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2-SULFONYLPYRIMIDINES

The invention relates to 2-sulfonylpyrimidine compounds and salts and solvates thereof for use in the treatment of a proliferative disease such as cancers. The 2- sulfonyl-primidine compounds may be administered, either simultaneously or sequentially, with one or more pharmacologically active compounds and salts and solvates thereof such as an inhibitor of glutamate cysteine ligase. The 2- sulfonylpyrimidine compound may be represented by formula (I): (I) wherein: R1 is selected from C1-6 alkyl, C6-12 aryl, C7-18 aralkyl, 6- to 15-membered heteroaralkyl and 6- to 12-membered heterocyclylalkyl wherein each of these groups are optionally substituted with from one to three optional substituents; R2 is selected from CF3, O-C(O)-R6, C(O)R7, C(O)NHR7 and NHC(O)R7; R3 is selected from H, F, CI, Br, I, OH, C1-6 alkyl, OC1-6 alkyl, CH2F, CHF2, CF3, CN, NO2, CO2R8, C(O)NHR10, NHC(O)R10, (CH2)z-NR8R9 and (CH2)z-NH-C(=NH)-NH2; R4 is selected from H, C1-6 alkyl and CH2R11; R5 is selected from C1-6 alkyl; R6 is selected from H and C1-6 alkyl; R7 is selected from 5 to 9-membered heteroaryl groups, and phenyl wherein these groups are optionally substituted with from one to three optional substituents; and wherein the heteroaryl group is attached to the rest of compound of formula (I) by a carbon ring atom; R8 and R9 are independently selected from H, C1-6 alkyl and benzyl; R10 is selected from 5- to 9-membered heteroaryl groups, 5- and 6-membered heterocyclyl, and phenyl wherein these groups are optionally substituted with from one to three optional substituents; R11 is phenyl optionally substituted; and z is selected from an integer selected from o to 6.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H165N | ChemSpider

Properties and Exciting Facts About 123536-14-1

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Synthetic Route of 123536-14-1, 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.123536-14-1, Name is (R)-3-Aminoquinuclidine dihydrochloride, molecular formula is C7H16Cl2N2. In a article£¬once mentioned of 123536-14-1

Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof

The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nACh receptors), activation of nACh receptors, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (e.g., indazoles and benzothiazoles), which act as ligands for the alpha7 nACh receptor subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H128N | ChemSpider

Top Picks: new discover of (R)-3-Aminoquinuclidine dihydrochloride

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Optimized synthesis and solid state investigations on the drug candidate encenicline hydrochloride

For the production of drug substances a robust, scalable process delivering the active pharmaceutical ingredient (API) in excellent chemical and polymorphic purity is required. For this purpose we developed a novel imidazole-mediated one-pot procedure for the preparation of encenicline hydrochloride monohydrate, which crystallizes directly from the reaction mixture as pure non-hygroscopic polymorph (Form I). Solid state studies revealed a series of additional new physical forms for which crystal structures have been determined by single crystal X-ray diffraction.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H149N | ChemSpider

Final Thoughts on Chemistry for (R)-3-Aminoquinuclidine dihydrochloride

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METHODS AND COMPOSITIONS COMPRISING DIAMINES AS NEW ANTI-TUBERCULAR THERAPEUTICS

Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising novel diamine compositions for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H161N | ChemSpider

The important role of 5291-32-7

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Mutant p53 tunes the NRF2-dependent antioxidant response to support survival of cancer cells

NRF2 (NFE2L2) is one of the main regulators of the antioxidant response of the cell. Here we show that in cancer cells NRF2 targets are selectively upregulated or repressed through a mutant p53-dependent mechanism. Mechanistically, mutant p53 interacts with NRF2, increases its nuclear presence and resides with NRF2 on selected ARE containing gene promoters activating the transcription of a specific set of genes while leading to the transcriptional repression of others. We show that thioredoxin (TXN) is a mutant p53-activated NRF2 target with pro-survival and pro-migratory functions in breast cancer cells under oxidative stress, while heme oxygenase 1 (HMOX1) is a mutant p53-repressed target displaying opposite effects. A gene signature of NRF2 targets activated by mutant p53 shows a significant association with bad overall prognosis and with mutant p53 status in breast cancer patients. Concomitant inhibition of thioredoxin system with Auranofin and of mutant p53 with APR-246 synergizes in killing cancer cells expressing p53 gain-of-function mutants.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H172N | ChemSpider

