12 Chapter 3 Synthesis and biological...

Chapter:- 3 Tetrahydro pyrimidine derivatives

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CHAPTER 3

Synthesis and biological evaluation of

1,2,3,4-tetrahydro pyrimidines

3.1 Introduction

The actions of many transferable diseases are demanding due to fighting to

antimicrobial. The surfacing of fighting surrounded by bacteria to a broad range of

structurally dissimilar antibacterial agents such as 6- lactams, macrolides, and fluoro-

quinolones as well as particular dyes and disinfectants has turn into a civic fitness worry

so makes it necessary to maintain the search for new antibacterial agents.

In recent scenario heterocycles is the different rule in drug synthesis. In that

respect pyrimidine plays a significant rule among other heterocycles. From the literature

survey, in modern years 1,2,3,4-tetrahydropyrimidines have engrossed significant

awareness because of their therapeutic and pharmacological properties. more than a few

of them has establish to demonstrate a wide spectrum of genetic property as well as

antimicrobial, antitumour, antihypertensive, alpha-1a adrenergic antagonist,

neuropeptide antagonist. So it was planned to synthesize a novel series of 1, 2, 3, 4-

tetrahydropyrimidins derivatives and to check as antimicrobial activity[1-2].

About 10 decade ago chemist Biginelli found that the two components in equal

amount reacts for example aldehyde, aceto acetic ester and urea reacts in alcoholic

solvent in presence of hydrochloric acid to give a novel compound and well-known as a

biginelli compound [3].


106

He did this reaction in a multi component method, and at present the progress of

multi component synthesis is an essential fraction of several study hard works

approximately the globe concerned in the drug progress agenda to get targets in prompt

way. It appear older innovation are novel way of the current moment. Succeeding

researcher has tried to know the path of reaction and they raise the contribution of the

Knoevenagel reaction.

About 200 years ago there was not a large amount reaction planned but in last 10

decade or so these reactions were involve grate interest with as an outcome about 500

publication were there, mainly some catalyst vary. In these time importance on accepting

the way of reaction. Pharmaceutical point of view these academic research was great

value because of this implication, study were extremely quick and mostly all journal was

publish paper with title Biginelli reaction.

Tetrahydropyrimidine is higher flooded pyrimidine nucleus with two less double

bonds. The Tetrahydro pyrimidines are small, highly soluble organic molecules, which do

not impede with normal cellular functions. They are zwitterion molecules, and the

amidine group of the THPs is positively charged [4, 5].

Tetrahydropyrimidine has the great property of their synthetic compatibility. It

can easily be modified[6]. Only few general methods for the synthesis of

tetrahydropyrimidine-2- thione derivatives have been reported. Biginelli[7] reports the

preparation of 3,4-dihydropyrimidine -2-one with multi reagent acid catalysed reaction

of aldehyde, urea and ethyl acetoacetate.

In few years back the multi reagent reactions has experienced a significant

renewal, due to the great pharmacological activity connected with this dihydropyrimidine

[8]. The low yield of pyrimidine is main drawback

Now atwal and et al [9-11] gives the smart approach to the preparation of this

compound. This reaction is supported on the reaction of arylidene of oxoesters with S-(4-

methoxybenzyl) isothio urea or o-methy lisourea in the presence of NaHCO3 followed by


107

change of the obtained dihydropyrimidine derivatives into tetrahydropyrimidine

derivative.

Many researchers have suggested various ways to synthesize various

tetrahydropyrimidine derivatives in protic solvents or without solvent [12-19].These

compounds can also be synthesized by benzene like aprotic solvents [20]. Some

environmentally benign processes can be employed to synthesize the

tetrahydropyrimidine. This reaction tries in microwave radiation to give the desire

product with good yield in comparison to old method [22-25]. Under different reduction

conditions, dihydropyrimidine are converted into tetrahydropyrimidine derivatives [26].

In recent years, tetrahydropyrimidine-2-thione derivatives obtained important

interest due to their miscellaneous range of biological activity [27]. These compounds are

reported to have calcium antagonist[28-31], anti-inflammatory[32-34], analgesic[35],

antitumor[36] antidepressant[37], antibacterial and antifungal activity[38-40].

Tetrahydropyrimidines are found to be accumulating in a significant amount and induces

thermo tolerance in E.coli[41].

In last few years, some new tetrahydropyrimidine like amidine compounds have

been prepared and checked for muscarinic agonist nactivity in rat brain [42-44]. Some new

Tetrahydro pyrimidine compounds exhibited muscarinic action in rat brain. This type of

products might be helpful in treating Alzheimer’s disease [45]. Chhillar et al. have

synthesized three different tetrahydropyrimidine along with ten dihydropyridine

derivatives and examined their activity against pathogenic strains of Aspergillus

fumigatus and Candida albicans [46].


108

3.2 Biological Activities of pyrimidines:

3.2.1 Antimicrobial activity:

Saundane et.al. synthesised 2- (2', 5' substituted indolideneamino- 3'- yl) - 4, 6-

diaryl pyrimidines (I) and 2 [2', 5'- substitutedindole- 3'- yl) (phenyl azo) methylene

imino]- 4, 6- Diaryl pyrimidine(II) with a view to screening then for their antimicrobial

activity. The compounds were screened for their activity at concentration 1000 µg/ml in

DMF against the gram-Ve bacteria E.Coli and Gram +Ve bacteria S. Aureous by cup

plate method and show antifungal activity against A. niger and A. flavus[47].

NH

N

N

N Ar

C6H5

R

R'NH

N

N

N Ar

C6H5

R

N

N

Ar'

1 2

Figure-3.1

Padamshali et.al.prepared Naptho [2, 1-b] furo [3, 2- a] pyrimidine which were useful in

the preparation of pharmacologically active compound like anti-inflammatory, anti-

anthelmintic, antimicrobial agents [48].

Synthesis of 1, 2, 3, 4- tetrahydro-4- oxo-2- thiobenzo furo [3, 2- d]pyrimidine

was reported by Basavaraja et al and examined for their action against S. Aureus and

E. coli. N- (N- Alkoxy phthalimido)- 4, 6-diaryl- 5, 6 Dihydropyrimidine - 2- Thiones

prepared by Talesara et.al.[49].


109

ON

NR

R'

O

NN

NN

O

R

3 4

Figure-3.2

Synthesized 5- [5'- substituted 1, 3, 4 oxadiazol- 2' yl) Dihydropyrimidinon and screened

for their antimicrobial action against S.Aureus and E.Coli using Norfloxacin as standard

antifungal activity was evaluated by using A.Niger and CAalbicans using Grisofulvin

as standard[50].

