1. INTRODUCTION:

Pain is an unpleasant feeling, which makes uncomfortable and reduces the physical and mental alertness. Although pain is also useful for us because it acts as a caution signal and it informs about something rare inside or outside our body, analgesics, which are the broadly, used drugs for the treatment of pain, it can be divided into 2 groups: morphine related drugs and NSAIDs (non-steroidal anti-inflammatory drugs). NSAIDs act basically by forbidding action of COX (cyclooxygenase) enzymes, which catalyze the first step in the prostaglandin biosynthesis [1-5]. The long-term use of NSAIDs may also lead to severe G.I. (gastrointestinal) side effects, which limits the use of these drugs.

The harmful effects associated with the use of non-selective NSAIDs arise from the reduction of the levels of protective prostaglandins in the GI (gastrointestinal) tract because of the restraint of COX-1(cyclooxygenase-1). Although selective COX-2 inhibitors cause less GI destructive effects than nonselective NSAIDs, their use in the treatment is also limited due to severe cardiovascular effects. From the above discussion, is clear that the search for new active compounds have gained significant importance. Derivatives of acetamide have been found to occupy analgesic activity [6-12].

Medicinal chemists have carried out considerable research for innovative analgesic agents which possess carboxylic acid moiety [13]. The prominent compounds bearing the R-COOH (carboxylic acid) group are aspirin, ibuprofen, and naproxen, all of which are extensively used as over-the-counter drugs for the alleviation of pain [14]. Many researchers have also studied tetrazole ring. Several studies have been confirmed that tetrazole derivatives possess analgesic activity [15]. The synthesis of various derivatives of acetamide has got massive attention in recent years as this class of compounds constitutes structural frameworks of several naturally occurring compounds displaying a wide range of biological activities for example anti-microbial [16], anti-cancer [17], anti-tubercular [18], anti-HIV [19], hemolytic [20], anthelmintic activity [21]. Since acetamide moiety exerts anti-inflammatory [22] and analgesic activities [22]. In view of these observations and as a part of an ongoing research program on development of newer analgesic agents, the novel and efficient strategy are developed to synthesize 2-(substituted phenoxy)-N-(substituted phenyl) acetamide derivatives, N-(substituted phenyl)-2-(naphthalen-1-yloxy) acetamide derivatives and 2-(o-tolyloxy)-N-(substituted phenyl) acetamide derivatives with wonderful yields. These compounds were further biologically estimated for analgesic activity, and few of them showed activity.

2. MATERIAL AND METHOD:

2.1 Chemistry:

All research chemicals used were from purchased from Spectrochem Pvt. Ltd., Mumbai, Central Drug House Pvt. Ltd., New Delhi, and Loba Chemie Pvt. Ltd. Mumbai. The melting points were resolved in an open capillary tube using electro thermal digital melting point apparatus. (Science Tech. Pvt. Ltd. Maharashtra India). TLC checked the purity of all the recently synthesized compounds on silica gel 60 F254 and spots were determined by UV-lamp at λ 254 nm. Spectroscopic data were recorded on PerkinElmer FT-IR Spectrometer using KBr pressed pellet technique, and νmax is expressed in cm^-1. NMR spectra were measured in DMSO-d6 as a solvent at Bruker DRX-300 (¹H NMR) spectrometer using tetramethylsilane (TMS) as the internal standard. δ (Chemical shift) was indicated in ppm (parts per million). All the solvent were distilled and dried with usual moisture less.

2.2 Synthesis:

A General method of synthesis of 2- chloro-N-(substituted phenyl) acetamide (3a-e):

Substituted aniline (0.01mol) was mixed in acceptable amount of glacial acetic acid to form a distinct solution. The amount of glacial acetic acid consumed was recorded. Chloro acetyl chloride (0.15mol) was added drop by drop with quickly shaking. Mixture heated on a hot water bath for 15 minute with whirling, mixture was then removed adequate amount of anhydrous sodium acetate solution in water was mixed to get the solid form. The mixture was cooled for few minutes, filtered, washed with water to remove the odor of glacial acetic acid altogether. The product was recrystallized from methanol and air dried. [23].

