- A preparation method for rosacea acetate hydrochloride
-
The present invention relates to the field of pharmaceutical preparation technology, in particular to a method for preparing rosatidine acetate hydrochloride. The present invention adopts m-hydroxybenzoic acid as a starting material, a wide range of sources, inexpensive, and it can be prepared by oxidation of m-hydroxytoluene, without involving a toxicity warning structure and nitrosamine impurities; at the same time, in this preparation process only involves a genotoxic warning structure substance, reducing the risk of medication of subsequent drugs.
- -
-
Paragraph 0105; 0109
(2021/12/07)
-
- Preparation method of high-purity medicinal roxatidine acetate hydrochloride
-
The invention discloses a preparation method of high-purity medicinal roxatidine acetate hydrochloride, and relates to the field of medicine synthesis. The invention provides the preparation method ofthe medicinal roxatidine acetate hydrochloride which is simple in production process, high in safety coefficient, low in cost, high in yield and extremely low in impurity content. The method comprises the following steps: 1) preparing 3-piperidine methylphenol; (2) preparing N-[3-(3-aminopropoxy)-benzyl] piperidine from the 3-piperidine methylphenol obtained in the step (1); and (3) preparing theroxatidine acetate hydrochloride by adopting the N-[3-(3-aminopropoxy)-benzyl] piperidine in the step (2). The yield of the roxatidine acetate hydrochloride prepared by the method disclosed by the invention can reach 87%, and the purity can reach 99.45%. The method is applied to the field of medicine synthesis.
- -
-
Paragraph 0038-0039; 0042-0043
(2021/02/06)
-
- An integrated approach toward nanobret tracers for analysis of gpcr ligand engagement
-
Gaining insight into the pharmacology of ligand engagement with G-protein coupled receptors (GPCRs) under biologically relevant conditions is vital to both drug discovery and basic research. NanoLuc-based bioluminescence resonance energy transfer (NanoBRET) monitoring competitive binding between fluorescent tracers and unmodified test compounds has emerged as a robust and sensitive method to quantify ligand engagement with specific GPCRs genetically fused to NanoLuc luciferase or the luminogenic HiBiT peptide. However, development of fluorescent tracers is often challenging and remains the principal bottleneck for this approach. One way to alleviate the burden of developing a specific tracer for each receptor is using promiscuous tracers, which is made possible by the intrinsic specificity of BRET. Here, we devised an integrated tracer discovery workflow that couples machine learning-guided in silico screening for scaffolds displaying promiscuous binding to GPCRs with a blend of synthetic strategies to rapidly generate multiple tracer candidates. Subsequently, these candidates were evaluated for binding in a NanoBRET ligand-engagement screen across a library of HiBiT-tagged GPCRs. Employing this workflow, we generated several promiscuous fluorescent tracers that can effectively engage multiple GPCRs, demonstrating the efficiency of this approach. We believe that this workflow has the potential to accelerate discovery of NanoBRET fluorescent tracers for GPCRs and other target classes.
- Boursier, Michelle E.,Hall, Mary P.,Hurst, Robin,Killoran, Michael P.,Kirkland, Thomas A.,Levin, Sergiy,Machleidt, Thomas,Ohana, Rachel Friedman,Zimmerman, Kristopher
-
-
- Hexacyclododecylamines with sigma-1 receptor affinity and calcium channel modulating ability
-
Recent research points to the Sigma Receptor (σR) as a possible neuromodulatory system with multi-functional action and σ1Rs have been suggested as a drug target for a number of CNS conditions. Hexacyclododecylamines have shown σ1R activity and provide an advantageous scaffold for drug design that can improve the blood-brain barrier permeability of privileged structures. A series of oxa-and aza-hexaxcyclododecylamines were synthesised and evaluated for sigma-1 receptor activity and voltage-gated calcium channel blocking ability to determine the effect of inclusion of amine containing heterocycles. The compounds had promising σ1R activities (Ki = 0.067 – 11.86 μM) with the aza-hexacyclododecylamines 12, 24 and 27 showing some of the highest affinities (Ki = 0.067 μM, 0.215 μM and 0.496 μM respectively). This confirms, as observed in previous studies, that the aza compounds are more favourable for σ1R binding than their oxa counterparts. The addition of the amine heterocycle showed affinities similar to that of related structures with only two lipophilic binding regions. This indicates that the inclusion of an amine heterocycle into these structures is a viable option in the design of new σ1R ligands. Significant voltage-gated calcium channel blocking ability was also observed for 12, 24 and 27, suggesting a link between σ1R activity and intracellular calcium levels.
