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114ꢀ ꢀS. Vladimirova and A. Bijev: N-Pyrrolylcarboxylic acids as potential COX-2 inhibitors
Ethylꢀ1-(1-carboxy-2-phenylethyl)-5-(4-chlorophenyl)-2-methyl-
1H-pyrrole-3-carboxylate (1f) White solid; yield 82%; mp 144–145°C;
Rf 0.56 (10:0.2); IR: ν 3600–2400 (COOH), 3400 (O-H), 1760, 1640 (Cꢀ= ꢀO),
840 cm-1 (p-C6H4); 1H NMR (CDCl3): δ 9.90 (s, 1H, COOH), 6.80–7.15 (m,
4H, C6H4), 6.35–6.60 (m, 5H, C6H5), 6.20 (s, 1H, H-4), 4.75–4.85 (m, 1H,
CH2-CH), 4.18 (q, 2H, J ꢀ= ꢀ 7.1 Hz, CH3CH2), 3.20–3.35 (m, 2H, CH2-CH), 2.58
(s, 3H, CH3-2), 1.30 (t, 3H, J ꢀ= ꢀ 7.1 , C H3CH2). Anal. Calcd for C23H22ClNO4:
C, 67.07; H, 5.38; N, 3.40. Found: C, 66.82; H, 5.55; N, 3.69.
185–186°C; Rf 0.56 (10:0.6); IR: ν 3300–2400 (COOH), 3250 (O-H),
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1770, 1610 (Cꢀ= ꢀO), 780, 750 cm-1 (C6H5); H NMR (CDCl3): δ 10.20 (s,
1H, COOH), 7.10–7.40 (m, 5H, C6H5), 6.00 (s, 1H, H-4), 4.85–4.95 (m,
1H, CHCOOH), 3.40–3.60 (m, 4H, 2 ꢀ× ꢀ NCH2CH3), 2.25 (s, 3H, CH3-2),
1.90–2.15 (m, 4H, CH2CH2S), 1.80 (s, 3H, S-CH3), 1.20 (t, 6H, J ꢀ= ꢀ 7.1 ,
2 ꢀ× ꢀ NCH2CH3). Anal. Calcd for C21H28N2O3S: C, 64.92; H, 7.26; N, 7.21.
Found: C, 64.57; H, 6.98; N, 7.01.
2-(3-Diethylcarbamoyl-2-methyl-5-phenylpyrrol-1-yl)-3-phenyl-
propionic acid (2f) White solid; yield 79%; mp 132–133°C; Rf 0.33
(10:0.6); IR: ν 3600–2200 (COOH), 3300 (O-H), 1720, 1570 (Cꢀ= ꢀO), 750,
700 cm-1 (C6H5); 1H NMR (DMSO-d6): δ 6.50–7.25 (m, 10H, 2 ꢀ× ꢀ C6H5), 5.95
(s, 1H, COOH), 5.80 (s, 1H, H-4), 4.85–4.95 (m, 1H, CH2-CH), 2.90–3.40
(m, 6H, 2 ꢀ× ꢀ NCH2CH3 + CH2CH), 2.25 (s, 3H, CH3-2), 1.00 (t, 6H, J ꢀ= ꢀ 7.1
Hz, 2 ꢀ× ꢀ NCH2CH3). Anal. Calcd for C25H28N2O3: C, 74.23; H, 6.98; N, 6.93.
Found: C, 73.94; H, 6.77; N, 6.75.
Ethylꢀ1-[1-carboxy-2-(1H-indol-3-yl)-ethyl]-5-(4-chlorophenyl)-
2-methyl-1H-pyrrole-3-carboxylate (1g) White solid; yield 72%;
mp 183–184°C; Rf 0.47 (10:0.3); IR: ν 3600–2300 (COOH), 3350 (O-H),
1700, 1580 (Cꢀ= ꢀO), 840 cm-1 (p-C6H4); 1H NMR (CDCl3): δ 9.20 (br, s, 2H,
COOH + NH), 6.35–7.30 [m, 9H, 4H (C6H4) + 5H (indolyl-H)], 6.10 (s,
1H, H-4), 4.85–4.95 (m, 1H, CHCOOH), 4.10 (q, 2H, J ꢀ= ꢀ 7.1 Hz, CH3CH2),
3.20–3.40 (m, 2H, CH2-CH), 2.55 (s, 3H, CH3-2), 1.20 (t, 3H, J ꢀ= ꢀ 7.1 Hz,
CH3CH2). Anal. Calcd for C25H23ClN2O4: C, 66.59; H, 5.14; N, 6.21. Found:
C, 66.24; H, 5.50; N, 6.44.
