15 results about "Isostere" patented technology

Disclosed are activation of tertiary alkylboronic esters with adamantyllithium generated in situ to enable stereoretentive boron-to-copper transmetalation and cross-coupling reaction of the resultant alkylcopper species with an array of electrophiles to furnish synthetically useful compounds bearing quaternary stereocenters. In addition, palladium-catalyzed asymmetric synthesis of nortricyclane derivatives from norbornene bis(boronate) through chiral boronate-containing nortricyclane intermediates and application of the nortricyclane derivatives as isosteres of the corresponding aromatic compounds in pharmaceutical motifs are also disclosed.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to an N-thioacyl homoserine lactone compound and a preparation method thereof, the compound is an analogue of a natural self-inducer N-acyl homoserine lactone AHLs, and thioamide is used as a biological isostere of amide to replace an amide group in the natural self-inducer. The compound has an obvious inhibition effect on a Vibrio fischeri Lux system and related toxic gene phenotypes regulated by the Vibrio fischeri Lux system and can be used as a Vibrio fischeri quorum sensing activity inhibitor, and thioamide is more stable in chemical structure than dithiocarbamate and has better enzyme hydrolysis stability.

Provided are embodiments of para-substituted 1,1-dialkyl-4-phenylpiperazin-1-ium iodides advantageous for modulating inflammation that have been synthesized and their electrophysiology activities for α9, α9α10, and α7 nAChRs compared. The para position contained alkyl or aryl amides, or heterocyclic isosteres for the amide, and the alkyl groups were varied at the ammonium piperazine nitrogen to see if compensatory changes in size at this position of the molecule impacted function. The compounds were characterized with two-electrode voltage-clamp measurements on Xenopus oocytes expressing nAChRs. General, the compounds were more potent for α9-containing receptors than for α7, and the majority were either full or strong partial agonists for α9-containing nAChR.

The invention provides an N-substituted benzene ring bioisostere and a preparation method thereof, and the N-substituted benzene ring bioisostere is generated by reacting a benzene-containing compound with alkyl carboxylic acid under photocatalysis and electrochemical conditions in the presence of an organic solvent, alkali, electrolyte and a catalyst. The synthesis method provided by the invention is simple to operate and high in atom economy, and the obtained target compound has the characteristics of good functional group compatibility and wide substrate. And the N-substituted benzene ring bioisostere prepared on the basis of the method can be applied to development and modification of pilot drugs, and has good application potential in pharmaceutical chemistry.

Disclosed are activation of tertiary alkylboronic esters with adamantyllithium generated in situ to enable stereoretentive boron-to-copper transmetalation and cross-coupling reaction of the resultant alkylcopper species with an array of electrophiles to furnish synthetically useful compounds bearing quaternary stereocenters. In addition, palladium-catalyzed asymmetric synthesis of nortricyclane derivatives from norbornene bis(boronate) through chiral boronate-containing nortricyclane intermediates and application of the nortricyclane derivatives as isosteres of the corresponding aromatic compounds in pharmaceutical motifs are also disclosed.

The invention relates to the technical field of organic chemistry, and particularly discloses a chiral bicyclo [1.1. 1] pentane derivative and a preparation method thereof.According to the chiral bicyclo [1.1. 1] pentane derivative, bicyclic hydrocarbon rich in C (sp3) is used for replacing aromatic rings, chiral bicyclo [1.1. 1] pentane is replaced by biological isosteres, and the chiral bicyclo [1.1. 1] pentane is used for preparing the chiral bicyclo [1.1. 1] pentane derivative. The invention plays a crucial role in modern medicine function research. Bicyclo [1.1. 1] pentane derivatives are particularly concerned due to its unique three-dimensional stereochemical complexity, the present invention provides a method for synthesizing bicyclo [1.1. 1] pentane through nitrogen atom insertion and deletion strategies, which has good stereoselectivity and couples chiral bicyclo [1.1. 1] pentane with a plurality of drugs for altering the properties and efficacy of the drugs, in order to improve the therapeutic effect of the drugs. For example, pharmacokinetic properties and water solubility are altered.

