Synthesis of nicotinonitrile derivatives as a new class of NLO materials

Disclosed are quinoline derivatives as hedgehog pathway inhibitors, especially as SMO inhibitors. Compounds of the present invention can be used in treating diseases relating to hedgehog pathway including cancer.

Quinoline derivatives as smo inhibitors

DFT calculations of the tautomerization and NLO properties of 5-amino-7-(pyrrolidin-1-yl)-2,4,4-trimethyl-1,4-dihydro-1,6-naphthyridine-8-carbonitrile (APNC)

Bioactive 1,6-naphthyridines were constructed through a one pot multicomponent method by reacting different ketones with malononitrile and pyrrolidine. In vitro anti-inflammatory and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activities for all the synthesized 1,6-naphthyridines were further carried out. These results clearly show that compound 3e exhibited excellent anti-inflammatory activity with a percentage inhibition of 81.24 ± 4.46 by membrane stabilization method and 77.85 ± 0.46 by the albumin denaturation method at a concentration of 100 μg ml−1, which is comparable to the standard diclofenac. A noticeable DPPH scavenging activity of 82.08 ± 1.81% was also observed for the synthesized compound 3e when compared with the standard, ascorbic acid.

Domino synthesis of functionalized 1,6-naphthyridines and their in vitro anti-inflammatory and anti-oxidant efficacies

Six-Membered Azaheterocycles Based on 1,3-Binucleophiles

In the title compounds, C17H15N3 and C20H22N4, the methyl derivative crystallizes with two mol­ecules in the asymmetric unit, while the N,N-diethyl­amino derivative crystallizes with one mol­ecule per asymmetric unit. The bi­phenyl twist angle for both mol­ecular structures is approximately 45°. The molecular packing is stabilized by N—H⋯N hydrogen bonds.

3-amino-4'-methyl-5-ethylbiphenyl-2,4-dicarbonitrile and 3-amino-4'-(n,n-diethylamino)-5-ethylbiphenyl-2,4-dicarbonitrile.

In the crystal of the title compound, C 26 H 23 N 5 O, there are two independent molecules in the asymmetric unit. The naphthyridine moiety in both molecules is slightly folded. The dihedral angles between the fused pyridine rings in the molecules are 5.7(1) and 8.2(1)°, respectively. The pyrrolidine ring in both molecules adopts a half-chair conformation. The molecular structure is stabilized by a C-H...N-type intramolecular hydrogen bond within the two molecules in the asymmetric unit and the packing is stabilized by intermolecular N-H…O hydrogen bonds.

http://journals.iucr.org/c/issues/1999/10/00/na1423/na1423.pdf

5‐Amino‐4‐(4‐methoxyphenyl)‐2‐phenyl‐7‐(pyrrolidin‐1‐yl)‐1,6‐naphthyridine‐8‐carbonitrile

The title compound [CCDC 199359], C 1 6 H 2 0 N 5 crystallized in Monoclinic system with the space group C2/c. The unit cell parameters are: a = 16.554(6), b = 12.145(4), c = 16.221(5)A and β = 102.67(1)°. The molecular structure is stabilized by an intramolecular C-H...N type hydrogen bond and the molecular packing by the intermolecular C-H...N and N-H...N type hydrogen bonds.

Crystal structure analysis of 5‐amino‐7‐(pyrrolidin‐1‐yl)‐2,4,4‐trimethyl‐1,4‐dihydro‐1,6‐naphthyridine‐8‐carbonitrile

The title compound, C24H23ClN4, crystallizes in space group P\overline 1, with two crystallographically independent mol­ecules in the asymmetric unit. In both mol­ecules, the pyrrolidine ring adopts a half-chair conformation. The molecular packing in the crystal is stabilized by intermolecular C—H⋯N hydrogen bonds, through the formation of hydrogen-bonded molecular chains.

6-(4-Chloro­phenyl)-4-[4-(di­methyl­amino)­phenyl]-2-(pyrrolidin-1-yl)­nicotino­nitrile

The pyrrolidine ring in the title mol­ecule, C23H21N3O, adopts a half-chair conformation. In the solid state, C—H⋯N intermolecular hydrogen bonds link inversion-related mol­ecules, forming cyclic dimers. The structure is further stabilized by weak C—H⋯O hydrogen bonds and van der Waals forces.

V. Raghukumar

Papers

3-amino-4'-methyl-5-ethylbiphenyl-2,4-dicarbonitrile and 3-amino-4'-(n,n-diethylamino)-5-ethylbiphenyl-2,4-dicarbonitrile.

5‐Amino‐4‐(4‐methoxyphenyl)‐2‐phenyl‐7‐(pyrrolidin‐1‐yl)‐1,6‐naphthyridine‐8‐carbonitrile

Crystal structure analysis of 5‐amino‐7‐(pyrrolidin‐1‐yl)‐2,4,4‐trimethyl‐1,4‐dihydro‐1,6‐naphthyridine‐8‐carbonitrile

6-(4-Chlorophenyl)-4-[4-(dimethylamino)phenyl]-2-(pyrrolidin-1-yl)nicotinonitrile

6-(4-Methoxyphenyl)-4-phenyl-2-(pyrrolidin-1-yl)nicotinonitrile

V. Raghukumar

Papers

3-amino-4'-methyl-5-ethylbiphenyl-2,4-dicarbonitrile and 3-amino-4'-(n,n-diethylamino)-5-ethylbiphenyl-2,4-dicarbonitrile.

5‐Amino‐4‐(4‐methoxyphenyl)‐2‐phenyl‐7‐(pyrrolidin‐1‐yl)‐1,6‐naphthyridine‐8‐carbonitrile

Crystal structure analysis of 5‐amino‐7‐(pyrrolidin‐1‐yl)‐2,4,4‐trimethyl‐1,4‐dihydro‐1,6‐naphthyridine‐8‐carbonitrile

6-(4-Chloro­phenyl)-4-[4-(di­methyl­amino)­phenyl]-2-(pyrrolidin-1-yl)­nicotino­nitrile

6-(4-Methoxy­phenyl)-4-phenyl-2-(pyrrolidin-1-yl)­nicotino­nitrile

6-(4-Chlorophenyl)-4-[4-(dimethylamino)phenyl]-2-(pyrrolidin-1-yl)nicotinonitrile

6-(4-Methoxyphenyl)-4-phenyl-2-(pyrrolidin-1-yl)nicotinonitrile