The antimicrobial action of the selected prepared products was checked by cup

plate process. The in-vitro antimicrobial action was taken against twenty four hrs cell

culture of two bacteria and two fungi. The bacterial strains used were S. Aureus and P.

Aerugenosa. The fungi used were A. Niger and C. Albicans[51].

NH

NH

HN

N

S

O

RN

N

R

R

5 6

Figure-3.3


110

3.2.2 Antiviral activity:-

Abs E1-galil E. amr et al [52] synthesized some pyrimidine like thiazalopyrinidine

and thiopyrimidine compound using 1-(5,6,7,8,-tetrahydro naphthalene-2-yl) ethanone as

starting material for all synthesized compounds and checked their activity in opposition

to HSv-1 virus. Screening of those compounds for anti viral shows good activities and its

very similar to acyclovir as a reference drug. Following compound gave more than 90%

inhibition and calculated to be largely capable activity and compare their antiviral activity

of Acyclovir.

N

N S

OO

CH3

OCH3

OCH3

7

Figure-3.4

Revankar et al [53] synthesized a sequence of Thiazolo [4,5-d] pyrimidine

compound from 5-aminothiazolo-[4,5-d] pyrimidine-2,7 (3H,6H)-dion as a starting

material. Prepared compounds were checked their antiviral activity in opposition to

human cytomegalovirus. Synthesized product 5-amino-3-(4-hydroxybut-2-enyl) thiazolo

[4,5-d] pyrimidine-2,7,(3H,6H)-dione checked their antiviral activity in opposition to

human cytomegalovirus.


111

HN

NH2N

O

S

NO

OH

8

Figure-3.5

3.2.3 Anticancer activity:-

Fahmy synthesized a sequence of novel fluorinated thiazole [4,5-d] pyrimidine

product and checked their activity against anti cancer in human tumor cell lines.

Fahmy et al [54] prepared a sequence of new fluorinated thiazolo[4,5-d]pyrimidine

compound and screened their anticancer activity against 60 human tumor cell lines.

Products showed well again anticancer action against tumor cell lines.

HN

NH3C

S

NS

NH

F

F

N

N

S

N S

O

F

N

HF

F9 10

Figure-3.6


112

3.3 Current Work

From last 100 years pyrimidine and its derivative were studied because of their

biological activity. The 1, 2, 3, 4-tetrahydropyrimidines have biological activity because

many pharmacological and medicinal application viz: antimicrobial and radio protective.

In keeping different biomedical advantage and with a idea to further consider the

pharmacological report of these class of products, three newly series of N-(2-chloro-4-

(trifluoromethyl)phenyl)-1,2,3,4-tetrahydro-6-isopropyl-4-(substitutedyphenyl)-2-

oxopyrimidine -5-carboxamide (ND- 146 to 190) are synthesized. The synthesis of (ND-

146 to 190) was achieved by acid catalysed cyclocondensation of N-(2-chloro-4-

(trifluoromethyl) phenyl)-4-methyl-3-oxopentanamide, substituted urea and

Benzaldehydes. The products were characterized by proton NMR, carbon NMR, IR, mass

spectra and CHNS analyses. The novel prepared products were tested to various

biological actions like, antimicrobial.etc.


113

3.3.1 Reaction scheme

R

H2N

O

NH2

CHO

HN

O O

R

NH

N

X

NH

O

+

ND-146 to ND-160

Conc.HCl

CF3

ClF3C Cl

R1

R=OCH3,CH3,Cl,F,Br......etcR1=H

R

H2N

O

NH2

CHO

HN

O O

R

NH

N

X

NH

O

+

ND-161 to ND-175

Conc.HCl

CF3

ClF3C Cl

R1

R=OCH3,CH3,Cl,F,Br......etcR1=H

R

H2N

O

NH2

CHO

HN

O O

R

NH

N

X

NH

O

+

ND-176 to ND-190

Conc.HCl

CF3

ClF3C Cl

R1

R=OCH3,CH3,Cl,F,Br......etcR1=CH3

X=O

X=S

X=O

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

CH3

H3C

CH3

H3C

Figure-3.7


114

Table 3.1 Physical Data Table of Series-4

TLC Solvent system Rf1:- Hexane: Ethyl acetate – 6:4,

Rf2:- Chloroform: methanol – 9;1.

Code R1 M.F. M.W. M.P.0

C

Yield % Rf1 Rf2

ND-146 2-OCH3 C22H21ClF3N3O3 468 217 62 0.48 0.65

ND-147 3-Cl C21H18Cl2F3N3O2 472 207 68 0.53 0.61

ND-148 2-F C21H18ClF4N3O2 456 203 59 0.49 0.58

ND-149 3,

4DiOCH3

C23H23ClF3N3O4 498 202 60 0.50 0.66

ND-150 4-OCH3 C22H21ClF3N3O3 468 205 65 0.55 0.70

ND-151 4-Cl C21H18Cl2F3N3O2 472 204 67 0.41 0.68

ND-152 4-CH3 C22H21ClF3N3O2 452 211 60 0.59 0.68

ND-153 4-F C21H18ClF4N3O2 456 195 59 0.55 0.71

ND-154 2-Cl C21H18Cl2F3N3O2 472 187 74 0.40 0.75

ND-155 3,4-DiCl C21H17Cl3F3N3O2 506 215 70 0.55 0.70

ND-156 3-OCH3 C22H21ClF3N3O3 468 217 63 0.41 0.69

ND-157 2,4-diCH3 C23H23ClF3N3O2 466 213 57 0.58 0.68

ND-158 4-Br C21H18BrClF3N3O2 517 211 68 0.58 0.65

ND-159 3-Br C21H18BrClF3N3O2 517 187 65 0.49 0.72

ND-160 H C21H19ClF3N3O2 438 203 67 0.57 0.63


115




Code R1 M.F. M.

W.

