[(4-羟基哌啶-1-基)甲二基]二(膦酸) | 144230-27-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: [(4-羟基哌啶-1-基)甲二基]二(膦酸)
• 英文名称: (4-hydroxypiperidin-1-yl)methylenebisphosphonic acid
• 英文别名: 4-Hydroxypiperidinomethylene bisphosphonic acid；[(4-Hydroxypiperidin-1-yl)methanediyl]bis(phosphonic acid)；[(4-hydroxypiperidin-1-yl)-phosphonomethyl]phosphonic acid
• CAS: 144230-27-3
• 化学式: C₆H₁₅NO₇P₂
• 分子量: 275.135
• InChiKey: MDCNNIRRNBNADF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  139
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-羟基-1-哌啶甲醛 在 甲醇 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 [(4-羟基哌啶-1-基)甲二基]二(膦酸)
  参考文献：
  名称：

  使用三（三甲基甲硅烷基）亚磷酸酯作为方便的合成子催化氨基烷醇和双氨基烷烃的 N-二膦酰基甲基化

  摘要：

  通过亚磷酸三（三甲基甲硅烷基）酯与各种N-甲酰基氨基烷醇或双（N-甲酰基氨基）烷烃在有效催化剂三氟甲磺酸三甲基甲硅烷基酯存在下的独特反应，首次合成了新的单和双（氨基亚甲基二膦酸）酸在温和的条件下。用过量的甲醇进一步处理最初形成的三甲基甲硅烷基中间体，得到高产率的结晶单-和双（氨基亚甲基二膦酸）。提出并详细讨论了目标物质形成的催化方案。目标酸的结构由1 H, 13 C, 31P NMR 谱和高分辨率质谱 (HRMS)。所得化合物作为具有多功能特性和有效多齿配体的前瞻性生物活性物质引起了极大的兴趣。

  DOI：

  10.1016/j.jorganchem.2021.122143

文献信息

• Synthesis and Evaluation of (Piperidinomethylene)bis(phosphonic acid) Derivatives as Anti-osteoporosis Agents.
  作者：Mitsuo MIMURA、Mitsuo HAYASHIDA、Kiyoshi NOMIYAMA、Satoru IKEGAMI、Yasuhito IIDA、Makoto TAMURA、Yoshiyuki HIYAMA、Yoshitaka OHISHI

  DOI：10.1248/cpb.41.1971

  日期：——

  Some (piperidinomethylene)bis(phosphonic acid) derivatives were prepared and their activity to inhibit a rise in serum calcium induced by parathyroid hormone in thyroparathyroidectomised rats was evaluated. Several (4-alkylidene-, 4,4-dialkyl-, or 4-alkyl-4-halopiperidinomethylene)bis(phosphonic acid) derivatives showed considerable inhibitory activity. But compounds having aromatic and polar substituents

  制备了一些（哌啶子基亚甲基）双（膦酸）衍生物，并评估了它们抑制甲状旁腺切除的大鼠的甲状旁腺激素诱导的血清钙升高的活性。几种（4-亚烷基-，4,4-二烷基-或4-烷基-4-卤代哌啶亚基）双（膦酸）衍生物表现出相当大的抑制活性。但是在哌啶环上具有芳族和极性取代基如叠氮基，羟基，氨基和酰胺基的化合物通常是无活性的。在这项研究中，两种4-亚烷基化合物（8a和8b）和4,4-环二烷基化合物（61）在静脉内或经口给药时均显示出强大的活性。
• Bisphosphonic acid derivatives and bone resorption inhibitors containing them
  申请人：Kaken Pharmaceutical Co., Ltd.

