Synthesis and biological evaluation of 2-thiopyrimidine derivatives.
Various 2-thiopyrimidine derivatives have been synthesized by an efficient, one-pot reaction of functionalized amines with either 4-isothiocyanato-4-methyl-2-pentanone or 3-isothiocyanatobutanal. All the synthesized compounds were fully characterized by elemental analysis (CHN), FT-IR, (1)H NMR, and mass spectral data. One of the compounds, 7,7,8a-trimethyl-hexahydro-thiazolo[3,2-c]pyrimidine-5-thione (17) showed good anti-inflammatory (37.4% at 100 mg/kg p.o.) and analgesic activity (75% at 100 mg/kg p.o.). 7-(1-Mercapto-3,3,4a-trimethyl-4,4a,5,9b-tetrahydro-3H-pyrido[4,3-b]indol-7-yl)-3,3,4a-trimethyl-3,4,4a,5-tetrahydro-benzo[4,5]imidazo[1,2-c]pyrimidine-1-thiol (3) showed moderate activity against CDK-1 (IC(50)=5 microM). The other compounds showed moderate anti-inflammatory (5-20%), analgesic (25-75%) and protein kinase (CDK-5, GSK-3) inhibitory activities (IC(50)> 10 microM).
Sondhi
Sham M
SM
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India. sondifcy@iitr.ernet.in
Goyal
Rajendra N
RN
Lahoti
Anand M
AM
Singh
Nirupma
N
Shukla
Rakesh
R
Raghubir
Ram
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002351:Carrageenan / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D038341:Glycogen Synthase Kinases / Q000037:antagonists & inhibitors; D051379:Mice; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D011743:Pyrimidines; D013457:Sulfur Compounds; C029322:phenylbenzoquinone; D002351:Carrageenan; D038341:Glycogen Synthase Kinases; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3