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Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly(ADP-ribose)polymerase.
Bioorg Med Chem Lett. 2006 Feb 15; 16(4):1040-4.BM

Abstract

We have previously described the discovery of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors based on a phthalazinone scaffold. Subsequent optimisation of inhibitory activity, metabolic stability and pharmacokinetic parameters has led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-one PARP-1 inhibitors which retain low nM cellular activity and show good stability in vivo and efficacy in cell based models.

Authors+Show Affiliations

Cockcroft XL
KuDOS Pharmaceuticals Ltd 327 Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK. xcockcroft@kudospharma.co.uk
Dillon KJ
No affiliation info available
Dixon L
No affiliation info available
Drzewiecki J
No affiliation info available
Kerrigan F
No affiliation info available
Loh VM
No affiliation info available
Martin NM
No affiliation info available
Menear KA
No affiliation info available
Smith GC
No affiliation info available

MeSH

AnimalsCell ProliferationCrystallography, X-RayDrug DesignDrug Evaluation, PreclinicalEnzyme InhibitorsModels, MolecularMolecular StructurePhthalazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsRatsStructure-Activity Relationship

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16290932

Citation

Cockcroft, Xiao-Ling, et al. "Phthalazinones 2: Optimisation and Synthesis of Novel Potent Inhibitors of Poly(ADP-ribose)polymerase." Bioorganic & Medicinal Chemistry Letters, vol. 16, no. 4, 2006, pp. 1040-4.
Cockcroft XL, Dillon KJ, Dixon L, et al. Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly(ADP-ribose)polymerase. Bioorg Med Chem Lett. 2006;16(4):1040-4.
Cockcroft, X. L., Dillon, K. J., Dixon, L., Drzewiecki, J., Kerrigan, F., Loh, V. M., Martin, N. M., Menear, K. A., & Smith, G. C. (2006). Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly(ADP-ribose)polymerase. Bioorganic & Medicinal Chemistry Letters, 16(4), 1040-4.
Cockcroft XL, et al. Phthalazinones 2: Optimisation and Synthesis of Novel Potent Inhibitors of Poly(ADP-ribose)polymerase. Bioorg Med Chem Lett. 2006 Feb 15;16(4):1040-4. PubMed PMID: 16290932.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly(ADP-ribose)polymerase. AU - Cockcroft,Xiao-Ling, AU - Dillon,Krystyna J, AU - Dixon,Lesley, AU - Drzewiecki,Jan, AU - Kerrigan,Frank, AU - Loh,Vincent M,Jr AU - Martin,Niall M B, AU - Menear,Keith A, AU - Smith,Graeme C M, Y1 - 2005/11/15/ PY - 2005/10/05/received PY - 2005/10/19/revised PY - 2005/10/22/accepted PY - 2005/11/18/pubmed PY - 2006/4/28/medline PY - 2005/11/18/entrez SP - 1040 EP - 4 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 16 IS - 4 N2 - We have previously described the discovery of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors based on a phthalazinone scaffold. Subsequent optimisation of inhibitory activity, metabolic stability and pharmacokinetic parameters has led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-one PARP-1 inhibitors which retain low nM cellular activity and show good stability in vivo and efficacy in cell based models. SN - 0960-894X UR - https://www.unboundmedicine.com/medline/citation/16290932/Phthalazinones_2:_Optimisation_and_synthesis_of_novel_potent_inhibitors_of_poly_ADP_ribose_polymerase_ DB - PRIME DP - Unbound Medicine ER -