• Archives of Pharmacal Research
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• v.23 no.1
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• pp.35-41
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• 2000

In order to investigate the stereochemical requirements of planar structure at 4-position of 4-phenyl-1-arylsulfonylimidazolidinones (1) for their cytoxicities against human cancer cell lines, the size, the distance from imidazolidinone ring, and the conformation of this moiety were variegated. Replacement of phenyl moiety with naphthyl in compounds 2 and 3 or benzyl moiety in compound 4 sharply reduced activity of 1. Conformational restriction on phenyl ring in compound 5 also resulted in the loss of activity of 1. Therefore, phenyl moiety without any substituents directly attached to imidazolidinone ring of 1 should be considered as an essential pharmacophore for this analog.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.499-502
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• 2001

To evaluate the role of imidazolidinone moiety of potential anticancer 4-phenyl-1-arylsulfonylimidazolidinones 1 for their cytotoxicity conformationally similar 4-phenyl-2-arylsulfonylaminooxazolines 2 were synthesized and compared their cytotoxicities with those of the corresponding 1. Compounds 2 showed much reduced activity compared to N-arylsulfonylimidazolidinones 1. This result might indicate that the imidazolidinone ring of 1 have the other roles for the activity as an essential structural motif in addition to conformational contribution .

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.167.2-167.2
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• 2000

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.344.3-345
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• 2002

For the development of novel anticancer agent. we have designed. synthesized. and tested novel 4-phenyl-1(N)-arylsulfonylimidazolidinones. As a result. much more potent cytotoxicities of these compounds against the various cancer cell lines than those of doxorubicin were demonstrated. Elaboration on aryl motif on sulfonyl moiety led us to find highly potent 4-phenyl-1-(N-acylindoline-5-sulfonyl)imidazolidinones. Among them, 4-phenyl-l- ［N-(p-aminobenzoyl)indoline-5-sulfonyl］imidazolidinone (PA) was proved to have good pharmacological profile. (omitted)

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.421-427
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• 2002

For probing the importance of planarity of imidazolidinone motif of 4-phenyl-1-(N-acylindoline-5-sulfonyl)imidazolidinones 1 for their cytotoxicity, 4-phenyl-1-(N-acylindoline-5-sulfonyl)[1,2,5]thiadiazolidine-1,1-dioxides 2 were prepared and their cytotoxicity were measured against human lung carcinoma (A549), human colon carcinoma (COLO205), human ovarian cancer (SK-OV-3), human leukemic cancer (K562), and murine colon adenocarcinoma (Colon26) cell lines in vitro. Although only carbonyl moiety of imidazolidinone ring was replaced with sulfonyl group, compounds 2 do not show any activity against all five cancer cell lines unlike 1. Therefore the planarity of imidazolidinone ring of 1 should be an important factor for their cytotoxic activity.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.9-14
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• 2003

For probing the importance of planarity of imidazolidinone motif of 4-phenyl-1-(benzenesulfonyl)imidazolidinones 1 for their cytotoxicity, 4-phenyl-2-(benzoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2a), 4-phenyl-2-(p-toluoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2b), 4-phenyl-2-(phenylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3a), and 4-phenyl-2-(p-tolylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3b) were prepared along with their regioisomers (5a, 5b, 9a, 9b) and their cytotoxicity were measured against human lung carcinoma (A549), human colon carcinoma (COLO205), human ovarian cancer (SK-OV-3), human leukemic cancer (K562), and murine colon adenocarcinoma (Colon26) cell lines in vitro. All compounds prepared do not show any activity against all five cancer cell lines unlike 1. Compounds 1 possess planarity of imidazolidinone, especially in sulfonylurea moiety ($-SO_2$NHCONH-). However compounds 2 and 3 have nonplanar 5-membered ring, [1,2,5]thiadiazolidine-1,1-dioxides. Such structural differentiation might result in the loss of activity. Therefore the inactivity of 2 and 3 could also be an indication for the necessity of planarity of imidazolidinone ring of 1 for their cytotoxic activity.

• Archives of Pharmacal Research
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• v.23 no.6
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• pp.579-584
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• 2000

To explore the effect of substituents' on phenyl motif on sulfonyl function of novel anticancer 4-phenyl-1-benzenesulfonylimidazolidinones (1), electron donating or withdrawing sub-stituents were introduced at 3 or 4-position and the analogs were tested against human lung (A549) and colon (HCT-15) cancer cell lines. Quantitative structure activity relation-ship of the 4-substituted series shows that only STERIMOL L values are well correlated. The increment of substituent's volume enhances the activity against both cell lines. The small substituent at 3-position additionally increases the activity. However naphthyl group in place of phenyl reduces the activity, Therefore the phenyl motif with sterically large substituent at 4-position and small substituent at 3-position may be important for their activity. Integration of these substituents' effects into the structural design led to discover the more potent analog, 4-phenyl-1-(N-acetylindoline-5-sulfonyl) imidazolidinone (1n).

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.570-580
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• 1996

Design and synthesis of novel 4-phenyl-1-arylsulfonylimidazolones 3 and 4-phenyl-3-arylsulfonylimidazolones 4 and evaluation of their cytotoxic activity against eleven human cancer cell lines and two murine leukemia cell lines in vitro were performed. As a result, a series of 4-phenyl-1(N)-arylsulfonylimidazolones (3) has been found to be the potential anticancer agent. Compounds 3b, 3c, and 3d exhibit strong activity as indicated by their $IC_{50}$ values 0.39, 3.19, $0.31{\mu}g/mL$ against A549 and 0.80, 0.48, $0.0007{\mu}g/mL$against SK-Mel-2, respectively. These compounds also possess much more potent activity (10-1000 times) than LY186641 against eleven other cell lines.

• Bulletin of the Korean Chemical Society
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• v.35 no.10
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• pp.2922-2928
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• 2014

To investigate the possible isosteric replacement of imidazolidinone moiety in 4-phenyl-1-arylsulfonylimidazolidinones (2) for broad and potent anti-cancer agents, a series of 5-phenyl-1H-pyrazol-3-yl 1-(acyl)indoline-5-sulfonates (4) and 1-(1-(acyl)indolin-5-ylsulfonyl)-5-phenylpyrazolidin-3-ones (5) were prepared and evaluated for their cytotoxicity against six human cancer cell lines. Although the pyrazoles 4 or pyrazolidinones 5 showed relatively good activity, still they showed lesser activity in comparison to imidazolidinones 2. These activity decreases could be interpreted with the effect of change of the hydrogen bonding characteristics and the substitution pattern on structural variations of five membered rings from imidazolidinones 2 to pyrazoles 4 and pyrazolidinones 5, respectively. Therefore, it can be concluded that 4-phenyl-1-arylsulfonylimidazolidinone is a basic pharmacophore of imidazolidinones 2.

• Archives of Pharmacal Research
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• v.29 no.9
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• pp.721-727
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• 2006

To continue exploration of structure activity relationship of novel 1-(indoline-5-sulfonyl)-4-phenylimidazolidinones (1) reported as anticancer agent with broad spectrum, three 1-(arylsulfonyl)-4-vinylimidazolidinones (2) were synthesized from methyl serinate (3) in 8 steps. Reaction of intermediate 2-phenoxycarbonylaminobut-3-enyl p-toluenesulfonate (10) with arylsulfonamide in the presence of potassium carbonate produced corresponding 2 and N-(4-vinyloxazolidin-2-yl)arylsulfonamide 11 in approximately equal ratio. This reaction is believed to undergo through urea intermediate 16 as shown in scheme 3. 1-Arylsufonyl-4-vinylimidazolidinones 2 show much reduced activity against human colon carcinoma (Colo205), human chronic myelogenous leukemia (K562), and human ovarian adenocarcinoma (SK-OV-3) and compatible activity against human lung carcinoma (A549) compared to 1. Therefore phenyl at 4-position should be the optimum planar motif for the activity of 1.