I-66b were prepared in a one-step procedure from racemic compound 1-10 and 5-hydroxypyrimidine using Method 5. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=364.6 m/z. Activity: A. Example 67 242 201043620

(1-67) 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-67a and I-67b using method 3 from racemic compound j; -10 and 5-hydroxypyridine Methyl decanoate is prepared in a one-step format. These compounds are isolated using a palmitic HPLC method known in the art, for example, with reference to the palmitic HPLC method disclosed herein. [M+H]+=392.1 m/z. Activity: a. Example 68

(1-68) 3-(1Η-吼 并[2,3-b].pyridin-5-yloxy)-4,5-dihydroisoxazole and I-68b use method 5 The compound 1_1〇 and 111 pyrrolo[2,3_b]pyridine-5-phenol were prepared in a one-step procedure. These compounds are isolated using the palmar HPL C method known in the art. For example, reference is made to the palm HPLC method disclosed herein. [M-H]-=370.0 m/z. Activity: A. Example 69

(149) Furan[3,2-b] from 6-(4,4,5,5-tetramethyl-1,3,2-dioxaboron_2_243 201043620). Preparation of furo[3,2-b]pyridine-6-phenol by pyridine, using Method 5 from racemic compound 1-10 and furo[3,2-b]pyridine-6-phenol in two-step preparation 6-(4,5-Dihydroisoxazol-3-yloxy)furo[3,2-b]pyridine I-69a and I-69b. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=374·2 m/z. Activity: A. Example 70

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-70a and I-70b were prepared in one step from racemic compounds 1-14 and 3-hydroxypyridine using Method 5. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=324.l m/z. Activity: A. Example 71

(1-71)

Off3 mb 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-71&amp; and 1-7113 using method 5 from racemic compounds 1-14 and 5-bromo-3-hydroxy Pyridine is prepared in a one step process. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=402.5 m/z. Activity: A. 244 201043620 Example 72

Racemic compound 1-71 (1.0 eq.), phenyl dihydroxyboronic acid (丨^ equivalent) 'potassium acetate (1.0 eq.), carbonic acid planer (3 〇 equivalent), and dichloro [u, 贰 (diphenyl) The phosphine)ferrocene]palladium(II) dichlorodecane adduct (14 m〇i%) was suspended in mM DMSO and scrubbed with argon. The resulting mixture was sealed and heated to 8 Torr. 〇 1 hour. The crude product mixture was transferred to a separatory funnel with excess water and extracted with decyl second butyl (2 times). The organic layers were combined, dehydrated with sodium sulfate and purified using rapid cerium oxide gel chromatography (gradient 2% to 1% sterol) to give the desired 3-(.pyridin-3-yloxy)-4. 5-Dihydroisoxazoles 1-72a and I-72b were obtained as a white solid. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=4〇2 3 m/z. Activity: B. Example 73

Racemic compound 1-71 (1. 〇 equivalent), 3-aminoformylphenyl dihydroxyboronic acid (1.1 eq.), potassium acetate (1.0 eq.), cesium carbonate (3,0 eq.), and Chloro[1,1 '-Wu (diphenylphosphino)ferrocene] (η) dichloromethane adduct (丨4 m〇i%) was suspended in 1 ml of DMSO and purged with argon. The resulting mixture was sealed and heated to 80 ° C for 1 hour. The crude product mixture was transferred to a separatory funnel 245 201043620 with excess water and extracted with methyl tert-butyl (2 times). The organic layers were combined, purified by sodium sulfate dehydration and purified using rapid pyrochlore gel chromatography (gradient 2% to 1% methanol) to obtain the desired 3-(.by _3-yloxy)-4 The 5-dihydroisosines saliva i_73a and I-73b were white solid. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm hplc method disclosed herein. [M-H]-=442_0 m/z. Activity: A. Example 74

Br l*T4e l-74b (1-74) 3-bromo-4,5-dihydroisoxazole is prepared in a one-step process using Method 1 from 4-methylbenzoic acid oxime ester. The compounds are isolated using the HPLC method known to the art. For example, refer to the palmitic HPLC method disclosed herein. [M+H]+=283.6 m/z. Activity: A. Example 75

3-Bromo-4,5-dihydroisoxazole I-75a and I-75b are prepared in two steps starting from the formation of alkene from 4'(trifluoromethoxy)acetophenone using method 6 followed by the method of use. 1 cyclization bonus. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=323.0 m/z. Activity: A. 246 201043620 Example 76

3-Bromo-4,5-dihydroisoxazoles I-76a and I-76b are prepared in two steps starting from the formation of alkene from 4'-phenoxyacetophenone using method 6 followed by the ring of method 2 Addition. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=331.0 m/z. Activity: A. Example 77

1-77* l-77b (1-77)

3-Bromo-4,5-dihydroisoxazole 1-77&amp; and 1-771) were prepared in a one-step procedure using Method 2 Reversal-Anise. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=269.0 m/z. Activity: C. Example 78

(1-78) 3-Bromo-4,5-dihydroisoxazoles I-78a and I-78b were prepared in two steps starting from 4-phenyloxybenzaldehyde using method 6 (but using bromine) Ethylene triphenyl 247 201043620 base scale replacement docking sulfhydryl triphenyl scale) followed by cyclization addition using method 2. These compounds are isolated using the palmar HPLc method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M_h]_=3310 m/z. Activity: a. Example 79

(Ϊ-82) 3_Land-4,5-dihydroisoxazole "and the oxime was prepared in 3 steps from 4-phenoxyfurfural as follows: 4-phenoxybenzaldehyde (1.0 eq.) was dissolved in tetra argon Furan (0.20 Μ vs. tetrahydrofuran) and cooled to (TC. Ethyl magnesium bromide (1. THF in THF '1 2 eq.) was added dropwise, then allowed to react at 2; rc was stirred for 2 hours. Ammonium quenching and concentration to remove the tetrahydrofuran. The mixture is then diluted with water and extracted with tributyl decyl ether. The organic layer is washed with water and brine, then dried over sodium sulfate and concentrated under reduced pressure. Purification by rapid phosgene gel chromatography (ethyl acetate/hexanes) gave the desired alcohol 1-80. The purified alcohol 1-80 was then dissolved in pyridine (0.80 Μ relative to the alcohol). The gas (1.1 eq.) and the mixture were heated to reflux for 2 hours. After this point the reaction was cooled to 0 ° C and quenched with excess water. The mixture was then diluted with acetic acid &amp; and the organic layer was washed with water and brine then Dehydrated with sodium sulfate and concentrated under reduced pressure. The concentrated reaction mixture is rapidly oxidized. Purification by ruthenium chromatography (ethyl acetate/hexanes) gave the desired ene 1-81. 248 201043620

Me

1-19 1-80 Ι-8Ϊ

The ene 1-81 is then converted to the desired 3-bromo-4,5-dihydroisoxazoles I-82a and I-82b using Method 2. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=331.0 m/z. Activity: B. Example 80

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-83a and I-83b were used from racemic compound I-14 and 3-(5-hydroxypyridine-2- Methyl benzoate is prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=460·1 m/z. Activity: B. Example 81

249 201043620 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-84a and I-84b using method 5 from racemic compounds 1-14 and 3-(5-hydroxypyridine- Ethyl 2-(meth)benzoate was prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=474.1 m/z. Activity: B. Example 82

The racemic compound 1-83 (1.0 eq.) was dissolved in 1:1 tetrahydrofuran/water (0.06 M) and lithium hydroxide (8.0 eq.) was added. The reaction was allowed to stir at room temperature for 1 h, then the tetrahydrofuran was removed under a nitrogen stream and the remaining solution was acidified to pH less than 2 to afford the desired acid I-85a and I-85b as a white solid which was isolated by vacuum filtration. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 443.0 m/z. Activity: B. Example 83

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-86a and I-86b were prepared from the racemic compounds 1-14 and 6-phenylpyridin-3-ol using Method 5 Prepared in one step. These compounds are isolated using the HPLC method known to the art in the art of 250 201043620. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=402.2 m/z. Activity: B. Example 84

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-87a and I-87b were prepared in a one-step procedure using races 5 from racemic compounds 1-12 and 3-hydroxypyridine. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=333.5 m/z. Activity: A. Example 85

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-88a and I-88b were prepared in a one-step procedure from racemic compound 1-75 and 3-hydroxypyridine using Method 5. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=34〇·2 m/z. Activity: B. Example 86 251 201043620

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-89a and I-89b were prepared in one step from racemic compound 1-76 and 3-hydroxypyridine using Method 5. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=348.4 m/z. Activity: A. Example 87

3-Phenoxy-4,5-dihydroisoxazole 1-9〇3 and 1-901) were prepared in one step from the racemic compounds 1-10 and 4-hydroxybenzenesulfonamide using Method 4. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=410.8 m/z. Activity: A. Example 88 b

Exactly b (1-91) trans 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-91a and I-91b using method 5 from racemic compound 1-78 or 1 -82 and 3-hydroxypyridine were prepared in one step 252 201043620. These chemical secrets are separated from the known method of sex muscle c. For example, refer to the age-cut f, _LC method. [m+h]+=346 2 m/z. Activity: C. Example 89

(1-92) l«92a 使用Using method 11 from 5_(4,4,5,5-tetramethyl-1,3,2-diπ boron-2-yl)t-l-aminocarbamic acid The formation of the third butanine (5___吼 bit_2·yl)_aminecarboxylic acid • After the third Ding®1, use method 5 from the racemic compound Ι·Η) and (5·经-吼.定· 2-Base)-Aminic acid tert-butyl S is prepared in a two-step process to prepare 3 octa-3-yloxy)-4,5-monohydroisoindole _92_-9213. These compounds are isolated using the method known in the art for the HP L C method. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=447.9 m/z. Activity: c. Example 90

T-93b (1-93) ο Η2Ν&lt;χ〇Ι&gt; l-93a Racemic 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole j_92 is dissolved in trifluoroacetic acid (0.20 Μ) Stirred for a few hours with respect to isoxazole) and at room temperature. Then, the solvent and the crude product residue were removed under reduced pressure, and the mixture was stirred and evaporated (2 times) to obtain ϊ-9% and I-93b as a TFA salt (white solid). These compounds are isolated using the HPLC method known to the art. For example, reference is made to the 253 201043620 HPLC method disclosed herein. [M+H]+=347.1 m/z. Activity: A. Example 91

'Mb _&gt; Racemic 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-93 is dissolved in dioxane (0.03 Μ relative to isoxazole), followed by addition of triethyl Base amine (4.0 equivalents) and acetic anhydride (3.0 equivalents). The reaction was allowed to stir for 16 h then diluted with ethyl acetate and brine (2times) and brine (1). The organic layer was then dried over sodium sulfate and concentrated under reduced pressure to afford ethyl acetate I-94a and I-94b as white solid. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm hplc method disclosed herein. [M-H]-=388.1 m/z. Activity: A. Example 92

3-/odor-4,5-dihydroiso-I_95a and I-95b are prepared in two steps starting from the use of method 8 from H4-phenoxyphenyl)propanone, followed by the formation of a ring of method 1 Addition. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+:=347.7 m/z. Activity: A. Example 93 254 201043620

l·働

OGFj I-96D (1-96)

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-96a and I-96b are in a one-step procedure from racemic compounds 1-14 and 5-n to n ratio according to the following procedure. Preparation of biting formic acid vinegar: odor-5-(4-(trifluoromethoxy)phenyl)_4,5-dihydroiso(I), 5-hydroxyl&lt;* than methyl benzoate (1) • 2 equivalents), and cesium hydrogencarbonate (15 〇 equivalent) suspended in hydrazine, hydrazine-dimercaptoguanamine (0.32 Μ relative to dihydroisoalpha 嗤). The mixture was then degassed with argon and then heated to 13 (TC for 4 hours, then only the desired product and the corresponding acid were visually observed by LC/MS. The reaction was allowed to cool to room temperature and poured into vaporized ammonium. The aqueous solution (30% by weight, 〇〇8 Μ vs. dihydroisoxazole) is quenched. The aqueous phase is extracted with ethyl acetate (2 times), dehydrated with sodium sulfate, and the mixture is solid and solid. Absolute ethanol recrystallization gave racemic 3-(acridin-3-yloxy)-4,5-dihydroisosin 0-sodium 1-96 which was isolated by filtration as a white solid (25% yield). The compounds are isolated using the PLC method known to the artisan. For example, refer to the palmitic HPLC method disclosed herein. [M+H]+=383.8 m/z. Activity: Α. Example 94

W7a |-97b (1-97) racemic 3-(° ratio β定-3-yloxy)-4,5-diazaiso-β-嗤]_96(ι 〇〇 equivalent) 255 201043620 Dissolved in 1: 1 tetrahydrofuran/water (0.06 Torr) and lithium hydroxide (8.0 eq.) added. The reaction was allowed to stir at room temperature for 1 hour, then the tetrahydrofuran was removed under a stream of nitrogen and the remaining solution was acidified to pH less than 2 to provide the desired acid I-97a and I-97b as a white solid, which was filtered through vacuum. Separation. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=369.3 m/z. Activity: A. Example 95

(1-98) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-98a and I-98b are used in the method 5 from racemic compounds I-10 and 3-(5- Methyl hydroxypyridin-2-yl)propionate was prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=418.1 m/z. Activity: A. Example 96

Racemic 3-(α-pyridin-3-yloxy)-4,5-dihydroisoxazole 1-98 (1.0 eq.) dissolved in 1:1 tetrahydrofuran/water (0·06 M) and added Lithium (8.0 equivalents). The reaction was allowed to stir at room temperature for 1 hour, then the tetrahydrofuran was removed under a stream of nitrogen and the remaining solution was acidified to pH less than 2 with 1 N HCl to afford the desired acid I-99a and 256 201043620 1-9% 'white solids Filter separation. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=402.8 m/z. Activity: A. Example 97

MOOb

The racemic compound 1-98 was dissolved in ammonia in methanol (7.0 Μ in methanol, 0.02 Μ relative to isoxazole). The reaction was sealed and allowed to stir at 23 ° C for 72 hours, then the solvent and excess ammonia were removed under a nitrogen stream to afford a pale brown solid. The solid was subjected to hexanes to obtain the desired amidoxime-lOOa and Ι-lOOb as a white solid. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=404·5 m/z. Activity: a. Example 98

Buy ι-_ (M01) 3 decapyridin-3-yloxy)-4,5-dihydroisoxazole i_i〇ia and i_i〇ib using method 5 from racemic compounds I - 9 and 3 -Hydroxypyridine is prepared in a one-step process. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=316.8 m/z. Activity: A. 257 201043620 Example 99

1-102a M 02b (1*102) 3-Bromo-4,5-dihydroisoxazole I-102a and I-102b were prepared in two steps starting from the use of Method 8 from 1-(biphenyl-4- The formation of ethyl ketone is followed by the cyclization addition using Method 1. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=315.7 m/z ° Activity: A. Example 100

The use of 3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole I-103a and I-103b was carried out in one step from the racemic compounds 1-9 and 5-hydroxypyrimidine. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=318·7 m/z. Activity: A. Example 101

258 201043620 3-(mouth bite _5__ know its oxygen)-4,5-dihydroisoxazole 丨〇4a and ι_ 1 〇4b use method 5 from the external compound ι ι〇2 and 5_ The shot was prepared in a one-step process. These zeros are separated using the palmar P L C method known in the art. For example, the test does not reveal the palmitic HPLC method. [M+H]+=332.6 m/z. Activity: A. Example 102

H〇$a (M05) M05b

Outside 'Xiao Xuan 3 ten bite · 3-yloxy)-4,5-dihydroiso-nine sitting 1-97 (1.0 eq.) ^ in dichloromethane (0.03 M vs. dissimilar). Add a gu Gu (2 〇 Tianli) and react to the temperature to give a small day, then concentrate under reduced pressure to form an eosinophilic solid 'solid and toluene azeotrope (2 times). The resulting solid was redissolved in tetrachloromethane (0.03 Torr vs. isotactic), followed by the addition of glycine acid (which was then added) followed by the addition of diethylamine (3 G equivalent). The reaction is stirred at room temperature! The hour was then transferred to the separatory funnel using excess water and acetic acid. Then, the organic layer is washed with saturated water and brine, dehydrated with sulfuric acid and concentrated under reduced pressure to obtain a crude product. The crude product is purified by rapid dioxide gel chromatography (ethyl acetate/hexane) to obtain the indoleamine. And Bu Na is a white solid. These compounds are isolated using the method known to the artisan for the palm muscle c. For example, reference is made to the palmitic HPLC method disclosed herein. [m_h]_=437 5 Activity: A. Example 103 259 201043620

M06b (ΜΘ6) racemic 3-(acridine_3_yloxy)_4,5-dihydroisoxazole 1-105 (lo equivalent) dissolved in 1:1 tetrahydrofuran/water (〇〇6 M) and Lithium hydroxide (8 〇 equivalent) was added. The reaction was allowed to stir at room temperature for 1 hour, then the tetrahydrofuran was removed under a stream of nitrogen and the residue was acidified to pH less than 2 to afford the desired acid I-106a and I-l 6b as a white solid which was isolated by vacuum filtration. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=423.7 m/z. Activity: A. Example 104

(10) 1 ^lOTb (1-107) 260 1 decazol-3-yloxy)·4,5-dihydroisoxazole I-107a and Il〇7b were prepared using a similar procedure of Example 102, but using methyl The amine replaces methyl glycinate. These compounds are isolated using the palmitic HpLC method known in the art. For example, refer to the palmar HpLc method disclosed herein. [m+h]+=382 5 m/z. Activity: A. Example 105 201043620 Ο

OCF^ Μ ο Me

OCF3 M08b α-108) Ο 3-(pyridine-3-yloxy)-4,5-dihydroisoxazole uoh and M〇8b were prepared using a similar procedure of Example 102, but using didecylamine instead of glycine Acid vinegar. These compounds are isolated using the palmar HPLc method known in the art. For example, reference is made to the palmitic HpLC method disclosed herein. [M+H]+=396 6 m/z. Activity: B. Example 106 〇

M 09a Ο

OCFs Ι·1 Κι (1-109) 3-(mouth ratio -3-yloxy)_4,5_diaza isotope sitting 11〇9&amp; and 11〇 external use

A similar procedure was followed for Example 102 except that ethanolamine was used instead of methyl methacrylate. These compounds are isolated using the palmar Hp L c method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=409·9 m/z. Activity: A. Example 107 Μ10·

(1410) racemic 3_(pyridine, 3-yloxy)-4,5-dihydroisoxazole 1-67 (1.0 eq.) dissolved in 1:1 tetrahydroanthine/sodium/water (0.06 M) and added Lithium hydroxide (8.0 equivalents). 261 201043620 Allow the reaction to stir at room temperature for 1 hour, then remove the four gas sigma and the remaining solution under a stream of nitrogen to acidify to a pH below 2 to provide the desired acid and I-ll 〇b as a white solid. Separated by vacuum filtration. Such human systems are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=376.5 m/z. Live, drop 1 soil · A. Example 108 Ο 0

Racemic 3-(° ratio _3_based oxygen)_4,5-dihydroiso. No. β is dissolved in _methylamine in methanol (2·〇 in methanol '0.02 Μ relative to isoxazole). The reaction was sealed and allowed to stir at 23 ° C for 72 hours, then the solvent and excess dimethylamine were removed under a nitrogen stream to give a light brown solid, which was obtained by wet-drying with hexanes to obtain the desired guanamine I-llla and I-lllb. White solid. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=405.1 m/z. Activity: A. Example 109

1-112* Uinb (1-112) 3-(pyrimidin-5-yloxy)-4,5-dihydroiso. The azoles 1-112a and 1-112b were prepared in one step from the racemic compounds 1-14 and 5-hydroxypyrimidine using the procedure 5. These compounds are isolated using the HPLC method known to the art. For example, 262 201043620 refers to the palmitic HPLC method disclosed herein. Activity: A. Example 110

3-(pyridin-3-yloxy)-4,5-diisoisoxazole I-113a and I-113b are used in the method 5 from racemic compounds 1-75 and 5_ The two-step preparation was followed by hydrolysis under the same conditions as in Example 94. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [μ-η]-=380·7 m/z. Activity: A. Example 111

1-114b

(W14) 3-(. than -3-yloxy)·4,5-dihydroiso-π-azole and was prepared using a similar procedure of Example 102, but using methylamine (2 〇 tetrahydrofuran) instead of glycine Methyl ester is prepared from a racemic compound. These compounds are isolated using the palmar Hp L c method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=396.4 m/z. Activity: A 〇 Example 112 263 201043620

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-115a and I-115b were prepared from racemic compound 1-113 using a similar procedure to Example 102, but using ethylamine instead. Methyl glycinate. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=411·1 m/z. Activity: A. Example 113 f3c eight

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole 1-1163 and 1-1161? were prepared from racemic compound 1-113 using a similar procedure to Example 102, but using trifluoroethyl The base amine replaces methyl glycinate. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=461.7 m/z. Activity: B. Example 114

(M17) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-117&amp; and 1-1171» were prepared using a similar procedure of Example 102 from racemic compound 1-113 using 264 201043620. However, hydroxylamine hydrochloride was used instead of methyl glycinate. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=398.4 m/z. Activity: A. Example 115 〇 0

Racemic 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-105 was dissolved in ammonia in methanol (7.0 Μ in methanol, 0.02 Μ vs. isoxazole). The reaction was sealed and allowed to stir at 23 &lt;0&gt;C for 72 hours, then solvent and excess ammonia was removed under a nitrogen stream to afford a pale brown solid, which was then triturated with hexanes to afford the desired amines I-118a and I-118b as a white solid. These compounds are isolated using the HPLC method known to those skilled in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=325.1 m/z. Activity: B. Example 116

3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole 1-119&amp; and 1-11913 are synthesized in a three-step process starting from the conversion of 4-bromodifluorobiphenyl to The corresponding alkene is then subjected to cycloaddition using Method 1, followed by the substitution of 5-hydroxypyrimidine using Method 5. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. 265 201043620 [M+H]+=354.3 m/z. Activity: A. Example 117 F e

Df M20a |·1 〇 cf3 3_bromo 4,5·dihydroisoxazole M2〇a and I_l20b are prepared in two steps, starting with the use of method 8 from 3-fluoro-4-(trifluoromethane The formation of benzaldehyde is followed by the cyclization addition using Method 1. These compounds are isolated using HPLC methods known to those skilled in the art. For example, reference is made to the palm-like method disclosed herein. [M+H]+=327 5 m/z. Activity: A. Example 118

(1-121) 3_(° 密 疋 base gas)-4,5-dihydroisox 0 carbazole I-121a and I-121b are used as '5' from racemic compounds 1-120 and 5-- Pyrimidines are prepared in a one step process. This ^ ° art world 6 knows the separation of the palmity ^ PLC method. For example, refer to the palmar HpLc method disclosed herein. [m+h]+=344_1 m/z. Activity: A. Example 119 266 201043620

(htm 3-indole-3-yloxy)-4,5-dihydroiso D-azole I-122a and I-122b are used Ο

Method 5 was prepared in one step from racemic compound i_i2 and 5-hydroxypicolinate. These compounds are isolated using the palmitic Hplc method known in the art. For example, reference is made to the palmar Hplc method disclosed herein. [Μ+Η]+=400·3 m/z. Activity: A. Example 120

(H23) H〇2Ct Excess %3-(β ratio bite_3_yloxy)-4,5-dihydroisoπ-number wowι_ΐ22 (1.〇 equivalent) Dissolved in 1:1 tetrahydrofuran/water (〇· 〇6 M) and add lithium hydroxide (8 〇 equivalent). The reaction was allowed to stir at room temperature for a few hours, then the tetrahydrobite was removed under a stream of nitrogen and the remaining solution was acidified to pH less than 2 with 1 N HCl to afford the desired acid I-123a and I-I23b as a white solid, which was passed through vacuum Filter separation. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=386.3 m/z. Activity: A. Example 121 267 201043620

(1-124) 3-Bromo-4,5-dihydroisoxazole 1-1243 and 1-12415 are prepared in two steps starting from the use of Method 8 from 3-chloro-4-(trifluorooxyloxy)benzyl The formation of the aldehyde is followed by the cyclization addition using Method 1. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=345.5 m/z. Activity: A. Example 122

(1-125) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-125a and I-125b are used in the method 5 from the racemic compounds 1-124 and 5-hydroxypyrimidine. Prepared in one step. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=359.7 m/z. Activity: A. Example 123

(1-126) 268 201043620 3-Bromo-4,5-dihydroisoπ-oxazolium 26a and I-126b are prepared in two steps starting from the use of method 8 from 2,2-difluoro-1,3- The formation of benzodiazepine-5-carboxaldehyde is followed by the cyclization addition using Method 1. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=3〇5 6 m/z. Activity: a. Example 124

3 Decidin-3-yloxy)-4,5-diisoisoxazole I-127a and I-127b were used in a one-step procedure from racemic compound 1-126 and 5-hydroxypyrimidine. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=321.8 m/z. Activity: B.