Some scientific research about Quinuclidin-3-yl acetate

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Pharmacological strategies for presbyopia correction

Purpose: To summarize the pharmacological strategies that are being explored for presbyopia correction. Methods: The review concentrates on pharmacologically induced pupillary miosis to increase depth-of-focus and lens softening or other measures to restore active accommodation. Results: Several studies suggest that near vision improves and distance vision is unaffected for many hours after either monocular or binocular instillation of any one of several drug combinations that cause miosis. Unfortunately, in most studies, measurements were limited to photopic visual acuity for near and distance vision, whereas it is anticipated that pupil constriction may have adverse effects on mesopic and scotopic vision. It is not clear whether improved near vision was due entirely to increased depth-of-focus, or whether, for example, a drug-induced myopic shift in refraction was also involved. Currently, no study has provided direct evidence for drug-induced restoration/enhancement of true accommodation involving an ocular power change. Conclusions: Although it is possible that, in the future, pharmacological drops may offer a safe and reliable solution for presbyopia correction, more evidence of their effectiveness and limitations is required.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H74N | ChemSpider

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Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5- carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: Synthesis and structure-activity relationship

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a novel agonist of the alpha7 neuronal nicotinic acetylcholine receptor (alpha7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective a7 nAChR agonist with an excellent in vitro profile. The compound is characterized by rapid brain penetration and high oral bioavailability in rat and demonstrates in vivo efficacy in auditory sensory gating and, in an in vivo model to assess cognitive performance, novel object recognition.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H157N | ChemSpider

Final Thoughts on Chemistry for Quinuclidin-4-ylmethanamine

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Pleuromutilin derivatives as antimicrobials

The present invention relates to pleuromutilin derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medical therapy, particularly antibacterial therapy.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H23N | ChemSpider

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Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Quality Control of Quinuclidin-3-yl acetate. In my other articles, you can also check out more blogs about 827-61-2

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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 and biological characterization of 1,4,5,6- tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists

Previous studies identified several novel tetrahydropyrimidine derivatives exhibiting muscarinic agonist activity in rat brain. Such compounds might be useful in treating cognitive and memory deficits associated with low acetylcholine levels, as found in Alzheimer’s disease. To determine the molecular features of ligands important for binding and activity at muscarinic receptor subtypes, the series of tetrahydropyrimidines was extended. Several active compounds were examined further for functional selectivity through biochemical studies of muscarinic receptor activity using receptor subtypes expressed in cell lines. Several amidine derivatives displayed high efficacy at m1 receptors and lower activity at m3 receptors coupled to phosphoinositide (PI) metabolism in A9 L cells. Four ligands, including 1b, 1f, 2b, and 7b, exhibited marked functional selectivity for m1 vs m3 receptors. Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cyclase in A9 L cells. Molecular modeling studies also were initiated to help understand the nature of the interaction of muscarinic agonists with the m1 receptor using a nine amino model of the m1 receptor. Several important interactions were identified, including interactions between the ester moiety and Thr192. Additional interactions were found for oxadiazoles and alkynyl derivatives with Asn382, suggesting that enhanced potency and selectivity may be achieved by maximizing interactions with Asp105, Thr192, and Ash382. Taken together, the data indicate that several amidine derivatives display functional selectivity for m1 muscarinic receptors, warranting further evaluation as therapeutic agents for the treatment of Alzheimer’s disease. In addition, several amino acid residues were identified as potential binding sites for m1 agonists. These data may be useful in directing efforts to develop even more selective m1 agonists.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H72N | ChemSpider