General method of synthesis of N-(substituted phenyl)-N-(substituted) acetamide (5aa-ec):

A mixture of substituted phenol (0.01mol) and 2- chloro-N-(substituted phenyl) acetamide (0.01mol) was refluxed using dry (CH₃)₂CO (acetone) in the presence of anhydrous K₂CO₃(potassium carbonate) for 6h. The reaction mixture was cooled and poured into crushed ice. The reliable product obtained was filtered, dried, and recrystallized using ethanol. The purity of the compound was validated by m.p. determination and TLC technique [24].

Scheme 1:

Spectroscopic data of the synthesized compounds (5aa-5ec):

2-(4-aminophenoxy)-N-(3-chlorophenyl) acetamide (5aa):

FTIR (KBr v, cm^-1): 761 (C-Cl stretch), 1078 (C-O stretch), 1217 (C-N stretch), 1530 (NH₂bend), 1595 (C=C Ar), 1677 (C=O stretch: ketone), 3395 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.28 (s, 2H, NH2), 4.76 (s, 2H, CH2), 6.21-6.67 (m, 4H, Ar H), 7.05-7.96 (m, 4H, Ar H), 8.09 (s, 1H, NH); Elemental analysis for C₁₄H₁₃ClN₂O₂: C, 60.77; H, 4.74; N, 10.12;Found: C, 60.75; H, 4.72; N, 10.11;

N-(3-chlorophenyl)-2-(naphthalen-1-yloxy) acetamide (5ab):

FTIR (KBr v, cm^-1): 678 (C-Cl stretch), 1160 (C-O stretch), 1271 (C-N stretch), 1535 (C=C Ar), 1671 (C=O stretch: ketone), 3387 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.50(s, 2H, CH2), 6.02-7.10 (m, 4H, Ar H), 7.13-7.95 (m, 4H, Ar H), 7.97 (s, 1H, NH), 7.98-8.23 (m, 3H, Ar H);Anal. Calcd. For C₁₈H₁₄ClNO₂: C, 69.35; H, 4.53; N, 4.49; Found: C, 69.33; H, 4.56; N, 4.47;

2-(o-tolyloxy)-N-(3-chlorophenyl) acetamide (5ac):

FTIR (KBr v, cm^-1): 677 (C-Cl stretch), 1223 (C-O stretch), 1302 (C-N stretch), 1534 (C=C Ar), 1681 (C=O stretch: ketone), 3395 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 2.35 (s, 3H, CH3), 4.88 (s, 2H, CH2), 6.66-6.98 (m, 4H, Ar H), 7.03-7.63 (m, 4H, Ar H), 8.31 (s, 1H, NH);Elemental analysis for C₁₅H₁₄ClNO₂: C, 65.34; H, 5.12; N, 5.08; Found: C, 65.36; H, 5.10; N, 5.10;

2-(4-aminophenoxy)-N-(4-chlorophenyl)acetamide (5ba):

FTIR (KBr v, cm^-1): 665 (C-Cl stretch), 1244 (C-O stretch), 1339 (C-N stretch), 1544 (C=C Ar), 1609 (NH₂bend), 1664 (C=O stretch: ketone), 3265 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.38 (s, 2H, NH2), 4.96 (s, 2H, CH2), 6.36-6.54 (m, 4H, Ar H), 7.26-7.60 (m, 4H, Ar H), 8.09 (s, 1H, NH);Anal. Calcd. For C₁₅H₁₄ClNO₂: C, 60.77; H, 4.74; N, 10.12; Found: C, 60.75; H, 4.76; N, 10.10;

N-(4-chlorophenyl)-2-(naphthalen-1-yloxy) acetamide (5bb):

