Bioactive compounds and methods thereof

Abstract

The present disclosure provides compounds, compositions, methods, uses for the prevention or treatment of various conditions, disorders, or diseases. In some embodiments, the condition, disorder, or disease is cancer.

Description

Technical Field

[0001] Among other things, the present invention provides techniques, such as compounds, compositions, methods, etc., that can be used, for example, to treat various diseases, disorders, or conditions. Background Art

[0002] The compounds are reported to be useful in a variety of applications, including the treatment of various diseases, disorders, or conditions, such as cancer. In some embodiments, ferroptosis dysfunction has been reported in many types of cancer. Summary of the Invention

[0003] Among other things, the present invention provides various compounds comprising an isourea or isothiourea moiety. In some embodiments, the present invention provides compounds comprising -TC(-N=)[-N(-)-], wherein T is O or S. In some embodiments, the isourea moiety has -OC(=NR w1 )N(R w2 )(R w3 ) or a salt thereof, wherein each group is independently as described herein. In some embodiments, the isothiourea moiety has -SC(=NR w1 )N(R w2 )(R w3 ) or a salt thereof, wherein each group is independently as described herein.

[0004] In some embodiments, the present invention provides a method comprising R w A compound wherein R w -TC(=NR w1 )N(R w2 )(R w3 ) or a salt form thereof, wherein:

[0005] T is O or S;

[0006] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable label, wherein:

[0007] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10an aliphatic or heteroaliphatic group in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0008] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0009] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R, or -S(O)OR; and

[0010] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0011] The two R groups optionally and independently form a covalent bond together, or:

[0012] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0013] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0014] In some embodiments, the present invention provides a method comprising: w -R w A compound or a salt form thereof, wherein L w is a covalent bond, or an optionally substituted divalent C 1-6an aliphatic or heteroaliphatic group in which one or more methylene units are optionally and independently substituted with -C(R')-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; and each group is independently as described herein.

[0015] For example, in some embodiments, the present invention provides a compound as shown in Formula A:

[0016]

[0017]

[0018] or a salt thereof, wherein:

[0019] Ring P is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-5 heteroatoms;

[0020] Each Y and Z is independently C or N;

[0021] Each R 7 and R 8 Each independently is R”;

[0022] Each R 2 and R 3 Each independently is R" or

[0023] Ring A is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0024] L A It is L;

[0025] R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ;

[0026] L w is a covalent bond, or an optionally substituted divalent C 1-6aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0027] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0028] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable moiety;

[0029] T is O or S;

[0030] Each R 5 and R 6 each independently represents R" or -C(O)OR";

[0031] Each R 9 and R s each independently is R", halogen, -CN, oxo, -NO2, or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl, and arylsulfonyl;

[0032] Each of p and q is independently 0-10;

[0033] each R″ is independently hydrogen, halogen, -LR′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester, and thioether;

[0034] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0035] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0036] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0037] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0038] The two R groups optionally and independently form a covalent bond together, or:

[0039] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0040] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0041] In some embodiments, the present invention provides a compound represented by formula A':

[0042]

[0043] or a salt thereof, wherein:

[0044] X is -O-, -S-, -C(R 1)=、-N(R 1 )-, or is optionally substituted -CH=, -CH=CH- or -NH-;

[0045] t is 0-9;

[0046] R 1 It is R 9 ; and each other group is independently as described herein.

[0047] In some embodiments, the compound of Formula A is a compound of Formula A'.

[0048] In some embodiments, the present invention provides a compound as shown in Formula AI:

[0049]

[0050] or a salt thereof, wherein each group is independently as described herein. In some embodiments, the compound represented by Formula A is a compound represented by Formula AI. In some embodiments, the compound represented by Formula A' is a compound represented by Formula AI.

[0051] In some embodiments, the present invention provides a compound as shown in Formula A-II:

[0052]

[0053] or a salt thereof, wherein each group is independently as described herein. In some embodiments, the compound shown in Formula A is a compound shown in Formula A-II. In some embodiments, the compound shown in Formula A' is a compound shown in Formula A-II. In some embodiments, the compound shown in Formula AI is a compound shown in Formula A-II.

[0054] In some embodiments, the present invention provides a compound as shown in Formula A-II:

[0055]

[0056] or a salt thereof, wherein each group is independently as described herein. In some embodiments, the compound shown in Formula A is a compound shown in Formula A-III. In some embodiments, the compound shown in Formula A' is a compound shown in Formula A-III. In some embodiments, the compound shown in Formula AI is a compound shown in Formula A-III.

[0057] In some embodiments, the present invention provides a compound as shown in Formula B:

[0058] R b -L b -L R -R 4 ;

[0059] B

[0060] or a salt thereof, wherein:

[0061] L R for L, -C≡C-, optionally substituted -CH=CH-, -C(O)-, -C(S)-, or -C(NR")-;

[0062] L b It is L;

[0063] R b It’s R”;

[0064] Ring L is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0065] R 4 is or contains an isourea or isothiourea moiety, or -L w -R w ;

[0066] L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0067] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0068] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable moiety;

[0069] T is O or S;

[0070] Each R is independently R", halogen, -CN, oxo, -NO2 、or is an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl, and arylsulfonyl;

[0071] q is 0-10;

[0072] each R″ is independently hydrogen, halogen, -LR′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester, and thioether;

[0073] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0074] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0075] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0076] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0077] The two R groups optionally and independently form a covalent bond together, or:

[0078] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0079] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0080] In some embodiments, the present invention provides a compound as shown in Formula BI:

[0081]

[0082] or a salt thereof, wherein:

[0083] Each R 4 , L b and R b each as defined above and described herein; and

[0084] Each R s1 、R s2 and R s3 Each is independently R", halogen, -CN, oxo, -NO2 or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl; and R' is as described above.

[0085] In some embodiments, L b is -Cy- as described herein. In some embodiments, L b is an optionally substituted phenyl ring. b is an optionally substituted 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. b is an optionally substituted bicyclic 9-10 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0086] In some embodiments, the present invention provides a compound as shown in formula B-1a, B-1b, B-1c or B-1d:

[0087]

[0088] or a salt thereof, wherein:

[0089] Each R s1 、R s2 、R s3 、R 4 and R b Each as described above.

[0090] In some embodiments, the present invention provides a compound as shown in formula B-2a, B-2b, B-2c, B-2d or B-2e:

[0091]

[0092] or a salt thereof, wherein:

[0093] Each R s1 、R 4 , L b and R b Each as described above.

[0094] In some embodiments, the present invention provides a compound as shown in formula B-3a, B-3b, B-3c or B-3d:

[0095]

[0096] or a salt thereof, wherein:

[0097] Each R s1 、R 4 and R b Each as described above.

[0098] In some embodiments, the present invention provides a compound as shown in formula B-4a, B-4b, B-4c or B-4d:

[0099]

[0100] or a salt thereof, wherein:

[0101] Each R s1 、R 4 and R b Each as described above.

[0102] In some embodiments, the present invention provides a compound as shown in formula B-5a, B-5b, B-5c or B-5d:

[0103]

[0104]

[0105] or a salt thereof, wherein:

[0106] Each Rs1 、R 4 and R b Each as described above.

[0107] In some embodiments, the present invention provides a compound as shown in formula B-6a, B-6b, B-6c or B-6d:

[0108]

[0109] or a salt thereof, wherein:

[0110] Each R s1 、R 4 and R b Each as described above.

[0111] In some embodiments, the present invention provides a compound as shown in formula B-7a, B-7b, B-7c or B-7d:

[0112]

[0113] or a salt thereof, wherein:

[0114] Each R s1 、R 4 and R b Each as described above.

[0115] In some embodiments, the present invention provides a compound as shown in Formula C:

[0116]

[0117] or a salt thereof, wherein:

[0118] R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ;

[0119] L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0120] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0121] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable moiety;

[0122] T is O or S;

[0123] Each R 10 , R 11 , R 12 , R 13 , and R 14 Each independently is R”;

[0124] each R″ is independently hydrogen, halogen, -LR′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH;

[0125] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0126] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0127] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0128] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0129] The two R groups optionally and independently form a covalent bond together, or:

[0130] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0131] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0132] In some embodiments, the present invention provides a compound as shown in Formula D:

[0133]

[0134] or a salt thereof, wherein:

[0135] Each R 15 , and R 16 Each independently is -L-R';

[0136] R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ;

[0137] L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0138] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0139] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable moiety;

[0140] T is O or S;

[0141] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0142] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0143] -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0144] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0145] The two R groups optionally and independently form a covalent bond together, or:

[0146] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0147] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0148] In some embodiments, the present invention provides a compound as shown in Formula E:

[0149]

[0150] or a salt thereof, wherein:

[0151] R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ;

[0152] L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0153] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0154] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable moiety;

[0155] T is O or S;

[0156] Each R 17 , and R 18 Each is independently an optionally substituted 5-20 membered aryl monocyclic, bicyclic or polycyclic ring having 0-5 heteroatoms;

[0157] Ring C is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-6 heteroatoms;

[0158] L is independently a covalent bond, or an optionally substituted divalent C 1-10aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0159] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0160] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0161] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0162] The two R groups optionally and independently form a covalent bond together, or:

[0163] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0164] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0165] In some embodiments, the present invention provides a compound as shown in Formula F:

[0166]

[0167] or a salt thereof, wherein:

[0168] R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ;

[0169] L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0170] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0171] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable moiety;

[0172] T is O or S;

[0173] Each R s6 , R s7 Each independently is R s ;

[0174] Each R s Each is independently R", halogen, -CN, oxo, -NO 2、 or is an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl, and arylsulfonyl;

[0175] each R″ is independently hydrogen, halogen, -LR′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester, and thioether;

[0176] Each of q, x and y is independently 0-4;

[0177] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0178] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0179] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0180] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0181] The two R groups optionally and independently form a covalent bond together, or:

[0182] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0183] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0184] In some embodiments, the present invention provides a compound as shown in Formula G:

[0185]

[0186] or a salt thereof, wherein:

[0187] Ring B is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0188] R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ;

[0189] L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0190] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0191] Each R w1 、R w2 and R w3 Each is independently -L-R' or a detectable moiety;

[0192] T is O or S;

[0193] R 8a R m or

[0194] L A It is L;

[0195] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0196] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0197] Ring A is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0198] Each R m Independently R s ;

[0199] Each R s R is independently R", halogen, -CN, oxo, -NO2 or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl;

[0200] each R″ is independently hydrogen, halogen, -LR′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester, and thioether;

[0201] q is independently 0-10;

[0202] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0203] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0204] The two R groups optionally and independently form a covalent bond together, or:

[0205] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0206] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0207] In some embodiments, the present invention provides a compound as shown in Formula H:

[0208]

[0209] or a salt thereof, wherein:

[0210] R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ;

[0211] L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0212] R w -TC(=NR w1 )N(R w2 )(R w3 );

[0213] Each R w1 、R w2 and Rw3 Each is independently -L-R' or a detectable moiety;

[0214] T is O or S;

[0215] R 5 are independently R" or -C(O)OR";

[0216] R 2 independently R" or

[0217] L A It is L;

[0218] Ring A is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0219] Each R 9 and R s R is independently R", halogen, -CN, oxo, -NO2 or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl;

[0220] Each p and q is independently 0-10;

[0221] each R″ is independently hydrogen, halogen, -LR′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester, and thioether;

[0222] each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR;

[0223] Each L is independently a covalent bond, or an optionally substituted divalent C 1-10aliphatic or heteroaliphatic, in which one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-;

[0224] Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms;

[0225] Each R is independently -H, or an optionally substituted 1-20 Fatty acid, C 1-20 Heteroaliphatic groups having 1-10 heteroatoms, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or

[0226] The two R groups optionally and independently form a covalent bond together, or:

[0227] Two or more R groups on the same atom optionally and independently form together with that atom an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to that atom; or

[0228] Two or more R groups on two or more atoms are optionally and independently taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms.

[0229] In some embodiments, the compound provided has biological activity and can be used for one or more characteristics and / or activity of various biological agents (such as polypeptides). In some embodiments, the compound provided is an inhibitor. In some embodiments, the compound provided is a covalent inhibitor. In some embodiments, after the compound comprising such a part contacts with a reagent comprising a nucleophile (such as -SH, -SeH, etc.), urea or isothiourea moiety is released. In some embodiments, the technology provided (such as compound, composition, method, etc.) selectively reacts with some nucleophile moieties, rather than with other moieties. In some embodiments, the technology provided selectively reacts with -SeH nucleophiles, rather than -SH nucleophiles. In some embodiments, the technology provided selectively reacts with selenocysteine ​​residues, rather than with cysteine ​​residues. In some embodiments, the selectivity is about or at least about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 1000-fold under comparable conditions.

[0230] In some embodiments, the present disclosure provides techniques for introducing moieties into the system. In some embodiments, the provided techniques include generating urea from an isourea moiety, or generating thiourea from an isothiourea moiety. In some embodiments, the compound has [LOAD]-R 4 or a salt thereof, wherein [LOAD] is or comprises one or more small molecules, nucleic acids, polypeptides, lipids, and / or carbohydrate moieties. In some embodiments, [LOAD] is linked to a nucleophilic moiety, such as -Se- or -S-. In some embodiments, [LOAD] is linked to a selenocysteine ​​residue via -Se-. In some embodiments, [LOAD] is linked to a cysteine ​​residue via -S-.

[0231] The provided technology can be used in a variety of applications. For example, in some embodiments, the provided technology can be used to modulate the properties and activity of polypeptides. In some embodiments, the present disclosure provides technology for modulating polypeptide properties. In some embodiments, the present disclosure provides technology for modulating polypeptide properties in a system, including administering or delivering a provided compound or composition to the system. In some embodiments, the present disclosure provides technology for inhibiting polypeptide properties. In some embodiments, the polypeptide comprises a nucleophilic moiety, such as -SeH, -SH, etc. In some embodiments, the polypeptide comprises a selenocysteine ​​residue. In some embodiments, the polypeptide comprises a cysteine ​​residue. In some embodiments, upon contact with the provided compound, the selenocysteine ​​residue is covalently modified. In some embodiments, upon contact with the provided compound, the cysteine ​​residue is covalently modified. In some embodiments, upon contact with the provided compound, the selenocysteine ​​residue is covalently modified to a higher level than cysteine ​​residues in the same polypeptide. In some embodiments, the polypeptide comprises a signature sequence element of GPX4. In some embodiments, the signature sequence element comprises an amino acid residue comprising -SeH. In some embodiments, the signature sequence element comprises selenocysteine. In some embodiments, the signature sequence element comprises an amino acid residue comprising -SH. In some embodiments, the signature sequence element comprises cysteine. In some embodiments, the polypeptide is GPX4. In some embodiments, the system is an in vivo system. In some embodiments, the system is an in vitro system. In some embodiments, the system is a cell or comprises a cell. In some embodiments, the system is a tissue or comprises a tissue. In some embodiments, the system is an organ or comprises an organ. In some embodiments, the system is a subject. In some embodiments, the system is an animal. In some embodiments, the system is a human. In some embodiments, the activity is modulated. In some embodiments, the activity is inhibited.

[0232] In some embodiments, provided technologies can inhibit cell proliferation. In some embodiments, provided technologies provide higher levels of ferroptosis compared to the absence of the technology or a reference technology. In some embodiments, provided technologies can induce or increase ferroptosis.

[0233] In some embodiments, provided compounds are useful for preventing or treating various conditions, disorders, or diseases. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders, or diseases comprising administering or delivering an effective amount of provided compounds or compositions to a subject susceptible to or suffering from the conditions, disorders, or diseases. In some embodiments, the conditions, disorders, or diseases are proliferative conditions, disorders, or diseases. In some embodiments, the conditions, disorders, or diseases are cancer. In some embodiments, the conditions, disorders, or diseases are associated with GPX4. In some embodiments, the subject benefits from an increase in ferroptosis levels.

[0234] In some embodiments, the present disclosure provides pharmaceutical compositions that contain or deliver provided compounds and a pharmaceutically acceptable carrier.

[0235] Those skilled in the art who read this disclosure will appreciate that the isourea and / or isothiourea moieties described herein can be used for a variety of purposes. For example, they can be used to replace leaving groups (e.g., halogens) in various pharmaceutical agents for many applications, including replacing leaving groups in various biologically active compounds. In some embodiments, the electrophilic portion (e.g., -C(O)-CH2-R) comprising the isourea and / or isothiourea moiety can be used to replace leaving groups (e.g., halogens) in various pharmaceutical agents. w , wherein -CH2- is optionally substituted) can be used to replace electrophilic groups (e.g., -C(O)-CH=CH2, -C(O)-C≡CH, etc.) in various pharmaceutical agents for many applications, including replacing such groups in various biologically active compounds.

[0236] In some embodiments, the present disclosure provides techniques for making various compounds.In some embodiments, the present disclosure provides methods comprising reacting a first compound comprising an -OH group, or a salt thereof, with a second compound comprising -CN to form an isourea moiety.

[0237] In some embodiments, the present disclosure provides methods comprising reacting a first compound comprising an -OH group, or a salt thereof, with a second compound comprising -N=C=N- to form an isourea moiety.

[0238] In some embodiments, the disclosure provides techniques for evaluating or characterizing various compounds and compositions. According to the disclosure, many techniques can be utilized, such as cells, animal models, clinical trials, etc. Certain useful techniques are described in the Examples. In some embodiments, mass spectrometry can be used to assess the modification of amino acid residues, such as selenocysteine ​​and / or cysteine ​​amino acid residues.

[0239] It will be appreciated by those skilled in the art that the compounds of the present disclosure may be provided in a variety of forms, such as salts, esters, solvates, prodrugs, and the like. In some embodiments, the compounds provided are in salt form. In some embodiments, the compounds provided are in pharmaceutically acceptable salt form. In some embodiments, the compounds provided are in solvate form. In some embodiments, the compounds provided are prodrugs. In some embodiments, the compounds provided are esters. In some embodiments, the compounds provided are provided in the form of a single stereoisomer. In some embodiments, the compounds provided are provided in the form of a mixture or two or more stereoisomers. DETAILED DESCRIPTION

[0240] The technology of the present disclosure may be understood more readily by reference to the following detailed description of certain embodiments.

[0241] definition

[0242] As used herein, the following definitions shall apply unless otherwise indicated. For ease of description, chemical elements are identified according to the Periodic Table of the Elements (CAS version), Handbook of Chemistry and Physics, 75th edition. In addition, the general principles of organic chemistry are described in "Organic Chemistry" (Thomas Sorrell, University Science Books, Sausalito: 1999) and "March's Advanced Organic Chemistry" (5th edition, eds. Smith, MB and March, J., John Wiley & Sons, New York: 2001).

[0243] As used in this disclosure, unless the context clearly dictates otherwise, (i) the terms "a" or "an" are understood to mean "at least one"; (ii) the term "or" is understood to mean "and / or"; (iii) the terms "include," "comprise," "includes" (whether or not used with "not limited to") and "includes" (whether or not used with "not limited to") are understood to cover the itemized components or steps, whether presented alone or with one or more additional components or steps; (iv) the term "another" is understood to mean at least one additional / second one or more; (v) the terms "about" and "approximately" are understood to allow for standard variations understood by one of ordinary skill in the art; and (vi) where ranges are provided, the endpoints are included. Unless the context clearly dictates otherwise, isomers of the compound are included. As known to those skilled in the art, the compound can be provided, administered or delivered in a variety of forms, such as salts (e.g., pharmaceutically acceptable salts), solvates, hydrates, esters, prodrugs, tautomers, etc.

[0244] Aliphatic group: As used herein, "aliphatic group" refers to a straight (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more unsaturated units (non-aromatic groups), or a substituted or unsubstituted monocyclic, bicyclic, or polycyclic hydrocarbon ring that is fully saturated or contains one or more unsaturated units (non-aromatic groups), or combinations thereof. In some embodiments, the aliphatic group comprises an aliphatic group of 1-50 carbon atoms. In some embodiments, the aliphatic group comprises an aliphatic group of 1-20 carbon atoms. In other embodiments, the aliphatic group comprises an aliphatic group of 1-10 carbon atoms. In other embodiments, the aliphatic group comprises an aliphatic group of 1-9 carbon atoms. In other embodiments, the aliphatic group comprises an aliphatic group of 1-8 carbon atoms. In other embodiments, the aliphatic group comprises an aliphatic group of 1-7 carbon atoms. In other embodiments, the aliphatic group comprises an aliphatic group of 1-6 carbon atoms. In still other embodiments, the aliphatic group comprises an aliphatic group of 1-5 carbon atoms, and in yet other embodiments, the aliphatic group comprises an aliphatic group of 1, 2, 3, or 4 carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups, and mixtures thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0245] Alkenyl: As used herein, the term "alkenyl" refers to an aliphatic group, as defined herein, having one or more double bonds.

[0246] Alkyl: The term "alkyl" as used herein has the common meaning in the art and may include saturated aliphatic groups, including straight chain alkyl, branched chain alkyl, cycloalkyl (cycloalkane) groups, alkyl substituted cycloalkyl and cycloalkyl substituted alkyl. In some embodiments, the alkyl group has 1-100 carbon atoms. In certain embodiments, the main chain of a straight chain or branched chain alkyl group has about 1-20 carbon atoms (e.g., a straight chain is C1-C 20 , the branch chain is C2-C 20 ), or about 1-10. In some embodiments, a cycloalkyl group has about 3-10 carbon atoms in its ring structure, wherein such ring is monocyclic, bicyclic, or polycyclic, or has about 5, 6, or 7 carbons in the ring structure. In some embodiments, an alkyl group can be a lower alkyl group, wherein the lower alkyl group contains 1-4 carbon atoms (e.g., a straight chain lower alkyl group is C1-C4).

[0247] Alkynyl: As used herein, the term "alkynyl" refers to an aliphatic group, as defined herein, having one or more triple bonds.

[0248] Animal: As used herein, the term "animal" refers to any member of the kingdom Animalia. In some embodiments, "animal" refers to a human being at any stage of development. In some embodiments, "animal" refers to a non-human animal at any stage of development. In certain embodiments, the non-human animal is a mammal (e.g., a rodent, mouse, rat, rabbit, monkey, dog, cat, sheep, cow, primate, and / or pig). In some embodiments, animals include, but are not limited to, mammals, birds, reptiles, amphibians, fish, and / or worms. In some embodiments, the animal can be a transgenic animal, a genetically engineered animal, and / or a cloned animal.

[0249] Aryl: As used herein, the term "aryl," used alone or as part of a larger moiety, such as "aralkyl," "aralkyloxy," or "aryloxyalkyl," refers to a monocyclic, bicyclic, or polycyclic ring system having a total of five to thirty ring members, wherein at least one ring in the system is aromatic. In some embodiments, an aryl group is a monocyclic, bicyclic, or polycyclic ring system having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic, and wherein each ring in the system comprises three to seven ring members. In some embodiments, each monocyclic ring member is aromatic. In some embodiments, an aryl group is a biaryl group. The term "aryl" can be used interchangeably with the term "aromatic ring." In certain embodiments of the present disclosure, "aryl" refers to an aromatic ring system, including but not limited to phenyl, biphenyl, naphthyl, binaphthyl, anthracenyl, and the like, which may bear one or more substituents. The term "aryl," as used herein, also includes within its scope groups in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl.

[0250] Characteristic portion: As used herein, the term "characteristic portion" refers in the broadest sense to a portion of a substance whose presence (or absence) is associated with the presence (or absence) of a particular characteristic, property, or activity of the substance. In some embodiments, a characteristic portion of a substance is a portion that is present in the substance and related substances that have the particular characteristic, property, or activity, but is not present in related substances that do not have the particular characteristic, property, or activity. In certain embodiments, a characteristic portion shares at least one functional characteristic with the intact substance. For example, in some embodiments, a "characteristic portion" of a protein or polypeptide is a portion comprising a continuous stretch or set of amino acids, in some embodiments, a set of continuous stretches of amino acids, which together constitute the characteristic of the protein or polypeptide. In some embodiments, each such continuous stretch typically comprises at least 2, 5, 10, 15, 20, 50, or more amino acids. In general, a characteristic portion of a substance (e.g., a protein, antibody, etc.) is a portion that, in addition to the sequence and / or structural identity described above, shares at least one functional characteristic with the relevant intact substance. In some embodiments, a characteristic portion may be biologically active.

[0251] Characteristic sequence element: As used herein, the phrase "characteristic sequence element" refers to a sequence element found in a polymer (e.g., in a polypeptide or nucleic acid) that represents a characteristic portion of the polymer. In some embodiments, the presence of a characteristic sequence element is associated with the presence or level of a specific activity or characteristic of a polymer. In some embodiments, the presence (or absence) of a characteristic sequence element defines a specific polymer as a member (or not a member) of a specific family or group of such polymers. A characteristic sequence element typically comprises at least two monomers (e.g., amino acids or nucleotides). In some embodiments, a characteristic sequence element comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 or more monomers (e.g., continuously connected monomers). In some embodiments, a characteristic sequence element comprises at least a first and a second segment of continuous monomers, which are separated by one or more spacers, the length of which may or may not vary between polymers sharing the sequence element.

[0252] Comparability: The term "comparable" is used herein to describe two (or more) sets of conditions or circumstances that are sufficiently similar to each other to allow comparison of the results obtained or phenomena observed. In some embodiments, comparable sets of conditions or circumstances are characterized by a plurality of substantially identical features and one or a small number of differing features. One of ordinary skill in the art will understand that sets of conditions are comparable to each other when they are characterized by a sufficient number and type of substantially identical features such that it is reasonable to conclude that differences in the results obtained or phenomena observed under the different conditions or circumstances are caused by or indicate variations in those differing features.

[0253] Alicyclic: The terms "alicyclic," "carbocycle," "carbocyclyl," "carbocyclic radical," and "carbocyclic ring" are used interchangeably as used herein to refer to a saturated or partially unsaturated, but non-aromatic, alicyclic monocyclic, bicyclic, or polycyclic ring system as described herein, having from 3 to 30 ring members, unless otherwise indicated. Alicyclic groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, norbornyl, adamantyl, and cyclooctadienyl. In some embodiments, the alicyclic group has 3-6 carbon atoms. In some embodiments, the alicyclic group is a saturated cycloalkyl group. The term "alicyclic group" may also include an alicyclic ring fused to one or more aromatic or non-aromatic rings, such as decahydronaphthyl or tetrahydronaphthyl. In some embodiments, the alicyclic group is bicyclic. In some embodiments, the alicyclic group is tricyclic. In some embodiments, the alicyclic group is polycyclic. In some embodiments, "alicyclic" refers to a C3-C6 monocyclic hydrocarbon or C8-C6 monocyclic hydrocarbon that is fully saturated or contains one or more unsaturated units but is not aromatic and has a single point of attachment to the rest of the molecule. 10 Bicyclic or polycyclic hydrocarbons, either fully saturated or containing one or more unsaturated units but not aromatic, having a single point of attachment to the rest of the molecule 16 Polycyclic hydrocarbons.

[0254] Heteroaliphatic: The term "heteroaliphatic" as used herein has the ordinary meaning in the art and refers to a fatty group as described herein in which one or more carbon atoms are independently substituted with one or more heteroatoms (e.g., oxygen, nitrogen, sulfur, silicon, phosphorus, etc.). In some embodiments, one or more units selected from C, CH, CH2, and CH3 are independently substituted with one or more heteroatoms (including oxidized and / or substituted forms thereof). In some embodiments, the heteroaliphatic group is a heteroalkyl group. In some embodiments, the heteroaliphatic group is a heteroalkenyl group.

[0255] Heteroalkyl: The term "heteroalkyl" as used herein has the ordinary meaning in the art and refers to an alkyl group as described herein, wherein one or more carbon atoms are independently substituted with one or more heteroatoms (e.g., oxygen, nitrogen, sulfur, silicon, phosphorus, etc.). Examples of heteroalkyl groups include, but are not limited to, alkoxy, polyethylene glycol, alkyl-substituted amino, tetrahydrofuranyl, piperidinyl, morpholinyl, and the like.

[0256] Heteroaryl: As used herein, the terms "heteroaryl" and "heteroar" used alone or as part of a larger moiety, such as "heteroaralkyl" or "heteroaralkoxy," refer to a monocyclic, bicyclic, or polycyclic ring system having a total of five to thirty ring members, wherein at least one ring in the system is aromatic and at least one aromatic ring atom is a heteroatom. In some embodiments, a heteroaryl group is a group having 5 to 10 ring atoms (i.e., monocyclic, bicyclic, or polycyclic), and in some embodiments, 5, 6, 9, or 10 ring atoms. In some embodiments, each monocyclic ring member is an aromatic ring. In some embodiments, a heteroaryl group has 6, 10, or 14 pi electrons shared in a cyclic array; and has from one to five heteroatoms in addition to carbon atoms. Heteroaryl includes but is not limited to thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl and pteridinyl. In some embodiments, heteroaryl is a heterobiaryl, such as bipyridyl and the like. The terms "heteroaryl" and "heteroaromatic" as used herein also include groups in which a heteroaromatic ring is fused to one or more aryl, alicyclic or heterocyclic groups, wherein the radical or point of attachment is located on the heteroaromatic ring. Non-limiting examples include indolyl, isoindolyl, benzothiophenyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzothiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolyl, tetrahydroisoquinolyl and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. Heteroaryl can be monocyclic, bicyclic or polycyclic. The term "heteroaryl" can be used interchangeably with the term "heteroaromatic ring", "heteroaryl group" or "aromatic heterocycle", any of which includes rings that can be optionally substituted. The term "heteroarylalkyl" refers to an alkyl group substituted with a heteroaryl group, wherein the alkyl and heteroaryl moieties are independent and optionally substituted.

[0257] Heteroatom: As used herein, the term "heteroatom" refers to an atom other than carbon or hydrogen. In some embodiments, the heteroatom is boron, oxygen, sulfur, nitrogen, phosphorus, or silicon (including oxidized forms of nitrogen, sulfur, phosphorus, or silicon; charged forms of nitrogen (e.g., quaternized forms, forms in imine groups, etc.), phosphorus, sulfur, oxygen; etc.). In some embodiments, the heteroatom is silicon, phosphorus, oxygen, sulfur, or nitrogen. In some embodiments, the heteroatom is silicon, oxygen, sulfur, or nitrogen. In some embodiments, the heteroatom is oxygen, sulfur, or nitrogen.