- Joubert, Jacques,Strydom, Natasha,Geldenhuys, Werner J.,Greyling, Yolande,Dyk, Sandra V.,Malan, Sarel F.
-
-
- Novel preparation method of intermediate namely 3-(1-piperidine methyl)phenol of roxatidine acetate hydrochloride
-
The invention relates to a preparation method of an intermediate namely 3-(1-piperidine methyl)phenol of roxatidine acetate hydrochloride. M-nitrobenzaldehyde is taken as the primary raw material; under the effect of a phase transfer catalyst, m- nitrobenzaldehyde is reduced by metal borohydride to obtain corresponding benzyl alcohol; in the presence of an alkali, benzyl alcohol reacts with organic sulfonyl chloride to generate active organic sulfonate; then in the presence of an alkali, organic sulfonate carries out N-alkylation reactions with piperidine to generate N-substituted piperidine derivatives; reducing the nitro groups of N-substituted piperidine derivatives to obtain corresponding amino compounds; and subjecting the amino compounds to diazotization, hydrolysis, and alkalizationin a sulfuric acid water solution to obtain 3-(1-piperidine methyl)phenol. The problem that the supply of the conventional raw material (m-hydroxyl benzaldehyde) is not enough and the cost is greatlyincreased is solved. The method is simple and safe, the raw materials are cheap and easily available, the reaction yield is high, and the method is very suitable for industrial production of 3-(1-piperidine methyl)phenol.
- -
-
Paragraph 0067-0068
(2018/04/02)
-
- Nitric oxide-releasing hypoglycemic compound, preparation method thereof, and use thereof
-
The invention belongs to the technical field of hypoglycemic drugs and provides a nitric oxide donor compound with the general formula I and a pharmaceutically acceptable salt thereof, wherein R1, R2 and R3 are defined as in the specifications. The invention also relates to a preparation of the compound and discloses a medicine composition using the compound or the pharmaceutically acceptable salt thereof as an active ingredient, and purpose thereof in the preparation of hypoglycemic drugs.
- -
-
-
- [3H]UR-DE257: Development of a tritium-labeled squaramide-type selective histamine H2 receptor antagonist
-
A series of new piperidinomethylphenoxypropylamine-type histamine H2 receptor (H2R) antagonists with different substituted "urea equivalents" was synthesized and characterized in functional in vitro assays. Based on these data as selection criteria, radiosynthesis of N-[6-(3,4-dioxo-2-{3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino}cyclobut-1-enylamino)hexyl]-(2,3-3H2)propionic amide ([3H]UR-DE257) was performed. The radioligand (specific activity: 63Cimmol-1) had high affinity for human, rat, and guinea pig H2R (hH2R, Sf9 cells: Kd, saturation binding: 31 nM, kinetic studies: 20 nM). UR-DE257 revealed high H2R selectivity on membranes of Sf9 cells, expressing the respective hHxR subtype (Ki values: hH1R: > 10000 nM, hH2R: 28 nM, hH3R: 3800 nM, hH4R: > 10000 nM). In spite of insurmountable antagonism, probably due to rebinding of [3H]URDE257 to the H2R (extended residence time), the title compound proved to be a valuable pharmacological tool for the determination of H2R affinities in competition binding assays.
