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Tryptophan hydroxylase 1 (Tph-1), the principal enzyme for peripheral serotonin biosynthesis, provides a novel target to design anabolic agents for osteoporosis. Here, we present a design, synthesis of a novel series of ursolic acid derivatives under the guidance of docking technique, and bioevaluation of the derivatives using RBL2H3 cells and ovariectomized (OVX) rats. Of the compounds, 9a showed a potent inhibitory activity on serotonin biosynthesis. Further investigations revealed that 9a, as an efficient Tph-1 binder identified by SPR (estimated KD: 6.82 muM), suppressed the protein and mRNA expressions of Tph-1 and lowered serotonin contents in serum and gut without influence on brain serotonin. Moreover, oral administration of 9a elevated serum level of N-terminal propeptide of procollagen type 1 (P1NP), a bone formation marker, and improved bone microarchitecture without estrogenic side effects in ovariectomized rats. Collectively, 9a may serve as a new candidate for bone anabolic drug discovery.

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Reference:
Piperidine – Wikipedia,
Piperidine | C5H4095N – PubChem

 

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The present invention concernssubstituted pyrazinone derivatives according to thegeneral Formula (I), a pharmaceutically acceptableacid or base addition salt thereof, a stereochemicallyisomeric form thereof, an yV-oxide form thereof ora quaternary ammonium salt thereof, wherein thevariables are defined in Claim 1, having selectivea2c-adrenoceptor antagonist activity. It further relatesto their preparation, compositions comprising themand their use as a medicine. The compounds according to the invention are usefull for the prevention and/or treatment of centralnervous system disorders, mood disorders, anxiety disorders, stress-related disorders associated with depression and/or anxiety,cognitive disorders, personality disorders, schizoaffective disorders, Parkinson’s disease, dementia of the Alzheimer’s type, chronicpain conditions, neurodegenerative diseases, addiction disorders, mood disorders and sexual dysfunction.

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Reference:
Piperidine – Wikipedia,
Piperidine | C5H4239N – PubChem

 

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 27578-60-5, name is N-(2-Aminoethyl)piperidine, introducing its new discovery. name: N-(2-Aminoethyl)piperidine

Compounds of the general structural formula (I) and use of the compounds and salts and solvates thereof, as therapeutic agents. 1

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Reference:
Piperidine – Wikipedia,
Piperidine | C5H4604N – PubChem

 

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In this study, we have investigated the roles of substituents on the terminal phenyl ring at the C(4)-position of the quinazoline core to complete the structure-activity relationships (SARs) of our NF-kappaB activation inhibitors. Among them, compound 12j afforded highly potent inhibitory activity toward NF-kappaB transcriptional activation with IC50 value of 2 nM, along with an excellent in vivo efficacy by reducing the edema formation seen in carrageenin-induced inflammation of the rat hind paw.

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Piperidine – Wikipedia,
Piperidine | C5H4512N – PubChem

 

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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, 27578-60-5, molcular formula is C7H16N2, introducing its new discovery. SDS of cas: 27578-60-5

Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling in part by dephosphorylating key tyrosine residues within the regulatory domain of the beta-subunit of the insulin receptor (IR), thereby attenuating receptor tyrosine kinase activity. Inhibition of PTP1B is therefore anticipated to improve insulin resistance and has recently become the focus of discovery efforts aimed at identifying new drugs to treat type II diabetes. We previously reported that the tripeptide Ac-Asp-Tyr(SO3H)-Nle-NH2 is a surprisingly effective inhibitor of PTP1B (Ki = 5 muM). With the goal of improving the stability and potency of this lead, as well as attenuating its peptidic character, an analogue program was undertaken. Specific elements of the initial phase of this program included replacement of the N- and C-termini with non-amino acid components, modification of the tyrosine subunit, and replacement of the tyrosine sulfate with other potential phosphate mimics. The most potent analogue arising from this effort was triacid 71, which inhibits PTP1B competitively with a Ki = 0.22 muM without inhibiting SHP-2 or LAR at concentrations up to 100 muM. Overall, the inhibitors generated in this work showed little or no enhancement of insulin signaling in cellular assays. However, potential prodrug triester 70 did induce enhancements in 2-deoxyglucose uptake into two different cell lines with concomitant augmentation of the tyrosine phosphorylation levels of insulin-signaling molecules. Key elements of the overall SAR reported herein include confirmation of the effectiveness and remarkable PTP1B-specificity of the novel tyrosine phosphate bioisostere, O-carboxymethyl salicylic acid; demonstration that the tyrosine skeleton is optimal relative to closely related structures; replacement of the p-1 aspartic acid with phenylalanine with little effect on activity; and demonstration that inhibitory activity can be maintained in the absence of an N-terminal carboxylic acid. An X-ray cocrystal structure of an analogue bearing a neutral N-terminus (69) bound to PTP1B is reported that confirms a mode of binding similar to that of peptidic substrates.