FTIR (KBr v, cm^-1): 770 (C-Cl stretch), 1089 (C-O stretch), 1270 (C-N stretch), 1532 (C=C Ar), 1666 (C=O stretch: ketone), 3273 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.55(s, 2H, CH2), 6.04-7.16 (m, 4H, Ar H), 7.18-7.97 (m, 4H, Ar H), 7.98 (s, 1H, NH), 8.0-8.17 (m, 3H, Ar H); Elemental analysis for C₁₈H₁₄ClNO₂: C, 69.35; H, 4.53N, 4.49; Found: C, 69.37; H, 4.55; N, 4.51;

2-(o-tolyloxy)-N-(4-chlorophenyl) acetamide (5bc):

FTIR (KBr v, cm^-1): 763 (C-Cl stretch), 1218 (C-O stretch), 1288 (C-N stretch), 1544 (C=C Ar), 1666 (C=O stretch: ketone), 3264 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 2.32 (s, 3H, CH3), 4.82 (s, 2H, CH2), 6.63-7.02 (m, 4H, Ar H), 7.23-7.62 (m, 4H, Ar H), 8.17 (s, 1H, NH); Anal. Calcd. For C₁₅H₁₄ClNO₂: C, 65.34; H, 5.12; N, 5.08; Found: C, 65.32; H, 5.14; N, 5.06;

2-(4-aminophenoxy)-N-(2,3-dichlorophenyl) acetamide (5ca):

FTIR (KBr v, cm^-1): 665 (C-Cl stretch), 1050 (C-O stretch), 1231 (C-N stretch), 1524 (C=C Ar), 1584 (NH₂bend), 1681 (C=O stretch: ketone), 3367 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.29 (s, 2H, NH2), 4.72 (s, 2H, CH2), 6.36-6.53 (m, 4H, Ar H), 6.97-7.48 (m, 3H, Ar H), 8.42 (s, 1H, NH);Elemental analysis for C₁₄H₁₂Cl₂N₂O₂: C, 54.04; H, 3.89; N, 9.00; Found: C, 54.02; H, 3.91; N, 8.98;

N-(2,3-dichlorophenyl)-2-(naphthalen-1-yloxy) acetamide (5cb):

FTIR (KBr v, cm^-1): 663 (C-Cl stretch), 1224 (C-O stretch), 1269 (C-N stretch), 1525 (C=C Ar), 1683 (C=O stretch: ketone), 3367 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.27(s, 2H, CH2), 6.35-6.95 (m, 3H, Ar H), 6.97-8.20 (m, 7H, Ar H), 8.46 (s, 1H, NH);Elemental analysis for C₁₈H₁₃Cl₂NO₂: C, 62.45; H, 3.78; N, 4.05; Found: C, 62.43; H, 3.76; N, 4.07;

2-(o-tolyloxy)-N-(2, 3-chlorophenyl) acetamide (5cc):

FTIR (KBr v, cm^-1): 662 (C-Cl stretch), 1280 (C-O stretch), 1320 (C-N stretch), 1531 (C=C Ar), 1679 (C=O stretch: ketone), 3271 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 2.37 (s, 3H, CH3), 4.48 (s, 2H, CH2), 6.62-6.99 (m, 4H, Ar H), 7.01-7.50 (m, 3H, Ar H), 8.09 (s, 1H, NH);Elemental analysis for C₁₅H₁₃Cl₂NO₂: C, 58.08; H, 4.22; N, 4.52; Found: C, 58.10; H, 4.24; N, 4.50;

2-(4-aminophenoxy)-N-(3,4-dichlorophenyl) acetamide (5da):

