Crystal structure and docking studies of hexahydrocycloocta[b]pyridine-3-carbonitriles

R Vishnupriya, A.V.K.M. Kowsalyadevi, Janakiraman Suresh, S Maharani, R Ranjith Kumar


The crystal structures of two new isomorphous pyridine structures, 2-ethoxy-4-(2-flurophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ia) and 2-methoxy-4-(4-isopropylphenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ib) were elucidated by single crystal X ray diffraction. Compound (Ia) C20H21FN2O, crystallizes in the monoclinic system, space group P21/nwith a = 7.0738 (3) Å, b = 17.3519(8) Å, c = 14.4239 (7) Å, b = 91.837 (2)° and Z = 4. The compound (Ib), C22H25N2O, crystallizes in the same crystal system as compound (Ib), space group P21/c with a = 9.7123(6) Å, b = 20.6046(9) Å, c = 10.4657(6) Å,  b = 117.208 (3)° and Z = 4. The central heterocyclic ring adopts a planar conformation and the cyclooctane ring adopts a twisted boat chair conformation in both (Ia) and (Ib).   The synthesized compounds were screened for their anti-tuberculosis activity and were used to identify lead structures through docking studies, by automated docking. This approach was used to determine the orientation of inhibitors bound in the active site with the enzyme N-acetyl-gamma-glutamyl-phosphate reductase that is involved in arginine biosynthesis in M. tuberculosis (MtbAGPR). Details of the preparation, crystal structure determination, intra and inter molecular interactions of the compounds and their docking studies are given.


Twisted boat Chair conformation, Intermolecular interactions, Chain motif, Antituberculosis activity, Molecular docking.


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