Synthesis of N-ω-phenylalkyl-4-(p-chlorophenyl)-piperidin-4-ol analogues with potent antiproliferative activity against HCT-116 cells

Article abstract of DOI:10.3987/COM-18-S(T)25

Some opioid analogues, such as morphine and loperamide, were reported to exhibit weak antiproliferative activity against tumor cells. In a study of loperamide analogues, we found that adding an N-ω-phenylalkyl group onto the 4-arylpiperidin-4-ol unit can have important effects on the antiproliferative activity of such compounds against HCT-116 cells. We optimized the distance between the phenyl group and 4-arylpiperidin unit to promote such activity.

Full text of DOI:10.3987/COM-18-S(T)25

Synthesis of N-ω-phenylalkyl-4-(p-chlorophenyl)-piperidin-4-ol analogues with potent
antiproliferative activities against HCT-116 cells
Noriyuki Hataea*, Eiko Kujimeb, Keigo Yanob, Mami Kizukaa, Rina Ashidaa, Tominari Choshic,
Takashi Nishiyamac, Chiaki Okadaa, Tatsunori Iwamurab, and Teruki Yoshimuraa*
aSchool of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu,
b
Hokkaido 061-0293, Japan, Department of medicinal chemistry, Faculty of Pharmaceutical
c
Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama 790-8578, Japan, Graduate School
of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Faculty of Pharmacy and
Pharmaceutical Sciences, Fukuyama, Hiroshima 729-0292, Japan:
Supporting Information
Spectral data for N-ω-phenylalkyl-4-(p-chlorophenyl)-piperidin-4-ol analogues S2-S15
S1

1H NMR for (4-chlorobutyl)benzene (5d)
13C NMR for (4-chlorobutyl)benzene (5d)
S2

1H NMR for (5-Chloropentyl)benzene (5e)
13C NMR for (5-Chloropentyl)benzene (5e)
S3

1H NMR for (6-Chlorohexyl)benzene (5f)
13C NMR for (6-Chlorohexyl)benzene (5f)
S4

1H NMR for N-benzyl-4-(p-chlorophenyl)piperidin-4-ol (7a)
13C NMR for N-benzyl-4-(p-chlorophenyl)piperidin-4-ol (7a)
S5

1H NMR for 4-(p-Chlorophenyl)-1-phenethylpiperidin-4-ol (7b)
13C NMR for 4-(p-Chlorophenyl)-1-phenethylpiperidin-4-ol (7b)
S6

1H NMR for 4-(p-Chlorophenyl)-1-(3-phenylpropyl)piperidin-4-ol (7c)
13C NMR for 4-(p-Chlorophenyl)-1-(3-phenylpropyl)piperidin-4-ol (7c)
S7

1H NMR for 4-(p-Chlorophenyl)-1-(4-phenylbutyl)piperidin-4-ol (7d)
13C NMR for 4-(p-Chlorophenyl)-1-(4-phenylbutyl)piperidin-4-ol (7d)
S8

1H NMR for 4-(p-Chlorophenyl)-1-(5-phenylpentyl)piperidin-4-ol (7e)
13C NMR for 4-(p-Chlorophenyl)-1-(5-phenylpentyl)piperidin-4-ol (7e)
S9

1H NMR for 4-(p-Chlorophenyl)-1-(6-phenylhexyl)piperidin-4-ol (7f)
13C NMR for 4-(p-Chlorophenyl)-1-(6-phenylhexyl)piperidin-4-ol (7f)
S10

1H NMR for 4-(p-Chlorophenyl)-1-(7-phenylheptyl)piperidin-4-ol (7g)
13C NMR for 4-(p-Chlorophenyl)-1-(7-phenylheptyl)piperidin-4-ol (7g)
S11

1H NMR for 4-(p-Chlorophenyl)-1-(8-phenyloctyl)piperidin-4-ol (7h)
13C NMR for 4-(p-Chlorophenyl)-1-(8-phenyloctyl)piperidin-4-ol (7h)
S12

1H NMR for 4-(p-Chlorophenyl)-1-(9-phenylnonyl)piperidin-4-ol (7i)
13C NMR for 4-(p-Chlorophenyl)-1-(9-phenylnonyl)piperidin-4-ol (7i)
S13

1H NMR for 4-(p-Chlorophenyl)-1-(10-phenyldecyl)piperidin-4-ol (7j)
13C NMR for 4-(p-Chlorophenyl)-1-(10-phenyldecyl)piperidin-4-ol (7j)
S14

1H NMR for 4-(p-Chlorophenyl)-1-(11-phenylundecyl)piperidin-4-ol (7k)
13C NMR for 4-(p-Chlorophenyl)-1-(11-phenylundecyl)piperidin-4-ol (7k)
S15