Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії
The rational expansion of chemical space through molecular hybridization is a key strategy in the discovery of novel bioactive scaffolds. In this study, we report on the synthesis and structural characterization of a new series of hybrid molecules that combine coumarin and 1,3,4-thiadiazole framewor...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2025
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| author | Rybina, Yelyzaveta Y. Moskvina, Viktoriia S. Khilya, Volodymyr P. |
| author_facet | Rybina, Yelyzaveta Y. Moskvina, Viktoriia S. Khilya, Volodymyr P. |
| author_institution_txt_mv | [
{
"author": "Yelyzaveta Y. Rybina",
"institution": "Taras Shevchenko National University of Kyiv, Kyiv, Ukraine"
},
{
"author": "Viktoriia S. Moskvina",
"institution": "Taras Shevchenko National University of Kyiv, Kyiv, Ukraine; V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine "
},
{
"author": " Volodymyr P. Khilya",
"institution": "Taras Shevchenko National University of Kyiv, Kyiv, Ukraine"
}
] |
| author_sort | Rybina, Yelyzaveta Y. |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:55Z |
| description | The rational expansion of chemical space through molecular hybridization is a key strategy in the discovery of novel bioactive scaffolds. In this study, we report on the synthesis and structural characterization of a new series of hybrid molecules that combine coumarin and 1,3,4-thiadiazole frameworks, bearing diverse cycloalkyl and phenyl substituents at the 3-position of the coumarin ring. The synthetic route involved Knoevenagel condensation of substituted salicylaldehydes with β-ketoesters, followed by condensation with thiosemicarbazide and subsequent heterocyclization in acetic anhydride. The resulting coumarin-1,3,4-thiadiazol hybrids were obtained in good yields and fully characterized by 1H and 13C NMR spectroscopy. The integration of privileged heterocyclic motifs with varied hydrophobic fragments led to the creation of structurally diverse molecules, contributing to the expansion of chemical space relevant to medicinal chemistry and providing valuable scaffolds for future biological studies |
| doi_str_mv | 10.15407/bioorganica2025.01.010 |
| first_indexed | 2025-07-17T12:20:08Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2025, Vol. 20, N 1
UDC 547.568.1+547.587.5
DOI: https://doi.org/10.15407/bioorganica2025.01.010
10
Ukrainica Bioorganica Acta
www.bi oorgan ica .org .ua
RESEARCH ARTICLE
Design, synthesis and structural characterization of coumarin-1,3,4-
thiadiazole hybrids bearing cycloalkyl and phenyl substituents:
expanding the chemical space for medicinal chemistry
Yelyzaveta Y. Rybina1, Viktoriia S. Moskvina1,2*, Volodymyr P. Khilya1
1 Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
2 V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine
Abstract: The rational expansion of chemical space through molecular hybridization is a key strategy in the discovery of novel bioactive
scaffolds. In this study, we report on the synthesis and structural characterization of a new series of hybrid molecules that combine
coumarin and 1,3,4-thiadiazole frameworks, bearing diverse cycloalkyl and phenyl substituents at the 3-position of the coumarin ring. The
synthetic route involved Knoevenagel condensation of substituted salicylaldehydes with β-ketoesters, followed by condensation with
thiosemicarbazide and subsequent heterocyclization in acetic anhydride. The coumarin-1,3,4-thiadiazol hybrids were obtained in good
yields and fully characterized by 1H and 13C NMR spectroscopy. The integration of privileged heterocyclic motifs with varied hydrophobic
fragments led to the creation of structurally diverse molecules, contributing to the expansion of chemical space relevant to medicinal
chemistry and providing valuable scaffolds for future biological studies.
Keywords: coumarin; benzopyran-2-one; thiosemicarbazone; 1,3,4-thiadiazole; Knoevenagel condensation; heterocyclization; molecular
hybridization; NMR spectroscopy.
Introduction
The development of novel bioactive molecules remains a
central challenge in contemporary medicinal chemistry. One
of the most powerful strategies to address this challenge is
molecular hybridization – a rational design approach that
involves the fusion of two or more pharmacophoric
fragments within a single molecular framework. This
strategy not only enables the enhancement or modulation of
biological activity but also supports the development of
multitarget-directed compounds, which is especially
valuable in the treatment of complex and multifactorial
diseases [1]. In this context, molecular hybridization serves
as a versatile tool for expanding chemical space and
generating new classes of functionally enriched compounds.
Received:
Revised:
Accepted:
Published online:
19.03.2025
26.03.2025
02.04.2025
30.06.2025
Corresponding author. Tel.: +380-66-791-0921;
e-mail: v.moskvina@gmail.com (V.S. Moskvina)
ORCID: 0000-0001-5556-9147
NHS
NN
F
F
F
O
OH
O
OH
OO
O O
N
N
N N
S
R
O
Ar
NO2
S
N
O
N
N
S
1
2
3
Figure 1. Examples of multifunctional agents based on coumarin,
1,3,4-thiadiazole, and cyclopropyl fragments.
Among the privileged heterocyclic scaffolds, coumarins
have attracted considerable attention due to their broad
spectrum of pharmacological activities, including
antioxidant [2], anti-inflammatory [3], antibacterial [4],
antitumor [5] and neuroprotective effects [6]. Structural
modification of the coumarin core, particularly through the
introduction of heterocyclic or aliphatic moieties, offers a
promising pathway to fine-tune their physicochemical and
© Rybina Y.Y. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
V.S. Moskvina et al.
11
O O
R
AcN
N
S
NHAc
R1
O O
(cyclo)alkyl-
or Ph
N N
S
R=Me,
cyclopropyl,
Ph;
R1=H, OMe
Figure 2. Molecular hybridization strategy combining coumarin, 1,3,4-thiadiazole, and cycloalkyl/phenyl fragments.
