Saudi Pharmaceutical Journal (2013) 21, 1–12

King Saud University

Saudi Pharmaceutical Journal

www.ksu.edu.sa
www.sciencedirect.com

REVIEW

Quinoline: A versatile heterocyclic

Akranth Marella, Om Prakash Tanwar, Rikta Saha, Mohammad Rahmat Ali,
Sandeep Srivastava, Mymoona Akhter, Mohammad Shaquiquzzaman,
Mohammad Mumtaz Alam *

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University),

New Delhi 110 062, India

Received 28 January 2012; accepted 20 March 2012

Available online 29 March 2012

KEYWORDS Abstract Quinoline or 1-aza-naphthalene is a weak tertiary base. Quinoline ring has been found to
Quinoline; possess antimalarial, anti-bacterial, antifungal, anthelmintic, cardiotonic, anticonvulsant, anti-
Synthesis; inflammatory, and analgesic activity. Quinoline not only has a wide range of biological and phar-
Biological activity macological activities but there are several established protocols for the synthesis of this ring. The
article aims at highlighting these very diversities of the ring.
ª 2012 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

1. Introduction
N
1
Quinoline [1] or 1-aza-napthalene or benzo[b]pyridine is nitro-
gen containing heterocyclic aromatic compound. It has a
molecular formula of C9H7N and its molecular weight is Quinoline nucleus occurs in several natural compounds
129.16. The log P value is 2.04 and has an acidic pKb of 4.85 (Cinchona Alkaloids) and pharmacologically active substances
and a basic pKa of 9.5. Quinoline is a weak tertiary base. It displaying a broad range of biological activity. Quinoline has
can form salt with acids and displays reactions similar to those been found to possess antimalarial, anti-bacterial, antifungal,
of pyridine and benzene. It shows both electrophilic and nucle- anthelmintic, cardiotonic, anticonvulsant, anti-inflammatory,
ophilic substitution reactions. It is nontoxic to humans on oral and analgesic activity. A few promising compounds [2–6] with
absorption and inhalation. quinoline ring system are given in Fig. 1.

2. Synthesis
* Corresponding author. Tel.: +91 11 26059681, +91
26059688x5645, mobile: +91 9540165915; fax: +91 11 26059686.
A number of established protocols are there for the synthesis
E-mail address: [email protected] (M.M. Alam). of quinoline ring, which can be well modified to prepare a
Peer review under responsibility of King Saud University. number of differently substituted quino-lines.
2-Phenylquinoline-4-carboxylic acid [7] has been synthe-
sized by treatment of 2-oxopropionic acid with aniline and
benzaldehyde in the presence of rare earth metal catalysts
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and refluxing in water (Wang et al., 2009a).
1319-0164 ª 2012 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jsps.2012.03.002
2 A. Marella et al.

N Cl
N O
H 3C
CH3
H 2C H CH3 N CH3
O HN
HN N CH3
OH N CH3
H CH3
N CH3

Quinine Pamaquine Chloroquine

2 3 4

O
H 3C
O
O CH3 N
O H
N
CF3 O N NH2 N CH3
H 3C CH3
N
H O
CH3 CH3
Tafenoquine Bulaquine

5 6

Figure 1 Few promising compounds with quinoline ring system.

Kouznetsov (2009) synthesized phenyl substituted quino-

COOH lines [11] by subjecting a mixture of ethyl vinyl ether or ethyl
NH2 CHO
O vinyl sulfide and N-arylaldimine to acidic catalysis in the pres-
OH Yb(PFO)3 ence of boron trifluoride etherate (BF3.OEt2) to yield 2,4-
+ + R2
H2O, reflux N substituted tetrahydroquinolines, which were then converted
O R2 R1
R1 to 2-phenyl substituted quinolines under vacuum distillation
7
with tosylic acid (p-TsOH).
2,4-Diphenyl-2-methyl-1,2 dihydroquinoline [8] has been
synthesized by using aniline and acetophenone in the presence OEt
OEt
of a small pore size E4a zeolite catalyst (Hegedus et al., 2007).
Et2O
N Ph
R H
NH2 BF3OEt2 p-TsOH
SEt SEt
O 1-2hr Vacuum N Ph
E4a, Toluene N Ph distillation
+ CH3 11
R CH3 110oC, 6h N C6H6
-2H2O H R N Ph
H
8
3,4-Dihydroquinolin-2-one [12] has been developed by
By stirring 2-amino substituted aromatic ketones and car-
treating 2-iodoanilines and ethyl acrylate with Azobisisobuty-
bonyl compounds having a reactive a-methylene group in ethyl
ronitrile (AIBN) in presence of tributyltin hydride (n-Bu3SnH)
ammonium nitrate (EAN) 2,3,4-trisubstituted quinolines [9]
(Zhou et al., 2009).
have been developed (Zhou et al., 2008).

