Antitumor Antibiotics

抗肿瘤抗生素

基本信息

批准号：
8007373
负责人：
DALE L BOGER
金额：
$ 47.22万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-02-01 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8007373
关键词：
Acids Address Affinity Alder plant Area Biological Biological Factors Bleomycin Bleomycin A(2)Cyclization DNA Binding Decarboxylation Development Diels Alder reaction Enzymes Evaluation Evolution Foundations Funding Grant Health Investigation Libraries Lipids Maintenance Mediating Methodology Methods Multi-Drug Resistance Oxadiazoles Pain Disorder Pancratistatin Pharmaceutical Preparations Phase Preparation Productivity Property Protein Binding Protein Phosphatase 2A Regulatory Subunit PR53 Protein Phosphatase Inhibitor Protein phosphatase Proteins Publications Publishing Pyrimidine Pyrroles Reaction Rebeccamycin Relative (related person)Signaling Molecule Sleep Sleep Disorders Solutions Staging Techniques Time Triazines Validation Vindoline Work abstracting analog antineoplastic antibiotics base cancer therapy combinatorial cordytropolone cycloaddition cyclopropenone cytostatin design diazine fatty acid amide hydrolase fostriecin insight ketal member oleylamide programs pyridine stereochemistry therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Abstract. Studies on the total synthesis and evaluation of antitumor antibiotics including (1) fendleridine, (2) lycorine, (3) pancratistatin, (4) (-)-vindoline, (5) an extensive library of ningalin derivatives as multidrug resistant (MDR) reversal drugs, (6) bleomycin derivatives, (7) indolocarbazoles including rebeccamycin, (8) cordytropolone, and (9) sultriecin and key structural analogues are detailed. In the course of the studies, the investigation, development, and implementation of: (1) heteroaromatic azadiene Diels- Alder reactions, (2) the LUMOdiene-controlled Diels-Alder reactions of N-sulfonyl-1- azadienes, (3) the thermal reactions of cyclopropenone ketals including those of reversibly generated p-delocalized singlet vinylcarbenes, and (4) tandem Diels- Alder/1,3-dipolar cycloadditions of 1,3,4-oxadiazoles will be pursued and provide the opportunity to comprehensively extend past studies. The proposed studies include the examination of antitumor compounds that mediate their cellular effects through selective target protein (e.g. PP2A, Pgp) or sequence selective DNA binding and provide well-defined problems on the design, preparation, and evaluation of synthetic, mechanism based analogues in which fundamental studies of the structural features responsible for protein or DNA binding affinity, selectivity, and functional reactivity may be addressed. PUBLIC HEALTH RELEVANCE: New insights into new classes of drugs for the treatment of cancer and methods for their preparation will emerge from the proposed studies.

描述（由申请人提供）：摘要。研究抗肿瘤抗生素的总合成和评估的研究，包括（1）芬德莱丁，（2）氨核，（（3）胰腺抑制素，（4）（ - ） - vindoline，（5）ningalin衍生物作为多种含量的ningalin衍生物文库，包括多饮用（MDR）反向药物，（MMDR）逆转药物，（6）bleiv iniviv ariviv arivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivrivriv somysrics（6） rebecamycin，（8）核查素和（9）Sultriecin和关键结构类似物已详细介绍。 In the course of the studies, the investigation, development, and implementation of: (1) heteroaromatic azadiene Diels- Alder reactions, (2) the LUMOdiene-controlled Diels-Alder reactions of N-sulfonyl-1- azadienes, (3) the thermal reactions of cyclopropenone ketals including those of reversibly generated p-delocalized singlet将追求乙烯基碳烯和（4）串联Diels-alder/1,3-二极性环加成1,3,4-氧化二氧化氮的二极化环载细分，并为全面扩展过去的研究提供了机会。拟议的研究包括检查抗肿瘤化合物，这些化合物通过选择性靶蛋白（例如PP2A，PGP）或序列选择性DNA结合介导其细胞作用，并在设计，制备和评估合成，机制的基于机制的类似物的基础上，在哪些基于蛋白质或DNA的基础上的基础研究中，对蛋白质或DNA结合的基础研究提供了明确定义的问题。公共卫生相关性：对癌症治疗的新药物的新见解，并从拟议的研究中出现了用于治疗癌症的方法的新见解。