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US 12,760,128 B2Granted
Cyclodextrin dimers and uses thereof
AssigneeCyclarity Therapeutics, Inc.
InventorsMatthew S. O'Connor, Maria de los Angeles Estiarte-Martinez, Amelia M. Anderson, Daniel M. Clemens, Christina A.T.M.B. Tom, Milo Malanga, Michael Kope, Keivan Sadrerafi
Life of this patent
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Abstract
CD dimers, CD compositions, and uses thereof are disclosed herein.
Claims15
A cyclodextrin (CD) dimer having the general formula Structure A-X:
- CD-[A-B-A′]-CD′ (Structure A-X)
- wherein
- CD has the Structure A-Xa:
- CD′ has the Structure A-Xb:
- wherein:
- L1, L2, L3, L1′, L2′, and L3′ can be the same or different in each instance, and each is independently selected from the group consisting of a bond, —O—, —NH—, —NR4- or —S—, or wherein at least one L1, L2, L3, L1′, L2, and L3′ is a bond and the corresponding R1, R2, R3, R1′, R2′, or R3′ group is N3, SH, or a halogen comprising F, Cl, Br, or I;
- R1, R2, R3, R4, R1′, R2′, and R3′ can be the same or different in each instance, and each is independently selected from the group consisting of hydrogen, and Group (I) consisting of methyl, hydroxypropyl, sulfobutyl, succinyl, a quaternary ammonium group, —CH2CH(OH)CH2N(CH3)3+, alkyl, lower alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, heteroalkoxy, alkylcarbonyloxyalkyl, alkylcarbonyl, alkylsufonyl, alkylsulfonylalkyl, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, aminoalkyl, alkylsulfonylamino, aminocarbonyloxyalkyl, alkylaminosulfonyl, dialkylaminosulfonyl, aryl, arylalkyl, aryloxy, haloaryl, arylcarbonyl, arylsulfanyl, cyanoalkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, cycloalkylalkyl, cycloalkylene, cycloalkylalkylene, glucosyl, heteroalkyl, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaralkyloxy, cycloalkoxy, heterocyclyalkoxy, haloalkyl, haloalkoxy, heterocycloamino, carbocyclyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyalkoxy, hydroxyalkylamino, hydroxyalkylaminoalkyl, hydroxyalkyl, hydroxycarbonyl alkyl, hydroxyalkylamino, hydroxyalkyl, hydroxycycloalkyl, ureido, carboxy, sulfuryl, phosphoryl, phenoxy, acetyl group, monosaccharide, disaccharide, palmitoyl, fatty acid, alkoxyamino, alkoxycarbonylamino, alkoxycarbonyloxy, alkylaminocarbonyl, alkylaminocarbonylalkyl, alkylsulfanyl, alkylsulfonamido, alkylureido, amino, aminosulfonyl, ammonium, arylamino, arylsulfonamido, arylsulfonyl, arylureido, carbalkoxy, carbamoyl, carboxamido, cyano, cycloamino, heterocyclyl cycloalkyl, heteroarylsulfonyl, heterocycloalkoxy, heterocycloamino thin, hydoxycarbonyl, hydroxyalkoxyalkyl, hydroxycarbonylalkyl, hydroxyl, nitrite, nitro, phosphate, phosphine oxide, sulfate alkyl, sulfonamido, thioalkyl, and trialkylammonium;
- [A-B-A′] are together defined as a linking group;
- A and A′ are independently selected from the group consisting of —O—, —NH—, —NR4-, —S—, a heteroatom, a substituted or unsubstituted alkylene, a substituted or unsubstituted heteroalkylene;
- B is selected from the group consisting of a bond, —O—, —NH—, —NR4-, —S—, a heteroatom, a substituted or unsubstituted alkylene, a substituted or unsubstituted heteroalkylene, a substituted or unsubstituted and saturated or unsaturated cycloalkylene, a substituted or unsubstituted and saturated or unsaturated heterocycloalkylene, a substituted or unsubstituted arylene, and a substituted or unsubstituted heteroarylene;
- CD and CD′ are connected by at least one linking group;
- A of each linking group is connected to at least one L1 or L2 and the corresponding R1 or R2 is omitted and replaced in this manner by A, and A′ of each linking group is connected to at least one L1′ or L2′ and the corresponding R1′ or R2′ is omitted and replaced in this manner by A′;
- and
- wherein optionally at least one L1, L2, L3, L1′, L2′, and/or L3′ is not O;
- wherein either or both of CD and CD′ have at least one substitution, wherein at least one of R1, R2, R3, R4, R1′, R2′, or R3 is not hydrogen and is selected from said Group (I), and further wherein CD and CD′ each comprise different substituents and/or different numbers of the same substituent;
- and
- wherein the CD dimer comprises no more than 20 methyl groups.