[0258] Heterocyclyl: As used herein, the terms "heterocyclyl," "heterocyclic," "heterocyclic radical," and "heterocycle" are used interchangeably to refer to a monocyclic, bicyclic, or polycyclic moiety (e.g., 3-30 members) that is saturated or partially unsaturated and has one or more heteroatom ring atoms. In some embodiments, a heterocyclyl is a stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic moiety that is saturated or partially unsaturated and has one or more (preferably one to four) heteroatoms in addition to carbon atoms, as defined above. The term "nitrogen" when used to refer to a ring atom of a heterocycle includes substituted nitrogen. For example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur, and nitrogen, the nitrogen may be N (e.g., 3,4-dihydro-2H-heterocyclyl may be pyrrolyl), NH (e.g., pyrrolidinyl), or + NR (such as N-substituted pyrrolidinyl). Heterocycle can be connected to any heteroatom or carbon atom on its side group, thereby producing a stable structure, and any ring atom can be optionally substituted. The example of this saturated or partially unsaturated heterocyclic radical includes but is not limited to tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, oxazolidinyl, piperazinyl, dioxane, dioxolane, diazepine, oxazepine, thiazepine, morpholinyl and quinuclidine. The terms "heterocyclic radical", "heterocyclic", "heterocycle", "heterocyclic group", "heterocyclic moiety" and "heterocyclic radical" are used interchangeably here, and also include groups in which heterocycle is fused to one or more aryl, heteroaryl or alicyclic groups, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl or tetrahydroquinolyl. Heterocyclic radical can be monocyclic, bicyclic or polycyclic. The term "heterocyclylalkyl" refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions are independently and optionally substituted.

[0259] Optionally substituted: As described herein, the compounds of the present disclosure may contain moieties that are optionally substituted and / or substituted. In general, the term "substituted", whether or not beginning with the term "optional", means that one or more hydrogens of the designated moiety are replaced by a suitable substituent. Unless otherwise stated, an "optionally substituted" group may have a suitable substituent at each substitutable position of the group, and when multiple positions in any given structure can be substituted by multiple substituents selected from a specified group, the substituents may be the same or different at each position. In some embodiments, the group that is optionally substituted is unsubstituted. The combination of substituents contemplated by the present disclosure is preferably a combination that results in the formation of stable or chemically feasible compounds. The term "stable" as used herein refers to a compound that does not undergo substantial change when subjected to conditions that allow its production, detection, and in certain embodiments, its recovery, purification, and use for one or more purposes disclosed herein. Certain substituents are described below.

[0260] Suitable monovalent substituents on a substitutable atom (e.g., a suitable carbon atom) are independently halogen; -(CH2) 0– 4R o ; –(CH2) 0–4 OR o ;-O(CH2) 0-4 R o , –O–(CH2) 0–4 C(O)OR o ; –(CH2) 0–4 CH(OR o )2;–(CH2) 0–4 Ph, can be R o Substitution; -(CH2) 0–4 O(CH2) 0–1 Ph, can be R o Substitution; –CH=CHPh, can be replaced by R o Substitution; –(CH2) 0–4 O(CH2) 0–1 -pyridyl, which can be R o Substitution; –NO2; –CN; –N3; -(CH2) 0–4 N(R o )2;–(CH2) 0–4 N(R o )C(O)R o ;–N(R o )C(S)R o ; -(CH2) 0–4 N(R o )C(O)NR o 2;-N(R o )C(S)NR o 2;–(CH2) 0–4 N(R o )C(O)OR o ;–N(R o )N(R o )C(O)R;-N(R o )N(R o )C(O)NR o 2;-N(R o )N(R o )C(O)OR o ; –(CH2) 0–4 C(O)R o ;–C(S)R o ; –(CH2) 0–4 C(O)OR o ; -(CH2) 0–4 C(O)SR o ；(CH2)0–4C(O)OSiR o 3;–(CH2) 0–4 OC(-O ) R o ;–OC(O)(CH2) 0–4 SR o ,-SC(S)SR o ;-(CH2) 0–4 SC(O)R o ;–(CH2) 0–4 C(O)NR o 2;–C(S)NR o 2;–C(S)SR o ;-(CH2) 0–4 OC(O)NR o 2;-C(O)N(OR o )R o ;–C(O)C(O)R o ;–C(O)CH2C(O)R o ;-C(NOR o )R o ;-(CH2) 0–4 SSR o ;–(CH2) 0–4 S(O)2R o ;–(CH2) 0–4 S(O)2OR o ;–(CH2) 0–4 OS(O)2R o ;-S(O)2NR o 2;-(CH2) 0–4 S(O)R o ;–N(R o )S(O)2NR o 2;–N(R o )S(O)2R o ;–N(OR o )R o ;-C(NH)NR o 2;–Si(R o )3;–OSi(R o )3;-B(R o )2;-OB(R o )2;-OB(OR o ) 2； -P(R o )2;-P(OR o )2;-P(R o )(OR o );-OP(R o)2;-OP(OR o )2;-OP(R o )(OR o );-P(O)(R o )2;-P(O)(OR o )2;-OP(O)(R o )2;-OP(O)(OR o )2;-OP(O)(OR o )(SR o );-SP(O)(R o )2;-SP(O)(OR o )2;-N(R o )P(O)(R o )2;-N(R o )P(O)(OR o )2;-P(R o )2[B(R o )3];-P(OR o )2[B(R o )3];-OP(R o )2[B(R o )3];-OP(OR o )2[B(R o )3];–(C 1-4 linear or branched alkylene)O–N(R o )2; or –(C 1-4 linear or branched alkylene) C(O)O–N(R o )2, where each R o Substituted as defined herein, and independently hydrogen, C1-20 aliphatic, C1-20 having 1-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon and phosphorus 1-20 Heteroaliphatic group, -CH 2- (C 6-14 aryl), –O(CH2) 0-1 (C 6-14 aryl), -CH2-(5-14 membered heteroaromatic ring), a 5-20 membered monocyclic, bicyclic or polycyclic saturated, partially unsaturated or aromatic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon and phosphorus, or, notwithstanding the above definitions, two independent occurrences of R o Together with its central atom, it forms a 5-20 membered monocyclic, bicyclic or polycyclic, saturated, partially unsaturated or aromatic ring, having 0-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon and phosphorus, which may be substituted according to the following definition.

[0261] R o (or two independent R ·Suitable monovalent substituents for the ring formed together with its middle atom are independently halogen, -(CH2) 0–2 R · 、–(halogenated R · ),–(CH2) 0–2 OH, –(CH2) 0–2 OR · 、–(CH2) 0–2 CH(OR · )2;-O(halogen R · ), –CN, –N3, –(CH2) 0–2 C(O)R · 、–(CH2) 0–2 C(O)OH, –(CH2) 0–2 C(O)OR · 、–(CH2) 0–2 SR · 、–(CH2) 0– 2SH, –(CH2) 0–2 NH2, –(CH2) 0–2 NHR · 、–(CH2) 0–2 NR · 2. –NO2, –SiR · 3. -OSiR · 3. -C(O)SR · 、–(C 1–4 linear or branched alkylene)C(O)OR · or –SSR · Each R · unsubstituted or preceded by "halogen" only by one or more halogens, and independently selected from C 1–4 Aliphatic groups, –CH2Ph, –O(CH2) 0–1 Ph and a 5-6 membered saturated, partially unsaturated or aromatic ring wherein 0-4 heteroatoms are independently selected from nitrogen, oxygen and sulfur. Suitable divalent substituents on a saturated carbon atom of R include =0 and =S.

[0262] Suitable divalent substituents (eg, on suitable carbon atoms) are independently the following: =O, =S, =NNR * 2. =NNHC(O)R * 、=NNHC(O)OR * 、=NNHS(O)2R * 、=NR * 、=NOR * 、–O(C(R * 2)) 2–3 O–or–S(C(R * 2))2–3 S–, where each R * independently selected from hydrogen, C 1–6 Aliphatic and unsubstituted 5-6 membered saturated, partially unsaturated or aromatic rings, wherein the heteroatoms are independently selected from 0-4 of nitrogen, oxygen and sulfur. Suitable divalent substituents attached to the ortho-substitutable carbon of the "optionally substituted" group include: -O(CR * 2) 2–3 O–, where each R * independently selected from hydrogen, C 1–6 Aliphatic and unsubstituted 5-6 membered saturated, partially unsaturated and aromatic rings, wherein the aromatic ring has 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0263] R * Suitable substituents on the aliphatic group are independently halogen, -R · 、-(halogenated R · ),–OH,–OR · 、–O(halogenated R · ), –CN, –C(O)OH, –C(O)OR · , –NH2, –NHR · ,–NR · 2 or –NO2, where each R · are unsubstituted or, when preceded by "halo", substituted only by one or more halogens, and are independently C 1-4 Aliphatic groups, –CH2Ph, –O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0264] In some embodiments, suitable substituents on the substitutable nitrogen are independently or Each of these is independently hydrogen, C 1-6 aliphatic, unsubstituted -OPh, or an unsubstituted 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or, notwithstanding the above definition, two independent occurrences of Together with the atoms between them, they form an unsubstituted 3-12 membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0265] Suitable substituents on the aliphatic group are independently halogen, -R· 、-(halogenated R · ),–OH,–OR · 、–O(halogenated R · ), –CN, –C(O)OH, –C(O)OR · , –NH2, –NHR · ,–NR · 2 or –NO2, where each R · are unsubstituted or, when preceded by "halo", substituted only by one or more halogens, and are independently C 1-4 Aliphatic groups, –CH2Ph, –O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0266] Partially unsaturated: As used herein, the term "partially unsaturated" refers to a ring moiety containing at least one double or triple bond. The term "partially unsaturated" is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties as defined herein.

[0267] Pharmaceutical composition: As used herein, the term "pharmaceutical composition" refers to an active agent formulated together with one or more pharmaceutically acceptable carriers. In some embodiments, the active agent is present in a unit dosage suitable for administration in a therapeutic regimen that, when administered to a relevant population, shows a statistically significant probability of achieving a predetermined therapeutic effect. In some embodiments, the pharmaceutical compositions can be specifically formulated for administration in solid or liquid form, including pharmaceutical compositions suitable for oral administration, e.g., douches (aqueous or non-aqueous solutions or suspensions), tablets, e.g., tablets for buccal, sublingual, and systemic absorption, boluses, powders, granules, pastes for application to the tongue; parenteral administration, e.g., by subcutaneous, intramuscular, intravenous, or epidural injection, e.g., sterile solutions or suspensions, or sustained-release formulations; topical application, e.g., as a cream, ointment, or controlled-release patch or spray to the skin, lungs, or oral cavity; intravaginal or rectal administration, e.g., as a vaginal suppository, cream, or foam; sublingual administration; ophthalmic administration; transdermal administration; or nasal administration, pulmonary administration, and other mucosal surfaces.

[0268] Pharmaceutically acceptable: As used herein, the phrase "pharmaceutically acceptable" refers to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications, and commensurate with a reasonable benefit / risk ratio.

[0269] Pharmaceutically acceptable carrier: As used herein, the term "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material, used to deliver or transport a compound of interest from one organ or body part to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol; pH buffered solutions; polyesters, polycarbonates, and / or polyanhydrides; and other nontoxic, compatible substances used in pharmaceutical formulations.

[0270] Pharmaceutically acceptable salts: The term "pharmaceutically acceptable salts" as used herein refers to salts of compounds suitable for pharmaceutical use, i.e., salts that are suitable for use in contact with the tissues of humans and lower animals without producing excessive toxicity, irritation, allergic reactions, etc., and that have a reasonable benefit / risk ratio, within the scope of sound medical judgment. Pharmaceutically acceptable salts are well known in the art. For example, SM Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66: 1-19 (1977). In some embodiments, pharmaceutically acceptable salts include, but are not limited to, non-toxic acid addition salts, which are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids such as acetic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or using other methods used in the art such as ion exchange. In some embodiments, pharmaceutically acceptable salts include, but are not limited to, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, dodecylsulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, valerate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, and the like. In some embodiments, the compound provided comprises one or more acidic groups, and the pharmaceutically acceptable salt is an alkali, alkaline earth metal or ammonium (e.g., an ammonium salt of N(R)3, wherein each R is independently defined and described in the present disclosure) salt. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. In some embodiments, the pharmaceutically acceptable salt is a sodium salt. In some embodiments, the pharmaceutically acceptable salt is a potassium salt. In some embodiments, the pharmaceutically acceptable salt is a calcium salt. In some embodiments, pharmaceutically acceptable salts include (if appropriate) non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions (e.g., halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, alkyl groups having 1 to 6 carbon atoms, sulfonates, and arylsulfonates). In some embodiments, the compound provided comprises two or more acidic groups. In some embodiments, the pharmaceutically acceptable salts or common salts of such compounds comprise two or more cations, which may be the same or different.In some embodiments, in pharmaceutically acceptable salts (or salts generally), all ionizable hydrogens in acidic groups (e.g., pKa no more than about 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 in aqueous solution; in some embodiments, no more than about 7; in some embodiments, no more than about 6; in some embodiments, no more than about 5; in some embodiments, no more than about 4; in some embodiments, no more than about 3) are replaced with cations.

[0271] Polypeptide: As used herein, the term refers to a polymeric chain of amino acids. In some embodiments, a polypeptide has an amino acid sequence that occurs in nature. In some embodiments, a polypeptide has an amino acid sequence that does not occur in nature. In some embodiments, a polypeptide has an engineered amino acid sequence that has been artificially designed and / or generated. In some embodiments, a polypeptide may comprise or consist of natural amino acids, non-natural amino acids, or both. In some embodiments, a polypeptide may comprise or consist of only natural amino acids or non-natural amino acids. In some embodiments, a polypeptide may comprise D-amino acids, L-amino acids, or both. In some embodiments, a polypeptide may comprise only D-amino acids. In some embodiments, a polypeptide may comprise only L-amino acids. In some embodiments, a polypeptide may include one or more side chain groups or other modifications, such as modifications or attachments to one or more amino acid side chains, the N-terminus of the polypeptide, the C-terminus of the polypeptide, or any combination thereof. In some embodiments, such side chain groups or modifications may be selected from the group consisting of acetylation, amidation, lipidation, methylation, pegylation, and the like, including combinations thereof. In some embodiments, a polypeptide may be cyclic and / or may include a cyclic portion. In some embodiments, the polypeptide is acyclic and / or does not include any cyclic portion. In some embodiments, the polypeptide is linear. In some embodiments, the polypeptide may be or include a stapled polypeptide. In some embodiments, the term "polypeptide" may be appended to the name of a reference polypeptide, activity, or structure; in this case, it is used herein to refer to polypeptides that have a related activity or structure and are therefore considered to be members of the same polypeptide class or family. For each such class, this specification provides and / or those skilled in the art will know exemplary polypeptides in the class whose amino acid sequence and / or function are known; in some embodiments, such exemplary polypeptides are reference polypeptides of a polypeptide class or family. In some embodiments, members of a polypeptide class or family have significant sequence homology or identity with the reference polypeptide of the class, share common sequence motifs (e.g., characteristic sequence elements), and / or share a common activity (in some embodiments, at comparable levels or within a specified range); in some embodiments, have a common activity with all polypeptides within the class). For example, in some embodiments, a member polypeptide has at least about 30-40% overall sequence homology or identity with a reference polypeptide, and typically greater than about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more and / or includes at least one region (e.g., a conserved region, which in some embodiments can be or contain a characteristic sequence element) having very high sequence identity, typically greater than 90% or even 95%, 96%, 97%, 98% or 99%.Such conserved regions typically comprise at least 3-4 amino acids, typically up to 20 or more amino acids; in some embodiments, a conserved region comprises at least one segment of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more consecutive amino acids. In some embodiments, a related polypeptide may comprise or consist of a fragment of a parent polypeptide. In some embodiments, a useful polypeptide may comprise or consist of a plurality of fragments, each of which is spatially arranged relative to one another in the same parent polypeptide differently from that found in the target polypeptide (e.g., fragments that are directly connected in the parent may be spatially separated in the target polypeptide or vice versa, and / or the order of presence of the fragments in the target polypeptide may be different from that in the parent), such that the target polypeptide is a derivative of its parent polypeptide.

[0272] Protecting group: The term "protecting group" as used herein is well known in the art and includes the protecting groups described in detail in "Protective Groups in Organic Synthesis" (TW Greene and PGM Wuts, 3rd edition, John Wiley & Sons, 1999), the entire contents of which are incorporated herein by reference. It also includes protecting groups specifically applicable to nucleoside and nucleotide chemistry as described in "Current Protocols in Nucleic Acid Chemistry" (Serge L. Beaucage et al., edited June 2012), the entire contents of Chapter 2 of which are incorporated herein by reference. Suitable amino protecting groups include methylcarbamate, ethylcarbamate, 9-fluorenylmethylcarbamate (Fmoc), 9-(2-sulfo)fluorenylmethylcarbamate, 9-(2,7-dibromo)fluoroalkenylmethylcarbamate, 2,7-di-tert-butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthenyl)]methylcarbamate (DBD-Tmoc), 4-methoxybenzamidocarbamate (Phenoc),

[0273] 2,2,2-trichloroethylcarbamate (Troc), 2-trimethylsilylethylcarbamate (Teoc), 2-phenylethylcarbamate (hZ), 1-(1-adamantyl)-1-methylethylcarbamate (Adpoc), 1,1-dimethyl-2-haloethylcarbamate, 1,1-dimethyl-2,2-dibromoethylcarbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethylcarbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethylcarbamate (Bpoc), 1-(3,5-di-tert-butylphenyl) )-1-methylethylcarbamate (t-Bumeoc), 2-(2'- and 4'-pyridyl)ethylcarbamate (Pyoc), 2-(N,N-dicyclohexylamido)ethylcarbamate, tert-butylcarbamate (BOC), 1-adamantylcarbamate (Adoc), vinylcarbamate (Voc), allylcarbamate (Alloc), 1-isopropylallylcarbamate (Ipaoc), cinnamylcarbamate (Coc), 4-nitrocinnamylcarbamate (Noc), 8-quinolinylcarbamate, N-hydroxypiperidinylcarbamate Esters, alkyl dithiocarbamates, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitrobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethylcarbamate, diphenylmethylcarbamate, 2-methylthioethylcarbamate, 2-methylsulfonylethylcarbamate, 2-(p-toluenesulfonyl)ethylcarbamate, [2-(1,3-dithianyl)]methylcarbamate (Dmoc), 4-methylthiobenzene carbamate (Mtpc), 2,4-dimethylthiophenylcarbamate (Bmpc), 2-phosphinoethylcarbamate (Peoc), 2-triphenylphosphinoisopropylcarbamate (Ppoc), 1,1-dimethyl-2-cyanoethylcarbamate, m-chloro-p-acyloxybenzylcarbamate, p-(dihydroxyboryl)benzylcarbamate, 5-benzisoxazolylmethylcarbamate, 2-(trifluoromethyl)-6-chromonylmethylcarbamate (Tcroc), m-nitrophenylcarbamate, 3,5-dimethoxybenzylcarbamate, o-nitrobenzylcarbamate, 3,4-dimethoxy-6-nitrobenzylcarbamate, phenyl (o-nitrophenyl) methylcarbamate, phenothiazinyl-(10)-carbonyl derivatives, N'-toluenesulfonylaminocarbonyl derivatives, N'-phenylaminothiocarbonyl derivatives, tert-amylcarbamate, S-benzylthiocarbamate, p-cyanobenzylcarbamate, cyclobutylcarbamate, cyclohexylcarbamate, cyclopentylcarbamate, cyclopropylmethylcarbamate, p-decyloxybenzylcarbamate, 2,2-dimethoxycarbonylvinylcarbamate, o-(N,N-dimethylformamido)benzylcarbamate, 1,1-dimethyl-3-(N,N-dimethylformamido)propylcarbamate, 1,1 -dimethylpropynylcarbamate, di(2-pyridyl)methylcarbamate, 2-furylmethylcarbamate, 2-iodoethylcarbamate, isobornylcarbamate, isobutylcarbamate, isonicotinoylcarbamate, p-(p'-methoxyphenylazo)benzylcarbamate, 1-methylcyclobutylcarbamate, 1-methylcyclohexylcarbamate, 1-methyl-1-cyclopropylmethylcarbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethylcarbamate, 1-methyl-1-(p-phenylazophenyl)ethylcarbamate, 1-methyl-1-phenylethylcarbamate, 1-methyl-1-(4-pyridyl)ethylcarbamate, phenylcarbamate Esters, p-(phenylazo)benzylcarbamate, 2,4,6-tri-tert-butylphenylcarbamate, 4-(trimethylammonium)benzylcarbamate, 2,4,6-trimethylbenzylcarbamate, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropionamide, picolinamide, 3-pyridylformamide, N-benzoylphenylalanyl derivatives, benzamide, p-phenylbenzamide, o-nitrophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N'-dithiobenzyloxycarbonylamino)acetamide, 3-(p-hydroxyphenyl)propionamide, 3-(o-nitrophenyl)propionamide, 2-methyl-2-(o-nitrophenoxy)propionamide, 2-methyl-2-(o-phenyl)propionamide 4-chlorobutyramide, 3-methyl-3-nitrobutyramide, o-nitrocinnamic acid, N-acetylmethionine derivatives, o-nitrobenzamide, o-(benzoyloxymethyl)benzamide, 4,5-diphenyl-3-oxazolin-2-one, N-phthalimide, N-dithiosuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, N-1,1,4,4-tetramethyldisilazane adduct (STABASE), 5-substituted 1,3-dimethyl-1,3,5-triazacyclohexane-2-one, 5-substituted 1,3-dibenzyl-1,3,5-triazacyclohexane-2-one, 1-substituted 3,5-Dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4-nitro-2-oxo-3-pyrrolidin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4-methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N-[(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenamine (PhF), N-2,7-dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-pyridylamino N'-oxide , N-1,1-dimethylthiomethyleneamine, N-benzylimine, N-p-methoxybenzylimine, N-diphenylmethyleneamine, N-[(2-pyridyl)mesityl]methyleneamine, N-(N',N'-dimethylaminomethylene)amine, N,N'-isopropyldiamine, N-p-nitrobenzylimine, N-salicylimine, N-5-chlorosalicylimine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N-cyclohexylimine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivatives, N-diphenylboronic acid derivatives, N-[phenyl(pentacarbonylchromium- or tungsten)carbonyl]amine, N-copper chelates, N-zinc chelates Compounds, N-nitrosamines, N-nitrosamines, amine N-oxides, diphenylphosphinamide (Dpp), dimethylphosphinothioamide (Mpt), diphenylphosphinothioamide (Ppt), dialkylphosphinamides, dibenzylphosphinamide, diphenylphosphinamide, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4-dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, 3-nitropyridinesulfenamide (Npys), p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6,-trimethyl-4-methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (M tb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4-methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4',8'-dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide and benzoylsulfonamide.

[0274] Suitable protected carboxylic acids also include, but are not limited to, carboxylic acids protected by silicon-, alkyl-, alkenyl-, aryl- and aralkyl-based groups. Examples of suitable silicon-based groups include trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, triisopropylsilyl, etc. Examples of suitable alkyl groups include methyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, trityl, tert-butyl, tetrahydropyran-2-yl. Examples of suitable alkenyl groups include allyl. Examples of suitable aryl groups include optionally substituted phenyl, biphenyl or naphthyl. Examples of suitable aralkyl groups include optionally substituted benzyl (e.g., p-methoxybenzyl (MPM), 3,4-dimethoxybenzyl, O-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl) and 2- and 4-pyridyl.

[0275] Suitable hydroxy protecting groups include methyl, methoxymethyl (MOM), methylthiomethyl (MTM), tert-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), tert-butoxymethyl, 4-pentenyloxymethyl (POM), silyloxymethyl, 2-methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2-(trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S, S-dioxide, 1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1,4-dioxane-2-yl, tetrahydrofuranyl, tetrahydrothiopyranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methylenebenzofuran-2-yl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1 -methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylseleno)ethyl, tert-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-pyridyl, 4-pyridyl, 3-methyl-2-pyridyl N-oxide, diphenylmethyl, p,p'-dinitrodiphenylmethyl, 5-dibenzocycloheptadienyl, triphenylmethyl, α-naphthyldiphenyl methyl, p-methoxyphenylbenzhydryl, bis(p-methoxyphenyl)phenylmethyl, tris(p-methoxyphenyl)methyl, 4-(4'-bromobenzoyloxyphenyl)benzhydryl, 4,4',4"-tris(4,5-dichlorophthalimidophenyl)methyl, 4,4',4"-tris(levulinyloxyphenyl)methyl, 4,4',4"-tris(benzoyloxyphenyl)methyl, 3-(imidazol-1-yl)bis(4',4"-dimethoxyphenyl)methyl, 1,1-bis(4-methoxyphenyl)-1'-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10-oxo)anthryl, 1,3-Benzodithiolan-2-yl, benzisothiazolyl S,S-dioxide, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylhexylsilyl, tert-butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), tert-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, Triphenyl methoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate (levulinic acid ester), 4,4-(ethylenedithio)pentanoate (levulinic acid ester), pivalate, adamantane ester, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate), alkyl methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), alkyl ethyl carbonate, alkyl 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl)ethyl carbonate ( Psec), 2-(triphenylphosphine)ethyl carbonate (Peoc), alkyl isobutyl carbonate, alkyl vinyl carbonate, alkyl allyl carbonate, alkyl p-nitrophenyl carbonate, alkyl benzyl carbonate, alkyl p-methoxybenzyl carbonate, alkyl 3,4-dimethoxybenzyl carbonate, alkyl o-nitrobenzyl carbonate, alkyl p-nitrobenzyl carbonate, alkyl S-benzylthiocarbonate, 4-ethoxy-1-naphthyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2-(methylthiomethoxy)ethyl, 4-(methylthiomethoxy)butyrate, 2 -(methylthiomethoxymethyl)benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinate, (E)-2-methyl-2-butenoate, o-(methoxycarbonyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N',N'-tetramethylphosphoramide, alkyl N-phenylcarbamate, borate, dimethylthiophosphono, alkyl 2,4-dinitrophenylsulfinate, sulfate, methanesulfonate (mesylate), benzylsulfonate and mesylate (Ts). For the protection of 1,2- or 1,3-diol, protecting groups include methylene acetal, ethylene acetal, 1-tert-butylethylene ketal, 1-phenylethylene ketal, (4-methoxyphenyl)ethylene acetal, 2,2,2-trichloroethylene acetal, acetonide, cyclopentyl ketal, cyclohexyl ketal, cycloheptyl ketal, benzylidene acetal, p-methoxybenzylidene acetal, 2,4-dimethoxybenzylidene ketal, 3,4-dimethoxybenzylidene acetal, 2-nitrobenzyl acetal, methoxymethylene acetal, ethoxymethylene acetal, dimethoxymethylene orthoester, 1-methoxyethylidene orthoester, 1- Ethoxyethyl orthoester, 1,2-dimethoxyethyl methylene orthoester, α-methoxybenzylmethylene orthoester, 1-(N,N-dimethylamino)ethyl methylene derivatives, α-(N,N'-dimethylamino)benzylmethylene derivatives, 2-oxacyclopentane methylene orthoester, di-tert-butylsilyl (DTBS), 1,3-(1,1,3,3-tetraisopropyldisiloxane methylene) derivative (TIPDS), tetra-tert-butoxydisiloxane-1,3-dimethylene derivative (TBDS), cyclic carbonates, cyclic boronates, ethyl boronates, and phenyl boronates.

[0276] In some embodiments, the hydroxy protecting group is acetyl, tert-butyl, tert-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-dinitrophenyl, benzyl, benzoyl, p-phenylbenzoyl, 2,6-dichlorobenzyl, diphenylmethyl, p-nitrobenzyl, triphenylmethyl (trityl), 4,4'-dimethoxytrityl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, triphenylsilyl, triisopropylsilyl, benzoylformate, chloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyl, 9-fluorenylmethyl carbonate, mesylate, tosylate, trifluoromethanesulfonate, trityl, monomethoxytrityl (MMTr), 4,4'-dimethoxytrityl, (DMTr), and 4,4'-dimethoxytrityl. ',4"-trimethoxytrityl (TMTr), 2-cyanoethyl (CE or Cne), 2-(trimethylsilyl)ethyl (TSE), 2-(2-nitrophenyl)ethyl, 2-(4-cyanophenyl)ethyl 2-(4-nitrophenyl)ethyl (NPE), 2-(4-nitrophenylsulfonyl)ethyl, 3,5-dichlorophenyl, 2,4-dimethylphenyl, 2-nitrophenyl, 4-nitrophenyl, 2,4, In some embodiments, the protecting group is selected from the group consisting of trityl, monomethoxytrityl, and 4,4'-dimethoxytrityl. In some embodiments, the protecting group is attached to the sulfur atom of the phosphorothioate group. In some embodiments, the protecting group is attached to the oxygen atom of the internucleotide phosphorothioate linkage. In some embodiments, the protecting group is attached to the oxygen atom of the internucleotide phosphate bond.In some embodiments, the protecting group is 2-cyanoethyl (CE or Cne), 2-trimethylsilylethyl, 2-nitroethyl, 2-sulfonylethyl, methyl, benzyl, o-nitrobenzyl, 2-(p-nitrophenyl)ethyl (NPE or Npe), 2-phenylethyl, 3-(N-tert-butylformamido)-1-propyl, 4-oxopentyl, 4-methylthio-1-butyl, 2-cyano-1,1-dimethylethyl, 4-N-methylaminobutyl, 3-(2-pyridyl)-1-propyl, 2-[N-methyl-N-(2-pyridyl)]aminoethyl, 2-(N-formyl,N-methyl)aminoethyl, or 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl.

[0277] Subject: As used herein, the term "subject" or "test subject" refers to any organism to which a compound or composition according to the present disclosure is administered, e.g., for experimental, diagnostic, prophylactic, and / or therapeutic purposes. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and humans; insects; worms; etc.) and plants. In some embodiments, the subject is a human. In some embodiments, the subject may be suffering from and / or susceptible to a disease, disorder, and / or condition.

[0278] Susceptible: An individual who is "susceptible" to a disease, disorder, and / or condition has a higher risk of developing the disease, disorder, and / or condition compared to the general public. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition tends to develop the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition may not have been diagnosed with the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition may exhibit symptoms of the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition may not exhibit symptoms of the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition will develop the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition will not develop the disease, disorder, and / or condition.

[0279] Therapeutic agent: As used herein, the term "therapeutic agent" generally refers to any agent that, when administered to a subject, can cause a desired effect (e.g., a desired biological, clinical, or pharmacological effect). In some embodiments, an agent is considered a therapeutic agent if it demonstrates a statistically significant effect in an appropriate population. In some embodiments, the appropriate population is a population of subjects suffering from and / or susceptible to a disease, disorder, or condition. In some embodiments, the appropriate population is a population of model organisms. In some embodiments, the appropriate population can be defined by one or more criteria, such as age group, sex, genetic background, pre-existing clinical condition, prior treatment received. In some embodiments, a therapeutic agent is a substance that, when administered to a subject in an effective amount, can alleviate, ameliorate, alleviate, inhibit, prevent, delay the onset, reduce the severity, and / or reduce the incidence of one or more symptoms or characteristics in a subject. In some embodiments, a "therapeutic agent" is an agent that has or requires approval from a governmental agency for marketing in humans. In some embodiments, a "therapeutic agent" is an agent that requires a doctor's prescription for use in humans. In some embodiments, a therapeutic agent is a provided compound.

