Antianexiety activity of pyridine derivatives synthesized from 2-chloro-6-hydrazino-isonicotinic acid hydrazide

Article abstract of DOI:10.1007/s00706-008-0949-6

A series of oxadiazole pyridine derivatives were synthesized by using 2-chloro-6-hydrazinoisonicotinic acid hydrazide as starting material. Treatment of the hydrazide with carbon disulfide to afford the oxadiazole derivative, which was treated with 5-methyl-2-furancarbaldehyde, formic acid, acetic acid/acetic anhydride, or phthalic anhydride to yield the corresponding pyridinodiazoles and on imide. Condensation of the hydrazide with p-fluorobenzaldehyde in ethanol or acetic acid in the presence of sodium acetate afforded hydrazone and oxadiazole derivatives, which were acetylated and cyclized with acetic anhydride to N-acetyloxadiazole derivatives. The hydrazone was treated with acetic acid in the presence of sodium acetate, or bromine water/sodium acetate to give on oxadiazole, while it was cyclized with chloroacetyl chloride in the presence of TEA to oxoazetidinaminoisonicotinamide. Finally, condensation of the hydrazide with acid anhydrides in refluxing glacial acetic acid afforded the corresponding bisimide derivatives. The pharmacological screening showed that many of these obtained compounds have good antianexiety activity comparable to diazepam as positive control.

Full text of DOI:10.1007/s00706-008-0949-6

Monatsh Chem 139, 1491–1498 (2008)
DOI 10.1007/s00706-008-0949-6
Printed in The Netherlands
Antianexiety activity of pyridine derivatives synthesized from 2-chloro-6-
hydrazino-isonicotinic acid hydrazide
Abd El-Galil E. Amr1, Salwa F. Mohamed1, Naglaa A. Abdel-Hafez1, Mohamed M. Abdalla2
1
National Research Center, Applied Organic Chemistry Department, Dokki, Cairo, Egypt
2
Research Unit, Hi-Care Pharmaceutical Co., Cairo, Egypt
Received 8 April 2008; Accepted 15 April 2008; Published online 6 August 2008
# Springer-Verlag 2008
Abstract A series of oxadiazole pyridine derivatives
were synthesized by using 2-chloro-6-hydrazinoisoni-
cotinic acid hydrazide as starting material. Treatment
of the hydrazide with carbon disulfide to afford the
oxadiazole derivative, which was treated with 5-meth-
yl-2-furancarbaldehyde, formic acid, acetic acid=
acetic anhydride, or phthalic anhydride to yield the
corresponding pyridinodiazoles and on imide. Con-
densation of the hydrazide with p-fluorobenzaldehyde
in ethanol or acetic acid in the presence of sodium
acetate afforded hydrazone and oxadiazole derivatives,
which were acetylated and cyclized with acetic anhy-
dride to N-acetyloxadiazole derivatives. The hydra-
zone was treated with acetic acid in the presence of
sodium acetate, or bromine water=sodium acetate to
give on oxadiazole, while it was cyclized with chlor-
oacetyl chloride in the presence of TEA to oxo-
azetidinaminoisonicotinamide. Finally, condensation
of the hydrazide with acid anhydrides in refluxing gla-
cial acetic acid afforded the corresponding bisimide
derivatives. The pharmacological screening showed
that many of these obtained compounds have good
antianexiety activity comparable to diazepam+ as pos-
itive control.
Introduction
In the previous work, acid hydrazides have been
shown to be very important for the hetero-organic
synthesis as key starting materials to form vari-
ous classes of biologically and pharmacologically
active candidates [1–7]. We have found that cer-
tain substituted isonicotinic acid hydrazide deriva-
tives show antimicrobial activity [8, 9] and also,
some of the reported pyridine derivatives can be
used as antimicrobial and anti-inflammatory [10–
13] and antitumor [14–16] agents. Recently, some
new pyridine derivatives have been synthesized
Keywords 2-Chloro-6-hydrazinoisonicotinic acid hydrazide;
Substituted pyridine; Oxadiazole; Oxoazetidine; Antianexiety
activity.
