QUINOLINYL HETEROCYCLES AS ANTIMYCOBACTERIAL AGENTS:

DESIGN DIVERSITY-ORIENTED SYNTHESIS, STRUCTURE ACTIVITY

RELATIONSHIP AND ACTIVE ANALOGUES OPTIMIZATION

Thesis Submitted

To

Department of Chemistry

Kakatiya University, WarangalFor the degree of

Doctor of Philosophy in Chemistry

By

Rachakonda Venkatesham, UGC-SRF,

Under the Supervision of

Dr. A. Manjula, Principal Scientist

Crop Protection Chemicals (Organic-II) Division

CSIR-I.I.C.T

Crop Protection Chemicals Division (Organic-II)

CSIR-Indian Institute of Chemical Technology

Hyderabad-500607, India

July-2014

Thesis

Conclusions

Acknowledgements

Chapter-I

Introduction of Mycobacterium tuberculosis, Quinoline and their

Biological importance

Tuberculosis (TB) Tuberculosis (TB) is the leading infectious disease in the world.

It is caused by the bacillus Mycobacterium tuberculosis (MTB) and was discovered

by Robert Koch in 1882.

Latent TB

Drug sensitive Tuberculosis-curable with first line drugs (INH, PZA, EMB, RIF)

MDR-TB-resistant to RIF and INH, treatment FQs & inject able drugs AMK,

KAN, CAP.

XDR-TB resistant to at least one FQs and inject able drugs

TDR-TB incurable form of TB

HIV- Co-Infection

DOTS strategy

BCG-Vaccination

Figure 2: M. tuberculosis aerosol transmission and progression to infectious TB or

non-infectious (latent) disease

Figure 1: Available TB drugs

Figure 5: Pictorial representation of recently approved and under clinical trial TB active

compounds and their targets

TMC-207 (Badaquiline) is a diaryl quinolinyl US-FDA approved TB drug.

Trade name is Sirturo.

Effectively inhibits the Mycobacterium smegmatis strain.

TMC-207 (Bedaquiline)TB Bacteria

Figure 2: TMC-207 activity on TB bacteria

Figure 4: Classification of quinoline synthesis, based on starting material

Bedaquiline

Figure 2. Extrapolation of isoniazid and bedaquiline

Isoniazid

Figure 5: Synthetic strategy of TMC-207 based analougues

Chapter-I

Design, diversity-oriented synthesis and structure activity

relationship studies of quinolinyl heterocycles as

antimycobacterial, antimicrobial and anti-inflammatory agents

Scheme 3: Oxidative condensation for C4 unsubtituted quinoline synthesis

Scheme 8: Synthesis of 2-(2-methylquinolin-3-yl)-5-phenethyl-1,3,4-oxadiazole

Scheme 9: Synthesis of 2-bromo-1-(2-methylquinoln-3-yl)ethanone

Scheme 10

Scheme 11: Synthesis of 3-(dimethylamino)-1-(2-methylquinoline-3-yl)prop-2-one

Scheme 12

Scheme 15: Synthesis of 1-(2-methylquinolin-3-yl)-3-(2,4,6-trimethoxyphenyl)prop-2-en-1-one

Scheme 16: Synthesis of 1-(3-(2-methylquinolin-3-yl)-5-(2,4,6-trimethoxyphenyl)-

4,5-dihydro-1H-pyrazol-1-yl)ethanone

Compound Antimycobacterial activity

(against M. smegmatis strain)

Cytotoxicity activity

(against A549 cells)

a &b MIC(μg/mL) cStd. Dev. dIC50 (μM) Std. Dev

86 >100 - 96.373 20.335

89a 34.97 4.2 144.839 28.677

91 >100 - >200 -

92 >100 - 117.724 32.516

94 >100 - 94.198 18.000

95 14.66 1.25 137.510 4.534

102a 57.87 13.18 170.745 48.263

Rifampicin (Control) 2.08 0.04 ----- ------

Isoniazid (Control) 12.07 0.98 ---- ----

aMycobacterium smegmatis ATCC 14468 (MC2).b Concentration of compounds inhibiting growth by 50%c GI50 values are indicated as mean ± SD (standard deviation) of three independent experiments.dIC50 (μM) against A549 cells

Table 1: Primary antimycobacterial and cytotoxicity screening of diverse quinolinyl

heterocycles

Figure 14: Graphical representation of activity results

Scheme 18: Synthesis of 2,5-disubstituted quinolinyl 1,3,4-oxadiazole (26) derivatives