14 more elements
A CD dimer having the general formula Structure C—X:
- CD-[A-B-A′]-CD′ (Structure C—X)
- wherein
- CD has the structure C-Xa:
- CD′ has the structure C-Xb:
- wherein:
- L1, L2, L3, L1′, L2′, and L3′ can be the same or a different in each instance, and each is independently selected from the group consisting of a bond, —O—, —NH—, —NR4- or —S— or wherein at least one L1, L2, L3, L1′, L2, and L3′ is a bond and the corresponding R1, R2, R3, R1′, R2′, or R3′ group is N3, SH, or a halogen comprising F, Cl, Br, or I;
- R1, R2, R3, R4, R1′, R2′, and R3′ can be the same or a different in each instance, and each is independently selected from the group consisting of hydrogen, and Group (I) consisting of methyl, hydroxypropyl, sulfobutyl, succinyl, a quaternary ammonium group comprising —CH2CH(OH)CH2N(CH3)3+, alkyl, lower alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, heteroalkoxy, alkylcarbonyloxyalkyl, alkylcarbonyl, alkylsufonyl, alkylsulfonylalkyl, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, aminoalkyl, alkylsulfonylamino, aminocarbonyloxyalkyl, alkylaminosulfonyl, dialkylaminosulfonyl, aryl, arylalkyl, aryloxy, haloaryl, arylcarbonyl, arylsulfanyl, cyanoalkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, cycloalkylalkyl, cycloalkylene, cycloalkylalkylene, glucosyl, heteroalkyl, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaralkyloxy, cycloalkoxy, heterocyclyalkoxy, haloalkyl, haloalkoxy, heterocycloamino, carbocyclyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyalkoxy, hydroxyalkylamino, hydroxyalkylaminoalkyl, hydroxyalkyl, hydroxycarbonyl alkyl, hydroxyalkylamino, hydroxyalkyl, hydroxycycloalkyl, ureido, carboxy, sulfuryl, phosphoryl, phenoxy, acetyl group, monosaccharide, disaccharide, palmitoyl, fatty acid, alkoxyamino, alkoxycarbonylamino, alkoxycarbonyloxy, alkylaminocarbonyl, alkylaminocarbonylalkyl, alkylsulfanyl, alkylsulfonamido, alkylureido, amino, aminosulfonyl, ammonium, arylamino, arylsulfonamido, arylsulfonyl, arylureido, carbalkoxy, carbamoyl, carboxamido, cyano, cycloamino, heterocyclyl cycloalkyl, heteroarylsulfonyl, heterocycloalkoxy, heterocycloamino thin, hydoxycarbonyl, hydroxyalkoxyalkyl, hydroxycarbonylalkyl, hydroxyl, nitrite, nitro, phosphate, phosphine oxide, sulfate alkyl, sulfonamido, thioalkyl, and trialkylammonium;
- [A-B-A′] are together defined as a linking group;
- A and A′ are independently selected from the group consisting of —O—, —NH—, —NR4-, —S—, a heteroatom, a substituted or unsubstituted alkylene, a substituted or unsubstituted heteroalkylene;
- B is selected from the group consisting of a bond, —O—, —NH—, —NR4-, —S—, a heteroatom, a substituted or unsubstituted alkylene, a substituted or unsubstituted heteroalkylene, a substituted or unsubstituted and saturated or unsaturated cycloalkylene, a substituted or unsubstituted and saturated or unsaturated heterocycloalkylene, a substituted or unsubstituted arylene, and a substituted or unsubstituted heteroarylene;
- CD and CD′ are connected by at least one linking group;
- A of each linking group is connected to at least one L1 or L2 and the corresponding R1 or R2 is omitted and replaced in this manner by A, and A′ of each linking group is connected to at least one L1′ or L2′ and the corresponding R1′ or R2′ is omitted and replaced in this manner by A′;
- wherein either or both of CD and CD′ have at least one substitution, wherein at least one of R1, R2, R3, R4, R1′, R2′, or R3 is not hydrogen and is selected from said Group (I) and further wherein CD and CD′ are asymmetrically substituted,
- wherein at least one:
- (a) the DS at position C2 in CD (corresponding to L1/R1) does not equal the DS at position C2 in CD′ (corresponding to L1′/R1′);
- or
- (b) the DS at position C3 in CD (corresponding to L2/R2) does not equal the DS at position C3 in CD′ (corresponding to L2′/R2′);
- or
- (c) the DS at position C6 in CD (corresponding to L3/R3) does not equal the DS at position C6 in CD′ (corresponding to L3′/R3′);
- or
- (d) at least one L1/R1, L2/R2, or L3/R3 pair differs from each L1′/R1′, L2′/R2′, and L3′/R3′ pair;
- or
- (e) at least one L1′/R1′, L2′/R2′, or L3′/R3′ pair differs from each L1/R1, L2/R2, and L3/R3 pair.
