- Modeling and spectroscopic studies of synthetic diazabicyclo analogs of the HIV-1 inhibitor BMS-378806 and evaluation of their antiviral activity
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Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference. Copyright
- Legnani, Laura,Colombo, Diego,Cocchi, Elena,Solano, Lucrezia,Villa, Stefania,Lopalco, Lucia,Asti, Valeria,Diomede, Lorenzo,Marinone Albini, Franca,Toma, Lucio
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Read Online
- Method for synthesizing di-tert-butyl dicarbonate ester by adopting phase transfer catalytic method
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The invention discloses a method for synthesizing di-tert-butyl dicarbonate ester by adopting a phase transfer catalytic method, and belongs to the technical field of organic synthesis process. Di-tert-butyl decarbonate ester is synthesized from raw materials such as triphosgene and tert-butyl alcohol under the condition of adding alkali and a phase transfer catalyst, phosgene is prevented from being used as a raw material, the reaction condition is moderate, and meanwhile, the reaction time is greatly shortened, and the method has a great application value.
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Paragraph 0018-0041
(2018/12/02)
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- Preparation method of di-tert-butyl dicarbonate
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The invention relates to a preparation method of di-tert-butyl dicarbonate and belongs to the technical field of synthesis of pharmaceutical intermediates. The preparation method comprises the following steps: adding metal sodium into xylol; heating to obtain sodium sand; then dropwise adding tert-butyl alcohol and carrying out pumping filtration to obtain sodium tert-butoxide; dissolving the sodium tert-butoxide into petroleum ether; introducing carbon dioxide and reacting to obtain a monoester sodium salt solution; adding a catalyst and slowly dropwise adding diphosgene to react; after reacting, standing and carrying out the pumping filtration; and washing with water, drying, distilling, cooling and crystallizing to obtain the di-tert-butyl dicarbonate. According to the preparation method, the sodium tert-butoxide is prepared from the metal sodium and the di-tert-butyl dicarbonate is prepared from the sodium tert-butoxide; a pumping filtration method is used for replacing a previous distillation method, so that the process is simpler and more energy is saved; the petroleum ether is used for replacing n-hexane and toluene, so that the production cost is reduced and a product is easier to purify; and finally, after the reaction, the pumping filtration is carried out and then water washing is carried out, so that the amount of wastewater is reduced and the environment-friendly treatment cost is reduced.
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Paragraph 0025
(2017/07/19)
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- Production technology of tert-butyl pyrocarbonate
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Tert-butyl pyrocarbonate is an important chemical engineering raw material. A production technology of the tert-butyl pyrocarbonate comprises the following steps: adding metered 98% sodium tert-butoxide and 99% 6# solvent oil to a reaction kettle, stirring and dissolving the 98% sodium tert-butoxide, controlling the temperature of the reaction kettle to be 5 DEG C, slowly introducing a proper amount of 99.99% carbon dioxide to increase the fluidity of a solution in the reaction kettle and reduce the density of the solution, slowing the stirring speed and accelerating the CO2 introduction speed until the solution does not absorb CO2, and carrying out a reaction for about 12 h to obtain sodium tert-butylcarbonate; controlling the temperature in the reaction kettle to be less than 5 DEG C after the reaction ends, slowly adding 99% trichloromethyl carbonate at a slow initial dropwise adding speed, controlling the temperature of the solution to be 0-5 DEG C, allowing the solution to be become thin and then become white, and dropwise adding all the 99% trichloromethyl carbonate in about 2 h; allowing a large amount of bubbles to be generated in the solution, and continuously keeping the temperature in a range of 0-5 DEG C for 1 h to generate bubbles (large CO2 release amount); heating the solution to 30 DEG C after low-temperature keeping ends, and continuously keeping the temperature for 3 h until no bubbles are generated and the reaction ends; and filtering a product obtained after a metathesis reaction ends, collecting the filtered product for external retail comprehensive utilization in order to obtain crude tert-butyl pyrocarbonate.
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Paragraph 0002; 0003
(2017/07/12)
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- NOVEL THIOPHENE DERIVATIVES AS SPHINGOSINE-1-PHOSPHATE-1 RECEPTOR AGONISTS
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The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
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- VLA-4 INHIBITOR
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An object of the present invention is to provide a compound which selectively inhibits binding of a ligand and ±421 integrin (VLA-4), a process for producing the compound, and a medicament containing the compound. A compound represented by the formula (I) etc. orasaltthereof, a process for producing the compound or a salt thereof, a medicament containing the compound or a salt thereof, as well as a preventive and/or a therapeutic agent for a disease caused by cell adhesion, for example, inflammatory reaction, autoimmune disease, cancer metastasis, bronchial asthma, nasal obstruction, diabetes, arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease and rejection reaction at transplantation, containing the compound or a salt thereof as a primary component. [wherein Y 1 represents a divalent aryl group etc. , V 1 represents an aryl group etc., and R 11 to R 14 represent H, OH or a halogen atom etc.]
