パミドロン酸

3-アミノ-1-ヒドロキシプロピリデンビスホスホン酸 · 1-ヒドロキシ-3-アミノプロピリデンビス(ホスホン酸) · 1-ヒドロキシ-3-アミノプロパン-1,1-ジイルビスホスホン酸 · 2-アミノエチルヒドロキシメチレンビスホスホン酸 · (1-ヒドロキシ-3-アミノプロパン-1,1-ジイル)ビスホスホン酸 · (3-アミノ-1-ヒドロキシプロピリデン)ビス(ホスホン酸) · [2-アミノエチル(ヒドロキシ)メチレン]ビスホスホン酸 · (3-アミノ-1-ヒドロキシプロピリデン)ビスホスホン酸

https://huagongshe.com/ja/chemical/4674

識別子と物理属性

CAS No.	40391-99-9
分子式	C3H11NO7P2
平均分子量	235.07 g/mol
単同位体質量	235.00107495 g/mol
SMILES	NCCC(O)(P(=O)(O)O)P(=O)(O)O
InChIKey	WRUUGTRCQOWXEG-UHFFFAOYSA-N
PubChem CID	4674
ChEMBL	CHEMBL834
ChEBI	CHEBI:7903
EC No.	254-905-2
DTXSID	DTXSID4023414
現地名	パミドロン酸

化学・物理的性質

XLogP	-6.9
極性表面積	161
水素結合供与体数	6
水素結合受容体数	8
回転可能結合数	4
重原子数	13
形式電荷	0
複雑度	243
医薬品	PharmaceuticalsPharmaceuticals -> Listed in ZINC15
LogP（分配係数）	-4.7
溶解度	1.58e+01 g/Lメタノール（ごくわずか、加熱、超音波処理）、水（わずかに、加熱、超音波処理）
Human Drugs	Breast FeedingLactationMilk, HumanBisphosphonatesBone Density Conservation AgentsDiphosphonates
融点	254-262226-228°C
Physical Description	Solid
沸点	658.7±65.0 °C(Predicted)
密度	1.998±0.06 g/cm3(Predicted)
貯蔵条件	under inert gas (nitrogen or Argon) at 2–8 °C
pKa（酸解離定数）	1.44±0.10(Predicted)
外観・状態	個体
色	ライトブラウンからベージュ
安定性	吸湿性
InChI	InChI=1S/C3H11NO7P2/c4-2-1-3(5,12(6,7)8)13(9,10)11/h5H,1-2,4H2,(H2,6,7,8)(H2,9,10,11)
InChIKey	WRUUGTRCQOWXEG-UHFFFAOYSA-N
SMILES	C(P(=O)(O)O)(P(=O)(O)O)(O)CCN

化学的特性

White Solid

安全性と法規制

GHS 分類	WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 24 reports by companies from 4 notifications to the ECHA C&L Inventory.
Hazard Classes and Categories	Acute Tox. 4 (100%)
Treatment	If overdosage occurs, symptomatic hypocalcemia could also resultsuch patients should be treated with short-term intravenous calcium. (L1712)
健康影響	Rare cases of uveitis, iritis, scleritis, and episcleritis have been reported, including one case of scleritis, and one case of uveitis upon separate rechallenges.
有害作用	Pamidronate correlates with numerous adverse effects, including hypocalcemia and resulting secondary hyperparathyroidism, acute phase response, musculoskeletal pain, various ocular events, and osteonecrosis of the jaw.
暴露経路	Parenteral (intravenous). Plasma concentration rises rapidly upon IV administration.
毒性の概要	A small number of cases describe symptomatic hypocalcemia following pamidronate administration. In each case, however, patients had pre-existing derangements contributing to their symptoms, including renal insufficiency and low vitamin D levels secondary to lifestyle, previous GI surgery, and medication history. Recommendations for the management of pamidronate overdose include appropriate correction of the electrolyte disturbance and pre-treatment supplementation with calcium and Vitamin D.The mechanism of action of pamidronate is inhibition of bone resorption. Pamidronate adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. Pamidronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

用途

使用

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