Example 125

3-(°°°-3-yloxy)-4,5-dihydroiso-saliva i_i28a and I-128b were prepared as analogous compound 1-99 in Example 96, but racemic compound _ 丨4 was used as a starting material in place of racemic compound 1-10. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=398.2 m/z. Activity: A. 269 201043620 Example 126

(1-129) 3-(Uridin-5-yloxy)_4,5-dihydroisoxazole M29a and I-129b are used in one step from racemic compounds 1-75 and 5-hydroxypyrimidine Preparation. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=339.8 m/z. Activity: A. Example 127

(H30) 3-Molybdenum-4,5-dihydroisoxazole is a two-step process starting from the coupling of 4_ oxo- phenyl benzoic acid with 2 bromo 3,3,3 trifluoropropane- ene Prepare as follows: A solution of sputum (〇25 Μ vs. di-tansolic acid) was cooled to 〇C in a sealed tube, followed by addition of 2-di- 3,3,3-trifluoropropene (〇·83 equivalent) followed by addition Palladium ruthenium (2.5 mol%). The mixture was purged with argon and then 2. 〇 Μ sodium carbonate solution (丨. 5 eq.) was then added, followed by the addition of dihydroboronic acid (1 eq. equivalents) to methanol (1.0 μ vs. dihydroxyboronic acid). The mixture was purged with argon for a second time and then heated to 70 ° C for 20 hours in an oil bath. The reaction was allowed to cool, then was transferred to a separatory funnel using excess water and ethyl acetate, washed with a 2.0 s sodium carbonate solution (1 time) and washed with water 270 201043620 (2 times). The organic layer was dehydrated and concentrated to obtain a black oil, and the oil was purified by rapid phosgene gel chromatography (ethyl acetate/hexanes) to obtain the desired alkene as an oil '35% yield'. Conversion to the desired racemic 3-bromo-4,5-dihydro-synchronous saliva. These compounds are isolated using the HPLC method known to the art. For example, refer to the palmar HpLC method disclosed herein. [M+H]+—385.6 m/z. Activity: B. Example 128

"131* |.131b (I-I31)

G 3-(mouth '1疋-5-base gas)_4,5-dihydroiso 11 saliva 1_1313 and 1_13113 were used. Method 5 was prepared in one step from racemic compound 1-130 and 5-hydroxypyrimidine. These compounds are isolated using methods known in the art for palmity 111 &gt; For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=401.4 m/Z. Activity: A. Example 129

First, using Method 11 to prepare 2-(methylsulfanyl)-purin-5 from 2-(methyl sulphate _5-yl di-sphingic acid), use Method 5 in a one-step procedure from racemic compound 1 -14 and 2-(methylthio)pyrimidin-5-phenol to prepare 3-(pyrimidin-5-oxy)4,5-dihydroiso-indenyl WhWb. These compounds are used in the (4) boundary known as 271 201043620 Method separation. For example, refer to the palmar HPLC method disclosed herein. [M+H]+=372.2 m/z. Activity: B. Example 130

Racemic 3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole 1-132 is dissolved in dichlorodecane (0.5 Μ relative to isoxazole), followed by addition of meta-benzoic acid (2.0 eq.) and allowed to react at room temperature for 1 hour. After the reaction was determined by LC/MS, the solvent was evaporated. The crude product mixture was then redissolved in tert-butyl methyl ether (0.5 Torr), followed by the slow addition of hexane until a solid precipitated. The solid was then collected by vacuum filtration and washed with 1:1 hexanes/t-butyl methyl ether to give the desired 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-133a and I- 133b is a white solid. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=404.1 m/z. Activity: A. Example 131

First, after the preparation of 6-(methylthio)pyridin-3-ol from 6-(methylthio)pyridin-3-yldihydroxyboronic acid using Method 11, the method 1 is used in a one-step procedure from the racemic compound 1-14. And 6-(decylthio)pyridin-3-ol were prepared as 3-(pyridin-3-yloxy)-4,5-272 201043620 dihydroisoxazole I-134a and I-134b. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=372.4 m/z. Activity: A. Example 132

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-135a and I-135b were prepared from 1-134 in the same manner as in Example 130. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=403.2 m/z. Activity: A. Example 133

Ι·13ββ Μ3βΙ» (Ι-ΙΜ) ❹ First use method 11 to prepare 5-fluoro-6-methoxy η than bite_5_ from 5-fluoro-6-曱ββ Preparation of 3-(pyridin-3-yloxy)-4,5-dihydrogen from the racemic compound 1-14 and 5-fluoro-6-oxopyridine-3-ol in a one-step process using the method 5 Isocarbazole i_i36a and I-136b. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+=373.4 m/z. Activity: b. Example 134 273 201043620

M 37a Μ 37b (1437)

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-137a and I-137b are prepared in three steps starting from 4-butoxybenzaldehyde using Method 8 followed by Method 1 Cyclization addition. The obtained bromo-4,5-dihydroisoxazole system and quinone 5-hydroxypyridinecarboxylate were reacted using Method 5. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=370.1 m/z. Activity: A. Example 135

1-138a M 38b (M38)

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole 1-1383 and 1-13813 were prepared in a one-step procedure from the compound 1-137 using the hydrolysis conditions analogous to that of Example 94. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=357.7 m/z. Activity: A. Example 136

3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole I-139a and 1-13% were prepared in three steps starting with 4-butoxybenzaldehyde using method 8 followed by method 1 274 201043620 cyclization bonus. The obtained bromo-4,5-dihydroisoxazole was reacted with 5-hydroxypyrimidine using Method 5. This proprietary compound is isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [m+H]+=314.9 m/z. Activity: a. Example 137

M40b (1-140)

G 3-(°-pyridyloxy)-4,5-dihydroiso-sigma I-140a and I-140b are prepared in four steps starting from 4-iso-propoxybenzylation using method 8 followed by method! The cyclization bonus. The resulting bromo-4,5-dihydroisoxazole system and 5-hydroxypyridinium hydrazide were hydrolyzed using the same procedure as in Example 94 using Method 5. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=343.5 m/z. Activity: A. Example 138

(1*141) 3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole was prepared in three steps starting from 4-isopropoxybenzaldehyde using Method 8 followed by cyclization of the user to make. The obtained bromo-4,5-dihydroisoxazole was reacted with 5-hydroxypyrimidine using Method 5. These compounds are isolated using the palmitic HpLC method known in the art. For example, refer to the method of palm Ηριχ disclosed herein. 275 201043620 [Μ+Η]+=299·3 m/z. Activity: A. Example 139

M42a Μ421» (!·142)

3-Bromo-4,5-dihydroisoxazole 1-142 &amp; and 1-14213 were prepared in three steps from 4-vinylphenyl acetate using the cyclization addition conditions of Method 1. The obtained acetate was dissolved in tetrahydrofuran (1.0 eq., 0. 18 Μ vs. bromoisoxazole) and cooled to 0 ° C in an ice bath. Lithium oxynitride (3 〇 equivalent, 1.0 Μ in water) was added and the reaction was allowed to stir for 30 minutes, then transferred to a sep. funnel using excess water and ethyl acetate. The organic layer was extracted with saturated ammonium chloride, dehydrated with sodium sulfate and evaporated to give the desired phenol. The phenol (1.00 equivalent) was dissolved in acetonitrile (0.20 Torr vs. starting material) and cooled to 〇 ° C in an ice bath. Propyne bromide (2.0 eq.) was added followed by the addition of a carbonic acid planer (3.0 eq.). The reaction was allowed to stir for 2 h then quenched with saturated aqueous ammonia and taken to a sep. funnel with excess water and ethyl acetate. The organic layer is dehydrated with sodium sulfate and evaporated to give the desired racemic alkyne 1_142' which is purified by rapid phosgene gel chromatography (ethyl acetate/hexanes) to give the desired racemic compound, 70% yield. rate. These compounds are isolated using the palmar HPL c method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [m+h]+=279.7 m/z. Activity: A. Example 140

276 201043620 3_(σMidine-5-yloxy)-4,5-dihydroisoxazole I-143a and I-143b are used in a one-step process from racemic compound _142 and 5-hydroxypyrimidine preparation. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=296.5 m/z. Activity: B. Example 141 Ο

Mo2c^,H

Μ 44a

3-(° ratio -3-yloxy)_4,5-dihydroiso-sigma azole was used in a one-step procedure from the racemic compound 1-142 and methyl 5-hydroxypyridinecarboxylate. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=353.5 m/z. Activity: A. Example 142

1*14Sb (I-14S) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-145a and I-145b were subjected to one-step self-elimination using hydrolysis conditions similar to those of Example 94. Spin compound 1-144 was prepared. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [m+H]+=338.8 m/z. Activity: A. Example 143 277 201043620

3·Phenoxy-4,5-dihydroisoxazole I-146a and I-146b were prepared in a one-step manner from racemic compound 1-61 using a similar hydrolysis condition. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=376.2 m/z. Activity: B. Example 144

(M47)

3-Phenoxy-4,5-dihydroisoxazole μ丨473 and 丨47b were prepared in a one-step procedure from the racemic compound 丨_62 using a similar hydrolysis. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=375.7 m/z. Activity: A. Example 145

Br

!·14β&amp;ι

(1-148) 3-Mos-4,5-dihydroisoxazole i48a and l i48b were prepared in a one-step procedure from 1-bromo-4-vinyl. These compounds were isolated by the HPLC method using the technique of 278 ^1〇4362〇. For example, reference is made to the palm-like C method disclosed herein. [M+H]+=350.5 m/z. Activity: a. Example 146, Ah-Br ij M4Sa M4Sb (1449) 3-(.pyridin-3-yloxy)-4,5-dihydroisoxazole i_149a and I-149b were used

Method 5 was prepared in the same manner from racemic compound 1-148 and methyl 5-hydroxypyridinium. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=378.4 m/z. Activity: A. Example 147

_«娜" MSOb (I-1S0)

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-150a and 1-150b were prepared in a one-step procedure from the racemic compound 1-1494 using the hydrolysis conditions similar to those in Example 94. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=362·6 m/z. Activity. A. Example 148

(M51) 279 201043620 M°tb pyridine_3_yloxy)_4,5-dihydroisoxazole I-151a and I-151b are used in the method 5 from racemic compounds 1-14 and 4-hydroxypyridinecarboxylic acid A The ester is prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=384.2 m/z. Activity: a. Example 149

1-153⁄4 M 52b (I-JS2) racemic 3-(.pyridin-3-yloxy)-4,5-dihydroisoxazole 1-151 (1.0 eq.) dissolved in 1:1 tetrahydrofuran/water ( 0.06 M) and lithium hydroxide (8.0 equivalents) were added. The reaction was allowed to stir at room temperature for a few hours, then the tetrahydrofuran was removed under a stream of nitrogen and the remaining solution was acidified to pH less than 2 to afford the desired acid l-l52a and LlUb as a white solid which was isolated by vacuum filtration. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [MH]-: =368.9 m/z 〇activity: A 〇example ISO /*TM-\ hQl, 〇A^\J^a M$3a l-1S3b (14S3) 3-(pyrimidin-5-yloxy) -4,5-Dihydroisoxazole M53a and I-153b were prepared in a two step from hydrazine_4-vinylbenzene in two steps. The obtained bromo-4,5-dihydroisoxazole was reacted with 5-hydroxypyrimidine using Method 5. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palm 280 201043620 HPLC method disclosed herein. [M+H]+=277.3 m/z. Activity: B. Example 151

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-154a and I-154b are used in Process 5 from racemic compounds 1-75 and 6-(furan-3-yl)pyridine The -3-phenol is prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=406.3 m/z ° Activity: A ° Example 152

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-155a and 1-155b were prepared from racemic acid M10 according to the following procedure: in a microwave reactor tube, acetonitrile ( 1.0 eq.) and the acid 1-110 (1.0 eq.) were dissolved in dry acetonitrile (0.1 M each). Polystyrene supported triphenylphosphine (3.0 equivalents) and tri-acetonitrile (2.0 equivalents) were added, and the mixture was sealed and heated in a microwave reactor for 2 hours. At this time, the reaction was judged to be incomplete by LC/MS, so 丨. 5 equivalents of triphenylphosphine resin was further added followed by 10 equivalents of trichloroacetonitrile. The container was again sealed and heated again at 130 ° C for 2 hours. Upon completion, the concentrated reaction mixture was purified by 281 201043620 rapid cerium oxide gel chromatography (hexane/ethyl acetate) to obtain the desired racemic compound such as dioxin, which is known to the art. Separated by HPLC method. For example, reference is made to the palmity 111^ (: method. [M+H]+=415.5 m/z. Activity: a. Example 153

(M56) 3-(n-Bitter-3-yloxy)-4,5-dihydroisoxazole μ156&amp; and was prepared using a similar procedure of Example 152&apos; but using the racemic compound MU as the starting acid. These compounds are isolated using the palmitic HpLC method known in the art. For example, refer to the street palm HpLC method disclosed herein. [M+H]+=422 〇 m/z. Activity: A. Example 154

Me

3-(pyridin-3-yloxy, ;~^ dihydroisoxazole 1-157&amp; and 1-15713 are similar procedures using Example 丨52, but using racemic compound 1-97 as a starting point Acids. These compounds are palmitic HPLC methods. [Μ+Η]+=407·2 'τ'1 is known by the artisan method for separation by palm HPLC method. For example, refer to the pair disclosed herein.

m/z. Activity: A 282 201043620 Example 155

(M5S) 3_(Pyridin-3-yloxy)-4,5-diisoisoxazole 1-1583 and 1-15813 were prepared from racemic acid 1-113 according to the following procedure: acetonitrile (1.0 eq. And the acid 1-113 (1·〇 equivalent) is dissolved in anhydrous dioxane (each 〇·1 M) and treated with EDC (1.05 eq.) and DMAP (0.10 eq.), then the reaction mixture is allowed to stir at 23 ° C. 6 hours. After completion of the reaction, it was diluted with an excess of methane and water into a separating funnel and an organic layer, and washed twice with 0.5 liter of aqueous citric acid and saturated aqueous sodium hydrogencarbonate. The organic layer was dried over sodium sulfate and concentrated to a white solid. This solid was dissolved in anhydrous THF and 1.2 equivalents of Lawson's reagent (Lawesson, s reagent) was added. The mixture was sealed in a test tube and at a microwave reactor at 115. 〇 Heat for 30 minutes. The deserted reaction mixture was purified by rapid silica dioxide chromatography (ethyl acetate/hexanes) to give the desired racemic thiadiazole 1-158. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=438.2 m/z. Activity: A. Example 156

283 201043620 3-Phenoxy-4,5-dihydroisoxazole 1-159&amp; and 1-15% were prepared using a similar procedure using Example 152, but using racemic compound 1-147 as starting acid. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=413.6 m/z. Activity: A. Example 157

3-Phenoxy-4,5-dihydroisoxazole I-160a and 1-160b were prepared using a similar procedure of Example 152, but using racemic compound 1-146 as starting acid. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=414.4 m/z. Activity: A. Example 158

(!·_ 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-162a and I-162b were prepared according to the following procedure: racemic dihydroisoxazole 1-161 series Use Method 5 to prepare from Compound 1-14 and 6-bromopyridin-3-ol in a step 284 201043620. The compound was placed in a microwave vial and then dissolved in Dijon (0.02 M). Add 2 &lt;2, 2 Butylstannyl)thiazole and palladium ruthenium and the reaction is scrubbed with argon. At this time, the reaction was simmered in the ~8 wave reactor for 20 minutes, and then by TLC analysis, there was no longer the starting material. The mixture should be concentrated and fine-speeded. Ester) purification affords the desired racemization. Plug η sit 1-162, 50% yield. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=1 2〇7.3 m/z. Activity. A 〇 Example 159

285 1 -( ° ratio bite-3 -yloxy)_2,5 -dihydroisoxazole μ! 63 3 and μ丨63 b were prepared using a similar procedure to Example 158 'but using 2_(tributylstannyl)哼The azole replaces 2-(tributylstannyl)thiazole. These compounds are isolated using a palmitic HPLC method known in the art. For example, refer to the palmar 1 € 1 &gt; 1 ^ 2 method disclosed herein. [M+H]+=393.2 m/z. Activity: a. Example 160 201043620 3 decimated oxygen) _4,5·Dihydroiso-Iso-I-l64a and I-lMb were prepared using a similar procedure to Example 158, but using racemic compound 1-75 instead of compound 1-14. Starting material. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=423.4 m/z. Activity·· a. Example 161

1β heat (M6S) 3-(pyridin-3-yloxy)_4,5-dihydroisoxazole M65a&amp;n65b was prepared according to the following procedure: racemic dihydroisoxazole 1-161 and sodium carbonate ( 10.0 equivalents) placed in a microwave vial. Add 2:2:1 mixture of hydrazine, ethanol and water (〇〇2 Μ relative to 1-161) followed by addition of tert-butyl 4_(4,4,5 5_tetramethyl_13 2_ 2 4 paste -2-yl)-lH-pyrazole-indole-carboxylic acid diboric acid (15 equivalents of a mixture of 1 hour gas after 20 minutes, adding palladium ruthenium (4 m〇l%), the reaction is sealed and in an oil bath Heat to 8 Torr for π hours. Then allow the reaction mixture to cool. Then transfer to the separatory funnel with excess ethyl acetate and water. The organic layer was washed with water and saturated sodium. The aqueous layer was taken with acetic acid. The organic layer was combined and dehydrated and concentrated with sodium sulfate to obtain a crude oil, which was purified by rapid phosgene gel chromatography (hexane/ethyl acetate) to obtain the desired racemic pyr. 165, 36% yield. These compounds are isolated using the HPLC method known to the art. For example, refer to the palm hplc square 286 201043620 method disclosed herein. [Μ+Η]+=392·4 m/ z. Activity: C. Example 162

1*166a 1.1 働(M66) 3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole I-166a and I-166b are used in a one-step process from racemic compound 1 and Preparation of 5-hydroxypyrimidine. [M-H]-=241.5 m/z. Activity: B.

Example 163

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-167a and I-167b were prepared in analogy to compound 1-135 in the manner of Example 132, but using racemic compound 1-75 As a starting material for bromine-isoxazole. These compounds are isolated using the HPLC method known to those skilled in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=417.3 m/z. Activity: A. Example 164

_·锄a Μ Μ (Μ68) 3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole I-168a and I-168b are the cyclization addition conditions of method 1 from 1-( Trifluoromethyl)-4-vinylbenzene was prepared in the two-step procedure 287 201043620. The obtained bromo-4,5-diazaisoxazole was reacted with 5-hydroxypyrimidine using Method 5 to give the racemic compound 1-168. These compounds are isolated using a palmitic HPLC method known in the art. For example, refer to the palmar HpLC method disclosed herein. [M+H]+=309.8 m/z. Activity: B. Example 165

CM69) 3 decapyridin-3-yloxy)-4,5-dihydroisoindoline l-i69a and l-169b are cyclized addition conditions using method 1 in a three-step manner 丨(trifluoromethyl) Base)_4• Vinylbenzene preparation. The obtained bromo-4,5-dihydroisoxazole is reacted with Method 6 and 6_(mercaptosulfuryl)pyridine-3-phenol (prepared by using n-(methylthio)pyridine-3-ylboronic acid) It was then oxidized under conditions similar to those of Example 130. These compounds are isolated using the scaly Η P L c method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=387.2 m/z. Activity: Α. Example 166

*·170* I pin b (M70) (mercapto-oxygen)_4,5-dihydroiso- 0, etc. 0 sit I-170a and I-l70b make the cyclization addition condition of 5 to three steps 1-(Trifluoromethyl b', prepared by > odor _4,5-dihydrotetramide β sitting system using method 5 and 5 _ D than armor reaction followed by hydrolysis of the condition of example 94. Isocratic compounds are isolated using the palmar (4) P LC method known in the art. For example, reference is made to 288 201043620 The palmitic HPLC method disclosed herein. [M+H]+=353.0 m/z. Activity: A 〇Example 167

H〇aC

M71b Ο 1-(4,5-Dihydroisoxazole_3_yl)-1,1,2,4-triazole-3-carboxylic acid 1-171&amp; and I-171b were prepared using a procedure similar to that of Example 35. However, the racemic compound 1-75 was used as the starting bromine-iso. No. • Sit and use ih-1,2,4-three oxa-3-oxo acid ester as a nucleophilic compound. In addition, at some point during the reaction or subsequent processing, the ester is hydrolyzed to the corresponding acid. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=356.6 m/z. Activity: C. Example 168

Ο 3-(pyridin-3-yloxy)-4,5-dihydroiso. The azoles I-172a and I-172b were prepared in a one-step procedure using racemic compound 1-75 and pyrazolo[1,5-a]pyridin-2-ol. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=378.1 m/z. Activity: C. 289 201043620 Example 169

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-173a and I-173b were prepared using a procedure analogous to Example 161, but using 2-(4, 4, 5, 5 - 4 Replacement of 4-(4,4,5,5-tetradecyl-1) with methyl-1,3,2-dioxaboron-2-yl)-1Η-pyrazole-1-carboxylic acid tert-butyl ester 3,2-Dioxaboron-2-yl)-1Η-pyrazole-1-carboxylic acid tert-butyl ester. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=390·6 m/z. Activity: A. Example 170

N=N N=N

3-Phenoxy-4,5-dihydroisoxazole 1-1743 and 1-17413 are used in one step from racemic compound 1-14 and 3-(1Η-tetrazol-5-yl)phenol. Preparation. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=392.3 m/z. Activity: B. Example 171 290 201043620

3-Phenoxy-4,5-diisoisoxazole 1-175&amp; and 1-1751) using Method 5 from racemic compounds 1-14 and 4-(1Η-tetrazol-5-yl)phenol Prepared in one step. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=391.6 m/z. Activity: B. Example 172

3-Phenoxy-4,5-dihydroisoxazole I-176a and I-176b were prepared in two steps from racemic compound 1-14. Bromo-4,5-dihydroisoxazole 1-14 was reacted with methyl 3-hydroxybenzoate using Method 5, followed by hydrolysis using similar conditions as in Example 94. [M+H]+=368_0 m/z. Activity: C. Example 173

3-Phenoxy-4,5-diisoisoxazole I-177a and I-177b were prepared in two steps from racemic compound 1-14. Bromo-4,5-diisoisoxazole 1-14 was reacted with methyl 4-hydroxybenzoate using Method 5, followed by similar conditions using water of Example 94. 291 201043620. These compounds were used in the palm of the hand. Separated by HPLC method. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=368.0 m/z. Activity: B. Example 174

1-178 « 卜 178b (1-178) Prepared from 5-(4,4,5,5-tetradecyl-1,3,2-dioxaboron-2-yl)pyridinecarbonitrile using Method 11 After 5-hydroxypyridinonitrile, 3-(pyridin-3-yloxy)-4,5-diazaisoazole I-178a and I-178b are used in a two-step procedure from racemic compound 1 using Method 5 Preparation of ~14 and 5-hydroxypyridine carbonitrile. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [m+h]+=350.0 m/z. Activity: Β. Example 175

1-17&amp; M 79b (1-179) 3-Bromo-4,5-dihydroisoxazole oxime 79a and I-179b were prepared in a one-step procedure from 1-pentyl-4-vinylbenzene. . These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+=283.6 m/z. Activity: A. Example 176

*1 a 1-1 e〇b 292 201043620 3-(pyrimidin-5-yloxy)-4,5-dihydroisoxazole 1-18〇3 and 1-18013 are used in a method 5 from a racemic compound 1-179 and 5-hydroxypyrimidine were prepared in a one-step procedure. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=298.7 m/z. Activity: B. Example 177

(1481). 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-181a and I-181b are prepared in two's step from racemic compound 1-179, via first use. Method 5 allows 1-179 to be reacted with 6-(methylthio)pyridin-3-ol (synthesized from 6-(methylthio)pyridin-3-yldihydroxyboronic acid using Method 11) followed by Example 130 Oxidation under conditions. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=375.4 ❹ m/z. Activity: A. Example 178

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-182a and I-182b are prepared in two steps from racemic compound 1-14, by first using Method 5 to allow 1- 14 was reacted with 6-(ethylthio)pyridin-3-ol (synthesized from 6-(ethylthio)pyridine 293 201043620-3-yldihydroxyboronic acid using Method 11), followed by oxidation under conditions analogous to Example 130. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=417.1 m/z. Activity: A. Example 179

1-133a 1-183b (1483) 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-183a and 1-183b were prepared in two steps from racemic compound 1-14. By first using Method 5 to allow 1-14 to react with 6-(cyclopentylthio)pyridin-3-ol (using Method 11 from 6-(cyclopentylthio)pyridin-3-yldihydroxyboronic acid), followed by Oxidation was carried out under conditions similar to those of Example 130. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=456_8 m/z. Activity: B. Example 180

M84a M 84b (I-1B4) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-1843 and 1-1841? were prepared in two steps from racemic compound 1-14. By first using Method 5 to allow 1-14 to react with 6-(isobutylthio)pyridin-3-ol (using Method 11 from 6-(isobutylsulfanyl)pyridin-3-yldihydroxyboronic acid), followed by Oxidation was carried out under conditions similar to those of Example 130. These compounds are isolated using the HPLC method 294 201043620 known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=444·7 m/z. Activity: B. Example 181

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I_185a and I-185b were prepared using a similar procedure as in Example 178, but using the racemic compound 1-75 to replace compound 1-75. The starting material and 2-(tributylstannyl)carbazole (as in Example 158) were used in place of 2-(tributylstannyl)thiazole. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the amniotic HPLC method disclosed herein. [M+H]+=407.2 m/z. Activity: Α. Example 182

3 octyl -3-yloxy) 4,5-dihydroisoxazole μ ΐ 86 &amp; and I-186b were prepared using a procedure similar to that of Example 161, but using 2 furanyl dihydroxyboronic acid instead of 4-(4,4, 5,5_Tetramethyl-1,3,2_dioxaboron-2-yl)_1Η_π-pyrazole small carboxylic acid tert-butyl vinegar. These compounds are isolated using the palmar HPLc method known in the art. For example, reference is made to the palmitic HpLC method disclosed herein. [M+H]+=392.2 m/z. Activity: a. 295 201043620 Example 183

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole 1-187&amp; and 1-18713 were prepared using procedures analogous to Example 161, but using 5-methylfuran-2-yldihydroxy Boric acid replaces 4-(4,4,5,5-tetradecyl-1,3,2-di-n-boron-2-yl)-1Η-°-terazole-carboxylic acid tert-butyl ester. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=406.3 m/z. Activity·· A ° Example 184

The enantiomers 1-3-a and 1-188b of 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole were prepared using a procedure analogous to Example 161, but using 5-bromofuran- Substituting 2-carboxylic acid for 4-(4,4,5,5-tetradecyl-1,3,2-di.-boraboroin-2-yl)-1Η-pyrazole-1-carboxylic acid tert-butyl ester . These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=435.5 m/z. Activity: C. Example 185

296 201043620 Bisdin-3-yloxy)-4,5-dihydroisoxazole I_i89a and I-189b were prepared using a procedure similar to that of Example 161, but using 1-methyl-5-(4,4,5 ,5-tetramethyl-1,3,2-dioxaboron-2-yl)-1Η-pyrazole instead of 4-(4,4,5,5-tetramethyl-1,3,2- _ζ_σ号 Boronium __2_ base)_1H_pyrazole small carboxylic acid third butyl. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [m+H]+=406.2 m/z. Activity: A. Example 186

Me

3-(.Bis-3-OH-oxy)-4,5-dihydroisoxazole was prepared using a procedure similar to that of Example 161, but using &amp; dimethyl-1H_n than 嗤_5_yl-decarboxylate Substitute 4·(4,4,5,5·tetramethyl_u, 2_二刊味_2_基)_1H_ 吼Sal-1_Resistance third s. These compounds are based on the analytical HPLC method (4) known to the art. For example, reference is made herein to the reading palm HpLC method. [M+H]+=419.4 m/z. Activity: A. Example 187

3-(«比.疋_3_yloxy)_4,5-dihydroisoxazole μΐ91&amp; and was prepared using a procedure similar to Example 161, but using fluorenyl-3-(trifluoromethyl)-1Η - 297 201043620 Pyrazol-5-yldihydroxyboronic acid in place of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)-1Η-pyrazole-1 - Tert-butyl carboxylate. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+=473.3 m/z. Activity: C. Example 188

1-1 S2b (1-192) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-192a and I-192b were prepared using a procedure similar to that of Example 161, but using 1H-pyrid. Substituting oxazol-5-yldihydroxyboronic acid for 4-(4,4,5,5-tetradecyl-1,3,2-dioxaboron-2-yl)-1Η-pyrazole-1-carboxylic acid Tributyl ester. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=391.4 m/z. Activity: Α. Example 189

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-193a and I-193b were prepared using procedures analogous to Example 161, but using 5-bromothiophene-2-carboxylic acid instead of 4- (4,4,5,5-tetradecyl-1,3,2-di-n-boron-2-yl)-111-pyrazole-1-carboxylic acid tert-butyl ester. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=450_6 m/z ° Activity: B ° 298 201043620 Example 190

Μβ1

Ο

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-194a and I-194b were prepared according to the following procedure: racemic dihydroisoxazole 1-161 'Tribasic phosphate Potassium (3.0 equivalents), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)isoxazole (1.2 equivalents) and palladium catalyst (10 mol° /.) placed in a microwave vial. Dioxane (〇.1 Μ vs. 1-161) and the mixture were purged with argon for 20 minutes, then the reaction was sealed and heated in an oil bath to 85 ° C for an hour. The reaction mixture was then allowed to cool and then transferred to a sep. funnel with excess ethyl acetate and water. The organic layer was washed with water and saturated sodium chloride. The aqueous layer was extracted back with ethyl acetate. The organic layer was combined, dehydrated and concentrated with sodium sulfate to obtain a crude oil, and the oil was purified by rapid phosgene gel chromatography (hexane/ethyl acetate) to obtain the desired racemic oxime &quot;sitting 1-194 , less than 5% yield. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=392.2 m/z. Activity: A. Example 191

M9Sa 299 201043620 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-195&amp; and 1-19513 were prepared according to the following procedure: racemic dihydroisoxazole oxime-Π8 ( 1.0 eq.) was dissolved in hydrazine, hydrazine-dimethylformamide (0.1 Torr vs. isoxazole), followed by addition of ammonium hydride (3.1 eq.) and sodium azide (1.5 eq.). The reaction was then heated to 120 °C in an oil bath for 4 hours, then the reaction was transferred to a sep. funnel with excess ethyl acetate and water. The organic layer is washed with water and saturated sodium chloride, dehydrated with sodium sulfate and concentrated to give a crude oil, which is purified by rapid sulphur dioxide gel chromatography (hexane/ethyl acetate) to obtain the desired racemic. Pyrazole 1-195, less than 5% yield. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=393.2 m/z. Activity: A. Example 192

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-196a and I-196b were prepared in two steps from racemic compound 1-75, by first using Method 5 to allow 1- 75 is reacted with 6-(ethylthio) ° pyridine-3-phenol (using method 11 from 6-(ethylsulfide) "bipyridin-3-yldihydroxyboronic acid synthesis", followed by a similar example 130 Oxidation. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=431.3 m/z. Activity: A. Example 193 300 201043620

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-197a and I-197b are prepared in a two-step procedure from racemic compound 1_1, via the first use of Method 5 to allow 1-10 Reacts with 6-(methylthio)pyridin-3-ol (synthesized from 6-(fluorenylthio)pyridin-3-yldihydroxyboronic acid using Method 11), followed by oxidation under conditions similar to Example 13 The compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=411.4 m/z. Activity: A. Example 194

(1498)

