New Aryl-1,3-thiazole-4-carbohydrazides, Their 1,3,4-Oxadiazole-2-thione, 1,2,4-Triazole, Isatin-3-ylidene and Carboxamide Derivatives. Synthesis and Anti-HIV Activity

Article abstract of DOI:10.5560/ZNB.2012-0095

A series of isatin-3-ylidene (6a-i) and arylthiazolyl-1,3,4-oxadiazole-2- thione derivatives 7a-i derived from arylthiazolyl carbohydrazide analogs 4a-i were synthesized. Analogously, coupling of 4f with various amino acid methyl esters in the presence of HOBt/DCC reagents afforded the carboxamide derivatives 9a-d. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. All compounds are inactive, except compounds 9b and 9c which showed inhibition of HIV-1 with EC₅₀ = 2:34 μgmL^-1, and 1.12 μgmL^-1 with therapeutic indexes (SI) of 9 and <1, respectively.

Full text of DOI:10.5560/ZNB.2012-0095

New Aryl-1,3-thiazole-4-carbohydrazides, Their 1,3,4-Oxadiazole-2-
thione, 1,2,4-Triazole, Isatin-3-ylidene and Carboxamide Derivatives.
Synthesis and Anti-HIV Activity
Mehwash Ziaa, Tashfeen Akhtarb, Shahid Hameeda, and Najim A. Al-Masoudic
a
Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan
Department of Chemistry, Mirpur University of Science and Technology (MUST), 10250
b
Mirpur, AJK, Pakistan
Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq
c
Reprint requests to Prof. Dr. S. Hameed. E-mail: shameed@qau.edu.pk or Prof. Dr. N. A.
Al-Masoudi. E-mail: najim.al-masoudi@gmx.de
Z. Naturforsch. 2012, 67b, 747 – 758 / DOI: 10.5560/ZNB.2012-0095
Received April 2, 2012
A series of isatin-3-ylidene (6a–i) and arylthiazolyl-1,3,4-oxadiazole-2-thione derivatives 7a–i de-
rived from arylthiazolyl carbohydrazide analogs 4a–i were synthesized. Analogously, coupling of 4f
with various amino acid methyl esters in the presence of HOBt/DCC reagents afforded the carbox-
amide derivatives 9a–d. The newly synthesized compounds were assayed against HIV-1 and HIV-2
in MT-4 cells. All compounds are inactive, except compounds 9b and 9c which showed inhibition
of HIV-1 with EC50 = 2.34 µg mL−1, and 1.12 µg mL−1 with therapeutic indexes (SI) of 9 and <1,
respectively.
Key words: anti-HIV Activity, Amino Acids, Imine Derivatives, Oxadiazoles, Thiazoles
Introduction
ported to show anti-HIV activity. In addition, the 1,3,4-
oxadiazole ring is of significant interest due to its
Acquired immune deficiency syndrome (AIDS) is chemotherapeutic history [13 – 15].
one of the major causes of death in many coun- A series of thiazolylthioureas has exhibited activity
tries of the world. This viral disease is caused by against two NNRTI resistant HIV-1 isolates [2]. Thi-
the retrovirus HIV-1 (human immunodeficiency virus azolidene benzenesulfonamides have inhibited HIV-
type-1), a retrovirus of the lentivirus family. Inte- 1 replication and exhibited potent activity against
grase, reverse transcriptase and protease (the three vi- the WT and Y181C RT and to a lesser extent
ral enzymes) play a prominent role in the virus repli- against the K103N RT [16]. Moreover, thiazoles
cation cycle. The formation of proviral DNA from serve as important pharmacodynamic nuclei, and their
viral RNA is catalyzed by viral reverse transcrip- incorporation in different heterocyclic scaffolds re-
tase (RT) and is responsible for viral replication [1], sults in varied biological activities such as antitu-
hence it is the main target in contemporary drug dis- mor [17], anticonvulsant [18], antimicrobial [19 – 22],
covery against HIV-1 [2]. Numerous classes of non- anti-inflammatory [23], antiprotozoal [24], and antity-
nucleoside reverse transcriptase inhibitors (NNRTIs) rosinase [25]. Furthermore, some amino acid deriva-
such as nevirapine [3], delaviridine [4] and efavirenz tives such as the lysyl amide prodrug of 2-(4-amino-3-
(EFV) [5], carrying a heterocyclic backbone, have methylphenyl)-5-fluorobenzothiazole [26], amino acid
been approved for the treatment of HIV infection [6], derivatives of paclitaxol [27], pyroglutamic acid [28],
due to their unique antiviral potency, high speci- cysteine-modifying agents [29], and isoquinoline car-
ficity and low toxicity [7, 8]. New types of NNR- boxylic acid derivatives [30] were reported as potential
TIs are continuously being developed, for example HIV protease inhibitors [31]. Recently, Al-Masoudi
some 2,5-disubstituted 1,3,4-oxadiazoles [9 – 11] and et al. [32 – 36] have reported the synthesis of various
certain adamantane derivatives [12] have been re- naphthalene, coumarin and sebacoyl derivatives bear-
c
ꢀ 2012 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

748
M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
ing amino acid moieties as potential anti-HIV candi- The carbohydrazides 4a–i were used as common
dates. precursors for the synthesis of various potential
In the present study, we selected 2-aryl-1,3-thiazole- analogs. Thus, treatment of 4a–i with isatin (5) af-
4-carbohydazide intermediates, of which some analogs forded the isatin-3-ylidene derivatives in 68% – 74%
have been reported previously [37], for the synthe- yield. Analogously, reaction of 4a–i with CS2 in
sis of 1,3,4-oxadiazole-2-thiones, their 1,2,4-triazole, refluxing MeOH led to the cyclization of the
isatin-3-ylidene and carboxamide derivatives and for carbohydrazide backbones, furnishing 5-(2-aryl-1,3-
the evaluation of their anti-HIV activiy.
Results and Discussion
Synthesis
thiazol-4-yl)-1,3,4-oxadiazole-2-thione analogs 6a–i
(65% – 75% yield). The reaction sequence is summa-
rized in Scheme 1.
The structures of 4a–i, 6a–i and 7a–i were assigned
on the basis of IR, 1H, 13C NMR and mass spec-
tra. The IR spectra of 7a–i showed strong absorp-
The synthesis of the target compounds was accom- tions in the range of 1241 – 1202 cm−1, attributed to
plished starting from arylthioamides 1a–i, by treat- the C=S group. In the H NMR spectra of 4a–i, the
1
ment with ethyl bromopyruvate to give ethyl 2-aryl- singlets in the region δ = 8.09 – 8.42 ppm were at-
1,3-thiazole-4-carboxylates 2a–i, which were used tributed to 5-H of the thiazole backbone. Proton 5-
directly without purification by treatment with hy- H of the isatin-3-ylidene (6a–i) and oxadiazole (7a–
drazine hydrate to furnish the corresponding car- i) derivatives appeared in the regions δ = 8.60–8.86
bohydrazide analogs 4a–i in 68% – 79% yield. and 8.68 – 8.86 ppm with chemical shift differences of
S
BrCH2COCO2Et (2)
C
S
N
EtOH, reflux
X
COOEt
X
NH2
3a−i
1a−i
S
S
N2H4⋅H2O
CS2, KOH
MeOH, reflux
NH NH2
MeOH, reflux
N
N
N
N
H
7a
−
i
X
4a
−
i
X
O
O
O
S
EtOH, reflux
O
N
H
5
O
N
N
NH
O
S
X
N
6a
−
i
H
1−6
X
X
1−6
f
p-CH3 o-Cl
m-CH3 p-OCH3
o-CH3 m-OCH3
a
b
c
d
e
g
h
i
p-Cl
o-OCH3
m-Cl
Scheme 1. Synthesis of 2-aryl-1,3-thiazole-4-carbohydrazide, imino-isatin, 1,3,4-oxadiazole, and 4-amino-1,3,4-triazole-5-
thione derivatives.
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
749
S
S
N
Cl
1. NaNO2/HCl/HOAc
2. R-CH(NH2)CO2Me
Cl
NHNH2
N3
N
O
O
4f
8
amino acids
9
a
R
S
2
5
H
glycine
Cl
b
c
d
e
CH2OH
CH2CH2SMe
Me
L-serine
8
NH
R
6
N
4
L-methionine
L-alanine
L-valine
CO2Me
O
9a−e
CH(Me)2
Scheme 2. Synthesis of alkyl 3-(4-chlorophenyl)thiazole-4-carboxamido-3-oxoalkanoate derivatives.
