R. Grzywa et al. / Bioorg. Med. Chem. 18 (2010) 2930–2936
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3H, CH3), 1.37–1.44 (m, 1H, CH2CH3), 1.72–1.76 (m, 1H, CH2CH3),
2.09 (d, J = 18.61 Hz, 6H, 2 ꢁ CH3), 2.71–2.76 (m, 1H, CHP), 6.75–
7.01 (m, 3H, Ar–H).
Compound 4d, 1-aminopropylphosphonic acid mono-(4-t-
butylphenyl) ester: White solid; mp 236–237 °C; HRMS m/z
271.1337/272.1409 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
24.49 (s); 1H NMR (300 MHz, D2O, ppm): d 0.88 (t, J = 15.01 Hz,
3H, CH3), 1.44 (s, 9H, 3 ꢁ CH3), 1.35–1.40 (m, 1H, CH2CH3), 1.67–
1.73 (m, 1H, CH2CH3), 2.64–2.72 (m, 1H, CHP), 6.96–7.32 (m, 4H,
Ar–H).
2.47–2.70 (m, 1H, PhCH2CH2), 2.64–2.77 (m, 1H, PhCH2CH2),
2.64–2.77 (m, 1H, PCHCH2), 6.59–7.20 (m, 7H, Ar–H).
Compound 6c, 1-amino-3-phenylpropylphosphonic acid mono-
(2,3,5-trimethylphenyl) ester: Obtained as a hydrobromide salt;
white solid; mp 201 °C; HRMS m/z 333.1494/356.1361 (M+Na)+;
31P NMR (300 MHz, D2O, ppm): d 23.70 (s); 1H NMR (300 MHz,
D2O, ppm): d 1.55–1.71 (m, 1H, PhCH2CH2), 1.89–2.02 (m, 1H,
PhCH2CH2), 1.89–2.02 (m, 9H, 3 ꢁ ArCH3), 2.47–2.57 (m, 1H,
PhCH2CH2), 2.69–2.78 (m, 1H, PhCH2CH2), 2.69–2.78 (m, 1H,
PCHCH2), 6.57–7.17 (m, 6H, Ar–H).
Compound 4e, 1-aminopropylphosphonic acid mono-(4-car-
boxyphenyl) ester: White solid; mp 180–184 °C; HRMS m/z
259.0610/260.0740 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
24.59 (s); 1H NMR (300 MHz, D2O, ppm): d 0.83–0.88 (m, 3H,
CH3), 1.31–1.47 (m, 1H, CH2CH3), 1.68–1.77 (m, 1H, CH2CH3),
2.68–2.72 (m, 1H, CHP), 6.40–6.44 (m, 2H, Ar–H), 7.51–7.54 (m,
2H, Ar–H).
Compound 5a, 1-aminopentylphosphonic acid mono-(4-me-
thylphenyl) ester: White solid; mp 235 °C; HRMS m/z 257.1181/
258.1259 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d 24.76 (s); 1H
Compound 6d, 1-amino-3-phenylpropylphosphonic acid mono-
(4-ethylphenyl) ester: White solid; mp 213 °C; HRMS m/z
319.1337/320.1416 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
21.91 (s); 1H NMR (300 MHz, D2O, ppm): d 0.89–0.94 (m, 3H,
ArCH2CH3), 1.31–1.49 (m, 1H, PhCH2CH2), 1.77–1.91 (m, 1H,
PhCH2CH2), 2.28–2.53 (m, 1H, PhCH2CH2), 2.28–2.53 (m, 2H,
ArCH2CH3), 2.58–2.73 (m, 1H, PhCH2CH2), 2.58–2.73 (m, 1H,
PCHCH2), 6.34–7.19 (m, 9H, Ar–H).
Compound 6e, 1-amino-3-phenylpropylphosphonic acid mono-
(4-isopropylphenyl) ester: Obtained as a hydrobromide salt; white
solid; mp 231–233 °C; HRMS m/z 333.1494/334.1558 (M+1)+; 31P
NMR (300 MHz, D2O, ppm): d 23.89 (s); 1H NMR (300 MHz, D2O,
ppm): d 1.00 (d, J = 6.90 Hz, 6H, 2 ꢁ CHCH3), 1.54–1.70 (m, 1H,
PhCH2CH2), 1.84–1.98 (m, 1H, PhCH2CH2), 2.46–2.56 (m, 1H,
PhCH2CH2), 2.63–2.77 (m, 1H, PhCH2CH2), 2.63–2.77 (m, 1H,
PCHCH2), 2.63–2.77 (m, 1H, ArCH), 6.78–7.20 (m, 9H, Ar–H).
