e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1, 7] and [1, 8] naphthyridine-3-carbonitriles

…, PR Hamann, R Nilakantan, LM Greenberger…

Index: Wissner, Allan; Hamann, Philip R.; Nilakantan, Ramaswamy; Greenberger, Lee M.; Ye, Fei; Rapuano, Timothy A.; Loganzo, Frank Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 6 p. 1411 - 1416

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Citation Number: 23

Abstract

The syntheses and EGFR kinase inhibitory activity of a series of 6-substituted-4-anilino [1, 7] and [1, 8] naphthyridine-3-carbonitriles are described. Both reversible and irreversible binding inhibitors were prepared. These series were compared with each other and with the corresponding 4-anilinoquinoline-3-carbonitriles. Compounds having a 1, 7-naphthyridine core structure can retain high potency while those with a 1, 8-naphthyridine core are ...

4-hydroxy-6-nitro-1,8-naphthyridine-3-carbonitrile Structure

4-hydroxy-6-nit...

~70%

4-chloro-6-nitro-1,8-naphthyridine-3-carbonitrile Structure

4-chloro-6-nitr...

2-Chloro-5-nitronicotinic acid Structure

2-Chloro-5-nitr...

~%

4-chloro-6-nitro-1,8-naphthyridine-3-carbonitrile Structure

4-chloro-6-nitr...

2-chloro-5-nitronicotinoyl chloride Structure

2-chloro-5-nitr...

~%

4-chloro-6-nitro-1,8-naphthyridine-3-carbonitrile Structure

4-chloro-6-nitr...

2-Fluoro-5-nitropyridine Structure

2-Fluoro-5-nitr...

~%

methyl 2-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyridine-4-carboxylate Structure

methyl 2-fluoro...

2-Chloro-5-nitropyridine Structure

2-Chloro-5-nitr...

~%

methyl 2-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyridine-4-carboxylate Structure

methyl 2-fluoro...

5-Amino-2-fluoropyridine Structure

5-Amino-2-fluor...

~%

methyl 2-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyridine-4-carboxylate Structure

methyl 2-fluoro...

Boc-5-Amino-2-fluoropyridine Structure

Boc-5-Amino-2-f...

~%

methyl 2-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyridine-4-carboxylate Structure

methyl 2-fluoro...

2-Fluoro-5-nitropyridine Structure

2-Fluoro-5-nitr...

~%

6-fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile Structure

6-fluoro-4-hydr...

2-Chloro-5-nitropyridine Structure

2-Chloro-5-nitr...

~%

6-fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile Structure

6-fluoro-4-hydr...

5-Amino-2-fluoropyridine Structure

5-Amino-2-fluor...

~%

6-fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile Structure

6-fluoro-4-hydr...

Boc-5-Amino-2-fluoropyridine Structure

Boc-5-Amino-2-f...

~%

6-fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile Structure

6-fluoro-4-hydr...

5-((TERT-BUTOXYCARBONYL)AMINO)-2-FLUOROISONICOTINIC ACID Structure

5-((TERT-BUTOXY...

~%

6-fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile Structure

6-fluoro-4-hydr...

methyl 2-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyridine-4-carboxylate Structure

methyl 2-fluoro...

~%

6-fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile Structure

6-fluoro-4-hydr...

2-Fluoro-5-nitropyridine Structure

2-Fluoro-5-nitr...

~%

4-chloro-6-fluoro-1,7- Structure

4-chloro-6-fluo...

2-Chloro-5-nitropyridine Structure

2-Chloro-5-nitr...

~%

4-chloro-6-fluoro-1,7- Structure

4-chloro-6-fluo...

5-Amino-2-fluoropyridine Structure

5-Amino-2-fluor...

~%

4-chloro-6-fluoro-1,7- Structure

4-chloro-6-fluo...

Boc-5-Amino-2-fluoropyridine Structure

Boc-5-Amino-2-f...

~%

4-chloro-6-fluoro-1,7- Structure

4-chloro-6-fluo...

5-((TERT-BUTOXYCARBONYL)AMINO)-2-FLUOROISONICOTINIC ACID Structure

5-((TERT-BUTOXY...

~%

4-chloro-6-fluoro-1,7- Structure

4-chloro-6-fluo...

methyl 2-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyridine-4-carboxylate Structure

methyl 2-fluoro...

~%

4-chloro-6-fluoro-1,7- Structure

4-chloro-6-fluo...

[6-FLUORO-4-(3-NITRILOPROPIONYL)PYRIDIN-3-YL]CARBAMIC ACID TERT-BUTYL ESTER Structure

[6-FLUORO-4-(3-...

~%

4-chloro-6-fluoro-1,7- Structure

4-chloro-6-fluo...

2-Fluoro-5-nitropyridine Structure

2-Fluoro-5-nitr...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

2-Chloro-5-nitropyridine Structure

2-Chloro-5-nitr...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

5-Amino-2-fluoropyridine Structure

5-Amino-2-fluor...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

Boc-5-Amino-2-fluoropyridine Structure

Boc-5-Amino-2-f...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

5-((TERT-BUTOXYCARBONYL)AMINO)-2-FLUOROISONICOTINIC ACID Structure

5-((TERT-BUTOXY...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

6-fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile Structure

6-fluoro-4-hydr...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

methyl 2-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyridine-4-carboxylate Structure

methyl 2-fluoro...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

[6-FLUORO-4-(3-NITRILOPROPIONYL)PYRIDIN-3-YL]CARBAMIC ACID TERT-BUTYL ESTER Structure

[6-FLUORO-4-(3-...

~%

4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile Structure

4-(3-chloro-4-f...

2-Fluoro-5-nitropyridine Structure

2-Fluoro-5-nitr...

~%

5-((TERT-BUTOXYCARBONYL)AMINO)-2-FLUOROISONICOTINIC ACID Structure

5-((TERT-BUTOXY...

2-Chloro-5-nitropyridine Structure

2-Chloro-5-nitr...

~%

5-((TERT-BUTOXYCARBONYL)AMINO)-2-FLUOROISONICOTINIC ACID Structure

5-((TERT-BUTOXY...