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

1, 1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4

AL Ruchelman, HW Man, R Chen, W Liu, L Lu…

Index: Ruchelman, Alexander L.; Man, Hon-Wah; Chen, Roger; Liu, Wei; Lu, Ling; Cedzik, Dorota; Zhang, Ling; Leisten, Jim; Collette, Alice; Narla, Rama Krishna; Raymon, Heather K.; Muller, George W. Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 21 p. 6356 - 6374

Full Text: HTML

Citation Number: 8

Abstract

A series of 1, 1-diarylalkene derivatives were prepared to optimize the properties of CC- 5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC50= 54nM) and antitubulin activity (HCT-116 IC50= ...

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

~48%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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6-Bromo-2-naphthoic acid Structure

6-Bromo-2-napht...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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6-bromo-N,N-diisopropyl-2-naphthamide Structure

6-bromo-N,N-dii...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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6-Bromo-N-methyl-2-naphthamide Structure

6-Bromo-N-methy...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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N,N-diisopropyl-6-[1-hydroxy-1-(1-trityl-1H-imidazol-4-yl)methyl]-2-naphthamide Structure

N,N-diisopropyl...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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N,N-diisopropyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide Structure

N,N-diisopropyl...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N,N-diisopropyl-2-naphthamide Structure

6-(7-hydroxy-6,...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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3-bromo-1-(1H-imidazol-4-yl)-1-propanone hydrobromide Structure

3-bromo-1-(1H-i...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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1-(1H-imidazol-4-yl)prop-2-en-1-one Structure

1-(1H-imidazol-...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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6-bromonaphthalene-2-carbonyl chloride Structure

6-bromonaphthal...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

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5H-PYRROLO[1,2-C]IMIDAZOL-7(6H)-ONE Structure

5H-PYRROLO[1,2-...

~%

Orteronel Structure

6-[(7R)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide Structure

6-[(7R)-7-hydro...

Learn More

6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N,N-diisopropyl-2-naphthamide Structure

6-(7-hydroxy-6,...

methylamine Structure

~81%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

6-Bromo-2-naphthoic acid Structure

6-Bromo-2-napht...

~%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

6-bromo-N,N-diisopropyl-2-naphthamide Structure

6-bromo-N,N-dii...

~%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

N,N-diisopropyl-6-[1-hydroxy-1-(1-trityl-1H-imidazol-4-yl)methyl]-2-naphthamide Structure

N,N-diisopropyl...

~%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

N,N-diisopropyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide Structure

N,N-diisopropyl...

~%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

1-(1H-imidazol-4-yl)prop-2-en-1-one Structure

1-(1H-imidazol-...

~%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

6-bromonaphthalene-2-carbonyl chloride Structure

6-bromonaphthal...

~%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

6-Bromo-N-methyl-2-naphthamide Structure

6-Bromo-N-methy...

5H-PYRROLO[1,2-C]IMIDAZOL-7(6H)-ONE Structure

5H-PYRROLO[1,2-...

~45%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

3-bromo-1-(1H-imidazol-4-yl)-1-propanone hydrobromide Structure

3-bromo-1-(1H-i...

~%

TAK-700 (Orteronel) Structure

TAK-700 (Orteronel)

Learn More

3-bromo-1-(1H-imidazol-4-yl)-1-propanone hydrobromide Structure

3-bromo-1-(1H-i...

~62%

5H-PYRROLO[1,2-C]IMIDAZOL-7(6H)-ONE Structure

5H-PYRROLO[1,2-...

Learn More

1-(1H-imidazol-4-yl)prop-2-en-1-one Structure

1-(1H-imidazol-...

~%

5H-PYRROLO[1,2-C]IMIDAZOL-7(6H)-ONE Structure

5H-PYRROLO[1,2-...

Learn More