2-(3-Diethylcarbamoyl-2-methyl-5-phenyl-pyrrol-1-yl)-3-(1H-
indol-3-yl)propionic acid (2g) White solid; yield 78%; mp
198–199°C; Rf 0.62 (10:0.7); IR: ν 3600–2200 (COOH), 3350 (O-H), 1710,
2-(3-Diethylcarbamoyl-2-methyl-5-phenylpyrrol-1-yl)propionic
acid (2a) Creamy solid; yield 75%; mp 178–179°C; Rf 0.38 (10:0.2);
IR: ν 3600–2200 (COOH), 3300 (O-H), 1720, 1580 (Cꢀ= ꢀO), 770, 700 cm-1
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1580 (Cꢀ= ꢀO), 760, 700 cm-1 (C6H5); H NMR (DMSO-d6): δ 7.20–7.45 (m,
7H, C6H5 + COOH + NH), 6.00 (s, 1H, H-4), 5.05–5.10 (m, 1H, CHCOOH),
3.20–3.40 (m, 6H, CH2-Ind + 2 ꢀ× ꢀ NCH2CH3), 2.25 (s, 3H, CH3-2), 1.10 (t,
6H, J ꢀ= ꢀ 7.1 Hz, 2 ꢀ× ꢀ NCH2CH3). Anal. Calcd for C27H29N3O3: C, 73.11; H,
6.59; N, 9.47. Found: C, 72.73; H, 6.71; N, 9.87.
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(C6H5); H NMR (DMSO-d6): δ 7.40–7.80 (m, 6H, C6H5 + COOH), 6.20
(s, 1H, H-4), 5.05–5.15 (m, 1H, CHCOOH), 3.60 (q, 4H, J ꢀ= ꢀ 7.1 Hz,
2 ꢀ× ꢀ NCH2CH3), 2.40 (s, 3H, CH3-2), 1.65 (d, 3H, J ꢀ= ꢀ 7.1 Hz, CHCH3), 1.35
(t, 6H, J ꢀ= ꢀ 7.1 Hz, 2 ꢀ× ꢀ NCH2CH3). Anal. Calcd for C19H24N2O3: C, 69.49; H,
7.37; N, 8.53. Found: C, 69.09; H, 7.21; N, 8.68.
3-(3-Diethylcarbamoyl-2-methyl-5-phenylpyrrol-1-yl)propionic
acid (2n) White solid; yield 81%; mp 82–83°C; Rf 0.54 (10:0.3); IR:
ν 3600–2200 (COOH), 3400 (O-H), 1700, 1590 (Cꢀ= ꢀO), 770, 720 cm-1
2-(3-Diethylcarbamoyl-2-methyl-5-phenylpyrrol-1-yl)-3-meth-
ylbutyric acid (2b) White solid; yield 76%; mp 211–212°C; Rf 0.65
(10:0.5); IR: ν 3600–2200 (COOH), 3400 (O-H), 1710, 1590 (Cꢀ= ꢀO), 780,
730 cm-1 (C6H5); 1H NMR (DMSO-d6): δ 7.40–7.50 (m, 6H, C6H5 + COOH),
6.10 (s, 1H, H-4), 4.50 (d, 1H, J ꢀ= ꢀ 10.7 Hz, CHCOOH), 3.50 (q, 4H, J ꢀ= ꢀ 7.1
Hz, 2 ꢀ× ꢀ NCH2CH3), 2.30–2.40 [m, 4H, CH3-2 + CH (i-pr)], 1.20 (t, 6H, J ꢀ= ꢀ
7.1, 2 ꢀ× ꢀ NCH2CH3), 0.95 [d, 3H, J ꢀ= ꢀ 6.3 Hz, CH3 (isopropyl)], 0.45 [d, 3H,
J ꢀ= ꢀ 6.8, CH3 (isopropyl)]. Anal. Calcd for C21H28N2O3: C, 70.76; H, 7.92;
N, 7.86. Found: C, 70.45; H, 7.88; N, 7.70.
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(C6H5); H NMR (CDCl3): δ 7.20–7.40 (m, 5H, C6H5), 6.20 (s, 1H, H-4),
5.20 (br, s, 1H, COOH), 4.15–4.25 (m, 2H, CH2N), 3.45–3.55 (m, 4H, 2 ꢀ× ꢀ
NCH2CH3), 2.20–2.40 (m, 5H, CH3-2 + CH2COOH), 1.20 (t, 6H, J ꢀ= ꢀ 7.1 Hz,
2 ꢀ× ꢀ NCH2CH3). Anal. Calcd for C19H24N2O3: C, 69.49; H, 7.37; N, 8.53.
Found: C, 69.10; H, 7.51; N, 8.13.
2-[3-Acetyl-5-(4-chlorophenyl)-2-methylpyrrol-1-yl]propionic
acid (3a) White solid; yield 78%; mp 225–226°C; Rf 0.42 (10:0.5); IR: ν
3600–2300 (COOH), 3300 (O-H), 1730, 1610 (Cꢀ= ꢀO), 830 cm-1 (p-C6H4);
1H NMR (CDCl3): δ 7.30 (s, 1H, COOH), 7.15–7.25 (m, 4H, C6H4), 6.30 (s,
1H, H-4), 4.60–4.80 (m, 1H, CHCOOH), 2.50 (s, 3H, CH3-2), 2.30 (s, 3H,
COCH3), 1.50 (d, 3H, J ꢀ= ꢀ 7.1 Hz, CHCH3). Anal. Calcd for C16H16ClNO3: C,
62.85; H, 5.27; N, 4.58. Found: C, 62.63; H, 5.04; N, 4.28.
