- Chemoselective: N-tert -butyloxycarbonylation of amines in glycerol
-
A catalyst-free, efficient and green protocol has been developed for the chemoselective N-Boc protection of amines by using glycerol as a solvent at room temperature. A variety of functionalized amines, such as aliphatic, aromatic as well as heteroaromatic were protected using the developed protocol. N-tert-Butyloxycarbonylation derivatives were formed without the formation of isocyanate, urea, N,N-di-t-Boc, or oxazolidinone as side products. The operational simplicity, cleaner reaction, rapid reaction convergence, functional group tolerance, excellent yield, high selectivity, catalyst-free feature and solvent recyclability are the distinct advantages of this protocol. Owing to these merits, this protocol is feasible, economical and environmentally benign.
- Ingale, Ajit P.,More, Vishal K.,Gangarde, Uddhav S.,Shinde, Sandeep V.
-
-
Read Online
- Nanoceria as an efficient and green catalyst for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions
-
Nanocerium oxide mediated an efficient and green protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at ambient temperature. Various aliphatic, aromatic and heteroaromatic amines were protected using developed protocol and several functional groups such as alcohol, phenol and ester were well tolerated under these conditions. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
- Garad, Dnyaneshwar N.,Ingale, Ajit P.,Shinde, Sandeep V.,Ukale, Dattatraya
-
-
Read Online
- Sulfated tungstate: A highly efficient, recyclable and ecofriendly catalyst for chemoselective N-tert butyloxycarbonylation of amines under the solvent-free conditions
-
Sulfated tungstate catalyzed an efficient and ecofriendly protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at room temperature. The variety of functionalized aliphatic, aromatic and heteroaromatic amines efficiently undergoes the N-tert-butyloxycarbonylation under the developed protocol. The aminoalcohol, aminophenol, aminoester as well as various chiral amines underwent the chemoselective N-Boc protection under the optimized reaction condition. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
- Ingale, Ajit P.,Shinde, Sandeep V.,Thorat, Nitin M.
-
-
Read Online
- De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus
-
Dengue fever is a mosquito-borne viral disease that has become a major public health concern worldwide. This disease presents with a wide range of clinical manifestations, from a mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, neither an approved drug nor an effective vaccine for the treatment are available to fight the disease. The envelope protein (E) is a major component of the virion surface. This protein plays a key role during the viral entry process, constituting an attractive target for the development of antiviral drugs. The crystal structure of the E protein reveals the existence of a hydrophobic pocket occupied by the detergent n-octyl-β-d-glucoside (β-OG). This pocket lies at the hinge region between domains I and II and is important for the low pH-triggered conformational rearrangement required for the fusion of the virion with the host's cell. Aiming at the design of novel molecules which bind to E and act as virus entry inhibitors, we undertook a de novo design approach by “growing” molecules inside the hydrophobic site (β-OG). From more than 240000 small-molecules generated, the 2,4 pyrimidine scaffold was selected as the best candidate, from which one synthesized compound displayed micromolar activity. Molecular dynamics-based optimization was performed on this hit, and thirty derivatives were designed in silico, synthesized and evaluated on their capacity to inhibit dengue virus entry into the host cell. Four compounds were found to be potent antiviral compounds in the low-micromolar range. The assessment of drug-like physicochemical and in vitro pharmacokinetic properties revealed that compounds 3e and 3h presented acceptable solubility values and were stable in mouse plasma, simulated gastric fluid, simulated intestinal fluid, and phosphate buffered saline solution.
