Cyclic enaminone as new chemotype for selective ......Cyclic enaminone as new chemotype for...
Transcript of Cyclic enaminone as new chemotype for selective ......Cyclic enaminone as new chemotype for...
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SUPPLEMENTARY DATA
Cyclic enaminone as new chemotype for selective
cyclooxygenase-2 inhibitory, anti-inflammatory, and
analgesic activities
Raj Kumar, †,£
Nirjhar Saha, † Priyank Purohit,
†Sanjeev K. Garg,
†Kapileswar Seth,
†Vachan S.
Meena, § Sachin Dubey,
§ Khyati Dave,
‡ Rohit Goyal,
$ Shyam S. Sharma,
‡ Uttam C. Banerjee
§
and Asit K. Chakraborti*†
†Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and
Research (NIPER), Sector 67, S.A.S. Nagar 160 062, Punjab, India.
§Department of Pharmaceutical Technology (Biotechnology), National Institute of
Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar 160 062, Punjab,
India.
‡Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education
and Research (NIPER), Sector 67, S. A. S. Nagar 160 062, Punjab, India.
$Indo-Soviet Friendship (ISF) College of Pharmacy, Moga, 142 001, Punjab, India (present
address: School of Pharmaceutical Sciences, Shoolini University, Solan, HP, 173212, India).
£Present Address: Department of Pharmaceutical Sciences and Natural Products, Central
University of Punjab, Mansa Road, Bathinda-151001, India.
*Corresponding Author: Tel: 91-(0)-172 229 2027; Fax: 91-(0)-172-2214692. E-mail:
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Table of Content
I. Necessity for the Development of Catalyst-free Synthetic Methodology for Cyclic
Enaminones- Disadvantages of the Reported Procedures S4
II. Spectral data for known compounds S5-7
III. Scanned spectra: S8-54
1H NMR spectrum of compound 7a (Entry 1, Table 2)
13C NMR spectrum of compound 7a (Entry 1, Table 2)
HPLC chromatogram of compound 7a
1H NMR spectrum of compound 7b (Entry 2, Table 2)
HPLC chromatogram of compound 7b
1H NMR spectrum of compound 7c (Entry 3, Table 2)
HPLC chromatogram of compound 7c
1H NMR spectrum of compound 7d (Entry 4, Table 2)
HPLC chromatogram of compound 7d
1H NMR spectrum of compound 7e (Entry 5, Table 2)
HPLC chromatogram of compound 7e
1H NMR spectrum of compound 7f (Entry 6, Table 2)
HPLC chromatogram of compound 7f
1H NMR spectrum of compound 7g (Entry 7, Table 2)
HPLC chromatogram of compound 7g
1H NMR spectrum of compound 7h (Entry 8, Table 2)
13C NMR spectrum of compound 7h (Entry 8, Table 2)
HPLC chromatogram of compound 7h
1H NMR spectrum of compound 7i (Entry 9, Table 2)
13C NMR spectrum of compound 7i (Entry 9, Table 2)
HPLC chromatogram of compound 7i
1H NMR spectrum of compound 7j (Entry 10, Table 2)
13C NMR spectrum of compound 7j (Entry 10, Table 2)
HPLC chromatogram of compound 7j
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1H and NMR spectrum of compound 7k (Entry 11, Table 2)
13C NMR spectrum of compound 7k (Entry 11, Table 2)
HPLC chromatogram of compound 7k
1H NMR spectrum of compound 7l (Entry 12, Table 2)
HPLC chromatogram of compound 7l
1H NMR spectrum of compound 7m (Entry 13, Table 2)
13C NMR spectrum of compound 7m (Entry 13, Table 2)
HPLC chromatogram of compound 7m
1H NMR spectrum of compound 7n (Entry 14, Table 2)
HPLC chromatogram of compound 7n
1H NMR spectrum of compound 7o (Entry 15, Table 2)
HPLC chromatogram of compound 7o
