Synthesis of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole moiety: their in vitro evaluation against PDE4B.
A number of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole or benzofuran moieties were synthesized by using Pd/C-Cu mediated coupling-cyclization strategy as a key step. The o-iodoanilides or o-iodophenol were coupled with 3-{2-(prop-2-ynyloxy)ethyl}-2H-benzo[e][1,3]oxazin-4(3H)-one using 10%Pd/C-CuI-PPh3 as a catalyst system and Et3N as a base to give the target compounds. All the synthesized compounds were tested for their PDE4B inhibitory potential in vitro using a cell based cAMP reporter assay. Some of them showed fold increase of the cAMP level when tested at 30 μM. A representative compound showed encouraging PDE4B inhibitory properties that were supported by its docking results.
Dr. Reddys Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 046, India.
Raja Mohan
RM
Rao
Department of Chemistry, Acharya Nagarjuna University, Guntur, Andhra Pradesh, India.
Bethala Jawahar
BJ
Luther
Department of Chemistry, Krishna University, Krishna Dist., Andhra Pradesh, India.
Chekuri Sharmila
CS
Rani
Department of Chemistry, Krishna University, Krishna Dist., Andhra Pradesh, India.
Namburi
N
Suresh
Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Ravikumar
R
Kapavarapu
Dr. Reddys Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 046, India.
Kishore V L
KV
Parsa
Department of Chemistry, Krishna University, Krishna Dist., Andhra Pradesh, India. Electronic address: vbrmandava@yahoo.com.
Mandava V Basaveswara
MV
Rao
Dr. Reddys Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 046, India. Electronic address: manojitpal@rediffmail.com.
Manojit
M
Pal
D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007211:Indoles; D010078:Oxazines; C065957:carsalam; C030374:indole; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human
2H-1,3-Benzoxazin-4(3H)-one; Benzofuran; Indole; PDE4; Pd/C