CH3
O R
I H3C OR3 CH3
CH3 AIBN, Bu3SnH
O
R EAN +
H3C O DMSO, 120oC N O
+ 45oC NH2
NH2 N CH3 Overnight H
9 12

Using 2-aminosubstituted ketone and ketone as reactants 2-Phenyl-4-alkoxy quinoline [13] has been synthesized by
poly-substituted quinolines [10] have been synthesized in aque- condensation and cyclization of 2-(2-trimethylsilyl)ethynyl)
ous media and solvent-free conditions in the presence of dode- aniline with arylaldehydes. The reaction is promoted by sulfu-
cylphosphonic acid (DPA) as catalyst (Ghassamipour and ric acid in the presence of methanol as solvent (Wang et al.,
Sardarian, 2009). 2009b).

O tms CHO OMe

Ph O
O O OEt Acid, MeOH
Ph DPA (0.1mmol) +
+ NH2
OEt reflux N
NH2 H2O N CH3
10 13
Quinoline: A versatile heterocyclic 3

Certain halogen-substituted quinolines [14] have been 2,4-Disubstituted quinolines [19] have been synthesized
synthesized by the condensation and cyclization of two mol- according to Meyer-Schuster rearrangement (Sarma and Praja-
ecules of o-haloacetophenones with urea or primary amines pati, 2008). In this method 2-aminoaryl ketones and phenyl-
(Qi et al., 2009). acetylenes rearrange in the presence of a catalytic amount of
zinc trifluoromethanesulfonate in the ionic liquid 1-hexyl-3-
Cl CH3 methylilmidazolium hexafluorophosphate [hmim][PF6] result-
ReBr(CO)5
3 mol%
ing in 2,4-disubstituted quinolines. The same product has also
H 3C + n-C3H7NH2 been obtained in the presence of indium(III)trifluoromethane-
toluene
N
O Cl
(Sealed tube) sulfonate (In(CF3SO3)3) under microwave irradiation without
150oC, 48h 14 any solvent (Lekhok et al., 2008).
R'
Iraj et al. (2010) synthesized 2,4-disubstituted quinolines R'
[15] through a one-pot reaction of structurally diverse 2- O
Zn(OTf)2
aminoaryl ketones with various arylacetylenes in the pres- + Ph
NH2
ence of potassium dodecatugstocobaltate trihydrate R [hmim]PF6 N Ph
85oC, 2-2.5hr R
(K5CoW12O40Æ3H2O) as a reusable and environmentally be- 19
nign catalyst under microwave irradiation and solvent-free
Palladium-catalysed Wacker-type oxidative cyclization has
conditions.
been proposed for the synthesis of 2-methylquinolines [20] with
good yields under mild conditions (Wang et al., 2011).
R' R'
OH R'
O
K5CoW12O40.3H2O Pd(OAc)2
+ R' R" R"
NH2 R N Ar 1,10-Phenanthroline
Ar MW (1000W)
R
110oC, 5-20min 15 NH2 air
MeOH, 25o or 40oC, 36hr N CH3
R R
Ultrasound promoted synthesis of quinolines [16] using basic 20
ionic liquids (BIL) in aqueous media has been reported by Kow-
Poly-substituted quinolines [21] have been developed by the
sari and Mallakmohammadi (2011). The advantage of such pro-
reaction of 2-aminobenzylic alcohol derivatives with ketones
cedure being that it is simple in operation and high yields are
or alcohols in the presence of base and benzophenone as hy-
obtained. The reaction involves treating isatin with aromatic
dride scavenger (Martinez et al., 2008).
methyl ketones at ultrasonic frequencies of 20–50 kHz.
OH R
R' KOtBu R'
R Ph2CO
COOH
O + O 1,4-Dioxane
O CH3 R" R"
NH2 N
BIL 90oC, 30min
O + 21
H2O
N N CH3 R = H, Ph
H
16
R' = H, Alkyl
One-step methodology has been introduced for the synthe- R" = Alkyl, Aryl
sis of quinoline alkaloid analogues [17] (Zografos et al., 1999).
The reaction is based on a modification of the Mukaiyama 2,4-Disubstituted quinolines [22] have been synthesized by
aldol condensation, making use of the high reactivity of cyclization of 2-iodoanilines with alkynyl aryl ketones in the
lactones or anhydrides. presence of nickel catalyst (Chen et al., 2006).
R"
NH2 R
O
O O NiBr2(dppe), Zn
H3C CH3 + R"
CH3 CH3 R I Ar CH3CN, 80oC, 12h N
O TiCl4 Ar
tms O +
25oC 22
O CH3 X N R X N O
R Horn et al. (2008) reported synthesis of quinolines [23] from
17 a,b-unsaturated ketones and o-aminophenylboronic acid
derivatives which is a modification of the traditional Skraup-
Diversified 2-alkoxy- and 2-aroxy-3-substituted quinolines
Doebner-von Miller synthesis. The method has an advantage
[18] have been synthesized from o-alkynylaryl isocyanides
that it can proceed under basic conditions rather than strongly
and alcohols and phenols promoted by 1,4-diazabicy-
acidic conditions.
clo[2.2.2]octane (DABCO) (Zhao et al., 2010).
R'
R' R'
R2 R2 B(OH)2
R1 R1 R2 [RhCl(COD)2] Pd/C
R1 + O
POCl3 , Pr2NEt R3OH, DABCO KOH Air
NH2 R N R N R
CH2Cl2, R.T. CH2Cl2 R3
NHCHO NC N O Toluene, R.T., 24hr reflux, 4hr
23
18 R = Me, Aryl
R1 = H, Me

