CHAPTER-2 REVIEW OF LITERATURE -...

Chapter-2 Review of Literature

Ph. D. Thesis 14

CHAPTER-2

REVIEW OF LITERATURE

Literature related to Benzofuran:

Benzofurans are bicyclic ring system with multiple applications. The Literature indicates

that compounds having Benzofuran nucleus possess broad range of biological activities,

like Griseofulvin as antifungal; Amiodarone as antiarrythmic; Benzbromarone as

uricosuric; Cloridarol as vasodilator; Oxetorone as antimigraine agent.

Antimicroabial Activity:

Koca et al. [1] synthesized new derivatives of (benzofuran-2-yl)(3-phenyl-3-methyl

cyclobutyl) ketoxime such as, O-glycidylketoxime (1), O-phenylacylketoxime (2), Alkyl,

allyl and aryl substituted N-oxime ethers (3). The syntheses of the compounds (4) were

carried out from the reaction of the compound (1) and different amines such as, isopropyl

amine, natrium azide, morpholine and piperazine. All of the synthesized compounds were

tested for antimicrobial activity against Staphylococcus aureus ATCC 6538,

Staphylococcus epidermidisATCC 12228, Escherichia coliATCC 8739, Klebsiella

pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi,

Shigella flexneri, Proteus mirabilis ATCC 14153 and Candida albicans ATCC 10231.

Among the synthesized compounds most of them are found to be active.

O N

H3C

Ph

O

O

O N

H3C

Ph

O

O

R1

(1) (2)

R1=Ph, PhCH2-, CH3


Ph. D. Thesis 15

O N

H3C

Ph

O

R2

O N

H3C

Ph

O

OHN

Z (3) (4)

R2= PhCH2-, CH3, PhCOCH2-, Z= -CH2, -NCH3, -NC6H5, O

CH2=CHCH2, C2H5OCOCH2-,

Alper-Hayta et al. [2] synthesized a new series of 2-(substitutedphenyl/benzyl)-5-[(2-

benzofuryl)carboxamido]benzoxazole derivatives (5). The in vitro antimicrobial activity

of the compounds was determined against some Gram-positive, Gram-negative bacteria

and fungi and their drug-resistant isolates in comparison with standard drugs.

Antimicrobial results indicated that the synthesized compounds possessed a broad

spectrum of activity.

O

NH

O

N

O

R1

R

(5)

R1=H, Br

R=H, C2H5, F, Br, Cl, CH3, C(CH3)3

Kirilmis et al. [3] synthesized some novel 1-(1-benzofuran-2-yl)-2-mesitylethanone

derivatives. Some of the synthesized compounds were tested for antimicrobial activity

against Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922 and Candida


Ph. D. Thesis 16

albicans ATCC 10231. Among the synthesized compounds (E )-1-(1-benzofuran-2-yl)-2-

mesitylethanone-O-benzoyloxime (6) was found the most active derivative against S.

aureus ATCC 6538 and E. coli ATCC 25922. The other compounds exhibited moderate

activity against the other test microorganisms.

ON

Mes

O

O

(6)

Abdel-Wahab et al. [4] synthesized 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones (7),

3-(Benzofuran-2-yl)-4,5-dihydro-5-arylpyrazole-1-carbothioamide (8) and 3-

(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles (9). All

the synthesized compounds were screened for their antibacterial and antifungal activities

at 100 mg concentration. Some of the compounds showed excellent antimicrobial

activities than control drugs.

O

O

Ar

NO2

O NN

Ar

S

NH2

(7) (8)

Ar= Ph, 4-Cl C6H4 Ar= Ph, 4-Cl C6H4

O NN

Ar

S

N

Ar'

(9)

Ar= Ph, 4-Cl C6H4 ; Ar’= Ph, 4-Br C6H4


Ph. D. Thesis 17

According to Babu et al. [5] chalcones were prepared from 2-acetyl benzofuran and

condensed with different aromatic acid hydrazides to get the corresponding pyrazolines

(10, 11). Among the compounds that were screened against two Gram-

positive(Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria

(Escherichia coli and Pseudomonas aeruginosa), compounds possessing p-chloro, p-

fluoro, 2-amino-5-bromo, 2-hydroxy-5-nitro and 3,5-dichloro substitutions on the phenyl

ring showed good activity against Escherichia coli and Bacillus subtilis. The activity is

comparable with the standard drug ciprofloxacin.

O NN

OCH2COOH

COAr O N

N

COAr

OCH2COOH

(10) (11)

Ar= Phenyl, 4-hydroxy phenyl, 4-chloro phenyl, 2-chloro phenyl, 4-nitro phenyl, 2-nitro

phenyl, o-tolyl, 2-hydroxy phenyl, 4-amino phenyl, isonicotinyl, 4-methoxy phenyl, 2-

amino 5-bromo phenyl, 2-hydroxy 5-nitro phenyl, 3,5-dichlorophenyl

Khan et al. [6] synthesized two series of 2-substituted benzofurans (12) and three new

diacetyl benzofurans (13). The compounds showed mild to significant growth inhibition

against antibiotic-susceptible standard and clinically isolated strains of Gram-positive and

Gram-negative bacteria as well as human fungal pathogens. Ampicillin and kanamycin

were used as references for antibacterial screening; nystatin and amphotericin B were

used for antifungal screening.

O

R

O

O CH3

O

R1R2

R3

(12) (13)

R= C6H5, 4-OCH3 C6H4, 4-CH3 C6H4 R1=R2=R3= H, Ac


Ph. D. Thesis 18

Rida et al. [7] synthesized and evaluated several benzofuran derivatives containing

heterocyclic ring substituents (14-18) linked to the benzofuran nucleus at C-2 by a two-

to four-atom spacer as potential antimicrobial agents. Some compounds exhibited mild

activity against S. aureus, while some compounds had mild activity towards S. aureus

and C. albicans.

O

N

CH3

N

N

S

O

R

O

N

CH3

N

N

S

CH3

R

(14) (15)

R= C4H9, CH2C6H5, C6H5, 4-CH3C6H4 R= CH2C6H5, C6H5, 4-CH3C6H4

O

N

CH3

N

N

S

R

R1

O

N

CH3

N

N

S

O

R

R1

(16) (17)

R= CH2C6H5, C6H5, 4-CH3C6H4 R= CH2C6H5, C6H5

R1=CH3, Cl R1= OCH3, Cl

O

N

CH3

N

N

O S

N

S

R

(18)

R= CH2C6H5, C6H5

Mahadevan et al. [8] synthesized some potent benzofuro Thiazolyl (19), Oxazolyl

(19), Thiadiazolyl (20) and Oxadiazolyl derivatives (20). The results revealed that the

compounds were showing antibacterial and antifungal activity.


Ph. D. Thesis 19

O

R1

R

N

X

NH2 O

R1

R

X

NN

NH2

(19) (20)

X= S, O; R= H, Br, NO2 X= S, O; R= H, Br, NO2

R1=H, CH3 R1=H, CH3

Basavaraja and Agasimundin [9]

synthesized Bis [2(4’-aryl-1’,2’,4’-triazol-5’-yl)]-3-

methoxybenzofuransulphides (21) and disulphides (22). The compounds synthesized

were found to exhibit appreciable antibacterial activity.

O

OCH3

NN

NS

N N

N

O

H3CO

RR

(21)

R= -C6H4 CH3(p), - C6H4 OCH3(p), C6H4 Br(p)

O

H3CO

N

N

NN

N

N

O

OCH3RRS S

(22)

R= -C6H5, -C6H4 CH3(p), - C6H4 OCH3(p)

Manna et al. [10] synthesized various 3-(1-benzofuran-2-yl)-5-phenylisoxazoles (23).

The benzofuran isoxazoles were evaluated for their antibacterial activity. Some of the

compounds have shown promising antibacterial activity.


Ph. D. Thesis 20

O

NO

R

(23)

R= -OH(o), -OCH3(o), -N(CH3)2(p), -COOH(o), -NO2(m), -OH(o)OCH3(p), -OH(p),

-Cl(p), -Cl(o), -NO2(o), -OCH3(p), -H, Furan ring, -Cl=CH-Ar

Prasad et al. [11] synthesized a new series of 3-[3-(3-hydroxy-1-benzofuran-2-yl)-5-

mercapto-4H-1,2,4-triazol-4-yl]-2-substituted phenyl-1,3- thiazolidin-4-ones (24). The

compounds showed moderate to weak antimicrobial activity.

O

OHNN

N

N

HS

S

O

R

(24)

R= H, 2-NO2, 3-Chloro, 2-Chloro, 2-Hydroxy, 2-Methoxy, 4-Bromo, 4-Chloro,

4-Dimethyl amino

Basawaraj et al. [12] synthesized 2-substituted-4-methoxy/ethoxy benzofuro [3,2-d]

pyrimidines (25) and 2-substituted-3,4-dihydro-4-thiobenzofuro [3,2-d] pyrimidines

(26). Some compounds shown significant activity against S. aureus and E. coli

compared with standard drug Ciprofloxacin while some compounds displayed

moderate activity against both bacteria.

ON

N R

R'

ON

N R

SH

(25) (26)


Ph. D. Thesis 21

R= ,

CH3

CH3

CH3 R= ,

CH3

CH3

CH3

R’= OCH3, OC2H5

Basavaraja et al. [13] synthesized a series of 3-alkyl-1,2,3,4-tetrahydro-2-thio-4-

oxobenzofuro[3,2-d] pyrimidines (27), 3,4-dihydro-3-N-alkyl/aryl-2-methylthio-4-

oxobenzofuro[3,2-d] pyrimidine (28), 3,4-dihydro-3-N-alkyl/aryl-2-hydrazino-4-

oxobenzofuro[3,2-d] pyrimidine (29), tetrazolo[1,5-a]-3-N-alkyl/aryl-4-oxopyrimido

[5,4-b] benzofurans (30), triazolo[1,5-a]-3-N-alkyl/aryl-4-oxopyrimido [5,4-b]

benzofurans (31) and 3,4-dihydro-3-N-alkyl/aryl-4-oxopbenzofuro-[3,2-d] pyrimidine-

2-thioacetic acids (32). Compounds (28) exhibited almost equivalent activity as that of

standard (Streptomycin) against both organism S. aureus and E. coli. Compounds (30)

was equally active as that of standard only against S. aureus and inactive against E.

coli only. Some compounds were active only against E. coli.

O

N

HN

S

R

O O

N

N

SCH3

R

O

(27) (28)

R= CH3, C6H5, C6H4CH3(4), C6H4OCH3(4), C6H4Cl(4)

O

N

N

NHNH2

R

O O

N

N

R

O

N

N

N

(29) (30)



Ph. D. Thesis 22

O

N

N

R

O

N

N

HC

ON

N

R

O

S COOH

(31) (32)


Basawaraj et al. [14] synthesized 2-N-arylaminoacetyl-5-chloro-3-methylbenzofurans

(33). Some compounds exhibited high antibacterial activity against S. aureus and

moderate activity against E. coli, remaining compounds have shown moderate activity

against both bacteria.

O

CH3

Cl

O

NH

R

(33)

R= H, 2-CH3, 4-CH3, 2-OCH3,4-OCH3, 2-Cl, 4-Br, 2-NO2

Gundogdu-Karaburun et al. [15] synthesized some aryl [3-(imidazol-1-yl/triazol-1-

ylmethyl/methyl) benzofuran-2-yl] ketones (34-36), aryl (3-methyl-benzofuran-2-yl)

ketoximes (37) and aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketoximes

(38). Antifungal activities of the compounds were examined and moderate activity was

obtained.

O

OH3C

R1

R2

R3

O

CH2

R1

R2

R3

N

N

XO

(34) (35,36)


Ph. D. Thesis 23

R1=H, CH3, Cl; R2= H, OCH3 R1=H, CH3, Cl; R2= H, OCH3

R3=H, Cl R3=H, Cl; X=CH, N

O

NOHH3C

R1

R2

R3

O

CH2

R1

R2

R3

N

N

XNOH

(37) (38)

R1=H, CH3, Cl; R2= H, OCH3 R1=H, CH3, Cl; R2= H, OCH3

R3=H, Cl R3=H, Cl, X=CH, N

Aslam et al. [16] described a novel method for the synthesis of antifungal cicerfuran

(oxygenated benzofuran) and its analogues (39).

OR2

O

OR1

O O

O

O

NHN

R1=OMe, H, Me; R2=OH, H (RO-09-4609)

(39)

According to Ebiike et al. [17] Modification of the C-2 position of a benzofuran

derivative (RO-09-4609), an N-myristoyltransferase (Nmt) inhibitor, has led us to

discover antifungal agents (40,41) that are active in a murine systemic candidiasis model.

O

O

O

NH

N

Z

X Y O

O

NH

N

(40) (41)


Ph. D. Thesis 24

X=H, F, CN; Y=H, F; Z= H, F, CN, Br, Cl

According to Masubuchi et al. [18] the C-4 side chain modification of lead compound

(42) has resulted in the identification of a potent and selective Candida albicans N-

myristoyltransferase (CaNmt) inhibitor RO-09-4609, which exhibits antifungal activity

against C. albicans in vitro. Further modification of its C-2 substituent has led to the

discovery of RO-09-4879, which exhibits antifungal activity in vivo.

O

O

O

O

NH

HO

O

O

O

HN N

F F

F

(42) RO-09-4879

Some aryl(benzofuran-2-yl)ketoximes (43) and their ethers (44-45) and esters (46) were

synthesized by Demirayak et al.[19] Antifungal activities of the compounds were

examined and notable activity was obtained.

O

NOH

R1

O

NOR2

R1

(43) (44)

R1=H, Cl, CH3, OCH3 R1=H, Cl, CH3, OCH3; R2= CH3,C2H5


Ph. D. Thesis 25

O

NOR3

R1

O

N

R1

O

O

R4

(45) (46)

R1=H, Cl, CH3, OCH3 R1=H, Cl, CH3, OCH3

R3=CH2C6H5, CH2C6H4-p-Cl R4= CH3,C6H5

Tirlapur et al. [20] synthesized 6-(5-bromo-1-benzofuran-2-yl)-2-oxo-4-9substituted

phenyl)-1,2-dihydropyridine-3-carbonitriles (47) and 6-(5-bromo-1-benzofuran-2-yl)-2-

amino-4-9substituted phenyl)-1,2-dihydropyridine-3-carbonitriles (48) by the

condensation of 5-bromo-2-acetylbenzofuran with substituted aldehydes and ethyl

cyanoacetate/malonitrile in ethanol in presence of ammonium acetate. All the synthesized

compounds were characterized and evaluated for their antitubercular, antibacterial and

antifungal activities. Some of the compounds showed significant antibacterial activity

against E. coli, p.aeruginosa, S. epidermidis and B. subtilis. Some compounds exhibited

good antifungal activity against A. niger and C. albicans.

O

Br HN

O

CN

R

O

Br N

NH2

CN

R

(47) (48)

R= C6H5, C6H4Cl(p), C6H4OH(p), C6H4Br(p), C6H4OCH3(p), C6H4N(CH3)2(p), O

Tirlapur et al. [21] synthesized a new series of Benzofuranopyrazoles (49-51). All the

synthsized compounds were characterized and screened for their analgesic, antibacterial

and antifungal activities. Some of the compounds showed good activity when compared

with standard drugs.


Ph. D. Thesis 26

O

Br

NNH

CH=CHCOAr

O

Br

NNH

CH=NR

(49) (50)

O

Br

NN

CHO

CH2NHR

(51)

Ar=C6H5, C6H4OCH3(p), C6H3OH(o)CH3(m), C6H3Cl(o)Cl(p), C6H4NH2(p)

R= C6H5, C6H4Cl(p), C6H4NO2(p), C6H4CH3(p), C6H4OCH3(p)

Basawaraj et al. [22] synthesized 3-Amino-5-bromo-N’-(1-substitutedphenyl-

ethylidene)-1-benzofuran carbohydrazides (52). 1-[3-Amino-5- bromo-benzofuran-2-yl

carbonyl-3-substitutedphenyl-1H-pyrazole-4-carbaldehydes were synthesized by the

reaction of X with Vilsmerier-Haack reagent. The structure of all the compounds were

established and were evaluated for anti-inflammatory and antimicrobial activities. Some

compounds exhibited high activity against P. aeruginosa and B. subtilis, when compared

to standard drug Ciprofloxacin. Some compounds showed good activity against A. niger

and C. albicans. Compounds showed good anti-inflammatory activity with percentage of

inhibition 52, 52, and 39 compared with standard drug Indomethacin whose percentage of

inhibition is 78.

O

Br

O

N

NH2 N

R

CHO

(52)

R= C6H5, C6H4Cl(p), C6H4Br(p), C6H4OCH3(p), C6H3Cl(o)Cl(p)


Ph. D. Thesis 27

Yadav et al. [23] synthesized a novel series of 3-aryl-1-(2-benzofuryl)-2-propen-1-one

analogues (53-54). These synthesized compounds were evaluated for their anti-

inflammatory and antimicrobial activities. Most of the compounds showed good activity

against bacteria E. coli and B. subtilis and fungi A. niger and C. albicans. Some

compounds showed significant anti-inflammatory activity while other compounds

showed weak to moderate activity.

O N

N

NHCOCH2R2

Ar

O N

N

N=CHR1

Ar

(53) (54)

Ar= C6H5, C6H4OCH3(p), C6H4Cl(p)

R1= C6H5, C6H4OCH3(p), C6H4Cl(p)

R2=NHCH3, NHC2H5, Morpholino, NHC6H5, NHC6H4Cl(p), NHC6H4CH3(p),

NHC6H4OCH3(p)

Kumar et al. [24] synthesized a new series of Benzofuran-2-carboxylic acid N’-[2-(3-

chloro-2-oxo-4-phenyl azetidin-1-yl)-thiazol-4-yl hydrazide (55). These synthesized

compounds were evaluated for their antimicrobial and anti-inflammatory activities. Three

compounds out of ten compounds were moderately active against B. subtilis and less

active against E. coli when compared to standard drug Ampicillin. These three

compounds showed weak antifungal activity against C. albicans when compared to

standard drug Griseofulvin. Three compounds out of ten compounds showed moderate

anti-inflammatory activity against standard drug Indomethacin. Remaining compounds

were less active.

O O

NHNH

S

NN

RCl

O

(55)


Ph. D. Thesis 28

R= C6H5, C6H4Cl(p), 3,4,5- OCH3C6H2, 4-OH 3-OCH3C6H3, C6H4N(CH3)2(p),

C6H4Br(p), C6H4I(p), 4-OCH3C6H4, 2-OHC6H4, C6H4Cl(m)

Basavaraja et al. [25] synthesized 3-Methoxy-5-nitro-2-(5’-arylamino-1’,3’,4’-

oxadiazol-2’-yl) Benzofurans (56), 3-Methoxy-5-nitro-2-(5’-arylamino-1’,2’,4’-triazol-

5’-yl) Benzofurans (57), 3-Methoxy-5-nitro-2-(5’-arylamino-1’,3’,4’-thiadiazol-2’-yl)

Benzofurans (58). All the synthesized compounds were characterized and screened for

their antimicrobial activity. Most of the compounds showed good antifungal activity.

Some of the compounds showed good antibacterial activity.

O

O2N

OCH3

NN

ONHR

(56)

O

O2N

OCH3

NN

NSH

R

(57)

O

O2N

OCH3

NN

SNHR

(58)

R= C6H5, 4-CH3C6H4, 4-OCH3C6H4, C6H4Br(p), C6H4Cl(p)

Basavaraj et al. [26] synthesized 3-(Benzofuran-2’-yl)-5-phenyl/1H pyrazolines (59-60).

These compounds were evaluated for their antimicrobial activity and some compounds

were also screened for analgesic activity. Most of the compounds showed good activity

against bacteria E. coli and S. aureus. Some compounds showed good antifungal activity

against C. albicans and A. niger. Some compounds showed good to moderate analgesic

activity.


Ph. D. Thesis 29

O NNH

R

(59)

O NN

R

(60)

R= C6H5, 4-OCH3C6H4, C6H4Cl(p), C6H4N(CH3)2(p), O , a-Naphthyl

Basavaraj et al. [27] synthesized a new series of 5-chloro-3-methylbenzofuran

incorporated pyrimidines (61,62) and isoxazolines (63). These compounds were

characterized and evaluated for their antimicrobial, analgesic and anti-inflammatory

activities. Most of the compounds showed good to moderate activity against bacteria E.

coli and S. epidermidis and against fungi C. albicans and A. niger.

O

ClCH3

N

NH

O

R

.

(61)

O

ClCH3

N

NH

S

R

(62)

O

ClCH3

NO

R

(63)

R= C6H5, C6H4Cl(p), 4-OCH3C6H4, C6H4N(CH3)2(p)


Ph. D. Thesis 30

Makrandi et al. [28] synthesized 3-Alkyl/Aryl-6-(2-Benzofuranyl)-7H-s-triazolo[3,4-

b][1,3,4]thaidiazines (64) by the condensation of 3-Alkyl/Aryl-4-amino-5-mercapto-s-

triazoles with 2-(2-bromoacetyl)benzofurans under reflux in abs ethanol. These

compounds were characterized and evaluated for their antibacterial and antifungal

activities. The compounds were found to possess mild to moderate antibacterial and

antifungal activity

O N N

S

N

N

R

(64)

R=H, CH3, C2H5, n-C3H7, n-C4H9, 4-OCH3C6H4, 3-CH3C6H4

Swamy et al. [29] synthesized 3-(3’-hydroxy benzofuranyl)-5-aryl-pyrazolines (65) by

the cyclization of 3-Hydroxy benzofuran chalcones with hydrazine hydrate in anhyd

ethanol. All the compounds were screened as antibacterial and antifungal agents. Some of

the compounds showed good antifungal activity. All the compounds showed weak

activity against S. aureus and E. coli.

O

OH

NNH

R

(65)

R= 2-OHC6H4, 4-OCH3C6H4, 2-NO2C6H4, C6H4N(CH3)2(p), 3-OCH3 4-OHC6H3, O

Makrandi et al. [30] synthesized 2-Alkyl/aryl-6-benzofuranyl imidazo [2,1-b]-1,3,4-

thiadiazoles (66) by condensation of 5-Alkyl/aryl-2-amino-1,3,4-thiadiazoles with 2-(2-

bromoacetyl)benzofurans under normal condition and under microwave irradiation. The

compounds were evaluated for their antibacterial and antifungal properties. The

compounds showed strong to moderate antibacterial activity. The compounds were found

to be inactive against fungi.


Ph. D. Thesis 31

O N

NR'

S

N

R

(66)

R= CH3, n-C5H11, n-C6H13, n-C7H15, C6H4Cl(p), C6H4Br(o), 3-CH3C6H4

R’=H, Cl, CH3

Basavaraj et al. [31] synthesized some triazolo thiazolidinones containing 5-chloro-3-

methyl-2-yl benzofuran moiety (67-68). All the synthesized compounds were

characterized and evaluated for antibacterial and antifungal activities. Some compounds

displayed good antibacterial and antifungal activity compared to standard drugs.

OS

N

Cl CH3

N

NS

R

S

(67)

O

ClCH3

S

N N

N

S

R

O

(68)

R=H, C6H5, 4-CH3C6H4 , 4-ClC6H4

Madhu et al. [32] synthesized some 5-substituted Benzofuran derivatives (69) and tested

for their antibacterial activities. All the derivatives showed significant activity against

gram positive and gram negative bacteria (Ciprofloxacin and Ampicillin were used as

standard).


Ph. D. Thesis 32

O

O2NCH3

N N

O

CH2R

S

(69)

R= 2-Hydroxy-1-naphthyl, 3,4,5-trimethoxy phenyl, 2-methoxyphenyl, 4-hydroxy-3-

ethoxy phenyl, 1-carboxypyridyl phenyl

Basavaraj et al. [33] synthesized 2-(3’,4’,5’-trimethoxyphenyl/α-naphthyl)-4-methoxy

benzofuro [3,2-d]pyrimidines (70), 2-(3,4,5-trimethoxyphenyl/α-naphthyl)-4-ethoxy

benzofuro [3,2-d]pyrimidines (71), 2-(3,4,5-trimethoxyphenyl/α-naphthyl)-3,4-dihydro-

4-thiobenzofuro [3,2-d]pyrimidines (72). All the synthesized compounds were

characterized and 1`evaluated for antibacterial and antifungal activities. Most of the

compounds showed good to moderate antibacterial and antifungal activities.

O

N

NR

OCH3, O

N

NR

OC2H5 , O

N

NR

SH

(70) (71) (72)

R=

CH3

CH3

CH3 ,

Anti-inflammatory Activity:

Dawood et al. [34] synthesized new benzotriazole and benzofuran-based heterocycles

(73-74). The newly synthesized compounds were found to possess anticonvulsant and

anti-inflammatory activities.


Ph. D. Thesis 33

O

O

N

N

NN S

O

R'

Ph

CH3

OS

NHPh

RO

N

N

N

(73) (74)

R’= CH3, OC2H5 R= 2-Benzofuryl, C6H5, 4-BrC6H4, CH3

Jadhav et al. [35] synthesized a series of 6-substituted and 5,6-disubstituted 2-(6-

methyl-benzofuran-3-ylmethyl)-imidazo[2,1-b][1,3,4]thiadiazoles (75). The new

compounds have been tested for their in vivo anti-inflammatory activity. Qualitative SAR

studies indicate that the chloro substitution in the imidazole ring and introduction of

formyl group at C-5 position of the imidazole ring increased the anti-inflammatory

activity.

OH3C

NN

S N

R

R'

(75)

R’= -H, -CH2OH, -CHO, -CN, CH=NOH,

O N CH2

; R= Br, Cl, NO2

Santana et al. [36] synthesized four benzofuran-3-acetic acids (76) by a novel and easily

generalized route and designed as potential non-steroidal anti-inflammatory agents.

O

COOH

R

(76)

R= 6-OH, 6-OH 7-CH3, 5-CH3, 5-OCH3


Ph. D. Thesis 34

Analgesic activity:

Radl et al. [37] synthesized and tested 3-Unsubstituted 1-Benzofurans, 3-amino-1-

Benzofurans (77) and 3-methyl-1-Benzofurans (78) as analgesics.

O

R1

R2

R3

NH2

R4

O

O

R3

MeO

R2

R1

O

(77) (78)

R1= H, OMe; R2= H, OMe; R3= H, OMe R1= H, Br; R2= H, Me; R3= H, OMe

R4=H, Br, Ph, 2,4-diFC6H3

Jadhav et al. [35] synthesized a series of 6-substituted and 5,6-disubstituted 2-(6-methyl-

benzofuran-3-ylmethyl)-imidazo[2,1-b][1,3,4]thiadiazoles (79). The new compounds

have been tested for their in vivo analgesic activity. Qualitative SAR studies indicate that

the chloro substitution in the imidazole ring and introduction of formyl group at C-5

position of the imidazole ring increased the analgesic activity.

OH3C

NN

S N

R

R'

(79)

R’= -H, -CH2OH, -CHO, -CN, CH=NOH, O N CH2

; R= Br, Cl, NO2

Basawaraj et al. [14] synthesized 2-N-arylaminoacetyl-5-chloro-3-methylbenzofurans

(80). Some of the compounds displayed significant analgesic activity against Analgin as

standard.


Ph. D. Thesis 35

O

CH3

Cl

O

NH

R

(80)

R= H, 2-CH3, 4-CH3, 2-OCH3, 4-OCH3, 2-Cl, 4-Br, 2-NO2

According to Radl et al. [38] 2-Benzoyl and 2-(pyridylcarbonyl)-1-benzofuran-3-amines

and 2-Benzoyl and 2-(pyridylcarbonyl)-1-benzothiophene-3-amines (81-84) were

prepared and from this various derivatives were synthesized. Several compounds were

found to exhibit considerable analgesic activity.

O

N

O

R2

R1

(81)

R1= Ac, COOC2H5, H, Me R2=CH2COOC2H5, Me

O

NH2

O

R1

R2

(82)

R1= OCH2COOC2H5, H, OCH2COOH, O(CH2)3NMe2, OMe, OH

R2= OCH2COOC2H5, H, OCH2COOH, O(CH2)3NMe2, OMe, OH


Ph. D. Thesis 36

X

NH2

O

N

(83)

X= O, S Position= 2,3,4

O

CH2

O

R

(84)

R=Me2N,

N N Me

, N MeS

Antidepressant Activity:

Dauzonnel et al. [39] synthesized a series of novel benzofuranylacryloylpiperazines (85)

which are structurally related to both cinnamamide derivatives and befuraline. Their

anticonvulsant and antidepressant activities against seizures induced by electroshock and

against tetrabenazine-induced palpebral ptosis have been evaluated in mice. Some of

them revealed interesting potencies since, although they are less active than the reference

drugs, they exhibited a higher protective index.

O

N

N

O

R4

R1

R2

R3

(85)

R1= H, OCH3, CN, Cl, CH3 ; R2= H, OCH3; R3= H, OCH3


Ph. D. Thesis 37

R4=phenyl, 3-CF3-phenyl, 2-C2H5O-phenyl, 2-pyridinyl, 2-pyrimidinyl, benzyl,

piperonyl, 4-Cl benzhydryl, 4-OCH3-benzyl, 4-Cl-benzyl, phenethyl,-

CH2CONHCH(CH3)2, cyclohexanyl

Venkatesan et. al. [40] prepared several benzofuran derivatives (86) linked to a 3-

indoletetrahydropyridine through an alkyl chain and evaluated for serotonin transporter

and 5-HT1A receptor affinities. The Selective serotonin reuptake inhibitors (SSRIs) have

achieved great success in treating depression and related conditions.

O

N

NH

R2

R3

R4

R1

R

(86)

R= H, 6-Cl, 5-F, 5-OCH3 R1= H, CH3 R2=H, CN, F R3=H, F R4=H, C2H5

Anticonvulsant activity:

Rajak et. al. [41] reported a series of novel N-({5-[(6-methyl-1-benzofuran-3-yl)methyl]-

1,3,4-thiadiazol-2-yl}carba-mothioyl)-2/3/4-substituted benzamide (87) were designed,

synthesized and evaluated for their anticonvulsant activity. Most of the compounds

showed anticonvulsant activity.

O

S

NN

NH

NH

S

R

O

H3C

(87)


Ph. D. Thesis 38

R= C6H5, (2-Cl)C6H4, (3-Cl)C6H4, (4-Cl)C6H4, (4-OCH3)C6H4,

(4-OC2H5)C6H4, (4-OH)C6H4, (4-NO2)C6H4

Patel et al. [42] synthesized new N-1’,N-3’-disubstituted-2’H,3H,5’H-spiro-(2-

benzofuran-1,4’-imidazolidine)-2’,3,5’-triones . The anticonvulsant effects of these

compounds were evaluated by standard pentylenetetrazol (scPTZ test) and maximum

electroshock seizure (MES test) models in mice. Most of the compounds showed ability

to protect against the pentylenetetrazol-induced convulsions. Compound (88) exhibited

maximum activity with ED50 of 41.8 mg/kg in scPTZ convulsion model.

O

O

NN

O

O

C2H5

NO2

(88)

Vaidya et al. [43] synthesized the Benzofuro[3,2-e]-1,4-diazepines by chloroacetylation

of 2-acyl-3-aminobenzofuran and subsequent treatment with hexamethylene tetramine in

ethanol via the complex salts. Similar reaction with ethyl 3-aminobenzofuran-2

carboxylate produced 3H-benzofuro[ 3,2-e]-1,4-diazepin2,5(1H,4H)-dione. All the newly

synthesized compounds were evaluated for anticonvulsant activities. The diazepine (89)

was found to possess considerable anticonvulsant activity, since it reduced the extensor

phase of the MES convulsions to a greater extent and comparable with that of standard

drug.

O

N

HN

O

(89)


Ph. D. Thesis 39

Basawaraj et al. [44] synthesized 4-Aryl-3-(5’-chloro-3’-methylbenzofuran-2’-yl)-1(H)

benzodiazepines (90) and 4-Aryl-3-(5’-chloro-3’-methylbenzofuran-2’-yl)-1(H)

dihydrobenzothiazepines (91). These compounds showed either reduction or abolition of

tonic extensor phase of convulsions produced by Chemical method using Diazepam as

standard drug.

O

CH3

Cl

N

HN

R

O

CH3

Cl

S

HN

R

(90) (91)

R= C6H5, C6H4 OH(o), C6H4 OH(p), C6H4 OCH3(p),

O

Antitumor activity:

Hayakawa et al.

[45] synthesized (4-hydroxy-3-methyl-6-phenylbenzofuran-2-

yl)phenylmethanone (92) as potent anti-tumor agent.

O

CH3OH

O

(92)

Baraldi et al. [46] synthesized a series of benzoyl and cinnamoyl nitrogen mustards (93)

tethered to different benzoheterocycles and to oligopyrroles structurally related to

netropsin consisting of two pyrrole-amide units and terminating with an amidine moiety.

The compounds with benzofuran showed 7- and 14-fold reduced cytotoxic potency than

tallimustine.


Ph. D. Thesis 40

O

NH

O N

NH

O

NH

NH2

HN

O

NCl

Cl

(93)

Asoh et. al. [47] synthesized a series of benzofuran-based farnesyl transferase inhibitors

(94) as antitumor agents. The compounds showed the most potent enzyme inhibitory

activity (IC50 = 1.1 nM) and antitumor activity in human cancer xenografts in mice.

O

N

N

NH2

CH3

R2

R1

R3

(94)

R1= CN,R2= NO2, CNR3= H, 3-OCH3, 3-CN, 3-F

Gaisina et. al. [48] reported the design, synthesis, and biological evaluation of

benzofuran-3-yl-(indol-3-yl)maleimides derivatives (95) and potent GSK-3β inhibitors

activities. The compounds showed antiproliferative activity against some or all of the

pancreatic cancer cells at low micromolar to nanomolar concentrations.

NH

X

HN

OO

O Y

(95)


Ph. D. Thesis 41

X= H, 5- F, 5-Br, 5-Cl,6-Cl, 5-I,6-I, 5-CN, 5-OCH3, 6-p-Cl-C6H4, 7-CH2OH etc.

Y= H, 5- F, 7-OCH3, 6-CH2OH, 6-CH2OCH3 etc.

Imaging activity:

Ono et al. [49] designed and synthesized small molecule-based benzofuran derivatives

(96-97) which acts as Aβ-aggregate-specific imaging agents for Alzheimer’s disease.

O

I

N

R O

I

R

(96) (97)

R= H, CH3 R= OH, OCH3

Ono et al. [50] were synthesized Novel benzofuran derivatives (98) for PET Imaging of

β-Amyloid Plaques in Alzheimer’s disease.

O

R1

R2

(98)

R1=-OMe, OH R2= -NH2, -NHCH3 -N(CH3)2

Anti-HIV activity:

Rida et al.

[7] synthesized and evaluated several benzofuran derivatives (99-103)

containing heterocyclic ring substituents linked to the benzofuran nucleus at C-2 by a

two- to four-atom spacer as potential anti-HIV-1 agents. Among these derivatives, two

compounds exhibited interesting anti-HIV-1 activity. Some compounds showed weak

anti-HIV-1 activity.


Ph. D. Thesis 42

O

N

CH3

N

N

S

O

R

O

N

CH3

N

N

S

CH3

R

(99) (100)

R= C4H9, CH2C6H5, C6H5, 4-CH3C6H4 R= CH2C6H5, C6H5, 4-CH3C6H4

O

N

CH3

N

N

S

R

R1

O

N

CH3

N

N

S

O

R

R1

(101) (102)

R= CH2C6H5, C6H5, 4-CH3C6H4 R= CH2C6H5, C6H5

R1=CH3, Cl R1= OCH3, Cl

O

N

CH3

N

N

O S

N

S

R

(103)

R= CH2C6H5, C6H5

Antidiabetic activity:

Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2,2,4,6,7-

pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-

2,4,6,7-tetramethylbenzofuran moieties were synthesized by Reddy et al. [51]. At a 100

mg/kg/day dose of the maleate salt, compound (104) reduced the plasma glucose and


Ph. D. Thesis 43

triglyceride to the level of lean littermate, i.e. 8±1 mM, and is the most potent and

efficacious compound.

O

OCH2C6H5

NO

NH

S

O

O

(104)

Antitubercular activity:

Manna et al. [20] synthesized various 3-(1-benzofuran-2-yl)-5-phenylisoxazoles (105).

The benzofuran isoxazoles were evaluated for their antitubercular activity. Some of the

compounds have shown promising antitubercular activity.

O

NO

R

(105)

R= -OH(o), -OCH3(o), -N(CH3)2(p), -COOH(o), -NO2(m), -OH(o)OCH3(p), -OH(p), -

Cl(p), -Cl(o), -NO2(o), -OCH3(p), -H, Furan ring, -Cl=CH-Ar

Manna et al. [52] synthesized newer 3-benzofuran-5-aryl-1- pyrazolylcarbonyl-4-oxo-

naphthyridin (106) and 3-benzofuran-5-aryl-1-pyrazolyl-pyridyl methanone analogs

(107) by microwave irradiation method and evaluated for in-vitro and in-vivo

antitubercular activity against multidrug-resistant M. tuberculosis stains. Structure

activity relationship study was carried out and found NO2 (o) substituted 3-benzofuran- 5-

aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin was most potent antitubercular agent

against M. tuberculosis, even better than standard drug isoniazid and comparable with

rifampin16

.


Ph. D. Thesis 44

ON

NO

N

ON

NO

N

N

C2H5

CH3

O

RR

(106) (107)

R= OH (o), OCH3 (o), OCH3 (p), N (CH3)2 (p), COOH (o), NO2 (m), OH (o),

OCH3 (p), OH (p), Cl (o), Cl (p), NO2 (o), H, Furan Ring, CH=CH-Ar

Antioxidant activity:

More et al. [53] synthesized 2-(7-methoxy-3-methyl-1-benzofuran-2-yl)-4H-chromon-4-

ones (108). Some of the compounds showed moderate antioxidant activity.

O

O

R1R2

R3

O

H3C

OCH3

(108)

R1= H, CH3, Cl; R2= H, CH3; R3= H, CH3, Cl, F, Br

Miscellaneous:

Hagihara et al.

[54] synthesized a series of 4-(6,7-dimethoxy-1,2,3,4

tetrahydroisoquinolin-2-yl)methyl-2-arylbenzofuran and 4-(6,7-dimethoxy-1,2,3,4-

tetrahydroisoquinolin-2-yl)methylbenzofuran-2-carboxamide derivatives as novel α2C-

adrenergic receptor antagonists. Compound (109) has been found to show the anti-L-

dopa-induced dyskinetic activity in marmosets.


Ph. D. Thesis 45

O

OMe

N

OMe

OMe

(109)

Choi et al. [55] synthesized a series of 2-(4-hydroxyphenyl)benzofurans. Then 5-Methyl-

3-p-toluoyl-2-[4-(3-diethylaminopropoxy) phenyl]benzofuran (110), a β-amyloid

aggregation inhibitor, was synthesized by three steps starting from 2-(4-hydroxyphenyl)

benzofurans.

O

O

O

N

(110)

Literature related to Piperazine, Piperidine and Morpholine:

Aridoss et al. [56] synthesized an array of novel N-morpholinoacetyl-2,6-diarylpiperidin-

4-ones (111) and their in vitro antibacterial activity against Staphylococcus aureus,

Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi and antifungal activity

against Candida albicans, Rhizopus sp., Aspergillus niger and Aspergillus flavus were

evaluated. The compounds were exhibited excellent antibacterial and antifungal

activities.


Ph. D. Thesis 46

N

N

O

O

R2 R1

OR R

(111)

R= H, Cl, OMe, Me; R1=H, Me, Et, i-Pr ; R2=H, Me

Aridoss et al. [57] synthesized a series of N-(N-methylpiperazinoacetyl)-2,6-

diarylpiperidin-4-ones (112) by the base catalyzed nucleophilic substitution of N-

chloroacetyl-2,6-diarylpiperidin-4-ones obtained from their corresponding 2,6-

diarylpiperidin-4-ones with N-methylpiperazine. All the compounds were screened for

their possible antibacterial and antifungal activities against a spectrum of microbial

agents besides analgesic and antipyretic activities. The compounds were exhibited

promising antimicrobial activities and beneficial analgesic and antipyretic profile at a

concentration of 60 mg/kg and were also found to be more potent than the reference drug.

N

N

N

O

R2 R1

OR R

CH3

(112)

R= H, Cl, OMe, Me; R1= Me, Et, i-Pr ; R2=H, Me


Ph. D. Thesis 47

Malinka et al. [58] described the synthesis and pharmacological investigation of a new

series of derivatives of pyrrole-3,4-dicarboximide (113) possessing the 4-substituted-

piperazin-1-ylalkyl group linked to the imide nitrogen. The products were evaluated for

acute toxicity, and effectiveness in a series of CNS and arterial blood pressure tests.

Several compounds demonstrated moderate to high analgesic activity in the ‘writhing

syndrome’ test.

N

N

R

H3C

CH3

O

O

CH2

CH2 CH2

NN

R1

(113)

R= n-C4H9, 2-Pyridine, 3-Pyridine, 2-Thiazole, C6H5, 2-C5H4N

n= 0, 1, 2

R1= o-CH3O-C6H4, o-Cl-C6H4, m-Cl-C6H4, m-CF3-C6H4, 2-Pyridine, 2-Pyrimidine

Mishra et al. [59] synthesized some new N-substituted acetyl derivatives of 2-amino-5-

alkyl-1,3,4-thiadiazoles (114) and investigated for antihistaminic and spasmolytic activity

on guinea pig ileum. A few of the compounds showed encouraging effect. Some of the

compounds also showed anti-inflammatory activity.

(114)

R= CH3, C2H5

S

NN

R NH

O

X


Ph. D. Thesis 48

X= N

,

N

H3C

N NH

, N N CH3

, N

C4H9

CH3 , N

CH2

CH3

Geronikaki et al. [60] synthesized 4,5-disubstituted-thizolyl amides, derivatives of 4-

hydroxy-piperidine and of 4-N-methyl piperazine (115), and tested as anti-inflammatory

agents. The effect of the synthesized compounds on inflammation, using the carrageenin

induced mice paw edema model was studied. It showed that anti-inflammatory activity

depended on some structural characteristics of the synthesized compounds.

S

N

R

NHCO(CH2)nX

(115)

R= H, CH3, C6H5,C6H4OCH3

X= N N CH3

,N OH

Lipnicka et al. [61] synthesized several new compounds 4 and 5-substituted derivatives

of 3-methyl-4-isothiazolecarboxylic acid (116). The biological activites of the obtained

compounds were analyzed in the humoral immune response and delayed type

hypersensitivity reaction to sheep red blood cells (SRBC) in the mouse model, as well as

in the proliferative response of splenocytes to T-cell and B-cell mitogens in vitro.

S

N

H3C

NHCO(CH2)nR

COOC2H5

(116)

R=N

,N O

,N

CH(CH)3

H ,HN Cl

, HN OC2H5


Ph. D. Thesis 49

Saxena et. al. [62] synthesized a series of 1-[3-(4-substituted phenylthio) propyl]-4-

(substituted phenyl) piperazines (117) and evaluated for hypotensive activity. The QSAR

study indicates that resonance and hydrophobic parameters of the aryl substituents are

important for hypotensive activity.

N N S R

R'

(117)

R= CH3, H, OCH3, NHC2H5, Cl, F, Br, NHCOCH3

R’= 2-CH3, 3-CH3, 3-Cl, 3-CF3, 3,4-Di Cl, 4-F, 3-F

Saxena et. al. [63] synthesized a series of 2-substituted octahydropyrazinopyridoindoles

(118). Three of the five newly synthesized 2-substituted octahydropyrazinopyridoindoles

have shown potent antihistaminic H1 activity with less toxicity and sedation potential.

NH

N

N NH

OR

(118)

R= NO2, OCH3, C2H5, Cl, F

Kowalski et. al. [64] described the synthesis of a series of new n-propyl and n-butyl

chain containing 1-aryl-piperazine derivatives of quinazolidin-4(3H)-one (119) 2-

phenyl-2,3-dihydrophthalazine-1,4-dione (120) and 1-phenyl-1,2-

dihydropyridazine-3,6-dione (121) as potential serotonin receptor ligands.

N

N

O

N

N

O

Ph

O

N

N

O

Ph

O

(119) (120) (121)


Ph. D. Thesis 50

a=

(CH2)3 N N

b=

(H2C)3 N N

N

N

c=

(CH2)4 N N

d=

(H2C)4 N N

N

N

Kuran et. al. [65] has synthesized a set of 36 arylpiperazine derivatives with two novel

complex terminal imide fragments, 8,11-dimethyl-3,5-dioxo-4-azatricyclo[ 5.2.2.02,6]

undec-8-en-1-yl acetate (122) and 1,11-dimethyl-4-azatricyclo[5.2.2.02,6]undecane-

3,5,8-trione (123), and tested for their affinity for 5-HT1A and 5-HT2A receptors. Three

Compounds out of 14 screened in a functional model of anxiety and depression

demonstrated antidepressant activity in the forced swimming tests in mice, and was

devoid of neurotoxic effects (chimney test in mice).

N

O

O

CH3

OAc

X

NNAr

H3C

(122)

N

O

O

O

CH3

CH3

X

NNAr

(123)

Ar= o-OCH3-Ph, Pyrimidyl, Pyridyl, Phenyl, p-F-Ph, Benzyl

X= CH2, O


Ph. D. Thesis 51

Barbaro et. al. [66] synthesized a series of benzodioxanes (124) by adding a N-alkyl

piperazine bearing a cyclic substituent (a substituted or unsubstituted phenyl group, a

pyridine or pyridazinone ring, a furoyl moiety) at the second nitrogen atom. Structure-

activity relationships have been derived for compounds 2–17 based on their fitting to a

pharmacophore model for α1-adrenoceptor antagonists.

O

O

HN

(CH2)nN

NR

(124)

R= o-Methoxyphenyl, o-Chlorophenyl, Phenyl, 2-Pyridinyl, p-Methoxyphenyl, o-

Fluorophenyl, 2-Methyl-4-chloropyridazin-3(2H)-one-5-yl, 2-Furoyl

n= 2,3

Jolanta Obniska et. al. [67] synthesized the series of N-[(4-arylpiperazin-1-yl)-alkyl]-3-

(2-methylphenyl)- (125) and 3-(2-trifluoromethyl-phenyl)-pyrrolidine-2,5-diones (126)

and tested for anticonvulsant activity using the maximal electroshock (MES),

subcutaneous pentylenetetrazole (scPTZ) screens. Their neurotoxicity were determined

applying the rotorod test. In this series, the most active were N-[(4-phenylpiperazin-1-yl)-

methyl]-3-(2-trifluoromethylphenyl)-pyrrolidine-2,5-dione with the ED50 =20.78 mg/kg,

when given orally to rats and N-[3-{4-(3-trifluoromethylphenyl)-piperazin-1-yl}-propyl]-

3-(2-trifluoromethylphenyl)-pyrrolidine-2,5-dione with the ED50= 132.13 mg/kg after

intraperitoneally injection to mice.

