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Nickel in Photocatalysis

Robust methods to forge C-C bonds selectively are treasured by the chemical community because of the inherent value of such processes in the convergent construction of complex molecules and the notorious challenges associated with creating such linkages. The advent of cross-coupling technologies (e.g., Suzuki, Negishi, and Heck processes) has revolutionized how synthetic chemists establish C(sp2)-C(sp2) bonds. However, the mechanistic features that make these transition-metal-catalyzed processes ideal for this type of transformation are the same ones that limit their abilities to involve C(sp3)-hybridized species. In this chapter, a recently developed solution to the underlying challenge of engaging C(sp3)-hybridized nucleophiles in cross coupling is outlined: nickel/photoredox dual catalysis. By proceeding through radical intermediates, the enthalpic penalty for two-electron transmetalation can be side-stepped, and cross coupling can proceed under mild, functional-group-tolerant conditions. Several variants of this dual catalytic process are presented which, taken together, demonstrate the breadth and scope of this new cross-coupling paradigm.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H66N | ChemSpider

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Nonaqueous fluorinated drug delivery suspensions

Nonaqueous pharmaceutical compositions for use in aqueous physiological systems are disclosed comprising drug delivery suspension of nonaqueous perfluorocarbon or fluorinated silicone liquid carriers. The suspended drug may be water labile or water stable and therapeutic or diagnostic compounds which will remain stable and pharmaceutically effective for extended periods. The pharmaceutical compositions have improved bioavailability, are capable of low dose volume delivery, and do not degrade the incorporated therapeutic or diagnostic compounds making them well suited for multi-dose packaging and administration.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H33N | ChemSpider

827-61-2, Children learn through play, and they learn more than adults might expect. Science experiments are a great way to spark their curiosity, get their minds active, and encourage them to do something that doesn¡¯t involve a screen. 827-61-2, C9H15NO2. A document type is Article, introducing its new discovery.

Estimation of agonist activity at g protein-coupled receptors: Analysis of M2 muscarinic receptor signaling through Gi/o, G s, and G15

We developed novel methods for analyzing the concentrationresponse curve of an agonist to estimate the product of observed affinity and intrinsic efficacy, expressed relative to that of a standard agonist. This parameter, termed intrinsic relative activity (RAi), is most applicable for the analysis of responses at G protein-coupled receptors. RAi is equivalent to the potency ratios that agonists would exhibit in a hypothetical, highly sensitive assay in which all agonists behave as full agonists, even those with little intrinsic efficacy. We investigated muscarinic responses at the M2 receptor, including stimulation of phosphoinositide hydrolysis through Galpha15 in HEK 293T cells, inhibition of cAMP accumulation through Gi in Chinese hamster ovary (CHO) cells, and stimulation of cAMP accumulation through Gs in CHO cells treated with pertussis toxin. The RAi values of carbachol, oxotremorine-M, and the enantiomers of aceclidine were approximately the same in the three assay systems. In contrast, the activity of 4-[[N-[3-chlorophenyl]carbamoy] oxy-2-butynyl]trimethylammonium chloride (McN-A-343) was ?10-fold greater at M2 receptors coupled to Galpha15 in HEK 293T cells compared with M2 receptors coupled to Gi in the same cells or in CHO cells. Our results show that the RAi estimate is a useful measure for quantifying agonist activity across different assay systems and for detecting agonist directed signaling. Copyright

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Quinuclidine – Wikipedia,
Quinuclidine | C7H58N | ChemSpider

827-61-2, In heterogeneous catalysis, the catalyst is in a different phase from the reactants. At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 827-61-2, name is Quinuclidin-3-yl acetate. In an article£¬Which mentioned a new discovery about 827-61-2

In vitro muscarinic activity of spiromuscarones and related analogs

The cholinergic hypothesis of Alzheimer’s disease suggests that cholinergic agonists may have therapeutic potential for treating the attendant memory deficits of the disease. As part of a program aimed at preparing metabolically stable, nonquaternary analogs of muscarone, 1-oxa- 2,8-dimethyl-8-azaspiro[4.5]decan-3-one, 2a, and related analogs have been synthesized and their in vitro muscarinic activity evaluated. The synthetic strategy in the formation of the 1-spiro[4.5]decan-3-one ring system of 2a involved cyclization of the diol 4 in the presence of Nafion-Hg. The spiromuscarone 2a was found to displace [3H]Oxo-M binding with a K(i) value of 7 nM. Affinities of the oxime and hydrazone analogs of 2a were lower than 2a. The compounds in these series were partial muscarinic agonists as demonstrated by stimulation of phosphatidyl inositol hydrolysis assay, with 2a showing the highest intrinsic activity (60% as compared with carbachol). The results from this study indicate that an exo double bond at the C-3 position is essential for the receptor binding.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H90N | ChemSpider

Chemistry is the experimental and theoretical study of materials on their properties at both the macroscopic and microscopic levels.In a patent£¬Which mentioned a new discovery about 827-61-2, molcular formula is C9H15NO2, introducing its new discovery. , 827-61-2

COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATMENT OF EYE DISORDERS AND SKIN DISEASES

Disclosed is a compound of formula I or a pharmaceutically acceptable hydrate, solvate, crystal, co-crystal, enantiomer, stereoisomer, polymorph or prodrug thereof, which is useful for treatment of eye disorders, skin diseases and/or complications associated therewith. Also disclosed is a pharmaceutical composition comprising as an active ingredient at least one compound of formula I and a pharmaceutically acceptable excipient. Also disclosed is a method of treating an eye disorder, skin disease and/or a complication thereof in a subject in need thereof by administering at least one compound of formula I or a pharmaceutically acceptable hydrate, solvate, crystal, co-crystal, enantiomer, stereoisomer, polymorph or prodrug thereof.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H40N | ChemSpider

827-61-2, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.827-61-2, Name is Quinuclidin-3-yl acetate, molecular formula is C9H15NO2. In a article£¬once mentioned of 827-61-2

Primary open angle glaucoma: an overview on medical therapy

The purpose of this review is to discuss the topics relevant to the use of intraocular pressure-lowering strategies, which remains the first line in the management of glaucoma. Estimates of blindness from glaucoma and identification of risk factors remain of interest for all ophthalmologists. New functional tests offer promise for better detection and more accurate diagnosis of glaucoma. We finally discuss the impact of various glaucoma therapies, the principles of monotherapy and fixed combinations, which offer benefits of convenience, cost, and safety.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H87N | ChemSpider

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Aceclidine effects on outflow facility after ciliary muscle disinsertion

Aceclidine increases outflow facility with little accomodative effect. To determine whether this dissociation resides in the ciliary muscle (CM) or trabecular meshwork (TM), we measured aceclidine effects on perfusion outflow facility in both eyes of 8 rhesus monkeys after unilateral disinsertion of the CM from the TM. Facility in the control eyes increased by ~250% following intravenous pilocarpine and by an additional ~250% following intravenous pilocarpine and by an additional ~250% following intracameral pilocarpine, relative to baseline and uncorrected for washout. In CM-disinserted eyes, the facility response to intravenous and intracameral pilocarpine averaged ~25% of that in contralateral controls. Cytochalasin B, which acts directly on the TM to increase facility but is not additive to maximal pilocarpine doses in normal eyes, had no additional effect beyond that of pilocarpine in control eyes but induced an additional 100% facility increase relative to baseline in CM-disinserted eyes. The accomodative response to carbachol in CM-disinserted eyes was ~80% of that in contralateral controls, consistent with retention of CM contractility and the gonioscopic appearance of shallow CM disinsertion. Intracameral aceclidine HCl doses of 5 and 50 mug increased outflow facility by ~80 and 250%, respectively, in control eyes, and by ~0 and 80% in Cm-disinserted eyes. Either the low aceclidine dose affected facility via the CM, while the high dose exerted an additional effect on the TM, or aceclidine acted only via the CM, with the low dose being ineffective and the high dose modestly effective in CM-disinserted eyes because only a few CM-TM attachments remained.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H64N | ChemSpider