Correspondence: Abd El-Galil E. Amr, National Research
Center, Applied Organic Chemistry Department, Dokki,
Cairo, Egypt. E-mail: aamr1963@yahoo.com
Scheme 1

1492
A. E. E. Amr et al.
and tested as analgesic, anticonvulsant, and anti-
parkinsonian activities [17]. In view of these ob-
servations and in continuation of our previous
work in pyridine and pyrimidine chemistry, we
synthesized some new heterocyclic compounds con-
taining the pyridine moiety and tested their antia-
nexiety activity.
Results and discussion
Chemistry
2-Chloro-6-hydrazino-isonicotinic acid hydrazide (4)
was synthesized according to the reported procedure
[8, 9]. Chlorination of 2,6-dihydroxyisonicotinic
acid (1) with phosphorus oxychloride afforded the
Scheme 2

Antianexiety activity of pyridine derivatives
1493
corresponding 2,6-dichloroisonicotinic acid (2),
which was esterified with absolute ethanol in the
presence of concentrated sulfuric acid to afford ethyl
2,6-dichloro-isonicotinate (3). The ester 3 was trea-
ted with hydrazine hydrate in refluxing ethanol to
afford 2-chloro-6-hydrazino isonicotinic acid hydra-
zide (4) in pure form and good yield (Scheme 1).
Treatment of 4 with carbon disulfide in the
presence of ethanolic potassium hydroxide afforded
the corresponding oxadiazole derivative 5, which
was reacted with 5-methyl-2-furancarbaldehyde or
formic acid to afford compounds 6 and 7, via the
intermediate A [18]. Compound 5 was treated
with acetic acid=acetic anhydride mixture to afford
compound 8, followed by rearrangement [19] to
compound 9 by using piperidine or sodium ethox-
ide in ethanol as a catalyst. Also, compound 5 was
reacted with phthalic anhydride in refluxing gla-
cial acetic acid to give the imide derivative 10
(Scheme 2).
Scheme 3

1494
A. E. E. Amr et al.
Scheme 4
Condensation of compound 4 with p-fluoro-
Table 1 Antianexiety activity of new synthesized
compounds
benzaldehyde in ethanol without catalyst or acetic
acid in the presence of sodium acetate afforded
compounds 11 and 12, which were cyclized and
acetylated with acetic anhydride to afford com-
pound 13. Compound 11 was treated with acetic
acid in the presence of sodium acetate and bromine
water to give 14, while 11 was cyclized with chlor-
oacetyl chloride in the presence of TEA in reflux-
ing dioxane according to the reported method [20,
21] to yield oxoazetidinaminoisonicotinamide 15
(Scheme 3).
Finally, condensation of 4 with acid anhydrides,
namely, 3,4,5,6-tetrachlorophthalic anhydride, 2,3-
pyridinedicarboxylic anhydride, or 1,8-naphthalene
dicarboxylic anhydride in refluxing glacial acetic ac-
id afforded the corresponding bisimide derivatives
16–18 (Scheme 4).
Compound
no.
Relative potency
to diazepam
LD50=mg kgꢀ1
4
5
6
7
8
9
10
11
12
13
14
16.20
18.30
17.40
16.18
35.16
25.11
12.16
13.18
26.11
22.13
21.16
18.25
27.16
16.20
1.00
183.54 ꢁ 0.01
213.67 ꢁ 0.02
172.78 ꢁ 0.01
213.56 ꢁ 0.02
224.45 ꢁ 0.02
235.76 ꢁ 0.02
226.87 ꢁ 0.02
217.78 ꢁ 0.03
208.65 ꢁ 0.02
219.65 ꢁ 0.01
256.54 ꢁ 0.03
234.76 ꢁ 0.02
214.76 ꢁ 0.01
183.44 ꢁ 0.01
108.23 ꢁ 0.01
15
16
17
Diazepam

Antianexiety activity of pyridine derivatives
1495
Varian EM-360–270 MHz spectrometer (DMSO-d6) and
the chemical shifts are given in ꢀ (ppm) downfield from
TMS as an internal standard. Splitting patterns were de-
signated as follows: s: singlet; d: doublet; t: triplet; m: mul-
tiplet. The mass spectra (MS) were measured using a VG
2AM-3F mass spectrometer. Follow up of the reactions and
checking the purity of the compounds were made by TLC
Pharmacological screening – antianexiety activity
Crawley et al. [22, 23] described a simple behavior
model in mice to detect compounds with anxiolytic
effects. Mice tend to explore a novel environment
but to retreat from the aversive properties of a bright-
ly-lit open field in a two-chambered system, where
mice can freely move between a brightly-lit open
field and a dark corner, animals show more crossing
between the two chambers and more locomotor ac-
tivity after treatment with anxiolytics.
on silica gel-precoated aluminum sheets (Type 60 F254
,
Merck) and the spots were detected by exposure to a UV
lamp at l ¼ 254 nm for few seconds. 2-Chloro-6-hydrazi-
noisonicotinic acid hydrazide (4) was synthesized accord-
ing to Refs. [8, 9].
5-(2-Chloro-6-methylpyridin-4-yl)[1,3,4]oxadiazole-2-thiol
(5, C7H6ClN5OS)
Evaluation
To a solution of 2.01 g 4 (10 mmol) in 25cm3 ethanolic potas-
sium hydroxide (5%), 1.5 cm3 carbon disulphide (20 mmol)
was added. The reaction mixture was stirred for 1 h at room
temperature and another 6 h under reflux, after cooling, it was
poured onto ice-water and acidified with HCl (pH ꢃ 3). The
formed solid was filtered off, washed with water, dried, and
crystallized to give 5 (95%). Mp 286ꢄC (DMF); IR (film):
ꢁꢀ¼ 3410–3330 (NH, NH2), 1600 (C¼N), 1260 (C¼S)
Dose-response curves are obtained and the num-
ber of crossings through the partition between
the light and the dark chamber are compared with
total activity counts during the 10 min. All the
tested compounds showed potent antianexiety ac-
tivities at least 12 times more active than diaze-
pam. Compound 8 is the most potent showing 35
times diazepam activities, the next potent com-
pounds 16, 12, 9, 13, and 14 where there relative
potency to diazepam are 27, 26, 25, 22, and 21.
The relative activities of other compounds to that
of diazepam lies between 12 (compound 10) and
18 (compound 15). The order of potency in des-
cending order is 15, 6, (17, 4), 7, 11, 10.
1
cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 6.80 (s, NH2 exchangeable
with D2O), 8.10, 8.18 (2s, pyr-H), 9.60, 14.90 (2s, 2NH ex-
changeable with D2O) ppm; MS (EI, 70eV): m=z ¼ 243 [Mþ,
20] and at 64 [100, base peak].
5-[5-Chloro-3-(5-methylfuran-2-yl)[1,2,4]thiazolo[4,3-a]pyri-
din-7-yl][1,3,4]oxadiazole-2-thiol (6, C13H8ClN5O2S)
To a solution of 2.4g 5 (10 mmol) in 30 cm3 absolute ethanol
containing 3 drops of glacial acetic acid, 1.1 g of 5-methyl-2-
furancarbaldehyde (10 mmol) was added. The reaction mix-
ture was heated under reflux, after cooling, the solid was
filtered off, dried and crystallized to afford 6 (60%). Mp
>300ꢄC (DMF); IR (film): ꢁꢀ¼ 3380 (NH), 1598 (C¼N), 1260
Structure activity relationship (SAR)
ꢂ 3-Methyl[1,2,4]triazolo[4,3-a]pyridine is more po-
tent than 2-methyl[1,2,4]triazolo[1,5-a]pyridine
ꢂ Chloropyridine nucleus is essential for activity
ꢂ Oxadiazole is not essential for activity; it may
decrease it as in compounds 12, 13, and 14.
ꢂ Triazolo moiety also not essential for activity
ꢂ Chloro derivatives increases the anti-anexity ac-
tivity sharply as clear in compounds 10 and 17.
1
(C¼S) cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 2.10 (s, CH3), 5.80,
6.40 (2d, 2 furon-H), 8.32, 8.38 (2s, pyr-H), 9.60 (s, NH
exchangeable with D2O) ppm; MS (EI, 70eV): m=z ¼ 333
[Mþ, 10] and at 76 [100, base peak].
5-(5-Chloro[1,2,4]triazolo[1,5-a]pyridin-7-yl)[1,3,4]-
oxadiazole-2-thiol (7, C8H4ClN5OS)
A solution of 2.4 g 5 (10 mmol) in 20cm3 formic acid was
heated under reflux for 8 h. The reaction mixture was cooled
then poured onto ice-water, the obtained solid was filtered off,
washed with water, dried, and crystallized to afford 7 (67%).
Mp >300ꢄC (DMF); IR (film): ꢁꢀ¼ 3320 (NH), 1605 (C¼N),
1262 (C¼S) cmꢀ1; 1H NMR (DMSO-d6): ꢀ ¼ 7.78–8.32 (m, 2
pyr-H, triazole-H), 9.50 (s, NH exchangeable with D2O) ppm;
MS (EI, 70eV): m=z ¼ 253 [Mþ, 15] and at 57 [100, base
peak].
Experimental
Chemistry
Melting points were determined on open glass capillaries
using a Electrothermal IA 9000 digital melting point appa-
ratus. Elemental analyses were performed on an Elementar,
Vario EL, Microanalytical Unit, National Research Center,
Cairo, Egypt and results were found within ꢁ0.4% of
the theoretical values. Infrared (IR) spectra were recorded
on a Pye Unicam SP-1000 spectrophotometer using the
5-(5-Chloro-3-methyl[1,2,4]triazolo[4,3-a]pyridin-7-yl)-
[1,3,4]oxadiazole-2-thiol (8, C9H6ClN5OS)
A solution of 2.4 g 5 (10 mmol) in 20 cm3 AcOH=Ac2O as a
mixture (1=1) was refluxed for 10 h. The reaction mixture
was cooled and the obtained red solid was filtered off,
1
KBr disc technique. H NMR spectra were recorded on a

1496
A. E. E. Amr et al.
washed with water, dried, and crystallized to give 8 (62%).
Mp 252ꢄC (DMF); IR (film): ꢁꢀ¼ 3340 (NH), 1609 (C¼N),
1256 (C¼S) cmꢀ1; 1H NMR (DMSO-d6): ꢀ ¼ 1.95 (s, CH3),
7.78, 8.12 (2s, 2 pyr-H), 9.60 (s, NH exchangeable with
D2O) ppm; MS (EI, 70 eV): m=z ¼ 266 [Mþ, 2] and at
251 [100, base peak].
(15 mmol) in 30 cm3 glacial acetic acid was refluxed for
10 h. The reaction mixture was concentrated under reduced
pressure, poured onto water, the formed solid was filtered
off, washed with water, dried and crystallized to yield 12
(80%). Mp 231ꢄC (EtOH); IR (film): ꢁꢀ¼ 3409 (NH), 1605
1
(C¼N) cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 5.65 (s, CH-oxadia-
zole-H), 7.20–8.10 (m, Ar–H), 8.24–8.32 (m, 2 pyr-H, hy-
drazone-H), 11.55, 12.15 (2s, 2NH exchangeable with D2O)
ppm; MS (EI, 70eV): m=z ¼ 413 [Mþ, 2] and at 171 [100,
base peak].
Method B. A mixture of 4 g 11 (10 mmol) and 1.2 g an-
hydrous sodium acetate (15 mmol) in 20 cm3 glacial acetic
acid was refluxed for 3 h. The reaction mixture was con-
centrated under reduced pressure, poured into water. The
obtained solid was filtered off, dried, and crystallized to
give 12 (85%).