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- BICYCLIC PYRROLE DERIVATIVES
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Compounds represented by the general formula (I), prodrugs thereof, or pharmaceutically acceptable salts of both are provided as compounds which have high DPP-IV inhibiting activity and are improved in safety, toxicity and so on: (I) wherein the solid line and dotted line between A1 and A2 represents a double bond (A1=A2) or the like; A1 is C(R4) or the like; A2 is nitrogen atom or the like; R1 is hydrogen atom, optionally substituted alkly group, or the like; R2 is hydrogen atom, optionally substituted alkyl group, or the like; R3 is hydrogen atom, halogen atom, or the like; R4 is hydrogen atom, hydroxyl, halogen atom, or the like; and Y is a group represented by the general formula (A) or the like; (A) [wherein m1 is 0, 1, 2 or 3; and the group (A) may be freed from R6 or substituted with one or two R6's which are each independently halogen atom or the like.]
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- Novel heterocyclic compounds, their preparation and their use as medicaments, in particular as antibacterials and beta-lactamase inhibitors
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The invention relates to novel heterocyclic compounds of general formula (I), and their salts with a base or an acid: The invention also relates to a method for preparing these compounds, and to their use as medicaments, in particular as antibacterials and β-lactamase inhibitors.
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- Substituted γ-phenyl-Δ-lactams and uses related thereto
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γ-Phenyl-substituted Δ-lactams are disclosed. They may be formulated into pharmaceutical compositions, and/or used in the treatment or prevention of inflammation or other conditions or disease states.
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- (α-aminophosphino) peptide derivatives, method for making same and therapeutic applications thereof
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The invention concerns compounds derived from (α-aminophosphino) peptides, of general formula (I), in which R1and R2each represents a hydrogen atom or taken together form an imine with the adjacent nitrogen atom; R3represents an alkyl group, an alkenyl group, a phenyl group, a benzyl group, all these groups capable of being substituted or not, a hydrogen atom, a cycloalkyl group, a cycloalkylmethyl group or finally, a methyl group substituted by a heterocyclic, aromatic or saturated group; R4represents a phenyl group, a benzyl group, these groups capable of being substituted or not, a hydrogen atom, an alkyl group, analkenyl group or a cycloalkyl group; R5represents an alkyl group, an alkenyl group, a phenyl group, a benzyl group, all these groups capable of being substituted or not, a hydrogen atom, a cycloalkyl, cycloalkylmethyl group or finally a methyl group substituted by a heterocyclic, aromatic or saturated group; R6, R7and R8can in particular represent a hydrogen atom, an alkyl group, a phenyl group substituted or not . . . n is equal to 0 or 1, in the form of enantiomers, diastereoisomers or racemic mixtures, their salts, their method of preparation and their therapeutic applications.
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- β-lactam compounds and process for producing the same
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Novel β-lactam compound of the formula [1]: wherein R1is lower alkyl or hydroxy-substituted lower alkyl, R2is H or lower alkyl, X is O or, S, R3is H, metal or protecting group, W is a 6- or 7-membered nitrogen-containing heterocycle optionally being substituted at carbon atoms. Said β-lactam compound shows excellent antibacterial activity against Gram-positive bacteria, particularly against methicillin-resistantStaphylococcus aureusand methicillin-resistant and coagulase-negativeStaphylococcus aureus.
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- Substituted gamma-phenyl-delta-lactams and uses related thereto
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gamma-Phenyl-substituted Delta-lactams are disclosed. They may be formulated into pharmaceutical compositions, and/or used in the treatment or prevention of inflammation or other conditions or disease states.
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- Novel processes for the preparation of adenosine compounds and intermediates thereto
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Novel processes for the preparation of adenosine compounds and intermediates thereto. The adenosine compounds prepared by the present processes may be useful as cardiovascular agents, more particularly as antihypertensive and anti-ischemic agents, as cardioprotective agents which ameliorate ischemic injury or myocardial infarct size consequent to myocardial ischemia, and as an antilipolytic agents which reduce plasma lipid levels, serum triglyceride levels, and plasma cholesterol levels. The present processes may offer improved yields, purity, ease of preparation and/or isolation of intermediates and final product, and more industrially useful reaction conditions and workability.