R2 = R3 = Aryl, Alkyl
R' = H, Alkyl, Aryl
4 A. Marella et al.

The reaction of benzimidoyl chlorides with 1-(1-(allyl- has a potent antimalarial activity at submicromolar levels.
oxy)prop-2-ynyl)benzene (1,6-enynes) forms quinoline deriva- Certain 4-aminoquinoline triazines [33] synthesized by Kumar
tives [24] via palladium-catalysed Sonogashira coupling and et al. (2008) also have antimalarial activity screened against
subsequent cyclization (Gao et al., 2010). chloroquinine (CQ) sensitive strain 3D7 of P. falciparum in
an in vitro model. Shiraki et al. (2011) developed certain 5-
aryl-8-aminoquinolines [34] with promising antimalarial
R R
activity which had lesser haemolytic activity compared to taf-
O O
+ enoquine. Acharya et al. (2008) synthesized and evaluated the
Pd(PPh3)2Cl2 antimalarial activity of some pyridine–quinoline hybrids [35–
N Cl 2.5mol% Cul 37] against chloroquine susceptible strain of P. falciparum.
N
Et3N, 80oC, 7hr
Ar Singh et al. (2011) developed antimalarial agents with 4-ani-
Ar
24 linoquinoline ring [38]. The compounds showed good activity
against chloroquine-sensitive P. falciparum strains as well as
Intramolecular cyclization of 1-azido-2-(2-propynyl)ben-
against rodent malaria parasite P. yoeii.
zene in the presence of electrophilic reagents in nitrometh-

Cl

H
H3C N N
HN N
H H
NEt N N O
(n) (n) HN CH3
H N
N N O
NH O
O H3C
NEt CH NEt
N NEt 3 n = 2,4,6,8
H
Cl n = 4,6,8 27
26

ane (CH3NO2) at room temperature or in the presence of

catalytic amounts of AuCl3/AgNTf2 in THF at 100 C gives N(CH3)2
corresponding quinolines [25] in good yields (Huo et al., (n)
HN N
2010). Fe
R