R1
OH
O
R
O
OEt
O
Piperidine, EtOH,
O O
R
O
R1
4-6 10-18
R = Me (7), Ph (8),
cyclopropyl (9)
O O
O
O O
O
MeO
MeOO O
O
O O
Ph
O
O O
Ph
O
MeO
MeOO O
Ph
O
O O
O
O O
O
MeO
MeOO O
O
10, 89%* 11, 78%* 12, 85%*
13, 92%* 14, 87%* 15, 91%*
16, 94%* 17, 89% 18, 91%
* Previously reported compounds; synthesis described in the literature, but physicochemical data were incomplete or only partially provided
(see Experimental section for references).
Scheme 1. Synthesis of 3-acetyl(benzoylcyclopropanecarbonyl)-2H-chromen-2-one derivatives 10-18 from substituted salicylaldehydes
and β-ketoesters via Knoevenagel condensation.
biological profiles. In parallel, 1,3,4-thiadiazole represents a
valuable heterocyclic motif in drug design owing to its
favorable electronic properties, ability to participate in
hydrogen bonding, and its proven bioactivity across diverse
therapeutic areas [7]. The inclusion of a thiadiazole ring
often enhances binding interactions with biological targets
and contributes to improved pharmacokinetic profiles.
Furthermore, cyclopropyl groups have emerged as
privileged motifs in medicinal chemistry due to their unique
conformational rigidity, high lipophilicity, and ability to
block metabolic hot spots [8]. Incorporation of cyclopropyl
fragments has been shown to improve metabolic stability,
oral bioavailability, and target affinity in various drug
candidates. The simultaneous integration of these three
fragments – coumarin, thiadiazole, and cyclopropyl – into a
single molecular entity provides a rational basis for the
development of new multifunctional agents with enhanced
pharmacodynamic and pharmacokinetic properties.
Literature reports support the potential of such hybrids to
exert potent anti-infective (compound 1, [9]), antibacterial
(compound 2, [10]) and anticancer (compound 3, [11])
activities (Figure 1).
In this work, we present a synthetic approach to
coumarin-based molecular hybrids incorporating both
thiadiazole and cyclopropyl moieties. This design is aimed
at combining the complementary pharmacological features
of each fragment to explore their synergistic potential in the
search for novel biologically active compounds.
Results and Discussion
Among the various synthetic approaches for the
preparation of 3-substituted coumarins [12], the
Knoevenagel condensation was selected as the method of
choice for constructing the coumarin scaffold [13]. This
strategy was favored due to several practical and synthetic
advantages:
- mild and operationally simple reaction conditions;
- broad flexibility in the selection of basic catalysts;
- ready availability and straightforward synthesis of the
starting materials;
- ease of product purification, often affording analytically
pure target compounds without the need for extensive
chromatographic separation.
ISSN 1814-9758. Ukr. Bioorg. Acta, 2025, Vol. 20, N 1
12
Accordingly, the synthesis of the coumarin core was
accomplished by condensing substituted salicylaldehydes –
namely, 2-hydroxybenzaldehyde (4), 2-hydroxy-5-metho-
xybenzaldehyde (5), and 2-hydroxy-4-methoxybenz-
aldehyde (6) – with a set of β-ketoesters, including ethyl
3-oxobutanoate (7), ethyl 3-oxo-3-phenylpropanoate (8),
and ethyl 3-cyclopropyl-3-oxopropanoate (9), in the
presence of a catalytic amount of piperidine (Scheme 1).
The reactions proceeded smoothly under reflux in ethanol,
leading to the formation of 3-substituted coumarin
O O
R
O
R1
O O
R
N
R1
H2NHN NH2
S
EtOH, HCl,
N
H
NH2
S
10-18 19-27
O O
Me
N
N
H
NH2
S
19, 93%*
O O
Me
N
N
H
NH2
S
20, 87%*
O O
Me
N
N
H
NH2
S
21, 91%*
MeO
MeO
O O
Ph
N
N
H
NH2
S
22, 96%
O O
Ph
N
N
H
NH2
S
23, 87%
O O
Ph
N
N
H
NH2
S
24, 89%
MeO
MeO
O O
N
N
H
NH2
S
25, 94%
O O
N
N
H
NH2
S
26, 89%
O O
N
N
H
NH2
S
27, 91%
MeO
MeO
* Previously reported compounds; synthesis described in the literature, but physicochemical data were incomplete or only partially provided
(see Experimental section for references).
Scheme 2. Synthesis of thiosemicarbazones 19-27 via condensation of 3-acetyl(benzoylcyclopropanecarbonyl)coumarins 10-18 with
thiosemicarbazide.
O O
R
N
N
H
NH2
S
Ac2O
O O
R
AcN
N
S
NHAc
19-27 28-36
R1R1
O O
Me
AcN
N
S
NHAc28, 78%*
O O
Me
AcN
N
S
NHAc29, 74%
O O
Me
AcN
N
S
NHAc30, 81%
MeO
MeO
O O
Ph
AcN
N
S
NHAc31, 81%
O O
Ph
AcN
N
S
NHAc32, 75%
O O
Ph
AcN
N
S
NHAc33, 83%
MeO
MeO
O O
AcN
N
S
NHAc34, 67%
O O
AcN
N
S
NHAc35, 56%
O O
AcN
N
S
NHAc36, 63%
MeO
MeO
* Previously reported compound; synthesis described in the literature, but physicochemical data were incomplete or only partially provided
(see Experimental section for references).
Scheme 3. Heterocyclization of thiosemicarbazones 19-27 to obtain 3-(1,3,4-thiadiazol-2-yl)coumarin hybrids 28-36.
V.S. Moskvina et al.
13
Figure 3. Characteristic signals in 1H and 13C NMR spectra of 3-acetyl(benzoylcyclopropanecarbonyl)coumarins 10-18.
Figure 4. Characteristic signals in 1H NMR spectra of thiosemicarbazone derivatives 19-27.
Figure 5. Characteristic signals in 1H and 13C NMR spectra of coumarin-1,3,4-thiadiazole hybrids 28-36.
derivatives with good to excellent yields. The introduction
of the cyclopropyl moiety via β-ketoester 9 was particularly
notable, as this structural element is expected to influence
the conformational rigidity and metabolic profile of the
resulting molecules. The synthesized coumarin
intermediates thus served as versatile platforms for further
molecular hybridization with heterocyclic fragments.
