ω-(2-Naphthyloxy) amino alkanes as a novel class of anti-hyperglycemic and lipid lowering agents

Article abstract of DOI:10.1016/j.bmc.2007.11.062

ω-(2-Naphthyloxy) amino alkanes, obtained as major by-product during course of synthesis of carbamate esters from ω-(2-naphthyloxy) alkyl halides and amines, showed significant anti-hyperglycemic and lipid lowering activities in various test models as a novel class of compounds. Compounds were tested in rat GLM, SLM, STZ, and STZ-S models at 100 mg/kg dose. Of these compound 13 was found to be the most active which caused lowering of sugar by 33.6%, 31.0%, 28.5%, and 73.8% in GLM, SLM, STZ, STZ-S, and db/db mice models, respectively. It also significantly effected lowering of LDL in rat model and also in Hamster model without reducing HDL. Most of the compounds showing anti-diabetic and lipid lowering activity have shown promising PPAR-α/γ/δ-activity. Compounds 6, 13, and 19 have shown very good PPAR-α/γ/δ activity.

Full text of DOI:10.1016/j.bmc.2007.11.062

Available online at www.sciencedirect.com
Bioorganic & Medicinal Chemistry 16 (2008) 2489–2498
x-(2-Naphthyloxy) amino alkanes as a novel class
of anti-hyperglycemic and lipid lowering agentsq
Devdutt Chaturvedi,a,* Suprabhat Ray,a Arvind K. Srivastavab and Ramesh Chanderb
aMedicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India
bBiochemistry Division, Central Drug Research Institute, Lucknow 226001, India
Received 20 May 2007; revised 20 November 2007; accepted 21 November 2007
Available online 28 November 2007
Dedicated to Dr. Nitya Anand for his constant inspiration for research.
Abstract—x-(2-Naphthyloxy) amino alkanes, obtained as major by-product during course of synthesis of carbamate esters from x-
(2-naphthyloxy) alkyl halides and amines, showed significant anti-hyperglycemic and lipid lowering activities in various test models
as a novel class of compounds. Compounds were tested in rat GLM, SLM, STZ, and STZ-S models at 100 mg/kg dose. Of these
compound 13 was found to be the most active which caused lowering of sugar by 33.6%, 31.0%, 28.5%, and 73.8% in GLM,
SLM, STZ, STZ-S, and db/db mice models, respectively. It also significantly effected lowering of LDL in rat model and also in Ham-
ster model without reducing HDL. Most of the compounds showing anti-diabetic and lipid lowering activity have shown promising
PPAR-a/c/d-activity. Compounds 6, 13, and 19 have shown very good PPAR-a/c/d activity.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
are often known to induce severe hyperglycemia5 and
weight gain. Another major class of anti-hyperglycemic
agents is thiazolidine-dione derivatives. These are
known to reverse insulin resistance without stimulating
insulin release from b-cells.6 Some of the potential com-
pounds belonging to this class are Pioglitazone7 A, Ros-
iglitazone8 B (Fig. 1), act through PPAR-c receptor
therefore are well-known PPAR-c agonists, which have
been marketed until 2004. Although these agents have
glucose lowering effect and improve the lipid lowering
profile like TG, LDL cholesterols, and HDL cholester-
ols, the crucial side effects like congestive heart failure,
edema, fluid retention, and weight gain still remain unre-
solved.9 It was visualized that a dual PPAR-a and -c
activator could be an effective drug for insulin resis-
tance, hyperglycemia, and dyslipidemia. Several drugs
of such dual activity were in clinical development like
Ragaglitazar10 C, KRP-29711 D, Tesaglitazar12 E,
Muraglitazar13 F, etc. (Fig. 1). Unfortunately, the first
two were discontinued following instances of carcinoge-
nicity in rodent models. The successful PPAR-a, c dual
agonists including Tesaglitazar E, Muraglitazar F have
not been marketed. Besides the above-mentioned poten-
tial dual PPAR-a, c agonists, some other series of poten-
tial dual PPAR-a, c agonists have also been reported
recently in compounds G,14 H,15 I16 shown in Figure
1. Nevertheless PPAR- a, c dual agonist would be well
Diabetes1 is the root cause of several chronic and pro-
gressive diseases, which adversely affect a number of or-
gans including the nervous and vascular systems. More
than 90% of the diabetic patients suffer from type-2 dia-
betes, that is, non-insulin dependent diabetes mellitus
(NIDDM), which is characterized by insulin resistance
and hyperglycemia. Type-2 diabetes is one of the major
causes of several chronic diseases such as retinopathy,
neuropathy, nephropathy, and cardiovascular diseases.2
Long term hyperglycemia, caused by insufficient insulin
secretion from pancreas and/or insulin resistance in
muscle, liver, and adipose tissues, caused an aggravation
of diabetes. Therefore, it is important to regulate the
blood glucose levels in order to control diabetes.3 The
treatment generally prescribed for NIDDM has been a
combination of diet, exercise, and an anti-hyperglycemic
agent.4 One such class of anti-hyperglycemic agents is
sulfonylureas. These are insulin secretagogues, which
stimulate insulin secretion from pancreatic b-cells but
Keywords: x-(2-Naphthyloxy)amino alkanes; Anti-hyperglycemic act-
ivity; Lipid lowering activity.
q
CDRI Communication No. 6357.
*
Corresponding
ddchaturvedi002@yahoo.co.in
author.
Tel.:
+91
522
2629558; e-mail:
0968-0896/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2007.11.062

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D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
O
O
NH
S
NH
O
N
S
O
O
O
B
N
N
A
O
O
O
OH
N
H
HN
O
N
S
O
CF3
OCH2.CH3
OMe
O
D
C
O
S
O
O
O
COOH
N
OH
N
O
O
O
O
OCH2.CH3
O
F
E
O
OMe
R
NH
O
O
O
S
O
O
HN
O
N
O
X
O
G
H
X= O, S
R= OAr
O
OH
OCH2.CH3
O
F
N
O
N
N
O
O
I
COOH
F
F
J
SAR corelations
Aromatic/Heterocyclic
O
R'
O
Aromatic/Heterocyclic
n
R
K
Figure 1. Structures of PPAR-c (A, B), dual PPAR-a, c (C–I), and dual PPAR-a/d (J) agonists with a detailed discussion of structure–activity
relationship.
suited for the treatment of diabetes and cardiovascular
diseases as long as it could reduce side effects as men-
tioned above. Therefore, there has been a resurgence
of interest in the development of novel dual PPAR-a,
c agonists which could be an effective drug for insulin
resistance, hyperglycemia, and dyslipidemia free, from
unwanted effects.
