- Method for synthesizing high-purity sartan side chain TTBB
-
The invention discloses a method for synthesizing high-purity sartan side chain TTBB. The method comprises the following steps: taking 4-methyl-2-cyanobiphenyl as a starting material; under a catalytic action of lewis acid triethylamine hydrochloride, carrying out cyclization reaction on the 4-methyl-2-cyanobiphenyl and sodium azide to generate a 5-[2-(4'-methyldiphenyl)]tetrazole compound; reacting the 5-[2-(4'-methyldiphenyl)] tetrazole compound with triphenylchloromethane under an alkaline condition to generate an N-(triphenylmethyl)-5-(4'-methylbiphenyl-2-yl)tetrazole compound; reacting togenerate a mixture of a compound TTBB and a compound Br-TTBB under the action of bromine-containing substances; promoting the compound Br-TTBB to be converted into the compound TTBB under the actionof diethyl phosphite by the mixture, thus finally obtaining the high-purity sartan side chain TTBB. The synthetic process disclosed by the invention has the advantages of better economical property, environment friendliness, high efficiency, simplicity and convenience; the mode of improving the purity of a target product through recrystallization for multiple times by adopting a conventional method is avoided.
- -
-
-
- Method for tubular reaction preparation of substituted benzylically brominated methyl biphenyl and reaction device of method
-
The invention discloses a method for tubular reaction preparation of substituted benzylically brominated methyl biphenyl and a reaction device of the method. According to the method, substituted methyl biphenyl is taken as a raw material and bromine is taken as a bromination reagent. The reaction materials are continuously fed into a high-efficiency mixer for mixing through a liquid conveying pump, and the formed mixture enters a reactor in a water bath for a reaction, after the reaction is finished, the reaction system enters a receiving tank, a reducing agent is added to the receiving tank for quenching, liquid separation is carried out, anhydrous sodium sulfate is added into the organic phase, suction filtration is performed, the organic phase is subjected to reduced-pressure concentration for solvent removal, a solvent is added for recrystallization, suction filtration is performed, and the filter cake is dried to obtain a pure product namely the substituted benzylically brominatedmethyl biphenyl. The method of the invention is simple and convenient to control, high in safety, less in generation of by-products and convenient for post-processing, a small trial process can be directly used for amplified production. The method meets the requirements of green chemistry and has a certain industrial application value.
- -
-
Paragraph 0022-0029
(2018/06/15)
-
- 1,(3,)5-substituted imidazoles, useful in the treatment of hypertension and methods for their preparation
-
The present invention provides novel 1,5 and 1,3,5-substituted imidazole compounds in hydrophilic or lipophilic form, which are useful as angiotensin II ATI receptor antagonists suitable for transdermal delivery. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing compounds and their use in methods of treating hypertension and cardiovascular diseases.
- -
-
-
- Bacterial Peptide Deformylase Inhibition of Tetrazole-Substituted Biaryl Acid Analogs: Synthesis, Biological Evaluations, and Molecular Docking Study
-
The synthesis and screening of tetrazole-substituted biaryl acid analogs 7a–l as bacterial peptide deformylase (PDF) enzyme inhibitors is reported. The compounds 7e (IC50 value = 5.50 μM) and 7g (IC50 value = 7.25 μM) showed good PDF inhibition activity. The compounds 7e (MIC range = 10.75–11.66 μg/mL) and 7g (MIC range = 8.91–12.83 μg/mL) also showed potent antibacterial activity when compared with the standard ciprofloxacin (MIC range = 25–50 μg/mL). Thus, the active derivatives were not only potent PDF enzyme inhibitors but also efficient antibacterial agents. In order to gain more insight into the binding mode of the compounds with the PDF enzyme, the most active compounds 7e and 7g, the moderately active compound 7k, and the least active compound 7h were docked against the PDF enzyme of Escherichia coli. The docking study of the most active compounds 7e and 7g against the PDF enzyme exhibited good binding properties. Hence, we believe our synthesized compounds 7a–l could serve as reservoir for bacterial PDF inhibitor development.