The next stage of our study involved the transformation
of the synthesized 3-substituted coumarins into
thiosemicarbazone derivatives, which serve as key
intermediates for the subsequent formation of 1,3,4-thiadi-
azole rings. Thiosemicarbazones are known to undergo
intramolecular cyclization under appropriate conditions,
enabling the construction of the thiadiazole moiety directly
on the coumarin framework. Accordingly, the obtained
coumarins (compounds 10-18) were reacted with
thiosemicarbazide in the presence of a catalytic amount of
hydrochloric acid. The condensation proceeded efficiently
under reflux conditions, affording the corresponding
thiosemicarbazones (compounds 19-27) in high yields
ranging from 87% to 96% (Scheme 2). This transformation
not only confirmed the reactivity of the coumarin carbonyl
group at C-3 toward nucleophilic condensation but also
demonstrated the synthetic feasibility of introducing a
bioactive linker unit that can be further cyclized into a
thiadiazole ring.
Finally, the heterocyclization of the obtained
thiosemicarbazones 19-27 was performed in acetic
anhydride under reflux conditions for 4-6 hours. This
reaction efficiently led to the formation of benzopyran-2-
one derivatives bearing a 1,3,4-thiadiazole ring at position 3
(compounds 28-36), thus completing the molecular
hybridization strategy (Scheme 3). The cyclization
proceeded smoothly, affording the target products in good
yields ranging from 74% to 83%. Notably, compound 28
had previously been synthesized as part of a broader effort
to expand the chemical space of substituted 1,3,4-
thiadiazoles with potential antitumor activity. In earlier
studies, this scaffold demonstrated promise as a
pharmacophore for the development of more selective and
effective anticancer agents, suitable for use either as
monotherapy or in combination with conventional
chemotherapeutic drugs [14, 15].
The structure of the synthesized compounds were
confirmed by NMR spectroscopy. In the 1H NMR spectra of
the starting 3-acetylcoumarins 10-12, 3-benzoylcoumarins
13-15 and 3-cyclopropanecarbonylcoumarins 16-18, a
characteristic singlet corresponding to the proton at C-4 of
the coumarin system was observed. Specifically, the signal
appeared at 8.54-8.59 ppm for products 10-12, at 8.27-8.34
ppm for 13-15, and at 8.49-8.54 ppm for 16-18. In the 13C
NMR spectra, distinctive resonances were recorded at
ISSN 1814-9758. Ukr. Bioorg. Acta, 2025, Vol. 20, N 1
14
159.4-160.1 ppm, corresponding to the carbonyl group of
the benzopyran-2-one core, and at 200.1-200.9 ppm,
attributed to the carbonyl group at C-3 (Figure 3).
The 1H NMR spectra of thiosemicarbazones 19-27
showed, in addition to the C-4 proton signals of the
coumarin system (at 7.52-7.96 ppm), new characteristic
signals corresponding to the thiosemicarbazide moiety.
These included singlets at 7.88-8.32 ppm (SH) and 8.19-
8.44 ppm (NH), confirming the successful formation of the
thiosemicarbazone functionality (Figure 4).
The 13C NMR spectra of the target thiadiazole
derivatives 28-36 featured characteristic signals at 159.4-
161.4 ppm, attributed to the lactone carbonyl of the
coumarin system. In addition, characteristic signals for the
quaternary carbon atoms of the thiadiazole ring were
observed in the range of 56.8-72.4 ppm, supporting
successful ring closure and formation of the desired
heterocyclic system (Figure 5).
Conclusions
In conclusion, we have developed an efficient synthetic
strategy for the preparation of a novel series of coumarin-
1,3,4-thiadiazole hybrids bearing cycloalkyl and aryl
substituents. This approach allowed us not only to access
new structurally diverse molecules through a three-step
sequence – Knoevenagel condensation, thiosemicarbazone
formation, and heterocyclization – but also to significantly
expand the chemical space of functionalized coumarin-
based compounds. The incorporation of privileged
heterocyclic cores with metabolically relevant hydrophobic
fragments enhances the molecular diversity and drug-like
potential of the resulting structures. The synthesized
compounds represent valuable platforms for further
biological evaluation and optimization, particularly in the
context of anticancer and anti-infective drug discovery.
Notes
Acknowledgments and finances. The authors thank all
brave defenders of Ukraine who made this publication
possible.
The authors declare no conflict of interest.
Experimental section
The solvents were purified according to the standard
procedures. All materials were purchased from commercial
sources and used without further purification. Reaction flow
and identity of obtained compounds was controlled with
TLC on Merck F254 plates using CHCl3 : MeOH (9:1, v/v)
system as eluents. The success rate was calculated as the
number of successful experiments divided by the total
number of experiments. NMR spectra were recorded on a
Mercury-400 spectrometer (spectrometer frequency for 1H:
400 MHz, 13C: 100 MHz) from DMSO-d6 solutions. The
TMS signal was used as an internal standard. Mass spectra
were recorded on an LC-MS instrument with chemical
ionization (CI). LC-MS data were acquired on an Agilent
1200 HPLC system equipped with DAD/ELSD/LCMS-
6120 diode matrix and mass-selective detector. Melting
points were determined using a Kofler-type Leica Galen III
micro hot stage microscope.
General procedure for the preparation of coumarins 10-
18.
The corresponding β-ketoester (1 mmol) was added to a
solution of the salicylaldehyde (1 mmol) in absolute ethyl
alcohol (20 mL). A catalytic amount of N-methylpiperidine
or piperidine was added to the resulting mixture. The
reaction mixture was refluxed for 1.5-2 hours. The reaction
progress was monitored by TLC. After the reaction, the
mixture was cooled to room temperature; the precipitate
formed was filtered and washed with precooled alcohol.
The corresponding coumarins were obtained in good yields
without additional purification and crystallization.
3-Acetyl-2H-chromen-2-one (10).
Yield: 342 mg, 89%. Mp 102 °C (lit: 99.7-101.0 °C
[16]). 1H NMR (400 MHz, DMSO-d6) δ 2.56 (s, 3H), 7.39-
7.26 (m, 2H), 7.66 (t, J = 8.0 Hz, 1H), 7.85 (d, J = 7.7 Hz,
1H), 8.58 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 26.7,
115.3, 116.7, 124.1, 127.2, 128.4, 129.2, 136.4, 152.3,
159.4, 198.6. APSI MS, m/z: 189.2 [M+H]+.
3-Acetyl-6-methoxy-2H-chromen-2-one (11).
Yield: 340 mg, 78%. Mp 182 °C (lit: 180.0-183 °C [17]).
1H NMR (400 MHz, DMSO-d6) δ 2.59 (s, 3H), 3.83 (s, 3H),
7.36-7.22 (m, 2H), 7.42 (d, J = 5.6 Hz, 1H), 8.57 (s, 1H).
13C NMR (100 MHz, DMSO-d6) δ 28.6, 56.02, 110.2,
117.9, 118.3, 124.2, 129.4, 136.6, 146.3, 156.8, 159.6,
198.8. APSI MS, m/z: 219.4 [M+H]+.
3-Acetyl-7-methoxy-2H-chromen-2-one (12).
Yield: 371 mg, 85%. Mp 176 °C (lit: 178-179 °C [18,
19]). 1H NMR (400 MHz, DMSO-d6) δ 2.57 (s, 3H), 3.91
(s, 3H), 6.98-6.89 (m, 2H), 7.77 (d, J = 8.5 Hz, 1H), 8.55 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 28.8, 55.03, 100.1,
110.7, 111.3, 129.6, 130.3, 136.8, 154.3, 159.6, 160.6,
198.9. APSI MS, m/z: 219.6 [M+H]+.
3-Benzoyl-2H-chromen-2-one (13).
Yield: 473 mg, 92%. Mp 151 °C (lit: 149.7-151.2 °C
[16]). 1H NMR (400 MHz, DMSO-d6) δ 7.47-7.34 (m, 2H),
7.52 (t, J = 7.8 Hz, 2H), 7.68 (dt, J = 14.6, 7.8 Hz, 2H), 7.83
(d, J = 7.7 Hz, 1H), 7.89 (d, J = 7.6 Hz, 2H), 8.35 (s, 1H).
13C NMR (100 MHz, DMSO-d6) δ 116.3, 118.3, 126.5,
127.6, 128.1, 128.3, 128.4, 128.6×2, 129.3, 135.4, 138.4,
140.1, 154.1, 159.6, 191.6. APSI MS, m/z: 251.2 [M+H]+.
3-Benzoyl-6-methoxy-2H-chromen-2-one (14).
Yield: 488 mg, 87%. Mp 146 °C (lit: 144.0-145.5 °C
[16]). 1H NMR (400 MHz, DMSO-d6) δ 3.83 (s, 3H), 7.24
V.S. Moskvina et al.
15
(d, J = 9.1 Hz, 1H), 7.34 (d, J = 9.6 Hz, 2H), 7.51 (t, J = 7.6
Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.86 (d, J = 7.6 Hz, 2H),
8.28 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 56.4, 111.3,
118.1, 118.8, 124.2, 128.2, 128.6, 129.1×2, 135.1, 138.1,
140.3, 146.2, 157.8, 158.2, 159.8, 192.4. APSI MS, m/z:
281.4 [M+H]+.
3-Benzoyl-7-methoxy-2H-chromen-2-one (15).
Yield: 512 mg, 91%. Mp 151 °C (lit: 149-150 °C [20]).
1H NMR (400 MHz, DMSO-d6) δ 3.92 (s, 3H), 6.93 (d, J =
8.7 Hz, 1H), 7.01 (s, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.63 (t,
J = 7.5 Hz, 1H), 7.72 (d, J = 8.7 Hz, 1H), 7.83 (d, J = 7.6
Hz, 2H), 8.30 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ
56.6, 101.4, 110.6, 111.5, 128.4, 128.6, 128.7, 129.4×2,
130.6, 134.8, 138.3, 140.4, 155.3, 159.6, 160.4, 192.1. APSI
MS, m/z: 281.2 [M+H]+.
3-Cyclopropanecarbonyl-2H-chromen-2-one (16).
Yield: 412 mg, 94%. Mp 131 °C (lit: 126-128 °C [21]).
1H NMR (400 MHz, DMSO-d6) δ 1.13-1.03 (m, 5H), 7.36
(q, J = 7.5 Hz, 2H), 7.67 (d, J = 8.1 Hz, 1H), 7.85 (d, J =
7.7 Hz, 1H), 8.51 (s, 1H). 13C NMR (100 MHz, DMSO-d6)
δ 14.6×2, 40.3, 116.3, 118.4, 125.6, 128.2, 128.6, 131.6,
137.6, 153.4, 159.6, 200.8. APSI MS, m/z: 215.4 [M+H]+.
3-Cyclopropanecarbonyl-6-methoxy-2H-chromen-2-one
(17).
Yield: 435 mg, 89%. Mp 168 °C. 1H NMR (400 MHz,
DMSO-d6) δ 1.13-1.04 (m, 4H), 3.07 (t, J = 6.6 Hz, 1H),
3.83 (s, 3H), 7.25 (d, J = 9.1 Hz, 1H), 7.33 (d, J = 9.1 Hz,
1H), 7.41 (s, 1H), 8.50 (s, 1H). 13C NMR (100 MHz,
DMSO-d6) δ 15.3×2, 40.4, 56.3, 111.3, 118.1, 118.6, 123.5,
131.4, 137.6, 145.5, 157.8, 159.8, 200.6. APSI MS, m/z:
245.3 [M+H]+.
3-Cyclopropanecarbonyl-7-methoxy-2H-chromen-2-one
(18).
