Pyrrolo[1,2-a][1,4]benzodiazepine: A novel class of non-azole anti-dermatophyte anti-fungal agents

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 14, 2005, Pages 3453-3458

  Meerpoel, Lieven ^a   Van Gestel, Jef ^a   Van Gerven, Frans ^a   Woestenborghs, Filip ^a   Marichal, Patrick ^a   Sipido, Vic ^a   Terence, Gilkerson ^b   Nash, Roger ^b   Corens, David ^a   Richards, Ray D ^c  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c Highfield Road Industrial Estate   (United Kingdom)

Author keywords

4H pyrrolo 1,2 a 1,4 benzodiazepine; Anti dermatophyte; Anti fungal

Indexed keywords

ANTIDERMATOPHYTIC AGENT; ANTIFUNGAL AGENT; BENZODIAZEPINE DERIVATIVE; PYRROLO[1,2 A][1,4]BENZODIAZEPINE; R 189106; SQUALENE MONOOXYGENASE; TERBINAFINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DERMATOPHYTE; DRUG MECHANISM; DRUG SCREENING; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VIVO STUDY; MICROSPORUM CANIS; MOUSE; MYCOSIS; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; TRICHOPHYTON;

ANTIFUNGAL AGENTS; ARTHRODERMATACEAE; AZEPINES; DRUG DESIGN; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP;

ARTHRODERMATACEAE;

EID: 20644457717     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.05.007     Document Type: Article

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27. 6) δ ppm 1.21 (t, J = 7.6 Hz, 3H) 2.66 (q, J = 7.5 Hz, 2H) 3.84 (d, J = 13.9 Hz, 1H) 4.53 (d, J = 13.9 Hz, 1H) 5.17 (s, 1H) 5.84 (ddd, J = 3.6, 1.6, 0.8 Hz, 1H) 6.28 (dd, J = 3.6, 2.9 Hz, 1H) 7.32 (d, J = 8.2 Hz, 2H) 7.40 (dd, J = 2.9, 1.6 Hz, 1H) 7.63 (m, 2H) 7.69 (m, 1H) 7.72 (d, J = 8.4 Hz, 2H) 10.61 (br s, 2H)
28. 2 and placed in a demountable KBr cell with a 0.09 mm Teflon spacer (1 h collection time). OPUS software (Bruker, Germany) was used for spectral processing. A thorough conformational search is performed at the molecular mechanics level. A MM3 stochastic search is performed in combination with a systematic MMFF search with a dihedral grid of 30°. The located minima were optimized using Gaussian03RB5 at the B3LYP/6-31G* level. All conformations within 5 kcal/mol interval were used to simulate VCD and IR spectrum. Dipole and rotational strengths were calculated at the same B3LYP/6-31G* level, using the standard Gaussian (75,302)p grid.
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34. Carbowax: polyethylene glycol PEG 1500 (60%) and PEG 400 (40%)