  公开号：EP0498424A1

  公开（公告）日：1992-08-12

  A bisphosphonic acid derivative of the formula (I) or a pharmaceutically acceptable salt thereof: wherein A is wherein each of R¹ and R², which may be the same or different, is a hydrogen atom, a halogen atom, a C₁₋₆ alkyl group or a single bond, each of j, k and ℓ is 0 or a positive integer, provided that (j+k+ℓ) is from 2 to 6, each of R³ and R⁴, which may be the same or different, is (i) a hydrogen atom, (ii) a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆ alkynyl group, a C₁₋₆ alkyl-carbonyl group, a C₂₋₆ alkenyl-carbonyl group, a C₂₋₆ alkynyl-carbonyl group (these groups may be substituted by at least one member selected from the group consisting of a substituted amino group, a halogen atom and a carboxyl group), or (iii) a halogen atom, each of R⁵ and R⁶, which may be the same or different, is a hydrogen atom, a hydroxyl group, a halogen atom, a cyano group, a carbamoyl group, an aralkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted amino group, a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆ alkynyl group or a heterocyclic group having a nitrogen atom as the hetero atom, provided that when either one of R⁵ and R⁶ is a hydrogen atom, the other is other than a hydrogen atom or a C₁₋₆ alkyl group;    each of m and n is 0 or a positive integer, provided that (m+n) is from 2 to 5; and    R is a hydrogen atom, a C₁₋₈ alkyl group or a C₇₋₁₅ aralkyl group.

  式 (I) 的双膦酸衍生物或其药学上可接受的盐： 其中 A 是 其中 R¹ 和 R² （可以相同或不同）分别为氢原子、卤素原子、C₁₋₆ 烷基或单键，j、k 和 ℓ 分别为 0 或正整数，条件是 (j+k+ℓ) 为 2 至 6，R³ 和 R⁴ （可以相同或不同）分别为 (i) 氢原子、(ii) C₁₋₆ 烷基、C₂₋₆ 烯基、C₂₋₆ 炔基、C₁₋₆ 烷基-羰基、C₂₋₆ 烯基-羰基、C₂₋₆炔基-羰基（这些基团可被至少一个选自取代氨基的成员取代、R⁵和 R⁶可以相同或不同，各自为氢原子、羟基、卤素原子、氰基、氨基甲酰基、芳烷基、取代或未取代的苯基、取代或未取代的氨基、C₁₋₆烷基、C₂₋₆烯基、C₂₋₆炔基或以氮原子作为杂原子的杂环基团、但当 R⁵ 和 R⁶ 中的一个是氢原子时，另一个不是氢原子或 C₁₋₆ 烷基； m 和 n 各为 0 或正整数，条件是 (m+n) 为 2 至 5；以及 R 是氢原子、C₁₋₈ 烷基或 C₇₋₁₅ 芳烷基。
• Effects of Bisphosphonates on the Growth of <i>Entamoeba histolytica</i> and <i>Plasmodium </i>Species in Vitro and in Vivo
  作者：Subhash Ghosh、Julian M. W. Chan、Christopher R. Lea、Gary A. Meints、Jared C. Lewis、Zev S. Tovian、Ryan M. Flessner、Timothy C. Loftus、Iris Bruchhaus、Howard Kendrick、Simon L. Croft、Robert G. Kemp、Seiki Kobayashi、Tomoyoshi Nozaki、Eric Oldfield

  DOI：10.1021/jm030084x

  日期：2004.1.1

  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 < 200 muM) versus E. histolytica growth in vitro. The most active compounds (IC50 similar to 4-9 muM) 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 similar to 10-20 muM), 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 IC50 values <200 muM in an in vitro assay. The most active compounds were also simple n-alkyl-1-hydroxy-1,1-bisphosphonates, having IC50 values around 1 muM. 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.
• POLYMER COMPOSITION COMPRISING PHOSPHONATE FLAME RETARDANT
  申请人：Chemische Fabrik Budenheim KG

  公开号：US20220389191A1

  公开（公告）日：2022-12-08

  Compounds containing polymer material and a phosphorous flame protection agent on the basis of an aminomethyl bisphosphonate, a method for manufacturing the compound, the use of the flame retardant, and selected structures of the flame retardant are disclosed.
• US5350743A
  申请人：——

  公开号：US5350743A

  公开（公告）日：1994-09-27