Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін»
Aim. To analyze commercially available fluorine containing compounds for the possibility of their use in the 19F NMR FAXS method.Materials and methods. The selection of fluorine-containing fragments for the study was performed using 3.9 million instock screening compounds and 248,000 in-stock buildi...
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Journal of Organic and Pharmaceutical Chemistry| _version_ | 1874364452248223744 |
|---|---|
| author | Oksiuta , Oleksandr V. Filatov, Yaroslav I. |
| author_facet | Oksiuta , Oleksandr V. Filatov, Yaroslav I. |
| author_institution_txt_mv | [
{
"author": "Oleksandr V. Oksiuta ",
"institution": "Institute of Organic Chemistry of the National Academy of Sciences of Ukraine; Chemspace LLC",
"orcid": ""
},
{
"author": "Yaroslav I. Filatov",
"institution": "Chemspace LLC; V.N. Karazin Kharkiv National University",
"orcid": ""
}
] |
| author_sort | Oksiuta , Oleksandr V. |
| baseUrl_str | https://ophcj.nuph.edu.ua/oai |
| collection | OJS |
| container_end_page | 28 |
| container_issue | 2 |
| container_start_page | 21 |
| container_title | Журнал органічної та фармацевтичної хімії |
| container_volume | 21 |
| datestamp_date | 2026-08-23T19:38:20Z |
| description | Aim. To analyze commercially available fluorine containing compounds for the possibility of their use in the 19F NMR FAXS method.Materials and methods. The selection of fluorine-containing fragments for the study was performed using 3.9 million instock screening compounds and 248,000 in-stock building-blocks from Enamine Ltd library. The selection and classification of the compounds was carried out using the DataWarrior and KNIME software. The Fluorinated Fragments library of Enamine Ltd. containing 6377 compounds, was also analyzed. To analyze the abovementioned sets of substances, the multistep workflows specially designed were used.Results and discussion. As a result of applying the workflow developed to the compound sets (both screening compounds and building blocks), 13 800 compounds were selected and further classified according to the presence of one out of 12 fluorine-containing groups. The Fluorinated Fragments library was also subjected to a similar workflow. For the latter, 8 out of 12 fluorine-containing groups were identified. Additionally, experimental 19F NMR chemical shift values for Fluorinated Fragments library compounds spectra were analyzed. It has been found that some structural classes have areas of chemical shifts intersection. On the other hand, the ranges from –40 to –60 ppm and beyond –160 ppm are free from any group of compounds from the library analyzed.Conclusions. The analysis has shown that commercially available fluorine-containing fragments do not satisfy the needs of the 19F NMR FAXS method, and further expansion of the chemical space of fluorine-containing compounds by increasing their diversity is required. |
| doi_str_mv | 10.24959/ophcj.23.281281 |
| first_indexed | 2025-07-23T04:43:19Z |
| format | Article |
| fulltext |
ISSN 2308-8303 (Print) / 2518-1548 (Online) 21
Original Research
http://ophcj.nuph.edu.ua
UDC 615:004.62:543.429.23:547-302
O. V. Oksiuta1,2, Ya. I. Filatov2,3
1 Institute of Organic Chemistry of the National Academy of Sciences of Ukraine,
5 Akademika Kukharya St., 02094 Kyiv, Ukraine
2 Chemspace LLC, 85 Winston Churchill St., 02094 Kyiv, Ukraine
3 V. N. Karazin Kharkiv National University, 4 Svobody Sq., 61022 Kharkiv, Ukraine
Assessment of the Commercially Available Chemical Space
for Using in the 19F NMR FAXS Method: a Enamine Ltd. Case
Abstract
Aim. To analyze commercially available fluorine containing compounds for the possibility of their use in the 19F NMR FAXS
method.
Materials and methods. The selection of fluorine-containing fragments for the study was performed using 3.9 million in-
stock screening compounds and 248,000 in-stock building-blocks from Enamine Ltd library. The selection and classification of
the compounds was carried out using the DataWarrior and KNIME software. The Fluorinated Fragments library of Enamine
Ltd. containing 6377 compounds, was also analyzed. To analyze the abovementioned sets of substances, the multistep work-
flows specially designed were used.
