Peptide vectors for delivering paclitaxel

• Main Authors: SHEN, YEELANA, COMSTOCK, JEANNE MARY, KIM, SUN H, DONG, ZHENG XIN
• Format: Patent
• Language: English
• Published: 28.01.2011
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A compound according to the formula "X-B1-B2-B3-B4-Z" wherein: X is paclitaxel or a paclitaxel derivative, B1, B2, B3, and B4 are independently for each occurrence: (Doc)m, (Aepa)n, -(C(O)-A1-A2-A3-A4-A5-C(O))s-, or (amino acid)p; wherein the amino acid is selected from the group consisting of Gly, Val, Abu, Gaba, Doc, and Sar; A1 and A5 are, independently for each occurrence, CR1R2; wherein R1 and R2 are independently for each occurrence, H; A2, A3, and A4 are independently for each occurrence, CR6R7, (CH2)t or absent; wherein each of R6 and R7 is, independently for each occurrence, H; m is, independently for each occurrence, 0, 1, 2, 3, 4, 5, or 6; n is, independently for each occurrence, 0, 1, or 2; p is, independently for each occurrence, 0, 1, or 2; s is, independently for each occurrence, 1, 2, or 3; t is, independently for each occurrence, 0, 1, 2, or 3; and Z is a somatostatin, luteinizing hormone releasing hormone (LHRH) or bombesin peptide. Provided that: when X is paclitaxel or a paclitaxel derivative, then B1 is (amino acid)p, wherein the amino acid is selected from the group consisting of Sar, Gly, Val, Doc, and Gaba, and p is 1 or 2; and when X is paclitaxel or a paclitaxel derivative, at least one of B1, B2, B3 and B4 is (Doc)m and m is not 0; or a pharmaceutically acceptable salt thereof. The compounds are used to deliver the cytotoxic drug paclitaxel to cells expressing receptors for the peptides to treat diseases selected from fibrosis, benign prostatic hyperplasia, atherosclerosis, restenosis, breast cancer, colon cancer, pancreas cancer, prostate cancer, lung cancer, small cell lung cancer, ovarian cancer, epidermal cancer and haematopoietic cancer. (62) Divided Out of 564694