Cyanine-containing compounds for cancer imaging and treatment

Abstract

This invention relates generally to cyanine-containing compounds; pharmaceutical compositions comprising cyanine-containing compounds; and methods of using cyanine-containing compounds for cancer cell imaging, cancer cell growth inhibition, and detecting cancer cells, for example. Compounds of the invention are preferentially taken up by cancer cells as compared to normal cells. This allows many uses in the cancer treatment, diagnosis, tracking and imaging fields.

1 .- 30 . (canceled) 
     
     
         31 . A method of imaging cancer cells, the method comprising:
 introducing to the cancer cells an imaging amount of a compound having the formula:   
       
         
           
           
               
               
           
         
         where X is selected from the group consisting of hydrogen, halogen, CN, Me, phenyl, OH, OMe, OPh, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, 4-O-Ph-CH 2 CH 2 CONHS, NH-Ph, NHEt, SEt, S-Ph, 4-S-Ph-COOH, 4-S-Ph-OH, 4-O-Ph-COOH, 4-O-Ph-NCS, and 4-S-Ph-NCS; q is 0 or 1; R 7  is selected from the group consisting of H and COOR 9 , where R 9  is H, CH 3 , or CH 2 CH 3 ; each R 1  is independently in each instance (CH 2 ) m R A , where m is an integer from 1 to 12, R A  is independently selected from the group consisting of CH 3 , NH 2 , SH, COOH, SO 3 H, OH, halogen and CO—N-hydroxysuccinimide; each R 10  is independently in each instance selected from the group consisting of H, OH, OMe, halogen, NH 2 , NHR, N(R) 2  and COOH, where each R is independently C 1 -C 6  alkyl; and each R 3  is independently in each instance selected from the group consisting of methyl and phenyl; 
         exposing the cancer cells to electromagnetic radiation; and 
         detecting light emission from the compound. 
       
     
     
         32 . The method of  claim 31 , wherein X is not halogen, CN, Me, phenyl, OH, OMe, OPh, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, NH-Ph, NHEt, or S-Ph when R 7  is H. 
     
     
         33 . The method of  claim 31 , wherein the cancer cells are imaged in vivo. 
     
     
         34 . The method of  claim 31 , wherein the cancer cells comprise lymphoma, myeloid leukemia, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, ovarian cancer, cervical cancer, bone cancer, thyroid cancer, adrenal gland cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, skin cancer, liver cancer, testicular cancer, colon cancer, or breast cancer cells. 
     
     
         35 . The method of  claim 31 , wherein the electromagnetic radiation is near infrared radiation. 
     
     
         36 . The method of  claim 31 , wherein X is OH, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, 4-O-Ph-CH 2 CH 2 CONHS, NH-Ph, SEt, 4-S-Ph-COOH, 4-S-Ph-OH, 4-O-Ph-COOH, 4-O-Ph-NCS, or 4-S-Ph-NCS. 
     
     
         37 . The method of  claim 31 , wherein X is Cl and each R 3  is CH 3 . 
     
     
         38 . The method of  claim 31 , wherein R 1  is (CH 2 ) m SO 3 H and m is 1-6. 
     
     
         39 . The method of  claim 31 , wherein R 1  is (CH 2 ) m CH 3  and m is 1-6. 
     
     
         40 . The method of  claim 31 , wherein q is 0. 
     
     
         41 . A method of treating cancer, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound having the formula: 
       
         
           
           
               
               
           
         
         where X is selected from the group consisting of hydrogen, halogen, CN, Me, phenyl, OH, OMe, OPh, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, 4-O-Ph-CH 2 CH 2 CONHS, NH-Ph, NHEt, SEt, S-Ph, 4-S-Ph-COOH, 4-S-Ph-OH, 4-O-Ph-COOH, 4-O-Ph-NCS, and 4-S-Ph-NCS; q is 0 or 1; R 7  is selected from the group consisting of H and COOR 9 , where R 9  is H, CH 3 , or CH 2 CH 3 ; each R 1  is independently in each instance (CH 2 ) m R A , where m is an integer from 1 to 12, R A  is independently selected from the group consisting of CH 3 , NH 2 , SH, SO 3 H, OH, halogen and CO—N-hydroxysuccinimide; each R 10  is independently in each instance selected from the group consisting of H, OH, OMe, halogen, NH 2 , NHR, N(R) 2  and COOH, where each R is independently C 1 -C 6  alkyl; and each R 3  is independently in each instance selected from the group consisting of methyl and phenyl. 
       
     
     
         42 . The method of  claim 31 , wherein X is not halogen, CN, Me, phenyl, OH, OMe, OPh, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, NH-Ph, NHEt, or S-Ph when R 7  is H. 
     
     
         43 . The method of  claim 41 , wherein the patient has a lymphoma, myeloid leukemia, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, ovarian cancer, cervical cancer, bone cancer, thyroid cancer, adrenal gland cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, skin cancer, liver cancer, testicular cancer, colon cancer, or breast cancer. 
     
     
         44 . The method of  claim 41 , wherein X is OH, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, 4-O-Ph-CH 2 CH 2 CONHS, NH-Ph, SEt, 4-S-Ph-COOH, 4-S-Ph-OH, 4-O-Ph-COOH, 4-O-Ph-NCS, or 4-S-Ph-NCS. 
     
     
         45 . The method of  claim 41 , wherein X is Cl and each R 3  is CH 3 . 
     
     
         46 . The method of  claim 41 , wherein R 1  is (CH 2 ) m SO 3 H and m is 1-6. 
     
     
         47 . The method of  claim 41 , wherein R 1  is (CH 2 ) m CH 3  and m is 1-6. 
     
     
         48 . The method of  claim 41 , wherein q is 0.