[0280] Therapeutically effective amount: As used herein, the term "therapeutically effective amount" refers to the amount of a substance (e.g., a therapeutic agent, composition, and / or formulation) that elicits a desired biological response when administered as part of a treatment regimen. In some embodiments, a therapeutically effective amount of a substance is an amount sufficient to treat, diagnose, prevent, and / or delay the onset of a disease, disorder, and / or condition when administered to a subject suffering from or susceptible to a disease, disorder, and / or condition. One of ordinary skill in the art will understand that the effective amount of a substance may vary depending on factors such as the desired biological endpoint, the substance to be delivered, the target cell or tissue, etc. For example, an effective amount of a compound in a formulation for treating a disease, condition, and / or condition is an amount that alleviates, ameliorate, alleviate, inhibit, prevent, delay onset, reduce severity, and / or reduce the incidence of one or more symptoms or characteristics of a disease, condition, and / or condition. In some embodiments, a therapeutically effective amount is administered in a single dose; in some embodiments, multiple unit doses are required to deliver a therapeutically effective amount.

[0281] Treatment: As used herein, the terms "treat" or "treating" refer to any method used to partially or completely alleviate, ameliorate, alleviate, inhibit, prevent, delay the onset of, lessen the severity of, and / or reduce the incidence of one or more symptoms or characteristics of a disease, disorder, and / or condition. Treatment can be administered to a subject who does not exhibit signs of the disease, disorder, and / or condition. In some embodiments, treatment can be administered to a subject who exhibits only early signs of the disease, disorder, and / or condition, e.g., to reduce the risk of developing pathology associated with the disease, disorder, and / or condition.

[0282] Unsaturated: As used herein, the term "unsaturated" refers to a moiety having one or more units of unsaturation.

[0283] Those skilled in the art will appreciate that the methods and compositions described herein with respect to provided compounds are generally also applicable to tautomers, pharmaceutically acceptable salts, solvates, etc. of such compounds. In some embodiments, the compounds may be provided as tautomers, salts, solvates, or combinations thereof (e.g., solvates of salts).

[0284] Description of Certain Embodiments

[0285] Among other things, the present disclosure provides compounds, compositions thereof, and methods thereof. In some embodiments, the present disclosure provides techniques that can be used to prevent or treat various conditions, disorders, or diseases. Certain embodiments of the provided techniques are described below as examples.

[0286] Certain embodiments of the compounds

[0287] Among other things, the present disclosure provides compounds comprising an isourea moiety. In some embodiments, the isourea moiety is R as described herein. w , wherein T is O. In some embodiments, the present disclosure provides compounds comprising an isothiourea moiety. In some embodiments, the isourea moiety is R as described herein w , wherein T is S. In some embodiments, the present disclosure provides urea compounds. In some embodiments, the urea compound has HR w or a tautomer and / or salt thereof, wherein T is O and each other variable is independently as described herein. In some embodiments, the present disclosure provides thiourea compounds. In some embodiments, the thiourea compounds have HR w的结构 Or its tautomers and / or salts, wherein T is S and each other variable is independently as described herein. In some embodiments, the compound comprises or consists of two parts, wherein one part is or comprises an isourea moiety, and the other part is a part that can provide, promote or enhance interaction with a target (e.g., a polypeptide). In some embodiments, the compound comprises or consists of two parts, wherein one part is or comprises an isothiourea moiety, and the other part is a part that can provide, promote or enhance interaction with a target (e.g., a polypeptide). In some embodiments, the compound comprises or consists of two parts, wherein one part is or comprises an isothiourea moiety, and the other part is a part that can provide, promote or enhance interaction with a target (e.g., a polypeptide). w or -L w -R w, and the other moiety is a moiety that can provide, promote or enhance interaction with a target (e.g., a polypeptide). In some embodiments, the isourea and isothiourea moieties can be used as leaving groups attached to electrophilic carbon atoms in the warhead. In some embodiments, the -L described herein w -R w Can be used as electrophilic warheads. In some embodiments, such warheads can be used to replace various electrophilic warhead moieties in various compounds, such as -C(O)CH=CH2, -C(O)C≡CH, -C(O)CH2Cl, -C(O)CH2Br, -C(O)CH2I, etc., to provide compounds that can be used for various purposes, such as inhibitors of various polypeptides (e.g., kinases, proteases, etc.).

[0288] In some embodiments, the isourea moiety is R w , where R w -TC(=NR w1 )N(R w2 )(R w3 ), T is -O-, and each other variable is independently as described herein. In some embodiments, the isothiourea moiety is R w , where R w -TC(=NR w1 )N(R w2 )(R w3 ), T is -S-, and each other variable is independently as described herein.

[0289] In some embodiments, the present disclosure provides a method comprising R w In some embodiments, the present disclosure provides a compound comprising -L w -R w In some embodiments, the present disclosure provides a compound comprising -C(O)-L w -R w wherein each variable is independently as described herein.

[0290] In some embodiments, R w =NR w1 )N(R w2 )(R w3 ), wherein each variable is independently as described herein. In some embodiments, R w =NR w1 )N(R w2 )(R w3 ), wherein each variable is independently as described herein.

[0291] The following is an illustration of certain compounds. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula A, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula B, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula C, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula D, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula E, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula F, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula G, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of Formula H, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound or a salt thereof having a structure of [PAYLOAD]-R 4 In some embodiments, the present disclosure provides compounds having N(CN)(R w2 )(R w3 ) structure, wherein each variable is independently as described herein. In some embodiments, the present disclosure provides a compound having R w1 -N=C=NR w3 In some embodiments, the present disclosure provides a compound having T=C(NHR w1 )N(R w2 )(R w3 ) or a salt thereof, wherein each variable is independently as described herein.

[0292] The following describes certain embodiments of various variables as examples. Those skilled in the art who read this disclosure will readily appreciate that the embodiments of various variables can be combined according to the disclosure. The following describes some combinations as examples. In some embodiments, embodiments of a variable (e.g., R) are described when describing embodiments of other variables (e.g., when describing R 1 、R 2 Various R embodiments are described when describing certain embodiments of R, etc.). Those skilled in the art who read this disclosure will readily understand that when describing any one variable, the embodiments of the variable described (e.g., when describing R 1 The R embodiment described when the variable is used may be applied to other variables that may be the variable (e.g., R that may be R2 、R 3 wait).

[0293] L w

[0294] In some embodiments, L w is a covalent bond, or is an optionally substituted divalent C having 1-6 (e.g., 1, 2, 3, 4, 5, or 6) heteroatoms 1-6 (e.g., C1, C2, C 3、C4、 C5 or C6) aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, in some embodiments, L w is a covalent bond or an optionally substituted divalent C 1-6 An aliphatic group wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L w is a covalent bond or an optionally substituted divalent C 1-2 An aliphatic group in which one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-.

[0295] In some embodiments, as shown in various compounds exemplified herein, L w Is or includes R w Bonded optionally substituted -CH 2- In some embodiments, as shown in various compounds exemplified herein, L wis an optionally substituted -CH2-. In some embodiments, as shown in various compounds exemplified herein, L w In some embodiments, L w In some embodiments, L is -CHD-. In some embodiments, L is -CD2-. w is a monosubstituted -CH2-. In some embodiments, L w Is a monosubstituted -CD2-. In some embodiments, this optionally substituted -CH2- is further activated by combining with an electron withdrawing group (e.g., -C(O)-) to make it more electrophilic. In some embodiments, the electron withdrawing group is or includes -C(O)-. In some embodiments, the electron withdrawing group is or includes -C(S)-. In some embodiments, L w is or comprises an optionally substituted -C(O)-CH2-. In some embodiments, L w Is -C(O)-CH2-. In some embodiments, L w is or contains an optionally substituted -C(S)-CH 2- In some embodiments, L w In some embodiments, the electron withdrawing group is or comprises -C(N(R'))-. In some embodiments, the electron withdrawing group is or comprises an optionally substituted aromatic ring. In some embodiments, the electron withdrawing group is or comprises an optionally substituted heteroaromatic ring. In some embodiments, the electron withdrawing group is L as described herein. R In some embodiments, L w is -C(N(R'))-CH2-, wherein -CH2- is optionally substituted and R' is as described herein. In some embodiments, L w is optionally substituted -C(O)-CHD-. In some embodiments, L w is optionally substituted -C(S)-CHD-. In some embodiments, L w is -C(N(R'))-CHD-, wherein -CHD- is optionally substituted. In some embodiments, L w is optionally substituted -C(O)-CD2-. In some embodiments, L w is optionally substituted -C(S)-CD2-. In some embodiments, L w is -C(N(R'))-CD2-, wherein -CD2- is optionally substituted. In some embodiments, -CH2-, -CHD-, or -CD2- is unsubstituted. In some embodiments, -CH2-, -CHD-, or -CD 2- With R wIn some embodiments, L w is -CH(CH3)-. In some embodiments, L w for In some embodiments, L w yes

[0296] R w

[0297] As described in this article, R w -TC(=NR w1 )N(R w2 )(R w3 ), wherein each variable is independently as described herein. In some embodiments, R w =NR w1 )N(R w2 )(R w3 ), wherein each variable is independently as described herein. In some embodiments, R w =NR w1 )N(R w2 )(R w3 ), wherein each variable is independently as described herein.

[0298] In some embodiments, R w1 、R w2 and R w3各自 is independently R as described herein. In some embodiments, R w1 、R w2 and R w2 In some embodiments, at least one of R w1 、R w2 and R w2 In some embodiments, R w1 、R w2 and R w2 No more than one of them is -H. In some embodiments, R w1 is -H. In some embodiments, R w2 is -H.

[0299] In some embodiments, R w3 is -H. In some embodiments, R w1 、R w2 and R w2 None of them is -H.

[0300] For example, in some embodiments, R w1 is -H, and R w2 and R w3 Each independently is an optionally substituted C1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 , etc.) aliphatic groups, or together with the nitrogen to which they are attached, form an optionally substituted ring as described herein. In some embodiments, R w1 is -H, and R w2 and R w3 Each independently is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 , etc.) aliphatic groups, or together with the nitrogen to which they are attached, form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w1 is -H, and R w2 and R w3 Each independently is an optionally substituted C 1-10 In some embodiments, R w1 is -H, and R w2 and R w3 Each independently is an optionally substituted C 1-10 In some embodiments, R w1 is -H, and R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w1 is -H, and R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w1 is -H, and R w2 and R w3Together with the nitrogen to which they are attached, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0 heteroatoms in addition to the nitrogen atom. In some embodiments, R w1 is -H, and R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having one heteroatom in addition to the nitrogen atom. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen.

[0301] In some embodiments, R w2 is -H, and R w1 and R w3 Each independently is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w2 is -H, and R w1 and R w3 Each independently is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 , etc.) aliphatic, or together with the intervening atoms form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the intervening atoms. In some embodiments, R w2 is -H, and R w1 and R w3 Each independently is an optionally substituted C 1-10 In some embodiments, R w2 is -H, and R w1 and R w3 Each independently is an optionally substituted C 1-10 In some embodiments, R w2 is -H, and R w1 and R w3Together with the atoms between them, they form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the middle atoms. In some embodiments, R w2 is -H, and R w1 and R w3 Together with the atoms between them, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the middle atoms. In some embodiments, R w2 is -H, and R w1 and R w3 Together with the atoms between them, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0 heteroatoms in addition to the middle atoms. In some embodiments, R w2 is -H, and R w1 and R w3 Together with the atoms between them, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring, which has 1 heteroatom in addition to the middle atom. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen.

[0302] R w2 and R w3 Together with the nitrogen atom to which they are attached, they form a ring, or a ring consisting of R w1和 R w2 and R w3 In some embodiments, the ring formed by one of the following, together with the atoms between them, is a 3-membered ring. In some embodiments, it is a 4-membered ring. In some embodiments, it is a 5-membered ring. In some embodiments, it is a 6-membered ring. In some embodiments, it is a 7-membered ring. In some embodiments, it is an 8-membered ring. In some embodiments, it is a 9-membered ring. In some embodiments, it is a 10-membered ring. In some embodiments, the ring formed is saturated (e.g., when R w2 and R w3In some embodiments, the ring formed is partially unsaturated. In some embodiments, the ring formed is aromatic. In some embodiments, the ring formed is substituted. In some embodiments, the ring formed is unsubstituted. In some embodiments, the ring formed has one heteroatom. In some embodiments, the ring formed has two heteroatoms. In some embodiments, the ring formed has three heteroatoms. In some embodiments, the ring formed has three heteroatoms. In some embodiments, the ring formed is monocyclic. In some embodiments, the ring formed is bicyclic. In some embodiments, the ring formed is polycyclic.

[0303] In some embodiments, -N(R w2 )(R w3 ) contains one or more substituents, for example, R w2 、R w3 、R w2 and R w3 Together with the nitrogen to which they are attached, they form a ring, R w1 and R w2 and R w3 One of them together with the atoms between them forms a ring, etc. In some embodiments, -N(R w2 )(R w3 ) contains one or more halogen substituents. In some embodiments, -N(R w2 )(R w3 ) contains one or more (e.g., 1, 2, 3, etc.) -F. In some embodiments, R w2 and R w3 The carbon atom at the beta position to the nitrogen to which it is attached (two chemical bonds per atom between the carbon atom and the nitrogen atom, for example, beta carbon-alpha carbon-nitrogen) is substituted. In some embodiments, it is substituted with -F. In some embodiments, it is monosubstituted with -F. In some embodiments, it is substituted with two -Fs. In some embodiments, it is substituted with three -Fs. For example, in some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2)(R w3 ))for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, -N(R w2 )(R w3 )for In some embodiments, R w2 -CH2CF 3。 In some embodiments, R w2 and R w3 The carbon atom at the γ position of the nitrogen atom to which it is attached (there are three chemical bonds / two atoms between the carbon atom and the nitrogen atom, for example, γ carbon-β carbon-α carbon-nitrogen) is substituted. In some embodiments, it is substituted with -F. In some embodiments, it is monosubstituted and the substituent is -F. In some embodiments, it is substituted with two -Fs. In some embodiments, it is substituted with three -Fs. For example, in some embodiments, -N(R w2 )(R w3 )for

[0304] In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, Rw for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, Rw for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, Rw for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for In some embodiments, R w for

[0305] T

[0306] In some embodiments, T is O. In some embodiments, T is S.

[0307] R w1

[0308] In some embodiments, R w1 is -LR', wherein each variable is independently as described herein. In some embodiments, R w1 is -LR', wherein the methylene unit of L to which R' is bound is replaced with a moiety, such as -N(R')- as described herein. In some embodiments, R w1 is R' as described herein. In some embodiments, R w1 is R as described herein.

[0309] In some embodiments, R w1 is R as described herein. For example, in some embodiments, R w1 is -H. In some embodiments, R w1 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w1 is an optionally substituted C 1-10 In some embodiments, R w1 is an optionally substituted methyl group. w1 In some embodiments, R w1 In some embodiments, R w1 In some embodiments, R w1 In some embodiments, R w1 In some embodiments, R w1 is an optionally substituted isopropyl. w1 In some embodiments, R w1 In some embodiments, R w1 is an optionally substituted C 3-10 In some embodiments, R w1 is an optionally substituted C 3-10 In some embodiments, R w1 is an optionally substituted cyclopropyl. w1 In some embodiments, R w1 In some embodiments, R w1 In some embodiments, R w1 In some embodiments, R w1 is an optionally substituted C having 1-6 (eg, 1-3, 1-2, 1, 2, 3, 4, 5, 6, etc.) heteroatoms 1-10 (For example, C 1-9、 C 1-8、 C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w1 is an optionally substituted C having 1, 2 or 3 heteroatoms 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w1 is an optionally substituted aryl. w1is an optionally substituted 6-14 membered (e.g., 6, 10, 14, etc.) aryl group. In some embodiments, R w1 is an optionally substituted phenyl. w1 is an optionally substituted 5-20 (e.g., 5-14, 5-10, 5-9, 5, 6, 8, 9, etc.) membered heteroaryl group having 1-10 (e.g., 1-5, 1-4, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R w1 is an optionally substituted 5-10 membered heteroaryl group having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms. w1 is an optionally substituted 5-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w1 is an optionally substituted 6-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w1 is an optionally substituted 9-membered bicyclic heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w1 is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heterocyclyl having 1-10 (e.g., 1-5, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R w1 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclyl having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, R w1 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms. w1 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered partially saturated ring having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms. w1 is an optionally substituted group, which is C 1-20 Aliphatic group, C1-20 heteroaliphatic group with 1-10 heteroatoms, C 6-20A combination of two or more of aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, and 3-20 membered heterocyclyl having 1-10 heteroatoms, wherein the combination has 1-30 (e.g., 1-20, 1-15, 1-10, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, etc.) carbon atoms and 0-10 (e.g., 0-5, 1-10, 1-5, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. As used in the present disclosure, in some embodiments, each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur.

[0310] In some embodiments, R w1 Is or contains a detectable label, such as a fluorescent label, a radioactive label, a label for proteomics, an antibody label, a peptide label, etc.

[0311] In some embodiments, R w1 and R w2 Together with the atoms therebetween, they form a ring which may be optionally substituted as described herein. w1 and R w2 Together with the atoms between them, they form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the atoms between them. In some embodiments, R w1 and R w2 Together with the atoms between them, they form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w2 Together with the atoms between them, they form an optionally substituted 5-14 (e.g., 5-10, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered ring having 0-6 (e.g., 1-6, 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w2Together with its middle atom, it forms an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring, and has 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w2 Together with its middle atom, it forms an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring, which has 0 heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w2 Together with its middle atom, it forms an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring, which has 1 heteroatom in addition to the middle atom. In some embodiments, R w1 and R w3 and its intermediate atoms together form an optionally substituted ring as described herein. w1 and R w3 Together with its middle atom, it forms an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring, and has 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w3 Together with the atoms between them, they form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w3 Together with the atoms between them, they form an optionally substituted 5-14 (e.g., 5-10, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered ring having 0-6 (e.g., 1-6, 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w3 Together with its middle atom, it forms an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring, and has 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the middle atom. In some embodiments, R w1 and R w3 Together with its middle atom, it forms an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring, which has 0 heteroatoms in addition to the middle atom. In some embodiments, Rw1 and R w3 Together with the atoms between them, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having one heteroatom in addition to the middle atom. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the formed ring is 3-membered. In some embodiments, it is 4-membered. In some embodiments, it is 5-membered. In some embodiments, it is 6-membered. In some embodiments, it is 7-membered. In some embodiments, it is 8-membered. In some embodiments, it is 9-membered. In some embodiments, it is 10-membered. In some embodiments, the formed ring is substituted. In some embodiments, the formed ring is unsubstituted. In some embodiments, there is one heteroatom in the formed ring. In some embodiments, there are two heteroatoms in the formed ring. In some embodiments, there are three heteroatoms in the formed ring. In some embodiments, there are three heteroatoms in the formed ring. In some embodiments, the formed ring is monocyclic. In some embodiments, the formed ring is bicyclic. In some embodiments, the ring formed is polycyclic. In some embodiments, the ring formed is partially unsaturated. For example, in some embodiments, the ring formed is an optionally substituted 5-6 membered partially unsaturated ring with 1-2 (in some embodiments, 1; in some embodiments, 2) heteroatoms, wherein one or more heteroatoms are nitrogen. In some embodiments, the ring formed is an optionally substituted 5-membered partially unsaturated ring with 1-2 heteroatoms, wherein each heteroatom is nitrogen. In some embodiments, the ring formed is aromatic. In some embodiments, the ring formed is an optionally substituted 5-6 membered heteroaryl with 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms, wherein one or more heteroatoms are nitrogen. In some embodiments, the ring formed is an optionally substituted 5-membered heteroaryl with 1-3 heteroatoms, wherein one or more heteroatoms are nitrogen. In some embodiments, the ring formed is an optionally substituted 5-membered heteroaryl with 1 or 2 nitrogen atoms. In some embodiments, the ring formed is an optionally substituted 6-membered partially unsaturated ring with 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring formed is an optionally substituted 6-membered partially unsaturated ring with 1, 2, or 3 nitrogen atoms. In some embodiments, the ring formed is an optionally substituted 6-membered partially unsaturated ring with 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring formed is an optionally substituted 6-membered heteroaryl with 1, 2, or 3 nitrogen atoms.

[0312] For example, in some embodiments, the ring formed is optionally substituted In some embodiments, -C(=NR w1 )N(R w2 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w3 ) is an optional replacement In some embodiments, the ring formed is optionally substituted In some embodiments, -C(=NR w1 )N(R w2 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w3 ) is an optional replacement In some embodiments, the ring formed is optionally substituted In some embodiments, -C(=NR w1 )N(R w2 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w3 ) is an optional replacement In some embodiments, the ring formed is optionally substituted wherein y is independently 0, 1, 2, 3 or 4. In some embodiments, -C(=NR w1 )N(R w2 ) is an optional replacement wherein y is independently 0, 1, 2, 3 or 4. In some embodiments, -C(=NR w1 )N(R w3 ) is an optional replacement wherein y is independently 0, 1, 2, 3 or 4. In some embodiments, the ring formed is optionally substituted wherein y is independently 0, 1, 2, 3 or 4, and is a single bond or a double bond. In some embodiments, -C(=NR w1 )N(R w2 ) is an optional replacement wherein y is independently 0, 1, 2, 3 or 4, and is a single bond or a double bond. In some embodiments, -C(=NR w1 )N(R w3 ) is an optional replacement wherein y is independently 0, 1, 2, 3 or 4, and is a single bond or a double bond. In some embodiments, y is 0. In some embodiments, y is 1. In some embodiments, y is 2. In some embodiments, y is 3. In some embodiments, y is 4. In some embodiments, the ring formed is optionally substituted In some embodiments, --C(=NR w1 )N(R w2 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w3 ) is an optional replacement

[0313] In some embodiments, -C(=NR w1 )N(R w2 )(R w3 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w2 )(R w3 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w2 )(R w3 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w2 )(R w3 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w2 )(R w3 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w2 )(R w3 ) is an optional replacement In some embodiments, -C(=NR w1 )N(R w2 )(R w3 )for In some embodiments, the loop formed is In some embodiments, the loop formed is In some embodiments, the loop formed is

[0314] R w2

[0315] In some embodiments, R w2is -LR', wherein each variable is independently as described herein. In some embodiments, R w2 is -LR', wherein the methylene unit of L to which R' is bound is replaced with a moiety, such as -N(R')- as described herein. For example, in some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 is -CH2-C=CH. In some embodiments, R w2 is R' as described herein. In some embodiments, R w2 is R as described herein.

[0316] In some embodiments, R w2 is R as described herein. For example, in some embodiments, R w2 is -H. In some embodiments, R w2 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w2 is an optionally substituted C 1-10 In some embodiments, R w2 is an optionally substituted methyl group. w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 is an optionally substituted isopropyl. w2 In some embodiments, R w2 In some embodiments, R w2 is an optionally substituted C 1-6 In some embodiments, R w2 is an optionally substituted C 3-10 In some embodiments, R w2 is an optionally substituted C 3-10In some embodiments, R w2 is an optionally substituted cyclopropyl. w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 In some embodiments, R w2 is an optionally substituted C1-10 (e.g., C 1-9、 C 1-8、 C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w2 is an optionally substituted C having 1, 2 or 3 heteroatoms 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w2 In some embodiments, R w2 is an optionally substituted aryl. w2 is an optionally substituted 6-14 membered (e.g., 6, 10, 14, etc.) aryl group. In some embodiments, R w2 is an optionally substituted phenyl. w2 is an optionally substituted 5-20 (e.g., 5-14, 5-10, 5-9, 5, 6, 8, 9, etc.) membered heteroaryl group having 1-10 (e.g., 1-5, 1-4, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R w2 is an optionally substituted 5-10 membered heteroaryl group having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms. w2 is an optionally substituted 5-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w2 is an optionally substituted 6-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms.w2 is an optionally substituted 9-membered bicyclic heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w2 is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heterocyclyl having 1-10 (e.g., 1-5, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R w2 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclyl having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, R w2 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms. w2 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered partially saturated ring having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms. w2 is an optionally substituted group, which is C 1-20 Aliphatic group, C1-20 heteroaliphatic group with 1-10 heteroatoms, C 6-20 and combinations of two or more of aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, and 3-20 membered heterocyclyl having 1-10 heteroatoms, wherein the combination has 1-30 (e.g., 1-20, 1-15, 1-10, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, etc.) carbon atoms and 0-10 (e.g., 0-5, 1-10, 1-5, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms.

[0317] In some embodiments, R w2 is or comprises a detectable label, such as a fluorescent label, a radioactive label, a label for proteomics, an antibody label, a peptide label, and the like.

[0318] In some embodiments, R w2 and R w3Together with the nitrogen atom to which they are attached, they form an optionally substituted ring as described herein. w2 and R w3 Together with the nitrogen atom to which they are attached, they form an optionally substituted 3-14 (e.g., 3-10, 3-8, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered ring having 0-6 (e.g., 1-6, 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w1 is -H, and R w2 and R w3 Each independently is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 , etc.) aliphatic groups, or together with the nitrogen to which they are attached, form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered ring having 0-5 (e.g., 1-5, 0, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 3-10 (e.g., 3-7, 4-10, 5-10, 5-7, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 3-8 (e.g., 3-7, 5-7, 3, 4, 5, 6, 7, 8, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0-3 (e.g., 0, 1-3, 1, 2, 3, etc.) heteroatoms in addition to the nitrogen atom. In some embodiments, Rw2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having 0 heteroatoms in addition to the nitrogen atom. In some embodiments, R w2 and R w3 Together with the nitrogen to which they are attached, they form an optionally substituted 5-10 (e.g., 5-9, 5-7, 5, 6, 7, 8, 9, or 10, etc.) membered ring having one heteroatom in addition to the nitrogen atom. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the ring formed is 3-membered. In some embodiments, it is 4-membered. In some embodiments, it is 5-membered. In some embodiments, it is 6-membered. In some embodiments, it is 7-membered. In some embodiments, it is 8-membered. In some embodiments, it is 9-membered. In some embodiments, it is 10-membered. In some embodiments, the ring formed is saturated. In some embodiments, the ring formed is partially unsaturated. In some embodiments, the ring formed is aromatic. In some embodiments, the ring formed is substituted. In some embodiments, the ring formed is unsubstituted. In some embodiments, the ring formed has one heteroatom. In some embodiments, the ring formed has two heteroatoms. In some embodiments, the ring formed has three heteroatoms. In some embodiments, there are three heteroatoms in the ring formed. In some embodiments, the ring formed is monocyclic. In some embodiments, the ring formed is bicyclic. In some embodiments, the ring formed is polycyclic. In some embodiments, the ring formed is optionally substituted, wherein x and y are each independently 0-4. In some embodiments, the ring formed is optionally substituted, wherein x and y are each independently 0-4. In some embodiments, the ring formed is optionally substituted, wherein x and y are each independently 0-4. In some embodiments, the ring formed is optionally substituted wherein y is 0-4. In some embodiments, the ring formed is optionally substituted wherein x and y are each independently 0-4, and Q is optionally substituted S, Si, or S(O)2. In some embodiments, Q is S(O)2. In some embodiments, Q is Si(CH3)2. In some embodiments, Q is S. In some embodiments, x is 0. In some embodiments, x is 1. In some embodiments, x is 2. In some embodiments, x is 3. In some embodiments, x is 4. In some embodiments, y is 0. In some embodiments, y is 1. In some embodiments, y is 2. In some embodiments, y is 3. In some embodiments, y is 4. In some embodiments, the ring formed is optionally substituted In some embodiments, the ring formed is optionally substituted In some embodiments, the ring formed is optionally substituted In some embodiments, the ring formed is optionally substituted In some embodiments, the loop formed is In some embodiments, the ring formed is optionally substituted In some embodiments, the loop formed is In some embodiments, the ring formed is optionally substituted In some embodiments, the loop formed is In some embodiments, the ring formed is optionally substituted In some embodiments, the ring formed is optionally substituted In some embodiments, the ring formed is optionally substituted

[0319] In some embodiments, -N(R w2 )(R w3 ) is optionally substituted -NH2, In some embodiments, -N(R w2 )(R w3 ) is -NH2, In some embodiments, it is one of such groups. In some embodiments, it is one of such groups that is further substituted as described herein.

[0320] R w3

[0321] In some embodiments, R w3 is -LR', wherein each variable is independently as described herein. For example, in some embodiments, R' is -H. In some embodiments, R' is an optionally substituted C1-6 In some embodiments, R w3 is -LR', wherein the methylene unit of L to which R' is bound is replaced with a moiety, e.g., -N(R')- as described herein. For example, in some embodiments, R w3 In some embodiments, R w3 is R' as described herein. In some embodiments, R w3 is R as described herein.

[0322] In some embodiments, R w3 is R as described herein. For example, in some embodiments, R w3 is -H. In some embodiments, R w3 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w3 is an optionally substituted C 1-10 In some embodiments, R w3 is an optionally substituted methyl group. w3 In some embodiments, R w3 In some embodiments, R w3 In some embodiments, R w3 In some embodiments, R w3 In some embodiments, R w3 is an optionally substituted isopropyl. w3 In some embodiments, R w3 In some embodiments, R w3 is an optionally substituted C 3-10 In some embodiments, R w3 is an optionally substituted C 3-10 In some embodiments, R w3 is an optionally substituted cyclopropyl. w3 In some embodiments, R w3 In some embodiments, R w3 In some embodiments, R w3 In some embodiments, Rw3 is an optionally substituted C1-10 (e.g., C 1-9、 C 1-8、 C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w3 is an optionally substituted C having 1, 2 or 3 heteroatoms 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R w3 is an optionally substituted aryl. w3 is an optionally substituted 6-14 membered (e.g., 6, 10, 14, etc.) aryl group. In some embodiments, R w3 is an optionally substituted phenyl. w3 is an optionally substituted 5-20 (e.g., 5-14, 5-10, 5-9, 5, 6, 8, 9, etc.) membered heteroaryl group having 1-10 (e.g., 1-5, 1-4, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R w3 is an optionally substituted 5-10 membered heteroaryl group having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms. w3 is an optionally substituted 5-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w3 is an optionally substituted 6-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w3 In some embodiments, R w3 In some embodiments, R w3 In some embodiments, R w3 is an optionally substituted 9-membered bicyclic heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. w3is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heterocyclyl having 1-10 (e.g., 1-5, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R w3 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclyl having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, R w3 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms. w3 is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered partially saturated ring having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms. w3 is an optionally substituted group, which is C 1-20 Aliphatic group, C1-20 heteroaliphatic group with 1-10 heteroatoms, C 6-20 and combinations of two or more of aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, and 3-20 membered heterocyclyl having 1-10 heteroatoms, wherein the combination has 1-30 (e.g., 1-20, 1-15, 1-10, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, etc.) carbon atoms and 0-10 (e.g., 0-5, 1-10, 1-5, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms.

[0323] In some embodiments, R w3 is or comprises a detectable label, such as a fluorescent label, a radioactive label, a label for proteomics, an antibody label, a peptide label, and the like.

[0324] In some embodiments, R w1 and R w3 are all R as described herein. In some embodiments, R w1 and R w3Together with its intermediate atoms, it forms an optionally substituted ring as described herein. w2 and R w3 are all R as described herein. In some embodiments, R w2 and R w3 Together with the nitrogen to which it is attached, it forms an optionally substituted ring as described herein. w1 、R w2 and R w3 are each independently R as described herein. In some embodiments, R w1 、R w2 and R w3 Together with its central atoms, it forms an optionally substituted ring as described herein.