∼ 0.45 and ∼ 0.35 ppm, respectively, from those of thiazole protons. The low-field broad singlets (δ =
carbohydrazides 4a–i. The 13C NMR spectra of 4a– 9.95 – 9.76 ppm) were assigned to NH signals, and
i, 6a–i and 7a–i were assigned (cf. Experimental Sec- the singlets in the range δ = 9.20 – 9.09 ppm were
tion) based on the analysis made for 7f. The spec- assigned to 5-H of the thiazole backbone. The C-
trum showed a down-field signal at δ = 177.7 ppm, 8 methylene protons of 9a appeared as a doublet at
attributed to the C=S group, which is indicative of 7f δ = 4.19 ppm (J = 2.2 Hz), whereas 8-H atoms of
existing predominantly in the thione form, as is also 9b–e resonated as multiplets at δ = 4.36, 4.39, 4.29,
1
suggested by the IR and H NMR spectra. The reso- and 4.32 ppm, respectively. In the 13C NMR spectra of
nances at δ = 164.9 and 156.9 ppm were assigned to 9a–e, the carbon atoms of the carboxylate groups res-
C-4 and C-5 of the thiazole and oxadiazole residues, onated in the range δ = 173.2 – 170.2 ppm, and C-2
respectively. The signals at δ = 138.9 and 137.6 ppm and C-4 of the thiazole residues appeared in the ranges
were assigned to C-4 and C-1 of the thiazole and the δ = 168.3–167.1 and 150.1 – 148.7 ppm, respectively.
aromatic ring, respectively. The aromatic C(4)-Cl and The carbonyl groups adjacent to the thiazole precur-
C(2)-Cl carbon atoms gave signals at δ = 137.6 and sor, C(6)=O, resonated at δ = 162.7 – 160.9 ppm. The
131.4 ppm, respectively, and C-4, C-3, C-6, and C-2 resonances at δ = 38.2, 55.2, 52.2, 49.3 and 54.2 ppm
appeared at δ = 131.1, 130.6, 128.9, and 126.4 ppm, were attributed to the C-8 atoms. The CH2OH car-
respectively.
bon signal of 9b appeared at δ = 59.5 ppm, while the
Next, our target was the synhesis of new com- CH2S carbon atom of 9c resonated at δ = 30.1 ppm
pounds having a thiazole backbone adjacent to an and the CH2CH2S carbon atom at δ = 32.2 ppm. Com-
amino acid precursor via an amide linkage, aiming to pound 9d was selected for further HMBC NMR stud-
evaluate their anti-HIV activity. The hydrazide 4f was ies [38]. A gradient-selected HMBC spectrum allowed
selected as starting material for the reaction with ap- the identification of C(4) and C(2) of the thiazole ring
propriate acylated amino acids, via the azide-coupling at δ = 167.7 and 149.8 ppm, respectively, from the
method. Thus, treatment of 4f at −5 ◦C in HOAc 2JC,H and JC,H correlations to 5-H of the thiazole
3
and 1 N HCl with NaNO2, followed by the treat-
ment of in situ-generated azide derivative 8 with the
acylated amino acid derivatives (glycine, L-serine, L-
methionine, L-alanine and L-valine acetates) in ethyl
acetate containing Et3N at 0 ◦C gave, after neutral-
ization, the desired carboxamides 9a–d in 65% – 77%
yield (Scheme 2).
The structures of 9a–e were assigned from their
1
1H and 13C NMR, and mass spectra. The H NMR
spectra of 9a–e showed a similar pattern of 1,3- Fig. 1. JC,H correlations in the HMBC NMR spectrum of 9d.
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

750
M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
Entry
HIV-1 (IIIB)
EC50 (µg mL−1
HIV-2 (ROD)
EC50 (µg mL−1
CC50
(µg mL−1
SIe
(IIIB)
SIe
Table 1. In-vitro anti-HIV-1a and HIV-2b
activity and cytotoxicity of some new 1,3-
thiazole derivatives.
c
c
d
)
)
)
(ROD)
6a
> 84.85
> 14.33
> 14.82
> 99.43
> 119.33
> 79.08
> 111.0
> 15.88
> 92.10
> 54.25
> 52.20
> 54.58
> 51.28
> 55.83
> 57.03
> 53.50
> 52.80
> 60.50
> 23.10
> 2.34
> 84.85
> 14.33
> 14,82
> 99.43
> 119.33
> 79.08
> 111.0
> 15.88
> 92.10
> 54.25
> 52.20
> 54.58
> 51.28
> 55.83
> 57.03
> 53.50
> 52.80
> 60.50
> 23.10
> 21.06
> 1.12
84.85
14.33
14.82
99.43
119.33
79.08
111.0
15.88
92.10
54.25
52.20
54.58
51.28
55.83
57.03
53.50
52.80
60.50
23.10
21.06
1.12
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
9
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
< 1
6b
6c
6d
6e
6f
6g
6h
6i
7a
7b
7c
7d
7e
7f
7g
7h
7i
9a
9b
9c
9d
9e
> 1.12
< 1
< 1
< 1
> 80
> 37.03
> 29.82
0.050
> 37.03
> 29.82
> 4.00
37.03
29.82
> 4.00
> 25
Nevirapine
AZT
0.0022
0.00094
> 11363 > 26596
a
b
Anti-HIV-1 activity measured with strain IIIB; anti-HIV-2 activity measured with
c
strain ROD; compound concentration required to achieve 50% protection of MT-4
cells from the HIV-1 and 2-induced cytopathogenic effect; compound concentration
that reduces the viability of mock-infected MT-4 cells by 50%; SI: selectivity index
d
e
(CC50/EC50).
backbone at δ = 9.12 ppm. Similarly, the CH3 sig- 2.34 µg mL−1 (SI = 9) and 1.12 µg mL−1 (SI ≤ 1), re-
nal at δ = 19.6 ppm and C-6 of the carbonyl group spectively, for which the data can be discussed. How-
at δ = 162.7 ppm were identified from their 2JC,H and ever, none of our compounds approached the activity
3JC,H correlations to 8-H at δ = 4.29 ppm (Fig. 1). The level of the reference compounds.
mass fragmentation patterns were consistent with the
Compounds 9b and 9c are equipotent against HIV-
suggested structures; however, the FAB-MS spectra 1 and HIV-2 replication in vitro and, therefore, most
showed the protonated molecular ions of these com- probably they are no NNRTI’s (Non-Nucleoside Re-
pounds.
verse Transcriptase Inhibitors). The anti-HIV activity
and the selectivity of these compounds are, however,
too limited to perform extensive mode-of-action stud-
ies. The synthesis of new analogs of thiazolo-amino
In-vitro anti-HIV assay
Compounds 6a–i, 7a–i and 9a–e were evaluated for acid derivatives (carboxamide analogs 9b and 9c) may
their in vitro anti-HIV activity by using the IIIB strain lead to the discovery of more potent and selective
for HIV-1 and the ROD strain for HIV-2 in human analogs that will allow the elucidation of their molec-
T-lymphocyte (MT-4) cells. Cytotoxicity induced by ular mode-of-action.
these compounds was also measured in MT-4 cells par-
allel with the antiviral activity. The results are sum- Conclusion
marized in Table 1, in which the data for Nevirapine
(BOE/BIRG587) [39] and azidothymidine (AZT) [40],
are included for comparison. All the compounds are the identification of the 1,3-thiazole backbone bear-
inactive except for 9a and 9b which showed EC50 ing amino acid derivatives 9b and 9c as new anti-HIV
In summary, in vitro anti-HIV screening led to
=
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
751
candidates and promising agents for further structural 2-(3-Methylphenyl)-1,3-thiazole-4-carbohydrazide (4b)
modification and pharmacological evaluation.
Yield: 265 mg (74%), m. p. 127 ◦C. Rf = 0.64 (petroleum
ether-acetone, 3 : 2). – IR (cm-1): νmax = 3299, 3207
(2 × NH stretch.), 1670 (C=O stretch.), 1624 (C=N
stretch.), 1557 (NH bend.). – 1H NMR (CDCl3): δ = 9.77
(1H, br s, NH), 8.26 (1H, s, 5-Hthiazole), 7.91 (1H, s, 2-
Harom), 7.85 (1H, d, J = 7.5 Hz, 6-Harom), 7.40 (1H, t,
J = 7.7 Hz, 5-Harom), 7.33 (1H, d, J = 7.5 Hz, 4-Harom),
4.58 (2H, s, NH2), 2.39 (3H, s, CH3). – 13CNMR (CDCl3):
δ = 167.7 (C=O), 160.3 (Cthiazole-4), 150.0 (Cthiazole-2),
139.0 (Carom-3), 131.8 (Cthiazole-5), 124.1, 123.6 (Carom),
21.3 (CH3). – MS (EI): m/z = 233 [M]+. – C11H11N3OS
(233.29): calcd. C 56.63, H 4.75, N 18.01; found C 56.39, H
4.62, N 18.21.
Experimental Section
Melting points are uncorrected and were measured on
a Gallenkamp melting point apparatus (MP-D). Microana-
lytical data were obtained with a Euro Vector EA 3000 Ele-
mental apparatus. NMR spectra were recorded on a Bruker
300 MHz NMR spectrometer. The multiplicities are abbrevi-
ated as br s = broad singlet, s = singlet, d = doublet, t =
triplet, q = quartet, at = apparent triplet, ddd = doublet of
doublets of doublets, qn = quintet. IR spectra were recorded
on a Schimadzu Fourier transform infrared spectrophotome-
ter model 270, using the ATR facility. EI-MS spectra were
recorded on an Agilent technologies 6890N (GC) mass spec-
trometer with an inert selective detector 5973. TLC plates 60
F254 were purchased from Merck.
2-(2-Methylphenyl)-1,3-thiazole-4-carbohydrazide (4c)
Yield: 256 mg (72%), m. p. 151 ◦C. Rf = 0.67 (petroleum
ether-acetone, 3 : 2). – IR (cm-1): νmax = 3424, 3315 (2 × NH
stretch.), 1681 (C=O stretch.), 1633 (C=N stretch.), 1524
(NH bend.). – 1H NMR (CDCl3): δ = 8.52 (1H, br s,
-NH), 8.19 (1H, s, 5-Hthiazole), 7.70 (1H, d, J = 7.8 Hz, 6-
Harom), 7.70 (3H, m, 3-Harom + 4-Harom + 5-Harom), 4.14
(2H, s, NH2), 2.60 (3H, s, CH3). – 13C NMR (CDCl3):
δ = 168.4 (C=O), 161.9 (Cthiazole-4), 148.4 (Cthiazole-2),
136.6 (Carom-2 + Carom-1), 131.7 (Cthiazole-5), 131.8, 130.1,
129.9, 126.3 (Carom), 21.6 (CH3). – MS (EI): m/z = 233
[M]+. – C11H11N3OS (233.29): calcd. C 56.63, H 4.75, N
18.01; found C 56.77, H 4.69, N 17.80.
