- Synthetic method of 1,3,4-thiadiazole derivative
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The invention discloses a synthetic method of a 1,3,4-thiadiazole derivative. The method comprises the following steps: (1) using hydrazine hydrate as a raw material, under the action of a catalyst, reacting with acid, to obtain a hydrazide compound I; (2) using alkyl chloroformate and thiocyanate to react in a condition of a solvent, to obtain an isothiocyanate compound II; (3) in a reaction system of the isothiocyanate compound II, adding solution containing the compound I, reacting to obtain solution containing a compound III; (4) processing the solution of the compound III by dehydrating,neutralizing, and washing, to obtain a compound IV; (5) in the conditions of an acid-binding agent and a solvent, adding alkyl halide or sulfuric acid diester into the compound IV, reacting to obtaina compound V; and (6) enabling the compound V to perform an amination reaction with primary amine, to obtain the 1,3,4-thiadiazole derivative VI. The preparation method has the advantages of green andno pollution, simple and convenient operation, higher yield, mild reaction condition and the like.
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Paragraph 0031; 0032
(2018/12/05)
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- Method for preparing 3-isopropyl-4-amino-1,2,4-triazoline-5-ketone
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The invention discloses a method for preparing 3-isopropyl-4-amino-1,2,4-triazoline-5-ketone. The method comprises the following steps: 1, reacting isobutyric acid and hydrazine hydrate in an n-butylalcohol solvent at the reaction temperature of 50-150 DEG C, and producing isobutyrohydrazide; 2, reacting the isobutyrohydrazide synthesized in the step 1 and phosgene or solid light and the n-butylalcohol serving as the solvent at the reaction temperature of 0-60 DEG C, and producing 2-isobutyl hydrazino-butyl formate; 3, reacting the 2-isobutyl hydrazino-butyl formate synthesized in the step 2with hydrazine hydrate in aqueous alkali at a reaction temperature of 80-120 DEG C, thereby obtaining the 3-isopropyl-4-amino-1,2,4-triazoline-5-ketone and n-butyl alcohol. According to the method disclosed by the invention, single n-butyl alcohol serves as the solvent in the whole reaction process, the intermediate process is not separated, and the method has the advantages of being simple in reaction system, high in reaction speed and less in amount of three wastes; the n-butyl alcohol can be repeatedly used; and the synthetic method has the yield of 85%.
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Paragraph 0015; 0027; 0028; 0030; 0031; 0033; 0034; 0036
(2018/11/22)
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- COMPOUNDS AS HEPATITIS C INHIBITORS AND USES THEREOF IN MEDICINE
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Provided herein are compounds as hepatitis C inhibitors and uses thereof in medicine. Specifically, provided herein is a compound of Formula (I) or a stereoisomer, a tautomer, an enantiomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or hepatitis C diseases. Also provided herein are a pharmaceutically acceptable composition containing such compound and a method of treating HCV infection or hepatitis C diseases comprising administering the compound or pharmaceutical composition thereof disclosed herein.
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Paragraph 00233
(2016/09/22)
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- Arylazolylthioacetanilide. Part 11: Design, synthesis and biological evaluation of 1,2,4-triazole thioacetanilide derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors
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A series of novel 1,2,4-triazole thioacetanilide derivatives has been designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. Half of these compounds showed moderate to potent activities against wild-type HIV-1 with an EC50 ranging from 38.0 μM to 4.08 μM. Among them, 2-(4-(2-fluorobenzyl)-5-isopropyl-4H-1,2,4-triazol-3-ylthio)-N-(2-nitrophenyl) acetamide 7d was identified as the most promising compound (EC50 = 4.26 μM, SI = 49). However, no compound was active against HIV-2. The preliminary structure-activity relationships among the newly synthesized congeners are discussed.
- Li, Zhenyu,Cao, Yuan,Zhan, Peng,Pannecouque, Christophe,Balzarini, Jan,De Clercq, Erik,Shen, Yuemao,Liu, Xinyong
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p. 968 - 973
(2014/01/06)
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- INHIBITION OF P38 KINASE ACTIVITY USING SUBSTITUTED HETEROCYCLIC UREAS
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This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases, other than cancer and proteolytic enzyme mediated diseases, other than cancer, and pharmaceutical compositions for use in such therapy.
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Page/Page column 16
(2012/03/10)
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- ORGANOMETALLIC COMPLEX, LIGHT-EMITTING ELEMENT, DISPLAY DEVICE, ELECTRONIC DEVICE, AND LIGHTING DEVICE
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Provided are organometallic complexes that can exhibit phosphorescence. One of the novel organometallic complexes is represented by General Formula (G1). In General Formula (G1), R1 represents any of an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms which may have a substituent, and an aralkyl group having 7 to 10 carbon atoms which may have a substituent. In addition, R2 represents any of an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms which may have a substituent, and an aryl group having 6 to 12 carbon atoms which may have a substituent. Further, Ar represents an arylene group having 6 to 13 carbon atoms which may have a substituent. Further, M represents a Group 9 element or a Group 10 element.
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Page/Page column 110-111
(2011/05/11)
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- INHIBITORS OF AKT ACTIVITY
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The invention relates to a series of compounds with particular activity as inhibitors of the serine-threonine kinase AKT. Also provided are pharmaceutical compositions comprising same as well as methods for treating cancer.
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Page/Page column 156
(2011/07/09)
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- INHIBITION OF RAF KINASE USING SUBSTITUTED HETEROCYCLIC UREAS
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Methods of treating tumors mediated by raf kinase, with substituted urea compounds, and such compounds per se.