FTIR (KBr v, cm^-1): 669 (C-Cl stretch), 1131 (C-O stretch), 1224 (C-N stretch), 1527 (C=C Ar), 1592 (NH₂bend), 1675 (C=O stretch: ketone), 3387 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.26 (s, 2H, NH2), 4.54 (s, 2H, CH2), 6.40-6.62 (m, 4H, Ar H), 7.18-7.62 (m, 3H, Ar H), 8.20 (s, 1H, NH);Elemental analysis for C₁₄H₁₂Cl₂N₂O₂: C, 54.04; H, 3.89; N, 9.00; Found: C, 54.02; H, 3.91; N, 9.02;

N-(3,4-dichlorophenyl)-2-(naphthalen-1-yloxy) acetamide (5db):

FTIR (KBr v, cm^-1): 667 (C-Cl stretch), 1216 (C-O stretch), 1267 (C-N stretch), 1523 (C=C Ar), 1678 (C=O stretch: ketone), 3400 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.57(s, 2H, CH2), 6.63-7.59 (m, 3H, Ar H), 6.61-8.18 (m, 7H, Ar H), 8.21 (s, 1H, NH);Elemental analysis for C₁₈H₁₃Cl₂NO₂: C, 62.45; H, 3.78; N, 4.05; Found: C, 62.43; H, 3.80; N, 4.07;

2-(o-tolyloxy)-N-(3, 4-chlorophenyl) acetamide (5dc):

FTIR (KBr v, cm^-1): 676 (C-Cl stretch), 1128 (C-O stretch), 1239 (C-N stretch), 1526 (C=C Ar), 1681 (C=O stretch: ketone), 3387 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 2.31 (s, 3H, CH3), 4.68 (s, 2H, CH2), 6.67-7.01 (m, 4H, Ar H), 7.20-7.60 (m, 3H, Ar H), 8.21 (s, 1H, NH);Elemental analysis for C₁₅H₁₃Cl₂NO₂: C, 58.08; H, 4.22; N, 4.52; Found: C, 58.06; H, 4.24; N, 4.54;

2-(4-aminophenoxy)-N-(2-Nitrophenyl)acetamide (5ea):

FTIR (KBr v, cm^-1): 1279 (C-O stretch), 1341 (C-N stretch), 1505 (NO₂stretch), 1546 (C=C Ar), 1589 (NH₂bend), 1696 (C=O stretch: ketone), 3325 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 4.32 (s, 2H, NH2), 4.81 (s, 2H, CH2), 6.40-6.54 (m, 4H, Ar H), 7.30-8.12 (m, 4H, Ar H), 8.19 (s, 1H, NH); Anal. Calcd. For C₁₄H₁₃N₃O₄: C, 58.53; H, 4.56; N, 14.63; Found: C, 58.51; H, 4.58; N, 14.61;

N-(2-Nitrophenyl)-2-(naphthalen-1-yloxy) acetamide (5eb):

FTIR (KBr v, cm^-1): 1279 (C-O stretch), 1344 (C-N stretch), 1506 (NO₂stretch), 1593 (C=C Ar), 1690 (C=O stretch: ketone), 3315 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm):4.80(s, 2H, CH2), 6.62-7.26 (m, 7H, Ar H), 7.28-8.01 (m, 4H, Ar H), 8.3 (s, 1H, NH); Elemental analysis for C₁₈H₁₄N₂O₄: C, 67.07; H, 4.38; N, 8.69; Found: C, 67.09; H, 4.40; N, 8.71;

2-(o-tolyloxy)-N-(2-Nitrophenyl) acetamide (5ec):

FTIR (KBr v, cm^-1): 1280 (C-O stretch), 1342 (C-N stretch), 1504 (NO₂stretch), 1593 (C=C Ar), 1700 (C=O stretch: ketone), 3326 (N-H stretch: 2° amide);¹HNMR (300 MHz, DMSO-d₆δ / ppm): 2.29 (s, 3H, CH3), 4.78 (s, 2H, CH2), 6.66-6.98 (m, 4H, Ar H), 7.28-7.92 (m, 4H, Ar H), 8.31 (s, 1H, NH); Anal. Calcd. For C₁₅H₁₄N₂O₄: C, 62.93; H, 4.93; N, 9.79; Found: C, 62.91; H, 4.95; N, 9.81;