20 more elements
A cyclodextrin (CD) dimer having the general formula Structure A-X:
- CD-[A-B-A′]-CD′ (Structure A-X)
- wherein
- CD has the Structure A-Xa:
- CD′ has the Structure A-Xb:
- wherein:
- L1, L2, L3, L1′, L2′, and L3′ can be the same or different in each instance, and each is independently selected from the group consisting of a bond, —O—, —NH—, —NR4- or —S—, or wherein at least one L1, L2, L3, L1′, L2, and L3′ is a bond and the corresponding R1, R2, R3, R1′, R2′, or R3′ group is N3, SH, or a halogen comprising F, Cl, Br, or I;
- R1, R2, R3, R4, R1′, R2′, and R3′ can be the same or different in each instance, and each is independently selected from the group consisting of hydrogen, and Group (I) consisting of methyl, hydroxypropyl, sulfobutyl, succinyl, a quaternary ammonium group, —CH2CH(OH)CH2N(CH3)3+, alkyl, lower alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, heteroalkoxy, alkylcarbonyloxyalkyl, alkylcarbonyl, alkylsufonyl, alkylsulfonylalkyl, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, aminoalkyl, alkylsulfonylamino, aminocarbonyloxyalkyl, alkylaminosulfonyl, dialkylaminosulfonyl, aryl, arylalkyl, aryloxy, haloaryl, arylcarbonyl, arylsulfanyl, cyanoalkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, cycloalkylalkyl, cycloalkylene, cycloalkylalkylene, glucosyl, heteroalkyl, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroaralkyloxy, cycloalkoxy, heterocyclyalkoxy, haloalkyl, haloalkoxy, heterocycloamino, carbocyclyl, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyalkoxy, hydroxyalkylamino, hydroxyalkylaminoalkyl, hydroxyalkyl, hydroxycarbonyl alkyl, hydroxyalkylamino, hydroxyalkyl, hydroxycycloalkyl, ureido, carboxy, sulfuryl, phosphoryl, phenoxy, acetyl group, monosaccharide, disaccharide, palmitoyl, fatty acid, alkoxyamino, alkoxycarbonylamino, alkoxycarbonyloxy, alkylaminocarbonyl, alkylaminocarbonylalkyl, alkylsulfanyl, alkylsulfonamido, alkylureido, amino, aminosulfonyl, ammonium, arylamino, arylsulfonamido, arylsulfonyl, arylureido, carbalkoxy, carbamoyl, carboxamido, cyano, cycloamino, heterocyclyl cycloalkyl, heteroarylsulfonyl, heterocycloalkoxy, heterocycloamino thin, hydoxycarbonyl, hydroxyalkoxyalkyl, hydroxycarbonylalkyl, hydroxyl, nitrite, nitro, phosphate, phosphine oxide, sulfate alkyl, sulfonamido, thioalkyl, and trialkylammonium;
- [A-B-A′] are together defined as a linking group having a length of 5-10 atoms;
- CD and CD′ are connected by at least one linking group;
- A of each linking group is connected to at least one L1 or L2 and the corresponding R1 or R2 is omitted and replaced in this manner by A, and A′ of each linking group is connected to at least one L1′ or L2′ and the corresponding R1′ or R2′ is omitted and replaced in this manner by A′;
- and
- wherein optionally at least one L1, L2, L3, L1′, L2′, and/or L3′ is not O;
- wherein B is an unsubstituted triazole having connectivity to A and A′ as shown in Structure Y:
- or A′ to A as shown in Structure Y′:
- wherein A and A′ are independently substituted or unsubstituted alkylene;
- and
- wherein either or both of CD and CD′ have at least one substitution, wherein at least one of R1, R2, R3, R4, R1′, R2′, or R3′ is not hydrogen and is selected from said Group (I).
14 more elements
Dependencies are inferred from the claim text.