42564-36-3Relevant academic research and scientific papers
(E)-2-(4′-Methyl-3′-pentenylidene)-4-butanolide, Named β-Acariolide: A New Monoterpene Lactone from the Mold Mite, Tyrophagus putrescentiae (Acarina: Acaridae)
Morino, Atsushi,Kuwahara, Yasumasa,Matsuyama, Sigeru,Suzuki, Takahisa
, p. 1906 - 1908 (1997)
Reinvestigation of the opisthonotal gland secretion of the mold mite, Tyrophagus putrescentiae, resulted in the isolation of a new monoterpene lactone, whose chemical structure was elucidated as (E)-2-(4′-methyl-3′-pentenylidene)-4-butanolide (3), to which we gave the trivial name β-acariolide in relation to β-acaridial {1, (E)-2-(4-methyl-3-pentenylidene)-butanedial}. The compound was synthesized by LiAlH3 (OEt) reduction of 1 and subsequent oxidation involving simultaneous cyclization by using Ag2CO3 on Celite. Both the E- and Z-isomers of β-acariolide (3 and 4) were also prepared by the reaction of α-ethoxaly-γ-butyrolactone (6) and 4-methyl-3-pentenal under basic conditions. Their NMR spectra were compared with each other, and the geometry of the pentenylidene double bond of the isolated compound was concluded as being E.
Production process of 5-(3, 3-dimethylguanidino)-2-oxopentanoic acid
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Paragraph 0025-0029, (2020/07/02)
The invention discloses a production process of 5-(3,3-dimethylguanidino)-2-oxopentanoic acid. The 5-(3,3-dimethylguanidino)-2-oxopentanoic acid is prepared by connecting two fragments; the first fragment is prepared by the following steps: carrying out a substitution reaction on diethyl oxalate, serving as an initial raw material, and 1,4-butyrolactone to generate an intermediate 1, carrying outa ring-opening bromination reaction on the intermediate 1 and an acetic acid solution of hydrobromic acid to obtain an intermediate 2, and carrying out an esterification reaction on the intermediate 2and methanol to prepare an intermediate 3; and the second fragment is prepared by reacting N,N'-bis-BOC-1H-1-guanidinopyrazole serving as an initial raw material with a methanol solution of dimethylamine to obtain an intermediate 4. An alkylation substitution reaction on the intermediates 4 and 3 to prepare an intermediate 5, the intermediate 5 is deprotected to obtain an intermediate 6, and ester is hydrolyzed to obtain the target product. By establishing strict internal control standards for initial raw materials and intermediates and strictly controlling key process step parameters, the qualified product can be stably prepared in multiple batches.
4-ethylydene -3, 4-dihydro -2H-pyrrolecarboxylic manufacturing method
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Paragraph 0106; 0107, (2018/10/25)
PROBLEM TO BE SOLVED: 4-ethylydene -3, 4-dihydro -2H-pyrrolecarboxylic novel manufacturing method. SOLUTION: the present invention, 4-ethylydene -3, 4-dihydro -2H-in the method for manufacturing the alkylpyrrole, γ-butyrolactone and oxalic acid diester and the presence of a base, a first step to obtain a second intermediate body 1 1, with a base and a first 1 after the intermediate body and the intermediate body 2 is obtained by reacting 2 processes the first, intermediate of the first 2 and a second part 3 by the reduction process to obtain the intermediate body 3, second 3 intermediate hydroxycarboxylate; after this better, Azidized agent 4 nonazide converted into 4 process to obtain the intermediate body, and intermediate the first 4 and reacting and triorganophosphine 4-ethylydene -3, 4-dihydro -2H -5 process to obtain alkylpyrrole, including method. Selected drawing: no
Pyrazole derivatives as partial agonists for the nicotinic acid receptor
Van Herk,Brussee,Van den Nieuwendijk,Van der Klein,IJzerman,Stannek,Burmeister,Lorenzen
, p. 3945 - 3951 (2007/10/03)
Nicotinic acid as a hypolipidemic agent appears unique due to its potential to increase HDL cholesterol levels to a greater extent than other drugs. However, it has some side effects, among which severe skin flushing is the most frequent and often limits patients' compliance. In a search for novel agonists for the recently identified and cloned G protein-coupled nicotinic acid receptor, we synthesized a series of substituted pyrazole-3-carboxylic acids that proved to have substantial affinity for this receptor. The affinities were measured by inhibition of [3H] nicotinic acid binding to rat spleen membranes. Potencies and intrinsic activities relative to nicotinic acid were determined by their effects on [35S]GTPγS binding to rat adipocyte and spleen membranes. Interestingly, most compounds were partial agonists. In particular, 2-diazabicyclo-[3,3,O 4,8]octa-3,8-diene-3-carboxylic acid (4c) and 5-propylpyrazole-3-carboxylic acid (4f) proved active with Ki values of approximately 0.15 μM and EC50 values of approximately 6 μM, while their intrinsic activity was only ～50% when compared to nicotinic acid. Even slightly more active was 5-butylpyrazole-3-carboxylic acid (4g) with a Ki value of 0.072 μM, an EC50 value of 4.12 μM, and a relative intrinsic activity of 75%. Of the aralkyl derivatives, 4q (5-(3-chlorobenzyl)pyrazole-3-carboxylic acid) was the most active with a relatively low intrinsic activity of 39%. Partial agonism of the pyrazole derivatives was confirmed by inhibition of G protein activation in response to nicotinic acid by these compounds. The pyrazoles both inhibited the maximum effect elicited by 100 μM nicotinic acid and concentration dependently shifted nicotinic acid concentration-response curves to the right, pointing to a competive mechanism of action.