Yield: 434 mg, 89%. Mp 155 °C. 1H NMR (400 MHz,
DMSO-d6) δ 1.09-0.99 (m, 4H), 3.10 (q, J = 6.3 Hz, 1H),
3.90 (s, 3H), 6.91 (d, J = 8.7 Hz, 1H), 6.97 (s, 1H), 7.76 (d,
J = 8.6 Hz, 1H), 8.50 (s, 1H). 13C NMR (100 MHz, DMSO-
d6) δ 15.1×2, 40.3, 56.2, 100.9, 110.1, 110.7, 130.3, 131.4,
137.6, 154.3, 159.6, 160.5, 200.9. APSI MS, m/z: 245.2
[M+H]+.
General procedure for the preparation of thiosemi-
carbazones 19-27.
The corresponding coumarin 10-18 (1 mmol) was
dissolved in absolute ethyl alcohol (20 mL), then
thiosemicarbazide (1 mmol) and a catalytic amount of
hydrochloric acid (2-3 drops) were added to the solution.
The resulting reaction mixture was refluxed for 2-4 hours.
The reaction progress was monitored by TLC. The reaction
mixture was cooled to room temperature; the precipitate
formed was filtered and washed with alcohol.
Thiosemicarbazones were obtained in pure form without
additional crystallization.
2-(1-(2-Oxo-2H-chromen-3-yl)ethylidene)hydrazine car-
bothioamide (19).
Yield: 486 mg, 93%. Mp 168 °C (lit: synthesis reported,
mp not given [22]). 1H NMR (400 MHz, DMSO-d6) δ 2.28
(s, 3H), 7.39-7.29 (m, 3H), 7.59 (t, J = 7.8 Hz, 1H), 7.73 (d,
J = 7.8 Hz, 1H), 7.82 (s, 1H), 8.31 (s, 1H), 8.46 (s, 1H),
10.33 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 5.6, 116.5,
118.4, 123.9, 125.6, 128.1, 128.6, 133.7, 153.6, 156.2,
160.1, 181.8. APSI MS, m/z: 262.4 [M+H]+.
2-(1-(6-Methoxy-2-oxo-2H-chromen-3-yl)ethylidene)hy-
drazine carbothioamide (20).
Yield: 508 mg, 87%. Mp 182 °C (lit: synthesis reported,
Mp not given [22]). 1H NMR (400 MHz, DMSO-d6) δ 2.26
(s, 3H), 3.82 (s, 3H), 7.20 (s, 1H), 7.27 (d, J = 8.9 Hz, 1H),
7.77 (s, 1H), 8.32 (s, 1H), 8.40 (s, 1H), 10.32 (s, 1H). 13C
NMR (100 MHz, DMSO-d6) δ 5.3, 56.4, 111.5, 118.1,
118.8, 123.7, 124.2, 134.5, 145.7, 155.9, 157.6, 160.2,
181.7. APSI MS, m/z: 292.4 [M+H]+.
2-(1-(7-Methoxy-2-oxo-2H-chromen-3-yl)ethylidene)hy-
drazine carbothioamide (21).
Yield: 532 mg, 91%. Mp 184 °C (lit: synthesis reported,
mp not given [22]). 1H NMR (400 MHz, DMSO-d6) δ 2.25
(s, 3H), 3.87 (s, 3H), 6.95-6.84 (m, 2H), 7.60 (d, J = 8.7 Hz,
1H), 7.75 (s, 1H), 8.24 (s, 1H), 8.38 (s, 1H), 10.21 (s, 1H).
13C NMR (100 MHz, DMSO-d6) δ 5.1, 56.3, 100.8, 110.1,
110.8, 123.7, 130.5, 133.6, 154.3, 155.8, 159.8, 160.4,
181.6. APSI MS, m/z: 292.3 [M+H]+.
2-((2-Oxo-2H-chromen-3-yl)(phenyl)methylene)hydrazi-
ne carbothioamide (22).
Yield: 622 mg, 96%. Mp 184 °C. 1H NMR (400 MHz,
DMSO-d6) δ 7.35 (br m, 4H), 7.80-7.61 (m, 5H), 7.94 (s,
1H), 7.98 (s, 1H), 8.24 (s, 1H), 11.02 (s, 1H). 13C NMR
(100 MHz, DMSO-d6) δ 116.4, 118.4, 123.7, 125.6, 128.2,
128.6, 128.9×2, 129.4, 129.6, 131.5, 134.2, 137.9, 153.6,
156.2, 160.2, 181.7. APSI MS, m/z: 324.4 [M+H]+.
2-((6-Methoxy-2-oxo-2H-chromen-3-yl)(phenyl)methyle-
ne)hydrazine carbothioamide (23).
Yield: 617 mg, 87%. Mp 182 °C. 1H NMR (400 MHz,
DMSO-d6) δ 3.84 (s, 3H), 7.28-7.16 (m, 2H), 7.33 (m, 4H),
7.75 (d, J = 6.9 Hz, 2H), 7.91 (s, 1H), 7.95 (s, 1H), 8.24 (s,
1H), 11.02 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 55.9,
111.4, 117.9, 118.5, 123.2, 123.5, 128.6×2, 129.4×2, 131.2,
134.2, 138.1, 145.6, 156.8, 157.5, 160.1, 181.3. APSI MS,
m/z: 354.6 [M+H]+.
2-((7-Methoxy-2-oxo-2H-chromen-3-yl)(phenyl)methyle-
ne)hydrazine carbothioamide (24).
Yield: 628 mg, 89%. Mp 184 °C. 1H NMR (400 MHz,
DMSO-d6) δ 3.92 (s, 3H), 6.92 (d, J = 8.7 Hz, 1H), 7.01 (s,
1H), 7.35 (s, 3H), 7.62 (d, J = 8.6 Hz, 1H), 7.75 (d, J = 6.3
Hz, 2H), 7.87 (s, 1H), 7.93 (s, 1H), 8.23 (s, 1H), 10.93 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 56.4, 100.9, 110.6,
ISSN 1814-9758. Ukr. Bioorg. Acta, 2025, Vol. 20, N 1
16
111.6, 123.7, 128.9×2, 129.4×2, 129.8, 131.6, 133.9, 138.2,
154.6, 156.4, 160.2, 160.8, 181.6. APSI MS, m/z: 354.2
[M+H]+.