Ι·1 b b

Synthesis from 2-(1Η-pyrazol-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)pyridine using Method 11 After 6-(1Η-pyrazol-1-yl)pyridin-3-ol, method 5 is used from racemic compound 1-75 and 6-(1Η-pyrazol-1-yl)pyridin-3-ol. 3-(°ipyridin-3-yloxy)-4,5-diisoisoxazole 1-198a and 1-198b were prepared in the following formula. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=405.3 m/z. Activity: A. Example 195 301 201043620

3-Phenoxy-4,5-dihydroisoxazole I-199a and 1-19% are used in Process 5 from racemic compounds 1-14 and 3-(3-methyl-1,2,4-indole The oxazol-5-yl)phenol is prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=406.3 m/z. Activity: C. Example 196

3-Phenoxy-4,5-dihydroisoxazole I-200a and I-200b using method 5 from racemic compounds 1-14 and 4-(2-methyl-2H-tetrazol-5-yl) Phenol is prepared in a one-step process. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=406.4 m/z. Activity: B. Example 197

302 201043620 A phenoxy 4,5-monohydrogen gas sputum and ugly and ^ (10) use method 5 from the 疋 疋 疋 σ ! ! _ _ 14 and 4 _ (1, 3, 4 4 4 2 2 2) The one-step isocratic alpha system is isolated using the HPLC method known to the art. For example, reference is made herein to a method of cutting the palms. [Μ+Η]+=392.2 m/z. Activity: a. Example 198 〇

\ 3_Bromo-4,5-dihydroisoxazole U〇2a and I-202b were prepared according to the following procedure: • Three-step preparation: 4 - ethyl benzophenone chlorinated chlorine (1.0 eq.) dissolved in dichloro The decane (0.375 Μ vs. styrene) was then added with porphyrin (3 〇 equivalent). The reaction was allowed to stir at room temperature for 14 hours and then a white precipitate formed. The reaction was then transferred to a separatory funnel using excess water and dichloromethane. The organic layer was washed with water (1 time), 丄ΝQ HdG), saturated sodium bicarbonate (1 time), and brine (1 time), followed by dehydration with sodium sulphate and a yellow oil. This crude product amount was then used directly to form the desired racemic bromoisoazole using Method 1. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=338.7 m/z. Activity: b. Example 199

|-2〇北(1-203) 303 201043620 Bromine-4,5. Λτ-Isoisoxazole j_2〇3a was prepared using a procedure similar to Example 1, 'but using dimethylamine in tetrahydrofuran (2.0 M ) Replace the porphyrin. These compounds are isolated. For example, refer to m/z here. Activity: a. An example of 200 ^ ° is based on the HPLC method known to the artisan HPLC method Μ n A, I AL · X. [M+H]+=299.3

"2〇4a HN^Me gr

L-204b HN-Me 3-act-4,5' (1-204) milky. The azoles I-2〇4a and I-204b were prepared using a procedure similar to that of Example 198, but using methylamine in tetrahydrofuran. (2_0 M) Alternative to the taste of the palm HPLC method. [M+H]+=282.6 These compounds are isolated using the HPLC method known to the art. For example, reference is made here to m/z. Activity: b. Example 201

丨·初8* NZOSb (1-205) 304 201043620 Oil. This crude product amount is then used directly to form the desired racemic bromoisoxazole using Method 1. These compounds are isolated using the palmitic HpLc method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=374.6 m/z. Activity: A. Example 202

(1-206) 3 -Bromo-4,5-dihydroiso D, etc. I_2〇6a and I-206b were prepared using a procedure similar to that of Example 2〇1, but using: mercaptoamine in tetrahydro M (2. GM) Substituting Weilin These compounds are isolated using the palmar HpLC method known in the art. For example, reference is made to the palmitic HpLC method disclosed herein. [m+h]+=332 6 m/z. Live 1 student: a. Example 203

〇Me S-NH II Ο (1-207) 3 / odor 4,5_-nitrogen-isoxazole I_2〇7a and I-207b were prepared using a similar procedure to Example 201, but using methylamine in tetrahydroanthracene (4) μ) Substituting Wei Lin These compounds are based on the method of separation of palmar HpLc methods known in the artisan community. [m+h]+=31826 m/z. Live,) Health: a. Example 204 305 201043620

(1-208) 3-Oxo-4,5-dihydroiso-n-β is prepared by using a procedure similar to that of Example 198, but using a phlegm to replace the syrup. These compounds are isolated by the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=339.3 m/z. Activity: A. Example 205

(1-Lion&gt; 3-bromo-4,5-dihydroisoxazole I-209a and I-209b were prepared using a procedure similar to that of Example 198 'but used. Billow. Separation is performed using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=322.6 m/z. Activity: a. Example 206

(1-210) 3-Bromo-4,5-dihydroisoxazole 1-21 Oa and 1-21 Ob were prepared using a procedure similar to that of Example 2, but using piperidine instead of porphyrin. These compounds are isolated by the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=472_6 m/z. Activity: a. 201043620 Example 207

(1-211) 3 -淳-4 5 - Know

, --oxoisoxazole l-211a and I-211b were prepared using a procedure similar to that of Example 2, except that the materials were each. t to replace 咮#. These compounds are isolated using the method known to the artisan for the palm muscle c. The age is referenced to the 4-based HPLC method disclosed herein. [M+H]+=358 6 m/z. Activity: A. Example 208

(1-212)

3-(Pyridin-3-yloxy)_4,5-dihydroisoxazole wna and I-212b are prepared in two steps from racemic compound 1-203, by first using Method 5 to allow 1-203 and 6 - (Methylsulfate) was reacted with ?-3-phenol (using η from 6-(methylsulfanyl)pyridin-3-yldihydroxyboronic acid synthesis), followed by oxidation under conditions similar to Example 130. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=390.4 m/z. Activity: B. Example 209

Me, / l.213a (1-213) 1413b 307 201043620 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 1-2133 and 1-2131) are self-exposed in two steps Spin-Compound 1-202 Preparation, by first using Method 5 to allow 1-202 and 6-(mercaptothio)pyridin-3-ol (Using Method 11 from 6-(methylthio)acridin-3-yldihydroxyboronic acid The reaction was synthesized and then oxidized under conditions similar to Example 130. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=426·2 m/z. Activity: Α. Example 210

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole 1-2143 and 1-21413 were prepared in two steps from racemic compound 1-21, by first using Method 5 to allow 1- 21 was reacted with 6-(mercaptothio)pyridin-3-ol (synthesized from 6-(methylthio)pyridin-3-yldihydroxyboronic acid using Method 11), followed by oxidation under conditions similar to Example 130. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=352.2 m/z. Activity: A. Example 211

(1-215) 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-215a and 1-215b were prepared from the racemic compound 1-21 in a two-step procedure. Bromo-4,5-dihydroisoxazole 1-21 308 201043620 was reacted with Method 5 and 5· Fresh formic acid, followed by hydrolysis with a similar example of T. These compounds are isolated using the palmitic HpLC method known in the art. For example, refer to the method of the palm book disclosed herein. [Μ+Η]+=418·3 m/z. Activity: B. Example 212

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-216a and I216b are cyclized addition conditions using Method 1 in a two-step procedure from (trifluoromethyl)-4-vinyl Stupid preparation. The obtained bromo-4,5-dihydroisoxazole was reacted with 2-bromo-5-hydroxypyridine using Method 5 to obtain a racemic compound 1-216. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [m+H]+=389.1 m/z. Activity: b. Example 213

(1-217) 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-217a and I-217b were prepared using a procedure similar to Example 212, but using 3-(1,3, 4-oxadiazol-2-yl)phenol replaces 2-bromo-5-hydroxypyridine. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=376.4 m/z. Activity: A. 309 201043620 Example 214 M\. Me

3-(°pyridin-3-yloxy)-4,5-dihydroisoxazole 1-218&amp; and 1-2181^ were prepared using a procedure analogous to Example 161, but using 丨_methyl_4_(4 ,4,5,5-tetradecyl-1,3,2-diterpenoid _2_yl"Η-pyrazole instead of 4-(4,4,5,5-tetradecyl-1,3 , 2-bis. Boronium-2-yl)-ih-pyrazole-1-carboxylic acid tert-butyl ester. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the disclosure disclosed herein. Palm HPLC method [M+H]+=404.8 m/z. Activity: A. Example 215

3-('1 to bit-3-yloxy)-4,5-dihydroiso. No. 1 219 &amp; and 1-21913 were prepared using procedures similar to Example 161, but using ι_methyl_4_(4,4,5,5-tetramethyl-1,3,2-di-4 side flavor-2 -基)-1Η-«Bit instead of 4-(4,4,5,5-tetramethyl-1,3,2-diindole-2-yl)-out-° than saliva-1- The acid tert-butyl ester and the use of racemic bromopyridine 1-216 instead of I-161 were used as starting materials. These compounds are isolated by the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=390.3 m/z. Activity: A. Example 216 310 201043620

3-(Bite-3-yloxy)-4,5-dihydroisoxazole oxime and preparation were prepared according to the following procedure: Acid 1-97 (1.0 eq.) was dissolved in dichloromethane (〇〇) 8M). Add grass cockroach (1.5 equivalents) followed by a drop of Mi: ^-dimercaptoamine. The reaction was stirred at room temperature for 20 minutes and then concentrated under reduced pressure. The crude material was then dissolved in dioxane followed by the addition of decylamine (12 equivalents), DMAp 〇 mol%) and triethylamine (1.5 eq.). After 3 hours, the reaction was determined by LC/MS analysis. The reaction mixture was then transferred to a sep. funnel using excess ethyl acetate and water. The organic layer was washed with 1 N EtOAc and brine, dried over sodium sulfate and evaporated. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=446.1 m/z. Activity: A. Example 217

3-(phenoxy)-4,5-dihydroisobarium.圭1-221 a and 1-22!b use method 5 from racemic compounds 1-14 and 3-(4Η-1,2,4-tris. sit_4_yl) are prepared in one step. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=392.0 m/z. Activity: C. 311 201043620 Example 218

□

L_222b 3-(phenoxy)-4,5-dihydroisoxazole 1-222&amp; and 1-22213 were prepared in a three-step procedure according to the following procedure: methyl 3-hydroxybenzoate and racemic bromo Carbazole I - 7 5 Reaction using Method 5. The obtained methyl ester (1.0 eq.) was dissolved in methanol (0.08 M), then hydrazine (50 eq., 50% by weight in water) was added and the reaction was allowed to stir for 14 hours. The reaction mixture was then concentrated under reduced pressure and used directly in the next step. Triethyl orthoacetate (8.0 equivalents) was added and the reaction was sealed and heated to reflux for 14 hours. The reaction was then transferred to a separatory funnel using excess ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to give a crude material which was purified by rapid s s. Racemic oxadiazole 1-222. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=42〇.5 m/z. Activity: A. Example 219

(1-223) 312 201043620 3-(phenoxy)-4,5-dihydroisoxazole [223a and prepared using a procedure analogous to Example 218, but using the racemic compound i_ 1 $ instead of the compound ι_75 as a starting point materials. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HpLC method disclosed herein. [M+H]+=406.5 m/z. Activity: a. Example 220

3-(Phenoxy)-4,5-dihydroisoxazole l-224a and I-224b were prepared in three steps according to the following procedure: methyl 3-fluoro-5-hydroxybenzoate and racemic bromine Isoxazole M4 is reacted using Method 5. The resulting methyl ester (1.0 eq.) was dissolved in methanol (EtOAc EtOAc), then EtOAc (50 eq., 50% by weight of water) was added and the reaction was allowed to stir for 14 hours. The reaction mixture was then concentrated under reduced pressure and used directly in the next step. Triethyl orthoacetate (8.0 equivalents) was added and the reaction was sealed and heated to reflux for 14 hours. The reaction was then transferred to a separatory funnel using excess ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to give a crude material which was purified by rapid s s. Racemic oxadiazole〗 _224. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=424.5 m/z. Activity: A. 313 201043620 Example 221 严*1 严Μ iS ΚΙ r\ κι

3-(Phenoxy)-4,5-dihydroisoxazole I-225a and I-225b were prepared using procedures analogous to Example 220, but using triethyl orthoformate in place of triethyl orthoacetate to form the desired oxime. Diazole. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=410.3 m/z. Activity: A. Example 222

3-(Phenoxy)-4,5-dihydroisoxazole I-226a and I-226b were prepared using procedures analogous to Example 220, but using 4-fluoro-5-hydroxybenzoic acid methyl ester instead of 3 in the first step. - Methyl fluoro-5-hydroxybenzoate. Racemic compound 1-15 was substituted for compound 1-75 as starting material. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ+Η]+=410.4 m/z. Activity: A. Example 223 314 201043620

3_(Phenoxy)-4,5-dihydroisoxazole I-227a and I-227b were prepared using a procedure analogous to Example 222, but using a racemic compound instead of Compound 114 as starting material. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm hplc method disclosed herein. [Μ+Η]+=424·2 m/z. Activity: A. Example 224

(1-228) 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole 1-228a and 1-228b were prepared in a three-step procedure according to the following procedure: 5-hydroxynicotinate The ester is reacted with racemic bromoisoxazole 1-75 using Method 5. The obtained methyl ester (1.0 eq.) was dissolved in decyl alcohol (0.08 M), then hydrazine (50 eq., 50% by weight in water) was added and the reaction was allowed to stir for 14 hours. The reaction mixture was then concentrated under reduced pressure and used directly in the next step. Triethyl orthoacetate (8.0 equivalents) was added and the reaction was sealed and heated to reflux for 14 hours. The reaction was then transferred to a separatory funnel using excess ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to give a crude material which was purified by rapid s s. Racemic oxadiazole 315 201043620 1_228. These compounds are isolated using the palmar hplc method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [m+h]+=4〇7.5 m/z. Activity: A. Example 225

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-229a and I-229b were prepared using a procedure analogous to Example 224, but using triethyl orthoacetate instead of triethyl orthoformate. The desired oxadiazole is formed. These compounds are isolated using the HPLC method known to those skilled in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+=422.0 m/z. Activity: A. Example 226

3-(Phenoxy)-4,5-dihydroisoxazole I-230a and I-230b were prepared using a procedure analogous to Example 224, but using the racemic compound 1-145 instead of Compound 75 as starting material. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=393.2 m/z. Activity: A. 316 201043620 Example 227

3-(° ratio. -3--3-oxygen)-4,5-digas π. The 1-23 la and 1-23 lbs were prepared in a three-step procedure according to the following procedure: methyl 5-hydroxynicotinate was reacted with racemic bromoiso D-azole 1-75 using Method 5. The obtained methyl ester (1·〇 equivalent) was dissolved in methanol (〇·〇 8 M), followed by addition of hydrazine (50 equivalents, 50 ° / ❶ weight ratio to water) and allowing the reaction to stir for 14 hours. The reaction mixture was then concentrated under reduced pressure and used directly in the next step.醯肼 dissolve in the second 噚&gt;&gt; mountain (0.12 Μ relative to 醯肼). N,N-carbonyldiimidazole (1.2 eq.) was added and the reaction was sealed and heated to reflux for 4 h. The reaction was then transferred to a separatory funnel using excess ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to give a crude material which was purified by rapid s s. Racemic 1,3,4-oxadiazole-2(3H)-one 1-231. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [m+H]+=423.4 m/z. Activity: B. Example 228

317 201043620 3-(benzene gas) 4 s - &amp; _-oxygen. Izodazole I-232a and I-232b use method 5 from the external compound disin-2-yl) in a one-step preparation of the compound is isolated by the HPLC method known in the art, for example, reference is not disclosed herein. For the palm muscle C method. [Μ+Η卜 =406.5 m/z. Activity: a. Example 229

3_( stupid)-4,5-dihydroisoxazole^2332 and I-233b use method 5 from racemic compound 1-75 and 3-hydroxy-indole, indole-dimercaptobenzenesulfonamide Prepared in one step. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=445.4 m/z. Activity: C. Example 230

3-(phenoxy)-4,5-dihydroisoxazole I-234a and I-234b use method 5 from racemic compound 1-75 and 4-(methylsulfonyl)phenol in one step preparation. These compounds are isolated using the palmar Η P L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=415.6 m/z. 318 201043620 Activity: Β. Example 231

235b (1-235) Ο 3-(phenoxy)-4,5-dihydroisoxazole 1-235&amp; and 1-23513 are used in a method 5 from racemic compounds 1-75 and 4-hydroxy-N N-dimethylbenzenesulfonamide is prepared in a one-step process. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=445_3 m/z. Activity: C. Example 232

M61 2)\^CCh 1) =TMStM03 Cul, DfEA 3&gt;TMSN3tnnw

t«23et&gt; (1-236) 3·(»Bite-3-yloxy&gt;4,5-dihydroisoxazole uhauwb was prepared in two steps according to the following procedure: racemic dihydroisoindole Zinc 1-161 (1.0 ali) is dissolved in N,N-dimethylformamide (0.1 M). Add copper telluride (1.0 eq.) Add dimethyl decyl acetylene (3 〇 equivalent) and qing _Diisopropylethyl cap) Add fun (15 mol%) and the reaction was sealed in a microwave reaction m and heated at 100 C for a few hours. The reaction was allowed to cool and then was transferred to a sifting funnel with ethyl acetate and water. The organic layer was then washed with water and brine, dried over sodium sulfate s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s The TMS group was then deprotected by dissolving this material in methanol (0.07 M) and adding potassium carbonate (3.0 eq.). After stirring at room temperature for 4 hours, the reaction was transferred to a sep. funnel with ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate, evaporated and evaporated. The resulting alkyne was then converted to the desired three-degree sitting by first dissolving in neat trimethyldecyl decylamine (80 equivalents), reacting the mixture with argon gas and heating in a microwave reactor to iio °c for 3 hours. After heating for another 4 hours, the reaction was analyzed by LC/MS to be 60% complete. At this time, the desired racemic triwax was obtained by concentration and purification by rapid phosgene gel chromatography (gradient methanol / di-methane). 1-236. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=392_9 m/z. Activity: A. Example 233

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole I-237a and I-237b were prepared in a two-step procedure from racemic compound 1-148, by first using Method 5 to allow 1- 148 was reacted with 6-(methylthio)pyridin-3-ol (synthesized from 6-(methylthio)pyridin-3-yldihydroborate using Method 11) followed by oxidation under conditions analogous to Example 130. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=396.6 320 201043620 m/z. Activity: A. Example 234

MeS CF3 ‘奶私 f-258b (1-238)

1,4-Azine _3_base gas-4,5-dihydroisoxazole I-238a and I-238b are cyclized addition conditions using Method 1 in a three-step procedure from 1-(trifluoromethyl) Preparation of -4-vinylbenzene. The obtained bromo-4,5-dihydroisoxazole is prepared by the method 5 and 6-(mercaptosulfur) ratio 0疋-3-盼(using method ^from methylsulfonate)pyridine_3_yldihydroxyboronic acid) And obtained the s material 1_238. These compounds are read using the HPLC HPLC method known to the art. Yarn ginseng material

law. [Μ+Η]+=355·3 m/z. Activity: A. Example 235

3-(Pyridin-3-yloxy)_45 _ oxaisoxazole I-240a and I-240b were prepared in a two-step process according to the following procedure. Benzene-6-bromopyridine _3_phenol (1 〇 equivalent) and sodium carbonate (1〇_〇 equivalent) add Qianbo vial. Add toluene, ethanol and water (〇16 Μ ' 2:2:1 v/v) followed by thiol-4-(4,4,5,5_tetramethyl_ι,3,2-dioxide 321 201043620 boron嗱-2-yl)-1 Η-«biazole (1.5 equivalents). The mixture was purged with argon for 15 minutes to add palladium ruthenium (4 mol%). The reaction tube was then covered with aluminum platinum and heated to 80 cC in an oil bath for 17 hours. After cooling, the reaction was transferred to a separating funnel with excess water and ethyl acetate. The organic layer was then washed with water (1 time), saturated ammonium sulfate (1 time), and saline (1 time). The aqueous layers were combined and washed with ethyl acetate (1 time). The organic layers were then combined, dehydrated with sodium sulfate, concentrated and purified using rapid cerium dioxide gel chromatography (gradient methanol/dichloromethane) to afford 6-(1_methyl-1H_°bazole_4_yl) Than set the ratio of 1-39 to white solid. This compound is then reacted with racemic 3-bromo-4,5-dihydroiso-beta azole 1-75 using Method 5 to give the desired external ss. compound 1-240. These compounds are isolated using the HPLC method known to the art. For example, refer to the method of palmity ^^1^ disclosed herein. [Μ+Η]+=419·3 m/z. Active · Α.

3-(0 to δ-3-yloxy)-4,5-dihydroiso- 0. ° 1_241&amp; and 1-24113 were prepared using a procedure similar to that of Example 235, but using the 1 - fluorenyl group in the first step. -5-(4,4,5,5_tetramethyl-1,3,2-di-2-a-2-yl)-1 heart ratio ° sitting instead of 1-methyl bucket (4,4,5,5 Tetramethyl-1,3,2-dioxaboron-2-yl)-ex-pyrazole as dihydroxyborate. These compounds are isolated using the muscles known to the artisan. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=406.2 m/z. Activity: A ° 322 201043620 Example 237

(1-242) ❹ 3 (bipyridin-3-yloxy)-4,5-dihydroisoxazole I-242a and I-242b were prepared using a procedure similar to that of Example 188, but with a ss. Substitute compound 1_14 is the starting material. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palm muscle c method disclosed herein. [M+H]+=406.3 m/z. Activity: Α. Example 238

L*243a (1-1243)

"243b

G 2-(4,5-Dihydroisoxazole-3-ylamine)ethanol [24% and oxime were prepared in two steps according to the following procedure: racemic 3_bromo-4,5-dihydrogen Isocarbazole 1-1 〇 (1.0 eq.) was dissolved in n-butanol (0.57 Å) followed by (t-butyldimethyl sulfonyloxy) methylamine (1.2 eq.) and sodium carbonate (2.5 eq.). The reaction was sealed in a microwave reaction vial and heated at 150 °C for 1 hour, followed by LC/MS analysis for very little product formation. The reaction is then sealed again and again at 120 in the microwave. (: heating for 24 hours, then moving to the separatory funnel with excess water and tert-butyl decyl ether. The aqueous layer was washed with tributyl methyl ether (2 times) and the combined organic layers were washed with brine and dried over magnesium sulfate. Concentrated to obtain an orange solid. The solid was purified by using a flash of 323 201043620 oxidized stone yttrium gel chromatography (gradient acetic acid s|/hexane) to obtain the desired succinyl ether d. This compound (1 〇 equivalent) was dissolved in Hydroxide (〇(10)M) and cooled to 叱 in an ice bath. Add _(5 〇 equivalent) to the county, then allow the reaction to mix at 0° (10) for 3G minutes. Then, under the nitrogen flow, the wrong solvent and the remaining acetamidine' The product material was purified by rapid dioxygen (10) gel chromatography (gradient ethyl acetate / methanol) to afford the racemate _ 243. These compounds were isolated using the palm-like HPL C method known in the art. For example, The palmar HPLC method revealed. [m+H]+=300.2 m/z. Activity: B. Example 239

2-((4,5-Dihydroisosanisin-3-yl)(indenyl)amine)acetic acid U44a and I-244b were prepared in two steps according to the following procedure: racemic 3-di-_4, 5-Dihydroisoxazole I-10 was converted to the corresponding 3-amine-4,5-dihydroisoxazole by reaction with creatinine under the same conditions as in Example 23 8. The ethyl ester was then hydrolyzed using similar conditions as in Example 119 to afford the racemic mixture 1-244. These compounds are isolated by the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-=327.5 m/z. Activity: b. Example 240

324 201043620

2-(4,5-Dihydroisoxazol-3-ylamine) alcohol was prepared in 4 steps according to the following procedure: racemic 3-bromo-4,5-dihydroiso The carbazole 1-10 do equivalent) was dissolved in n-butanol (0.64 Torr) followed by (S)-2-amine-1-phenylethanol (1.2 eq.) and sodium carbonate (2.5 eq.). The reaction was sealed and heated to 120 ° C in an oil bath for 18 hours then allowed to cool and then transferred to a sep. funnel using excess water and &lt;RTIgt; The aqueous layer was washed with tert-butyl methyl ether (2 times) and the combined organic layers were washed with brine, dried over magnesium sulfate and concentrated to give an orange solid. solids using rapid cerium dioxide gel chromatography (gradient benzene/hexanes) Purification to benzene/ethyl acetate afforded the racemate 1-245 as a white solid. These compounds are isolated using a palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=374.20 m/z. Activity: C. Example 241

OCF, l-246a

OCF3 l-246b

(1*246) 2-(4,5-Dihydroisoxazol-3-ylamine)ol 1-246 &amp; 1-2461) was prepared using a procedure analogous to Example 240, but using racemic 3-bromo -4,5-Dihydroisoxazole 1-14 instead of 3-bromo-4,5-dihydroisoxazole 1-10 as starting material and using (R)-2-amine-1-phenylethanol instead (S)-2-Amine-1-phenylethanol. These compounds are isolated using the palmitic HpLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=365.6 m/z. Activity: C. Example 242 325 201043620

(1-248) 3-(phenylthio)-4,5-dihydroisoxazole I-248a and I-248b were prepared in two steps according to the following procedure: N,N-dibromofurfural oxime ( 1·0 equivalent) was dissolved in tetrahydrofuran. Thiophene (2.0 equivalents) was added followed by sodium hydride (1.98 equivalents). After stirring for 1 hour, the reaction was concentrated and purified by flash chromatography on silica gel (yield ethyl acetate / hexanes) to afford the desired phenyl succinimide diphenyl ester 1-247. The dithioester (1.0 eq.) was then redissolved in acetonitrile (1.0 Torr) followed by 1-(trifluoromethoxy)-4-vinylbenzene (2.4 eq.), silver nitrate (1.0 eq.) and potassium carbonate (1.0 eq. ). The reaction was allowed to stir at room temperature for three hydrazines, followed by concentration and purification by flash chromatography on silica gel (gradient ethyl acetate / hexanes) to give racemic 3-(phenylthio)-4,5- Dihydroisoxazole 1-248. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=339.9 m/z. Activity: C. Example 243

3-(phenylsulfinyl)-4,5-dihydroisoxazole I-249a and I-249b via racemic 3-(phenylthio)-4,5-dihydroisoxazole 1 -248 oxidation preparation. 3-(phenylthio)-4,5-dihydroisoxazole 1-248 (1.0 eq.) was dissolved in ethanol (0.15 326 201043620 M) followed by the addition of excess hydrogen peroxide to water (30% by weight greater than 50 equivalents) And 1 N HC1 (〇_29 M). The reaction was stirred at room temperature for 14 hours and then transferred to a sep. funnel with excess water and dichloromethane. The aqueous layer is extracted with dichloromethane (1 time), dehydrated and concentrated by sulfuric acid to obtain a crude product, and the alkane is recrystallized to obtain the desired racemic 3-(phenylsulfinyl)-4,5-dihydrogen. Isoxazole 1-249. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=355.5 m/z. Activity: C. Example 244 〇

- a-2sa) — 3_(phenylsulfonyl)-4,5-dihydroisoxazole I_25〇a&amp;i_250b via racemic 3-(phenyl arginyl)-4,5-di Hydrogen is different from $β by the oxidation of 1-249. 3-(phenylsulfinyl)-4,5-dihydroisoindole was dissolved in di-methane (0.03 Μ). The m-chloroperbenzoic acid (77% by weight, 2.95 Å) equivalent was added in two portions and the reaction was allowed to stir for 14 hours and then transferred to a separatory funnel with excess water and dioxane. The organic layer was washed with saturated sodium bicarbonate (2×), dried over magnesium sulfate and concentrated to give a crude solid, which was recrystallized from dichloromethane/hexanes to afford the desired racemic. )_4,5_Dihydroisosaki. Take 1-250. These compounds are isolated using the palm muscle c method known in the art. For example, reference is made to the palmitic HpLC method disclosed herein. [M+H]+=371'7 m/z. Activity: c. Example 245 327 201043620 h〇2c

〇CF3 1*251 a

HOaC

l-2S1b (1-251) 3-(stupylthio)-4,5-dihydroisoxazole 1_251&amp; and 1-2511) were prepared using a procedure similar to that of Example 242, but using 'methyl benzoate The thiophenol is replaced to form the desired transimine dithioester. The resulting methyl ester cyclo adduct was then hydrolyzed using similar conditions as in Example 94 to give racemic 3-(phenylthio)-4,5-dichloroiso-l-1-251. These compounds are isolated using the HPLC method known to the art. For example, refer to the palm method disclosed herein. [M+H]+=384.1 m/z. Activity: c. Example 246