Synthesis of 2-phenyl-1,3-thiazole-4-carbohydrazides 4a–i
A mixture of ethyl bromopyruvate (2) (1.5 mmol) and
arylthioamide (1.5 mmol) in EtOH (25 mL) was refluxed for
8 h. After completion of the reaction (TLC), the mixture was
concentrated, and water was added to the reaction mixture,
followed by extraction with CH2Cl2 (3 × 50 mL). The com-
bined organic extracts were dried (Na2SO4) and filtered, and
the filtrate was evaporated to dryness. The crude esters 3a–i
were used for the synthesis of carbohydrazides 4a–i, with-
out further purification. To a solution of ethyl 2-aryl-1,3-
thiazole-4-carboxylates 3a–i (1.3 mmol) in MeOH (25 mL)
was added slowly 80% hydrazine hydrate (2.6 mmol), and
the reaction mixture was heated under reflux for 8–10 h. The
progress of the reaction was monitored by TLC. After com-
pletion the mixture was concentrated in vacuo, followed by
addition of cold water. The precipitated solid was filtered and
recrystallized from aq. EtOH.
2-(4-Chlorophenyl)-1,3-thiazole-4-carbohydrazide (4d)
Yield: 277 mg (72%), m. p. 169 ◦C. Rf = 0.59 (petroleum
ether-acetone, 3 : 2). – IR (cm-1): νmax = 3444, 3243 (2 × NH
stretch.), 1653 (C=O stretch.), 1614 (C=N stretch.), 1538
(N-H bend.), 1087 (C-Cl stretch). – 1H NMR (CDCl3): δ =
9.82 (1H, br s, NH), 8.30 (1H, s, 5-Hthiazole), 8.09 (2H, d,
J = 8.7 Hz, 2-Harom + 6-Harom), 7.60 (2H, d, J = 8.4 Hz, 3-
Harom + 5-Harom), 4.58 (2H, s, NH2). – 13C NMR (CDCl3):
δ = 166.2 (Cthiazole-4), 160.2 (C=O), 150.1 (Cthiazole-2),
135.7 (Carom-Cl), 131.7, 129.7 (Carom), 128.6 (Cthiazole-5). –
MS (EI): m/z = 252/254 [M]+. – C10H8ClN3OS (253.71):
calcd. C 47.34, H 3.18, N 16.56; found C 47.02, H 3.04, N
16.37.
2-(4-Methylphenyl)-1,3-thiazole-4-carbohydrazide (4a)
Yield: 236 mg (78%), m. p. 181 ◦C. Rf = 0.69 (petroleum
ether-acetone, 3 : 2). – IR (cm-1): νmax = 3400, 3284
(2 × NH stretch.), 1655 (C=O stretch.), 1649 (C=N
stretch.), 1557 (NH bend.). – 1H NMR (CDCl3): δ = 8.58
(1H, br s, NH), 8.09 (1H, s, 5-Hthiazole), 7.84 (2H, d, J =
2-(3-Chlorophenyl)-1,3-thiazole-4-carbohydrazide (4e)
Yield: 296 mg (70%), m. p. 146 ◦C. Rf = 0.69 (petroleum
7.8 Hz, 2-Harom + 6-Harom), 7.28 (2H, d, J = 8.1 Hz, 3- ether-acetone, 3 : 2). – IR (cm-1): νmax = 3414, 3314 (2 × NH
Harom + 5-Harom), 4.14 (2H, s, NH2), 2.42 (3H, s, CH3). sterch.), 1654 (C=O stretch.), 1614 (C=N strech.), 1525
–
13C NMR (CDCl3): δ = 168.7 (Cthiazole-2), 161.9 (C=O), (NH bend.), 1084 (C-Cl stretch.). – 1H NMR (CDCl3):
148.8 (Cthiazole-4), 141.1 (Carom-1), 130.0 (Carom), 129.7 δ = 9.92 (1H, br s, N-H), 8.32 (1H, s, 5-Hthiazole), 8.25
(Cthiazole-5), 126.5, 123.1 (Carom), 21.5 (CH3). – MS (EI): (1H, s, 2-Harom), 7.97 (1H, at, J = 5.1 Hz, 5-Harom), 7.56
m/z = 233 [M]+. – C11H11N3OS (233.29): calcd. C 56.63, (2H, t, J = 7.8 Hz, 4-Harom + 6-Harom), 4.62 (2H, s,
H 4.75, N 18.01; found C 56.42, H 4.64, N 17.79.
NH2) – 13C NMR (CDCl3): δ = 165.7 (Cthiazole-2), 160.1
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

752
M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
stretch.), 1531 (NH bend.). – 1H NMR (CDCl3): δ =
(C=O), 150.1 (Cthiazole-4), 134.8 (Carom-Cl), 131.6 (Carom
-
1), 130.8 (Cthiazole-5), 126.3, 125.7 (Carom). – MS (EI): 9.81 (1H, br s, N-H), 8.26 (1H, s, 5-Hthiazole), 8.54 (1H,
m/z = 252/254 [M]+. – C10H8ClN3OS (253.71): calcd. C dd,J = 1.8, 8.1 Hz, 6-Harom), 7.49 (1H, m, 4-Harom), 7.24
47.34, H 3.18, N 16.56; found C 47.08, H 3.07, N 16.29.
(1H, d, J = 8.1 Hz, Ar-H3), 7.12 (1H, qn, J = 7.8 Hz, 5-
Harom), 4.57 (2H, s, NH2), 4.03 (3H, s, OCH3). – 13C
NMR (CDCl3): δ = 161.7 (Cthiazole-2), 160.6 (C=O), 156.6
2-(2-Chlorophenyl)-1,3-thiazole-4-carbohydrazide (4f)
Yield: 220 mg (67%), m. p. 158 ◦C. Rf = 0.68 (petroleum
ether-acetone, 3 : 2). – IR (cm-1): νmax = 3423, 3318 (2 × NH
stretch.), 1678 (C=O stretch.), 1631 (C=N stretch.), 1524
(NH bend.), 1089 (C-Cl stretch.). – 1H NMR (CDCl3): δ =
9.88 (1H, br s, NH), 8.54 (1H, m, 6-Harom), 8.31 (1H, s, 5-
Hthiazole), 7.67 (1H, m, 4-Harom), 7.55 (2H, m, 3-Harom+ 5-
Harom), 4.59 (2H, s, NH2). – 13C NMR (CDCl3): δ = 162.7
(Carom-2), 148.3 (Cthiazole-4), 132.0 (Carom-4), 128.8 (Carom
-
6), 128.7 (Cthiazole-5), 124.1 Carom-1), 121.3 (Carom-5), 112.6
(Carom-3), 56.3 (OCH3). – MS (EI): m/z = 249 [M]+. –
C11H11N3O2S (249.29): calcd. C 53.00, H 4.45, N 16.86;
found C 52.86, H 4.36, N 16.66.
Synthesis of N0-(2-oxoindolin-3-ylidene)-2-aryl-1,3-
thiazole-4-carbohydrazides 6a–i
(Cthiazole-2), 160.2 (C=O), 148.9 (Cthiazole-4), 135.2 (Carom
-
-
1), 132.1 (Carom-Cl), 131.6, 131.0 (Carom), 128.1 (Cthiazole
Compound 4 (1.0 mmol) and isatin (5) (1.0 mmol) were
dissolved in warm EtOH (25 mL) containing glacial HOAc
(0.5 mL). The reaction mixture was refluxed for 6–8 h. On
completion of the reaction (TLC), excess solvent was re-
moved under reduced pressure, and the precipitate obtained
on cooling was collected by filtration and recrystallized from
a DMF-water mixture.
5), 125.3 (Carom.). – MS (EI): m/z = 252/254 [M]+. –
C10H8ClN3OS (253.71): calcd. C 47.34, H 3.18, N 16.56;
found C 46.98, H 3.02, N 15.27.
2-(4-Methoxyphenyl)-1,3-thiazole-4-carbohydrazide (4g)
Yield: 237 mg (73%), m. p. 161 ◦C. Rf = 0.67 (petroleum
ether-acetone, 3 : 2). – IR (cm-1): νmax = 3448, 3307 (2 × NH
stretch.), 1663 (C=O stretch.), 1610 (C=N stretch.), 1522 N0-(2-Oxoindolin-3-ylidene)-2-(4-methylphenyl)-1,3-
(NH bend). – 1H NMR (CDCl3): δ = 9.72 (1H, br s, N-H), thiazole-4-carbohydrazide (6a)
8.17 (1H, s, 5-Hthiazole), 8.01 (2H, d, J = 8.7 Hz, 2-Harom
+
From 4a (233 mg). Yield: 268 mg (74%), m. p. 315 ◦C.
