Compounds, devices and uses thereof

Abstract

Implantable elements (eg, devices and materials) and compounds useful for, eg, treating or preventing a disease, disorder, or condition are provided. The present invention provides a compound represented by formula (II-c) or a salt thereof (wherein: ring M 1 Each contains 1 to 5 R 3 cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; Z 1 are each one or more R 5 wherein R is an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with R. TIFF2026016478000253.tif31149

Description

[Background technology]

[0001] The function of implanted devices is highly dependent on the recipient's biological immune response pathways (Anderson et al., Semin. Immunol. 20:86-100 (2008); Langer, Adv. Mater. 21:3235-3236 (2009)). Modulation of the immune response can have beneficial effects on the fitness and function of these devices. Therefore, there is a need in the art for new compounds, compositions, and devices that achieve this goal. Summary of the Invention [Means for solving the problem]

[0002] Described herein are compounds (e.g., compounds of Formula (I)), compositions, and implantable elements (e.g., devices and materials) comprising the same, as well as methods of use thereof. In particular, the compounds (e.g., compounds of Formula (I)) and related compositions and implantable elements can be used in methods for the prevention and treatment of diseases, disorders, or conditions in patients. In some embodiments, the compounds (e.g., compounds of Formula (I)), and their pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions, and implantable elements comprising the same, are capable of modulating an immune response in a patient, e.g., upregulating or downregulating an immune response in a patient.

[0003] In one aspect, the present invention provides a compound of formula (I): AL 1 -ML 2 -PL 3 -Z (I) or a salt thereof, wherein A is selected from A1 or A2, where A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)RB , -OC(O)R B , -N(R C )(R D ), -N(R C )C(O)R B , -C(O)N(R C )(R D ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCNR C , -C(=N(R C )(R D ))OR A , -SR E , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 A2 is optionally substituted by alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D ))O-, -S-, -S(O) x -, -OS(O) x -, -N(R C )S(O) x-, -S(O) x N(R C )-, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A )- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 and optionally substituted by L 1 , L 2 and L 3 is independently a bond, alkyl, alkenyl, alkynyl, or heteroalkyl, wherein each of the alkyl, alkenyl, alkynyl, and heteroalkyl is selected from 1 to 5 R 2 M is optionally substituted with one or more R 3 P is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 4 cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , R E , R F and R G are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from one or more R6 or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 and R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by R A1 , R B1 , R C1 , R D1 , R E1 and R F1are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4.

[0004] In some embodiments, A is A. In some embodiments, A is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D In some embodiments, A is —N(R C )(R D ) (e.g., NH2). In some embodiments, A1 is NH2 or NHC(O)C(CH2)CH3.

[0005] In some embodiments, A is A2. In some embodiments, A2 is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -Si(OR A )2-, -Si(R G )(OR A )-OR-B(OR A In some embodiments, A2 is —N(R C)—(e.g., NH—). In some embodiments, A2 is NH— or NH(C(O)C(CH3)CH2—. In some embodiments, a compound comprises A2, and the compound is, e.g., covalently attached to an implantable element, e.g., a device. In some embodiments, A2 is directly attached to the device. In some embodiments, A2 is attached to the device by a linking group (e.g., a linking group described herein). In some embodiments, the device is, e.g., covalently attached to a linking group, and A2 is, e.g., covalently attached to a linking group.

[0006] In some embodiments, L 1 , L 2 and L 3 Each of L is independently a bond, alkyl, or heteroalkyl. 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is C1-C6 alkyl (e.g., -CH2- or -CH2CH2-). 2 is a bond. In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is C1-C6 alkyl (e.g., -CH2-) or heteroalkyl (e.g., -CH2O-).

[0007] In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (—OCH2CH2—)z, where z is an integer selected from 1 to 10. In some embodiments, M is aryl (e.g., phenyl).

[0008] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl (e.g., tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl). In some embodiments, P is a triazolyl (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl). In some embodiments, P is [ka] In some embodiments, P is selected from [ka] is.

[0009] In some embodiments, Z each represents one or more R 5 In some embodiments, Z is alkyl, heterocyclyl, or aryl, optionally substituted by: In some embodiments, Z is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, Z is nitrogen-containing heterocyclyl, oxygen-containing heterocyclyl, or sulfur-containing heterocyclyl (e.g., tetrahydropyranyl or thiomorpholinyl-1,1-dioxide). In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0010] In some embodiments, Z is aryl (e.g., phenyl). In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5is an amine-containing group (e.g., NH). In some embodiments, Z is a monosubstituted phenyl, where one R 5 is an oxygen-containing group (e.g., OCH). In some embodiments, one R 5 is in the ortho or para position.

[0011] In some embodiments, Z is alkyl (e.g., C1-C 12 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is -OH or -C(O)OH.

[0012] In some embodiments, Z is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z is (—OCH2CH2—)zOCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10).

[0013] In some embodiments, the compound of formula (I) is a compound of formula (II): [ka] or a salt thereof, wherein A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -ORA , -C(O)OR A , -C(O)R B , -OC(O)R B , -N(R C )(R D ), -N(R C )C(O)R B , -C(O)N(R C )(R D ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCN(R C ), -C(=N(R C )(R D ))OR A , -SR E , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 and optionally substituted by L 1 and L 3 is independently a bond, alkyl, or heteroalkyl, wherein each of the alkyl and heteroalkyl is selected from one or more R 2 and optionally substituted by L 2 is a bond; M is each one or more R 3 P is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with one or more R 4and Z is heteroaryl optionally substituted with one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , R E , R F and R G is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x R E1 , -OS(O) x R E1 , -N(R C1 )S(O) x R E1 , -S(O) x N(RC1 )(R D1 ), -P(R F1 ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by R A1 , R B1 , R C1 , R D1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4.

[0014] In some embodiments, A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D In some embodiments, A is —N(R C )(R D ) (e.g., NH2). In some embodiments, A1 is NH2 or NHC(O)C(CH2)CH3.

[0015] In some embodiments, L 1 , L 2 and L3 Each of L is independently a bond, alkyl, or heteroalkyl. 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is C1-C6 alkyl (e.g., -CH2- or -CH2CH2-). 2 is a bond. In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is C1-C6 alkyl (e.g., -CH2-) or heteroalkyl (e.g., -CH2O-).

[0016] In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (—OCH2CH2—)z, where z is an integer selected from 1 to 10. In some embodiments, M is aryl (e.g., phenyl).

[0017] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl (e.g., tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl). In some embodiments, P is a triazolyl (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl). In some embodiments, P is [ka] In some embodiments, P is selected from [ka] is.

[0018] In some embodiments, Z each represents one or more R 5 In some embodiments, Z is alkyl, heterocyclyl, or aryl, optionally substituted by: In some embodiments, Z is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, Z is nitrogen-containing heterocyclyl, oxygen-containing heterocyclyl, or sulfur-containing heterocyclyl (e.g., tetrahydropyranyl or thiomorpholinyl-1,1-dioxide). In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0019] In some embodiments, Z is aryl (e.g., phenyl). In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is an amine-containing group (e.g., NH). In some embodiments, Z is a monosubstituted phenyl, where one R 5 is an oxygen-containing group (e.g., OCH). In some embodiments, one R 5 is in the ortho or para position.

[0020] In some embodiments, Z is alkyl (e.g., C1-C 12 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R5 is -OH or -C(O)OH.

[0021] In some embodiments, Z is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z is (—OCH2CH2—)zOCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10).

[0022] In some embodiments, the compound of formula (II) has the formula (II-c): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; Z 1 are each one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C and R Dare independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —C(O)R B1 , -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x , cycloalkyl or heterocyclyl; R A1 , R B1 , R C1 , R D1 and R E1are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each m and n is independently 0, 1, 2, 3, 4, 5, or 6; and x is 1 or 2.

[0023] In some embodiments, ring M 1 is aryl or heteroaryl. In some embodiments, M is aryl (e.g., phenyl).

[0024] In some embodiments, P is [ka] In some embodiments, P is selected from [ka] is.

[0025] In some embodiments, ring Z 1 is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, ring Z 1 is a nitrogen-containing heterocyclyl, an oxygen-containing heterocyclyl, or a sulfur-containing heterocyclyl (e.g., tetrahydropyranyl or phthalic anhydridyl). In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0026] In some embodiments, the compound of Formula (II) has the formula (II-k): [ka] or a salt thereof, wherein Z 1 is 1 to 5 R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; and q is an integer from 0 to 25.

[0027] In some embodiments, triazolyl is [ka] In some embodiments, triazolyl is selected from [ka] is.

[0028] In some embodiments, Z 1 are each one or more R 5 In some embodiments, Z is alkyl, heterocyclyl, or aryl, optionally substituted by 1 is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, Z 1is a nitrogen-containing heterocyclyl or a sulfur-containing heterocyclyl (e.g., thiomorpholinyl-1,1-dioxide). 1 is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl or pyrrolidinyl.

[0029] In some embodiments, Z 1 is aryl (e.g., phenyl). In some embodiments, Z is a monosubstituted phenyl (e.g., one R 5 In some embodiments, Z 1 is a monosubstituted phenyl, where one R 5 is an amine-containing group (e.g., NH). In some embodiments, Z is a monosubstituted phenyl, where one R 5 is an oxygen-containing group (e.g., OCH). In some embodiments, one R 5 is in the ortho or para position.

[0030] In some embodiments, Z is alkyl (e.g., C1-C 12 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is -OH or -C(O)OH.

[0031] In some embodiments, the compound of formula (I) has formula (III): [ka] or a salt thereof, wherein A2 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —O—, —C(O)O—, —C(O)—, —OC(O)—, —N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D ))O-, -S-, -S(O) x -, -OS(O) x -, -N(R C )S(O) x -, -S(O) x N(R C )-, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A )- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 and optionally substituted by L 1 and L 3 is independently a bond, alkyl, or heteroalkyl, wherein each of the alkyl and heteroalkyl is selected from one or more R 2 and optionally substituted by L 2 is a bond; M is each one or more R 3 P is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with one or more R 4 and Z is heteroaryl optionally substituted with one or more R 5alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , R E , R F and R G is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x R E1 , -OS(O) x R E1 , -N(R C1 )S(O) x R E1 , -S(O) x N(R C1 )(R D1 ), -P(R F1 ) y, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by R A1 , R B1 , R C1 , R D1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4. The compound of any one of the preceding claims, wherein the compound (e.g., a compound of Formula (I) or Formula (II)) is disposed on a surface, e.g., an interior or exterior surface, of a device.

[0032] In some embodiments, the compound (eg, a compound of Formula (I) or Formula (II)) is disposed on a surface, such as an interior or exterior surface, of the device.

[0033] In some embodiments, A2 is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —O—, —C(O)O—, —C(O)—, —OC(O)—, —N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -Si(OR A )2-, -Si(R G )(OR A )-OR-B(OR AIn some embodiments, A2 is —N(R C )—(e.g., NH—). In some embodiments, A2 is NH— or NH(C(O)C(CH3)CH2—. In some embodiments, the compound comprises A2, and, e.g., the compound is covalently attached to the device. In some embodiments, A2 is directly attached to the device. In some embodiments, A2 is attached to the device by a linking group (e.g., a linking group described herein). In some embodiments, the device is, e.g., covalently attached to the linking group, and A2 is, e.g., covalently attached to the linking group.

[0034] In some embodiments, L 1 , L 2 and L 3 Each of L is independently a bond, alkyl, or heteroalkyl. 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is C1-C6 alkyl (e.g., -CH2- or -CH2CH2-). 2 is a bond. In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is C1-C6 alkyl (e.g., -CH2-) or heteroalkyl (e.g., -CH2O-).

[0035] In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (—OCH2CH2—)z, where z is an integer selected from 1 to 10. In some embodiments, M is aryl (e.g., phenyl).

[0036] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl (e.g., tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl). In some embodiments, P is a triazolyl (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl). In some embodiments, P is [ka] In some embodiments, P is selected from [ka] is.

[0037] In some embodiments, Z each represents one or more R 5 In some embodiments, Z is alkyl, heterocyclyl, or aryl, optionally substituted by: In some embodiments, Z is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, Z is nitrogen-containing heterocyclyl, oxygen-containing heterocyclyl, or sulfur-containing heterocyclyl (e.g., tetrahydropyranyl or thiomorpholinyl-1,1-dioxide). In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0038] In some embodiments, Z is aryl (e.g., phenyl). In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5is an amine-containing group (e.g., NH). In some embodiments, Z is a monosubstituted phenyl, where one R 5 is an oxygen-containing group (e.g., OCH). In some embodiments, one R 5 is in the ortho or para position.

[0039] In some embodiments, Z is alkyl (e.g., C1-C 12 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is -OH or -C(O)OH.

[0040] In some embodiments, Z is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z is (—OCH2CH2—)zOCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10).

[0041] In some embodiments, the compound described herein is selected from the compounds shown in any one of Figures 1-6, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is selected from the compounds shown in any one of Figures 1-6, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is selected from the compounds shown in any one of Figures 1-6 and is associated with an implantable element (e.g., a device or material) described herein. In some embodiments, the compound of Formula (I) is covalently attached to the implantable element (e.g., a device or material) via a linking group (e.g., a linking group described herein).

[0042] In some embodiments, the invention features a pharmaceutical composition including a compound described herein (eg, a compound of Formula (I)) and a pharmaceutically acceptable excipient.

[0043] In one aspect, the present invention provides a method of treating a disease, disorder or condition, e.g., at a site in a patient, e.g., at the site of an implanted cell or device, or modulating an immune response in a patient, comprising administering to a subject a compound of formula (I): AL 1 -ML 2 -PL 3 -Z (I) wherein A is A1 or A2; A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B , -N(R C )(R D ), -N(R C )C(O)R B , -C(O)N(R C )(R D ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCNR C, -C(=N(R C )(R D ))OR A , -SR E , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 A2 is optionally substituted by alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D ))O-, -S-, -S(O) x -, -OS(O) x -, -N(R C )S(O) x -, -S(O) x N(R C )-, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A)- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 and optionally substituted by L 1 , L 2 and L 3 is independently a bond, alkyl, alkenyl, alkynyl, or heteroalkyl, wherein each of the alkyl, alkenyl, alkynyl, and heteroalkyl is selected from 1 to 5 R 2 M is optionally substituted with one or more R 3 P is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 4 cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , R E , R F and R G are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from one or more R 6 or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 and R 1 , R2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by R A1 , R B1 , R C1 , R D1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7x is 1 or 2; and y is 2, 3, or 4) to a patient, e.g., at a site, thereby treating the patient or modulating the patient's immune response.

[0044] In some embodiments, the providing step comprises providing an implantable element, e.g., a device or material described herein, to the patient. In some embodiments, the providing step comprises providing a device, e.g., a device described herein, to the patient. In some embodiments, the providing step comprises administering a compound systemically or locally.

[0045] In some embodiments, the method includes treating a patient for, e.g., a disorder or condition (e.g., the condition is characterized by an unwanted immune response). In some embodiments, the method includes treating a patient for, e.g., a disorder or condition (e.g., the condition is characterized by an inappropriate immune response).

[0046] In some embodiments, the method includes providing a compound of formula (I) or a pharmaceutically acceptable salt or composition thereof, e.g., to downregulate an immune response. In some embodiments, the method includes providing a compound of formula (I) or a pharmaceutically acceptable salt or composition thereof, e.g., to upregulate an immune response.

[0047] In some embodiments, the method includes reducing an undesirable response to the implanted device or cells, e.g., reducing fibrosis or inflammation or inactivation in the implanted device or cells, hi some embodiments, the device includes cells, e.g., recombinant cells, that provide a substance, e.g., a therapeutic agent.

[0048] In some embodiments, A is A. In some embodiments, A is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D In some embodiments, A is —N(R C )(R D ) (e.g., NH2). In some embodiments, A1 is NH2 or NHC(O)C(CH2)CH3.

[0049] In some embodiments, A is A2. In some embodiments, A2 is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -Si(OR A )2-, -Si(R G )(OR A )-OR-B(OR A In some embodiments, A2 is —N(R C )—(e.g., NH—). In some embodiments, A2 is NH— or NH(C(O)C(CH3)CH2—. In some embodiments, the compound comprises A2, and, e.g., the compound is covalently attached to the device. In some embodiments, A2 is directly attached to the device. In some embodiments, A2 is attached to the device by a linking group (e.g., a linking group described herein). In some embodiments, the device is, e.g., covalently attached to the linking group, and A2 is, e.g., covalently attached to the linking group.

[0050] In some embodiments, L 1, L 2 and L 3 Each of L is independently a bond, alkyl, or heteroalkyl. 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is C1-C6 alkyl (e.g., -CH2- or -CH2CH2-). 2 is a bond. In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is C1-C6 alkyl (e.g., -CH2-) or heteroalkyl (e.g., -CH2O-).

[0051] In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (—OCH2CH2—)z, where z is an integer selected from 1 to 10. In some embodiments, M is aryl (e.g., phenyl).

[0052] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl (e.g., tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl). In some embodiments, P is a triazolyl (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl). In some embodiments, P is [ka] In some embodiments, P is selected from [ka] is.

[0053] In some embodiments, Z each represents one or more R 5 In some embodiments, Z is alkyl, heterocyclyl, or aryl, optionally substituted by: In some embodiments, Z is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, Z is nitrogen-containing heterocyclyl, oxygen-containing heterocyclyl, or sulfur-containing heterocyclyl (e.g., tetrahydropyranyl or thiomorpholinyl-1,1-dioxide). In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0054] In some embodiments, Z is aryl (e.g., phenyl). In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is an amine-containing group (e.g., NH). In some embodiments, Z is a monosubstituted phenyl, where one R 5 is an oxygen-containing group (e.g., OCH). In some embodiments, one R 5 is in the ortho or para position.

[0055] In some embodiments, Z is alkyl (e.g., C1-C 12 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5C1-C8 alkyl substituted with, where R 5 is -OH or -C(O)OH.

[0056] In some embodiments, Z is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z is (—OCH2CH2—)zOCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10).

[0057] In another aspect, the invention features an implantable element (e.g., a device or material). In some embodiments, the implantable element is a device or material that includes a compound of Formula (I). AL 1 -ML 2 -PL 3 -Z (I) wherein A is A1 or A2; A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B , -N(R C )(R D ), -N(R C )C(O)R B , -C(O)N(R C )(R D ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCNR C , -C(=N(R C )(R D ))OR A , -SR E , -S(O) x R E , -OS(O) x R E , -N(RC )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 A2 is optionally substituted by alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D ))O-, -S-, -S(O) x -, -OS(O) x -, -N(R C )S(O) x -, -S(O) x N(R C )-, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A )- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 and optionally substituted by L 1 , L 2 and L 3is independently a bond, alkyl, alkenyl, alkynyl, or heteroalkyl, wherein each of the alkyl, alkenyl, alkynyl, and heteroalkyl is selected from 1 to 5 R 2 M is optionally substituted with one or more R 3 P is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 4 cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , R E , R F and R G are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from one or more R 6 or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 and R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1, -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by R A1 , R B1 , R C1 , R D1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 are independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4.

[0058] In some embodiments, the compound is disposed on a surface, e.g., an inner or outer surface, of an implantable element (e.g., a device or material). In some embodiments, the implantable element is a device. In some embodiments, the compound is disposed on a surface, e.g., an inner or outer surface, of the device. In some embodiments, the compound is distributed evenly across the surface. In some embodiments, the compound is distributed unevenly across the surface.

[0059] In some embodiments, an implantable element (e.g., a device or material) is administered or provided to a patient for the treatment of a disease, disorder, or condition. In some embodiments, the implantable element is a device. In some embodiments, the device is administered or provided to a patient for the treatment of a disease, disorder, or condition. In some embodiments, the disease, disorder, or condition is a neurodegenerative disease, diabetes, heart disease, autoimmune disease, cancer, liver disease, lysosomal storage disease, blood clotting disorder or coagulation disorder, orthopedic condition, or amino acid metabolism disorder.

[0060] In some embodiments, the disease, disorder, or condition is a neurodegenerative disease such as Alzheimer's disease, Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and cerebral palsy (CP), dentatorubral-pallidoluysian atrophy (DRPLA), neuronal intranuclear inclusion disease (NIHID), dementia with Lewy bodies, Down's syndrome, Hallervorden-Spatz syndrome, prion diseases, argyrophilic grain dementia, corticobasal degeneration, dementia pugilistica, diffuse neurofibrillary tangle disease, Gerstmann-Straussler-Scheinker syndrome, Creutzfeldt-Jakob disease, Niemann-Pick disease type 3, progressive supranuclear palsy, subacute sclerosing panencephalitis, spinocerebellar ataxia, Pick's disease, and dentatorubral-pallidoluysian atrophy.

[0061] In some embodiments, the disease, disorder, or condition is a lysosomal storage disorder, such as exemplary lysosomal storage disorders including Gaucher disease (e.g., Type I, Type II, Type III), Tay-Sachs disease, Fabry disease, Farber disease, Hurler syndrome, Hunter syndrome, lysosomal acid lipase deficiency, Niemann-Pick disease, Salla disease, Sanfilippo syndrome, multiple sulfatase deficiency, Maroteaux-Lamy syndrome, metachromatic leukodystrophy, Krabbe disease, Scheie syndrome, Hurler-Scheie syndrome, Sly syndrome, hyaluronidase deficiency, Pompe disease, Danon disease, gangliosidosis, or Morquio syndrome.

[0062] In some embodiments, the disease, disorder, or condition is a blood clotting disorder or coagulation disorder, such as hemophilia (e.g., hemophilia A or hemophilia B), von Willebrand disease, thrombocytopenia, uremia, Bernard-Soulier syndrome, factor XII deficiency, vitamin K deficiency, or congenital afibrinogenemia.

[0063] In some embodiments, the disease, disorder, or condition is an amino acid metabolism disorder, such as, for example, phenylketonuria, tyrosinemia (e.g., type 1 or type 2), alkaptonuria, homocystinuria, hyperhomocysteinemia, or cyclosporinemia.

[0064] In some embodiments, the disease, disorder, or condition is a fatty acid metabolism disorder, eg, hyperlipidemia, hypercholesterolemia, galactosemia.

[0065] In some embodiments, a first portion of the surface of the device comprises a compound of formula (I) that modulates (e.g., downregulates or upregulates) an immune response, and a second portion of the device is free of the compound or has a substantially lower density of the compound. In some embodiments, a first portion of the surface of the device comprises a compound of formula I that modulates (e.g., downregulates) an immune response, and a second portion of the surface comprises a second compound of formula I that, for example, upregulates an immune response, and the second portion of the device is free of the compound or has a substantially lower density of the compound.

[0066] In some embodiments, the device comprises cells, e.g., recombinant cells, that provide a substance, e.g., a therapeutic agent. In some embodiments, the substance comprises a polypeptide. In some embodiments, the polypeptide is a replacement therapy or replacement protein (e.g., a clotting factor, enzyme, or antibody).

[0067] In some embodiments, the disorder is diabetes and the agent (e.g., therapeutic agent) is insulin. In some embodiments, the disorder is a blood clotting disorder (e.g., hemophilia) and the agent (e.g., therapeutic agent) is a blood clotting factor (e.g., factor VIII or factor IX). In some embodiments, the disorder is a lysosomal storage disease (e.g., Fabry disease, Gaucher disease, Pompe disease, or MPS I) and the agent (e.g., therapeutic agent) is an enzyme (e.g., α-galactosidase, α-glucosidase, or glucocerebrodisase). In some embodiments, the disorder is a neurodegenerative disorder and the agent is a hormone or neurotransmitter, or an analog, precursor, or derivative thereof.

[0068] In some embodiments, A is A. In some embodiments, A is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D In some embodiments, A is —N(R C )(R D ) (e.g., NH2). In some embodiments, A1 is NH2 or NHC(O)C(CH2)CH3.

[0069] In some embodiments, A is A2. In some embodiments, A2 is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -Si(OR A )2-, -Si(R G )(OR A )-OR-B(OR A In some embodiments, A2 is —N(R C )—(e.g., NH—). In some embodiments, A2 is NH— or NH(C(O)C(CH3)CH2—. In some embodiments, the compound comprises A2, and, e.g., the compound is covalently attached to the device. In some embodiments, A2 is directly attached to the device. In some embodiments, A2 is attached to the device by a linking group (e.g., a linking group described herein). In some embodiments, the device is, e.g., covalently attached to the linking group, and A2 is, e.g., covalently attached to the linking group.

[0070] In some embodiments, L 1 , L 2 and L 3 Each of L is independently a bond, alkyl, or heteroalkyl. 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is C1-C6 alkyl (e.g., -CH2- or -CH2CH2-). 2 is a bond. In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is C1-C6 alkyl (e.g., -CH2-) or heteroalkyl (e.g., -CH2O-).

[0071] In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (—OCH2CH2—)z, where z is an integer selected from 1 to 10. In some embodiments, M is aryl (e.g., phenyl).

[0072] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl (e.g., tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl). In some embodiments, P is a triazolyl (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl). In some embodiments, P is [ka] In some embodiments, P is selected from [ka] is.

[0073] In some embodiments, Z each represents one or more R 5 In some embodiments, Z is alkyl, heterocyclyl, or aryl, optionally substituted by: In some embodiments, Z is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, Z is nitrogen-containing heterocyclyl, oxygen-containing heterocyclyl, or sulfur-containing heterocyclyl (e.g., tetrahydropyranyl or thiomorpholinyl-1,1-dioxide). In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0074] In some embodiments, Z is aryl (e.g., phenyl). In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is an amine-containing group (e.g., NH). In some embodiments, Z is a monosubstituted phenyl, where one R 5 is an oxygen-containing group (e.g., OCH). In some embodiments, one R 5 is in the ortho or para position.