- Khan, Firoz A. Kalam,Patil, Rajendra H.,Patil, Manjiri,Arote, Rohidas,Shinde, Devanand B.,Sangshetti, Jaiprakash N.
-
p. 934 - 943
(2016/12/09)
-
- A process for the preparation of olmesartan
-
The invention discloses a preparation method of Olmesartan Medoxomil. The method is used for synthesizing an important intermediate 4-[2-(2-triphenylmethyl tetrazole-5-yl) phenyl] benzyl bromide (a compound III) so as to prepare the compound Olmesartan Medoxomil. The method is high in yield, easy to separate and purify, simple to operate and suitable for industrial production.
- -
-
-
- Preparation of 5 - (4 the [...] -bromo methyl-2-biphenyl) - 1-trityl tetrazazole method
-
The invention discloses a method for preparing 5-(4'-bromomethyl-2-biphenyl)-1-triphenyl methyl tetrazole. According to the method, 2-cyano biphenyl is used for replacing 2-cyano 4'-methyl biphenyl in the conventional process and is used as a starting material, and a target product, the 5-(4'-bromomethyl-2-biphenyl)-1-triphenyl methyl tetrazole, is obtained by means of hydroxymethylation, cyclization, protection, and substitution reaction. The method has the advantages of low cost of the raw materials, convenience for recovery of solvent, less comprehensive pollution and the like and is suitable for industrialized production.
- -
-
Paragraph 0030; 0034
(2017/02/24)
-
- Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies
-
New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards ?-tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of β-tubulin. Indian Academy of Sciences.
- Shashikumar, Nellisara D.,Krishnamurthy, Ganganaika,Bhojyanaik, Halehatti S.,Lokesh, Mayasandra R.,Jithendrakumara, Kaginalli S.
-
p. 205 - 212
(2014/04/03)
-
- Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies
-
New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards β-tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of β-tubulin.
- Shashikumar, Nellisara D,Krishnamurthy, Ganganaika,BhojyaNaik, Halehatti S,Lokesh, Mayasandra R,Jithendrakumara, Kaginalli S
-
p. 205 - 212
(2016/03/01)
-
- Synthesis and evaluation of quinazoline derivatives as phosphodiesterase 7 inhibitors
-
The latest scientific findings concerning PDE7 and PDE4 inhibition suggest that selective small-molecule inhibitors of both enzymes could provide a novel approach to treat a variety of immunological diseases. In this context, we describe a new series of quinazoline derivatives from quinazolin-4-thiones which include a substituted biphenyl fragment. Some of these compounds show inhibitory potencies at sub-micromolar levels against the catalytic domain of PDE7.
- Sánchez, Ana I.,Martínez-Barrasa, Valentín,Burgos, Carolina,Vaquero, Juan J.,Alvarez-Builla, Julio,Terricabras, Emma,Segarra, Víctor
-
p. 2370 - 2378
(2013/05/09)
-
- N-ARYLYLMETHYLINDAZOLE MODULATORS OF PPARG
-
The invention provides molecular entities that bind with high affinity to PPARG (PPARy), inhibit cdJk5-mediated phosphorylation of PP ARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes or obesity. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.
- -
-
-
- An efficient synthesis, X-ray and spectral characterization of biphenyl derivatives
-
Derivatives of 1,3-thiazolidin-2,4-dione appended to biphenyl ring viz., 7-9, 16-18 were prepared. The newly synthesized compounds were confirmed by IR, NMR (1H and 13(C) MS and elemental analyses. Single crystal X-ray diffraction study was carried out for one of the final compounds 9. Indian Academy of Sciences.
