Synthesis of 13C3, 15N4-labeled factor Xa inhibitor

被引：12
作者：
Guilford, WJ [1 ]
Dallas, J [1 ]
Arnaiz, D [1 ]
机构：
[1] Berlex Biosci, Med Chem, Richmond, CA 94804 USA
来源：
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS | 2001年 / 44卷 / 04期
关键词：
factor Xa inhibitor; ZK 807834 (CI 1031); mass label; tetralabeled N-methyl ethylenediamine;
D O I：
10.1002/jlcr.452
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
The synthesis of an isotopically-labeled, diphenoxypyridine factor Xa inhibitor, 3-[[6-[3-(4,5-dihydro-1-(C-13)-methyl-1H-(4-C-13, N-15(2)-imidazol-2-yl)phenoxy)-3,5-difluoro-4-(4-morpholinyl)-2-pyridinyl]oxy]-4-hydroxybenzene-C-13-carbox-N-15-imid-N-15-amide, is reported for use in factor Xa binding studies using REDOR NMR. N-benzyl protected tetralabeled N-methylethylene diamine was an intermediate in the preparation of 3-[4,5-1-(C-13)-methyl-1H-(4-C-13, N-15(2)-imidazol-2-yl)]phenol.
引用
收藏
页码：247 / 256
页数：10
相关论文
共 9 条
  • [1] SOLID-STATE NUCLEAR-MAGNETIC-RESONANCE ANALYSIS OF THE CONFORMATION OF AN INHIBITOR BOUND TO THERMOLYSIN
    BEUSEN, DD
    MCDOWELL, LM
    SLOMCZYNSKA, U
    SCHAEFER, J
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (14) : 2742 - 2747
  • [2] Design, synthesis, and biological activity of novel purine and bicyclic pyrimidine factor Xa inhibitors
    Buckman, BO
    Mohan, R
    Koovakkat, S
    Liang, A
    Trinh, L
    Morrissey, MM
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (16) : 2235 - 2240
  • [3] DAVIE E, 1990, BIOCHEM, V30, P10363
  • [4] Ewing William R., 1999, Drugs of the Future, V24, P771, DOI 10.1358/dof.1999.024.07.858624
  • [5] Fevig JM, 1999, ANNU REP MED CHEM, V34, P81
  • [6] Conformations of trypsin-bound amidine inhibitors of blood coagulant factor Xa by double REDOR NMR and MD simulations
    McDowell, LM
    McCarrick, MA
    Studelska, DR
    Guilford, WJ
    Arnaiz, D
    Dallas, JL
    Light, DR
    Whitlow, M
    Schaefer, J
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (19) : 3910 - 3918
  • [7] Discovery of N-[2-[5-[amino(imino)methyl]-2-hydroxyphenoxy]-3,5-difluoro-6-[3-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine (ZK-807834):: A potent, selective, and orally active inhibitor of the blood coagulation enzyme factor Xa
    Phillips, GB
    Buckman, BO
    Davey, DD
    Eagen, KA
    Guilford, WJ
    Hinchman, J
    Ho, E
    Koovakkat, S
    Liang, A
    Light, DR
    Mohan, R
    Ng, HP
    Post, JM
    Shaw, KJ
    Smith, D
    Subramanyam, B
    Sullivan, ME
    Trinh, L
    Vergona, R
    Walters, J
    White, K
    Whitlow, M
    Wu, S
    Xu, W
    Morrissey, MM
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (19) : 3557 - 3562
  • [8] Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin
    Whitlow, M
    Arnaiz, DO
    Buckman, BO
    Davey, DD
    Griedel, B
    Guilford, WJ
    Koovakkat, SK
    Liang, A
    Mohan, R
    Phillips, GB
    Seto, M
    Shaw, KJ
    Xu, W
    Zhao, ZC
    Light, DR
    Morrissey, MM
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 1999, 55 : 1395 - 1404
  • [9] XU W, AM CHEM SOC M DALL T
1