R' R' Cl N
E
n = 2-6
EX
R" R = H, CONHBn
N3 CH3NO2, R.T. R"
R R 28
1-60hr 25
S S
EX = NIS, Br2 R' = H, OAc R
HN N HN N
R" = Alkyl, Aryl R' NH

Cl N Cl N
3. Biological activity R = (CH2)2OH, (CH2)3N(Et)2, (CH2)3N(Me)2, (CH2)2NH2 30

3.1. Antimalarial R' = H, C6H5, CH2C6H5, COOC2H5

29
Most important use of the quinoline ring is its antimalarial
O
potential. Bisquinolines [26, 27] developed by Raynes et al.
R
(1996) are found to possess a good degree of antimalarial HN
activity against both chloroquine-resistant and chloroquine-
sensitive parasites. Analogues of ferrochloroquine [28] were CH3
H
also found to have antimalarial activity by Chibale et al. H
N N
(2000). In these analogues carbon chain of chloroquine is re- N
placed by hydrophobic ferrocenyl group. Certain 7-chloro- R' O
quinolinyl thioureas [29, 30] synthesized by Mahajan et al.
(2007) are potential antimalarial agents. Modapa et al. R = Me, Ph, CH2Cl, 2-ClC6H5,3-ClC6H5,2-Furyl
(2009) synthesized few ureido-4-quinolinamides [31] which
showed antimalarial effect at MIC of 0.25 mg/mL against R' = F, Cl, Br, CF3
chloroquine-sensitive Plasmodium falciparum strain. Chloro- 31
quinolyl derivative [32] developed by Kovi et al. (2009) also
Quinoline: A versatile heterocyclic 5

CH3
O O O
N
N S CH3 R2
HN N SCF3 N
H O O H
R1 = OCH3, H
HN N R1 N
H
Cl N 32

R1 N
H3C R1 NHR2 N R2 =
N 41
N N N O
H Ar N
N N
42
Cl R2
MeO N CH3
H 3.3. Anti-inflammatory activity
N
R1 = OCH3, CF3
R1 = p-Fluoroaniline, Piperidine
2-(Furan-2-yl)-4-phenoxy-quinoline [43, 44] derivatives devel-
R2 = H or C(O)OC(CH3)3 oped by Chen et al. (2006) are found to be inhibitors of lyso-
R2 = Piperidine, Cyclohexylamine
34 zyme and b-glucuronidase release. Baba et al. (1996) developed
33
a quinoline derivative [45] with potent anti-inflammatory effect
in adjuvant arthritis rat model. Certain quinoline derivatives
Br
[46, 47] have been developed for treating osteoarthritis by Gil-
Br N
O bert et al. (2008). These are amino-acetamide inhibitors of
Cl Aggrecanase-2.
N O
N O O N
N O
O O N OR
O
N CH3 HN CH3
N Br HN

35 37 R = H, CH3
36

N N
OH O O

43 44
HN
N
H R
N
MeO N CH2S
Cl N
N
MeO COOEt CH3
R = H, Phenyl, Butyl, Isopropyl, n-Butyl
38

OMe

OMe
3.2. Analgesic activity
45

4-Substituted-7-trifluoromethylquinolines [39, 40] synthesized

by Abadi et al. (2005) have been found to have a good analge- R1 Cl
sic activity. The activity is attributed to their nitric oxide
R2
releasing properties. Gomtsyan et al. (2005) developed a quin- R1
oline [41] based analgesic agent whose activity was attributed N
N
to its antagonism at Vanilloid receptors. A few quinoline deriv- OH HN R2
OH HN
atives [42] developed by Manera et al. (2007) by acting as selec- O O
tive agonists at Cannabinoid CB2 receptors show their O O
analgesic activity. R1 = H, F, NO2, Cl R1 = H, 4-OCH3, 3-NO2