M.P.0C Yield % Rf1 Rf2

ND-161 2-OCH3 C22H21ClF3N3O2S 484 205 66 0.44 0.64

ND-162 3-Cl C21H18Cl2F3N3OS 488 210 60 0.43 0.63

ND-163 2-F C21H18ClF4N3OS 472 191 58 0.50 0.70

ND-164 3, 4DiOCH3 C23H23ClF3N3O3S 514 194 71 0.42 0.62

ND-165 4-OCH3 C22H21ClF3N3O2S 484 201 65 0.56 0.66

ND-166 4-Cl C21H18Cl2F3N3OS 488 211 71 0.48 0.58

ND-167 4-CH3 C22H21ClF3N3OS 468 208 63 0.52 0.72

ND-168 4-F C21H18ClF4N3OS 472 199 59 0.59 0.69

ND-169 2-Cl C21H18Cl2F3N3OS 488 189 71 0.54 0.64

ND-170 3,4-DiCl C21H17Cl3F3N3OS 523 195 66 0.52 0.72

ND-171 3-OCH3 C22H21ClF3N3O2S 484 200 70 0.44 0.64

ND-172 2,4-diCH3 C23H23ClF3N3OS 482 203 55 0.40 0.70

ND-173 4-Br C21H18BrClF3N3O S 533 201 68 0.48 0.58

ND-174 3-Br C21H18BrClF3N3O S 533 201 70 0.48 0.58

ND-175 H C21H19ClF3N3OS 454 203 62 0.58 0.58


116




Code R1 M.F. M.W. M.P.0C Yield % Rf1 Rf2

ND-176 2-OCH3 C23H23ClF3N3O3 482 200 62 0.49 0.58

ND-177 3-Cl C22H20Cl2F3N3O2 486 210 63 0.51 0.61

ND-178 2-F C22H20ClF4N3O2 470 201 66 0.52 0.70

ND-179 3, 4DiOCH3 C24H25ClF3N3O4 512 211 72 0.54 0.71

ND-180 4-OCH3 C23H23ClF3N3O3 482 191 70 0.47 0.75

ND-181 4-Cl C22H20Cl2F3N3O2 486 214 70 0.56 0.65

ND-182 4-CH3 C23H23ClF3N3O2 466 201 68 0.51 0.69

ND-183 4-F C22H20ClF4N3O2 470 175 58 0.49 0.59

ND-184 2-Cl C22H20Cl2F3N3O2 486 186 75 0.48 0.60

ND-185 3,4-DiCl C22H19Cl3F3N3O2 520 215 70 0.52 .067

ND-186 3-OCH3 C23H23ClF3N3O3 482 207 68 0.58 0.75

ND-187 2,4-diCH3 C24H25ClF3N3O2 480 188 58 0.54 0.72

ND-188 4-Br C22H20BrClF3N3O2 531 201 66 0.50 0.68

ND-189 3-Br C22H20BrClF3N3O2 531 190 70 0.49 0.67

ND-190 H C22H21ClF3N3O2 452 189 65 0.42 0.57


117

3.3.2 Plausible Reaction Mechanism

The reaction mechanism of pyrimidine formation can be depicted as under:

H+

+

H+

-H2O

H

OH

+

H2N

H2NX

..

-H2O

-H+

H+

O

O

NH

H

..

O

H H

OH

O+

O

NH

H

OH

H

O+

O

NH

H

H

O

O

NH

H

NH

H2NX

O

O

NH

NH

NH

X

HO

NH

X = O, S

(b) (c)

(d)

(e) (f)

:

+(i)

(ii)

dehydration

ClF3C F3C Cl

F3C Cl F3C Cl

ClF3CClF3C

CH3

H3C

CH3

H3C

CH3

H3C

CH3

H3C

CH3

H3C

CH3

H3C

Figure-3.8


118

3.3.3 Experimental

3.3.3.1 Materials and Methods

Product formed was determined by TLC analysis and all the compounds melting

point were checked. IR, NMR and elemental analysis were done and reported.

3.3.3.2 Synthesis of N-(2-chloro-4-(trifluoro methyl) phenyl)-4-methyl-3-

oxopentanamide.

Syntheses of N-(2-chloro-4-(trifluoro methyl) phenyl)-4-methyl-3-

oxopentanamide were achieved using previously published methods [55].

3.3.3.3 General procedure for the synthesis 1, 2, 3, 4- tetrahydro pyrimidine.

(ND-146 to190)

A mixture of N-(2-chloro-4-(trifluoromethyl)phenyl)-4-methyl-3-oxopentanamide

(0.01 M), Benzaldehydes (0.01 M), urea derivatives and small quantity of HCl in ethyl

alcohol (30 ml) was heat to 80-85°C for 15 to 20 hrs. After that cool the reaction mixture

to 25-35°C and stir for 18-20 hrs. Crude product was crystallizing in ethanol.

Series No. 4 from urea

3.3.3.3.1 N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-4-(2-methoxy) phenyl-6-

(propan-2-yl)-1, 2, 3 ,4-tetrahydropyrimidine-5-carboxamide (ND-146)


119

NH

NH

O

O

NH

ClF3C OCH3

CH3

H3C

Practical yield: 62%; Melting point 217ºC; Molecular formula C22H21ClF3N3O3: Carbon:

56.48; Hydrogen: 4.52; Chlorine: 7.58; Fluorine: 12.18; Nitrogen: 8.98; Oxygen: 10.26.

Obtained : Carbon: 56.38; Hydrogen: 4.42; Chlorine: 7.48; Fluorine: 12.08; Nitrogen:

8.88; Oxygen; 10.16%; IR spectra: 3439 (for N-H), 3013 (For -C-H of Phenyl ring), 2985

(For -CH group), 2855 (for -CH group), 1651 (-C=O carbonyl group), 1597 (C=O cyclic

stretching) 1597 (N-H, pyrimidine ring), 1529 (C=C Phenyl ring stretching), 1475 (C-H,

CH3 group asy-deformation), 1402 (C-H, CH3 group s-deformation of), 1346 (C-N-C

pyrimidine ring stretching), 1274 (C-N, stretching), 1194 (C-O-C, OCH3 stretching),

1064 (C-F, stretching), 1038 (C-O-C, OCH3 stretching) 835 (p-substituted), 682 (C-Cl

stretching); Mass: 468; 1H NMR: δ ppm: 1.47 (s, 3(H),Ha), 1.58 (s, 3(H),Hb), 3.32 (s,

3H,Hc), 3.85 (s, 1H,Hd), 4.83 (s, 1H,He), 7.09-7.11 (d, 1(H),Hf,), 7.27-7.29 (d, 1(H),Hg),

7.38-7.40 (d, 1H,Hh,), 7.43-7.46 (m, 1H,Hi), 7.50-7.54 (m, 1H,Hj), 7.90 (s, 1H,Hk), 7.93-

7.95 (m, 1H,Hl), 8.47-8.50 (m, 1(H), Hm), 8.90 (s, 1(H),Hn), 10.09 (s, 1(H),Ho).