1H NMR spectrum of compound 7p (Entry 16, Table 2)
HPLC chromatogram of compound 7p
1H NMR spectrum of compound 7q (Entry 17, Table 2)
HPLC chromatogram of compound 7q
1H NMR spectrum of compound 7r (Entry 18, Table 2)
13C NMR spectrum of compound 7r (Entry 18, Table 2)
HPLC chromatogram of compound 7r
1H NMR spectrum of compound 7s (Entry 19, Table 2)
HPLC chromatogram of compound 7s
1H NMR spectrum of compound 7t (Entry 20, Table 2)
HPLC chromatogram of compound 7t
1H NMR spectrum of compound 7u (Entry 21, Table 2)
13C NMR spectrum of compound 7u (Entry 21, Table 2)
HPLC chromatogram of compound 7u
1H NMR spectrum of compound 8
13C NMR spectrum of compound 8
HPLC chromatogram of compound 8
1H NMR spectrum of compound 9
HPLC chromatogram of compound 9
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IV. Determination of Interaction of 7d, 8, and 9 with the COX-2 active site S55-61
V. References S62-63
I. Necessity for the Development of Catalyst-free Synthetic Methodology for
Cyclic Enaminones- Disadvantages of the Reported Procedures:
A convenient route for the synthesis of cyclic enaminones involves the condensation of an
amine with cyclic 1,3-diones (Scheme S1).[1] The reported procedures involve performing the
reaction in boiling solvents[2-4] (EtOH-EtOAc or EtOH-benzene or EtOAc-benzene) with
azeotropic removal of water using Dean-Stark water separator, the use of special equipment
(microwave oven) in the presence[5] or absence of a catalyst,[6] and the use of corrosive and
costly catalyst.[7-9] Heterogeneous catalyst systems such as HClO4-SiO2[10] invented by
Chakraborti et al[11] and silica chloride (as well as ionic liquid)[12] have also been used for the
purpose. Apart from the inherent disadvantages (e.g., special efforts for catalyst preparation, use
of moisture sensitive, corrosive and costly catalysts and requirement of special apparatus) most
of the reported synthetic procedures require heating and chromatographic purification. These
made us to realize the necessity to develop an efficient and catalyst-free methodology for a
convenient synthesis of cyclic β-enaminones.
Scheme S1. Generalized synthetic strategy for the preparation of cyclic β-enaminones.
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II. Spectral data for known compounds:
3-(4-Methylphenylamino)cyclohex-2-enone[13] (7b, Entry 2, Table 1)
Pale yellow solid (0.407 g, 81%). mp: 122-124 °C; IR (KBr): 3214, 3030, 2936, 1536, 1243,
1184 cm-1
; 1
H NMR (400 MHz, CDCl3): δ 1.98-2.04 (m, 2H, CH2), 2.32 (s, 3H, CH3), 2.34 (t, J
= 6.2 Hz, 2H, CH2), 2.48 (t, J = 6.2 Hz, 2H, CH2), 5.50 (s, 1H, C=C-H), 6.50 (brs, 1H, NH),
7.01-7.04 (m, 2H, Ar-H), 7.12 (d, J = 8.0 Hz, 2H, Ar-H); 13
C NMR (100 MHz, CDCl3): δ 20.95,
21.88, 29.73, 36.48, 99.55, 124.11, 129.88, 135.36, 135.51, 162.54, 198.15; MS (APCI) m/z:
202.1 (MH+).
3-(4-Methoxyphenylamino)cyclohex-2-enone[12] (7c, Entry 3, Table 1)
Yellow solid (0.397 g, 82%). mp: 164-166 °C; 1H NMR (400 MHz, CDCl3): δ 1.97-2.02 (m, 2H,
CH2), 2.31-2.34 (m, 2H, CH2), 2.48 (t, J = 6.2 Hz, 2H, CH2), 3.80 (s, 3H, OCH3), 5.36 (s, 1H,
C=C-H), 6.31 (brs, 1H, NH), 6.85 (d, J = 8.8 Hz, 2H, Ar-H), 7.07 (d, J = 8.8 Hz, 2H, Ar-H); 13
C
NMR (100 MHz, CDCl3): δ 21.90, 29.58, 36.46, 55.51, 99.20, 114.52, 126.32, 130.62, 157.71,
163.29, 197.99; MS (APCI) m/z: 218.2 (MH+).