[0325] R wh

[0326] In some embodiments, R wh In some embodiments, R wh It is -SH.

[0327] X

[0328] As described herein, X is -O-, -S-, -C(R 1 )=、-N(R 1 )- or is optionally substituted -CH=, -CH=CH- or -NH-. In some embodiments, X is -O-. In some embodiments, X is -S-. In some embodiments, X is -C(R 1 )=, where R 1 As described herein. In some embodiments, X is -N(R 1 )-, where R 1 As described herein. In some embodiments, X is an optionally substituted -CH=. In some embodiments, X is -CH=. In some embodiments, X is an optionally substituted -CH=CH-. In some embodiments, X is -CH=CH-. In some embodiments, X is -NH-. In some embodiments, X is -NH-.

[0329] Y

[0330] As described herein, Y is C or N. In some embodiments, Y is C. In some embodiments, Y is N.

[0331] Z

[0332] As described herein, Z is C or N. In some embodiments, Z is C. In some embodiments, Z is N.

[0333] For example, the bond between Y and Z can be a single bond or a double bond. In some embodiments, it is a single bond. In some embodiments, it is a double bond. For example, in some embodiments, Y and Z are C, and the bond is a double bond.

[0334] R 1

[0335] As described in this article, R 1 is R as described herein 9 In some embodiments, R 1 R ', halogen, -CN, oxo, -NO2 or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, thioalkyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl. In some embodiments, R 1 is R' as described herein. In some embodiments, R 1 is R as described herein.

[0336] In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 is R' as described herein. In some embodiments, R 1 is R as described herein.

[0337] R 2

[0338] As described in this article, R 2 R" or wherein each variable is independently as described herein.

[0339] In some embodiments, R 2 is R as described herein. In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 is R' as described herein. In some embodiments, R 2 is R as described herein. For example, in some embodiments, R is an optionally substituted phenyl group. In some embodiments, R is 4-fluorophenyl. In some embodiments, R is 4-aminophenyl. In some embodiments, R is an optionally substituted 5-6 membered heteroaryl group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0340] In some embodiments, R 2is -LR', wherein L and R' are each independently as described herein. For example, in some embodiments, L is a covalent bond. In some embodiments, L is an optionally substituted -CH2-. In some embodiments, L is -Cy- as described herein. In some embodiments, L is an optionally substituted phenylene. In some embodiments, L is an optionally substituted 1,4-phenylene. In some embodiments, R' is R as described herein. In some embodiments, R' is an optionally substituted C 1-6 (For example, C 1-5 , C1, C2, C3, C4, C5, C6, etc.) aliphatic. In some embodiments, R' is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, R' is an optionally substituted

[0341] In some embodiments, R 2 for wherein each variable is independently as described herein.

[0342] In some embodiments, L A In some embodiments, the compound of formula A has a structure of formula AI. In some embodiments, the compound of formula A has a structure of formula A-II. In some embodiments, the compound of formula A has a structure of formula A-III.

[0343] R 3

[0344] As described in this article, R 3 R" or wherein each variable is independently as described herein.

[0345] In some embodiments, R 3 is R as described herein. In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 is R' as described herein. In some embodiments, R 3 is R as described herein. For example, in some embodiments, R is an optionally substituted phenyl group. In some embodiments, R is 4-fluorophenyl. In some embodiments, R is 4-aminophenyl. In some embodiments, R is an optionally substituted 5-6 membered heteroaryl group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0346] In some embodiments, R 3 for wherein each variable is independently as described herein.

[0347] In some embodiments, R 2 and R 3 In some embodiments, R 2 and R 3 In some embodiments, one of R is -H and the other is not -H. 2 is -H, and R 3 is not -H. In some embodiments, R 2 Not -H, but R 3 is H. In some embodiments, R 2 and R 3 The atom to which it is attached is chiral. In some embodiments, it is R. In some embodiments, it is S. In some embodiments, R 2 and R 3 The stereopurity of the attached carbon atom is about or at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%. In some embodiments, the two R / S configurations are present at about 50% the same level.

[0348] R 4

[0349] In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 -L w -R w , wherein each variable is independently as described herein. In some embodiments, R 4 R w , as described herein. In some embodiments, R 4 =NR w1 )N(R w2 )(R w3 ), wherein each variable is independently as described herein. In some embodiments, R 4 =NR w1 )N(R w2 )(R w3 ), wherein each variable is independently as described herein.

[0350] In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for In some embodiments, R 4 for

[0351] In some embodiments, R 4 -L w-R wh , wherein each variable is independently as described herein.

[0352] R 5

[0353] In some embodiments, R 5 is R as described herein. In some embodiments, R 5 is -C(O)OR" wherein R" is as described herein. In some embodiments, R 5 is -C(O)N(R')2 wherein each R' is independently as described herein. In some embodiments, R 5 is -C(O)NHR' wherein R' is as described herein. In some embodiments, R 5 In some embodiments, R 5 -C(O)OR' wherein R' is as described herein. For example, in some embodiments, R' is an optionally substituted C 1-6 In some embodiments, R 5 In some embodiments, R 5 for In some embodiments, R 5 for

[0354] In some embodiments, R 5 is R as described herein. For example, in some embodiments, R 5 is -H. In some embodiments, R 5 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 、C 2-10 、C 3-10 、C 4-10 、C1、C2、C3、C4、C 5、 C6, C7, C8, C9, C 10 In some embodiments, R 5 is an optionally substituted C 1-6 In some embodiments, R 5 -CH 3。 In some embodiments, R 5 is an optionally substituted C 2-10 In some embodiments, R 5 is an optionally substituted C 3-10 In some embodiments, R 5 is an optionally substituted C 4-10 In some embodiments, R5 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 、C 2-10 、C 3-10 、C 4-10 ,C1,C2,C3,C4,C5,C6,C7,C 8、 C 9、 C 10 In some embodiments, R 5 is an optionally substituted C 1-6 In some embodiments, R 5 is an optionally substituted C 2-10 In some embodiments, R 5 is an optionally substituted C 3-10 In some embodiments, R 5 is an optionally substituted C 4-10 In some embodiments, R 5 C 1-6 Alkyl or halogenated C 1-6 In some embodiments, R 5 is C optionally substituted by one or more -F 1-6 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 It is n-butyl.

[0355] R 6

[0356] In some embodiments, R 6 is R as described herein. In some embodiments, R 6 is -C(O)OR", wherein R" is as described herein. In some embodiments, R 6 is -C(O)N(R')2, wherein each R' is independently as described herein. In some embodiments, R 6 is -C(O)NHR', wherein R' is as described herein. In some embodiments, R 6 In some embodiments, R 6 is -C(O)OR', wherein R' is as described herein. For example, in some embodiments, R' is an optionally substituted C 1-6 In some embodiments, R 6 In some embodiments, R 6 for In some embodiments, R 6 for

[0357] In some embodiments, R 6 is R as described herein. For example, in some embodiments, R 6 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 、C 2-10 、C 3-10 、C 4-10 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R 6 is an optionally substituted C 2-10 In some embodiments, R 6 is an optionally substituted C 3-10 In some embodiments, R 6 is an optionally substituted C 4-10 In some embodiments, R 6 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 、C 2-10 、C 3-10 、C 4-10 、C1、C2、C3、C4、C 5、 C6, C7, C8, C9, C 10 In some embodiments, R 6 is an optionally substituted C 2-10 In some embodiments, R 6 is an optionally substituted C 3-10 In some embodiments, R 6 is an optionally substituted C 4-10 In some embodiments, R 6 In some embodiments, R 6 It is n-butyl.

[0358] R 5 and R 6 In some embodiments, at least one of R 5 In some embodiments, one of R is -H and the other is not -H. 5 and R 6The carbon atom to which it is attached is chiral. In some embodiments, it is R. In some embodiments, it is S. In some embodiments, R 5 and R 6 The stereopurity of the attached carbon atom is about or at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%. In some embodiments, the two R / S configurations are present at about 50% the same level.

[0359] R 2 and R 3 One of them is -H, and R 5 and R 6 One of is -H. Alternatively or additionally, in some embodiments, R 2 and R 3 One of them is not -H, and R 5 and R 6 In some embodiments, R 2 and R 3 One of them is not -H, R 5 and R 6 In some embodiments, R 2 and R 3 One of them is not -H, R 5 and R 6 In some embodiments, R 2 and R 3 One of them is -H, R 5 and R 6 One of them is -H, and they are trans. In some embodiments, R 2 and R 3 One of them is -H, R 5 and R 6 One of them is -H, and they are cis. In some embodiments, R 5 The attached carbon has configuration, in which the carbon is connected to R via a bond 7 In some embodiments, R 5 The attached carbon has configuration, in which the carbon is connected to R via a bond 7 The carbon atom is connected to the nitrogen atom through bond b.

[0360] R 7

[0361] In some embodiments, R 7 is R as described herein. In some embodiments, R7 is R' as described herein. In some embodiments, R 7 is R as described herein. In some embodiments, R 7 is -H.

[0362] R 8

[0363] In some embodiments, R 8 is R as described herein. In some embodiments, R 8 is R' as described herein. In some embodiments, R 8 is R as described herein. In some embodiments, R 8 is -H.

[0364] R 9

[0365] In some embodiments, R 9 is R as described herein. In some embodiments, R 9 is R' as described herein. In some embodiments, R 9 is R as described herein.

[0366] In some embodiments, R 9 is -OR, wherein R is as described herein. In some embodiments, R 9 -OR, wherein R is an optionally substituted C 1-6 In some embodiments, R 9 It is -OCH3.

[0367] In some embodiments, R 9 is -N(R')2, wherein each R' is independently as described herein. In some embodiments, R 9 -N(R')2, wherein one R' is -H and the other is an optionally substituted C 10 In some embodiments, the other is an optionally substituted adamantyl. In some embodiments, the other is 1-adamantyl.

[0368] In some embodiments, R 9 is -H. In some embodiments, R 9 Not -H.

[0369] In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 is an optionally substituted amino acid. In some embodiments, R 9 is an optionally substituted amine. In some embodiments, R 9 is an optionally substituted amide. 9 is an optionally substituted carbamate. 9 is an optionally substituted ester. In some embodiments, R 9 is an optionally substituted ether. In some embodiments, R 9 is an optionally substituted carboxylic acid. 9 In some embodiments, R 9 In some embodiments, R 9 is an optionally substituted thioester. 9 In some embodiments, R9 is an optionally substituted sulfate. 9 is an optionally substituted sulfonamide. 9 is an optionally substituted sulfoxide. 9 is an optionally substituted sulfonate. In some embodiments, R 9 is an optionally substituted sulfone. 9 is an optionally substituted alkylsulfonyl. 9 is an optionally substituted arylsulfonyl. In some embodiments, when there are two or more R 9 When , they may be the same or different and are each independently as described herein.

[0370] R 9 One occurrence of is bonded to a moiety (e.g., a ring). In some embodiments, R 9 Two or more occurrences of are bonded to a moiety (e.g., a ring), wherein each occurrence of R 9 In some embodiments, R 9 In some embodiments, R9 One occurrence of is -F. In some embodiments, R 9 One occurrence of is -N(R')2. In some embodiments, each occurrence of R 9 are independently -H, -N(R)2, -OR, -CN and are optionally substituted C 1-6 In some embodiments, R 9 One occurrence is -N(R)2, wherein each R is independently -H or an optionally substituted C 1-20 In some embodiments, R 9 One occurrence is -N(R)2, wherein each R is independently -H or an optionally substituted C 1-10 In some embodiments, R 9 One occurrence is -NHR, wherein each R is independently -H or an optionally substituted C 1-20 In some embodiments, R 9 One occurrence is -NHR, wherein each R is independently -H or an optionally substituted C 1-10 In some embodiments, each R 9 are independently -H, -NH2, -CN, -CH3. In some embodiments, R 9 One occurrence is for the optionally substituted C 1-6 In some embodiments, R 9 One occurrence of is for optional replacement In some embodiments, R 9 One occurrence of is for optional replacement In some embodiments, R 9 One occurrence of is para relative to the position where Ring A is attached to the rest of the compound. In some embodiments, each R 9 is independently halogen, or is optionally substituted C 1-20 Aliphatic or C with 1-10 heteroatoms 1-20 In some embodiments, R 9 It is -OCH3.

[0371] R 10

[0372] In some embodiments, R 10 is R as described herein. In some embodiments, R 10 is R' as described herein.

[0373] In some embodiments, R 10 is R as described herein. For example, in some embodiments, R 10is -H. In some embodiments, R 10 is an optionally substituted C 1-6 In some embodiments, R 10 is an optionally substituted C 2-6 In some embodiments, R 10 is an optionally substituted C 2-6 In some embodiments, R 10 C 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc. membered) cycloalkyl. In some embodiments, R 10 is an optionally substituted C 6-14 In some embodiments, R 10 is an optionally substituted C 6-10 In some embodiments, R 10 is an optionally substituted C 7-15 In some embodiments, R 10 is an optionally substituted 5-10 membered heteroaryl group having 1-4 heteroatoms. 10 is an optionally substituted 3-10 membered heterocyclic group having 1-4 heteroatoms. 10 is an optional replacement for C 1-10 In some embodiments, R 10 is an optional replacement for C 6-20 In some embodiments, R 10 In some embodiments, R 10 is 2,4-dimethoxy-phenyl. In some embodiments, R 10 It is 3-chloro-4-methoxyphenyl.

[0374] R 11

[0375] In some embodiments, R 11 is R as described herein. In some embodiments, R 11 is R' as described herein.

[0376] In some embodiments, R 11 is R as described herein. For example, in some embodiments, R 11 is -H. In some embodiments, R 11 is an optionally substituted C 1-10 In some embodiments, R 11 is an optionally substituted C 1-6 In some embodiments, R 11 is an optionally substituted C1-6 In some embodiments, R 11 is an optionally substituted C 2-6 In some embodiments, R 11 is an optionally substituted C 2-6 In some embodiments, R 11 C 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc. membered) cycloalkyl. In some embodiments, R 11 is an optionally substituted C 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) aryl. In some embodiments, R 11 is an optionally substituted C 6-14 In some embodiments, R 11 is an optionally substituted C 6-10 In some embodiments, R 11 is an optionally substituted phenyl. 11 is an optional replacement for C 7-15 In some embodiments, R 11 is an optionally substituted 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, etc.) membered heteroaryl group having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R 11 is an optionally substituted 5-10 membered heteroaryl group having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms. 11 is an optionally substituted 5-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. 11 is an optionally substituted thienyl. 11 It is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclic group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms.

[0377] R 12

[0378] In some embodiments, R 12 is R as described herein. In some embodiments, R 12 is R' as described herein.

[0379] In some embodiments, R 12 is R as described herein. For example, in some embodiments, R 12 is -H. In some embodiments, R 12 is an optionally substituted C 1-10 In some embodiments, R 12 is an optionally substituted C 1-6 In some embodiments, R 12 is an optionally substituted C 1-6 In some embodiments, R 12 is an optionally substituted C 2-6 In some embodiments, R 12 is an optionally substituted C 2-6 In some embodiments, R 12 C 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc. membered) cycloalkyl. In some embodiments, R 12 is an optionally substituted C 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) aryl. In some embodiments, R 12 is an optionally substituted C 6-14 In some embodiments, R 12 is an optionally substituted C 6-10 In some embodiments, R 12 is an optionally substituted phenyl. 12 is an optional replacement for C 7-15 In some embodiments, R 12 is an optionally substituted 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, etc.) membered heteroaryl group having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R 12 is an optionally substituted 5-10 membered heteroaryl group having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms. 12 is an optionally substituted 5-membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. 12 is an optionally substituted thienyl.12 It is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclic group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms.

[0380] In some embodiments, R 11 and R 12 are each independently hydrogen, or an optionally substituted group selected from the following: C 1-20 (For example, C 1-15 、C 1-10 、C 1-9 、C 1-8 、C 1-6 , C1, C 2、 C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18、 C 19 、C 20 etc.) fatty groups, C 1-20 (For example, C 1-15 、C 1-10 、C1-9、C 1-8 、C 1-6 , C1, C2, C3, C having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms 4、C5 、C6、C7、C8、C9、C 10 、C 11 、C 12 、C 13 、C 14 、C 15、 C16, C 17 、C 18 、C 19、 C 20etc.) heteroaliphatic, C3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, C11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) heterocyclic, C5-20 (e.g., 5-15, 5-14, 5-10, 5, 6, 7, 8, 9, 10, etc.) heteroatoms , 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heteroaryl; or R 11 and R 12 Together with the carbon atoms to which they are attached, they form optionally substituted C3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) non-aromatic units having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms.

[0381] In some embodiments, R 11 and R 12 are all R, and together with the carbon atoms to which they are attached, form a ring as described herein. In some embodiments, R 11 and R 12 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered ring having 0-5 (e.g., 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, etc.) heteroatoms. In some embodiments, R 11 and R 12 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered ring having 0, 1, 2, or 3 heteroatoms. 11 and R 12 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-14 (e.g., 3-10, 3-9, 5-14, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered alicyclic group. 11 and R12 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered cycloalkyl. 11 and R 12 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-14 (e.g., 3-10, 3-9, 5-14, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered heterocyclyl, wherein the heterocyclyl has 1, 2, or 3 heteroatoms.

[0382] R 13

[0383] In some embodiments, R 13 is R as described herein. In some embodiments, R 13 is R' as described herein. In some embodiments, R 13 is R as described herein. In some embodiments, R 13 is -H.

[0384] In some embodiments, R 13 is an optionally substituted C 1-10 In some embodiments, R 13 is an optionally substituted C 1-6 In some embodiments, R 13 is an optionally substituted C 1-6 alkyl.

[0385] In some embodiments, R 13 -LR', wherein L and R' are each independently as described herein. In some embodiments, L is an optionally substituted divalent linear or branched C 1-6 In some embodiments, L is an optionally substituted divalent linear C 1-6 In some embodiments, L is an optionally substituted -CH 2-。 In some embodiments, L is -CH2-. In some embodiments, L is optionally substituted -CH2-CH2-. In some embodiments, L is -CH2-CH2-. In some embodiments, R' is R as described herein. In some embodiments, R' is not -H. In some embodiments, R' is optionally substituted aryl. In some embodiments, R' is optionally substituted phenyl. In some embodiments, R' is -C(O)OR. In some embodiments, R' is -C(O)OEt. In some embodiments, R 13 is an optionally substituted cycloalkyl C 0-4 In some embodiments, R 13is an optionally substituted aryl C 0-4 In some embodiments, R 13 is an optionally substituted heteroaryl C 0-4 In some embodiments, R 13 is an optionally substituted aryl-S(O)2C 0-4 alkyl.

[0386] R 14

[0387] In some embodiments, R 14 is R as described herein. In some embodiments, R 14 is R' as described herein. In some embodiments, R 14 is R as described herein. In some embodiments, R 14 is -H.

[0388] In some embodiments, R 14 is an optionally substituted C 1-10 In some embodiments, R 14 is an optionally substituted C 1-6 In some embodiments, R 14 is an optionally substituted C 1-6 alkyl.

[0389] In some embodiments, R 14 -LR', wherein L and R' are each independently as described herein. In some embodiments, L is an optionally substituted divalent linear or branched C 1-6 In some embodiments, L is an optionally substituted divalent linear C 1-6 In some embodiments, L is an optionally substituted -CH2-. In some embodiments, L is -CH2-. In some embodiments, L is an optionally substituted -CH2-CH2-. In some embodiments, L is -CH2-CH2-. In some embodiments, R' is R as described herein. In some embodiments, R' is not -H. In some embodiments, R' is an optionally substituted aryl. In some embodiments, R' is an optionally substituted phenyl. In some embodiments, R' is -C(O)OR. In some embodiments, R' is -C(O)OEt. In some embodiments, R 14 is an optionally substituted cycloalkyl C 0-4 In some embodiments, R 14 is an optionally substituted aryl C 0-4 In some embodiments, R 14 is an optionally substituted heteroaryl C 0-4 In some embodiments, R14 is an optionally substituted aryl-S(O)2C 0-4 alkyl.

[0390] R 15

[0391] In some embodiments, R 15 is -LR', wherein L and R' are each independently as described herein. In some embodiments, L is an optionally substituted divalent C 1-6 In some embodiments, -Cy- is an optionally substituted phenylene group. In some embodiments, -Cy- is an optionally substituted 1,2-phenylene group. In some embodiments, L is an optionally substituted divalent C 1-6 In some embodiments, L is an optionally substituted -CH2-(1,2-phenylene)-O-, wherein -CH2- is bonded to the nitrogen atom. In some embodiments, R 15 -LR', wherein L is an optionally substituted C 1-6 alkylene, and R' is as described herein. In some embodiments, R 15 is -LR', wherein L is -CH2-C(O)N(R')-, wherein -CH2- is optionally substituted and is bonded to the nitrogen atom, and each R' is independently as described herein. 15 is -LR', wherein L is -C(R')2-C(O)N(R')-, wherein -C(R')2- is bonded to the nitrogen atom, and each R' is independently as described herein.

[0392] In some embodiments, L is -L"-L x -L y -L z -, wherein L" is a covalent bond or an optionally substituted divalent C having 1-6 heteroatoms 1-7 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; and L x , L y and L zand L are each independently a covalent bond or an optionally substituted methylene group, which is optionally substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L x is a covalent bond, -N(R') or -O-. In some embodiments, L y is a covalent bond, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, or -C(NR')(NR')-. In some embodiments, L z is a covalent bond, -N(R')-, -N(R')O- or -O-. In some embodiments, L x is a covalent bond. In some embodiments, L x is -N(R')-, wherein R' is as described herein. In some embodiments, L x In some embodiments, L y is a covalent bond. In some embodiments, L y In some embodiments, L y In some embodiments, L y is -C(NR')-, wherein R' is as described herein. In some embodiments, L y is -C(O)N(R')-, wherein R' is as described herein. In some embodiments, L y is -C(S)N(R')-, wherein R' is as described herein. In some embodiments, L y is -C(NR')(NR')-, wherein each R' is independently as described herein. In some embodiments, L z is a covalent bond. In some embodiments, L z is -N(R')-, wherein R' is as described herein. In some embodiments, L z is -N(R')O-, wherein R' is as described herein. In some embodiments, L z It is -O-.

[0393] In some embodiments, L" is bound to a nitrogen atom.

[0394] In some embodiments, R 15 is R' as described herein. In some embodiments, R15 is R as described herein. In some embodiments, R 15 is -H.

[0395] In some embodiments, R 15 is an optionally substituted group selected from the following groups: C 1-10 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic, C with 1-10 heteroatoms 3-20 Heterocyclic group 、 C 5-20 Aryl 、 5-20 membered heteroaryl having 1-10 heteroatoms, C 0-10 Fatty-C 3-20 Cycloalkyl, C 0-10 Fatty-C 3-20 Heterocyclic group 、C0-10 Fatty-C 5-20 Aryl, C 0-10 In some embodiments, R 15 is an optionally substituted C 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) aliphatic. In some embodiments, R 15 is an optionally substituted C 1-6 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 is an optionally substituted C 1-2 Fatty-C 5-20 In some embodiments, R 15 is an optionally substituted C 5-20 In some embodiments, R 15 is an optionally substituted 6-14 membered aryl. 15 is an optionally substituted 6-10 membered aryl. 15 is an optionally substituted phenyl. 15 is an optionally substituted 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, etc.) membered heteroaryl group having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R 15In some embodiments, R is 3-cyanophenyl, 4-cyanophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-fluorophenyl, 3-hydroxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 2,3-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-2-fluorophenyl, 5-chloro-2-iodophenyl, 3-chloro-4-methoxyphenyl, 2,4-dimethoxyphenyl, 3-methylsulfonylphenyl, 4-methylsulfonylphenyl, 3-(pyrazol-3-yl)phenyl, 3-(1-methylpyrazol-3-yl)phenyl, 2-morpholinylphenyl, 4-dimethylaminophenyl, or 1-oxo-2,3-dihydro-1H-inden-4-yl. 15 is optionally substituted indazolyl, chloropyridinyl, indolyl, methylindolyl, indazolyl, methylindazolyl, methylbenzo[d]imidazolyl, benzo[d]thiazolyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, benzo[d]thiazolyl, 1H-indazolyl or [1,2,4]triazolo[4,3-a]pyridinyl. In some embodiments, R 15 5-chloropyridin-3-yl, indol-5-yl, 1-methylindol-5-yl, indazol-5-yl, 1-methylindazol-7-yl, 1-methylbenzo[d]imidazol-5-yl, 1-methylbenzo[d]imidazol-6-yl, benzo[d]thiazol-5-yl, benzo[c][1,2,5]oxadiazol-4-yl, benzo[c][1,2,5]thiadiazol-4-yl, benzo[c][1 ,2,5]thiadiazol-5-yl, benzo[d]thiazol-5-yl, benzo[d]thiazol-6-yl, 1-methyl-1H-indazol-5-yl, 1-methyl-1H-indazol-6-yl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, [1,2,4]triazolo[4,3-a]pyridin-7-yl or [1,2,4]triazolo[4,3-a]pyridin-8-yl. In some embodiments, R 15 is an optionally substituted C3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) heterocyclyl having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R 15 is benzo[d][1,3]dioxol-5-yl, 3-oxo-1,3-dihydroisobenzofuran-5-yl, benzo[d][1,3]dioxol-4-yl, 6-iodobenzo[d][1,3]dioxol-5-yl or 2,2-difluorobenzo[d][1,3]dioxol-5-yl.

[0396] R 16

[0397] In some embodiments, R 16 is -LR', wherein L and R' are each independently as described herein. In some embodiments, L is an optionally substituted divalent C 1-6 In some embodiments, -Cy- is an optionally substituted phenylene group. In some embodiments, -Cy- is an optionally substituted 1,2-phenylene group. In some embodiments, L is an optionally substituted divalent C 1-6 In some embodiments, L is an optionally substituted -CH2-(1,2-phenylene)-O-, wherein -CH2- is bonded to the nitrogen atom. In some embodiments, R 16 -LR', wherein L is an optionally substituted C 1-6 alkylene, and R' is as described herein. In some embodiments, R 16 is -LR', wherein L is -CH2-C(O)N(R')-, wherein -CH2- is optionally substituted and is bonded to the nitrogen atom, and each R' is independently as described herein. 16 is -LR', wherein L is -C(R')2-C(O)N(R')-, wherein -C(R')2- is bonded to the nitrogen atom, and each R' is independently as described herein.

[0398] In some embodiments, L is -L"-L x -L y -L z -, wherein L" is a covalent bond or an optionally substituted divalent C having 1-6 heteroatoms 1-7 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; and L x , L y and L zand L are each independently a covalent bond or an optionally substituted methylene group, which is optionally substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L x is a covalent bond, -N(R') or -O-. In some embodiments, L y is a covalent bond, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, or -C(NR')(NR')-. In some embodiments, L z is a covalent bond, -N(R')-, -N(R')O- or -O-. In some embodiments, L x is a covalent bond. In some embodiments, L x is -N(R')-, wherein R' is as described herein. In some embodiments, L x In some embodiments, L y is a covalent bond. In some embodiments, L y In some embodiments, L y In some embodiments, L y is -C(NR')-, wherein R' is as described herein. In some embodiments, L y is -C(O)N(R')-, wherein R' is as described herein. In some embodiments, L y is -C(S)N(R')-, wherein R' is as described herein. In some embodiments, L y is -C(NR')(NR')-, wherein each R' is independently as described herein. In some embodiments, L z is a covalent bond. In some embodiments, L z is -N(R')-, wherein R' is as described herein. In some embodiments, L z is -N(R')O-, wherein R' is as described herein. In some embodiments, L z It is -O-.

[0399] In some embodiments, L" is bound to a nitrogen atom.

[0400] In some embodiments, R 16 is R' as described herein. In some embodiments, R16 is R as described herein. In some embodiments, R 16 is -H.

[0401] In some embodiments, R 16 is an optionally substituted group selected from the following groups: C 1-10 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic, C with 1-10 heteroatoms 3-20 Heterocyclic group, C 5-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, C 0-10 Fatty-C 3-20 Cycloalkyl, C 0-10 Fatty-C 3-20 Heterocyclic group, C 0-10 Fatty-C 5-20 Aryl, C 0-10 In some embodiments, R 16 is an optionally substituted C1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) aliphatic group. In some embodiments, R 16 is an optionally substituted C 1-10 In some embodiments, R 16 is an optionally substituted C 1-6 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 is an optionally substituted aryl C 0-4 In some embodiments, R 16 is an optionally substituted C 1-2 Fatty-C 5-20 In some embodiments, R 16 is an optionally substituted C 5-20 In some embodiments, R 16 is an optionally substituted 6-14 membered aryl. 16 is an optionally substituted 6-10 membered aryl. 16 is an optionally substituted phenyl. 16is an optionally substituted 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, etc.) membered heteroaryl group having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R 16 is an optionally substituted C 3-14 (e.g., 3-10, 4-14, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) alicyclic. In some embodiments, wherein R 16 is an optionally substituted 3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heterocyclyl having 1-6 (e.g., 1-5, 1-4, 1-3, 1, 2, 3, 4, 5, 6, etc.) heteroatoms. In some embodiments, R 16 is an optionally substituted phenyl, thienyl, thiazolyl, tetrahydropyranyl or cyclohexyl. 16 R is 4-chlorophenyl, 4-methoxyphenyl, benzyl, 4-hydroxyphenyl, 3-cyanophenyl, 3-fluorophenyl, 3-hydroxyphenyl, 4-cyanophenyl, 4-fluorophenyl, methyl, cyclopropylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methoxycarbonylcyclohexyl, phenyl, 3-aminophenyl, 4-aminophenyl, 2-fluorophenyl, 4-fluorophenyl, 3-nitrophenyl, 4-nitrophenyl, 1-methoxycarbonylmethoxyphenyl, 3-(2-hydroxyethyl)phenyl, 4-(2-hydroxyacetamido)phenyl, 2-thienyl, 5-thiazolyl, 4-pyridyl or tetrahydro-2H-pyran-4-yl. In some embodiments, R 16 In some embodiments, R 16 for In some embodiments, R 16 In some embodiments, R 16 for

[0402] In some embodiments, R 15 and R 16 is R, and together with the atoms to which they are attached, form an optionally substituted ring as described herein. 15 and R 16Together with the nitrogen atom to which they are attached, they form an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated or unsaturated ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms in addition to the nitrogen atom to which they are attached. In some embodiments, R 15 and R 16 Together with the nitrogen atom to which they are attached, they form an optionally substituted 3-10 membered saturated or partially unsaturated ring having 0-4 heteroatoms in addition to the nitrogen atom to which they are attached.

[0403] R 17

[0404] In some embodiments, R 17 is an optionally substituted 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered monocyclic, bicyclic, or polycyclic aromatic ring having 0-5 heteroatoms. 17 is an optionally substituted 5-6 membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. 17 is an optionally substituted phenyl. 17 is an optionally substituted 8-10 membered bicyclic aromatic ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms. 17 In some embodiments, one or more substituents are independently halogen. In some embodiments, one or more substituents are independently -F or -Cl. In some embodiments, each substituent is independently -F or -Cl. In some embodiments, there are 1 or 2 substituents. In some embodiments, R 17 is phenyl, optionally substituted with 1, 2, or 3 substituents, each of which is independently -F or -Cl. 17 Not replaced.

[0405] R 18

[0406] In some embodiments, R 18 is an optionally substituted 5-20 (e.g., 5-15, 5-14, 5-10, 5-9, 5-6, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered monocyclic, bicyclic, or polycyclic aromatic ring having 0-5 heteroatoms. 18is an optionally substituted 5-6 membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. 18 is an optionally substituted phenyl. 18 is an optionally substituted 8-10 membered bicyclic aromatic ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms. 18 In some embodiments, one or more substituents are independently halogen. In some embodiments, one or more substituents are independently -F or -Cl. In some embodiments, each substituent is independently -F or -Cl. In some embodiments, there are 1 or 2 substituents. In some embodiments, R 18 is phenyl, optionally substituted with 1, 2, or 3 substituents, each of which is independently -F or -Cl. 18 Not replaced.

[0407] L A

[0408] As described in this article, L A is L as described herein. In some embodiments, L A is a covalent bond. In some embodiments, L A is an optionally substituted divalent C 1-10 (For example, C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, L is an aliphatic group or a heteroaliphatic group having 1-6 (e.g., 1, 2, 3, 4, 5, or 6) heteroatoms, wherein one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. A is an optionally substituted divalent C 1-10 (For example, C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10In some embodiments, L is an aliphatic group wherein one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. A is an optionally substituted divalent C 1-6 (e.g., C1, C2, C3, C4, C5, or C6) aliphatic groups, wherein one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L A is an optionally substituted divalent C 1-4 An aliphatic group wherein one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L A is an optionally substituted divalent C 1-2 An aliphatic group wherein one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L A is an optionally substituted divalent C 1-10 (For example, C 1-6,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, the divalent fatty group is linear. In some embodiments, it is branched. In some embodiments, it is saturated. In some embodiments, it is partially unsaturated. In some embodiments, L A is or comprises an optionally substituted -CH2-. In some embodiments, L A is or comprises -CH2-. In some embodiments, L A is or comprises -Cy- as described herein. For example, in some embodiments, L A is an optionally substituted phenylene. A is an optionally substituted 1,4-phenylene group.

[0409] ring

[0410] As described herein, various groups or moieties in the present disclosure are or include rings, such as Ring A, Ring C, Ring P, -Cy-, groups consisting of two or more R groups (and / or groups that can be R, such as R', R", R", s 、R w1 、R w2 、R w3 The ring is formed by combining the ring with its intermediate atoms. Unless otherwise specified, the ring is optionally substituted. Some rings are described as examples herein.

[0411] In some embodiments, the ring is an optionally substituted 3-20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) membered monocyclic, bicyclic, or polycyclic ring having 0-5 (e.g., 0, 1, 2, 3, 4, or 5) heteroatoms. In some embodiments, the ring is monocyclic. In some embodiments, the ring is bicyclic. In some embodiments, the ring is polycyclic. In some embodiments, the ring is saturated. In some embodiments, the ring is partially unsaturated. In some embodiments, the ring is aromatic. In some embodiments, the ring is 3-membered. In some embodiments, the ring is 4-membered. In some embodiments, the ring is 5-membered. In some embodiments, the ring is 6-membered. In some embodiments, the ring is 7-membered. In some embodiments, it is 8-membered. In some embodiments, it is 9-membered. In some embodiments, it is 10-membered. In some embodiments, it is 11-membered. In some embodiments, it is 12-membered. In some embodiments, it is 13-membered. In some embodiments, it is 14-membered. In some embodiments, it is 15-membered. In some embodiments, it is 16-membered. In some embodiments, it is 17-membered. In some embodiments, it is 18-membered. In some embodiments, it is 19-membered. In some embodiments, it is 20-membered. In some embodiments, the ring is bicyclic or polycyclic, comprising two or more monocyclic units. For example, the indole ring is bicyclic and has two monocyclic units, one of which is 5-membered and the other is 6-membered. In some embodiments, each monocyclic unit is independently an optionally substituted 3-10, 3-8, 3-7, 3-6, 4-10, 5-10, 5-9, 5-8, 5-7, 5-6, 3, 4, 5, 6, 7, 8, 9 or 10-membered saturated, partially unsaturated or aromatic ring having 0-4 (e.g., 0, 1, 2, 3 or 4) heteroatoms. In some embodiments, each monocyclic ring unit is independently 3-7 members. In some embodiments, the monocyclic ring unit is 3 members. In some embodiments, the monocyclic ring unit is 4 members. In some embodiments, the monocyclic ring unit is 5 members. In some embodiments, the monocyclic ring unit is 6 members. In some embodiments, the monocyclic ring unit is 7 members. In some embodiments, the monocyclic ring unit is 8 members. In some embodiments, the monocyclic ring unit is 9 members. In some embodiments, the monocyclic ring unit is 10 members. In some embodiments, as described herein, each heteroatom is independently selected nitrogen, oxygen, and sulfur. In some embodiments, the monocyclic ring unit is saturated. In some embodiments, the monocyclic ring unit is partially unsaturated. In some embodiments, the monocyclic ring unit is aromatic. In some embodiments, the monocyclic ring unit is heteroaromatic. In some embodiments, one of the ring atoms in the monocyclic ring unit is a heteroatom.In some embodiments, there are two or more ring atoms in a monocyclic ring unit, each of which is independently a heteroatom. In some embodiments, there are three or more ring atoms in a monocyclic ring unit, each of which is independently a heteroatom. In some embodiments, there are three or more ring atoms in a monocyclic ring unit, each of which is independently a heteroatom. In some embodiments, there are three or more ring atoms in a monocyclic ring unit, each of which is independently a heteroatom.

[0412] In some embodiments, the ring or a monocyclic ring member thereof is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) alicyclic group. In some embodiments, the ring or a monocyclic ring member thereof is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) cycloalkyl group. In some embodiments, the ring or a monocyclic member thereof is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) heteroatoms having 1-6 (e.g., 1, 2, 3, 4, 5, or 6, etc.) heteroatoms. In some embodiments, the ring or its monocyclic ring unit is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) heterocyclic ring having 1-6 (e.g., 1, 2, 3, 4, 5, or 6, etc.) heteroatoms. In some embodiments, the ring or its monocyclic ring unit is an optionally substituted phenyl ring. In some embodiments, the ring or its monocyclic ring unit is an optionally substituted 5-membered heteroaromatic ring having 1-4 heteroatoms. In some embodiments, the ring or its monocyclic ring unit is an optionally substituted 6-membered heteroaromatic ring having 1-4 heteroatoms. In some embodiments, at least one heteroatom is nitrogen. In some embodiments, each heteroatom is independently selected from nitrogen, oxygen, and sulfur.

[0413] Ring A

[0414] In some embodiments, Ring A is an optionally substituted 3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered monocyclic, bicyclic, or polycyclic ring having 0-10 (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, Ring A is an optionally substituted ring as described herein.

[0415] In some embodiments, Ring A is an optionally substituted aromatic ring having 0-6 (e.g., 1-6, 1-4, 1-3, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms. In some embodiments, Ring A is or comprises an optionally substituted monocyclic aromatic ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring A is an optionally substituted phenyl group. In some embodiments, Ring A is an optionally substituted pyridinyl group. In some embodiments, Ring A is an optionally substituted pyrazolyl group. In some embodiments, Ring A is phenyl. In some embodiments, Ring A is an optionally substituted tetrahydro-2H-pyranyl group. In some embodiments, Ring A is a tetrahydro-2H-pyranyl group. In some embodiments, Ring A is or comprises an optionally substituted monocyclic non-aromatic ring unit having 0-6 heteroatoms. In some embodiments, Ring A is an optionally substituted piperidinyl group. In some embodiments, Ring A is an optionally substituted Where "*" indicates the same as L A In some embodiments, Ring A is optionally substituted Where "*" indicates the same as L A In some embodiments, Ring A is optionally substituted Where "*" indicates the same as L A In some embodiments, ring A is Where "*" indicates the same as L A Bonded atoms.

[0416] In some embodiments, Ring A and one or more R s Bonding, each R s In some embodiments, R s is an optionally substituted C 1-20 In some embodiments, R s is an optionally substituted C having 1 to 10 heteroatoms 1-20 In some embodiments, R s is an optionally substituted heterocyclic group C 0-4In some embodiments, R s In some embodiments, Rs is -C(O)N(R')2 wherein each R' is independently as described herein. s is -S(O)N(R') wherein R' is as described herein. In some embodiments, R s is -S(O)2N(R')2 wherein each R' is independently as described herein. In some embodiments, R s Optional replacement In some embodiments, R s Optional replacement

[0417] In some embodiments, Ring A is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms.

[0418] Ring B

[0419] In some embodiments, Ring B is an optionally substituted 3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered monocyclic, bicyclic, or polycyclic ring having 0-6 (e.g., 1-6, 1-5, 1-4, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms. In some embodiments, Ring B is an optionally substituted ring as described herein. In some embodiments, Ring B is an optionally substituted 3-8 (e.g., 4-8, 5-8, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered monocyclic ring having 0-6 (e.g., 1-6, 1-5, 1-4, 1-3, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms. In some embodiments, Ring B is an optionally substituted 5-6 membered partially unsaturated ring having 1, 2, or 3 heteroatoms. In some embodiments, Ring B is an optionally substituted 5-6 membered partially unsaturated ring having 1, 2, or 3 heteroatoms. In some embodiments, Ring B is The “*” indicates Bonded atoms; X 1 、X 2 、X 3 and X 4 are each independently -O-, -S-, -N(-)-, -C(-)= or optionally substituted -CH(-)-, -CH= or -NH-, wherein X 1 、X 2 、X 3 and X 4At least one of -N(-)-, -C(-)= or -CH(-)- is optionally substituted. In some embodiments, Ring B is The “*” indicates Bonded atoms; X 1 、X 3 and X 4 are each independently -O-, -S-, or optionally substituted -CH= or -NH-, and X 2 is -N(-)-, -C(-)= or is optionally substituted -CH(-)-.

[0420] In some embodiments, X 1 In some embodiments, X is -O-. 1 In some embodiments, X 1 for - N(-)-. In some embodiments, X 1 In some embodiments, X 1 is optionally substituted -CH(-)-. In some embodiments, X 1 is an optionally substituted -CH=. In some embodiments, X 1 is optionally substituted -NH-.

[0421] In some embodiments, X 2 In some embodiments, X is -O-. In some embodiments, X2 is -S-. In some embodiments, X 2 In some embodiments, X 2 In some embodiments, X 2 is optionally substituted -CH(-)-. In some embodiments, X 2 is an optionally substituted -CH=. In some embodiments, X 2 is optionally substituted -NH-.

[0422] In some embodiments, X 3 In some embodiments, -O-. In some embodiments, X 3 In some embodiments, X 3 In some embodiments, X 3 In some embodiments, X 3 In some embodiments, X 3 is an optionally substituted -CH=. In some embodiments, X 3 is optionally substituted -NH-.

[0423] In some embodiments, X 4 In some embodiments, X is -O-. In some embodiments, X4 is -S-. In some embodiments, X 4 for -N (-)-. In some embodiments, X 4 In some embodiments, X 4 In some embodiments, X 4 is an optionally substituted -CH=. In some embodiments, X 4 is optionally substituted -NH-.

[0424] In some embodiments, Ring B is an optionally substituted 5-8 membered (e.g., 5, 6, 7, or 8 membered) monocyclic ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring B is an optionally substituted 5-8 membered (e.g., 5, 6, 7, or 8 membered) monocyclic ring having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring B is an optionally substituted 5-membered ring having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring B is an optionally substituted 6-membered ring having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring B is an optionally substituted 5-membered ring having 2 heteroatoms. In some embodiments, Ring B is an optionally substituted 6-membered ring having 2 heteroatoms. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is sulfur. For example, in some embodiments, Ring B is optionally substituted In some embodiments, Ring B is

[0425] Ring C

[0426] In some embodiments, Ring C is an optionally substituted 3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered monocyclic, bicyclic, or polycyclic ring having 0-6 (e.g., 1-6, 1-5, 1-4, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms. In some embodiments, Ring C is an optionally substituted ring as described herein.

[0427] In some embodiments, Ring C is an optionally substituted 5-8 (e.g., 5, 6, 7, or 8) membered monocyclic non-aromatic ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring C is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered monocyclic saturated ring having 0-4 (e.g., 1-4, 1-3, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring C is an optionally substituted 5-10 (e.g., 5-9, 5, 6, 7, 8, 9, 10, etc.) membered monocyclic saturated ring having 1 or 2 nitrogen atoms. In some embodiments, Ring C is an optionally substituted 5-membered monocyclic saturated ring having two nitrogen atoms. In some embodiments, Ring C is an optionally substituted 6-membered monocyclic saturated ring having two nitrogen atoms. In some embodiments, Ring C is an optionally substituted 7-membered monocyclic saturated ring having two nitrogen atoms. In some embodiments, Ring C is an optionally substituted 8-membered monocyclic saturated ring having two nitrogen atoms. In some embodiments, Ring C is an optionally substituted 9-membered monocyclic saturated ring having two nitrogen atoms. In some embodiments, Ring C is an optionally substituted 10-membered monocyclic saturated ring having two nitrogen atoms. In some embodiments, Ring C is bonded to the rest of the compound through the two nitrogen atoms. In some embodiments, Ring C is an optionally substituted divalent piperidinyl. In some embodiments, Ring C is an optionally substituted divalent piperazinyl. In some embodiments, Ring C is an optionally substituted divalent 2,7-diazaspiro[3.5]nonyl.

[0428] In some embodiments, Ring C has a structure such that the compound of formula E or a salt thereof is a compound of formula F or a salt thereof

[0429] Ring P

[0430] As described herein, as described herein, Ring P is an optionally substituted 3-20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) membered monocyclic, bicyclic, or polycyclic ring having 0-5 (e.g., 0, 1, 2, 3, 4, or 5) heteroatoms. In some embodiments, Ring P is monocyclic. In some embodiments, Ring P is bicyclic. In some embodiments, Ring P is polycyclic. In some embodiments, Ring P is saturated. In some embodiments, Ring P is partially unsaturated. In some embodiments, Ring P is aromatic. In some embodiments, Ring P is 3-membered. In some embodiments, it is 4-membered. In some embodiments, it is 5-membered. In some embodiments, it is 6-membered. In some embodiments, it is 7-membered. In some embodiments, it is 8-membered. In some embodiments, it is 9-membered. In some embodiments, it is 10-membered. In some embodiments, it is 11-membered. In some embodiments, it is 12-membered. In some embodiments, it is 13-membered. In some embodiments, it is 14-membered. In some embodiments, it is 15-membered. In some embodiments, it is 16-membered. In some embodiments, it is 17-membered. In some embodiments, it is 18-membered. In some embodiments, it is 19-membered. In some embodiments, it is 20-membered. In some embodiments, the monocyclic unit in Ring P is an optionally substituted 5-6-membered aromatic ring having 0-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms and comprising Z and Y as ring atoms. In some embodiments, such an aromatic ring is 5-membered. In some embodiments, it is a 6-membered ring. In some embodiments, it is substituted. In some embodiments, it is unsubstituted. In some embodiments, such an aromatic ring has one heteroatom; in some embodiments, two heteroatoms; in some embodiments, three heteroatoms; in some embodiments, four heteroatoms; in some embodiments, at least one heteroatom is nitrogen. In some embodiments, Ring P is an optionally substituted benzene ring. In some embodiments, Ring P is an optionally substituted pyrrole ring. In some embodiments, Ring P is an optionally substituted indole ring.

[0431] In some embodiments, each monocyclic ring unit in Ring P is independently an optionally substituted 3-10, 3-8, 3-7, 3-6, 4-10, 5-10, 5-9, 5-8, 5-7, 5-6, 3, 4, 5, 6, 7, 8, 9 or 10-membered saturated, partially unsaturated or aromatic ring having 0-4 (e.g., 0, 1, 2, 3 or 4) heteroatoms. In some embodiments, each monocyclic ring unit is independently 3-7 members. In some embodiments, the monocyclic ring unit is 3 members. In some embodiments, the monocyclic ring unit is 4 members. In some embodiments, the monocyclic ring unit is 5 members. In some embodiments, the monocyclic ring unit is 6 members. In some embodiments, the monocyclic ring unit is 7 members. In some embodiments, the monocyclic ring unit is 8 members. In some embodiments, the monocyclic ring unit is 9 members. In some embodiments, the monocyclic ring unit is 10 members. In some embodiments, each heteroatom is independently selected as nitrogen, oxygen and sulfur as described herein. In some embodiments, the monocyclic ring unit is saturated. In some embodiments, the monocyclic unit is partially unsaturated. In some embodiments, the monocyclic unit is aromatic. In some embodiments, the monocyclic unit is heteroaromatic. In some embodiments, one of the ring atoms in the monocyclic unit is a heteroatom. In some embodiments, there are two or more ring atoms in the monocyclic unit, each of which is independently a heteroatom. In some embodiments, there are three or more ring atoms in the monocyclic unit, each of which is independently a heteroatom. In some embodiments, there are three or more ring atoms in the monocyclic unit, each of which is independently a heteroatom. In some embodiments, there are three or more ring atoms in the monocyclic unit, each of which is independently a heteroatom. In some embodiments, there are three or more ring atoms in the monocyclic unit, each of which is independently a heteroatom.

[0432] R s

[0433] In some embodiments, R s is R as described herein. In some embodiments, R s is R' as described herein. In some embodiments, R s is R as described herein.

[0434] In some embodiments, R s is -H. In some embodiments, R s Not -H.

[0435] In some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R sIn some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R s is an optionally substituted amino acid. In some embodiments, R s is an optionally substituted amine. In some embodiments, R s is an optionally substituted amide. s is an optionally substituted carbamate. s is an optionally substituted ester. In some embodiments, R s is an optionally substituted ether. In some embodiments, R s is an optionally substituted carboxylic acid. s In some embodiments, R s In some embodiments, R s is an optionally substituted thioester. s is an optionally substituted thioether. s is an optionally substituted sulfate. In some embodiments, R s is an optionally substituted sulfonamide. s is an optionally substituted sulfoxide. s is an optionally substituted sulfonate. In some embodiments, R s is an optionally substituted sulfone. s is an optionally substituted alkylsulfonyl. s is an optionally substituted arylsulfonyl. In some embodiments, when there are two or more R s When , they may be the same or different and are each independently as described herein.

[0436] In some embodiments, there is one R bonded to a moiety (eg, a ring). s In some embodiments, there are two or more R bonded to a moiety (eg, ring). s , where each R s In some embodiments, R s In some embodiments, R s In some embodiments, Rs In some embodiments, R s is -N(R')2. In some embodiments, each R s are independently -H, -N(R)2, -OR, -CN and are optionally substituted C 1-6 In some embodiments, R s -N(R)2, wherein each R is independently -H or an optionally substituted C 1-20 In some embodiments, R s -N(R)2, wherein each R is independently -H or an optionally substituted C 1-10 In some embodiments, R s is -NHR, wherein each R is independently -H or an optionally substituted C 1-20 In some embodiments, R s is -NHR, wherein each R is independently -H or an optionally substituted C 1-10 In some embodiments, each R s In some embodiments, R s is an optionally substituted C 1-6 In some embodiments, R s is an optionally substituted methyl group. s is methyl optionally substituted by 1-3 fluorine. s In some embodiments, R S为可选取代的 In some embodiments, R s One occurrence of is for optional replacement In some embodiments, R s One occurrence of is para relative to the position where Ring A is attached to the rest of the compound. In some embodiments, each R s is independently halogen, or an optionally substituted C 1-20 Fatty acid or C 1-20 In some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R s In some embodiments, R s is -S(O)2-CH3.

[0437] R s6

[0438] In some embodiments, R s6 is R as described herein s In some embodiments, R s6 is R as described herein. In some embodiments, R s6 is R' as described herein. In some embodiments, R s6 is R as described herein.

[0439] In some embodiments, R s6 is -H. In some embodiments, R s6 is not -H. In some embodiments, R s6 In some embodiments, R s6 In some embodiments, R s6 In some embodiments, R s6 In some embodiments, R s6 In some embodiments, R s6 In some embodiments, each R s6 is independently halogen or -CN. In some embodiments, each R s6 are independently -F or -Cl.

[0440] R s7

[0441] In some embodiments, R s7 is R as described herein s In some embodiments, R s7 is R as described herein. In some embodiments, R s7 is R' as described herein. In some embodiments, R s7 is R as described herein.

[0442] In some embodiments, R s7 is -H. In some embodiments, R s7 is not -H. In some embodiments, R s7 In some embodiments, R s7 In some embodiments, R s7 In some embodiments, R s7 In some embodiments, R s7 In some embodiments, R s7 In some embodiments, each R s7 is independently halogen or -CN. In some embodiments, each R s7are independently -F or -Cl.

[0443] R 8a

[0444] In some embodiments, R 8a R s In some embodiments, R 8a is an optionally substituted C 1-6 In some embodiments, R 8a is an optionally substituted methyl group.

[0445] In some embodiments, R 8a is -LR', wherein each variable is independently described as described herein. In some embodiments, R' is an optionally substituted 6-10 membered aryl. In some embodiments, R' is an optionally substituted phenyl. In some embodiments, R 8a In some embodiments, L is -LR, wherein each variable is independently described as described herein. In some embodiments, L is optionally substituted -CH2-. In some embodiments, L is -CH2-. In some embodiments, R is not -H. In some embodiments, R is optionally substituted phenyl. For example, in some embodiments, R is 2-chlorophenyl.

[0446] In some embodiments, R 8a for wherein each variable is independently as described herein. In some embodiments, L A is an optionally substituted -CH2-. In some embodiments, L A -CH 2- In some embodiments, Ring A is an optionally substituted phenylene. In some embodiments, Ring A is an optionally substituted 1,2-phenylene. In some embodiments, q is 0. In some embodiments, q is 1-10. In some embodiments, q is 1. In some embodiments, each R m are independently R as described herein s In some embodiments, R m In some embodiments, each R m In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, each R is halogen. mIn some embodiments, each substituent on Ring A (if any) is independently halogen. In some embodiments, it is independently -F or -Cl. In some embodiments, it is -Cl.

[0447] R m

[0448] In some embodiments, R m is R as described herein s In some embodiments, R m is R as described herein. In some embodiments, R m is R' as described herein. In some embodiments, R m is R as described herein.

[0449] In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, R m In some embodiments, R m is an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl, and arylsulfonyl.

[0450] L R

[0451] In some embodiments, L R for wherein each variable is independently as described herein. In some embodiments, L R for Where "*" indicates the same as R 4 In some embodiments, L R for Where "*" indicates the same as R 4 The atoms to which the ring is bonded are as described herein. For example, in some embodiments, L R Optional replacement The nitrogen atom and L b bonding.

[0452] In some embodiments, L R is an optionally substituted bicyclic or tricyclic ring, wherein the monocyclic ring is an optionally substituted 6-membered heteroaromatic ring containing =NC*(-)=N-, wherein "*" represents the same as R 4 In some embodiments, L b In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement Where "*" indicates the same as R 4 In some embodiments, L R Optional replacement The nitrogen atom and R 4 In some embodiments, the rings can exist in tautomeric forms (eg, -C(OH)= and -C(O)-).

[0453] In some embodiments, L R is -Cy- as described herein.

[0454] In some embodiments, L R for where R s1 、R s2 and R s3 Each independently is R as described herein s In some embodiments, L R for where R s1 、R s2 and R s3 Each independently is R as described herein s In some embodiments, the nitrogen atom is b In some embodiments, L R for Each variable is independently as described herein, and "*" indicates the same as R 4 In some embodiments, LR for Each variable is independently as described herein, and "*" indicates the same as R 4 In some embodiments, L R for Each variable is independently as described herein, and "*" indicates the same as R 4 Bonded atoms.

[0455] In some embodiments, Z' is -C(R s4 ), where R s4 R s In some embodiments, Z' is -C(R s4 ), where R s4 In some embodiments, Z' is -C(R s4 ), where R s4 is R as described herein. In some embodiments, R s4 is an optionally substituted group selected from C 1-10 (For example, C 1-9 、C 1-8、 C 1-6 、C 2-10 、C 3-10 、C 4-10 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 etc.) aliphatic groups, C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 、C 2-10 、C 3-10 、C 4-10 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 , 1-4, 1, 2, 3, 4, 5, etc.) heteroatoms, 6-10 (e.g., 6, 7, 8, 9, 10, etc.) membered aryl, 5-10 (e.g., 5, 6, 7, 8, 9, 10, etc.) membered heteroaryl having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms, and 3-10 (e.g., 4-10, 5-10, 5-7, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclyl having 1-5 (e.g., 1-4, 2-5, 1, 2, 3, 4, 5, etc.) heteroatoms. In some embodiments, Rs4 为 -H. In some embodiments, R s4 In some embodiments, R s4 In some embodiments, R s4In some embodiments, R s4 In some embodiments, R s4 In some embodiments, R s4 In some embodiments, R s4 is -N(R')2, wherein each R' is independently as described herein. In some embodiments, R s4 In some embodiments, Rs4 is -N(R')2, wherein each R' is independently -H or an optionally substituted C1-6 aliphatic group. 1-6 In some embodiments, R s4 is an optionally substituted -NH2. s4 In some embodiments, R s4 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 、C 2-10 、C 3-10 、C 4-10 、C1、C2、C3、C4、C 5、 C6, C7, C8, C9, C 10 In some embodiments, R s4 is an optionally substituted C1-10 (e.g., C 1-9、 C 1-8 、C 1-6 、C 2-10、 C 3-10 、C 4-10 、C 1、C2 , C3, C4 、 C 5、 C6, C7 、 C8, C9, C 10 In some embodiments, R s4 is an optionally substituted 3-10 (e.g., 3-9, 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclyl having 1-5 (e.g., 1-4, 2-5, 1, 2, 3, 4, 5, etc.) heteroatoms. In some embodiments, R s4 Optional replacement

[0456] In some embodiments, Z" is -C(R s5 ), where R s5 is R as described herein sIn some embodiments, Z" is -C(R s5 ), where R s5 is R' as described herein. In some embodiments, Z" is -C(R s5 ), where R s5 is R as described herein. In some embodiments, R s5 is -H. In some embodiments, R s5 In some embodiments, R s5 In some embodiments, R s5 In some embodiments, R s5 In some embodiments, R s5 In some embodiments, R s5 In some embodiments, R s5 is -N(R')2, wherein each R' is independently as described herein. In some embodiments, R s5 is -N(R')2, wherein each R' is independently -H or an optionally substituted C 1-6 In some embodiments, R s5 -N(R')2, wherein each R' is independently an optionally substituted C 1-6 In some embodiments, R s5 is an optionally substituted -NH2. s5 In some embodiments, R s5 is an optionally substituted C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 、C 2-10 、C 3-10 、C 4-10 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, R s5 is an optionally substituted C1-10 (e.g., C 1-9、C 1-8 、 C 1-6 、C 2-10、 C 3-10 、C 4-10 、C 1、C2 , C3, C4 、 C 5、 C6, C7 、 C8, C9, C 10 In some embodiments, Rs5 is an optionally substituted 3-10 (e.g., 3-9, 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclic group having 1-5 (e.g., 1-4, 2-5, 1, 2, 3, 4, 5, etc.) heteroatoms. s5 is -OR, wherein R is as described herein. In some embodiments, R s5 -OR, wherein R is an optionally substituted C 1-6 In some embodiments, Rs5 为 -OH. In some embodiments, R s5 It is -OCH3.

[0457] In some embodiments, R s1 R s In some embodiments, R s1 is R' as described herein. In some embodiments, R s1 is R as described herein. In some embodiments, R s1 is -N(R')2, wherein each R' is independently as described herein. In some embodiments, R s1 is -N(R')2, wherein each R' is independently -H or an optionally substituted C 1-6 In some embodiments, R s1 -NHR', wherein R' is an optionally substituted C 1-6 In some embodiments, R s1 -NHR', wherein R' is -H or an optionally substituted C 1-6 In some embodiments, R s1 is an optionally substituted -NH2. s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 is -NHCH(CH3)2. In some embodiments, R s1 is -N(CH3)2. In some embodiments, R s1 for In some embodiments, R s1 for In some embodiments, R s1In some embodiments, R s1 In some embodiments, R s1 is -NHCH2C=CH. In some embodiments, R s1 In some embodiments, R s1 Optional replacement In some embodiments, R s1 for In some embodiments, R s1 for In some embodiments, R s1 is -OR' wherein R' is as described herein. In some embodiments, R s1 is -OR, wherein R is as described herein. In some embodiments, R s1 -OR, wherein R is an optionally substituted C 1-6 In some embodiments, R s1 In some embodiments, when R s1 When -OH, the ring or compound can exist in tautomeric forms. In some embodiments, -C(OH)= can exist as -C(O)-. In some embodiments, -C(OH)=N- can exist as -C(O)-NH-. In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 In some embodiments, R s1 is -CHF2.

[0458] In some embodiments, R s4 Optional replacement In some embodiments, R s4 for In some embodiments, R s4 Optional replacement In some embodiments, R s4 for In some embodiments, R s4 Optional replacement In some embodiments, R s4 for In some embodiments, R s4 is -N(R')2. In some embodiments, R s4 -NH 2。 In some embodiments, R s4 In some embodiments, R s4 is -O(CH(CH3)2. In some embodiments, R s4 is an optionally substituted C 1-6 In some embodiments, R s4 For optional -OR o Substituted C 1-6 Aliphatic group, where R o -H or C 1-6 In some embodiments, R s4 It is C(CH3)2OH.

[0459] In some embodiments, R s2 R s In some embodiments, R s2 is R' as described herein. In some embodiments, R s2 is R as described herein. In some embodiments, R s2 is -H. In some embodiments, R s2 is an optionally substituted C 1-6 In some embodiments, R s2 is an optionally substituted C 1-6 alkyl.

[0460] In some embodiments, R s3 R s In some embodiments, R s3 is R' as described herein. In some embodiments, R s3 is R as described herein. In some embodiments, R s3 is -H. In some embodiments, R s3 is an optionally substituted C 1-6 In some embodiments, R s3 is an optionally substituted C 1-6 alkyl.

[0461] In some embodiments, R s2 and R s3 Each is independently R as described herein. In some embodiments, both are -H. In some embodiments, each is independently -H or C 1-6 In some embodiments, each independently is an optionally substituted C 1-6In some embodiments, each is independently an optionally substituted C1-6 alkyl. s2 and R s3 In some embodiments, R s2 and R s3 In some embodiments, R s2 and R s3 In some embodiments, R s2 -H, R s3 It is a methyl group.