Hence, it was further concluded that for dual PPAR a/
d agonists both of the hetero-atoms are required. These
aromatic and hetero-aromatic systems were further
substituted through different kinds of substitutions.
The present invention was aimed at the modification of
cyclic and rigid thiazolidine-dione moiety into a non-ri-
gid open chain carbamate moiety (Fig. 2). During the
course of synthesis of acyclic carbamate compound re-
ported by our group18 as shown in Scheme 1, through
the condensation of x-(2-naphthyloxy) alkyl halides
with amines, the major by-product obtained was x-(2-
naphthyloxy) alkyl amines. Although the anti-diabetic
activity of the designed carbamates was tested, none of
the compounds have shown promising anti-diabetic
activity. Lateron, It has been realized after careful study
Typical structure–activity relationship (SAR) study of
most of the potential dual PPAR-a, c agonists reveals
that there should be atleast one substituted aromatic
and one hetero-aromatic system inter-connected
through atleast 2–3 carbon chain separated through het-
ero-atom. Moreover, it was realized from the structure
of a PPAR-a/d, agonist, that is, compound J,17 where
both of the heterocyclic systems were inter-connected.

D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
2491
we report19 here evaluation of such x-(2-naphthyloxy)
alkyl amines as a novel class of anti-hyperglycemic
and lipid lowering agents. Later on, the synthetic proto-
col for these amines was changed. These have been sim-
ply prepared directly from the condensation of alkyl
halides with amines using K2CO3 system.
O
O
R1
NH
O
O
N
S
R2
Figure 2. Modification of thiazolidine-dione moiety into carbamate
moiety.
The general structures of the designed prototypes have
been mentioned in Figure 4.
of the structure–activity relationship (SAR) of dual
PPAR- a/c and PPAR-a/d agonists as discussed above
(Fig. 1) that the x-(2-naphthyloxy) alkyl substituted
aromatic amines particularly compounds 6–20 have
shown very close co-relations with the above-mentioned
dual agonists depicted in Figure 3. It became further
clear that the two aromatic rings of the substituted
amine derivatives were inter-connected with the 2–4 car-
bon chains separated by O and N heterocycles, respec-
tively. Keeping all the above considerations, we
became interested to investigate the anti-diabetic activity
profile of these amine derivatives. Interestingly, most of
the phenyl substituted amine derivatives have shown
promising anti-diabetic activity, indicating the further
confirmation about the proposed SAR study. Further-
more, keeping the designing of the dual agonists we have
tested these compounds for lipid lowering activity where
we have observed promising lipid lowering profile. Thus,
2. Chemistry
Initially, these by-products formed during the synthesis
of carbamates, that is, x-(2-naphthyloxy) amino al-
kanes, were isolated and tested for biological activity.
Interestingly, after getting the unexpected promising
biological activity in these compounds, we became inter-
ested in the preparation of amine derivatives through di-
COOEt
R1
O
O
( )n
N
( )n
N
R2
R2
I
II
Figure 4. General structure of the prepared prototypes.
O
R1
R1
O
O
Dry DMSO, CO2 bubbling
( )n
( )n
O
N
+
X
HN
Triton-B, 90-100 ºC
R2
R2
Carbamate
derivative (A)
+
120-130 ºC
Dry DMSO, anhyd. K2CO3
R1
R2
O
( )n
N
Amine derivative (B)
Scheme 1. Formation of side product, that is, amine derivative, during carbamate synthesis from alkyl halides and amines.
Aromatic/Heterocyclic
O
R'
O
Aromatic/Heterocyclic
n
R
K
R1
N
O
R2
( )n
n = 1-3
R1 = H, CH3, C2H5, n-C3H7, n-C4H9, CH2COOEt, CH2COOH
R2 = methoxy, methyl
Figure 3. SAR co-relations of dual PPAR-a/c and PPAR-a/d agonists with designed substituted amines.

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D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
rect condensation of the corresponding x-(2-naphthyl-
oxy) alkyl halides with various amines. Thus, the syn-
thetic procedure for the preparation of x-(2-
naphthyloxy) amino alkanes and its substituted deriva-
tives is shown in Scheme 2. Reaction of b-naphthol or
its derivatives 1 with different dihaloalkanes 2 (where
X1 and X2 may be same or different halogens) gave hal-
ogen substituted compound 3, which was further reacted
with amines 4 to afford desired compounds 5–14 of the
general structure I. All the prepared compounds of
structure I are shown in Table 1 and were evaluated
for their anti-hyperglycemic and lipid lowering activi-
ties. Out of the various compounds (5–14) tested, com-
pound 13 was found to be the most active and has
shown very promising anti-diabetic activity and lipid
lowering activity compared with the corresponding stan-
dard drugs.
To optimize further SAR of 13, various N-substituted
derivatives of compound 13 were prepared. Compound
13 was treated with various alkyl halides to afford N-al-
kyl derivatives of general structure II (15–18) (Scheme
3). Compound 13 was also converted into N-substituted
esters using corresponding halo ester. This N-substi-
tuted ester was subjected to basic hydrolysis to afford
the corresponding N-substituted acid. The activity data
of all the compounds are shown in Table 1.
3. Results and discussion
All the compounds synthesized were evaluated for
in vivo anti-hyperglycemic activity in male and female
albino rats (Sprague–Dawley) of body weight of
ꢀ160 g in four different models namely GLM, SLM,
O
OH
X
( )n
a
( )n
X
X
+
1
2
3
R1
b
NH
R2
4
R1
R2
O
( )n
N
I (5-14)
Scheme 2. Reagents and conditions: (a) bromochloro alkane/dihalo alkanes, anhyd K2CO3, dry acetone, reflux, 12–15 h; (b) anhyd K2CO3, dry
DMSO, 130–140 °C, 12–15 h.