Scheme 19: Synthesis of N-acyl quinolinyl pyrazoline (16) derivatives

Scheme 20: Synthesis of N-phenyl quinolinyl pyrazoline derivatives

Scheme 21: BDMS catalyzed synthesis of 3-(tetrahydro-2H-pyran-2-yl)pentane-2,4-dione

Scheme 22

Scheme 24: Synthesis of 1-(3-(2-methylquinolin-3-yl)-1H-pyrazol-1-yl)ethanone

52 compounds synthesized

40 compounds tested

Mycobacterium

Tuberculosis

Antimicrobial

Biological

Activities

Anti-Inflammatory

Antimycobacterial activity Cytotoxicity activity Antimycobacterial activity Cytotoxicity activity

A Ba&b CC Dd CcA Ba&b CC Dd Cc

89b 35.93 9.62 164.512 13.317 102d >70 - 110.856 21.568

89c 35.04 14.92 174.567 22.078 102e 52.09 13.77 >200 -

89d >70 - 145.988 24.743 102f >70 - >200 -

89e >70 - 72.159 20.916 102h >70 - >200 -

89f 41.05 13.0 103.472 16.873 102i >70 - 93.330 14.414

89g 29.18 10.71 134.278 51.084 102j 50.70 1.59 >200 -

89h 61.88 15.23 113.023 2.596 102k 64.90 12.13 72.726 4.731

89i 43.29 10.0 …….. 0.657 102l >70 - >200 -

89j 22.71 4.0 138.767 17.112 102m >70 - 114.596 6.073

89k 47.53 9.03 93.314 11.475 102n >70 - 166.047 83.831

89l >70 - 91.132 4.406 106a >70 - 92.976 11.253

89m 16.83 5.93 111.013 4.083 106b >70 - >200 -

89n 39.73 10.61 99.364 15.649 106c 43.52 4.36 142.803 61.457

89o >70 - >200 - 109a 24.11 6.71 97.873 21.434

102b >70 - 110.429 21.661 109b >70 - 142.528 38.767

102c >70 - 115.977 15.083 112 17.34 4.21 87.025 8.86

X 2.15 0.57 ----- ----- X 2.15 0.57 ----- -----

Y 11.78 0.86 ----- ----- Y 11.78 0.86 ----- -----

A: Compunds, B: MIC (µg/mL), C: Std dev, D: IC50 (µm/mL), a Mycobacterium smegmatis ATCC 14468 (MC2). b Concentration of compounds inhibiting growth by 90 %. c MIC values are indicated as mean ± SD (standard deviation), dIC50

(μg/mL) against A549 cells, X: Rifampicin, Y: Isoniazid

Table 2: Antimycobacterial activity of quinolinyl oxadiazoles pyrazolines and

pyrazoles

Figure 16: Graphical representation of antimycobacterial active compounds

Design and diversity oriented synthesis of novel quinoline containing heterocycles has been

achieved employing simple reaction protocols and common intermediates. Simultaneous screening for

antimycobacterial activity led to the identification of quinolinyl oxadiazole and pyrazole frameworks as

active molecules. The synthetic protocols have been successfully extended for generation of library of

uinolinyl oxadiazoles, pyrazolines and pyrazoles. In all, 40 compounds were tested for antimycobacterial

activity and lead identification gave of 20 active molecules and 3 (8, 12j and 12m) promising

compounds. Further, lowcytotoxic effects of these compounds against A549 cell line underline their

potential as antitubercular agents.

• Finding of this results have been published in Eur. J. Med. Chem. 70 (2013) 536-547

Venkatesham Rachakonda, Manjula Alla, Sudha Sravanti Kotapalli, Ramesh Ummanni

Gram negative bacterial strains Gram positive bacterial strains

Comp a b c d e f g h i j

89n -- -- -- -- 0.14 0.14 0.13 -- -- --

89r -- 0.14 -- 0.13 -- -- -- -- -- --

89s 0.14 -- -- 0.13 0.11 -- 0.11 0.14 -- --

89w 0.14 -- -- -- -- -- -- -- -- --

89y -- -- -- -- 0.15 -- 0.15 -- -- --

Std -- 0.18 0.22 -- -- 0.18 0.14 0.16 0.22 0.18

Std (Standard): Streptomycin (Concentration 10μg/mL)

a= Eschericha coli, b= Proteus vulgaris, c= Proteus mirabilis, d= Klebsiela

pneumoniae, e= Enterobacter aerogens, f= Bacillus subtilis, g= Bacillum

megaterium, h= Bacillus pumilis, i= Staphylococcus aureus, j= Streptococcus

pyogens and-- = Not active

Antibacterial activity (MIC 10µg/mL) of 2-(2-methylquinolin-3-yl)-5-substituted-1, 3, 4-oxadiazoles

