- Palladium-Catalyzed Migratory Insertion of Carbenes and C-C Cleavage of Cycloalkanecarboxamides
-
A palladium catalyzed reaction of cycloalkanecarboxamides and diazomalonates or bis(phenylsulfonyl)diazomethane has been developed. The reaction proceeds via carbene migratory insertion and cascade C-C cleavage pathways. Cycloalkanecarboxamides with four to seven membered rings are applicable in the transformation. A series of ring opening products were prepared with moderate yields. The finding provides valuable clues for the development of new reactions involving carbene migratory insertion and the cleavage of unstrained C(sp3)-C(sp3) bonds.
- Zhang, Peng,Zeng, Jia,Pan, Ping,Zhang, Xue-Jing,Yan, Ming
-
supporting information
p. 536 - 541
(2022/01/20)
-
- Lappaconitine derivative with analgesic activity, and preparation method and application thereof
-
The invention provides a lappaconitine derivative with analgesic activity, and a preparation method and application thereof. The structure of the lappaconitine derivative is as shown in formula I in the specification. The lappaconitine derivative provided by the invention is high in analgesic activity, good in water solubility and low in biotoxicity, can be used for preparing low-toxicity analgesic drugs, and is wide in application prospect.
- -
-
Paragraph 0363-0368
(2021/07/14)
-
- The parmodulin NRD-21 is an allosteric inhibitor of PAR1 Gq signaling with improved anti-inflammatory activity and stability
-
Novel analogs of the allosteric, biased PAR1 ligand ML161 (parmodulin 2, PM2) were prepared in order to identify potential anti-thrombotic and anti-inflammatory compounds of the parmodulin class with improved properties. Investigations of structure-activi
- Gandhi, Disha M.,Rosas, Ricardo,Greve, Eric,Kentala, Kaitlin,D.-R. Diby, N'Guessan,Snyder, Vladyslava A.,Stephans, Allison,Yeung, Teresa H.W.,Subramaniam, Saravanan,DiMilo, Elliot,Kurtenbach, Khia E.,Arnold, Leggy A.,Weiler, Hartmut,Dockendorff
-
supporting information
p. 3788 - 3796
(2019/07/17)
-
- Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug Discovery
-
The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps—synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future.
- Kirichok, Alexander A.,Shton, Irina O.,Pishel, Irina M.,Zozulya, Sergey A.,Borysko, Petro O.,Kubyshkin, Vladimir,Zaporozhets, Olha A.,Tolmachev, Andrei A.,Mykhailiuk, Pavel K.
-
supporting information
p. 5444 - 5449
(2018/04/23)
-
- Improved method used for preparing quinazoline drugs
-
The invention relates to an improved method used for preparing quinazoline drugs, and provides a synthesis route taking 2-chloro-4-amino-6,7-dimethoxyquinazoline as an intermediate. The synthesis route comprises following steps: acrylonitrile and a methylamine alcohol solution are subjected to amination reaction so as to obtain intermediate (I); triethylamine is taken as an acid binding agent, andbenzyl chloride is taken as a protective group so as to obtain an intermediate (II); a metal hydride is adopted so as to obtain an intermediate (III) through reduction; acylation with tetrahydro-2-furancarbonylchloride is carried out so as to obtain an intermediate (IV); the intermediate (IV) and ammonium formate are subjected to hydrogenolysis under catalytic effect of palladium on carbon so asto obtain an intermediate (V); and at least condensation reaction with 2-chloro-4-amino-6,7-dimethoxyquinazoline is carried out so as to obtain quinazoline drug Alfuzosin Hydrochloride (VI). Comparedwith the prior art, the improved method possesses following advantages: operation is simple and safe; reaction conditions are convenient to control; energy consumption is low; yield is stable; and industrialized application prospect is promising.
- -
-
Paragraph 0032; 0038
(2018/07/06)
-
- A process for the preparation of alfuzosin hydrochloride method (by machine translation)
-
The invention relates to a process for the preparation of alfuzosin hydrochloride method, method comprises the following steps: (1) 15 °C following, acrylonitrile into the the methylamine is mellow solution to stir, by distillation to obtain (I); (2) to (I) is dripped reducing agent in an organic solvent, heating to reflux, then slowly sequentially into the 25% sodium hydroxide solution and distilled water, by the distillation treatment to obtain the (II); (3) under dry condition, the thionyl chloride is slowly dripped into the 2 - tetrahydrofuran formic acid, a 2 - tetrahydrofuran chloride; (4) the temperature control in the 5 - 15 °C conditions, will be 2 - tetrahydrofuran formyl the chlorine drips into containing acid, organic solvent and (II) of the mixed solution, then completing the stirring 3 hours, for 25% sodium hydroxide solution to neutralize, by organic solvent extraction, (III) be; (5) to (III) with 2 - chloro - 4 - amino - 6, 7 - dimethoxy quinazoline in presence of organic solvent, reflux stirring 4 - 10 hours, cooling and filtering, and steaming and removing the organic solvent, acetone dispersed precipitate solid, then re-crystallizing mixed solvent, to get the alfuzosin hydrochloride (IV). (by machine translation)
- -
-
Paragraph 0023; 0024; 0027
(2017/08/29)
-
- 2-thioquinazolinedione derivatives
-
The invention belongs to the field of medicine and chemical industry, and in particular, relates to 2-thioquinazolinedione derivatives and a use thereof in drugs. Specifically, the invention relates to compounds having the use of inhibiting poly(ADP-ribose) polymerase activity, wherein the enzyme is also known as poly(ADP-ribose) synthetase and polyADP-ribosyltransferase, and is commonly known as PARP. The compounds have the following characteristics described in the specification. In the compounds represented by the formula (I), A and D together represent substituted fused aromatic rings; X can be NRX or CRXRY; if X is NRX, n is 1 or 2; if X is CRXRY, n is 1; RX can be selected from H, substitutive C1-20 alkyl, C5-20 aryl, C3-20 heterocyclic group, amide, thioamide, ester, acyl and sulfonyl; RY is selected from H, hydroxyl, amino and the like; or RX and RY can together form a spiro-C3-7 cyclic hydrocarbon group or a heterocyclic group; R2 and R3 are both H, or when X=CRXRY, R2, R3, RX, and RY and carbon atoms connected therewith can form a substitutive fused aromatic ring; and R1 is selected from H or halogen.
- -
-
Paragraph 0076; 0077; 0078
(2017/07/20)
-
- Industrial preparation method of acetyl tetrahydrofuran with high optical purity
-
The invention discloses an industrial preparation method of acetyl tetrahydrofuran with a high optical purity, and belongs to the field of chemical synthesis. According to the preparation method, tetrahydrofuroic acid is taken as the raw material and then is chlorinated to obtain tetrahydrofuran carbonyl chloride, tetrahydrofuran carbonyl chloride and Meldrum's acid carry out condensation reactions, and reaction product is hydrolyzed to obtain the target compound namely acetyl tetrahydrofuran. The preparation method has the advantages that the raw material cost is low, the preparation method does not need any Grignard reagent, the product property is stable, the purity can reach 98% or more, the optical purity can reach 99% or more, and the yield can reach 70% or more. The method has applied to industrial production. The product quality is stable. The reaction conditions are mild. The operation is safe and reliable. Dichloromethane can be recycled. The technology has the advantages of good repeatability and low preparation cost, and is a reliable industrial production method of acetyl tetrahydrofuran with a high optical purity.
- -
-
Paragraph 0011; 0029
(2016/10/08)
-
- Safe, selective, and high-yielding synthesis of acryloyl chloride in a continuous-flow system
-
Acid chlorides are an important class of compounds and their high reactivity and instability has prompted us to develop a straightforward procedure for their synthesis with ondemand and on-site synthesis possibilities. The focus of this report is acryloyl chloride, mainly important for the acrylate and polymer industry. A continuous-flow methodology was developed for the fast and selective synthesis of the otherwise highly unstable acryloyl chloride. Three routes were investigated in a microreactor setup and all three can potentially be used for its production. The methodology was further expanded to the synthesis of other unstable acid chlorides by both the thionyl chloride and the oxalyl chloride mediated processes. The most sustainable method was the oxalyl chloride mediated procedure under solvent-free conditions, in which nearequimolar amounts of carboxylic acid and oxalyl chloride were used in the presence of catalytic amounts of DMF at room temperature. Within 1 to 3 min, nearly full conversions into the acid chlorides were achieved.