[0075] In some embodiments, Z is alkyl (e.g., C1-C 12 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is -OH or -C(O)OH.

[0076] In some embodiments, Z is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z is (—OCH2CH2—)zOCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10).

[0077] In another aspect, the present invention provides a compound of formula (I): AL 1 -ML2 -PL 3 -Z (I) wherein A is A1 or A2; and A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B , -N(R C )(R D ), -N(R C )C(O)R B , -C(O)N(R C )(R D ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCNR C , -C(=N(R C )(R D ))OR A , -SR E , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 A2 is optionally substituted by alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C)C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D ))O-, -S-, -S(O) x -, -OS(O) x -, -N(R C )S(O) x -, -S(O) x N(R C )-, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A )- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 and optionally substituted by L 1 , L 2 and L 3 is independently a bond, alkyl, alkenyl, alkynyl, or heteroalkyl, wherein each of the alkyl, alkenyl, alkynyl, and heteroalkyl is selected from 1 to 5 R 2 M is optionally substituted with one or more R 3 P is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 4 cycloalkyl, heterocyclyl, aryl, or heteroaryl, each optionally substituted with one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , RE , R F and R G are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from one or more R 6 or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 and R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by RA1 , R B1 , R C1 , R D1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4, wherein the compound of Formula (I) is attached to a device (e.g., via a linking group).

[0078] In some embodiments, A is A. In some embodiments, A is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D In some embodiments, A is —N(R C )(R D ) (e.g., NH2). In some embodiments, A1 is NH2 or NHC(O)C(CH2)CH3.

[0079] In some embodiments, A is A2. In some embodiments, A2 is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -Si(ORA )2-, -Si(R G )(OR A )-OR-B(OR A In some embodiments, A2 is —N(R C )—(e.g., NH—). In some embodiments, A2 is NH— or NH(C(O)C(CH3)CH2—. In some embodiments, the compound comprises A2, and, e.g., the compound is covalently attached to the device. In some embodiments, A2 is directly attached to the device. In some embodiments, A2 is attached to the device by a linking group (e.g., a linking group described herein). In some embodiments, the device is, e.g., covalently attached to the linking group, and A2 is, e.g., covalently attached to the linking group.

[0080] In some embodiments, L 1 , L 2 and L 3 Each of L is independently a bond, alkyl, or heteroalkyl. 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is C1-C6 alkyl (e.g., -CH2- or -CH2CH2-). 2 is a bond. In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is C1-C6 alkyl (e.g., -CH2-) or heteroalkyl (e.g., -CH2O-).

[0081] In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (—OCH2CH2—)z, where z is an integer selected from 1 to 10. In some embodiments, M is aryl (e.g., phenyl).

[0082] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl (e.g., tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl). In some embodiments, P is a triazolyl (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl). In some embodiments, P is [ka] In some embodiments, P is selected from [ka] is.

[0083] In some embodiments, Z each represents one or more R 5 In some embodiments, Z is alkyl, heterocyclyl, or aryl, optionally substituted by: In some embodiments, Z is heterocyclyl (e.g., 6-membered heterocyclyl). In some embodiments, Z is nitrogen-containing heterocyclyl, oxygen-containing heterocyclyl, or sulfur-containing heterocyclyl (e.g., tetrahydropyranyl or thiomorpholinyl-1,1-dioxide). In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0084] In some embodiments, Z is aryl (e.g., phenyl). In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5is an amine-containing group (e.g., NH). In some embodiments, Z is a monosubstituted phenyl, where one R 5 is an oxygen-containing group (e.g., OCH). In some embodiments, one R 5 is in the ortho or para position.

[0085] In some embodiments, Z is alkyl (e.g., C1-C 12 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is -OH or -C(O)OH.

[0086] In some embodiments, Z is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z is (—OCH2CH2—)zOCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10).

[0087] In any and all aspects of the invention, in some embodiments, the compound, composition, or implantable element (e.g., device or material) described herein is a composition or implantable element (e.g., device or material) other than the compounds, compositions, or implantable elements (e.g., devices or materials) described in WO 2012 / 112982, WO 2012 / 167223, WO 2014 / 153126, WO 2016 / 187225, WO 2016 / 019391, WO 2017 / 075630, WO 2017 / 075631, and U.S. Patent No. 2016-0030359. In some embodiments, the compound of Formula (I) or a device comprising the same is a compound or device other than those described in WO 2012 / 112982, WO 2012 / 167223, WO 2014 / 153126, WO 2016 / 187225, WO 2016 / 019391, WO 2017 / 075630, WO 2017 / 075631, and U.S. Patent No. 2016-0030359. In some embodiments, the device comprises materials other than those described in WO2012 / 112982, WO2012 / 167223, WO2014 / 153126, WO2016 / 187225, WO2016 / 019391, WO2017 / 075630, WO2017 / 075631 and U.S. Patent No. 2016-0030359.In some embodiments, the device is attached to the compound of Formula (I) via a linking group other than those described in WO2012 / 112982, WO2012 / 167223, WO2014 / 153126, WO2016 / 187225, WO2016 / 019391, WO2017 / 075630, WO2017 / 075631 and U.S. Patent No. 2016-0030359.

[0088] The details of one or more embodiments of the invention are described herein. Other features, objects, and advantages of the invention will be apparent from the detailed description, drawings, examples, and claims. [Brief explanation of the drawings]

[0089] [Figure 1-6] Figures 1-6 are tables of exemplary compounds, e.g., compounds of Formula (I). Numerous species labeled compounds 3271-3431 in Figures 1-6 overlap with compounds 100-3270 described herein. DETAILED DESCRIPTION OF THE INVENTION

[0090] The present invention provides compounds and compositions, e.g., compounds of Formula (I), and implantable elements (e.g., devices and materials) comprising the same, as well as methods of use thereof. In particular, compounds of Formula (I) and compositions, and devices comprising the compounds, can be used in methods for the prevention and treatment of diseases, disorders, or conditions in patients. In some embodiments, compounds of Formula (I), and their pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, compositions, and devices, are capable of modulating an immune response in a patient, e.g., upregulating or downregulating an immune response in a patient.

[0091] definition chemical definition Definitions of specific functional groups and chemical terms are provided in more detail below. Chemical elements are defined as defined in Handbook of Chemistry and Physics, 75 th The general principles of organic chemistry, as well as the moieties and reactivities of specific functional groups, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987.

[0092] The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulas set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts.

[0093] When a range of values ​​is listed, it is intended that each value and subrange within the range be included. For example, "C1-C6 alkyl" is intended to include C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5 and C5-C6 alkyl.

[0094] The following terms are intended to have the meanings presented below and are useful in describing and understanding the intended scope of the present invention.

[0095] As used herein, "alkyl" refers to an alkyl group having 1 to 24 carbon atoms ("C1-C 24 In some embodiments, an alkyl group has 1 to 12 carbon atoms ("C1-C 12In some embodiments, an alkyl group has 1 to 8 carbon atoms ("C1-C8 alkyl"). In some embodiments, an alkyl group has 1 to 6 carbon atoms ("C1-C6 alkyl"). In some embodiments, an alkyl group has 1 to 5 carbon atoms ("C1-C5 alkyl"). In some embodiments, an alkyl group has 1 to 4 carbon atoms ("C1-C4 alkyl"). In some embodiments, an alkyl group has 1 to 3 carbon atoms ("C1-C3 alkyl"). In some embodiments, an alkyl group has 1 to 2 carbon atoms ("C1-C2 alkyl"). In some embodiments, an alkyl group has 1 carbon atom ("C1 alkyl"). In some embodiments, an alkyl group has 2 to 6 carbon atoms ("C2-C6 alkyl"). Examples of C1-C6 alkyl groups include methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), t-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), and n-hexyl (C6). Additional examples of alkyl groups include n-heptyl (C7), n-octyl (C8), and the like. Each instance of an alkyl group can independently be optionally substituted, i.e., unsubstituted ("unsubstituted alkyl") or substituted with one or more substituents (e.g., illustratively, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent) ("substituted alkyl"). In certain embodiments, an alkyl group is an unsubstituted C 1-10 In certain embodiments, the alkyl group is a substituted C 1-6 It is alkyl.

[0096] As used herein, "alkenyl" refers to the radical of a straight-chain or branched hydrocarbon group having 2 to 24 carbon atoms, one or more carbon-carbon double bonds, and no triple bonds ("C2-C 24In some embodiments, an alkenyl group has 2 to 10 carbon atoms ("C-C"). 10 In some embodiments, an alkenyl group has 2 to 8 carbon atoms ("C2-C8 alkenyl"). In some embodiments, an alkenyl group has 2 to 6 carbon atoms ("C2-C6 alkenyl"). In some embodiments, an alkenyl group has 2 to 5 carbon atoms ("C2-C5 alkenyl"). In some embodiments, an alkenyl group has 2 to 4 carbon atoms ("C2-C4 alkenyl"). In some embodiments, an alkenyl group has 2 to 3 carbon atoms ("C2-C3 alkenyl"). In some embodiments, an alkenyl group has 2 carbon atoms ("C2 alkenyl"). The one or more carbon-carbon double bonds can be intermediate (such as in 2-butenyl) or terminal (such as in 1-butenyl). Examples of C2-C4 alkenyl groups include ethenyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), etc. Examples of C2-C6 alkenyl groups include the above-mentioned C 2-4 Alkenyl groups include pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Additional examples of alkenyl include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like. Each instance of an alkenyl group can independently be optionally substituted, i.e., unsubstituted (an "unsubstituted alkenyl") or substituted with one or more substituents (e.g., illustratively, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent) (a "substituted alkenyl"). In certain embodiments, an alkenyl group is an unsubstituted C 2-10 In certain embodiments, the alkenyl group is a substituted C 2-6 It is alkenyl.

[0097] As used herein, the term "alkynyl" refers to an alkyl group having 2 to 24 carbon atoms, one or more carbon-carbon triple bonds ("C2-C 24In some embodiments, an alkynyl group has 2 to 10 carbon atoms ("C-C"). 10 In some embodiments, an alkynyl group has 2 to 8 carbon atoms ("C2-C8 alkynyl"). In some embodiments, an alkynyl group has 2 to 6 carbon atoms ("C2-C6 alkynyl"). In some embodiments, an alkynyl group has 2 to 5 carbon atoms ("C2-C5 alkynyl"). In some embodiments, an alkynyl group has 2 to 4 carbon atoms ("C2-C4 alkynyl"). In some embodiments, an alkynyl group has 2 to 3 carbon atoms ("C2-C3 alkynyl"). In some embodiments, an alkynyl group has 2 carbon atoms ("C2 alkynyl"). The one or more carbon-carbon triple bonds can be intermediate (such as in 2-butynyl) or terminal (such as in 1-butynyl). Examples of C2-C4 alkynyl groups include ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), etc. Each instance of an alkynyl group can independently be optionally substituted, i.e., unsubstituted (an "unsubstituted alkynyl") or substituted with one or more substituents (e.g., illustratively 1-5 substituents, 1-3 substituents, or 1 substituent) (a "substituted alkynyl"). In certain embodiments, an alkynyl group is an unsubstituted C 2-10 In certain embodiments, the alkynyl group is a substituted C 2-6 It is alkynyl.

[0098] As used herein, the term "heteroalkyl" refers to an acyclic, stable, straight or branched chain, or combination thereof, containing at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. The heteroatoms O, N, P, S, and Si may be located at any position of the heteroalkyl group. Exemplary heteroalkyl groups include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2, -S(O)-CH3, -CH2-CH2-S(O)-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, and -O-CH2-CH3. Up to two or three heteroatoms may be consecutive (e.g., -CH2-NH-OCH3 and -CH2-O-Si(CH3)3). When "heteroalkyl" is referenced followed by a specific heteroalkyl group (e.g., -CHO, -NR C R D etc.), the terms heteroalkyl, and -CHO or -NR C R D It will be understood that the heteroalkyl groups are not redundant or mutually exclusive. Rather, specific heteroalkyl groups are recited for added clarity. Thus, the term "heteroalkyl" includes -CHO, -NR C R D Nothing in this specification should be construed as excluding specific heteroalkyl groups such as, for example, aryl, aryloxy ...

[0099] The terms "alkylene," "alkenylene," "alkynylene," or "heteroalkylene," by themselves or as part of another substituent, mean, unless otherwise stated, a divalent radical derived from an alkyl, alkenyl, alkynyl, or heteroalkyl, respectively. The term "alkenylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkene. An alkylene, alkenylene, alkynylene, or heteroalkylene group may be described, for example, as C-C-membered alkylene, C-C-membered alkenylene, C-C-membered alkynylene, or C-C-membered heteroalkylene, where the term "member" refers to a non-hydrogen atom in the moiety. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Additionally, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula -C(O)R'- can represent both -C(O)R'- and -R'C(O)-.

[0100] As used herein, "aryl" refers to an aromatic ring system having 6 to 14 ring carbon atoms and zero heteroatoms ("C6-C 14 "aryl" refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in the cyclic array). In some embodiments, an aryl group has 6 ring carbon atoms ("C6 aryl"; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms ("C 10 aryl"; e.g., naphthyl, such as 1-naphthyl and 2-naphthyl). In some embodiments, the aryl group has 14 ring carbon atoms ("C 14 Aryl"; for example, anthracyl). The aryl group is, for example, C6-C 10In certain embodiments, an aryl group may be described as an unsubstituted C6-C6 alkyl group, where the term "membered" refers to a non-hydrogen ring atom in the moiety. Aryl groups include phenyl, naphthyl, indenyl, and tetrahydronaphthyl. Each instance of an aryl group may independently be optionally substituted, i.e., unsubstituted (an "unsubstituted aryl") or substituted with one or more substituents (a "substituted aryl"). In certain embodiments, an aryl group is an unsubstituted C6-C6 alkyl group. 14 In certain embodiments, the aryl group is a substituted C-C 14 It is aryl.

[0101] As used herein, "heteroaryl" refers to the radical of a 5- to 10-membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 π-electrons shared in the cyclic array) having ring carbon atoms and 1 to 4 ring heteroatoms in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 10-membered heteroaryl"). In heteroaryl groups containing one or more nitrogen atoms, the point of attachment can be at a carbon or nitrogen atom, as valence allows. Heteroaryl bicyclic ring systems can contain one or more heteroatoms in one or both rings. "Heteroaryl" also includes ring systems in which a heteroaryl ring, as defined above, is fused to one or more aryl groups, with the point of attachment being at either the aryl or heteroaryl ring; in such instances, the number of ring members refers to the number of ring members in the fused (aryl / heteroaryl) ring system. In bicyclic heteroaryl groups in which one ring does not contain heteroatoms (e.g., indolyl, quinolinyl, carbazolyl, etc.), the point of attachment can be at either ring, i.e., the point of attachment can be at either the ring with a heteroatom (e.g., 2-indolyl) or the ring without a heteroatom (e.g., 5-indolyl). Heteroaryl groups can be described, for example, as 6- to 10-membered heteroaryl, where the term "member" refers to a non-hydrogen atom in the moiety.

[0102] In some embodiments, heteroaryl groups are 5- to 10-membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 10-membered heteroaryl"). In some embodiments, heteroaryl groups are 5- to 8-membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 8-membered heteroaryl"). In some embodiments, heteroaryl groups are 5- to 6-membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 6-membered heteroaryl"). In some embodiments, 5- to 6-membered heteroaryls have 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, 5- to 6-membered heteroaryls have 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5- to 6-membered heteroaryl has one ring heteroatom selected from nitrogen, oxygen, and sulfur. Each instance of a heteroaryl group can independently be optionally substituted, i.e., unsubstituted ("unsubstituted heteroaryl") or substituted with one or more substituents ("substituted heteroaryl"). In certain embodiments, the heteroaryl group is an unsubstituted 5- to 14-membered heteroaryl. In certain embodiments, the heteroaryl group is a substituted 5- to 14-membered heteroaryl.

[0103] Exemplary 5-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to, tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, but are not limited to, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Other exemplary heteroaryl groups include heme and heme derivatives.

[0104] As used herein, the terms "arylene" and "heteroarylene," alone or as part of another substituent, mean a divalent radical derived from an aryl and heteroaryl, respectively.

[0105] As used herein, "cycloalkyl" refers to a group having 3 to 10 ring carbon atoms ("C3-C 10 "Cycloalkyl" refers to the radical of a non-aromatic cyclic hydrocarbon group having 3 to 8 ring carbon atoms ("C3-C8 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms ("C5-C 10 Cycloalkyl groups may be described, for example, as C4-C7 membered cycloalkyl, where the term "membered" refers to a non-hydrogen atom in the moiety. Exemplary C3-C6 cycloalkyl groups include, but are not limited to, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. Exemplary C3-C8 cycloalkyl groups include, but are not limited to, the aforementioned C3-C6 cycloalkyl groups as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), cubanyl (C8), bicyclo[1.1.1]pentanyl (C5), bicyclo[2.2.2]octanyl (C8), bicyclo[2.1.1]hexanyl (C6), bicyclo[3.1.1]heptanyl (C7), and the like. 10The cycloalkyl group is not particularly limited, but includes the above-mentioned C3 to C8 cycloalkyl groups as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C 10 ), spiro[4.5]decanyl (C 10 As illustrated in the examples above, in certain embodiments, a cycloalkyl group is monocyclic ("monocyclic cycloalkyl") or contains fused, bridged, or spiro ring systems, such as bicyclic ring systems ("bicyclic cycloalkyl"), and can be saturated or partially saturated. "Cycloalkyl" also includes ring systems in which a cycloalkyl ring, as defined above, is fused to one or more aryl groups, and the point of attachment is at the cycloalkyl ring; in such instances, the number of carbons continues to refer to the number of carbons in the cycloalkyl ring system. Each instance of a cycloalkyl group can independently be optionally substituted, i.e., unsubstituted ("unsubstituted cycloalkyl") or substituted with one or more substituents ("substituted cycloalkyl"). In certain embodiments, a cycloalkyl group is an unsubstituted C3-C6 10 In certain embodiments, the cycloalkyl group is a substituted C-C 10 It is cycloalkyl.

[0106] As used herein, "heterocyclyl" refers to the radical of a 3- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3- to 10-membered heterocyclyl"). In heterocyclyl groups containing one or more nitrogen atoms, the point of attachment can be at a carbon or nitrogen atom, as valence allows. Heterocyclyl groups can be monocyclic ("monocyclic heterocyclyl") or fused, bridged, or spiro ring systems, such as bicyclic ring systems ("bicyclic heterocyclyl"), and can be saturated or partially saturated. Heterocyclyl bicyclic ring systems can contain one or more heteroatoms in one or both rings. "Heterocyclyl" also includes ring systems in which a heterocyclyl ring, as defined above, is fused to one or more cycloalkyl groups, with the point of attachment being at either the cycloalkyl or heterocyclyl ring, or in which a heterocyclyl ring, as defined above, is fused to one or more aryl or heteroaryl groups, with the point of attachment being at the heterocyclyl ring; in such instances, the number of ring members continues to indicate the number of ring members in the heterocyclyl ring system. A heterocyclyl group may be described, for example, as a 3- to 7-membered heterocyclyl, where the term "member" refers to the non-hydrogen ring atoms in the moiety, i.e., carbon, nitrogen, oxygen, sulfur, boron, phosphorus, and silicon. Each instance of heterocyclyl may independently be optionally substituted, i.e., unsubstituted ("unsubstituted heterocyclyl") or substituted with one or more substituents ("substituted heterocyclyl"). In certain embodiments, the heterocyclyl group is an unsubstituted 3- to 10-membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3-10 membered heterocyclyl.

[0107] In some embodiments, a heterocyclyl group is a 5- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("5- to 10-membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5- to 8-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 8-membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5- to 6-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 6-membered heterocyclyl"). In some embodiments, a 5- to 6-membered heterocyclyl has 1 to 3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5- to 6-membered heterocyclyl has 1 to 2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5- to 6-membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur.

[0108] Exemplary 3-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azirdinyl, oxiranyl, and thiorenyl. Exemplary 4-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclyl groups containing three heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing one heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, triazinanyl. Exemplary 7-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl. Exemplary 8-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azocanyl, oxecanyl, and thiocanyl. Exemplary 5-membered heterocyclyl groups (also referred to herein as 5,6-bicyclic heterocycles) fused to a C6 aryl ring include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, and the like.Exemplary 6-membered heterocyclyl groups (also referred to herein as 6,6-bicyclic heterocycles) fused to an aryl ring include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like.

[0109] As used herein, "amino" refers to the radical -NR 70 R 71 where R 70 and R 71 are each independently hydrogen, C1-C8 alkyl, C3-C 10 Cycloalkyl, C4-C 10 Heterocyclyl, C6-C 10 Aryl and C5-C 10 Heteroaryl. In some embodiments, amino refers to NH2.

[0110] "Cyano" refers to the radical -CN.

[0111] As used herein, "halo" or "halogen," independently or as part of another substituent, means, unless otherwise stated, a fluorine (F), chlorine (Cl), bromine (Br), or iodine (I) atom.

[0112] "Hydroxy" refers to the radical --OH.

[0113] As defined herein, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted (e.g., a "substituted" or "unsubstituted" alkyl, a "substituted" or "unsubstituted" alkenyl, a "substituted" or "unsubstituted" alkynyl, a "substituted" or "unsubstituted" heteroalkyl, a "substituted" or "unsubstituted" cycloalkyl, a "substituted" or "unsubstituted" heterocyclyl, a "substituted" or "unsubstituted" aryl, or a "substituted" or "unsubstituted" heteroaryl group). The term "substituted," whether preceded by the term "optionally," means that at least one hydrogen present in a group (e.g., a carbon or nitrogen atom) is replaced with a permissible substituent, for example, one that results in a stable compound (e.g., a compound that does not undergo spontaneous transformation, such as by rearrangement, cyclization, elimination, or other reaction). Unless otherwise specified, a "substituted" group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituents may be the same or different at each position. The term "substituted" is contemplated to include substitution with all permissible substituents of organic compounds, including any of the substituents described herein, that result in the formation of stable compounds. The present invention contemplates any and all such combinations that result in stable compounds. For purposes of this invention, heteroatoms such as nitrogen may have hydrogen substituents and / or any suitable substituents described herein that satisfy the valence of the heteroatom and result in the formation of a stable moiety.

[0114] Two or more substituents may optionally be linked to form an aryl, heteroaryl, cycloalkyl, or heterocyclyl group. Such so-called ring-forming substituents are typically, but not necessarily, found attached to a ring base structure. In one embodiment, the ring-forming substituents are attached to adjacent members of the base structure. For example, two ring-forming substituents attached to adjacent members of a ring base structure form a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single member of the base structure. For example, two ring-forming substituents attached to a single member of a ring base structure form a spirocyclic structure. In yet another embodiment, the ring-forming substituents are attached to non-adjacent members of the base structure.

[0115] The compounds described herein may contain one or more asymmetric centers and therefore may exist in various isomeric forms, such as enantiomers and / or diastereomers. For example, the compounds described herein may be in the form of individual enantiomers, diastereomers, or geometric isomers, or may be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomers. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric synthesis. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions p. 268 (EL Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). The present invention further includes the compounds described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers.

[0116] As used herein, a pure enantiomer is substantially free of other enantiomers or stereoisomers of the compound (i.e., in enantiomeric excess). In other words, the "S" form of the compound is substantially free of the "R" form of the compound, and therefore the "R" form is in enantiomeric excess. The terms "enantiomerically pure" or "pure enantiomer" indicate that a compound contains more than 75%, more than 80%, more than 85%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 99%, more than 99.5%, or more than 99.9% by weight of an enantiomer. In certain embodiments, the weight is based on the total weight of all enantiomers or stereoisomers of the compound.

[0117] In the compositions provided herein, enantiomerically pure compounds can be present together with other active or inactive ingredients. For example, a pharmaceutical composition containing an enantiomerically pure R-compound can contain, for example, about 90% excipients and about 10% enantiomerically pure R-compound. In certain embodiments, the enantiomerically pure R-compound in such a composition can contain, for example, at least about 95% by weight of the R-compound and up to about 5% by weight of the S-compound, based on the total weight of the compound. For example, a pharmaceutical composition containing an enantiomerically pure S-compound can contain, for example, about 90% excipients and about 10% of the enantiomerically pure S-compound. In certain embodiments, the enantiomerically pure S-compound in such a composition can contain, for example, at least about 95% by weight of the S-compound and up to about 5% by weight of the R-compound, based on the total weight of the compound. In certain embodiments, the active ingredient can be formulated with few or no excipients or carriers.

[0118] The compounds described herein may also contain one or more isotopic substitutions. For example, H is: 1 H, 2 H (D or deuterium) and3 H can be in any isotopic form, including T or tritium; C can be 12 C. 13 C, and 14 C can be any isotopic form, including 16 O and 18 It can be in any isotopic form, including O, etc.