Five of the seventeen

compounds tested showed

impressive MIC values

(10μg/mL). Compounds 89w,

89s showed effective inhibition

on E. coli at 10µg/mL

concentration. Compounds 82r,

82s and 89n, 89s, 89y showed

effective inhibition on Klebsiella

pneumoniae and Enterobacter

aerogenes, at 10µg/mL

concentration, respectively. At

this concentration (10μg/mL),

standard has not shown any

inhibition of these species.

Among all the tested

compounds, 89w, 89n, 89r, 89s,

89y effectively inhibited the

growth of resistant gram

negative bacteria compared to

gram positive bacteria at

10µg/mL concentration

Antifungal activity of 2-(2-methylquinolin-3-yl)-5-substituted-1, 3, 4-oxadiazoles

Zone of inhibition ( mm)

A B a b c d A B a b c d

89a600 4.50 5.03 7.59 5.56

89o600 NA 4.35 3.54 5.09

900 8.45 10.73 14.45 10.67 900 NA 8.45 6.23 10.45

89b600 4.26 5.35 3.32 5.92

89q600 5.56 4.32 7.65 6.32

900 7.72 10.85 6.54 11.23 900 11.05 8.25 14.34 12.35

89c600 5.05 6.32 6.59 6.90

89r600 6.25 4.05 3.50 3.45

900 10.23 13.16 14.12 13.06 900 12.24 8.25 6.45 6.56

89d600 5.32 5.56 4.56 3.23

89s600 4.56 6.32 8.56 4.45

900 10.82 11.32 8.89 6.67 900 8.23 12.34 16.24 9.05

89e600 3.34 5.54 4.34 2.12

89v600 4.12 5.03 5.23 4.05

900 6.21 10.21 8.21 4.34 900 8.45 10.34 10.56 8.10

89f600 3.42 4.26 3.25 3.45

89w600 5.65 4.45 3.32 5.56

900 6.75 8.59 6.50 7.14 900 10.25 9.08 6.67 10.54

89g600 3.12 4.98 3.92 5.39

89I600 2.13 5.32 6.87 5.23

900 6.23 9.43 7.42 11.12 900 4.32 10.64 12.21 10.54

89n600 6.50 6.25 NA 5.35

……..……… ……… ……… ……… ……….

900 12.23 12.87 NA 11.05 ……… ……… ……… ……… ………

X600 5.35 10.80 7.56 9.34

X600 5.35 10.80 7.56 9.34

900 12.01 20.03 14.76 18.26 900 12.01 20.03 14.76 18.26

a=Candida albicans, b=Fusarium oxysporium, c=Dreschleria halides, d=Colletotrichum falcatum; NA=No Activity; B: Itraconazole

(Standard)

An extra heterocycle substitution on oxadiazole enhances the antifungal activity. 3-[5-(4-

Methoxyphenyl)-[1,3,4]oxadiazol-2-yl]2-methylquinoline (89r) is the other compound which

inhibited fungal growth to significant extent.

Table 7: Anti-inflammatory activity of 2-(2-methylquinolin-3-yl)-5-substituted-1, 3, 4-oxadiazoles by

carrageenan-induced rat paw edema assay (acute inflammatory model)

Comp Dose

(mg/kg)

Percentage of Edema Inhibition

(%)

30 mins 1h 2h 3h

89b 100 28 35.2 51.6 51.7

89c 100 24 35.2 60 49.4

89d 100 16 26.4 28 24.1

89f 100 32 38.2 57.3 48.2

89g 100 16 35.2 45.3 24.1

89n 100 40 41.1 60 67.8

89o 100 36 44.1 54.6 58.6

89q 100 20 35.2 41.3 42.5

89r 100 12 17.6 40 42.5

89y 100 20 38.2 56 50.5

89I 100 36 50 50.6 57.4

Std

(Diclofenac)

10 40 41.1 52 68.9

The anti-inflammatory activity profile indicates that compounds with heterocyclic substitution at 5th

position of oxadiazole is again the best candidate among the tested molecules. Thiophene substitution

shows better anti-inflammatory activity than standard at 1 h, 2 hrs, 3 hrs time but activity falls at 4

hrs, while in case of pyrazole substitution activity falls from 3 hrs. 2-(2-Methylquinolin-3-yl)-5-(1-

phenylethyl)-1,3,4-oxadiazole (89b) is the only alkyl substitution that exhibits good activity.