Results and discussion. As a result of applying the workflow developed to the compound sets (both screening compounds
and building blocks), 13 800 compounds were selected and further classified according to the presence of one out of 12 fluo-
rine-containing groups. The Fluorinated Fragments library was also subjected to a similar workflow. For the latter, 8 out
of 12 fluorine-containing groups were identified. Additionally, experimental 19F NMR chemical shift values for Fluorinated
Fragments library compounds spectra were analyzed. It has been found that some structural classes have areas of chemical
shifts intersection. On the other hand, the ranges from –40 to –60 ppm and beyond –160 ppm are free from any group of
compounds from the library analyzed.
Conclusions. The analysis has shown that commercially available fluorine-containing fragments do not satisfy the needs of
the 19F NMR FAXS method, and further expansion of the chemical space of fluorine-containing compounds by increasing
their diversity is required.
Keywords: fluorinated fragments; fragment-based drug design; 19F NMR; FAXS method; chemoinformatics; chemical space
analysis of compounds
О. В. Оксюта1,2, Я. І. Філатов2,3
1 Інститут органічної хімії Національної академії наук України,
вул. Академіка Кухаря, 5, м. Київ, 02094, Україна
2 ТОВ «Кемспейс», вул. Вінстона Черчилля, 85, м. Київ, 02094, Україна
3 Харківський національний університет імені В. Н. Каразіна,
майдан Свободи, 4, 61022, Харків, Україна
Аналіз застосовності комерційно доступного хімічного простору для використання
у 19F ЯМР FAXS методі на прикладі НВП «Єнамін»
Анотація
Мета. Проаналізувати комерційно доступні флуоровмісні сполуки на можливість їх застосування в конкурентному
скринінгу за допомогою 19F ЯМР FAXS методу.
Матеріали та методи. Відбір флуоровмісних фрагментів для дослідження проводили з використанням наявних на скла-
ді компанії ТОВ «НВП «Єнамін» 3,9 млн скринінгових сполук та 248000 будівельних блоків. Відбір та розподіл сполук
по групах виконували за допомогою програм DataWarrior та KNIME. Проаналізували бібліотеку флуорованих фраг-
ментів ТОВ «НВП «Єнамін», що містить 6377 сполук. Для аналізу вищезазначених наборів речовин використовували
спеціально розроблені багатоступеневі алгоритми.
Результати та їх обговорення. У результаті застосування розробленого алгоритму до скринінгових сполук та будівель-
них блоків відібрано 13800 представників, які додатково класифіковано за наявністю однієї з 12 флуоровмісних груп.
ISSN 2308-8303 (Print) / 2518-1548 (Online) 22
Журнал органічної та фармацевтичної хімії 2023, 21 (2)
Бібліотеку флуорованих фрагментів також піддано подібній процедурі. Для останньої групи досліджуваних сполук
ідентифіковано наявність 8 з 12 флуоровмісних фрагментів. Крім того, проаналізовано експериментальні значення
хімічного зсуву, отримані із 19F ЯМР спектрів бібліотеки флуорованих фрагментів. З’ясовано, що деякі структурні класи
мають зони перетину хімічних зсувів. З іншого боку, у діапазонах від –40 до –60 м.д. і більше –160 м.д. не представ-
лено жодної сполуки з аналізованої бібліотеки.
Висновки. Аналіз засвідчив, що наявні комерційно доступні флуоровмісні фрагменти не задовольняють потреби 19F NMR
FAXS методу, а тому необхідно розширювати хімічний простір флуоровмісних сполук шляхом збільшення їх різноманіття.
Ключові слова: флуоровмісні фрагменти; дизайн лікарських препаратів на основі фрагментів; 19F ЯМР; метод FAXS;
хемоінформатика; аналіз хімічного простору сполук
Citation: Oksiuta, O. V.; Filatov, Ya. I. Assessment of the commercially available chemical space for using in the 19F NMR FAXS method:
a Enamine Ltd. case. Journal of Organic and Pharmaceutical Chemistry 2023, 21 (2), 21 – 28.
https://doi.org/10.24959/ophcj.23.281281
Supporting information: A list of SMARTS used in REOS filters. A list of SMARTS used for in-house Custom Filtering.
Sdf-files with 13 800 compounds comprising one of the 12 fluorine-containing groups (Set_A_SC_and_BB.7z) and 4403 compounds
with experimentally measured 19F NMR spectra (Set_B.7z).