Rf = 0.67 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax = 3254
(NH stretch.), 1685 (C=O stretch.), 1621 (C=N stretch.),
1585 (NH bend.). – 1H NMR ([D6]DMSO): δ = 14.52 (1H,
br s, NH), 11.24 (1H, br s, NH), 8.63 (1H, s, 5-Hthiazole),
7.98 (1H, d, J = 7.8 Hz, 2-Harom + 6-Harom), 7.63 (1H, d,
J = 7.5 Hz, 16-Harom), 7.42 (3H, t, J = 7.8 Hz, 3-Harom + 5-
Harom + 15-Harom), 7.13 (1H, t, J =7.5 Hz, 14-Harom), 6.98
(1H, d, J =7.8 Hz, 13-Harom), 2.38 (3H, s, CH3). – 13C NMR
([D6]DMSO): δ = 168.5 (Cthiazole-2), 163.2 (Cisatin =O),
6-Harom), 7.08 (2H, d, J = 8.7 Hz, 3-Harom + 5-Harom), 4.56
(2H, s, NH2), 3.83 (3H, s, OCH3). – 13C NMR (CDCl3): δ =
167.5 (Cthiazole-4), 161.6 (C=O), 160.3 (Carom-OMe), 149.8
(Cthiazole-2), 128.5 (Carom-2 + Carom-6), 127.6 (Cthiazole-5),
115.1 (Carom-3 + Carom-5), 55.9 (OCH3). – MS (EI): m/z =
249 [M]+. – C11H11N3O2S (249.29): calcd. C 53.00, H 4.45,
N 16.86; found C 53.19, H 4.28, N 16.64.
2-(3-Methoxyphenyl)-1,3-thiazole-4-carbohydrazide (4h)
Yield: 250 mg (77%), m. p. 125 ◦C. Rf = 0.63 (petroleum
ether-acetone, 3 : 2). – IR (cm-1): νmax = 3422, 3316 (2 × NH
stretch.), 1654 (C=O stretch.), 1624 (C=N stretch.), 1527
(NH bend.). – 1H NMR (CDCl3): δ = 9.85 (1H, br s, NH),
8.28 (1H, s, 5-Hthiazole), 7.71 (1H, at, J = 2.4 Hz, 2-Harom),
7.58 (1H, d, J = 7.5 Hz, 6-Harom), 7.44 (1H, t, J = 7.8 Hz, 5-
Harom), 7.09 (1H, dd, J = 2.1, 7.8 Hz, 4-Harom), 4.59 (2H, s,
NH2), 3.85 (3H, s, OCH3). – 13CNMR (CDCl3): δ = 167.3
(Cthiazole-2), 160.3 (C=O + Carom-3), 150.0 (Cthiazole-4),
134.2 (Carom-1), 130.8 (Carom-5), 128.2 (Cthiazole-5), 124.2
(Carom-6), 117.2 (Carom-4), 111.4 (Carom-2), 56.2 (OCH3). –
MS (EI): m/z = 249 [M]+. – C11H11N3O2S (249.29): calcd.
C 53.00, H 4.45, N 16.86; found C 53.19, H 4.28, N 16.64.
157.5 (Ccarbohydr =O), 148.5 (Cthiazole-4), 143.2 (Cisatin
-
7a), 141.6 (Carom-1), 139.0 (Cisatin-3), 132.4 (Me-Carom-1
+ Cisatin-6), 129.8 (Cisatin-4 + Carom), 127.4 (Cthiazole-5
+ Carom), 123.0 (Carom), 121.5 (Cisatin-7), 118.2 (Cisatin
-
3a), (21.5 (Me-Carom-4). – MS (EI): m/z = 362 [M]+. –
C19H14N4O2S (362.41): calcd. C 62.97, H 3.89, N 15.46;
found C 62.72, H 3.79, N 15.21.
N0-(2-Oxoindolin-3-ylidene)-2-(3-methylphenyl)-1,3-
thiazole-4-carbohydrazide (6b)
From 4b (233 mg). Yield: 261 mg (72%), m. p. 328 ◦C.
Rf = 0.58 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax = 3348
(N-H stretch.), 1694 (C=O stretch.), 1615 (C=N stretch.),
1520 (NH bend.). – 1H NMR ([D6]DMSO): δ = 14.52
2-(2-Methoxyphenyl)-1,3-thiazole-4-carbohydrazide (4i)
Yield: 230 mg (71%), m. p. 208 ◦C. Rf = 0.55 (petroleum (1H, br s, NH), 10.90 (1H, br s, NH), 8.70 (1H, s, 5-
ether-acetone, 3 : 2). – IR (KBr, cm-1): νmax = 3406, Hthiazole), 6.97 (1H, t, J = 7.8 Hz, 4-Harom), 7.14 (1H, m,
3310 (2 × NH stretch.), 1681 (C=O stretch.), 1644 (C=N 14-Harom), 7.44 (3H, m, 2-Harom + 4-Harom + 13-Harom),
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
753
7.99 (3H, m, 5-Harom + 15-Harom + 16-Harom), 2.41 (3H, N0-(2-Oxoindolin-3-ylidene)-2-(3-chlorophenyl)-1,3-
s, CH3). – 13C NMR ([D6]DMSO): δ = 167.1 (Cthiazole-2), thiazole-4-carbohydrazide (6e)
164.1 (Cisatin =O), 156.9 (Ccarbohydr =O), 148.5 (Cthiazole
4), 143.1 (Cisatin-7a), 139.3 (Me-Carom-3), 138.4 (Cisatin-3),
132.4 (Cisatin-5), 129.8 (Carom-1 + Carom), 127.6 (Cthiazole-5
-
From 4e (253 mg). Yield: 268 mg (70%), m. p. 326 ◦C.
Rf = 0.55 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
3276 (NH stretch.), 1683 (C=O stretch.), 1622 (C=N
stretch.), 1570 (NH bend.), 1099 (C-Cl stretch.). – 1H NMR
([D6]DMSO): δ = 14.55 (1H, br s, NH), 11.31 (1H, br s,
NH), 8.76 (1H, s, 5-Hthiazole ), 8.19 (1H, d, J = 1.6 Hz,
2-Harom), 8.03 (1H, m, 6-Harom), 7.64 (1H, d, J =5.1
Hz,16−Harom), 7.60 (1H, d, J =8.1 Hz, 13-Harom), 7.51
(1H, t, J = 7.5 Hz, 15-Harom), 7.43 (1H, t, J = 7.8 Hz, 14-
Harom), 7.14 (1H, m, 5-Harom), 6.97 (1H, t, J = 7.5 Hz, 4-
Harom). – 13C NMR ([D6]DMSO): δ = 166.5 (Cthiazole-2),
163.2 (Cisatin =O), 157.3 (Ccarbohydr =O), 148.6 (Cthiazole-4),
142.0 (Cisatin-7a), 139.1 (Carom-3), 136.0 (Cisatin =N), 134.6
+ Carom), 125.6 (Cisatin-5), 121.5 (Cisatin-7), 120.4 (Cisatin
-
3a), 21.4 (Me-Carom-4). – MS (EI): m/z = 362 [M]+. –
C19H14N4O2S (362.41): calcd. C 62.97, H 3.89, N 15.46;
found C 62.75, H 3.72, N 15.59.
N0-(2-Oxoindolin-3-ylidene)-2-(2-methylphenyl)-1,3-
thiazole-4-carbohydrazide (6c)
From 4c (233 mg). Yield: 250 mg (69%), m. p. 283 ◦C.
Rf = 0.64 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax = 3250
(N-H stretch.), 1694 (C=O stretch.), 1620 (C=N stretch.),
1557 (NH bend.). – 1H NMR ([D6]DMSO): δ = 14.41 (1H,
br s, NH), 11.25 (1H, br s, NH), 8.74 (1H, s, 5-Hthiazole),
6.96 (1H, d, J = 7.8 Hz, 13-Harom), 7.13 (1H, t, J = 7.5 Hz,
(Carom-1), 132.3 (Cisatin-4), 130.6 (Cisatin-6), 127.0 (Cthiazole
-
5), 126.1, 125.6, 123.1 (Carom + Cisatin), 122.2 (Cisatin
-
7), 116.2 (Cisatin-3a). – MS (EI): m/z = 381/383 [M]+. –
C18H11ClN4O2S (382.82): calcd. C 56.47, H 2.90, N 14.64;
found C 56.19, H 2.81, N 14.44.
14-Harom), 7.43 (4H, m, 4-Harom + 5-Harom + 6-Harom
+
15-Harom), 7.63 (1H, d, J = 7.5 Hz, 3-Harom), 7.87 (1H,
d, J =7.5 Hz, 16-Harom), 2.71 (3H, s, CH3). – 13C NMR
([D6]DMSO): δ = 168.5 (Cthiazole-2), 163.1 (Cisatin =O),
157.7 (Ccarbohydr =O), 148.3 (Cthiazole-4), 143.1 (Cisatin-7a),
138.9 (Carom-1 + Me-Carom-1), 137.0 (Cisatin =N), 132.3
N0-(2-Oxoindolin-3-ylidene)-2-(2-chlorophenyl)-1,3-
thiazole-4-carbohydrazide (6f)
From 4f (253 mg). Yield: 264 mg (69%), m. p. 315 ◦C.
Rf = 0.56 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
(Cisatin-5), 131.6 (Cisatin-6), 130.8, 130.3, 128.1 (Carom
+
3352 (NH stretch.), 1650 (C=O stretch.), 1619 (C=N
stretch.), 1588 (NH bend.), 1085 (C-Cl stretch.). – 1H NMR
([D6]DMSO): δ = 11.73 (1H, br s, NH), 10.91 (1H, br s,
NH), 8.86 (1H, s, 5-Hthiazole), 8.36 (1H, d, J = 6.6 Hz, 16-
Harom), 7.96 (1H, d, J = 7.2 Hz, 15-Harom), 7.72 (4H, t,
J = 7.2 Hz, 3-Harom + 4-Harom + 5-Harom + 6-Harom), 7.14
(1H, t, J = 7.5 Hz, 14-Harom), 6.98 (1H, d, J = 7.5 Hz, 13-
Harom). – 13C NMR ([D6]DMSO): δ = 166.0 (Cthiazole-2),
163.2 (Cisatin =O), 156.1 (Ccarbohydr =O), 147.5 (Cthiazole-4),
144.5 (Cisatin-7a), 143.1 (Carom-1), 135.0 (Cisatin =N), 133.7
Cisatin), 127.0 (Cthiazole-5), 120.9 (Cisatin-7), 120.4 (Cisatin
-
3a), 22.0 (Me-Carom-4). – MS (EI): m/z = 362 [M]+. –
C19H14N4O2S (362.41): calcd. C 62.97, H 3.89, N 15.46;
found C 62.72, H 3.79, N 15.21.
N0-(2-Oxoindolin-3-ylidene)-2-(4-chlorophenyl)-1,3-
thiazole-4-carbohydrazide (6d)
From 4d (253 mg). Yield: 279 mg (73%), m. p. 341 ◦C.
Rf = 0.59 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
(Carom-2), 132.6 (Cisatin-6), 131.6 (Carom-4), 131.5 (Cisatin
-
3200 (NH stretch.), 1685 (C=O stretch.), 1619 (C=N
stretch.), 1091 (C-Cl stretch.), 1521 (NH bend.). – 1H NMR
([D6]DMSO): δ = 14.48 (1H, br s, NH), 11.63 (1H, br
6), 129.2 (Carom), 127.4 (Cthiazole-5), 126.8, 125.0, 123.1,
122.4 (Carom + Cisatin), 121.6 (Cisatin-7), 116.0 (Cisatin
-
3a). – MS (EI): m/z = 381/383 [M]+. – C18H11ClN4O2S
(382.82): calcd. C 56.47, H 2.90, N 14.64; found C 56.19, H
2.77, N 14.43.
s, NH), 8.70 (1H, s, 5-Hthiazole), 8.06 (2H, m, 2-Harom
+
6-Harom), 7.67 (2H, dd, J = 10.5, 7.5 Hz, 3-Harom + 5-
Harom), 7.47 (1H, m, 15-Harom), 7.25 (1H, t, J = 7.2 Hz,
16-Harom), 7.12 (1H, t, J = 7.2 Hz, 14-Harom), 6.96 (1H,
d, J = 6.0 Hz, 13-Harom). – 13C NMR ([D6]DMSO): δ =
167.1 (Cthiazole-2), 164.9 (Cisatin =O), 162.8 (Ccarbohydr =O),
148.6 (Cthiazole-4), 144.4 (Carom-1), 141.8 (Cisatin-7a), 136.2
N0-(2-Oxoindolin-3-ylidene)-2-(4-methoxyphenyl)-1,3-
thiazole-4-carbohydrazide (6g)
From 4g (249 mg). Yield: 268 mg (71%), m. p. 320 ◦C.
(Cisatin =N), 133.6 (Carom-4), 131.3 (Cisatin-6), 130.0 (Cisatin
4), 129.5 (Carom-3 + Carom-5), 128.1 (Carom-2 + Carom
-
-
Rf = 0.68 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
3345 (NH stretch.), 1693 (C=O stretch.), 1608 (C=N
6), 125.8 (Cisatin-5), 127.2 (Cthiazole-5), 122.7 (Cisatin-7), stretch.), 1574 (NH bend.), 1159 (C-O stretch.). – 1H NMR
116.0 (Cisatin-3a). – MS (EI): m/z = 381/383 [M]+. – ([D6]DMSO): δ = 14.50 (1H, br s, NH), 11.66 (1H, br
C18H11ClN4O2S (382.82): calcd. C 56.47, H 2.90, N 14.64; s, NH), 8.60 (1H, s, 5-Hthiazole), 8.02 (2H, m, 2-Harom
+
found C 56.19, H 2.81, N 14.44. 6-Harom), 7.62 (1H, d, J =7.5 Hz, 16-Harom), 7.47 (1H,
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

754
M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
m, 15-H15), 7.13 (3H, m, 4-Harom + 5-Harom + 6-Harom MS (EI): m/z = 378 [M]+. – C19H14N4O3S (378.40): calcd.
+ 15-Harom Ar-H3,5,14), 6.99 (1H, d, J = 7.8 Hz, Ar- C 60.31, H 3.73, N 14.81; found C 60.11, H 3.62, N 15.01.
Harom), 3.84 (3H, s, OCH3). – 13C NMR ([D6]DMSO: δ =
Synthesis of 5-(2-(substituted-phenyl)-1,3-thiazol-4-yl)-
1,3,4-oxadiazole-2-thiones 7a–i
168.0 (Cthiazole-2), 163.2 (Cisatin =O), 160.2 (OMe-Carom
4), 157.4 (Ccarbohydr =O), 148.4 (Cthiazole-4), 143.1 (Cisatin
-
-
7a), 139.0 (Carom-1), 133.6 (Cisatin =N), 132.3 (Cisatin-6),
131.1, 129.4, 128.3 (Carom), 127.8 (Cthiazole-5), 123.1 (Carom
To a mixture of hydrazide 4 (2.0 mmol) and KOH
(2.4 mmol) in MeOH (30 mL) was added CS2 (2.4 mmol)
dropwise. The yellow solution obtained was refluxed till the
evolution of hydrogen sulfide ceased (Pb(OAc)4 test). After
3 h, the solution was cooled and filtered. The filtrate was
poured into ice-cooled water and acidified with 6 N HCl
to pH 3–4. The solid product obtained was filtered, dried
(Na2SO4) and recrystallized from CHCl3.
+ Cisatin), 121.5 (Cisatin-7), 119.3 (Cisatin-3a), 111.6 (Carom
-
3 + Carom-5), 55.7 (OMe). – MS (EI): m/z = 378 [M]+. –
C19H14N4O3S (378.40): calcd. C 60.31, H 3.73, N 14.81;
found C 60.11, H 3.62, N 15.01.
N0-(2-Oxoindolin-3-ylidene)-2-(3-methoxyphenyl)-1,3-
thiazole-4-carbohydrazide (6h)
5-[2-(4-Methylphenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-2-
thione (7a)
From 4h (249 mg). Yield: 280 mg (74%), m. p. 266 ◦C.
Rf = 0.65 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
3200 (NH stretch.), 1698 (C=O stretch.), 1601 (C=N
From 4a (466 mg). Yield: 412 mg (75%), m. p. 258 ◦C.
stretch.), 1581 (NH bend.), 1175 (C-O stretch.). – 1H NMR Rf = 0.67 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax = 3313
([D6]DMSO): δ = 14.56 (1H, br s, NH), 11.28 (1H, br s, (NH stretch.), 1633 (C=N stretch.), 1530 (NH bend.), 1222
NH), 8.67 (1H, s, H5thiazole), 7.69 (1H, d, J = 1.5 Hz, 2- (C=S stretch.). – 1H NMR ([D6]DMSO): δ = 14.82 (1H, br
Harom), 7.62 (2H, d, J = 7.2 Hz, 13-Harom + 16-Harom), 7.50 s, N-H), 8.54 (1H, s, 5-Hthiazole), 7.91 (2H, d, J = 8.1 Hz,
(1H, t, J = 8.1 Hz, 14-Harom), 7.42 (1H, dt, J = 0.9, 7.5 Hz, 2-Harom + 6-Harom), 7.36 (2H, d, J = 8.1 Hz, 3-Harom
+
15-Harom), 7.15 (2H, m, 4-Harom + 5-Harom), 6.96 (1H, d, 5-Harom), 2.37 (3H, s, CH3). – 13C NMR ([D6]DMSO):
J = 7.8 Hz, 6-Harom), 7. 3.88 (3H, s, OCH3). – 13C NMR δ = 177.6 (C=S), 169.8 (Cthiazole-2), 157.0 (Coxadiazole
([D6]DMSO): δ = 168.3 (Cthiazole-2), 163.1 (Cisatin =O), 5), 141.6 (Cthiazole-4), 139.1 (Carom-1), 130.4 (Me-Carom
-
-
162.0 (OMe-C-3), 157.6 (Ccarbohydr =O), 148.3 (Cthiazole
-
4), 129.8 (Carom-3 + Carom-5), 126.9 (Carom-2 + Carom-6),
4), 143.1 (Cisatin-7a), 138.9 (Carom-1), 135.0 (Cisatin =N), 21.4 (CH3). – MS (EI): m/z = 275 [M]+. – C12H9N3OS2
128.5 (Cisatin-6), 128.4 (Carom-5), 126.8 (Cisatin-5), 123.1 (275.35): calcd. C 52.34, H 3.29, N 15.26; found C 52.01, H
(Carom-6), 120.4 (Cisatin-7), 119.3 (Cisatin-3a), 115.2 (Carom
-
3.18, N 14.96.
4), 111.6 (Carom-2), 55.9 (OMe). – MS (EI): m/z = 378
[M]+. – C19H14N4O3S (378.40): calcd. C 60.31, H 3.73, N
14.81; found C 60.11, H 3.62, N 15.01.
5-[2-(3-Methylphenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-2-
thione (7b)
From 4b (466 mg). Yield: 402 mg (73%), m. p. 226 ◦C.
Rf = 0.62 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax = 3291
(NH stretch.), 1632 (C=N stretch.), 1576 (NH bend.), 1230
(C=S stretch.). – 1H NMR ([D6]DMSO): δ = 14.83 (1H, br
s, N-H), 8.56 (1H, s, 5-Hthiazole), 7.82 (1H, d, J = 6.3 Hz,
6-Harom), 7.77 (1H, s, 2-Harom), 7.42 (1H, t, J = 7.5 Hz,
5-Harom), 7.36 (1H, d,J = 7.5, Hz, 4-Harom), 2.39 (3H,
s, CH3). – 13C NMR ([D6]DMSO): δ = 177.6 (C=S),
169.8 (Cthiazole-2), 156.9 (Coxadiazole-2), 139.3 (Cthiazole-4),
139.1 (Me-Carom-3), 132.3 (Carom-2), 132.2 (Carom-1), 129.7
(Carom-4 + Carom-5), 127.3 (Carom-6), 21.2 (CH3). – MS
(EI): m/z = 275 [M]+. – C12H9N3OS2 (275.35): calcd. C
52.34, H 3.29, N 15.26; found C 51.94, H 3.19, N 15.95.
N0-(2-Oxoindolin-3-ylidene)-2-(2-methoxyphenyl)-1,3-
thiazole-4-carbohydrazide (6i)
From 4i (249 mg). Yield: 261 mg (68%), m. p. 335 ◦C.
Rf = 0.69 (CHCl3-MeOH, 3 : 2). IR (cm-1): νmax
=
3424 (NH stretch.), 1666 (C=O stretch.), 1619 (C=N
stretch.), 1161 (C-O stretch.), 1524 (NH bend.). – 1H
NMR ([D6]DMSO): δ = 14.63 (1H, br s, NH), 11.25 (1H,
br s, NH), 8.74 (1H, s, 5-Hthiazole), 7.60 (1H, d, J =
7.5 Hz, 6-Harom), 8.50 (1H, d, J = 7.8 Hz, 16-Harom), 7.54
(1H, t, J = 7.8 Hz, 4-Harom), 7.39 (1H, t, J = 7.8 Hz, 5-
Harom), 7.31 (1H, d, J = 8.4 Hz, 3-Harom), 7.19 (1H, t,
J = 7.5 Hz, 15-Harom), 7.13 (1H, t, J = 7.8 Hz, 14-Harom),
6.98 (1H, d, J = 7.5 Hz, 13-Harom), 4.05 (3H, s, OCH3).
5-[2-(2-Methylphenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-2-
thione (7c)
–
13C NMR ([D6]DMSO): δ = 168.0 (Cthiazole-2), 163.2
(Cisatin =O), 157.7 (Ccarbohydr =O), 156.9 (OMe-Carom-2),
146.8 (Cthiazole-4), 143.0 (Cisatin-7a), 134.1 (Cisatin =N),
From 4c (466 mg). Yield: 385 mg (70%), m. p. 203 ◦C.
Rf = 0.65 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax = 3213
132.5 (Cisatin-6), 130.1 (Cisatin-4), 128.0 (Carom-4 + Carom
-
6), 125.4 (Cisatin-5), 123.0 (Carom-6), 121.5 (Carom-1), 120.8 (NH stretch.), 1625 (C=N stretch.), 1555 (NH bend.), 1211
(Carom-5), 120.4 (Cisatin-7), 118.9. (Cisatin-3a), 56.4 (OMe). – (C=S stretch.). – 1H NMR ([D6]DMSO): δ = 14.83 (1H, br
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
755
s, NH), 8.56 (1H, s, 5-Hthiazole), 7.79 (1H, d, J = 7.2 Hz, 6- (Cthiazole-4), 137.6 (Carom-1), 131.4 (Carom-2), 131.1 (Carom
-
Harom), 7.42 (3H, m, 3-Harom + 4-Harom + 5-Harom), 2.51 4), 130.6 (Carom-3), 128.9 (Carom-6), 126.4 (Carom-5). – MS
(3H, s, CH3). – 13C NMR ([D6]DMSO): δ = 177.7 (C=S), (EI): m/z = 294/296 [M]+. – C11H6 ClN3OS2 (295.77):
169.3 (Cthiazole-2), 157.0 (Coxadiazole-5), 138.7 (Cthiazole-4), calcd. C 44.67, H 2.04, N 14.21; found C 44.48, H 1.95, N
136.6 Carom-1), 132. 2 (Me-Carom-2), 130.2 (Carom-3), 130.0 14.40.
(Carom-4), 127.0 (Carom-6), 125.4 (Carom-5), 21.6 (CH3). –
5-[2-(4-Methoxyphenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-
MS (EI): m/z = 275 [M]+. – C12H9N3OS2 (275.35): calcd.
2-thione (7g)
C 52.34, H 3.29, N 15.26; found C 52.31, H 3.20, N 15.02.
From 4g (498 mg). Yield: 431 mg (74%), m. p. 270 ◦C.
5-[2-(4-Chlorophenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-
2(3H)-thione (7d)
Rf = 0.74 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
3292 (NH stretch.), 1633 (C=N stretch.), 1572 (NH bend.),
1221 (C=S stretch.), 1162 (C-O stretch.). – 1H NMR
([D6]DMSO): δ = 14.80 (1H, br s, NH, 8.49 (1H, s, 5-
Hthiazole), 7.96 (2H, d, J = 8.7 Hz, 2-Harom + 6-Harom),
7.36 (2H, d, J = 8.7 Hz, 3-Harom + 5-Harom), 3.84 (3H,
s, OCH3). – 13C NMR ([D6]DMSO): δ = 177.6 (C=S),
From 4d (506 mg) Yield: 395 mg (67%), m. p. 252 ◦C.
Rf = 0.67 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
3314 (NH stretch.), 1634 (C=N stretch.), 1539 (NH bend.),
1217 (C=S stretch.), 1092 (C-Cl stretch.). – 1H NMR
([D6]DMSO): δ = 14.84 (1H, br s, NH), 8.61 (1H, s, 5-
Hthiazole), 8.62 (2H, d, J = 8.7 Hz, 2-Harom + 6-Harom),
7.60 (2H, d, J = 8.7 Hz, 3-Harom + 5-Harom). – 13C
NMR ([D6]DMSO): δ = 177.6 (C=S), 168.3 (Cthiazole
2), 156.8 (Coxadiazole-5), 139.4 (Cthiazole-4), 139.0 (Carom
1), 131.2 (Carom-4), 129.9 (Carom-3 + Carom-5), 128.7
(Carom-2 + Carom-6). – MS (EI): m/z = 294/296 [M]+. –
C11H6ClN3OS2 (295.77): calcd. C 44.67, H 2.04, N 14.21;
found C 44.42, H 1.95, N 13.97.
169.5 (Cthiazole-2), 162.0 (OMe-Carom-4), 157.0 (Coxadiazole
-
5), 141.0 (Cthiazole-4), 136.2 (Carom-1), 130.4 (Carom-2 +
Carom-6), 116.9 (Carom-3 + Carom-5), 55.9 (OCH3). – MS
(EI): m/z = 291 [M]+. – C12H9N3O2S2 (291.35): calcd. C
49.47, H 3.11, N 14.42; found C 49.31, H 3.20, N 14.22.
-
-
5-[2-(3-Methoxyphenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-
2-thione (7h)
From 4h (498 mg). Yield: 419 mg (72%), m. p. 259 ◦C.
Rf = 0.62 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax = 3274
(NH stretch.), 1224 (C=S stretch.), 1632 (C=N stretch.),
1579 (NH bend.), 1224 (C=S stretch.), 1159 (C-O stretch.).
5-[2-(3-Chlorophenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-2-
thione (7e)
From 4e (506 mg). Yield: 395 mg (67%), m. p. 242 ◦C.
–
1H NMR ([D6]DMSO): δ = 14.80 (1H, br s, NH), 8.59
Rf = 0.57 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
(1H, s, 5-Hthiazole), 7.58 (1H, dd, J = 0.9, 7.5 Hz, 6-
Harom), 7.50 (1H, m, 2-Harom), 7.46 (1H, d, J = 7.8 Hz, 5-
Harom), 7.14 (1H, m, 4-Harom), 3.85 (3H, s, OCH3). – 13C
NMR ([D6]DMSO): δ = 177.0 (C=S), 169.4 (Cthiazole-2),
3237 (NH stretch.), 1629 (C=N stretch.), 1591 (NH bend.),
1222 (C=S stretch.), 1080 (C-Cl stretch.). – 1H NMR
([D6]DMSO): δ = 14.83 (1H, br s), 8.63 (1H, s, 5-Hthiazole),
8.01 (1H, d, J = 1.5 Hz, 2-Harom), 7.97 (1H, m, 5-Harom),
7.60 (2H, m, 4-Harom + 6-Harom). – 13C NMR ([D6]DMSO):
δ = 177.6 (C=S), 167.9 (Cthiazole-2), 156.8 (Coxadiazole-5),
139.4 (Cthiazole-4), 134.2 Carom-3), 131.3 (Carom-1), 129.1
(Carom-5 + Carom-6), 126.8 (Carom-4), 125.8 (Carom-2). –
MS (EI): m/z = 294/296 [M]+. – C11H6 ClN3OS2 (295.77):
calcd. C 44.67, H 2.04, N 14.21; found C 44.39, H 1.96, N
13.99.
160.2 (OMe-Carom-3), 156.9 (Coxadiazole-5), 141.8 (Cthiazole
-
4), 134.5 (Carom-1), 131.1 (Carom-5), 125.2 (Carom-6), 117.5
(Carom-4), 111.5 (Carom-2), 55.8 (OCH3). – MS (EI): m/z =
291 [M]+. – C12H9N3O2S2 (291.35): calcd. C 49.47, H 3.11,
N 14.42; found C 49.58, H 3.00, N 14.18.
5-[2-(2-Methoxyphenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-
2-thione (7i)
From 4i (498 mg). Yield: 419 mg (72%), m. p. 210 ◦C.