Chapter-III

Quinolinyl Heterocycles as Antimycobacterial Agents: Towards

Structure Optimization of the Acive Analogues 2-Methyl-3-(1H-

pyrazol-5-yl)quinoline and 3-(5-(2-methylquinolin-3-yl)-1,3,4-

oxadiazol-2-yl)4H-chromen-4-one

In all, 40 compounds were tested for antimycobacteium activity and lead identification

gave of 20 active molecules and 2 (1, 2) promising compounds

Compound MIC(μg/mL)

2 14.66

Rifampicin (Control) 2.08

Isoniazid (Control) 12.07

Compound MIC(μg/mL)

1 16.83

Rifampicin(Control) 2.15

Isoniazid (Control) 11.78

Scheme 1: Synthesis of 2-methylquinoline-3-carbohydrazone (10) derivatives

Figure 6: Various positions for the synthesis of substituted 2-methyl-3-(1H-pyrazol-5-yl)quinoline

Scheme 4: Synthesis of 2-methyl-3-(1-(N-aryl/alkyl)-1H-pyrazol-3-yl)quinoline derivatives

Figure 8: Retrosynthetic analysis for ring functionalization of pyrazole

Scheme 5: Reaction of active methylene group with triethyl orthoformate and DMF-DMA.

Reactive intermediate

Scheme 2: Synthesis of ethyl 3-(2-methylquinolin-3-yl)-3-oxopropanoate

Scheme 7: Synthesis of ethyl 3-(2-methylquinolin-3-yl)-1H-pyrazole-4-carboxylate

Scheme 8: Synthesis of 3-(2-methylquinolin-3-yl)-1H-pyrazol-5-ol (23)

Scheme 10: Synthesis of 2-methyl-3-(1-(prop-2-ynyl)-1H-pyrazol-3-yl)quinoline or

ethyl 3-(2-methylquinolin-3-yl)-1-(prop-2-ynyl)-1H-pyrazole-4-carboxylate

Figure 15: Molecular hybridization approach for structure optimization

Scheme 3. Synthesis of quinolinepyrazolyl 1,2,3-triazole hybridized moecules (21 molecules)

starting from common intermediates 13 and 14

Antimycobacteria

l activity

Cytotoxicity Antimycobacterial

activity

Cytotoxicity

A Ba&b Cc Dd Cc A Ba&b Cc Dd Cc

12a 28.8 0.032 >100 52b 33.76 0.01 36.6 17.52

12b >100 22.16 13.2 52c >100 12.35 0.26

12c 19.57 0.004 >100 52d >100 21.02 1.23

12d 17.26 0.003 >100 52e >100 >100

12e 21.62 0.050 >100 52f NA 23.65 8.13

12f >100 >100 52g >100 >100

12g 23.5 0.038 8.29 6.63 52h >100 15.49 8.71

12h >100 10.86 2.09 52i NA >100

12i 14.92 0.012 15.82 8.29 53a >100 20.44 9.75

12j >100 17.08 11.84 53b 33.27 0.012 16.04 0.75

12k >100 23.85 2.3 53c 25.17 0.013 >100

36 NA 10.52 6.49 53d 26.34 0.004 22.88 15.36

20a >100 24.29 22.97 53e 29.87 0.006 16.442 4.69

20b 20.64 0.06 11.14 5.84 53f >100 22.25 11.79

20c >100 15.19 2.93 53g >100 >100

20d NA >100 53h >100 >100

22 NA >100 54a NA 20.114 6.92

37 28.26 13.19 3.96 54b 40.5 >100

23 >100 15.26 5.92 54c >100 >100

52a NA >100 55 >100 16.85 9.22

X 12.07 ------- X 12.07 -------

Y 2.15 ------- Y 2.15 -------

Z ------- ------- 0.16 Z ------- -------

A: Compound, B: MIC (µg/mL), C: STD Dev; aMycobacterium smegmatis ATCC 14468 (MC2155).b Minimum concentration of compounds inhibiting visible bacterial growth. c MIC values are indicated as mean ±SD (standard deviation) of

three independent. d IC50 (µg/mL) against A549 cells.