Compound 6f, 1-amino-3-phenylpropylphosphonic acid mono-
(4-t-butylphenyl) ester: Yellow oil; HRMS m/z 347.1650/348.1967
(M+1)+; 31P NMR (300 MHz, D2O, ppm): d 23.70 (s); 1H NMR
(300 MHz, D2O, ppm): d 1.00 (s, 9H, ArC(CH3)3), 1.35–1.50 (m,
1H, PhCH2CH2), 1.75–1.89 (m, 1H, PhCH2CH2), 2.28–2.50 (m, 1H,
PhCH2CH2), 2.62–2.76 (m, 1H, PhCH2CH2), 2.28–2.50 (m, 1H,
PCHCH2), 6.34–7.17 (m, 9H, Ar–H).
Compound 6g, 1-amino-3-phenylpropylphosphonic acid mono-
(4-methoxyphenyl) ester: Obtained as a hydrobromide salt; white
solid; mp 236 °C; HRMS m/z 321.1130/322.1170 (M+1)+; 31P NMR
(300 MHz, D2O, ppm): d 24.14 (s); 1H NMR (300 MHz, D2O, ppm):
d 1.56–1.71 (m, 1H, PhCH2CH2), 1.86–2.00 (m, 1H, PhCH2CH2),
2.42–2.58 (m, 1H, PhCH2CH2), 2.68–2.79 (m, 1H, PhCH2CH2),
2.68–2.79 (m, 1H, PCHCH2), 3.59 (d, J = 18.9 Hz, 3H, ArOCH3),
6.31–7.21 (m, 9H, Ar–H).
Compound 6h, 1-amino-3-phenylpropylphosphonic acid mono-
(4-carboxyphenyl) ester: White solid; mp 164–166 °C; HRMS m/z
335.0923/336.1001 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
21.86 (s); 1H NMR (300 MHz, D2O, ppm): d 1.40–1.53 (m, 1H,
PhCH2CH2), 1.83–1.96 (m, 1H, PhCH2CH2), 2.35–2.53 (m, 1H,
PhCH2CH2), 2.35–2.53 (m, 1H, PCHCH2), 2.69–2.79 (m, 1H,
PhCH2CH2), 6.40–7.52 (m, 9H, Ar–H).
NMR (300 MHz, D2O, ppm):
d
0.68 (t, J = 13.21 Hz, 3H,
CH3(CH2)3CHP), 1.02–1.34 (m, 5H, CH3(CH2)3CHP), 1.51–1.69 (m,
1H, CH3(CH2)2CH2CHP), 1.97–2.10 (m, 3H, ArCH3), 2.67–2.75 (m,
1H, PCHCH2), 6.34–7.02 (m, 4H, Ar–H).
Compound 5b, 1-aminopentylphosphonic acid mono-(3,4-
dimethylphenyl) ester: Obtained as a hydrobromide salt; white so-
lid; mp 224 °C; HRMS m/z 271.1337/272.1400 (M+1)+; 31P NMR
(300 MHz, D2O, ppm): d 24.65 (s); 1H NMR (300 MHz, D2O, ppm):
d 0.72 (t, J = 12.31 Hz, 3H, CH3(CH2)3CHP), 1.12–1.45 (m, 5H,
CH3(CH2)3CHP), 1.57–1.69 (m, 1H, CH3(CH2)2CH2CHP), 2.05 (d,
J = 7.20 Hz, 6H, 2 ꢁ ArCH3), 2.69–2.73 (m, 1H, PCHCH2), 6.72–6.99
(m, 3H, Ar–H).
Compound 5c, 1-aminopentylphosphonic acid mono-(2,5-
dimethylphenyl) ester: White solid; mp >250 °C; HRMS m/z
271.1337/272.1416 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
24.59 (s); 1H NMR (300 MHz, D2O, ppm): d 0.63–0.69 (m, 3H,
CH3(CH2)3CHP), 1.07–1.13 (m, 5H, CH3(CH2)3CHP), 1.22–1.38 (m,
1H, CH3(CH2)2CH2CHP), 1.96–1.99 (m, 3H, ArCH3), 2.03–2.07 (m,
3H, ArCH3), 2.67–2.76 (m, 1H, PCHCH2), 6.70–7.02 (m, 3H, Ar–H).