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Page/Page column 16
(2010/11/28)
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- Keto-1,3,4-oxadiazoles as cathepsin K inhibitors
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We have prepared a series of cathepsin K inhibitors bearing the keto-1,3,4-oxadiazole warhead capable of forming a hemithioketal complex with the target enzyme. By modifying binding moieties at the P1, P2, and prime side positions of the inhibitors, we have achieved selectivity over cathepsins B, L, and S, and have achieved sub-nanomolar potency against cathepsin K. This series thus represents a promising chemotype that could be used in diseases implicated by imbalances in cathepsin K activity such as osteoporosis.
- Palmer, James T.,Hirschbein, Bernard L.,Cheung, Harry,McCarter, John,Janc, James W.,Yu, Z. Walter,Wesolowski, Gregg
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p. 2909 - 2914
(2008/09/21)
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- Synthesis and in vitro leishmanicidal activity of some hydrazides and their analogues
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Twenty-one hydrazides were synthesized by treating different esters with hydrazine hydrate. Substituted hydrazides were obtained by treating hydrazides with alkyl/aryl/acyl halides. Some of these compounds exhibit potential in vitro leishmanicidal activity. The structures of all the synthesized compounds were confirmed by spectroscopic analysis.
- Khan, Khalid Mohammad,Rasheed, Maimona,Ullah, Zia,Hayat, Safdar,Kaukab, Farhana,Choudhary, M. Iqbal,Ur-Rahman, Atta,Perveen, Shahnaz
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p. 1381 - 1387
(2007/10/03)
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- Development of orally active nonpeptidic inhibitors of human neutrophil elastase
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5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an α-keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-l(F), 11d,e,k(H), 21d,e,k(F), and 21d,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure -activity relationships (SARs) are discussed.
- Ohmoto,Yamamoto,Okuma,Horiuchi,Imanishi,Odagaki,Kawabata,Sekioka,Hirota,Matsuoka,Nakai,Toda,Cheronis,Spruce,Gyorkos,Wieczorek
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p. 1268 - 1285
(2007/10/03)
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- REACTION DES O,O-DIETHYL OXO-1 ALKANEPHOSPHONATES AVEC LES DERIVES DE L'HYDRAZINE: UNE VOIE DE SYNTHESE DES HYDRAZONES α-PHOSPHONATEES ET DES HYDRAZIDES
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Under the normal conditions, the reaction of hydrazine and methylhydrazine with O,O-diethyl 1-oxoalkane phosphonates 1 proceeds by cleavage of the phosphorus-carbon bond and leads to the formation of diethylphosphite 2 and N-acylhydrazide 3.A procedure has been developed for the synthesis of new primary hydrazone of O,O-diethyl 1-oxoalkane phosphonates 4.A mechanism is proposed.The structure of those compounds 4 was confirmed by NMR and IR spectroscopy. Key words: Phosphore; O,O-diethyl 1-oxoalkane phosphonates; hydrazine; methylhydrazine; hydrazone; RMN(31)P; RMN(13)C; RMN(1)H; IR.
- Akacha, Azaiez Ben,Barkallah, Salim,Baccar, Belgacem
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p. 163 - 166
(2007/10/02)
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- Antihypertensive actions of hydrazidones: Study of acylated dichloroarylhydrazones
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A series of acylated dichloroarylhydrazones has been prepared and evaluated on spontaneously hypertensive rats (SHR). The presence of 2-Cl and 6-Cl aromatic substituents in a clonidine like position is not required since derivatives bearing 2- and 4-chloro as well as 3- and 4-chloro substituents exert antihypertensive activities. Activity is also maintained in certain 2,6 disubstituted derivatives where one of the chlorine atoms is replaced by F or NO2.
- Cave,Galons,Miocque,Rinjard,Tran,Binet
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- Unsaturated Compounds containing Nitrogen. Part 4. Further Reactions of 1-Chloro-2,3-diazabutadienes with S-Nucleophiles
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1-Chloro-1,4-diaryl-2,3-diazabutadienes (Ar1CCl=NN=CHAr2), prepared by the reaction of thionyl chloride with aroylhydrazones (Ar1CONHN=CHAr2), react with thiosemicarbazide or thiocarbohydrazide to give 2-arylidenehydrazino-5-aryl-1,3,4-thiadiazoles, and with potassium thiocyanate to give 1-thiocyanato-1,4-diaryl-2,3-diazabutadienes which isomerize thermally to arylideneamino-5-aryl-1,3,4-thiadiazoles. 1-Chloro-1,4-diphenyl-2,3-diazabutadiene reacts with potassium ethylxanthate to give a 1-ethylxanthyl-2,3-diazabutadiene which on pyrolysis yields 2,5-diphenyl-1,3,4-thiadiazole.
- Flowers, William T.,Robinson, John F.,Taylor, David R.,Tipping, Anthony E.
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p. 349 - 355
(2007/10/02)
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- Constitution and Redox Stability of Copper(II)-Complexes with Substituted Hydrazines
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CuCl2 reacts with substituted hydrazines forming chelates of the Cu(II)L2Cl2 type (L = RCONHNH2, RCONHN(C6H5)2, RCONHNHCOR, H2NNHCO(CH2)nCONHNH2) which are characterized by quantitative analysis, i.r. and e.p.r. spectra.The complex polyhedron exhibits the geometry of a tetragonally distorted octahedron of C2v symmetry.The complexes undergo intramolecular redox decomposition in acetonitril forming Cu(I) species.The rate constants increase with decreasing half wave oxydation potential and decreasing HOMO energy of the hydrazine ligands, respectively.
- Kempe, G.,Boegel, M.,Roewer, G.
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p. 360 - 366
(2007/10/02)
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