- Baumeister, Paul,Erdmann, Daniela,Biselli, Sabrina,Kagermeier, Nicole,Elz, Sigurd,Bernhardt, Günther,Buschauer, Armin
-
supporting information
p. 83 - 93
(2015/06/01)
-
- Synthesis and pharmacological characterization of novel fluorescent histamine H2-receptor ligands derived from aminopotentidine
-
In an effort to develop a non-radioactive alternative to the [3H]tiotidine and [125I]iodoaminopotentidine binding assays for the histamine H2-receptor (H2R), primary amines related to aminopotentidine were prepared and coupled with the succinimidyl esters of the bulky fluorescent dyes S0536 and BODIPY 650/665-X. The primary amines exhibited different degrees of antagonistic potency at the human and guinea pig H2R. Surprisingly, one compound (5) coupled to the cyanine dye S0536 acted as potent partial agonist/antagonist at the H2R (KB ~ 50 nM; EC50 ~ 100-150 nM). Compounds coupled to the BODIPY dye exhibited moderately high H2R-affinity, too. Thus, the H2R accommodates bulky fluorophores, probably through interaction with extracellular receptor domains. The compounds presented herein provide a starting point for the optimization of fluorescent H2R ligands with respect to affinity and fluorescence as valuable tools to analyze the molecular mechanisms of H2R activation.
- Xie, Sheng-Xue,Petrache, Georgiana,Schneider, Erich,Ye, Qi-Zhuang,Bernhardt, Guenther,Seifert, Roland,Buschauer, Armin
-
p. 3886 - 3890
(2008/09/21)
-
- INHIBITORS OF HISTONE DEACETYLASE
-
This invention relates to compounds for the inhibition of histone deacetylase. More particularly, the invention provides for compounds of formula (I); wherein Y, L, Z, W, X, Q, R1, R2 and R3 are as defined in the specification.
- -
-
Page/Page column 134; 135
(2010/11/24)
-
- Synthesis and pharmacological activity of fluorescent histamine H2 receptor antagonists related to potentidine
-
Fluorescently labeled histamine H2 receptor antagonists were synthesized starting from N-cyano-N′-[3-(3-piperidin-1-ylmethylphenoxy)propyl]guanidines with an additional N″-ω-aminoalkyl substituent (chain lengths 2-8 methylene groups) or from 3-(3-piperidin-1-ylmethylphenoxy)propylamine. The primary amino group was derivatized with various fluorophores (fluorescein, acridine, dansyl, nitrobenzoxadiazole (NBD), indolo[2,3-a]quinolizine). On the isolated spontaneously beating guinea pig right atrium most of the fluorescent probes were only weakly active, however, the NBD-labeled substances proved to be potent histamine H2 receptor antagonists achieving pA2 values in the range of 7.5-8.0, comparable to the activity of famotidine.
- Li, Liantao,Kracht, Julia,Peng, Shiqi,Bernhardt, Guenther,Elz, Sigurd,Buschauer, Armin
-
p. 1717 - 1720
(2007/10/03)
-
- A new synthesis of roxatidine acetate
-
A new four-step synthesis of N-{3-[3-(1-piperidinylmethyl)- phenoxy]propyl}acetoxyacetamide hydrochloride has been performed. The key aralkyl ether was synthesized in high yield under moderate conditions. A suitable scaling up permits a bulky production of the drug in 98.5% purity.
- Tarpanov, Velichko,Vlahov, Radoslav,Penkov, Miho,Krikorian, Dikran,Parushev, Stoyan,Mechkarova, Pepa,Angelova, Nely,Schunack, Walter
-
-
- Benzothiadiazine derivatives
-
A benzothiadiazine derivative, hydrate thereof and acid addition salt thereof, the derivative being represented by the general formula (I) STR1 wherein X is methylene or a nitrogen atom substituted with a lower alkyl, Y and Z are each methylene or carbonyl, A is phenylene or phenylene substituted with methoxycarbonyl, R4 is lower alkylene or lower alkenylene, R1 is a hydrogen atom, acetoxyacetyl, cyclohexylmethyl or benzyl wherein the benzene ring may be substituted with lower alkoxyl, halogen atom, nitro, lower alkyl, methylenedioxy or hydroxyl, R2 is lower alkyl or phenyl, and R3 is a hydrogen atom, halogen atom or lower alkoxyl with the exception of the case where X, Y and Z are each methylene, A is unsubstituted phenylene, R4 is lower alkylene and R1 is a hydrogen atom; and a peptic ulcer treating agent containing as an effective component the above derivative, hydrate thereof or acid addition salt thereof.