[0119] The term "pharmaceutically acceptable salts" is intended to include effective salts of compounds prepared with relatively non-toxic acids or bases, depending on the specific substituents found in the compounds described herein.When a compound of the present invention contains a relatively acidic functional group, a base addition salt can be obtained by contacting such a neutral form of the compound with a sufficient amount of the desired base, either directly or in a suitable inert solvent.Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino or magnesium salts, or similar salts.When a compound of the present invention contains a relatively basic functional group, an acid addition salt can be obtained by contacting such a neutral form of the compound with a sufficient amount of the desired acid, either directly or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrogensulfuric acid, hydroiodic acid, or phosphorous acid, as well as salts derived from organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid, and the like. Also included are salts of amino acids such as arginic acid, and salts of organic acids such as glucuronic acid or galacturonic acid (see, for example, Berge et al., Journal of Pharmaceutical Science 66:1-19 (1977)). Certain compounds of the present invention contain both basic and acidic functional groups, which allow the compounds to be converted into base or acid addition salts. These salts can be prepared by methods known to those skilled in the art. Other pharmaceutically acceptable carriers known to those skilled in the art are suitable for the present invention.

[0120] In addition to salt forms, the present invention provides compounds in prodrug form. Prodrugs of the compounds described herein are compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Furthermore, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.

[0121] Certain compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. Generally, solvated forms are equivalent to unsolvated forms and are included within the scope of the present invention. Certain compounds of the present invention can exist in multiple crystalline or amorphous forms. Generally, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention.

[0122] The term "solvate" refers to a form of a compound associated with a solvent, usually by solvolysis. This physical association may involve hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, etc. Compounds of formula (I) may be prepared, for example, in crystalline form, and may be solvated. Suitable solvates include pharmaceutically acceptable solvates, and further include both stoichiometric and non-stoichiometric solvates.

[0123] The term "hydrate" refers to a compound associated with water. Typically, a hydrate of a compound contains a defined ratio of water molecules to the number of compound molecules in the hydrate. Thus, a hydrate of a compound can be represented, for example, by the general formula R x HO, where R is the compound and x is a number greater than 0.

[0124] The term "tautomer," as used herein, refers to interconvertible forms of a particular compound structure, in which the displacement of hydrogen atoms and electrons varies. Thus, two structures can be in equilibrium through the movement of π electrons and atoms (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either acid or base. Tautomeric forms can be relevant for obtaining optimal chemical reactivity and biological activity of a compound of interest.

[0125] Other definitions The following definitions are of more general terms used throughout this application.

[0126] As used herein, "acquire" or "acquiring" refers to achieving the acquisition of a value (e.g., a numerical value or image) or a physical entity (e.g., a sample) by "directly acquiring" or "indirectly acquiring" the value or physical entity. "Directly acquiring" means performing a process (e.g., performing an analytical method or protocol) to obtain a value or physical entity. "Indirectly acquiring" refers to receiving a value or physical entity from another party or provider (e.g., a third-party laboratory that directly acquired the physical entity or value). Directly acquiring a value or physical entity includes performing a process that involves a physical change in a physical substance or the use of an instrument or device. An example of directly acquiring a value is obtaining a sample from a human patient. Directly acquiring a value includes performing a process using an instrument or device, such as a fluorescence microscope to acquire fluorescence microscopy data or a nuclear magnetic resonance (NMR) instrument to acquire an NMR spectrum. As used herein, the terms "administer," "administering," or "administration" refer to, for example, implantation, absorption, ingestion, injection, or other method of introduction of a compound of the invention (e.g., a compound described herein, e.g., a compound of Formula (I)), or a composition or implantable element comprising the same, into a patient.

[0127] As used herein, "cell" refers to a recombinant or non-recombinant cell.

[0128] For example, an "effective amount" of a compound of formula (I) or a composition or implantable element comprising the same refers to an amount sufficient to elicit a desired biological response, for example, to treat a disease, disorder, or condition. As will be recognized by those skilled in the art, the effective amount may vary depending on factors such as the desired biological endpoint, the pharmacokinetics of the compound, composition, or device, the condition being treated, the mode of administration, and the age and health of the patient. An effective amount encompasses therapeutic and prophylactic treatments. For example, to treat a fibrotic condition, an effective amount of a compound may reduce fibrosis or halt the growth or metastasis of fibrous tissue.

[0129] As used herein, an "endogenous nucleic acid" is a nucleic acid that occurs naturally within a patient's cells.

[0130] As used herein, an "endogenous polypeptide" is a polypeptide that occurs naturally within a patient's cells.

[0131] As used herein, a "recombinant cell" is a cell with a non-naturally occurring modification, typically comprising a nucleic acid sequence (e.g., DNA or RNA) or polypeptide that is not present (or is present at different levels) in other similar cells under similar conditions that have not been modified (an exogenous nucleic acid sequence). In embodiments, a recombinant cell comprises an exogenous nucleic acid (e.g., a vector or modified chromosomal sequence). In embodiments, a recombinant cell comprises an exogenous polypeptide. In embodiments, a recombinant cell comprises an exogenous nucleic acid sequence, e.g., a sequence, e.g., DNA or RNA, that is not present in a similar cell that has not been modified. In embodiments, the exogenous nucleic acid sequence is chromosomal, e.g., the exogenous nucleic acid sequence is an exogenous sequence placed within an endogenous chromosomal sequence. In embodiments, the exogenous nucleic acid sequence is chromosomal or extrachromosomal, e.g., a non-integrating vector. In embodiments, the exogenous nucleic acid sequence comprises an RNA sequence, e.g., mRNA. In embodiments, the exogenous nucleic acid sequence comprises a chromosomal or extrachromosomal exogenous nucleic acid sequence that includes a sequence that is expressed as RNA, e.g., mRNA or regulatory RNA. In embodiments, exogenous nucleic acid sequences include chromosomal or extrachromosomal nucleic acid sequences that encode a polypeptide or that contain a sequence that is expressed as a polypeptide. In embodiments, exogenous nucleic acid sequences include a first chromosomal or extrachromosomal exogenous nucleic acid sequence that regulates the conformation or expression of a second nucleic acid sequence, where the second amino acid sequence can be exogenous or endogenous. For example, recombinant cells can contain exogenous nucleic acids that control the expression of an endogenous sequence. In embodiments, recombinant cells can contain polypeptides that are present at levels or distributions that differ from those found in similar cells that have not been modified. For example, recombinant cells can contain exogenous nucleic acid sequences, including chromosomal or extrachromosomal exogenous nucleic acid sequences that contain sequences that are expressed as RNA, such as mRNA or regulatory RNA.In embodiments, the recombinant cell comprises an exogenous nucleic acid sequence, including a chromosomal or extrachromosomal nucleic acid sequence that comprises a sequence that encodes a polypeptide or a sequence that is expressed as a polypeptide. In embodiments, the recombinant cell comprises an exogenous nucleic acid sequence that regulates the conformation or expression of an endogenous sequence.

[0132] As used herein, the term "immunomodulator" refers to a compound, composition, material, or device capable of altering the immune response, immune system function, or components thereof. In some embodiments, an immunomodulator upregulates or downregulates the immune response or components thereof. In some embodiments, an immunomodulator is capable of modulation over a range. An immunomodulator may modulate (e.g., increase or decrease) one or more of the following in a patient: inflammation, cytokine production, complement cascade, leukocyte production or response, lymphocyte production or response, antibody production or response, fibrosis, growth factor production or response (e.g., TGF-b, CTGF, PDGF production or response), or molecular markers of an immune response, such as levels of TNF-α, IL-13, IL-6, G-CSF, GM-CSF, IL-4, CCL2, or CCL4, measured, for example, by ELISA, at the site of an implanted device or cell.

[0133] As used herein, an "implantable element" includes a cell, e.g., a plurality of cells, e.g., a cluster of cells, where the cell or active cells are completely or partially disposed within an encapsulating component (the encapsulating component is other than the cell), e.g., the encapsulating component includes a non-cellular component. The term "implantable element" includes any device or material described herein. In embodiments, the implantable element inhibits immune attack or inhibits the effects of an immune attack on the encapsulated cell or cells. In embodiments, the implantable element includes a semipermeable membrane or semipermeable polymer matrix or coating. Typically, the implantable element allows the flux of small molecules, e.g., nutrients and waste products. Typically, the implantable element allows the flux of products (e.g., therapeutic polypeptides) released by cells disposed within the encapsulating component. In embodiments, the placement within the implantable element minimizes the impact of a host response (e.g., an immune response, e.g., a fibrotic response) directed toward the implantable element, e.g., on the cells within the implantable element, compared to, e.g., similar cells not disposed within the implantable element. In embodiments, the implantable element includes a moiety, e.g., a moiety described herein, that minimizes the impact of a patient's immune response (e.g., a fibrotic response) directed against the implantable element, e.g., against the encapsulating component or cells in the implantable element, e.g., compared to a similar implantable element that does not include the moiety. In some embodiments, the moiety is a compound, e.g., a compound described herein (e.g., a compound of Formula (I)). In some embodiments, the implantable element (e.g., a device or material) is associated (e.g., directly associated) with a compound described herein, e.g., a compound of Formula (I).

[0134] As used herein, "polypeptide" refers to a polymer comprising amino acid residues joined via peptide bonds and having at least 2 amino acid residues, and in embodiments at least 10, 100 or 200 amino acid residues.

[0135] As used herein, "prevention," "prevent," and "preventing" refer to treatments that include the administration or application of a therapy, such as administering a compound described herein (e.g., a compound of Formula (I)) or a composition or implantable element (e.g., a device or material) comprising a compound described herein (e.g., a compound of Formula (I)) prior to the onset of a disease, disorder, or condition, to prevent the physical manifestations of the disease, disorder, or condition. In some embodiments, "prevention," "prevent," and "preventing" require that signs or symptoms of the disease, disorder, or condition have not yet occurred or been observed. In some embodiments, treatment includes prevention, and in other embodiments it does not.

[0136] A "replacement therapy" or "replacement protein" is a therapeutic protein or functional fragment thereof that replaces or augments a protein that is reduced, present in insufficient amounts, altered (e.g., mutated), or deficient in a patient with a disease or condition associated with protein reduction, alteration, or deficiency. Examples are certain blood clotting factors in certain blood clotting disorders or certain lysosomal enzymes in certain lysosomal storage diseases. In embodiments, the replacement therapy or replacement protein provides the function of the endogenous protein. In embodiments, the replacement therapy or replacement protein has an amino acid sequence identical to a naturally occurring variant, e.g., a wild-type allele or an allele not associated with a disorder, of the protein being replaced. Alternatively, in embodiments, the replacement therapy or replacement protein differs in amino acid sequence from a naturally occurring variant, e.g., a wild-type allele or an allele not associated with a disorder, e.g., an allele carried by a patient, at no more than about 1, 2, 3, 4, 5, 10, 15, or 20% of the amino acid residues.

[0137] The term "patient," as used herein, refers to a recipient of, for example, a compound, composition, device, or method of use described herein. Patients can include humans (i.e., male or female of any age group, e.g., pediatric patients (e.g., infants, children, adolescents) or adult patients (e.g., young adults, middle-aged adults, or geriatrics)) and / or other non-human animals, such as mammals (e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys); commercially relevant mammals such as cows, pigs, horses, sheep, goats, cats, and / or dogs) and birds (e.g., commercially relevant birds such as chickens, ducks, geese, and / or turkeys). In certain embodiments, the animal is a mammal. The animal can be male or female and at any stage of development. The non-human animal can be a genetically modified animal.

[0138] As used herein, the terms "treatment," "treat," and "treating" refer to the reversal, alleviation, delay of the onset of a disease, disorder, or condition (e.g., those described herein), or the inhibition of the progression of one or more symptoms, signs, or underlying causes of a disease, disorder, or condition (e.g., those described herein), for example, by administration or therapeutic application (e.g., administration of a compound described herein (e.g., a compound of Formula (I)), or a composition or implantable element (e.g., a device or material) comprising a compound described herein (e.g., a compound of Formula (I))). In embodiments, treatment includes the reduction, reversal, alleviation, delay of the onset of a disease, disorder, or condition, or the inhibition of the progression of a symptom of a disease, disorder, or condition. In embodiments, treatment includes the reduction, reversal, alleviation, delay of the onset of a disease, disorder, or condition, or the inhibition of the progression of a sign ... reduction, or delay of the onset of an underlying cause of a disease, disorder, or condition. In some embodiments, "treatment," "treat," and "treating" require that signs or symptoms of a disease, disorder, or condition have occurred or been observed. In other embodiments, treatment may be administered in the absence of signs or symptoms of the disease or condition, e.g., as a prophylactic treatment. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of the condition and / or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, e.g., to delay or prevent recurrence. Treatment may also be continued after symptoms have resolved, e.g., to delay or prevent recurrence. In some embodiments, treatment includes prevention, while in other embodiments it does not.

[0139] compound The present invention provides compounds of formula (I): AL 1 -ML 2 -PL 3 -Z (I) or a salt, solvate, hydrate, tautomer, stereoisomer or isotopically labeled derivative thereof, wherein: A is selected from A1 or A2, where: A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B , -N(R C )(R D ), -N(R C )C(O)R B , -C(O)N(R C )(R D ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCN(R C ), -C(=N(R C )(R D ))OR A , -SR E , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 is optionally replaced by; A2 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(RC )-, -N(R C )C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D ))O-, -S-, -S(O) x -, -OS(O) x -, -N(R C )S(O) x -, -S(O) x N(R C )-, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A )- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 is optionally replaced by; L 1 , L 2 and L 3 is independently a bond, alkyl, alkenyl, alkynyl, or heteroalkyl, wherein each of the alkyl, alkenyl, alkynyl, and heteroalkyl is selected from one or more R 2 is optionally replaced by; Each M is one or more R 3 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with; Each P is one or more R 4 cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with; Each Z is one or more R 5alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with; R A , R B , R C , R D , R E , R F and R G is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 is optionally replaced by Or, R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 forming an optionally substituted ring (e.g., a 5- to 7-membered ring) Or, R C and R D One or both of these may be bonded to an atom in L or M, or may be bonded to one of the substituents of L or M, and may be bonded to one or more R 6 forming a ring optionally substituted with; R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) xR E1 , -OS(O) x R E1 , -N(R C1 )S(O) x R E1 , -S(O) x N(R C1 )(R D1 ), -P(R F1 ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally replaced by; R A1 , R B1 , R C1 , R D1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally replaced by; Each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4.

[0140] As generally described herein, A is selected from A1 and A2. In some embodiments, A is A1. In some embodiments, A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B , -N(RC )(R D ), -N(R C )C(O)R B , -C(O)N(R C ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCN(R C ), -C(=N(R C )(R D ))OR A , -SR E , -S(O) x R E , -OS(O) x R E , -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 is optionally replaced by

[0141] In some embodiments, A is hydrogen. In some embodiments, A is alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl or C1-C 12 In some embodiments, A is unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, or unsubstituted heteroalkyl. In some embodiments, A is each one or more R 1 is a substituted alkyl, substituted alkenyl, substituted alkynyl, or substituted heteroalkyl substituted by

[0142] In some embodiments, A is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In some embodiments, A is unsubstituted methyl, unsubstituted ethyl, unsubstituted propyl, unsubstituted butyl, unsubstituted pentyl, or unsubstituted hexyl. In some embodiments, A is each one or more R 1 and substituted methyl, substituted ethyl, substituted propyl, substituted butyl, substituted pentyl, or substituted hexyl.

[0143] In some embodiments, A1 is -OR A where R A is hydrogen, alkyl, or alkenyl. In some embodiments, A1 is -OH, -OCH3, or -OCH2CH3, or -OCH2CH=CH2.

[0144] In some embodiments, A is —C(O)R B where R A is hydrogen, alkyl (e.g., methyl or ethyl), halogen, or azide. In some embodiments, A is —C(O)R B where R A is hydrogen or alkyl (e.g., methyl or ethyl).

[0145] In some embodiments, A1 is -OC(O)R B where R B is alkyl, alkenyl, or alkynyl. In some embodiments, A is —OC(O)R B where R A is ethenyl (e.g., —CH═CH). In some embodiments, A is —OC(O)R B where R B is methyl (e.g., halomethyl).

[0146] In some embodiments, A is —C(O)OR A where R Ais hydrogen, alkyl, alkenyl, alkynyl, C(O)OR A1 , heterocyclyl, or aryl. In some embodiments, A is —C(O)OR A where R A is succinimidyl or phenyl (e.g., 2,3,4,5,6-pentafluorophenyl). In some embodiments, A is -N(R C )C(O)R B where R C is hydrogen or methyl, and R B is alkyl (e.g., haloalkyl) or alkenyl (e.g., ethenyl).

[0147] In some embodiments, A1 is —N(R C )(R D In some embodiments, A is —N(R C )(R D ), where R C or R D is hydrogen. In some embodiments, A is -N(R C )(R D ), where R C or R D is hydrogen and R C or R D and the other is alkyl. In some embodiments, A is —NH. In some embodiments, A is NH or NHC(O)C(CH)CH. In some embodiments, A is —N(R C )(R D ), where R C and R D form a ring (for example, a 5- to 7-membered ring) together with the nitrogen atom to which they are attached.

[0148] In some embodiments, A is -NCO. In some embodiments, A is -NCS. In some embodiments, A is -NC. In some embodiments, A is -N3.

[0149] In some embodiments, A1 is -S(O) x R E (e.g., where x is 2 and R E is alkyl, alkenyl, or halogen). In some embodiments, A is -S(O)(CH=CH). In some embodiments, A is -OS(O) x R E (e.g., where x is 2 and R E is aryl).

[0150] In some embodiments, A1 is —Si(OR A ) (e.g., —Si(OH) , —Si(OMe) , or —Si(OEt) ). In some embodiments, A is —Si(R G )(OR A )2 (e.g., —Si(OH)2(alkyl)). In some embodiments, A1 is —B(OR A )2 (e.g., —B(OH)2). In some embodiments, A1 is —P(R F ) y (e.g., -P(CH2OH)3) + )

[0151] In some embodiments, A is cycloalkyl (e.g., a 3-membered cycloalkyl, a 4-membered cycloalkyl, a 5-membered cycloalkyl, or a 6-membered cycloalkyl). In some embodiments, A is heterocyclyl (e.g., a 3-membered heterocyclyl, a 4-membered heterocyclyl, a 5-membered heterocyclyl, or a 6-membered heterocyclyl). In some embodiments, A is a nitrogen-containing heterocyclyl (e.g., a 3-membered nitrogen-containing heterocyclyl, a 4-membered nitrogen-containing heterocyclyl, a 5-membered nitrogen-containing heterocyclyl, or a 6-membered nitrogen-containing heterocyclyl). In some embodiments, A is a 5-membered nitrogen-containing heterocyclyl (e.g., maleimidyl). In some embodiments, A is an oxygen-containing heterocyclyl (e.g., a 3-membered oxygen-containing heterocyclyl, a 4-membered oxygen-containing heterocyclyl, a 5-membered oxygen-containing heterocyclyl, or a 6-membered oxygen-containing heterocyclyl). In some embodiments, A is a 3-membered oxygen-containing heterocyclyl (e.g., oxiranyl).

[0152] In some embodiments, A1 is aryl (e.g., phenyl). In some embodiments, A1 is selected from 1 to 2 R 1 (e.g., -OR A OR-B(OR A In some embodiments, A is phenyl substituted with -OR A (e.g., OH) or -B(OR A )2 (e.g., -B(OH)2).

[0153] In some embodiments, A is heteroaryl (e.g., 5-membered heteroaryl, 6-membered heteroaryl). In some embodiments, A is nitrogen-containing heteroaryl (e.g., 5-membered nitrogen-containing heteroaryl, 6-membered nitrogen-containing heteroaryl). In some embodiments, A is 6-membered nitrogen-containing heteroaryl (e.g., imidazolyl).

[0154] In some embodiments, A1 is a metal (eg, Fe, Ti, Au, Ni, Ca) or a metal alloy or mixture (eg, stainless steel, alumina, Ni—Ti).

[0155] In some embodiments, A1 is: [ka] is selected from.

[0156] In some embodiments, A1 is: [ka] is selected from.

[0157] In some embodiments, A1 is: [ka] is selected from.

[0158] In some embodiments, [ka] A1 and L 1 It refers to the bond between

[0159] In some embodiments, A is A2. In some embodiments, A2 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-, -C(O)O-, -C(O)-, -OC(O)-, -N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D))O-, -S-, -S(O) x -, -OS(O) x -, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A )- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 is optionally replaced by

[0160] In some embodiments, A2 is O. In some embodiments, A2 is -C(O)O-. In some embodiments, A2 is -C(O)-. In some embodiments, A2 is -OC(O)-. In some embodiments, A2 is S.

[0161] In some embodiments, A2 is alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl or C1-C 12 In some embodiments, A2 is unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, or unsubstituted heteroalkyl. In some embodiments, A2 is each one or more R 1 is a substituted alkyl, substituted alkenyl, substituted alkynyl, or substituted heteroalkyl substituted by

[0162] In some embodiments, A2 is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In some embodiments, A2 is unsubstituted methyl, unsubstituted ethyl, unsubstituted propyl, unsubstituted butyl, unsubstituted pentyl, or unsubstituted hexyl. In some embodiments, A2 is each one or more R1 and substituted methyl, substituted ethyl, substituted propyl, substituted butyl, substituted pentyl, or substituted hexyl.

[0163] In some embodiments, A2 is —N(R C In some embodiments, A2 is —N(R C )-, where R C is hydrogen or alkyl. In some embodiments, A2 is -NH-. In some embodiments, A2 is NH- or NH(C(O)C(CH3)CH2-.

[0164] In some embodiments, A2 is -S(O) x -or-OS(O) x - (for example, where x is 2).

[0165] In some embodiments, A2 is —Si(OR A )2- (e.g., -Si(OH)2-, -Si(OCH3)2-, or -Si(OCH2CH3)2-).

[0166] In some embodiments, A2 is cycloalkyl (e.g., a 3-membered cycloalkyl, a 4-membered cycloalkyl, a 5-membered cycloalkyl, a 6-membered cycloalkyl). In some embodiments, A2 is heterocyclyl (e.g., a 3-membered heterocyclyl, a 4-membered heterocyclyl, a 5-membered heterocyclyl, a 6-membered heterocyclyl). In some embodiments, A2 is a nitrogen-containing heterocyclyl (e.g., a 3-membered nitrogen-containing heterocyclyl, a 4-membered nitrogen-containing heterocyclyl, a 5-membered nitrogen-containing heterocyclyl, a 6-membered nitrogen-containing heterocyclyl). In some embodiments, A2 is a 5-membered nitrogen-containing heterocyclyl. In some embodiments, A2 is an oxygen-containing heterocyclyl (e.g., a 3-membered oxygen-containing heterocyclyl, a 4-membered oxygen-containing heterocyclyl, a 5-membered oxygen-containing heterocyclyl, a 6-membered oxygen-containing heterocyclyl). In some embodiments, A2 is a 3-membered oxygen-containing heterocyclyl (e.g., oxiranyl).

[0167] In some embodiments, A2 is aryl (e.g., phenyl). In some embodiments, A2 is selected from 1 to 2 R 1 (e.g., -OR A OR-B(OR A In some embodiments, A2 is -OR A (e.g., OH) or -B(OR A )2 (e.g., -B(OH)2).

[0168] In some embodiments, A2 is heteroaryl (e.g., 5-membered heteroaryl, 6-membered heteroaryl). In some embodiments, A2 is nitrogen-containing heteroaryl (e.g., 5-membered nitrogen-containing heteroaryl, 6-membered nitrogen-containing heteroaryl). In some embodiments, A2 is 6-membered nitrogen-containing heteroaryl (e.g., imidazolyl).

[0169] In some embodiments, A2 is a metal (eg, Fe, Ti, Au, Ni, Ca) or a metal alloy or mixture (eg, stainless steel, alumina, Ni—Ti).

[0170] In some embodiments, A2 is: [ka] is selected from.

[0171] In some embodiments, [ka] A2 and L 1 and a linking group (e.g., as described herein).

[0172] In some embodiments, L 1 , L 2 and L 3In some embodiments, at least one of L 1 , L 2 and L 3 In some embodiments, at least two of L 1 , L 2 and L 3 Each of is a bond.

[0173] In some embodiments, L 1 , L 2 and L 3 At least one of L is alkyl. 1 , L 2 and L 3 At least two of L are alkyl. 1 , L 2 and L 3 Each of R is alkyl. In some embodiments, the alkyl is unsubstituted alkyl. In some embodiments, the alkyl is substituted alkyl (e.g., one or more R 2 is alkyl substituted with, where R 2 is as described herein).

[0174] In some embodiments, alkyl is C1-C 12 In some embodiments, alkyl is a C1-C8 alkyl. In some embodiments, alkyl is a C1-C4 alkyl. In some embodiments, alkyl is a C1 alkyl (e.g., unsubstituted C1 alkyl, substituted C1 alkyl (e.g., —C(R 2 )2), where R 2 are as described herein (e.g., each R 2 are independently selected from the group: hydrogen, alkyl, aryl, oxo, and heteroaryl; or two R 2together with the atoms to which they are attached form a ring). In some embodiments, alkyl is a C2 alkyl (e.g., unsubstituted C2 alkyl, substituted C2 alkyl). In some embodiments, alkyl is a C3 alkyl (e.g., unsubstituted C3 alkyl, substituted C3 alkyl). In some embodiments, alkyl is a C4 alkyl (e.g., unsubstituted C4 alkyl, substituted C4 alkyl).

[0175] In some embodiments, alkyl is, for example, at least one R 2 In some embodiments, each R 2 are independently selected from the group of hydrogen, alkyl, aryl, oxo, and heteroaryl. A The groups, taken together with the atoms to which they are attached, form a ring. In some embodiments, one R 2 The group, taken together with an atom of M, P, or Z (eg, M, P, or Z as described herein), forms a ring.