Table 1. Anti-hyperglycemic and lipid lowering activity of various derivatives of compound I in different models
Entry
R1
R2
n
Dose: 100 mg/kg
Anti-diabetic activity (% inhibition)
Lipid lowering activity (%
inhibition) (Triton model)
GLM
SLM
STZ
STZ-S
Chol
Phosp
TG
5
H
C8H17
CH2C6H5
2
1
2
3
2
1
3
1
2
3
2
2
2
2
2
2
17
32
64
NT
13
NT
69.5
NT
NT
NT
NT
NT
NT
73.8
NT
NT
NT
NT
NT
5.6
NT
31
NT
34
NT
37
6
H
37.6
13.8
8.89
1.23
2.45
3.21
10.6
33.6
3.89
8.20
6.88
11.6
13.5
25.9
15.5
7
H
CH2C6H5
CH2C6H5
40.5
16.0
8.30
6.99
6.90
19.4
31
NT
NT
NT
NT
NT
NT
28.5
NT
NT
NT
NT
NT
6.9
NT
10.1
14
NT
18
NT
5
8
H
9
10
H
m-OCH3C6H4CH2
p-CH3C6H4–
p-CH3C6H4–
p-OCH3C6H4
p-OCH3C6H4
p-OCH3C6H4
p-OCH3C6H4
p-OCH3C6H4
p-OCH3C6H4
p-OCH3C6H4
p-OCH3C6H4
p-OCH3C6H4
22
30
22
18
H
27.0
NT
NT
32.4
24.0
11.0
NT
14
11
12
H
NT
NT
38
NT
NT
28
H
13
14
H
H
CH3
5.09
14.5
13.5
37.2
4.40
45.4
21.5
33.9
44.8
NA
36
19
22
15
15
16
C2H5
C3H7
NT
27
NT
12
17
18
C4H9
CH2COOEt
CH2COOH
15
25
26
17
15
19
20
21.2
23.8
NA
NA
34
NT
32.8
27.7
NA
NT
NT
NT
NA
16.9
NA
NA
33
13.0
NA
NA
30
Gybenclamide
Glyclazide
Gugulipid
NA
NT, not tested; NA, not applicable.

D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
2493
O
O
( )n
a
( )n
NH
OCH3
N
R
OCH3
13
b
(15-18)
R = Me, Et, Pr, Bu
O
O
c
( )n
( )n
N
OCH3
N
OCH3
COOH
19
20
COOEt
II (15-20)
Scheme 3. Reagents and conditions: (a) alkyl halides, dry acetone, reflux; (b) bromo-ethyl acetate, dry acetone, reflux; (c) NaOH, ethanol, reflux,
basic hydrolysis.
STZ, and STZ-S. Compounds showing sugar lowering
activity (more than 7%) were evaluated for in vivo lipid
lowering activity in Triton model taking male Charles
Faster rats (200–225 g) and some in hamster model tak-
ing male golden Syrian hamster (120–130 g). The anti-
diabetic activity profile and lipid lowering activity of
compounds are given in Table 1.
Compounds 6 and 13 showed promising activity in
STZ and STZ models, while compound 19 could not
show promising activity in both the models (Table 1).
Those compounds which have shown anti-diabetic activ-
ity in STZ as well as STZ-S model were than evaluated
for their anti-diabetic activity in db/db mice (degree of
mean glucose lowering as percentage of the difference
between vehicle treated db/db mice versus lean control
mice), PPAR-c binding activity and only compound 13
has shown promising activity (Table 2).
Among the 16 compounds screened, compound nos. 5,
6, 7, 8, 12, 13, 15, 17, 18, 19, and 20 demonstrated
anti-hyperglycemic activity (more than 7%) in GLM
model, while 5, 6, 7, 8, 9, 12, 13, 15, 16, 17, 19, and 20
displayed blood sugar lowering activity in SLM model.
In general compounds showing activity in GLM model
were also found to be active in SLM model as well.
Structure–activity relationship (SAR) of compounds
studied suggested that in the case of benzyl substituent
(R2) on the nitrogen, the anti-hyperglycemic activity of
the compounds was maximum with n = 1 and decreased
on the increasing of their chain length. However, when
R2 is an aryl residue, compounds with n = 1 were less ac-
tive. Most promising activity was encountered with p-
methoxyphenyl substituent (R2) on the nitrogen having
a three-carbon chain (n = 2) (compound no. 13). In this
anisyl series, introduction of an additional alkyl substi-
tuent on the nitrogen (R1) caused lowering in anti-
hyperglycemic activity. Shifting of the methoxy substitu-
ent on the phenyl to m-position or its replacement by a
methyl substituent resulted in diminished or total loss of
activity. An alkyl/ester/acid substitution on the nitrogen
of x-(2-naphthyloxy) amino alkane compounds (15–20)
was not showing good anti-diabetic activity but these
compounds have lipid lowering activity.
The most promising compounds 6 and 13 were also as-
sayed in STZ and STZ-S models. Both of the com-
pounds 6, 13 were found active in STZ and STZ-S
models.
Compounds 6, 9, 13, 15, and 19 showing sugar lowering
activity in SLM model were also evaluated for their lipid
lowering activity in Triton model. Lipid lowering activ-
ity of 6 and 13 was comparable to the standard drug
Gugulipid. Compound 13 was also evaluated for lipid
lowering activity in hamster model and compared with
Fenofibrate (standard drug). Although the activity pro-
file of 13 was inferior to that of Fenofibrate, it showed
that the test compound 13 besides having significant su-
gar lowering activity had the added advantage of anti-
hyperlipidemic activity as well.
It has already been realized from the structural co-rela-
tions of x-(2-naphthyloxy) amino alkanes with the gen-
eral structural SAR of the dual PPAR-a, c and PPAR-a,
d agonists that this class of compounds should be prom-
ising PPAR dual agonists. Thus, keeping all the above
The promising compounds 6, 13, 19 in GLM and SLM
models were also assayed in STZ and STZ-S models.
Table 2. PPAR-c and lipid lowering activity (in hamster model) of compound nos. 6, 13, 19, and 20
Entry
Anti-diabetic activity (% inhibition)
Lipid lowering activity (% inhibition, hamster model)
db/db mice % efficacy day 3 (100 mg/kg)
PPAR-binding
TG
Chol
HDL
GLU
GLY
FFA
5 h
24 h
PPAR-c EC50 (lM)
6
13
7
11.6
28.9
15.4
NT
0.4
33.8
4.8
NT
41
37.0
48
14.0
14
13.0
15
9.5
31
34
22
33
10
14
7.3
23
52
NT
NT
48
22.4
12.0
NT
19
20
68
44
22
21
16
11
NT
53
Fenofibrate
77
30
33

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D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
considerations the compounds which have shown prom-
ising anti-diabetic activity were further tested for PPAR-
a/c/d agonistic activity. Thus, compounds 5, 6, 7, 8, 12,
13, 14, 15, 16, 17, 18, 19, and 20 were tested for PPAR-a/
c/d activity using Rosiglitazone and Tesaglitazar as stan-
dard drugs (Table 3). It is clear from Table 3 that most
of the compounds showing anti-diabetic and lipid lower-
ing activity have shown promising PPAR-a/c/d activity.
Out of the above-mentioned compounds tested, com-
pounds 6, 13, and 19 have shown very good activity.
excess), and bromochloroalkane 2 (0.14 mol) was re-
fluxed in dry acetone (200 mL) for 12–15 h. Reaction
mixture was filtered and filtrate was concentrated to
get oily compound, which was crystallized with ben-
zene-hexane to give the colorless crystals of pure de-
sired compound.
4.1.1.1. 2-(2-Naphthyloxy)-1-chloroethane (3a). Yield:
27.5 g (96%); mp: 94 °C; IR (KBr, cmÀ1): m = 1455 (Ar),
1508 (Ar), 1585 (Ar), 2878 (CH), 2927 (CH); H NMR
1
(400 MHz, CDCl3): d = 3.81 (t, 2H, CH2Cl), 4.26 (t,
2H, OCH2), 6.97–7.64 (m, 7H, Ar–H); 13C NMR
(100 MHz, CDCl3): d = 45.3, 75.1, 105.8, 118.6, 123.6,
126.4, 129.5, 134.5, 157.7 ppm; Mass (EIMS): m/z =
206; Analysis: C12H11ClO, Calcd: C, 69.74; H, 5.36;
Obsd: C, 70.04, H, 5.66%.
4. Experimental
4.1. Chemistry
All the reactions were monitored by thin layer chro-
matography over silica gel coated TLC plates. The
spots on TLC plates were visualized by warming the
CeSO4 (1% 2 N H2SO4) sprayed plates in an oven
at 100 °C. Other developers used were iodine vapors
and KMNO4 spray. For column chromatography, sil-
ica gel (100–200 mesh) was used. The melting points
were recorded on electrically heated melting point
apparatus and are uncorrected. IR spectra were re-
corded on Perkin-Elmer 881 and FTIR 8210 PC Shi-
madzu spectrophotometers either as KBr disks or neat
4.1.1.2. 3-(2-Naphthyloxy)-1-chloropropane (3b).
Yield: 29.7 g (97%); mp: 98 °C; IR (KBr, cmÀ1):
m = 1461 (Ar), 1512 (Ar), 1596 (Ar), 2855 (CH), 2940
(CH) cmÀ1 1H NMR (400 MHz, CDCl3): d = 2.27–
;
2.33 (m, 2H, CH2), 3.80 (t, 2H, CH2Cl), 4.25 (t, 2H,
OCH2), 7.12–7.77 (m, 7H, Ar–H) ppm; Mass (EIMS):
m/z = 220; Analysis: C13H13ClO, Calcd: C, 70.75; H,
5.94; Obsd: C, 70.79; H, 6.21%.
4.1.1.3. 4-(2-Naphthyloxy)-1-chlorobutane (3c). Yield:
32 g (98%); mp: 112 °C; IR (KBr, cmÀ1):m = 1464 (Ar),
1510 (Ar), 1599 (Ar), 2887 (CH), 2941 (CH); H NMR
1
and the values are expressed in cmÀ1. H NMR spec-
1
tra were recorded on Brucker WM 400 MHz spec-
trometer in deuterated solvents with TMS as internal
reference. EI spectra of all the compounds were mea-
sured on JEOL JMS-D 300 spectrometer with the ion-
ization potential of 70 eV. FAB mass spectra were
recorded on JEOL SX 102/DA 6000 mass spectrome-
ter using Argon/Xenon (6 kV, 10 mA) as the FAB gas.
Microanalyses were carried out on Carlo Erba EA-
1108 element analyzer.
(CDCl3): d = 2.15–2.20 (m, 4H, CH2ÆCH2), 3.79 (t, 2H,
CH2Cl), 4.24 (t, 2H, OCH2), 7.13–7.78 (m, 7H, Ar–
H) ppm;
Mass
(EIMS):
m/z = 234;
Analysis:
C14H15ClO, Calcd: C, 71.64; H, 6.44; Obsd: C, 71.43;
H, 6.31%.
4.1.2. General procedure for the preparation of
x-naphthyloxy amino alkanes (I, compound nos. 5–14).
A mixture of anhydrous potassium carbonate (10 g, in
excess) and amine (3 mmol) was taken in dry DMSO
(40 mL). x-(2-Naphthyloxy)-1-chloroalkane (0.5 g,
2 mmol) was added to it. Reaction mixture was refluxed
at 130–140 °C for 7–9 h when the reaction was com-
pleted as checked by TLC. Reaction mixture was poured
into distilled water (60 mL) and extracted with ethyl ace-
tate thrice. The organic layer was separated and concen-
trated to get oily compound, which was later crystallized
by benzene-hexane to get the desired compound.