- Movsisyan, Marine,Heugebaert, Thomas S. A.,Dams, Rudy,Stevens, Christian V.
-
p. 1945 - 1952
(2018/08/17)
-
- Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp3 C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems
-
An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp3 C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp3)-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities. The stereochemistry of the products obtained in this work were unambiguously assigned on the basis of the X-ray structure analyses of representative compounds 3b, 3e, 4p, and 7.
- Parella, Ramarao,Babu, Srinivasarao Arulananda
-
p. 2339 - 2355
(2015/06/01)
-
- Quinoline-based compound and selective androgen receptor agonist comprising the same
-
Provided are a novel quinoline-based compound, a pharmaceutical composition containing the quinoline-based compound, and a method for producing the quinoline-based compound. The quinoline-based compound acts on an androgen receptor to increase activities of the androgen receptor, and thus can be favorably used as an agent for treating and preventing diseases or conditions, in which the increased activities of the androgen can lead to improvement of symptoms or the responsiveness to treatment, for example, various hormone-related diseases of the male or female, muscle-wasting disease, osteoporosis, and the like.COPYRIGHT KIPO 2016
- -
-
Paragraph 0404-0406
(2016/10/08)
-
- HETEROCYCLIC COMPOUND
-
Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.
- -
-
Page/Page column 59
(2013/02/28)
-
- PYRONE COMPOUND AND ITS USE FOR PEST CONTROL
-
A pyrone compound represented by formula (1) has an excellent controlling effect on pests. Since the compound of formula (1) has a controlling activity on pests, the compound is useful as an active ingredient of a pest control agent.
- -
-
Page/Page column 207-208
(2011/05/06)
-
- THIAZOLOPYRIMIDINONE DERIVATIVES AS PI3 KINASE INHIBITORS
-
This invention relates to the use of thiazolopyrimidinone derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3' OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ
- -
-
Page/Page column 75-76
(2010/12/18)
-
- Process for the Preparation of Alfuzosin Hydrochloride
-
A process for preparing alfuzosin or a salt thereof comprising: (a) condensing 4-amino-2-chloro-6,7-dimethoxyquinazoline with 3-methylaminopropionitrile in the presence of a polar aprotic solvent selected from the group consisting of diglyme, dimethyl formamide, t-butanol, hexamethylphosphoramide or mixtures thereof to form N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine (b) hydrogenating the N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine using a hydrogenating agent under a pressure of less than 10 kg/cm2 to form N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine and optionally converting the N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine to an acid addition salt thereof; and (c) converting tetrahydrofuroic acid to an intermediate form and condensing the intermediate form with the N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine or with the acid addition salt to yield alfuzosin base, and optionally converting alfuzosin base to a salt of alfuzosin.
- -
-
Page/Page column 8
(2010/10/19)
-
- Sulfonamidolactam inhibitors of coagulation factor Xa
-
As part of an effort to identify novel backups for previously reported pyrazole-based coagulation Factor Xa inhibitors, the pyrazole 5-carboxamide moiety was replaced by 3-(sulfonylamino)-2-piperidone. This led to the identification of a structurally dive
- Smallheer, Joanne M.,Wang, Shuaige,Laws, Mia L.,Nakajima, Suanne,Hu, Zilun,Han, Wei,Jacobson, Irina,Luettgen, Joseph M.,Rossi, Karen A.,Rendina, Alan R.,Knabb, Robert M.,Wexler, Ruth R.,Lam, Patrick Y.S.,Quan, Mimi L.
-
p. 2428 - 2433
(2008/09/21)
-
- ION CHANNEL MODULATORS
-
The present teachings provide compounds of Formula (I): and pharmaceutically acceptable salts, hydrates, and esters thereof, wherein Ar, R1, R2, R3, p, and X are defined herein. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
- -
-
Page/Page column 123
(2008/12/06)
-
- Benzoimidazolone-carboxamide compounds as 5-HT4 receptors agonists
-
The invention provides novel benzoimidazolone-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.