[0176] In some embodiments, L 1 , L 2 and L 3 At least one of L is heteroalkyl. 1 , L 2 and L 3 At least two of L are heteroalkyl. 1 , L 2 and L 3 Each of is heteroalkyl. In some embodiments, heteroalkyl is C1-C 12 In some embodiments, heteroalkyl is C1-C8 heteroalkyl. In some embodiments, heteroalkyl is C1-C4 heteroalkyl.

[0177] In some embodiments, heteroalkyl is unsubstituted heteroalkyl. In some embodiments, heteroalkyl is substituted heteroalkyl (e.g., one or more R 2 heteroalkyl substituted with a group, where R 2 and R is as described herein. 2 is hydrogen, alkyl, aryl, or heteroaryl. In some embodiments, the substituted heteroalkyl contains a carbonyl group (e.g., an amide, an ester, or a keto). In some embodiments, one R 2 The group, taken together with an atom of M, P, or Z (eg, M, P, or Z as described herein), forms a ring.

[0178] In some embodiments, heteroalkyl includes one or more heteroatoms. In some embodiments, heteroalkyl includes oxygen, sulfur, nitrogen, boron, silicon, or phosphorus atoms. In some embodiments, heteroalkyl includes oxygen, sulfur, or nitrogen atoms. In some embodiments, heteroalkyl includes oxygen atoms. In some embodiments, heteroalkyl includes -C(R 2 )O, where R 2 (wherein R is as described herein). In some embodiments, heteroalkyl is —CHO.

[0179] In some embodiments, the heteroalkyl comprises a polyethylene glycol (PEG) group. For example, in some embodiments, the heteroalkyl is -(CH) m -(OCH2CH2) n -), where each of m and n is an integer independently selected from 0 to 100 (e.g., 0 to 75, 0 to 50, 0 to 20, 0 to 10, or 0 to 5).

[0180] In some embodiments, L 1 , L 2 or L 3 At least one of the following independently: [ka] wherein each of m and n is independently an integer selected from 0 to 100 (e.g., 0 to 75, 0 to 50, 0 to 20, 0 to 10, or 0 to 5.

[0181] In some embodiments, L 1 , L 2 or L 3 Each of the following is independent: [ka] wherein each of m and n is independently an integer selected from 0 to 100 (e.g., 0 to 75, 0 to 50, 0 to 20, 0 to 10, or 0 to 5.

[0182] In some embodiments, L 1 , L 2 or L 3 Each of the following is independent: [ka] is a heteroalkyl selected from:

[0183] In some embodiments, [ka] L 1 , L 2 and L 3 and the bond between each of A, M, P or Z.

[0184] In some embodiments, L 1 , L 2 and L 3At least one of is a heteroalkyl. In some embodiments, the heteroalkyl comprises a positive charge (e.g., a quaternary amine). In some embodiments, the heteroalkyl comprises a negative charge (e.g., a carboxylate, sulfonate, or phosphinate). In some embodiments, the heteroalkyl is a zwitterion (e.g., a neutral molecule containing both positive and negative charges). In some embodiments, the heteroalkyl comprises a quaternary amine and a carboxylate.

[0185] In some embodiments, L 1 , L 2 or L 3 Each of the following is independent: [ka] wherein each of x, m, and n is independently an integer selected from 0 to 100 (e.g., 0 to 75, 0 to 50, 0 to 20, 0 to 10, or 0 to 5).

[0186] In some embodiments, L 1 , L 2 or L 3 At least one of the 2 In some embodiments, R 2 is oxo, halo, or alkyl (e.g., where alkyl is R 7 In some embodiments, L 1 , L 2 or L 3 At least one of the 2 In some embodiments, R 2 is oxo, halo, or alkyl (e.g., where alkyl is R 7 In some embodiments, L 1 is R 2(e.g., oxo, halo, or alkyl (e.g., where alkyl is R 7 In some embodiments, L 2 is R 2 is not substituted with (e.g., oxo, halo, or alkyl (e.g., where alkyl is R 7 In some embodiments, L 3 is R 2 is not substituted with (e.g., oxo, halo, or alkyl (e.g., where alkyl is R 7 (optionally replaced by

[0187] As generally described herein, each M is selected from one or more R 3 refers to an alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with

[0188] In some embodiments, M is alkyl. In some embodiments, M is unsubstituted alkyl. In some embodiments, M is substituted alkyl (e.g., one or more R 3 alkyl substituted with a group, where R 3 is as described herein).

[0189] In some embodiments, M is C1 to C 12 In some embodiments, M is a C1-C8 alkyl. In some embodiments, M is a C1-C4 alkyl. In some embodiments, M is a C1 alkyl (e.g., an unsubstituted C1 alkyl, a substituted C1 alkyl (e.g., —C(R 3 )2)) where R 3 are as described herein (e.g., each R 3 are independently selected from alkyl, aryl, halogen, oxo, and heteroaryl; or two R 3form a ring together with the atoms to which they are attached). In some embodiments, M is a C2 alkyl (e.g., unsubstituted C2 alkyl, substituted C2 alkyl). In some embodiments, M is a C3 alkyl (e.g., unsubstituted C3 alkyl, substituted C3 alkyl). In some embodiments, M is a C4 alkyl (e.g., unsubstituted C4 alkyl, substituted C4 alkyl).

[0190] In some embodiments, M is one or more R 3 In some embodiments, each R 3 are independently alkyl, halogen, oxo, cycloalkyl, heterocyclyl, aryl, and heteroaryl. In some embodiments, one R 3 The group, taken together with an atom of M, P, or Z (eg, M, P, or Z as described herein), forms a ring.

[0191] In some embodiments, M is C1 to C 12 In some embodiments, M is a C1-C8 heteroalkyl. In some embodiments, M is a C1-C4 heteroalkyl. In some embodiments, heteroalkyl is unsubstituted or is substituted with one or more R 3 In some embodiments, each R 3 are independently selected from alkyl, halogen, aryl, oxo, and heteroaryl; or two R 3 are taken together with the atoms to which they are attached to form a ring. In some embodiments, M is C3 heteroalkyl (e.g., unsubstituted C3 heteroalkyl, substituted C3 heteroalkyl). In some embodiments, M is C4 heteroalkyl (e.g., unsubstituted C4 heteroalkyl, substituted C4 heteroalkyl). In some embodiments, M is C5 heteroalkyl (e.g., unsubstituted C5 heteroalkyl, substituted C5 heteroalkyl). In some embodiments, M is C6 heteroalkyl (e.g., unsubstituted C6 heteroalkyl, substituted C6 heteroalkyl).

[0192] In some embodiments, heteroalkyls include one or more heteroatoms. In some embodiments, heteroalkyls include oxygen, sulfur, nitrogen, boron, silicon, or phosphorus atoms. In some embodiments, heteroalkyls include oxygen, sulfur, or nitrogen atoms. In some embodiments, heteroalkyls include oxygen atoms. In some embodiments, heteroalkyls include polyethylene glycol (PEG) groups. For example, in some embodiments, heteroalkyls include -(CH2) m -(OCH2CH2) n -), where each of m and n is an integer independently selected from 0 to 100 (e.g., 0 to 75, 0 to 50, 0 to 20, 0 to 10, or 0 to 5). In some embodiments, M is: [ka] wherein each n is an integer independently selected from 0 to 100 (e.g., 0 to 75, 0 to 50, 0 to 20, 0 to 10, or 0 to 5), and each R 3 are independently as described herein.

[0193] In some embodiments, [ka] M and L 1 and L 2 It refers to the bond between

[0194] In some embodiments, M is: [ka] is.

[0195] In some embodiments, M is cycloalkyl, heterocyclyl, aryl, or heteroaryl. In some embodiments, M is unsubstituted cycloalkyl, unsubstituted heterocyclyl, unsubstituted aryl, or unsubstituted heteroaryl. In some embodiments, M is substituted cycloalkyl, unsubstituted heterocyclyl, unsubstituted aryl, or unsubstituted heteroaryl (e.g., one or more R 3 where R 3 (wherein M is as described herein). In some embodiments, M is a 3- to 12-membered ring. In some embodiments, M is a 3- to 7-membered ring. In some embodiments, M is a 5-membered ring. In some embodiments, M is a 5-membered ring.

[0196] In some embodiments, M is aryl (e.g., phenyl). In some embodiments, M is 1 to 4 R 3 In some embodiments, R 3 is halo or alkyl (e.g., where alkyl is R 7 In some embodiments, M is: [ka] is selected from.

[0197] In some embodiments, M is: [ka] is selected from.

[0198] In some embodiments, M is cycloalkyl. In some embodiments, M is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 3 are independently described herein.

[0199] In some embodiments, M is heterocyclyl. In some embodiments, heterocyclyl contains an oxygen, sulfur, nitrogen, boron, silicon, or phosphorus atom. In some embodiments, heterocyclyl contains an oxygen, sulfur, or nitrogen atom. In some embodiments, M is an oxygen-containing heterocyclyl. In some embodiments, M is oxiranyl, dioxiranyl, oxetanyl, dioxetanyl, tetrahydrofuranyl, dioxolanyl, oxanyl, dioxanyl, trioxanyl, or oxepanyl. In some embodiments, M is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 3 are independently described herein.

[0200] In some embodiments, M is: [ka] is.

[0201] In some embodiments, M is a nitrogen-containing heterocyclyl. In some embodiments, M is aziridinyl, azetidinyl, diazetidinyl, pyrrolidinyl, imidazolyl, oxazolidinyl, isoxazolidinyl, piperazolidinyl, piperazinyl, piperidinyl, or homopiperazinyl. In some embodiments, M is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 3are independently described herein.

[0202] In some embodiments, M is heteroaryl. In some embodiments, M is furanyl, pyrrolyl, thiofuranyl, oxazolyl, isoxazolyl, oxaziridinyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, or pyrimidinyl. In some embodiments, M is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 3 are independently described herein.

[0203] In some embodiments, M is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 3 are independently described herein.

[0204] As generally described herein, each P may be one or more R 4 refers to an alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with

[0205] In some embodiments, P refers to a ring. In some embodiments, the ring is a 3-12 membered ring. In some embodiments, P is a cycloalkyl, heterocyclyl, aryl, or heteroaryl ring. In some embodiments, P is a 3-12 membered ring. In some embodiments, P is a 3-7 membered ring. In some embodiments, P is a 5 membered ring.

[0206] In some embodiments, P is cycloalkyl. In some embodiments, P is unsubstituted cycloalkyl or substituted cycloalkyl (e.g., one or more R 4 In some embodiments, P is a 4-membered cycloalkyl, a 5-membered cycloalkyl, a 6-membered cycloalkyl, a 7-membered cycloalkyl, or an 8-membered cycloalkyl. In some embodiments, P is t-cyclooctene.

[0207] In some embodiments, P is heterocyclyl. In some embodiments, P is unsubstituted heterocyclyl or substituted heterocyclyl (e.g., one or more R 4 In some embodiments, P is a heterocyclyl containing an oxygen, sulfur, nitrogen, boron, silicon, or phosphorus atom. In some embodiments, P is a heterocyclyl containing an oxygen, sulfur, or nitrogen atom. In some embodiments, P is a 4-membered heterocyclyl, 5-membered heterocyclyl, 6-membered heterocyclyl, 7-membered heterocyclyl, or 8-membered heterocyclyl.

[0208] In some embodiments, P is aryl. In some embodiments, P is unsubstituted aryl or substituted aryl (e.g., one or more R 4 In some embodiments, P is a 6-membered aryl (e.g., phenyl). ... 4 In some embodiments, P is a fused aryl ring (e.g., dibenzocyclooctyne).

[0209] In some embodiments, P is heteroaryl. In some embodiments, P is unsubstituted heteroaryl or substituted heteroaryl (e.g., one or more R 4In some embodiments, P is a 3- to 12-membered heteroaryl ring. In some embodiments, P is a 3- to 7-membered heteroaryl ring. In some embodiments, P is a heteroaryl containing a nitrogen, oxygen, or sulfur atom. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is tetrazolyl, imidazolyl, pyrazolyl, or pyrrolyl.

[0210] In some embodiments, P is a 6-membered heteroaryl (eg, P comprises a tetrazine). In some embodiments, P is a 5-membered heteroaryl.

[0211] Exemplary heteroaryls include: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 4 are independently described herein.

[0212] In some embodiments, the heteroaryl is tetrazole, e.g. [ka] It is a tetrazole represented by the formula:

[0213] In some embodiments, the heteroaryl is imidazole or pyrazole, for example: [ka] The compound is an imidazole or pyrazole represented by the formula:

[0214] In some embodiments, heteroaryl is selected from the group: [ka] wherein each n is an integer independently selected from 0 to 5, and each R 4 are independently as described herein.

[0215] In some embodiments, the heteroaryl is pyrrole. For example, the heteroaryl is pyrrole, such as: [ka] wherein each n is an integer independently selected from 0 to 5, and each R 4 are independently as described herein.

[0216] In some embodiments, the heteroaryl is a fused heteroaryl. Exemplary fused heteroaryls include: [ka] wherein each n is an integer independently selected from 0 to 5, and each R 4 are independently as described herein.

[0217] In some embodiments, P is a triazole (e.g., a 1,2,3-triazole or a 1,2,4-triazole). In some embodiments, P is a triazole of formula (P-2): [ka] where: R P2 is hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, -OR P20 , -SR P20 , -N(R P20 )2, -OC(=O)R P20 , -OC(=O)OR P20, -OC(=O)SR P20 , -OC(=O)N(R P20 )2, -SC(=O)R P21 , -SC(=O)OR P20 , -SC(=O)SR P20 , -SC(=O)N(R P20 )2, -NHC(=O)R P20 , -NHC(=O)OR P20 , -NHC(=O)SR P20 , -NHC(=O)N(R P20 )2, -OS(=O)2R P21 , -OS(=O)2OR P20 , -SS(=O)2R P21 , -SS(=O)2OR P20 , -S(=O)R P21 , -SO2R P21 or -S(=O)2OR P20 where R P20 Each instance of is independently hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or two R P20 groups are joined to form a heterocyclic or heteroaryl ring; and R P21 is alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl or heteroaryl; and [ka] represents a single or double bond, where one [ka] is a double bond, and the other [ka] is a single bond.

[0218] In some embodiments, P has the formula (P-3): [ka] is a triazole of the formula: R P3 is hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, -OR P20 , -SR P20 , -N(R P20 )2, -OC(=O)R P20 , -OC(=O)OR P20 , -OC(=O)SR P20 , -OC(=O)N(R P20 )2, -SC(=O)R P21 , -SC(=O)OR P20 , -SC(=O)SR P20 , -SC(=O)N(R P20 )2, -NHC(=O)R P20 , -NHC(=O)OR P20 , -NHC(=O)SR P20 , -NHC(=O)N(R P20 )2, -OS(=O)2R P21 , -OS(=O)2OR P20 , -SS(=O)2R P21 , -SS(=O)2OR P20 , -S(=O)R P21 , -SO2R P21 or -S(=O)2OR P20 where R P20 Each instance of is independently hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or two R P20 groups are joined to form a heterocyclic or heteroaryl ring; and R P21 is alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl or heteroaryl; and [ka] represents a single or double bond, where one [ka] is a double bond, and the other [ka] is a single bond.

[0219] Exemplary triazoles include: [ka] In the formula, R 4 is as described herein. In some embodiments, P is triazole and R 4 is alkyl, aryl, or heteroaryl, or R 4 is L 2 or L 3 (e.g., the L 2 and L 3 ) to form a ring. In some embodiments, P is an unsubstituted triazole.

[0220] As generally described herein, each Z is selected from one or more R 5 refers to an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted by

[0221] In some embodiments, Z is alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl or C1-C 12 In some embodiments, Z is an unsubstituted alkyl, an unsubstituted alkenyl, an unsubstituted alkynyl, or an unsubstituted heteroalkyl. In some embodiments, Z is each one or more R 5is a substituted alkyl, substituted alkenyl, substituted alkynyl, or substituted heteroalkyl substituted by

[0222] In some embodiments, Z is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In some embodiments, Z is unsubstituted methyl, unsubstituted ethyl, unsubstituted propyl, unsubstituted butyl, unsubstituted pentyl, or unsubstituted hexyl. In some embodiments, Z each represents one or more R 5 and substituted methyl, substituted ethyl, substituted propyl, substituted butyl, substituted pentyl, or substituted hexyl.

[0223] In some embodiments, Z is heteroalkyl (e.g., unsubstituted heteroalkyl, substituted heteroalkyl). In some embodiments, heteroalkyl contains one or more heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus). In some embodiments, heteroalkyl is unsubstituted heteroalkyl. In some embodiments, heteroalkyl is substituted heteroalkyl (e.g., containing one or more R A heteroalkyl substituted with a group, where R A is as described herein.

[0224] In some embodiments, heteroalkyl is C1-C 12 In some embodiments, heteroalkyl is C1-C8 heteroalkyl. In some embodiments, heteroalkyl is C1-C4 heteroalkyl.

[0225] In some embodiments, heteroalkyls comprise one or more heteroatoms. In some embodiments, heteroalkyls comprise oxygen, sulfur, nitrogen, boron, silicon, or phosphorus atoms. In some embodiments, heteroalkyls comprise oxygen, sulfur, or nitrogen atoms. In some embodiments, heteroalkyls comprise sulfur atoms. In some embodiments, heteroalkyls comprise nitrogen atoms. In some embodiments, heteroalkyls comprise secondary amines. In some embodiments, heteroalkyls comprise tertiary amines.

[0226] In some embodiments, Z is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl.

[0227] In some embodiments, Z is a group of formula -OR A where R A is hydrogen, alkyl, or alkenyl. In some embodiments, Z is -OH, -OCH3, or -OCH2CH3, -OCH2CF3, or -OCH2CH=CH2.

[0228] In some embodiments, Z is: [ka] is selected from.

[0229] In some embodiments, Z is [ka] wherein n is an integer selected from 0 to 50. In some embodiments, n is an integer selected from 1 to 10 (e.g., n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10). In some embodiments, n is an integer selected from 1, 2, 3, 4, or 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.

[0230] In some embodiments, Z is (—OCH2CH2—)zOCH3, where z is an integer selected from 1-10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10). In some embodiments, z is 1. In some embodiments, z is 2. In some embodiments, z is 3. In some embodiments, z is 4. In some embodiments, z is 5. In some embodiments, z is 6. In some embodiments, z is 7. In some embodiments, z is 8. In some embodiments, z is 9. In some embodiments, z is 10.

[0231] Exemplary alkyl and heteroalkyl include: [ka] In the formula, m and n each independently represent an integer selected from 0 to 50.

[0232] In some embodiments, a heteroalkyl is a zwitterion (e.g., a heteroalkyl is a neutral molecule containing both positive and negative charges). In some embodiments, a heteroalkyl contains a positive charge (e.g., a quaternary amine). In some embodiments, a heteroalkyl contains a negative charge (e.g., a carboxylate, sulfonate, or phosphinate). In some embodiments, a heteroalkyl contains a quaternary amine and a carboxylate. Exemplary zwitterionic heteroalkyl groups include, but are not limited to: [ka] Examples include:

[0233] In some embodiments, Z is silyl (e.g., a group of formula -Si(R G ) 3 silicon-containing groups), where R G is as described herein. Exemplary silyls include: [ka] Examples include:

[0234] In some embodiments, Z is one or more R 5 Exemplary cycloalkyls include: [ka] wherein each n is independently an integer selected from 0 to 20, and R 5 is as described herein.

[0235] In some embodiments, Z is heterocyclyl (e.g., a 3-membered heterocyclyl, a 4-membered heterocyclyl, a 5-membered heterocyclyl, a 6-membered heterocyclyl). In some embodiments, the heterocyclyl comprises an oxygen, sulfur, nitrogen, boron, silicon, or phosphorus atom. In some embodiments, the heterocyclyl comprises an oxygen, sulfur, or nitrogen atom. In some embodiments, Z is a nitrogen-containing heterocyclyl (e.g., a 3-membered nitrogen-containing heterocyclyl, a 4-membered nitrogen-containing heterocyclyl, a 5-membered nitrogen-containing heterocyclyl, a 6-membered nitrogen-containing heterocyclyl). In some embodiments, Z is a 5-membered nitrogen-containing heterocyclyl. In some embodiments, Z is a 6-membered nitrogen-containing heterocyclyl. In some embodiments, Z is an oxygen-containing heterocyclyl (e.g., a 3-membered oxygen-containing heterocyclyl, a 4-membered oxygen-containing heterocyclyl, a 5-membered oxygen-containing heterocyclyl, a 6-membered oxygen-containing heterocyclyl). In some embodiments, Z is a 5-membered ...tetrahydrofuranyl). In some embodiments, Z is a 6-membered oxygen-containing heterocyclyl (e.g., tetrahydropyranyl). In some embodiments, Z is a 5-membered sulfur-containing heterocyclyl. In some embodiments, Z is a 6-membered sulfur-containing heterocyclyl.

[0236] In some embodiments, Z is an oxygen-containing heterocyclyl. In some embodiments, Z is oxiranyl, oxetanyl, tetrahydrofuranyl, or tetrahydropyranyl. In some embodiments, Z is oxiranyl. In some embodiments, Z is oxetanyl. In some embodiments, Z is tetrahydrofuranyl. In some embodiments, Z is tetrahydropyranyl.

[0237] Exemplary oxygen-containing heterocyclyls include: [ka] wherein each n is independently an integer selected from 0 to 20, and R5 is as described herein.

[0238] In some embodiments, Z is a nitrogen-containing heterocyclyl. In some embodiments, Z is aziridinyl, azetidinyl, diazetidinyl, pyrrolidinyl, imidazolyl, oxazolidinyl, isoxazolidinyl, piperazolidinyl, piperazinyl, piperidinyl, or homopiperazinyl. In some embodiments, Z is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 5 are independently described herein.

[0239] In some embodiments, Z is [ka] wherein n is an integer independently selected from 0 to 10, and each R 5 are independently described herein. In some embodiments, R 5 is alkyl (e.g., methyl, ethyl, isopropyl, or propyl).

[0240] In some embodiments, Z is represented by the formula (Z-1): [ka] wherein each R Z1 is alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, halogen, cyano, -OR A , -C(O)R A , -C(O)N(R B )(R C ), -C(O)OR A , -S(O) 2-x RA or two R Z1 The groups together with the atoms to which they are attached form an oxo group or a ring.

[0241] In some embodiments, n is 1. In some embodiments, Z is: [ka] is selected from.

[0242] In some embodiments, n is 2. In some embodiments, n is 2 and two R Z1 The groups together with the atom to which they are attached form oxo. In some embodiments, Z is: [ka] is selected from.

[0243] In some embodiments, two R Z1 The groups together with the carbon atoms to which they are attached form a ring. In some embodiments, the heterocyclyl of formula (Z-1) is a heterocyclyl of formula (Z-1-i): [ka] wherein ring Z is selected from A is a 4-, 5-, 6-, or 7-membered ring. In some embodiments, the heterocyclyl of formula (Z-1-i) is: [ka] is.

[0244] In some embodiments, Z is aryl. In some embodiments, Z is phenyl. In some embodiments, Z is selected from 1 to 4 R 5In some embodiments, Z is phenyl optionally substituted by: [ka] is selected from.

[0245] Exemplary aryl groups include: [ka] Examples include:

[0246] In some embodiments, Z is selected from two R 5 In some embodiments, two R 5 The groups, taken together with the atoms to which they are attached, form a ring (e.g., a fused ring). In some embodiments, the substituted aryl group is [ka] is.

[0247] In some embodiments, the substituted aryl group is: [ka] is.

[0248] In some embodiments, Z is heteroaryl. In some embodiments, Z is unsubstituted heteroaryl or substituted heteroaryl (e.g., one or more R 5In some embodiments, the heteroaryl is a 3- to 7-membered heteroaryl. In some embodiments, the heteroaryl is a 5- or 6-membered heteroaryl. In some embodiments, the heteroaryl is a nitrogen-, oxygen-, or sulfur-containing heteroaryl. In some embodiments, the heteroaryl is a nitrogen-containing heteroaryl. In some embodiments, the heteroaryl is an oxygen-containing heteroaryl. In some embodiments, the heteroaryl is a sulfur-containing heteroaryl. In some embodiments, the heteroaryl contains at least one nitrogen. In some embodiments, the heteroaryl contains at least one oxygen. In some embodiments, the heteroaryl contains at least one sulfur.

[0249] In some embodiments, heteroaryl is a 5-membered heteroaryl. In some embodiments, Z is furanyl, pyrrolyl, thiofuranyl, oxazolyl, isoxazolyl, oxaziridinyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, or pyrimidinyl. In some embodiments, Z is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 5 are independently described herein.

[0250] In some embodiments, Z is: [ka] wherein each n is an integer independently selected from 0 to 10, and each R 5 are independently described herein.

[0251] In some embodiments, Z is: [ka] is selected from.

[0252] In some embodiments, Z is heteroaryl substituted with at least one R. In some embodiments, one R 5 L 3 The substituents (e.g., R 2 ) together to form a ring. In some embodiments, -L 3 -Z: [ka] is

[0253] In some embodiments, the compound of Formula (I) is selected from the compounds shown in any one of Figures 1-5, or a pharmaceutically acceptable salt thereof.