4.1.1. General procedure for the preparation of x-
naphthyloxy halo alkanes (3a–c). A mixture of b-naph-
thol 1 (20 g, 0.14 mol), anhydrous K2CO3 (100 g, in
Table 3. PPAR (a, c, d) activities of compounds 5, 6, 7, 8, 12, 13, 14,
15, 16, 17, 18, 19, and 20
Entry
PPAR (EC50) (% inhibition)
PPAR-a
(50 lM)
PPAR-c
(1 lM)
PPAR-d
(3 lM)
4.1.2.1. N-(n-Octyl)-(3-(naphthalene-2-yloxy)propyl)-
amine (5). Yield: 0.7 g (96.7%); mp: 109 °C; IR (KBr,
cmÀ1): m = 1470 (Ar), 1527 (Ar), 1623 (Ar), 2874 (CH),
5
11.4
36.2
28.4
21.3
22.2
44.5
18.3
22.5
20.3
10.9
8.5
8.5
34.6
27.6
20.5
25.3
43.5
17.2
24.6
19.4
11.4
7.7
7.9
31.3
29.1
22.4
24.6
42.6
16.3
19.3
17.3
9.6
6
2925 (CH), 3396 (NH) cmÀ1 1H NMR (400 MHz,
;
7
8
12
CDCl3): d = 0.96 (t, 3H, CH3), 1.25–1.30 (m, 8H, CH2
of n-octyl group), 1.30–1.34 (m, 2H, CH2ÆCH3), 1.38–
1.42 (m, 2H, CH2CH2N), 1.80–1.83 (m, 2H, O–CH2
CH2CH2N), 2.1 (br, H, NH), 2.53–2.56 (m, 4H,
NHCH2CH2), 2.97 (t, 2H, O–CH2 CH2NH), 4.21 (t,
2H, OCH2-naphthyl), 6.97–7.66 (m, 7H, Ar–H of naph-
thyloxy); 13C NMR (100 MHz, CDCl3): d = 14.5, 23.1,
27.7, 30.6, 32.2, 32.5, 45.8, 49.6, 70.2, 105.8, 118.8,
123.6, 126.7, 129.6, 134.5, 157.6 ppm; Mass (EIMS):
m/z = 313; Analysis: C21H31NO, Calcd: C, 80.46; H,
9.97; N, 4.47; Obsd: C, 80.93; H, 9.70; N, 4.23%.
13*
14
15
16
17
18
8.4
19
20
33.5
25.4
55.5
—
34.9
22.5
59.4
46.4
29.6
20.2
—
Tesaglitazar
Rosiglitazone
—

D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
2495
4.1.2.2. N-Benzyl-[2-naphthalen-2-yloxy]amine (6).
Yield: 0.6 g (93%); mp: 94 °C; IR (KBr, cmÀ1):
m = 1460 (Ar), 1508 (Ar), 1604 (Ar), 2864 (CH), 2927
157 ppm; Mass (EIMS): m/z = 277; Analysis:
C19H19NO, Calcd: C, 82.28; H, 6.90; N, 5.05; Obsd:
C, 81.87; H, 7.47; N, 4.83%.
1
(CH), 3389 (NH) cmÀ1; H NMR (400 MHz, CDCl3):
d = 2.2 (br, H, NH), 2.94 (t, 2H, O–CH2CH2–N),
3.79–3.82 (m, 2H, CH2Ph), 4.15 (t, 2H, CH2–O–naph-
thyl), 6.97–7.68 (m, 12H, Ar–H); 13C NMR (100 MHz,
CDCl3): d = 49.5, 55.6, 74.5, 105.7, 118.6, 123.6, 126.7,
128.1, 128.7, 129.6, 134.5, 137.2, 157.6 ppm; Mass
(EIMS): m/z = 277; Analysis: C19H19NO, Calcd: C,
82.28; H, 6.90; N, 5.05; Obsd: C, 81.97; H, 7.24; N,
4.83%.
4.1.2.7. N-(4-Methylphenyl)-[4-(2-naphthyloxy)butyl]-
amine (11). Yield: 0.63 g (97%); mp: 98°C; IR (KBr,
cmÀ1): m = 1472 (Ar), 1529 (Ar), 1623 (Ar), 2879 (CH),
2940 (CH), 3402 (NH) cmÀ1 1H NMR (400 MHz,
;
CDCl3): d = 1.49–1.52 (m, 2H, NHCH2CH2CH2CH2–
O–), 1.91–1.94 (m, 2H, CH2CH2CH2CH2NH), 2.35 (s,
3H, CH3), 3.01–3.05 (m, 2H, NHCH2), 4.05 (br, H,
NH), 4.15 (t, 2H, OCH2), 6.32–7.66 (m, 12H, Ar–H);
13C NMR (100 MHz, CDCl3): d = 21.4, 28.3, 29.2,
52.5, 72.5, 105.6, 118.8, 123.7, 126.9, 128.8, 129.6,
134.5, 137.8, 157.6 ppm; Mass (EIMS): m/z = 293; Anal-
ysis: C21H23NO, Calcd: C, 82.58; H, 7.59; N, 4.59; Obsd:
C, 82.34; H, 7.93; N, 4.73%.
4.1.2.3. N-Benzyl-[3-(2-naphthyloxy)-propyl]amine (7).
Yield: 0.62 g (93.6%); mp: 109 °C; IR (KBr, cmÀ1):
m = 1467 (Ar), 1522 (Ar), 1609 (Ar), 2874 (CH), 2938
(CH) cmÀ1 1H NMR (400 MHz, CDCl3): d = 1.80–
;
1.84 (m, 2H, O–CH2CH2CH2N), 2.3 (br, H, NH), 2.56
(t, 2H, NCH2), 3.78–3.82 (m, 2H, CH2Ph), 4.10 (t, 2H,
OCH2), 6.94–7.68 (m, 12H, Ar–H); 13C NMR
(100 MHz, CDCl3): d = 32.5, 45.6, 55.4, 69.7, 105.3,
118.8, 123.8, 126.8, 128.9, 128.8, 129.6, 134.6, 137.5,
157.6 ppm; Mass (EIMS): m/z = 291; Analysis:
C20H21NO, Calcd: C, 82.44; H, 7.26; N, 4.81; Obsd:
C, 82.69; H, 6.91; N, 4.53%.
4.1.2.8. N-(4-Methoxyphenyl)-[2-(2-naphthyloxy)ethyl]-
amine (12). Yield: 0.67 g (94%), mp: 92 °C; IR (KBr,
cmÀ1): m = 1464 (Ar), 1512 (Ar), 1603 (Ar), 2866 (CH),
2927 (CH), 3388 (NH) cmÀ1 1H NMR (400 MHz,
;
CDCl3): d = 3.43–3.49 (m, 2H, O–CH2CH2NH), 3.73
(s, 3H, OCH3), 4.12 (br, H, NH), 4.22 (t, 2H, OCH2),
6.32–7.69 (m, 12H, Ar–H); 13C NMR (100 MHz,
CDCl3): d = 52.3, 56.7, 73.8, 105.6, 118.6, 123.6, 126.7,
128.6, 128.8, 129.9, 134.7, 137.5, 157.8 ppm; Mass
(EIMS): m/z = 293; Analysis: C19H19NO2, Calcd: C,
77.79; H, 6.53; N, 4.77; Obsd: C, 77.58; H, 6.99; N,
4.54%.