- -
-
Page/Page column 23
(2010/11/25)
-
- PROCESSES FOR THE PREPARATION OF ALFUZOSIN AND SALTS THEREOF AND NOVEL CRYSTALLINE FORMS OF ALFUZOSIN
-
The present invention provides novel crystalline forms of a.lfuzosin and alfuzosin hydrochloride and processes for their preparation. Also provided are pharmaceutical compositions containing the new crystalline forms.
- -
-
Page/Page column 30
(2008/06/13)
-
- Electrochemical fluorination of several esters derived from oxolane-2-yl-carboxylic acid, oxolane-2-yl-methanol and oxane-2-yl-methanol
-
Electrochemical fluorination (ECF) of the ester derivatives of oxolane-2-yl-carboxylic acid (1), oxolane-2-yl-methanol (2) and oxane-2-yl-methanol (3) were investigated. Perfluoro(oxolane-2-yl- carbonylfluoride) (4) was obtained from derivatives of 1 and 2, and perfluoro(oxane-2-yl-carbonylfluoride) (5) was obtained from derivatives of 3 as the desired compounds, respectively. From the ECF of acetates of 2 and 3, perfluorospiroethers having a dioxolane ring were also obtained as the cyclization product in low yield together with the desired perfluoroacid fluoride (4 and 5). The structure of these perfluorospiroethers was confirmed by analyzing the chlorinated products, which were obtained by the reaction with AlCl3.
- Abe, Takashi,Tamura, Masanori,Sekiya, Akira
-
p. 325 - 332
(2007/10/03)
-
- USE OF SELECTIVE ANTAGONISTS OF THE ALPHA 1b-ADRENERGIC RECEPTOR FOR IMPROVEMENT OF SEXUAL DYSFUNCTION
-
Described is the use in the treatment of either male or female sexual dysfunction of selective antagonists of the alpha1B-adrenergic receptor and the pharmaceutical compositions containing them as compounds capable of helping the sexual act avoiding at th
- -
-
Page/Page column 13
(2010/02/14)
-
- N-phenacylpyridinium bromides as acid corrosion inhibitors
-
The inhibiting effect of N-phenacylpyridinium bromides with the amide group in the pyridine ring on corrosion of carbon steel in 3 M sulfuric acid is studied. A relationship between the nature of substituents at the amide group and the corrosion-protectiv
- Yurchenko,Pogrebova,Pilipenko,Shubina
-
p. 1117 - 1120
(2007/10/03)
-
- Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors
-
The present application describes sulfonylaminovalerolactams and derivatives thereof of Formula I: or pharmaceutically acceptable salt forms thereof, wherein ring G is a mono- or bicyclic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.
- -
-
Page/Page column 43
(2008/06/13)
-
- Remote Effects Modulating the Spin Equilibrium of the Resting State of Cytochrome P450cam - An Investigation Using Active Site Analogues
-
The crystal structure of the resting state of cytochrome P450 cam (CYP101), a heme thiolate protein, shows a cluster of six water molecules in the substrate binding pocket, one of which is coordinating to iron(III) as sixth ligand. The resting
- Lochner, Martin,Mu, Linjing,Woggon, Wolf-D.
-
p. 743 - 765
(2007/10/03)
-
- Contrast media
-
The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents of formula I wherein n is 0 or 1, and where n is 1 each C6R5moiety may be the same or different; X denotes a bond or a group providing a 1
- -
-
-
- Staudinger reactions of unsymmetrical cyclic ketenes: A synthetically useful approach to spiro β-lactams and derivatives. Reaction mechanism and theoretical studies
-
An efficient and operationally simple synthesis of tetrahydrofuran-derived spiro-β-lactams using the ketene-imine cycloaddition route is described. Also the preparation of spiro-N-sulfonyl-β-lactam derivatives, which are analogs of monobactams, is reported. As far as we know, this is the first time that an unsymmetrical cyclic ketene is used in a Staudinger-type reaction. The experimental evidence suggests the involvement of a ketene derived from the acyl chloride precursor in the reaction. High-level ab initio calculations have been performed in order to get insight into the electronic effects controlling the stereochemical outcome of the reactions.