- Kamble, Ravindra R.,Biradar, Dharesh B.,Meti, Gangadhar Y.,Taj, Tasneem,Gireesh, Tegginamath,Khazi, Imthiyaz Ahmed M.,Vaidyanathan, Sundar T.,Mohandoss, Raju,Sridhar, Balasubramanian,Parthasarathi, Viraraghav
-
p. 393 - 401
(2012/04/04)
-
- PROCESS FOR THE PREPARATION OF 4-BROMOMETHYL-[1,1'-BIPHENYL]-2'-CARBONITRILE
-
Process for the preparation of the compounds of the general formula (I) - where in the formula R represents cyano group, - COOR1or -CONR2R3 group - where R1, R2 and R3 stand for identical or non-identical substituents chosen from the following atom or groups: hydrogen atom, straight or branched C1-7 alkyl group, C3-6 cycloalkyl group; or in one given case a tetrazolyl group substituted with a C1-4 alkyl group or triphenylmethyl group - wherein a compound of the general formula (II) - where the meaning of R is as defined above - is reacted with one of the following reagent pairs as bromine sources: bromate with hydrogen sulfite, or bromate with pyrosulfite, or bromide with percarbonate, or bromide with perborate, in aqueous-organic binary systems, and optionally the resulting compound of the general formula (I) is isolated from the reaction mixture by a method known per se.
- -
-
Page/Page column 6-7
(2011/07/07)
-
- DUAL-ACTING THIOPHENE, PYRROLE, THIAZOLE AND FURAN ANTIHYPERTENSIVE AGENTS
-
In one aspect, the invention relates to compounds having the formula:wherein: Ar, Z, R3, R4 and R5 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
- -
-
Page/Page column 31
(2011/08/04)
-
- DUAL-ACTING ANTIHYPERTENSIVE AGENTS
-
In one aspect, the invention relates to compounds having the formula: wherein: Ar, r, Z, X, R3, and R5-7 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
- -
-
Page/Page column 42
(2010/02/17)
-
- DUAL-ACTING ANTIHYPERTENSIVE AGENTS
-
The invention relates to compounds having the formula: (I) wherein: Ar, r, R3, Z, X, and R5-7 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
- -
-
Page/Page column 81
(2009/04/25)
-
- DUAL-ACTING BENZOIMIDAZOLE ANTIHYPERTENSIVE AGENTS
-
The invention relates to compounds having the formula: wherein Ar, r, n, X, R2, R2′, R3, and R5-7 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and a process and intermediates for preparing such compounds.
- -
-
Page/Page column 39-40
(2009/06/27)
-
- Synthesis and characterization of 4′-bromomethyl-2-(N-trityl-1H- tetrazol-5-yl) biphenyl
-
Biphenyl tetrazole ring is an important component of the Sartan family of novel drugs. 4′-Bromomethyl-2-(N-trityl-1H-tetrazol-5-yl)biphenyl was synthesized in this article from 4′-methyl-2-cyano-biphenyl through three steps. 4′-Methyl-2-cyano-biphenyl was reacted with azide ions with the help of ammonium chloride as catalyst in an autoclave with high conversion to afford the tetrazole compounds in 70.6% yield. After being protected by the trityl group with 92.6% yield, 4′-methyl-2-(N-trityl-1H-tetrazol-5-yl) biphenyl was brominated with N-bromosuccinimide (NBS) in cyclohexane with 2,2′-azo-isobutyronitrile (AIBN) acting as an initiator to provide the title compound in 83.8% yield. Copyright Taylor & Francis Group, LLC.
- Wang, Guo-Xi,Sun, Bao-Ping,Ru, Zong-Ling
-
p. 3577 - 3581
(2008/12/23)
-
- Dual-acting antihypertensive agents
-
The invention is directed to compounds having the formula: wherein: Ar, r, Y, Z, Q, W, X, and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
- -
-
Page/Page column 47
(2008/12/04)
-
- Dual-acting antihypertensive agents
-
The invention is directed to compounds of formula I: wherein Ar, r, R3, X, and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula I have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and a process and intermediates for preparing such compounds.
- -
-
Page/Page column 38
(2008/12/07)
-
- Nonpeptide angiotensin II receptor antagonists: Synthesis and biological activity of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives
-
A series of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives have been obtained and tested as non peptide AII receptor antagonists. Modification of the classical biphenyl moiety to a 4-arylthienyl fragment afforded interesting activities.