[0462] In some embodiments, R s2 and R s3 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-10 (e.g., 3-9, 3-8, 4-10, 5-10, 5-9, 5-8, 5-7, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated or partially unsaturated ring having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, R s2 and R s3 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-6 membered saturated or partially unsaturated carbocyclic ring. s2 and R s3 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-6 membered saturated or partially unsaturated ring having 1-4 heteroatoms. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur. In some embodiments, the ring formed is saturated. In some embodiments, the ring formed is partially unsaturated. In some embodiments, the ring formed is 3-membered. In some embodiments, the ring formed is 4-membered. In some embodiments, the ring formed is 5-membered. In some embodiments, the ring formed is 6-membered. In some embodiments, R s2 and R s3 Together with the carbon atoms to which they are attached, they form an optionally substituted cyclopropyl group. s2 and R s3 Together with the carbon atom to which they are attached, they form a cyclopropyl group. s2 and R s3 Together with the carbon atoms to which they are attached, they form a cyclobutyl ring. s2 and R s3 Together with the carbon atom to which they are attached, they form a cyclopentyl ring. s2 and R s3 Together with the carbon atoms to which they are attached, they form a cyclohexyl ring. s2and R s3 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-6 membered saturated ring having an oxygen atom. s2 and R s3 Together with the carbon atom to which they are attached, they form an optionally substituted In some embodiments, R s2 and R s3 Together with the carbon atoms to which they are attached, they form In some embodiments, R s2 and R s3 与 The carbon atoms to which they are attached In some embodiments, R s2 and R s3 Together with the carbon atoms to which they are attached, they form

[0463] In some embodiments, L R is L as described herein. In some embodiments, L R In some embodiments, L R is an optionally substituted -CH=CH-. In some embodiments, L R In some embodiments, L R In some embodiments, L R is -C(NR")-, wherein R" is as described herein. In some embodiments, L R is a covalent bond. In some embodiments, L R is L as described herein. In some embodiments, L R is an optionally substituted C 1-6 (For example, C 1-4 , C1, C2, C3, C4, C5, C6, etc.) alkylene. In some embodiments, L R is an optionally substituted C 2-6 (e.g., C2, C3, C4, C5, C6, etc.) alkenylene. In some embodiments, L R is an optionally substituted C 2-6 (e.g., C2, C3, C4, C5, C6, etc.) alkynylene. In some embodiments, L R is -Cy- as described herein. In some embodiments, L R is an optionally substituted C 3-10 (For example, C 4-10 、C 5-10 , C3, C 4、 C5, C6, C7, C8, C9, C 10In some embodiments, L R is an optionally substituted C 6-14 (e.g., C6, C 10 In some embodiments, L R is an optionally substituted C 7-15 In some embodiments, L R is an optionally substituted 5-14 (e.g., 5-10, 5-9, 5, 6, 9, 10, 14, etc.) membered heteroarylene group having 1-5 (e.g., 1-2, 1, 2, 3, 4, 5, etc.) heteroatoms. In some embodiments, L R is an optionally substituted 3-14 (e.g., 3-20, 5-10, 5-10, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered heteroatom or heterocyclylene having 1-5 (e.g., 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms.

[0464] Ring L

[0465] As described herein, in some embodiments, ring L is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring as described herein, having 0-10 heteroatoms. In some embodiments, ring L is a ring as described herein, for example, in the ring A portion. In some embodiments, ring L is or comprises an optionally substituted single aromatic ring unit having 0-4 (e.g., 0-3, 2-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, ring L is or comprises an optionally substituted single aromatic ring unit having 1-4 heteroatoms. In some embodiments, ring L comprises -N=C*(-)-, wherein "*" represents an optionally substituted single aromatic ring unit with R 4 In some embodiments, ring L comprises -N=C*(-)-N=, wherein "*" represents an atom bonded to R 4 In some embodiments, ring L is In some embodiments, Ring L is Ring L is or contains an optionally substituted bicyclic aromatic unit having 0-6 heteroatoms.

[0466] In some embodiments, ring L is an optionally substituted 5-20 (e.g., 5-15, 5-10, 5-9, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered monocyclic, bicyclic, or polycyclic ring having 1-10 (e.g., 2-10, 3-10, 2-5, 2-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, ring L is monocyclic. In some embodiments, ring L is bicyclic. In some embodiments, ring L is polycyclic. In some embodiments, ring L is or comprises an optionally substituted 6-membered monoaromatic ring unit having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Ring L is or comprises an optionally substituted monocyclic non-aromatic ring unit having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. 4 The combined monocyclic unit is an optionally substituted 5-6 membered heteroaromatic ring having 1-5 (e.g., 1-4, 2-5, 2-4, 1, 2, 3, 4, 5, etc.) heteroatoms. 4 The bonded monocyclic unit is an optionally substituted 6-membered heteroaromatic ring having 1-5 (e.g., 1-4, 2-5, 2-4, 1, 2, 3, 4, 5, etc.) heteroatoms. 4 The bonded monocyclic unit is an optionally substituted 6-membered heteroaromatic ring with 2-5 (e.g., 2-4, 2, 3, 4, 5, etc.) heteroatoms. In some embodiments, it has at least one nitrogen atom. In some embodiments, it has at least two nitrogen atoms. In some embodiments, ring L is bicyclic or polycyclic. In some embodiments, ring L comprises an optionally substituted partially unsaturated monocyclic unit. In some embodiments, ring L comprises a 3-10 (e.g., 5-10, 5-10, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered partially unsaturated ring having 0-6 (e.g., 1-6, 1-3, 0, 1, 2, 3, 4, 5, 6, etc.) heteroatoms. In some embodiments, ring L comprises a 5-6 membered partially unsaturated ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, the unsaturation is due to fusion with an aromatic ring unit (e.g., a monocyclic unit bonded to R4). In some embodiments, in addition to R 4In addition to the bonded monocyclic units, Ring L further comprises a monocyclic unit, which is a monocyclic aromatic ring unit. In some embodiments, this monocyclic aromatic unit is an optionally substituted 5-6 membered aromatic ring having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, this monocyclic aromatic unit is an optionally substituted 5-membered heteroaryl having 1-4 (e.g., 1-4, 1-3, 1-2, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, at least one heteroatom is nitrogen. In some embodiments, each heteroatom is nitrogen.

[0467] In some embodiments, Ring L is or comprises an optionally substituted bicyclic aromatic unit having 0-6 heteroatoms. In some embodiments, Ring L is or comprises an optionally substituted 9-membered bicyclic aromatic unit having 0-6 heteroatoms.

[0468] In some embodiments, Ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 Bonded Atoms In some embodiments, Ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted Where "*" indicates the same as R 4 In some embodiments, ring L is optionally substituted The nitrogen atom and R 4 bonding.

[0469] In some embodiments, ring L is not bound to R 4 The combined single ring unit and L b combination.

[0470] L b

[0471] In some embodiments, L b is L as described herein. In some embodiments, L b -L b1 -L b2 -L b3 -L b4 -L b5 -, where L b1 , L b2 , L b3 , L b4 and L b5 Each is independently L' as described herein. In some embodiments, L b1 Bonded to ring L.

[0472] In some embodiments, L b is -C(R')2-N(R')-C(O)-, wherein each R' is independently as described herein. In some embodiments, L b is -C(R')2-N(R')-C(O)-C≡C-, wherein each R' is independently as described herein. In some embodiments, L bis -C(R')2-N(R')-C(O)-C(R')2-OS(O)2-, wherein each R' is independently as described herein. In some embodiments, L b is -C(R')2-N(R')-C(O)-C(R')2-OS(O)2-, wherein each R' is independently as described herein. In some embodiments, -C(R')2- is substituted with L R In some embodiments, L b is -CH2-N(R')-C(O)-, wherein -CH2- is optionally substituted and R' is as described herein. In some embodiments, L b is -CH2-N(R')-C(O)-C≡C-, wherein -CH2- is optionally substituted and R' is as described herein. In some embodiments, L b is -CH2-N(R')-C(O)-C(R')2-OS(O)2-, wherein -CH2- is optionally substituted and each R' is independently as described herein. In some embodiments, L b is -CH2-N(R')-C(O)-C(R')2-OS(O)2-, wherein -CH2- is optionally substituted and each R' is independently as described herein. In some embodiments, -CH2- and L R In some embodiments, -L R -L b - does not contain -C(R')2-N(R')-C(O)-C≡C-, wherein each R' is independently as described herein. In some embodiments, -L R -L b - does not contain -C(R')2-N(R')-C(O)-C(R')2-OS(O)2- wherein each R' is independently as described herein. In some embodiments, -L R -L b - does not contain -C(R')2-N(R')-C(O)-C(R')2-OS(O)2- wherein each R' is independently as described herein. In some embodiments, -L R -L b -does not contain -C(R')2-N(R')-C(O)-C(R')2- wherein each R' is independently as described herein. In some embodiments, -C(R')2- and R 4 bonding.

[0473] In some embodiments, L b is -Cy- as described herein.

[0474] In some embodiments, L b is an optionally substituted phenyl group. In some embodiments, Lb is phenyl optionally substituted with -OMe or halogen (e.g., -F, -Cl, -Br, or -I). b In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, L b In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, R b is -H, and L b for Where "*" indicates the same as L R In some embodiments, R b is -H, and L b for Where "*" indicates the same as L R In some embodiments, L b for Where "*" indicates the same as L R connection point.

[0475] In some embodiments, L b is a divalent optionally substituted 5- or 6-membered heteroaromatic ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms. b is a divalent optionally substituted 5- or 6-membered heteroaromatic ring having 1 nitrogen heteroatom. b is a divalent optionally substituted pyridyl. b is a divalent pyridyl group, optionally substituted by halogen (e.g., (-F, -Cl, -Br or -I) or -OR o Substituted, where R o C 1-6 In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, L b In some embodiments, Lb for Where "*" indicates the same as L R In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, L b is a divalent optionally substituted 5- or 6-membered heteroaromatic ring having 2 nitrogen heteroatoms. b is a divalent optionally substituted pyrimidinyl. b In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, L b is a divalent optionally substituted pyridazinyl. In some embodiments, L b In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, L b is a divalent optionally substituted 5- or 6-membered heteroaromatic ring having 1 nitrogen and 1 sulfur heteroatom. b is a divalent optionally substituted thiazolyl group. In some embodiments, L b In some embodiments, L b for Where "*" indicates the same as L R connection point.

[0476] In some embodiments, L b is a divalent optionally substituted 6 to 12 membered cycloalkyl. b is a divalent optionally substituted 5- to 6-membered cycloalkyl. b is a divalent optionally substituted 6-membered cycloalkyl. b In some embodiments, Lb is a divalent optionally substituted 5-membered cycloalkyl. In some embodiments, L b is a divalent cyclohexyl group, optionally substituted by C 1-6 In some embodiments, L b for

[0477] In some embodiments, L bis a divalent optionally substituted 6- to 12-membered heterocyclyl having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms. b is a divalent optionally substituted 6- to 12-membered heterocyclyl having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, or sulfur. In some embodiments, L b is a divalent optionally substituted 9- to 10-membered heteroaryl ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, or sulfur. In some embodiments, L b is a divalent optionally substituted 9-membered heteroaryl ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, or sulfur. In some embodiments, L b is an optionally substituted divalent 9-membered heteroaryl ring having 1 oxygen heteroatom.

[0478] In some embodiments, L b is a divalent optionally substituted 2,3-dihydrobenzofuranyl. In some embodiments, L b is a divalent 2,3-dihydrobenzofuranyl group, optionally substituted by C 1-6 In some embodiments, L b is a divalent 2,3-dihydrobenzofuranyl. In some embodiments, L b for Where "*" indicates the same as L R In some embodiments, R b is -H, and L b for Where "*" indicates the same as L R connection point.

[0479] In some embodiments, L b is a divalent optionally substituted 10-membered heteroaromatic ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, or sulfur. b is a divalent optionally substituted 10-membered heteroaromatic ring having 1 oxygen heteroatom. b is a divalent optionally substituted chroman group. In some embodiments, R b is -H, and L b In some embodiments, R b is -H, and L b for In some embodiments, R b is -H, and L b for Where "*" represents L R The connection point with .

[0480] In some embodiments, L b is a divalent optionally substituted 10- to 15-membered tricyclic heterocyclyl having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms. b is a divalent optionally substituted 10- to 15-membered tricyclic heterocyclyl having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from oxygen, nitrogen, or sulfur. In some embodiments, L b is a divalent optionally substituted 10- to 15-membered tricyclic heterocyclyl having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from oxygen, nitrogen, or sulfur, wherein the tricyclic heterocyclyl comprises two spiro rings and two fused rings. In some embodiments, L b is a divalent optionally substituted 12-membered tricyclic heterocyclic group having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from oxygen, nitrogen, or sulfur. b is a divalent optionally substituted spiro[chroman-4,1'-cyclopropyl]. In some embodiments, L b为二 In some embodiments, R b is -H, and L b is spiro[chroman-4,1'-cyclopropyl]. In some embodiments, R b is -H, and L b for

[0481] In some embodiments, L b is a divalent optionally substituted 6- to 12-membered heteroaryl ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms. b is a divalent optionally substituted 6- to 12-membered heteroaromatic ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, or sulfur. In some embodiments, L b is a divalent optionally substituted 9- to 10-membered heteroaryl ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, or sulfur. In some embodiments, L b is a divalent optionally substituted 9-membered heteroaryl ring having 1-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, or sulfur. In some embodiments, L b is a divalent optionally substituted 9-membered heteroaromatic ring having 2 nitrogen heteroatoms.

[0482] In some embodiments, L b is a divalent optionally substituted imidazopyridinyl group.b is a divalent optionally substituted imidazo[1,5-a]pyridinyl. b is a divalent imidazo[1,5-a]pyridinyl group, optionally substituted by C 1-6 In some embodiments, L b is a divalent imidazo[1,5-a]pyridinyl group. In some embodiments, L b for The “*” represents the R connection point.

[0483] In some embodiments, L b is a divalent optionally substituted indazolyl. In some embodiments, L b is a divalent indazolyl group, optionally substituted by C 1-6 In some embodiments, L b Optional replacement Where "*" indicates the same as L R In some embodiments, L b Optional replacement Where "*" indicates the same as L R connection point.

[0484] In some embodiments, L b is a divalent optionally substituted benzimidazolyl group. In some embodiments, L b is a divalent optionally substituted benzo[d]imidazolyl group. b is a divalent benzo[d]imidazolyl group, optionally substituted by C 1-6 In some embodiments, L b Optional replacement Where "*" indicates the same as L R In some embodiments, L b Optional replacement Where "*" indicates the same as L R In some embodiments, L b Optional replacement Where "*" indicates the same as L R In some embodiments, L b Optional replacement Where "*" indicates the same as LR connection point.

[0485] In some embodiments, L b is a divalent optionally substituted 9-membered heteroaromatic ring having 3 nitrogen heteroatoms. b is a divalent optionally substituted pyrazolylpyrimidinyl. In some embodiments, L b is a divalent optionally substituted pyrazolyl[1,5-a]pyrimidinyl. In some embodiments, L b is a divalent pyrazolyl[1,5-a]pyrimidinyl group, optionally substituted by C 1-6 In some embodiments, L b Optional replacement Where "*" indicates the same as L R In some embodiments, L b for Where "*" indicates the same as L R connection point.

[0486] In some embodiments, L b *-N(R')-Cy-, where "*" indicates the same as L R In some embodiments, L b *-N(H)-Cy-, where "*" indicates the same R In some embodiments, L b for In some embodiments, L b for In some embodiments, L b for

[0487] L b1

[0488] In some embodiments, L b1 is L' as described herein. In some embodiments, L b1 is a covalent bond. In some embodiments, L b1 In some embodiments, L b1 is or contains an optionally substituted -CH 2-。 In some embodiments, L b1 is or comprises -CH2-. In some embodiments, L b1is or comprises -C(R')2-, wherein each R' is independently as described herein. In some embodiments, the two R's of -C(R')2-, together with the carbon atoms to which they are attached, form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated or partially unsaturated ring having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, -C(R') 2- The two R's in the formula (a) are taken together with the carbon atoms to which they are attached to form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-2 (e.g., 1-2, 0, 1, 2, etc.) heteroatoms. In some embodiments, L b1 is or comprises -CHR'-, wherein R' is as described herein. In some embodiments, Lb1 is or comprises -CHR'-, wherein R' is an optionally substituted aryl or heteroaryl. In some embodiments, Lb1 is or comprises -CHR'-, wherein R' is an optionally substituted phenyl. In some embodiments, L b1 is or comprises -N(R')-, wherein R' is as described herein. In some embodiments, L b1 is or comprises -NH-. In some embodiments, L b1 is or comprises -C(O)-. In some embodiments, L b1 is or comprises -Cy-, as described herein. In some embodiments, L b1 is or comprises -Cy-, wherein -Cy- is an optionally substituted divalent saturated or partially unsaturated 3-7 (e.g., 3-6, 3, 4, 5, 6, 7, etc.) membered ring having 0-2 (e.g., 1-2, 0, 1, 2, etc.) heteroatoms. In some embodiments, L b1 is or comprises -Cy-, wherein -Cy- is an optionally substituted divalent saturated 6-membered ring having 1-2 nitrogen heteroatoms.

[0489] L b2

[0490] In some embodiments, L b2 is L' as described herein. In some embodiments, L b2 is a covalent bond. In some embodiments, L b2 In some embodiments, L b2 is or contains an optionally substituted -CH 2-。 In some embodiments, L b2 is or comprises -CH2-. In some embodiments, L b2is or comprises -C(R')2-, wherein each R' is independently as described herein. In some embodiments, the two R's of -C(R')2-, together with the carbon atoms to which they are attached, form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated or partially unsaturated ring having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, -C(R') 2- The two R's in the formula (a) are taken together with the carbon atoms to which they are attached to form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-2 (e.g., 1-2, 0, 1, 2, etc.) heteroatoms. In some embodiments, L b2 is or comprises -CHR'-, wherein R' is as described herein. In some embodiments, Lb2 is or comprises -CHR'-, wherein R' is an optionally substituted aryl or heteroaryl. In some embodiments, L b2 is or comprises -CHR'-, wherein R' is an optionally substituted phenyl. In some embodiments, L b2 is or comprises -N(R')-, wherein R' is as described herein. In some embodiments, L b2 is or comprises -N(R')-, wherein R' is or comprises an optionally substituted ring, such as alicyclic (e.g., an optionally substituted saturated or partially unsaturated 3-10 membered (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) alicyclic), cycloheteroaliphatic (e.g., an optionally substituted saturated or partially unsaturated 3-10 membered (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms), aryl (e.g., an optionally substituted 6-10 membered (e.g., 6, 8, 9, 10, etc.) aryl), heteroaryl (e.g., an optionally substituted 5-10 membered (e.g., 5-6, 5-9, 5, 7, 8, 9, 10, etc.) heteroaryl having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms), etc. In some embodiments, L b2 is or comprises -N(R')-, wherein R' is an optionally substituted 5-10 membered (e.g., 6-10, 5-9, 5, 6, 7, 8, 9, 10, etc.) aryl or heteroaryl group having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, Lb2 is or comprises -N(R')-, wherein R' is an optionally substituted phenyl group. In some embodiments, L b2 is or comprises -NH-. In some embodiments, L b2 is or comprises -C(O)N(R')-, wherein R' is as described herein. In some embodiments, L b2is or comprises -C(O)N(R')-, wherein R' is an optionally substituted 5-10 (e.g., 6-10, 5-9, 5, 6, 7, 8, 9, 10, etc.) membered aryl or heteroaryl group having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, L b2 is or comprises -C(O)N(R')-, wherein R' is an optionally substituted phenyl. In some embodiments, L b2 is or comprises -C(O)NH-. In some embodiments, L b2 is or comprises -C(O)-. In some embodiments, L b2 is or comprises -Cy-, as described herein. In some embodiments, L b2 is or comprises -Cy-, as described herein. In some embodiments, L b2 is or comprises -Cy-, wherein -Cy- is an optionally substituted divalent saturated or partially unsaturated 3-7 (e.g., 3-6, 3, 4, 5, 6, 7, etc.) membered ring having 0-2 (e.g., 1-2, 0, 1, 2, etc.) heteroatoms. In some embodiments, L b2Is or comprises -Cy-, wherein -Cy- is an optionally substituted divalent saturated 6-membered ring with 1-2 nitrogen heteroatoms. In some embodiments, -Cy- is an optionally substituted bicyclic ring, wherein at least one monocyclic ring is an optionally substituted phenyl ring. In some embodiments, -Cy- is an optionally substituted bicyclic ring, wherein at least one monocyclic ring is an optionally substituted 5-6 membered heteroaromatic ring with 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted bicyclic ring, wherein each monocyclic ring is independently an optionally substituted phenyl ring or a 5-6 membered heteroaromatic ring with 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted bicyclic ring, wherein one monocyclic ring is an optionally substituted phenyl ring or a 5-6 membered heteroaromatic ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms, and the other monocyclic ring is an optionally substituted 3-10 membered (e.g., 3-9, 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) non-aromatic ring having 1-4 (e.g., 1-2, 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted bicyclic ring, wherein one monocyclic ring is an optionally substituted phenyl ring or a 5-6 membered heteroaromatic ring having 1-3 heteroatoms, and the other monocyclic ring is an optionally substituted 5-6 membered non-aromatic ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered divalent alicyclic group. In some embodiments, -Cy- is an optionally substituted 6-membered cycloalkyl group. In some embodiments, -Cy- is an optionally substituted phenylene group. In some embodiments, -Cy- is an optionally substituted 1,4-phenylene group. In some embodiments, -Cy- is a 1,4-phenylene group. In some embodiments, -Cy- is an optionally substituted divalent cyclohexyl group. In some embodiments, -Cy- is an optionally substituted 1,4-cyclohexyl group. In some embodiments, -Cy- is a 1,4-cyclohexyl group. In some embodiments, -Cy- is an optionally substituted divalent piperidine ring. In some embodiments, -Cy- is a divalent piperidine ring. In some embodiments, the divalent piperidine ring is a divalent 1,2-piperidinyl group. In some embodiments, the divalent piperidine ring is substituted with L at 1'. b1键合In some embodiments, the divalent piperidine ring is a divalent 1,4-piperidinyl group. In some embodiments, -Cy- is an optionally substituted divalent piperazine ring. In some embodiments, -Cy- is a divalent piperazine ring. In some embodiments, the divalent piperidine ring is a divalent 1,2-piperazinyl group. In some embodiments, the divalent piperidine ring is a divalent 1,4-piperazinyl group. In some embodiments, -Cy- is an optionally substituted 5-6-membered divalent heteroaromatic ring. In some embodiments, -Cy- is an optionally substituted 5-membered divalent heteroaromatic ring. In some embodiments, -Cy- is an optionally substituted 6-membered divalent heteroaromatic ring having 1 or 3 nitrogen atoms. In some embodiments, -Cy- is an optionally substituted 6-membered divalent heteroaromatic ring having a nitrogen atom. In some embodiments, -Cy- is an optionally substituted divalent pyridine ring. In some embodiments, -Cy- is a divalent pyridine ring. In some embodiments, the divalent pyridine ring is a 2,5-divalent pyridine ring. In some embodiments, the divalent pyridine ring is connected to L at the 2' position. b1 In some embodiments, the divalent pyridine ring is bonded to L b1 In some embodiments, the divalent pyridine ring is a 3,5-divalent pyridine ring. In some embodiments, the divalent pyridine ring is bonded to L b1 In some embodiments, the divalent pyridine ring is bonded to L b1 Bonded at 5'.

[0491] L b3

[0492] In some embodiments, L b3 is L' as described herein. In some embodiments, L b3 is a covalent bond. In some embodiments, L b3 In some embodiments, L b3 is or contains an optionally substituted -CH 2-。 In some embodiments, L b3 is or comprises -CH2-. In some embodiments, L b3 is or comprises -C(R')2-, wherein each R' is independently as described herein. In some embodiments, both R' of -C(R')2- 与 The carbon atoms to which they are attached together form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated or partially unsaturated ring having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, -C(R') 2-The two R's in the formula (a) are taken together with the carbon atoms to which they are attached to form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-2 (e.g., 1-2, 0, 1, 2, etc.) heteroatoms. In some embodiments, L b3 is or comprises -CHR'-, wherein R' is as described herein. In some embodiments, L b3 is or comprises -CHR'-, wherein R' is an optionally substituted aryl or heteroaryl. In some embodiments, L b3 is or comprises -CHR'-, wherein R' is an optionally substituted phenyl. In some embodiments, L b3 is or comprises -N(R')-, wherein R' is as described herein. In some embodiments, L b3 is or comprises -NH-. In some embodiments, L b3 is or comprises -C(O)-. In some embodiments, L b3 is or comprises -Cy- as described herein. In some embodiments, L b3 is or comprises -O-. In some embodiments, L b3 For or containing -S-.

[0493] L b4

[0494] In some embodiments, L b4 is L' as described herein. In some embodiments, L b4 is a covalent bond. In some embodiments, L b4 In some embodiments, L b4 In some embodiments, L b4 is or comprises an optionally substituted -CH2-. In some embodiments, L b4 is or comprises -CH2-. In some embodiments, L b4 is or comprises an optionally substituted -CH2-O-. In some embodiments, L b4 is or comprises -CH2-O-. In some embodiments, L b4 is or comprises -C(R')2-, wherein each R' is independently as described herein. In some embodiments, -C(R') 2-In some embodiments, the two R' in -C(R')2-, together with the carbon atoms to which they are attached, form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated or partially unsaturated ring having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, the two R' in -C(R')2-, together with the carbon atoms to which they are attached, form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-2 (e.g., 1-2, 0, 1, 2, etc.) heteroatoms. In some embodiments, L b4 is or comprises -CHR'-, wherein R' is as described herein. In some embodiments, L b4 is or comprises -CHR'-, wherein R' is an optionally substituted aryl or heteroaryl. In some embodiments, L b4 is or comprises -CHR'-, wherein R' is an optionally substituted phenyl. In some embodiments, L b4 is or comprises -N(R')-, wherein R' is as described herein. In some embodiments, L b4 is or comprises -NH-. In some embodiments, L b4 is or comprises -C(O)-. In some embodiments, L b4 Is or comprises -Cy-, as described herein. In some embodiments, wherein -Cy- is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) divalent alicyclic group. In some embodiments, -Cy- is an optionally substituted 6-membered cycloalkyl group. In some embodiments, -Cy- is an optionally substituted divalent cyclohexyl group. In some embodiments, -Cy- is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) divalent heterocyclic group having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted 6-membered divalent heterocyclic group having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted 5-membered divalent heterocyclic group having 1 or 2 heteroatoms. In some embodiments, -Cy- is an optionally substituted saturated ring. In some embodiments, -Cy- is an optionally substituted 5-6-membered divalent heteroaromatic ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted divalent phenylene. In some embodiments, -Cy- is an optionally substituted divalent 1,4-phenylene. In some embodiments, -Cy- is a divalent 1,4-phenylene. In some embodiments, -Cy- is an optionally substituted divalent naphthyl. In some embodiments, L b4is or comprises -O-. In some embodiments, L b4 Is or contains -S-.

[0495] L b5

[0496] In some embodiments, L b5 is L' as described herein. In some embodiments, L b5 is a covalent bond. In some embodiments, L b5 In some embodiments, L b5 is or comprises an optionally substituted -CH2-. In some embodiments, L b5 is or comprises -CH2-. In some embodiments, L b5 is or contains an optionally substituted -CH2O- 。 In some embodiments, L b5 is or comprises -CH2O-. In some embodiments, L b5 is or comprises -C(R')2-, wherein each R' is independently as described herein. In some embodiments, -C(R') 2- In some embodiments, the two R' in -C(R')2-, together with the carbon atoms to which they are attached, form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated or partially unsaturated ring having 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, the two R' in -C(R')2-, together with the carbon atoms to which they are attached, form an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered saturated ring having 0-2 (e.g., 1-2, 0, 1, 2, etc.) heteroatoms. In some embodiments, L b5 is or comprises -CHR'-, wherein R' is as described herein. In some embodiments, L b5 is or comprises -CHR'-, wherein R' is an optionally substituted aryl or heteroaryl. In some embodiments, L b5 is or comprises -CHR'-, wherein R' is an optionally substituted phenyl. In some embodiments, L b5 is or comprises -N(R')-, wherein R' is as described herein. In some embodiments, L b5 is or comprises -NH-. In some embodiments, L b5 is or comprises -C(O)-. In some embodiments, L b5 is or comprises -Cy-, as described herein. In some embodiments, L b5是 Or contains -O-. In some embodiments, L b5is or comprises -S-. In some embodiments, wherein L b5 is or comprises -S(O)2-. In some embodiments, L b5 Is or contains -OS(O)2-.

[0497] L'

[0498] In some embodiments, L' is a covalent bond, or an optionally substituted divalent C 1-2 An aliphatic or heteroaliphatic group wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L' is a covalent bond. In some embodiments, L' is an optionally substituted divalent C(O) with 1-2 heteroatoms. 1-2 An aliphatic or heteroaliphatic group wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L' is an optionally substituted divalent C 1-2 In some embodiments, L' is an optionally substituted divalent C 1-2Alkylene, wherein one or more methylene units are optionally and independently substituted with —C(R′)—, —Cy—, —O—, —S—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, O—, —S—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—. In some embodiments, L' is an optionally substituted divalent -CH2-CH2-, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L' is or comprises an optionally substituted -CH2-. In some embodiments, L' is or comprises -CH2-. In some embodiments, L' is or comprises an optionally substituted -CH2-CH2-. In some embodiments, L' is or comprises -CH2-CH2-. In some embodiments, a methylene unit is replaced by -C(R')2-, wherein each R' is independently as described herein. In some embodiments, a methylene unit is replaced by CHR', wherein R' is as described herein. In some embodiments, a methylene unit is replaced by -N(R')-, wherein R' is as described herein. In some embodiments, a methylene unit is replaced by -C(O)N(R')-, wherein R' is as described herein. In some embodiments, a methylene unit is replaced by -Cy-, wherein Cy is as described herein. In some embodiments, a methylene unit is replaced by -C(O)-, as described herein. In some embodiments, a methylene unit is replaced by -O-, as described herein. In some embodiments, a methylene unit is replaced by -S-, as described herein.

[0499] In some embodiments, L' is L as described herein b1 In some embodiments, L' is L as described herein. b2 In some embodiments, L' is L as described herein. b3 In some embodiments, L' is L as described herein. b4 In some embodiments, L' is L as described herein. b5 .

[0500] R b

[0501] As described herein, in some embodiments, R b is R as described herein. In some embodiments, R b is R' as described herein. In some embodiments, R b is R as described herein. In some embodiments, R b In some embodiments, R b For hydrogen.

[0502] In some embodiments, R b In some embodiments, R b is -OR, wherein R is as described herein. In some embodiments, R b In some embodiments, R b -OCH 3。 In some embodiments, R b is -OCH(CH2CH3)2. In some embodiments, R b In some embodiments, R b In some embodiments, R b -CF 3。 In some embodiments, R b is -N(R')2. In some embodiments, R b is -N(CH2CH3)2. In some embodiments, R b is an optionally substituted sulfone. b In some embodiments, R b It is -S(O2)CH3.