N-ethyl-N-phenyl_4,5-dihydroisoxazole_3_amine and ^253b were prepared in two steps according to the following procedure: N,N-dibromoformaldehyde oxime (i 〇 5 equivalents) ) Dissolved in acetonitrile. Add thiophenol (1_〇 equivalent) and N-ethylaniline (1 〇 equivalent) and allow the reaction to stir at room temperature for 2 hours, then add triethylamine (5 〇 卜 授 授 1 1 1 1 1 1 1 The solid from the reaction in the reaction is transitioned out and the filtrate is concentrated and directly purified by rapid phosgene gel chromatography (Ladder Acetyl burned with 1% triethylamine) to obtain the desired chitoimine. Thioester 1-252. Then the formazan imide thioester (1.0 eq.) is then redissolved in B 328 201043620 (1·0 Μ) followed by 1-(trifluoroanthracene)-4-vinylbenzene (2.4 equivalents), silver nitrate equivalent) and potassium carbonate (1.17 equivalents). The reaction was allowed to stir at room temperature for 1 Torr and then purified by flash chromatography on silica gel (gradient ethyl acetate / hexanes containing 1 〇 / 〇 diethylamine) to give racemic 4,5-dihydroiso Carbazole-3-amine 1-253. These compounds are isolated using the palmar HP L C method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=352.l m/z. Activity: C. Example 247

L-255b (1-255) N-methyl-N-phenyl-4,5-dihydroisoxazol-3-amine 1-2553 and 1-25515 were prepared in three steps according to the following procedure: hydrazine, Ν-二溪甲经 (1 .〇5 equivalent) was dissolved in acetonitrile. Sulfur (1_〇 equivalent) and methyl 4-(methylamine)benzoate (1·〇 equivalent) were added, followed by the addition of triethylamine (3.0 equivalents) in three portions. After 3 hours of mixing, the reaction was transferred to a separatory funnel with excess water and two mice. The organic layer was washed with 1 N HCl (2 times), dehydrated with magnesium sulfate 'concentrated and subjected to rapid cerium oxide gel chromatography (gradient ethyl acetate / hexanes containing 0.5% triethylamine followed by gradient sterol) Purification with /dichloromethane containing 0.5% triethylamine) afforded the desired chitoimine thioester 1-254. The formazan imide thioester (1 〇 equivalent) is then redissolved in acetonitrile (1.0 Μ) followed by 1-(trifluoromethoxy)vinylbenzene (18 equivalents), silver nitrate (2.3 equivalents) and carbonated (2.1 equivalent). Allow reaction in chamber 329 201043620 Stirring for 1 day followed by rapid phosgene gel chromatography (gradient ethyl acetate / hexane containing 0.5% triethylamine followed by gradient methanol / dichloromethane containing 0.5% triethyl) Base amine) purification. The resulting racemic methyl ester cyclized adduct was then hydrolyzed using conditions similar to the one obtained in Example 94 to afford ss. N-methyl-N-phenyl-4,5-dihydroisos-s-zolidine-3-amine 1-255. These compounds are isolated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=381.5 m/z. Activity: C. Example 248

L-258a i-256b (1-256) 3-(pyrrolidin-1-yl)-4,5-dihydroisoxazole I-256a and I-256b were prepared using a similar procedure as in Example 238, but using pyrrole The pyridine is substituted for (S)-2-amine-1-phenylethanol. These compounds are isolated using the palmitic HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+=310.3 m/z. Activity: C. Example 249

3-(1-methyl-3-(trifluoromethyl)-1Η-.bazol-5-yloxy)-4,5-dihydroisoxazole I-257a and I-257b use method 5 Compound 1-10 and 1-methyl 330^1〇4362〇, 3, (Tris&amp;~虱methyl)-1Η-pyrazole-5-phenol were prepared in a one-step procedure. These compounds are isolated by the HPLC method known to the art. For example, refer to the palmar HPLC method shown here. [m+h]+=403.7 m/z. Activity: B. Example 2S〇

I^SBa

OCF3 - (stupyloxy)-4,5-dioxaisoxazole I 258a and I 258b are used from racemic compounds 1-14 and 3_(1,3,4-oxadiazol-2-yl) Phenols can be isolated by the procedure of the palmitic HpLC method known in the art, for example, with reference to the palmitic HpLC method disclosed herein. [m+h]+ = 3Μ·4 m/ζ. Activity: a. Example 251

3_(° is more than 唆_3_based oxygen &gt; 4'5, dihydroisotaxel and μ25% are prepared using f W 15 21 g 'but using the racemic compound I _ 17 g as the starting acid. These compounds can be isolated using the known palmar HpLc method known in the 彳transfer group. For example, refer to this $$&lt;对胄(四)pLG#法[m+h]+ = ·7 m/z. Activity: A. Example 252 331 201043620

卜26 gamma-260b (1*260) 4,5-dihydroiso 4 ° sit-3-yl acetate was prepared in 3 steps according to the following procedure: racemic bromoisoxazole ^ 0 (10 equivalents) dissolved In tetrahydrofuran (1.0 Μ). A 1 Torr sodium hydroxide solution (4 eq. equivalent) was added followed by propylene glycol (45 eq.). The reaction was sealed and heated to 6 ° C for 3 hours. The reaction mixture was allowed to cool and then transferred to a sep. funnel using excess water and ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by flash chromatography (eluent ethyl acetate/hexanes). The resulting allyl ether (10 equivalents) was then dissolved in tetrahydrofuran (0.2 M). Niobic acid (5_〇 equivalent) was added followed by tetrahydroindenyl palladium (10 mol%), and then the reaction was allowed to stir at room temperature for 2 hours. The reaction mixture was transferred to a separatory funnel with excess water and ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate and purified with EtOAc (EtOAc). The obtained isoxazolidine-3-one (1.0 eq.) was dissolved in dichloromethane (0.3 M), then hydrazine, dimethyl-dimethylamine pyridine (1.0 eq.) and acetic anhydride (1.0 eq.). After stirring at room temperature for 14 hours, the reaction was transferred to a sep. funnel with excess water and ethyl acetate. The organic layer was washed with 1 mL of hydrochloric acid and brine, dried over sodium sulfate and concentrated to afford the desired racemic acetate 1-260. Such compounds can be separated using the palmitic HpLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+ = 297.8 m/z. Activity: D. 332 201043620 Example 253

L-261a 1-261 b (1-261)

3-(pyridin-3-yloxy)-4,5-diisoisoxazole 1-261 &amp; and 1-2611) was used first from Example 11 from 6-(mercaptothio)pyridin-3-yldihydroxy After the preparation of 6-(mercaptothio)pyridin-3-ol by boric acid, it was prepared in 1 step from racemic compound 1-75 and 6-(mercaptothio)pyridin-3-ol using Method 5. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+ = 386.2 m/z. Activity: A. Example 254

Ll-1a 11-1 b (IM)

3-Bromo-4,5-dihydroisoxazole 11-13 and 11-113 were prepared in a 1 step from 4-vinylpyridine using Method 2. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 226.0 m/z. Activity: C. Example 255

(H-2) 3-Bromo-4,5-dihydroisoxazole 11-23 and 11-2 oxime Method 2 was prepared from 3-ethylene 333 201043620-based pyridine in 1 step. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. 226.0 m/z. Activity: C. Example 256

Br

Ll-3a H-3b (II-3) 3-bromo-4,5-dihydroisoxazole II-3a and II-3b were prepared in a 1-step from 2-vinylpyridine using Method 2. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 226.0 m/z. Activity: C. Example 257

Llb-4a IMb (II-4) · 3-Bromo-4,5-dihydroisoxazole 11-4&amp; and 11-413 are starting from the use of method 8 from 1-phenyl-1H-pyrazole-4- The furfural alkene was formed and then prepared in 2 steps by a cycloaddition using Method 2. Such compounds can be separated using a palm-by-pure HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 291.0 m/z. Activity: B. Example 258

ll-Sa ll*5b (II-5) 334 201043620 3-Bromo-4,5-dihydroisoxazole II-5a and II-5b starting from the use of method 8 from 2-phenyl-1,3-thiazole The formation of -4-formaldehyde is then carried out in two steps by the addition of cyclization using Method 2. Such compounds can be separated using a palm-by-pure HPLC method known in the art. For example, reference is made to the method of palm sputum disclosed herein. 308.0 m/z. Activity: c. Example 259 Ο

3-Bromo-4,5-dihydroisoxazole is formed by the use of Method 8 from 2-phenyl-1,3-thiazole-5-furaldehyde aldehyde, followed by cyclization addition 2 steps were prepared. Such compounds can be separated using a palm-by-pure HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 308.0 m/z. Activity: A. Example 260

3-Derivative-4,5-dihydroiso'•ββ n_7a and n_7b are formed from 5-phenylthiophene-2-carbaldehyde by using Method 8, followed by cyclization addition using Method 1. 2 steps were prepared. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 309.6 m/z. Activity: A. Example 261 335 201043620 KT0, ,s

3-Bromo-4,5-dihydroisoxazole II-8a and II-8b are formed starting from 4-phenylthiophene-2-carbaldehyde using Method 8, followed by cyclization addition using Method 2 Prepared in 2 steps. Such compounds can be isolated using the palmitic HpLC method known in the art. For example, refer to the method of palmity ^11&gt;1^ disclosed herein. = 307·0 m/z. Activity: a. Example 262

3_演_4,5_Di-argon-isospin II-9a and II-% are formed by the method 8 from 6-quinoline formaldehyde olefin, followed by the method 2 using cyclone addition to prepare in 2 steps . These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ-Η]-= 276·0 m/z. Activity: a. Example 263

The 3 genera _4,5-dihydroisoxazole oxime-lOa and II-l〇b are formed by the method 8 using 3-quinoline formaldehyde olefin, followed by the method 2 by cyclization addition and 2 steps. Preparations These compounds can be separated using the HPLC method 336 201043620 known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [Μ_Η]·= 276.0 m/z. Activity: a. Example 264

3-Molybdenum-4,5-dihydroisoxazole H-lla and n_llb are formed by the method 1 method for the formation of alkene from 6-bromoquinoxaline'. Then, using the method 2, the cycloaddition is carried out and the preparation is carried out in 2 steps. . These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 277.0 m/z. Activity: A. Example 265

Me Me 11.12» (II-12) 3-Molybdenum-4,5-dihydroiso-salt H-12a and II-12b start from use method 9 from 5-bromo-1-methyl-1H-indole The alkene is formed and then prepared in 2 steps using cyclization addition using Method 2. Such compounds can be separated using a palm-by-pure HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 278.0 m/z. Activity: A. Example 266

337 201043620 3-Bromo-4,5-dihydroisoxazole π-13a and II-13b are prepared in two steps starting with Boc to protect 2-amine-6-bromo benzothiazole as follows: benzothiazole (1〇) Equivalent) dissolved in dioxane (〇·12 M relative to thiazole). Then, dibutyl phthalate (3.0 eq.) was added, followed by hydrazine (0.20 eq.) in five portions. The reaction was allowed to stir at 23 ° C for 2 hours and then no longer contained in the mixture by TLC. The reaction was quenched by the addition of methanol (75 eq.) and allowed to stir for 1 hr. then the reaction was dissolved in water and dichloromethane, and the organic layer was washed with 〇5 Μ citric acid solution (2 times) and saturated sodium bicarbonate The solution is washed once (1 time), dehydrated with magnesium sulfate and concentrated under reduced pressure to give a crude solid which can be directly transferred to the desired 3-bromo-4,5-dihydroisoxazole using Method 9 followed by Method 2. Such compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-Η]- = 397.0 m/z. Activity: Β. Example 267

1-Allyl n-morphine was dissolved in methylene chloride (1.1 M relative to morphine). Potassium carbonate (1.5 equivalents) was added followed by ditributyl dicarbonate (1.1 equivalent). The reaction was allowed to stir for 16 hours, then dissolved in water and a third butyl methyl ether. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to give a crude product. Desirable 3-bromo-4,5-dihydroisoxazole 11-143 and 11-1 flutter. Such compounds can be separated using the HPLC method known to those skilled in the art. For example, reference is made to the palm 338 201043620 HPLC method disclosed herein. [M-H]- = 347.1 m/z. Activity: A. Example 268

(Π*15)

3-Bromo-4,5-dihydroisoxazole II-15a and II-15b are formed starting from the olefin of 4-methylmercaptopiperidine-1-carboxylate using Method 8, followed by Method 2 The cycloaddition was prepared in 2 steps. These compounds can be separated using a palm-by-peach HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 366.1 m/z. Activity: B. Example 269

H-16a il-16b (IM6)

3-Bromo-4,5-dihydroisoxazole II-16a and II-16b are formed starting from the olefin of 4-methylmercaptopiperidine-1-carboxylic acid tert-butyl ester using Method 8, and then used. 2 Prepared in 2 steps by cyclization addition. Such compounds can be separated using the palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M-H]-= 332.1 m/z. Activity: A. Example 270

(Π-Π) 339 201043620 3 -Bromo-4,5-dihydroisoxazole II-17a and II-17b are starting from the use of method 8 from 2-(4-chlorophenyl)thiazole-5-formaldehyde Formation, followed by the addition of Method 1 by cycloaddition and preparation in 2 steps. These compounds can be separated using a palm-by-peach HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 342.5 m/z. Activity: A. Example 271

3-Bromo-4,5-dihydroisoxazole Ii_i8a and II-18b are formed starting from the olefin of 1-(2-phenylthiazol-5-yl)ethanone using Method 8, followed by the use of Method 1 Addition is carried out in 2 steps. These compounds can be separated using a palm-by-peach HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 322_3 m/z. Activity: A. Example 272

3-Bromo-4,5-dihydroisoxazole 11_19a and II-19b are formed starting from the olefin of 2-phenylthiazole-5-formaldehyde using Method 8, followed by cyclization addition using Method 1 to 2 The procedure was followed but the bromomethyltriphenylphosphonium was replaced with bromoethyltriphenylphosphine. [M+H]+= 325.1 m/z. Activity: A. Example 273 340 201043620

3-Di-4,5-dihydroisoxazole oxime and n_2〇b are trans diastereoisomers which were also formed during the cycloaddition of Example 272. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the single-plex HPLC method disclosed herein. [m+H]+= 324.9 m/z. Activity: C. Example 274

Pyridine_3_yloxy)-1 2,3-dihydroiso. The azoles II-21a and II-21b were prepared by the procedure 3 from the racemic compound II-6 and 3-hydroxypyridine. Such compounds can be separated using the method known to the art for the palmar tendon method, for example, by reference to the palmitic HPLC method disclosed herein. [M+H]+= 325.1 m/z. Activity: Example 275

341 1 ten-bit _3~yloxy)-4,3-dihydroisoxazole II-22a and II-22b are prepared by the method 3 from the racemic compounds 11-18 and 5-hydroxypyrimidine in 1 step. . These 3 compounds can be separated using the palmitic HpLC method known in the art. For example, refer to 201043620 to test the palm of the hand 1^!^: method. [M+H]+= 34〇_4 m/z. Activity: A. Example 276

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole II-23a and II-23b were prepared in a small amount of 1 from racemic compound H-18 and 3-hydroxypyridine. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 339·3 m/z. Activity: A. Example 277

3-bromo-4,5-dihydroisoxazole n_24a and II-24b are formed starting from the use of olefins from 1-(4-methyl-2-phenylthiazole-5-yl)ethanone, followed by Method 1 was prepared in 2 steps by cycloaddition. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+= 339.0 m/z. Activity: b. Example 278

342 201043620 3 · Bromo-4,5-dihydroisoxazole II-25a and II-25b are formed by the use of the method 8 1 5_° ratio °疋_3_ base ° cephene-2-carbaldehyde, followed by Method 1 was prepared in 2 steps by cycloaddition. These compounds can be separated using the HPLC method known to the art. For example, refer to the palmar hPLC* method disclosed herein. [M+H]+n , 1〇·3 m/z. Activity: A. Example 279

3_(spray °~5'-based oxygen)_4,5-dihydroisoxazole II_26a and II-26b were prepared by substep 5 from racemic compounds 11-25 and 5-hydroxypyrimidine in 1 step. Such aliquots can be separated using a palm-to-Purpose HPLC method known in the art. For example, reference is made to the word palm HPLC method disclosed herein. [M+H]+= 325.1 m/z. Activity: A. Example 280

(11-27) 3 apyrimidine·3-yloxy)-4,5-dihydroisoxazole II-27a and II-27b were prepared from racemic compound 11-25 in 2 steps according to the following procedure: 5 - Methotrexate is reacted using Method 5 followed by hydrolysis of the methyl ester. Racemic 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole 11-27 oxime ester (1 〇 equivalent) dissolved in hydrazine:] tetrahydrofuran/water (0.06 M) and Lithium hydroxide (8. 〇 equivalent) was added. The reaction was allowed to stir for 1 hour, then the tetrahydrofuran was removed under a stream of nitrogen, and the remaining solution 343 201043620 mN hydrochloric acid was acidified to pH less than 2 to provide the desired acid-like % and (10) as a white solid, which was taken care of. This chelate can be isolated using the poetic muscle c method known in the art. For example, refer to this (d) for the palm HPLC method. [M+H]+= 367.5 m/z. Activity: a. Example 281

3-(pyridin-3-yloxy)_4,5-dihydroisoxazole and n_28b are prepared in two steps from racemic compound II-6, which is prepared by first using method 5 to allow II·6 With 6-(methylsulfonium) hydrazine. The reaction of _3_alcohol (prepared by the method 11|6 (mercaptosulfuryl)pyridin-3-yldihydroxyboronic acid), followed by oxidation according to the following procedure · · racemic 3-(6-(mercaptosulfuryl) hydrazine Pyridin-3-yloxy)_4,5-dihydroisoxazole is dissolved in a gas-fired product (in the case of iso-f. It is 0·5 M in sitting). The acid (2.0 equivalents) was allowed to stir at room temperature for a few hours. After the completion of the reaction by l^/1^^, the solvent was removed by evaporation. The crude product mixture was then dissolved again in the third butyl methyl ether (0.5 M). Then hexane was added slowly until the solid precipitated. The solid was then collected by vacuum filtration and washed with hydrazine: hexanes/MTBE to give the desired 3-(pyridin-3-yloxy)-4,5-dihydrocarbazole π 2% and II-29b as a white solid. These compounds can be separated using the HPLC method known to the art. For example, refer to the palmar HpLc method disclosed herein. [M+H]+= 404.1 m/z. Activity: A. Example 282 344 201043620

*l*29a ||-29b (0*29) 3-(pyridin-3-yloxy)_4,5-dihydroisoxazole n_29a and II-29b are prepared in two steps from racemic compound II_18, The preparation method is prepared by first using Method 5 to allow the preparation of noon 11-18 and 6-(methylthio)D ratio to be determined by the method η from 6-(mercaptosulfuryl)pyridin-3-yldihydroxyboronic acid. The reaction is then oxidized under similar conditions to the example of scorpion. These compounds can be isolated using the palmitic HpLC method known in the art. For example, refer to the palmitic HpLC method disclosed herein. [M+H]+= 417.9 m/z. Activity: a. Example 283

The procedure was prepared in 1 step: racemic 3_in_4,5 dihydroisoxazole 18 (1 〇 equivalent) was dissolved in n-butanol (0.64 M), followed by (S)_2-amine phenylethyl alcohol (1.2) Equivalent) and sodium carbonate (2.5 equivalents). The reaction was sealed and heated in an oil bath to 120 C for 18 hours, allowing the P to cool and then transferring water and tributyl decyl ether to a separatory funnel. The aqueous layer was washed with tert-butyl methyl ether (2-man) and the combined organic layer was washed with brine, dehydrated with magnesium sulfate and concentrated to give an orange IU. The solid was purified by rapid disulfide 11 gel chromatography (gradient Benzene/hexane to toluene/acetic acid ethyl acetate) obtained racemic π_3 〇 as white solid 345 201043620. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 374.20 m/z. Live j students: C. Example 284

(11-31) 2-(4,5-Dihydroisoxazol-3-ylamine) alcohols II-31a and II-31 b were prepared using a similar procedure of Example 283, but using (R)-2- Amine-1 - phenylethanol replaces (S)-2-amine-1-phenylethanol. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 366.4 m/z. Activity: C. Example 285

(1IH) 3-Bromo-4,5-dihydroisoxazole III-1 was prepared in a 1-step cyclodecylcyclohexane using Method 1. [M-H]-= 217.0 m/z. Activity: A. Example 286

_&quot;*2a (m-2) 8r 3-bromo-4,5-dihydroiso. The azoles 111-2 &amp; and 111-21) were formed starting from 4-tert-butylcyclohexanone olefin using Method 6, followed by cyclization addition using Method 1 346 201043620. Such compounds can be separated using a palm-by-pure HPLC method known in the art. For example, refer to the method for the palm of the hand disclosed herein. [M-H]-= 273.1 m/z. Activity: b. Example 287

3-Bromo-4,5-dihydroisoxazole m_3a and m_3b were formed starting from the dilute of 4-phenylcyclohexanyl using Method 6, followed by the addition of cyclization using Method 1 in 2 steps. These compounds can be isolated using the palm muscle c method known in the art. For example, refer to the method for the palm of the hand disclosed herein. Bu = 293.0 m/z. Activity: a. Example 288

Br iiu^) 3-漠-4,5_二气异十坐m-4 begins at the user's side ^ from i 4_ snail [4.5] 癸相之埽, ^ step system H no 1 fine maiden addition Take 2 〆娜衣275.0 m/z. Activity: C 0 Example 289

(111-8) 347 201043620 The procedure is reduced to compound III-5: 4-indane cyclohexanoic acid B is added to a solution of lithium aluminum hydride (4.0 eq.) in diethyl ether (1 〇Μ relative to nitride) Ethyl ether (2.0 相对 relative to the ester). The reaction was heated to reflux for 2 hours, then cooled in an ice bath and quenched with water and water then isopropyl alcohol &lt;RTIgt; The ketone is then filtered and the cake is washed with an excess of diethyl ether; The filtrate was washed with water and brine, dried over sodium sulfate and evaporated. Compound 111-5 (1.0 eq.) was then dissolved in the pyridine bit (0.90 M relative to the alcohol). P-Phenylbenzenesulfonate (1.1 eq.) was added and the reaction was allowed to stir for 16 hours, then quenched with a few drops of water, diluted with an excess of two gas and washed with water, dilute hydrochloric acid and brine. The organic layer was dried with sodium sulfate and EtOAc evaporated. The phenol (1.2 equivalents) was then dissolved in N,N-dimethylformamide (0.20 M relative to the fluorite). Cesium carbonate (1.3 eq.) was added followed by the addition of compound 111-6 (1.0 eq.) and hydrazine (0.10 eq.). The reaction was heated to 4 Torr. It was then diluted with tert-butyl methyl ether and washed with dilute sodium hydroxide, water and brine, and then dehydrated with sodium sulfate. Concentration under reduced pressure afforded the compound y-7 as a crude oil, which was used without further purification.

The crude olefin was directly converted to the desired diastereoisomers 3-bromo-3,4-dihydroisoxazoles III-8a and III-8b using the procedure 2 in one step. Such compounds can be isolated using the palmitic HPLC method known in the art of 348 201043620. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 323.6 m/z. Activity: A. Example 290

(ΙΠ-9)

3-Bromo-4,5-dihydroisoxazole 111-9 is formed from the olefin of 1-(t-butoxycarbonyl)-4-piperidone using Method 7, followed by Method 1 or Method 2 The cycloaddition was prepared in 2 steps. [M-H]-=318.1 m/z. Activity: A. Example 291

The 3-bromo-4,5-dihydroisoxazolium-lOa and ΙΙΙ-lOb systems are formed starting from the olefin of 1-(t-butoxycarbonyl)-3-piperidone using Method 7, followed by Method 1 It was prepared in 2 steps by cyclization addition. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 318.1 m/z. Activity: C. Example 292

(111-11) 3-Bromo-4,5-dihydroisoxazole ΙΙΙ-lla and ΙΙΙ-llb are formed from the formation of alkene from N-(t-butoxycarbonyl)-3-pyrrolidone using method 7 Then, using Method 1 349 201043620, it was prepared in 2 steps by cyclization addition. Such compounds can be separated using the palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+= 304.7 m/z. Activity: B. Example 293

(ΙΙΪ&quot;Ί 2) 3-Bromo-4,5-dihydroisoxazole III-12a and III-12b start from the use of method 7 from 1-(t-butoxycarbonyl)-4-indene Formation, followed by the addition of Method 1 by cycloaddition and preparation in 2 steps. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. 332.1 m/z. Activity: A. Example 294

(ΙΠ-13) 3-bromo-4,5-dihydroisoxazole IIl-i3a and in_i3b are formed from the N-(t-butoxycarbonyl)-deindenyl ketone olefin starting from method 7, and then Method 1 was prepared in 2 steps by cycloaddition. Such compounds can be separated using the palmitic HP L C method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. 344.1 m/z. Activity: C. Example 295

(UI-I4) 350 201043620 3-Bromo-4,5-dihydroisoxazole III-9 was dissolved in trifluoroacetic acid (0.20 Torr relative to isoxazole) and stirred at room temperature for 1 hour. Then, the solvent and the crude product residue were removed under reduced pressure and azeotrope distilled with toluene (2 times) to obtain yttrium-14 as a TFA salt (white solid). [Μ-Η]-= 218.0 m/z. Activity: C. Example 296

{ΙΠ-15) 3-Bromo-4,5-dihydroisoxazole III-14 was dissolved in dichloromethane (0.03 M relative to isoxazole) followed by the addition of triethylamine (4.0 eq.) and acetic anhydride ( 3.0 equivalents). The reaction was allowed to stir for 16 hours then diluted with ethyl acetate and washed with dilute hydrochloric acid, dilute sodium hydroxide and then brine. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford crude material (yield of ethyl acetate/hexanes). [M-H]-= 260.0 m/z. Activity: C. Example 297

(ΙΠ-16) 3-Bromo-4,5-dihydroisoxazole III-14 was dissolved in dioxane (0.05 M relative to isoxazole) followed by the addition of triethylamine (4.0 eq.) and benzamidine Chlorine (1.25 equivalents). The reaction was allowed to stir for 16 hours then diluted with ethyl acetate and washed with dilute hydrochloric acid, dilute sodium hydroxide and then brine. The organic layer was then dehydrated with sodium sulfate and concentrated under reduced pressure to afford ethyl acetate. [M-H]-= 332.0 m/z. Activity: A. 351 201043620 Example 298

3-Bromo-4,5-dihydroisoxazole III-14 was dissolved in dioxane (0.05 相对 relative to isoxazole) followed by addition of triethylamine (4.0 eq.) and benzene sulfonium (1.25 eq.) ). The reaction was allowed to stir for 16 hours then diluted with ethyl acetate and washed with dilute hydrochloric acid, dilute sodium hydroxide and then brine. The organic layer was then dehydrated with sodium sulfate and concentrated under reduced pressure to give sulfonamide-1 as a white solid. [Μ-Η]-= 358.0 m/z. Activity: Β. Example 299

Ιιι-ΐ8) 3-bromo-4,5-dihydroisoxazole III-14 was dissolved in dichloromethane (0.05 M relative to isoxazole) followed by the addition of triethylamine (4.0 eq.) and benzyl chloroformate Ester (1.25 equivalents). The reaction was allowed to stir for 16 hours, then diluted with ethyl acetate and washed with dilute hydrochloric acid, dilute sodium hydroxide and then brine. The organic layer was then dried over sodium sulfate and concentrated under reduced pressure to give a crude material (yield of ethyl acetate/hexanes). . [M-H]-= 352.0 m/z. Activity: A. Example 300

(111-19) 352 201043620 3-Bromo-4,5-diisoisoxazole III-14 was dissolved in dioxane (0.06 相对 relative to isoxazole) followed by the addition of triethylamine (2.5 equivalents) Benzaldehyde (1.25 equivalents) was then added sodium triacetoxyborohydride (1.5 eq.). The reaction was allowed to stir for 16 h then diluted with ethyl acetate and washed with dilute sodium hydroxide and then brine. The organic layer was then dehydrated with sodium sulfate and concentrated under reduced pressure to give a crude material which was purified using EtOAc (ethyl acetate/hexanes). White solid. [M-H]-= 308.1 m/z. Activity: A. Example 301

