91374-21-9Relevant articles and documents
Method for preparing ropinirole hydrochloride
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, (2018/09/12)
The invention belongs to the technical field of medicinal chemistry and organic chemistry, and particularly relates to a method for preparing ropinirole hydrochloride. A novel compound 4 is synthesized by the aid of the method and is used as a raw material for preparing the ropinirole hydrochloride. The particular method includes dissolving the compound 4 in one or a plurality of types of ethyl alcohol/methanol/ethyl acetate to obtain liquid, adding Pd/C into the ethyl alcohol/methanol/ethyl acetate, and carrying out reaction to obtain compounds 5; dissolving the compounds 5, p-toluenesulfonylchloride and pyridine in one or a plurality of types of dichloromethane/trichloromethane/1, 2-dichloroethane/pyridine, and carrying out reaction to obtain compounds 6; dissolving the compounds 6, NaIand dipropyl amine in one or a plurality of types of DMF (dimethyl formamide)/DMSO (dimethylsulfoxide)/Toluene, and carrying out reaction to obtain ropinirole; dissolving the ropinirole in 1, 4 dioxane with hydrochloric acid, and carrying out reduced-pressure compression to obtain the ropinirole hydrochloride. A proportion of the compounds 5 to the p-toluenesulfonyl chloride to the pyridine is equal to 1:1.2:1.2. A proportion of the compounds 6 to the NaI to the dipropyl amine is equal to 1:1:1.2. The novel method for preparing the ropinirole hydrochloride has the advantages that the method includes simple and convenient steps and can be practically put into production, and raw materials for the ropinirole hydrochloride are simple and are easily available.
Synthesis and pharmacological evaluation of dual acting ligands targeting the adenosine A2A and dopamine D2 receptors for the potential treatment of parkinsons disease
J?rg, Manuela,May, Lauren T.,Mak, Frankie S.,Lee, Kiew Ching K.,Miller, Neil D.,Scammells, Peter J.,Capuano, Ben
supporting information, p. 718 - 738 (2015/01/30)
A relatively new strategy in drug discovery is the development of dual acting ligands. These molecules are potentially able to interact at two orthosteric binding sites of a heterodimer simultaneously, possibly resulting in enhanced subtype selectivity, higher affinity, enhanced or modified physiological response, and reduced reliance on multiple drug administration regimens. In this study, we have successfully synthesized a series of classical heterobivalent ligands as well as a series of more integrated and drug-like dual acting molecules, incorporating ropinirole as a dopamine D2 receptor agonist and ZM 241385 as an adenosine A2A receptor antagonist. The best compounds of our series maintained the potency of the original pharmacophores at both receptors (adenosine A2A and dopamine D2). In addition, the integrated dual acting ligands also showed promising results in preliminary blood-brain barrier permeability tests, whereas the classical heterobivalent ligands are potentially more suited as pharmacological tools.
Investigation of novel ropinirole analogues: Synthesis, pharmacological evaluation and computational analysis of dopamine D2 receptor functionalized congeners and homobivalent ligands
J?rg, Manuela,Kaczor, Agnieszka A.,Mak, Frankie S.,Lee, Kiew Ching K.,Poso, Antti,Miller, Neil D.,Scammells, Peter J.,Capuano, Ben
supporting information, p. 891 - 898 (2014/07/08)
Herein, we report the development of novel functionalized congeners of ropinirole toward the design of pharmacological tools to probe structural requirements at the dopamine D2 receptor. Subsequently, we have used the functionalized amine congener 11 and synthesized and pharmacologically evaluated a series of homobivalent ligands of ropinirole with designated spacer lengths ranging from 14 to 30 atoms. The most potent homobivalent ligands (22-, 26- and 30-atom spacers) showed approximately 20- to 80-fold greater potency (EC50 = 3.9, 6.2 and 14 nM, respectively) than ropinirole (304 nM) in a [35S]GTPγS functional assay. Molecular modeling studies suggest that the observed increase in potency of the homobivalent ligands is possibly due to a bitopic binding mode involving the orthosteric site and an allosteric interaction at the dopamine D2 receptor protomer rather than bridging interactions at two orthosteric sites across a dopamine D 2 receptor dimer. This research has the potential to advance the development of structurally related bitopic ligands, biomarkers such as radioligands and fluorescently labeled probes, and furnish new homo- and heterobivalent ligands towards a better understanding of the dopamine D 2 receptor and potential novel treatment for Parkinson's disease.
