2-((5-(3-(2-Fluorophenyl)acryloyl)-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of the Title Compound 3
2.2. In Vitro Evaluation of the Anticancer Activity of Compound 3
2.3. Molecular and Pharmacokinetic Properties
3. Materials and Methods
3.1. General Information and Compound 3 Synthesis
3.1.1. 2-((5-Acetyl-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione (2)
3.1.2. (E)-2-((5-(3-(2-Fluorophenyl)acryloyl)-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione (3)
3.2. In Vitro Anticancer Assay
3.3. Molecular and Pharmacokinetic Properties
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | 60 Cell Lines Assay in One Dose, 10 μM | ||
---|---|---|---|
Mean Growth, % | Range of Growth, % | Most Sensitive Cell Line(s) Growth Inhibition Percent 1/Line/Panel 2 | |
3 | 12.53 | −49.97 to 62.87 | −3.50/RPMI-8226/L −17.47/HOP-62/NSCLC 3.87/KM12/CC −49.97/SF-539/CNSC 4.88/SNB-19/CNSC 3.98/U251/CNSC −22.59/MDA-MB-435/M 4.94/SK-MEL-5/M 0.65/UACC-62/M −5.19/OVCAR-3/OC −27.71/OVCAR-8/OC −3.97/NCI/ADR-RES/OC 1.87/RXF 393/RC −2.72/SN12C/RC −44.35/DU-145/PC −10.35/T-47D/BC −15.65/MDA-MB-468/BC |
Disease | Cell Line | GI50, μM 1 | SI (GI50) | TGI, μM | SI (TGI) | LC50, μM |
---|---|---|---|---|---|---|
NSC lung cancer | HOP-62 NCI-H460 | 3.18 6.25 | 4.94 2.51 | >100.0 28.1 | - 1.80 | >100.0 >100.0 |
Colon cancer | COLO 205 | 1.70 | 9.24 | No data | No data | No data |
Ovarian cancer | SK-OV-3 | 3.28 | 4.79 | >100.0 | - | >100.0 |
Breast cancer | T-47D | 2.78 | 5.65 | >100.0 | - | >100.0 |
Physicochemical Properties | ||
---|---|---|
1 | Molecular weight | 407.42 |
2 | Num. of heavy atoms | 29 |
3 | Num. of arom. heavy atoms | 17 |
4 | Num. of rotatable bonds | 5 |
5 | Num. of H-bond acceptors | 5 |
6 | Num. of H-bond donors | 1 |
7 | Molar refractivity | 111.14 |
8 | TPSA Å2 | 107.61 |
9 | Consensus log Po/w | 3.82 |
10 | LipinskiˈRule | Yes |
Pharmacokinetics | ||
11 | GI absorption | High |
12 | BBB permeant | No |
13 | P-gp substrate | No |
14 | CYP1A2 inhibitor | Yes |
15 | CYP2C19 inhibitor | Yes |
16 | CYP2C9 inhibitor | Yes |
17 | CYP2D6 inhibitor | No |
18 | CYP3A4 inhibitor | Yes |
19 | Log Kp (SP) (cm/s) (skin permeation) | −5.42 |
20 | Bioavailability score | 0.55 |
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Fedusevych, O.-M.; Lozynskyi, A.; Sulyma, M.; Lesyk, R. 2-((5-(3-(2-Fluorophenyl)acryloyl)-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione. Molbank 2024, 2024, M1785. https://doi.org/10.3390/M1785
Fedusevych O-M, Lozynskyi A, Sulyma M, Lesyk R. 2-((5-(3-(2-Fluorophenyl)acryloyl)-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione. Molbank. 2024; 2024(1):M1785. https://doi.org/10.3390/M1785
Chicago/Turabian StyleFedusevych, Olha-Maria, Andrii Lozynskyi, Marta Sulyma, and Roman Lesyk. 2024. "2-((5-(3-(2-Fluorophenyl)acryloyl)-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione" Molbank 2024, no. 1: M1785. https://doi.org/10.3390/M1785