3.3.3.3.2 4-(3-chlorophenyl)-N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-6-(propan-

2-yl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxamide (ND-147)

NH

NH

O

O

NH

ClF3C

Cl

CH3

H3C


120

Practical yield: 68%; Melting point 207ºC; Molecular formula C21H18Cl2F3N3O2: Carbon:

(53.40%) Hydrogen (3.84%) Nitrogen (8.90%) Obtained : Carbon: 53.50; Hydrogen:

3.74; Nitrogen: 8.88 IR spectra: (-C-H Phenyl ring stretching), 2980 (C-H, CH3 group

asy stretching ), 2850 (C-H, CH3 group sym stretching ), 1653 (C=O amide carbonyl

stretching), 1599 (C=O, Cyclic stretching) 1593 (N-H, pyrimidine ring deformation),

1523 (C=C Phenyl ring stretching), 1475 (C-H CH3 group asy deformation), 1401 (C-H,

CH3 group sym deformation), 1345 (C-N-C pyrimidine ring stretching), 1275 (C-N,

stretching), 1067 (C-F, stretching), 837 (p-substituted), 685 (C-Cl, stretching. Mass: 472. 1H NMR δppm: 1.47 (s, 3(H),Ha), 1.58 (s, 3(H),Hb), 3.85 (s, 1(H),Hc), 4.83 (s, 1(H),Hd),

7.09-7.11 (d, 1H,He), 7.27-7.29 (d, 1H,Hf), 7.38-7.40 (d, 1H,Hg,), 7.43-7.46 (m, 1H,Hh),

7.50-7.54 (m, 1(H),Hi), 7.90 (s, 1(H),Hj), 7.93-7.95 (m, 1H,Hk), 8.47-8.50 (m, 1H,Hl),

8.90 (s, 1H,Hm), 10.09 (s, 1H,Hn).

3.3.3.3.3 N-[2-chloro-4-(trifluoro methyl) phenyl]-4-(2-fluorophenyl)-2-oxo-6-(propan-

2-yl)-1, 2, 3, 4-tetrahydro pyrimidine-5-carboxamide (ND-148)

NH

NH

O

O

NH

ClF3C F

CH3

H3C

Practical yield: 59%; Melting point 203ºC; Molecular formula C21H18ClF4N3O2 Carbon:

(55.33%) Hydrogen (3.98%) Nitrogen (9.22%) Obtained: Carbon: 55.35; Hydrogen:

3.94; Nitrogen: 9.21 IR spectra: 3245, 3140 (N-H, amide stretching), 2970 (C-H Phenyl

ring stretching), 1710 (-C=O carbonyl group), 1070 (For -C-F, group). MS: m/z 456.

3.3.3.3.4 N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-4-(3, 4-dimethoxy)phenyl-6-

(propan-2-yl)-1, 2, 3, 4-tetrahydro pyrimidine-5-carboxamide (ND-149)


121

NH

NH

O

O

NH

ClF3C

OCH3

OCH3

CH3

H3C


55.48; Hydrogen: 4.66; Nitrogen: 8.44; Oxygen: 12.85; Obtained : Carbon: 55.28;

Hydrogen: 4.36; Nitrogen: 8.14; Oxygen: 12.45; IR spectra: 3240, 3135 (For -N-H,

group), 2972 (C-H, Phenyl ring stretching), 1712 (For -C=O, carbonyl), 1072 (For -C-F,

stretching). MS: m/z 498.



NH

NH

O

O

NH

ClF3C

OCH3

CH3

H3C



Hydrogen: 4.22; Nitrogen: 8.58; Oxygen: 10.06%; IR spectra: 3242, 3137 (N-H, amide

stretching), 2971 (C-H, Phenyl ring stretching), 1715 (For -C=O, carbonyl), 1070 (For -

C-F, group) MS: m/z 468.

3.3.3.3. 4-(4-chlorophenyl)-N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-6-(propan-

2-yl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxamide (ND-151)


122

NH

NH

O

O

NH

ClF3C

Cl

CH3

H3C



Hydrogen: 3.54; Nitrogen, 8.40; Oxygen: 6.48%; IR spectra: 3240, 3133 (For -N-H,

group), 2975 (For -C-H, Phenyl ring), 1712 (For -C=O, carbonyl), 1076 (For -C-F,

group) MS: m/z 472;

3.3.3.3.7 N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-4-(4-methyl) phenyl-6-


NH

NH

O

O

NH

ClF3C

CH3

CH3

H3C



Hydrogen: 4.68; Nitrogen: 9.10; Oxygen: 7.04%; IR spectra: 3238, 3135 (For -N-H,


group) MS: m/z 452.


123

3.3.3.3. N-[2-chloro-4-(trifluoro methyl) phenyl]-4-(4-fluorophenyl)-2-oxo-6-(propan-

2-yl)-1, 2, 3, 4 tetrahydro pyrimidine-5-carboxamide (ND-153)

NH

NH

O

O

NH

ClF3C

F

CH3

H3C




group), 2976 (For -C-H, Phenyl ring ), 1709 (For -C=O, carbonyl), 1073 (For -C-F,

group) MS: m/z 456.

3.3.3.3.9 4-(2-chlorophenyl)-N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-6-(propan-

2-yl)-1, 2, 3, 4-tetrahydro pyrimidine-5-carboxamide (ND-154)

NH

NH

O

O

NH

ClF3C Cl

CH3

H3C



Hydrogen: 3.86; Nitrogen: 8.80; Oxygen: 6.72%; IR spectra: 3239, 3134 (For -N-H


124


group) MS: m/z 472

3.3.3.3.10 N-[2-chloro-4-(trifluoromethyl) phenyl]-4-(3,4-dichloro phenyl)-2-oxo-6-


NH

NH

O

O

NH

ClF3C

Cl

Cl

CH3

H3C



Hydrogen: 3.30; Nitrogen: 8.20; O: 6.26%; IR spectra: 3235, 3130 (For -N-H, group),

2970 (For -C-H, Phenyl ring), 1708 (For -C=O, carbonyl), 1072 (For -C-F, group) MS:

m/z 506.



NH

NH

O

O

NH

ClF3C

OCH3

CH3

H3C


56.48; Hydrogen: 4.52; Nitrogen: 8.98; Oxygen: 10.26. Obtained: Carbon: 56.20;


125



group) MS: m/z 468.