3-(4-Chlorophenylamino)cyclohex-2-enone[12] (7d, Entry 4, Table 1)
Yellow solid (0.419 g, 76%). mp: 189-191 °C; IR (KBr): 3250, 2949, 1601, 1574, 1519, 1244,
1181, 1138, 1085, 816 cm-1
; 1H NMR (400 MHz, CDCl3): δ 1.97-2.03 (m, 2H, CH2), 2.33 (t, J =
6.4 Hz, 2H, CH2), 2.49 (t, J = 6.4 Hz, 2H, CH2), 5.47 (s, 1H, C=C-H), 7.05-7.08 (m, 2H, Ar-H),
7.25-7.28 (m, 2H, Ar-H); 13
C NMR (100 MHz, CDCl3): δ 21.78, 29.58, 36.44, 99.73, 125.15,
129.41, 130.76, 136.73, 162.51, 198.54; MS (APCI) m/z: 222.1 (MH+).
3-(4-Fluorophenylamino)cyclohex-2-enone[13] (7e, Entry 5, Table 1)
Pale yellow solid (0.399 g, 78%). mp: 164-166 °C; IR (KBr): 3246, 2934, 1601, 1577, 1508,
1409, 1244, 1178, 1142, 819 cm-1
; 1H NMR (400 MHz, CDCl3): δ 1.97-2.03 (m, 2H, CH2), 2.32
(t, J = 6.4 Hz, 2H, CH2), 2.49 (t, J = 6.4 Hz, 2H, CH2), 5.36 (s, 1H, C=C-H), 6.96 (brs, 1H, NH),
6.97-7.03 (m, 2H, Ar-H), 7.07-7.12 (m, 2H, Ar-H); 13
C NMR (100 MHz, CDCl3): δ 21.82, 29.49,
36.45, 99.20, 116.01, 116.24, 126.28, 126.36, 133.95, 133.98, 159.14, 161.58, 163.26, 198.30.
3-(4-Nitrophenylamino)cyclohex-2-enone[13] (7f, Entry 6, Table 1)
Yellow solid (0.406 g, 70%). mp: 165-167 °C; 1H NMR (400 MHz, CD3OD): δ 2.01-2.07 (m,
2H, CH2), 2.38 (t, J = 6.4 Hz, 2H, CH2), 2.63 (t, J = 6.4 Hz, 2H, CH2), 5.76 (s, 1H, C=C-H), 7.39
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(d, J = 8.4 Hz, 2H, Ar-H), 8.24 (d, J = 8.4 Hz, 2H, Ar-H); 13
C NMR (100 MHz, CD3OD): δ
21.37, 28.66, 35.72, 100.50, 121.59, 124.75, 143.44, 145.24, 163.30, 200.61.
3-(4-Cyanophenylamino)cyclohex-2-enone[13] (7g, Entry 7, Table 1)
Off-white solid (0.429 g, 81%). mp: 199-201 °C; 1H NMR (400 MHz, CDCl3): δ 2.02-2.10 (m,
2H, CH2), 2.40 (t, J = 6.2 Hz, 2H, CH2), 2.54 (t, J = 6.2 Hz, 2H, CH2), 5.77 (s, 1H, C=C-H), 6.79
(brs, 1H, NH), 7.23-7.26 (m, 2H, Ar-H), 7.59-7.62 (m, 2H, Ar-H); 13
C NMR (100 MHz, CDCl3):
δ 21.64, 29.89, 36.52, 102.62, 107.30, 118.57, 122.08, 133.52, 142.85, 159.56, 198.69; MS
(APCI) m/z: 213.3 (MH+).