[0254] In some embodiments, the compound of formula (I) has formula (II): [ka] or a salt thereof, wherein A1 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B , -N(R C )(R D ), -N(R C )C(O)R B , -C(O)N(R C )(R D ), -N3, -NC, -CN, -NCO, -NCS, -N(R C )N(R D )2, -NCN(R C ), -C(=N(R C )(R D ))OR A, -SR E , -S(O) x R E , -OS(O) x R E , -N(R C )S(O) x R E , -S(O) x N(R C )(R D ), -P(R F ) y , -Si(OR A )3, -Si(R G )(OR A )2, -B(OR A )2 or a metal, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R 1 and optionally substituted by L 1 and L 3 is independently a bond, alkyl, or heteroalkyl, wherein each of the alkyl and heteroalkyl is selected from one or more R 2 and optionally substituted by L 2 is a bond; M is each one or more R 3 P is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with one or more R 4 and Z is heteroaryl optionally substituted with one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , R E , R F and R Gis independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x R E1 , -OS(O) x R E1 , -N(R C1 )S(O) x R E1 , -S(O) x N(R C1 )(R D1 ), -P(R F1 ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by R A1 , R B1 , R C1 , RD1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4.

[0255] In some embodiments, A1 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D In some embodiments, A1 is alkyl, alkenyl, alkynyl, heteroalkyl, -OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D In some embodiments, A1 is alkyl, OR A , -C(O)OR A , -C(O)R B , -OC(O)R B or -N(R C )(R D ). In some embodiments, A1 is N(R C )(R D ). In some embodiments, A1 is N(R C )(R D ) and R C and RD are independently hydrogen or alkyl. In some embodiments, A1 is NH2. In some embodiments, A1 is NH2 or NHC(O)C(CH2)CH3.

[0256] In some embodiments, L 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is alkyl. In some embodiments, L 1 is C1-C6 alkyl. In some embodiments, L 1 is -CH2- or -CH2CH2-.

[0257] In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is a bond. In some embodiments, L 3 is alkyl. In some embodiments, L 3 is C1-C6 alkyl. In some embodiments, L 3 is -CH-. In some embodiments, L 3 is heteroalkyl. In some embodiments, L 3 is C1-C6 heteroalkyl. In some embodiments, L 3 is -CH2O-.

[0258] In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (-OCH2CH2-)z, where z is an integer selected from 1 to 10. In some embodiments, M is -OCH2CH2-, (-OCH2CH2-)2, (-OCH2CH2-)3, or (-OCH2CH2-)4. In some embodiments, M is (-OCH2CH2-)3. In some embodiments, M is aryl. In some embodiments, M is phenyl. In some embodiments, M is unsubstituted phenyl.

[0259] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a monocyclic, nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl. In some embodiments, P is tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl. In some embodiments, P is tetrazolyl, imidazolyl, pyrazolyl or triazolyl, or pyrrolyl. In some embodiments, P is triazolyl. In some embodiments, P is 1,2,3-triazolyl or 1,2,4-triazolyl. In some embodiments, P is 1,2,4-triazolyl.

[0260] In some embodiments, Z is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl. In some embodiments, Z is heterocyclyl. In some embodiments, Z is monocyclic or bicyclic heterocyclyl. In some embodiments, Z is an oxygen-containing heterocyclyl. In some embodiments, Z is a 6-membered heterocyclyl. In some embodiments, Z is a 6-membered oxygen-containing heterocyclyl. In some embodiments, Z is tetrahydropyranyl. In some embodiments, Z is a bicyclic oxygen-containing heterocyclyl. In some embodiments, Z is phthalic anhydride. In some embodiments, Z is a sulfur-containing heterocyclyl. In some embodiments, Z is a 6-membered sulfur-containing heterocyclyl. In some embodiments, Z is a 6-membered heterocyclyl containing a nitrogen atom and a sulfur atom. In some embodiments, Z is thiomorpholinyl-1,1-dioxidyl. In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0261] In some embodiments, Z is aryl. In some embodiments, Z is monocyclic aryl. In some embodiments, Z is phenyl. In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is a nitrogen-containing group. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is NH. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is an oxygen-containing group. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5is an oxygen-containing heteroalkyl. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is OCH. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is in para position.

[0262] In some embodiments, Z is alkyl. In some embodiments, Z is C1-C 12 In some embodiments, Z is C1-C 10 In some embodiments, Z is C1-C8 alkyl. In some embodiments, Z is selected from 1 to 5 R 5 In some embodiments, Z is C1-C8 alkyl substituted with one R 5 In some embodiments, Z is C1-C8 alkyl substituted with one R 5 C1-C8 alkyl substituted with, where R 5 is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 HA-OR A1 or -C(O)OR A1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 is -OH or -C(O)OH.

[0263] In some embodiments, the compound of formula (II) is selected from the compounds shown in any one of Figures 1-6, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (II) is selected from the compounds shown in any one of Figures 1-6, and is attached to an implantable element (e.g., a device or material) described herein, e.g., via a linking group (e.g., one described herein).

[0264] In some embodiments, the compound of formula (II) has the formula (II-a): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 is a cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with; Y 1 and Y 4 each independently is C(R') or N; Y 2 , Y 3 and Y 5 each independently represents C(R')(R"), N(R 10 ), S, or O, where Y 2 , Y 3 and Y 5 and wherein only two of Y may be O or S; and 1 , Y 2 , Y 3 , Y 4 and Y 5 are each bonded by a single or double bond to achieve the appropriate valence; X is absent, N(R 10 )(R 11 ), O or S; Z 1 are each one or more R 5R' and R" are each independently hydrogen, alkyl, halogen, or cycloalkyl; or R' and R" are each taken together to form an oxo group; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1, cycloalkyl, heterocyclyl, aryl, heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —C(O)R B1 , -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x , cycloalkyl or heterocyclyl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each m and n is independently 0, 1, 2, 3, 4, 5, or 6; and x is 1 or 2.

[0265] In some embodiments, the compound of Formula (II) has the formula (II-b): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 is a cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with; Y 1 and Y 4 each independently is C(R') or N; Y 2 , Y 3 and Y 5 each independently represents C(R')(R"), N(R10 ), S, or O, where Y 2 , Y 3 and Y 5 and wherein only two of Y may be O or S; and 1 , Y 2 , Y 3 , Y 4 and Y 5 are each bonded by a single or double bond to achieve the appropriate valence; X is absent, N(R 10 )(R 11 ), O or S; Z 1 are each one or more R 5 R' and R" are each independently hydrogen, alkyl, halogen, or cycloalkyl; or R' and R" are each taken together to form an oxo group; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —C(O)R B1 , -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x , cycloalkyl or heterocyclyl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each m and n is independently 0, 1, 2, 3, 4, 5, or 6; and x is 1 or 2.

[0266] In some embodiments, the compound of formula (II) has the formula (II-c): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; Z 1 are each one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(RD1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —C(O)R B1 , -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x , cycloalkyl or heterocyclyl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each m and n is independently 0, 1, 2, 3, 4, 5, or 6; and x is 1 or 2.

[0267] In some embodiments, the compound of Formula (II) has the formula (II-d): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted by; ring Z 1 is 1 to 5 R 5cycloalkyl, heterocyclyl, aryl or heteroaryl optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; X is absent, N(R 10 )(R 11 ), O or S; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, —C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -C(O)N(R C1), cycloalkyl, heterocyclyl, aryl or heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0268] In some embodiments, the compound of Formula (II) has the formula (II-e): [ka] or a salt thereof, wherein Z 1 are each one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R2c and R 2d together form an oxo group; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —CN, oxo, hydroxyl, cycloalkyl, or heterocyclyl; and each of m and n is independently 0, 1, 2, 3, 4, 5, or 6.

[0269] In some embodiments, Z 1 is alkyl or heteroalkyl. In some embodiments, Z 1 is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is heteroalkyl. 1 is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z 1 is (-OCH2CH2)3OCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10). In some embodiments, Z 1 is (-OCH2CH2)3OCH3. In some embodiments, X is absent. In some embodiments, m is 1. In some embodiments, n is 1. In some embodiments, R 2a , R 2b , R 2c and R 2d Each of R is independently hydrogen. C and R D is independently hydrogen, alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C(O)C(C=CH2)CH3). C and R D is independently hydrogen, and R C and R D and the other is independently alkenyl (e.g., C(O)C(C=CH2)CH3). In some embodiments, R C and R D Each of is independently hydrogen.

[0270] In some embodiments, the compound of formula (II) has the formula (II-f): [ka] or a salt thereof, wherein the ring M 2 is one or more R 3 aryl or heteroaryl optionally substituted by 2 is cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; X is absent, O, or S; each R 3 or R 5 are independently alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 or -C(O)R B1 or two R 5 Together, we form Ring Z 2 forms a 5- to 6-membered ring fused to R A1 , R B1 , R C1 , R D1 and R E1 each independently is hydrogen, alkyl, heteroalkyl; m and p are each independently 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0271] In some embodiments, the compound of Formula (II) has the formula (II-g): [ka] or a salt thereof, wherein ring Z 2 is cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl; or R 2c and R 2d together form an oxo group; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 5 each independently represents alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 or -C(O)R B1 and each R A1 or R B1 is independently hydrogen, alkyl, or heteroalkyl; p is 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0272] In some embodiments, the compound of Formula (II) has the formula (II-g-2): [ka] or a salt thereof, wherein M 1 is one or more R 3 alkyl, alkenyl, alkynyl optionally substituted by W 1 and W 2each independently represents C(R')(R"), N(R 20 ) or S(O)x; R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; each R 5 are independently alkyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 each R' and R" is independently hydrogen, alkyl, alkenyl, halogen, cyano, or cycloalkyl; 20 is hydrogen, alkyl or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1is independently hydrogen, alkyl, or heteroalkyl; each m is independently 1, 2, 3, 4, 5, or 6; o is 1, 2, 3, 4, or 5; and x is 0, 1, or 2.

[0273] In some embodiments, W 1 and W 2 and one of W is independently O. 1 is O. In some embodiments, W 2 is O. In some embodiments, W 1 is C(R')(R") (e.g., CH2), and W 2 is O. In some embodiments, o is 1, 2, or 3. In some embodiments, m is 1. In some embodiments, ring M 2 is alkyl (e.g., methyl, ethyl, or propyl). In some embodiments, R 2c and R 2d Each of R is independently hydrogen. C and R D is independently hydrogen, alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C(O)C(C=CH2)CH3). C and R D is independently hydrogen, and R C and R D and the other is independently alkenyl (e.g., C(O)C(C=CH2)CH3).

[0274] In some embodiments, the compound of Formula (II) has the formula (II-h): [ka] or a salt thereof, wherein the ring M 2 Each contains 1 to 5 R 4 Y is an aryl or heteroaryl optionally substituted with 1 to 5 R5 optionally substituted with O, S or N(R 10 ) and R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; X is absent, N(R 10 )(R 11 ), O or S; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 or R C and R D one or both of which are bonded to an atom in L or M, or to one of the substituents of L or M, and are bonded to one of 1 to 6 R 6 forming a ring optionally substituted with 4 , R 5 , R 6 , R 10 and R 11 are independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(RD1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —CN, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 1, 2, 3, 4, 5, or 6; and o is 1, 2, 3, 4, or 5.

[0275] In some embodiments, the compound of formula (II) has the formula (II-i): [ka] or a salt thereof, wherein the ring M 2 is aryl or heteroaryl; W 1 and W 2 each independently represents C(R')(R"), N(R 20 ) or S(O)x; R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; each R 5 are independently alkyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)RB1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 each R' and R" is independently hydrogen, alkyl, alkenyl, halogen, cyano, or cycloalkyl; 20 is hydrogen, alkyl or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1 is independently hydrogen, alkyl, or heteroalkyl; each m is independently 1, 2, 3, 4, 5, or 6; o is 1, 2, 3, 4, or 5; and x is 0, 1, or 2.

[0276] In some embodiments, the compound of Formula (II) has the formula (II-i-2): [ka] or a salt thereof, wherein the ring M 2 is aryl or heteroaryl; W 1 and W 2each independently represents C(R')(R"), N(R 20 ) or S(O)x; R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; each R 5 are independently alkyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 each R' and R" is independently hydrogen, alkyl, alkenyl, halogen, cyano, or cycloalkyl; 20 is hydrogen, alkyl or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1is independently hydrogen, alkyl, or heteroalkyl; each m is independently 1, 2, 3, 4, 5, or 6; o is 1, 2, 3, 4, or 5; and x is 0, 1, or 2.

[0277] In some embodiments, W 1 and W 2 and one of W is independently O. 1 is O. In some embodiments, W 2 is O. In some embodiments, W 1 is C(R')(R") (e.g., CH2), and W 2 is O. In some embodiments, o is 1, 2, or 3. In some embodiments, m is 1. In some embodiments, ring M 2 is aryl (e.g., phenyl). In some embodiments, R 2c and R 2d Each of R is independently hydrogen. C and R D is independently hydrogen, alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C(O)C(C=CH2)CH3). C and R D is independently hydrogen, and R C and R D and the other is independently alkenyl (e.g., C(O)C(C=CH2)CH3).

[0278] In some embodiments, the compound of formula (II) has the formula (II-j): [ka] or a salt thereof, wherein the ring M 2 is aryl or heteroaryl; ring Z 2 is aryl or heteroaryl; R 2c and R 2deach is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; X is absent, O, or S; R 5a and R 5b each independently represents alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 or -C(O)R B1 or R 5a and R 5b Together, we form Ring Z 2 form a 5- to 6-membered ring fused to each R A1 and R B1 is independently hydrogen, alkyl, heteroalkyl; and each m is independently 0, 1, 2, 3, 4, 5, or 6.

[0279] In some embodiments, the compound of Formula (II) has the formula (II-k): [ka] or a salt thereof, wherein Z 1 is 1 to 5 R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C and R Dare independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 are independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —CN, oxo, hydroxyl, cycloalkyl, or heterocyclyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; and q is an integer from 0 to 25.

[0280] In some embodiments, the compound of formula (II) has the formula (II-1): [ka] or a salt thereof, wherein ring Z 2 is 1 to 5 R 5 heterocyclyl, aryl or heteroaryl optionally substituted with; R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, or halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C and R D are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form 1 to 6 R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 are independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —CN, oxo, hydroxyl, cycloalkyl, or heterocyclyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; and q is an integer from 0 to 25.

[0281] In some embodiments, the compound of formula (II) has the formula (II-m): [ka] or a salt thereof, wherein ring Z 2 is 1 to 5 R 5 heterocyclyl or heteroaryl optionally substituted with; R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, or halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(RC1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and each R 5 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1 each of m and n is independently 1, 2, or 3; and each of p and q is independently 0, 1, 2, 3, or 4.

[0282] In some embodiments, for example, a compound of any one of the formulae described herein (e.g., a compound of formula (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-j), (II-k), (II-l), (II-m)), Z 1 , ring Z 1 or ring Z 2 is heterocyclyl. In some embodiments, Z 1 , ring Z 1 or ring Z 2 is a 6-membered heterocyclyl, a 5-membered heterocyclyl, or a 4-membered heterocyclyl. 1 , ring Z 1 or ring Z 2 is an oxygen-, nitrogen- or sulfur-containing heterocyclyl.

[0283] In some embodiments, Z 1 , ring Z 1 or ring Z 2 is an oxygen-containing heterocyclyl. In some embodiments, Z 1 , ring Z 1 or ring Z 2is tetrahydropyranyl, dioxanyl, tetrahydrofuranyl, oxetanyl, or oxiranyl. 1 , ring Z 1 or ring Z 2 teeth: [ka] wherein n is an integer of 0 to 10.

[0284] In some embodiments, Z 1 , ring Z 1 or ring Z 2 is a nitrogen-containing heterocyclyl. In some embodiments, Z 1 , ring Z 1 or ring Z 2 is piperidinyl, piperazinyl, hexahydropyrimidinyl, pyrrolidinyl, imidazolidinyl, azetidinyl, or aziridinyl. 1 , ring Z 1 or ring Z 2 teeth: [ka] wherein n is an integer of 0 to 10.

[0285] In some embodiments, the compound of formula (II) has the formula (II-n): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and each R 5 are independently alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; and q is an integer from 0 to 25.

[0286] In some embodiments, the compound of formula (II) has the formula (II-o): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, or halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1)(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R 5 is alkyl, halogen, -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1 , R B1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; and q is an integer from 0 to 25.

[0287] In some embodiments, the compound of Formula (II) has the formula (II-p): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, heteroalkyl, or halo, or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SRE1 and;R 5 is alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; and q is an integer from 0 to 25.

[0288] In some embodiments, the compound of formula (II) has the formula (II-q): [ka] or a salt thereof, wherein X is C(R')(R"), N(R'), or S(O)x; each of R' and R" is independently hydrogen, alkyl, halogen, or cycloalkyl; R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and each R 5 are independently alkyl, heteroalkyl, halogen, cyano, -ORA1 , -C(O)OR A1 , -C(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1 , R B1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m, n, and o are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, or 5; q is an integer from 0 to 25; x is 0, 1, or 2; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0289] In some embodiments, X is, for example, N(R'), and R' is hydrogen or alkyl. In some embodiments, X is, for example, S(O)x, and x is 0, 1, or 2. In some embodiments, X is not S(O)2.

[0290] In some embodiments, the compound of Formula (II) has the formula (II-r): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each independently represents hydrogen, alkyl, heteroalkyl, halo, cyano, nitro, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(RC1 )(R D1 ), -N(R C1 )C(O)R B1 or -C(O)N(R C1 ) or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R 5a and each of 5b independently represents alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1 , R B1 , R C1 , R D1 and R E1 each is independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; q is an integer from 0 to 25; and r is an integer from 0 to 10.

[0291] In some embodiments, a compound of Formula (I) or Formula (II) (e.g., a compound of Formula (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-g-2), (II-h), (II-i), (II-i-2), (II-j), (II-k), (II-l), (II-m), (II-n), (II-o), (II-p), (II-q), or (II-r)) is selected from a compound depicted in any one of Figures 1-6, or a pharmaceutically acceptable salt thereof.

[0292] In some embodiments, a compound of Formula (I) or Formula (II) (e.g., a compound of Formula (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-g-2), (II-h), (II-i), (II-i-2), (II-j), (II-k), (II-l), (II-m), (II-n), (II-o), (II-p), (II-q), or (II-r)) is prepared according to the methods described in WO 2012 / 11444. The compound is not a compound disclosed in any of International Publication Nos. 2012 / 167223, 2014 / 153126, 2016 / 187225, 2016 / 019391, 2017 / 075630, 2017 / 075631, and U.S. Patent No. 2016-0030359.

[0293] In some embodiments, a compound of Formula (I) or Formula (II) (e.g., a compound of Formula (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-g-2), (II-h), (II-i), (II-i-2), (II-j), (II-k), (II-l), (II-m), (II-n), (II-o), (II-p), (II-q), or (II-r)) is selected from the following: [ka] or a salt thereof.

[0294] In some embodiments, a compound of Formula (I) or Formula (II) (e.g., a compound of Formula (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-g-2), (II-h), (II-i), (II-i-2), (II-j), (II-k), (II-l), (II-m), (II-n), (II-o), (II-p), (II-q), or (II-r)) is selected from the following: [ka] or a salt thereof.

[0295] In some embodiments, the compound of formula (I) has formula (III): [ka] or a salt thereof, wherein A2 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —O—, —C(O)O—, —C(O)—, —OC(O)—, —N(R C )-, -N(R C )C(O)-, -C(O)N(R C )-, -N(R C )N(R D )-, -NCN-, -C(=N(R C )(R D ))O-, -S-, -S(O) x -, -OS(O) x -, -N(R C )S(O) x -, -S(O) x N(R C )-, -P(R F ) y -, -Si(OR A )2-, -Si(R G )(OR A )-, -B(OR A)- or a metal, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is bonded to a linking group (e.g., a linking group as defined herein), and one or more R 1 and optionally substituted by L 1 and L 3 is independently a bond, alkyl, or heteroalkyl, wherein each of the alkyl and heteroalkyl is selected from one or more R 2 and optionally substituted by L 2 is a bond; M is each one or more R 3 P is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with one or more R 4 and Z is heteroaryl optionally substituted with one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R A , R B , R C , R D , R E , R F and R G is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, azido, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 optionally substituted with; or R C and R D together with the nitrogen atom to which they are attached, form one or more R 6 forming a ring (e.g., a 5- to 7-membered ring) optionally substituted with R 1 , R 2 , R 3 , R 4 , R 5and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x R E1 , -OS(O) x R E1 , -N(R C1 )S(O) x R E1 , -S(O) x N(R C1 )(R D1 ), -P(R F1 ) y , cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 is optionally substituted by R A1 , R B1 , R C1 , R D1 , R E1 and R F1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; x is 1 or 2; and y is 2, 3, or 4.

[0296] In some embodiments, A2 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —O—, —C(O)O—, —C(O)—, —OC(O)—, or —N(R C In some embodiments, A2 is alkyl, alkenyl, alkynyl, heteroalkyl, —O—, —C(O)O—, —C(O)—, —OC(O—, or —N(R C In some embodiments, A2 is alkyl, —O—, —C(O)O—, —C(O)—, —OC(O), or —N(R C In some embodiments, A2 is —N(R C In some embodiments, A2 is —N(R C )- and R C and R D is independently hydrogen or alkyl. In some embodiments, A2 is -NH-. In some embodiments, A2 is NH- or NH(C(O)C(CH3)CH2-.

[0297] In some embodiments, L 1 is a bond, alkyl, or heteroalkyl. In some embodiments, L 1 is alkyl. In some embodiments, L 1 is C1-C6 alkyl. In some embodiments, L 1 is -CH2- or -CH2CH2-. In some embodiments, L 1 is R 3 has been replaced by

[0298] In some embodiments, L 3 is a bond, alkyl, or heteroalkyl. In some embodiments, L 3 is a bond. In some embodiments, L 3 is alkyl. In some embodiments, L 3 is C1-C6 alkyl. In some embodiments, L3 is -CH-. In some embodiments, L 3 is heteroalkyl. In some embodiments, L 3 is C1-C6 heteroalkyl. In some embodiments, L 3 is —CH2O—. In some embodiments, L 3 is R 3 has been replaced by

[0299] In some embodiments, M is alkyl, heteroalkyl, aryl, or heteroaryl. In some embodiments, M is alkyl (e.g., methyl, ethyl, propyl). In some embodiments, M is heteroalkyl, aryl, or heteroaryl. In some embodiments, M is heteroalkyl. In some embodiments, M is (-OCH2CH2-)z, where z is an integer selected from 1 to 10. In some embodiments, M is -OCH2CH2-, (-OCH2CH2-)2, (-OCH2CH2-)3, or (-OCH2CH2-)4. In some embodiments, M is (-OCH2CH2-)3. In some embodiments, M is aryl. In some embodiments, M is phenyl. In some embodiments, M is unsubstituted phenyl.

[0300] In some embodiments, P is a tricyclic, bicyclic, or monocyclic heteroaryl. In some embodiments, P is a monocyclic heteroaryl. In some embodiments, P is a nitrogen-containing heteroaryl. In some embodiments, P is a monocyclic, nitrogen-containing heteroaryl. In some embodiments, P is a 5-membered heteroaryl. In some embodiments, P is a 5-membered nitrogen-containing heteroaryl. In some embodiments, P is tetrazolyl, imidazolyl, pyrazolyl or triazolyl, pyrrolyl, oxazolyl, or thiazolyl. In some embodiments, P is tetrazolyl, imidazolyl, pyrazolyl or triazolyl, or pyrrolyl. In some embodiments, P is triazolyl. In some embodiments, P is 1,2,3-triazolyl.

[0301] In some embodiments, Z is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl. In some embodiments, Z is heterocyclyl. In some embodiments, Z is monocyclic or bicyclic heterocyclyl. In some embodiments, Z is an oxygen-containing heterocyclyl. In some embodiments, Z is a 6-membered heterocyclyl. In some embodiments, Z is a 6-membered oxygen-containing heterocyclyl. In some embodiments, Z is tetrahydropyranyl. In some embodiments, Z is a bicyclic oxygen-containing heterocyclyl. In some embodiments, Z is phthalic anhydride. In some embodiments, Z is a sulfur-containing heterocyclyl. In some embodiments, Z is a 6-membered sulfur-containing heterocyclyl. In some embodiments, Z is a 6-membered heterocyclyl containing a nitrogen atom and a sulfur atom. In some embodiments, Z is thiomorpholinyl-1,1-dioxidyl. In some embodiments, Z is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl-1,1-dioxide, piperidinyl, piperazinyl, or pyrrolidinyl.

[0302] In some embodiments, Z is aryl. In some embodiments, Z is monocyclic aryl. In some embodiments, Z is phenyl. In some embodiments, Z is monosubstituted phenyl (e.g., one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is a nitrogen-containing group. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is NH. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is an oxygen-containing group. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is an oxygen-containing heteroalkyl. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is OCH. In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 In some embodiments, Z is a monosubstituted phenyl, wherein one R 5 is in para position.

[0303] In some embodiments, Z is alkyl. In some embodiments, Z is C1-C 12 In some embodiments, Z is C1-C 10 In some embodiments, Z is C1-C8 alkyl. In some embodiments, Z is selected from 1 to 5 R 5 In some embodiments, Z is C1-C8 alkyl substituted with one R 5 In some embodiments, Z is C1-C8 alkyl substituted with one R 5 C1-C8 alkyl substituted with, where R 5is alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 or -N(R C1 )(R D1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 -OR A1 or -C(O)OR A1 In some embodiments, Z is one R 5 C1-C8 alkyl substituted with, where R 5 HA-OR A1 Or -C(O)OH.

[0304] In some embodiments, the compound of Formula (III) is selected from any one of the compounds shown in any one of Figures 1-6, or a pharmaceutically acceptable salt thereof.

