- Production process of 2, 6-dimethylphenoxyacetic acid
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The invention discloses a production process of 2, 6-dimethylphenoxyacetic acid, and belongs to the technical field of organic chemical industry. The upstream product 2, 6-dimethyl phenoxy acetic acidof 2, 6-dimethyl phenoxy acetyl chloride is prepared by controlling the two steps of substitution reaction and ester hydrolysis reaction, and the prepared 2, 6-dimethyl phenoxy acetic acid is high inpurity, does not generate large impurities, and is beneficial to subsequent preparation of lopinavir.
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Paragraph 0018-0023; 0033-0037
(2021/03/31)
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- Synthesis and characterization of novel analogues of lopinavir
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The present work describes the identification, origin, synthesis, characterization and control of four novel analogues of lopinavir viz. leucine analogue of lopinavir, isoleucine analogue of lopinavir, methyl analogue of lopinavir and dihydroxy analogue of lopinavir.
- Reddy, Peketi Rajesh,Musunuri, Sivanadh,Ramasekhara Reddy,Subrahmanyam Chittala,Murthy,Krishnamohan
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p. 151 - 158
(2021/01/06)
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- Formation of calix[4]arenes with acyloxycarboxylate functions
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Calix[4]arenes are an exciting class of multifunctional compounds. Their ability to bind small molecules and ions actively makes them useful tools for many applications. While looking for a suitable chelating agent, a particular modification of the calix[4]arene led to an unexpected side reaction. In this work, we will describe the selective formation of the observed acyloxyacetate derivatives. The according yields can be regulated by controlling the water content of the solvent system. All new compounds were obtained in yields higher than 45percent and fully characterized by NMR, MS, EA, and X-ray crystallography. By performing and analyzing several reactions with different calix[4]arenes and monomeric derivatives, an explanation for the reaction mechanism was postulated. Further, we report on the modification of reaction conditions which were investigated to verify our findings’ veracity. In total, three acyloxyacetate derivatives were synthesized and characterized to support our conclusions.
- Bauer, David,Stipurin, Sergej,K?ckerling, Martin,Mamat, Constantin
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- Molecular tools that block maturation of the nuclear lamin A and decelerate cancer cell migration
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Lamin A contributes to the structure of nuclei in all mammalian cells and plays an important role in cell division and migration. Mature lamin A is derived from a farnesylated precursor protein, known as prelamin A, which undergoes post-translational cleavage catalyzed by the zinc metalloprotease STE24 (ZPMSTE24). Accumulation of farnesylated prelamin A in the nuclear envelope compromises cell division, impairs mitosis and induces an increased expression of inflammatory gene products. ZMPSTE24 has been proposed as a potential therapeutic target in oncology. A library of peptidomimetic compounds were synthesized and screened for their ability to induce accumulation of prelamin A in cancer cells and block cell migration in pancreatic ductal adenocarcinoma cells. The results of this study suggest that inhibitors of lamin A maturation may interfere with cell migration, the biological process required for cancer metastasis.
- Matralis, Alexios N.,Xanthopoulos, Dimitrios,Huot, Geneviève,Lopes-Paciencia, Stéphane,Cole, Charles,de Vries, Hugo,Ferbeyre, Gerardo,Tsantrizos, Youla S.
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p. 5547 - 5554
(2018/10/15)
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- Synthesis and anticonvulsant activity of phenoxyacetyl derivatives of amines, including aminoalkanols and amino acids
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A series of 17 new phenoxyacetamides has been prepared via multistep chemical synthesis as a continuation of the research carried out by our group on di- and tri-substituted phenoxyalkyl and phenoxyacetyl derivatives of amines. The obtained compounds vary in an amide component, for example aminoalkanol or (un)modified amino acid moieties were introduced. The structures of selected products were confirmed by means of crystallographic methods. All 17 compounds were the subject of preliminary screening for potential anticonvulsant activity (MES, 6 Hz and/or scMET tests) and neurotoxicity (rotarod) in mice after intraperitoneal administration, while several active compounds were subsequently examined in additional models (e.g. MES and rotarod-rats, p.o. or i.p., hippocampal kindling-rats, i.p.). Finally, safety studies (cytotoxicity and cell proliferation assays on astrocytes, metabolic stability assessment, mutagenicity evaluation) were performed for several active compounds, including the most promising one (R-(?)-2-(2,6-dimethylphenoxy)-N-(1-hydroxypropan-2-yl)acetamide, MES ED50 = 12.00 mg per kg b.w., rats, p.o.).
