NEW HETEROCYCLIC COMPOUNDS CONTAINING NITROGEN ATOMS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME FOR TREATMENT OF CANCER

• Main Authors: PARK, SONG KYU, WON, MI SUN, HAN, GYOON HEE, YANG, JEE SUN, LEE, CHANG WOO, HONG, SUNG HEE, YOO, HYANG SOOK, CHUNG, KYUNG SOOK, KIM, DONG MYUNG, KIM, HWAN MOOK, KIM, MYUNG SOOK, LEE, KI HO, CHOI, EUN HYUN
• Format: Patent
• Language: English
• Published: 14.02.2008
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

A novel compound is provided to activate c-abl and p53 by inducing DNA damage due to reactive oxygen species, induce RhoB to cause apoptosis, and induce cell death by down-regulating Bcl2 involved in cell survival, which is generated by dysregulated signals via the mitochondria pathway, thereby inhibiting tumor cell growth and inducing apoptosis. A heterocyclic compound containing nitrogen atoms is represented by the formula(1), where R1 is straight or branched C1-30 alkyl or C2-30 alkenyl; R2 is straight or branched C1-6 alkyl; R3 is straight or branched C1-6 alkyl, C2-30 alkenyl, allyl or benzyl substituted or unsubstituted with one group selected from the group consisting of straight or branched C1-6 alkyl, C1-6 alkoxy, OCF3, nitro, and halogen; A is C(=O) or S(=O)2; X is a halogen atom; and n is an integer of 2 and 3. A method for preparing the compound of the formula(1) comprises the steps of: (a) reacting an organic acid compound of the formula(2) with thionyl chloride in an organic solvent, and then reacting with an alkylpiperazine derivative to prepare a compound of the formula(3); and (b) reacting the compound of the formula(3) with a halide compound to prepare a compound of the formula(1-1), where R2, R3, and X are same as defined above, and m is an integer from 1-30. A pharmaceutical composition for treating cancer comprises the heterocyclic compound of the formula(1) or a pharmaceutically acceptable salt thereof as an active ingredient, where the cancer is one selected from the group consisting of lung cancer, non- small cell lung cancer, colon cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or ocular melanoma, uterine cancer, ovarian cancer, rectal cancer, gastric cancer, anal cancer, breast cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine gland cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft- tissue sarcoma, uterine cancer, penis cancer, prostate cancer, chronic or acute leukemia, lymphocyte lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, primary central nervous system lymphoma, spinal tumor, brain stem glioma, and pituitary adenoma.