Antitumor platinum (II) compound using camphor acid radical as ligand

A technology of camphoric acid and complexes, applied in the field of new platinum complexes, can solve the problems of compound inactivity and increased toxicity of compounds

Inactive Publication Date: 2005-05-25
NANJING UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compounds become more toxic if labile leaving groups are used...

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Antitumor platinum (II) compound using camphor acid radical as ligand
  • Antitumor platinum (II) compound using camphor acid radical as ligand
  • Antitumor platinum (II) compound using camphor acid radical as ligand

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: Synthesis of cis-(DL-camphorate) diammine platinum (II)

[0032] cis-diiododiammine platinum (II) (0.97 g, 2 mmol) and silver nitrate (0.68 g, 4 mmol) were mixed and added to water (50 ml), and reacted at 60° C. for 24 hours in the dark and nitrogen. Diatomaceous earth assisted filtration, the aqueous solution of DL-camphoric acid (0.40 g, 4 mmol) and sodium hydroxide (0.16 g, 4 mmol) was added to the filtrate, and the reaction was carried out under nitrogen at 60 ° C for 16 hours in the dark, and the solution was concentrated , a large amount of white solid was precipitated. Filter, wash repeatedly with water, ethanol and ether, and dry under vacuum at 60°C to obtain 0.41 g (48%) of the product.

[0033] IR(KBr): 3424vs(br), 3266vs(br), 2967m, 2881w, 1594vs, 1544vs, 1460m, 1384vs, 1355vs

[0034] 1 H-NMR (D 2 O / TMS): δ0.47-0.67(m, 3H), 0.91-1.08(m, 6H), 1.24-1.31(s, 1H), 1.60(s, 1H), 1.74-1.75(s, 1H), 2.08(m, 1H), 2.55-2.56(s, 1H)

[0035] ESI-MS: [...

Embodiment 2

[0036] Example 2: Synthesis of cis-(DL-camphorate) two (isopropylamine) platinum (II)

[0037] cis-diiodo·bis(isopropylamine)platinum(II) (1.13 g, 2 mmol), silver nitrate (0.68 g, 4 mmol) were mixed and added to water (50 ml), and reacted in the dark at 60°C under nitrogen gas After 24 hours, diatomaceous earth was assisted to filter, and the aqueous solution of DL-camphoric acid (0.40 g, 4 mmol) and sodium hydroxide (0.16 g, 4 mmol) was added to the filtrate, and it was reacted in the dark at 60° C. for 16 hours, The solution was concentrated and a large amount of white solid precipitated out. It was filtered, washed repeatedly with water, ethanol and ether, and dried under vacuum at 60°C to obtain 0.39 g (38%) of the product.

[0038] IR(KBr): 3430s(br), 3217s(sh,br), 2971vs, 2880w, 1595vs(br), 1462m, 1383vs, 1351vs, 1164w, 1118w

[0039] 1 H-NMR (DMSO-d 6 / TMS): δ0.70-0.85 (m, 3H), 0.97-1.26 (m, 18H), 1.44-2.36 (br, 4H), 2.64-2.70 (br, 1H, CH), 2.96-3.18 (m, 2H), 5.85-...

Embodiment 3

[0041] Example 3: Synthesis of cis-(D-camphorate)·[(1R,2R)-1,2-trans-cyclohexanediamine] platinum(II)

[0042]Cis-dichloro[(1R, 2R)-1,2-trans-cyclohexanediamine] platinum (II) (0.76 g, 2 mmol), silver nitrate (0.68 g, 4 mmol) were mixed and added to water ( 50 milliliters), under 60 ℃, shielded from light and reacted with nitrogen for 24 hours, diatomaceous earth assisted filtration, added the aqueous solution of D-camphoric acid (0.40 gram, 4 mmol) and sodium hydroxide (0.16 gram, 4 mmol) in the filtrate , React at 60°C for 16 hours in the dark and pass through nitrogen, the solution is concentrated, and a large amount of white solid is precipitated. Filter, wash repeatedly with water, ethanol and ether, and dry under vacuum at 60°C to obtain 0.65 g (64%) of the product.

[0043] IR(KBr): 3424vs(br), 3226s(sh,br), 2939s, 2872w, 1598vs(br), 1457m, 1381vs, 1350s, 1169w, 1126w, 1063w

[0044] 1 H-NMR (DMSO-d 6 / TMS): δ0.84-0.91(m, 3H), 1.09-1.20(m, 6H), 1.28(m, 4H), 1.48(m, ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The present invention discloses platinum (II) complexes with effective anticancer activity, characterized in that the new platinum (II) complexes are formed by reacting the anionic ligand of Camphoric radicals with the cationic ligand of amine platinum. The preparation process of these complexes and the in vitro inhibition effect of leukemic cell, oophoroma cell, hepatoma cell and pulmonary carcinoma cell with the typical compounds of the present invention are also disclosed. The structures of the present complexes are represented by the following formulas: (1), (2) and (3), wherein the Camphoric radicals in formula (l), (2) and (3) can be DL type raceme, D type optical isomer [1R, 3S) - (+) -Camphoric radical] or L type optical isomer [(1S, 3R)-(-)-Camphoric radical]. In formula (1) R is the same, representing hydrogen atom, C1-5alkyl or Cl-8oxaalkyl; In formula (2) the cyclohexanediamine is 1,2-t­rans-cyclohexanediamine, wherein both of the two chiral carbon atoms (marked with *) have the absolute configuration of R or S; In formula (3) R1 and R2 linked to the 4, 5-bis (aminomethyl) -2-alkyl-1, 3-­dioxolane, same or different, independently represent hydrogen atoms or C1-5 alkyl, or link to one carbon to form a cycle, wherein both of the two chiral carbon atoms(marked with *) have the absolute configuration of R or S. The platinum complexes of the present invention include all stereomers and mixtures of compounds represented by above formulas.

Description

technical field [0001] The present invention relates to novel platinum(II) complexes having potent antitumor activity, processes for their preparation and in vitro antitumor properties of typical compounds of said platinum(II) complexes. Background technique [0002] In the research of cisplatin anticancer drugs, the characteristics of the anion as the leaving group have a great influence on the activity of the drug. If an unstable leaving group is used, the toxicity of the compound will increase; if an inert leaving group is used, the compound is generally inactive. Since the successful development of carboplatin containing cyclosuccinate, dicarboxylic acids have been playing an important role in the research and development of anti-tumor platinum (II) complex drugs. Such as oxalic acid, malonic acid and norcantharidic acid have been practically used. Therefore, it is an important way to design and synthesize cisplatin compounds with low toxicity and good water solubility...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C61/06C07C211/65C07D317/28
CPCA61P35/00C07C61/06C07C211/65C07D317/28
Inventor 苟少华王联红
Owner NANJING UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap