61380-07-2Relevant academic research and scientific papers
Improved method for the total synthesis of thiofentanyl
Hosseini, S. J.,Moosavi, S. M.,Parsa, H.,Taghizadeh, M. J.
, (2020/04/16)
Thiofentanyl is a potent analgesic and anesthetic drug that belongs to the microreceptor agonist group and is mainly used in animal's anesthesia. We present an optimized synthesis route for synthesis of thiofentanyl using nanocatalysts such as MCM-41-SO3H and SBA-15-Ph-PrSO3H as green, heterogeneous and recyclable catalysts according to the strategy. The intermediate 2-(thiophen-2-yl) ethyl methanesulfonate (1) easily obtained after conversion of the alcohol functional group into the mesylate leaving group using methanesulfonyl chloride (97% yield). The alkylation of commercially available 4-piperidone monohydrate hydrochloride with 2-(thiophen-2-yl) ethyl methanesulfonate in the presence of phase transfer catalyst was then carried out giving N-[2-(2-thienyl) ethyl]-4-piperidone (2) with 90% yield. N-[2-(2-thienyl)ethyl]-4-piperidone was then reacted with aniline in the presence of MCM-41-SO3H catalyst giving the imine derivative which reduced with sodium triacetoxyborohydride to N-phenyl-1-(2-(thiophen-2-yl)ethyl) piperidine-4-amine (ANTP) (4) with 80% yield. ANTP was finally acylated using propionyl chloride to achieve thiofentanyl (5) with 90% yield. High yields, mild reaction conditions, decreased reaction times, and convenient workup were the advantages of this method compared to the previous work.
Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides
Lebel, Hélène,Mathieu, Gary,Patel, Heena
, p. 2157 - 2168 (2020/11/23)
The first continuous flow process was developed to synthesize N-methyl secondary amines from alkyl mesylates and epoxides via a nucleophilic substitution using aqueous methylamine. A variety of N-methyl secondary amines were produced in good to excellent yields, including a number of bioactive compounds or their precursors. Up to 10.6 g (88% yield) of an N-methyl secondary amine was produced in 140 min process time. The amination procedure included an in-line workup, and the starting mesylate material was also produced in continuous flow from the corresponding alcohol. Finally, an in-line process combining the mesylate synthesis and nucleophilic substitution was developed.
1,2,5-oxadiazole derivative used as indoleamine 2,3-dioxygenase inhibitor
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Paragraph 0113-0114; 0117-0118, (2019/10/01)
The invention belongs to the technical field of 1,2,5-oxadiazole derivatives, and particularly relates to a 1,2,5-oxadiazole derivative or a pharmaceutically acceptable salt thereof which is used as an indoleamine 2,3-dioxygenase inhibitor. The structure of the 1,2,5-oxadiazole derivative or the pharmaceutically acceptable salt thereof used as the IDO inhibitor is shown in the following formula I.The invention provides a general formula compound I with a novel structure. Experimental results show that some compounds have excellent IDO inhibitory activity and permeation performance at the sametime. The compound is expected to be marketed as a tumor molecular immunotherapeutic drug for cancer treatment.
Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist
Chaturvedi, Radha Nandan,Pendem, Krishnaiah,Patel, Vipul P.,Sharma, Mukta,Malhotra, Sunita
, p. 2069 - 2084 (2018/08/22)
Abstract: The present work describes the design, synthesis, molecular docking, biological evaluation, and assessment of structure–activity relationship of new derivatives based upon the molecular skeleton of the drug pioglitazone, a compound which is currently used for the management of type 2 diabetes mellitus. Pioglitazone has several side effects such as weight gain, edema, congestive heart failure, and bladder cancer. Therefore, there is a strong demand for identification of new lead candidates in the treatment of type 2 diabetes mellitus. A series of 24 compounds were prepared and evaluated for their peroxisome proliferator-activated receptor-γ (PPARγ) binding affinity assay and the IC50 values were determined. Among these compounds, six compounds exhibited promising IC50 values as compared to standard drugs pioglitazone and rosiglitazone. Furthermore, in order to confirm the target of these molecules, molecular docking study was carried out with peroxisome proliferator-activated receptor-γ (PPARγ) protein. Molecular modeling studies suggested that these compounds appropriately interact in the active sites of receptor. Graphical abstract: [Figure not available: see fulltext.].
Preparation method of alfentanil and sufentan and compounds used for preparation of sufentanil and alfentan
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Paragraph 0256; 0257; 0258, (2017/06/02)
The invention discloses a preparation method of alfentanil and sufentan and compounds used for preparation of sufentanil and alfentan. Specifically, the method for preparation of a compound shown as formula V includes: carrying out BOC reaction on a compound shown as formula IV to obtain the compound shown as formula V in the specification. The method can conveniently, efficiently and safely prepare an intermediate product for synthesis of alfentanil and sufentan, i.e. the compound shown as formula V. And then, the compound shown as formula V can be effectively used for preparation of alfentanil and sufentan.
Substituted piperidine amide derivative, preparation method thereof, and application of derivative to pharmacy
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Paragraph 0160; 0161; 0162; 0163, (2017/08/30)
The invention relates to a substituted piperidine amide derivative as shown in a general formula (I) or a stereisomer and pharmaceutically acceptable salt thereof, a preparation method of the derivative, medicinal combination as well as application of the derivative to the aspects of local anaesthesia or analgesia. The definition of each group of the general formula (I) is consistent with that of the description. (The general formula (I) is as shown in the description).
SUBSTITUTED 1-ARYLETHYL-4-ACYLAMINOPIPERIDINE DERIVATIVES AS OPIOID/ALPHA-ADRENORECEPTOR MODULATORS AND METHOD OF THEIR PREPARATION
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Page/Page column 19, (2016/03/13)
The invention provides compounds that bind with high affinities to the μ-, δ- and κ- opioid receptors and α2 - adrenoreceptor. In addition to providing these compounds with novel pharmacological binding properties, the invention also describes detailed novel methods for the preparation of representative compounds and a scheme for the synthesis of related compounds that bind to the opioid receptors and/or α2 - adrenoreceptor.
An efficient, optimized synthesis of fentanyl and related analogs
Valdez, Carlos A.,Leif, Roald N.,Mayer, Brian P.
, (2015/02/19)
The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73-78%) along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids.
SUBSTITUTED 4-AMINO-PIPERIDINES
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Page/Page column 26, (2010/02/17)
The present invention relates to new substituted 4-amino-piperidine opioid receptor modulators, pharmaceutical compositions thereof, and methods of use thereof
Heterocyclic compound and use thereof
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Page/Page column 102-103, (2010/06/16)
Compounds represented by the formulas wherein each symbol is as defined in the specification, and a prodrug thereof have a superior renin inhibitory activity, and are useful as agents for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension and the like.