2-(Cyclopropyl(2-oxo-2H-chromen-3-yl)methylene)hy-
drazine carbothioamide (25).
Yield: 536 mg, 93%. Mp 184 °C. 1H NMR (400 MHz,
DMSO-d6) δ 0.17-0.19 (m, 2H), 0.36-0.45 (m, 3H), 7.38-
7.43 (m, 2H), 7.61 (d, J = 8.7 Hz, 1H), 7.83 (s, 1H), 8.26 (s,
1H), 8.48 (s, 1H), 10.34 (s, 1H). 13C NMR (100 MHz,
DMSO-d6) δ 2.6, 8.3×2, 116.3, 118.4, 123.6, 125.6, 128.3,
128.6, 134.4, 153.5, 156.7, 159.6, 181.6. APSI MS, m/z:
288.6 [M+H]+.
2-(Cyclopropyl(6-methoxy-2-oxo-2H-chromen-3-yl)me-
thylene)hydrazine carbothioamide (26).
Yield: 634 mg, 88%. Mp 185 °C. 1H NMR (400 MHz,
DMSO-d6) δ 0.16-0.18 (m, 2H), 0.36-0.41 (m, 3H), 3.86 (s,
3H), 7.13 (s, 1H), 7.28 (d, J = 8.9 Hz, 1H), 7.75 (d, J = 8.9
Hz, 1H), 7.86 (s, 1H), 8.31 (s, 1H), 8.43 (s, 1H), 10.46 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 2.4, 8.4×2, 56.8,
111.3, 118.1, 118.5, 123.4, 124.3, 134.4, 145.6, 155.8,
157.4, 160.1, 181.6. APSI MS, m/z: 318.4 [M+H]+.
2-(Cyclopropyl(7-methoxy-2-oxo-2H-chromen-3-yl)me-
thylene)hydrazine carbothioamide (27).
Yield: 580 mg, 91%. Mp 182 °C. 1H NMR (400 MHz,
DMSO-d6) δ 0.16-0.18 (m, 2H), 0.36-0.43 (m, 3H), 3.89 (s,
3H), 6.95-7.04 (m, 2H), 7.63 (d, J = 8.7 Hz, 1H), 7.76 (s,
1H), 8.25 (s, 1H), 8.36 (s, 1H), 10.29 (s, 1H). 13C NMR
(100 MHz, DMSO-d6) δ 2.6, 8.3×2, 56.4, 100.9, 110.3,
110.9, 123.8, 130.3, 133.5, 154.4, 155.7, 159.9, 160.2,
181.4. APSI MS, m/z: 318.5 [M+H]+.
General procedure for the preparation of thiosemi-
carbazones 28-36.
Acetic anhydride (5 mL) was added to the corresponding
thiosemicarbazone 19-27 (1 mmol) and a catalytic amount
of hydrochloric acid (2-3 drops). The resulting reaction
mixture was refluxed on a water bath for 5-6 hours. The
reaction progress was monitored by TLC. The reaction
mixture was cooled to room temperature and poured into
ice water (100 mL). The precipitate formed was filtered,
washed with distilled water and dried. Then the resulting
product was crystallized from a small amount of isopropyl
alcohol.
N-(4-Acetyl-5-methyl-5-(2-oxo-2H-chromen-3-yl)-4,5-di-
hydro-1,3,4-thiadiazol-2-yl)acetamide (28).
Yield: 540 mg, 78%. Mp 246 °C (lit: 247-249 °C [23]).
1H NMR (400 MHz, DMSO-d6) δ 2.02 (s, 3H), 2.21 (s, 3H),
2.27 (s, 3H), 7.34 (t, J = 6.9 Hz, 2H), 7.57 (t, J = 7.9 Hz,
1H), 7.77 (d, J = 7.4 Hz, 2H), 11.50 (s, 1H). 13C NMR (100
MHz, DMSO-d6) δ 24.1, 25.1, 27.6, 57.7, 116.5, 120.4,
125.6, 127.9, 128.3, 128.8, 140.2, 144.4, 153.4, 162.4,
168.8, 169.5. APSI MS, m/z: 346.4 [M+H]+.
N-(4-Acetyl-5-methyl-5-(6-methoxy-2-oxo-2H-chromen-
3-yl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (29).
Yield: 554 mg, 74%. Mp 168 °C. 1H NMR (400 MHz,
DMSO-d6) δ 2.02 (s, 3H), 2.22 (s, 3H), 2.28 (s, 3H), 3.82 (s,
3H), 7.11 (d, J = 9.1 Hz, 1H), 7.28 (m, 2H), 7.70 (s, 1H),
11.48 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 24.3, 25.4,
28.2, 56.3, 57.6, 111.3, 117.8, 118.3, 124.7, 127.8, 139.8,
144.6, 146.4, 157.6, 162.6, 168.9, 169.6. APSI MS, m/z:
376.2 [M+H]+.
N-(4-Acetyl-5-methyl-5-(7-methoxy-2-oxo-2H-chromen-
3-yl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (30).
Yield: 610 mg, 81%. Mp 168 °C. 1H NMR (400 MHz,
DMSO-d6) δ 2.01 (s, 3H), 2.18 (s, 3H), 2.24 (s, 3H), 3.86 (s,
3H), 6.95-6.83 (m, 2H), 7.68-7.59 (m, 2H), 11.44 (s, 1H).
13C NMR (100 MHz, DMSO-d6) δ 22.6, 23.4, 25.9, 56.3,
57.6, 100.6, 111.3, 112.6, 127.9, 128.4, 130.2, 140.1, 157.4,
159.8, 162.4, 168.6, 169.4. APSI MS, m/z: 376.4 [M+H]+.
N-(4-Acetyl-5-methyl-5-(2-oxo-2H-chromen-3-yl)-5-phe-
nyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (31).