5-[2-(2-Chlorophenyl)-1,3-thiazol-4-yl]-1,3,4-oxadiazole-2-
thione (7f)
Rf = 0.57 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
=
3424 (NH stretch.), 1635 (C=N stretch.), 1525 (NH bend.),
From 4f (506 mg). Yield: 384 mg (65%), m. p. 210 ◦C. 1241 (C=S stretch.), 1159 (C-O stretch.). – 1H NMR
Rf = 0.65 (CHCl3-MeOH, 3 : 2). – IR (cm-1): νmax
([D6]DMSO): δ = 14.81 (1H, br s, NH), 8.57 (1H, s, 5-
=
3273 (NH stretch.), 1632 (C=N stretch.), 1579 (NH bend.), Hthiazole), 8.32 (1H, d, J = 7.8 Hz, 6-Harom), 7.56 (1H, d,
1202 (C=S stretch.), 1084 (C-Cl stretch.). – 1H NMR J = 7.5 Hz, 4-Harom), 7.30 (1H, d, J = 8.4 Hz, 3-Harom),
([D6]DMSO): δ = 14.78 (1H, br s), 8.74 (1H, s, 5-Hthiazole), 7.15 (1H, t,J = 7.5 Hz, 5-Harom), 4.05 (3H, s, OCH3). – 13
C
8.25 (1H, m, 6-Harom), 7.71 (1H, m, 4-Harom), 7.60 (2H, NMR ([D6]DMSO): δ = 177.6 (C=S), 168.2 (Cthiazole-2),
m, 3-Harom + 5-Harom). – 13C NMR ([D6]DMSO): δ = 163.6 (OMe-Carom-2), 157.7 (Coxadiazole-5), 157.3 (Cthiazole
177.7 (C=S), 164.9 (Cthiazole-2), 156.9 (Coxadiazole-5), 138.3 4), 132.5 (Carom-4), 128.0 (Carom-6), 125.4 (Carom-1), 121.5
-
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

756
M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
(Carom-5), 112.8 (Carom-3), 56.5 (OCH3). – MS (EI): m/z = C14H13ClN2O4S (340.78): calcd. C 49.34, H 3.85, N 8.22;
291 [M]+. – C12H9N3O2S2 (291.35): calcd. C 49.47, H 3.11, found C 49.03, H 3.77, N 7.98.
N 14.42; found C 49.25, H 2.98, N 14.61.
Methyl (2-(2-(4-chlorophenyl)thiazole)-4-carboxamido)-4-
(methylthio)butanoate (9c)
General preparation of carboxamido-thiazoles 9a–d
To a cold solution (∼ −5 ◦C) of 4f (507 mg, 2.0 mmol)
in HOAc (14 mL), 1 N HCl (7 mL), and water (30 mL) was
added a solution of NaNO2 (172 mg, 2.5 mmol) in cold wa-
ter (4 mL). After stirring at −5 ◦C for 15 min, a yellow
syrup was formed. The azide was taken in cold ethyl acetate
(30 mL), washed with a 3% solution of NaHCO3, washed
with water, and finally dried (Na2SO4). A solution of amino
acid methyl ester (2.33 mmol) in ethyl acetate (20 mL) con-
taining 3.5 mL of Et3N was stirred at 0 ◦C for 20 min and
filtered, and the filtrate was added to the acid solution. The
mixture was kept at −5 ◦C for 12 h, then at 23 ◦C for an-
other 12 h, followed by washing with 0.5 N HCl, water and
a 3% solution of NaHCO3, and finally dried (Na2SO4). The
solution was evaporated to dryness, and the residue was ei-
ther an oil, purified on an SiO2 column, or a solid, recrystal-
lized from ethyl acetate-petroleum ether to give the desired
products.
From L-methionine methyl ester (380 mg). Yield: 498 mg
(65%), m. p. 183–186 ◦C. – 1H NMR ([D6]DMSO): δ =
9.77 (1H, br s, NH), 9.20 (1H, s, 5-Hthiazole), 8.00 (2H,
d, J = 8.6 Hz, 2-Harom + 6-Harom), 7.52 (2H, d, J =
8.6 Hz, 3-Harom + 5-Harom), 4.39 (1H, m, 8-H), 3.75 (3H,
s, CO2Me), 2.58 (2H, t, J = 7.1 Hz, CH2CH2SMe), 2.41
(2H, t, J = 7.1 Hz, CH2CH2SMe), 2.09 (SMe). – 13C
NMR ([D6]DMSO): δ = 173.2 (CO2Me), 167.7 (Cthiazole
-
2), 160.9 (C=O), 148.7 (Cthiazole-4), 139.2 (Carom-1), 133.9
(Carom-4), 129.5 (Carom-3 + Carom-5), 128.3 (Carom-2 +
Carom-6), 52.2 (C-8), 51.3 (CO2Me), 32.2 (CH2CH2SMe),
30.1 (CH2CH2SMe), 15.2 (SMe). – MS ((+)-FAB): m/z =
382/384 [M+H]+. – C16H17ClN2O3S2 (384.90): calcd. C
49.93, H 4.45, N 7.28; found C 49.76, H 4.33, N 7.00.
Methyl (3-(2-(4-chlorophenyl)thiazole)-4-carboxamido)-2-
methyl-3-oxopropanoate (9d)
Methyl (2-(2-(4-chlorophenyl)thiazole)-4-carboxamido)-
acetate (9a)
From L-alanine methyl ester (240 mg). Yield: 422 mg
(65%), m. p. 149–152 ◦C. – 1H NMR ([D6](DMSO): δ =
9.82 (1H, br s, NH), 9.12 (1H, s, 5-Hthiazole), 7.95 (2H, d,
J = 8.4 Hz, 2-Harom + 6-Harom), 7.51 (2H, d, J = 8.4 Hz, 3-
Harom + 5-Harom), 3.74 (3H, s, CO2Me), 4.29 (1H, m, 8-H),
1.42 (3H, d, J = 7.0 Hz, C8-Me). – 13C NMR ([D6]DMSO):
δ = 172.8 (CO2Me), 167.7 (C2thiazole), 162.7 (C=O), 149.8
From glycine methyl ester (207 mg). Yield: 415 mg
(67%), m. p. 163–166 ◦C. – 1H NMR ([D6]DMSO): δ =
9.86 (1H, m, NH), 9.21 (1H, s, H5thiazole), 7.97 (2H, d, J =
8.5 Hz, 2-Harom + 6-Harom)), 7.42 (2H, d, J = 8.5 Hz, 3-
Harom + 5-Harom), 4.19 (2H, d, J = 2.2 Hz, CH2-8), 3.71
(3H, s, CO2Me). – 13C NMR ([D6]DMSO): δ = 170.2
(Cthiazole-4), 137.1 (Carom-1), 133.3 (Carom-4), 129.6 (Carom
-
3 + Carom-5), 128.7 (Carom-2 + Carom-6), 49.3 (C-8), 51.0
(CO2Me), 19.6 (Me-C-8). – MS ((+)-FAB): m/z = 323/325
[M+H]+. – C14H13ClN2O3S (324.78): calcd. C 51.77, H
4.03, N 8.63; found C 51.49, H 3.89, N 8.82.
(CO2Me), 167.6 (Cthiazole-2), 162.7 (C=O), 149.8 (Cthiazole
-
4), 137.1 (Carom-Cl), 133.3 (Carom-4), 129.6 (Carom-3 +
Carom-5), 128.7 (Carom-2 + Carom-6), 51.0 (CO2Me), 38.2
(CH2). – MS ((+)-FAB): m/z = 309/311 [M+H]+. –
C13H11ClN2O3S (310.76): calcd. C 50.24, H 3.57, N 9.01;
found C 49.98, H 3.46, N 9.20.
Methyl (3-(2-(4-chlorophenyl)thiazole)-4-carboxamido)-2-
methylbutanoate (9e)
Methyl (3-(2-(4-chlorophenyl)thiazole)-4-carboxamido)-3-
(hydroxymethyl)-3-oxopropanoate (9b)
From L-valine methyl ester (306 mg). Yield: 534 mg
(65%), m. p. 139–142 ◦C. – 1H NMR ([D6](DMSO): δ =
From L-serine methyl ester (278 mg). Yield: 523 mg 9.76 (1H, br s, NH), 9.09 (1H, s, 5-Hthiazole), 7.89 (2H, d,
(77%), m. p. 172–175 ◦C. – 1H NMR ([D6]DMSO): δ = J = 8.6 Hz, 2-Harom + 6-Harom), 7.47 (2H, d, J = 8.5 Hz,
9.92 (1H, br s, NH), 9.15 (1H, s, 5-Hthiazole), 7.89 (2H, d, 3-Harom + 5-Harom), 3.69 (3H, s, CO2Me), 4.32 (1H, m, 8-
J = 8.7 Hz, 2-Harom + 6-Harom), 7.48 (2H, d, J = 8.7 Hz, H), 2.18 (1H, m, CH(Me)2), 0.87, 0.85 (6H, 2d, J = 6.5 Hz,
3-Harom + 5-Harom), 4.29 (2H, m, CH2OH), 4.36 (1H, CH(Me)2). – 13C NMR ([D6]DMSO): δ = 170.9 (CO2Me),
m, 8-H), 3.72 (3H, s, CO2Me), 3.54 (1H, t, J = 5.0 Hz, 168.3 (Cthiazole-2), 161.9 (C=O), 150.1 (Cthiazole-4), 138.2
CH2OH). – 13C NMR ([D6]DMSO): δ = 172.1 (CO2Me), (Carom-1), 133.9 (Carom-4), 129.6 (Carom-3 + Carom-5),
167.8 (Cthiazole-2), 161.0 (C=O), 148.9 (Cthiazole-4), 138.2 128.3 (Carom-2 + Carom-6), 54.2 (C-8), 51.3 (CO2Me),
(Carom-1), 133.8 (Carom-4), 129.6 (Carom-3 + Carom-5), 29.7 (CH(Me)2), 18.5 (CH(Me)2). – MS ((+)-FAB): m/z =
128.5 (Carom-2 + Carom-6), 59.5 (CH2OH), 55.2 (C-8), 51.1 351/353 [M+H]+. – C16H17ClN2O3S (352.84): calcd. C
(CO2Me). – MS ((+)-FAB): m/z = 339/341 [M+H]+. – 54.46, H 4.86, N 7.94; found C 54.22, H 4.69, N 7.74.
