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Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).
Bioorg Med Chem Lett. 2010 Apr 01; 20(7):2250-3.BM

Abstract

Highly potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors, including 9-hydroxy-1,2-dihydro-4H-thiopyrano[3,4-c]quinolin-5(6H)-one derivatives with a non-aromatic A-ring, were synthesized. Among the derivatives, 12a showed low nanomolar enzyme and cellular activity (IC(50) = 42 nM, ED(50) = 220 nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo.

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Authors+Show Affiliations

Park CH
Drug Discovery Laboratory, R&D Center, Jeil Pharmaceutical Co., Ltd. 117-1, Keungok-Ri, Baekam-Myun, Cheoin-Gu, Yongin-City, Kyunggi-Do 449-861, Republic of Korea.
Chun K
No affiliation info available
Joe BY
No affiliation info available
Park JS
No affiliation info available
Kim YC
No affiliation info available
Choi JS
No affiliation info available
Ryu DK
No affiliation info available
Koh SH
No affiliation info available
Cho GW
No affiliation info available
Kim SH
No affiliation info available
Kim MH
No affiliation info available

MeSH

AmidesAnimalsBrainCHO CellsCricetinaeCricetulusEnzyme InhibitorsHumansMicrosomes, LiverModels, MolecularPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesPolycyclic CompoundsRatsStructure-Activity Relationship

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20189385

Citation

Park, Chun-Ho, et al. "Synthesis and Evaluation of Tricyclic Derivatives Containing a Non-aromatic Amide as Inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)." Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 7, 2010, pp. 2250-3.
Park CH, Chun K, Joe BY, et al. Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). Bioorg Med Chem Lett. 2010;20(7):2250-3.
Park, C. H., Chun, K., Joe, B. Y., Park, J. S., Kim, Y. C., Choi, J. S., Ryu, D. K., Koh, S. H., Cho, G. W., Kim, S. H., & Kim, M. H. (2010). Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). Bioorganic & Medicinal Chemistry Letters, 20(7), 2250-3. https://doi.org/10.1016/j.bmcl.2010.02.014
Park CH, et al. Synthesis and Evaluation of Tricyclic Derivatives Containing a Non-aromatic Amide as Inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). Bioorg Med Chem Lett. 2010 Apr 1;20(7):2250-3. PubMed PMID: 20189385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). AU - Park,Chun-Ho, AU - Chun,Kwangwoo, AU - Joe,Bo-Young, AU - Park,Ji-Seon, AU - Kim,Young-Chul, AU - Choi,Ji-Soo, AU - Ryu,Dong-Kyu, AU - Koh,Seong-Ho, AU - Cho,Goang Won, AU - Kim,Seung Hyun, AU - Kim,Myung-Hwa, Y1 - 2010/02/08/ PY - 2009/10/21/received PY - 2010/02/01/revised PY - 2010/02/03/accepted PY - 2010/3/2/entrez PY - 2010/3/2/pubmed PY - 2010/7/6/medline SP - 2250 EP - 3 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 20 IS - 7 N2 - Highly potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors, including 9-hydroxy-1,2-dihydro-4H-thiopyrano[3,4-c]quinolin-5(6H)-one derivatives with a non-aromatic A-ring, were synthesized. Among the derivatives, 12a showed low nanomolar enzyme and cellular activity (IC(50) = 42 nM, ED(50) = 220 nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/20189385/Synthesis_and_evaluation_of_tricyclic_derivatives_containing_a_non_aromatic_amide_as_inhibitors_of_poly_ADP_ribose_polymerase_1__PARP_1__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(10)00204-0 DB - PRIME DP - Unbound Medicine ER -