Yield: 538 mg, 81%. Mp 216 °C. 1H NMR (400 MHz,
DMSO-d6) δ 2.03 (s, 2H), 2.20 (s, 3H), 7.51-7.22 (m, 9H),
7.61 (d, J = 7.7 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 11.57 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 23.6, 24.4, 67.6,
116.4, 120.5, 125.6, 127.1, 127.4, 127.8, 127.9, 128.1,
128.4, 128.8×2, 140.2, 141.2, 144.4, 153.3, 162.2, 168.9,
169.6. APSI MS, m/z: 408.5 [M+H]+.
N-(4-Acetyl-5-methyl-5-(6-methoxy-2-oxo-2H-chromen-
3-yl)-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide
(32).
Yield: 656 mg, 75%. Mp 212 °C. 1H NMR (400 MHz,
DMSO-d6) δ 2.04 (s, 3H), 2.22 (s, 3H), 3.82 (s, 3H), 7.17
(dd, J = 16.9, 9.2 Hz, 1H), 7.39-7.25 (m, 5H), 7.46 (d, J =
7.7 Hz, 1H), 7.59 (d, J = 10.7 Hz, 1H), 7.84 (s, 1H), 11.53
(s, 1H). 13C NMR (100 MHz, DMSO-d6) δ 23.4, 24.1, 56.4,
67.8, 111.3, 117.8, 118.4, 123.2, 124.7, 127.1, 127.6, 127.8,
128.1, 128.7×2, 139.9, 144.4, 146.3, 157.7, 162.4, 168.9,
169.4. APSI MS, m/z: 438.5 [M+H]+.
N-(4-Acetyl-5-methyl-5-(7-methoxy-2-oxo-2H-chromen-
3-yl)-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide
(33).
Yield: 624 mg, 73%. Mp 218 °C. 1H NMR (400 MHz,
DMSO-d6) δ 2.20 (s, 3H), 2.42 (s, 3H), 3.90 (s, 3H), 7.00-
6.89 (m, 1H), 7.01 (s, 1H), 7.39-7.22 (m, 3H), 7.47 (d, J =
7.6 Hz, 1H), 7.74-7.52 (m, 3H), 11.53 (s, 1H). 13C NMR
(100 MHz, DMSO-d6) δ 22.8, 23.6, 56.5, 67.5, 100.8,
111.2, 112.7, 127.1, 127.7×2, 127.9, 128.7×2, 130.1, 139.8,
141.3, 144.4, 157.3, 160.4, 162.6, 168.8, 169.6. APSI MS,
m/z: 438.4 [M+H]+.
N-(4-Acetyl-5-cyclopropyl-5-(2-oxo-2H-chromen-3-yl)-
4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (34).
Yield: 496 mg, 67%. Mp 198 °C. 1H NMR (400 MHz,
DMSO-d6) δ 0.16-0.18 (m, 2H), 0.37-0.40 (m, 3H), 2.18 (s,
V.S. Moskvina et al.
17
3H), 2.23 (s, 3H), 7.41 (t, J = 6.9 Hz, 1H), 7.57 (t, J = 7.9
Hz, 2H), 7.77 (d, J = 7.4 Hz, 2H), 11.50 (s, 1H). 13C NMR
(100 MHz, DMSO-d6) δ 4.6×2, 20.4, 21.3, 24.1, 25.2, 71.5,
116.4, 120.3, 125.4, 127.9, 128.3, 134.4, 144.4, 153.4,
162.6, 168.8, 169.5. APSI MS, m/z: 372.4 [M+H]+.
N-(4-Acetyl-5-cyclopropyl-5-(6-methoxy-2-oxo-2H-chro-
men-3-yl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (35).
Yield: 452 mg, 56%. Mp 184 °C. 1H NMR (400 MHz,
DMSO-d6) δ 0.16-0.18 (m, 2H), 0.37-0.41 (m, 2H), 1.06
(m, 1H), 2.24 (s, 3H), 2.29 (s, 3H), 3.86 (s, 3H), 6.96 (d, J =
9.1 Hz, 1H), 7.16 (d, J = 9.1 Hz, 1H), 7.73 (s, 1H), 7.86 (s,
1H), 11.48 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ
4.3×2, 20.4, 24.2, 25.3, 56.4, 69.6, 111.3, 117.8, 118.3,
124.7, 127.8, 139.8, 144.6, 146.4, 157.4, 162.6, 168.6,
169.4. APSI MS, m/z: 402.6 [M+H]+.
N-(4-Acetyl-5-cyclopropyl-5-(2-oxo-2H-chromen-3-yl)-
4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (36).
Yield: 508 mg, 63%. Mp 188 °C. 1H NMR (400 MHz,
DMSO-d6) δ 0.17-0.19 (m, 2H), 0.38-0.41 (m, 2H), 1.05
(m, 1H), 2.22 (s, 3H), 2.28 (s, 3H), 3.88 (s, 3H), 7.05 (d, J =
9.1 Hz, 1H), 7.09 (s, 1H), 7.69 (d, J = 9.1 Hz, 1H), 7.76 (s,
1H), 11.56 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ
4.4×2, 20.1, 22.7, 23.3, 56.3, 71.4, 100.8, 111.4, 112.6,
130.2, 134.6, 140.1, 144.4, 157.4, 159.8, 162.4, 168.6,
169.4. APSI MS, m/z: 402.5 [M+H]+.
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Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів
з циклоалкільними та фенільним замісниками: розширення хімічного простору для
медичної хімії
Є.Ю. Рибіна1, В.С. Москвіна1,2*, В.П. Хиля1
1 Київський національний університет імені Тараса Шевченка, Київ, Україна.