Table 1: Physico-chemical parameters of synthesized compounds (3a-e)

Compound code	R	Molecular Formula	Molecular weight	% Yield	R_fValue	M.P. (⁰C)
3a	3-Cl	C₈H₇Cl₂NO	204.05	70.32	0.89	82-84
3b	4-Cl	C₈H₇Cl₂NO	204.05	68.45	0.45	128-130
3c	2,3-(Cl)₂	C₈H₆Cl₃NO	238.94	74.65	0.68	86-88
3d	3,4-(Cl)₂	C₈H₆Cl₃NO	238.5	63.54	0.76	87-90
3e	2-NO₂	C₈H₇ClN₂O₃	214.61	58.32	0.71	80-82

Solvent system: Ethyl acetate: Chloroform (9:1 v/v)

Table 2: Physico-chemical parameters of synthesized compounds (5aa-5ec)

Compound code	R₁	Molecular Formula	Molecular weight	% Yield	R_fValue	M.P. (⁰C)
5aa	NH₂	C₁₄H₁₃ClN₂O₂	276.72	54.05	0.91	75-77
5ab	C₆H₆	C₁₈H₁₄ClNO₂	311.76	61.02	0.92	105-107
5ac	CH₃	C₁₅H₁₄ClNO₂	275.73	78.40	0.93	81-84
5ba	NH₂	C₁₄H₁₃ClN₂O₂	276.72	62.12	0.90	122-124
5bb	C₆H₆	C₁₈H₁₄ClNO₂	311.76	58.26	0.88	102-104
5bc	CH₃	C₁₅H₁₄ClNO₂	275.73	76.45	0.88	101-103
5ca	NH₂	C₁₄H₁₂Cl₂N₂O₂	311.16	45.06	0.87	86-88
5cb	C₆H₆	C₁₈H₁₃Cl₂NO₂	346.21	64.24	0.89	76-78
5cc	CH₃	C₁₅H₁₃Cl₂NO₂	310.18	85.32	0.88	101-103
5da	NH₂	C₁₄H₁₂Cl₂N₂O₂	311.16	58.26	0.89	75-78
5db	C₆H₆	C₁₈H₁₃Cl₂NO₂	346.21	62.28	0.88	84-88
5dc	CH₃	C₁₅H₁₃Cl₂NO₂	310.18	82.45	0.85	78-82
5ea	NH₂	C₁₄H₁₃N₃O₄	287.27	59.23	0.89	78-82
5eb	C₆H₆	C₁₈H₁₄N₂O₄	322.31	67.36	0.88	76-80
5ec	CH₃	C₁₅H₁₄N₂O₄	286.28	88.56	0.86	77-79

Solvent system: Ethyl acetate: Chloroform (9:1 v/v)

2.3 Pharmacological Screening:

2.3.1 Animals:

Wistar albino rats of both sexual categories weighing 100-120g were obtained. The animals were separated into several groups. All the animals were housed under standard ambient environment of temperature (25±2°C) and relative humidity of 35-60%. 12 h light and dark cycles were maintained. All the animals were allowed to have the generosity to water and standard palletized laboratory animal diet 12 h previous to pharmacological studies [25-28]. All the investigational procedures and protocols used in this study were reviewed and recognized by the IAEC (Institutional Animal Ethical Committee), Hygia Institute of Pharmaceutical Education and Research, Lucknow, India Approval No. HIPER/IAEC/31/18/10).

