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VASOPRESSIN RECEPTOR ANTAGONISTS AND PRODUCTS AND METHODS RELATED THERETO

Compounds are provided that antagonize vasopressin receptors, particularly the V1a receptor products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof: (I) wherein Q1, Q2, Q3, R2a, R2b, R3 and X are as defined herein.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Synthesis of trans-7-Hydroxymethyl-2-(2-benzisoxazol-3-yl)octahydro-2H-pyrido<1,2-a>pyrazine

An efficient synthesis of trans-7-hydroxymethyl-2-(2-benzisoxazol-3-yl)octahydro-2H-pyrido<1,2-a>pyrazine 2 is presented which relies on the equilibration of cis-dimethyl piperidinedicarboxylate followed by alkylation with phthalimidoethyl triflate.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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An efficient synthesis of oxazolines: Via a cascade reaction between azaoxyallyl cations and 1,2-benzisoxazoles

A formal [3 + 2] cycloaddition reaction between the C and O terminals of azaoxyallyl cations formed in situ and 1,2-benzisoxazoles has been realized. This one-pot cycloaddition method provided an effective and practical pathway to synthesize oxazoline in good yields under mild conditions. The title products exhibited unique fluorescence properties.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Synthesis and inhibitory effects on platelet aggregation of 3-(2-thienyl)- and 3-(1-imidazolyl)-1,2-benzisoxazole derivatives

A series of 3-(2-thienyl)- and 3-(1-imidazolyl)-1,2-benzisoxazoles as well as some isomeric benzoxazoles were synthesized and tested in vitro for their inhibitory effect on arachidonic acid-induced human platelet aggregation.The most active compound (7-methoxy-3-(2-thienyl)-1,2-benzisoxazole 5c) was nearly 20-30-fold more potent than acetylsalicylic acid in inhibiting platelet aggregation.Structure-activity relationships within the series are briefly discussed. 1,2-benzisoxazole / platelet aggregation inhibitor

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Novel benzisoxazole derivatives as potent and selective inhibitors of acetylcholinesterase

A series of N-benzylpiperidine benzisoxazoles has been developed as potent and selective inhibitors of the enzyme acetylcholinesterase (AChE). The benzisoxazole heterocycle was found to be an appropriate bioisosteric replacement for the benzoyl functionality present in the N-benzylpiperidine class of inhibitors. The title compounds were synthesized by alkylating 3- methyl-1,2-benzisoxazoles with an iodo piperidine derivative as the key step. Benzisoxazoles 1b-j,o displayed potent inhibition of AChE in vitro with IC50’s = 0.8-14 nM. Particularly interesting were N-acetyl and morpholino derivatives 1g (IC50 = 3 nM) and 1j (IC50 = 0.8 nM), respectively, which displayed outstanding selectivity for acetyl- over butyrylcholinesterase, in excess of 3 orders of magnitude. N-acetyl 1g also displayed a favorable profile in vivo. This analog showed a dose-dependent elevation of total acetylcholine in mouse forebrain after oral administration with an ED50 = 2.4 mg/kg. In addition, 1g was able to reverse amnesia in a mouse passive avoidance model at doses of 3.2 and 5.6 mg/kg with an average reversal of 89.7%. Molecular dynamics simulations were used to study the possible binding modes of N-benzylpiperidine benzisoxazoles to AChE from Torpedo californica. Key structural insights were obtained regarding the potency of this class of inhibitors. Specifically, Asp-72, Trp-84, Trp-279, Phe-288, and Phe-330 are implicated in the binding of these inhibitors. The N-benzylpiperidine benzisoxazoles may be suitable compounds for the palliative treatment of Alzheimer’s Disease.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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TRICYCLIC DELTA-3-PIPERIDINES AS ALPHA2- ANTAGONISTS

The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Alk is C 1-6alkanediyl; n is 1 or 2; X 1is–O–,–S–,–S(=O)–or–S(=O) 2–; each R 1is independently hydrogen, halogen, C 1-6alkyl, nitro, hydroxy or C 1-4alkyloxy; D is an optionally substituted mono, bi-or tricyclic nitrogen containing heterocycle, a 2H-benzopyranone, a benzamide, a benzophenone or a phenoxyphenyl having central alpha 2-adrenoceptor antagonist activity. It further relates to their preparation, pharmaceutical use and compositions.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

A new application about 3-Chloro-1,2-benzisoxazole

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Substituted 1-(4-aminophenyl)pyrazoles and their use as anti-inflammatory agents

1-(4-aminophenyl)pyrazoles optionally substituted on the 3- and 5-positions of the pyrazole ring and on the amino group at the 4-position of the phenyl ring are disclosed and described, which pyrazoles inhibit IL-2 production in T-lymphocytes.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

A new application about 3-Chloro-1,2-benzisoxazole

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Substituted 3-(aminoalkylamino)-1,2-benzisoxazoles and related compounds

This application relates to compounds of the formula STR1 wherein R1, X, Y and n are as defined in the specification; and pharmaceutically acceptable addition salts thereof and optical and geometric isomers or racemic mixtures thereof; which compounds are useful for the treatment of various memory dysfunctions characterized by a decreased cholinergic function such as Alzheimer’s disease. Compounds of this invention also inhibit monoamine oxidase and hence are useful as antidepressants.

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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3,8-DIAZA-BICYCLO[4.2.0]OCT-3-YL AMIDES

The present invention relates to 3,8-diaza-bicyclo[4.2.0]oct-3-yl amide derivatives of formula (I), wherein the relative configuration of the diazabicyclooctane moiety is cis; and wherein Ar1, and Ar2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Synthesis of a bicyclic piperazine from l-aspartic acid and application of a fluoride-promoted SNAr coupling

The process development is reported of a pivotal C-N bond formation involving ((7R,9aS)-octahydro-1H-pyrido[1,2-a]pyrazin-7-yl)methanol (2) undergoing nucleophilic aromatic substitution with 3-chlorobenzo[d]isoxazole (3) to furnish ((7R,9aS)-2-(benzo[d]isoxazol-3-yl)octahydro-1H-pyrido[1,2-a] pyrazin-7-yl)methanol (4) as a key intermediate for a family of compounds (1). Essential to the success of the coupling is the use of fluoride in combination with a phase transfer catalyst. The development of an alternative route to bicyclic piperazine 2 that uses l-aspartic acid (20) as a starting material to avoid the need for a classical salt resolution is described.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics