Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents

Chou, Li‐Chen; Huang, Li‐Jiau; Yang, Jai Sing; Lee, Fang‐Yu; Teng, Che-Ming; Kuo, Sheng‐Chu

doi:10.1016/j.bmc.2006.12.001

Cited by 78 publications

(24 citation statements)

References 16 publications

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“…Therefore, the synthesis and selective functionalization of pyrazoleshas been thefocus of active research over theyears [1][2][3]. A survey of the literature reveals that some pyrazoles have been employed as antileukemic [4,5], antitumor [6, 7], anti-proliferative agents [8], anti-inflammatory and antimicrobial agents [9,10]. Schiff base ligands synthesized from pyrazole rings have also been employed in adiverse range of applications.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of 2-(3-chloro-phenyl)-5-methyl-4-[1-(5-methyl-4-ptolyl- thiazol-2-ylimino)-ethyl]-2,4-dihydro-pyrazol-3-one, C23H-ClN4OS

Thakar

Friedrich

Joshi³

et al. 2013

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of materialAs olution of 4-acetyl-2-(3-chloro-phenyl)-5-methyl-2,4-dihydro-pyrazol-3-one (1.0 g, 3.99 mmol) in methanol (30 mL) was added to asolution of 5-methyl-4-p-tolyl-thiazol-2-ylamine (0.815 g, 3.99 mmol) in methanol (20 mL) under an inert atmosphere. The reaction mixture was refluxed for three hours. Completion of the reaction was monitored by silica TLC using hexane/ethyla cetate (8:2).T he reaction was allowed to cool to room temperature and then stirred overnight. Ayellow precipitete formed which wast hen filtered and washed with methanol (10 mL). Thec rude product, which was purified by crystallization from ethanol gave brown crystals. (1.22 g, 70% yield). M.p. = 451-452 K. Crystals suitable for X-ray diffraction were obtained by slow evaporation of the title compound from ad ichloromethane:hexane solution at room temperature. Experimental detailsAll Hatomswere positioned geometrically and allowed to ride on their respective parent atoms. The absorpton correction was based on fitting afunction to the empirical transmission surface as sampled by multiple equvalent measurements [14]. DiscussionThe pyrazole ring is aprominent structural motif found in numerous pharmaceutically active compounds. This is mainly due to the easy preparation and the important pharmacological activity. Therefore, the synthesis and selective functionalization of pyrazoleshas been thefocus of active research over theyears [1][2][3]. A survey of the literature reveals that some pyrazoles have been employed as antileukemic [4,5], antitumor [6, 7], anti-proliferative agents [8], anti-inflammatory and antimicrobial agents [9,10]. Schiff base ligands synthesized from pyrazole rings have also been employed in adiverse range of applications. We previously have reported the synthesis of the title structure and from NMR deduced that the Schiff base is present as the keto-imine tautomeric form [11]. Thediffraction data in this report clearly indicates that the nitrogen atom from 2-aminothiazole exists as a secondaryamine. Theketo-amine tautomeric formrather than the keto-imine predominates in the solid state. There areseveral examples from thel iterature wheret hish as been observed previously [12,13]. In the crystal lattice as ingle intramolcular hydrogen bonding arrangement is observed i.e. N3-H3···O1 3.0132(13) Å (Fig.).

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Section: Discussionmentioning

confidence: 99%

Crystal structure of 2-(3-chloro-phenyl)-5-methyl-4-[1-(5-methyl-4-ptolyl- thiazol-2-ylimino)-ethyl]-2,4-dihydro-pyrazol-3-one, C23H-ClN4OS

Thakar

Friedrich

Joshi³

et al. 2013

Zeitschrift Für Kristallographie - New Crystal Structures

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“…3,4,5 trimethoxy substituted have shown good activity against these cell lines having IC 50 value in the range of 0.037-0.019 µM (2) [20]. Furopyrazole compound 3 induces terminal differentiation of HL-60 cells toward granulocyte lineage and promoted HL-60 cell differentiation by regulation of Bcl-2 and c-Myc proteins [21]. Dhar et al synthesized chalcones and their corresponding analogues and found that introduction of pyrazole moiety increases the rigidity of the molecule and show better cytotoxic activity then their corresponding chalcones 4 [22], compound 5 has shown the ability to inhibit P-glycoprotein-mediated multidrug resistance by direct binding to a purified protein domain containing an ATP-binding site and a modulator interacting region [23] whereas compound 6 was assayed for anticancer activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI 50 values ranging from 0.04 to 11.4 µM [24].…”

Section: Analogues Of Chalcones Pyrazoline Analogues With Various Phamentioning

confidence: 99%

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

Sapra¹,

Sharma²

2016

Chem Sci J

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Although chalcones symbolize an important pharmacophore for variety of biological actions, however their analogues are also reported to be equally important for plethora of biological actions. In the present review, a comprehensive study of chalcones derived molecules (like pyrazoles, isoxazoles, pyridine, pyrimidine) their pharmacological actions, mechanism of action, structure activity relationship studies have been described. which includes anti-proliferative, anti-inflammatory, antioxidant, proapoptotic, anti-bacterial and anti-adhesive effects [18]. Analogues of chalcones Pyrazoline analogues with various pharmacological activities:Pyrazole nucleus present in compounds exhibit wide range of biological activity. Introduction of a pyrazole ring in the chalcones between the two aryl rings increase the cytotoxic activity against a series of human cancer cell lines. Dhar et al. [19] synthesized a series of 1-acetyl-3,5-diaryl-4,5-dihydro-(H)-pyrazoles and assayed for in vitro cytotoxicity against PC-3, OVCAR, IMR-32, HEP-2 human cancer cell lines, compound 1 showed broad spectrum cytotoxic activity against all the four cell lines. The activity shown by the compounds conclude that (i) Substitution on phenyl ring showed marked effect on cytotoxic activity, (ii) Presence of electron donating groups on phenyl ring led to enhanced activity whereas electron withdrawing group except NO 2 reduces the cytotoxic activity, (iii) Replacement of phenyl ring with heterocyclic ring also reduces the cytotoxic potential and napthyl ring on both sides are more beneficial for cytotoxic potential Chemical Sciences JournalChem ic a l S cience s J o u rnal

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“…Numerous structure-activity relationships and biochemical assay data indicate that 1-benzyl-3-(5-hydroxymethyl-2-furyl) indazole (YC-1) displays high potential as a new anticancer drug candidate (14,15). In vivo xenograft studies have also revealed that YC-1 exhibits marked antitumor activity against various cancer cell lines and prolongs the survival time of tumor-bearing mice, but without evident toxic effects (16,17).…”

Section: Clc604 Preferentially Inhibits the Growth Of Her2-overexpresmentioning

confidence: 99%

“…In our previous study, we reported that YC-1 furopyrazole and thienopyrazole isosteric analogues exhibit greater cytotoxicity against HL-60 cells than YC-1, and their physiochemical properties and biological mechanisms appear to be at variance to YC-1 (15,21). As part of our continuing search for potential anticancer drug candidates among YC-1 analogues, we further investigated the anticancer activity and biological mechanisms of various YC-1 isosteric analogues in vitro and in vivo.…”

Section: Clc604 Preferentially Inhibits the Growth Of Her2-overexpresmentioning

confidence: 99%

CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo

et al. 2013

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Abstract. HER2 has become a solicitous therapeutic target in metastatic and clinical drug-resistant cancer. Here, we evaluated whether or not 1-benzyl-3-(5-hydroxymethyl-2-furyl) indazole (YC-1) and its furopyrazole and thienopyrazole analogues repress the expression of the HER2 protein. Among the test compounds, (1-benzyl-3-(p-hydroxymethylphenyl)-5-methylfuro[3,2-c]pyrazol) (CLC604), an isosteric analogue of YC-1, significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing cancer cells. Our results revealed that CLC604 reduced HER2 expression through a post-transcriptional mechanism and involvement of proteasomal activity. CLC604 disrupted the association of 90-kDa heat shock protein (Hsp90) with HER2 resulting from the inhibition of Hsp90 ATPase activity. Moreover, we found that CLC604 significantly enhanced the antitumor efficacy of clinical drugs against HER2-overexpressing tumors and efficiently reduced HER2-induced drug resistance in vitro and in vivo. These findings suggest that CLC604 should be developed further as a novel antitumor drug candidate for the treatment of drug-resistant cancer.

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Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents

Cited by 78 publications

References 16 publications

Crystal structure of 2-(3-chloro-phenyl)-5-methyl-4-[1-(5-methyl-4-ptolyl- thiazol-2-ylimino)-ethyl]-2,4-dihydro-pyrazol-3-one, C23H-ClN4OS

Crystal structure of 2-(3-chloro-phenyl)-5-methyl-4-[1-(5-methyl-4-ptolyl- thiazol-2-ylimino)-ethyl]-2,4-dihydro-pyrazol-3-one, C23H-ClN4OS

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo

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