2 Інститут біоорганічної хімії та нафтохімії ім. В.П. Кухаря НАН України, Київ, Україна
Резюме: Розширення хімічного простору шляхом молекулярної гібридизації є ключовою стратегією у відкритті нових біологічно активних
структур. У даній роботі представлено синтез і структурну характеристику нової серії гібридних молекул, що поєднують фрагменти кумарину та
1,3,4-тіадіазолу і містять різноманітні (цикло)алкільні та фенільні замісники в положенні 3 кумаринового ядра. Синтетична послідовність
включала проведення конденсації Кневенагеля між заміщеними саліциловими альдегідами та β-кетоестерами, подальшу взаємодію з
тіосемікарбазидом та гетероциклізацію при дії оцтового ангідрида. Кумарин-1,3,4-тіадіазольні гібриди були синтезовані з високими виходами та
повністю охарактеризовані за допомогою методів 1Н та 13С ЯМР спектроскопії. Поєднання привілейованих гетероциклічних фрагментів із
різноманітними гідрофобними замісниками дозволило отримати структурно різноманітні молекули, що сприятиме розширенню хімічного
простору, релевантного для медичної хімії, та створенню перспективних сполук для подальшого біологічного вивчення.
Ключові слова: кумарин; бензопіран-2-он; тіосемікарбазон; 1,3,4-тіадіазол; конденсація Кневенагеля; гетероциклізація; молекулярна
гібридизація; ЯМР-спектроскопія.
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| id | oai:ojs2.bioorganica.com.ua:article-95 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:01:37Z |
| publishDate | 2025 |
| publisher | V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine |
| record_format | ojs |
| resource_txt_mv | bioorganicacomua/d8/aca097f4aab0d1f55341c7b5716457d8.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-952026-07-19T14:56:55Z Design, synthesis and structural characterization of coumarin-1,3,4-thiadiazole hybrids bearing cycloalkyl and phenyl substituents: expanding the chemical space for medicinal chemistry Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії Rybina, Yelyzaveta Y. Moskvina, Viktoriia S. Khilya, Volodymyr P. coumarin benzopyran-2-one thiosemicarbazone 1,3,4-thiadiazole Knoevenagel condensation heterocyclization molecular hybridization NMR spectroscopy кумарин бензопіран-2-он тіосемікарбазон 1,3,4-тіадіазол конденсація Кневенагеля гетероциклізація молекулярна гібридизація ЯМР-спектроскопія The rational expansion of chemical space through molecular hybridization is a key strategy in the discovery of novel bioactive scaffolds. In this study, we report on the synthesis and structural characterization of a new series of hybrid molecules that combine coumarin and 1,3,4-thiadiazole frameworks, bearing diverse cycloalkyl and phenyl substituents at the 3-position of the coumarin ring. The synthetic route involved Knoevenagel condensation of substituted salicylaldehydes with β-ketoesters, followed by condensation with thiosemicarbazide and subsequent heterocyclization in acetic anhydride. The resulting coumarin-1,3,4-thiadiazol hybrids were obtained in good yields and fully characterized by 1H and 13C NMR spectroscopy. The integration of privileged heterocyclic motifs with varied hydrophobic fragments led to the creation of structurally diverse molecules, contributing to the expansion of chemical space relevant to medicinal chemistry and providing valuable scaffolds for future biological studies Розширення хімічного простору шляхом молекулярної гібридизації є ключовою стратегією у відкритті нових біологічно активних структур. У даній роботі представлено синтез і структурну характеристику нової серії гібридних молекул, що поєднують фрагменти кумарину та 1,3,4-тіадіазолу і містять різноманітні (цикло)алкільні та фенільні замісники в положенні 3 кумаринового ядра. Синтетична послідовність включала проведення конденсації Кневенагеля між заміщеними саліциловими альдегідами та β-кетоестерами, подальшу взаємодію з тіосемікарбазидом та гетероциклізацію при дії оцтового ангідрида. Отримані кумарин-1,3,4-тіадіазольні гібриди були синтезовані з високими виходами та повністю охарактеризовані за допомогою методів 1Н та 13С ЯМР спектроскопії. Поєднання привілейованих гетероциклічних фрагментів із різноманітними гідрофобними замісниками дозволило отримати структурно різноманітні молекули, що сприятиме розширенню хімічного простору, релевантного для медичної хімії, та створенню перспективних сполук для подальшого біологічного вивчення V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2025-06-30 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/95 10.15407/bioorganica2025.01.010 Ukrainica Bioorganica Acta; Vol. 20 No. 1 (2025): Ukrainica Bioorganica Acta; 10-18 Ukrainica Bioorganica Acta; Том 20 № 1 (2025): Ukrainica Bioorganica Acta; 10-18 1814-9766 1814-9758 10.15407/bioorganica2025.01 en https://bioorganica.com.ua/index.php/journal/article/view/95/92 Copyright (c) 2025 Yelyzaveta Y. Rybina, Viktoriia S. Moskvina, Volodymyr P. Khilya https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | кумарин бензопіран-2-он тіосемікарбазон 1,3,4-тіадіазол конденсація Кневенагеля гетероциклізація молекулярна гібридизація ЯМР-спектроскопія Rybina, Yelyzaveta Y. Moskvina, Viktoriia S. Khilya, Volodymyr P. Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії |
| title | Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії |
| title_alt | Design, synthesis and structural characterization of coumarin-1,3,4-thiadiazole hybrids bearing cycloalkyl and phenyl substituents: expanding the chemical space for medicinal chemistry |
| title_full | Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії |
| title_fullStr | Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії |
| title_full_unstemmed | Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії |
| title_short | Дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії |
| title_sort | дизайн, синтез та структурна характеристика кумарин-1,3,4-тіадіазольних гібридів з циклоалкільними та фенільним замісниками: розширення хімічного простору для медичної хімії |
| topic | кумарин бензопіран-2-он тіосемікарбазон 1,3,4-тіадіазол конденсація Кневенагеля гетероциклізація молекулярна гібридизація ЯМР-спектроскопія |
| topic_facet | coumarin benzopyran-2-one thiosemicarbazone 1,3,4-thiadiazole Knoevenagel condensation heterocyclization molecular hybridization NMR spectroscopy кумарин бензопіран-2-он тіосемікарбазон 1,3,4-тіадіазол конденсація Кневенагеля гетероциклізація молекулярна гібридизація ЯМР-спектроскопія |
| url | https://bioorganica.com.ua/index.php/journal/article/view/95 |
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