Compound 5d, 1-aminopentylphosphonic acid mono-(4-
methoxyphenyl) ester: White solid; mp >250 °C; HRMS m/z
273.1130/274.1208 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
22.71 (s); 1H NMR (300 MHz, D2O, ppm): d 0.62–0.75 (m, 3H,
CH3(CH2)3CHP), 0.94–1.27 (m, 5H, CH3(CH2)3CHP), 1.40–1.67 (m,
1H, CH3(CH2)2CH2CHP), 2.14–2.33 (m, 1H, PCHCH2), 3.49–3.51
(m, 3H, ArOCH3), 6.31–6.91 (m, 4H, Ar–H).
Compound 5e, 1-aminopentylphosphonic acid mono-(4-car-
boxyphenyl) ester: White solid; mp 143–185 °C; HRMS m/z
287.0923/288.1502 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
22.63 (s); 1H NMR (300 MHz, D2O, ppm): d 0.68 (t, J = 14.40 Hz,
3H, CH3(CH2)3CHP), 1.03–1.32 (m, 5H, CH3(CH2)3CHP), 1.45–1.59
(m, 1H, CH3(CH2)2CH2CHP), 2.26–2.33 (m, 1H, PCHCH2), 6.36–
7.49 (m, 4H, Ar–H).
Compound 6i, 1-amino-3-phenylpropylphosphonic acid mono-
(4-(1,1,3,3-tetramethyl)butylphenyl) ester: Yellow solid; mp
120–122 °C; HRMS m/z 403.2276/426.2174 (M+Na)+; 31P NMR
(300 MHz, D2O, ppm): d 21.85 (s); 1H NMR (300 MHz, D2O, ppm):
d 0.57 (s, 9H, C(CH3)3), 1.13 (s, 6H, ArC(CH3)2CH2), 1.39–1.51 (m,
2H, ArC(CH3)2CH2), 1.39–1.51 (m, 1H, PhCH2CH2), 1.84–1.97 (m,
1H, PhCH2CH2), 2.36–2.54 (m, 1H, PhCH2CH2), 2.36–2.54 (m, 1H,
PCHCH2), 2.64–2.79 (m, 1H, PhCH2CH2), 6.38–7.20 (m, 9H, Ar–H).
Compound 6a, 1-amino-3-phenylpropylphosphonic acid
mono-(2,5-dimethylphenyl) ester: White solid; mp 235 °C;
HRMS m/z 319.1337/320.1400 (M+1)+; 31P NMR (300 MHz,
D2O, ppm):
d d
23.85 (s); 1H NMR (300 MHz, D2O, ppm):
1.58–1.73 (m, 1H, PhCH2CH2), 1.84–2.06 (m, 1H, PhCH2CH2),
1.84–2.06 (m, 6H, 2 ꢁ ArCH3), 2.50–2.60 (m, 1H, PhCH2CH2),
2.71–2.80 (m, 1H, PhCH2CH2), 2.71–2.80 (m, 1H, PCHCH2),
6.15–7.18 (m, 7H, Ar–H).
Compound 6b, 1-amino-3-phenylpropylphosphonic acid mono-
(3,4-dimethylphenyl) ester: White solid; mp 223 °C; HRMS m/z
319.1337/320.1367 (M+1)+; 31P NMR (300 MHz, D2O, ppm): d
23.85 (s); 1H NMR (300 MHz, D2O, ppm): d 1.58–1.67 (m, 1H,
PhCH2CH2), 1.84–1.95 (m, 1H, PhCH2CH2), 2.02 (s, 6H, 2 ꢁ ArCH3),
Acknowledgements
This work was supported by Ministry of Science and Higher
Education, Grants N405 008 31/0559 and N401 1888 32/3917,
and by the European Union Socrates/Erasmus program. We thank
Karolina Madeła, MSc. for synthesis of some inhibitors. The
Authors thank Dr. Keri Smith for critical reading of the manuscript,
and Dr. Séverine Cruet-Hennequart for training in cell biology and
helpful discussions.