5-(5-Chloro-2-methyl[1,2,4]triazolo[1,5-a]pyridin-7-yl)-
[1,3,4]oxadiazole-2-thiol (9, C9H6ClN5OS)
Method A. A solution of 2.6 g 8 (10 mmol) in 20 cm3 absolute
ethanol in the presence of few drops of pipridine was refluxed
for 6 h. The reaction mixture was evaporated under reduced
pressure, the residue was triturated with ether, the formed solid
was filtered off, dried and crystallized to give 9 (68%). Mp
268ꢄC (EtOH=ether); IR (film): ꢁꢀ¼ 3409 (NH), 1610 (C¼N),
1
1257 (C¼S) cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 1.90 (s, CH3),
7.90, 8.30 (2s, 2 pyr-H), 9.75 (s, NH exchangeable with D2O)
ppm; MS (EI, 70 eV): m=z ¼ 266 [Mþ, 2] and at 171 [100,
base peak].
1-[5-{2-Chloro-6-[2-(4-fluorophenyl)vinylamino]pyridin-4-
yl}-2-(4-fluorophenyl)-[1,3,4]oxa-diazol-3-yl]ethanone
(13, C22H16ClF2N5O2)
Method B. A mixture of 2.6 g 8 (10 mmol) and sodium
ethoxide (0.5g sodium metal in 30 cm3 absolute ethanol)
was heated under reflux for 4 h. After cooling, the reaction
mixture was concentrated under reduced pressure, poured onto
water, acidified with 1 N HCl. The product was extracted with
ethyl acetate, dried over sodium sulphate anhydrous, evapo-
rated under reduced pressure, the residue was solidified with
ether, filtered off, dried, and crystallized to give 9 (72%).
Method A. A solution of 2.10 g 11 (5mmol) in 30cm3 acetic
anhydride was heated under reflux for 6 h. The reaction mix-
ture was concentrated under reduced pressure and cooled, the
separated solid was filtered off, washed with petroleum ether,
dried, and crystallized to yield 13 (76%). Mp 195ꢄC (diox-
ane); IR (film): ꢁꢀ¼ 3320 (NH), 1704 (C¼O), 1605 (C¼N)
1
cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 2.10 (s, CH3), 5.62 (s, CH-
oxadiazole-H), 7.75–8.00 (m, Ar–H), 8.18–8.34 (m, 2 pyr-H,
hydrazone-H), 10.95 (s, NH exchangeable with D2O) ppm;
MS (EI, 70 eV): m=z ¼ 455 [Mþ, 65] and at 122 [100, base
peak].
2-[6-Chloro-4-(5-mercapto[1,3,4]oxadiazol-2-yl)pyridin-2-
ylamino)isoindole-1,3-dione (10, C15H8ClN5O3S)
A mixture of 2.4 g 5 (10 mmol) and 1.48 g of phthalic anhy-
dride (10 mmol) in 50cm3 glacial acetic acid was heated under
reflux for 6 h. The reaction mixture was concentrated under
reduced pressure, the obtained solid was filtered off and crys-
tallized to yield 10 (72%). Mp >300ꢄC (dioxane); IR (film):
Method B. A solution of 4 g 12 (10 mmol) in 15cm3 acetic
anhydride was refluxed for 2 h. The separated solid was fil-
tered off, dried, and crystallized to give 13 (70%).
1
ꢁꢀ¼ 3331 (NH), 1600 (C¼N), 1258 (C¼S) cmꢀ1; H NMR
N-{6-Chloro-4-[5-(4-fluorophenyl)[1,3,4]oxadiazol-2-yl]-
pyridin-2-yl}-N0-(4-fluorobenzylidine)-hydrazine
(DMSO-d6): ꢀ ¼ 7.95–8.42 (m, 2 pyr-H, 4H–Ar–H), 8.65, 9.62
(2s, 2NH exchangeable with D2O) ppm; MS (EI, 70 eV):
m=z ¼ 373 [Mþ, 10] and at 313 [100, base peak].