- Alonso, Eduardo,Del Pozo, Carlos,Gonzalez, Javier
-
p. 571 - 576
(2007/10/03)
-
- Iodinated x-ray contrast media
-
The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula C6R6wherein three non-adjacent R groups are iodine and the remaining R groups are non-ionic, hydrophilic moieties, said compou
- -
-
-
- Use of selective antagonists of the α1B-adrenergic receptor for improvement of sexual dysfunction
-
Described is the use in the treatment of either male or female sexual dysfunction of selective antagonists of the α1B-adrenergic receptor and the pharmaceutical compositions containing them as compounds capable of helping the sexual act avoidin
- -
-
-
- Nonionic radiographic contrast agents
-
New nonionic radiographic contrast agents having the formula STR1 wherein Y is a single bond, --CH2 CH2 --, --CH2 O--, --OCH2 --, STR2 --CH2 --, --CH2 --CH2 --CH2 --,
- -
-
-
- Heterocyclic nonionic X-ray contrast agents V: A facile conversion of 2-tetrahydrofuroamides into α-hydroxy-δ-valerolactams and a general synthesis of lactams conjugated to 2,4,6-triiodoisophthalamides
-
The synthesis of 2,4,6-triiodoisophthalamides substituted by a lactam moiety is described. A tandem ring opening-ring closure methodology consisting of a regiospecific ether cleavage of the tetrahydrofuroanilide 14b, followed by lactamization to α-oxygenated anilides 15b or 16b, gave α-O-functionalized-δ-valerolactams 12b or 13b, respectively. This approach is also compatible with the presence of ester and carbonyl chloride functions on the triiodophenyl moiety. A general synthesis of lactams 34-39 was also achieved. Further chemical modifications led to water soluble unsubstituted-lactams (34d, 35d, 37d) and α-hydroxyl-lactams [42(d,e), 13(d,e) and 43d] that are of interest as X-ray contrast agents.
- Marinelli,Arunachalam,Diamantidis,Emswiler,Fan,Neubeck,Pillai,Wagler,Chen,Natalie,Soundararajan,Ranganathan
-
p. 11177 - 11214
(2007/10/03)
-
- Nonionic radiographic contrast agents
-
Novel nonionic contrast agents of the formula STR1 or dimers of the formula STR2 are disclosed where X, Z and R1 -R5 are as defined herein.
- -
-
-
- Process for preparation of 2-oxo-1 piperidinyl derivatives
-
The process involves ring opening and ring closure of compounds containing a tetrahydrofuroyl group STR1 to provide facile synthesis of compounds containing a piperidin-2-one group of the formula STR2
- -
-
-
- Synthesis of C-Nucleosides via Radical Coupling Reaction
-
Photolysis of O-acyl derivatives of N-hydroxy-2-thiopyridone, prepared from tetrahydrofuran-2-carboxylic acid, D-ribofuranosylmethanoic acid, and D-ribopyranosylmethanoic acid, gave the corresponding C-nucleoside derivatives in the presence of heteroaromatic compounds via radical pathways.The essential step in this method is a radical coupling reaction of D-ribofuranosyl radical or D-ribopyranosyl radical and some heteroaromatic bases.This is a new method for the preparation of C-nucleosides using sugar carboxylic acids.
- Togo, Hideo,Ishigami, Sachiko,Fujii, Misa,Ikuma, Toshihiro,Yokoyama, Masataka
-
p. 2931 - 2942
(2007/10/02)
-
- Enolate Claisen Rearrangement of Esters from Furanoid and Pyranoid Glycals
-
A general method is described for the formation of furanoid and pyranoid glycals.Thus, lithium-ammonia reduction of the corresponding 1-chloro-2,3-O-isopropylidene furanoid and pyranoid carbohydrate derivatives affords the desired glycals in 87-92percent yields.Several examples that reveal the scope of this process are described .The formation of C-glycosides from the glycal esters through application of the ester enolate Claisen rearrangement is explored.The characteristics and stereochemistry of this process in both the acyclic and cyclic series of glycal derivatives are described.
- Ireland, Robert E.,Thaisrivongs, Suvit,Vanier, Noel,Wilcox, C. S.
-
-