Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors

Dhilli Rao Gorja; Soumita Mukherjee; Chandana Lakshmi T Meda; Girdhar Singh Deora; K. Lalith Kumar; Ankit Jain; Girish H. Chaudhari; Keerthana Sarma Chennubhotla; Rakesh K. Banote; Pushkar Kulkarni; Kishore V L Parsa; K. Mukkanti; Manojit Pal

doi:10.1039/c3ob27424a

Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors

Dhilli Rao Gorja, Soumita Mukherjee, Chandana Lakshmi T Meda, Girdhar Singh Deora, K. Lalith Kumar, Ankit Jain, Girish H. Chaudhari, Keerthana Sarma Chennubhotla, Rakesh K. Banote, Pushkar Kulkarni, Kishore V L Parsa, K. Mukkanti, Manojit Pal

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29 Citations (Scopus)

Abstract

A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC₅₀ 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.

Original language	English
Pages (from-to)	2075-2079
Number of pages	5
Journal	Organic & Biomolecular Chemistry
Volume	11
Issue number	13
DOIs	https://doi.org/10.1039/c3ob27424a
Publication status	Published - 7 Apr 2013
Externally published	Yes

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Gorja, D. R., Mukherjee, S., Meda, C. L. T., Deora, G. S., Lalith Kumar, K., Jain, A., Chaudhari, G. H., Chennubhotla, K. S., Banote, R. K., Kulkarni, P., Parsa, K. V. L., Mukkanti, K., & Pal, M. (2013). Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors. Organic & Biomolecular Chemistry, 11(13), 2075-2079. https://doi.org/10.1039/c3ob27424a

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title = "Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors",

abstract = "A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.",

author = "Gorja, {Dhilli Rao} and Soumita Mukherjee and Meda, {Chandana Lakshmi T} and Deora, {Girdhar Singh} and {Lalith Kumar}, K. and Ankit Jain and Chaudhari, {Girish H.} and Chennubhotla, {Keerthana Sarma} and Banote, {Rakesh K.} and Pushkar Kulkarni and Parsa, {Kishore V L} and K. Mukkanti and Manojit Pal",

year = "2013",

month = apr,

day = "7",

doi = "10.1039/c3ob27424a",

language = "English",

volume = "11",

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journal = "Organic & Biomolecular Chemistry",

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Gorja, DR, Mukherjee, S, Meda, CLT, Deora, GS, Lalith Kumar, K, Jain, A, Chaudhari, GH, Chennubhotla, KS, Banote, RK, Kulkarni, P, Parsa, KVL, Mukkanti, K & Pal, M 2013, 'Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors', Organic & Biomolecular Chemistry, vol. 11, no. 13, pp. 2075-2079. https://doi.org/10.1039/c3ob27424a

TY - JOUR

T1 - Novel N-indolylmethyl substituted olanzapine derivatives

T2 - their design, synthesis and evaluation as PDE4B inhibitors

AU - Gorja, Dhilli Rao

AU - Mukherjee, Soumita

AU - Meda, Chandana Lakshmi T

AU - Deora, Girdhar Singh

AU - Lalith Kumar, K.

AU - Jain, Ankit

AU - Chaudhari, Girish H.

AU - Chennubhotla, Keerthana Sarma

AU - Banote, Rakesh K.

AU - Kulkarni, Pushkar

AU - Parsa, Kishore V L

AU - Mukkanti, K.

AU - Pal, Manojit

PY - 2013/4/7

Y1 - 2013/4/7

N2 - A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.

AB - A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.

UR - http://www.scopus.com/inward/record.url?scp=84874873978&partnerID=8YFLogxK

U2 - 10.1039/c3ob27424a

DO - 10.1039/c3ob27424a

M3 - Article

C2 - 23436140

AN - SCOPUS:84874873978

SN - 1477-0520

VL - 11

SP - 2075

EP - 2079

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 13

ER -

Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors

Abstract

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