X: Isoniazid, Y: Rifampicin, Z: Doxorubicin

Antimycobacterial evaluation of optimized quinolinyl heterocycles

• The MIC values (µg/ml) of compounds 14a (28.8±0.032), 14c (19.57±0.004),

14d (17.26±0.003), 14e (21.62±0.05), 37b (33.76 ± 0.01), 38c (25.17±0.013)

and 39b (40.5) compared to their cytotoxicity in IC50 (>100) highlight that these

are promising scaffolds to design and develop

quinolinyl based antimycobacterial agents.

• 14i showed cytotoxicity with IC50 value 32.70±8.29 µM while its MIC was found

to be 14.92±0.012 (µg/ml).

• Thus, this compound may not be a good antitubercular agent.

• Interestingly quinolinyl hydrazones were shown good antimycobacterial activity

than the corresponding pyrazolyl1,2,3-triazoles.

• It was initiated to gone for antibacterial activity of quinolinyl hydrazone

In vitro antibacterial activity of quinolinyl hydrazones

MIC (10μg/mL)

Gram Negative bacterial strains Gram Positive bacterial strains

Comp a b c d e f g h i j

12a 0.14 -- -- 0.11 -- -- 0.11 -- -- --

12b -- -- -- -- 0.15 0.15 -- 0.12(

25)

-- --

12c 0.11 -- -- -- 0.14 0.14 0.12 - -- --

12d 0.14 -- -- 0.13 0.11 -- 0.11 014 -- --

12e -- -- -- -- 0.14 -- 0.13 -- -- --

12f -- -- -- -- 0.15 -- 0.15 -- -- --

Std --- 0.18 0.22 --- --- 0.18 0.14 0.16 0.22 0.18

Std (Standard): Streptomycin a= Eschericha coli, b= Proteus vulgaris, c= Proteus mirabilis,

d= Klebsiela pneumoniae, e= Enterrobacter aerogens, f= Bacillus subtilis, g= Bacillum

megaterium, h= Bacillus pumilis, i= Staphylo coccusaureus, j= Streptococcus pyogens and -

-- Not Active.

Six of the ten

compounds tested showed

impressive MIC values

compared to streptomycin

which was used as standard

(10μg/mL) on different strains.

Among all the tested

compounds, 12(a-f) effectively

inhibited the growth of drug

resistant gram negative bacteria

compared to gram positive

bacteria at 10µg/mL

concentration. Graphical

representation of antibacterial

activity of quinolinyl

hydrazones in MIC is shown

• Selective structure optimization of the hits was attempted on 3-(5-(2-methylquinolin-

3-yl)-1,3,4- oxadiazol-2-yl)-4H-chromen-4-one and 2-methyl-3-(1H-pyrazol-5-

yl)quinoline molecules by both forward and reverse synthetic approaches.

• Molecular hybridization of 2-methyl-3-(1H-pyrazol-5-yl)quinoline employing the

copper catalyzed Huisgen’s 1,3-dipolar cycloaddition (Click reaction) led to

introduction of 1,2,3-triazole ring.

• 40 compounds synthesized were evaluated for their antimycobacterial activity and

cytotoxicity against A549 cell line.

• All Among the 14 antitubercular active compounds, 3 have shown promising activity

coupled with low cytotoxicity profile.

• Quinolinyl hydrazones were also evaluated for anti bacterial activity which shown

good results

• Finding of this results have been Communicated to

Eur. J. Med. Chem. Venkatesham Rachakonda, Manjula Alla, Sudha Sravanti

Kotapalli, Ramesh Ummanni, Ramakrishna Munnaluri, Yamini Lingala, Vijjulatha

Manga.

Results

Chapter-IV

(Bromodimethylsulfonium)bromide Catalyzed Organic

Transformations Under Solvent Free Conditions

Figure 1: Catalytic and chemical nature of BDMS

Figure 5. BDMS catalyzed solvent free synthesis of imidazo[1,2-a]pyridines and quinoline

Section-A

(Bromodimethylsulfonium)bromide catalyzed solvent free one pot three

component synthesis of imidazo[1,2-a]pyridine

H

an

tzsc

h

syn

thes

is

Bu

cherer-B

ergs

reactio

n

isocyanide based

multicomponent

reactions

Figure 2: Pictorial representation of various multicomoponent reactions

Figure 3: Pictorial representation of isonitrile based MCRs

Figure 4: Pictorial representation of Strecker, Blackburn and Hulme

imidazo[1,2-a]pyridine synthesis.