[0305] In some embodiments, the compound of Formula (III) has the formula (III-a): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 is a cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with; Y 1 and Y 4 each independently is C(R') or N; Y 2 , Y 3 and Y 5 each independently represents C(R')(R"), N(R 10 ), S, or O, where Y 2 , Y 3 and Y 5 and wherein only two of Y may be O or S; and 1 , Y 2 , Y 3, Y 4 and Y 5 are each bonded by a single or double bond to achieve the appropriate valence; X is absent, N(R 10 )(R 11 ), O or S; Z 1 are each one or more R 5 R' and R" are each independently hydrogen, alkyl, halogen, or cycloalkyl; or R' and R" are each taken together to form an oxo group; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1, cycloalkyl, heterocyclyl, aryl, heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —C(O)R B1 , -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x , cycloalkyl or heterocyclyl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 0, 1, 2, 3, 4, 5, or 6; x is 1 or 2; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0306] In some embodiments, the compound of formula (II) has formula (III-b): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3is a cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with; Y 1 and Y 4 each independently is C(R') or N; Y 2 , Y 3 and Y 5 each independently represents C(R')(R"), N(R 10 ), S, or O, where Y 2 , Y 3 and Y 5 and wherein only two of Y may be O or S; and 1 , Y 2 , Y 3 , Y 4 and Y 5 are each bonded by a single or double bond to achieve the appropriate valence; X is absent, N(R 10 )(R 11 ), O or S; Z 1 are each one or more R 5 R' and R" are each independently hydrogen, alkyl, halogen, or cycloalkyl; or R' and R" are each taken together to form an oxo group; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —C(O)R B1 , -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x , cycloalkyl or heterocyclyl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 0, 1, 2, 3, 4, 5, or 6; x is 1 or 2; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0307] In some embodiments, the compound of formula (III) has formula (III-c): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; Z 1 are each one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)RB1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R 10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —C(O)R B1 , -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , S(O) x , cycloalkyl or heterocyclyl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 0, 1, 2, 3, 4, 5, or 6; x is 1 or 2; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0308] In some embodiments, the compound of formula (III) has formula (III-d): [ka] or a salt thereof, wherein the ring M 1 Each contains 1 to 5 R 3 cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted by; ring Z 1 is 1 to 5 R 5 is a cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; X is absent, N(R 10 )(R 11 ), O or S; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, or heteroaryl; R10 and R 11 each independently represents hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, —C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -C(O)N(R C1 ), cycloalkyl, heterocyclyl, aryl or heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0309] In some embodiments, the compound of formula (III) has the formula (III-e): [ka] or a salt thereof, wherein Z 1 are each one or more R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —CN, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0310] In some embodiments, Z 1 is alkyl or heteroalkyl. In some embodiments, Z 1 is heteroalkyl (e.g., C1-C 12 In some embodiments, Z is heteroalkyl. 1 is an oxygen-containing heteroalkyl or a nitrogen-containing heteroalkyl. In some embodiments, Z 1 is (-OCH2CH2)3OCH3, where z is an integer selected from 1 to 10 (e.g., z is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10). In some embodiments, Z 1 is (-OCH2CH2)3OCH3. In some embodiments, X is absent. In some embodiments, m is 1. In some embodiments, n is 1. In some embodiments, R 2a , R 2b , R 2c and R 2d Each of R is independently hydrogen. C is hydrogen, alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C(O)C(C=CH2)CH3). In some embodiments, R C is hydrogen. In some embodiments, R C is alkenyl (e.g., C(O)C(C=CH2)CH3).

[0311] In some embodiments, the compound of formula (III) has the formula (III-f): [ka] or a salt thereof, wherein the ring M 2 is one or more R 3 aryl or heteroaryl optionally substituted by 2 is cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; X is absent, O, or S; each R 3 or R 5 are independently alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 or -C(O)R B1 or two R 5 Together, we form Ring Z 2 forms a 5- to 6-membered ring fused to R A1 , R B1 , R C1 , R D1 and R E1 each independently is hydrogen, alkyl, heteroalkyl; m and p are each independently 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0312] In some embodiments, the compound of Formula (III) has the formula (III-g): [ka] or a salt thereof, wherein ring Z 2 is cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl; or R 2c and R 2d together form an oxo group; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 5 each independently represents alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 or -C(O)R B1 and each R A1 or R B1 is independently hydrogen, alkyl, or heteroalkyl; p is 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0313] In some embodiments, the compound of formula (III) has the formula (III-g-2): [ka] or a salt thereof, wherein M 1 is one or more R 3 alkyl, alkenyl, alkynyl optionally substituted by W 1 and W 2each independently represents C(R')(R"), N(R 20 ) or S(O)x; R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; each R 5 are independently alkyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 each of R' and R" is independently hydrogen, alkyl, alkenyl, halogen, cyano, or cycloalkyl; 20 is hydrogen, alkyl or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1 is independently hydrogen, alkyl, or heteroalkyl; each m is independently 1, 2, 3, 4, 5, or 6; o is 1, 2, 3, 4, or 5; and x is 0, 1, or 2.

[0314] In some embodiments, W 1 and W 2 and one of W is independently O.1 is O. In some embodiments, W 2 is O. In some embodiments, W 1 is C(R')(R") (e.g., CH2), and W 2 is O. In some embodiments, o is 1, 2, or 3. In some embodiments, m is 1. In some embodiments, ring M 2 is alkyl (e.g., methyl, ethyl, or propyl). In some embodiments, R 2c and R 2d Each of R is independently hydrogen. C and R D is independently hydrogen, alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C(O)C(C=CH2)CH3). C and R D is independently hydrogen, and R C and R D and the other is independently alkenyl (e.g., C(O)C(C=CH2)CH3).

[0315] In some embodiments, the compound of Formula (III) has the formula (III-h): [ka] or a salt thereof, wherein the ring M 2 Each contains 1 to 5 R 4 Y is an aryl or heteroaryl optionally substituted with 1 to 5 R 5 optionally substituted with O, S or N(R 10 ) and R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R2a and R 2b Or R 2c and R 2d together form an oxo group; X is absent, N(R 10 )(R 11 ), O or S; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 or R C is bonded to an atom in L or M, or to one of the substituents of L or M, and is bonded to 1 to 6 R 6 forming a ring optionally substituted with 4 , R 5 , R 6 , R 10 and R 11 are independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —CN, oxo, hydroxyl, cycloalkyl, or heterocyclyl; each of m and n is independently 1, 2, 3, 4, 5, or 6; o is 1, 2, 3, 4, or 5; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0316] In some embodiments, the compound of formula (III) has the formula (III-i): [ka] or a salt thereof, wherein the ring M 2 is aryl or heteroaryl; W 1 and W 2 each independently represents C(R')(R"), N(R 20 ) or S(O)x; R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; each R 5 are independently alkyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R Cis hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 each of R' and R" is independently hydrogen, alkyl, alkenyl, halogen, cyano, or cycloalkyl; 20 is hydrogen, alkyl or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1 is independently hydrogen, alkyl, or heteroalkyl; each m is independently 1, 2, 3, 4, 5, or 6; o is 1, 2, 3, 4, or 5; and x is 0, 1, or 2.

[0317] In some embodiments, the compound of formula (III) has the formula (III-i-2): [ka] or a salt thereof, wherein the ring M 2 is aryl or heteroaryl; W 1 and W 2 each independently represents C(R')(R"), N(R 20 ) or S(O)x; R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; each R 5 are independently alkyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(RC1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 each of R' and R" is independently hydrogen, alkyl, alkenyl, halogen, cyano, or cycloalkyl; 20 is hydrogen, alkyl or -C(O)R B1 and;R A1 , R B1 , R C1 , R D1 and R E1 is independently hydrogen, alkyl, or heteroalkyl; each m is independently 1, 2, 3, 4, 5, or 6; o is 1, 2, 3, 4, or 5; and x is 0, 1, or 2.

[0318] In some embodiments, W 1 and W 2 and one of W is independently O. 1 is O. In some embodiments, W 2 is O. In some embodiments, W 1 is C(R')(R") (e.g., CH2), and W 2 is O. In some embodiments, o is 1, 2, or 3. In some embodiments, m is 1. In some embodiments, ring M 2 is aryl (e.g., phenyl). In some embodiments, R 2c and R 2d Each of R is independently hydrogen. C and R Dis independently hydrogen, alkyl, alkenyl, alkynyl, or heteroalkyl (e.g., C(O)C(C=CH2)CH3). C and R D is independently hydrogen, and R C and R D and the other is independently alkenyl (e.g., C(O)C(C=CH2)CH3).

[0319] In some embodiments, the compound of formula (III) has the formula (III-j): [ka] or a salt thereof, wherein the ring M 2 is aryl or heteroaryl; ring Z 2 is aryl or heteroaryl; R 2c and R 2d each is independently hydrogen, alkyl, or heteroalkyl; or R 2c and R 2d together form an oxo group; X is absent, O, or S; R 5a and R 5b each independently represents alkyl, heteroalkyl, halogen, oxo, -OR A1 , -C(O)OR A1 or -C(O)R B1 or R 5a and R 5b Together, we form Ring Z 2 form a 5- to 6-membered ring fused to each R A1 and R B1 is independently hydrogen, alkyl, or heteroalkyl; each m is independently 0, 1, 2, 3, 4, 5, or 6; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0320] In some embodiments, the compound of Formula (III) has the formula (III-k): [ka] or a salt thereof, wherein Z 1 is 1 to 5 R 5 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with; R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R C is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , RB1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; q is an integer from 0 to 25; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0321] In some embodiments, the compound of formula (III) has the formula (III-l): [ka] or a salt thereof, wherein ring Z 2 is 1 to 5 R 5 heterocyclyl, aryl or heteroaryl optionally substituted with; R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, or halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; R Cis hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from 1 to 6 R 6 optionally substituted with R 3 , R 5 and R 6 each independently represents alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azido, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 , cycloalkyl, heterocyclyl, aryl, heteroaryl; R A1 , R B1 , R C1 , R D1 and R E1 are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl is selected from 1 to 6 R 7 and each R 7 is independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, —CN, oxo, hydroxyl, cycloalkyl, or heterocyclyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; q is an integer from 0 to 25; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0322] In some embodiments, the compound of formula (III) has the formula (III-m): [ka] or a salt thereof, wherein ring Z 2 is cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and each R 5 are independently alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ), SR E1 and;R A1 , R B1 , R C1 , R D1 and R E1each is independently hydrogen, alkyl, or heteroalkyl; m, n, and o are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, or 5; q is an integer from 0 to 25; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0323] In some embodiments, for example, a compound of any one of the formulae described herein (e.g., a compound of formula (III-a), (III-b), (III-c), (III-d), (III-e), (III-f), (III-g), (III-h), (III-j), (III-k), (III-l), or (III-m)), Z 1 , ring Z 1 or ring Z 2 is heterocyclyl. In some embodiments, Z 1 , ring Z 1 or ring Z 2 is a 6-membered heterocyclyl, a 5-membered heterocyclyl, or a 4-membered heterocyclyl. 1 , ring Z 1 or ring Z 2 is an oxygen-, nitrogen- or sulfur-containing heterocyclyl.

[0324] In some embodiments, Z 1 , ring Z 1 or ring Z 2 is an oxygen-containing heterocyclyl. In some embodiments, Z 1 , ring Z 1 or ring Z 2 is tetrahydropyranyl, dioxanyl, tetrahydrofuranyl, oxetanyl, or oxiranyl. 1 , ring Z 1 or ring Z 2 teeth: [ka] wherein n is an integer of 0 to 10.

[0325] In some embodiments, Z 1 , ring Z 1 or ring Z 2 is a nitrogen-containing heterocyclyl. In some embodiments, Z 1 , ring Z 1 or ring Z 2 is piperidinyl, piperazinyl, hexahydropyrimidinyl, pyrrolidinyl, imidazolidinyl, azetidinyl, or aziridinyl. 1 , ring Z 1 or ring Z 2 teeth: [ka] wherein n is an integer of 0 to 10.

[0326] In some embodiments, the compound of formula (III) has the formula (III-n): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(RC1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and each R 5 are independently alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1 , R B1 , R C1 , R D1 and R E1 each is independently hydrogen, alkyl, or heteroalkyl; m, n, and o are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, or 5; q is an integer from 0 to 25; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0327] In some embodiments, the compound of Formula (III) has the formula (III-o): [ka] or a salt thereof, wherein each R 5 are independently alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1 , RB1 , R C1 , R D1 and R E1 each is independently hydrogen, alkyl, or heteroalkyl; o is 0, 1, 2, 3, 4, 5, or 6; q is an integer from 0 to 25; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0328] In some embodiments, the compound of formula (III) has the formula (III-p): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, or halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R 5 is alkyl, halogen, -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1, R B1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; q is an integer from 0 to 25; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0329] In some embodiments, the compound of formula (III) has the formula (III-q): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each is independently hydrogen, alkyl, heteroalkyl, or halo, or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R 5 is alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 or -C(O)R B1 and;R A1 , RB1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; q is an integer from 0 to 25; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0330] In some embodiments, the compound of formula (III) has the formula (III-r): [ka] or a salt thereof, wherein X is C(R')(R"), N(R'), or S(O)x; each of R' and R" is independently hydrogen, alkyl, halogen, or cycloalkyl; R 2a , R 2b , R 2c and R 2d each independently is hydrogen, alkyl, heteroalkyl, halo; or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and each R 5 are independently alkyl, heteroalkyl, halogen, cyano, -ORA1 , -C(O)OR A1 , -C(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1 , R B1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, or 5; q is an integer from 0 to 25; x is 0, 1, or 2; and [ka] refers to a bond to a device or material (e.g., a device or material described herein).

[0331] In some embodiments, X is, for example, N(R'), and R' is hydrogen or alkyl. In some embodiments, X is, for example, S(O)x, and x is 0, 1, or 2. In some embodiments, X is not S(O)2.

[0332] In some embodiments, the compound of formula (III) has the formula (III-s): [ka] or a salt thereof, wherein R 2a , R 2b , R 2c and R 2d each independently represents hydrogen, alkyl, heteroalkyl, halo, cyano, nitro, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(RC1 )(R D1 ), -N(R C1 )C(O)R B1 or -C(O)N(R C1 ) or R 2a and R 2b Or R 2c and R 2d together form an oxo group; each R 3 are independently alkyl, heteroalkyl, halogen, cyano, oxo, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R 5a and each of 5b independently represents alkyl, heteroalkyl, halogen, cyano, -OR A1 , -C(O)OR A1 , -C(O)R B1 , -OC(O)R B1 , -N(R C1 )(R D1 ), -N(R C1 )C(O)R B1 , -C(O)N(R C1 ) or SR E1 and;R A1 , R B1 , R C1 , R D1 and R E1 are each independently hydrogen, alkyl, or heteroalkyl; m and n are each independently 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, or 4; q is an integer from 0 to 25; r is an integer from 0 to 10; and [ka] refers to a bond to a binding group (e.g., a binding group described herein) or a device or material (e.g., a device or material described herein).

[0333] In some embodiments, a compound of Formula (I) or Formula (III) (e.g., a compound of Formula (III-a), (III-b), (III-c), (III-d), (III-e), (III-f), (III-g), (III-g-2), (III-h), (III-i), (III-i-2), (III-j), (III-k), (III-l), (III-m), (III-n), (III-o), (III-p), (III-q), (III-r), or (II-s)) is selected from a compound depicted in any one of Figures 1-6, or a pharmaceutically acceptable salt thereof.

[0334] In some embodiments, a compound of Formula (I) or Formula (III) (e.g., a compound of Formula (III-a), (III-b), (III-c), (III-d), (III-e), (III-f), (III-g), (III-g-2), (III-h), (III-i), (III-i-2), (III-j), (III-k), (III-l), (III-m), (III-n), (III-o), (III-p), (III-q), (III-r), or (III-s)) is not a compound disclosed in any of WO 2012 / 112982, WO 2012 / 167223, WO 2014 / 153126, WO 2016 / 187225, WO 2016 / 019391, WO 2017 / 075630, WO 2017 / 075631, and U.S. Patent No. 2016-0030359.

[0335] In some embodiments, a compound of Formula (I) or Formula (III) (e.g., a compound of Formula (III-a), (III-b), (III-c), (III-d), (III-e), (III-f), (III-g), (III-g-2), (III-h), (III-i), (III-i-2), (III-j), (III-k), (III-l), (III-m), (III-n), (III-o), (III-p), (III-q), (III-r), or (II-s)) is selected from the following: [ka] or a salt thereof.

[0336] In some embodiments, a compound of Formula (I) or Formula (III) (e.g., a compound of Formula (III-a), (III-b), (III-c), (III-d), (III-e), (III-f), (III-g), (III-g-2), (III-h), (III-i), (III-i-2), (III-j), (III-k), (III-l), (III-m), (III-n), (III-o), (III-p), (III-q), (III-r), or (II-s)) is selected from the following: [ka] or a salt thereof.

[0337] In some embodiments, a compound of Formula (I) or Formula (III) (e.g., a compound of Formula (III-a), (III-b), (III-c), (III-d), (III-e), (III-f), (III-g), (III-g-2), (III-h), (III-i), (III-i-2), (III-j), (III-k), (III-l), (III-m), (III-n), (III-o), (III-p), (III-q), (III-r), or (II-s)) is not bound to a polymer selected from alginate, carboxypolystyrene, polystyrene, glass, PDMS, or silicone.

[0338] bonding group The compounds, materials, and devices described herein can be linked via any linking chemistry known in the art. A list of exemplary linking chemistries is outlined in Bioconjugate Techniques (3rd ed., Greg T. Hermanson, Waltham, MA: Elsevier, Inc., 2013), which is incorporated herein by reference in its entirety.

[0339] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via an amine. The amine bond can be generated via an isothiocyanate, isocyanate, acyl azide, NHS ester, sulfonyl chloride, tosylate ester, aldehyde, glyoxal, epoxide, oxirane, carbonate, arylating agent, imidoester, carbodiimide, anhydride, fluorophenyl ester, hydromethylphosphine derivative, via guanidination or any of its derivatives, for example, as described in Techniques (Id), pp. 229-240.

[0340] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via a thiol. Exemplary thiol bonds can be prepared using haloacetyls, alkyl halide derivatives, maleimides, aziridines, acryloyls, arylating agents, thiol-disulfide exchange reagents, vinyl sulfone reagents, metal-thiol dative bonds, native chemical ligation, metal modification (e.g., via cisplatin), or derivatives of any of these, as described in Techniques (Id), pp. 240-246.

[0341] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via a carboxylate. Exemplary carboxylate linkages can be prepared using diazoalkanes, diazoacetyls, N,N'-carbonyldiimidazoles, carbodiimides, or derivatives of any of these, as described in Techniques (Id), pp. 246-248.

[0342] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via a hydroxyl group. Attachments made via a hydroxyl group can be prepared via epoxides, oxiranes, N,N'-carbonyldiimidazole, N,N'-disuccinimidyl carbonate, N-hydroxysuccinimidyl chloroformate, periodate oxidation, enzymatic oxidation, alkyl halogens, isocyanates, or derivatives of any of these, for example, as described in Techniques (Id), pp. 248-250.

[0343] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via an aldehyde or ketone. Exemplary attachments via aldehydes or ketones can be made via hydrazine, hydrazide, Schiff base formation, reductive amination, aminooxy derivatives, Mannich condensation, or any derivative thereof, e.g., as described in Techniques (Id), pp. 251-252.

[0344] In some embodiments, the compounds described herein (e.g., compounds of Formula (I) described herein) are attached to materials or devices via active hydrogen reactions. Examples of such attachments can be made via diazonium derivatives, Mannich condensation, iodination reactions, or derivatives of any of these, for example, as described in Techniques (Id), pp. 252-253.

[0345] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via a photochemical reaction. Examples of such attachments can be made via aryl azides, halogenated aryl azides, benzophenones, anthraquinones, diazo compounds, diazo derivatives, psoralen derivatives, or derivatives of any of these, for example, as described in Techniques (Id), pp. 253-256.

[0346] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via a cycloaddition reaction. Examples of such attachments can be made via Diels-Alder reactions, boronic acid derivatives, click chemistry (e.g., Cu-promoted azide-alkyne [3+2] cycloaddition), or any derivative thereof, as described, for example, in Techniques (Id), pp. 257-258.

[0347] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device through the use of a crosslinker. Exemplary crosslinkers include zero-length crosslinkers, homobifunctional crosslinkers, heterobifunctional crosslinkers, and trifunctional crosslinkers, as described, for example, on pages 259-339 of Techniques (Id). In some embodiments, the crosslinker is a zero-length crosslinker (e.g., a carbodiimide (e.g., EDC, CMC, DCC, or DIC), Woodward's reagent K, N,N'-carbonyldiimidazole, a Schiff base or a derivative thereof). In some embodiments, the crosslinker is a homobifunctional crosslinker (e.g., an NHS ester (e.g., DSP, DTSSP, DSS, BS). 3, DST, sulfo-DST, BSOCOES, sulfo-BSOCOES, EGS, sulfo-EGS, DSG or DSC), imidoesters (DMA, DMP, DMS, DTBP), sulfhydryl reactive groups (e.g., DPDPB, BMH), difluorobenzene derivatives (e.g., DFDNB, DFDNPS), photoreactive groups (e.g., BASED), aldehydes (e.g., formaldehyde, glutaraldehyde), bis-epoxides (1,4-butanediol diglycidyl ester), hydrazides (e.g., adipic acid dihydrazide), bis-diazonium or bis-alkyl halides), bis-diazonium derivatives (e.g., o-tolidine diazotized, bis-diazotized benzidine), crosslinkers containing bis-alkyl halides or derivatives thereof). In some embodiments, the crosslinker is a heterobifunctional crosslinker (e.g., amine-reactive and sulfhydryl-reactive crosslinkers (e.g., SPDP, LC-SPDP, Sulfo-LC-SPDP, SMPT, Sulfo-LC-SMPT, SMCC, Sulfo-SMCC, MBS, Sulfo-MBS, SIAB, Sulfo-SIAB, SMPB, Sulfo-SMPB, GMBS, Sulfo-GMBS, SBAP, SIA), carbonyl-reactive and sulfhydryl-reactive crosslinkers (e.g., MPBH, MCH, PDPH), amine-reactive and photoreactive crosslinkers (e.g., NHS-ASA, Sulfo-NHS-ASA, Sulfo-NHS-LC-ASA, S), ASD, HSAB, sulfo-HSAB, SANPAH, sulfo-SANPAH, ANB-NOS, SAND, SADP, sulfo-SADP, sulfo-SAPB, SAED, sulfo-SAMCA, p-nitrophenyl diazopyruvic acid, PNP-DTP), sulfhydryl-reactive and photoreactive crosslinkers (e.g., ASIB, APDP, benzophenone-4-iodoacetamide, benzophenone-4-maleimide), carbonyl-reactive and photoreactive crosslinkers (e.g., ABH), carboxylate-reactive and photoreactive crosslinkers (e.g., ASBA), arginine-reactive and photoreactive crosslinkers (e.g., APG) or derivatives thereof.In some embodiments, the crosslinker is a trifunctional crosslinker (e.g., 4-azido-2-nitrophenyl biocytin-4-nitrophenyl ester, sulfo-SBED, MTS-ATF-biotin, MTS-ATF-LC-biotin, hydroxymethylphosphine derivatives, or tricepts reagent).

[0348] In some embodiments, the compounds described herein (e.g., compounds of Formula (I) described herein) are attached to materials or devices through the use of dendrimers or dendrons. Exemplary dendrimers and dendrons include amine-containing dendrimers, dendrimer-chelate derivatives, dendrimeric fluorescent quantum dots or derivatives thereof, as described, for example, in Techniques (Id), pp. 351-384.

[0349] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is attached to a material or device via the use of a crossbridge or cleavable reagent system. Exemplary crossbridge and cleavable reagent systems include disulfides, periodate-cleavable glycols, dithionite-cleavable bonds, hydroxylamine-cleavable esters, base-labile sulfones, acylhydrazine-cleavable linkers, photocleavable linkers, or derivatives thereof, as described, for example, in Techniques (Id), pp. 387-392.

[0350] In some embodiments, a compound described herein (e.g., a compound of Formula (I) described herein) is conjugated to a material or device through the use of a fluorescent probe, a streptavidin-biotin system, an avidin-biotin system, an isotope label, a silane, a microparticle, a nanoparticle, a chromatographic support, a buckyball, a fullerene, a carbon nanotube, a bioorthogonal reagent, polyethylene glycol (e.g., or other synthetic polymer modifications), a vaccine, an immunogen, an antibody, a liposome, an enzyme, a nucleic acid, an oligonucleotide, or a protein-protein interaction, or a derivative thereof, e.g., as described in Techniques (Id) pp. 395-1014.

[0351] Additional examples of conjugation chemistries contemplated in the present invention are described in Veiseh et al (2010) Adv Drug Deliv Rev 62:284-304, the entire contents of which are incorporated herein by reference.

[0352] Devices and Materials In some aspects of the present invention, a compound (e.g., a compound of Formula (I)) or a composition comprising the same is disposed completely or partially within an implantable element. The implantable element may include an encapsulation element that encapsulates or coats cells in part or in whole. In embodiments, the implantable element includes an encapsulation element that is formed or formable in situ around cells, e.g., a plurality of cells, e.g., a cell cluster, or a microcarrier, e.g., a bead or matrix containing cells (referred to herein as an "in situ encapsulated implantable element"). In embodiments, the implantable element includes an encapsulation element that is pre-formed prior to combination with the encapsulated cells, e.g., a plurality of cells, e.g., a cell cluster, or a microcarrier, e.g., a bead or matrix containing cells (referred to herein as a device-based implantable element or DB-implantable element).