[0503] In some embodiments, R b is an optionally substituted C 1-20 (For example, C 1-15 、C 1-10 、C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 、C 11 、C 12 、C 13 、C 14 、C 15、C16 、C 17 、C18 、 C 19 、C20等 ) aliphatic group. In some embodiments, R b is an optionally substituted C 1-15 In some embodiments, R b is an optionally substituted C 1-10 In some embodiments, R b is an optionally substituted C 1-6 In some embodiments, the optionally substituted aliphatic group is an optionally substituted alkyl group. In some embodiments, R b is an optional replacement for C 1-6 In some embodiments, R b In some embodiments, R b In some embodiments, R b In some embodiments, R b In some embodiments, R b In some embodiments, R b In some embodiments, R b In some embodiments, R b In some embodiments, R b is an optional replacement for -C 0-4 In some embodiments, R b In some embodiments, R b is an optionally substituted C 3-20 (For example, C 3-15 、C 3-10 、C 3-9 、C 3-8 、C 3-6 、C3、C4、C5、C6、C7、C 8、 C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C17、C 18 、C19 、 C 20 In some embodiments, R b is an optionally substituted C 3-10 In some embodiments, R b is an optionally substituted C 3-10 In some embodiments, R bis an optionally substituted cyclopropyl. b In some embodiments, R b In some embodiments, R b In some embodiments, R b is an optionally substituted C having 1-10 (e.g., 1-5, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms 1-20 (For example, C 1-15 、C1-10 、 C1-9 、 C1-8 、 C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C 8、 C 9、 C 10、 C 11、 C 12、 C 13 、C 14、 C 15 、C 16 、C 17、 C 18 、C 19 In some embodiments, R b is an optionally substituted C having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms 1-10 (For example, C 1-9 、C 1-8 、C 1-6 , C1, C 2、 C3, C4, C5, C6, C7, C8, C9, C 10 In some embodiments, R b is an optionally substituted C 6-20 (e.g., 6-10, 6, 8, 9, 10, 14, etc.) aryl. In some embodiments, R b is an optionally substituted phenyl. b In some embodiments, R b is an optionally substituted naphthyl. In some embodiments, R b In some embodiments, R b is an optionally substituted 5-20 (e.g., 5-14, 5-10, 5, 6, 8, 9, 10, 14, etc.) membered heteroaryl group having 1-10 (1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R bis an optionally substituted 5-10 membered heteroaryl group having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms. b is an optionally substituted 5-6 membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) heteroatoms. b is an optionally substituted 5-6 membered heteroaryl group having 1-4 (e.g., 1-3, 1, 2, 3, 4, etc.) nitrogen atoms. b is an optionally substituted 5-6 membered heteroaryl group having 1 or 2 nitrogen atoms. b is an optionally substituted pyridinyl. b is an optionally substituted 3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heterocyclyl having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R b is an optionally substituted 3-10 (e.g., 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclyl having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms. In some embodiments, R b is an optionally substituted 3-7 membered heterocyclic group having 1 or 2 heteroatoms. b is an optionally substituted 3-7 membered heterocyclic group having one heteroatom. b is an optionally substituted tetrahydro-2H-pyranyl. b for In some embodiments, R b for In some embodiments, R b for In some embodiments, R b for In some embodiments, R b In some embodiments, R b is an optionally substituted 3,6-dihydro-2H-pyranyl. b In some embodiments, R b Optional replacement In some embodiments, R b for In some embodiments, R b In some embodiments, R b To be optionally C 1-6 In some embodiments, R b Optional replacement In some embodiments, R b for In some embodiments, R b In some embodiments, R b To be optionally C 1-6 In some embodiments, R b Optional replacement In some embodiments, R b for In some embodiments, R b In some embodiments, R is an optionally substituted piperidinyl. In some embodiments, R is a piperidinyl optionally substituted by a C1-6 aliphatic group (e.g., methyl, ethyl, n-propyl, sec-propyl, or isopropyl) or a halogen (e.g., -F, -Cl, -Br, or -I). b Optional replacement In some embodiments, R b for In some embodiments, R b for In some embodiments, R b for In some embodiments, R b In some embodiments, R is an optionally substituted morpholinyl. In some embodiments, R is an optionally substituted 4-morpholinyl. b for In some embodiments, R b for In some embodiments, R b Optional replacement In some embodiments, R b for In some embodiments, R b for In some embodiments, R b In some embodiments, R b is an optionally substituted silyl group.b for In some embodiments, R b Optional replacement In some embodiments, R b for In some embodiments, R b Optional replacement In some embodiments, R b for In some embodiments, R b is an optionally substituted 7-10 membered heterocyclic group having two heteroatoms. b is an optionally substituted 2-oxa-5-azabicyclo[2.2.1]heptyl. In some embodiments, R b for In some embodiments, R b is optionally substituted 3-oxa-8-azabicyclo[3.2.1]octyl. In some embodiments, R b for

[0504] In some embodiments, R b is an optionally substituted 7- to 12-membered heterospirocyclyl containing 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur. b is an optionally substituted 7-membered heterospirocyclyl containing 1 nitrogen heteroatom. b Optional replacement In some embodiments, R b for

[0505] In some embodiments, R b is -LR', wherein R' is R as described herein. In some embodiments, R b is -O-R', wherein R' is R as described herein.

[0506] In some embodiments, R b is -O-R', wherein R' is an optionally substituted 3- to 8-membered saturated or partially unsaturated carbocyclic ring. b In some embodiments, R b -O-R', wherein R' is optionally substituted with C 1-6 In some embodiments, R b for In some embodiments, R b In some embodiments, R b for

[0507] In some embodiments, R b In some embodiments, R b -O-R', where R' is optionally C 1-6 In some embodiments, R b for In some embodiments, R b for

[0508] In some embodiments, R b is -O-R', wherein R' is an optionally substituted 3- to 7-membered heterocyclyl containing 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur. In some embodiments, R b In some embodiments, R b -O-R', wherein R' is optionally substituted with C 1-6 In some embodiments, R b for

[0509] In some embodiments, R b is or comprises a reactive group. Various reactive groups are known in the art, for example, for amidation, esterification, cycloaddition, elimination, displacement, condensation, reduction, oxidation, coupling, etc., including various biocompatible reactions, and can be used in accordance with the present disclosure.

[0510] P

[0511] In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is 6. In some embodiments, p is 7. In some embodiments, p is 8. In some embodiments, p is 9. In some embodiments, p is 10.

[0512] In some embodiments, in formula (eg, formula A, A', etc.), p is 1. In some embodiments, R9 Located opposite to Y.

[0513] q

[0514] As described herein, in some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, q is 2. In some embodiments, q is 3. In some embodiments, q is 4. In some embodiments, q is 5. In some embodiments, q is 6. In some embodiments, q is 7. In some embodiments, q is 8. In some embodiments, q is 9. In some embodiments, q is 10.

[0515] In some embodiments, in the formula, such as formula A, A', etc., q is 1. In some embodiments, R s Located para to the other attachment site of ring A.

[0516] t

[0517] In some embodiments, t is 0. In some embodiments, t is 1. In some embodiments, t is 2. In some embodiments, t is 3. In some embodiments, t is 4. In some embodiments, t is 5. In some embodiments, t is 6. In some embodiments, t is 7. In some embodiments, t is 8. In some embodiments, t is 9.

[0518] In some embodiments, in formula (eg, formula A, A', etc.), t is 1. In some embodiments, R 9 Located opposite to Y.

[0519] x

[0520] In some embodiments, x is 0. In some embodiments, x is 1. In some embodiments, x is 2. In some embodiments, x is 3. In some embodiments, x is 4.

[0521] y

[0522] In some embodiments, y is 0. In some embodiments, y is 1. In some embodiments, y is 2. In some embodiments, y is 3. In some embodiments, y is 4.

[0523] L

[0524] In some embodiments, L is a covalent bond. In some embodiments, L is an optionally substituted divalent C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C 8、 C9, C 10In some embodiments, L is an optionally substituted divalent C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 ) heteroaliphatic groups having 1-6 (e.g., 1-5, 1-4, 1-3, 1, 2, 3, 4, 5, 6, etc.) heteroatoms, wherein one or more methylene units are optionally and independently replaced by -C(R')-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-, and each R' is independently as described herein. In some embodiments, L is an optionally substituted divalent C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, L is an optionally substituted divalent linear C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 In some embodiments, L is an optionally substituted divalent branched chain C 1-10 (For example, C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10In some embodiments, one or more methylene units are independently as described herein. In some embodiments, L is or comprises -C(R')2-, wherein each R' is independently as described herein. In some embodiments, L is or comprises an optionally substituted -CH 2- In some embodiments, L is or comprises -Cy- as described herein. For example, in some embodiments, L is an optionally substituted 3-10 membered cycloalkylene. In some embodiments, L is or comprises -O-. In some embodiments, L is or comprises -S-. In some embodiments, L is or comprises -N(R')-, wherein R' is as described herein. In some embodiments, L is or comprises -N(R')-, wherein R' is an optionally substituted C 1-6 In some embodiments, L is or comprises -NH-. In some embodiments, L is or comprises -C(O)-. In some embodiments, L is or comprises -Cy-C(O)O-. In some embodiments, L is -Cy-C(O)O-, wherein -Cy- is an optionally substituted 3-10 membered cycloalkylene. In some embodiments, L is or comprises -C(S)-. In some embodiments, L is or comprises -C(NR')-, wherein R' is as described herein. In some embodiments, L is or comprises -C(NH)-. In some embodiments, L is or comprises -C(O)N(R')-, wherein R' is as described herein. In some embodiments, L is or comprises -Cy-C(O)N(R')-, wherein each -Cy- and R' are independently as described herein (e.g., in some embodiments, R' is -H; in some embodiments, R' is an optionally substituted C 1-6In some embodiments, L is or comprises -C(O)NH-. In some embodiments, L is or comprises -C(S)N(R'), wherein R' is as described herein. In some embodiments, L is or comprises -C(S)NH-. In some embodiments, L is or comprises -C(NR')N(R')-, wherein each R' is independently as described herein. In some embodiments, L is or comprises -C(NH)NH-. In some embodiments, L is or comprises -N(R')C(O)N(R')-, wherein each R' is independently as described herein. In some embodiments, L is or comprises -NHC(O)NH-. In some embodiments, L is or comprises -N(R')C(O)O-, wherein R' is as described herein. In some embodiments, L is or comprises -NHC(O)O-. In some embodiments, L is or comprises -S(O)-. In some embodiments, L is or comprises -S(O)2-. In some embodiments, L is or comprises -S(O)2N(R')-, wherein R' is as described herein. In some embodiments, L is or comprises -S(O)2NH-. In some embodiments, L is or comprises -C(O)S-. In some embodiments, L is or comprises -C(O)O-.

[0525] In some embodiments, L is -L"-L x -L y -L z -, wherein L" is a covalent bond or an optionally substituted divalent C having 1-6 heteroatoms 1-7 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; and L x , L y and L zand L are each independently a covalent bond or an optionally substituted methylene group, which is optionally substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L x is a covalent bond, -N(R') or -O-. In some embodiments, L y is a covalent bond, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, or -C(NR')(NR')-. In some embodiments, L z is a covalent bond, -N(R')-, -N(R')O- or -O-. In some embodiments, L x is a covalent bond. In some embodiments, L x is -N(R')-, wherein R' is as described herein. In some embodiments, L x In some embodiments, L y is a covalent bond. In some embodiments, L y In some embodiments, L y In some embodiments, L y is -C(NR')-, wherein R' is as described herein. In some embodiments, L y is -C(O)N(R')-, wherein R' is as described herein. In some embodiments, L y is -C(S)N(R')-, wherein R' is as described herein. In some embodiments, L y is -C(NR')(NR')-, wherein each R' is independently as described herein. In some embodiments, L z is a covalent bond. In some embodiments, L z is -N(R')-, wherein R' is as described herein. In some embodiments, L z is -N(R')O-, wherein R' is as described herein. In some embodiments, L z It is -O-.

[0526] Cy

[0527] As described herein, -Cy- can be optionally substituted (except for the two groups to which it is bound). In some embodiments, -Cy- is substituted. In some embodiments, -Cy- is unsubstituted.

[0528] In some embodiments, -Cy- is an optionally substituted ring as described herein. In some embodiments, -Cy- is a 3-20, 3-15, 3-10, 3-8, 3-6, 5-6, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20-membered ring. In some embodiments, -Cy- is a 3-membered ring. In some embodiments, -Cy- is a 4-membered ring. In some embodiments, -Cy- is a 5-membered ring. In some embodiments, -Cy- is a 6-membered ring. In some embodiments, -Cy- is a 7-membered ring. In some embodiments, -Cy- is an 8-membered ring. In some embodiments, -Cy- is a 9-membered ring. In some embodiments, -Cy- is a 10-membered ring. In some embodiments, -Cy- is an 11-membered ring. In some embodiments, -Cy- is a 12-membered ring. In some embodiments, -Cy- is a saturated ring. In some embodiments, -Cy- is a partially unsaturated ring. In some embodiments, -Cy- is an aromatic ring. In some embodiments, -Cy- is a monocyclic ring. In some embodiments, it is a bicyclic ring. In some embodiments, it is a polycyclic ring. In some embodiments, each monocyclic ring unit is independently saturated, partially unsaturated, or aromatic and has 0-4 heteroatoms and a 3-15 (e.g., 3-15, 3-10, 3-8, 3-6, 5-6, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15, etc.) membered ring. In some embodiments, each monocyclic unit is independently saturated, partially unsaturated or aromatic and has 0-4 (e.g., 0, 1, 2, 3 or 4, etc.) 3-10 (e.g., 3-10, 3-8, 3-6, 5-6 or 3, 4, 5, 6, 7, 8, 9 or 10, etc.) membered rings independently selected from nitrogen, oxygen and sulfur heteroatoms. In some embodiments, each monocyclic unit is independently a 3-7 membered ring. In some embodiments, each monocyclic unit is independently a 3-6 membered ring. In some embodiments, each monocyclic unit is independently a 5-7 membered ring. In some embodiments, each monocyclic unit is independently a saturated or partially unsaturated ring. In some embodiments, at least one monocyclic unit is a saturated ring. In some embodiments, at least one monocyclic unit is a partially unsaturated ring. In some embodiments, at least one monocyclic unit is an aromatic ring. In some embodiments, -Cy- has 1-10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, etc.) heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, -Cy- has 1-5 (e.g., 1, 2, 3, 4, or 5, etc.) heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, Cy has no heteroatoms. In some embodiments, Cy contains one heteroatom. In some embodiments, contains two heteroatoms. In some embodiments, contains three heteroatoms.In some embodiments, there are 4 heteroatoms. In some embodiments, there are 5 heteroatoms. In some embodiments, there are 6 or more heteroatoms. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur.

[0529] In some embodiments, -Cy- is an optionally substituted 5-10 membered aromatic ring having 0-5 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is an optionally substituted 5-6 membered aromatic ring having 0-5 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is an optionally substituted benzene ring. In some embodiments, -Cy- is a benzene ring. In some embodiments, -Cy- is an optionally substituted 10 membered bicyclic aromatic ring. In some embodiments, -Cy- is an optionally substituted 5-9 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted 5-4 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted 6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted 9-membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroatom is nitrogen.

[0530] In some embodiments, -Cy- is an optionally substituted bicyclic ring wherein at least one monocyclic ring is an optionally substituted phenyl ring. In some embodiments, -Cy- is an optionally substituted bicyclic ring wherein at least one monocyclic ring is an optionally substituted 5-6 membered heteroaryl ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted bicyclic ring wherein each monocyclic ring is independently an optionally substituted phenyl ring or a 5-6 membered heteroaryl ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted bicyclic ring in which one monocyclic ring is an optionally substituted phenyl ring or a 5-6 membered heteroaryl ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms, and the other monocyclic ring is an optionally substituted 3-10 (e.g., 3-9, 4-10, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered non-aromatic ring having 1-4 (e.g., 1-2, 1-3, 1, 2, 3, 4, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted bicyclic ring in which one monocyclic ring is an optionally substituted phenyl ring or a 5-6 membered heteroaryl ring having 1-3 heteroatoms, and the other monocyclic ring is an optionally substituted 5-6 membered non-aromatic ring having 1-3 (e.g., 1-2, 1, 2, 3, etc.) heteroatoms. In some embodiments, -Cy- is an optionally substituted 3-10 (e.g., 3-9, 5-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered divalent alicyclic group. In some embodiments, -Cy- is an optionally substituted 6-membered cycloalkyl group. In some embodiments, -Cy- is an optionally substituted phenylene group. In some embodiments, -Cy- is an optionally substituted 1,4-phenylene group. In some embodiments, -Cy- is a 1,4-phenylene group. In some embodiments, -Cy- is an optionally substituted divalent cyclohexyl group. In some embodiments, -Cy- is an optionally substituted 1,4-cyclohexyl group. In some embodiments, -Cy- is a 1,4-cyclohexyl group. In some embodiments, -Cy- is an optionally substituted divalent piperidine ring. In some embodiments, -Cy- is a divalent piperidine ring. In some embodiments, the divalent piperidine ring is a divalent 1,2-piperidinyl group. In some embodiments, the divalent piperidine ring is a divalent 1,4-piperidinyl group. In some embodiments, -Cy- is an optionally substituted divalent piperazine ring. In some embodiments, -Cy- is a divalent piperazine ring. In some embodiments, the divalent piperidine ring is a divalent 1,2-piperazinyl group. In some embodiments, the divalent piperidine ring is a divalent 1,4-piperazinyl group. In some embodiments, -Cy- is an optionally substituted 5-6-membered divalent heteroaromatic ring. In some embodiments, -Cy- is an optionally substituted 5-membered divalent heteroaromatic ring. In some embodiments, -Cy- is an optionally substituted 6-membered divalent heteroaromatic ring having 1 or 3 nitrogen atoms. In some embodiments, -Cy- is an optionally substituted 6-membered divalent heteroaromatic ring having a nitrogen atom.In some embodiments, -Cy- is an optionally substituted divalent pyridine ring. In some embodiments, -Cy- is a divalent pyridine ring. In some embodiments, the divalent pyridine ring is a 2,5-divalent pyridine ring. In some embodiments, the divalent pyridine ring is a 3,5-divalent pyridine ring. In some embodiments, -Cy- is a divalent pyrimidine ring. In some embodiments, the divalent pyrimidine ring is a 2,5-divalent pyrimidine ring. In some embodiments, -Cy- is a divalent thiazole ring. In some embodiments, the divalent thiazole ring is a 2,5-divalent thiazole ring.

[0531] R”

[0532] In some embodiments, R" is -H.

[0533] In some embodiments, R" is halogen. In some embodiments, R" is -F. In some embodiments, R" is -Cl. In some embodiments, R" is -Br. In some embodiments, R" is -I.

[0534] In some embodiments, R" is -LR, wherein each variable is independently as described herein. In some embodiments, R" is R' as described herein. In some embodiments, R" is -LR, wherein each variable is independently as described herein. In some embodiments, R" is R as described herein.

[0535] In some embodiments, R" is -L-OR'. In some embodiments, R" is -L-SR'. In some embodiments, R" is -LC(O)OR'. In some embodiments, R" is -LC(O)SR'. In some embodiments, R" is -LC(O)N(R')2. In some embodiments, R" is -L-OC(O)N(R')2. In some embodiments, R" is -LC(O)R'. In some embodiments, R" is -LN(R')2. In some embodiments, R" is -CN. In some embodiments, R" is -OC(R')2COOH. In some embodiments, R" is -SC(R')2COOH. In some embodiments, R" is -N(R')C(R')2COOH. In some embodiments, R" is optionally substituted alkylsulfonyl. In some embodiments, R" is arylsulfonyl. In some embodiments, R" is a carboxylate. In some embodiments, R" is an ester. In some embodiments, R" is an ether. In some embodiments, R" is an amide. In some embodiments, R" is a carbohydrate. In some embodiments, R" is an amino acid. In some embodiments, R" is an acyl group. In some embodiments, R" is an acyl group substituted with an alkoxy group. In some embodiments, R" is a sugar alcohol. In some embodiments, R" is sulfate. In some embodiments, R" is a sulfonamide. In some embodiments, R" is a sulfoxide. In some embodiments, R" is a sulfonate. In some embodiments, R" is a sulfone. In some embodiments, R" is a sulfanyl group. In some embodiments, R" is a thioester. In some embodiments, R" is a thioether. In some embodiments, R" is or comprises a peptide moiety. In some embodiments, R" is or comprises a carbohydrate moiety.

[0536] R'

[0537] In some embodiments, R' is R as described herein. In some embodiments, R' is -H. In some embodiments, R' is -OR, wherein R is as described herein. In some embodiments, R' is -C(O)R, wherein R is as described herein. In some embodiments, R' is -C(O)R, wherein R is as described herein. In some embodiments, R' is -C(O)OR, wherein R is as described herein. In some embodiments, R' is -C(O)N(R)2, wherein each R is independently as described herein. In some embodiments, R' is -S(O)R, wherein R is as described herein. In some embodiments, R' is -S(O)2R, wherein R is as described herein. In some embodiments, R' is -S(O)2CH3. In some embodiments, R' is -C(O)CH3. In some embodiments, R' is -C(O)R, wherein R is optionally substituted C6-14 In some embodiments, R' is -C(O)R, wherein R is an optionally substituted phenyl. In some embodiments, R' is -C(O)R, wherein R is 3-iodophenyl. In some embodiments, R' is -C(O)OR, wherein R is as described herein. In some embodiments, R' is -C(O)OH. In some embodiments, R' is an optionally substituted C 1-10 In some embodiments, R' is an optionally substituted C1-6 aliphatic group. In some embodiments, R' is an optionally substituted C 1-6 In some embodiments, R' is methyl.

[0538] R

[0539] Various embodiments of R are broadly described herein, including various moieties that may be other variables of R (e.g., R s 、R 1 、R 2 , R', etc.).

[0540] In some embodiments, R is -H. In some embodiments, R is not -H.

[0541] In some embodiments, each R is independently hydrogen, or selected from C 1-20 (For example, C 1-15 、C 1-10 、C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 、C 19 、C 20 etc.) fatty groups, C 1-20 (For example, C 1-15 、C 1-10 、C 1-9 、C 1-8 、C 1-6 ,C1,C2,C3,C4,C5,C6,C7,C8,C9,C 10、 C 11、 C 12、 C 13、 C 14、 C 15、 C 16、 C 17、 C18、 C 19 、C 20 wait ) Heteroaliphatic groups having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms, C 3-20 (e.g., 3-15, 3-10, 4-20, 5-20, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc. membered) heterocyclic radicals having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc. membered) heteroatoms, C 5-20 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heteroaryl, and 5-20 (e.g., 5-15, 5-14, 5-10, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heteroaryl having 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms.

[0542] In some embodiments, R is an optionally substituted C 1-20 (For example, C 1-15 、C 1-10 、C 1-9 、C 1-8 、C 1-6 、C1、C2、C3、C4、C5、C 6、 C7, C 8、 C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15、 C 16 、C 17 、C 18、 C 19 、C 20 In some embodiments, R is an optionally substituted C 1-10 In some embodiments, the fatty group is an alkyl group. In some embodiments, R is C 1-6 In some embodiments, R is C 1-6In some embodiments, R is an alkyl group. In some embodiments, R is an optionally substituted methyl group. In some embodiments, R is an optionally substituted ethyl group. In some embodiments, R is an optionally substituted n-propyl group. In some embodiments, R is an optionally substituted isopropyl group. In some embodiments, R is an n-butyl group. In some embodiments, R is a tert-butyl group. In some embodiments, R is a pentyl group. In some embodiments, R is a hexyl group.

[0543] In some embodiments, the aliphatic group is or comprises an alicyclic group. In some embodiments, R is an optionally substituted C 3-15 (For example, C 3-15 、C 3-12 、C 3-10 、C 4-10 、C 3-9 、C 3-7 or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, etc.) alicyclic. In some embodiments, R is an optionally substituted C 3-10 In some embodiments, the alicyclic group is a cycloalkyl group. In some embodiments, the alicyclic group is monocyclic. In some embodiments, the alicyclic group is bicyclic. In some embodiments, the alicyclic group is polycyclic. In some embodiments, each monocyclic unit is independently 3-10 (e.g., C 4-10 、C 3-9、 C 3-7 In some embodiments, the alicyclic group is saturated. In some embodiments, it is partially unsaturated. In some embodiments, R is an optionally substituted cyclopropyl group. In some embodiments, R is an optionally substituted cyclobutyl group. In some embodiments, R is an optionally substituted cyclopentyl group. In some embodiments, R is an optionally substituted cyclohexyl group. In some embodiments, R is an optionally substituted cycloheptyl group.

[0544] In some embodiments, R is an optionally substituted C having 1-10 (e.g., 1-5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. 1-20 (For example, C 1-15 、C 1-10 、C 1-9 、C 1-8 、C 1-6 , C1, C 2、 C3, C 4、 C5, C6, C7, C 8、 C 9、 C 10 、C 11 、C 12 、C 13 、C 14 、C15 、C 16、 C 17 、C 18、 C 19 、C 20 In some embodiments, R is an optionally substituted C 1-15 (For example, C 1-15 、C 1-12 、C 1-10 In some embodiments, R is an optionally substituted C 1-15 (For example, C 1-15 、C 1-12 、C 1-10 In some embodiments, R is C 1-10 Heteroaliphatic groups having 1-5 (e.g., 1, 2, 3, 4, or 5, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is a C1-10 heteroaliphatic group having 1 or 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is a C1-10 heteroaliphatic group having one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur.

[0545] In some embodiments, R is an optionally substituted C 6-20 (For example, C 6-14 、C 6-10 、C6、C 10 、C 14 In some embodiments, R is an optionally substituted C 6-14 (For example, C 6-14 、C 6-10 、C 6-9 In some embodiments, R is an optionally substituted C 6-10 In some embodiments, R is an optionally substituted 6-, 10-, or 14-membered hydrocarbon aryl group. In some embodiments, the aromatic ring is monocyclic. In some embodiments, the aromatic ring is bicyclic. In some embodiments, the aromatic ring is polycyclic. In some embodiments, each monocyclic ring unit is independently a 6-membered aromatic ring. In some embodiments, R is an optionally substituted phenyl group. In some embodiments, R is a phenyl group. In some embodiments, R is an optionally substituted 10-membered aryl group. In some embodiments, R is an optionally substituted naphthyl group. In some embodiments, R is a naphthyl group.

[0546] In some embodiments, R is a 5-20 (e.g., 5-14, 5-10, 5-9, 5, 6, 7, 8, 9, 10, etc.) membered heteroaryl having 1-10 (e.g., 1-9, 1-8, 1-6, 1-5, 1-4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R is an optionally substituted 5-14 (e.g., 5-10, 5-9, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered heteroaryl having 1-5 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, etc.) heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, R is an optionally substituted 5-14 (e.g., 5-10, 5-9, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, etc.) membered heteroaryl having 1-5 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is a 5-10 (e.g., 5-9, 5, 6, 9, 10, etc.) membered heteroaryl having 1-4 (e.g., 1-3, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl ring is monocyclic. In some embodiments, the heteroaryl ring is bicyclic. In some embodiments, the heteroaryl ring is polycyclic. In some embodiments, each monocyclic unit is independently a 5- or 6-membered aromatic ring with 0-4 heteroatoms (e.g., independently selected from nitrogen, oxygen, and sulfur), wherein at least one monocyclic unit contains 1-4 heteroatoms. In some embodiments, R is an optionally substituted 5-membered monocyclic heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 6-membered monocyclic heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 9-membered bicyclic heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 10-membered bicyclic heteroaryl with 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroaromatic ring has one heteroatom. In some embodiments, the heteroaromatic ring has two or more heteroatoms. In some embodiments, the heteroaromatic ring has three or more heteroatoms. In some embodiments, the heteroaromatic ring has four or more heteroatoms. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur.

[0547] In some embodiments, R is an optionally substituted 5-14 membered heteroaryl-C having 1-5 heteroatoms. 1-15In some embodiments, R is an optionally substituted 5-14 membered heteroaryl-C having 1-5 heteroatoms. 1-15 In some embodiments, R is an optionally substituted 5-10 membered heteroaryl-C 1-15 In some embodiments, R is an optionally substituted 5-10 membered heteroaryl-C 1-10 Various suitable heteroaryl and aliphatic groups are described herein.

[0548] In some embodiments, R is an optionally substituted 3-20 (e.g., 3-15, 3-10, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocyclyl having 1-10 (e.g., 1-6, 1-3, 1-2, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms. In some embodiments, R is a 3-20 (e.g., 3-15, 3-10, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heterocyclyl having 1-10 (e.g., 1-5, 1-3, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is a 3-20 (e.g., 3-20, 3-15, 3-10, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.) membered heterocyclyl having 1-5 (e.g., 1-4, 1-3, 1, 2, 3, 4, 5, etc.) heteroatoms independently selected from nitrogen, oxygen, and su...

Claims

1. A compound represented by the general formula B-1: or a salt thereof, wherein: L b is L; R b for R”; R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ; L w is a covalent bond, or is an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; R w is - T - C(=NR w1 ),N(R w2 )(R w3 ); Each R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; Each R" is independently hydrogen, halogen, -L-R', -L-OR', -L-SR', -LC(O)OR', -LC(O)SR', -LC(O)N(R')2, -L-OC(O)N(R')2, -LC(O)R', -LN(R')2, -CN, -OC(R')2COOH, -SC(R') 2COOH, -N(R')C(R')2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester and thioether; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Each R is independently -H, or is an optionally substituted 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms between them to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms between them; R s1 , R s2 and R s3 Each is independently R", halogen, -CN, oxo, -NO2, or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl.

2. A compound having a structure of formula B: R b- L b -L R -R 4 B or a salt thereof, wherein: L R for L, -C≡C-, is optionally substituted -CH=CH-, -C(O)-, -C(S)-, or -C(NR")-; L b It is L; R b It is R”; Ring L is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ; L w is a covalent bond, or is an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; R w is -T-C(=NR w1 ),N(R w2 )(R w3 ); R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; Each R s R" is independently halogen, -CN, oxo, -NO2, or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl; q is 0-10; each R″ is independently hydrogen, halogen, -L-R′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester and thioether; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Each R is independently -H, or is an optionally substituted 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms therebetween to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms therebetween.

3. The compound as claimed in claim 2, wherein L R yes 4. The compound of claim 2, wherein: L R For optional replacement The nitrogen atom and L b Bonding; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R for The nitrogen atom and L b Bonding, where R s1 , R s2 and R s3 Each independently is R s ;or L R for The nitrogen atom and L b Bonding, where R s1 , R s2 and R s3 Each independently is R s .