3.3.3.4.12 N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-4-(2, 4-dimethyl) phenyl-6-


NH

NH

O

O

NH

ClF3C CH3

CH3

CH3

H3C




group), 2973 (For -C-H, Phenyl ring), 1712 (For -C=O, carbonyl), 1074 (For -C-F,) MS:

m/z 466.

3.3.3.4.13 4-(4-bromophenyl)-N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-6-


NH

NH

O

O

NH

ClF3C

Br

CH3

H3C


126

Practical yield: 68%; Melting point 211ºC; Molecular formula C21H18BrClF3N3O2:

Carbon: 48.81; Hydrogen: 3.51; Nitrogen: 8.13; Oxygen: 6.19; Obtained : Carbon: 48.80;



group) MS: m/z 517.

3.3.3.4.14 4-(3-bromophenyl)-N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-6-


NH

NH

O

O

NH

ClF3C

Br

CH3

H3C

Practical yield: 65%; Melting point 187ºC; Molecular formula C21H18BrClF3N3O2 :

Carbon: 48.81; Hydrogen: 3.51; Nitrogen: 8.13; Oxygen: 6.19; Obtained : Carbon: 48.72;



group) MS: m/z 517

3.3.3.4.15 N-[2-chloro-4-(trifluoro methyl) phenyl]-2-oxo-4-phenyl-6-(propan-2-yl)-1,

2, 3, 4-tetrahydro pyrimidine-5-carboxamide (ND-160)

NH

NH

O

O

NH

ClF3C

CH3

H3C


127




group), 2975 (For -C-H, Phenyl ring ), 1711 (For -C=O, carbonyl), 1070 (For -C-F,

group) MS: m/z 438

Series No. 5 from Thiourea

3.3.3.3.16 N-(2-chloro-4-(trifluoro methyl) phenyl)-1, 2, 3, 4-tetrahydro-6-isopropyl-4-

(2-methoxy -phenyl)-2-thioxo pyrimidine-5-carboxamide (ND-161)

NH

NH

S

O

NH

ClF3C OCH3

CH3

H3C

Practical yield: 66%; Melting point 205ºC; Molecular formula C22H21ClF3N3O2S:

Carbon: 54.60; Hydrogen: 4.37; Chlorine, 7.33; Fluorine, 11.78; Nitrogen: 8.68; Oxygen:

6.61; Sulfur, 6.63; Obtained: Carbon: 54.50; Hydrogen: 4.27; Chlorine, 7.23; Fluorine,

11.68; Nitrogen: 8.58; Oxygen: 6.51; Sulfur, 6.53 %; MS: m/z 484.

3.3.3.3.17 N-(2-chloro-4-(trifluoromethyl) phenyl)-1, 2, 3, 4-tetrahydro-6-isopropyl-4-

(3-chloro -phenyl)-2-thioxopyrimidine-5-carboxamide (ND-162)

NH

NH

S

O

NH

ClF3C

Cl

CH3

H3C


128

Practical yield: 60%; Melting point 210ºC; Molecular formula C21H18Cl2F3N3OS:

Carbon: 51.65; Hydrogen: 3.72; Chlorine, 14.52; Fluorine, 11.67; Nitrogen: 8.60;

Oxygen: 3.28; Sulfur, 6.57; Obtained: Carbon: 51.55; Hydrogen: 3.62; Chlorine, 14.42;

Fluorine, 11.57; Nitrogen: 8.50; Oxygen: 3.18; Sulfur, 6.47%; MS: m/z 488.


(2-fluorophenyl)-2-thioxo pyrimidine-5-carboxamide (ND-163)

NH

NH

S

O

NH

ClF3C F

CH3

H3C

Practical yield: 58%; Melting point 191ºC; Molecular formula C21H18ClF4N3OS: Carbon:

53.45; Hydrogen: 3.84; Chlorine, 7.51; Fluorine, 16.10; Nitrogen: 8.90; Oxygen: 3.39;

Sulfur, 6.79; Obtained: Carbon: 53.35; Hydrogen: 3.74; Chlorine, 7.41; Fluorine, 16.00;

Nitrogen: 8.80; Oxygen: 3.29; Sulfur, 6.69%; MS: m/z 472.


(3,4,-dimethoxyphenyl)-2-thioxo pyrimidine-5-carboxamide (ND-164)

NH

NH

S

O

NH

ClF3C

OCH3

OCH3

CH3

H3C


129



9.34; S, 6.24; Obtained : Carbon: 53.55; Hydrogen: 4.41; Chlorine, 6.40; Fluorine, 11.19;

Nitrogen: 8.28; Oxygen: 9.14; Sulfur, 6.04 %; MS: m/z 514.



NH

NH

S

O

NH

ClF3C

OCH3

CH3

H3C




11.48; Nitrogen: 8.08; Oxygen: 6.01; Sulfur, 6.03%; MS: m/z 484.


(4-chloro -phenyl)-2-thioxopyrimidine-5-carboxamide (ND-166)


130

NH

NH

S

O

NH

ClF3C

Cl

CH3

H3C



Oxygen: 3.28; Sulfur, 6.57; Obtained : Carbon: 51.15; Hydrogen: 3.12; Chlorine, 14.12;

Fluorine, 11.17; Nitrogen: 8.45; Oxygen: 3.41; Sulfur, 6.57%; IR spectra: 3520 (For -N-

H, group), 3101 (For -C-H, Phenyl ring), 2944 (C-H, CH3 group asy stretching), 2841 (C-

H, CH3 group sym stretching), 1658 (C=O, amide carbonyl stretching), 1602 (C=O,

cyclic stretching) 1602 (N-H, pyrimidine ring deformation), 1535 (C=C, Phenyl ring

stretching), 1423 (C-H, CH3 group asy deformation), 1404 (C-H, CH3 group sym

deformation), 1346 (C-N-C pyrimidine ring stretching), 1269/1205 (C-N, stretching),

1081 (C-F, stretching), 680 (C-Cl, starching)MS: m/z 488; 1H NMR δppm: 1.48 (s,

1H,Ha), 1.58 (s, 1H,Hb), 3.86 (m, 1(H),Hc), 4.82-4.83 (s, 1H,Hd), 7.15-7.21 (dd’,

2(H),Hff’ ), 7.44-7.46 (dd’, 2H,Hgg’), 7.61-7.65 (m, 1H,Hh), 7.88 (s, 1H,Hi), 8.47-8.50 (m,

1H,Hj), 8.90 (s, 1H,Hk), 9.93 (s, 1H,Hl).


