Synthesis of selective SRPK-1 inhibitors: Novel tricyclic quinoxaline derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 13, 2005, Pages 3241-3246

  Székelyhidi, Zsolt ^a   Pató, János ^b   Wáczek, Frigyes ^a   Bánhegyi, Péter ^a   Hegymegi Barakonyi, Bálint ^a   Eros, Dániel ^b   Mészáros, György ^a   Hollósy, Ferenc ^a   Hafenbradl, Doris ^c   Obert, Sabine ^c   Klebl, Bert ^c   Kéri, György ^a,b   Orfi, László ^a,b  

^a SEMMELWEIS UNIVERSITY   (Hungary)

^b Vichem Chemie Ltd   (Hungary)

^c Axxima Pharmaceuticals AG   (Germany)

Author keywords

Kinase inhibitor; Quinoxaline; SRPK 1

Indexed keywords

PHOSPHOTRANSFERASE INHIBITOR; SR PROTEIN KINASE 1 INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG DESIGN; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; PROTEIN TARGETING; VALIDATION PROCESS;

ANTIVIRAL AGENTS; ENZYME INHIBITORS; HEPATITIS B; HEPATITIS B VIRUS; HUMANS; INHIBITORY CONCENTRATION 50; PROTEIN-SERINE-THREONINE KINASES; QUINOXALINES; STRUCTURE-ACTIVITY RELATIONSHIP;

HEPATITIS B VIRUS;

EID: 20444383142     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.04.064     Document Type: Article

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13. 10 (concentration (mg/ml)/molecular weight)
14. Measurement of Log P and Log S by HPLC: During high performance liquid chromatography measurements, the following system was applied. RP-C18 column (LiChrospher), 10 cm, 4.6 I.D. with a particle size of 10 μm. Eluents: A eluent: 50 mM ammonium acetate, pH 7.4 B eluent: 100% acetonitrile Linear gradient system: Time (min) B (%) 0-1 0 1-8 100 8-11 100 11-12 0 12-16 0 The flow rate was 1 mL/min. Temperature: 25°C Detection: λ = 230 and 254 nm. For Log P calibration, the following test compounds were used. No. Name Log P 1 Theophylline -0.05 2 Colchicine 0.92 3 5-Phenyl-1H-tetrazole 1.42 4 Benzimidazole 1.55 5 Acetophenone 1.66 6 8-Phenyl-theophylline 2.05 7 Indole 2.14 8 Propiophenone 2.2 9 Butyrophenone 2.73 10 Valerophenone 3.26
15. m for the substrate. The reaction was incubated for 1 h at room temperature and stopped by addition of 10 μl of 50 mM EDTA. The assay was transferred to a 96-well MAPH filter plate (Millipore). The radioactivity was counted on a Microbeta microplate counter