3-Bromo-4,5-dihydroisoxazole III-20 was prepared using a similar procedure of Example 300 except that 4-benzylaldehyde was used to replace the benzylaldehyde. [M+H]+= 342.6 m/z. Activity: A. Example 302

3-Bromo-4,5-dihydroisoxazole III-21 was prepared using a similar procedure of Example 300, but using 4-methoxybenzylaldehyde to afford benzylaldehyde. [M+H]+= 338.7 m/z. Activity: A. Example 303 353 201043620

3-Bromo-4,5-dihydroisoxazolium-22 was prepared using a similar procedure of Example 300, but using 2-pyridinecarboxaldehyde to replace the benzylaldehyde. [M+H]+= 312.1 m/z. Activity: B. Example 304

3-Bromo-4,5-dihydroisoxazole III-23 was prepared using a similar procedure of Example 300, but using 3-pyridinecarboxaldehyde to replace the benzylaldehyde. [Μ+Η]+= 312·4 m/z. Activity: B. Example 305

3-Bromo-4,5-dihydroisoxazole III-24 was prepared using a similar procedure of Example 300, but using 4-methylbenzylaldehyde to replace the benzylaldehyde. [M+H]+= 322.5 m/z. Activity: A. Example 306

354 201043620 3-Bromo-4,5-dihydroisoxazole III-25 was prepared using a similar procedure of Example 300 except that 3,4-dibenzylaldehyde was used to replace the benzylaldehyde. [M+H]+= 378.6 m/z. Activity: A. Example 307

3-Bromo-4,5-dihydroisoxazole III-26 was prepared using a similar procedure of Example 300, but using 4-trifluoromethylbenzylaldehyde to replace the benzylaldehyde. [M+H]+= 376.6 m/z. Activity: A. Example 308

(III-27)

3-Bromo-4,5-dihydroisoxazole III-27 was prepared using a similar procedure of Example 300, but using 3-chlorobenzylaldehyde to replace the benzylaldehyde. [M+H]+= 342.6 m/z. Activity: A. Example 309 (III-28) 3-Bromo-4,5-dihydroisoxazole III-28 was prepared using a similar procedure of Example 300, but using cinnamic aldehyde to replace the benzyl aldehyde. [M+H]+= 336.7 m/z. Activity: A. 355 201043620 Example 310

(ΙΠ-29) I 3_bromo-4,5-dihydroisoxazole oxime-14 was dissolved in N,N-didecylguanamine (0.05 相对 relative to isoxazole) followed by potassium carbonate (3.0 Equivalent) Then potassium iodide (0.2 eq.) and 2-bromoethylbenzene (3.0 eq.) were added. The reaction was heated to 70 ° C in an oil bath for 16 hours, followed by direct purification (ethyl acetate / hexanes) using a rapid sm. [M+H]+= 324.6 m/z. Activity: A. Example 311

(1H-30) 3-Bromo-4,5-dihydroisoxazole III-30 was prepared using a similar procedure as in Example 290, but using 1-phenyl-4-piperidone to replace 1-(t-butoxy) Carbonyl)-4-piperolidine. [M+H]+= 297.0 m/z. Activity: B. Example 312 (III-31) 3-Bromo-4,5-dihydroisoxazole III-30 was dissolved in chloroform (0.01 M relative to isoxazole) followed by bromine (1.0 eq.). The reaction was allowed to stir for 16 hours, then diluted with water and washed with saturated sodium carbonate. The organic layer was then dehydrated with sodium sulfate and concentrated under reduced pressure to afford compound III-31 as a yellow solid. [M+H]+= 377.0 m/z. Activity: B. 356 201043620 Example 313

3-Bromo-4,5-dihydroisoxazole III-32 was prepared using a similar procedure of Example 300 except that the benzylaldehyde was replaced with cyclohexanecarboxaldehyde. [M+H]+= 390.5 m/z. Activity: A. Example 314

Br (III-33) 3-bromo-4,5-dihydroisoxazole III-33 was prepared using a similar procedure to that of Example 300 except that the benzylaldehyde was replaced with pivalaldehyde. [M+H]+= 290.5 m/z. Activity: B. Example 315

3-Bromo-4,5-dihydroisoxazole III-34 was prepared using a similar procedure of Example 297, but using cinnamic aldehyde to replace benzalkonium chloride. [M+H]+= 352.8 m/z. Activity: A. Example 316

(III-35) 3-Bromo-4,5-dihydroisoxazole III-35 was prepared using a similar procedure of Example 299 357 201043620, but using methyl phthalate to replace benzyl chloroformate. [M+H]+= 378.8 m/z. Activity: B. Example 317

Me (111-36) 3-bromo-4,5-dihydroisoxazole oxime-36 was prepared using a similar procedure to that of Example 299, but using hexanes succinate. [Μ+Η]+= 318.7 m/z. Activity: Α. Example 318

3-Bromo-4,5-dihydroisoxazole III-37 was prepared using a similar procedure as in Example 299, but using phenyl chlorophenyl phthalate to replace benzyl chloroformate. [M+H]+= 340.7 m/z. Activity: A. Example 319

(ΙΠ-38) 3-bromo-4,5-dihydroisoxazole III-38 was prepared using a similar procedure of Example 299, but using hexane 2,2,2-triethyl ester ester. [Μ+Η]+= 394·5 m/z. Activity: B. Example 320 358 201043620

C^le atum 3_bromo-4,5-dihydroisoxazole III-14 is dissolved in di-methane (relative to iso-oxazole = 〇.〇5 M) followed by the addition of triethylamine (5. And carbonyl diimidazole (1.25 equivalents). The reaction was allowed to stir for 2 hours, followed by the addition of anisole (25 hrs) followed by the addition of catalytic tetrabutylammonium hydrogen sulfate and aqueous sodium hydroxide (relative to the isotactic 〇.1 〇 M). The heterogeneous mixture is allowed to be removed, and then diluted with acetic acid. The aqueous layer was washed twice with ethyl acetate, and then the organic layer was dehydrated with sodium chloride and concentrated under reduced pressure to obtain a crude product; and purified by heart-speed gas chromatography (ethyl acetate). Hexanes) obtained a fine amine 39, which was white _. [M+H]+ = say 9 _. Activity: A. Example 321

, 3 / odor -4,5--gas isotazole IIM oxime system using a similar procedure of Example 32 象 但 但 使用 使用 使用 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 [M+H]+= 388.8 m/z. Activity: A. Example 322 359 201043620

3-/odor, 4,5-dihydroisoxazole m_4 i &amp; and ΙΠ_4!b were prepared in a similar private order using Example 32, except that aniline was replaced with second phenylethanol. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [m+H]+= 368.8 m/z. Activity: Α. Example 323

(IIM2) 3_cyclopenten-1-ol (1.0 eq.) is dissolved in hydrazine, hydrazine-dimethylformamide (0.80 Å relative to alcohol) and hydrazine (0.10 eq.) Treated with sodium hydroxide (2.0 eq.). Then benzyl bromide (L2 equivalent) was added and the reaction allowed to stir at room temperature for 48 h. The reaction was then diluted with tert-butyl decyl ether and washed with dilute Na 2 S 2 3 and brine. The organic layer was then dehydrated with sodium sulfate and concentrated under reduced pressure to give crude material (yield: ethyl acetate/hexanes). This compound is then converted to the desired 3-bromo-4,5-dihydroisoxazole III-42 using the cycloaddition procedure outlined in Method 1. These compounds can be separated using a palm-by-peach HPLC method known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]- = 295_0 m/z. Activity: B. Example 324 360 201043620

tR-43&amp;&quot;M3b (IIM3) 3_Bromo-4,5-dihydroisoxazole III-43a and III-43b using Method 1 in 1 step from N-(T-butoxycarbonyl)-2, Preparation of 5-dihydro-1H-pyrrole. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M-H]-= 290.0 m/z. Activity: B. Example 325

ΙΙΙ·44β ||L (ΙΙΙ-44) racemic 3-bromo-4,5-dihydroisoxazole m_43 dissolved in trifluoroacetic acid (0·20 M relative to isoxazole) and stirred at room temperature 1 hour. Then, the solvent was removed under reduced pressure and the crude residue was purified (yield) with toluene (yield twice) to give trifluoroacetic acid as a white solid which was dissolved in dichloromethane (0.05 相对 relative to isoxazole) Triethylamine (4 eq equivalents) and benzyl chloroformate are then added. The reaction was allowed to mix for 16 hours, then diluted with ethyl acetate and washed with dilute hydrochloric acid, dilute sodium hydroxide and then brine. Then, the organic layer was dehydrated with sodium sulfate and concentrated under reduced pressure to obtain a crude material which was purified by rapid sulphur dioxide (Ethyl acetate/hexane) to obtain the amine formic acid melon 44 as a white solid. . These compounds can be isolated using the palm muscle C method known in the art. For example, reference is made to the palmitic HpLC method disclosed herein. [m+h]+= 324 6 361 201043620 m/z. Activity: a. Example 326

The racemic 3-bromo-4,5-dihydroisoxazole III-43 was dissolved in trifluoroacetic acid (0.20 M relative to the iso-sigma saliva) and stirred at room temperature for 1 hour. Then the solvent and the crude product residue were removed under reduced pressure and azeotropic distillation with toluene (2 times) to give the trifluoroacetate as a white solid, which was dissolved in di- methane (0.06 相对 relative to isoxazole). Triethylamine (2.5 equivalents) and 4-chlorobenzylaldehyde (L25 equivalents) were then added sodium triacetoxyborohydride (1.5 eq.). The reaction was allowed to stir for 16 h then diluted with ethyl acetate and washed with dilute sodium hydroxide then brine. The organic layer was then dehydrated with sodium sulfate and concentrated under reduced pressure to give a crude material, which was purified by flash chromatography (ethyl acetate/hexanes) to afford s-benzylpiperidine in- 45 is a white solid. Such compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 316.6 m/z. Activity: C. Example 327

3-(π is more than -3-yloxy)-4,5--51. No. iii_46 was prepared by the method 5 using a step 1 from the compound III-18 and 3-super ratio. [M+H]+= 369.4 m/z. Activity: A. 362 201043620 Example 328

{111-47) 3-Gas-4,5-dihydroisoxazole III-47 is prepared in two steps starting from the use of Method 6 from 1-(T-butoxycarbonyl)-4-piperidone Formation, followed by cyclization addition using Method 2, but replacing N-bromosetamine with N-gas butylamine. [M+H]+= 274_9 m/z. Activity: A.

Example 329

3-Gas-4,5-dihydroisoxazole III-48 was prepared using a similar procedure as in Example 301, but using 3-chloro-4,5-diarisoisoxazole III-47 to replace 3-bromo-4, 5-Dihydroisoxazole III-9. [M+H]+= 298.6 m/z. Activity: A.

Example 330

3-Bromo-4,5-dihydroisoxazole III-49 was prepared using a similar procedure of Example 300, but using 4-ethynylcarboxaldehyde as the benzylaldehyde. [M+H]+= 335.1 m/z. Activity: A. Example 331 363 201043620

(ΙΠ-50) 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole oxime-50 was prepared in a one-step procedure using the compound y-49 and 3-hydroxypyridine. [M+H]+= 348.6 m/z. Activity: A. Example 332

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole III-51 was prepared in a 1 step from compound III-20 and 3-hydroxypyridine. [M-H]-= 358.1 m/z. Activity: A. Example 333

3-(Pyrimidine-5-yloxy)-4,5-dihydroisoxazole III-52 was used in a procedure 1 from compound III-20 and 5-hydroxy. Preparation. [M+H]+= 360.2 m/z. Activity: A. Example 334 364 201043620

The base oxygen)_4,5-dihydroiso-π-wow m_54 is prepared in a 3-step self-chemical mouth III.9, starting from the use of the method 5 to synthesize 3-(t疋_3_ based from the compound m_9 and 5♦ mer. Oxygen) _4,5_ dihydroisoindole. The compound was then deprotected using similar conditions as in Example 295, and then converted to the desired product m-54 using a similar private sequence of Example 297. [Μ+Η]+~367.6 m/z. Activity: β. Example 335

(HI-5S) 3 cicutidine·5-yloxy)-4,5-dihydroisoxazole 111_55 was prepared in a 3-step procedure from the compound ΠΙ -9 using a similar procedure of Example 334, but using 4- benzyl hydrazide. Replacement of hydrogen cinnamaldehyde. [M-H]-= 372.9 m/ζ. Activity: A. Example 336

(ΠΙ-56), (o-pyridin-5-yloxy)_4,5-dihydroisoxazole III-56 was used as Example 295 = similar conditions starting from deprotection and being synthesized from compound III-53 in two steps. 4 found that ~ acetate (1 · 〇 equivalent) and then dissolved in di-methane (relative to isoindole as Ο.11 Μ), followed by the addition of phenyl isocyanate (1.5 equivalents) followed by the addition of pyridine 'in) . The reaction was allowed to stand overnight at room temperature, then the reaction was transferred to a sep. funnel with excess water 365 201043620 and dichloromethane. The organic layer was washed with EtOAc EtOAc (EtOAc)EtOAc. [M+H]+= 353.6 m/z. Activity: C. Example 337

(III-S7) 3-(pyridin-3-yloxy)-4,5-dihydroiso. No. III-57 was synthesized using the similar conditions of Example 295 starting from deprotection and from compound III-53 in two steps. The resulting trifluoroacetate salt (1.0 eq.) was then dissolved in dichloromethane (0.11:\1 relative to isoxazole) followed by 5,5,5-trifluoropentanoic acid (1.5 eq.). (1.5 eq.) and triethylamine (3.0 eq.). The reaction was allowed to stir at room temperature for 14 h then the reaction was transferred to a sep. funnel with excess water and dichloromethane. Dehydrated and concentrated over magnesium sulfate to give a white solid, which was purified by EtOAc EtOAc (EtOAc:EtOAc)

(III-Individual 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole III-58 was prepared from compound III-16 in 3 steps according to the following procedure: Method 11 from 6-(曱Preparation of 6-(methylthio)pyridin-3-ol from thiopyridin-3-yldihydroxyboronic acid. Then 3-bromo-4,5-dihydroisoxazole III-16 and 6-(methylsulfur) Pyridin-3-ol is reacted using Method 5. The obtained 366 201043620 3 (than 疋3 methoxy)_4,5-one sigma sigma is dissolved in dioxane (0.5 Μ relative to iso-oxazole) and then Add _ gas perbenzoic acid (2 〇 equivalent), and allow the reaction to stir at room temperature for 丨 hours. After the reaction is completed, the reaction is transferred to the separatory funnel using excess water and di-methane. The organic layer is saturated sodium bicarbonate. Washing (2 times) and 1 N N a Η rinsing (1 time), dehydrated with magnesium sulfate and concentrated to give a white solid. +H]+= 415.8 m/z. Activity: Β. Example 339

an-S9) 3-(° ratio: each bit-1-yl)-4,5-dihydroisoxazole oxime-59 was prepared in 1 step according to the following procedure: 3-bromo-4,5-dihydrogen Isoxazolium ΠΙ18 (1 〇 equivalent) was dissolved in n-butanol (0.64 Torr) followed by pyrrolidine (丨2 equivalent) and sodium carbonate (2.5 eq.). The reaction was sealed and heated in an oil bath to 12 ° C for 18 hours then allowed to cool and then transferred to a sep. funnel using excess water and tri-butyl methyl ether. The aqueous layer was washed with tributyl butyl ether (2 times) and the combined organic layer was washed with brine, dried over magnesium sulfate and concentrated to give an orange solid which was purified by flash The alkanes obtained ΙΠ-59 as a white solid. [M+H]+= 345.4 m/z. Activity: C. Example 340

367 201043620 —Hydroisoxazole-3·yl)_1_mercapto iodide pyrrolidine 锵III-60 system=Synthesis of the following materials: 3 咖 ················· (G.G44 is squatting to add 曱基帅Q22 μ). The reaction was allowed to stand for 72 hours, followed by concentration and purification using high pressure liquid chromatography (0.1% formic acid). Dessert fractions were obtained; to dryness to obtain the desired product with several impurities, and the solids were removed by washing the solids with hexanes. Activity: c. Example 341 ΗΟ 0

〇

111-61

(111-62) 3_Bromo-4,5-dihydroisoxazole m_62a and III-62b were synthesized in the following procedure according to the following procedure: Phenyldihydroxyboronic acid (2 〇 equivalent) was suspended in toluene (relative to rotten The acid was 0.23 M) and plus $ to obtain a solution. The solvent was removed by evaporation and the treatment was repeated. The resulting anhydride is then redissolved in the second gas institute (〇 23 M). Add indole-3,4-monohydronaphthalene-indole (2Η)-_(ι·〇 equivalent), triethylamine (5 〇 equivalent) and copper acetate (0_95 eq.) and the reaction is sealed and at room temperature Granted 16 hours. The mixture was then transferred to a separatory funnel using excess di-methane and water. The organic layer was then washed with water, dilute sodium hydroxide and brine. The organic layer was dehydrated with sodium sulfate and concentrated to give yt-61 as a brown oil, which was directly transferred to the product of &lt;RTI ID=0.0&gt;&gt;&gt; Such compounds can be separated by 368 201043620 by the HPLC method known to the art. For example, reference is made to the &lt;Planar HPLC method. [M+H]+= 359.5 m/z. Activity: a. t example 342

(111-63)

3~Bromo-4,5-dihydroisoxazole III-63a and III-63b were prepared using the procedure of Example 341, but using 5-|%-2,3-dihydro-1H-member-1 Ketones are used in the first bucket. 6-Hydroxy-3,4-dihydronaphthalene_1(2H)one was used as a starting material. These combinations are separated by the palmar HpLC method known in the art. For example, refer to this to uncover the palmar HpLC method. [M+H]+= 343.7 m/z. Activity: a. Example 343

〇(ΙΠ-64) 3·(Mouth 0--5-yloxy)-4,5-dihydroisoxazole Ill-60a and III_6〇b are made from phase, έΊ in 1 step from racemic compound ΙΙΙ -63 and 5-hydroxy ρ close bite preparation. This I product can be isolated using the HPLC method known to the art. For example, the palmitic HPLC method disclosed herein is specifically disclosed. [M+H]+=361.2 m/z. Live ‘Change: A. Example 344 369 201043620 ο f3co

1) SOCI3 1)Α〇Γ

F3CO ο

III-65 1) Method 5 2) Method l

3-Bromo-4,5-dihydroisoxazole IH_66a and III-66b were synthesized in four steps according to the following procedure: a 250 ml round bottom bottle with a 10/30 thermometer rinse was equipped with a drawbar, analog thermometer and Ai Lin (Allihn) condenser. Add 3_(3_(difluoromethyl milk) benzyl) propionic acid (0.22 mol, 1.0 eq.) dissolved in sub-continuous helium (6.0 §) and in the oil blL for 1 hour' across the hour during reflux The internal temperature is 78 ° C to 82 ° C. At this time, the condenser was replaced with a short-diameter head and a thermometer having an anhydrous argon flow inlet, and the volatiles were removed by distillation. When the distillation was completed, cyclohexane (100 ml) was added to the flask, and distilled in the same manner to obtain the desired helium gas, quantitatively yielded as a brown oil, which was used directly. A 2 liter, 3-neck round bottom bottle was then fitted with a mechanical stirrer, a thermocouple carbon rod and a 25 cc pressure balanced dropping funnel. The round bottom bottle was fed with three aluminum hydrides (〇233 Mo, 1.08 eq.) and dioxane (0.24 M), and then stirred for 45 minutes to dissolve as much as possible. The reaction was then cooled in an ice bath until the internal temperature was below 2.5. Hey. Add a solution of ruthenium chloride (ι·〇 equivalent, 0.215 mol) to a house of 200 liters of turpentine in a 15 minute period by adding a funnel. After the addition was completed, the ice was removed from the bath and replaced with room temperature water (bath temperature 18 〇, and the reaction was allowed to proceed for an additional 2 hours, at which time the reaction was completed by TLC and LC/MS analysis. Ice (500 g) and then treated with water (6 ml), then the mixture was stirred. 370 201043620 hours to all solids were dissolved. The layers were separated and the aqueous layer was extracted with diethyl ether (350 mL). (250 ml, 1 time), half-saturated sodium bicarbonate (250 ml '1 time), brine (250 ml, 1 time), dehydrated with magnesium sulfate and concentrated to give 5-(trifluoromethoxy)-2,3_ Dihydrogen is a pink solid, yield is obtained. This material is then directly converted to racemic 3-bromo-4,5-dihydroisoxazole oxime-66 using Method 5. These compounds can be used. Separation of the palmitic HPLC method is known in the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+ = 335·6 m/z. Activity: a.

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole III-67a and III-67b were first prepared from 6-(methylthio)pyridin-3-yldihydroxyboronic acid using Method 11. After 6-(methylthio)-pyridin-3-ol, it was prepared in two steps from the racemic compound ΙΠ-66 and 6-(methylthio)-pyridin-3-ol using Method 5. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palm HPLC method disclosed herein. [M+H]+= 396_7 m/z. Activity: A ° Example 346

371 201043620 3 derivatized _3_yloxy), 4 $ ^, dihydroisoxazole III-68a and III-68b were similarly oxidized using Example 338, &amp; Spinning compound ΙΙΙ-67 was prepared. These compounds can be used to separate the palmar HPLC methods known to the art world. For example, reference is made to the dry HPLC method disclosed herein. [Μ+Η]+= 429.4 m/z. Activity: a ^ Example 347 Βγ + ^mine 0 Pd(PPh3)4_ Νθ2〇〇3 Ν—Μ

&quot;•69

3 (ratio. mercaptooxy)·4,5-dihydroisoxazole III-70a and III-70b were prepared in two steps according to the following procedure: 6_,; odorin _3·alcohol (1 G equivalent) Add the sodium sulphate (10.0 tianli) to the microwave bottle. Add toluene ethanol and water (〇16M, 2: 2*1 V/V) followed by 1-methyl-4-(4,4,5,5-tetradecyl-1,3,2-diboron boron $ -2-yl)_1Η_Π is more than saliva (15 equivalents). The mixture was purged with argon for 5 minutes and then added with tetramethyl (4 m 〇 1%). The reaction tube was then covered with aluminum foil and heated to 8 Torr for π hours. After cooling, the reaction was transferred to a separatory funnel with excess water and acetic acid. The organic layer was then washed with water (1 time), saturated ammonium sulfate (1 person) and brine (1 time). The aqueous layers were combined and washed with ethyl acetate (1 time). The organic layer is then combined, dehydrated with sodium sulfate, concentrated and purified using rapid silica dioxide chromatography (gradient sterol/dichlorodecane) to obtain 6-(1-mercapto-1H~° ratio saliva_ 4-Pyridin-3-ol III-69 is a white solid. This compound is then reacted with racemic 3-bromo-4,5-dihydroisoxazole III-66 using Method 5 to give the desired racemic compound m-7. Such compounds can be separated using the palmitic HPLC method known in the art. For example, reference is made to the palmar HPLC method disclosed herein. [M+H]+= 430.0 m/z. Activity: A. Example 348

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole III-71a and III-71b were prepared using a similar procedure of Example 347, but using 1-methyl-5- in the first step. 4,4,5,5-tetramethyl-1,3,2-di. Boron-2-yl)-1Η-pyrazole in place of 1-indolyl-4-(4,4,5,5- Tetramethyl-1,3,2-dioxaboron-2-yl)-1Η-pyrazole is used as the dihydroxyborate. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 430.0 m/z. Activity: A. Example 349

3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole III-73a and III-73b are root 373 201043620 Prepared in 3 steps according to the following procedure: 5-hydroxynicotinate decyl ester (1.0 Equivalent) was dissolved in methanol (0.08 M) followed by hydrazine (50 equivalents, 50% by weight in water) and allowed to stir for 14 hours. The reaction mixture was then concentrated under reduced pressure and used directly in the next step. Triethyl orthoformate (8.0 equivalents) was added and the reaction was sealed and heated to reflux for 14 hours. The reaction was then transferred to a separatory funnel using excess ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure to give a crude material, which was purified by rapid enthalation of silica gel chromatography (gradient methanol / di-methane) to obtain the desired Azole III-72. This compound is then reacted with racemic 3-bromo-4,5-dihydroisoxazole III-66 using Method 5 to give the desired racemic compound m-73. These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 419.5 m/z. Activity: A. Example 350

The enantiomer of 3-(pyridin-3-yloxy)-4,5-dihydroiso D, etc., azole m_74a &amp; m_74b was prepared in 2 steps according to the following procedure: racemic 3 bromo _ 4 5 _ Dihydroisoindole·66 uses method 5 and 5__ acid test. The obtained vinegar (1.0 equivalent) was dissolved in 1:1 tetrahydrofuran/water (〇〇6 Μ) and an oxidized chain (8.0 equivalent) was added. The reaction was carried out at room temperature, then the tetrahydrofuran was removed under a stream of nitrogen, and the remaining solution was acidified with (7) hydrochloric acid until the ρ Η was less than 2 to provide the racemic desired acid m-74 as a white solid, which was separated by vacuum filtration. . 374 201043620 These compounds can be separated using the HPLC method known to the art. For example, reference is made to the palmitic HPLC method disclosed herein. [M+H]+= 395.5 m/z. Activity: A. Example 351 Inhibition of human FAAH Preparation of human FAAH: c〇S-7 cells were split into 1:15 mm 乂25 细胞 cell culture dishes on the previous day (C〇rning inc.), catalogue No. 430599). Transient transfection was performed at 30% to 40% confluency according to FuGENE 6 transfection reagent (R0 Che, catalog number 11814 443 〇〇1). Transfection procedure: FuGENE transfection 6 reagent (45 μl) was added to a 15 ml conical tube of 1410 μl medium (DMeM, serum free of penicillin/streptomycin (pen/strep)) and cultured at room temperature After 5 minutes, FAAH plastid DNA (15 μg) (Origin HGene) catalogue number TC119221, gene stock number ΝΜ_001441·1, 0.67 μg/μl) was added and further incubated at room temperature for 15 minutes. The resulting solution was added dropwise to 30% to 40°/. A culture dish of one of the COS-7 cells. The COS-7 cell culture dish was then cultured for 48 hours. The cells are then harvested. Harvesting procedure: The medium was aspirated from the culture dish and the cells were washed with 10 ml of PBS. Remove the PBS and add 3 ml of PBS to the culture solitary. The culture dish was scraped and the cells were again suspended, and then the cell suspension was collected in a 15 ml conical tube. The cells were pelleted by centrifugation at 1200 rpm for 5 minutes in a bench top centrifuge. Remove PBS and cell pellets in liquid nitrogen for rapid freezing and storage at -80〇C 〇375 201043620 COS-7 cells-FAAH purification: (1) Sorting: cold from transient transfection; The ice was decomposed and resuspended in 12.5 mM Hepes pH 8. 〇〇, 1 〇〇 Na Na, i _ EDTA (10 ml / 0.2 g cell pellet). The pellets were homogenized by a Dunes homogenizer (d〇Unce), and then ultrasonically oscillated to produce cell extracts. The cell extract was then centrifuged at 1000 g to remove cell debris. The pellet and supernatant were discarded and centrifuged at 13,000 g for 20 minutes. The pellet contains FAAH bound to the membrane. The supernatant was discarded and the pellets were again dissolved. (7) Re-dissolution: The selected fraction (13, 〇〇〇G, membrane fraction) was resuspended in 2 3 liter resuspension buffer (20 mM Hepes pH 7.8, 10% v/v glycerol' 1 mM EDTA, 1°/. Triton X-100) and the sample were incubated on ice for 1 hour' and then centrifuged to remove any particulate matter. A whole portion of the supernatant containing dissolved human FAAH was taken and quickly frozen in liquid nitrogen and stored at -80 ° C until use. (3) Determining characteristics: Protein concentration was determined by Bradford assay. SDS gel method and Western blot method confirmed the presence of FAAH FAAH activity assay Km assay - 96 well assay linear dependence - 96 well assay analysis standard compound Ki assay - 84 hole assay analysis Human FAAH assay analysis; experimental protocol: A 0.1 mg/ml human FAAH solution was prepared in FAAH reaction buffer and a 24 microliter drop to a 384 well plate. One microliter of the 376 201043620 series of diluted inhibitors from the DMS0 stock solution was added to it. The FAAH solution and inhibitor were incubated for 30 minutes at room temperature. The reaction was initiated by adding 25 μl of 40 μL AMC arachidonic acid in FAAH reaction buffer to obtain a final reaction human FAAH concentration of 0.05 mg/ml and a concentration of 20 μΜ AMC arachidase substrate with a reaction volume of 50 μm. Rise. The reaction was allowed to proceed for 4 hours at room temperature. The reaction was stopped by the addition of 25 μl of 12 μΜ α-ketone heterocycle (Cayman Chemicals catalog number 10435). The micro-force orifice plate was read in an envisi〇n plate reader. The original fluorescence mapping was plotted on the y-axis and the inhibitor concentration was plotted on the X-axis to obtain a dose response inhibition curve. The data was brought into a single-site competitive inhibition equation, and the Km of the human enzyme was fixed at 12 μΜ and 9 μΜ, respectively. Other assays that can be used to determine inhibition of FAAH by the compounds of the invention include: (1) Fluorescence-based assays for fatty acid indoleamine hydrolase compatible with high throughput screening, as illustrated by Manjunath et al. Analytical Biochemistry (2005) 343: 143-151; and (2) High throughput screening for the discovery of fatty acid indoleamine hydrolase inhibitors based on microsomal fluorescence assays. Wang et al., Biomolecular Screening (2〇〇6) 1_9. Example 352 Evidence for the formation of a covalent complex between FAAH's serine-241 and isoxazoline The treatment of rat FAAH protein with an active site-directed irreversible inhibitor, methoxyantimonylidene fluorophosphonate, resulted in a crystal structure. Among them, methoxyantimonylidene phosphonate is covalently bonded to the Ser_24丨 branch (Bracey et al., Science (2002) 298: 1793-1796). Based on this data, a hypothesis was obtained in which the iso-D-oxazoline compound 377 201043620 of the present invention forms a covalent complex with the nucleophilic branch of Ser-241. This hypothesis is consistent with the kinetic data, suggesting that the combination involves the attack of the isoxazoline electrophilic group at the active site Ser-241, resulting in the disappearance of the leaving group from the cytosolic gargle, followed by the formation of the covalent enzyme-isoxazole. A morphine adduct. Subsequent recovery of the activity involves desulfurization, and for the covalent enzyme-isosaki beta selenium adduct, the deuteration reaction is inefficient (if any). The activity recovery assay was performed by a jump dilution method involving rapid dilution enzyme-inhibitor complexes less than 5 times their name Ki and measuring activity as a function of time. The aforementioned hypothesis was confirmed by little or no re-acquisition of the enzyme activity over 2 hours, indicating a substantially irreversible inhibition, or an extremely slow hydrolyzable complex. Other Embodiments Those skilled in the art will recognize or be able to determine, without departing from routine routines, various equivalents of the specific embodiments of the invention described herein. These equivalents are intended to be covered by the scope of the patent application below. I: Simple description of the diagram 3 (none) [Explanation of main component symbols] (none) 378