5. The compound according to claim 1 or 2, wherein: The compound has the structure of B-1a, B-1b, B-1c or B-1d: or its salts; The compound has the structure of B-2a, B-2b, B-2c, B-2d or B-2e: or its salts; The compound has the structure of B-3a, B-3b, B-3c or B-3d: or its salts; The compound has the structure of B-4a, B-4b, B-4c or B-4d: or its salts; The compound has the structure of B-5a, B-5b, B-5c or B-5d: or its salts; Wherein the compound has the structure of B-6a, B-6b, B-6c or B-6d: or a salt thereof; or Wherein the compound has the structure of B-7a, B-7b, B-7c or B-7d: or a salt thereof.

6. A compound as described in any one of claims 1 to 5, wherein R s1 is -N(R')2, -OR, is an optionally substituted C 1-6 Aliphatic groups (such as -CF3 or CHF2), halogens.

7. A compound as described in any one of claims 1 to 5, wherein R s1 -H, -NH2, -Cl, -NHCH3, -CHF2, -CF3, -NHCD3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -N(CH3)2, -NHCH2CF3、-NHCH2CHF2、-NHCH2CH=CH2、-OH、-OCH3、 8. A compound as described in any one of claims 1 to 7, wherein each R s2 and R s3 is independently -H or an optionally substituted C 1-6 Fat based.

9. A compound as described in any one of claims 1 to 7, wherein R s2 and R s3 Together with the carbon atoms to which they are attached, they form an optionally substituted 3-10 membered saturated or partially unsaturated ring having 0-4 heteroatoms; an optionally substituted 3-6 membered saturated or partially unsaturated carbocyclic ring; or an optionally substituted 3-6 membered saturated or partially unsaturated ring having 1-4 heteroatoms.

10. The compound according to claim 9, wherein: R s2 and R s3 together with the carbon atoms to which they are attached form an optionally substituted cyclopropyl; R s2 and R s3 Together with the carbon atom to which they are attached they form a cyclopropyl group; Where R s2 and R s3 together with the carbon atoms to which they are attached form an optionally substituted cyclobutyl group; R s2 and R s3 Together with the carbon atom to which they are attached they form a cyclobutyl group; R s2 and R s3 Together with the carbon atom to which they are attached, they form an optionally substituted cyclopentyl group; R s2 and R s3 Together with the carbon atom to which they are attached they form a cyclopentyl group; R s2 and R s3 Together with the carbon atoms to which they are attached they form an optionally substituted cyclohexyl group; R s2 and R s3 Together with the carbon atom to which they are attached they form a cyclohexyl group; R s2 and R s3 Together with the carbon atom to which they are attached, they form an optionally substituted R s2 and R s3 Together with the carbon atoms to which they are attached, they form R s2 and R s3 Together with the carbon atom to which they are attached, they form an optionally substituted or R s2 and R s3 Together with the carbon atoms to which they are attached, they form 11. The compound as claimed in claim 2, wherein L R yes in: "*" indicates the same as R 4 Bonded atoms; R s1 YesR s ; Z' is -N= or -C(R s4 )=; Z" is -N= or -C(R s5 )=; and Any R s4 and R s5 Each independently is R s .

12. The compound according to claim 11, wherein: L R for Where "*" indicates the same as R 4 bonded atoms; or L R for Where "*" indicates the same as R 4 Bonded atoms.

13. A compound according to any one of claims 11 to 12, wherein: R s1 is -N(R')2 or -OR; or R s1 It is -H, -NH2 or -NHCH3.

14. A compound as described in any one of claims 11 to 13, wherein R s4 is -H, -halogen, -CN, -N(R')2 (eg, -NH2) or is an optionally substituted 1-10 Aliphatic, C with 1-5 heteroatoms 1-10 heteroaliphatic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms, and 3-10 membered heterocyclyl having 1-5 heteroatoms.

15. The compound according to claim 11 or 12, wherein R s4 is optionally substituted -OCH(CH3) 2、 16. A compound as described in any one of claims 11 to 15, wherein R s5 is -H, -halogen (eg -F), -N(R')2 (eg -NH2 or -NHCH3), -OR (eg -OH or -OCH3) or is an optionally substituted 1-10 Aliphatic, C with 1-5 heteroatoms 1-10 Heteroaliphatic group, C 5-8 The invention also includes aryl, 5- to 8-membered heteroaryl having 1 to 4 heteroatoms and 3- to 10-membered heterocyclyl having 1 to 5 heteroatoms.

17. A compound according to any one of claims 11 to 16, wherein: L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms; L R For optional replacement Where "*" indicates the same as R 4 bonded atoms; or L R For optional replacement Where "*" indicates the same as R 4 Bonded atoms.

18. A compound as claimed in any one of the preceding claims, wherein the compound is in a tautomeric form comprising =0 bonded to the ring, or another tautomeric form in which =O exists as -OH (e.g., wherein -OH is R s1 ).

19. The compound as claimed in claim 2, wherein L R is a covalent bond, is an optionally substituted C 1-6 Alkylene, optionally substituted methylene, optionally substituted C 2-6 Alkenylene, optionally substituted C 2-6 Alkyne, optionally substituted C 3-10 Cycloalkylene, optionally substituted C 6-14 Arylene, optionally substituted C 7-15 Aralkylene, an optionally substituted 5-14-membered heteroarylene group having 1-5 heteroatoms, or L R It is an optionally substituted 3-14-membered heterocyclylene group having 1-5 heteroatoms.

20. A compound as claimed in any one of the preceding claims, wherein L b For -L b1 -L b2 -L b3 -L b4 -L b5 -, where L b1 , L b2 , L b3 , L b4 and L b5 Each is independently L', wherein each L' is independently a covalent bond, or an optionally substituted diisocyanate having 1-2 heteroatoms. Price C 1-2 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-, wherein L b1 Bonded to ring L.

21. A compound as claimed in any one of the preceding claims, wherein L b It's -Cy-.

22. The compound of claim 21, wherein L b is an optionally substituted phenyl group; or has 0-4 (e.g., 1-4, 0, 1, 2, 3, 4, etc.) heteroatoms and optionally substituted divalent 5- or 6-membered heteroaryl rings.

23. The compound of claim 21, wherein L b is optionally substituted phenyl, pyridyl, pyridazinyl, pyrimidinyl or thiazolyl.

24. The compound of claim 21, wherein L b is phenyl, pyridyl, pyridazinyl, pyrimidinyl, thiazolyl, which may be optionally substituted with halogen (e.g., -F, -Cl, -Br or -I) or -OR°, wherein R° is C 1-6 Aliphatic group (eg, methyl, ethyl, n-propyl, sec-propyl or isopropyl).

25. The compound of claim 21, wherein L b for "*" indicates the same as L R Bonded atoms.

26. The compound of claim 21, wherein L b is a divalent optionally substituted 6- to 12-membered heterocyclic group having 1-4 (eg, 0, 1, 2, 3 or 4) heteroatoms; L b is a divalent optionally substituted 10- to 15-membered tricyclic heterocyclic group having 1-4 (eg, 0, 1, 2, 3 or 4) heteroatoms; L b is a divalent optionally substituted 6- to 12-membered heteroaryl ring having 1-4 (eg, 0, 1, 2, 3 or 4) heteroatoms.

27. The compound of claim 21, wherein L b is a divalent optionally substituted 2,3-dihydrobenzofuranyl, chromanyl or spiro[chroman-4,1'-cyclopropyl].

28. The compound of claim 21, wherein L b is a divalent 2,3-dihydrobenzofuranyl, or chromanyl or spiro[chroman-4,1'-cyclopropyl], optionally substituted by C 1-6 The alkylene groups are substituted with aliphatic groups (e.g., methyl, ethyl, n-propyl, sec-propyl or isopropyl) or halogen (e.g., -F, -Cl, -Br, -I).

29. The compound of claim 21, wherein: L b for The "*" represents the same as L R The connection point; L b is a divalent optionally substituted chroman group; or R b -H,L b for The "*" represents the same as L R The connection point; R b -H,L b for The "*" represents the same as L R The connection point; R b -H,L b for The "*" represents the same as L R The connection point; R b is -H, and L b for 30. The compound of claim 21, wherein L b is a divalent optionally substituted 6- to 12-membered heteroaryl ring having 1-4 (eg, 0, 1, 2, 3 or 4) heteroatoms.

31. The compound of claim 21, wherein L b is a divalent optionally substituted imidazo[1,5-a]pyridinyl, indazolyl, benzo[d] Imidazolyl or pyrazolyl[1,5-a]pyrimidinyl.

32. The compound of claim 21, wherein L b is imidazo[1,5-a]pyridinyl, L b is a divalent imidazo[1,5-a]pyridinyl, indazolyl, benzo[d]imidazolyl or pyrazolyl[1,5-a]pyrimidinyl group, optionally substituted by C 1-6 The residues may be substituted with aliphatic groups (e.g., methyl, ethyl, n-propyl, sec-propyl or isopropyl) or halogen (e.g., -F, -Cl, -Br, -I).

33. The compound of claim 21, wherein L b for The "*" represents the same as L R connection point.

34. The compound of claim 21, wherein L b *-N(R')-Cy-, where "*" represents L R connection point.

35. The compound of claim 21, wherein L b yes The "*" represents the same as L R connection point.

36. The compound of claim 21, wherein L b for The "*" represents the same as L R connection point.

37. A compound as claimed in any one of the preceding claims, wherein R b Not hydrogen.

38. A compound as claimed in any one of the preceding claims, wherein R b is hydrogen, is optionally substituted C 1-20 Aliphatic groups (e.g., methyl, (e.g., -CF3), ethyl, isopropyl, -C 0-4 alkyl-C≡CH or propargyl), is an optionally substituted C 3-20 Alicyclic groups (such as cyclopropyl, cyclopentyl or cyclohexyl), optionally substituted C 1-20 Heteroaliphatic, -CN, -OH, -OCH3, -OCH(CH2CH3)2, -OCH2CH2CH2CH3, -OCH2CH2CH2CH2CH2CH3, -N(R')2 (e.g., -N(CH2CH3)2), sulfone (e.g., -S(O2)CH3), optionally substituted C 6-20 Aryl (e.g., phenyl or naphthyl), optionally substituted 5-20 membered heteroaryl (e.g., pyridyl), optionally substituted 3-20 membered heterocyclyl having 1-10 heteroatoms (e.g., tetrahydro-2H-pyranyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptyl or 3-oxa-8-azabicyclo[3.2.1]octyl).

39. A compound as described in any one of claims 1 to 38, wherein R b is optionally substituted tetrahydro-2H-pyranyl, morpholinyl, 3,6-dihydro-2H-pyranyl, azetidinyl, pyrrolidinyl, piperidinyl, silanyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 3-oxa-8-azabicyclo[3.2.1]octyl.

40. A compound as described in any one of claims 1 to 38, wherein R b is 4-tetrahydro-2H-pyranyl, 41. A compound as described in any one of claims 1 to 38, wherein R b is -O-R', wherein R' is an optionally substituted 3- to 8-membered saturated or partially unsaturated carbon ring; is an optionally substituted phenyl; or is an optionally substituted 3- to 8-membered saturated or partially unsaturated carbon ring containing 1 to 3 heteroatoms selected from nitrogen, oxygen or sulfur. to 7-membered heterocyclic group.

42. A compound as described in any one of claims 1 to 38, wherein R b for 43. A compound having a structure of formula A': or a salt thereof, wherein: Ring P is an optionally substituted 5-20 membered monocyclic, bicyclic or polycyclic ring having 0-5 heteroatoms; is a single bond or a double bond; Y and Z are each independently C or N; Any R 2 and R 3 Each independently is R" or R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ; L w is a covalent bond, or is an optionally substituted divalent C 1-6 an aliphatic or heteroaliphatic group in which one or more methylene units are optionally and independently replaced by -C(R') 2 - 、 -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R' )-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- or -C(O)O- substitution; R w is -T-C(=NR w1 ),N(R w2 )(R w3 ); Any R w1 , R w2 and R w3 Each is independently -L-R', or a detectable moiety; T is O or S; R 5 and R 6 each independently is R" or -C(O)OR"; Any R 7 and R 8 Each independently is R”; Ring A is an optionally substituted 3-20-membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; L A It is L; Any R 9 and R s each independently represents R", halogen, -CN, oxo, -NO2 or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl; p and q are each independently 0-10; Each R" is independently hydrogen, halogen, -L-R', -L-OR', -L-SR', -LC(O)OR', -LC(O)SR', -LC(O)N(R')2, -L-OC(O)N(R')2, -LC(O)R', -LN(R')2, -CN, -OC(R')2COOH, -SC(R') 2COOH, -N(R')C(R')2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester and thioether; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Each R is independently -H, or an optionally substituted group selected from C 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms therebetween to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms therebetween. X is -O-, -S-, -C(R 1 )=、-N(R 1 )-, or is optionally substituted -CH=, -CH=CH- or -NH-; t is 0-9; and R 1 YesR 9 ; or Compounds having the structure of formula C: or a salt thereof, wherein: R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ; L w is a covalent bond, or is an optionally substituted divalent C 1-6 an aliphatic or heteroaliphatic group in which one or more methylene units are optionally and independently replaced by -C(R') 2-、 -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R' )-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- or -C(O)O- substitution; R w is - T - C(=NR w1 ), N(R w2 )(R w3 ); Each R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; R 10 , R 11 , R 12 , R 13 and R 14 Each independently is R”; Each R" is independently hydrogen, halogen, -L-R', -L-OR', -L-SR', -LC(O)OR', -LC(O)SR', -LC(O)N(R')2, -L-OC(O)N(R')2, -LC(O)R', -LN(R')2, -CN, -OC(R')2COOH, -SC(R') 2COOH or -N(R')C(R')2COOH; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Each R is independently halogen, -H, or an optionally substituted group selected from C 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms optionally and independently form with the atoms between them an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms between them; or Compounds having the structure of formula D: or a salt thereof, wherein: R 15 and R 16 Each independently is -L-R'; R 4 is or contains an isourea or isothiourea moiety, or is -L w -R w ; L w is a covalent bond, or is an optionally substituted divalent C1-6 aliphatic or heteroaliphatic group having 1 to 6 heteroatoms, wherein one or more methylene units are optionally and independently substituted by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- or -C(O)O-; R w is - T - C(=NR w1 ),N(R w2 )(R w3 ); R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Each R is independently halogen, -H, or an optionally substituted group selected from C 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms optionally and independently form with the atoms between them an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms between them; or Compounds having the structure of formula E: or a salt thereof, wherein: R 4 is or contains an isourea or isothiourea moiety, or -L w -R w ; L w is a covalent bond, or is an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; R w is -T-C(=NR w1 ),N(R w2 )(R w3 ); Each R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; R 17 and R 18 Each is independently an optionally substituted 5-20 membered monocyclic, bicyclic or polycyclic aromatic ring having 0-5 heteroatoms; Ring C is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-6 heteroatoms; L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each R is independently -H, or an optionally substituted group selected from C 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms optionally and independently form with the atoms between them an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms between them; or Compounds having the structure of formula F: or a salt thereof, wherein: R 4 is or contains an isourea or isothiourea moiety, or -L w -R w ; L w is a covalent bond, or is an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently replaced by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O) 2N (R')-, -C(O)S- or -C(O)O- substituted; R w is - T - C(=NR w1 ),N(R w2 )(R w3 ); Each R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; Each R s6 , R s7 Each independently is R s ; Each R s R" is independently halogen, -CN, oxo, -NO2 、 or a group selected from optionally substituted acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl; each R″ is independently hydrogen, halogen, -L-R′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or a group selected from optionally substituted alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester and thioether; q, x and y are each independently 0-4; L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each R is independently -H, or an optionally substituted group selected from C 1-20脂肪 A C group having 1 to 10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms optionally and independently form with the atoms between them an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms between them; or Compounds having the structure of formula G: or a salt thereof, wherein: Ring B is an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; R 4 is or contains an isourea or isothiourea moiety, or -L w -R w ; Lw is a covalent bond, or an optionally substituted divalent C1-6 aliphatic or heteroaliphatic group having 1-6 heteroatoms, wherein one or more methylene units are optionally and independently substituted by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- or -C(O)O-; R w is -T-C(=NR w1 ),N(R w2 )(R w3 ); Each R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; R 8a For R m ,or L A It is L; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Ring A is an optionally substituted 3-20-membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Each R m Independently for R s ; Each R s R" is independently halogen, -CN, oxo, -NO2 、 or a group selected from optionally substituted acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl; each R″ is independently hydrogen, halogen, -L-R′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or a group selected from optionally substituted alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester and thioether; q is independently 0-10; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each R is independently -H, or an optionally substituted group selected from C 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms optionally and independently form with the atoms between them an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms between them; or Compounds having the structure of formula H: or a salt thereof, wherein: R 4 is or contains an isourea or isothiourea moiety, or -L w -R w ; Lw is a covalent bond, or an optionally substituted divalent C1-6 aliphatic or heteroaliphatic group having 1-6 heteroatoms, wherein one or more methylene units are optionally and independently substituted by -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- or -C(O)O-; R w is - T - C(=NR w1 ),N(R w2 )(R w3 )); Each R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; R 5 are independently R" or -C(O)OR"; R 2 independently R" or L A It is L; Ring A is an optionally substituted 3-20-membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; R 9 and R s each independently represents R", halogen, -CN, oxo, -NO2 or an optionally substituted group selected from acyl, amido, hydroxy, amino acid, amine, amide, carbamate, ester, ether, carboxylic acid, thio, sulfanyl, thioester, thioether, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, alkylsulfonyl and arylsulfonyl; p and q are each independently 0-10; each R″ is independently hydrogen, halogen, -L-R′, -L-OR′, -L-SR′, -LC(O)OR′, -LC(O)SR′, -LC(O)N(R′)2, -L-OC(O)N(R′)2, -LC(O)R′, -LN(R′)2, -CN, -OC(R′)2COOH, -SC(R′)2COOH, -N(R′)C(R′)2COOH, or an optionally substituted group selected from alkylsulfonyl, arylsulfonyl, carboxylate, ester, ether, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, sugar alcohol, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, sulfanyl, thioester and thioether; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; Each R is independently -H, or an optionally substituted group selected from C 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 Aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms therebetween to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms therebetween.

44. A compound as claimed in any one of the preceding claims, wherein R 4 For -L w -R w ,in: L w is a covalent bond, or is an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; R w Yes-TC(=NR w1 )N(R w2 )(R w3 ); Each R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; and Each R is independently -H, or is an optionally substituted 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms therebetween to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms therebetween.

45. A compound as claimed in any one of the preceding claims, wherein R 4 For -L w -R wh ,in: L w is a covalent bond, or is an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; R wh YES-TH; T is O or S; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; and Each R is independently -H, or is an optionally substituted 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms therebetween to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms therebetween.

46. ​​A compound according to any preceding claim, wherein L w is a covalent bond, is optionally substituted -CH2-, -CHD-, -CD2-, a monosubstituted -CH2-, -CH(CH3)-, -CHD-, monosubstituted -CD2-, -C(O)-CH2-, optionally substituted -C(S)-CH2-, -C(N(R'))-CH2- (wherein -CH2- is optionally substituted), optionally substituted -C(O)-CHD-, optionally substituted -C(S)-CHD-, -C(N(R'))-CHD- (wherein -CHD- is optionally substituted), optionally substituted -C(O)-CD2-, optionally substituted -C(S)-CD2-, -C(N(R'))-CD2- (wherein -CD2- is optionally substituted).

47. A compound as claimed in any one of the preceding claims, wherein T is O.

48. A compound as described in any one of the preceding claims 1-46, wherein T is S.

49. A compound as claimed in any preceding claim, wherein R w1 for -L-R'.

50. A compound as claimed in any preceding claim, wherein R w1 is H, is an optionally substituted C 1-10 aliphatic, optionally substituted C 1-10 Alkyl, methyl, ethyl, isopropyl, optionally substituted C 3-10 Cycloalkyl, cyclohexyl, optionally substituted C 1-10 Heteroaliphatic 、 is an optionally substituted C 6-14 aryl, phenyl which is optionally substituted, 5-10 membered heteroaryl which is optionally substituted having 1-4 heteroatoms, 3-10 membered heterocyclyl which is optionally substituted having 1-4 heteroatoms, or a detectable moiety.

51. A compound as claimed in any one of the preceding claims, wherein R w2 Yes-L-R'. A compound as described in any of the above embodiments, wherein R w2 is H, is an optionally substituted C 1-10 aliphatic, optionally substituted C 1-10 Alkyl, optionally substituted C 1-6 Halogenated alkyl, methyl, ethyl, isopropyl, -C(CH2)2-C≡C-CH3, -CH2-C≡CH, optionally substituted C 3-10 Cycloalkyl, cyclopropyl, cyclohexyl, optionally substituted adamantyl, 1-adamantyl, -CH2-CF3, optionally substituted C with 1 to 3 heteroatoms 1-10 Heteroaliphatic, optionally substituted C 6-14 The aryl group is an optionally substituted phenyl group, an optionally substituted 5- to 10-membered heteroaryl group having 1 to 4 heteroatoms, an optionally substituted 3- to 10-membered heterocyclyl group having 1 to 4 heteroatoms, or an optionally substituted oxetanyl group.

52. A compound as described in any one of claims 1 to 48, wherein: R w1 and R w2 Together with the atoms between them, they form an optionally substituted 5-14 membered ring having 0-6 heteroatoms in addition to the middle atom; or R w1 and R w2 Together with the atoms between them, they form an optionally substituted 5-14 membered partially unsaturated ring, and have 0-6 heteroatoms in addition to the middle atom.

53. A compound as claimed in any preceding claim, wherein -C(=NR w1 )N(R w2 )-optional replacement where y is independently 0-4, wherein y is independently 0, 1, 2, 3 or 4, wherein y is independently 0, 1, 2, 3 or 4, and It is a single bond or a double bond.

54. A compound as claimed in any preceding claim, wherein R w3 for -L-R'.

55. A compound as claimed in any preceding claim, wherein R w3 is H, is an optionally substituted C 1-10 aliphatic, optionally substituted C 1-10 Alkyl, optionally substituted C 1-6 haloalkyl, methyl, ethyl, isopropyl, optionally substituted C 3-10 Cycloalkyl, cyclopropyl, cyclohexyl, optionally substituted adamantyl, 1-adamantyl, -CH2-CF3, optionally substituted C with 1 to 3 heteroatoms 1-10 Heteroaliphatic, optionally substituted C 6-10 The invention also includes but is not limited to aryl, phenyl, 5-10-membered heteroaryl, 3-10-membered heterocyclyl, 0-5-heteroatoms, 3-10-membered saturated ring, 0-5-heteroatoms, phenyl, 5-6-membered heteroaryl, 2-pyridyl, 3-pyridyl or 4-pyridyl.

56. A compound as described in any one of claims 1 to 50, wherein: R w2 and R w3 Together with the nitrogen atom to which they are attached, they form an optionally substituted 3-14 membered ring having 0-6 heteroatoms in addition to the nitrogen atom; R w2 and R w3 Together with the nitrogen atom to which they are attached, they form an optionally substituted 3-10 membered aromatic ring having 0-5 heteroatoms in addition to the nitrogen atom; or R w2 and R w3 Together with the nitrogen atom to which they are attached, they form an optionally substituted 3-8 membered monocyclic non-aromatic ring having 0-3 heteroatoms in addition to the nitrogen atom.

57. A compound as described in any one of claims 1 to 50, wherein: -N(R w2 )(R w3 ) is an optional replacement Wherein x and y are independently 0-4; or -N(R w2 )(R w3 ) is an optional replacement Wherein x and y are independently 0-4; or -N(R w2 )(R w3 ) is an optional replacement Wherein x and y are independently 0-4; or -N(R w2 )(R w3 ) is optional where y0-4; or -N(R w2 )(R w3 ) is optional wherein x and y are each independently 0-4, and Q is optionally substituted S, Si, or S(O)2.

58. A compound as described in any one of claims 1-50, wherein -N(R w2 )(R w3 ) is -NH2, 59. A compound as described in any one of claims 1 to 43, wherein R 4 for 60. A pharmaceutical composition comprising or delivering a compound as claimed in any one of the preceding claims, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

61. A method for inhibiting the activity of a polypeptide comprising a nucleophilic portion, comprising contacting the polypeptide with a compound or composition as described in any one of the preceding claims; preferably: wherein the nucleophilic moiety is -SH or -SeH or a salt thereof; or wherein the polypeptide is GPX4; or A method for inhibiting cell proliferation in a system, comprising administering to the system any one of the compounds or compositions as claimed in claim 1; or A method of inducing cell death in a system, comprising administering to the system any one of the compounds or compositions as claimed in claim 1 ; or A method for inducing ferroptosis in a system, comprising administering to the system a compound or composition as described in any one of claims 1 to 5.

62. A method of preventing a condition, disorder or disease comprising administering or delivering to a susceptible subject an effective amount of a compound or composition as described in any one of claims 1 to 63; or A method for preventing a condition, disorder or disease associated with a polypeptide comprising -SeH or a salt form, comprising administering or delivering to a susceptible subject an effective amount of a compound or composition as described in any one of claims 1 to 5; or A method for treating a condition, disorder or disease associated with a polypeptide comprising -SeH or a salt form, comprising administering or delivering an effective amount of any of the aforementioned compounds or compositions as claimed in claim 1 to a subject suffering from the condition, disorder or disease.

63. A method of treating a condition, disorder or disease comprising administering or delivering to a subject suffering from the condition, disorder or disease an effective amount of a compound or composition according to any preceding claim.

64. The method of claim 62 or 63, wherein the condition, disorder or disease is cancer.

65. The method of claim 64, wherein: the cancer is adrenocortical carcinoma, anal cancer, biliary tract cancer, bladder cancer, bone cancer, brain cancer, breast cancer, cervical cancer, colon cancer, endometrial cancer, esophageal cancer, head and neck cancer, intestinal cancer, liver cancer, lung cancer, oral cancer, ovarian cancer, pancreatic cancer, kidney cancer, prostate cancer, salivary gland cancer, skin cancer, stomach cancer, testicular cancer, laryngeal cancer, thyroid cancer, uterine cancer, vaginal cancer, sarcoma, or soft tissue cancer; or The cancer is osteosarcoma, glioma, astrocytoma, neuroblastoma, small intestinal cancer, bronchial cancer, small cell lung cancer, non-small cell lung cancer, basal cell carcinoma or melanoma.

66. The method of claim 65, wherein the cancer is a hematological cancer.

67. The method of claim 66, wherein the blood cancer is acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), lymphoma (e.g., Hodgkin's lymphoma, non-Hodgkin's lymphoma, Burkitt's lymphoma), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), hairy cell chronic myeloid leukemia (CML), or multiple myeloma.

68. A compound comprising an isourea moiety or a salt thereof.

69. A compound comprising an isothiourea moiety or a salt thereof.

70. A compound as claimed in any one of the preceding claims, wherein: The compound inhibits the activity of a polypeptide containing a selenocysteine ​​residue; The compound reacts with selenocysteine ​​or a salt thereof, or a selenocysteine ​​residue in a polypeptide; -SeH substituted isourea moiety in the form of selenocysteine ​​or a salt thereof; The compound is capable of inhibiting or preventing cell growth or proliferation; The compound is able to induce cell death; The compound is able to induce ferroptosis; In the presence of ferroptosis inhibitors, the compound's effectiveness was reduced; The IC50 observed for the compound in the presence of a ferroptosis inhibitor is about or at least about 2-5000, such as about or at least about 10-1000, 50-1000, 100-1000, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, or 1000 times greater than that in the absence of the ferroptosis inhibitor; An IC50 of the indicated compound is observed to be about 10-fold or at least about 10-fold higher in the presence of a ferroptosis inhibitor than in the absence of the ferroptosis inhibitor; The IC50 of the indicated compound is observed to be about 20-fold or at least about 20-fold higher in the presence of the ferroptosis inhibitor than in the absence of the ferroptosis inhibitor; An IC50 of the compound is observed to be about 50-fold or at least about 50-fold higher in the presence of a ferroptosis inhibitor than in the absence of the ferroptosis inhibitor; The IC50 of the indicated compound is observed to be about 100-fold or at least about 100-fold higher in the presence of the ferroptosis inhibitor than in the absence of the ferroptosis inhibitor; In the presence of a ferroptosis inhibitor, the compound has an observed IC50 for ferroptosis ability of about or at least about 1-100, such as about or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100 uM; When ferroptosis inhibitors are evaluated individually, the concentration of the ferroptosis inhibitor is about or at least about the EC50 of the ferroptosis inhibitor; The concentration of the ferroptosis inhibitor is about or at least about 0.1-100, such as about or at least about 1-20, 2-10, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40 or 50 uM; The concentration of the ferroptosis inhibitor is about or at least about 1 uM; The concentration of the ferroptosis inhibitor is about or at least about 2 uM; The compound inhibits the activity of GPX4; The compound binds to GPX4; or The isourea or isothiourea part has R w , where R w = NR w1 )N(R w2 )(R w3 ) or a salt thereof, wherein R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; T is O or S; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; and Each R is independently -H, or is an optionally substituted 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms therebetween to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms therebetween.

71. A method comprising R w A compound or a salt form thereof, wherein R w = NR w1 )N(R w2 )(R w3 ), where R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; T is O or S; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; and Each R is independently -H, or is an optionally substituted 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intervening atoms. Contains R w A compound wherein R w = NR w1 )N(R w2 )(R w3 ) or a salt thereof, wherein R w1 , R w2 and R w3 Each is independently -L-R' or a detectable moiety; Each L is independently a covalent bond, or an optionally substituted divalent C 1-10 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted, 3-20-membered, monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; and Each R is independently -H, or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-10 heteroatoms, C6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or: The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be combined with their intermediate atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the intermediate atoms.

72. The compound of claim 71 or 72, comprising -L w -R w , where L w is a covalent bond, or an optionally substituted divalent C 1-6 aliphatic or heteroaliphatic, wherein one or more methylene units are optionally and independently substituted with -C(R')2-, -Cy-, -O-, -S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(S)N(R')-, -C(NR')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms; each R' is independently R, -OR, -C(O)R, -C(O)OR, -C(O)N(R)2, -S(O)R or -S(O)OR; and Each R is independently -H, or is an optionally substituted 1-20 Aliphatic, C with 1-10 heteroatoms 1-20 Heteroaliphatic group, C 6-20 aryl, 5-20 membered heteroaryl having 1-10 heteroatoms, 3-20 membered heterocyclyl having 1-10 heteroatoms, and combinations thereof, wherein each combination independently has 1-30 carbon atoms and 0-10 heteroatoms; or The two R groups optionally and independently form a covalent bond together, or: Two or more R groups on the same atom may optionally and independently be taken together with the atom to form an optionally substituted 3-20 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atom; or: Two or more R groups on two or more atoms may optionally and independently be taken together with the atoms therebetween to form an optionally substituted 3-30 membered monocyclic, bicyclic or polycyclic ring having 0-10 heteroatoms in addition to the atoms therebetween.

73. The compound of any one of claims 73-75, wherein the compound comprises -C(=O)-L w -R w .

74. A compound shown in Table C1 or C2, or a pharmaceutically acceptable salt thereof.

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