title: 6-Amino-2,4,5-trimethylpyridin-3-ols: a new general synthetic route and antiangiogenic activity.
abstract: A new synthetic strategy for preparation of a wide range of 6-amino-2,4,5-trimethylpyridin-3-ols from pyridoxine·HCl via a six-step sequence has been developed. This approach features an introduction of various amino groups to C(6)-position of 3-benzyloxy-6-bromo-2,4,5-trimethylpyridine (13), a key intermediate, by a Buchwald-Hartwig amination reaction using palladium(0) transition metal, which certainly renders an expanded scope of amino substituents. Some analogs prepared using the methods described here showed high level of antiangiogenic and antitumor activities in chick chorioallantoic membrane (CAM) assay, demonstrating the potential of these new aminopyridinols as antiangiogenic agents.
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Dong-Guk
authors.initials: DG
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Youra
authors.initials: Y
authors.lastname: Kang
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Hyunji
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Republic of Korea. Electronic address: tnam@hanyang.ac.kr.
authors.forename: Tae-gyu
authors.initials: TG
authors.lastname: Nam
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: jakim@yu.ac.kr.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: jeongb@ynu.ac.kr.
authors.forename: Byeong-Seon
authors.initials: BS
authors.lastname: Jeong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011728:Pyridones; D042461:Vascular Endothelial Growth Factor A
keywords: Aminopyridinol; Angiogenesis; Antiangiogenic; Antitumor; Chick chorioallantoic membrane assay