3-(4-Chlorophenylamino)-5,5-dimethylcyclohex-2-enone[14] (7l, Entry 12, Table 1)
Pale yellow solid (0.529 g, 85%). mp: 207-209 °C; IR (KBr): 3221, 3032, 1598, 1530, 1495,
1255, 1181, 803 cm-1
; 1H NMR (400 MHz, CD3OD): δ 1.10 (s, 6H, 2CH3), 2.21 (s, 2H, CH2),
2.45 (s, 2H, CH2), 5.45 (s, 1H, C=C-H), 7.20 (d, J = 8.0 Hz, 2H, Ar-H), 7.39 (d, J = 8.0 Hz, 2H,
Ar-H); 13
C NMR (100 MHz, CD3OD): δ 28.37, 33.70, 43.53, 43.56, 50.67, 97.64, 126.54,
126.58, 130.51, 131.98, 138.64, 165.59, 165.68, 200.75; MS (EI) m/z: 249 (M+), 251 (M+2)
+.
3-(4-Chlorophenylamino)cyclopent-2-enone[15] (7n, Entry 14, Table 1)
Yellow solid (0.414 g, 80%). mp: 217-219 °C; IR (KBr): 3390, 3130, 1610, 1408 cm-1
; 1H NMR
(400 MHz, CD3OD): δ 2.44 (t, J = 4.6 Hz, 2H, CH2), 2.83 (t, J = 4.6 Hz, 2H, CH2), 5.49 (s, 1H,
C=C-H), 7.21 (d, J = 8.4 Hz, 2H, Ar-H), 7.38 (d, J = 8.4 Hz, 2H, Ar-H); 13
C NMR (100 MHz,
CD3OD): δ 29.77, 34.11, 69.01, 101.93, 123.87, 130.51, 131.09, 140.05, 177.08, 209.53; MS
(EI) m/z: 207 (M+).
3-Benzylaminocyclohex-2-enone[12] (7o, Entry 15, Table 1)
Pale yellow solid (0.452 g, 90%). mp: 124-126 °C; IR (KBr): 3313, 2934, 1594, 1574, 1519,
1368, 1236, 1187, 1144 cm-1
; 1H NMR (300 MHz, CDCl3): δ 1.94-1.97 (m, 2H, CH2), 2.26-2.29
(m, 2H, CH2), 2.36-2.40 (m, 2H, CH2), 4.20-4.21 (m, 2H, NHCH2), 5.15 (s, 1H, C=C-H), 5.41
(brs, 1H, NH), 7.25-7.36 (m, 5H, Ar-H); 13
C NMR (75 MHz, CDCl3): δ 21.97, 29.60, 36.49,
47.13, 97.39, 127.73, 127.85, 128.84, 136.77, 164.40, 197.40. MS (APCI) m/z: 202.1 (MH+).
3-[(Furan-2-ylmethyl)amino]cyclohex-2-enone[16] (7p, Entry 16, Table 1)
Off-white solid (0.429 g, 90%). mp: 108-110 °C; IR (KBr): 3195, 3012, 2929, 1543, 1262, 1188,
749 cm-1
; 1H NMR (400 MHz, CDCl3): δ 1.94-2.01 (m, 2H, CH2), 2.30-2.37 (m, 4H, CH2), 4.23
(d, J = 5.2 Hz, 2H, NHCH2), 4.85 (brs, 1H, NH), 5.22 (s, 1H, C=C-H), 6.27 (d, J = 3.2 Hz, 1H,
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Het-H), 6.33-6.35 (m, 1H, Het-H), 7.37-7.38 (m, 1H, Het-H); 13
C NMR (100 MHz, CDCl3): δ
21.92, 29.60, 36.43, 40.06, 97.70, 108.39, 110.58, 142.60, 149.79, 163.50, 197.52; MS (APCI)
m/z: 191.9 (MH+).
3-Pyrrolidin-1-yl-cyclohex-2-enone[17] (7q, Entry 17, Table 1)
Yellow solid (0.363 g, 88%). mp: 84-86 °C; 1H NMR (300 MHz, CDCl3): δ 1.98-2.03 (m, 6H,
3CH2), 2.24-2.28 (m, 2H, CH2) 2.47-2.51 (m, 2H, CH2), 3.23 (m, 2H, CH2), 3.48 (m, 2H, CH2)
5.04 (s, 1H, C=C-H); 13
C NMR (75 MHz, CDCl3): δ 21.34, 23.99, 24.60, 27.19, 34.92, 47.34,
97.27, 163.44, 195.34; MS (APCI) m/z: 166.6 (MH+).