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Reference:
Piperidine – Wikipedia,
Piperidine | C5H4409N – PubChem

 

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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, 27578-60-5, molcular formula is C7H16N2, introducing its new discovery. Application In Synthesis of N-(2-Aminoethyl)piperidine

Novel 2-aminoanilide histone deacetylase (HDAC) inhibitors were designed to increase their contact with surface residues surrounding the HDAC active site compared to the contacts made by existing clinical 2-aminoanilides such as SNDX-275, MGCD0103, and Chidamide. Their HDAC selectivity was assessed using p21 and klf2 reporter gene assays in HeLa and A204 cells, respectively, which provide a cell-based readout for the inhibition of HDACs associated either with the p21 or klf2 promoter. A subset of the designed compounds selectively induced p21 over klf2 relative to the clinical reference compound SNDX-275. A representative lead compound from this subset had antiproliferative effects in cancer cells associated with induction of acetylated histone H4, endogenous p21, cell cycle arrest, and apoptosis. The p21- versus klf2-selective compounds described herein may provide a chemical starting point for developing clinically-differentiated HDAC inhibitors for cancer therapy.

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Piperidine – Wikipedia,
Piperidine | C5H4455N – PubChem

 

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Cyclic nucleotide cAMP is a ubiquitous secondary messenger involved in a plethora of cellular responses to biological agents involving activation of adenylyl cyclase. Its intracellular levels are tightly controlled by a family of cyclic nucleotide degrading enzymes, the PDEs. In recent years, cyclic nucleotide phosphodiesterase type 4 (PDE4) has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases, particularly in the management of asthma and COPD. Here we describe our efforts to discover novel, highly potent inhaled inhibitors of PDE4. Through structure based design, with the inclusion of a variety of functional groups and physicochemical profiles in order to occupy the solvent-filled pocket of the PDE4 enzyme, we modified the structure of our oral PDE4 inhibitors to reach compounds down to picomolar enzymatic potencies while at the same time tackling successfully an uncovered selectivity issue with the adenosine receptors. In vitro potencies were demonstrated in a rat lung neutrophilia model by administration of a suspension with a Penn-Century MicroSprayer Aerosolizer.

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We report 1,4-azaindoles as a new inhibitor class that kills Mycobacterium tuberculosis in vitro and demonstrates efficacy in mouse tuberculosis models. The series emerged from scaffold morphing efforts and was demonstrated to noncovalently inhibit decaprenylphosphoryl-beta-D-ribose2?-epimerase (DprE1). With “drug-like” properties and no expectation of pre-existing resistance in the clinic, this chemical class has the potential to be developed as a therapy for drug-sensitive and drug-resistant tuberculosis.

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Two small series of quinoline derivatives were designed starting from previously published quinoline derivatives 7a and b in order to obtain information about their interaction with the 5-HT4R binding site. Initially, the structure of 7a and b was modified by replacing their basic moiety with that of partial agonist 4 (ML10302) or with that of reference ligand 6 (RS-67-333). Then, the aromatic moieties of 4-quinolinecarboxylates 7a, d-f, and h-k or 4-quinolinecarboxamides 7b, c, and g were modified into those of 2-quinolinecarboxamides 9a-e. Very interestingly, this structure-affinity relationship study led to the discovery of 7h-j as novel 5-HT4R ligands showing Ki values in the subnanomolar range. The structures of all these compounds contain the N-butyl-4-piperidinylmethyl substituent, which appear to behave as an optimized basic moiety in the interaction of these 4-quinolinecarboxylates with the 5-HT4R binding site. However, this basic moiety was ineffective in providing 5-HT4R affinity in the corresponding 4-quinolinecarboxamide 7g, but it did in 2-quinolinecarboxamide ligands 9c-e. Thus, a subtle interrelationship of several structural parameters appeared to play a major role in the interaction of the ligands with the 5-HT4R binding site. They include the kind of basic moiety, the position of the carbonyl linking group with respect to the aromatic moiety and its orientation, which could be affected by the presence of the intramolecular H-bond as in compounds 9c-e.

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Piperidine – Wikipedia,
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Optically active ferrocenylbisphosphine ligands containing 2-(dialkylamino)ethylamino group on the ferrocenylmethyl position have been prepared and used for the gold(I)-catalyzed asymmetric aldol reaction of isocyanoacetate with aldehydes. Six-membered ring amines, such as morpholino or piperidino group, at the terminal of the side chain were most stereoselective to give optically active trans-4- methoxycarbonyl-5-alkyl-2-oxazolines (up to 97% ee) with high enantio- and diastereoselectivity in a quantitative yield.

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Reference:
Piperidine – Wikipedia,
Piperidine | C5H4438N – PubChem