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  • 02월 26일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제115회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Novel dianilinopyrimidine derivatives as ALK inhibitors

등록일
2015년 2월 12일 10시 18분 35초
접수번호
0758
발표코드
MEDI.O-3 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
금 10시 : 40분
발표형식
구두발표
발표분야
의약화학 - Oral Presentation for Young Medicinal Chemists
저자 및
공동저자
윤정인, 김형래1,*, 윤창수2
충남대학교 약학대학, Korea
1한국화학연구원 난치성질환치료제연구센터, Korea
2한국화학연구원 신약연구본부 의약화학연구센터, Korea
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) belongs to the insulin receptor superfamily. Recently, ALK has been elucidated as an interesting target for various cancers due to its implications of tumorigenesis by ALK fusion gene mutations and point mutations. ALK with chromosomal rearrangements have been detected in anaplastic large cell lymphoma (ALCL, 50-60%), inflammatory myofibroblastic tumors (IMT, 27%), and non-small-cell lung cancer (NSCLC, 4-7%). The representative of ALK fusion gene NPM-ALK (ALCL, IMT) and EML4-ALK (NSCLC) is known. Activating EML4-ALK mutations are key driven of NSCLC malignancy in approximately in of 4-7% patients. In 2011, Crizotinib (Xalkori) is the first EML4-ALK inhibitor in clinical use for NSCLC treatment. However, despite dramatic responses to Crizotinib, its efficacy is ultimately limited by the development of acquired drug resistance that occurred within a year. We already reported bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) derivatives as a potent ALK inhibitor, however they were lack of metabolic stability due to 1,4-diaminobenzene moiety. In this report, we designed and synthesized new series of bis-ortho-alkoxy-para-piperidinesubstituted-2,4-dianilinopyrimidines derivatives in order to improve metabolic stability as well as its potency. Most pyrimidine derivatives showed good inhibitory activities and also showed good anti-proliferative activity against a panel of H3122 cell line. (H3122 cell line was contained with ALK fusion gene of EML4-ALK.)

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