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Synthesis of (R) and (S)-3-aminoquinuclidine from 3-quinuclidinone and (S) and (R)-1-phenethylamine

The synthesis of (R) and (S)-3-amino quinuclidine, an important building block for the synthesis of chiral 5-HT3 serotonin receptor antagonists, is described. The key reaction is the reduction by NaBH4 of the imine prepared from the 3-quinuclidinone and chiral (S) or (R)-1-phenethylamine.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H67N | ChemSpider

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Classics in Chemical Neuroscience: Xanomeline

Xanomeline (1) is an orthosteric muscarinic acetylcholine receptor (mAChR) agonist, often referred to as M1/M4-preferring, that received widespread attention for its clinical efficacy in schizophrenia and Alzheimer?s disease (AD) patients. Despite the compound?s promising initial clinical results, dose-limiting side effects limited further clinical development. While xanomeline, and related orthosteric muscarinic agonists, have yet to receive approval from the FDA for the treatment of these CNS disorders, interest in the compound?s unique M1/M4-preferring mechanism of action is ongoing in the field of chemical neuroscience. Specifically, the promising cognitive and behavioral effects of xanomeline in both schizophrenia and AD have spurred a renewed interest in the development of safer muscarinic ligands with improved subtype selectivity for either M1 or M4. This Review will address xanomeline?s overall importance in the field of neuroscience, with a specific focus on its chemical structure and synthesis, pharmacology, drug metabolism and pharmacokinetics (DMPK), and adverse effects.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H46N | ChemSpider

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The interaction of the enantiomers of aceclidine with subtypes of the muscarinic receptor

The pharmacological activity of the enantiomers of aceclidine was investigated in Chinese hamster ovary cells transfected with the M1 through M5 subtypes of the muscarinic receptor and also in the rat heart and parotid gland that express primarily M2 and M3 receptors, respectively. When measured by stimulation of phosphoinositide hydrolysis in Chinese hamster ovary cells transfected with the M1, M3 and M5 muscarinic subtypes, the potency of S-(+)-aceclidine was approximately 2- to 4-fold greater than that of R-(-)-aceclidine, whereas the maximal response of the R-(-)-isomer was only 44 to 64% that of the S-(+)-isomer. When measured by inhibition of forskolin-stimulated cyclic AMP accumulation in Chinese hamster ovary cells transfected with the M2 and M4 muscarinic subtypes, the potency of S-(+)- aceclidine was approximately 3.5-fold greater than that of R-(-)-aceclidine. In cells transfected with the M2 muscarinic receptor, the maximal responses of the enantiomers were the same, whereas the maximal response of R-(-)- aceclidine was 86% that of S-(+)-aceclidine in cells transfected with the M4 muscarinic subtype. The activities of the enantiomers of aceclidine at native M2 and M3 muscarinic receptors coupled to inhibition of adenylyl cyclase activity in the heart and stimulation of phosphoinositide hydrolysis in the parotid gland, respectively, were similar to those observed in Chinese hamster ovary cells transfected with the corresponding receptor subtypes. We devised a simple quantitative method for using our data in Chinese hamster ovary cells to predict the relative potencies of agonists in a more sensitive assay in which the agonists produce a full maximum response. By using this method, we were able to predict the relative potencies of the enantiomers for eliciting contractions in the guinea pig ileum, an M3 muscarinic response, from their activity in Chinese hamster ovary cells transfected with the M3 muscarinic subtype. Our method of analysis should have application in a variety of studies in which transfected cells are used to determine the pharmacological activity of agonists.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H55N | ChemSpider