N

O

OR

CH2

N

NR1

(125)

R= CH3, CF3

R1= H, 2-F, 2-OCH3, 3-Cl, 3-CF3


Ph. D. Thesis 52

N

O

OR

(CH2)nN

NR1

(126)

R= CH3, CF3

R1= H, 2-F, 2-OCH3, 3-Cl, 3-CF3

n= 2,3

Pawlowski et. al. [68] synthesized a series of new 3-[4-(4-arylpiperazinyl)-butyl]-β-

tetralonohydantoins (127). The compounds exhibited high affinity for 5-HT1A receptors

(Ki = 6 to 55 nM) combined with moderate-to-high 5-HT2A receptor affinities (Ki = 45 to

213 nM).

HNN

O

O

(CH2)4

N

N R

(127)

R= H, 2-OCH3, 2-F, 3-Cl, 4-F, 3-CF3

Santana et. al. [69] synthesized a series of novel long-chain arylpiperazines (128)

bearing a coumarin fragment and the compounds were evaluated for their affinity at α1A,

D2 and 5-HT2A receptors. Most of the new compounds showed high affinity for the three

types of receptors α1A, D2 and 5-HT2A which depends, fundamentally, on the

substitution of the N4 of the piperazine ring.


Ph. D. Thesis 53

O

R

OON

NAr

(128)

R=-OCH3, -CH3,

Ar= ,

OCH3

,

N

, N

N

Pawlowski et. al. [70] synthesized and reported the 5HT1A and 5HT2A receptor

affinities of several γ-(3’-chloro- or 2’-methoxyphenyl)-piperazinopropyl derivatives of

pyrimido[2,1-f]purines (129) or 1,3-diazepino[2,1-f]purines (130).

N

N

O

O

N

N

H3C

H3CN

(H2C)3 NN

Z

O

(129)

N

N

O

O

N

N

H3C

H3C

(CH2)n

N

(H2C)3

X

N N

Z

(130)


Ph. D. Thesis 54

X=CH2, CO

n= 3,4

Ar= , N

N

Z= 3’-Cl, 2’-OCH3,

Geronikaki et. al. [71] synthesized a series of thiazolyl/benzothiazolyl-N-phenyl

piperazines (131-132) and tested for anti-inflammatory activity. Their RM values were

determined as an expression of their lipophilicity. Theoretical calculation of their

lipophilicity, as clog P and logPsk also performed. The effect of the synthesized

compounds on inflammation, using the carrageenin induced mouse paw oedema model

was studied. In general, the studied compounds were found to be potent anti-

inflammatory agents (44–74.1%).

N

S

R

NHCO(CH2)nN N

(131)

R= H, CH3, Ph, Ph-OCH3,

n=1,2

N

SNHCO(CH2)nN N

R

(132)

R= H, F, OC2H5

n=1,2


Ph. D. Thesis 55

Achaiah et. al. [72] synthesized a series of (6-Substituted 4-Oxo-4H-chromene-3yl)

methyl N-substituted Aminoacetates (133). All the compounds were evaluated for in vitro

antihistaminic activity by inhibition of isotonic contractions induced by histamine on

isolated guinea pig ileum. These compounds exhibited significant protection against

histamine induced convulsions in guinea pig at the dose of 50 μmol.

O

R

O

CH2OCOCH2NR1R2

(133)

R=H, CH3, Cl

-NR1R2= R1= H, R2= pyridyl, Morpholino, 4-Methyl pipaerazino, 4-ethyl pipaerazino

piperidino,

Strappaghetti et. al. [73] designed and synthesized a new series of arylpiperazine

derivatives (134-135). The pharmacological profile of these compounds was evaluated

for their affinity and selectivity toward α1-AR, α2-AR and toward 5HT1A serotoninergic

receptor.

NN

(CH2)n

O CH3

NN

R

(134)

R=H, o-OCH3, o-C2H5, o-OCH(CH3)2, m-Cl, m-CF3

n=2,4,7

NN

(CH2)n

O CH3

R


Ph. D. Thesis 56

(135)

R=

NN

O

,

NN

N

N

, N

N

O

O

n=4,7

New arylpiperazines (136) related to buspirone, gepirone and NAN-190 were designed

by Ashwell et. al. [74] and screened in silico for their 5-HT1A affinity and potential sites

of metabolism by human cytochrome P450 (CYP3A4). Modifications to these structures

were assessed in silico for their influence on both 5HT1A affinity and metabolism.

N

O

O

R3

R2

NNR4

R1

(136)

R1= H, Me

R2= H, Me, OH

R3= H, Me

R4= Pyrimidine, 5-F Pyrimidine, p-F Phenyl, 2-Pyrazine, p-OMe Phenyl


Ph. D. Thesis 57

References:

1. Koca, M., Sevi, S., Kirilmis, C., Kazaz, C., Ozbek, B., & Otuk, G. (2005).

Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part

1. Synthesis and antimicrobial activity of Benzofuran-2-yl-(3-phenyl-3-

methylcyclobutyl)-ketoxime derivatives. European Journal of Medicinal

Chemistry, 40, 1351-1358.

2. Alper-Hayta, S., Arisoy, M., Temiz-Arpaci, O., Yildiz, I., Aki, E. et al. (2008).

Synthesis, antimicrobial activity, pharmacophore analysis of some new 2-

(substitutedphenyl/benzyl)-5-[(2 benzofuryl) carboxamido]benzoxazoles.

European Journal of Medicinal Chemistry, xx, 1-11.

3. Kirilmis, C., Ahmedzade, M., Servi, S., Koca, M., Kizirgil, A., & Kazaz, C.

(2008). Synthesis and antimicrobial activity of some novel derivatives of

benzofuran: Part 2. The synthesis and antimicrobial activity of some novel 1-(1-

benzofuran-2-yl)-2-mesitylethanone derivatives. European Journal of Medicinal

Chemistry, 43, 300-308.

4. Wahab, B.F.A., Aziz, H.A.A., & Ahmed, E.M. (2008). Synthesis and

antimicrobial evaluation of 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones and 3-

(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles.

European Journal of Medicinal Chemistry, xxx, 1–4.

5. Babu, V.H., Sridevi, C., Joseph, A., & Srinivasan, K.K. (2007). Synthesis and

biological evaluation of some novel pyrazolines. Indian Journal of Pharmaceutical

Sciences, 69(3), 470-473.

6. Khan, W., Alam, M.J., Rashid, M., & Chowdhury, R. (2005). A new structural

alternative in benzo[b]furans for antimicrobial activity. Bioorganic & Medicinal

Chemistry, 13, 4796-4805.

7. Rida, S.M., El-Hawash, S.A.M., Fahmy, H.T.Y., Hazzaa, A.A., & El-Meligy,

M.M.M. (2006). Synthesis of Novel Benzofuran and Related Benzimidazole

Derivatives for Evaluation of In Vitro Anti-HIV-1, Anticancer and Antimicrobial

Activities. Archives of Pharmacal Research, 29(10), 826-833.

8. Kumar D.B.A., Prakash G.K., Nandeshwarappa B.P., Kiran B.M., Sherigara B.S.,

& Mahadevan K.M. (2006). Microwave assisted synthesis and pharmacological


Ph. D. Thesis 58

evaluation of some potent naphtho and benzofuro Thiazolyl, Oxazolyl, Thio and

Oxadiazolyl derivatives. Indian Journal of Pharmaceutical Sciences, 68(6), 809-

814.

9. Basavaraja, K.M., & Agasimundin, Y.S. (2008). Synthesis of Bis [2(4’-aryl-

1’,2’,4’-triazol-5’-yl)]-3-methoxybenzofuransulphides and disulphides of

biological interest. Indian Journal of Heterocyclic Chemistry, 17 (3), 279-280.

10. Manna, K., Agarwal, Y.K., & Srinivasan, K.K. (2008). Synthesis and biological

evaluation of new benzofuranyl isoxazoles as antitubercular, antibacterial and

antifungal agents. Indian Journal of Heterocyclic Chemistry, 18 (1), 87-88.

11. Prasad, V.V.S., Mayur, Y.C., Babu, Y.R., Satish, N.K., & Kumar, S.M.S. (2006).

Synthesis of new Thiazolidin-4-one substituted 1,2,4-triazoles as antimicrobial

agents. Indian Journal of Heterocyclic Chemistry, 16 (2), 199-200.

12. Basawaraj, R., Goled, S.N., Kalaskar, G., & Sangapure, S.S. (2008). Reaction

products of 2-substituted-4-Chlorobenzofuro [3,2-d] pyrimidines and their

antimicrobial activities. Indian Journal of Heterocyclic Chemistry, 18 (1), 1-4.

13. Basavaraja, K.M., Patil, & V.M., Agasimundin, Y.S., (2006). Synthesis and

Reactions of Biologically active 1,2,3,4-tetrahydro-4-oxo-2-thiobenzofuro[3,2-d]

pyrimidine derivative. Indian Journal of Heterocyclic Chemistry, 16 (2), 159-162.

14. Basawaraj, R., Parameshwarappa, G., & Sangapure, S.S. (2006). Synthesis and

Biological screening of some new 2-N-arylaminoacetyl-5-chloro-3-

methylbenzofurans. Indian Journal of Heterocyclic Chemistry, 16 (1), 75-76.

15. Gundogdu-Karaburun, N., Benkli, K., Tunali, Y., Ucucu, U., & Demirayak, S.

(2006). Synthesis and antifungal activities of some aryl [3-(imidazol-1-yl/triazol-

1-ylmethyl) benzofuran-2-yl] ketoximes. European Journal of Medicinal

Chemistry, 41, 651-656.

16. Aslam, S.N., Stevenson, P.C., Phythian, S.J., Veitch, N.C., & Hall, D.R. (2006).

Synthesis of cicerfuran, an antifungal benzofuran, and some related analogues.

