A mild and efficient one-pot synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids. Preparation of new tripod ligands

Lecouvey, Marc; Mallard, Isabelle; Bailly, Théodorine; Burgada, R.; Leroux, Yves

doi:10.1016/s0040-4039(01)01844-5

Cited by 95 publications

(60 citation statements)

References 13 publications

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“…We used the Merck method 37 for production of compounds 1-3, 5, 7, 8, 16, and 18-30. Compounds 4, 6, and 9-15 were synthesized following the method of Lecouvey et al: 38 Compounds 17 and 32-36 were produced using the method of Mikhalin et al: 39 The synthesis of 31 has been described in detail elsewhere. 40 The 1,2-bisphosphonates 37-39 were produced using the method described by Allen et al: 41 The aminomethylene bisphosphonates 40-97, 101, and 102 were made following the method of Soloducho et al: 42 Compounds 98-100 were produced via the method of Hutchinson and Thornton: 43 An exception to the synthesis procedures above is compound 93, which was orignally intended to be synthesized as the methoxy pyridine derivative.…”

Section: Methodsmentioning

confidence: 99%

Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

et al. 2003

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The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC 50 < 200 µM) versus E. histolytica growth in vitro. The most active compounds (IC 50 ∼ 4-9 µM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC 50 ∼ 10-20 µM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pK a values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC 50 values <200 µM in an in vitro assay. The most active compounds were also simple n-alkyl-1-hydroxy-1,1-bisphosphonates, having IC 50 values around 1 µM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.

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Section: Methodsmentioning

confidence: 99%

Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

et al. 2003

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“…The following reagents were used in the work: 1-phenyl-1-hydroxymethylene bisphosphonic acid (PhHMBP, H 4 L) synthesized by the procedure presented in [10], concentrated solution of pure carbonate-free potassium hydroxide, palladium black. Potassium tetrachloropalladate was prepared according to the standard scheme [11]:…”

Section: Methodsmentioning

confidence: 99%

Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity

Kozachkova¹,

Tsaryk²,

TRACHEVSKYI³

et al. 2017

Ukr.Biochem.J.

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complex formation of K 2 [Pdcl 4 ] with 1-phenyl-1-hydroxymethylene bisphosphonic acid (PhhMBP, h 4 K e y w o r d s: palladium(II) complexes, bisphosphonic acid, cytotoxic activity, toxicity.C isplatin is still one of the most famous and efficient anticancer drugs used in the clinical practice [1]. Nevertheless, searching for new compounds with antineoplastic action continues to eliminate the serious side effects, to improve the clinical efficacy and to broaden the antitumor spectrum. In particular, palladium(II) bisphosphonates are promising species for the treatment of bone cancer and metastases: complexes include a cytotoxic metal (palladium) and a bisphosphonic acid, which possesses affinity for bone tissue and can ensure targeted delivery of the cytotoxic metal to the lesion site [2][3][4][5][6][7][8][9]. The P-C-P moiety present in bisphospho nic acids provides their active link to the bone matrix, and two side substituents determine their physicochemical and pharmacologic properties. To study the effect of the structure of complex and chemical nature of the substituents bonded to the carbon atom of bisphosphonate moiety on the biological activity, the formation of palladium(II) complexes with 1-phenyl-1-hydroxymethylene bisphosphoniс acid was investigated, which, besides two phosphonic groups, contain a hydroxy group and a phenyl moiety.

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“…78,79 Thus, treatment of acyl chlorides with two equivalents of tris-(trimethylsilyl) phosphite at RT leads to the tetrakis-(trimethylsilyl) ester of 1-trimethylsiloxy-1,1-bisphosphonic acids 99. Hydrolysis of 99 was carried out in methanol at room temperature for 1 h, to produce the free acids, 100, as in Scheme 35.…”

Section: Scheme 34mentioning

confidence: 99%

The development of bisphosphonates for therapeutic uses, and bisphosphonate structure-activity consideration

Abdou¹,

Shaddy²

2008

Arkivoc

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A mild and efficient one-pot synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids. Preparation of new tripod ligands

Cited by 95 publications

References 13 publications

Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity

The development of bisphosphonates for therapeutic uses, and bisphosphonate structure-activity consideration

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