Article

Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy.

Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.65). 07/2008; 18(11):3392-9. DOI: 10.1016/j.bmcl.2008.04.018
Source: PubMed

ABSTRACT Replacement of the carboxylic acid group in a series of previously described methylene-linked pyrazole EP(1) receptor antagonists led to the discovery of amide, reversed amide and carbamate derivatives. Two compounds, 10a and 10b, were identified as brain penetrant compounds and both demonstrated efficacy in the CFA model of inflammatory pain.

0 Bookmarks
 · 
80 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The asymmetric unit of the title salt, C3H6N3 (+)·C2F3O2 (-), contains two independent 3-amino-pyrazolium cations and two independent tri-fluoro-acetate anions. The F atoms of both anions were refined as disordered over two sets of sites, with common occupancy ratios of 0.639 (12):0.361 (12). In the crystal, the cations and anions are linked via N-H⋯O hydrogen bonds, forming chains along [100] and [010].
    Acta Crystallographica Section E Structure Reports Online 01/2013; 69(Pt 9):o1425-6. · 0.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel series of N'-(1-(aryl)ethylidene)-2-(5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(1H)-yl)acetohydrazides was synthesized. The synthesis was carried out by thermal method as well as ultrasonic bath to reduce reaction time and to enhance product yields. The synthesized compounds were characterized by spectroscopic techniques like NMR, infrared and EIMS. The structure of compound 5w was elucidated by X-ray crystallography. The titled compounds were evaluated for anti-human immunodeficiency virus type 1 (anti-HIV-1) and cytotoxic activities. Biological studies indicated that amongst these compounds, 5a, b, j, h and i showed the activity with median effective concentration (EC50) values less than 20 μM. Compound 5i exhibited the most potent anti-HIV-1 activity (EC50 = 3.2 μM) while 5h showed anti-HIV-1 activity (EC50 = 3.8 μM) with no toxicity at all in primary human lymphocytes, CEM and VERO cells.
    Archives of Pharmacal Research 07/2013; · 1.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this work novel organic based compounds, acyl thiourea derivatives were synthesized and their anticancer activities were investigated. A new series of acyl thiourea derivatives containing pyrazole ring were prepared in good yield through one pot reaction of 4-benzoyl-1, 5-diphenyl-1H-pyrazole-3-carbonyl chloride with ammonium thiocyanate and various amines. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and elemental analysis. Anticancer activities of synthesized compounds were evaluated on human colon, liver and leukemia cancer cell lines. Cell culture studies have demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity have altered in the presence of various side groups. These results confirm that novel pyrazolyl acyl thioureas derived compounds may be utilized for cancer treatment. Furthermore, these compounds have a great potential and significance for further investigations.
    Bioorganic & medicinal chemistry 04/2013; · 2.82 Impact Factor