R2 = H, 4-Cl, 4-CH3, 4-OCH3 R2 = Nitrogen Heterocyclic

R 46 47

3.4. Antineoplastic
HN
HN
R Some of the amido-anilinoquinolines [48] developed by Scott
F
F et al. (2009) act as anti-tumour agents by inhibiting CSF-1R
N
N F kinase. Novel 4-hydroxyquinolines [49] synthesized by Mai et
F F
F 40 al. (2009) are histone acetyltransferase (HAT) inhibitors.
39 Miller et al. (2009) developed a few 3-cyanoquinolines [50] as
6 A. Marella et al.

inhibitors of insulin like growth factor receptors (IGF-1R) for

the treatment of cancer. O
H3COC CH3
+
R N N
NHCOCH3
R2
OH O S

NH O R1 R3 N Cl
MeO R1
NH2 N R2
R1 = OH, OEt R1 = R2 = R3 = H, CH3, OCH3
MeO N
55
R2 = CH3, C5H11, C10H21, C15H31
R = F, Cl, Br, CH3
49
3.5. Antibacterial
48
Ma et al. (2009) synthesized phenoxy, phenylthio and benzyl-
oxy substituted quinolones [56] with a fair amount of anti-bac-
Cl
terial activity. Sanchez et al. (1988) developed certain 8-
R1
substituted quinoline carboxylic acids [57] with anti-bacterial
activity. Upadhayaya et al. (2009) developed quinoline deriva-
HN R1 = Substituted-2-thioimidazole
tives [58] through molecular modelling techniques which were
MeO CN
R2 = Substituted nitrogen heterocyclic found to be active against Mycobacterium tuberculosis H37Rv
strain. These were derivatives of 3-benzyl-6-bromo-2-methoxy
R2 N
50
quinolines. De Souza et al. (2009) developed 7-chloro quino-
line derivatives [59] effective against multi-drug resistant tuber-
culosis. Lilienkampf et al. (2009) developed quinoline based
A few 4-anilinoquinolines [51] developed by Assefa et al. compound bearing an isoxazole containing side chain [60] ac-
(2003) have been found to be tyrosine kinase inhibitors. Potent tive against Mycobacterium tuberculosis. Some novel anti-
quinoline carboxylic acids [52] have been developed by Chen tubercular quinolines [61] have been developed by Eswaran
et al. (2009) which act by inhibiting insulin like growth factors. et al. (2010) using mefloquine as the lead, wherein active phar-
Linomide [53] has been found to have action against androgen macophores viz. hydrazones, ureas, thioureas and pyrazoles
responsive cancer and rat prostatic cancer by Vukanovic et al. have been attached at the 4th position.
(1993). c-Met kinase inhibitory quinolines [54] with IC50 less
than 1 nM have been developed by Wang et al. (2011). It pro- O O O
duces the inhibition of c-Met phosphorylation in c-Met depen- F COOH F
dent cell lines. OH
Marganakop et al. (2012) developed certain 6,7,8-substi- R7 N X N
X = CH, N, CF
R7
tuted thiosemicarbazones of 2-chloro-3-formyl-quinoline F R1 R1 R1 = Et, 4-F-phenyl, Cyclopropyl
derivatives [55] which had anticancer activities. The com-
R1 = Ethyl, Cyclopropyl, FCH2CH2
pounds had a better drug score and c log P values.
57 R7 = N N R'
R7 = Substituted phenyl

R O NHEt
56 R' = H, CH3 , N
R1 N
OH
HN
R1 CN R2
(n)
OH HN NH2

R2 N
OH
Br
R = 3'-Br, 3'-Cl, 3'-CF3, 3'-CN R1 = OH, H, COOH, F, Cl, NH2 R1 Cl N
R1 = R2 = OMe, OEt N O
R2 = OH, OMe, COOH n = 8-10
51 52 R1 = Imidazolyl, Pyrazolyl, 1-(3-Trifluoromethyl-phenyl)-
piperazinyl, 6-Amino-chromen-2-one 59
58
NO2

OH O
O CF3
O
NH N CH3 CF3 O N
CH3
N O N O O R N CF3
N N
CH3 R = R1 = Alkyl, Aryl,
F3C N F3C N CF3 R1 Heteroaryl
53
54 61
60
Quinoline: A versatile heterocyclic 7