Received: 29 March 2023; Revised: 15 May 2023; Accepted: 22 May 2023
Copyright© 2023, O. V. Oksiuta, Ya. I. Filatov. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0).
Funding: The authors received no specific funding for this work.
Conflict of interests: The authors have no conflict of interests to declare.
■ Introduction
Fluorine-containing substances have recent-
ly gained considerable attention and relevance
from a scientific and practical point of view [1 – 5].
This increased attention can be explained by the
unique properties of the fluorine atom. It can form
strong bonds with the carbon atom, but that is
not what makes it special. Due to the small ra-
dius of the atom, fluorine (like deuterium) is the
bioisosteric substitute for the hydrogen atom, and
due to its high electronegativity, it can participate
in the formation of hydrogen bonds. This combi-
nation of properties makes it possible to replace
hydrogen atoms in molecules with fluorine, and
it can lead to changes in the physicochemical and
pharmacokinetic properties of biologically active
compounds and the metabolic stability as well [6 – 9].
In addition, the presence of a fluorine atom in a
molecule makes it possible to determine the pre-
sence or absence of ligand-protein interactions for
the compound studied with further hit-to-lead
optimization. Herewith, the modified molecules
do not inevitably contain fluorine atoms [10].
One of the available and highly effective bio-
physical tools for detecting ligand-protein inter-
actions is 19F NMR screening [11 – 17]. The FAXS
method (Fluorine Chemical Shift Anisotropy and
Exchange for Screening) is used in both direct
and competitive modes and allows identification
of an interaction between a fluorine-containing
fragment and the target under study. As a rule,
well-characterized libraries of fluorine-containing
compounds are required for using in the FAXS
method [11]. This method also allows the analysis
of large mixtures (or “cocktails”) of the fluorinated
molecules-candidates simultaneously, which ma-
kes it one of the most relevant for the fragment
screening against highly scarce and/or expensive
protein targets.
However, for such a procedure, it is necessa-
ry to have pre-validated cocktails of fluorine-
containing substances. An increased number of
compounds in a cocktail, which contains insuf-
ficiently diverse structural groups, leads to an
uneven distribution of chemical shifts of fluorine
atoms and a decrease in the distance between
shift signals, curbing the potential of the FAXS
method.
Thus, to assess the possibility of a widespread
use of the FAXS method, we decided to analyze
all fluorine-containing in-stock screening com-
pounds (SCs) and building blocks (BBs) offered
by Enamine Ltd. [18, 19], one of the largest sup-
pliers of small molecules, in terms of applicabili
ty in a competitive fragment screening.
■ Materials and methods
The mining of fluorine-containing fragments
for further analysis was carried out from 3.9M
in-stock SCs [20] and 248K in-stock BBs [21] de-
posited on the Enamine website since compounds
suitable for fragment-based methods occupy an
intermediate region between the given classes.
The selection and classification of compounds
were implemented using the DataWarrior [22]
and KNIME [23 – 25] software. For the analysis
of the abovementioned sets of substances, the
workflow shown in Figure 1 was used.
ISSN 2308-8303 (Print) / 2518-1548 (Online) 23
Journal of Organic and Pharmaceutical Chemistry 2023, 21 (2)
According to the presented step-by-step pro-
cedure, we performed the following operations:
Step 1 – Initial filtering:
1.1 Only fluorine-containing compounds were
filtered out;
1.2 The “Rule of 3” criteria from Astex were
applied (100 < MW < 300, logP ≤ 3, HBA ≤ 3,
HBD ≤ 3, MW was calculated for unsalted forms)
[26 – 28];
1.3 Possible covalent binders (various Michael
acceptors, terminal alkynes methylene-active com-
pounds, etc.) were removed.
Step 2 – Substances that might exhibit high
reactivity according to REOS (Rapid Elimination
of Swill) were removed in order to eliminate pos-
sible competing processes in the screening pro-
cess (for list of SMARTS see Supporting Infor-
mation file) [29].
Step 3 – Due to peculiarities of the experi-
ment (water solution and single signal in 19F NMR
per substance), the following compounds were re-
moved:
3.1 Those unstable in water due to the hydro
lysis or other processes;
3.2 Those displaying two or more signals (con-
taining several different fluorine-containing
groups, diastereomers mixture, tautomers);
3.3 Those containing highly reactive fluorine-
containing groups that were not included in the
filter of Step 2 (arylators, sulfonyl fluorides, etc.)