- Pańczyk, Katarzyna,Zelaszczyk, Dorota,Koczurkiewicz, Paulina,S?oczyńska, Karolina,P?kala, El?bieta,Zes?awska, Ewa,Nitek, Wojciech,Zmudzki, Pawe?,Marona, Henryk,Waszkielewicz, Anna
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p. 1933 - 1948
(2018/11/24)
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- 2,6-dimethyl phenoxyacetic acid synthesis and purification method
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The invention relates to the field of pharmaceutical intermediates, in particular to a 2,6-dimethyl phenoxyacetic acid synthesis and purification method. The method includes: dropwise adding a sodium hydroxide solution for the first time after dropwise adding haloacetic acid into a water solution of 2,6-dimethylphenol for the first time, and controlling the temperature below 35 DEG C in a sodium hydroxide solution adding process; heating after dropwise adding is finished, and refluxing for 1-4h; dropwise adding the sodium hydroxide solution for the second time after adding haloacetic acid for the second time; after dropwise adding is finished, refluxing for 6-8h until reaction is completed. According to the 2,6-dimethyl phenoxyacetic acid synthesis and purification method, haloacetic acid and sodium hydroxide are dropwise added separately and respectively added in two times; reaction procedures are monitored according to pH values, and when PH of reaction liquid is larger than or equal to 13 or smaller than or equal to 7 in a reaction process, raw materials are timely replenished after reaction is stopped, so that reaction time is shortened. By the 2,6-dimethyl phenoxyacetic acid synthesis and purification method, consumption of the haloacetic acid is greatly reduced, and reaction time is not longer than 24 hours.
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Paragraph 0031; 0032
(2017/06/13)
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- DERIVATIVES OF AMINOALKANOLS, METHOD OF OBTAINING OF AMINOALKANOLS AND THEIR USE
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The subject of the invention is a group of new derivatives of aminoalkaπols, more specifically [(phenoxy)alkyl]aminoalkanols and [(phenoxy)acyl)aminoalkanols, their method of obtaining and their use for production of a medicine which is used in the prophylaxis, prevention and/or treatment of diseases or symptoms having neurological background and for production of a medicine with anticonvulsant activity, which is used in seizures of various origin, also in the limbic system, in myoclonic or sound-induced seizures, in psychomotor epilepsy, as well as in relieving neuropathic or inflammatory pain.
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Page/Page column 7
(2011/02/25)
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- Preliminary evaluation of anticonvulsant activity and neurotoxicity of some 1,4-substituted piperazine derivatives
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A series of 1,4-piperazine derivatives was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The compounds were only moderately effective. The anticonvulsant activity was accompanied by neurotoxicity. 1-[(4-Chlor-3- methylphenoxy)-acetyl]-4-(2-methoxyphenyl)-piperazine was also evaluated in six hertz seizure test (6-Hz) and showed good activity. At the dose of 100 mg/kg b. w. the compound produced 100% protection after 0.5 h without neurotoxic effect.
- Marona, Henryk,Gunia, Agnieszka,Sloczyska, Karolina,Rapacz, Anna,Filipek, Barbara,Cegla, Marek,Opoka, Wlodzimierz
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scheme or table
p. 571 - 578
(2010/03/03)
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- Anti-coronavirus compounds
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A method of treating coronavirus infection. The method includes administering to a subject suffering from or being at risk of suffering from such infection an effective amount of a compound of formula (I). Each variable in this formula is defined in the specification.