2.3.2 Acute Toxicity:

The acute oral toxicity test was performed according to OECD 423 guideline (OECD, 2000) [25] to establish the safety profile of the compounds and further to obtain the adequate dose of the test compounds. Wister albino rats of either sex weighing between 100-120g were divided into several groups of 6 animals in each for each compound. Animals were famished for 24 h before the test. On the day of the experiment, animals were treated with different compounds to different groups in increasing order of 5, 50, 300, 2000, and 5000mg/kg b.w. (bodyweight) orally. Following dosing, the animals were observed for general behavioral, autonomic, and neurological profiles for 3h and further every 30 min for the next 3h and finally for the next 14 days or till death. From the acute toxicity study, it was concluded that animals were found to be safe up to a maximum dose of 200mg/kg body weight. However, there were few changes in the behavioral response like restlessness, touch response, and alertness. Therefore, 1/10th of the maximum suffer dose, i.e., 20mg/kg b.w. (bodyweight) was chosen for in vivo studies [29-31].

2.3.3 Eddy’s Hot Plate Method:

The compounds exhibit an important analgesic activity measured by Eddy’s hot plate method. Animals were divided into different groups. Animals were kept deprived of food 12 h before drug administration till the activity gets completed. Animals were weighed and numbered appropriately. Animals were individually placed on a Hot plate maintained at a temperature (55 ±1°C) and the reaction of animals, such as paw licking or jump response (whichever appears first) was taken as the end point. A cut-off time of 15 seconds was taken as a maximum analgesic response to escape injury to the paws. The Standard group received diclofenac sodium (10 mg/kg) intra-peritoneal. Synthesized compounds were administered orally to the test groups (20mg/kg). Analgesic activity of synthesized compounds was estimated at equimolar doses. The basal reaction time was recorded at 30, 60, 90, and 120 min administration of the standard or the test compound [32,33].

3. RESULTS AND DISCUSSION:

3.1 Chemistry:

A series of titled derivatives 2-(substituted phenoxy)-N-(substituted phenyl) acetamide, N-(substituted phenyl)-2-(naphthalen-1-yloxy) acetamide and 2-(o-tolyloxy)-N-(substituted phenyl) acetamide derivatives (5aa-5ec) were synthesized as per scheme. Derivatives of amine and ClCH₂COCl (chloroacetyl chloride) were separately treated with glacial acetic acid warmed on the water bath for 15 min. and added anhydrous sodium acetate solution in water gives amide derivatives (3a-e). Compound 3a-e converted to 5aa-5ec by the reaction with different substituted phenols in the presence of potassium carbonate in dry acetone as a solvent at 75⁰C for 6 h. The structure of newly synthesized compounds was confirmed by spectral data (IR, NMR). IR spectra of all final compounds (5aa-5ec) showed an intense peak in the region 3400-3264 cm-¹ due to the N-H stretching vibration, which indicates the presence of N-H in acetamide ring. A strong, characteristic band in the region 1344-1217 cm-¹ is due to the C-N stretching vibration. The peak appeared at 770-662 cm-¹ due to C-Cl stretching. Band for aromatic C-H stretching vibrations was observed at 3107-2926 cm-¹. Peak for C=O was observed at 1700-1664 cm-¹. Peak at range of 1280-1050 cm-¹ indicates the presence of C-O-C linkage. Peak for aromatic C-H are generally appeared at longer wavelength than the aliphatic C-H. It is due to the higher stretching of pi electrons present in the aromatic ring.

The ¹H NMR spectra of the compounds (5aa-5ec) showed a singlet of two protons for NH₂group has appeared at δ 4.26-4.38 ppm. Singlet of two protons for methylene group has appeared between δ 4.27-4.96 ppm. Multiplet for four aromatic protons was appeared at δ 6.02-8.12 ppm. Multiplet for seven aromatic protons appeared at δ 6.61-8.20 ppm. Multiplet for three aromatic protons was appeared at δ 6.35-8.23 ppm. Singlet of 1 proton for NH group appeared at δ 7.97-8.46 ppm, and presence of other groups like CH₃ was confirmed by shift value δ 2.21-2.37 respectively on synthesized derivatives. All the other aromatic and aliphatic protons were observed at expected regions.