(see “Custom Filters” in Supporting Information
file).
Step 4 – The comparison of the filtered com-
pounds was performed, and all duplicates were
removed.
Step 5 – Classification of the remaining fluo
rine-containing compounds. For this, an analysis of
articles covering the Fluorine fragments libraries
topic and the use of fluorine-containing substances
in medicinal chemistry was carried out [1 – 5, 30 – 36].
For further classification, we used the substructural
search with SMARTS of fluorine-containing groups
[37] since such an approach has long been practiced
in analyzing large sets of compounds [38 – 40]. As a
result, we created a library of different SMARTS,
consisting of the 12 frequently encountered and
used fluorine-containing fragments (Table 1).
Enamine Ltd. also offers a Fluorinated Frag-
ments library, which contains 6377 compounds
and is available for download on the website [41].
Among the initial data for compounds presented
in this library, there are chemical shifts of 19F NMR
(in DMSO-d6 and/or D2O), which are of signifi-
cant value for further analysis of their applica-
bility in cocktails for competitive screening.
Several filters from the workflow earlier men-
tioned were applied to this set of compounds
(Figure 2):
Step 1 – Pre-filtering:
1.1 The “Rule of 3” criteria were applied to this
set [26 – 28];
1.2 Custom Filters (listed in the Supporting
Information file) were used to eliminate compounds
that might exhibit multiple signals (such as a mix-
ture of diastereomers or tautomers), as well as
undesirable reactive groups (e.g., arylators, sul-
fonyl fluorides, etc.).
Step 2 – Classification of the fluorine-con-
taining compounds with SMARTS mentioned in
Table 1.
1. Only
F-containing
cmpds
2. Ro3 criteria
3. No covalent
binders
R
E
O
S
Custom
Filters
Duplicates
removing
Dividing in
TOP-12
F groups-
(by SMARTS)
Analysis of selected
F containing cmpds-
and physсhem
parameters
(13800)
Enamine in-stock
SCs (3.9 M)
Enamine in-stock
BBs (248 K)
Figure 1. The workflow 1 for in-stock compound sets (Set A)
Enamine
Fluorinated
Fragments (6377)
Dividing in TOP-12
groups by SMARTS
(only groups8
detected)
Analysis
of experimental
19
F NMR chemical
shifts (4403)
1. Ro3 criteria
2. Custom Filters
Figure 2. The workflow 2 for Fluorinated Fragments library (Set B)
ISSN 2308-8303 (Print) / 2518-1548 (Online) 24
Журнал органічної та фармацевтичної хімії 2023, 21 (2)
Table 1. TOP-12 fluorine-containing groups and their SMARTS notations
# Group SMARTS Structure
1 CF3S FC(F)(F)[#16]
2 CF3n [#7;a]C(F)(F)F
3 CF3O [#8]C(F)(F)F
4 CF3c [#6;a]C(F)(F)F
5 CF3C [#6;A]C(F)(F)F
6 CF3SO2N [#7]S(=O)(=O)C(F)(F)F
7 OCF2C [#6;A]C([#8])(F)F
8 CCF2C [#6;A]C([#6;A])(F)F
9 CCF2c [#6;A]C([#6;a])(F)F
10 c(Aryl)F ([#6;a;$([#6]-1=[#6]-[#6]=[#6]-
[#6]=[#6]-1)])F
(with only phenyl ring)
11 c(Hetaryl)F ([#6;a;!$([#6]-1=[#6]-[#6]=[#6]-
[#6]=[#6]-1)])F (all aromatic systems, except phenyl)
12 tert-CF [#6]C([#6])([#6])F
Note: ‘n’ or N(a) – endocyclic nitrogen included into the aromatic system; ‘c’ or C(a) – carbon included into the aromatic system;
‘N’ or N(A) – aliphatic nitrogen atom; ‘C’ or C(A) – aliphatic carbon atom.
ISSN 2308-8303 (Print) / 2518-1548 (Online) 25
Journal of Organic and Pharmaceutical Chemistry 2023, 21 (2)
The chemical shift values from the 19F NMR
spectra for each subgroup from the Fluorinated
Fragments library were analyzed, compiled into
a joint table, and displayed on a common chemi-
cal shift scale. These data are discussed in the
next section.
■ Results and discussion
As a result of the implementation of Work-
flow 1 (Figure 1) to 3.9M in-stock SCs [20] and
248K in-stock BBs [21], 13 800 compounds (Set
A) comprising one of the 12 fluorine-containing
groups listed in Table 2 were classified. Next, we
applied Workflow 2 (Figure 2) for the Fluorina-
ted Fragments library. Finally, only 8 out of
12 fluorine-containing groups were identified.
The experimental data of 19F NMR spectra (in
DMSO-d6 and D2O) for a part of the substances
(Set B, 4403 compounds) from the Fluorinated
Fragments library presented on the Enamine Ltd.
website were analyzed [41]. The chemical shift
values for each group fall within a definite range,
the minimum and maximum values of which, as
well as the number of compounds sharing cer-
tain structural groups, are given in Table 2.
Based on the data obtained, it is obvious that
some structural classes have certain areas of
chemical shift intersection, which makes it dif-
ficult to create cocktails without considering the
initial experimental data. To solve this problem,
we decided to combine some of them into more
general groups. The main criterion for combin-
ing was the absence of the chemical shift over-
lap regions in a potential cocktail of fluorine-
containing molecules.
Thus, we observe several groups with practi-
cally no intersection between themselves in the
range of location on the chemical shift axis.
Figure 3 shows eight fluorine-containing groups
divided into three ranges. The first range (weak
field) contains F-aryl and F-heteroaryl deriva-
tives and tertiary F-compounds. There are two
types of difluoro compounds in the middle of the
shift axis. In the strong field, three types of tri-
fluoromethyl derivatives are located. Correspon-
dingly, the range from –40 to –60 ppm is not oc-
cupied by any group of compounds from the li-
brary analyzed, and the span with values be-
yond –160 ppm is also abandoned.
Thus, it has been found that combining se-
veral groups, including a variety of fluorinated
fragments, allows improving and simplifying the
preparation of cocktails for further screening.
However, to realize all the possibilities of the
FAXS method, the use of the most common fluo-
rine-containing groups is insufficient since they
do not cover the entire range of the chemical
shifts. This point requires further study, consi-
dering the deeper structural features of the com-
pounds.
Based on the values of the range for some
structural groups obtained, it can be assumed that
to realize the maximum possible number of com-
pounds in a cocktail, it is necessary to collect more
experimental spectral data for different fluorine-
containing compounds or, in an alternative way –
develop a powerful mathematical algorithm for
predicting the chemical shift for 19F NMR.
The disadvantage of both sets – Set A (Figure 4)
and Set B, is the apparent overpopulation of some
groups, which leads to a pronounced limitation of
the chemical diversity of compounds in probable
Table 2. Fluorine-containing groups, the number of compounds in each (for Set A and Set B), and the range of chemical shift values
(only for Set B)
# Group Set A, cmpds Set B, cmpds
Experimental 19F NMR for the Set B
dmin, ppm dmax, ppm
1 CF3S 21 0 – –
2 CF3n 2 0 – –
3 CF3O 161 15 –57 –60
4 CF3c 1413 451 –57 –71
5 CF3C 2267 323 –61 –84
6 CF3SO2N 5 0 – –
7 OCF2C 18 1 – –
8 CCF2C 1113 2 –92 –92
9 CCF2c 113 2 –100 –103
10 c(Aryl)F 8078 3247 –104 –150
11 c(Hetaryl)F 297 342 –109 –159
12 tert-CF 312 20 –137 –144
Total 13800 4403
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Журнал органічної та фармацевтичної хімії 2023, 21 (2)
cocktails. Therefore, it is necessary either to re-
duce the total number of possible cocktails of the
fluorine-containing compounds included in the
cocktails or to populate already existing groups
with compounds to obtain a uniform distribution
both in chemical diversity and in the signal shift
for the fluorine atom.