(14, C20H12ClF2N5O)
To a suspension solution of 4.13g 11 (10 mmol), 1.2 g anhy-
drous sodium acetate (15 mmol) in 20 cm3 glacial acetic acid,
1.6 g bromine (10 mmol) in 10cm3 glacial acetic acid was
added. The reaction mixture was refluxed for 1 h, after cool-
ing, it was poured onto water, the formed solid was filtered off,
washed with water, dried, and crystallized to afford 14 (85%).
Mp 266ꢄC (EtOH); IR (film): ꢁꢀ¼ 3328 (NH), 1605 (C¼N)
2-Chloro-6-[N0-(4-fluorobenzylidene)hydrazino]isonicotinic
acid (4-fluorobenylidine)hydrazide (11, C20H14ClF2N5O)
A mixture of 2.10 g 4 (10 mmol) and 2.4 g of p-flourobenzal-
dehyde (20 mmol) in 50 cm3 absolute ethanol was refluxed
for 3 h. After, cooling, the separated solid was filtered off,
dried, and crystallized to give 11 (98%). Mp 279ꢄC (dioxane);
IR (film): ꢁꢀ¼ 3260–3230 (NH), 1665 (C¼O), 1602 (C¼N)
cmꢀ1; 1H NMR (DMSO-d6): ꢀ ¼ 7.65–8.05 (m, Ar–H), 8.25–
8.42 (m, 2 pyr-H, 2H hydrazone-H), 11.60, 12.20 (2s, 2 NH
exchangeable with D2O) ppm; MS (EI, 70eV): m=z ¼ 413
[Mþ, 40] and at 171 [100, base peak].
1
cmꢀ1; H NMR (DMSO-d6): ꢀ ¼ 7.82–8.5 (m, Ar–H), 8.22–
8.30 (m, 2 pyr-H, hydrazone-H), 11.24 (s, NH exchangeable
with D2O) ppm; MS (EI, 70eV): m=z ¼ 411 [Mþ, 100, base
peak].
2-Chloro-N-[3-chloro-2-(4-fluorophenyl)-4-oxoazetidin-1-yl]-
6-[3-chloro-2-(4-fluorophenyl)-4-oxoazetidin-1-ylamino]-
isonicotinamide (15, C24H16Cl3F2N5O3)
To a solution of 4.1 g 11 (10 mmol) in 20 cm3 dioxane
containing few drops of TEA as a catalyst, 2.24 cm3 chlor-
oacetyl chloride (20 mmol) was added drop-wise with
stirring at room temperature. The solution was heated
2-Chloro-N-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-6-
(1,3-dioxo-1H,3H-benzo[de]iso-quinolin-2-ylamino)iso-
nicotinamide (12, C20H14ClF2N5O)
Method A. A mixture of 2.1g 4 (10 mmol), 2.4 g p-fluoro-
benzaldehyde (20 mmol) and 1.2 g anhydrous sodium acetate

Antianexiety activity of pyridine derivatives
1497
under reflux for 3 h, after cooling, the formed solid was
filtered off and crystallized to yield 15 (96%). Mp 260ꢄC
(DMF); IR (film): ꢁꢀ¼ 3280–3230 (NH), 1665, 1660
activity. As electronic system using four sets of photocells
across the partition automatically counts movements
through the partition and clocks the time spent in the light
(C¼O), 1605 (C¼N) cmꢀ1
;
1H NMR (DMSO-d6): ꢀ ¼
and dark compartments. Naıve male albino mice with a
¨
6.65, 6.75 (2s, 4CH), 7.72–7.96 (m, Ar–H), 8.24, 8.32
(2s, pyr-H), 9.40, 10.60 (2s, 2NH exchangeable with
D2O) ppm; MS (EI, 70 eV): m=z ¼ 579 [Mþ, 10] and at
479 [100, base peak].
body weight between 18 and 25 g are placed into the cage,
the animals are treated 30 min before the experiment with
the test drugs or the vehicle intraperitoneally, and are then
observed for 10 min [24, 25].