Tetrahedron, 62, 4214-4226.

17. Ebiike, H, Masubuchi, M, Liu, P, Kawasaki, K, Morikami, K et al. (2002). Design

and Synthesis of Novel Benzofurans as a New Class of Antifungal Agents


Ph. D. Thesis 59

Targeting Fungal N-Myristoyltransferase. Part 2. Bioorganic & Medicinal

Chemistry Letters, 12, 607-610.

18. Masubuchi, M., Ebiike, H., Kawasaki, K., Sogabe, S., Morikami, K. et al., (2003).

Synthesis and Biological Activities of Benzofuran Antifungal Agents Targeting

Fungal N-Myristoyltransferase. Bioorganic & Medicinal Chemistry, 11, 4463-

4478.

19. Demirayak, S., Ucucu, U., Benkli, K., Gundogdu-Karaburun, N., Karaburun, A.C.

et al., (2002). Synthesis and antifungal activities of some aryl(benzofuran-2-

yl)ketoximes. IL Farmaco, 57, 609-612.

20. Tirlapur, V.K., Basawaraj, R., & Prasad, Y.R. (2010). Synthesis and biological

activities of some new substituted Benzofuranopyridines. Indian Journal of

Heterocyclic Chemistry, 20 (1), 49-52.

21. Tirlapur, V.K., Prasad, Y.R., & Basawaraj, R. (2010). Synthesis and biological

activities of some new Benzofuranopyrazoles. Indian Journal of Heterocyclic

Chemistry, 20 (1), 57-60.

22. Basawaraj, R., Chavan, V., Patil, A., Upendra, C. H, Gandhi, N., Noola, S.,

Kumar, V., & Naubade, K. (2010). Synthesis of some pyrazole incorporated

benzofurans and their anti-inflammatory activity. Indian Journal of Heterocyclic

Chemistry, 20 (2), 129-132.

23. Yadav, D.B., Venkatesh, K.B., & Sangapure, S.S. (2009). Synthesis and

biological evaluation of 3-aryl-1-(2-benzofuryl)-2-propen-1-one analogues. Indian

Journal of Heterocyclic Chemistry, 19 (2), 117-120.

24. Kumar H., Karvekar M. D., & Das A.K. (2009). Synthesis of Benzofurans and

their antimicrobial and anti-inflammatory activity. Indian Journal of Heterocyclic

Chemistry, 19 (2), 133-136.

25. Giri, S.K., Hanumanagoud, H., Londonkar, R., & Basavaraja, K.M. (2009).

Synthesis and antimicrobial evaluation of 3-Methoxy-5-nitro-2-(1,3,4-

oxadiazolyl, 1,3,4-thiadiazolyl and 1,2,4-triazolyl) Benzofurans. Indian Journal of



Ph. D. Thesis 60

26. Basavaraj, R., Goled, S., & Sangapure, S.S. (2009). Synthesis and biological

activities of some pyrazolines derived from Benzofuran. Indian Journal of


27. Basavaraj, R., Patil, A. & Prasad, Y.R. (2009). Synthesis and Pharmacological

activities of 5-chloro-3-methylbenzofuran incorporated pyrimidines and

isoxazolines. Indian Journal of Heterocyclic Chemistry, 18 (3), 235-238.

28. Rani, R., & Makrandi, J.K. (2009). Synthesis and Bioactivity of 3-Alkyl/Aryl-6-

(2-Benzofuranyl)-7H-s-triazolo[3,4-b][1,3,4]thaidiazines. Indian Journal of


29. Swamy, P.M.G., & Agasimundin, Y.S. (2009). Synthesis and Antimicrobial

activity of 3-(3’-hydroxy benzofuranyl)-5-aryl-pyrazolines. Indian Journal of


30. Rani, R., & Makrandi, J.K. (2008). Microwave assisted facile synthesis and

antimicrobial activity of some new Imidazo[2,1-b]-1,3,4-thiadiazoles. Indian

Journal of Heterocyclic Chemistry, 18 (2), 121-124.

31. Basavaraj, R. & Sangapure, S.S. (2008). Synthesis and Biological activities of

some thiazolo triazines and thiazolo thiazolidinones containing 5-chloro-3-

methyl-2-yl benzofuran moiety. Indian Journal of Heterocyclic Chemistry, 18 (2),

173-176.

32. Madhu R., Patel S., & Sarkar S. (2008). Synthesis and antibacterial activity of

some new 5-substituted Benzofurans. Indian Journal of Heterocyclic Chemistry,

18 (2), 195-196.

33. Basawaraj, R., Goled, S.N., Kalaskar, G., & Sangapure, S.S. (2008). Reaction

products of 2-substituted-4-Chlorobenzofuro [3,2-d] pyrimidines and their

antimicrobial activities. Indian Journal of Heterocyclic Chemistry, 18 (1), 1-4.

34. Dawood, K.M., Abdel-Gawad, H., Rageb, E.M., Ellithey, M., & Mohamed, H.A.

(2006). Synthesis, anticonvulsant, and anti-inflammatory evaluation of some new

benzotriazole and benzofuran-based heterocycles. Bioorganic & Medicinal

Chemistry, 14, 3672-3680.

35. Jadhav V.B., Kulkarni M.V., Rasal V.P., Biradar S.S., & Vinay M.D. (2008).

Synthesis and anti-inflammatory evaluation of methylene bridged benzofuranyl


Ph. D. Thesis 61

imidazo[2,1-b][1,3,4]thiadiazoles. European Journal of Medicinal Chemistry, 43,

1721-1729.

36. Santana, L., Teijeira, M., Uriarte, E., Teran, C., Linares, B. et al. (1998). AM1

theoretical study, synthesis and biological evaluation of some benzofuran

analogues of anti-inflammatory arylalkanoic acids. European Journal of

Pharmaceutical Sciences, 7, 161-166.

37. Radl, S., Hezky, P., Urbankova, J., Vachal, P., & Krejcf, I. (2000). Synthesis and

Analgesic activity of some 1-Benzofurans, 1-Benzothiophenes and Indoles.

Collection of Czechoslovak Chemical Communications, 65, 280-296.

38. Radl, S., Hezky, P., Konvicka, P., & Krejci, I. (2000). Synthesis and analgesic

activity of some substituted 1-Benzofurans and 1-Benzothiophenes. Collection of

Czechoslovak Chemical Communications, 65, 1093-1108.

39. Dauzonnel, D., Gillardin, J.M., Lepage F., Pointetl R., Risk S., Lamottel G., &

Demerseman P. (1995). Synthesis and some CNS activities of new

benzofuranylacryloylpiperazines. European Journal of Medicinal Chemistry,

995(30), 53-59.

40. Venkatesan, A.M., Dos S., Ellingboe, J., Evrard, D.A., Harrison, B.L., Smith,

D.L., Scerni, R., Hornby, G.A., Schechter, L.E. & Andree, T.H. (2010). Novel

benzofuran derivatives with dual 5-HT1A receptor and serotonin transporter

affinity. Bioorganic & Medicinal Chemistry Letters, 2010, 20, 824–827.

41. Rajak, H., Behera, C.K., Pawar, R.S., Singour, P.K. & Kharya, M.D. (2010). A

novel series of 2,5-disubstituted1,3,4-thiadiazoles as potential anti-convulsant

agent. Chinese Chemical Letters, 21(10), 1149-1152.

42. Patel, H.J., Sarra, J., Caruso, F., Rossi, M., Doshi, U. & Stephani, R.A. (2006).

Synthesis and anticonvulsant activity of new N-1’,N-3’-disubstituted-

2’H,3H,5’H-spiro-(2-benzofuran-1,4’-imidazolidine)-2’,3,5’-triones. Bioorganic

& Medicinal Chemistry Letters, 16, 4644–4647.

43. Basavaraja, K.M., Vaidya, V.P. & Chandrashekhar, C. (2008). Synthesis of

Benzofuro[3,2-e]-1,4-diazepines of Pharmacological Interest. E-Journal of

Chemistry, 5(3), 567-571.


Ph. D. Thesis 62

44. Basawaraj, R., Naubade, K., & Sangapure, S.S. (2008). Synthesis of some

benzodiazepines and Benzothiazepinesb bearing Benzofuran moiety as possible

CNS Depressants. Indian Journal of Heterocyclic Chemistry, 17 (3), 217-220.

45. Hayakawa, I., Shioya, R., Agatsuma, T., Furukawa, H., & Sugano, Y. (2004).

Thienopyridine and benzofuran derivatives as potent anti-tumor agents possessing

different structure–activity relationships. Bioorganic & Medicinal Chemistry

Letters, 14, 3411–3414.

46. Baraldi, P.G., Romagnoli, R., Pavani, M.G., Nunez, M.C., Bingham, J.P. &

Hartley, J.A. (2002). Benzoyl and Cinnamoyl Nitrogen Mustard Derivatives of

Benzoheterocyclic Analogues of the Tallimustine: Synthesis and Antitumour

Activity. Bioorganic & Medicinal Chemistry, 10, 1611–1618.

47. Asoh, K., Kohchi, M., Hyoudoh, I., Ohtsuka, T., Masubuchi, M., Kawasaki, K.,

Ebiike, H., Shiratori, Y., Fukami, T.A., Kondoh, O., Tsukaguchi, T., Ishii, N.,

Aoki, Y., Shimma, N., & Sakaitani, M. (2009). Synthesis and structure–activity

relationships of novel benzofuran farnesyltransferase inhibitors. Bioorganic &

Medicinal Chemistry Letters, 19, 1753–1757.