■ Conclusions
The analysis has revealed that relying solely
on the most commonly used fluorine-containing
fragment groups is inadequate for achieving the de-
sired cocktail outcomes. It necessitates more pre-
cise fragment modifications based on the structural
Figure 3. Distribution of chemical shift ranges of eight fluoridated groups for Set B
Figure 4. Distribution of compounds among 12 fluorine-containing groups for Set A (13800 cmpds)
ISSN 2308-8303 (Print) / 2518-1548 (Online) 27
Journal of Organic and Pharmaceutical Chemistry 2023, 21 (2)
characteristics of the compounds. Two possible ways
of enhancing compound collections suitable for the
FAXS method have been suggested. The first one
is collecting experimental spectral data for vari-
ous promising fluorine-containing compounds.
The second one is to develop a high-performance
mathematical tool for predicting the chemical shift
for fluorinated compounds with a desirable diver-
sity. The analysis has also shown the presence of
a pronounced overpopulation and underpopulation
of several structural groups of fluorine-containing
substances. As a result, to effectively use commer-
cially available collections of fluorine-containing
compounds and realize the full power of fragment
screening methods, it is necessary to increase the
representation in underpopulated areas to create
ideal and full-fledged cocktails.
■ Acknowledgments
The authors express their gratitude to
Enamine Ltd. for granting access to their data
sets. We also thank Prof. Dr. Dmitriy M. Voloch-
nyuk and Dr. Yurii S. Moroz for insightful dis-
cussions, and Prof. Dr. Andrey A. Tolmachev for
his encouragement and support, as well as all
the brave defenders of Ukraine for making this
publication possible.
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Information about the authors:
Oleksandr V. Oksiuta (corresponding author), Ph.D. Student of the Biologically Active Compounds Department, Institute of Organic
Chemistry of the National Academy of Sciences of Ukraine; Data Scientist at Chemspace LLC; https://orcid.org/0000-0003-3049-0373;
e-mail for correspondence: aloksyuta2010@gmail.com.
Yaroslav I. Filatov, Ph.D. Student of the Inorganic Chemistry Department, V. N. Karazin Kharkiv National University; Data Scientist
at Chemspace LLC; https://orcid.org/0009-0008-8693-1135.
|
| id | oai:ojs.journals.uran.ua:article-281281 |
| institution | Journal of Organic and Pharmaceutical Chemistry |
| issn | 2518-1548 |
| keywords_txt_mv | |
| language | English |
| last_indexed | 2026-08-24T01:00:37Z |
| publishDate | 2023 |
| publisher | National University of Pharmacy |
| record_format | ojs |
| resource_txt_mv | ophcjnupheduua/47/bab8f60b84f2a7b122a7e8874b0b4e47.pdf |
| spelling | oai:ojs.journals.uran.ua:article-2812812026-08-23T19:38:20Z Assessment of the Commercially Available Chemical Space for Using in the 19F NMR FAXS Method: a Enamine Ltd. Case Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін» Oksiuta , Oleksandr V. Filatov, Yaroslav I. fluorinated fragments fragment-based drug design 19F NMR FAXS method chemoinformatics chemical space analysis of compounds флуоровмісні фрагменти дизайн лікарських препаратів на основі фрагментів 19F ЯМР метод FAXS хемоінформатика аналіз хімічного простору сполук Aim. To analyze commercially available fluorine containing compounds for the possibility of their use in the 19F NMR FAXS method.Materials and methods. The selection of fluorine-containing fragments for the study was performed using 3.9 million instock screening compounds and 248,000 in-stock building-blocks from Enamine Ltd library. The selection and classification of the compounds was carried out using the DataWarrior and KNIME software. The Fluorinated Fragments library of Enamine Ltd. containing 6377 compounds, was also analyzed. To analyze the abovementioned sets of substances, the multistep workflows specially designed were used.Results and discussion. As a result of applying the workflow developed to the compound sets (both screening compounds and building blocks), 13 800 compounds were selected and further classified according to the presence of one out of 12 fluorine-containing groups. The Fluorinated Fragments library was also subjected to a similar workflow. For the latter, 8 out of 12 fluorine-containing groups were identified. Additionally, experimental 19F NMR chemical shift values for Fluorinated Fragments