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Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors.
Bioorg Med Chem Lett. 2009 Aug 01; 19(15):4042-5.BM

Abstract

PARP inhibitors have been demonstrated to retard intracellular DNA repair and therefore sensitize tumor cells to cytotoxic agents or ionizing radiation. We report the identification of a novel class of PARP1 inhibitors, containing a pyrrolo moiety fused to a dihydroisoquinolinone, derived from virtual screening of the proprietary collection. SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay.

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Authors+Show Affiliations

Branca D
IRBM--Merck Research Laboratories Rome, Via Pontina km 30,600-Pomezia, 00040 Rome, Italy. danila_branca@merck.com
Cerretani M
No affiliation info available
Jones P
No affiliation info available
Koch U
No affiliation info available
Orvieto F
No affiliation info available
Palumbi MC
No affiliation info available
Rowley M
No affiliation info available
Toniatti C
No affiliation info available
Muraglia E
No affiliation info available

MeSH

Antineoplastic AgentsBinding SitesChemistry, PharmaceuticalCrystallography, X-RayDNA RepairDrug DesignHumansHydrogen BondingInhibitory Concentration 50LigandsModels, ChemicalPoly(ADP-ribose) Polymerase InhibitorsPolymersQuinolonesStructure-Activity Relationship

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19553107

Citation

Branca, Danila, et al. "Identification of Aminoethyl Pyrrolo Dihydroisoquinolinones as Novel poly(ADP-ribose) Polymerase-1 Inhibitors." Bioorganic & Medicinal Chemistry Letters, vol. 19, no. 15, 2009, pp. 4042-5.
Branca D, Cerretani M, Jones P, et al. Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors. Bioorg Med Chem Lett. 2009;19(15):4042-5.
Branca, D., Cerretani, M., Jones, P., Koch, U., Orvieto, F., Palumbi, M. C., Rowley, M., Toniatti, C., & Muraglia, E. (2009). Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors. Bioorganic & Medicinal Chemistry Letters, 19(15), 4042-5. https://doi.org/10.1016/j.bmcl.2009.06.031
Branca D, et al. Identification of Aminoethyl Pyrrolo Dihydroisoquinolinones as Novel poly(ADP-ribose) Polymerase-1 Inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4042-5. PubMed PMID: 19553107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors. AU - Branca,Danila, AU - Cerretani,Mauro, AU - Jones,Philip, AU - Koch,Uwe, AU - Orvieto,Federica, AU - Palumbi,Maria Cecilia, AU - Rowley,Michael, AU - Toniatti,Carlo, AU - Muraglia,Ester, Y1 - 2009/06/13/ PY - 2009/04/29/received PY - 2009/06/03/revised PY - 2009/06/05/accepted PY - 2009/6/26/entrez PY - 2009/6/26/pubmed PY - 2009/12/16/medline SP - 4042 EP - 5 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 19 IS - 15 N2 - PARP inhibitors have been demonstrated to retard intracellular DNA repair and therefore sensitize tumor cells to cytotoxic agents or ionizing radiation. We report the identification of a novel class of PARP1 inhibitors, containing a pyrrolo moiety fused to a dihydroisoquinolinone, derived from virtual screening of the proprietary collection. SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/19553107/Identification_of_aminoethyl_pyrrolo_dihydroisoquinolinones_as_novel_poly_ADP_ribose__polymerase_1_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(09)00846-4 DB - PRIME DP - Unbound Medicine ER -