(4-methyl -phenyl)-2-thioxopyrimidine-5-carboxamide (ND-167)

NH

NH

S

O

NH

ClF3C

CH3

CH3

H3C


131




Nitrogen: 8.58; Oxygen: 3.32; Sulfur, 6.45%; MASS: m/z 468.


(4-fluoro -phenyl)-2-thioxo pyrimidine-5-carboxamide (ND-168)

NH

NH

S

O

NH

ClF3C

F

CH3

H3C






(2-chloro -phenyl)-2-thioxo pyrimidine-5-carboxamide (ND-169)


132

NH

NH

S

O

NH

ClF3C Cl

H3C

CH3

Practical yield: 71%; Melting point 189ºC; Molecular formulaC21H18Cl2F3N3OS: Carbon:



Nitrogen: 8.00; Oxygen: 3.08; Sulfur, 6.27%; MASS: m/z 488;


(3,4-dichlorophenyl)-2-thioxo pyrimidine-5-carboxamide (ND-170)

NH

NH

S

O

NH

ClF3C

Cl

Cl

CH3

H3C



Oxygen: 3.06; Sulfur, 6.13; Obtained: Carbon: 48.05; Hydrogen: 3.18; Chlorine, 20.30;

Fluorine, 10.40; Nitrogen: 8.01; Oxygen: 3.01; Sulfur, 6.10%; MASS: m/z 523.


133



NH

NH

S

O

NH

ClF3C

OCH3

CH3

H3C




11.70; Nitrogen: 8.60; Oxygen: 6.60; Sulfur, 6.60%; MASS: m/z 484.


(3.4-dimethylphenyl)-2-thioxo pyrimidine-5-carboxamide (ND-172)

NH

NH

S

O

NH

ClF3C CH3

CH3

CH3

H3C

Practical yield: 55%; Melting point 203ºC; Molecular formulaC23H23ClF3N3OS: Carbon:

57.29; Hydrogen: 4.79; Chorine, 7.35; Fluorine, 11.80; Nitrogen: 8.69; Oxygen: 3.32;




134


(4-bromo -phenyl)-2-thioxo pyrimidine-5-carboxamide (ND-173)

NH

NH

S

O

NH

ClF3C

Br

CH3

H3C

Practical yield: 68%; Melting point 201ºC; Molecular formula C21H18BrClF3N3OS:

Carbon: 47.34; Hydrogen: 3.41; Bromine, 15.00; Chlorine, 6.65; Fluorine, 10.70;

Nitrogen: 7.89; Oxygen: 3.00; Sulfur, 6.02; Obtained: Carbon: 47.14; Hydrogen: 3.21;

Bromine, 14.40; Chlorine, 6.65; Fluorine, 10.60; Nitrogen: 7.49; Oxygen: 2.98; Sulfur,

5.87%; MASS: m/z 533.


(3-bromo -phenyl)-2-thioxo pyrimidine-5-carboxamide (ND-174)

NH

NH

S

O

NH

ClF3C

Br

CH3

H3C

Practical yield: 70%; Melting point 201ºC; Molecular formula C21H18BrClF3N3OS:


Nitrogen: 7.88; Oxygen: 2.99; Sulfur, 6.02; Obtained: Carbon: 47.24; Hydrogen: 3.11;

Bromine, 15.10; Chlorine, 6.45; Fluorine, 10.50; Nitrogen: 7.79; Oxygen: 2.98; Sulfur,

5.98%; MASS: m/z 533.


135


(phenyl)-2-thioxo pyrimidine-5-carboxamide (ND-175)

NH

NH

S

O

NH

ClF3C

CH3

H3C





Series No 6 from N- methyl Urea


(2-methoxy -phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-176)

N

NH

O

O

NH

ClF3C OCH3

CH3

CH3

H3C



Obtained: Carbon: 57.31; Hydrogen: 4.81; Chlorine, 7.36; Fluorine, 11.83; Nitrogen:

8.72; Oxygen: 9.96%; MASS: m/z 482.


136


(3-chloro -phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-177)

N

NH

O

O

NH

ClF3C

Cl

CH3

CH3

H3C

Practical yield: 63%; Melting point 210ºC; Molecular formula C22H20Cl2F3N3O2:


Oxygen: 6.58; Obtained: Carbon: 54.33; Hydrogen: 4.15; Chlorine, 14.58; Fluorine,

11.72; Nitrogen: 8.64; Oxygen: 6.58%; MASS: m/z 486.

3.3.3.3.33 N-(2-chloro-4-(trifluoro methyl) phenyl)-1, 2, 3,6-tetrahydro-4-isopropyl-6-

(2-fluoro -phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-178)

N

NH

O

O

NH

ClF3C F

CH3

CH3

H3C




8.94; Oxygen: 6.81%; MASS: m/z 470.


137


(3,4-di-methoxyphenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-179)

N

NH

O

O

NH

ClF3C

OCH3

OCH3

CH3

CH3

H3C




8.21; Oxygen: 12.50%; MASS: m/z 512.



N

NH

O

O

NH

ClF3C

OCH3

CH3

CH3

H3C




9.12; Oxygen: 10.42%; MASS: m/z 482.


138



N

NH

O

O

NH

ClF3C

Cl

CH3

CH3

H3C



Obtained : Carbon: 54.33; Hydrogen: 4.15; Chlorine, 14.58; Fluorine, 11.72; Nitrogen:

8.64; O: 6.58%; IR spectra: 3471 (For -N-H, group), 3057 (For -C-H Phenyl ring), 2980

(C-H, CH3 group), 2852 (C-H, CH3 group), 1716 (For -C=O, carbonyl), 1654 (For -C=O,

group) 1600 (N-H, pyrimidine ring deformation), 1537 (C=C, Phenyl ring stretching),

1496 (C-H, CH3 group asym deformation), 1396 (C-H, CH3 group sym deformation),

1346 (C-N-C pyrimidine ring stretching), 1274 (C-N, stretching), 1066 (C-F, stretching),

742 (C-Cl, starching). MASS: m/z 486; 1H NMR δppm: 1.50 (s, 3(H),Ha), 1.66 (s,

3H,Hb), 2.26 (s, 3H,Hc), 3.90 (m, 1(H),Hc), 4.90-4.91 (s, 1H,Hd), 7.12-7.15 (dd’,

2(H),Hff’ ), 7.28-7.30 (dd’, 2(H),Hgg’), 7.36-7.38 (dd’, 1H,Hh), 7.43-7.45 (m, 1H,Hi), 7.47-

7.49 (m, 1H,Hj), 9.10 (s, 1H,Hk), 9.75 (s, 1H,Hl).