Design, synthesis, and evaluation of 6-carboxyalkyl and 6-phosphonoxyalkyl derivatives of 7-oxo-8-ribitylaminolumazines as inhibitors of riboflavin synthase and lumazine synthase
Cushman, Mark,Yang, Donglai,Gerhardt, Stefan,Huber, Robert,Fischer, Markus,Kis, Klaus,Bacher, Adelbert
, p. 5807 - 5816 (2007/10/03)
A series of 6-carboxyalkyl and 6-phosphonoxyalkyl derivatives of 7-oxo-8-D-ribityllumazine were synthesized as inhibitors of both Escherichia coli riboflavin synthase and Bacillus subtilis lumazine synthase. The compounds were designed to bind to both the ribitylpurine binding site and the phosphate binding site of lumazine synthase. In the carboxyalkyl series, maximum activity against both enzymes was observed with the 3′-carboxypropyl compound 22. Lengthening or shortening the chain linking the carboxyl group to the lumazine by one carbon resulted in decreased activity. In the phosphonoxyalkyl series, the 3′-phosphonoxypropyl compound 33 was more potent than the 4′-phosphonoxybutyl derivative 39 against lumazine synthase, but it was less potent against riboflavin synthase. Molecular modeling suggested that the terminal carboxyl group of 6-(3′-carboxypropyl)-7-oxo-8-D-ribityllumazine (22) may bind to the side chains of Arg127 and Lys135 of the enzyme. A hypothetical molecular model was also constructed for the binding of 6-(2′-carboxyethyl)-7-oxolumazine (15) in the active site of E. coli riboflavin synthase, which demonstrated that the active site could readily accommodate two molecules of the inhibitor.
Pyrrolo[3,2-e]pyrazolo[1,5-a]pyrimidine remedies/preventives for respiratory diseases
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, (2008/06/13)
The invention relates to a therapeutic and preventive medicament for respiratory diseases, comprising, as an active ingredient, a compound represented by the general formula (1): wherein R1represents a linear, branched or cyclic alkyl group hav
Pyrrolopyrazolopyrimidine compound and medicine comprising the same as active ingredient
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, (2008/06/13)
The invention relates to compounds represented by the following general formula (1): STR1 wherein R1 represents an alkyl group, R2 represents an amino group, alkyl group or the like, and R3 represents a nitro group, amino group, heterocyclic group, alkylsulfonylamino group or the like, or salts thereof, medicines comprising such a compound, a preparation process of the compounds, and intermediates useful for preparation thereof. The compounds (1) are useful for the prevention and treatment of a respiratory disease.
Synthesis and serotonergic activity of substituted 2,N- benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N,N-dimethyltryptamine derivatives: Novel antagonists for the vascular 5-HT(1B)-like receptor
Moloney, Gerard P.,Martin, Graeme R.,Mathews, Neil,Milne, Aynsley,Hobbs, Heather,Dodsworth, Susan,Sang, Pang Yih,Knight, Cameron,Williams, Marnie,Maxwell, Miles,Glen, Robert C.
, p. 2504 - 2526 (2007/10/03)
The synthesis and vascular 5-HT(1B)-like receptor activity of a novel series of substituted 2,N-benzylcarboxamido-5-(2-ethyl-1- dioxoimidazolidinyl)-N,N-dimethyltryptamine derivatives are described. Modifications to the 5-ethylene-linked heterocycle and to substituents on the 2-benzylamide side chain have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B)-like receptor of pK(B) > 7.0, up to 100-fold selectivity over α1-adrenoceptor affinity and 5-HT(2A) receptor affinity, and which exhibited a favorable pharmacokinetic profile. N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2,5-dioxo-1- imidazolidinyl)ethyl]-1H-indole-2-carboxamide (23) was identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5- HT(1B)-like receptor-mediated agonist activity in the rabbit femoral artery), and competitive vascular 5-HT(1B)-like receptor antagonist with a plasma elimination half-life of ~4 h in dog plasma and with good oral bioavailability. The selectivity of compounds from this series for the vascular 5-HT(1B)-like receptors over other receptor subtypes is discussed as well as a proposed mode of binding to the receptor pharmacophore. It has been proposed that the aromatic ring of the 2,N-benzylcarboxamide group can occupy an aromatic binding site rather than the indole ring. The resulting conformation allows an amine-binding site to be occupied by the ethylamine nitrogen and a hydrogen-bonding site to be occupied by one of the hydantoin carbonyls. The electronic nature of the 2,N-benzylcarboxamide aromatic group as well as the size of substituents on this aromatic group is crucial for producing potent and selective antagonists. The structural requirement on the 3-ethylamine side chain incorporating the protonatable nitrogen is achieved by the bulky 2,N-benzylcarboxamide group and its close proximity to the 3- side chain.