- -
-
-
- Acetamide derivative and application thereof
-
2-Substituted-N-{3-[3-(1-piperidinomethyl)phenoxy]propyl}acetamide, derivatives thereof, and pharmaceutically acceptable salts thereof. The substitution group may be aminomethylcyclohexane carbonyl group or N-carbobenzoxy-p-aminomethylhexane carbonyl group. The compounds having the first-mentioned group can be an effective component of an antiulcer drug composition, and the compounds of the last-mentioned group are intermediates for producing the compounds having the first-mentioned group. Disclosed also is an antiulcer drug composition comprising the above compound as an effective component. The antiulcer drug composition exhibits both the gastric acid secretion inhibitive activity and the gastric mucosa protective activity, and is effective as suppression and cure of ulcers.
- -
-
-
- Isohistamines and homologues as components of H2-antagonists. 22nd Comm.: H2-antihistaminics
-
Starting with isohistamines and their homologues or from appropriately hydrogenated imidazo[1,2-c]pyrimidines, imidazo[1,2-c][1,3]diazepines and -diazocines, H2-antihistaminics with cyanoguanidine and 2-nitro-1,1-ethenediamine structure were prepared and tested for their H2-antagonistic activity on the isolated guinea-pig atrium and on the histamine-stimulated acid secretion of the anaesthetized rat. While four of the cyanoguanidines were weaker in comparison to cimetidine, or inactive, thirteen others possessed markedly stronger activity, whereby the activity reaches a maximal effect at the rat stomach when cyanoguanidine and imidazole ring are connected with a three-membered chain. The activity of the 2-nitro-1,1-ethenediamines exceeds that of the comparable cyanoguanidines in both test models.
- Buschauer,Postius,Szelenyi,Schunack
-
p. 1025 - 1029
(2007/10/02)
-
- 1,2,4-TRIAZOLE-3,5-DIAMINE DERIVATIVES
-
The invention relates to compounds of the formula (I) STR1 and physiologically acceptable salts, hydrates and bioprecursors thereof, in whichR 1 and R 2 represent hydrogen, an aliphatic or cycloaliphatic group, or R 1 and R 2 together with the nitrogen atom form a 5 to 10 membered heterocyclic ring:Alk represents a straight or branched alkylene chain;Q represents furan, thiophen or benzene ring which is incorporated into the rest of the molecule; X represents--CH 2--, STR2--O--or--S--where R 6 represents hydrogen or methyl;n represents zero, 1 or 2; m represents 2, 3 or 4;R 3 represents hydrogen, a substituted or unsubstituted aliphatic or aryl group and;R 4 and R 5, which may be the same or different, each represent hydrogen, a substituted or unsubstituted aliphatic, aryl, or together with the nitrogen atom form a heterocyclic group.
- -
-
-
- Antiulcer phenoxypropylamine derivatives
-
Phenoxypropylamine derivatives of the general formula STR1 wherein R1 represents a hydrogen atom or a methyl or ethyl group, R2 and R3, independently from each other, represent a lower alkyl group, or together form a linear alkylene group having 4 to 7 carbon atoms which may be optionally substituted by a hydroxyl or hydroxymethyl group, and R4 represents a hydrogen atom or a group of the formula --R5 --Z in which R5 represents a lower alkylene group, and Z represents a hydrogen atom or an amino, mono- or di-(lower alkyl)-amino, hydrdoxy lower alkylamino, lower alkanoylamino, hydroxyl, lower alkoxy, lower alkanoyloxy, phenoxy, halophenoxy, benzoyloxy or halobenzoyloxy group, and the salts thereof; to a process for production thereof; and to their medicinal use, particularly to antiulcer agents comprising these phenoxypropylamine derivatives or their salts.
- -
-
-