3-[(Furan-2-ylmethyl)-amino]-5,5-dimethylcyclohex-2-enone[12] (7t, Entry 20, Table 1)
Yellow solid (0.479 g, 86%). mp: 143-145 °C; IR (KBr): 3234, 3067, 1600, 1543, 1450, 1251,
1154 cm-1
; 1H NMR (400 MHz, CD3OD): δ 1.07 (s, 6H, 2CH3), 2.18 (s, 2H, CH2), 2.32 (s, 2H,
CH2), 4.33 (s, 2H, NHCH2), 5.24 (s, 1H, C=C-H), 6.33 (s, 1H, Het-H), 6.38 (s, 1H, Het-H), 7.47
(s, 1H, Het-H); 13
C NMR (100 MHz, CD3OD): δ 28.32, 33.71, 40.64, 43.54, 50.53, 95.03,
109.06, 111.46, 143.74, 151.70, 167.98, 199.46; MS (APCI) m/z: 220.1 (MH+).
S8
III. Scanned spectra
1H NMR spectrum of compound 7a (Entry 1, Table 2)
13C NMR spectrum of compound 7a (Entry 1, Table 2)
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HPLC chromatogram of compound 7a
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
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Column= C18
UV Wavelength = 305 nm
1H NMR spectrum of compound 7b (Entry 2, Table 2)
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HPLC chromatogram of compound 7b
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Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
1H NMR spectrum of compound 7c (Entry 3, Table 2)
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HPLC chromatogram of compound 7c
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7d (Entry 4, Table 2)
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HPLC chromatogram of compound 7d
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7e (Entry 5, Table 2)
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HPLC chromatogram of compound 7e
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7f (Entry 6, Table 2)
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HPLC chromatogram of compound 7f
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7g (Entry 7, Table 2)
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HPLC chromatogram of compound 7g
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7h (Entry 8, Table 2)
13C NMR spectrum of compound 7h (Entry 8, Table 1)
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HPLC chromatogram of compound 7h
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7i (Entry 9, Table 2)
13C NMR spectrum of compound 7i (Entry 9, Table 1)
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HPLC chromatogram of compound 7i
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7j (Entry 10, Table 2)
13C NMR spectrum of compound 7j (Entry 10, Table 1)
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HPLC chromatogram of compound 7j
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7k (Entry 11, Table 2)
13C NMR spectrum of compound 7k (Entry 11, Table 1)
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HPLC chromatogram of compound 7k
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7l (Entry 12, Table 2)
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HPLC chromatogram of compound 7l
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7m (Entry 13, Table 2)
13C NMR spectrum of compound 6m (Entry 13, Table 2)
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HPLC chromatogram of compound 7m
Water: Acetonitrile = 70:30
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7n (Entry 14, Table 2)
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HPLC chromatogram of compound 7n
Water: Acetonitrile = 70:30
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7o (Entry 15, Table 2)
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HPLC chromatogram of compound 7o
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7p (Entry 16, Table 2)
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HPLC chromatogram of compound 7p
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7q (Entry 17, Table 2)
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HPLC chromatogram of compound 7q
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7r (Entry 18, Table 2)
13C NMR spectrum of compound 7r (Entry 18, Table 1)
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HPLC chromatogram of compound 7r
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7s (Entry 19, Table 2)
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HPLC chromatogram of compound 7s
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7t (Entry 20, Table 2)
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HPLC chromatogram of compound 7t
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 7u (Entry 21, Table 2)
1H NMR spectrum of compound 7u (Entry 21, Table 1)
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HPLC chromatogram of compound 7u
Water: Acetonitrile = 80:20
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 8
13C NMR spectrum of compound 8
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HPLC chromatogram of compound 8
Water: Acetonitrile = 60:40
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
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1H NMR spectrum of compound 9
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HPLC chromatogram of compound 9
Water: Acetonitrile = 60:40
Flow Rate = 1 mL/min
Column= C18
UV Wavelength = 305 nm
S55
IV. Determination of Interaction of the Compounds 7d, 8, and 9 Belonging
to the Newly Designed Scaffold I in the COX-2 Active Site:
The X-ray crystal structures of COX-1 (3KK6.pdb),[18] COX-2(6COX.pdb)[19] with compound SC-
558 were used. ‘PyMOL 1.3’ was used to optimize the enzyme by removing water molecules, residues
and fragments of enzyme. The file was saved in pdb file format. After protein optimization a standard
mode of ‘GOLD 4.1.2’ software was used for the docking purpose. ‘GOLD’ gives the best poses by a
Genetic algorithm search strategy. In ‘GOLD’ software ‘hermes 1.3.1’ was used as the visualizer.
