Pd-mediated functionalization of polysubstituted pyrroles: Their evaluation as potential inhibitors of PDE4

T. Bhaskar Kumar; Ch Sumanth; S. Vaishaly; M. Srinivasa Rao; K. B. Chandra Sekhar; Chandana Lakshmi T. Meda; Ajit Kandale; D. Rambabu; G. Rama Krishna; C. Malla Reddy; K. Shiva Kumar; Kishore V.L. Parsa; Manojit Pal

doi:10.1016/j.bmcl.2012.06.100

Pd-mediated functionalization of polysubstituted pyrroles: Their evaluation as potential inhibitors of PDE4

T. Bhaskar Kumar, Ch Sumanth, S. Vaishaly, M. Srinivasa Rao, K. B. Chandra Sekhar, Chandana Lakshmi T. Meda, Ajit Kandale, D. Rambabu, G. Rama Krishna, C. Malla Reddy, K. Shiva Kumar, Kishore V.L. Parsa, Manojit Pal

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17 Scopus citations

Abstract

Novel polysubstituted pyrroles have been designed and accessed via a one-pot multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All the compounds synthesized were tested for their PDE4B inhibitory properties in vitro and two of them obtained via Heck reaction showed significant inhibition. The docking results suggested that these alkenyl derivatives containing ester moiety interact well with the PDE4B protein in silico where the ester carbonyl oxygen played a key role. The pyrrole framework presented here could be a new template for the identification of small molecule based novel inhibitors of PDE4. The single crystal X-ray data of a representative compound is presented.

Original language	English
Pages (from-to)	5639-5647
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2012.06.100
State	Published - 1 Sep 2012
Externally published	Yes

Keywords

Coupling
MCR
PDE4
Palladium
Pyrrole

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Bhaskar Kumar, T., Sumanth, C., Vaishaly, S., Srinivasa Rao, M., Chandra Sekhar, K. B., Meda, C. L. T., Kandale, A., Rambabu, D., Rama Krishna, G., Malla Reddy, C., Shiva Kumar, K., Parsa, K. V. L., & Pal, M. (2012). Pd-mediated functionalization of polysubstituted pyrroles: Their evaluation as potential inhibitors of PDE4. Bioorganic and Medicinal Chemistry Letters, 22(17), 5639-5647. https://doi.org/10.1016/j.bmcl.2012.06.100

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title = "Pd-mediated functionalization of polysubstituted pyrroles: Their evaluation as potential inhibitors of PDE4",

abstract = "Novel polysubstituted pyrroles have been designed and accessed via a one-pot multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All the compounds synthesized were tested for their PDE4B inhibitory properties in vitro and two of them obtained via Heck reaction showed significant inhibition. The docking results suggested that these alkenyl derivatives containing ester moiety interact well with the PDE4B protein in silico where the ester carbonyl oxygen played a key role. The pyrrole framework presented here could be a new template for the identification of small molecule based novel inhibitors of PDE4. The single crystal X-ray data of a representative compound is presented.",

keywords = "Coupling, MCR, PDE4, Palladium, Pyrrole",

author = "{Bhaskar Kumar}, T. and Ch Sumanth and S. Vaishaly and {Srinivasa Rao}, M. and {Chandra Sekhar}, {K. B.} and Meda, {Chandana Lakshmi T.} and Ajit Kandale and D. Rambabu and {Rama Krishna}, G. and {Malla Reddy}, C. and {Shiva Kumar}, K. and Parsa, {Kishore V.L.} and Manojit Pal",

year = "2012",

month = sep,

day = "1",

doi = "10.1016/j.bmcl.2012.06.100",

language = "English",

volume = "22",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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Bhaskar Kumar, T, Sumanth, C, Vaishaly, S, Srinivasa Rao, M, Chandra Sekhar, KB, Meda, CLT, Kandale, A, Rambabu, D, Rama Krishna, G, Malla Reddy, C, Shiva Kumar, K, Parsa, KVL & Pal, M 2012, 'Pd-mediated functionalization of polysubstituted pyrroles: Their evaluation as potential inhibitors of PDE4', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 17, pp. 5639-5647. https://doi.org/10.1016/j.bmcl.2012.06.100

TY - JOUR

T1 - Pd-mediated functionalization of polysubstituted pyrroles

T2 - Their evaluation as potential inhibitors of PDE4

AU - Bhaskar Kumar, T.

AU - Sumanth, Ch

AU - Vaishaly, S.

AU - Srinivasa Rao, M.

AU - Chandra Sekhar, K. B.

AU - Meda, Chandana Lakshmi T.

AU - Kandale, Ajit

AU - Rambabu, D.

AU - Rama Krishna, G.

AU - Malla Reddy, C.

AU - Shiva Kumar, K.

AU - Parsa, Kishore V.L.

AU - Pal, Manojit

PY - 2012/9/1

Y1 - 2012/9/1

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AB - Novel polysubstituted pyrroles have been designed and accessed via a one-pot multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All the compounds synthesized were tested for their PDE4B inhibitory properties in vitro and two of them obtained via Heck reaction showed significant inhibition. The docking results suggested that these alkenyl derivatives containing ester moiety interact well with the PDE4B protein in silico where the ester carbonyl oxygen played a key role. The pyrrole framework presented here could be a new template for the identification of small molecule based novel inhibitors of PDE4. The single crystal X-ray data of a representative compound is presented.

KW - Coupling

KW - MCR

KW - PDE4

KW - Palladium

KW - Pyrrole

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U2 - 10.1016/j.bmcl.2012.06.100

DO - 10.1016/j.bmcl.2012.06.100

M3 - Article

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SN - 0960-894X

VL - 22

SP - 5639

EP - 5647

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 17

ER -

Pd-mediated functionalization of polysubstituted pyrroles: Their evaluation as potential inhibitors of PDE4

Abstract

Keywords

ASJC Scopus subject areas

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