3.2 Biological Evaluation:

3.2.1 Analgesic activity:

Eddy’s hot plate method was utilized to evaluate the test compounds for their in vivo analgesic activity. Analgesic activity obtained for the test compounds were compared with the control group. Data are expressed as Mean reaction time ± S.E.M. analyzed by two-way ANOVA, followed by Dunnett’s test. Diclofenac at a dose of 10 mg/ kg exhibited significant analgesic activity (p < 0.01) at all-time intervals as compared to the control group. As shown in Table 3allthe compounds (5aa-ec) exhibited varying degrees of analgesic activity. Compounds 5cb and 5cc were found to exhibit potent antipyretic activity [34, 35].

Table 3: Analgesic activity data of compounds using Eddy’s hot plate method

Compound	Basal Reaction time (sec) before treatment	Basal reaction time (sec) after treatment
Compound	Basal Reaction time (sec) before treatment	30 min	60 min	90 min	120 min
Control	4.82±0.42	4.31±0.33	3.27±0.27	3.50±0.35	3.02±0.33
Standard	3.38±1.40	7.10±0.62	8.00±0.60	10.50±1.31	12.8±0.80
5aa	3.33±0.42	4.66±0.33	5.50±0.22	6.16±0.40	8.15±0.47
5ab	2.5±0.54	5.16±0.75	5.5±0.83	6.95±0.68	8.71±0.63
5ac	3.6±0.49	5.30±0.28	5.76±0.36	7.60±0.83	8.60±0.97
5ba	4.61±0.60	5.70±0.38	6.95±0.86	7.10 ± 0.62	6.16 ± 0.40
5bb	3.16±0.30	4.43±0.44	5.30±0.28	6.95±0.86	7.33±0.49
5bc	2.33±0.21	4.51±0.29	5.70±0.38	7.16±0.60	8.61±1.01
5ca	3.1±0.2	6.16±0.40	7.10±0.62	8.51±0.99	9.86±0.96
5cb	2.83±0.30	5.00±0.36	7.33±0.49	9.83±0.47	10.50±0.50
5cc	3.00±0.36	6.16±0.40	8.15±0.47	9.66±0.61	11.33±0.49
5da	2.66±0.33	3.83±0.47	5.33±0.33	6.50±0.42	7.16±0.30
5db	2.67±0.78	4.62±0.10	5.17±0.31	6.83±0.78	8.33±0.21
5dc	4.43±0.44	5.33±0.33	6.33±0.21	8.00±0.26	8.90±0.21
5ea	3.14±0.56	4.7±0.2	5.16±0.44	6.83±1.30	7.5±0.3
5eb	4.67±0.78	6.50±0.42	7.67±0.98	4.50±1.00	5.00±0.85
5ec	3.83±1.40	5.16±0.75	6.67±0.98	7.16±0.30	7.60 ± 0.83

4. CONCLUSION:

An innovative series of different derivatives of acetamide were synthesized and screened for analgesic activity by using Eddy’s hot plate method respectively. Physical and analytical parameters of the newly synthesized acetamide derivatives were confirmed by melting point, TLC, IR, ¹HNMR and elemental analysis. Subsequently, in biological screening, the compound 5cb and 5cc showed potent analgesic as compared to other derivatives. Further research on acetanilide core is needed for discovery as a potent analgesic agent. Thus we observed that there is enough scope for further study in developing such compounds as a good lead molecule with best pharmacological profile.

5. ACKNOWLEDGEMENTS:

Authors would like to thank management of Hygia Institute of Pharmaceutical Education and Research, Lucknow for providing research facilities. CDRI, Lucknow is acknowledged for providing the spectral data of the synthesized compounds.

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Received on 31.12.2019 Modified on 12.02.2020

Research J. Pharm. and Tech. 2020; 13(11):5158-5164.

DOI: 10.5958/0974-360X.2020.00902.6