Narrow emission dyes, compositions comprising same, and methods for making and using same
AssigneeNIRvana Sciences Inc.
InventorsChristopher J. MacNevin, James Bruce Pitner, Chih-Yuan Chen
Life of this patent
Estimating the term…
Abstract
Provided are chlorin derivatives with narrow band emission. In some embodiments, the bacteriochlorin derivatives are PEGylated. In some embodiments, the chlorin derivatives have high water solubility (e.g., 10 mg/mL or more). In some embodiments, the chlorin derivatives are PEGylated and have high water solubility. The chlorin derivatives can include bioconjugatable groups for forming conjugates, for example, with antibodies and nanoparticles. The chlorin derivatives and their conjugates can be used in imaging and therapeutic applications. Methods of synthesizing the chlorin derivatives are also provided.
Claims18
A compound of Formula (I):
- wherein:
- M is a metal or is two hydrogens (—H, —H);
- R5, R10, and R15 are independently selected from H, alkoxy, and a linker group having the formula:
- -Li-(X1-L2)p-G;
- wherein p is 0 or 1;
- L1 is alkylidene;
- X1 is —C(═O)NH— or —NHC(═O)—;
- L2 is —(CH2CH2O)q-alkylene-, wherein q is an integer between 1 and 24, alkylene, or substituted alkylene, optionally wherein substituted alkylene is alkylene substituted by a one or more groups comprising a polyoxyethylene chain and/or an amide group;
- and G is a bioconjugatable group;
- and
- R2, R3, R12, and R13 are independently selected from H, cyano, halo, perhaloalkyl, sulfonate, sulfonamide, ester, carboxylic acid, formyl, acetyl, a linker group having the formula -L1-(X1-L2)p-G, and a solubilizing group, wherein the solubilizing group is selected from -aryl-(Rs)w and -alkynyl-aryl-(Rs)w, wherein w is an integer between 0 and 5 inclusive, and RS is a group having the formula:
- -X2-(L3)z-R17,
- wherein:
- z is 0 or 1;
- X2 is —CH2NHC(═O)—, —C(═O)NH-alkylene-NH—, or triazolyl;
- L3 is —C(═O)-alkylene-C(═O)—NH—, and R17 is selected from —(C2H4O)m—R18, —C(═O)C2H4—(OC2H4)mOR18, and —(C2H4O)n—C2H4—C(═O)NH—C(R19)3, wherein m is an integer of 4 or more, optionally wherein m is an integer of 8 or more;
- n is an integer between 1 and 5;
- R18 is loweralkyl, optionally methyl;
- and R19 is —CH2O—C2H4—C(═O)NH—(C2H4O)mR18;
- subject to the proviso that at least one of R2, R3, R12, and R13 is -aryl-(Rs)w or -alkynyl-aryl-(Rs)w.
A water-soluble chlorin dye having a solubility of above about 1 mg/ml in an aqueous solution, optionally having a solubility of about 2.5 mg/ml or more in an aqueous solution;
- further optionally having a solubility of about 10 mg/ml or more in an aqueous solution.
A method of preparing a synthetic intermediate of a compound of Formula (I):
- wherein:
- M is a metal or is —H, —H;
- R5, R10, and R15 are independently selected from H, alkoxy, and a linker group having the formula:
- -L1-(X1-L2)p-G;
- wherein p is 0 or 1;
- L1 is alkylidene;
- X1 is —C(═O)NH— or —NHC(═O)—;
- L2 is —(CH2CH2O)q-alkylene-, wherein q is an integer between 1 and 24, alkylene, or substituted alkylene, optionally wherein substituted alkylene is alkylene substituted by a one or more groups comprising a polyoxyethylene chain and/or an amide group;
- and G is a bioconjugatable group;
- and
- R2, R3, R12, and R13 are independently selected from H, halo, cyano, perhaloalkyl, sulfonate, sulfonamide, ester, carboxylic acid, formyl, acetyl, a linker group having the formula -L1-(X1-L2)p-G, and a solubilizing group, wherein the solubilizing group is selected from -aryl-(Rs)w and -alkynyl-aryl-(Rs)w, wherein w is an integer between 0 and 5 inclusive, and Rs is a group having the formula:
- -X2-(L3)z-R17,
- wherein:
- z is 0 or 1;
- X2 is —CH2NHC(═O)—, —C(═O)NH-alkylene-NH—, or triazolyl;
- L3 is —C(═O)-alkylene-C(═O)—NH—, and R17 is selected from —(C2H4O)m—R18—C(═O)C2H4—(OC2H4)m—OR18, and —(C2H4O)n—C2H4—C(═O)NH—C(R19)3, wherein m is an integer of 4 or more, optionally wherein m is an integer of 8 or more;
- n is an integer between 1 and 5;
- R18 is loweralkyl, optionally methyl;
- and R19 —CH2O—C2H4—C(═O)NH—(C2H4O)mR18;
- subject to the proviso that at least one of R2, R3, R12, and R13 is -aryl-(Rs)w or -alkynyl-aryl-(Rs)w;
- wherein the method comprises:
- (a) providing a compound having the formula (I′):
- wherein:
- M is a metal or is —H, —H;
- R5′, R10′, and R15′ are independently selected from H, alkoxy,
- and
- R2′, R3′, R12 ′, and R13′ are independently selected from H, ester, carboxylic acid, formyl, acetyl,
- subject to the proviso that at least one of R2′, R3′, R12′, and R13′ is
- and
- (b) contacting the compound provided in step (a) with a solution comprising 4 molar (M) HCl in dioxane to provide a compound of the formula (I″):
- wherein:
- M is a metal or is —H, —H;
- R5″, R10″, and R15″ are independently selected from H, alkoxy,
- and
- R2″, R3″, R12″, and R13″ are independently selected from H, ester, carboxylic acid, formyl, acetyl,
- subject to the proviso that at least one of R2″, R3″, R12″, and R13″ is
A compound having one of the following formulas:
- or a conjugate thereof, wherein the compound is conjugated to one or more of the group consisting of a small molecule, an antigen, a microparticle, a nanoparticle, a polymer, a peptide, a protein, an antibody or an antibody fragment, a nucleic acid, a hormone, and a growth factor.
Dependencies are inferred from the claim text.