[0353] The implantable elements described herein include devices or materials, such as devices or materials associated with a compound described herein (e.g., a compound of Formula (I)). In some embodiments, the device or material may be associated with a compound described in Figures 1-6, or a pharmaceutically acceptable salt thereof. In some embodiments, the device or material may be covalently attached to a compound described in Figures 1-6, or a pharmaceutically acceptable salt thereof, for example, via a linking group (e.g., a linking group described herein). Any of the devices or materials described herein may be associated with any of the compounds described herein (e.g., a compound of Formula (I) or a compound described in Figures 1-6).

[0354] Devices encompassed herein include devices, e.g., tubular devices, configured with a lumen, e.g., a lumen having one, two, or more openings. A typical stent is an example of a device configured with a lumen and two openings. Other examples include shunts.

[0355] Devices encompassed herein include flexible devices, for example, devices configured to conform to the shape of the body.

[0356] Devices encompassed herein include devices that include elements that stabilize the position of the device, such as adhesives or fasteners, e.g., torque-based or friction-based fasteners, e.g., screws or pins.

[0357] Devices encompassed herein include devices configured to monitor a substance, such as an exogenous substance (e.g., a therapeutic drug or toxin) or an endogenous body product (e.g., insulin). Such devices include diagnostic devices.

[0358] Devices encompassed herein include devices configured to release a substance, for example, an exogenous substance (e.g., a therapeutic agent). In some embodiments, the therapeutic agent is a compound described herein (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutic agent is a biomaterial. In some embodiments, the therapeutic agent is a cell, a cell product, a tissue, a tissue product, a protein, a hormone, an enzyme, an antibody, an antibody fraction, an antigen, an epitope, a drug, a vaccine, or any derivative thereof.

[0359] Devices herein include joint devices, such as artificial joints (eg, knee, hip or other artificial joints), that are configured to change conformation in response to signals or body movements.

[0360] A detailed overview of exemplary devices of the present invention is provided below.

[0361] stents Devices encompassed herein include stents or other devices configured to be partially or completely placed within a body lumen. A vascular stent is a stent configured to be completely or partially placed within a lumen of the vasculature (e.g., a coronary, urinary, biliary, venous, or coronary stent). Stents can be configured to be expandable or have other properties, such as to release or elute a substance, e.g., a therapeutic agent. Stents can be configured to conform to the shape of adjacent tissue, e.g., to maintain a flow path open. Typically, stents can be made of metal, plastic, or a material described herein. Stents can be configured for use in coronary heart disease, carotid artery disease, high blood pressure, peripheral artery disease, aneurysm, stroke, atherosclerosis, elderly patients (e.g., at least 60 years of age), or patients undergoing coronary angioplasty. Exemplary stents include: coronary, aortic, drug-eluting, intracranial, pancreatic, carotid, iliac, renal, femoral, ureteral, fetal bladder, duodenal, and biliary shunts. The shunts can comprise stainless steel, gold, titanium, cobalt-chromium alloys, tantalum alloys, nitinol, silicone, polyurethane, polyester, polyorthoesters, polyanhydrides, or collagen.

[0362] shunt Devices encompassed herein include shunts or other devices configured to form a connection, typically a fluid connection, between a first body portion (e.g., a first organ) and a second body portion or the outside. Shunts can be configured to be permanent or temporary. Typically, shunts can be made of metal, plastic, or a material described herein. Shunts can be configured to have other properties, such as being expandable or to release or elute a substance, e.g., a therapeutic agent. Shunts can be configured for use in the eye, e.g., glaucoma shunts, the CNS, e.g., the brain or spinal column, cavities, e.g., the peritoneal cavity, or organs. Shunts can be configured for use in the treatment of coronary heart disease, carotid artery disease, hypertension, peripheral artery disease, aneurysm, stroke, atherosclerosis, or in the treatment of patients (e.g., at least 60 years of age) or in patients undergoing coronary angioplasty. Exemplary shunts include peritoneal, endolymphatic, intracranial, and tympanostomy shunts.

[0363] dressing Devices encompassed herein include dressings, e.g., bandages, or other devices, configured to be the surface of a dressing that contacts a site on a body, e.g., a wound, e.g., a traumatic or surgical wound. Dressings can be configured for internal use, e.g., on the surface of an organ or cavity, or external use, e.g., on the skin. Dressings can be configured to be permanent or temporary. Typically, dressings can be formed from metal, plastic, or materials described herein. Dressings can be configured to have any of a variety of properties, e.g., to promote healing, promote coagulation, or release or elute a substance, e.g., a therapeutic agent. Dressings can be constructed from a flexible material to promote contact or attachment to a site on a body. In embodiments, a dressing includes an element configured to contact the site, e.g., a porous element, and an element configured to stabilize the position of the dressing, e.g., an adhesive element.

[0364] Scaffold Devices encompassed herein include scaffoldings (also referred to as "scaffolds") configured to allow infiltration of the device by bodily tissue. Scaffolds can be configured as meshes, networks, or porous structures. Typically, scaffolds will include elements that provide dimensional stability. Scaffolds can be configured to be permanent or temporary. Typically, scaffolds can be formed of metal, plastic, or materials described herein. Scaffolds can be configured to have any of a variety of properties, e.g., to promote growth, or to direct growth or regeneration in a desired direction, or to release or elute substances, e.g., therapeutic agents. Scaffolds can be constructed of flexible or non-flexible materials. Scaffolds include bone scaffolds that promote growth of bone or surrounding tissue, e.g., those configured for use in fractures, fractures, osteoporosis, or joint replacement.

[0365] cochlear implant Devices encompassed herein include cochlear implants, which can be configured to have any of a variety of properties, such as to promote growth or to release or elute substances, such as therapeutic agents.

[0366] Ophthalmic Devices Devices encompassed herein include ophthalmic devices configured to be placed on or in the eye, or in or on tissues surrounding the eye. Such devices include ophthalmic devices, such as contact lenses. Such devices also include intraocular lenses (e.g., phakic intraocular lenses), implantable lenses (e.g., polymeric lenses) (e.g., for cataract treatment / surgery), shunts (e.g., glaucoma shunts), or intraocular devices, including devices for releasing a substance, such as a therapeutic drug. Ophthalmic devices can be configured to monitor a substance, such as a therapeutic drug, or a body component, such as a biomarker, for example, in tears. Ophthalmic devices can be permanent or temporary. Typically, ophthalmic devices can be made of metal, plastic, or materials described herein. Ophthalmic devices can be configured to release or elute a substance, such as a therapeutic drug.

[0367] Articulating Devices Devices herein include articulatable devices configured to change conformation in response to signals or movements of the body, e.g., an artificial joint, e.g., a knee, hip, or other artificial joint. Typically, articulatable devices will include elements that provide dimensional stability. Typically, articulatable devices can be formed of metal, plastic, or materials described herein. Articulatable devices can be configured to have any of a variety of properties, e.g., to promote growth or a desired direction of growth or regeneration, or to release or elute a substance, e.g., a therapeutic agent.

[0368] Soft tissue prosthetic devices Devices encompassed herein include soft tissue prosthetic devices, which can be configured to have any of a variety of properties, such as to promote growth or to release or elute a substance, such as a therapeutic agent.

[0369] Fasteners, e.g., surgical fasteners Devices encompassed herein include fasteners, e.g., surgical fasteners, e.g., flexible surgical fasteners, e.g., sutures (e.g., configured to stabilize the position of a first body part relative to a second body part). Surgical fasteners also include inflexible devices, e.g., staples. Surgical fasteners can be configured to be permanent or temporary. Surgical fasteners include ligating clips and tissue staples. Surgical fasteners can be configured to release or elute substances, e.g., therapeutic agents. Exemplary fasteners include fasteners for fixating hard and soft tissue, cranioplasty plates, and bone fixation (including metallic and ceramic staples and pins). Fasteners for fastening body parts include those comprising bioabsorbable polymers, e.g., poly(p-dioxane), polylactic acid, polyglycolide, polycaprolactone, poly(orthoesters), trimethylene carbonate polymers, copolymers, and / or blends. The device can be reinforced with fibers of, for example, polymeric or ceramic materials. Exemplary sutures include: absorbable, non-absorbable, and recombinant. The suture can comprise polyglycolic acid, poly(ethylene terephthalate), Nitinol, stainless steel, silk, polyamide, polyester, polypropylene, poly(hydroxybutyrate), polydioxanone, or polytetrafluoroethylene.

[0370] Stabilizing Device Devices encompassed herein include, for example, stabilization devices (e.g., pins, screws, plates, collars, or cages) configured to hold and immobilize a first body part relative to a second body part. Such devices can be configured to stabilize broken or fractured bones. Such devices can be made of metal, plastic, or any of the materials described herein.

[0371] catheter Devices encompassed herein include catheters, e.g., balloon catheters, configured to promote patency of a lumen, typically a vascular lumen, e.g., a coronary lumen. Catheters can be configured as either permanent or temporary. Typically, catheters can be formed of metal, plastic, or materials described herein. Catheters can be configured with any of a variety of properties, e.g., to promote healing, be expandable, or release or elute a substance, e.g., a therapeutic agent. Exemplary catheters include hemodialysis, biliary, peritoneal, subclavian, suprapubic, ventricular, atrial, intravascular, and subcutaneous catheters. They can be constructed of silicone rubber, nylon, polyurethane, polyethylene terephthalate (PET), latex, or thermoplastic elastomers. Some catheters have a thin hydrophilic surface coating.

[0372] port Devices encompassed herein include ports or other devices configured to provide access to the body. Ports can be configured to achieve continuous or intermittent connection to a reservoir containing a substance, e.g., a therapeutic agent. Ports can be configured to have other properties, e.g., closable or to release or elute a substance, e.g., a therapeutic agent. Ports can be configured to conform to a body surface. Typically, ports can be formed from metal, plastic, or a material described herein. Ports can be configured for use in patients with chronic illnesses or cancer.

[0373] prosthetic organ Devices encompassed herein include prosthetic devices, such as acetabular cup impaction plates, prosthetic acetabular cup inserters or impactors, rhomboid metacarpal prostheses, and spinal prostheses, such as intervertebral disc prostheses. Prostheses can be configured with other properties, such as the ability to release or elute substances, such as therapeutic agents. Prostheses include those for the hip, ankle, breast, jaw, mandible, ear, elbow, esophagus, eye, artificial corneal implant, face, finger, ligament, nose, penis, shoulder, testicle, tendon, toe, trachea, vascular, dental, or digit. These can include nylon, polyacrylate, polyester resin, polypropylene, polyethylene, polyurethane, silicone, fiber reinforcement (glass and carbon), aluminum, titanium, or steel.

[0374] Extracorporeal devices Devices encompassed herein include extracorporeal devices, e.g., devices through which tissue or bodily fluids (e.g., blood or spinal fluid) pass, including, e.g., kidney dialysis devices, ports, and tubes, e.g., dialysis tubing. Extracorporeal devices can be configured to have other properties, e.g., be closable, or to release or elute a substance, e.g., a therapeutic agent.

[0375] sensor Devices encompassed herein include those that include a sensor. The sensor can sense or monitor a signal, e.g., a chemical moiety (e.g., glucose, insulin, or a therapeutic agent), an electromagnetic wave (e.g., light or electrical current). The device can be configured to respond to the signal, e.g., by releasing a substance, e.g., a therapeutic agent. The device can be configured to respond to the signal, e.g., by generating a signal that can be received by a receiver (e.g., a receiver located inside or outside the body). The generated signal can be a chemical moiety, an electromagnetic wave (e.g., light or electrical current). The compounds described herein can minimize interference by immune responders, e.g., within the first 12, 24, 36, or 48 hours after implantation.

[0376] Orthopedic Devices and Implants Devices encompassed herein include orthopedic devices and implants (eg, pins, rods, screws and plates). Such devices can be configured for: bone replacement (e.g., hip, knee replacement), bone repair (e.g., repair of fragmented bone (e.g., ribs, vertebrae, skull, facial bones (e.g., nasal bone, maxilla, lacrimal bone, zygomatic bone, palate, inferior turbinate, vomer, mandible, hyoid bone), arm bones (e.g., clavicle, scapula, humerus, ulna, radius, metacarpal bones, phalanges of the hand), leg bones (e.g., hip bone, femur, patella (kneecap), tibia, fibula, foot bones, metatarsal bones, phalanges of the foot)). The devices can be configured to have other properties, for example, to be expandable or to release or elute substances, such as therapeutic agents. The devices can be made of metal, plastic, or materials described herein. Non-mechanical or non-rigid devices are also encompassed. Such devices include Synvisc-One® (Hylan), which is approved for the treatment of pain in osteoarthritis (OA) of the knee. Hylan GF 20 (Hylan GF 20 is a viscoelastic, high molecular weight liquid containing hylan A and hylan B polymers derived from rooster combs. Hylan is a derivative of hyaluronan (sodium hyaluronate). Hylan GF 20 is a chemically crosslinked hyaluronan.

[0377] Cosmetic or reconstructive surgery devices Devices encompassed herein include cosmetic devices or devices used in reconstructive surgery, e.g., implants, e.g., breast implants, prosthetic devices, e.g., nasal prostheses, fillers (e.g., dermal fillers (e.g., injectable dermal fillers), e.g., comprising hyaluronic acid (HA), calcium hydroxyapatite (CaHA), poly-L-lactic acid, or polymethyl methacrylate (PMMA)).

[0378] Encapsulated or entrapped cells or tissues The device includes encapsulated or entrapped cells or tissue (e.g., pancreatic islet cells or pancreatic tissue). The cells or tissue can be encapsulated or entrapped in a polymer.

[0379] Other implantable devices Devices encompassed herein include orthopedic fixation devices, dental implants, skin covering devices; dialysis media and drug delivery devices, and artificial or engineered organs (eg, the heart). Other devices encompassed herein include: silicone implants, drainage devices (e.g., bladder drainage devices), cell selection systems, adhesives (e.g., cements), clamps, clips, contraceptives, intrauterine devices, corneal implants, dermal implants, dental implants, intraocular implants, intragastric implants, facial implants, penile implants, implants for controlling incontinence (e.g., urinary or fecal), defibrillators, dosimeters, electrodes, pumps (e.g., infusion pumps), filters, embolization devices, fasteners, filling materials, fixation agents, grafts, hearing aids, cardio or heart-related devices (e.g., pacemakers and valves, batteries or power sources), hemostatic agents, incontinence devices, interbody fusion devices, intraoral devices, lenses, meshes, needles, nervous system stimulators, patches, peritoneal access devices, plates, plugs, pressure monitoring devices, rings, transponders, hip implants, bone implants, or valves. Also included are devices used in one or more of anesthesiology, cardiovascular, clinical chemistry, dentistry, ear, nose, and throat, gastroenterology, urology, general hospitals, hematology, immunology, microbiology, neurology, obstetrics / gynecology, ophthalmology, orthopedics, medical conditions, physical preparations, radiology, general or plastic surgery, and / or clinical toxicology. Devices include clips, such as anchor fascial, aneurysm, hemostasis, coronary artery bypass, ophthalmic tantalum, tubal occlusion, vascular, and marker radiographic clips. Clips can include titanium, titanium-aluminum alloy, or cobalt-chromium-nickel-molybdenum-iron alloy. Devices include defibrillators, which can include a battery, a case (e.g., a titanium case), and flexible insulated wires or leads. The entire structure can be sealed in a polymeric encapsulation. Devices include implanted dosimeters and pressure monitoring devices, such as intraperitoneal, cranial, and cerebral aneurysm pressure monitoring devices.The devices include valves, such as cardiac, pulmonary, and ureteral vesical valves. Valves can include mechanical, synthetic, and biological valves. Valves can be made from stainless steel, titanium, silicone, pyrolytic carbon, polytetrafluoroethylene, polyethylene terephthalate, bovine pericardium, or porcine heart.

[0380] Devices include meshes, such as absorbable / non-absorbable, collagen, synthetic / non-synthetic meshes, which can include: polyglycolic acid, polypropylene, polyethylene terephthalate, nonocryl (poliglecaprone 25), cellulose, macroporous polyester, poly-4-hydroxybutyrate, polytetrafluoroethylene, biologics (human dermis, porcine dermis, porcine small intestinal submucosa, bovine pericardium), or fibroin.

[0381] A device for stimulating the nervous system, for example, the peripheral nervous system or the central nervous system (e.g., the spinal cord). The device can include a Medtronic Model 3998 Lead or a device substantially similar in structure and / or function. The lead can include a polyurethane lead body connected to a silicone rubber paddle. The lead can have two parallel rows of four platinum-iridium electrodes at its distal end. The proximal end of each lead body is a lead terminal, which attaches to a Medtronic in-line, 4-conductor connector.

[0382] Devices include, for example, plates for use with bone, such as cranioplasty or mandibular plates, made of, for example, titanium, titanium alloys, high nitrogen stainless steel, or cobalt-chromium-tungsten-nickel alloys.

[0383] Devices include plugs, e.g., biopsy plugs, e.g., lung biopsy plugs (e.g., made from polyethylene glycol (PEG) hydrogel). Other plugs are configured for cerebrospinal fluid leaks (Dural), arteries (BioGlue), and lung tissue (AeriSeal). Exemplary materials include polyethylene glycol ester and trilysine amine (Dural), bovine serum albumin and glutaraldehyde (BioGlue), or aminated polyvinyl alcohol and glutaraldehyde (AeriSeal).

[0384] Devices encompassed herein include FDA Class 1, 2, or 3 devices, e.g., devices that are unclassified or not classified or classified as a humane use device (HUD).

[0385] Non-medical devices The devices encompassed herein include non-medical devices. Such devices can be wearable or implantable. Such devices can be configured to operate in conjunction with a telecommunications device (e.g., a telephone or smartphone) and can be contact lenses, devices that identify or transmit signals correlated to a patient's location, for example, by GPS tracking, RFI chips, devices that monitor or optimize physical performance (e.g., implantable "Fitbit"-type devices, e.g., capable of providing information on one or more biomarkers), military implantable devices, implantable devices for determining a patient's health or condition, devices for tracking animals, such as agricultural animals (e.g., horses, cows, pigs, or goats), pets (e.g., dogs, cats, etc.), wildlife (e.g., endangered animals), or desired individuals (e.g., prisoners).

[0386] Device components or contents The devices encompassed herein are capable of containing, delivering or presenting cellular components, such as human cells, e.g., immune cells, e.g., T cells, NK cells, B cells, red blood cells; tissues, organs or artificial organs, or cellular sensors.

[0387] The devices encompassed herein can contain electronic components, such as transmitters, receivers, transponders, microchips, power sources (e.g., batteries) (e.g., self-powered active devices).

[0388] The devices encompassed herein can include multiple components or materials. Exemplary components or materials can be purely structural, therapeutic, or both. The devices can include biomolecular components, such as carbohydrates, e.g., polysaccharides, e.g., marine polysaccharides such as alginate, agar, agarose, carrageenan, cellulose, and amylose, chitin, and chitosan; cross-linked polysaccharides, e.g., cross-linked with diacrylates; or polysaccharides or derivatives / modifications thereof, e.g., as described in Laurienzo (2010), Mar. Drugs. 8.9:2435-65.

[0389] The device can contain a protein or polypeptide, such as an antibody, protein, enzyme, or growth factor. The device can contain active or inactive fractions of a protein or polypeptide. Enzymes include glucose oxidase (e.g., for glucose sensors), kinases, phosphatases, oxygenases, hydrogenases, and reductases.

[0390] The device can include a polymer (e.g., hydrogel, plastic) component. Exemplary polymers include polyethylene, polypropylene, polystyrene, polyester (e.g., PLA, PLG, or PGA, polyhydroxyalkanoates (PHAs), or other bioabsorbable plastics), polycarbonate, polyvinyl chloride (PVC), polyethersulfone (PES), polyacrylates (e.g., acrylic or PMMA), hydrogels (e.g., acrylic polymers or blends of acrylic and silicone polymers), polysulfone, polyetheretherketone, thermoplastic elastomers (TPE or TPU), thermoset elastomers (e.g., silicones (e.g., silicone elastomers)), poly-p-xylylene (parylene), fluorinated polymers (e.g., PTFE), and polyacrylates such as poly(acrylic acid) and / or poly(acrylamide), or mixtures thereof.

[0391] Exemplary polyethylenes include: ultra-low density polyethylene (ULDPE) (e.g., 0.890 to 0.905 g / cm 3 polymers with densities in the range of 0.905 to 0.915 g / cm3; very low density polyethylene (VLDPE) (e.g., 0.905 to 0.915 g / cm3) 3 and polymers having a density in the range of 0.915 to 0.935 g / cm3. 3 and polymers having a density in the range of 0.915 to 0.935 g / m². 3 and polymers having a density in the range of 0.926 to 0.940 g / cm; medium density polyethylene (MDPE) (e.g., 0.926 to 0.940 g / cm 3 and polymers having a density in the range of 0.940 to 0.970 g / cm 3, which may or may not contain comonomers; high density polyethylene (HDPE) (e.g., 0.940 to 0.970 g / cm 3) 3 and polymers having densities in the range of 0.1 to 1.0, which may or may not contain comonomers.

[0392] Exemplary polypropylenes include: homopolymers, random copolymers (homophasic copolymers), and impact copolymers (heterophasic copolymers), as described, for example, in McKeen, Handbook of Polymer Applications in Medicine and Medical Devices, 3—Plastics Used in Medical Devices, (2014):21-53, which is incorporated by reference herein in its entirety.

[0393] Exemplary polystyrenes include: general purpose or crystal polystyrene (PS or GPPS), high impact polystyrene (HIPS), and syndiotactic polystyrene (SPS).

[0394] Exemplary TPEs include: (i) TPA - Polyamide TPE, which comprises a block copolymer of alternating hard and soft segments with amide chemical bonds in the hard block and ether and / or ester linkages in the soft block; (ii) TPC - Copolyester TPE, which consists of a block copolymer of alternating hard and soft segments with ester and / or ether chemical bonds in the backbone; (iii) TPO - Olefin-based TPE, which consists of a blend of polyolefin and conventional rubber, where the rubber phase in the blend has little or no crosslinking; (iv) TPS - Styrene-based TPE, which consists of at least a triblock copolymer of styrene and certain dienes, where two terminal blocks are bonded together. (v) TPU-urethane TPEs, consisting of block copolymers of alternating hard and soft segments with urethane chemical linkages in the hard blocks and ether, ester, or carbonate linkages or mixtures thereof in the soft blocks; (vi) TPV-thermoplastic rubber vulcanizates, consisting of a blend of thermoplastic materials and conventional rubbers, where the rubber is crosslinked by a dynamic vulcanization process during the blending and mixing step; and (vii) TPZ-unclassified TPEs, which include any composition or structure other than those classified as TPA, TPC, TPO, TPS, TPU, and TPV.

[0395] The devices can include linear, branched, or crosslinked polymers or polymers of a selected molecular weight range, degree of polymerization, viscosity, or melt flow rate. Branched polymers can include one or more of the following types: star polymers, comb polymers, brush polymers, dendronized polymers, ladders, and dendrimers. Linear polymers include, but are not limited to, polyethylene, polyvinyl chloride (PVC), nylon 66, and polymethyl methacrylate (PMMA). Thermoresponsive polymers, such as gels (e.g., that become solid or liquid upon exposure to heat or a certain temperature), can also be used. Photocrosslinkable polymers, such as gels (e.g., that become solid upon photocrosslinking), can also be used.

[0396] The devices comply with ASTM International standards (e.g., F451-08, F602-09(2015), F624-09(2015)e1, F639-09(2015), F641-09(2014), F648-14, F665-09(2015), F702-10, F754-08(2015), F755-99(2011), F997-10, F1855-00(2011), F1925-09, F2026-16, F203 The present invention may include polymeric components or materials such as those described in F2011, F2042-00(2011), F2313-10, F2565-13, F2579-10, F2695-12, F2759-11, F2820-12, F2848-16, F2902-12, F3087-15).

[0397] The device can include plastic and reconstructive surgery components or materials such as those described in ASTM International (e.g., F881-94(2014), F1441-03(2014), and F2051-00(2014)).

[0398] The device can include inorganic or metallic components or materials, such as steel (e.g., stainless steel), titanium, other metals or alloys. The device can include non-metallic components or materials, such as ceramic or hydroxyapatite elements.

[0399] The device can include components or materials formed from electrically conductive materials (eg, gold, platinum, palladium, titanium, copper, aluminum, silver, metals, any combination thereof, etc.).

[0400] Devices comply with ASTM International (e.g., F67-13, F75-12, F86-13, F90-14, F136-13, F138-13a, F139-12, F560-13e1, F562-13, F601-13, F620-11(2015), F621-12, F629-15, F688-14, F799-11, F899-12b, F961-14, F1058-08, F1091-12, F1108-14, F1295-11, F1314-13ae1, F1350-15, F1377-13, F1472-14, F1537-11, F1580-1 2, F1586-13e1, F1713-08(2013), F1813-13, F2005-05(2015), F2063-12, F2066-13e1, F2146-13, F2181-14, F2229-12, F2257-14, F2834-10(2016), F2527-16, F2581-12, F2633-13, F2885-11, F2886-10, F2895-15, F2989-13, F3046-13 or F3160-16).

[0401] A device can include more than one component, such as more than one component disclosed herein, such as more than one metal, plastic, ceramic, composite, or hybrid material.