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- Pyrocarbonic acid diesters and the preparation and use thereof
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The invention relates to the preparation of pyrocarbonic acid diesters by an improved process and to the novel pyrocarbonic acid diesters prepared according to said process as well as to the use thereof.The core of the invention is a process for the preparation of a pyrocarbonic acid diester of formula (I) wherein R1 and R1′ are each independently of the other branched or straight-chain C1-C24alkyl, C3-C24alkenyl, C3-C24alkynyl, C4-C12cycloalkyl, C4-C12cycloalkenyl or C7-C24aralkyl, each of which is unsubstituted or substituted by one or more than one substituent which is inert under the reaction conditions,by reacting at least one ester carbonate of formula (II) ?with 40-50 mol % of a sulfochloride of formula (IV) ?in the presence of 0.8-5 mol % of a catalyst of formula (V) and with minor amounts of a heterocyclic aromatic amine in a nonpolar inert solvent,in which process the amount of heterocyclic aromatic amine is 1-3 mol % and the reaction is carried out in the temperature range from ?10° C. to ±25° C., all molar amounts being based on 100 mol % of ester carbonate of formula (II).
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- Azolidines as beta-3 adrenergic receptor agonists
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This invention provides compounds of Formula I having the structure wherein, A, X, Y, Z, W, R1, R2, R3, R4, R5, and R6 are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
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- Substituted γ-phenyl-Δ-lactones and analogs thereof and uses related thereto
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γ-Phenyl-substituted Δ-lactones and analogs thereof, including lactams, are disclosed. They may be formulated into pharmaceutical compositions, and/or used in the treatment or prevention of inflammation or other conditions or disease states.
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- Oxazolidinone antibacterial agents having a thiocarbonyl functionality
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The present invention provides compounds of Formula 1 or pharmaceutical acceptable salts thereof wherein A, G and R, are as defined in the claims which are antibacterial agents.
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- Lactam metalloprotease inhibitors
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The present application describes novel lactams and derivatives thereof of formula I: or pharmaceutically acceptable salt forms thereof, wherein rings ring B is a 4-8 membered cyclic amide containing from 0-3 additional heteroatoms selected from N, O, and S, which are useful as metalloprotease inhibitors.
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- Process for producing di-tert-butyl dicarbonate
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A process for producing di-tert-butyl dicarbonate by continuously carrying out the following steps of reacting tert-butyl alcohol with sodium to form sodium tert-butoxide, reacting the sodium tert-butoxide with carbon dioxide to form mono-tert-butyl sodium carbonate, and reacting the mono-tert-butyl sodium carbonate with an aromatic sulfonyl halide such as p-toluenesulfonyl chloride in the presence of a tertiary amine such as N,N,N',N'-tetramethylethylenediamine, without isolating an intermediate in the middle of each reaction stage. This process is an industrially advantageous process for producing di-tert-butyl dicarbonate from tert-butyl alcohol and an alkali metal.
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- Nitrogenous macrocyclic compounds
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PCT No. PCT/US96/04215 Sec. 371 Date Sep. 19, 1997 Sec. 102(e) Date Sep. 19, 1997 PCT Filed Mar. 27, 1996 PCT Pub. No. WO96/30377 PCT Pub. Date Oct. 3, 1996Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring system. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.
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- Pyrocarbonic acid diesters and the preparation and use thereof
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This invention is a process for the preparation of a pyrocarbonic acid diester of formula (I) STR1 wherein R1 and R1 ' are each, independently of the other, an optionally substituted branched or straight-chain C1 -C24 alkyl, C3 -C24 alkenyl, C3 -C24 alkynyl, C4 -C12 cycloalkyl, C4 -C12 cycloalkenyl or C7 -C24 aralkyl, by reacting at least one ester carbonate of formula (II) STR2 with 40-50 mol % of a sulfochloride of formula (IV) STR3 in the presence of 0.8-5 mol % of a catalyst of formula (V) STR4 and with minor amounts of a heterocyclic aromatic amine in a nonpolar inert solvent, in which process the amount of heterocyclic aromatic amine is 1-3 mol % and the reaction is carried out in the temperature range from -10° C. to +25° C., all molar amounts being based on 100 mol % of ester carbonate of formula (II).
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- Acetic acid derivatives
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Acetic acid derivatives of the formula STR1 wherein L, M, T and Q have the significance given in the description, can be used for the treatment or prophylaxis of illnesses which are caused by the binding of adhesive proteins to blood platelets and by blood platelet aggregation and cell-cell adhesion, and are manufactured by cleaving protecting groups in the corresponding protected compounds or by converting the cyano group into the amidino group in corresponding nitriles.