48. Gaisina, I.N., Gallier, F., Ougolkov, A.V., Kim, K.H., Kurome, T., Guo, S.,

Holzle, D., Luchini, D.N., Blond, S.Y., Billadeau, D.D. & Kozikowski, A.P.

(2009). From a Natural Product Lead to the Identification of Potent and Selective

Benzofuran-3-yl-(indol-3-yl)maleimides as Glycogen Synthase Kinase 3

Inhibitors That Suppress Proliferation and Survival of Pancreatic Cancer Cells.

Journal of Medicinal Chemistry, 52, 1853-1863.

49. Ono, M., Kung, M.P., Hou, C., & Kung, H.F. (2002). Benzofuran derivatives as

Aβ-aggregate-specific imaging agents for Alzheimer’s disease, Nuclear Medicine

and Biology, 29, 633-642.

50. Ono, M., Kawashima, H., Nonaka, A., Kawai, T., Haratake, M., Mori, H., Kung,

M.P., Kung, H.F., Saji, H., & Nakayama, M. (2006). Novel benzofuran

derivatives for PET imaging of β-Amyloid plaques in Alzheimer’s disease brains.


51. Reddy, K.A., Lohray, B.B., Bhushan, V., Bajji, A.C., Reddy, K.V., Reddy, P.R.,

Krishna, T.H., Rao, I.N., Jajoo, H.K., Rao, N.V.S., Chakrabarti, R., Kumar,


Ph. D. Thesis 63

T.D., & Rajagopalan R. (1999). Novel Antidiabetic and Hypolipidemic Agents. 3.

Benzofuran-Containing Thiazolidinediones. Journal of Medicinal Chemistry, 42,

1927-1940.

52. Manna, K., &. Agrawal, Y.K. (2010). Design, synthesis, and antitubercular

evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone

and 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin analogs.

European Journal of Medicinal Chemistry, 45, 3831-3839.

53. More, M.S., Kale, S.B., Jagdhani, S.G., & Karale, B.K. (2007). Synthesis,

Antioxidant and Antimicrobial activities of some 7-methoxy-3-methyl benzofuran

incorporated chromon-4-ones. Indian Journal of Heterocyclic Chemistry, 16 (4),

379-382.

54. Hagihara, K., Kashima, H., Iida, K., Enokizono, J., Uchida, S., Nonaka, H.,

Kurokawa, M., & Shimada, J. (2007). Novel 4-(6,7-dimethoxy-1,2,3,4-

tetrahydroisoquinolin-2-yl)methylbenzofuran derivatives as selective α2C-

adrenergic receptor antagonists’, Bioorganic & Medicinal Chemistry Letters, 17,

1616-1621.

55. Choi, H.D., Seo, P.J., Son, B.W., Kang, & B.W. (2004). Synthesis of 2-(4-

Hydroxyphenyl)benzofurans and Their Application to β-Amyloid Aggregation

Inhibitor. Archives of Pharmacal Research, 27(1), 19-24.

56. Aridoss, G., Balasubramanial, S., Parthiban, P., & Kabilan, S. (2007). Synthesis,

stereochemistry and antimicrobial evaluation of some N-morpholinoacetyl-2,6-

diarylpiperidin-4-ones. European Journal of Medicinal Chemistry, 42, 851-860.

57. Aridoss, G., Parthiban, P., Ramachandran R., Kabilan, S., & Jeong, Y.T. (2009).

Synthesis and spectral characterization of a new class of N-(N-methyl

piperazinoacetyl)-2,6-diarylpiperidin-4-ones: Antimicrobial, analgesic and

antipyretic studies. European Journal of Medicinal Chemistry, 44, 577-592.

58. Malinka, W., Sieklucka-Dziuba, M., Rajtar, G., Rubaj, A., & Kleinrok, Z. (1999).

Synthesis and pharmacological screening of some N-(4-substituted-piperazin-1-

ylalkyl)-3,4-pyrroledicarboximides. IL Farmaco, 54, 390–401.


Ph. D. Thesis 64

59. Shakya, A.K., Patnaik, G.K. & Mishra, P. (1992). Synthesis and biological

evaluation of 2-[substituted acetyl]amino-5-alkyl-1,3,4-thiadiazoles. European


60. Geronikaki, A., Hadjipavlou-Litina, D., Chatziopoulos, C., & Soloupis, G. (2003).

Synthesis and Biological Evaluation of New 4,5-Disubstituted-Thiazolyl Amides,

Derivatives of 4-Hydroxy-Piperidine or of 4-N-Methyl Piperazine. Molecules, 8,

472-479.

61. Lipnicka U., & Zimecki M. (2007). New derivatives of 5-amino-3-methyl-4-

isothiazolecarboxylic acid and their immunological activity. Acta Poloniae

Pharmaceutica-Drug Research, 64(3), 233-240.

62. Saxena, A.K., Rao, J., Chakrabarty, R., Saxena, M., & Srimal, R.C. (2007).

Synthesis and QSAR studies on hypotensive 1-[3-(4-substituted phenylthio)

propyl]-4-(substituted phenyl) piperazines. Bioorganic & Medicinal Chemistry

Letters, 17, 1708–1712.

63. Saxena, M., Gaur S., Prathipati, P., & Saxena, AK. (2006). Synthesis of some

substituted pyrazinopyridoindoles and 3D QSAR studies along with related

compounds: Piperazines, piperidines, pyrazinoisoquinolines, and

diphenhydramine, and its semi-rigid analogs as antihistamines (H1). Bioorganic &

Medicinal Chemistry, 14, 8249-8258.

64. Kowalski, P., Kowalska, T., Mokrosz, M.J., Bojarski, A.J. & Charakchieva-

Minol, S. (2001). Biologically Active 1-Arylpiperazines. Synthesis of New N-

(4-Aryl-1-piperazinyl)alkyl Derivatives of Quinazolidin-4(3H)-one, 2,3-

Dihydrophthalazine-1,4-dione and 1,2-Dihydropyridazine-3,6-dione as

Potential Serotonin Receptor Ligands. Molecules, 6, 784-795.

65. Bojarski, A.J., Kuran, B., Kossakowski, J., Koziol, A., Jagiello-Wojtowicz, E., &

Chodkowska, A. (2009). Synthesis and serotonin receptor activity of the

arylpiperazine alkyl/propoxy derivatives of new azatricycloundecanes. European


66. Barbaro, R., Betti, L., Botta, M., Corelli, F., Giannaccini, G., Maccari, L.,

Manetti, F., Strappaghetti, G. & Corsano, S. (2002). Synthesis and Biological

Activity of New 1,4-Benzodioxanarylpiperazine Derivatives. Further Validation


Ph. D. Thesis 65

of a Pharmacophore Model for α1-Adrenoceptor Antagonists. Bioorganic &

Medicinal Chemistry, 10, 361–369.

67. Obniska, J., Kaminski, K., Skrzynska, D., & Pichor, J. (2009). Synthesis and

anticonvulsant activity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 3-

phenyl-pyrrolidine-2,5-dione. European Journal of Medicinal Chemistry, 44,

2224-2233.

68. Byrtus, H., Pawlowski, M., Czopek, A., Bojarski, A.J., Duszynska, B., Nowak,

G., Klodzinska, A., Tatarczynska, E., Wesolowska, A., & Chojnacka-Wojcik, E.

(2005). Synthesis and 5-HT1A, 5-HT2A receptor activity of new β-

tetralonohydantoins. European Journal of Medicinal Chemistry, 40, 820–829.

69. Gonzalez-Gomez, J.C., Santana, L., Uriarte, E., Brea, J., Villazon, M., Loza, M.I.,

Luca, M.D., Rivas, M.E., Montenegro, G.Y., & Fontenla, J.A. (2003). New

Arylpiperazine Derivatives with High Affinity for α1A, D2 and 5-HT2A

Receptors. Bioorganic & Medicinal Chemistry Letters, 13, 175-178.

70. Pawlowski, M., Katlabi, J., Drabczynska, A., Duszynska, B., Charakchieva-

Minol, S., Deren-Wesolek, A., Tatarczynska, E., Chojnacka-Wojcik, E., Mokrosz,

M., & Bojarski, A.J. (1999). New 9- or 10-arylpiperazinoalkyl substituted

pyrimido- or diazepino[2,1-f]purines with partial or full 5-HT1A agonistic

activity. European Journal of Medicinal Chemistry, 34, 167-175.

71. Papadopoulou, C., Geronikaki, A., & Hadjipavlou-Litina, D. (2005). Synthesis

and biological evaluation of new thiazolyl/benzothiazolyl-amides, derivatives of

4-phenyl-piperazine. IL Farmaco, 60, 969–973.

72. Gajbhiye, A., Mallareddy, V. & Achaiah, G. (2008). Synthesis and

pharmacological evaluation of (6-Substituted 4-Oxo-4H-chromene-3yl) methyl N-

substituted Aminoacetates. Indian Journal of Pharmaceutical Sciences, 70(1),

118-120.

73. Strappaghetti, G., Brodi, C., Giannaccini, G. & Betti, L. (2006). New 4-(4-

methyl-phenyl) phthalazin-1(2H)-one derivatives and their effects on α1-

receptors. Bioorganic & Medicinal Chemistry Letters, 16, 2575–2579.

74. Tandon, M., Donnell, M., Porte, A., Vensel, D., Yang, D., Palma, R., Beresford,

A., & Ashwell, M. (2004). The design and preparation of metabolically protected


Ph. D. Thesis 66

new arylpiperazine 5-HT1A ligands. Bioorganic & Medicinal Chemistry Letters,

14, 1709-1712.

CHAPTER-2 REVIEW OF LITERATURE -...

Documents

Transcript of CHAPTER-2 REVIEW OF LITERATURE -...