Disclosed are various synthetic methods to prepare structural analogs of largazole and derivatives thereof. One structural analog is an amide isostere of largazole. Another structural analog replaces the thiazole ring of largazole with a pyridine moiety or an oxazole moiety. Also disclosed are various intermediate compounds obtained when preparing structural analogs of largazole and derivatives thereof, including macrocycle analogs having an alcohol functionality.

The invention discloses a selenium-containing compound as well as a preparation method and application thereof. The structural general formula of the selenium-containing compound is shown as any one of formulas (I), (II), (III), (IV), (V) and (VI): # imgabs 0, wherein R1 is # imgabs 1 #, R8 is # imgabs 2 #, and R9 is one of H, F, Cl, Br and substituted or unsubstituted C1-C5 alkyl. In consideration of the special property of selenium and the effect of selenium in an isostere, a PD-1 / PD-L1 inhibitor of a selenium-containing small molecule targeted PD-L1 protein is designed and synthesized, the biological activity of the inhibitor is investigated, and experiments prove that the compound can remarkably inhibit interaction of PD-1 and PD-L1 at the molecular level, so that the compound can be used for preparing a medicine for preventing and treating the PD-1 and the PD-L1, and can be used for preparing a medicine for preventing and treating the PD-1 and the PD-L1. Therefore, the compound can be used for treating diseases related to interaction of PD-1 / PD-L1.

In the field of biomedicine, the importance and potential value of the carbon-glycoside compounds are increasingly prominent. Carbon-glucoside widely existing in medicinal plants shows remarkable physiological activity in the aspects of oxidation resistance, inflammation resistance, bacteria resistance and the like; wherein the natural product of beta-acyl-carbon-glucoside, namely Sclerpentasides A-F, is separated from a semi-parasitic plant Dendrophthoe pentras, and is used for treating the hypertension and the diabetes mellitus in the Thailand traditional medicine, so that the Sclerpentasides A-F can be used for treating the hypertension and the diabetes mellitus. Beta-acyl-carbon-glycoside is formed by acyl and glycosyl, keto carbonyl of the beta-acyl-carbon-glycoside has potential chemical conversion capacity, and a new thought is provided for modification of existing carbon-glycoside drugs. In pharmaceutical chemistry, carbon-glycosides are often used as stable mimetics of oxygen-glycosides and nitrogen-glycosides, which are designed according to the characteristics that carbon-glycosides are used as electron isosteres of oxygen glycosides in pharmaceutical chemistry and can resist hydrolase and other decomposition pathways in vivo. A high-efficiency synthetic route is designed, and beta-acyl-carbon-glucoside can be successfully constructed through two-step reaction from sugar bromoglycoside. Wherein the beta-acyl-carbon-glucoside has excellent SGLT2 inhibitory activity, can effectively inhibit glucose absorption, and can be used for controlling blood sugar and treating diabetes mellitus.

The invention belongs to the technical field of medicinal chemistry, and particularly discloses a cycloastragenol tetrazole derivative and a preparation method and anti-inflammatory application thereof, and the method comprises the following steps: synthesizing an intermediate; the preparation method comprises the following steps: synthesizing cycloastragenol tetrazole derivatives such as A1-A7, B1-B7, C1-C8, D1-D3, E1-E2 and F1-F4; according to the cycloastragenol tetrazole derivative as well as the preparation method and the anti-inflammatory application thereof, 31 novel tetrazole derivatives are designed and synthesized through two ways by taking cycloastragenol as a lead compound on the basis of a biological isostere and molecule combination strategy, and the application of the cycloastragenol tetrazole derivative in anti-inflammatory treatment is realized. The prepared cycloastragenol tetrazole derivative shows the anti-inflammatory activity superior to that of parent cycloastragenol, the cycloastragenol tetrazole derivative A2 shows remarkable anti-inflammatory potential, and an important theoretical and structural foundation can be laid for follow-up research.

This invention belongs to the fields of organic chemistry, medicinal chemistry, and pharmacology, specifically relating to the synthesis of lometapeptide bioelectron isosteres and their application in the preparation of therapeutic drugs for lipid-lowering diseases. A method for preparing lometapeptide bioelectron isosteres mainly includes six steps: 1) Using A and B as starting materials, under nickel catalysis and the action of phosphine ligands, a reaction occurs... endo The reaction [2+2] yielded intermediate I; 2) Intermediate I underwent intramolecular cyclization under thioxanthracene-9-one and photocatalysis to yield intermediate II; 3) Intermediate II was oxidized under alkaline potassium permanganate to yield intermediate III; 4) Intermediate III and C reacted under the action of a condensing agent to prepare amide intermediate IV; 5) Intermediate IV was debenzylated under the action of palladium on carbon and a hydrogen source to prepare amine intermediate V; 6) Intermediate V and D under alkaline conditions underwent a substitution reaction to obtain the final product, lometapetine bioelectron isostere VI. This bioelectron isostere can dose-dependently inhibit the secretion of apolipoprotein B in HepG2 cells and exhibits good kinetic solubility. This compound shows promise for development as a therapeutic drug for hypercholesterolemia-related diseases.

The invention relates to the technical field of organic synthesis, and particularly discloses an oxabicyclo [2.1. 1] hexane derivative, the structural formula of the oxabicyclo [2.1. 1] hexane derivative is # imgabs0 #, and R is selected from a methoxy group, an ethyoxyl group, a trifluoroethyoxyl group and a phenyl group. Ar is selected from the group consisting of phenyl, 4-fluorophenyl, 4-chlorphenyl, 4-methylphenyl, 4-methoxyphenyl, 4-ethylphenyl, 4-trifluoromethylphenyl, 3-bromophenyl, 2-bromophenyl, 3, 4-difluorophenyl, 2-naphthyl, and 2-thienyl, and a pharmaceutically acceptable salt thereof. The oxabicyclo [2.1. 1] hexane derivative disclosed by the invention has a relatively wide substrate range and can be used as an isostere of m-substituted benzene. Therefore, the derivative has certain application value in the fields of medicinal chemistry and organic synthesis. The oxabicyclo [2.1. 1] hexane derivative disclosed by the invention is high in synthesis yield, mild in synthesis reaction condition and safe, simple and convenient to operate.

The invention discloses a gem-difluoro-2-oxabicyclo [2.1. 1] hexane compound and a preparation method thereof, 1, 1-difluoro-3-(vinyloxy) prop-1-ene and 3, 3-difluoro-3-(vinyloxy) prop-1-ene are used as initial raw materials, under the catalysis of a photocatalyst and the irradiation of visible light, intramolecular cycloaddition is carried out to obtain 6, 6-difluoro-2-oxabicyclo [2.1. 1] hexane and 3, 3-difluoro-3-(vinyloxy) prop-1-ene, and the gem-difluoro-2-oxabicyclo [2.1. 1] hexane compound is synthesized through the intramolecular cycloaddition of 6, 6-difluoro-2-oxabicyclo [2.1. 1] hexane. The invention relates to a 1, 3-difluoro-2-oxabicyclo [2.1. 1] hexane product. According to the gem-difluoro-2-oxabicyclo [2.1. 1] hexane compound provided by the invention, two different types of electron isosteres (2-oxabicyclo [2.1. 1] hexane and difluoromethylene) are combined together, so that a brand new mixed biological electron isostere is obtained, and a new structural unit is provided for the design and synthesis of drug molecules.

This disclosure relates to a series of small molecule agonists that mimic liver receptor homolog-1 (LRH-1). The compounds display exceptional potency and efficacy. Also disclosed are pharmaceutical compounds and methods of treating or preventing various conditions including cancer, cardiovascular disease, diabetes, colitis, or ulcerative colitis. Further disclosed are methods of modulating activity of LRH-1 in cells.