63132-39-8

Usage

Uses

Used in Pharmaceutical Industry:
Olpadronate Sodium is used as an anti-osteoporosis agent for its ability to inhibit bone resorption and promote bone mineralization. This helps in the treatment and management of osteoporosis, a condition characterized by reduced bone mass and increased risk of fractures.
Additionally, Olpadronate Sodium can be used in the preparation of bisphosphonic acid derivatives, which may have further applications in the medical field for bone-related disorders and conditions.

InChI:InChI=1/C5H15NO7P2/c1-6(2)4-3-5(7,14(8,9)10)15(11,12)13/h7H,3-4H2,1-2H3,(H2,8,9,10)(H2,11,12,13)

Upstream product

• 6300-04-5 3-dimethylaminopropionic acid 
• 50-00-0 formaldehyd 
• 40391-99-9 pamidronate 
• 1738-25-6 3-dimethylaminopropiononitrile 
• 63132-38-7 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid 

Relevant academic research and scientific papers

Preparation and application of sulfonic acid-phosphonic acid ligands

The invention relates to preparation and application of a sulfonic acid-phosphonic acid ligand. The structure of the sulfonic acid-phosphonic acid ligand comprises sulfonic acid, quaternary ammonium and phosphonic acid groups, and specifically comprises a sulfonic acid betaine-phosphonic acid ligand, a sulfonic acid-zoledronic acid ligand and a sulfonic acid-risedronic acid ligand. The molecular formula of the sulfobetaine-phosphonic acid ligand is C8H21NO10P2S, and the molecular weight of the sulfobetaine-phosphonic acid ligand is 384.2. The molecular formula of the sulfonic acid-zoledronic acid ligand is C8H16O10N2P2S, and the molecular weight of the sulfonic acid-zoledronic acid ligand is 394.23. The molecular formula of the sulfonic acid-risedronate ligand is C10H17O10NP2S, and the molecular weight of the sulfonic acid-risedronate ligand is 405.25. The sulfonic acid-phosphonic acid ligand disclosed by the invention has excellent hydrophilicity and can be coordinated with various metal elements. The molecules have important applications in the following two aspects: 1, the sulfonic acid-phosphonic acid ligand is used for modifying a hydrophobic nano material, so that the hydrophilicity of the material is remarkably improved, and the sulfonic acid-phosphonic acid ligand can be dispersed in a water phase; and 2, a certain inhibition effect is achieved on tumors.

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

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 (IC50 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 (IC50 ～ 10-20 μM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pKa 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 IC50 values 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.

Enteric coated formulation for bisphosphonic acids and salts thereof

Pharmaceutical compositions, processes for preparing the compositions and methods of using the composition are provided. The pharmaceutical composition comprises an inert core surrounded by an active coating containing one or more bisphosphonic acids or salts thereof, a seal coating surrounding the active coating and an enteric coating surrounding the seal coating. Alendronic acid and alendronate sodium trihydrate are the preferred active ingredients. The composition may be provided in the form of pellets in a capsule or Peltabs. The invention further provides methods for the treatment of disorders caused by the abnormal dissolution or deposition of calcium salts using the inventive compositions.

Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa)

Bisphosphonates (BPs) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED50 of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.

Formulation for treatment of osteoporosis

The present invention provides pharmaceutical formulations comprising at least one bisphosphonate and an absorption enhancing agent essentially consisting of a medium chain glyceride or a mixture of medium chain glycerides. The said pharmaceutical formulations are useful for the inhibition of bone resorption and for the treatment and prevention of osteoporosis.

Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: A potential route to chemotherapy

We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC50 activity values against parasite replication (e.g. o-risedronate, I50 = 220 nM for T. brucei rhodesiense; risedronate, IC50 = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.

Pharmaceutical tablets

The present invention relates to novel pharmaceutical tablets useful for administering pharmaceutical active ingredients, such as bisphosphonates. These tablets have improved surface properties which can aid esophageal transit, thereby reducing the potential for adverse gesture intestinal effects. The present invention also relates to processes for making said novel pharmaceutical tablets.

Bone mass anabolic composition comprising olpadronate

The present invention provides methods for bone mass anabolic preservation or augmentation in human or other animal subjects affected by osteoporosis or other metabolic bone disorder characterized by systemic or regional bone loss, using bisphosphonates formulations, wherein the bone mass anabolic composition contains effective non-toxic doses of ?3-(N,N-dimethylamine)-1-hydroxypropylidene!-bisphosphonic acid or olpadronate or the monosodium or other pharmaceutically acceptable salt thereof.

Regimen for treatment or prophylaxis of osteoporosis

Methods for treating or preventing osteoporosis, including regimens for intermittent dosing of bone resorption inhibiting polyphosphonate compound or a pharmaceutically acceptable salt or ester of any such compound.

1-Hydroxy-3-amino-alkane-1,1-diphosphonic acids and salts

1-Hydroxy-3-amino-alkane-1,1-diphosphonic acids having the formula STR1 wherein X is a member selected from the group consisting of STR2 and STR3 wherein R1 is a member selected from the group consisting of hydrogen and alkyl having 1 to 3 carbon atoms and R2 is alkyl having 1 to 3 carbon atoms; as well as their water-soluble salts. The 1-hydroxy-3-amino-alkane-1,1-diphosphonic acids are excellent sequestering agents especially for alkaline earth metal ions. The compounds are useful in pharmaceutical preparations for treatment of disturbances of calcium or phosphate metabolism or cosmetic preparations such as toothpastes or mouthwashes for the prevention of tartar and plaque depositions.