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- Tumor metastasis inhibiting compounds and methods
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A peptide derivative containing 1 to 20 units of peptide unit represented by the following general formula [I] or a pharmaceutically acceptable salt thereof; wherein Arg represents L- or D-arginine residue, Asp represents L-aspartic acid residue, X represents L- or D-leucine, D-isoleucine, L- or D-norleucine, L- or D-phenylalanine, D-phenylglycine or D-alanine residue, and [Z] and [Y] each represents an amino acid or a peptide residue, which may be present or absent, selected from glycine, L-serine, L-threonine, L- and D-aspartic acid, L-alanine, L- and D-glutamic acid, L-proline residues and a peptide residue constituted by the foregoing amino acid residues, and a pharmaceutical composition comprising the peptide derivative. The composition of the present invention is useful as an agent for inhibiting tumor metastasis.
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- Antithrombotic agents
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Thrombin inhibitors represented by the formula STR1 as provided wherein A is e.g. phenylglycyl, and phenylalanyl, α-methylphenylalanine and α-methylphenylglycine wherein the amino group is preferably substituted with lower alkyl alkanoyl or lower alkoxycarbonyl, or a bicyclo group e.g. 1,2,3,4-tetrahydroisoquinolin-1-yl. Also provided are a method for inhibiting clot formation in man and animals, pharmaceutical formulations useful in the method and intermediates for the inhibitors.
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- Process for the preparation of secondary of tertiary dialkyl dicarbonate
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A process for the preparation of a secondary or tertiary dialkyl dicarbonate. An alkali metal salt of an alkyl pyrocarbonate is contacted with (CO)n X2 wherein X is defined as a leaving group and n is an integer from 1 to 2, in the presence of a complexing agent.
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- Process for preparing di-tert.-butyl dicarbonate
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Di-tert.-butyl dicarbonate having a high purity is prepared by reacting alkali metal tert.-butyl carbonate with methanesulfonyl chloride optionally in the presence of a phase transfer catalyst or an aromatic amine.
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- NEW REAGENTS FOR EXHAUSTIVE ALKOXYCARBONYLATION OF AMIDES AND URETHANS. DI-1-ADAMANTYL DI- AND TRICARBONATE
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Di-1-adamantyl di- and tricarbonate, and di-t-butyltricarbonate were found to be useful reagents for the DMAP-catalyzed alkoxycarbonylation of amides and urethans.
- Koennecke, Andreas,Grehn, Leif,Ragnarsson, Ulf
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p. 2697 - 2700
(2007/10/02)
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- Color-shifted dyes with thermally unstable carbamate moiety comprising T-alkoxycarbonyl group
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This invention relates to a color-shifted dye compounds containing at least one thermally unstable carbamate moiety which are useful in thermal imaging. These compounds may be represented by the formula [M--(X)q ]p D wherein M is a carbamate moiety; X is --N=, --SO2 -- or --CH2 --; D taken with X and M represents the radical of a color-shifted organic dye, said carbamate moiety M comprising a tert-alkoxycarbonyl group, STR1 wherein R' is halomethyl or alkyl.
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- STEREOREGULATION OF THE C(12b)H-C(2)H RELATIONSHIP IN THE PREPARATION OF 2-SUBSTITUTED 1,2,3,4,6,7,12,12b-OCTAHYDROINDOLOQUINOLIZINES
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Stereochemical control in the preparation of 2-substituted 1,2,3,4,6,7,12,12b-octahydroindoloquinolizines possessing at will the C(12b)H-C(2H) cis or trans configuration was achieved by catalytic reduction of the 2,3-dehydro analoques, which were either unsubstituted on the indole nitrogen or substituted with a BOC-group, respectively.The contribution of different conformations to the conformational equilibrium of the prepared compounds was estimated by 13C NMR spectral analysis.
- Lounasmaa, Mauri,Jokela, Reija
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p. 3975 - 3992
(2007/10/02)
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- Antitumor amino acid and peptide derivatives of 1,4-bis(aminoalkyl and hydroxy-aminoalkyl)amino)-5,8-dihydroxyanthraquinones
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Antitumor amino acid and peptide derivatives of 1,4-bis[(aminoalkyl and hydroxyaminoalkyl)amino]-5,8-dihydroxyanthraquinones.
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- Oligopeptide prodrugs
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Prodrugs are described whose structures have a oligopeptide chain which is substituted by a nucleophilic chemotherapeutic residue at the α-position. The products have increased cell membrane permeability and beneficial physico-chemical properties.
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