[0402] In metal-containing devices, the amount of metal (e.g., weight %, actual weight) can be: at least 5%, e.g., at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% or more (e.g., w / w); less than 20%, e.g., less than 20%, 15%, 10%, 5%, 1%, 0.5%, 0.1% or less.

[0403] In plastic-containing devices, the amount of plastic (e.g., by % weight, actual weight) can be: at least 5%, e.g., at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% or more, w / w; or less than 20%, e.g., less than 20%, 15%, 10%, 5%, 1%, 0.5%, 0.1% or less.

[0404] In ceramic-containing devices, the amount of ceramic (e.g., by % weight, actual weight) can be: at least 5%, e.g., at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% or more, w / w; or less than 20%, e.g., less than 20%, 15%, 10%, 5%, 1%, 0.5%, less than 0.1% or less.

[0405] Device features The components or materials used in the device (or the entire device) can be optimized for one or more of the following: biocompatibility, e.g., minimizing immune rejection or fibrosis; heat resistance; elasticity; tensile strength; chemical resistance (e.g., resistance to oils, greases, disinfectants, bleaches, processing aids, or other chemicals used in the production, use, cleaning, sterilization, and disinfection of the device); electrical properties; surface and volume conductivity or resistivity, dielectric strength; tracking index; mechanical properties; shelf life, long-term durability; sterilization ability (e.g., ability to withstand sterilization processes such as steam, dry heat, ethylene oxide (EtO), electron beam, and / or gamma radiation while maintaining properties relevant to the intended use of the device), e.g., heat resistance to autoclave / steam conditions, hydrolytic stability to steam sterilization, chemical resistance to EtO, resistance to high-energy radiation (e.g., electron beam, UV, and gamma); or crystalline structure.

[0406] The devices can be assembled in vivo (eg, an injectable material that forms a structured shape in vivo (eg, at body temperature)) or ex vivo.

[0407] The device can have nano-dimensional dimensions and can include, for example, nanoparticles, such as nanoparticles made of polymers described herein, for example, PLA. The nanoparticles can be chemically modified nanoparticles that are modified to prevent uptake by macrophages and Kupffer cells (e.g., a process called opsonization); or to change the circulatory half-life of the nanoparticles. The nanoparticles can include iron nanoparticles (injectable) (e.g., iron nanoparticles made by Advanced Magnetics). Exemplary nanoparticles are described in Veiseh et al. (2010) Adv Drug Deliv Rev 62:284-304, the entire contents of which are incorporated herein by reference.

[0408] The device can be configured for implantation or grafting or placement in a patient's omentum, a patient's subcutaneous fat, a patient's muscle. The device can be configured for implantation or grafting or placement in: on or in the skin; a mucous surface, a body cavity, the peritoneal cavity; the CNS, e.g., the brain or spinal cord; an organ, e.g., the heart, liver, kidney, spleen, lung, lymphatic system, vasculature, oral cavity, nasal cavity, teeth, gums, gastrointestinal tract; bone; hip joint; adipose tissue; muscle tissue; circulatory blood; eye (e.g., intraocular); breast, vagina; uterus, a joint, e.g., the knee or hip joint, or the spine.

[0409] The device may include an electrochemical sensor, such as an electrochemical sensor having a working electrode and a reference electrode. For example, the electrochemical sensor includes a working electrode and a reference electrode that react with an analyte to generate a sensor measurement related to the concentration of the analyte in a bodily fluid to which the ophthalmic device is exposed. The device may include a window, such as a transparent polymeric material, having a concave and convex substrate at least partially embedded in the transparent polymeric material. The device may also include an antenna; and an electronic module including one or more of a controller electrically connected to the electrochemical sensor and the antenna, where the controller is configured to control the electrochemical sensor to obtain a sensor measurement related to the concentration of the analyte in a bodily fluid to which the device, such as a wearable device, is exposed, and to display the sensor measurement using the antenna.

[0410] The device can be used for a variety of times, including from 1 or 2 days to 1, 2, 3, 4 or more years. The device can be configured for the duration of implantation, e.g., configured to resist fibrotic inactivation by fibrosis for all or part of the expected duration.

[0411] The device can be configured for limited exposure (e.g., less than 2 days, e.g., 2 days, 1 day, 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, 8 hours, 6 hours, 5 hours, 4 hours, 3 hours, 2 hours, less than 1 hour or less).

[0412] The device can be configured for sustained exposure (e.g., at least 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years or more).

[0413] The device can be configured for permanent exposure (e.g., at least 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years or more).

[0414] The device may be coated with a compound described herein (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof, or a material comprising a compound described herein (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof. In embodiments, the compound (e.g., a compound of Formula (I)) is disposed on a surface, such as an interior or exterior surface, of the device. In embodiments, the compound (e.g., a compound of Formula (I)) is evenly distributed over the surface. In embodiments, the compound (e.g., a compound of Formula (I)) is unevenly distributed over the surface.

[0415] In some embodiments, the device is coated (e.g., partially or completely coated) with a compound (e.g., a compound of Formula (I)) or a material comprising a compound (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof. In some embodiments, the device is coated with a single layer of a compound (e.g., a compound of Formula (I)). In some embodiments, the device is coated with multiple layers (e.g., at least 2, 3, 4, 5, 10, 20, 50 or more layers) of a compound (e.g., a compound of Formula (I)).

[0416] In embodiments, a first portion of the surface of the device comprises a compound (e.g., a compound of Formula (I)) that modulates (e.g., downregulates or upregulates) a biological function, and a second portion of the device is free of the compound or has a substantially lower density of the compound.

[0417] In embodiments, a first portion of the surface of the device comprises a compound (e.g., a compound of formula (I)) that modulates (e.g., downregulates) an immune response, and a second portion of the surface comprises a second compound (e.g., a compound of formula (I)) that, for example, upregulates an immune response, wherein the second portion of the device is free of the compound (e.g., a compound of formula (I)) or has a substantially lower density of the compound.

[0418] In some embodiments, the device is symmetrically coated or chemically derivatized with a compound (e.g., a compound of Formula (I)) or a material comprising the compound (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof. In some embodiments, the device is asymmetrically coated or chemically derivatized with a compound (e.g., a compound of Formula (I)) or a material comprising the compound (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof. For example, exemplary devices may be partially coated (e.g., at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 99.9% coated) with a material comprising the compound (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof.

[0419] Exemplary devices coated or chemically derivatized with a compound (e.g., a compound of Formula (I)) or a material comprising a compound (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof can be prepared using any method known in the art, such as through self-assembly (e.g., via block copolymers, adsorption (e.g., competitive adsorption), phase separation, micronization, or masking).

[0420] In some embodiments, the device comprises a surface exhibiting two or more distinct physicochemical properties (e.g., 3, 4, 5, 6, 7, 8, 9, 10, or more distinct physicochemical properties). In some embodiments, the device is or comprises a Janus particle (e.g., a Janus nanoparticle). For example, one or more regions of the device (e.g., a Janus particle) can be hydrophobic, hydrophilic, or amphiphilic. Exemplary devices can be characterized by Janus particles, or properties thereof, disclosed in Walther et al. (2013) Chem Rev 113:5194-5261, the entire contents of which are incorporated herein by reference.

[0421] In some embodiments, the coating or chemical derivatization of the exemplary devices with a compound (e.g., a compound of Formula (I)), a material comprising a compound (e.g., a compound of Formula (I)), or a pharmaceutically acceptable salt thereof, is described as the average number of compounds bound per given area, e.g., density. For example, the density of the coating or chemical derivatization of the exemplary devices can be 0.01, 0.1, 0.5, 1, 5, 10, 15, 20, 50, 75, 100, 200, 400, 500, 750, 1,000, 2,500, or 5,000 compounds per square micrometer or square millimeter, e.g., on or within the device.

[0422] In some embodiments, the device comprises a compound (e.g., a compound of Formula (I)) comprising A1 (e.g., as described herein) or a material comprising a compound (e.g., a compound of Formula (I)) or a pharmaceutically acceptable salt thereof, and the compound or material is incorporated into the device. In some embodiments, the device comprising a compound of Formula (I) comprising A1 is non-covalently bound to the device, for example, on the surface or within the device.

[0423] In some embodiments, the device comprises a compound of Formula (I) or a material comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof comprising A2, and is, e.g., covalently attached to the device. In embodiments, A2 is directly attached to the device. In embodiments, A2 is attached to the device by a linking group (e.g., a linking group described herein). In embodiments, the device is, e.g., covalently attached to a linking group, and A2 is, e.g., covalently attached to a linking group.

[0424] A device comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof may have a reduced immune response (e.g., a marker of an immune response) compared to a device not comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof. The marker of an immune response is one or more of the following: in vivo cathepsin activity, as described in Example 7 or Example 9, or the level of a marker of an immune response, e.g., TNF-α, IL-13, IL-6, G-CSF, GM-CSF, IL-4, CCL2, or CCL4, measured, e.g., by ELISA. In some embodiments, the marker of an immune response is the rate of macrophage adhesion to a surface in vitro, e.g., as described in Example 8. In some embodiments, the marker of an immune response is the amount of tissue adherent to a disc in vivo (e.g., placed in a patient (e.g., a mouse)), as described in Example 10. In some embodiments, a device comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof exhibits about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% reduction in immune response (e.g., marker of immune response) compared to a device not comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the reduced immune response (e.g., marker of immune response) is measured after about 30 minutes, about 1 hour, about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 1 week, about 2 weeks, about 1 month, about 2 months, about 3 months, about 6 months, or more. In some embodiments, the device comprising the compound of formula (I) is coated with the compound of formula (I) or encapsulated with the compound of formula (I).

[0425] A device comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof may have an increased immune response (e.g., a marker of an immune response) compared to a device not comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof. The marker of an immune response is one or more of the following: in vivo cathepsin activity, as described in Example 7 or Example 9, or the level of a marker of an immune response, e.g., TNF-α, IL-13, IL-6, G-CSF, GM-CSF, IL-4, CCL2, or CCL4, as measured, e.g., by ELISA. In some embodiments, the marker of an immune response is the rate of macrophage adhesion to a surface in vitro, e.g., as described in Example 8. In some embodiments, the marker of an immune response is the amount of tissue adherent to a disc in vivo (e.g., placed in a patient (e.g., a mouse)), as described in Example 10. In some embodiments, a device comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof increases an immune response (e.g., a marker of an immune response) by about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, or about 100%, or about 1000%, relative to a device not comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the increased immune response (e.g., a marker of an immune response) is measured after about 30 minutes, about 1 hour, about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 1 week, about 2 weeks, about 1 month, about 2 months, about 3 months, about 6 months or more. In some embodiments, the device comprising the compound of Formula (I) is coated with the compound of Formula (I) or encapsulated compound of Formula (I).

[0426] The device may have a smooth surface or may have ridges, depressions, holes, slits, or pores, or any combination thereof. The ridges, depressions, holes, slits, or pores may be of any size, for example, 10 μm to about 1 nm, about 5 μm to about 1 nm, about 2.5 μm to about 1 nm, 1 μm to about 1 nm, 500 nm to about 1 nm, or about 100 nm to about 1 nm. The smooth surface or the ridges, depressions, holes, slits, or pores, or any combination thereof, may be coated with or chemically derivatized with a material comprising a compound of Formula (I), a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

[0427] The device may be of any suitable shape, such as a sphere, spheroid, ellipsoid, disk, cylinder, torus, cube, stadiumoid, cone, pyramid, triangle, rectangle, square, or rod, or may include curved or flat portions. Any shaped, curved, or flat device may be coated or chemically derivatized with a compound of Formula (I), a material comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

[0428] The devices can have a range of sizes or diameters. In some embodiments, the devices have an average diameter or size greater than 1 mm. In some embodiments, the devices have an average diameter or size greater than 1.5 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, or more.

[0429] In some embodiments, the device is not a device disclosed in any of WO 2012 / 112982, WO 2012 / 167223, WO 2014 / 153126, WO 2016 / 019391, U.S. Patent No. 2012-0213708, U.S. Patent No. 2016-0030359, and U.S. Patent No. 2016-0030360.

[0430] In embodiments, the device comprises a cell as described herein. In embodiments, the device comprises a cell, e.g., a recombinant cell or a stem cell, that provides a substance, e.g., a therapeutic agent. Examples of therapeutic agents include cell products, tissue products, proteins, enzymes, antibodies, antigens, epitopes, drugs, and vaccines. In some embodiments, the therapeutic agent is a biomaterial.

[0431] In embodiments, the device is a recombinant cell or stem cell that provides a substance. In embodiments, the substance comprises a polypeptide. In embodiments, the cell is a human cell and the polypeptide is a human polypeptide. In embodiments, the cell is a non-human cell and the polypeptide is a human polypeptide. In embodiments, the cell provides a substance that alleviates a disease, disorder, or condition (e.g., those described herein). In embodiments, the substance is insulin and the disorder is diabetes.

[0432] Additional Exemplary Devices Devices encompassed herein include those described in one or more of the following Google (Verily) patent documents, or devices substantially similar in structure or function to those described herein: U.S. Patent No. 20160117532A1, WO 2016115018A1, U.S. Patent No. 9282920B2, U.S. Patent No. 9289123B2, U.S. Patent No. 9289954B2, U.S. Patent No. 9295403B1, U.S. Patent No. 9298020B1 No. 9,307,901 B1, U.S. Pat. No. 9,320,460 B2, U.S. Pat. No. 9,326,710 B1, U.S. Pat. No. 9,332,935 B2, U.S. Pat. No. 9,366,570 B1, U.S. Pat. No. 9,372,168 B2, U.S. Pat. No. 9,398,868 B1, U.S. Pat. No. 9,400,904 B2, U.S. Design Patent No. 754,861 S1, U.S. Design Patent No. 755,786 S1, WO 2015,191,203 A8, or WO 2016,115,035 A1.

[0433] Devices encompassed herein include devices described in one or more of Establishment Labs' patent documents, or devices substantially similar in structure or function to the devices described herein: U.S. Patent No. 20150150675A1 or U.S. Patent No. 20150282926A1.

[0434] Devices encompassed herein include those described in one or more of the following Becton Dickinson patent documents, or devices substantially similar in structure or function to the devices described herein: EP 1003586B1, EP 1005909B1, U.S. Pat. No. 9095849B2, EP 101012B1, EP 1011764B1, U.S. Pat. No. 7972578B2, EP 1393764B1, EP 1433705B1, U.S. Pat. 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Claims

1. Formula (II-c): 【Chemistry 1】 Compounds or salts thereof (In the formula: Ring M １ Each of these has 1 to 5 R ３ The cycloalkyl, heterocyclyl, aryl, or heteroaryl elements are optionally substituted; Z １ Each of them has one or more R ５ The alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl elements are optionally substituted; R ２ａ , R ２ｂ , R ２ｃ and R ２ｄ Each of them independently is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halo, cyano, nitro, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or R ２ａ and R ２ｂ or R ２ｃ and R ２ｄ together form an oxo group; R Ｃ and R Ｄ are independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, where each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with 1 to 6 R ６ ; Or, R Ｃ and R Ｄ These, together with the nitrogen atom to which they are bonded, form 1 to 6 R ６ This forms a ring (e.g., a 5- to 7-membered ring) which is substituted by arbitrary selection; R ３ , R ５ and R ６ Each of these can independently be alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, azide, oxo, -OR Ａ１ , -C(O)OR Ａ１ , -C(O)R Ｂ１ , -OC(O)R Ｂ１ , -N(R Ｃ１ ) (Caution Ｄ１ ), -N(R Ｃ１ ) C(O)R Ｂ１ , -C(O)N(R Ｃ１ ), SR Ｅ１ , cycloalkyl, heterocyclyl, aryl, heteroaryl; R １０ and R １１ Each of these independently consists of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, halogen, and -C(O)R. Ｂ１ , -N(R Ｃ１ ) C(O)R Ｂ１ , -C(O)N(R Ｃ１ ), SR Ｅ１ , S(O) ｘ , cycloalkyl or heterocycline; R Ａ１ , R Ｂ１ , R Ｃ１ , R Ｄ１ and R Ｅ１ Each of these is independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, where each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl has 1 to 6 R ７ It is replaced by optional selection; Each R ７ These are independently alkyl, alkenyl, alkynyl, heteroalkyl, halogen, cyano, oxo, hydroxyl, cycloalkyl, or heterocyclyl; Each m and n is independently 0, 1, 2, 3, 4, 5, or 6; and x is 1 or 2).

2. M １ The compound according to claim 1, wherein is an aryl (e.g., phenyl).

3. The triazolyl ring 【Chemistry 2】 The compound according to claim 1 or 2.

4. R ２ａ , R ２ｂ , R ２ｃ and R ２ｄ Each of them independently is hydrogen or alkyl, or R ２ａ and R ２ｂ , or R ２ｃ and R ２ｄ The compound according to any one of claims 1 to 3, wherein one of the members combines to form an oxo group.

5. R ２ａ , R ２ｂ , R ２ｃ and R ２ｄ The compound according to claim 4, wherein each of them is independently a hydrogen atom.

6. The compound according to any one of claims 1 to 5, wherein m and n are each 1.

7. The compound according to any one of claims 1 to 6, wherein X is absent or is O.

8. The compound according to any one of claims 1 to 7, wherein Z is a heterocyclyl (e.g., a 6-membered heterocyclyl).

9. The compound according to claim 8, wherein Z is a nitrogen-containing heterocycline, an oxygen-containing heterocycline, or a sulfur-containing heterocycline (for example, oxetanil, tetrahydrofuranil, tetrahydropyranil, thiomorpholinyl-1,1-dioxide, piperidinil, piperazinil, or pyrrolidinil).

10. The compound according to any one of claims 1 to 7, wherein Z is an aryl (for example, phenyl).

11. Z is a monosubstituted phenyl (for example, one R ５ The compound according to claim 10, wherein (by means of).

12. Z is a monosubstituted phenyl, where the one R ５ is an amine-containing group (e.g., NH ２ ) or oxygen-containing group (e.g., OCH ３ The compound according to claim 10, which is the compound described in claim 10.

13. The aforementioned one R ５ The compound according to claim 11 or 12, wherein the compound is located in the ortho or para position.

14. The compound according to any one of claims 1 to 13, wherein the compound (for example, the compound of formula (I)) is disposed on a surface such as the inner or outer surface of a device.

15. The compound according to any one of claims 1 to 14, wherein the compound is selected from the compounds shown in any one of Figures 1 to 6, or from pharmaceutically acceptable salts thereof.

16. A pharmaceutical composition comprising a compound according to any one of claims 1 to 15, and a pharmaceutically acceptable excipient.

17. A composition comprising a compound according to any one of claims 1 to 15, for use in a site in the patient, for example, on the site of an implantable element (e.g., a device or material), for the treatment of a disease, disorder or condition, or for modulating the immune response in a patient.

18. The composition according to claim 17, wherein the composition comprises an implantable element (for example, a device or material, as described herein).

19. The composition according to claim 17 or 18, wherein the composition is provided whole-body or locally.

20. The composition according to any one of claims 17 to 19, wherein the disorder or condition is, for example, a condition characterized by an undesirable immune response.

21. The composition according to any one of claims 17 to 20, wherein the disorder or condition is, for example, a condition characterized by an inappropriate immune response.

22. The composition according to any one of claims 17 to 21, wherein the composition is provided for downregulating the immune response.

23. The composition according to any one of claims 17 to 21, wherein the composition is provided for upregulating an immune response.

24. The composition according to any one of claims 17 to 23, wherein the composition reduces or can reduce undesirable reactions to the implantable element, for example, fibrosis or inflammation in the implanted device or cells, or inactivation of the implanted device or cells.

25. The composition according to claim 18, wherein the implantable element (e.g., a device or material) includes cells, such as recombinant cells, that provide a substance, such as a therapeutic agent.

26. The composition according to claim 25, wherein the cells are retinal epithelial cells (e.g., human RPE cells) or RPE-like cells.

27. The composition according to any one of claims 24 to 26, wherein the cells comprise exogenous nucleic acids (e.g., RNA (e.g., mRNA) or DNA).

28. The composition according to claim 27, wherein the exogenous nucleic acid encodes a polypeptide.

29. The composition according to claim 28, wherein the polypeptide comprises an antibody (for example, an anti-nerve growth factor antibody).

30. The composition according to claim 28, wherein the polypeptide is an enzyme (for example, α-galactosidase).

31. The composition according to claim 28, wherein the polypeptide comprises a coagulation factor (for example, a blood coagulation factor, for example, an activated blood coagulation factor).

32. The composition according to claim 28, wherein the polypeptide comprises factor I, factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor XI, or factor XIII.

33. The composition according to claim 28, wherein the sequence of the polypeptide comprises at least one amino acid deletion, addition, or substitution with respect to the sequence of factor I, factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor XI, or factor XIII (e.g., the natural human sequence).

34. The composition according to claim 28, wherein the polypeptide is a replacement therapy or replacement protein (for example, a coagulation factor, enzyme, or antibody).

35. The composition according to any one of claims 28 to 34, wherein the disease is a blood coagulation disorder or a lysosomal storage disorder (e.g., hemophilia (e.g., hemophilia A or hemophilia B), Fabry disease, Gaucher disease, Pompe disease or MPS I).

36. The composition according to any one of claims 18 to 35, wherein the transplantable element is provided as a preventive measure.

37. The composition according to any one of claims 18 to 36, wherein the transplantable element is formulated for injection into a patient (e.g., intraperitoneal, intramuscular, or subcutaneous injection).

38. The composition according to any one of claims 18 to 36, wherein the transplantable element is formulated for transplantation into a patient (for example, into the peritoneal cavity, for example, into the small peritoneal sac).

39. The composition according to any one of claims 18 to 38, wherein the transplantable element is transplanted or injected into the patient's minor peritoneal sac, retina, or subcutaneous fat.

40. The composition according to any one of claims 18 to 39, wherein the transplantable element is administered to a first patient in whom, compared to a second patient (e.g., a healthy patient), the polypeptide (e.g., blood coagulation factors, e.g., factor I, factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor XI or factor XIII) is less than approximately 50%, 40%, 30%, 25%, 20%, 15%, 10%, 5%, 2%, or 1% as measured, for example, by a blood test.

41. For example, the composition according to any one of claims 18 to 40, wherein the level of a biomarker (e.g., a serum biomarker) in the patient is monitored in order to determine the level of efficacy of the treatment.

42. An implantable element (e.g., a device or material) comprising the compound according to any one of claims 1 to 15 or the composition according to claim 16.

43. A device comprising a compound according to any one of claims 1 to 15 or a composition according to claim 16.

44. The device according to claim 43, wherein the compound is disposed on a surface of the device, such as the inner surface or the outer surface.

45. The device according to claim 43 or 44, wherein the compound is uniformly distributed across the entire surface.

46. The device according to claim 43 or 44, wherein the compound is unevenly distributed across the entire surface.

47. The device according to any one of claims 43 to 46, wherein the device is administered to or provided to a patient for the treatment of the disease, disorder or condition.

48. The device according to any one of claims 43 to 47, wherein a first portion of the surface of the device contains a compound of formula (I) that modulates (e.g., downregulation or upregulation) an immune response, and a second portion of the device does not contain the compound or has a substantially low density of the compound.

49. The device according to any one of claims 43 to 47, wherein a first portion of the surface of the device contains a compound of formula I that modulates (e.g., downregulates) the immune response, and a second portion of the surface contains a second compound of formula I that, for example, upregulates the immune response, and the second portion of the device does not contain the compound or has a substantially low density of the compound.

50. The device according to any one of claims 43 to 49, wherein the device includes cells, such as recombinant cells, that provide a substance, such as a therapeutic agent.

51. The device according to claim 50, wherein the cells are retinal epithelial cells (e.g., human RPE cells) or RPE-like cells.

52. The device according to any one of claims 43 to 51, wherein the cell comprises an exogenous nucleic acid (e.g., RNA (e.g., mRNA) or DNA).

53. The device according to claim 52, wherein the exogenous nucleic acid encodes a polypeptide.

54. The device according to claim 53, wherein the polypeptide comprises an antibody (for example, an anti-nerve growth factor antibody).

55. The device according to claim 53, wherein the polypeptide is an enzyme (e.g., α-galactosidase).

56. The device according to claim 53, wherein the polypeptide comprises a coagulation factor (for example, a blood coagulation factor, for example, an activated blood coagulation factor).

57. The device according to claim 53, wherein the polypeptide comprises factor I, factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor XI, or factor XIII.

58. The device according to claim 53, wherein the sequence of the polypeptide comprises at least one amino acid deletion, addition, or substitution with respect to the sequence of factor I, factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor XI, or factor XIII (e.g., a natural human sequence).

59. The device according to claim 53, wherein the polypeptide is a replacement therapy or replacement protein (e.g., a coagulation factor, enzyme, or antibody).

60. The device according to any one of claims 47 to 59, wherein the disease is a blood coagulation disorder or a lysosomal storage disorder (e.g., hemophilia (e.g., hemophilia A or hemophilia B), Fabry disease, Gaucher disease, Pompe disease or MPS I).

61. The device according to any one of claims 43 to 60, wherein the device is provided as a preventative measure.

62. The device according to any one of claims 43 to 61, wherein the device is formulated for injection into a patient (e.g., intraperitoneal, intramuscular, or subcutaneous injection).

63. The device according to any one of claims 43 to 61, wherein the device is formulated for implantation into a patient (for example, into the peritoneal cavity, for example, the small peritoneal sac).

64. The device according to any one of claims 43 to 63, wherein the device is implanted or injected into the patient's minor peritoneal sac, retina, or subcutaneous fat.

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