885-70-1Relevant articles and documents
AZABICYCLO AND DIAZEPINE DERIVATIVES FOR TREATING OCULAR DISORDERS
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Page/Page column 71-72, (2019/05/22)
The present invention provides in one aspect azabicycio and diazepine derivatives useful as modulators of muscarinic receptors. In another aspect, the present invention provides pharmaceutical compositions for treating ocular diseases, the compositions comprising at least one muscarinic receptor modulator. Formulae (I) & (II):
An intestinal gastric pirenzepine hydrochloride is an important intermediate for simple synthesis process (by machine translation)
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Paragraph 0028; 0033, (2019/05/04)
The invention discloses an intestinal gastric pirenzepine hydrochloride is an important intermediate for simple and convenient synthetic process, against the 5, 11 - dihydro - 11 - chloracetyl - 6 H - pyrido [2.3 - b] [1, 4] benzodiazepine - 6 - one synthetic, develops a piece of raw materials are simple and easy, simple operation of the synthesis process, in order to O-nitro benzoic acid and 2 - chloro - 3 - aminopyridine as a main raw material, five-step synthesis of the target compound, low cost, high yield, high purity, the final drug has far-reaching practical significance. (by machine translation)
Pirenzepine hydrochloride key intermediate preparation method
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Paragraph 0019; 0020, (2017/06/13)
The present invention discloses a pirenzepine hydrochloride key intermediate preparation method, wherein (2-halo-3-pyridyl) carbamic acid and aniline are adopted as starting raw materials, aniline is adopted as a reaction solvent, and under the effect of an alkali and cuprous iodide, a one-step reaction is performed to obtain 5,11-dihydro-6H-pyrido[2,3-B][1,4]benzodiazepine-6-ketone. According to the present invention, the novel 5,11-dihydro-6H-pyrido[2,3-B][1,4]benzodiazepine-6-ketone synthesis method is provided, the step of the method is simple, and the yield is up to more than 99%; the aniline is the reaction solvent, and is further the raw material, such that the raw material (2-halo-3-pyridyl) carbamic acid can completely react, the reaction yield is increased, the cost increase and the environmental pollution due to the use of other solvents are avoided, and the excess aniline can be continuously used after the treatment distillation so as to substantially save the cost and protect the environment; and the synthesis method has good industrial prospects.
MUSCARINIC ANTAGONISTS WITH PARP AND SIR MODULATING ACTIVITY AS CYTOPROTECTIVE AGENTS
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Page/Page column 20, (2010/02/15)
The present invention relates to generally to the cytoprotective activity of mixed muscarinic inhibition/PARP modulation and in particular to the use of dual inhibitors of M1 muscarinic receptor and poly(ADP-ribose) polymerase (PARP) as neuroprotective medicaments, particularly as medicaments for the prevention and/or treatment of neurological diseases. Particularly preferred compounds are condensed diazepinones, e.g. condensed benzodiazepinones such as pirenzepine or compounds which are metabolized to condensed benzodiazepinones such as olanzapine.
Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor
Tahtaoui, Chouaib,Parrot, Isabelle,Klotz, Philippe,Guillier, Fabrice,Galzi, Jean-Luc,Hibert, Marcel,Ilien, Brigitte
, p. 4300 - 4315 (2007/10/03)
Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains.
A new synthetic route to compounds of the AFDX-type with affinity to muscarinic M2-receptor
Holzgrabe, Ulrike,Heller, Eberhard
, p. 781 - 787 (2007/10/03)
[3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-propyl]dimethyl-{6-[(1-{2-[(6-oxo-5, 6-dihydro-benzo[e]pyrido[3,2-b][1,4]diazepine-11-carbonyl)amino]ethyl} piperidin-2-yl-methyl)-propylamino]hexyl}ammonium bromide a hybride containing a fragment of the antagonist of muscarinic receptor AFDX-384 and a W84 moiety known as allosteric modulator of antagonist binding, was synthesized in a divergent synthesis starting from pipecolic acid, phthalic anhydride and 3-amino-2-chloropyridine. This new microwave assisted route is very convenient and allows to modify the piperidine ring, the benzodiazepine system, the phthalimide moiety and the chains connecting the ring systems. Yields and reproducibility were satisfying.
Synthesis of some substituted dibenzodiazepinones and pyridobenzodiazepinones
Cohen, Victor I.,Jin, Biyun,Cohen, Emil I.,Zeeberg, Barry R.,Reba, Richard C.
, p. 675 - 686 (2007/10/03)
Some fluoro- and iodo-derivative of 5-[[4-[(4-diisobutylamino)butyl]-1- phenyl]acetyl]-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-11-one and 11-[[4- [(dialkylamino)butyl]-1-phenyl]acetyl]-5,11-dihydro-6H-pyrido[2,3- b][1,4]benzodiazepin-6-ones 6 (Scheme 1) and their analogues were synthesized. The synthesis of dibenzodiazepinones 1 (Scheme 1) is based on the reaction between 1,4-phenylenediamine and substituted benzoic acids. The intermediate pyridobenzodiazepinones 3 (Scheme 1) were prepared by condensation of 2-chloro-3-aminopyridine with methyl anthranilate and its chlorine derivative. The condensation of 4-[(halo)alkyl]phenylacetyl chloride with dibenzodiazepinones and pyridobenzodiazepinones followed by the reaction of mono- or dialkyl- or dialkenylamine provides 6 (Scheme 1).