(4-methyl -phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-182)


139

N

NH

O

O

NH

ClF3C

CH3

CH3

CH3

H3C




9.02; Oxygen: 6.87%; MASS: 466.


(4-fluoro -phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-183)

N

NH

O

O

NH

ClF3C

F

CH3

CH3

H3C




8.94; Oxygen: 6.81%; MASS: m/z 470.


140



N

NH

OH3C

O

NH

ClF3C Cl

CH3



Obtained : Carbon: 54.33; Hydrogen: 4.15; Chlorine, 14.58; Fluorine, 11.72; Nitrogen:

8.64; Oxygen: 6.58%; MASS: m/z 486;


(3, 4-dichlorophenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-185)

N

NH

O

O

NH

ClF3C

Cl

Cl

CH3

CH3

H3C

Practical yield: 70%; Melting point 215ºC; Molecular formulaC20H15Cl3F3N3O2: Carbon:

50.74; Hydrogen: 3.68; Chlorine, 20.42; Fluorine, 10.94; Nitrogen: 8.06; Oxygen: 6.14


8.05; Oxygen: 6.14%; MASS: m/z 520.




141

N

NH

O

O

NH

ClF3C

OCH3

CH3

CH3

H3C




8.72; Oxygen: 9.96%; MASS: m/z 482.


(2, 4-dimethylphenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-187)

N

NH

O

O

NH

ClF3C CH3

CH3

CH3

CH3

H3C




8.76; Oxygen: 6.67%; MASS: m/z 480.


(4-bromo -phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-188)


142

N

NH

O

O

NH

ClF3C

Br

CH3

CH3

H3C



Nitrogen: 7.92; Oxygen: 6.03; Obtained: Carbon: 49.78; Hydrogen: 3.80; Bromine,

15.05; Chlorine, 6.68; Fluorine, 10.74; Nitrogen: 7.92; Oxygen: 6.03%; MASS: m/z 531.


(3-bromo -phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-189)

N

NH

O

O

NH

ClF3C

Br

CH3

CH3

H3C



Nitrogen: 7.92; Oxygen: 6.03; Obtained: Carbon: 49.78; Hydrogen: 3.80; Bromine,

15.05; Chlorine, 6.68; Fluorine, 10.74; Nitrogen: 7.92; Oxygen: 6.03%; MASS: m/z 531.

3.3.3.4.45 N-(2-chloro-4-(trifluoromethyl) phenyl)-1,2,3,6-tetrahydro-4-isopropyl-6-

(phenyl)-1-methyl-2-oxopyrimidine-5-carboxamide (ND-190)


143

N

NH

O

O

NH

ClF3C

CH3

CH3

H3C




9.30; Oxygen: 7.08%; MASS: m/z 452.

3.4 Spectral discussion

3.4.1 Mass spectral study

Mass analysis was performed on GCMS with DIPT. Systematic fragmentation pattern

was observed in mass spectral analyses. Base peak was obtained at mol.wt of compound.

Mass fragmentation pattern for a representative compound of each series is depicted

below.


144

Mass fragmentation pattern for ND-146

m/z =433

m/z =468

NH

NH

O

O

NH

ClF3C OCH3

NH

NH

O

O

NH

ClF3C

NH

NH

O

O

NH

F3C OCH3

NH

NH

O

O

NH

ClOCH3

NH

NH

O

O

NH

F3C

NH

NH

OH3C

O

NHNH

NH

OH3C

O

H2N

OCH3NH

NH

O

O

H2N

OCH3

NH

NH

O

OCH3

NH

NH

O

NH

NH

O

NH

NH

O

O

NH

ClOCH3

m/z =468 m/z =438

m/z =386

m/z =400

m/z =389

m/z =307m/z =261m/z =247

m/z =204

m/z =174

m/z =98

CH3

H3C

NH

NH

O

O

NH

ClF3C OCH3

CH3

H3C

CH3

H3C

CH3

H3C

CH3

CH3

H3C

CH3

Figure-3.9


145


m/z =419

m/z =486

NH

NH

S

O

NH

ClF3C

NH

NH

S

O

NH

ClF3C

NH

NH

S

O

NH

F3C

NH

NH

S

O

NH

Cl

NH

NH

S

O

NH

F3C

NH

NH

SH3C

O

NH

NH

NH

SH3C

O

H2N

NH

NH

S

O

H2N

NH

NH

S

NH

NH

S

NH

NH

S

NH

NH

S

O

NH

Cl

m/z =486 m/z =456

m/z =406

m/z =420

m/z =417

m/z =325

m/z =282m/z =268

m/z =225

m/z =192

m/z =116

CH3

H3C

NH

NH

S

O

NH

ClF3C

CH3

H3C

CH3

H3C

CH3

H3C

CH3

CH3

H3C

CH3

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Figure-3.10


146


m/z =452

m/z =486

N

NH

O

O

NH

ClF3C

N

NH

O

O

NH

ClF3C

N

NH

O

O

NH

F3C

N

NH

O

O

NH

Cl

N

NH

OH3C

O

NH

N

NH

OH3C

O

H2N

OCH3N

NH

O

O

H2N

OCH3

N

NH

O

N

NH

O

NH

NH

O

NH

NH

O

O

NH

Cl

m/z =486 m/z =452

m/z =390

m/z =414

m/z =321

m/z =310m/z =296

m/z =223

m/z =188

m/z =98

CH3

H3C

N

NH

O

O

NH

ClF3C

CH3

H3C

CH3

H3C

CH3

H3C

CH3

CH3

H3C

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

Cl

Cl

Cl

Cl

Cl

ClCl

Cl

Figure-3.11


147

3.4.2 IR spectral study

Infrared spectra were record on Shimadzu IR-8400 model using potassium bromide pellet

method. Various functional groups present in molecule were identified by characteristic

frequency obtained for them. For Tetrahydro pyrimidines ND-146 to 190, confirmatory

bands for secondary amine and amidic carbonyl groups was at 3450-3200 and 1715-1600

correspondingly. Another characteristic C-N-C (pyrimidine ring stretching) was observed

at 1360- 1300 cm-1, which suggested formation of desired products.