Claims (1)

201043620 VII. Patent application scope: 1. A compound of formula (1): (I) or a pharmaceutically acceptable form thereof, wherein: 〇(v) Ra, Rb 'and ^ are each selected from the group consisting of hydrazine, CM() alkyl and Cmo perhaloalkyl, and Rd is a -LZ group, and Z is selected from C6.14 aryl; (vi) Ra, Rb, and Rc are each selected from the group consisting of -H, Cmo:^ and C^o perhaloalkyl, and 1^ is 丄-2. And Z is selected from the group consisting of a 3-14 membered heterocyclic group and a 5-14 membered heteroaryl group; (vii) Ra and Rd are joined to form a C3_1() carbocyclic group or a 3-14 membered heterocyclic fused ring, And Rb&amp;Re are respectively selected from -H, CM0 alkyl and Cl. 10 perhalogenated groups; or (viii) Re&amp;Rd is bonded to form C3_1() carbocyclic group or 3-14 membered heterocyclic snail- The fused ring, and Ra&amp;Rb are respectively selected from -H'C^o alkyl and C 1-10 perhalogen; L is a covalent bond or a divalent Ci_6 hydrocarbon group, wherein one, two or three of L The fluorenylene unit is selectively and independently substituted with one or more oxygen, sulfur or nitrogen atoms; the G system is selected from the group consisting of -CN, -N02, -S(=0)Re, -S02Re, -S02NRfRe, 379 201043620 -P02Re' -P020Re, -P〇2NRfRe, -(C=0)Re, _(C=0)0Re, -(C=0)NRfRe, _Br, -I, -F, -Cl, -ORe, _ 〇NRfRe, -ONRf(C=0)Re, -0N RfS02Re, -0NRfP02Re, -0NRfP020Re, -SRe, -0S02Re, -NRfS02Re, -OP02Re, -OP02ORe, -NRfP02Re, -NRfP020Re ' -〇P〇2NRfRe, -0(C=0)Re, -0(C=0 0Re, -NRfRe, -NRf(C=0)Re, _NRf(C=0)0Re, -〇(C=0)NRfRe, -NRf(C=NRf)NRfRe, -0(C=NRf)NRfRe, -NRf(C=NRf)〇Re, -[N(Rf)2Re]+x- wherein X is a counter ion; each Re is selected from Cm. Alkyl, C2.1Q alkenyl, (^.alkynyl, c31〇 carbocyclyl, C6_H aryl, 3-14 membered heterocyclyl and 5-14 membered heteroaryl; each Rf attached to a nitrogen atom is selected From a _H, Cmq alkyl group, or an amine sulfhydryl group, or a Re&amp;Rf linkage to form a 3-14 membered heterocyclyl ring or a 5-14 membered heteroaryl ring. 2. A compound of claim i, wherein Ra, Rb, and ^ are each selected from the group consisting of H, Ch, alkyl and Cl_1〇 all-toothed base, Rd is a group -LZ ' and Z is selected from (:6-丨4 aryl; 3. The compound of the above item i, wherein Ra, Rb, and each of the knives are selected from the group consisting of ruthenium, CM() silk, and Cl!. all (tetra) groups, Rd is a group - LZ, and z is selected from 3 to 14 members. a compound of the formula i, wherein Ra, Rb, and ^ are each selected from the group consisting of H, CM, silk and Ci, a whole New Zealand, Rd is a group _L_Z, and a Z system is selected. From a 5 to 14 membered heteroaryl; 5. A compound of the scope of claim 2, wherein l is a covalent bond or l is 380 201043620 a divalent Cu hydrocarbyl group, wherein one, two or three methylene units are L Replaced with one or more oxygen atoms. 6. A compound of claim 5, wherein L is a covalent bond. 7. A compound according to claim 5, wherein L is an unsubstituted divalent CN6 hydrocarbyl group, wherein one of L is a methylene group The unit is replaced by an oxygen atom. 8. The compound of claim 5, wherein L is -Ο-. 9. The compound of claim 1 wherein Ra, Rb, and Re are each selected from the group consisting of - Η, Cw alkyl and (^_3 perhaloalkyl. 10. The compound of claim 9 wherein Ra, Rb, and Re are each selected from the group consisting of -Η, -CH3, and -CF3. The compound of claim 10, wherein Ra &amp; Rb is -Η and Re is selected from -CH3 and -CF3. 12. A compound according to claim 10, wherein Rb and Re are -H and Ra It is selected from the group consisting of -CH3 and -CF3. 13. As the compound of claim 10, Ra, Rb, and Re are each -Η. 14. The compound of claim 1 wherein 1^ is bonded to 1^ Forming a C3.1G carbocyclic fused ring, and Rb&amp;Re are selected from the group consisting of -Η, Cw alkyl and (^_3 all-alkyl. 15. As claimed in claim 15 A compound wherein Rb &amp; Re is -H. 16. The compound of claim 1, wherein the compound is bonded to form a 3-14 membered heterocyclic fused ring, and Rb and Re are each selected from the group consisting of -H, Cw alkyl and C 1-3 perhalogen. 17. The compound of claim 16, wherein both Rb and Re are -H. 381 201043620 18. The compound of claim 1, wherein the rule is taken. Joining with ^^ forms a C3-10 carbocyclic fused-fused ring, and Ra&amp;Rb is selected from the group consisting of _H, Ci 3 and ^1_3 all-burning. 19. The compound of claim 18, wherein Ra &amp; Rb is _h. 2. A compound according to claim 1, wherein Rc and Rd are joined to form a 3-14 membered heterocyclic fused fused ring, and Ra&amp;Rb is selected from the group consisting of ruthenium, Ci 3 alkyl and Cu total dentate. 21. The compound of claim 20, wherein both Ra and Rb are _H. 22. A compound as claimed in claim 2, wherein z is phenyl. 23. A compound as claimed in claim 22, wherein the compound has the formula: Or a pharmaceutically acceptable form thereof; wherein z is 0, 1, 2, 3, 4 or 5; and each Rl5 is selected from the group consisting of fluorine (-F), bromine (-Br), chlorine (-C1), and Iodine (-1), -CN, -N02, -N3, -S02H, -S03H, -OH, -OR16, -〇n(r18)2, -n(r18)2 ' -n(r18)3+x ·, -N(ORi7)Rl8, _SH, -SR16, -SSR17, -C(=0)R16, _c〇2H, -CHO, -C(OR17)2, -C02R16^ -0C(=0)R16 &gt ; -〇C02R16 &gt; -C(=0)N(R18)2 &gt; -〇C(=0)N(R18)2 ^ -NRI8C(=0)R16 , -nr18co2r16 ' -NR C(=0) N(R18)2, -C(=NR18)R16, _c(=NR18)OR16, 382 201043620 -OC(=NR18)R16, -OC(=NR18)OR16, -C(=NR18)N(R18)2 , -oc(=nr18)n(r18)2, -nr18c(=nr18)n(r18)2, -C(=0)NR18S02R16, -NR18S02R16, -S02N(R18)2, -S02R16, -S〇2 〇R16, -0S02R16, -S(=0)R16, -OS(=0)R16, -Si(R16)3, -OSi(R16)3, -C(=S)N(R18)2, -C (=0) SR16, -C(=S)SR16, -SC(=S)SR16, -P(=0)2R16, -OP(=〇)2R16, -P(=0)(R16)2, - 0P(=0)(R16)2, -0P(=0)(0R17)2, -p(=o)2n(r18)2, -op(=o)2n(r18)2, -p(=o )(nr18)2, -op(=o)(nr18)2, -nr18p(=o)(or17)2, -nr18p(=o)(nr18)2, -P(R17)2, -P(R17 3, -〇P(R17)2, -〇p(R17)3, -B(OR17)2, -BR16(OR17), Cb丨0 炫基, Cwo perhalogenyl, C2.i fluorenyl , c2.1q alkynyl, 〇3_14 carbocyclyl, 3-14 membered heterocyclic, c6_丨4 aryl, and 5-14 membered heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl And a heterocyclic group, an aryl group, and a heteroaryl group are each substituted with 〇, 1, 2, 3, 4 or 5 R19 groups; or two 偕R15 groups are substituted with a group wherein R 2 is Η, Ci_6 alkyl Or a pixel; each of Rl6 is selected from the group consisting of Cmq alkyl, Cmo all-alkyl, c2_1{) alkenyl, C2_10 alkynyl, (: 3-14 carbocyclyl, 3-14 membered heterocyclyl, (: 6.14 aryl) And a 5-14 membered heteroaryl group wherein the alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are each independently 〇, 1, 2, 3, 4 or 5 Each of R18 is substituted with hydrogen, -OH, -〇R16, -N(R17)2, -CN, -C(=0)R16, -C(=〇)N(R17) 2. -C02R16, -S02R16, _c(=nr17)or16, _c(=nr17)n(r17)2, -so2n(r17)2, 383 201043620 -S02R, -S020R", _s〇r16, _c(=s )N(8)7) C(=0)SRP, _C(=S)SR17, medium 0)2R16, ridge 0)(R162/ -P (4) Na 1 V 0) (NRl7) 2, Cm. Burning base, Ci, Quannan 2 burnt soil 2 10 alkenyl hydrazine 2_10 block, c3_1 fluorene carbocyclic group, 3_i4 membered heterocyclic group, 6 143⁄4 earth and 5 14 membered heteroaryl group, or attached to the nitrogen atom The R17 groups are joined to form a 3·14 member heterocyclic ring minus a 5-14 membered heteroaryl ring, wherein each of the indenyl, dilute, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups respectively Substituted by 〇, 1, 2, 3, 4 or hiuRi9 groups; each of R17 is selected from the group consisting of hydrogen, c丨] decyl, c丨丨〇 perhaloalkyl, Cwo dilute, (: (tetra) alkyne a group, a C3_iq carbocyclic group, a 3-14 membered heterocyclic group, a Gh aryl group, and a 5-14 membered heteroaryl group, or two groups attached to a nitrogen atom to form a 3-14 membered heterocyclic group or a 5-14 member An aryl ring wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is substituted with 0, 1, 2, 3, 4 or 5 R19 groups, respectively; Each of R19 is selected from the group consisting of hydrogen, -CN, -N〇2, -N3, -S0&amp;, -S03H, -0H, -OR2(), -0N(R21)2, -N(R2I)2. -N(R21)3+X- -n(or2())r21, -SH, -sr2q, -ssr2Q, -c(=o)r2G, -(:〇2, -C02R2° ' -0C(= 0)R2° ' -0C02R2° ' -C(=0 N(R2l)2 λ _0C(=0)N(R21)2, -NR21C(=0)R20, -NR21C02R20, _NR21C(=0)N(R21)2, -C(=NR21)OR20, -OC (=NR21) R2〇, OC(=NR21)OR2, -C(=NR21)N(R21)2, -OC(=NR21)N(R2l)2, -nr21c(=nr21)n(r21)2 , -nr21so2r2, so2n(r21)2, -S02R20, -S〇2〇R20, -OS02R20, -S(=0)R20, -Si(R20)3, -OSi(R20)3, -C(= S)N(R21)2, _C(=0)SR20, -C(=S)SR2〇, 384 201043620 _SC(=S)SR20, P(-〇)2r2, _P(=〇)(r2G) 〇 P(=〇)(〇r^)2 , cn ( 〇)(R )2, c Weng cw carbon di(tetra)yl, C2·6 alkenyl, heteroaryl, wherein: base, 3 cyclyl, &amp; ❶ aryl, and 5-1. Each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, and heteroaryl is substituted with hydrazine, b, 2, or two fluorene (10) 2 Substituents can be joined to form =〇 or =s; each of R2G is selected from Cw alkyl, Ci^all-alkyl, Cw Sulfhydryl (: 2_6 alkynyl, c3 carbocyclyl, c6 1. aryl, 3, membered heterocyclyl, and 3-10 membered heteroaryl, each of which is an alkyl group, a dilute group, a fast group, a carbocyclic group, The heteroaryl aryl group and the heteroaryl group are each substituted with 0, 1, 2, 3, 4 or 5 R22 groups; each of 〆r21 is selected from the group consisting of hydrogen, C"6 alkyl, CV6 full teeth An alkyl group, a C2_6 alkenyl group, a C2-6 alkynyl group, a C3_1Q carbocyclic group, a 3_1 membered heterocyclic group, a c6 i〇 aryl group, and a 5-10 membered heteroaryl group, or two R21 attached to a nitrogen atom The base is bonded to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring, wherein each of the alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl groups is 0, respectively. 1, 2 '3, 4 or 5 R22 group substitutions; and each of R22 is halogen, -CN, -N02, -N3, -S02H, -S03H, -OH, -OCw alkyl, alkyl) 2 , -NCCw alkyl) 2, -Nfw alkyl) 3X, -NHfw alkyl) 2X, -NHKCw alkyl) X, -NH3X, -NCOCw alkyl XCm alkyl), -NCOHXCw alkyl), -NH ( OH), -SH, -SCw alkyl, -SSCCw alkyl), -ctoxcw alkylalkyl v-ocpoxc^alkyl), -OCO/Cw alkyl), -C(=0)NH2, -CbCOlSKC U alkane 385 201043620 base) 2, _OC b CONHCCk alkyl), -nhc (=o) (c "6 alkyl", - Ν ((^-6 alkyl) ¢: (=0) ((^.6 Alkyl), -NHCC^Ck alkyl), NHCpCONCCu alkyl)2, -NHCpCONHde alkyl), -NHC(=0)NH2 ' -C(=NH)0(Ci.6^, '-OC(= NH)(Ci.6 alkyl), -OCpN^OCw alkyl, -CpNH^CCw alkyl)2, -CpNI^NHCCw alkyl), -C(=NH)NH2, alkyl)2, -OC^ NI^NHCCu alkyl), -OC(NH)NH2, -NHC^NH^CCw alkyl)2, -NHC(=NH)NH2, -NHSCMCk alkyl), -SC^NCCm alkyl)2, -SC ^NHCCw alkyl), -so2nh2, -SC^Ck alkyl, -SC^OCm alkyl, -OSOfM alkyl, -SOCk alkyl, -SKCw alkyl)3, -OSKCw alkyl)3, alkyl) 2. Alkyl), -C(=S)NH2, -CtCOSCCK alkyl), -CCDSC!-6 alkyl, -SCpSpCw alkyl, 4(=0)2((:,-6 alkyl), - PCKDXCw alkyl) 2, -oppoxcw alkyl) 2, -0P (=0) (0C)-6 alkyl) 2, Cw alkyl, Ci_6 perhaloalkyl, C2-6 alkenyl, c2-6 alkynyl , c3_1G carbocyclyl, c6_1() aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two 22 22 substituents may be joined to form =〇 or two S; wherein X—is anti- Ions. 24_ The compound of claim 23, wherein R15 is selected from the group consisting of fluorine-so2n(r18)2, Cl_1〇 alkyl, c丨丨. Perhaloalkyl, c2_i. Alkenyl, c2i. Alkynyl, C6_M aryl, and 5-14 membered heteroaryl wherein each alkyl, alkenyl, fast-radical, aryl, and heteroaryl group is 〇, i, 2, 3, 4, or 5 386 201043620 R19 Replace. 25. The compound of claim 23, wherein 2 is 1 or 2. 26. A compound of the scope of claim patent, wherein 2 is 1. 27. The compound of claim 26, wherein the compound is of the formula: 〇 or a pharmaceutically acceptable form thereof. 28. The compound of claim 27, wherein the compound is of the formula: Or a pharmaceutically acceptable form thereof; Wherein R16 is independently selected from the group consisting of C0 alkyl, (^_10), c^-10 alkenyl, c2-10 alkynyl, c3_1() carbocyclyl, 3-14 heterocyclyl, heptaaryl, and 5-14 A heteroaryl group in which each of the alkyl, alkenyl, alkynyl, carbonic, heterocyclyl, aryl, and heteroaryl groups is substituted with 0, 2, 3, 4 or 5 R19 groups, respectively. 29_ The compound of claim 28, wherein the compound is of the formula: 387 201043620 or a pharmaceutically acceptable form thereof. The compound of the 28th patent scope of the patent, wherein the compound is Off3 or a pharmaceutically acceptable form thereof. 31· = the compound of the 27th patent application area where the compound is the lower G Cf3 Or a pharmaceutically acceptable form thereof. 2. If you apply for a compound that is specifically for the 25th item, 2 is 2. 3. If the compound of claim 32 is applied, the compound of the towel is as follows: CJ or a pharmaceutically acceptable form thereof. 34 'A compound as claimed in claim 33, wherein the compound is of the formula: ’, ,, 388 201043620 or a pharmaceutically acceptable form thereof. 35. A compound of claim 4, wherein 2 is a 5-membered heteroaryl group. 36. The compound of claim 35, wherein the compound has the formula: Or a pharmaceutically acceptable form thereof; wherein γ1, Y2, γ3 and γ4 are respectively selected from CH, CR15, 〇, s, -N, or NR, but the restriction conditions are γΐ, γ2, γ3 and γ4 At least - selected from Ο, S, -Ν or NR18; and each R15 is selected from the group consisting of fluorine (_F), bromine (-Br), gas (-C1), and iodine (-1), -CN, - N02, -N3, -S02H, -S03H, -OH, -OR16, -ON(R18)2, -N(R18)2, -N(R18)3+X·, -N(OR17)R18, -SH , -SR16, -SSR17, -C(=0)R16, -C02H, -CHO, -C(OR17)2, -C02R16, -〇C(=0)R16, -〇C02R16, -C(=0) N(R丨8)2, -0C(=0)N(R18)2, -NR18C(=0)R16, -NR18C02R16, -NR18C(=0)N(R18)2, -C(=NR18)R16 , -C(=NR18)OR16, -OC(=NR18)R16, -oc(=nr18)or16, -C(=NR18)N(R18)2, -OC(=NR18)N(R18)2, - NR,8C(=NR,8)N(R,8)2 , -C(=0)NR18S02R16, -NR18S02R16, -S02N(R18)2, -S02R16, -S〇2〇R16, -0S02R16, -S (=0) R16, -〇S(=0)R16, -Si(R16)3, -OSi(R16)3, -C(=S)N(R18)2, -C(=0)SR16, 389 201043620 -C(=S)SR16, _SCBu S)SRl6, _p(=〇)2Rl6, _〇p(=〇)2Rl6, -P(=0)(R 丨6)2, _OP(=〇)( Ri6)2, _〇p(=〇 )(〇R 丨, , -P(=0)2N(RI8)2 , -OP(=〇)2N(R18)2 &gt; -P(=〇)(NR18)2 . -〇p(=o) (nr18)2, _nr, = 0) (0r17)2, 撼18p(=〇)(NRl8)2, _P(R 7)2, _P(Rl7)3, -OP(Rl7)2, -〇P( R17) 3, -B (OR丨7) 2, BR (OR), cM. Alkyl, Cm〇 perhaloalkyl, C2丨. Alkenyl, q丨. Block group, (: 3.14 carbocyclic group, 3-14 membered heterocyclic group, ^ i4 aryl group, and μ member heteroaryl group) wherein a silk, an alkenyl group, an alkynyl group, a carbocyclic group, a heterocyclic group, an aryl group, and a hetero Each of the aryl groups is substituted with 〇, 1, 2, 3, 4 or 5 r19 groups, respectively; or two 偕R 55 groups are substituted with a group wherein R is oxime, Ci-6 alkyl or a phytin; Each case is selected from the group consisting of Cl_1G alkyl, 〇11 () all-alkyl, &amp; 1 nonenyl, C2-decynyl, C3_丨4, cyclohexyl, 3-14 heterocyclyl, C6丨4 a group, and a 5-14 membered heteroaryl group, wherein the alkene group, an alkenyl group, an alkynyl group, a carbocyclyl group, a heteroaza group, an aryl group, and a heteroaryl group are each 〇, 丨, 2, 3, 4 or 5 R19 groups are substituted; each of R is selected from the group consisting of hydrogen, 〇H, _〇R16, _N(R17)2, -CN, -C(=0)R16, -C(=0)N(R丨7)2, _c〇2R, 6 s〇2R〗 6 -C(=NR,7)0R16 ^ -C(=NR17)N(R17)2 &gt; -S02N(R17)2 s ~so2r17, _so2oh17, _sor16, _c(=s)n(r17)2 -C(=0)SR17, -C(=S)SR17, _p(=0)2r16, _p(K)XRl6:b -ρ(=0)2ν( 〇2, -ρ(=ο)_ν CM. The hospital base all-tooth alkyl, C2.|decenyl, C2_l() alkynyl, c3 1() carbocyclic, 3_14 a C6-14 aryl group, and a 5-14 membered heteroaryl group, or two Rl7 390 201043620 groups attached to a nitrogen atom to form a 3·14 membered heterocyclic group or a 5-14 M wire ring, wherein each cyclist or alkene The radicals, fast radicals, carbocyclic radicals, heterocyclic radicals, aryl radicals, and heteroaryl radicals are substituted by 0, 1, 2, 3, 4 or 5, 9 丨 9 groups, respectively; From hydrogen, Ci i decyl, Ci 1 〇 all-self, c2-1 () alkenyl, c 2 ·] alkynyl, C 3 ] carbocyclyl, 3-14 heterocyclyl, C 6-h aryl And a 5-14 membered heteroaryl group, or two guanidine groups attached to a nitrogen atom to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring, wherein each 0 alkyl group, alkenyl group, The alkynyl-carbocyclyl, heterocyclyl, aryl, and heteroaryl systems are each substituted with 0, 1 '2, 3, 4, or 5 R19 groups; each of R19 is selected from the group consisting of hydrogen, _CN, -N〇2, -N3, -S〇2jj, - -s〇3h, -〇H, -〇R2°, -on(r21)2, -n(r21)2, _n(r21)3+x- , -N(OR2°)R21, -SH, -SR2, _SSR2, _c(=〇)r2, _c〇2H, -C02R20, -0C(=0)R20, _〇c〇2R20, _c (=〇)N(R21)2, -0C(=0)N(R21) 2. _NR21C(=0)R20, -NR21C02R20, -NR21C(=0)N(R21)2, _c(=NR21)OR20, -〇C(=NR2l)R20, O_OC(=Nr2))0r2°, -C(=NR2丨)N(R21)2, -〇C(=NR21)N(R21)2, -NR21C(=NR21)N(R21)2, _NR21S02R2(), so2n(r21)2, -S02R20 , -S〇2〇R2〇, _〇s〇2r20, _s(=〇)R20, _si(R2〇L, -OSi(R20)3, -C(=S)N(R21)2, -C( =0) SR20, -C(=S)SR20, -SC(=S)SR20 - -P(=〇)2r20 . -P(=〇)(R20)2 , -〇P(=〇)(R20) 2 λ _〇p(=o)(or2°) 2, Cl 6-based, Cl 6 perhaloalkyl, c 2 6-dilute, C 2-6 alkynyl, C3-i〇 carbocyclyl, 3-10 member a heterocyclic group, a c6.1()aryl group, and a 5-10 membered heteroaryl group in which each of an alkyl group, an alkenyl group, an alkynyl group, a carbocyclic group, a heterocyclic group, an aryl group, and a heteroaryl group is respectively subjected to Substituting 0, 2, 3, 4 or 5 R22 391 201043620 groups, or two 偕R19 substituents may be joined to form =〇 or; each of the knives is selected from c丨4 alkyl, c]_6 Fully halogenated base, c2 6 soil C2.6 fast radical &lt;^3_丨0 carbocyclic group, q_1〇 aryl group, 3_i 杂环 heterocyclic group, and 3-10 member heteroaryl group, , county, alkynyl, carbocyclic, heterocyclic, ke, and miscellaneous The base system is substituted by G, 丨, 2, 3, 4 or 5 R22 groups respectively; each of R21 is selected from the group consisting of hydrogen, Ci-6 alkyl, Ci 6 perhaloalkyl, C2-6 alkenyl, C2. 6 alkynyl, C:M()carbocyclyl, 3_1〇heterocyclyl, aryl, and 5-10 membered heteroaryl, or two R2 attached to a nitrogen atom, the group bonded to form 3-14 members a heterocyclic group or a 5-14 membered heteroaryl ring wherein each of the alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups is 0, 1, 2, 3, 4, respectively. Or 5 R22 group substitutions; and 22 R each of which are _, _CN, _n 〇 2, -N3, -S02H, -S03H, -OH, -OCk alkyl, _ON (Cl 6 alkyl) 2 _N(Ci 6 alkyl) 2, -MCw alkyl) 3x, -NHCCu alkyl) 2X, -NHzCCw alkyl) X, -NH3X, -NCOCk, XCw alkyl, -NCOHXCu alkyl), -NH (OH), -SH, -SC&quot;alkyl, -SSfw alkyl), -CbOXCM alkyl, -C02H, -CO/Cm alkyl, -OCXOXCw alkyl), -OCO/Cw alkyl), -C(=〇)NH2, -(:(=0)1^((^-6 alkyl)2, -OCbCONHCCK alkyl), -NHCpOXCu alkyl), -N(Ci.6 alkyl)C^ OXCk base), -NHC〇2 (Ci_6 alkyl), -NHC(=0)N(C!-6 Base) 2, -NHCpCON^Cu alkyl), -NHC(=0)NH2 ' '-OC(=NH)(C1.6 alkyl), -OCtNt^OCw alkyl, alkyl) 2, 392 201043620 Base), -C(=NH)NH2, -◦CpNH^CCu alkyl)2, -OC(NH)NH(Ci-6 alkyl), -〇C(NH)NH2, -NHQNI^NKmalkyl) 2. -NHC(=NH)NH2, -NHSCMCw alkyl), -S02N(CN6 alkyl)2, -SC^NHCCw alkyl), -S02NH2, -SO2C1-6, and -S〇2〇Ci_6 * group, -OSO2C1.6 alkyl, -SOC1.6 alkyl, -SKCw alkyl)3, -OSKCw alkyl)3, -ChSWCCw alkyl)2, alkyl), -C(=S)NH2 -CPCOSCCw ^ alkyl), -cespcw alkyl, -SCPSPCm alkyl, 4(=0)2((^.6 alkyl), +(=0)((:,-6 alkyl)2 ' -OPtOXCw Alkyl) 2, -OPOOXOCw alkyl) 2, Cw alkyl, Cw perhaloalkyl, C2-6 alkene, C2-6 alkynyl, C3-1() carbocyclyl, c6.1() a 3-10 membered heterocyclic group, a 5-10 membered heteroaryl group; or two fluorene R22 substituents which may be joined to form =? or =s; wherein X is a counterion. 37. A compound according to claim 36, wherein R15 is selected from the group consisting of fluoroindole (-F), desert, (_Br), gas (_C1), and iodine (-1), -OR16, -C (=0) N(Ri8)2, -S〇2N(R18)2, Cwo alkyl, Cwo functional alkyl, c2_10 alkenyl, c2 l decynyl, C6_H aryl, and 5-14 heteroaryl, wherein each alkane The base, alkenyl, fast-radical, aryl, and heteroaryl groups are each substituted with hydrazine, hydrazine, 2, 3, 4 or 5 V9 groups. 