4.1.2.4. N-Benzyl-[4-(2-naphthyloxy)-butyl]amine (8).
Yield: 0.62 g (95.3%); mp: 105 °C; IR (KBr, cmÀ1):
m = 1472 (Ar), 1522 (Ar), 1613 (Ar), 2874 (CH), 2939
1
(CH), 3399 (NH) cmÀ1; H NMR (400 MHz, CDCl3):
d = 1.38–1.42 (m, 2H, NHCH2CH2CH2CH2–O–),
1.70–1.74 (m, 2H, O–CH2CH2CH2CH2–N–), 2.10 (br,
H, NH), 2.532–2.56 (m, 2H, NHCH2), 3.80–3.83 (m,
2H, CH2Ph), 4.21 (t, 2H, OCH2), 6.95–7.69 (m, 12H,
Ar–H); 13C NMR (100 MHz, CDCl3): d = 28.3, 28.8,
49.6, 55.6, 73.4, 105.7, 118.9, 123.6, 126.5, 128.5,
128.9, 129.5, 134.5, 137.6, 157.5 ppm; Mass (EIMS):
m/z = 305; Analysis: C21H23NO, Calcd: C, 82.58; H,
7.59; N, 4.59; Obsd: C, 82.22; H, 7.31; N, 4.27%.
4.1.2.9. N-(4-Methoxyphenyl)-[3-(2-naphthyloxy)pro-
pyl]amine (13). Yield: 0.66 g (95.6%); mp: 110 °C; IR
(KBr, cmÀ1): m = 1468 (Ar), 1521 (Ar), 1611 (Ar), 2874
(CH), 2930 (CH), 3394 (NH) cmÀ1
;
1H NMR
2H, O–
(400 MHz,
CDCl3):
1.91–1.94
(m,
CH2CH2CH2NH), 3.10–3.15 (m, 2H, CH2NH), 3.75
(s, 3H, OCH3), 4.01 (br, H, NH), 4.14 (t, 2H, O–CH2),
6.32–7.64 (m, 12H, Ar–H); 13C NMR (100 MHz,
CDCl3): d = 32.4, 47.9, 56.2, 69.7, 105.7, 118.8, 123.8,
126.5, 128.3, 128.6, 129.9, 134.8, 137.6, 157.6 ppm; Mass
(EIMS): m/z = 307; Analysis: C20H21NO2, Calcd: C,
78.15; H, 6.89; N, 4.56; Obsd: C, 78.59; H, 6.65; N,
4.28%.
4.1.2.5. N-(3-Methoxybenzyl)-[3-(2-naphthyloxy)pro-
pyl]amine (9). Yield: 0.68 g (92.8%); mp: 97°C; IR
(KBr, cmÀ1): m = 1469 (Ar), 1519 (Ar), 1610 (Ar), 2872
(CH), 2934 (CH), 3392 (NH) cmÀ1
;
1H NMR
(m, 2H,
(400 MHz,
CDCl3):
d = 1.81–1.84
CH2CH2NH), 2.21 (br, H, NH), 2.53–2.57 (m, 2H,
NCH2), 3.73 (s, 3H, OCH3), 3.79–3.85 (m, 2H, CH2Ph),
4.14 (t, 2H, OCH2), 6.98–7.66 (m, 12H, Ar–H); 13C
NMR (100 MHz, CDCl3): d = 32.5, 45.4, 55.3, 56.7,
69.7, 105.3, 118.7, 123.8, 126.8, 128.9, 128.8, 129.6,
134.6, 137.5, 157.6 ppm; Mass (EIMS): m/z = 321; Anal-
ysis: C21H23NO2, Calcd: C, 78.47; H, 7.21; N, 4.36;
Obsd: C, 78.07; H, 7.75; N, 4.27%.
4.1.2.10.
N-(4-Methoxyphenyl)-[4-(2-naphthyloxy)-
butyl]amine (14). Yield: 0.67 g (97.8%); mp: 95 °C; IR
(KBr, cmÀ1): m = 1474 (Ar), 1530 (Ar), 1623( Ar), 2880
(CH), 2940 (CH), 3405 (NH) cmÀ1
;
1H NMR
(400 MHz, CDCl3):d = 1.91–1.94 (m, 2H, O–CH2CH2
CH2CH2NH), 3.12–3.16 (m, 2H, O–CH2CH2CH2
CH2NH), 3.73 (s, 3H, OCH3), 4.05 (br, H, NH), 4.22 (t,
2H, OCH2), 6.35–7.80 (m, 12H, Ar–H); 13C NMR
(100 MHz, CDCl3): d = 28.3, 28.6, 51.6, 56.3, 72.5,
105.5, 118.6, 123.6, 126.7, 128.6, 128.8, 129.9, 134.7,
137.5, 157.8 ppm; Mass (EIMS): m/z = 321; Analysis:
C21H23NO2, Calcd: C, 78.47; H, 7.21; N, 4.36; Obsd: C,
78.09; H, 7.48; N, 4.21%.
4.1.2.6.
N-(4-Methylphenyl)-[2-(2-naphthyloxy)-
ethyl]amine (10). Yield: 0.62 g (91.7%); mp: 92 °C; IR
(KBr): m = 1465 (Ar), 1515 (Ar), 1606 (Ar), 2868 (CH),
2931 (CH), 3391 (NH) cmÀ1 1H NMR (400 MHz,
;
CDCl3): d = 2.35 (s, 3H, CH3), 3.43–3.48 (m, 2H, O–
CH2CH2NH), 4.10 (br, H, NH), 4.21 (t, 2H, CH2–O–
naphthyl), 6.34–7.64 (m, 12H, Ar–H); 13C NMR
(100 MHz, CDCl3): d = 21.3, 51.9, 73.8, 105.9, 112.3,
118.8, 123.5, 126.9, 128.1, 128.4, 129.6, 134.5, 137.5,
4.1.3. General procedure for the preparation of N-alkyl
derivatives of compound no. 13. A mixture of (4-methoxy-
phenyl)-[3-(2-naphthyloxy)propyl]amine (13) (0.5 g,
2 mmol) and alkyl iodide (3 mmol) was taken in dry ace-

2496
D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
tone (40 mL). It was refluxed for 10–12 h and the progress
of the reaction was checked by TLC. Reaction mixture
was filtered and filtrate was concentrated to get oily com-
pound, which was further crystallized using benzene-hex-
ane mixture to get the desired compound.