Validation of process was done by calculating root-mean-square deviation (RMSD), which was 0.49. For
docking of the molecules, optimized protein was loaded in the ‘GOLD’ software, followed by addition of
hydrogen and deletion of ligand. The atom and residue were selected in 10 Å range. Then celecoxib (1),
lumiracoxib (4) and compounds 7d, 8, 9 were separately added to the active site of enzyme. The analysis
of the interactions was done in ‘PyMOL’ software. Results are summarized in Table S1 and S2 with
interaction and comparison of docking pose/score are summarized in Figure S1.
Table S1. Compounds with their docking score and interaction.
COMPOUND DOCKING POSE INTERACTION GOLD
SCORE
Celecoxib (1)
1- Gln192 (N-H….O=C-
Gln192, 2.5 Å)
2- Leu352 (N-H…O=C-
Leu352, 1.9 Å)
3- Ser353 (NH…
O=C-Ser353, 2.8 Å).
4- His90 (S=O…H-N-
His90, 2.8 Å).
66.61
S56
Lumiracoxib (4)
1- Tyr 385 (C=O…..O-H -
Tyr 385 2.62 Å)
2- Ser 530 (C=O …. O-H –
Ser 530 2.5 Å)
3- Leu 385 ( CH3- Leu 385
Hydrophobic
interaction)
53.74
O
NH
(1)
No strong interaction. 41.82
(7d)
1- Val 523 ( N-H….O=C-
Val 523, 2.9 Å)
2- Ser 530 ( C=O….H –O-
Ser 530 3.0 Å)
3- Tyr 385 (C=O…H-
O-Tyr 385
3.1 Å).
43.94
S57
(8)
1- Cyclohexanone C=O,
Ser 530 ( C=O….H –O-Ser
530 2.85 Å)
2- Cyclohexanone C=O,
Tyr 385 (C=O…H-O-
Tyr 385
2.73 Å).
58.74
(9)
1- Cyclohexanone C=O,
Ser 530 ( C=O….H –O-Ser
530 2.88 Å)
2- Cyclohexanone C=O,
Tyr 385 (C=O…H-O-
Tyr 385
2.28 Å).
47.07
S58
Table S2. Compounds with their docking score and interaction in COX-1.
COMPOUND DOCKING POSE INTERACTION
(7d)
Cyclohexanone C=O, Ser
530 ( C=O….H –O-Ser 530
3.2 Å)
(8)
t-butyl C=O, Tyr 355
(C=O…H-O-Tyr 355
2.3 Å).
S59
(9)
Cyclohexanone C=O, Tyr
385 (C=O…H-O-Tyr 385
3.0 Å).
S60
Figure S1: Comparison of the docking poses of celecoxib (1), lumiracoxib (4) with that of the
compounds 7d, 8, and 9 inside the active site of COX-2.
Celecoxibi (1) in green color, 7d in yellow color. Lumiracoxib (4) is in red color, 7d in yellow color.
Lumiracoxib (4) is in red color, 7d is in cyano Lumiracoxib (4) is in red color, 7d is in cyano.
8 is in orange, 9 is in gray white.
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Lumiracoxib (4) is in red color, compound 8 is in orange Lumiracoxib (4) is in red color, compound 9 is in
gray white
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V. References
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