C-C bond formation at C-2 of a quinoline ring: Synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors

K. Shiva Kumar; S. Kiran Kumar; B. Yogi Sreenivas; Dhilli Rao Gorja; Ravikumar Kapavarapu; D. Rambabu; G. Rama Krishna; C. Malla Reddy; M. V. Basaveswara Rao; Kishore V.L. Parsa; Manojit Pal

doi:10.1016/j.bmc.2012.02.027

C-C bond formation at C-2 of a quinoline ring: Synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors

K. Shiva Kumar, S. Kiran Kumar, B. Yogi Sreenivas, Dhilli Rao Gorja, Ravikumar Kapavarapu, D. Rambabu, G. Rama Krishna, C. Malla Reddy, M. V. Basaveswara Rao, Kishore V.L. Parsa, Manojit Pal

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl ₃-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC ₅₀ ∼0.89 μM) is presented.

Original language	English
Pages (from-to)	2199-2207
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	7
DOIs	https://doi.org/10.1016/j.bmc.2012.02.027
State	Published - 1 Apr 2012
Externally published	Yes

Keywords

AlCl
Indole
PDE4
Quinoline
X-ray

ASJC Scopus subject areas

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

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10.1016/j.bmc.2012.02.027

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Kumar, K. S., Kiran Kumar, S., Yogi Sreenivas, B., Gorja, D. R., Kapavarapu, R., Rambabu, D., Rama Krishna, G., Reddy, C. M., Basaveswara Rao, M. V., Parsa, K. V. L., & Pal, M. (2012). C-C bond formation at C-2 of a quinoline ring: Synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors. Bioorganic and Medicinal Chemistry, 20(7), 2199-2207. https://doi.org/10.1016/j.bmc.2012.02.027

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title = "C-C bond formation at C-2 of a quinoline ring: Synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors",

abstract = "A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl 3-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC 50 ∼0.89 μM) is presented.",

keywords = "AlCl, Indole, PDE4, Quinoline, X-ray",

author = "Kumar, {K. Shiva} and {Kiran Kumar}, S. and {Yogi Sreenivas}, B. and Gorja, {Dhilli Rao} and Ravikumar Kapavarapu and D. Rambabu and {Rama Krishna}, G. and Reddy, {C. Malla} and {Basaveswara Rao}, {M. V.} and Parsa, {Kishore V.L.} and Manojit Pal",

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doi = "10.1016/j.bmc.2012.02.027",

language = "English",

volume = "20",

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journal = "Bioorganic and Medicinal Chemistry",

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Kumar, KS, Kiran Kumar, S, Yogi Sreenivas, B, Gorja, DR, Kapavarapu, R, Rambabu, D, Rama Krishna, G, Reddy, CM, Basaveswara Rao, MV, Parsa, KVL & Pal, M 2012, 'C-C bond formation at C-2 of a quinoline ring: Synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors', Bioorganic and Medicinal Chemistry, vol. 20, no. 7, pp. 2199-2207. https://doi.org/10.1016/j.bmc.2012.02.027

TY - JOUR

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T2 - Synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors

AU - Kumar, K. Shiva

AU - Kiran Kumar, S.

AU - Yogi Sreenivas, B.

AU - Gorja, Dhilli Rao

AU - Kapavarapu, Ravikumar

AU - Rambabu, D.

AU - Rama Krishna, G.

AU - Reddy, C. Malla

AU - Basaveswara Rao, M. V.

AU - Parsa, Kishore V.L.

AU - Pal, Manojit

PY - 2012/4/1

Y1 - 2012/4/1

N2 - A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl 3-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC 50 ∼0.89 μM) is presented.

AB - A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl 3-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC 50 ∼0.89 μM) is presented.

KW - AlCl

KW - Indole

KW - PDE4

KW - Quinoline

KW - X-ray

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SN - 0968-0896

VL - 20

SP - 2199

EP - 2207

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 7

ER -

C-C bond formation at C-2 of a quinoline ring: Synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors

Abstract

Keywords

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