3.6. Antifungal

Gholap et al. (2007) developed certain tetrahydroquinolines

[62] which are found to have a good degree of activity against N N
N
fungi Candida albicans, Fusarium oxysporum and Mucor sp. N
Kharkar et al. (2009) developed a series of quinoline deriva-
70
tives [63] using terbenafine as lead as antifungal agents. The 69
developed compounds contained different bulky aromatic
3.8. Anthelmintic
rings in the side chain. The compounds were designed using
LeapFrog drug design program. Kumar et al. (2011) developed Rossiter et al. (2005) synthesized substituted 2,4-arylquinolines
certain secondary amines [64] containing 2-chloroquinoline [71–74] which have a good degree of activity against the nem-
and evaluated them for their antimycotic activity against atode Haemonchus contortus. These arylquinolines maintain
Aspergillus niger, A. flavus, Monascus purpureus and Penicil- their activity against levamisole, ivermectin and thiabendazole
lium citrinum. These are non-azole antimycotic agents. resistant strains of H. contortus.
R X
OMe OMe

N Y
O N

CN N R N OMe N OMe
CH3

N NH2 N Cl
63
R = 4-Cl, 4-F, 3-NO2, 4-CH3, X = F, Cl, Br, CH3, NO2, Dichloro
71 OMe
2-Cl, 3,4,5-(OCH3)3 72
62 Y = H, CH3
64

3.7. Antiviral OMe MeO

OMe

Anilidoquinoline [65] derivatives synthesized by Ghosh et al.

(2008) are found to have a good degree of in vitro activity N OMe N OMe
against Japanese encephalitis virus. Certain quinoline deriva- 73 74
tives [66] synthesized by Chen et al. (2009) act by behaving
as HIV-1 Tat–TAR interaction inhibitors. Massari et al. 3.9. Anti-protozoal
(2009) developed certain desfluoroquinolines [67] for the treat-
ment of HIV infection. Certain mono and polysubstituted Fournet et al. (1993) found that 2-substituted quinoline alka-
quinolines [68–70] synthesized by Fakhfakh et al. (2003) have loids isolated from G. longiflora plant used for the treatment
activity against HIV-1. of new world cutaneous leishmaniasis have in vitro antileishma-
nial activity against the extracellular forms of Leishmania spp.
CH3 These include 2-substituted 3-carbon chain quinoline alkaloids
R7 R1
O
H
and 2-substituted aryl quinoline alkaloids [75, 76]. Alkenyl and
Cl N
H N
alkynyl quinolines [77, 78] developed by Fakhfakh et al. (2003)
N H R2
N show activity against the causal agents of cutaneous leish-
H
O R3
N maniasis, visceral leishmaniasis, African trypanosomiasis and
Chagas’ disease. Ma et al. (2009) developed certain quinolones
65 66
[79] which had activity against Trypanosoma cruzi. Franck et al.
(2004) developed quinoline derivatives [80, 81] which showed
activity against T. cruzi.
O
COOH

N N N R N N N SiCH3
N CH3 O
Ar R = C2H5, C3H7, C12H25 75 76 77
67 68

O
F R2 R1 = Et, Pr, CH=CH2

N
R3 = COOH, COOMe, COOet, CONH2
R1 N
78 O
R8 R1 R7 = R8 = Substituted Phenyl
O
79
8 A. Marella et al.

OH OCF3

N N
N NO2
N
80 F 81
N
OCF2CF2H
N
F3C
3.10. Cardiovascular activity 86 CH3 OH
87
Certain biarylether amide quinolines [82] developed by Berno-
tas et al. (2009) act as liver X receptor agonists and are useful
in conditions of dyslipidaemia. These agents also reverse the
conditions of arteriosclerosis. A few phenyl acetic acid based CH3
N CH3 CH3
quinolines [83] developed by Hu et al. (2007) also act as ago- H
CH3 N
nists at liver X receptors. These agents have good binding
H
affinity for LXRb and LXRa receptors. 4-Thiophenyl quino- N N
N CH3
lines [84] developed by Cai et al. (2007) are HMG-CoA reduc- R
O
tase inhibitors and have utility as hypocholesterolaemic agents. O
Quinoline-4-carboxylic acids [85] synthesized by Lloyd et al. R = 3-Cl, 3-Br, 3-OCH3
CH3O
(1994) are angiotensin II receptor antagonists and hence act
89
as hypotensive agents. Hypotensive activity of centhaquin 88
[86] has been demonstrated by Srimal et al. (1990) and it has
3.11. CNS effects
been shown to reduce the blood pressure in cat in a dose
dependent manner. Tetrahydroquinolines [87] which inhibit Quinoline based NK3 receptor antagonists [90, 91] with CNS
cholesteryl ester transfer protein have been developed by Rano activity have been developed by Smith et al. (2009).
et al. (2009). Tetrahydroquinolinamines [88, 89] developed by
Ramos et al. (2008) have been found to be inhibitors of platelet
aggregation. F