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Page/Page column 11
(2008/06/13)
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- A novel dipeptide-based HIV protease inhibitor containing allophenylnorstatine
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Dipeptide analogues incorporating allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition state mimic at the scissile bond were designed and synthesized in the hope of obtaining a novel KNI series of HIV protease inhibitors. The precursors, N-P2′- 3-(2S,3S)-3-(tert-butyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoyl)-5, 5-dimethylthiazolidine-4-carboxamide (N-Boc-Apns-Dmt-P2′) 4a-p were prepared by deprotection of the synthones N-P2′-(tert- butyloxycarbonyl)-5,5-dimethylthiazolidine-4-carboxamide (Boc-Dmt-P 2′) 2a-p, then coupling with (2S,3S)3-(tert-butyloxycarbonyl) amino-2-hydroxy-4-phenylbutanoic acid (N-Boc-Apns-OH) 3. The deprotected intermediates 4 were coupled with the activated carboxyl groups of the P 2 ligands to afford the target dipeptides. In this work, we fixed at the P2 site either a 2,6-dimethylphenoxyacetyl or a 3-hydroxy-2-methylbenzoyl group. Substitutes at the P2′ site were varied to afford the members of the series 7 and 8. Improved activity of most of the members of series 8 relative to their analogues of series 7 can be partially attributed to the differences in the structures of the P2 moieties. Positional isomerism in the P2′ moieties significantly affected the activity and polarity of the target.
- Abdel-Rahman, Hamdy M.,El-Koussi, Nawal A.,Alkaramany, Gamal S.,Youssef, Adel F.,Kiso, Yoshiaki
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p. 587 - 598
(2007/10/03)
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- Inhibitors of aspartyl protease
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The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.
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- Synthesis and structure-activity relationships of a novel series of HIV-1 protease inhibitors encompassing ABT-378 (Lopinavir)
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The HIV protease inhibitor ABT-378 (Lopinavir) has a 2,6-dimethylphenoxyacetyl group in the P-2′ position. Analogues in which this group is replaced with various substituted phenyl or heteroaryl groups were synthesized and the structure-activity relationships explored.
- Sham, Hing L.,Betebenner, David A.,Chen, Xiaoqi,Saldivar, Ayda,Vasavanonda, Sudthida,Kempf, Dale J.,Plattner, Jacob J.,Norbeck, Daniel W.
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p. 1185 - 1187
(2007/10/03)
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- Retroviral protease inhibiting compounds
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A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.
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- Synthesis of analogs of juvenile hormons proceeding from phenol derivatives
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New potential juvenoids, esters of alkenoic and alkadienoic acids with phenoxy-and phenoxy-phenoxyethanol were synthesized, and also esters of phenoxyacetic acid with alkenols amd alkadienols.
- Yamansarova,Kukovinets,Kukovinets,Zainullin,Galin,Kunakova,Zorin,Tolstikov
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p. 246 - 255
(2007/10/03)
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- Hydroxyethylamino sulphonamides useful as retroviral protease inhibitors
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PCT No. PCT/US94/09139 Sec. 371 Date Jan. 24, 1996 Sec. 102(e) Date Jan. 24, 1996 PCT Filed Aug. 23, 1994 PCT Pub. No. WO95/06030 PCT Pub. Date Mar. 2, 1995The invention relates to sulfonamide-containing hydroxyethylamine protease inhibitor compounds, their process of making, composition and method of use for inhibiting retroviral proteases such as human immunodeficiency virus.
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- 2',6'-Dimethylphenoxyacetyl: A new achiral high affinity P3-P2 ligand for peptidomimetic-based HIV protease inhibitors
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Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P3-P2 quinaldic-valine portion of 1 was replaced by 2',6'-dimethylphenoxyacetyl. With EC50's in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P3-P2 position of hydroxyethylamine-based HIV protease inhibitors.