2-(3-Diethylcarbamoyl-2-methyl-5-phenylpyrrol-1-yl)-4-methyl-
pentanoic acid (2c) White solid; yield 72%; mp 158–159°C; Rf 0.38
(10:0.3); IR: ν 3600–2300 (COOH), 3300 (O-H), 1740, 1590 (Cꢀ= ꢀO), 780,
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710 cm-1 (C6H5); H NMR (CDCl3): δ 6.95–7.20 (m, 6H, C6H5 + COOH),
5.90 (s, 1H, H-4), 4.65–4.70 (m, 1H, CHCOOH), 3.40 (q, 4H, J ꢀ= ꢀ 7.1 Hz,
2 ꢀ× ꢀ NCH2CH3), 2.10 (s, 3H, CH3-2), 1.50–1.55 (m, 2H, CH-CH2-CH),
1.10–1.20 [m, 7H, CH (i-Pr) + 2 ꢀ× ꢀ NCH2CH3)], 0.40–0.50 [m, 6H, 2 ꢀ× ꢀ
CH3 (isopropyl)]. Anal. Calcd for C22H30N2O3: C, 71.32; H, 8.16; N, 7.56.
Found: C, 71.09; H, 8.02; N, 7.40.
2-[3-Acetyl-5-(4-chlorophenyl)-2-methylpyrrol-1-yl]-3-methylb-
utyric acid (3b) Creamy solid; yield 82%; mp 202–203°C; Rf 0.55
(10:0.4); IR: ν 3600–2400 (COOH), 3350 (O-H), 1720, 1610 (Cꢀ= ꢀO),
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820 cm-1 (p-C6H4); H NMR (DMSO-d6): δ 7.35–7.50 (m, 4H, C6H4), 6.60
(s, 1H, H-4), 5.70 (s, 1H, COOH), 4.30–4.35 (m, 1H, CHCOOH), 2.60 [br,
s, 4H, CH3-2 + CH (isopropyl)], 2.40 (s, 3H, COCH3), 1.00 [d, 3H, J ꢀ= ꢀ 6.3
Hz, CH3 (isopropyl)], 0.45 [d, 3H, J ꢀ= ꢀ 6.3 Hz, CH3 (isopropyl)]; Anal.
Calcd for C18H20ClNO3: C, 64.77; H, 6.04; N, 4.20. Found: C, 64.62; H,
5.82; N, 4.07.
2-(3-Diethylcarbamoyl-2-methyl-5-phenylpyrrol-1-yl)-3-methyl-
pentanoic acid (2d) White solid; yield 74%; mp 237–238°C; Rf 0.51
(10:0.4); IR: ν 3500–2200 (COOH), 3400 (O-H), 1720, 1580 (Cꢀ= ꢀO), 770,
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710 cm-1 (C6H5); H NMR (CDCl3): δ 10.00 (s, 1H, COOH), 7.10–7.30 (m,
5H, C6H5), 5.95 (s, 1H, H-4), 4.35–4.40 (m, 1H, CHCOOH), 3.35–3.55
(m, 4H, 2 ꢀ× ꢀ NCH2CH3), 2.20–2.30 (m, 4H, CH3-2 + CHCH3), 1.20 (t, 6H,
J ꢀ= ꢀ 7.1 Hz, 2 ꢀ× ꢀ NCH2CH3), 0.90 (d, 3H, J ꢀ= ꢀ 6.3 Hz, CHCH3), 0.50–0.60
(m, 5H, CH2CH3). Anal. Calcd for C22H30N2O3: C, 71.32; H, 8.16; N, 7.56.
Found: C, 71.11; H, 8.10; N, 7.43.
2-[3-Acetyl-5-(4-chlorophenyl)-2-methylpyrrol-1-yl]-4-methyl-
pentanoic acid (3c) Creamy solid; yield 75%; mp 178–179°C; Rf 0.53
(10:0.3). IR: ν 3600–2200 (COOH), 3400 (O-H), 1710, 1610 (Cꢀ= ꢀO),
830 cm-1 (p-C6H4); 1H NMR (CDCl3): δ 9.20 (s, 1H, COOH), 7.15–7.30 (m,
4H, C6H4), 6.35 (s, 1H, H-4), 4.75–4.80 (m, 1H, CHCOOH), 2.50 (s, 3H,
CH3-2), 2.35 (s, 3H, COCH3), 1.80–1.90 (m, 2H, CH-CH2-CH), 1.10–1.15
[m, 1H, CH (isopropyl)], 0.65 [d, 3H, J ꢀ= ꢀ 6.3 Hz, CH3 (isopropyl)], 0.50
2-(3-Diethylcarbamoyl-2-methyl-5-phenylpyrrol-1-yl)-
4-(methylthio)butyric acid (2e) White solid: yield 75%; mp
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