- 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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- AN IMPROVED PROCESS FOR PREPARATION OF LOPINAVIR AND ITS INTERMEDIATES THEREOF
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The present invention generally relates to an improved process for preparation of lopinavir and its intermediates through formation of tartrate salt of compound of Formula (III).
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Page/Page column 22; 24
(2019/10/23)
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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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supporting information
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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- 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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- Calix[4]arene with lower-rim β-amino α,β-unsaturated ketones containing bis-chelating sites as a highly selective fluorescence turn-on chemosensor for two copper(II) ions
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We report herein the synthesis of a fluorescence turn-on chemosensor, 25,27-bis{N-[1-(4-{[4-amino-4-(1-naphthyl)-2-oxo-3-butenyl]oxy}phenyl) aminocarbonyl]methoxy}-26,28-dihydroxycalix[4]arene (3b), which is highly selective toward Cu2+. The fluorescence intensity of 3b was enhanced upon adding [Cu(ClO4)2], which reached a maximum with approximately 4 equiv. of Cu2+ but then started to decrease in intensity at higher Cu2+ concentrations. Job plot experiments revealed a 1:2 binding stoichiometry of 3b with Cu2+. Based on 1H NMR titration results, we infer that there are two possible binding sites for Cu2+ in 3b: one at the lower-rim phenolic-OH and amide groups, and the second at the β-amino α,β-unsaturated ketone groups. It is important to note that during the complexation of 3b with [Cu(ClO4)2], the Cu2+ ions were reduced to Cu+ by both the phenolic OH and the amines of the β-amino α,β-unsaturated ketones. Furthermore, control compounds 6 and 9b were synthesized to clarify the possible binding sites of Cu2+ in 3b. By comparing the binding constants of 3b, 6, and 9b with Cu2+, we found that 3b exhibited a positive allosteric behavior toward the coordination of two Cu2+ ions. Calix[4]arene 3b shows high binding selectivity toward Cu2+ ions, which causes a dramatic enhancement of the fluorescence intensities at 341 and 452 nm by 4- and 40-fold, respectively. Chemosensor 3b can recognized two Cu2+ ions; both ions are reduced to Cu+ by both the phenolic-OH and the amines of the β-amino α,β- unsaturated ketones. Copyright
- Ho, I-Ting,Chu, Jean-Ho,Chung, Wen-Sheng
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experimental part
p. 1472 - 1481
(2011/04/17)
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- Synthesis and anticonvulsant activity of trans- and cis-2-(2,6- dimethylphenoxy)-N-(2- or 4-hydroxycyclohexyl)acetamides and their amine analogs
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A group of trans- and cis-2-(2,6-dimethylphenoxy)-N-(2-hydroxycyclohexyl) acetamides (1-7) and -ethylamines (8-9) have been synthesized and investigated for their anticonvulsant activity. One of them, racemic trans-2-(2,6- dimethylphenoxy)-N-(2-hydroxycyclohexyl)acetamide proved to be the most effective in MES (mice, ip), exhibiting ED50 = 42.97 mg/kg b.w. and TD50 = 105.67 mg/kg b.w. It also proved protection in focal seizures (electric kindling, rats, ip) and it raises seizure threshold. The mechanism of action is inhibition of voltage-gated sodium currents and enhancement of GABA effect. Safety pharmacology assay on threshold tonic extension revealed no lowering of the seizure threshold.
- Pkala, Elbieta,Waszkielewicz, Anna M.,Szneler, Edward,Walczak, Maria,Marona, Henryk
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scheme or table
p. 6927 - 6934
(2012/01/06)
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- PROCESS FOR THE PREPARATION OF SUBSTANTIALLY PURE (2S,3S,5S)-5-AMINO-2-N,N-DIBENZYLAMINO-3-HYDROXY-1,6-DIPHENYLHEXANE
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The present invention relates to the purification of (2S,3S,5S)-5-amino-2-N,N-dibenzylamino-3-hydroxy-1,6-diphenylhexane (III) by making its crystalline acid addition salt, which can be used as such to produce Lopinavir/Ritonavir with high purity and yield. Formula III
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Page/Page column 4
(2010/12/29)
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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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- AN IMPROVED PROCESS FOR THE PREPARATION OF SUBSTANTIALLY PURE (2S,3S,5S)-5-AMINO-2-N,N-DIBENZYLAMINO-3-HYDROXY-1,6-DIPHENYLHEXANE
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The present invention relates to the purification of (2S,3S,5S)-5-amino-2-N,N-dibenzylamino-3-hydroxy-1,6-diphenylhexane (III) by making its crystalline acid addition salt, which can be used as such to produce Lopinavir /Ritonavir with high purity and yield. Formula III
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Page/Page column 11; 14
(2009/01/24)
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- Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2′ ligands in pseudosymmetric dipeptide isosteres
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A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2′ ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
- Reddy, G. S. Kiran Kumar,Ali, Akbar,Nalam, Madhavi N. L.,Anjum, Saima Ghafoor,Cao, Hong,Nathans, Robin S.,Schiffer, Celia A.,Rana, Tariq M.
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p. 4316 - 4328
(2008/02/12)
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- A PROCESS FOR THE SYNTHESIS OF 2-AMINO-5-PROTECTED AMINO-3-HYDROXY-1, 6-DIPHENYLHEXANE OR A SALT THEREOF - AN INTERMEDIATE FOR ANTIVIRAL DRUGS
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The present invention relates to an improved process for preparing 2-amino-5-protected-amino-3-hydroxy-1,6-diphenylhexane compounds or acid addition salts thereof, which can be useful intermediates for preparing compounds with antiviral activity. The present invention further provides a process for preparing HIV protease inhibitors, lopinavir and ritonavir.
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Page/Page column 20
(2008/06/13)
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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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- Synthesis of HIV protease inhibitor ABT-378 (lopinavir)
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A large scale process for the synthesis of HIV protease inhibitor candidate ABT-378 has been developed which utilizes an intermediate common to the synthesis of ritonavir, Abbott's first generation compound. The synthesis relies on the sequential acylation of this intermediate which is carried through as a mixture of diastereomers until the penultimate step. A synthesis of acid 5, derived from L-valine, is also reported.
- Stoner, Eric J.,Cooper, Arthur J.,Dickman, Daniel A.,Kolaczkowski, Lawrence,Lallaman, John E.,Liu, Jih-Hua,Oliver-Shaffer, Patricia A.,Patel, Ketan M.,Paterson Jr., Joseph B.,Plata, Daniel J.,Riley, David A.,Sham, Hing L.,Stengel, Peter J.,Tien, Jien-Heh J.
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p. 264 - 269
(2013/09/07)
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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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- Process for preparing oxiranemethanamine derivatives
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A process for preparing oxiranemethane derivatives which are useful as intermediates for preparing aspartyl protease inhibitors comprising the steps of activating an aminodiol, acylating the aminodiol and reacting the acylated aminodiol with a base to form an epoxy compound.
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