- Acosta Dávila, John Alejandro,Adler, Natalia S.,Aucar, Maria G.,Battini, Leandro,Bollini, Mariela,Cavasotto, Claudio N.,Cordo, Sandra M.,Fernández, Gabriela A.,Gamarnik, Andrea V.,García, Cybele C.,Gebhard, Leopoldo G.,Hernández de los Ríos, Alejandro,Leal, Emilse S.,Monge, María Eugenia,Morell, María L.,Videla, Mariela
-
supporting information
(2019/08/30)
-
- 3-(ureido-methyl)-4-aryl-pyridine compound, preparation method thereof and application thereof as anti-hepatoma medicament
-
The invention discloses a 3-(ureido-methyl)-4-aryl-pyridine compound, a preparation method thereof and application thereof as an anti-hepatoma medicament. The invention discloses a compound shown as aformula I or a pharmacologically-acceptable salt, crystal form and solvate thereof, wherein X is O or S; n is an integer of 0 to 3; R1, R2, R3, R4 and R5 are independently selected from H, cyan, COOR11, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, trifluoromethyl, amino, nitro, hydroxyl, mercapto or halogen; R11 is selected from H or alkyl having 1 to 4 carbon atoms. Meanwhile, the invention also discloses a preparation method of the compound shown as the formula I. The compound disclosed by the invention has lower median inhibitory concentration (IC50), and a very good inhibition function on hepatoma carcinoma cells; moreover, the preparation method of the compound disclosed by the invention is simple and convenient, and has the advantages of mild reaction condition, convenience in operation and control, low energy consumption, high yield and low cost, and can be suitable for industrial production. The formula I is shown in the description.
- -
-
Paragraph 0071; 0072; 0075
(2018/03/26)
-
- Pd-catalyzed Suzuki-Miyaura cross-coupling reactions between sulfamates and potassium Boc-protected aminomethyltrifluoroborates
-
Sulfamates were studied as the electrophilic partners in the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction with potassium Boc-protected primary and secondary aminomethyltrifluoroborates. A broad range of substrates was successfully coupled to provide the desired products. Complex molecules containing a new carbon-carbon bond and an aminomethyl moiety could be prepared through this developed method.
- Molander, Gary A.,Shin, Inji
-
supporting information
p. 2534 - 2537
(2013/06/27)
-
- Control of site of lithiation of 3-(Aminomethyl)pyridine derivatives
-
Lithiation of N-(pyridin-3-ylmethyl)pivalamide, tert-butyl N-(pyridin-3-ylmethyl)carbamate, and N,N-dimethyl-N′-(pyridin-3-ylmethyl) urea with tert-butyllithium (3 equiv) in anhydrous tetrahydrofuran at -78 °C takes place on the nitrogen and on the ring at the 4-position. The dilithium reagents thus obtained react with various electrophiles to give the corresponding substituted derivatives in high yields. On the other hand, regioselective side-chain lithiation occurs with lithium diisopropylamide (3.3 equiv) at -20 to 0 °C. A mixture of ring and side-chain substitution products is obtained with n-butyllithium as the lithium reagent. Treatment of one of the ring-substituted products with trifluoroacetic anhydride in dichloromethane under reflux conditions led to formation of the corresponding 1H-pyrrolo[3,4-c]pyridine in high yield. Georg Thieme Verlag Stuttgart . New York.
- Smith, Keith,El-Hiti, Gamal A.,Alshammari, Mohammed B.,Fekri, Ahmed
-
p. 3426 - 3434
(2014/01/06)
-
- Suzuki-Miyaura cross-coupling reactions of potassium boc-protected aminomethyltrifluoroborate with aryl and hetaryl mesylates
-
Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions were studied with potassium Boc-protected aminomethyltrifluoroborate through C-O activation of various mesylate derivatives to afford the corresponding products in moderate to good yields.
- Molander, Gary A.,Shin, Inji
-
supporting information; experimental part
p. 3138 - 3141
(2012/08/07)
-
- ANTICANCER DERIVIATIVES, PREPARATION THEREOF, AND THERAPEUTIC USE THEREOF
-
The invention relates to nicotinamide derivatives which can be used as anticancer drugs.
- -
-
Page/Page column 14
(2012/04/23)
-
- Synthesis and application of a new fluorous-tagged ammonia equivalent
-
A novel fluorous-tagged ammonia equivalent has been developed. It is based on a nitrogen-oxygen bond, which can be cleaved in a traceless manner by a molybdenum complex or samarium diiodide. The application in the synthesis of ureas, amides, sulfonamides, and carbamates is described. The scope of the fluo-rous N-O linker is exemplified by the synthesis of itopride, a drug used for the treatment of functional dyspepsia. Itopride was synthesized with the aid of fluorous purification methods and the product was isolated in good overall yield, with high purity.
- Nielsen, Simon D.,Smith, Garrick,Begtrup, Mikael,Kristensen, Jesper L.
-
supporting information; experimental part
p. 4557 - 4566
(2010/08/20)
-
- Process and intermediates for the synthesis of (3-alkyl-5-piperidin-1-yl-3,3a-dihydro-pyrazolo[1,5-a]pyrimidin-7-yl)-amino derivatives and intermediates
-
This application discloses a novel process to synthesize (3-alkyl-5-piperidin-1-yl-3,3a-dihydro-pyrazolo[1,5-a]pyrimidin-7-yl)-amino derivatives, and intermediates useful in the synthesis thereof. The subject (3-alkyl-5-piperidin-1-yl-3,3a-dihydro-pyrazolo[1,5-a]pyrimidin-7-yl)-amino derivatives are useful as cyclin-dependent kinase inhibitor compounds (CDK inhibitors) in pharmaceutical preparations.
- -
-
Page/Page column 12
(2008/06/13)
-
- Pyrimidine derivatives useful as inhibitors of PKC-theta
-
Disclosed are novel compounds of formula (I): wherein X, Y, R1, R2 and R3 are as defined herein, which are useful as inhibitors of PKC-theta and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC-theta, including immunological disorders and type II diabetes. This invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
- -
-
Page/Page column 128-129
(2008/06/13)
-
- Pyrazolotriazines as kinase inhibitors
-
In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]triazine compounds as inhibitors of kinases such as, for example, cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing
- -
-
Page/Page column 16
(2008/06/13)
-
- PYRAZOLOPYRIMIDINES AS CYCLIN-DEPENDENT KINASE INHIBITORS
-
In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
- -
-
-
- Design and synthesis of potent and highly selective thrombin inhibitors
-
Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in th
- Hilpert,Ackermann,Banner,Gast,Gubernator,Hadvary,Labler,Muller,Schmid,Tschopp,Van de Waterbeemd
-
p. 3889 - 3901
(2007/10/02)
-
- Symmetry-Based Inhibitors of HIV Protease. Structure-Activity Studies of Acylated 2,4-Diamino-1,5-diphenyl-3-hydroxypentane and 2,5-Diamino-1,6-diphenylhexane-3,4-diol
-
The structure-activity relationships in two series of novel, symmetry-based inhibitors of HIV protease, the enzyme responsible for maturation of the human immunodeficiency virus, are described.Beginning with lead compounds 3-6, the effect of adding polar, heterocyclic end groups to one or both ends of the symmetric or pseudosymmetric inhibitors was probed.Aqueous solubility was enhanced >1000-fold while maintaining potent inhibition of purified HIV-1 protease and anti-HIV activity in vitro.Pharmacokinetic studies in rats indicated a substantial difference in the absorption properties of mono-ol-based and diol-based inhibitors.The oral bioavailability of inhibitor 19 in rats was 19percent; however, the Cmax obtained failed to exceed the anti-HIV EC50 in vitro.Substantial plasma levels of potent inhibitors of the diol class were not obtained after oral administration in rats; however, the optimal combination of aqueous solubility and in vitro antiviral activity of several inhibitors support their potential use in intravenous therapy.
- Kempf, Dale J.,Codacovi, Lynnmarie,Wang, Xiu Chun,Kohlbrenner, William E.,Wideburg, Norman E.,et al.
-
p. 320 - 330
(2007/10/02)
-
- Aryl Diazo Compounds and Diazonium Salts as Potential Irreversible Probes of the γ-Aminobutyric Acid Receptor
-
The synthesis of different diazonium salts derived from homo- and heterocyclic aromatic amines bearing anionic residues is described.The chemical stabilities of these compounds were established at different pH's, and the compounds were tested accordingly
- Bouchet, Marie-Jeanne,Rendon, Alvaro,Wermuth, Camille G.,Goeldner, Maurice,Hirth, Christian
-
p. 2222 - 2227
(2007/10/02)
-