Long‐chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

Abstract

FIGURE 1Structures of geminal bisphosphonates in clinical use.

Carbamoylphosphonates Control Tumor Cell Proliferation and Dissemination by Simultaneously Inhibiting Carbonic Anhydrase IX and Matrix Metalloproteinase-2. Toward Nontoxic Chemotherapy Targeting Tumor Microenvironment

“…Furthermore, the pair of enantiomers, 8 and 9, also show similar inhibition constants, in contrast to their differing inhibition constants on MMPs. 24 Finally, Table 1 also contains 1,4-butanebiscarbamoylphosphonic acid and its tetraethyl ester (compounds 10 and 11, respectively), 34 both of which show similar inhibition characteristics to the mono-CPO compounds mentioned above. Among the compounds in Table 1, an in-depth study was devoted to cyclopentyl-CPO (3, CPCPA), 23 which revealed significantly inhibited cellular invasion and capillary formation in vitro.…”

Ring–chain tautomerism and protolytic equilibria of 3-hydroxy-3-phosphonoisobenzofuranone studied by 1H, 13C and 31P NMR-controlled titrations

“…mp 208-209 1C. NMR (D 2 O): 31 P, 10.2 ppm (q, J POCH = 9.7 Hz); Disodium ortho-(methylphosphonato)formylbenzoate (7). To a solution of compound 5 (60 mg) dissolved in D 2 O (0.4 mL) solid Na 2 CO 3 was added until pH 10.…”

“…4 The antiviral pyrophosphate analogs, phosphonoacetic and phosphonoformic acids have also been reported to accumulate in bone and teeth which detracts from their value as drugs. 5 In another approach, it was reported in previous papers from our laboratory that bisacylphosphonates 6 and to a lesser extent, other long-chain bisphosphonates 7 are also biologically active in calcium related disorders. X-Ray crystallographic results indicate that bisacylphosphonates interact with calcium ions to form polynuclear structures in which each terminus of the molecule is bound to a separate calcium ion, which is bound to additional bisacylphosphonates.…”

Fluorinated Phosphonates: Synthesis and Biomedical Application

“…However, subsequent workers have found that alkyl halides do not always readily undergo displacement reactions with [(RO) 2 P(O)CF 2 ] - anions and that some of Obayashi's work is not reproducible at the published yields. The reported yields vary from 0% to 43% with simple primary alkyl iodides and bromides. ,− A recent work brings an example of the good-yielding reaction between [( i PrO) 2 P(O)CF 2 ] - anion and 1,3-dibromopropane (63%), but when 1,4-dibromobutane and bis-chloromethyl ether were allowed to react in similar conditions, the corresponding phosphonates 133 − 135 were obtained in poor yields (Scheme ) . The problem seems to lie in the relatively weak nucleophilicity and thermal instability of the difluoromethylphosphonate anion .…”

“…The reported yields vary from 0% to 43% with simple primary alkyl iodides and bromides. 34,[197][198][199][200][201][202][203] A recent work brings an example of the goodyielding reaction between [( i PrO) 2 P(O)CF 2 ]anion and 1,3dibromopropane (63%), but when 1,4-dibromobutane and bis-chloromethyl ether were allowed to react in similar conditions, the corresponding phosphonates 133-135 were obtained in poor yields (Scheme 44). 204 The problem seems to lie in the relatively weak nucleophilicity and thermal instability of the difluoromethylphosphonate anion.…”