Determination of LD50
Synthesis of bisimide derivatives 16–18
Determination of median lethal dose (Lorke 5) Phase 1: Three-
groups of three mice=group. One dose was given to each
group intraperitoneally. The treated mice were monitored for
24h for mortality and general behavior.
Phase 2: After 24 h 3–4 groups of one mouse were given
doses based on the findings of phase 1, intraperitoneally. The
mice were again monitored for 24h. The geographic mean
of the least dose that killed mice and the highest dose that
did not kill mice was taken as the median lethal dose [26–28]
(Table 2).
A mixture of 2.10 g 4 (10 mmol) and acid anhydride, namely,
1,2,4,5-tetrachlorophthalic anhydride, 2,3-pyridinedicarbox-
ylic anhydride, or 1,8-naphthalenedicarboxylic anhydride
(20 mmol) in 50 cm3 glacial acetic acid was heated un-
der reflux for 6 h. The reaction mixture was concentrated
under reduced pressure, the residue was solidified with
ether and filtered off to yield 16 (65%), 17 (72%), and 18
(68%).
2-Chloro-N-[4,5,6,7-tetrachloro-1,3-dioxo-1,3-dihydro-
isoindol-2-yl)-6-(4,5,6,7-tetrachloro-1,3-dioxo-1,3-dihydro-
isoindol-2-ylamino)isonicotinamide (16, C22H4Cl9N5O5)
Mp 256–258ꢄC (AcOH=H2O); IR (film): ꢁꢀ¼ 3331 (NH),
References
1665 (C¼O), 1600 (C¼N) cmꢀ1
;
1H NMR (DMSO-d6):
ꢀ ¼ 8.15, 8.24 (2s, pyr-H), 9.62, 11.50 (2s, 2NH exchangeable
with D2O) ppm; MS (EI, 70 eV): m=z ¼ 737 [Mþ, 12] and at
438 [100, base peak].
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3. Amr AE, Mohamed AM, Ibrahim AA (2003) Z Natur-
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5. Amr AE (2005) Z Naturforsch 60b:990
6. Amr AE, Abo Ghalia MH, Abdalah MM (2006) Z
Naturforsch 61b:1335
2-Chloro-N-[5,7-dioxo-5,7-dihydropyrrolo[3,4-b]pyridin-6-
yl)-6-(5,7-dioxo-5,7-dihydropyrrolo-[3,4-b]pyridin-6-
ylamino)isonicotinamide (17, C20H10ClN7O5)
Mp 234–236ꢄC (AcOH=H2O); IR (film): ꢁꢀ¼ 3338, 3295
1
(NH), 1668 (C¼O), 1605 (C¼N) cmꢀ1; H NMR (DMSO-
d6): ꢀ ¼ 8.15–8.85 (m, pyr-H), 9.65, 13.35 (2s, 2NH ex-
changeable with D2O) ppm; MS (EI, 70 eV): m=z ¼ 463
[Mþ, 100, base peak].
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2-Chloro-N-[1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-6-
(1,3-dioxo-1H,3H-benzo[de]iso-quinolin-2-ylamino)-
isonicotinamide (18, C30H16ClN5O5)
Mp>300ꢄC (AcOH=H2O); IR (film): ꢁꢀ¼ 3342, 3320 (NH),
1665 (C¼O), 1610 (C¼N) cmꢀ1
;
1H NMR (DMSO-d6):
ꢀ ¼ 7.95, 8.10 (2s, pyr-H), 8.24–8.75 (m, Ar–H), 9.55, 13.20
(2s, 2NH exchangeable with D2O) ppm; MS (EI, 70eV):
m=z ¼ 561 [Mþ, 8] and at 350 [100, base peak].
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