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Electric Literature of 67496-78-0, A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 67496-78-0, Name is Quinuclidin-4-ylmethanamine, molecular formula is C8H16N2. In a Patent£¬once mentioned of 67496-78-0

BRIDGED, BICYCLIC HETEROCYCLIC OR SPIRO BICYCLIC HETEROCYCLIC DERIVATIVES OF PYRAZOLO[1,5-A]PYRIMIDINES, METHODS FOR PREPARATION AND USES THEREOF

Compounds of formula A: Formula (1) pharmaceutically acceptable salts thereof are described, which selectively inhibit Raf kinase activity and are useful for treating disorders mediated by Raf kinases.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H18N | ChemSpider

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Application of 67496-78-0, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 67496-78-0, molcular formula is C8H16N2, introducing its new discovery.

Discovery of highly potent and selective type I B-Raf kinase inhibitors

A series of pyrazolo[1,5-alpha]pyrimidine analogs has been prepared and found to be potent and selective B-Raf inhibitors. Molecular modeling suggests they bind to the active conformation of the enzyme.

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BRIDGED, BICYCLIC HETEROCYCLIC OR SPIRO BICYCLIC HETEROCYCLIC DERIVATIVES OF PYRAZOLO[1,5-A]PYRIMIDINES, METHODS FOR PREPARATION AND USES THEREOF

Compounds of formula A: Formula (1) pharmaceutically acceptable salts thereof are described, which selectively inhibit Raf kinase activity and are useful for treating disorders mediated by Raf kinases.

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Quinuclidine | C7H119N | ChemSpider

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Soft drugs. 2. Soft alkylating compounds as potential antitumor agents.

A class of soft alkylating compounds as potential anticancer agents was developed. The first examples include alpha-halo esters of various carboxylic acids. A new method for quantitative evaluation of the alkylating reactivity was developed, using a competitive alkylation reactivity was developed, using a competitive alkylation reaction, followed by NMR analysis of the reaction mixture. The method is sensitive and reproducible. One of the two selected soft alkylating agents, chloromethyl hexanoate, was found to have anticancer activity.

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Piperlongumine and p53-reactivator APR-246 selectively induce cell death in HNSCC by targeting GSTP1

TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC) patients without human papillomavirus infection. The recurrence rate for these patients is distinctly high. It has been actively explored to identify agents that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC. PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its methylated analogue PRIMA-1Met (also called APR-246) were found to be able to reestablish the DNA-binding activity of p53 mutants and reinstate the functions of WT p53. Herein we report that piperlongumine (PL), an alkaloid isolated from Piper longum L., synergizes with APR-246 to selectively induce apoptosis and autophagic cell death in HNSCC cells, whereas primary and immortalized mouse embryonic fibroblasts and spontaneously immortalized non-tumorigenic human skin keratinocytes (HaCat) are spared from the damage by the co-treatment. Interestingly, PL-sensitized HNSCC cells to APR-246 are TP53 mutation-independent. Instead, we demonstrated that glutathione S-transferase pi 1 (GSTP1), a GST family member that catalyzes the conjugation of GSH with electrophilic compounds to fulfill its detoxification function, is highly expressed in HNSCC tissues. Administration of PL and APR-246 significantly suppresses GSTP1 activity, resulting in the accumulation of ROS, depletion of GSH, elevation of GSSG, and DNA damage. Ectopic expression of GSTP1 or pre-treatment with antioxidant N-acetyl-l-cysteine (NAC) abrogates the ROS elevation and decreases DNA damage, apoptosis, and autophagic cell death prompted by PL/APR-246. In addition, administration of PL and APR-246 impedes UMSCC10A xenograft tumor growth in SCID mice. Taken together, our data suggest that HNSCC cells are selectively sensitive to the combination of PL and APR-246 due to a remarkably synergistic effect of the co-treatment in the induction of ROS by suppression of GSTP1.

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Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease

The invention provides compounds of Formula I: 1wherein Azabicyclo is any of: 2These compounds may be in the form of pharmaceutical salts or compositions, and racemic mixtures or pure enantiomers thereof. The compounds of Formula I are useful in pharmaceuticals in which alpha7 is known to be involved.

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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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PHARMACEUTICAL COMPOUNDS

The invention relates to compounds and compositions for inhibiting the enzyme fatty acid amide hydrolase (FAAH), the use of the compounds in therapy and, in particular, for treating or preventing conditions whose development or symptoms are linked to substrates of the FAAH enzyme, and methods of treatment or prevention using the compounds and compositions.

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1,2,5-thiadiazole analogues of aceclidine as potent m1 muscarinic agonists

The acetyl group of the muscarinic agonist aceclidine 4 was replaced by various 1,2,5-thiadiazoles to provide a new series of potent m1 muscarinic agonists 17 and 18. Optimal m1 muscarinic agonist potency was achieved when the 1,2,5-thiadiazole substituent was either a butyloxy, 17d, or butylthio, 18d, group. Although 1,2,5-oxadiazole 37 and pyrazine 39 are iso-pi- electronic with 1,2,5-thiadiazole 17d, both analogues were substantially less active than 17d. Compounds with high muscarinic affinity and/or m1 muscarinic agonist efficacy were also obtained when the 3-oxyquinuclidine moiety of 17d or 18c was replaced by ethanolamines, hydroxypyrrolidines, hydroxyazetidine, hydroxyisotropanes, or hydroxyazanorbornanes. The structure-activity data support the participation of the oxygen or sulfur atom in the substituent on the 1,2,5-thiadiazole in the activation of the m1 receptor. Several of these new 1,2,5-thiadiazoles have m1 agonist efficacy, potency, and selectivity comparable to those of xanomeline 2 in the muscarinic tests investigated.

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COMPOUNDS AS RADIOLIGANDS FOR THE DIAGNOSIS OF DISEASE

Radiolabeled ligands useful as probes for determining the relative abundance, receptor occupancy, and/or function of nicotinic acetylcholine receptors. The compounds of Formula I as described herein are labeled with a radioactive isotopic moiety such as 11C, 18F, 76Br, 123I or 125I. Disorders are diagnosed by administering to a mammal a detectably labeled compound and detecting the binding of that compound to the nAChR. The compounds that have been administered are detected using methods including, but not limited to, position emission topography and single-photon to emission computed tomography. The present invention is useful in diagnosing a wide variety of diseases and disorders as discussed herein.

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Quinuclidine | C7H96N | ChemSpider