38. The compound of claim 36, wherein Y1 is S, Y3 is N, and Y2 and Y4 are CH or CR15, respectively. 39. A compound according to claim 38, wherein the compound is of the formula: 393 201043620 Or a pharmaceutically acceptable form thereof. 4〇 'The compound of claim 36, wherein V is s, and each Υ 'γ3 and γ4 are CH or CR15, respectively. 41. The compound of claim 4G, wherein the compound is of the formula: Or a pharmaceutically acceptable form thereof. 42. The compound of claim 1, wherein the compound has the formula: lower Rc Or a pharmaceutically acceptable form thereof; wherein: CHR15, -C(R,5)2 w20, W21, W22 and W23 are respectively ch2 or NR18; s is 0, 1 or 2; and each ruler is selected from Fluorine (-F), bromine (-Br), gas (-C1), and moth 394 201043620 (-1), -CN, -N〇2, -N3, -S02H, -S03H, -OH, -OR16, -ON(R18)2, -N(R18)2, -N(R18)3+X., -N(OR17)R18, -SH, -SR16, -SSR17, -C(=0)R16, -C02H , -CHO, -C(OR17)2, -C02R16, -0C(=0)R16, -0C02R16, -C(=0)N(R18)2, -0C(=0)N(R18)2, - NR18C(=0)R16 &gt; -nr18co2r16 ' -nr18c(=o)n(r18)2, -C(=NR18)R16, -C(=NR18)OR16, -OC(=NR18)R16, -OC( =NR18)OR16, -C(=NR18)N(R18)2, -oc(=nr18)n(r18)2, -nr18c(=nr18)n(r18)2, o -c(=o)nr18so2r16, -nr18so2r16, -S02N(R18)2, -S02R16, -S〇2〇R16, -0S02R16, -S(=0)R16, -0S(=0)R16, ^ -Si(R16)3, -OSi( R16)3, -C(=S)N(R18)2, -C(=0)SR16, -C(=S)SR16, -SC(=S)SR16, _P(=〇)2R16, _〇P (=〇) 2R16, -P(=0)(R16)2, -〇P(=〇)(R16)2, -〇P(=〇)(〇R17)2, -P(=o)2N( R18)2, -〇P(=〇)2N(R18)2, -p(=〇)(NR18)2, -OP( =〇)(NR18)2, -NR18P(=〇)(〇R17)2, -NR18P(=〇)(NR18)2, 〇-p(Rl7)2, -P(R丨7)3, -〇 p(r17)2, -〇p(r17)3, -B(〇R17)2, -BR16(〇r17), Cwo alkyl group, CM. All i alkyl, Cu. Alkenyl, C2-i decynyl, C3-14 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein alkyl, alkenyl 'alkynyl, Carbocyclyl, heterocyclyl, ruthenyl, and heteroaryl are each substituted with 0, 1, 2, 3, 4 or 5 R19 groups; or two 偕R15 groups are via _〇(C(r2) 2) 1-2〇_yl substitution where R is Η, Ck, or halogen; each of R is selected from the group consisting of Cl-ίο, C!_10 all-toothed, C2-10 alkenyl, C2_1() Alkynyl, C3-14 carbocyclyl, 3-14 membered heterocyclyl, c6-14 aryl 395 201043620, and 5-14 membered heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl, hetero The nucleobase, the aryl group, and the heteroaryl group are each substituted with 〇i, 2, 3, 4 or 5 R19 groups; each of R18 is selected from the group consisting of hydrogen, 〇H, _R16, and VII , -CN, -C(=0)R16, -C(==〇)N(Rn)2, _c〇2Rl6, _s〇2Rl6, -C(=NR17)OR16 ^ -C(=NR17)N( R17)2, -S02N(Rn)2 -so2r, -s〇2〇Rn, -sor16, _c(=s)n(r")2 -C(=0)SR17, -C(=S)SR" , _p(=〇)2Rl6, _p(=〇)(Rl6)2 _P(=〇)2N(Rl7)2, ·Ρ(=〇)(cis-17)2, Cu1G alkyl, Cl, all (tetra) base, C2_10 olefin a group, a C2_10 block group, a C31 carbocyclyl group, a 3-14 membered heterocyclic group, a C6-14 aryl group, and a 5'-based group, or two f groups attached to a nitrogen atom are bonded to form a 3·14 member a cyclic group or a 5·14 anthracene ring wherein each of the alkyl, dilute, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl groups is 0, 1, 2, 3, 4, or 5, respectively Each of the subunits of the formula R17 is selected from the group consisting of hydrogen, c]', c(10) all (tetra), c2.1 (), C2.1 (), c3, carbocyclyl a 3-14 membered heterocyclic group, a c6.14 aryl group, and a 5-14 membered heteroaryl group, or two Ri7 groups attached to a nitrogen atom are bonded to form a 3-14 membered heterocyclic group or a 5-14 membered heterocyclic ring in which each is sintered. The base, alkene, block, post-cyclic, heterocyclic, aryl, and heteroaryl are substituted by 0, 1, 2, 3, 4 or 5 R 9 groups, respectively; ' -1N3 ' -S〇2H S03H, -OH, -OR20 ' -〇N(r21)2, _n(r21)2, _n(r2, +x -N(OR20)R21, -SH, -SR20 -C02R20 , -OC(=0)R20, , -ssr2°, -C(=0)R2〇, _c〇2H -0C02R20, -C(=〇)n(r2i)2, 396 201043620 -OC(=0)N (R21)2, -NR21C(=0)R20, -NR21C〇2R20, -nr2 1c(=o)n(r2I)2, -C(=NR21)〇R20, -〇C(=NR21)R20, -OC(=NR21)OR20, -C(=NR21)N(R21)2,- 〇C(=NR21)N(R21)2, -nr21c(=nr21)n(r21)2, -NR21S02R2〇, so2N(R21)2, -S02R20, -S02OR20, -〇S02R20,,S(=0) R20, -Si(R20)3, -〇Si(R20)3, -C(=S)N(R2丨)2, -C(=〇)SR20, _C(=S)SR20, -SC(=S ) SR2°, -P(=〇)2R2. , _p(=〇xR20)2, _〇p(=〇)(R20)2, Ο -〇P(=〇)(〇R20)2, C16 alkyl group, Ci 6 perhaloalkyl group, alkenyl group, C2·6 alkynyl group, Cl丨o carbocyclic group, 3-10 membered heterocyclic group, Cw. An aryl group, and a 5 1 member heteroaryl group, wherein each of the alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups is respectively 〇, 卜 2, 3, 4 or 5 R22 group substitutions, or two 偕R19 substituents may be joined to form =〇 or =s; each of R20 is selected from the group consisting of Cn6 silk, Cm all-based, &amp; alkenyl, C2-6 alkynyl, a ChG carbocyclic group, a C6.1Q aryl group, a 3·10 membered heterocyclic group, and a 3-1 member heteroaryl group in which each of the alkyl group, the dilute group, the block group, the carbon group, and the heteroaryl group , Bu 2, 3, and Bixin Valley are selected from nitrogen, Ci6 alkyl, Ci6 all c2-6 dilute 'c2.6 block, C3 iQ carbocyclic group, 3_iq member base ^ aryl group, and 5 · drink aryl, or attached to the gas primordial group:: base, dilute, alkynyl 1 ring group, heterocyclic group, aryl group, each burning ship 2, 10, 4 or 5, 1 substitution; The examples of the base protection are ", -CN'_N02, N3, Na H, 397 201043620 -S03H, -OH, -OCi-6 alkyl, -ONCQ-6 alkyl) 2, -ΝΘμ alkyl)2 , -NCCi-6 alkyl)3Χ, -NHCCmalkyl)2Χ, -NHdCw alkyl)X, -NH3X, -NCOCyalkyl XCw alkyl), -NeHXCw alkyl), -NH(OH) , -SH, -SCw alkyl, -SSCCw alkyl), -(:(=0)((^.6 alkyl h-CC^H'-CC^Cw alkyl h-OCpOXCw alkyl), -OCOdCM Alkyl), -C(=0)NH2, -(:(=0)1^((^-6 alkyl)2, -(ΧχΚ^ΝΗγκalkyl), -NHC^OXCmalkyl), -N (C)-6 alkyl) ¢: (=0) ((:, -6 alkyl), -NHCCMCw alkyl), -NHCPCOISKCk alkyl) 2, -NHC (=0) NH (C丨-6 alkane -) -NHC(=0)NH2 &gt; -C(=NH)0(Ci.6^,^) '-OC(=NH)(C1,6 alkyl), -OCpN^OCw alkyl,- CpNP^IsKCw alkyl)2, -C(=NH)NH(Cn6 alkyl), -C(=NH)NH2, -OCpNH^fK alkyl)2, -OC^NP^N^Ck alkyl), -OC(NH)NH2, -NHC^NI^NCCk alkyl)2, -NHC(=NH)NH2, -NHSOXCk alkyl), -SC^NCCw alkyl)2, -SC^NHCCw alkyl), - S02NH2, -SOsCu alkyl, -SOsOCu alkyl, -OSC^Cm alkyl, -SOCi.6 alkyl, -skCm alkyl)3, -osKCw alkyl)3,alkyl)2,6 alkyl), -C(=S)NH2, -(:(=0)8((^.6 alkyl), -CpspCw alkyl, -scespcwalkyl, 4(=0)2((:,.6 alkyl) , -PtOXCM alkyl) 2, -OPtCOCCw alkyl) 2, -OPeOXOCw alkyl) 2, Cu alkyl, CN6 perhaloalkyl, c2.6 alkenyl, C2-6 alkynyl, C3.10 carbocycle , C6.1Q aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two geminal substituents R22 may be joined to form a square or = = s; 398 201043620 x_ wherein a counterion. 43. A compound as claimed in claim 42 wherein s is zero. 44. The compound of claim 42 wherein W2Q, W21 and W22 are CH2, CHR15, -C(R15)2 or NR18, respectively. 45. For the compound of claim 44, wherein the compound is of the formula: Or a pharmaceutically acceptable form thereof. 46. The compound of claim 1, wherein the compound has the formula: Or a pharmaceutically acceptable form thereof; wherein W24, W25, W26, W27, W28 and W29 are CH2, CHR15, -C(R15)2 or NR18, respectively, or alternatively wherein W25 and W26 are fused to C6 An aryl ring or a fused 6-membered heteroaryl ring; t and v are 0 or 1 respectively; and each R15 is selected from the group consisting of fluorine (-F), bromine (-Br), chlorine (-C1), and iodine. (-1), -CN, -N02, -N3, -S02H, -S03H, -OH, -OR16, -on(r18)2, -n(r18)2, -n(r18)3+x-, -N(OR17)R18, -SH, -SR16, -SSR17, -C(=0)R16, -C02H, -CHO, -C(OR17)2, 399 201043620 -C02R16, -0C(=0)R16, -oco2r16, -c(=o)n(r18)2, -0C(=0)N(R18)2, -NR18C(=0)R16 ' -NR18C02R16 ' -nr18c(=o)n(r18)2 -C(=NR18)R16, -C(=NR18)OR16, -OC(=NR18)R16, -OC(=NR18)OR16, -C(=NR18)N(R18)2, -oc(=nr18) n(r18)2, -nr18c(=nr18)n(r18)2, -C(=0)NR18S02R16, -NR18S02R16, -S02N(R18)2, -S02R16, -S〇2〇R16, -OS02R16,- S(=0)R16' -0S(=0)R16, -Si(R16)3, -〇Si(R16)3, -C(=S)N(R18)2, -C(=0)SR16, -C(=S)SR16, -SC(=S)SR16, -P(=0)2R16, -0P(=0)2R16, -P(=〇)(R,6)2, -OP(=〇 )(R16)2 -〇p(=〇x〇r17)2, -p(=o)2n(r18)2, -〇P(=〇)2N(R18)2, -p(=o)(nr18)2, -0P (=0)(NR丨8)2, -NR18P(=〇X〇R丨7)2, -NR18P(=〇)(NR18)2, -P(R17)2^-P(R17)3^ - 〇P(R17)2 &gt; -OP(R17)3 ^ -B(〇R17)2' -BR (OR ), C〗 _丨〇烧基, C]-】〇Full halogenated base, C2-10 a dilute group, a C2-10 alkynyl group, a C3_丨4 carbocyclic group, a 3-14 membered heterocyclic group, a C6_丨4 aryl group, and a 5-14 membered heteroaryl group, wherein an alkyl group, an alkenyl group, an alkynyl group , carbocyclyl, heterocyclyl, aryl, and heteroaryl are each substituted with 〇, 1, 2, 3, 4 or 5 R19 groups; or two 偕R15 groups are preceded by -0((:( 1^)2)^0-yl substitution wherein R2 is Η, (^6 alkyl or halogen; each of R16 is selected from the group consisting of cM0, Cwo perhalogen, c2-10 alkenyl, C2_1() alkyne a c3_14 carbocyclic group, a 3-14 membered heterocyclic group, (:6.|4 aryl, and a 5-14 membered heteroaryl group, wherein an alkyl group, an alkenyl group, an alkynyl group, a carbocyclic group, a hetero-based group , aryl, and heteroaryl are each substituted with 〇, 1, 2, 3, 4 or 5 R19 groups; 400 201043620 Rl8 examples are selected from the group consisting of hydrogen, -OH, -OR16, -N (R17) ) 2, -C(=〇)N(R17) 2, -co2R16, -so2r16, -CN, -C(=0)R16, -C(=NR17)OR16, -——a "-w&quot;, must · ν-3·ΐ (τ/火难, j - 丄碎潍潍基, a CVm aryl group, and a 5-14 membered heteroaryl group, or two Rn groups attached to a nitrogen atom, are bonded to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring, wherein each alkyl group, alkenyl group , alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl are substituted by 0, 1, 2, 3, 4 or 5 W9 groups, respectively; each of Rl7 is selected from 氲, CM0 Alkyl, CM0 perhaloalkyl, C2_decenyl, Cm alkynyl, Cyo carbocyclyl, 3-14 membered heterocyclyl, phenyl, and 5-14 membered heteroaryl, or attached to a nitrogen atom The two y7 groups are joined to form a 3-14 membered heterocyclic or 5-14 membered heteroaryl ring wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl The base system is substituted with 0, 1, 2, 3, 4 or 5 R19 groups, respectively; each of R19 is selected from the group consisting of hydrogen, -CN, -N02, -N3, -so2h, -S03H, -OH, - OR20, -〇N(R21)2, -N(R21)2, -N(R21)3+X-, -N(OR20)R21, -SH, -SR2°, -SSR20, -C(=0) R20, -C02H, -co2r20, -oc(=o)r20, -oco2r20, -c(=o) n(r21)2, -0C(=0)N(R21)2, -NR21C(=0)R20, -NR21C02R20, -nr21c(=o)n(r21)2, -C(=NR21)OR20,- OC(=NR21)R20, -OC(=NR21)OR20, -C(=NR21)N(R21)2, -OC(=NR21)N(R2l)2, 401 201043620 视2=(STEP 21)Which 21 ) 2, _nr21s 〇 2r2, (10) hetero, S02R, _s 〇 2 〇 r2, _ 〇 s 〇 2r20, _s (= 〇) r20,, - 〇 skr2V - c (= s) N (R21) 2 -c(=〇)SR2., c(=s)sr20, -SC(=S)SR20 &gt; -P(=〇)2R20, -P(=O)(R20)2, _〇P(=〇 )(r2〇)2 , -〇p(=〇X(10).)2, Ci thiol, Ci 6 perhalogenated group, dilute group, C2-6 alkynyl group 'C3, carbocyclic group, 3-10 member a cyclic group, a C6_10 aryl group, and a 5_1 member heteroaryl group wherein each of the alkyl group, the alkenyl group, the alkynyl group, the carbocyclic group, the heterocyclic group, the aryl group, and the heteroaryl group are respectively subjected to 0, 3, 4 or 5 r22 group substitutions, or two 偕R!9 substituents may be joined to form or; each of R20 is selected from the group consisting of Cl-6 alkyl, €1-6 all-alkyl, C2 6 alkenyl Alkynyl, C3-indole carbocyclyl, C6_10 aryl, 3-10 membered heterocyclic, and 3-1 anthracene heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocycle Base, aryl, and hetero Each of the R22 groups is selected from the group consisting of hydrogen, Cl-6 alkyl, Cm perhaloalkyl, C2-6 alkenyl, C2_6 alkynyl, c3_1G. Carbocyclic group, 3-10 member heterocyclic ring, its it sulphate. a 6-10 aryl group, and a 5-10 membered heteroaryl group, or two groups attached to a nitrogen atom, are bonded to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring, wherein each alkyl group, alkenyl group, An alkynyl group, a carbocyclic group, a heterocyclic group, an aryl group, and a heteroaryl system are substituted with 0, 1, 2, 3, 4 or 5 R22 groups, respectively; and each of ', R22 is a element, _CN , -N02, -N3, S() H -S03H, -OH, -Ο. Alkyl, -N (Cl-6 alkyl) 2, _N (Ci 6 alkyl) 2, -I^Cu (3), _NH(C) 6 alkyl) 2χ, _Nh 俨 )) X, -NH3X, alkyl XCm alkyl), -N(〇h) (Ci 402 201043620 alkyl), -NH(OH), -SH, -SC&quot;alkyl, -SSfw alkyl), -CCOXCm alkyl h -CC^H'-COXCK alkyl h-OCpOXCw alkyl), -OCOXCk alkyl), -C(=0)NH2, -CPCONCCk alkyl)2, -OCeCONI^Cw alkyl), -NHCPOXC^alkyl ), -NCCm alkyl)CtOXCK alkyl), -NHCO/Cw alkyl), NHCtCONCCu alkyl)2, -NHCpCONHCCu alkyl), -NHC(=0)NH2 '-C(=NH)0(C, .6^1.) '-OC(=NH)(Ci.6 alkyl), -OCPNHPCkalkyl, alkyl)2, -CpN^N^Caalkyl), -C(=NH)NH2,- OCpNH^CCu alkyl)2, -OC^NH^I^Ck alkyl), -OC(NH)NH2, -NHCCNJ^NCCw alkyl)2, -NHC(=NH)NH2, -NHSCMCw alkyl), -SOx^Cw alkyl)2, -SCbNHCCw alkyl), -S02NH2, -SC^Ck alkyl, -SOaOCw alkyl, -OSC^Cw alkyl, -SOCk alkyl, -Si(Ci-6 alkyl 3, _ 〇 Si (Cl-6 alkyl) 3, _C (-S) N (Ci. 6 alkyl) 2, -C (= S) NH (C 丨. 6 alkyl), -C (= S) NH2, -CpCOSde alkyl), -cpspcw alkyl, -SCpSfCk alkane , -p(=〇)2(Cl 6 alkyl), 4(=0)((^-6 alkyl)2, -〇P(=〇)(Ci-6 alkyl) 2, -OPHDXOCw alkyl 2, Cw alkyl, C "6 perhaloalkyl, c2_6 alkenyl, c2.6 block, C3.1 () carbocyclyl, c6-i aryl, 3-10 membered heterocyclic, 5 - 10 member heteroaryl; or two 偕R22 substituents may be joined to form =0 or two S; wherein X· is a counter ion. 47. The compound of claim 46, wherein the compound is of the formula. 403 201043620 Or a pharmaceutically acceptable form thereof. 48. 49. The compound of claim 46, wherein t is 〇, 乂 is i and w25 and w is substituted with a fused C6 aryl ring, and w27 and w28 are CH2, CHR15 and C, respectively (R15 )2. Such as the compound of the 48th patent scope of the patent, wherein the compound has Or a pharmaceutically acceptable form thereof; wherein z is 0, 1, 2, 3 or 4; and each R15 is selected from the group consisting of fluorine (_F), bromine (-Br), chlorine (_cl), and iodine (-1) , -CN, -N02, -N3, -S〇2H, -S03H, -OH, -OR16, -ON(R18)2 ' -N(R18)2 ' -N(R18)3+x- &gt; - N(OR17)R18 ' -SH ' -SR16, -SSR17, -C(=0)R16, _c〇2h, -CHO, -C(OR丨7)2, -C02R16, -0C(=0)R16, -〇c〇2R16, -C(=0)N(R18)2, -0C(=0)N(R18)2, -NR18C(=〇)R16, -NR18C02R16, -nr18c(=o)n(r18 2, -C(=NR18)R16, -C(=NR18)OR16, -OC(=NR,8)R16 &gt; -OC(=NR,8)〇r16 . -C(=NR18)N(R18 ) 2 &gt; 404 201043620 -OC(=NR18)N(R18)2 , -nr18c(=nr18)n(r18)2 , -C(=0)NR18S02R16, -NR18S02R16, -S02N(R18)2, -S02R16 , -S〇2〇R16, -0S02R16, -S(=0)R16, -0S(=0)R16, -Si(R16)3, -OSi(R16)3, -C(=S)N(R18 2, -C(=0)SR16, -C(=S)SR16, -SC(=S)SR16, -P(=〇)2R16, -〇p(=〇)2R16, -P(=0) (R16)2, -OP(=〇)(R16)2, _〇P(=〇)(〇r17)2, -P(=0)2N(R18)2, -〇P(=〇)2N( R18)2, -P(=〇)(NR18)2, 〇-〇P(=〇)(NR18)2, -NR18P(=〇)(〇R17)2, -NR18P( =0)(NR18)2, -P(R17)2, -P(R17)3, _〇P(R17)2, -OP(R17)3, -B(OR17)2, -BR16(〇R17) ,Cho alkyl, cM0 perhaloalkyl, c2.decenyl, c2-10 „alkynyl, C3_H carbocyclyl, 3-14 membered heterocyclyl, c6_14 aryl, and 5-14, shellfish a group wherein the alkyl group, the dilute group, the fast group, the carbocyclic group, the heterocyclic group, the aryl group, and the heteroaryl group are each substituted with 〇, 1, 2, 3, 4 or 5 R19 groups; or two The 偕R15 group is replaced by a group wherein R is Η, Ci_6 alkyl or a gemin; each of Q Rl6 is selected from the group consisting of Cum alkyl, C丨-丨〇 perhaloalkyl, C2-10 alkenyl, C2-1 () alkynyl, c3_14 carbocyclyl, 3-14 membered heterocyclyl, c6_14 aryl, and 5-14 membered heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl The base and the heteroaryl are each substituted with 〇, 1 ' 2, 3, 4 or 5 R19 groups; each of R18 is selected from the group consisting of hydrogen, -OH, -〇R16, -N(R17)2 -CN, -C(=0)R16, -C(=0)N(R17)2, -C02R16, -S02R16, -C(=NR17)〇R16 . -C(=NR17)N(R17)2 &gt ; -S02N(R,7)2 ' -S02R17, -S〇2〇R17, -SOR16, -C(=S)N(R17)2, 405 201043620, 0) 2R,6, _p(, yl, c2_10 alkenyl, c2_l 〇 block base Q says 丨〇 slave % base, 3-14 occupies a base interface and I becomes a 3.14 member heterocyclic group or heterozygous The alkyl group, the alkenyl group, the alkynyl group, the fluorenyl group, the fluorenyl group, the heterocyclic group, the aryl group and the basic group are respectively 〇, l, n 19 heterotetrazed 1, 3, 4 or 5 R19 Each of R17 is selected from the group consisting of hydrogen, Ci, and Cm. All · base, c2_10 alkenyl,. 2_丨. Alkynyl,. 31〇 carbocyclyl, 3_14 membered heterocyclic, C6-14 aryl, and 5-14 membered heteroaryl, or two groups attached to a nitrogen atom to form a 3·14 membered heterocyclic group or 5-14M a heterofilament wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is substituted with 0, 1, 2, 3, 4 or 5 RB groups, respectively; Each of R19 is selected from the group consisting of hydrogen, -CN, _N〇2, _N3, _s〇2H, -S03H, -OH, -OR2(), -〇N(R21)2, -N(R21)2, - N(R21)3+x--N(OR20)R21, -SH, -SR20, -SSR20, -C(=0)R20, -C02h, -C02R20, -OC(=0)R20, -oco2r20,- C(=Q)N(R21)2, -0C(=0)N(R21)2 ' -NR2IC(=0)R20 &gt; -NR21C02R20 . -NR21C(=0)N(R21)2, -C( =NR21)OR20, -OC(=NR21)R20, -OC(=NR21)OR20, _c(=nr21)n(r21)2, -oc(=nr21)n(r21)2, -nr21c(=nr21) n(r21)2, -nr21so2r2°, S02N(R21)2, -S02R20, -S〇2〇R2. , -〇S〇2R2. , -S(=0)R20, -Si(R20)3, -OSi(R20)3, -C(=S)N(R21)2, -C(=0)SR20, -C(=S)SR20 -SC(=S)SR20 &gt; -P(=0)2R20' -P(=〇)(R20)2' -〇P(=〇)(R20)2 , 406 201043620 -OP(=〇)( OR20) 2, Cl-6 appearance, And 3_1G bethole aryl, wherein each leuco, C2-6 phenyl, aryl, aryl, and 5-10 alkynyl, carbocyclyl, heterocycle = 0 or; &lt;^_6 all-alkyl, &gt; aryl, 3-10 membered heterocyclic group, alkenyl group, alkynyl group, carbocyclyl group, heterocyclic group, and heteroaryl group are substituted by hydrazine, b, 2, and 3 R22 groups, respectively; Each of the examples is selected from the group consisting of hydrogen, Ci's base, CiA-alkyl, c2_6 alkenyl, c2_6 alkynyl, C31G carbocyclyl, 3_1〇 heterocyclyl, a ^ square, and 5-10. , or two r21 groups attached to a nitrogen atom are joined to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring, wherein each alkyl group, alkenyl group, alkynyl group, carbocyclyl group, heterocyclic group, aryl group And the heteroaryl group are substituted by 0, 1, 2, 3, 4 or 5 R22 groups, respectively; and each of 22 R is anthracene, -CN, -N〇2, -N3, -S02H, -S03H, -OH, -OCw alkyl, -ΟΝγΜalkyl) 2, -Nfw alkyl) 2, -Nfw alkyl) 3x, -NHCCw alkyl) 2X, -NHJCm alkyl)X, -NH3X, - NCOCu base XCk alkyl), -NCOHXCu alkyl), -NH(OH), -SH, -SCu alkyl, -SSfw alkyl), 4(=0)((^.6 alkyl h-COzH' -CO/ C^alkyl), -0(:(=0)((^-6 alkyl), -occmCkalkyl), -c(=o)nh2, -ctoyNCCK alkyl)2, -OCXK^NHCCw alkyl ), -NHCpOXCw alkyl), 407 201043620 -Nde alkyl)CtOXCM alkyl), -NHCCMC^alkyl), -NHCpC^i^Cu alkyl)2, -NHCpC^NHde alkyl), -NHC(= 0) NH2 '-C(=NH)0(C1,6^^) '-OC(=NH)(Ci.6 alkyl), -OCpN^OCw alkyl, -CpNHONCCw alkyl)2, -C( =NH)NH(C!-6 alkyl), -C(=NH)NH2, -OCpNHONCCa alkyl)2, -OC^NH^P^Cm alkyl), -OC(NH)NH2, -NHCXNt^ NCCM alkyl) 2, -NHC(=NH)NH2, -NHSOWCu alkyl), -SC^NCCw alkyl)2, -SC^NHCCm alkyl), -S02NH2, -SCM^.ealkyl, -SC ^OCw alkyl, -OSC^Cm alkyl, -SOCk alkyl, -Si(Ci.6 alkyl)3, _〇Si(Ci_6 alkyl)3, -C(=S)N(Ci.6 Base) 2, alkyl), -c(=s)nh2, alkyl), -C(=S)SCi.6 alkyl, _SC(=S)SCi.6 alkyl, 4(=0)2( (^-6 alkyl), 4 (=0) ((:, -6 alkyl) 2, -OPpOXC^ alkyl) 2, -OPPOXOCk alkyl) 2, Ci_6 alkyl, Cu perhalogenated, c2_6 Mercapto, C2_6 alkynyl, C3-10 carbocyclyl, C6-i aryl, 3-10 membered heterocyclic, 5-10 membered heteroaryl; Two geminal R22 groups may be joined to form a substituted or = s; wherein X · is a counterion. 50. The compound of claim 49, wherein both W27 and w28 are (: a base). 