(FAB): m/z = 363; Analysis: C24H29NO2, Calcd: C,
79.30; H, 8.04; N, 3.85; Obsd: C, 79.58; H, 8.26; N,
4.33%.
4.1.3.5. {N-(4-Methoxyphenyl)-[3-(2-naphthyloxy)pro-
pyl]amino} acetic acid ethyl ester (19). A mixture of com-
pound 13 (0.5 g, 2 mmol) and ethyl bromoacetate
(0.62 mL, 3 mmol) was taken in dry acetone (40 mL).
It was refluxed for 10 h and the completion of reaction
was checked by TLC. Reaction mixture was filtered
and the filtrate was concentrated to get the desired
compound.
4.1.3.1. N-(4-Methoxyphenyl)-N-methyl-[3-(2-naph-
thyloxy)propyl]amine (15). Yield: 0.5 g (94%); mp:
112 °C; IR (KBr, cmÀ1): m = 1464 (Ar), 1512 (Ar),
1600 (Ar), 2864 (CH), 2927 (CH) cmÀ1 1H NMR
;
(400 MHz, CDCl3): d = 1.90–1.94 (m, 2H, O–
CH2CH2CH2N), 2.85 (s, 3H, N–CH3), 3.30–3.33 (m,
2H, O–CH2CH2CH2N), 3.74 (s, 3H, OCH3), 4.20 (t,
2H, OCH2), 6.48–7.64 (m, 12H, Ar–H); 13C NMR
(100 MHz, CDCl3): d = 29.6, 41.4, 54.6, 56.7, 105.6,
118.7, 123.7, 126.6, 128.4, 128.6, 129.8, 134.9, 137.7,
157.5 ppm; Mass (FAB): m/z = 321; Analysis:
C21H23NO2, Calcd: C, 78.47; H, 7.21; N, 4.36; Obsd:
C, 78.75; H, 7.69; N, 4.18%.
Yield: 0.62 g (96%), mp: oil; IR (neat, cmÀ1): m = 1479
(Ar), 1519 (Ar), 1617 (Ar), 1689 (C@O), 2877 (CH),
2937 (CH) cmÀ1
;
1H NMR (400 MHz, CDCl3):
d = 1.30 (9t, 2H, COOCH2CH3), 1.92–1.96 (m, 2H, O–
CH2CH2CH2–N–), 3.35 (t, 2H, O–CH2CH2CH2N),
3.73 (s, 3H, OCH3), 4.22 (t, 2H, OCH2), 4.25–4.30(m,
2H, COOCH2CH3), 4.33 (s, 2H, NCH2COOEt), 6.50–
7.66 (m, 12H, Ar–H); 13C NMR (100 MHz, CDCl3):
d = 13.6, 29.6, 52.7, 56.6, 59.6, 105.5, 118.7, 123.6,
126.8, 128.7, 128.9, 129.7, 134.8, 137.9, 157.8,
171.5 ppm; Mass (FAB): m/z = 393; Analysis:
C24H27NO4, Calcd: C, 73.26; H, 6.92; N, 3.56; Obsd:
C, 73.59; H, 7.34; N, 3.48%.
4.1.3.2. N-(4-Methoxyphenyl)-N-ethyl-[3-(2-naphthyl-
oxy)propyl]amine (16). Yield: 0.52 g (94.6%); mp:
117 °C; IR (KBr, cmÀ1): m = 1470 (Ar), 1519 (Ar),
1612 (Ar), 2872 (CH), 2938 (CH) cmÀ1 1H NMR
;
(400 MHz, CDCl3): d = 1.14 (t, 3H, NCH2CH3),
1.92–1.97 (m, 2H, O–CH2CH2CH2N), 3.31–3.35 (m,
2H, O–CH2CH2CH2N), 3.38–3.42 (m, 2H, NCH2CH3),
3.76 (s, 3H, OCH3), 4.22 (t, 2H, OCH2), 6.50–7.69
(m, 12H, Ar–H); 13C NMR (100 MHz, CDCl3):
d = 13.3, 29.7, 49.1, 52.6, 56.5, 105.2, 118.5, 123.8,
126.7, 128.6, 128.7, 129.6, 134.8, 137.8, 157.5 ppm; Mass
(FAB): m/z = 335; Analysis: C22H25NO2, Calcd: C,
78.77; H, 7.51; N, 4.18; Obsd: C, 78.45; H, 7.96; N,
4.06%.
4.1.3.6. {N-(4-Methoxyphenyl)-[3-(2-naphthyloxy)pro-
pyl]amino} acetic acid (20). Compound 19 (0.5 g) was ta-
ken in ethanol (30 mL) and to this stirring solution
NaOH (80 mg) in ethanol (15 mL) was added and re-
fluxed for 1 h to afford acid 20. Yield: 200 mg, 1H
NMR (400 MHz, CDCl3): d = 1.92–1.96 (m, 2H,
OCH2CH2CH2N), 3.32–3.35 (m, 2H, OCH2CH2CH2N),
3.76 (s, 3H, OMe), 4.05–4.11 (t, 2H, CH2–O–naphthyl),
4.25–4.31 (s, 2H, NCH2COOH), 6.48–7.66 (m, 12H, Ar–
H of naphthyloxy and phenyl ring) ppm, Mass (FAB):
m/z = 365; Analysis: C22H23NO4, Calcd: C, 72.31, 6.34,
N, 3.83; Obsd: C, 72.69, H, 5.64, N, 3.49%.
4.1.3.3. N-(4-Methoxyphenyl)-N-propyl-[3-(2-naph-
thyloxy)propyl]amine (17). Yield: 0.55 g (95.7%); mp:
116 °C; IR (KBr, cmÀ1): m = 1474 (Ar), 1520 (Ar),
1621 (Ar), 2874 (CH), 2937 (CH) cmÀ1 1H NMR
;
(400 MHz, CDCl3): d = 0.96 (t, 3H, NCH2CH2CH3),
1.51–1.56 (m, 2H, NCH2CH2CH3), 1.92–1.96 (m, 2H,
4.2. Biological assay
O–CH2CH2CH2N),
3.30–3.36
(m,
4H,
O–
CH2CH2CH2N and NCH2CH2CH3), 3.38–3.42 (m,
2H, NCH2CH3), 3.75 (s, 3H, OCH3), 4.24 (t, 2H,
OCH2), 6.51–7.70 (m, 12H, Ar–H); 13C NMR
(100 MHz, CDCl3): d = 11.7, 22.5, 29.8, 49.2, 52.7,
56.6, 105.6, 118.6, 123.9, 126.6, 128.6, 128.7, 129.6,
134.9, 137.8, 157.7 ppm; Mass (FAB): m/z = 349; Anal-
ysis: C23H27NO2, Calcd: C, 79.05; H, 7.79; N, 4.01;
Obsd: C, 79.39; H, 7.43; N, 4.15%.