library compounds spectra were analyzed. It has been found that some structural classes have areas of chemical shifts intersection. On the other hand, the ranges from –40 to –60 ppm and beyond –160 ppm are free from any group of compounds from the library analyzed.Conclusions. The analysis has shown that commercially available fluorine-containing fragments do not satisfy the needs of the 19F NMR FAXS method, and further expansion of the chemical space of fluorine-containing compounds by increasing their diversity is required. Мета. Проаналізувати комерційно доступні флуоровмісні сполуки на можливість їх застосування в конкурентному скринінгу за допомогою 19F ЯМР FAXS методу.Матеріали та методи. Відбір флуоровмісних фрагментів для дослідження проводили з використанням наявних на складі компанії ТОВ «НВП «Єнамін» 3,9 млн скринінгових сполук та 248000 будівельних блоків. Відбір та розподіл сполук по групах виконували за допомогою програм DataWarrior та KNIME. Проаналізували бібліотеку флуорованих фрагментів ТОВ «НВП «Єнамін», що містить 6377 сполук. Для аналізу вищезазначених наборів речовин використовували спеціально розроблені багатоступеневі алгоритми.Результати та їх обговорення. У результаті застосування розробленого алгоритму до скринінгових сполук та будівельних блоків відібрано 13800 представників, які додатково класифіковано за наявністю однієї з 12 флуоровмісних груп. Бібліотеку флуорованих фрагментів також піддано подібній процедурі. Для останньої групи досліджуваних сполук ідентифіковано наявність 8 з 12 флуоровмісних фрагментів. Крім того, проаналізовано експериментальні значення хімічного зсуву, отримані із 19F ЯМР спектрів бібліотеки флуорованих фрагментів. З’ясовано, що деякі структурні класи мають зони перетину хімічних зсувів. З іншого боку, у діапазонах від –40 до –60 м.д. і більше –160 м.д. не представлено жодної сполуки з аналізованої бібліотеки.Висновки. Аналіз засвідчив, що наявні комерційно доступні флуоровмісні фрагменти не задовольняють потреби 19F NMR FAXS методу, а тому необхідно розширювати хімічний простір флуоровмісних сполук шляхом збільшення їх різноманіття. National University of Pharmacy 2023-08-30 Article Article application/pdf application/pdf application/x-7z-compressed application/x-7z-compressed https://ophcj.nuph.edu.ua/article/view/281281 10.24959/ophcj.23.281281 Journal of Organic and Pharmaceutical Chemistry; Vol. 21 No. 2 (2023); 21-28 Журнал органической и фармацевтической химии; Том 21 № 2 (2023); 21-28 Журнал органічної та фармацевтичної хімії; Том 21 № 2 (2023); 21-28 2518-1548 2308-8303 en https://ophcj.nuph.edu.ua/article/view/281281/277042 https://ophcj.nuph.edu.ua/article/view/281281/277043 https://ophcj.nuph.edu.ua/article/view/281281/277045 https://ophcj.nuph.edu.ua/article/view/281281/277046 Copyright (c) 2023 Oleksandr V. Oksiuta , Yaroslav I. Filatov http://creativecommons.org/licenses/by/4.0 |
| spellingShingle | флуоровмісні фрагменти дизайн лікарських препаратів на основі фрагментів 19F ЯМР метод FAXS хемоінформатика аналіз хімічного простору сполук Oksiuta , Oleksandr V. Filatov, Yaroslav I. Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін» |
| title | Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін» |
| title_alt | Assessment of the Commercially Available Chemical Space for Using in the 19F NMR FAXS Method: a Enamine Ltd. Case |
| title_full | Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін» |
| title_fullStr | Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін» |
| title_full_unstemmed | Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін» |
| title_short | Аналіз застосовності комерційно доступного хімічного простору для використання у 19F ЯМР FAXS методі на прикладі НВП «Єнамін» |
| title_sort | аналіз застосовності комерційно доступного хімічного простору для використання у 19f ямр faxs методі на прикладі нвп «єнамін» |
| topic | флуоровмісні фрагменти дизайн лікарських препаратів на основі фрагментів 19F ЯМР метод FAXS хемоінформатика аналіз хімічного простору сполук |
| topic_facet | fluorinated fragments fragment-based drug design 19F NMR FAXS method chemoinformatics chemical space analysis of compounds флуоровмісні фрагменти дизайн лікарських препаратів на основі фрагментів 19F ЯМР метод FAXS хемоінформатика аналіз хімічного простору сполук |
| url | https://ophcj.nuph.edu.ua/article/view/281281 |
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