51. The compound of claim 50, wherein the compound is of the formula: 201043620 or a pharmaceutically acceptable compound thereof 52. A compound according to any one of the patent claims, wherein the α is selected from the group consisting of -Cb-Br, -I, -〇Re, 〇NRfRe, _〇NRf(c=〇)Re, -0NRfS02Re, _〇NRfp〇2Re, _〇NRfp〇2〇Re, _SRe, -OS02Re, -NRfS〇2Re, -〇p〇2Re, _〇p〇2〇Re, _NRfp〇2Re, NRfP〇2〇Re , _〇p〇2NRfRe, _〇(c=〇)Re, _〇(c = 〇)〇Re, Ο-NRfRe, -NRf(C=0)Re, -NRf(C=0)0Re,-0 (C=0) NRfRe, -NRf(C=NRf)NRfRe, -〇(C=NRf)NRfRe, -NRf(C=NRf)ORe, and -[N(Rf)2Re]+x_where χ- 53. A compound according to claim 52, wherein Gg_〇Re. 54. A compound according to claim 53 wherein Re is a C6_14 aryl group. 55_ as claimed in claim 54 A compound, wherein Re is a phenyl group. 56. A compound according to claim 55, wherein Re is a monosubstituted phenyl group 57. A compound as claimed in claim 54 wherein Re is a phenyl group of the formula: Wherein: X is 0, 1, 2, 3, 4, or 5, and each Rh is selected from the group consisting of fluorine (-F), &gt; odor (-Br), chlorine (-C1), and broken (-1). , -CN, -N02, -N3, -S02H, -S03H, -OH, -OR1, -ON(Rk)2, _N(Rk)2, -N(Rk)3+X., -N(ORj) Rk, -SH, -SR1, -SSRj, -C(=〇)Ri, -C02H, -CHO, -C02Ri, -0C(=0)Ri, -0&lt;:02β, -C(=0)N(( Rk)2, _〇C(=0)N(Rk)2, -NRkC(=0)Ri, 409 201043620 - dish as gray, -NRkC(=0)N(Rk)2, -C(=NRk) Ri &gt; -C(=NRk)〇Ri , -OCC^NR^R1 , -OC(=NRk)ORi , -C(=NRk)N(Rk)2, -〇C(=NRk)N(Rk) 2. -NRkC(=NRk)N(Rk)2, -C(=0)NRkS02Ri, -NRkS02Ri, -S02N(Rk)2, -S02Ri, -S02ORi, -〇S〇2Ri, 4(=0)1 ^, -08(=0)1^, -S'R%, -(^(3, -C(=S)N(Rk)2, -CH^SRi, -CbSARi, -SC(S)SR_ , -P(=〇)2R·, -〇ρ(=〇)2β, _p(=〇)(Ri)2, -OP(=〇)(R')2 . -0P(=0)(0Rj) 2 . -P(=〇)2N(Rk)2, -0P(=0)2N(Rk)2, -P(=0)N(Rk)2, _〇p(=〇)N(Rk)2 -NRkP(=〇)(〇RJ)2, _NRkP(=〇)(NRk)2, _p(Rj)2, _p(Rj)3, -OP(RJ)2, -〇P(RJ)3, -B(0R』)2, _BRi(〇Rj), cl i〇alkyl, CMG all-i-alkyl, c2_丨Alkenyl, C2.1G alkynyl, (: 3-14 carbocyclyl, 3-14 membered heterocyclyl, Qm aryl, and 5-14 membered heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclyl, The heterocyclyl 'aryl and heteroaryl are each substituted with 〇' 1, 2, 3, 4 or 5 Rm groups; β is selected from Cm 〇 alkyl, Ci hk ^ _ at each occurrence Alkyl, C2_1G alkenyl, C2.1Q alkynyl, (: 314 carbocyclyl, 3-14 membered heterocyclyl, Qm aryl and 5-14 membered heteroaryl, wherein alkyl, alkenyl, alkynyl, carbocyclic The base, the hetero group, the aryl group, and the heteroaryl group are each substituted with hydrazine, b, 2, 3, 4 or 5 groups; R is selected from 氲, _〇H, _ at each occurrence. 〇Ri, -N(R〇2, -CN, -(:(=0)111' -C(=〇)N(Rj)2, -C〇2Ri, -SO#, -C^NROOR1 ^ -C (=NRj)N(RJ)2 . -S〇2N(Rj)2 ^ -S02Rj . -S02ORj, -SOR1, -C(=S)N(Rj)2, _c(=〇)sRj, _c(= S) SRj, 4l〇201043620 -p (iv) π, _P(=〇)(R1)2, 吟_(10)2, 〇) (Na, Cl-10 alkyl, 〇1, all-alkyl, h. Alkenyl, c2_10 alkynyl, C314 carbocyclyl, 3·14 membered heterocyclyl '% aryl and 5·heteroaryl, or two Rj groups attached to a gas atom are bonded to form a disperser a cyclic group or a 5-14 membered heteroaryl ring wherein each of a decyl group, a dilute group, a aryl group, a carbocyclic group, a heterocyclic group, an aryl group, and a heteroaryl group is respectively 0, 2, 3, 4 or 5 Rm* substitutions; Rj is selected from the group consisting of hydrogen, ‘silk, Cl.1〇 all-toothed base, and C2·1. a dilute group, a C2, a block group, a CW carbon ring group, a 3-14 membered heterocyclic group, a C6.14 wire, and a 5-14M heterocycle, or two Rj groups attached to a money atom are bonded to form a 3-14 membered heterocyclic group or 5-14 a heteroaryl ring in which an alkyl group, an alkenyl group, an alkynyl group, a carbocyclic group, a heterocyclic group, an aryl group, and a heteroaryl group are each substituted with 0, 1, 2, 3, 4 or 5 Rm groups, respectively. ; R at each occurrence is selected from fluorine (_F), bromine (_Br), gas (-C1), and 峨 (-1), -CN, -N〇2, -N3, -S02H, -S03H , -OH, -OR. , -ON(Rn)2, -N(Rn)2, -N(Rn)3+X-, -N(OR°)Rn, -SH, -SR0, -SSR0, -C(=0)R0, -C02H, -C02R0, -0C(=0)R°, -OCO2R0, -C(=0)N(Rn)2, -0C(=0)N(Rn)2, -NRnC(=0)R0, -NRnC02R0, -NRnC(=0)N(Rn)2, -C(=NR&quot;)OR°, -OC(=NRn)R°, -OC(=NRn)OR°, -C(=NRn)N (Rn)2, -OC(=NRn)N(Rn)2, -NRnC(=NRn)N(Rn)2, -NRnS02R. , -S02N(Rn)2, -S02R. , -S02OR°, -0S02R. -S(=0)R°, -Si(R°)3, -OSi(R〇)3, -C(=S)N(Rn)2, -C(=0)SR°, -C( =S)SR. , -SC(=S)SR. , -P(=0)2R0, 411 201043620 =(=〇), -〇P(=〇)(m2, _op(=0)(〇rq)2, Ci 6 burnt base, 6 king base, c2 6 Alkenyl, c26 block, C3_14 carbocyclyl, 314 heteroalkyl, c6.14 aryl and 5-14 membered heteroaryl, wherein alkyl, dilute, alkynyl, carbocyclyl, heterocyclyl, aryl The base and the heteroaryl group are each substituted by 1, 2, 3, 4 or 5 Rp groups, or two ruthenium substituents can be joined to form =0 or =S; R° is respectively present at each occurrence Is selected from the group consisting of Cl_6 alkyl, 〇1_6 all-alkyl, c2.6 alkenyl, c2 6 alkynyl, C31. Carbocyclyl, c(tetra)aryl, 3_1〇 heterocyclic, and 3-H) a group, wherein the alkene group, an alkenyl group, a aryl group, a fluorenyl group, a heterocyclic group, an aryl group, and a heteroaryl group are each substituted with 〇, 丄, 2, 3' 4 or 5 Rp groups; Each occurrence is selected from the group consisting of hydrogen, Cl 6 alkyl, Ci 6 all from alkyl, C 2-6, C 2 · 6 alkynyl, C 3 — 1 G carbocyclyl, 3-10 membered heterocyclyl, CVio aryl and 5 a 10-membered heteroaryl group, or two Rn* attached to a nitrogen atom, to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring, wherein the group, alkenyl, alkynyl, carbocyclic ring , a heterocyclic group, an aryl group, and a heteroaryl group are each substituted with 0, 1, 2, 3, 4 or 5 Rp groups; and Rp is respectively a fluorine (-F), bromine (- Br), gas (-C1), and hydrazine (-1), -CN, -N〇2, -N3, -SO2H, -SO3H, -OH, -OCi.6 alkyl, -OI^Cw alkyl) 2, -N(CV6 alkyl) 2, alkyl) 3X, -N^Ck alkyl) 2X, -NH/Cw alkyl) X, -NH3X, -NpCu alkyl XCk alkyl), -NaHKCu alkyl ), -NH(OH), -SH, -SC1-6 炫*, -SS (Ci-6 alkyl), -C(=0) (Ci-6 alkyl), _co2h, -C〇2 ( Ci.6 alkyl), _〇C(=〇) (Ci_6 alkyl), -〇C〇2 (Ci.6 alkyl), 412 201043620 -C(=0)NH2, -CtCONiCK alkyl) -0(:(=0^11((^.6 alkyl), -NHCpOXC^alkyl), -N(c"6 alkyl)CtOXCw alkane 1.) '-NHC02(C,.6^&amp; '-NHC(=0)N(Ci.6^ 1-)2 '-NHCeCONHCCM alkyl), -NHC(=0)NH2, -CeN^CKCu alkyl), -OCpNHXCw alkyl), -OCpNI^ OCw alkyl, alkyl) 2, -C^NP^NHCCk alkyl), -C(=NH)NH2, -OCpNHONCCw alkyl)2, -OC^NI^NHCCk alkyl), -OC(NH)NH2 , -NHC^NP^NCCk alkyl)2, -NHC(=NH)NH2, -NHSOXCk alkyl), -SOzNCCk alkyl)2 -SOsNHCCu alkyl), -S02NH2, -SOsCw alkyl, -SCbOCw alkyl, -OS02CK alkyl, -SOCi.6 alkyl, -SKCw alkyl)3, -OSKCw alkyl)3, -CPSMCCk alkyl) 2, -C(=S)NH(C丨·6 alkyl), -C(=S)NH2, -(:(=0)8((^.6 alkyl), -cpspc^alkyl, - Scpspcw alkyl, -PhOMCw alkyl), -ppoxc^alkyl)2,_0P(=0)(Ci.6 alkyl)2, -OPPOXOC^alkyl)2, Cm alkyl, &lt;^_6 all_ An alkyl group, a c2.6 alkenyl group, a c2.6 alkynyl group, a C3_1G carbocyclic group, a C6_14 aryl group, a 3-14 membered heterocyclic group, a 5-14 membered heteroaryl group; or two fluorene Rp substituents may be bonded Form = 0 or = s; where x_ is the counter ion. 58. The compound of claim 57, wherein Rh is selected from the group consisting of fluorine (-F), bromine (-Br), chlorine (-C1), and iodine (-1), -CN, -N02, _OH, -ORj, -SR1, -N(Rk)2, -N(Rk)3+X., -(:(=0)1^, -(:02Ι^, -C02H ' -0. (=0政, -〇C02Ri, -C(=0)N(Rk)2, -OC(=0)N(Rk)2, -NRkCpO)!^, -NRkC02Ri, 413 201043620 -NRkC(=0)N(Rk)2 '-C(=0)NRkS02Ri ' -NRkS02R' ' -S02N(Rk)2, -S02Ri, Cmo alkyl, C6 aryl and 5-6 membered heteroaryl, each alkyl, aryl, and heteroaryl The base is substituted by Ο, 1, 2, 3 or 4, respectively; and Χ is a counter ion. 59. The compound of claim 58 wherein Rh is selected from 0 or 1 respectively. Rm* replaces -C(=0)Ri, -C02H, -S02Ri, and a 5-membered heteroaryl group. 60. The compound of claim 59, wherein the 5-membered heteroaryl is selected from the group consisting of α, D, thiol, D., sylylene, sigma, sigma, σ Sitting base, different 0 σ sitting base, α plug β sitting base, different ° plug β sitting base, triterpene base, 4 2 α sitting base, 0 plug 2 ° sitting base, and 4 ° sitting base. 61. The compound of claim 57, wherein the phenyl group is a monosubstituted phenyl group of any of the following formulae: 62. The compound of claim 57, wherein the phenyl group is a disubstituted phenyl group of any of the following formulae: 63. A compound as claimed in claim 53 wherein G is -0Re selected 414 201043620 64. A compound according to claim 53 wherein ^ is a heteroaryl group. 65. A compound according to claim 64, wherein R&gt; 6 members are heteroaryl. A compound of the formula 65, wherein Re is pyridine 67. A compound according to claim 66, wherein Re is a monosubstituted pyridine group. 415 201043620 68. A compound of claim 66, wherein Re is 3-pyridyl. 69. A compound according to claim 66, wherein Re is pyridyl of the formula: X is 0, 1, 2, 3 or 4, and each Rh is selected from the group consisting of fluorine (-F), bromine (-Br), chlorine (-C1), and iodine (-1), -CN, -N02, -N3, -S02H, -S03H, -OH, -OR1, -ON(Rk)2, -N(Rk)2, -N(Rk)3+X·, -N(ORj)Rk, -SH, - SR1, -SSRj, -(:(=0)1^, -C02H, -CHO, -0C(=0)Ri, -OCC^Ri, -C(=0)N(Rk)2, -0C( =0) N(Rk)2, -NRkC(=0)Ri, -NRkcC^Ri, -NRkC(=0)N(Rk)2, -C(=NRk)Ri ' -C(=NRk)ORi , -OC(=NRk)Ri, -OC(=NRk)ORi, -C(=NRk)N(Rk)2, -OC(=NRk)N(Rk)2, -NRkC(=NRk)N(Rk) 2. -ChC^NR^C^Ri, -NRkSC^i, -S02N(Rk)2, -SC^Ri, -S02〇Ri, -OSOA, -8(=0)11丨, -08(=0 ) 11丨, -SYR%, -OS^R% ' -C(=S)N(Rk)2, -C(=0)SRi, -C(=S)SRi, -SC(S)SRi,- PpOhR1, -0Ρ(=0)2Ι^, -Ρ(=〇)(Ι^)2, -OP(=〇)(R')2 &gt; -OP(=0)(ORj)2 &gt; -P (=0)2N(Rk)2 &gt; -〇P(=0)2N(Rk)2 ' -P(=0)N(Rk)2, -〇p(=0)N(Rk)2, _NRkP (=〇)(〇Rj)2, -NRkP(=〇)(NRk)2, -P(Rj)2, -P(Rj)3, -〇P(Rj)2, -OP(Rj)3, -B(OR")2, Cl.1 decyl, Ci-i〇* _ alkyl, C2.1G thiol, C2-1() alkynyl, (: 3-14 carbon ring, 3-14 members Heterocyclic group a C6-h square group and a 5-14 membered heteroaryl group, wherein the decyl group, the fluorenyl group, the 416 201043620 alkynyl group, the carbocyclic group, the miscellaneous, the aryl group, and the (iv) group are each 0, 1, 2, and 3, respectively. , 4 or 5 substituents; R1 is selected from Cm in each occurrence. Silk, &amp;, full secret, c2.10 alkenyl, c2., 0 alkynyl, C314 carbocyclyl, 3-14 a heterocyclic group, a C6.14 aryl group and a 5.14 member base, each of which has a stalk, an alkenyl group, an alkynyl group, a cyclyl group, a heterocyclic group, an aryl group, and a heteroaryl group, respectively , 3, 4 or 5 1 ^ group substitution; 0 # in each occurrence is selected from hydrogen, -OH, -OR1, -N (RV -CN, -. (Which ^, _C(=〇)N(Rj)2, _c〇2Ri, _s〇2Ri, -C(=NRj)ORi, _s〇2N(Rj)2, _s〇2Rj, - _S〇2〇Rj , -S0R1, -C(=S)N(Rj)2, -C(=0)SRj, -C(=S)SRj, -P(=〇)2Rl, -P(=0)(Ri)2 , _P(=〇)2N(Rj)2, _P(=0)(NRj)2, Cmo alkyl, alkyl, C2_1G alkenyl, C21G alkynyl, C314 carbocyclyl, 3-14 membered heterocyclic group, a C6_M aryl group and a 5-14 membered heteroaryl group, or two Rj groups attached to a nitrogen atom, are bonded to form a 3 to 14 membered heterocyclic ring group or a 5-14 membered heteroaryl ring, wherein the alkyl group and the alkenyl group are alkyl groups. , alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl are each substituted with hydrazine, b, 2, 3, 4 or 5 Rm groups; Rj is selected from hydrogen, Cm decyl, cardamom, C2-10 alkenyl, c2-10 alkynyl, C3_14 carbocyclyl, 3-14 membered heterocyclyl, CVh aryl and 5-14 membered heteroaryl, or attached to nitrogen The two W groups of the atom are joined to form a 3-14 membered heterocyclic group or a 5-14 membered heteroaryl ring wherein alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl The bases are each substituted with 0, 1, 2, 3, 4 or 5 Rm groups; 417 201043620 Rm Each occurrence is selected from the group consisting of fluorine (-F), bromine (-Br), gas (-C1), and iodine (-1), -CN, -N〇2, -N3, -S〇2H, - S03H, -OH, -OR°, -ON(Rn)2, -N(Rn)2, -N(Rn)3+X·, _N(OR°)Rn, -SH, SR, -SSR. -C(=0)R., -C02H, -C〇2R., -OC(=0)R〇, -〇C02R°, -C(=0)N(Rn)2, -〇C(=0 N(Rn)2, -NRnC(=0)R0, -NRnC02R0, -NRnC(=0)N(Rn)2, -C(=NRn)OR, -〇C(=NRn)R.,_ 〇c(=NRn)OR., -C(=NRn)N(Rn)2, -〇C(=NRn)N(Rn)2, -NRnCbNRn)N(Rn)2, -NRnS02R. , -S02N(Rn)2, -S02R. , -S〇2〇R. , -〇S〇2R. , -S(=0)R. , _Si(R, _〇Si(R〇)3, _c(=s)N(Rn)2, -C(=0)SR, -C(=S)SR, _SC(=S)SR , _p(=〇)2R. -P(=0)(RQ)2, _0Pb0)(I〇2, _〇p(=〇)(〇rQ)2, Cl 6 alkyl, Ci-6 All i alkyl, c2-6 alkenyl, c2-6 alkynyl, (^~carbocyclyl, 3-14 heterocyclyl, C6_14 aryl and 5-14 heteroaryl, wherein alkyl, alkenyl, block, Carbocyclyl, heterocyclyl, aryl, and heteroaryl are each substituted with 0, 1, 2, 3, 4, or 5 RP groups, or two 偕Rm substituents may be joined to form =〇 or = s ; K in each occurrence is selected from Ci6 alkyl, all-toothed: C2.6 alkenyl, c2.6 alkynyl, c3.-cyclo, c(tetra)aryl, (iv) heterocyclic, and 3_1G heteroaryl, in which the silk, the dilute base, the base, the surface, the miscellaneous, the silk, and the base are replaced by 2, 3, 4 or 5 Rp groups; Rn is selected in each occurrence Self-alkane, its rw, 11, alkyl, Ci-6, fully dentate, C2, alkynyl, cyclic, 3, heterocyclic, 418 201043620 C^o aryl and 5-10 members a heteroaryl group, or two bases attached to a nitrogen atom, to form a 3-14 membered heterocyclic group or 5 a 14-membered heteroaryl ring wherein each of a decyl group, an alkenyl group, an alkynyl group, a carbocyclic group, a heterocyclic group, an aryl group, and a heteroaryl group is respectively 0, 1, 2, 3, 4 or 5 Rp Base substitution; and Rp in each occurrence are fluorine (-F), bromine (-Br), gas (_C1), and iodine (-1), -CN, -N〇2, -N3, -S02H, -S03H, -OH, -〇CN6 alkyl, alkyl) 2, -NCCw alkyl) 2, -NiCM alkyl) 3X, -NHfw alkyl) 2X, -NHXC!-6 alkyl)X, -NH3X , ^ (OCm alkyl XCk alkyl), -NCOHXCw alkyl), -NH(OH), -SH, -SC!_6 alkyl, -SS (Ci.6 alkyl), -C (=0) ( Ci.6 alkyl), -CO2H, -CCMCw alkyl), -OCtOXCM alkyl), -OCOXCw alkyl), -C(=0)NH2, -(:(=0^((^.6 alkyl) 2, -OCPCONHCCk alkyl), -NHCpOXCw alkyl), -Νγκ alkyl)CPOXCk alkyl), -NHCOXCk alkyl), -NHCeO)]^:^ alkyl)2, -NHC(=0)NH (C!-6 alkyl), -NHC(=0)NH2, -CbN^CKC^alkyl), -OCpNHXCu alkyl), -OCpNHeCw alkyl, -CPNP^ISKCk alkyl)2, alkyl), -C(=NH)NH2, -OCPNI^ISKCk alkyl)2, alkyl), -OC(NH)NH2, -NHC^NI^Nd6 alkyl)2, -NHC(=NH)NH2, -NHSO ^Ck炫基), -SC^ISKCk), -SC^NP^Cu base, -S02NH2, -SO2CM alkyl, -SOzOCm alkyl, -OSOfw alkyl, -SOCw alkyl, -SiCCu Alkyl)3, -OSKCu alkyl)3, -CpSMCw (base group) 2, alkyl group, -C(=S)NH2, -(:(=0)8((^.6 alkyl), -Cpspcw Alkyl, 419 201043620 -SC^SCw alkyl, evaluation) 2 (Ci 6 alkyl), _p (=〇) (Ci 6 appearance) 2, -OPpOXC^alkyl) 2, _〇p (=〇 (〇Ci 6 alkyl, c "6 alkyl, Cm dentate alkyl, c2.6 alkenyl, c2 6 alkynyl, ^(7) carbocyclyl, Cm4 aryl, 3-14 membered heterocyclyl, 5-14 a heteroaryl group; or two oxime p substituents may be joined to form =〇 or :; wherein X—is a counter ion. 70. The compound of claim 69, wherein Rh is selected from the group consisting of fluorine (-F), desert (-ΒΓ), chlorine (4), and 峨 (1), said, _N〇2, _〇h, -OR1 , -SR1, -N(Rk)2, _N(Rk)3+x·, _c(=〇)Ri, _c〇2Ri, -C02H, -OCPCOR1, _〇c〇Ri c(=〇)N(Rk ) 2 -oc(=o)N(Rk)2, _NRkc(=0)Ri, NRkc02R1 -NRkC(=0)N(Rk)2, _c(=〇)NRks〇2Ri, NRks〇, -S〇 2N(Rk)2, _S〇2Ri, Cmq, and C6 aryl, and 5-6 membered heteroaryl, wherein each of the alkyl, green, and base groups is substituted by (4) G, Bu, 2, 3 or 4, respectively; - for counter ions. 71. The compound of claim 70, wherein Rh# is selected from -C(=〇)Ri, -C〇2H '-S〇2r, and heteroaryl substituted by 0 or 1 ... respectively. . 72. For the application of the compound of the 71st item, the % heteroaryl group is selected from the group consisting of a specific group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, a carbazolyl group, an isodecyl group, a decyl group. a di-salt group such as iso-saltyl, tris-s-yl, etc., a sputum-sitting base, and a four-seat base. 73. If the compound of claim 36 is applied, the base of the towel is the following formula 3 -pyridyl. 420 201043620 74. The compound of claim 66, wherein G is -ORe 421 201043620 422 201043620 75. The compound of claim i, wherein the compound is substantially enantiomerically pure. A pharmaceutical composition comprising a compound according to any one of claims 1 to 2, or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient. 77. A method of treating a condition of a *FAAH vector comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of claims 1%, or a pharmaceutically acceptable form thereof. 78· A treatment for pain conditions, inflammatory conditions, immune conditions, skin conditions, anxiety or anxiety related conditions, (4), sleep conditions, schizophrenia, eating behavior, dyskinesia, learning disability, glaucoma, nerve 423 201043620 Degeneration 'Nerve health or money tubular method, the body is administered a therapeutically effective amount as in the second patent application scope:::: One of the compounds or 7 of them acceptable 75. 9. If the scope of patent application is 7 The method of 8 items ^ pain condition. In order to include the treatment of pain 8 〇 · as in the patent application scope item 79, wherein the pain is widespread pain - central pain, afferent pain, ::: selected from Zhao, acute pain, non-fat Erlang pain, cancer-related pain, trauma, pain, preoperative pain, postoperative pain, pain associated with pre-menopausal dysfunction in medical procedures, and premenstrual syndrome = pain, and slow stress syndrome Phase pain, pain associated with early pain and/or phlegm, joint pain p' * waist recommendation, muscle bone _, headache, muscle pain, lower back pain, neck pain, cancer pain, toothache Two pains, visceral pain, and pain associated with multiple sclerosis _ 81::::: method of the _ item, the nerve must be as in the method of claim 81, wherein the neuropathic line is selected from Peripheral neuropathy, diabetic neuropathy, sitting = neuralgia, non-specific low back pain, multiple sclerosis pain;: syndrome, fibromyalgia, HIV-related neuropathy, neuralgia, post-rash neuralgia, Trigeminal neuralgia, pain caused by physical trauma: Pain of limb leads, because of the pain caused by cancer, chemotherapy hair embroidered 2424201043620 Pain, chemotherapy-induced peripheral neuropathy, pain caused by chemotherapy, pain caused by surgery, pain caused by invasive medical procedures, pain caused by toxins, pain caused by burns, pain caused by infection, pain caused by inflammatory conditions Pain caused by peripheral neurological disorders, pain caused by neuroma, pain caused by nerve compression; pain caused by nerve crushing, nerve extension or incomplete nerve section, pain caused by mono-neuropathy, multiple neuropathy Pain, pain caused by dorsal root ganglion compression, pain caused by spinal cord inflammation, spinal cord insertion, pain caused by tumor or hemisection, pain caused by brain stem, hypothalamic or cerebral cortical tumor, and brain stem, hypothalamus or brain Pain caused by cortical trauma. 83. The method of claim 79, wherein the pain condition is lesion pain. @84. The method of claim 83, wherein the joint lesion pain and rheumatoid arthritis, osteoarthritis, crystalline arthritis, dry-valve, fire, gouty arthritis, reactive arthritis Or the pain associated with Reiter's arthritis. Lang 85. If you apply for the method of section 78, the towel will contain the disease. ', Go team, such as the method of claim 85, the towel of the inflamed rheumatoid arthritis, inflammatory bowel disease, asthma and dryness. 87.^ Please take the method of Section 78, which includes treatment of the treatment. The method includes treatment of the treatment. 88. For example, the method of applying for the scope of patents is considered to be related to the condition. 425. The method of claim 78, wherein the method comprises treating epilepsy. 426 201043620 IV. Designation of representative drawings: (1) The representative representative of the case is: ( ). (none) (2) A brief description of the symbol of the representative figure: 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: 2