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
757
Acknowledgement
Rega Institute for Medical Research, Katholieke Universiteit
Leuven, Belgium, for the anti-HIV screening.
Prof. Al-Masoudi would like to thank Basrah Universiy
for the sabbatical leave. We thank Prof. C. Pannecouque of
[1] V. Ravichandran, B. R. P. Kumar, S. Sankar, R. K. [20] A. M. Vijesh, A. M. Isloor, V. Prabhu, S. Ahmad,
Agrawal, Eur. J. Med. Chem. 2009, 44, 1180 – 1187. S. Malladi, Eur. J. Med. Chem. 2010, 45, 5460 – 5464.
[2] T. K. Venkatachalam, E. K. Sudbeck, C. Mao, F. M. [21] M. A. Gouda, M. A. Berghot, G. E. Abd El-Ghani,
Uckun, Bioorg. Med. Chem. 2001, 11, 523 – 528.
A. M. Khalil, Eur. J. Med. Chem. 2010, 45,
[3] K. D. Hargrave, J. R. Proudfoot, K. G. Grozinger,
1338 – 1345.
E. Cullen, S. R. Kapadia, U. R. Patel, V. U. Fuchs, [22] S. K. Bharti, G. Nath, R. Tilak, S. K. Singh, Eur. J.
S. C. Mauldin, J. Vitous, J. Med. Chem. 1991, 34,
2231 – 2241.
Med. Chem. 2010, 45, 651 – 660.
[23] C. M. Moldovan, O. Oniga, A. Paˆrvu, B. Tiperciuc,
P. Verite, A. Pˆırnau, O. Crisan, M. Bojita, R. Pop, Eur.
J. Med. Chem. 2011, 46, 526 – 534.
[24] D. Branowska, A. A. Farahat, A. Kumar, T. Wenzler,
R. Brun, D. W. Boykin, Bioorg. Med. Chem. 2010, 18,
3551 – 3558.
[4] D. L. Romero, R. A. Morge, C. Biles, N. Berrios-Pena,
P. D. May, J. R. Palmer, P. D. Johnson, H. W. Smith,
M. Busso, J. Med. Chem. 1994, 37, 999 – 1014.
[5] S. D. Young, S. F. Britcher, L. O. Tran, L. S. Payne,
W. C. Lumma, T. A. Lyle, J. R. Huff, P. S. Ander-
son, D. B. Olsen, S. S. Carroll, Antimicrob. Agents [25] Y. M. Ha, J. Y. Park, Y. J. Park, D. Park, Y. J. Choi,
Chemother. 1995, 39, 2602 – 2605.
[6] E. De Clercq, Pure Appl. Chem. 2001, 73, 55 – 66.
[7] E. De Clercq, J. Med. Chem. 2005, 48, 1297 – 1313.
J. M. Kim, E. K. Lee, Y. K. Han, J. Kim, J. Y. Lee,
H. R. Moon, H. Y. Chung, Bioorg. Med. Chem. 2011,
21, 2445 – 2449.
[8] G. Barbaro, A. Scozzafava, A. Mastrolorenzo, C. T. Su- [26] T. D. Bradshaw, M. C. Bibby, J. A. Double, I. Fichtner,
puran, Curr. Pharm. Des. 2005, 11, 1805 – 1843.
[9] H. Zhao, N. Neamati, S. Sunder, H. Hong, S. Wang,
G. W. A. Milne, Y. Pommier, T. R. Burke, J. Med.
Chem. 1997, 40, 937 – 941.
P. A. Cooper, M. C. Alley, S. Donohue, S. F. Stinson,
J. E. Tomaszewjski, E. A. Sausville, M. F. G. Stevens,
Mol. Cancer Ther. 2002, 239 – 246.
[27] M. D. Wittman, J. F. Kadow, Bristol-Myers Squibb
Company, US Patent 548, 589 1996, Int. Cl. A61K
31/335; Chem. Abstr. 1996, 124, 289947a.
[10] M. Zareef, R. Iqbal, N. A. Al-Masoudi, J. H. Zaidi,
M. Arfan, Heteroatom Chem. 2007, 18, 425 – 431.
[11] W. A. El-Sayed, F. A. El-Essawy, O. M. Ali, M. M. Ab- [28] I. A. Nizova, V. P. Krasnov, G. L. Levit, M. I. Kodess,
dalla, A. A. H. Abdel-Rahman, Monatsh. Chem. 2010,
141, 1021 – 1028.
[12] A. A. El-Emam, O. A. Al-Deeb, M. Al-Omara, J. Leh-
Amino Acids 2002, 22, 179 – 186.
[29] A. Casini, A. Scozzafava, C. T. Supuran, Environ.
Health Perspect. 2002, 110, 801 – 806, and refs.
therein.
mann, Bioorg. Med. Chem. 2004, 12, 5107 – 5113.
[13] X. Zou, Z. Zhang, G. Jin, J. Chem. Res. 2002, 5, [30] K.-L. Yu, W. E. Harte, P. Spinazze, J. C. Martin,
228 – 230.
M. M. Mansuri, Bioorg. Med. Chem. Lett. 1993, 3,
535 – 538.
[14] K. Mogilaiah, G. R. Sudhakar, Ind. J. Heterocycl.
Chem. 2001, 11, 163 – 166.
[15] G. Sahin, E. Palaska, M. Ekizoglu, M. Ozalp, IL Far-
maco 2002, 57, 539 – 545.
[31] K. C. Santhosh, E. De Clercq, C. Pannecouque,
M. Witvrouw, T. L. Loftus, J. A. Turpin, R. W. Buck-
heit, M. Cushman, Bioorg. Med. Chem. Lett. 2000, 10,
2505 – 2508.
[16] N. Masuda, O. Yamamoto, M. Fujii, T. Ohgami, J. Fu-
jiyasu, T. Kontani, A. Moritomo, M. Orita, H. Kurihara, [32] I. A. I. Ali, I. A. Al-Masoudi, B. Saeed, N. A. Al-
H. Koga, S. Kageyama, M. Ohta, H. Inoue, T. Hatta,
M. Shintani, H. Suzuki, K. Sudo, Y. Shimizu, E. Ko-
Masoudi, P. La Colla, Heteroatom Chem. 2005, 16,
148 – 155.
dama, M. Matsuoka, M. Fujiwara, T. Yokota, S. Shige- [33] N. A. Al-Masoudi, I. A. Al-Masoudi, I. A. I. Ali,
tad, M. Baba, Bioorg. Med. Chem. 2005, 13, 949 – 961.
[17] T. Akhtar, S. Hameed, N. A. Al-Masoudi, R. Loddo,
P. L. Colla, Acta Pharm. 2008, 58, 135 – 149.
[18] N. Siddiqui, W. Ahsan, Eur. J. Med. Chem. 2010, 45,
1536 – 1543.
B. Saeed, P. La Colla, Heteroatom Chem. 2005, 16,
576 – 586.
[34] I. A. I. Ali, I. A. Al-Masoudi, Y. A. Al-Soud, B. Saeed,
N. A. Al-Masoudi, P. La Colla, Acta Pharm. 2006, 56,
175 – 188.
[19] K. Liaras, A. Geronikaki, J. Glamocˇlija, A. C´ıricˇ, [35] N. S. Hamad, N. H. Al-Haidery, I. A. Al-Masoudi,
M. Sokovicˇ, Bioorg. Med. Chem. 2011, 19, 3135 –
3140.
M. Sabri, L. Sabri, N. A. Al-Masoudi, Arch. Pharm.
2010, 343, 397 – 403.
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM

758
M. Zia et al. · New Aryl-1,3-thiazole-4-carbohydrazides
[36] N. A. Al-Masoudi, N. N. H. Al-Haidery, N. T. Faili, and
C. Pannecouque, Arkivoc 2010, ix, 185 – 195.
[37] V. A. Mamedov, I. A. Nuretdinov, F. G. Sibgatullina,
Bull. Russ. Acad. Sci. 1992, 41, 534 – 536.
[38] M. F. Summers, L. G. Marzilli, A. Bax, J. Am. Chem.
Soc. 1986, 108, 4285 – 4294.
[39] K. D. Hargrave, J. R. Proudfoot, K. G. Grozinger,
E. Cullen, S. R. Kapadia, U. R. Patel, V. U. Fuchs,
S. C. Mauldin, J. Vitous, M. L. Behnke, J. M. Klun-
der, K. Pal, J. W. Skiles, D. W. McNeil, J. M. Rose,
G. C. Chow, M. T. Skoog, J. C. Wu, G. Schmidt,
W. W. Engel, W. G. Eberlein, T. D. Saboe, S. J. Camp-
bell, A. S. Rosenthal, J. Adam, J. Med. Chem. 1991,
34, 2231 – 2241.
[40] H. Mitsuya, K. J. Weinhold, P. A. Furman, M. H.
St. Clair, S. N. Lehrmann, R. Gallo, D. Bolognesi,
D. W. Barry, S. Broder, Proc. Natl. Acad. Sci. USA
1985, 82, 7096 – 7100.
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 5/19/15 6:33 PM