3.4.3 1H NMR spectral study

1H NMR analysis was reported and it’s done in Dimethyl sulfoxide-d6 solution on a

bruker Ac 400 MHz instrument. Tetra methyl silane as a standard. Number of protons

and their chemical shifts were found to confirm the compound was form.1H NMR

spectra confirmed the structures of Tetrahydro pyrimidines ND- 146 to 190 on the basis

of following signals: a singlet for the methane proton of pyrimidine ring at 5.90-4.30 δ

ppm, and singlets for N-H of primidine at 7.80-9.60 δ ppm and amide group protons at

9.10-10.32 δ ppm, respectively. The aromatic ring protons and J value were found to be

in accordance with substitution pattern on phenyl ring.


148

IR spectrum of ND - 146

Figure-3.12

Mass spectrum of ND -146

Figure-3.13


149

1H NMR spectrum of ND - 146

Figure-3.14

Expanded 1H NMR spectrum of ND - 146

Figure-3.15


150

IR spectrum of ND -166

Figure-3.16

Mass spectrum of ND - 166

Figure-3.17


151

1H NMR spectrum of ND- 166

Figure-3.18

Expanded 1H NMR spectrum of ND - 166

Figure-3.19


152

IR spectrum of ND - 181

Figure-3.20

Mass spectrum of ND - 181

Figure-3.21


153

1H NMR spectrum of ND - 181

Figure-3.22

Expanded 1H NMR spectrum of ND -181

Figure-3.23


154

3.5 Biological evaluation

3.5.1 Antimicrobial evaluation

Activity of compound confirm against bacteria like grampositive and gram

negative. In gram positive includes staphylococcus aureus, streptococcus pyogenes and

for gram negative Escherichia coli, pseudomonas aeruginosa. For anti fungal activity

yeast including candida and asperginosa clavatus is used. Amplicilline and

chloramphenicol are used for antibiotic. Reference anti fungal drug fluconazole used for

comparization of antifungal activity. Summary of the antimicrobial activity in Table 2.4.

From the result of antifungal data, compounds 3e, 3f were active against

C.albicans. while compounds 3c, 3h, 3f, 3n were active against A.clavatus. Further in

Antibacterial study shows compounds 3f, 3g, 3o were active against S.aures and

compounds 3a, 3c, 3i, 3j shows activity against S.pyrogenes. In case of E.coli compounds

3h, 3i, 3m, 3n, 3o shows good activity while in case of P.aeruginosh compounds 3a, 3e,

3l, 3o shows good activity. Other compounds did not show any hopeful activity against

tested bacteria and fungi.

Minimal Inhibition Concentration [MIC]:-

Method: ‘Broth Dilution Method’

Advantage:

1. For primary and secondary screening, serial dilutions were prepared.

2. The control tube contain no antibiotic is instantly sub cultured through dispersion

a loopful uniformly, proper for the increase of the test organism and plant for

store at 36 0C during the night.

3. To check the accuracy of the drug concentrations is interpret by the MIC of the

control organism

4. MIC record the lowest concentration inhibiting growth of the organism.


155

5. The total expansion of the control tube prior to storage is compare.

Methods used for primary and secondary screening: -

Synthesized compound was diluted to 2000 µg mL-1 concentration as a stock

solution. Size for inoculums test, strain was adjusted to 108 colony forming unit per

milliliter for compare the turbidity.

Primary screen: - Concentration for primary screening of all synthesized compound were

(1) 1000 µg mL-1 (2) 500 µg mL-1 and (3) 250 µg mL-1.If active compound found in

primary test it was further tested in a second set of dilution against all microorganisms.

Secondary screen: - The compound found active in primary test were similarly diluted to

(1) 200 µg mL-1(2) 100 µg mL-1 (3) 50 µg mL-1, (4) 25 µg mL-1(5) 12.5 µg mL-1 and (6)

6.250 µg mL-1 concentrations.

Reading Result: - The maximum dilution shows at least 99 % inhibition zone is taken as

IC. The result of this is much depended on the size of the inoculums. The mixture for test

should have 108 organism/ml.

Table 3.4. The results obtained from antimicrobial susceptibility testing.

Compound No.

Zone of inhibition (in mm)

Antibacterial activity Antifungal activity

Gram +ve Gram -ve C. albicans

A.clavatus S.

aureus S.

pyrogenes E.

coli P.

aeruginosa

ND-146 15 NA 17 12 21 09

ND-147 23 05 09 16 16 11 ND-148 16 13 11 13 15 17 ND-149 11 22 24 09 16 24 ND-150 12 19 23 08 17 18 ND-151 13 11 20 10 19 23 ND-152 22 10 19 09 15 16 ND-153 20 17 16 12 22 16


156

ND-154 19 15 10 06 25 19 ND-155 16 14 14 05 17 18 ND-156 21 09 16 08 17 24 ND-157 10 17 19 13 19 23 ND-158 11 14 12 11 18 16 ND-159 09 10 11 14 15 08 ND-160 18 13 14 21 14 09 ND-161 11 12 15 11 22 09 ND-162 12 10 20 11 23 10 ND-163 13 11 18 13 15 16 ND-164 14 14 19 11 18 23 ND-165 12 13 18 12 19 18 ND-166 13 11 21 10 17 22 ND-167 17 09 20 09 16 19 ND-168 12 10 18 10 09 10 ND-169 11 10 11 13 25 17 ND-170 10 13 14 15 24 15 ND-171 12 12 13 12 17 14 ND-172 15 14 11 11 19 24 ND-173 13 11 19 09 18 25 ND-174 14 19 13 10 19 18 ND-175 18 13 19 19 13 19 ND-176 15 17 20 16 21 23 ND-177 17 18 19 13 18 20 ND-178 14 13 17 19 19 20 ND-179 13 14 15 16 21 18 ND-180 16 18 12 17 12 19 ND-181 15 19 19 17 15 20 ND-182 17 15 21 15 17 23 ND-183 18 17 18 16 21 20 ND-184 18 17 16 18 23 23 ND-185 16 17 16 21 23 17 ND-186 16 16 14 15 21 17 ND-187 16 19 16 17 21 24 ND-188 17 17 17 18 21 22 ND-189 19 04 12 10 20 13 ND-190 16 18 17 19 19 22

Amplicilline 18 19 20 20 - - Chloramphenicol 21 20 23 21 - -

Fluconazole - - - - 24 24


157

3.6 References

1. Lanjewar KR, and Rahatgaonkar AM. (2009), “Synthesis and Anti-microbial

activity of 5-(2 aminothiazol-4-yl)- 3,4-dihydro-4-phenyl pyrimidine-2(1H)-

one” Indian Journal of Chemistry, 48B, 1732-1737.

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