New pyridobenzodiazepine derivatives as potential antipsychotics: Synthesis and neurochemical study
Liegeois,Bruhwyler,Damas,Thuy Phuong Nguyen,Chleide,Mercier,Rogister,Delarge
, p. 2107 - 2114 (2007/10/02)
The discovery of a new, safe, atypical antipsychotic remains an important challenge. To achieve this goal, a series of N-methylpiperazinopyrido[2,3- b][1,4]- and -[1,5]- and -pyrido[4,3-b][1,4]- and -[1,5]-benzodiazepines were synthesized. The dopaminergic (D1, D2), serotonergic (5-HT2), and cholinergic (M) affinities, frequently remarked in the action mechanisms of antipsychotic drugs, were determined using their respective in vitro receptor binding assays. All affinities were reduced for each compound. Optimal substituents were found to be in the 2- or 8-position for the retention of affinities, while substitution at the 5-position by acyl or alkyl groups dramatically diminished binding affinities. Pyridobenzodiazepine derivatives, such as clozapine, were found to be inactive or only weakly effective against apomorphine-mediated stereotypes in rats. In an original and complex behavioral model developed in dogs and successfully used to differentiate distinct classes of psychotropic drugs and to discriminate between typical and atypical neuroleptic drugs, 8-chloro-6-(4-methyl-1-piperazinyl)-11H- pyrido[2,3-b][1,4]benzodiazepine (9), 8-methyl-6-(4-methyl-1-piperazinyl)- 11H-pyrido[2,3-b][1,4]benzodiazepine (12), and 5-(4-methyl-1-piperazinyl)- 11H-pyrido[2,3-b][1,5]benzodiazepine (16) showed most of the behavioral characteristics previously described for neuroleptics. Their neurochemical profiles, particularly their 5-HT2/D2 pK(i) ratios, were compatible with an atypical antipsychotic effect. These compounds were selected for further investigation. The proposed modulations could lead to new possibilities for the pharmacochemistry of diarylazepines.
Tricyclic Compounds as Selective Muscarinic Receptor Antagonists. 3. Structure-Selectivity Relationships in a Series of Cardioselective (M2) Antimuscarinics
Engel, Wolfhard W.,Eberlein, Wolfgang G.,Mihm, Gerhard,Hammer, Rudolf,Trummlitz, Guenter
, p. 1718 - 1724 (2007/10/02)
On the basis of the cardioselective muscarinic receptor antagonist AF-DX 116 (2), a series of 11-substituted pyridobenzodiazepinones (9-35) was prepared and screened for their binding affinity to muscarinic receptors located in cardiac (M2) and glandular (M3) tissue.The ratio of IC50 values of the test compounds in the two different tissues was taken as a measure of cardiac (M2) receptor selectivity.Qualitative structure-selectivity relationships point to the fact that it is the spartial orientation of the protonated side-chain nitrogen atom in relation to the tricycle that is the main determinant for receptor subtype recognition and hence is important for the achievement of cardiac (M2) selectivity.
EXPERIMENTAL ANTIULCER AGENTS: N-SUBSTITUTED 2-(4-METHYL-1-PIPERAZINYL)ACETAMIDES AS PIRENZEPINE MODELS AND SOME RELATED COMPOUNDS
Hulinska, Hana,Polivka, Zdenek,Jilek, Jiri,Sindelar, Karel,Holubek, Jiri,et al.
, p. 1820 - 1844 (2007/10/02)
Reactions of N-cyclohexyl-2-chloroacetamide, N-phenyl-2-chloroacetamide, N-(4-dimethylaminophenyl)-2-chloroacetamide, N-(2-nitrophenyl)-N-phenyl-2-chloroacetamide, its 3-nitrophenyl and 4-nitrophenyl analogues, N-(2-benzylphenyl)-2-chloroacetamide, 5-(chloroacetyl)dibenzazepine, and its 10,11-dihydro derivative with piperazine, 1-methylpiperazine, 2-(1-piperazinyl)ethanol, and 3-(1-piperazinyl)propanol resulted in compounds II, III, V -XV, XVIII, XXI, and XXIII, simple analogues of the antiulcer agent pirenzepine (I).Contributions to the syntheses and characterization of mianserin (XIX), bisnor analogue of imipramine (XXV), and pirenzepine (I) are presented.Two 2-aryl-2-(2-pyridyl)thioacetamides XXXVIII and XL were synthesized via nitriles XXXIX and XLI.Compounds XI (VUFB-17 104) and XXI (VUFB-17 113) were found to be rather effective as anti-ulcer agents and anticholinergics.
