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Biomedical subjects

D A Dudley

Publications and source records attributed to D A Dudley.

3 recordsLinked to original sources
PubMed2000

Rational design, synthesis, and biological activity of benzoxazinones as novel factor Xa inhibitors.

Inappropriate thrombus formation within blood vessels is the leading cause of mortality in the industrialized world. Factor Xa (FXa) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade and represents an attractive target for anticoagulant drug development. From a high-throughput in vitro mass screen of our chemical library, we identified 4-[5-[(2R,6S)-2, 6-dimethyltetrahydro-1(2H)-pyridinyl]pentyl]-2-phenyl-2H-1, 4-benzoxazin-3(4H)-one (1a) as an inhibitor of FXa with an IC(50) of 27 microM. Through a combination of SAR studies and molecular modeling, we synthesized 3-(4-[5-[(2R,6S)-2, 6-dimethyltetrahydro-1(2H)-pyridinyl]pentyl]-3-oxo-3,4-dihydro-2H- 1,4-benzoxazin-2-yl)-1-benzenecarboximidamide (1n) which was a potent FXa inhibitor with an IC(50) of 3 nM. This compound exhibited high selectivity for FXa over other related serine proteases and was efficacious when dosed intravenously in rabbit and dog antithrombotic models.

Administration, Oral↗
PubMed1995

Amniotic fluid embolism: analysis of the national registry.

OBJECTIVE: We analyzed the clinical course and investigated possible pathophysiologic mechanisms of amniotic fluid embolism. STUDY DESIGN: We carried out a retrospective review of medical records. Forty-six charts were analyzed for 121 separate clinical variables. RESULTS: Amniotic fluid embolism occurred during labor in 70% of the women, after vaginal delivery in 11%, and during cesarean section after delivery of the infant in 19%. No correlation was seen with prolonged labor or oxytocin use. A significant relation was seen between amniotic fluid embolism and male fetal sex. Forty-one percent of patients gave a history of allergy or atopy. Maternal mortality was 61%, with neurologically intact survival seen in 15% of women. Of fetuses in utero at the time of the event, only 39% survived. Clinical and hemodynamic manifestations were similar to those manifest in anaphylaxis and septic shock. CONCLUSIONS: Intact maternal or fetal survival with amniotic fluid embolism is rare. The striking similarities between clinical and hemodynamic findings in amniotic fluid embolism and both anaphylaxis and septic shock suggest a common pathophysiologic mechanism for all these conditions. Thus the term amniotic fluid embolism appears to be a misnomer.

Adolescent↗