COOH O NH
O NH
CONR1R2 H
O N H2 CH
NH2 3CH
C 3
N S O
F
N O
Y N
X

N 90 91
N
Y Y 3.12. Hypoglycaemic activity
X = CF3, Cl; Y = CH2Ph
X = CH2Ph, COPh, CN, CONH2

NR1R2 = Methyl ester, Pyrrolidine, Quinoline carboxyguanides [92] prepared by Edmont et al.
Y = CF3, CH3, Cl
Piperidine, Morpholine (2000) are hypoglycaemic agents.
83
82

O O
H
MeO N NHR
N
H
R2 NH . HCl
R N
OH Et
N
S H R = H, C(NH)NH2
R1 R1 COOH N N
O O N 92
O N

R2 N 3.13. Reproductive System

R3 Certain tetrahydroquinolines [93] developed by Wallace et al.

R = 4-CH(CH3)2, 4-F, 3-OCH3; R1 = H, F
R1 = Pr; R2 = H (2003) are selective oestrogen receptor modulators.
R2 = H, F, Cl or Substituted thiophenyl group;
R3 = H, F or Substituted thiophenyl group
85
84
Quinoline: A versatile heterocyclic 9

Bachiller et al. (2010a,b) have developed some novel ta-

O crine–8-hydroxyquinoline hybrids [99] with activity against
N
Alzheimer’s. Tacrine has cholinesterase inhibition action while
X R
8-hydroxyquinoline derivatives have metal-chelating, neuro-
N protective and anti-oxidant properties.

HO R2

R = H, 3-OH, 4-OH; X = CH2, O Z = Alkyl chain;

93 H H Str-I: R1 = R2 = H
N N
Tacrine z N R1 Str-II: R1 = CH3; R2 = H
Bi et al. (2004) developed certain quinolines [94] which act OH Str-III: R1 = H; R2 = Cl
as potent PDE5 inhibitors thus having utility in the treatment
of erectile dysfunction. 99

Tetrahydroquinolin-6-yloxy propanes [100] have been

R1 developed by Shakya et al. (2009) which are b-3 agonists.
N
Cl R4
N
H MeO OH
MeO R3 H O
N
MeO
R2
N
R1 = COOEt; R2 = H, CN; R3 = H, CF3; R4 = H, Et
100 SO2Ar
94

3.14. Miscellaneous Certain aminoalkoxyquinolines [101] as somatostatin

receptor subtype-2 agonists have been reported by Wolkenberg
Quinolines have been found to possess a number of other et al. (2011) which have utility in proliferative diabetic retinop-
activities as well. athy and exudative age related macular degeneration.
Evans et al. (1991) developed certain quinoline based leuko-
triene synthesis inhibitors [95].
NH

CH3
O
O
HO OH R = Aromatic ring
R
CH3
N O
Cl N
95 101

Selective PDE4 inhibitor quinolines [96, 97] have been The 1,2,3,4-tetrahydroquinoline-2,2,4-trione oximes devel-
developed by Lunniss et al. (2009) with utility in chronic oped by Cai et al. (1996) [102] act as antagonists of NDMA
obstructive pulmonary disorder. in glycine receptors. These compounds can be used as agents
against neurodegenerative diseases (e.g., Alzheimer’s disease).
OMe CN R5 O
F R6 NOH

R = H,Cl,CH3,F
O NH O O NH O N O
R7
H
O S O S
NH2 NH2 R8
CH3 CH3 102
N N
CH3 CH3 References
96 97

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