4.2.1. Anti-diabetic activity. Activity of various com-
pounds was tested in different four models as discussed
one by one.
4.2.1.1. Glucose-loaded model (GLM). Overnight
fasted male Sprague–Dawley rats were used for the glu-
cose-loaded experiment. Blood was collected initially
and thereafter test compounds were given to the test
group consisting of five rats by oral gavage at a dose
of 100 mg/kg body weight. After half an hour post-test
sample treatment, a glucose-load of 2 g/kg body weight
was given to each rat. The blood was collected at 30, 60,
90, and 120 min. post glucose-load. The % fall in blood
glucose level was calculated according to the AUC
method.
4.1.3.4. N-(4-Methoxyphenyl)-N-butyl-[3-(2-naphthyl-
oxy)propyl]amine (18). Yield: 0.58 g (98%); mp: 123 °C;
IR (KBr, cmÀ1): m = 1481 (Ar), 1526 (Ar), 1623 (Ar),
2881 (CH), 2942 (CH) cmÀ1 1H NMR (400 MHz,
;
CDCl3): d = 0.95 (t, 3H, NCH2CH2CH2CH3), 1.51–
1.56 (m, 2H, NCH2CH2CH3), 1.92–1.96 (m, 2H, O–
CH2CH2CH2N), 3.30–3.36 (m, 4H, O–CH2CH2CH2N
and NCH2CH2CH3), 3.38–3.42 (m, 2H, NCH2CH3),
3.75 (s, 3H, OCH3), 4.24 (t, 2H, OCH2), 6.51–7.70 (m,
12H, Ar–H); 13C NMR (100 MHz, CDCl3): d = 13.7,
20.5, 29.8, 31.8, 52.7, 56.6, 105.5, 118.7, 123.6, 126.8,
128.7, 128.9, 129.7, 134.8, 137.9, 157.6 ppm; Mass
4.2.1.2. Sucrose-loaded model (SLM). Overnight
fasted male Sprague–Dawley rats were used for the su-
crose-loaded experiment. Blood was collected initially
and thereafter test compounds were given to the test
group consisting of five rats by oral gavage at a dose

D. Chaturvedi et al. / Bioorg. Med. Chem. 16 (2008) 2489–2498
2497
of 100 mg/kg body weight. After half an hour post-test
sample treatment, a sucrose-load of 100 g/kg body
weight was given to each rat. The blood was collected
at 30, 60, 90, and 120 min post sucrose-load. The % fall
in blood glucose level was calculated according to the
AUC method.
dyslipidemic, and dyslipidemic plus drug treated groups
of 8 animals each. Dyslipidemia was produced by feed-
ing with fructose-rich high fat diet (HFD). Dyslipidemic
hamsters had free access to HFD and were ad. Lib for
10 days (day 1 to day 100). Compounds (300 lmol/kg)/
Fenofibrate (1000 lmol/kg) macerated in vehicle con-
taining 0.2% CMC + 0.4% Tween-80 in distilled water
were fed orally from day 4 to day 10 simultaneously
with HFD feeding to hamster. Control animals received
same amount of vehicle. At the end of the experiment on
10th day, blood was withdrawn and plasma was used for
assay of triglyceride (Tg), cholesterol (chol), High den-
sity lipo-protien (HDL), glucose, glycerol, and free fatty
acids (FFA) by standard spectrophotometric methods
on auto analyzer. The data are reported in Table 2.
4.2.1.3. Streptozotocin model (STZ). A solution of
streptozotocin (60 mg/kg) in 100 mM citrate buffer, pH
4.5, was prepared and calculated amount of the fresh
solution was dosed to overnight fasted rats (60 mg/kg)
intra-peritoneally. The blood sugar level was measured
after 48 h by glucometer. Animals showing 200–
400 mg/dl were selected for anti-diabetic screening. The
diabetic animals were divided into groups of six animals
each. Rats of experimental group were administered a
suspension of desired sample (prepared in 1% gum aca-
cia) orally (100 mg/kg body weight). Controlled group
animals were also fed with 1% gum acacia. The blood
glucose levels were measured at 1-, 2-, 3-, 4-, 5-, 6-, 7-,
and 24-h intervals. The percentage fall in the blood glu-
cose in 1–24 h by test sample was calculated according
to the area under curve (AUC) method. The average fall
in AUC in experimental group compared to control
group provided % anti-hyperglycemic activity.
5. Conclusion
x-(2-Naphthyloxy) amino alkanes and its substituted
derivatives were conveniently prepared in two steps
starting from b-naphthol, providing a novel class of
compounds showing significant anti-diabetic activity
with the added advantage of their effect in lipid lower-
ing. Most of the compounds showing anti-diabetic activ-
ity have shown promising PPAR-a/c/d agonistic
activity. Compound 13 has been picked-up for detailed
evaluation.
4.2.1.4. Sucrose challenged streptozotocin-induced
(STZ-S) model. A calculated amount of the fresh solu-
tion of STZ dissolved in 100 mM citrate buffer (pH
4.5) was injected to overnight fasted rats (60 mg/kg) in-
tra-peritoneally. Blood was checked for glucose content
48 h later by glucometer and animals showing blood glu-
cose profile between 150 and 250 mg/dl were selected
and were divided into different groups. Half an hour
post-test sample treatment, a sucrose-load of 2.5 g/kg
body weight was given to each rat. Blood glucose levels
were again tested at 30, 60, 90, 120, 180, 240, 300 min,
and 24 h post-test sample/drug administration. Food
but not water was withdrawn from the cages during
the experiment.
Acknowledgments
Authors are grateful to Dr. Nitya Anand for fruitful
suggestions and SIAF Division of CDRI for providing
spectroscopic and analytical data.
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