Syntheses of trans-5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles and trans-5- oxo-hexahydro-furo[3,2-b]pyrroles (pyrrolidine trans-lactams and trans- Lactones): New pharmacophores for elastase inhibition

Journal of Medicinal Chemistry

Volumn 41, Issue 21, 1998, Pages 3919-3922

  Macdonald, Simon J F ^a   Belton, David J ^a   Buckley, Doreen M ^a   Spooner, Julie E ^a   Anson, Michael S ^a   Harrison, Lee A ^a   Mills, Keith ^a   Upton, Richard J ^a   Dowle, Michael D ^a   Smith, Robin A ^a   Molloy, Christopher R ^a   Risley, Catherine ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 OXO HEXAHYDROFURO[3,2 B]PYRROLE; 5 OXO HEXAHYDROPYRROLO[3,2 B]PYRROLE; ELASTASE INHIBITOR; LACTAM; LEUKOCYTE ELASTASE; PYRROLIDINE DERIVATIVE; UNCLASSIFIED DRUG;

CHRONIC BRONCHITIS; CYSTIC FIBROSIS; DRUG STRUCTURE; DRUG SYNTHESIS; EMPHYSEMA; ENZYME INHIBITION; LETTER; REACTION ANALYSIS; RESPIRATORY DISTRESS SYNDROME; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

AZETIDINES; HUMANS; LACTAMS; LACTONES; LEUKOCYTE ELASTASE; NEUTROPHILS; PIPERAZINES; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 7844236806     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm981026s     Document Type: Letter

References (35)

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18. 1H NMR.
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31. Purified on a Chiralcel-OD column (25 mm × 4.6 mm) eluting with 85:15 hexane:2-isopropanol at 1 mL/min with UV detection at 200 nm. Under these conditions the enantiomers of 2 eluted at 21.14 and 23.94 min and 22 at 22.81 and 26.23 min.
32. 50's were calculated after a 15-min preincubation.
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35. Up to millimolar concentrations of analogous hydroxy acids did not inhibit HNE.