- Delgado,Pastor,Garcia-Navio,Vaquero,Alvarez-Builla,Sunkel,De Casa-Juana,Priego,Santos,Statkow,Straumann
-
p. 147 - 155
(2007/10/03)
-
- SUBSTITUTED PYRAZOLE ANGIOTENSIN II ANTAGONISTS
-
Substituted pyrazoles such as STR1 and their pharmaceutically suitable salts are useful as antihypertensive agents and for treatment of congestive heart failure.
- -
-
-
- 4-(1H-PYRROL-1-YL)IMIDAZOLES WITH ANGIOTENSIN II ANTAGONIST ACTIVITY
-
Novel substituted 4-(1-H-pyrrol-1-yl)imidazoles are disclosed as well as methods of preparing them, pharmaceutical compositions containing them, and methods of using them. Novel intermediates useful in the preparation of the compounds of the invention are also disclosed and synthetic methods for preparing the novel intermediates. The compounds are useful as antagonists of angiotensin II and thus are useful in the control of hypertension, hyperaldosteronism, congestive heart failure, glaucoma, vascular smooth muscle proliferation associated with atherosclerosis, and with postsurgical vascular restenosis.
- -
-
-
- A novel 3-substituted benzazepinone growth hormone secretagogue (L- 692,429)
-
The 3-substituted benzazepinone, L-692,429 (compound 1), is the prototype compound of a novel class of compounds that stimulate release of growth hormone (GH). The molecule evolved from efforts to identify a non-peptide mimic of the growth hormone-releasing hexapeptide, GHRP-6. Compound 1 is prepared by sequential attachment of dimethyl-β-alanine and 2'- biphenylyltetrazole side chains to a chiral 3-aminobenzolactam nucleus. Comparison of the biological activity of 1 with the corresponding six- and eight-membered lactam analogs shows the seven-membered benzazepinone skeleton to be preferred. Molecular modeling of the structurally diverse GH secretagogues, L-692,429 and GHRP-6, was performed.
- Schoen,Pisano,Prendergast,Wyvratt Jr.,Fisher,Cheng,Chan,Butler,Smith,Ball
-
p. 897 - 906
(2007/10/02)
-
- 4-(1H-PYRROL-1-YL) IMIDAZOLES WITH ANGIOTENSION II ANTAGONIST ACTIVITY
-
Novel substituted 4-(1-H-pyrrol-1-yl)imidazoles are disclosed as well as methods of preparing them, pharmaceutical compositions containing them, and methods of using them. Novel intermediates useful in the preparation of the compounds of the invention are also disclosed and synthetic methods for preparing the novel intermediates. The compounds are useful as antagonists of angiotensin II and thus are useful in the control of hypertension, hyperaldosteronism, congestive heart failure, glaucoma, vascular smooth muscle proliferation associated with atherosclerosis, and with postsurgical vascular restenosis.
- -
-
-
- Fused aryl substituted imidazole angiotensin II receptor inhibitors
-
Substituted imidazoles such as STR1 which are useful as angiotensin II receptor inhibitors. These compounds have activity in treating hypertension and congestive heart failure.
- -
-
-
- N-SUBSTITUTED HETEROCYCLIC DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS IN WHICH THEY ARE PRESENT
-
The invention relates to N-substituted heterocyclic derivatives and its salts. These derivatives have the formula (I) in which the substituents are as defined in the specification. Application: Angiotensin II antagonists
- -
-
-
- ANGIOTENSIN II RECEPTOR BLOCKING IMIDAZOLES
-
Substituted imidazoles such as STR1 are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.
- -
-
-
- Treatment of congestive heart failure with angiotensin 11 receptor blocking imidazoles
-
Substituted imidazoles such as STR1 are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.
- -
-
-
- TREATMENT OF HYPERTENSION WITH 1,2,4-ANGIOTENSIN II ANTAGONISTS
-
Substituted pyrroles, pyrazoles and traizoles such as STR1 and their pharmaceutically suitable salts are useful as antihypertensive agents and for treatment of congestive heart failure.
- -
-
-