- Beaulieu, Pierre L.,Anderson, Paul C.,Cameron, Dale R.,Croteau, Gilbert,Gorys, Vida,Grand-Ma?tre, Chantal,Lamarre, Daniel,Liard, Francine,Paris, William,Plamondon, Louis,Soucy, Fran?ois,Thibeault, Diane,Wernic, Dominik,Yoakim, Christiane,Pav, Susan,Tong, Liang
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p. 1094 - 1108
(2007/10/03)
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- RETROVIRAL PROTEASE INHIBITING COMPOUNDS
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A compound of the formula: STR1 is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
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- Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine
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We designed and synthesized a new class of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy- 4-phenylbutyric acid], with a hydroxymethylcarbonyl (HMC) isostere as the active moiety. A systematic evaluation of structure - activity relationships for HIV protease inhibition, anti-HIV activities, and pharmacokinetic profiles has led to the delineation of a set of structural characteristics that appear to afford an orally available HIV protease inhibitor. Optimum structures, exemplified by 21f (JE-2147), incorporated 3-hydroxy-2- methylbenzoyl groups as the P2 ligand, (R)-5,5-dimethyl-1,3-thiazolidine-4- carbonyl (Dmt) residue at the P1' site, and 2-methylbenzylcarboxamide group as the P2' ligand. The present study demonstrated that JE-2147 has potent antiviral activities in vitro and exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals.
- Mimoto, Tsutomu,Kato, Ryohei,Takaku, Haruo,Nojima, Satoshi,Terashima, Keisuke,Misawa, Satoru,Fukazawa, Tominaga,Ueno, Takamasa,Sato, Hideharu,Shintani, Makoto,Kiso, Yoshiaki,Hayashi, Hideya
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p. 1789 - 1802
(2007/10/03)
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- Solvent-free synthesis of substituted phenoxyacetic acids under microwave irradiation
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A comparison of microwave-activated vs. classical organic synthesis is presented for a variety of growth-regulator compounds with a phenoxyacetic acid structure. Microwave-assisted nucleophilic substitutions are safely and conveniently carried out in an open vessel, without any solvent. Yields are very good, and reaction times are extremely short.
- Nagy, Gabriela,Filip, Sorin V.,Surducan, Emanoil,Surducan, Vasile
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p. 3729 - 3736
(2007/10/03)
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- Skeletal Rearrangements Preceding CO Loss from Metastable Phenoxymethylene Ions Derived from Phenoxyacetic Acid and Anisole
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The loss of CHO2(.) from the molecular ion of phenoxyacetic acid and the expulsion of an H(.) atom from ionized anisole lead to phenoxymethylene ions, which fragment predominantly by CO loss on the microsecond time-scale.Carbon-13 labelling reveals that ca. 90percent of the CO molecules expelled from the metastable ions derived from phenoxyacetic acid incorporate the carbon atom from the 1-position of the phenyl group of the parent compound, whereas the residual CO molecules contain one of the other carbon atoms of the aromatic ring.The 2-fluoro- and 2-methylphenoxymethylene ions derived from the appropriate aryloxyacetic acids behave similarly, i.e. the carbon atom of the methylene group of the parent compound is not incorporated in the expelled CO molecules.In contrast, ca. 45percent of the CO molecules eliminated from the metastable phenoxymethylene ions formed from ionized anisole contain the carbon atom of the methyl group, while the remaining part contains the carbon atom from the 1-position of the phenyl ring of the parent compound.This result is taken as evidence for the occurrence of a skeletal rearrangement of the anisole molecular ion leading to an interchange between the carbon atom of the methyl group and the carbon atom at the 1-position of the ring.The elimination of CO from the metastable ions generated from either phenoxyacetic acid or anisole gives rise to a composite metastable peak.Conclusive evidence as to the formation of (+) isomers other than the phenoxymethylene ion is not obtained, indicating that the composite metastable peak is a result of two competing reactions both leading to CO loss.Possible mechanisms of these reactions are discussed together with the mechanism of the skeletal rearrangement of the molecular ion of anisole prior to H(.) loss.
- Molenaar-Langeveld, Tineke A.,Ingemann, Steen,Nibbering, Nico M. M.
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p. 1167 - 1178
(2007/10/02)
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