Scheme 11: BDMS catalyzed synthesis of N-benzylidene-2-phenylimidazo[1,2-a]pyridine derivatives

S.No Addition Sequence Catalyst Solvent Tempa Timeb Yieldc

1 1 9a (1eq) BDMS 7 MeOH r.t 8 41

2 1 9a (1eq) BDMS 7 …….. r.t 8 40

3 1 9a (2eq) BDMS 7 MeOH r.t 8 93

4 1 9a (2eq) BDMS 7 …….. r.t 8 91

5 Schiff’s base of 4-chlorobenzaldehyde, 2-amino

pyridine and catalyst then TMSCN (1:2:1)…….. r.t 3 91

6 4-chlorobenzaldehyde (2eq), TMSCN and BDMS

stirred for 3 hrs then 2-aminopyridine.…….. r.t 8 90

Tempa=reaction temparature; Timeb= reaction time in hrs; Yieldc= isolated yield in %.

The above experiments indicate that, both imine and cyanohydrin formation are plausible pathways

for this reaction

Plausible mechanism

via imine formation

via cyanohydrin formation

Comp Product Time (hrs) Yield (%) Mp (OC) Comp Product Time (hrs) Yield (%) Mp (OC)

10a 10 91 170-174 10i 10 65 182-185

10b 11 70 145-148 10j 10 80 125-128

10c 11 60 93-95 10k 10.5 82 95-98

10d 10 79 184-190 10l

11

72 205-210

10e 10 60 88-90 10m 11 68 173-175

10f 11 70 105-108 1on 11 50 278-281

10g 11 50 200-205 10o 11 55 200- 203

10h 10.5 61 244-247

Scheme 12: Hydrolysis of N-(4-chlorobenzylidene)-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-amine

Section-A

(Bromodimethylsulfonium)bromide catalyzed solvent free Friedlander synthesis of

Quinoline

Scheme 14: Friedländer synthesis of quinoline derivatives

S.No BDMSa Yield (%)b Timec

1 0 Traces 24 hrs

2 5 50 2 hrs

3 10 80 50 min

4 20 80 50 min

a; BDMS mol%, b; isolated yield; c; reaction time

Figure 7. Plausible mechanism of BDMS catalyzed quinoline synthesis

Compound Product Yield (%) M.p (OC) Compound Product Yield (%) M.p (OC)

14a 80 98-100 14l 62 Yellow Oil

14b 81 114-116 14m 83 Yellow Oil

14c 81 105-107 14n 84 178-180

14d 80 153-156 14o 92 130-132

14e 85 94-95 14p 72 217-220

14f 81 196-198 14q 93 144-148

14g 64 116-118 14r 81 315-318

14h 40 90-92 14s 88 136-138

14i 32 74-76 14t 80 154-157

14j 41 188-191 14u 60 Yellow Oil

14k 81 Yellow Oil

Total 129 compounds were synthesized. Design, diversity oriented synthesis of

bedaquiline related N-heterocycles were succesfully achieved and evaluated against

M.smegmatis strain for anti TB activity. Based on hits observed, lead generation, SAR and

structure optimization was carried out. In all 100 novel quinolinyl heterocycles, 80

compounds were tested for antimycobacterial activity 34 active and 6 promising

compounds were observed. Low cytotoxocity of the compounds highlighted their

efficiency. In addition to this, these compounds also having good antimicrobial as well as

anti-inflammatiry activities. Synthesis of imidazo[1,2-a]pyridine derivatives (16

compounds) were completely studied and a variety of cyclic, acyclic quinolinyl derivatives

(21 compounds) were achieved under solvent free conditions without involving tedious

purification techniques

Conclusions

Ihe End

But journey will cotinue…………

Acknowledgements

• Dr. A. Manjula, Principal Scientist, Supervisor, CPC Division CSIR-IICT

• Dr. B. Vittal Rao, Retired Scientist, CPC Division CSIR-IICT

• Head CPC and DIICT

• Proff. V. Ravinder, Head, Dept of Chemistry, KU

• Proff. G. Dayakar, Chairmen, BOS, Dept of Chemistry, KU

• Proff Sadanandam, Dean Faculty of Science

• Teaching Staff Kakatiya University

• Proff. K. Rajareddy, KITS Warangal

• Proff. Komal Reddy, Dean Faculty of Science, Satavahana University, Karimnagar

• Proff. M. Thirumala Chary, Chairmen, BOS, JNTU Hyderabad

• Dr. Madhukar Reddy, KITS Warangal

• Dr. Ramesh Babu, KITS Warangal

• Dr. D. Prabhakara Chary, KITS Warangal

• Dr. Ranadeer Kumar, KITS Warangal

• S. Ramakrishna Reddy (Degree Lecturer)

Friends

& My Family

Thank You