60494-73-7Relevant academic research and scientific papers
Discovery and characterization of [(cyclopentyl)ethyl]benzoic acid inhibitors of microsomal prostaglandin E synthase-1
Partridge, Katherine M.,Antonysamy, Stephen,Bhattachar, Shobha N.,Chandrasekhar, Srinivasan,Fisher, Matthew J.,Fretland, Adrian,Gooding, Karen,Harvey, Anita,Hughes, Norman E.,Kuklish, Steven L.,Luz, John G.,Manninen, Peter R.,McGee, James E.,Mudra, Daniel R.,Navarro, Antonio,Norman, Bryan H.,Quimby, Steven J.,Schiffler, Matthew A.,Sloan, Ashley V.,Warshawsky, Alan M.,Weller, Jennifer M.,York, Jeremy S.,Yu, Xiao-Peng
, p. 1478 - 1483 (2017)
We describe a novel class of acidic mPGES-1 inhibitors with nanomolar enzymatic and human whole blood (HWB) potency. Rational design in conjunction with structure-based design led initially to the identification of anthranilic acid 5, an mPGES-1 inhibitor with micromolar HWB potency. Structural modifications of 5 improved HWB potency by over 1000×, reduced CYP2C9 single point inhibition, and improved rat clearance, which led to the selection of [(cyclopentyl)ethyl]benzoic acid compound 16 for clinical studies. Compound 16 showed an IC80of 24 nM for inhibition of PGE2formation in vitro in LPS-stimulated HWB. A single oral dose resulted in plasma concentrations of 16 that exceeded its HWB IC80in both rat (5 mg/kg) and dog (3 mg/kg) for over twelve hours.
MONO HALOGEN OR METHYL-SUBSTITUTED 5-HT2B ANTAGONISTS WITH INCREASED ACTIVITY
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Paragraph 0094, (2020/05/13)
Disclose herein are mono halogen or methyl-substituted 5-HT 2B antagonist compounds, which have been found with increased binding activity to 5-HT 2B receptor due to the substitution of halogen or methyl, and the method of using the compounds of treating or preventing a disorder mediated by 5-HT 2B.
Development of Novel Inhibitors for Histone Methyltransferase SET7/9 based on Cyproheptadine
Hirano, Tomoya,Fujiwara, Takashi,Niwa, Hideaki,Hirano, Michitake,Ohira, Kasumi,Okazaki, Yusuke,Sato, Shin,Umehara, Takashi,Maemoto, Yuki,Ito, Akihiro,Yoshida, Minoru,Kagechika, Hiroyuki
, p. 1530 - 1540 (2018/08/01)
The histone methyltransferase SET7/9 methylates not only histone but also non-histone proteins as substrates, and therefore, SET7/9 inhibitors are considered candidates for the treatment of diseases. Previously, our group identified cyproheptadine, used clinically as a serotonin receptor antagonist and histamine receptor (H1) antagonist, as a novel scaffold of the SET7/9 inhibitor. In this work, we focused on dibenzosuberene as a substructure of cyproheptadine and synthesized derivatives with various functional groups. Among them, the compound bearing a 2-hydroxy group showed the most potent activity. On the other hand, a 3-hydroxy group or another hydrophilic functional group such as acetamide decreased the activity. Structural analysis clarified a rationale for the improved potency only by tightly restricted location and type of the hydrophilic group. In addition, a SET7/9 loop, which was only partially visible in the complex with cyproheptadine, became more clearly visible in the complex with 2-hydroxycyproheptadine. These results are expected to be helpful for further structure-based development of SET7/9 inhibitors.
From cholapod to cholaphane transmembrane anion carriers: Accelerated transport through binding site enclosure
Judd, Luke W.,Davis, Anthony P.
supporting information; experimental part, p. 2227 - 2229 (2010/07/08)
Cyclosteroidal "cholaphane" anion transporters show increased activities compared to acyclic "cholapod" analogues.
PHENYLCARBOXYLIC ACID DERIVATIVES AND USE THEREOF FOR THE TREATMENT OF DIABETES
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Page/Page column 65-66, (2010/02/15)
The invention relates to compounds of general formula (1): in which R1, R2, R3, R4, R5, A, B, D and E are as defined in Claim 1, and also to the preparation process therefor and the therapeutic use thereof. These compounds can be used in the treatment of pathologies associated with hyperglycaemia.
DIBENZOCYCLOHEPTANE COMPOUNDS AND PHARMACEUTICALS CONTAINING THESE COMPOUNDS
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Page/Page column 38, (2008/06/13)
The present invention relates to compounds of formula (I), in which R1, R2, R3, R4, X and Y have the meanings indicated in the description. These compounds have immuno-modulating effects, as well as an inhibiting or regulating effect on the release of IL-1β and/or TNF-α. They can therefore be used for the treatment of diseases associated with a disturbance of the immune system.
Design, synthesis, and biological evaluation of phenylamino-substituted 6,11-dihydro-dibenzo[b,e]oxepin-11-ones and dibenzo[a,d]cycloheptan-5-ones: Novel p38 MAP kinase inhibitors
Laufer, Stefan A.,Ahrens, Gabriele M.,Karcher, Solveigh C.,Hering, J?rg S.,Niess, Raimund
, p. 7912 - 7915 (2007/10/03)
The pathogenesis of chronic inflammatory diseases is promoted by various pro-inflammatory cytokines. p38 MAP kinase seems to be a valid target as it controls proinflammatory cytokine levels on both transcriptional and translational levels. Starting from benzophenone-type inhibitors, a rigidisation strategy lead to 3-amino-6,11-dihydro-dibenzo[b,e]thiepin-11-one, phenylamino-substituted 6,11-dihydro-dibenzo-[b,e]oxepin-11-ones, and dibenzo[a,d]cyclohepten-5-ones. Synthesis, p38 inhibition, and CYP-inhibition of selected compounds are described.
DIBENZOCYCLOHEPTENE COMPOUND
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Page 109, (2010/11/30)
The present invention discloses a dibenzocycloheptene compound represented by the formula (I): ???wherein R1: hydrogen atom, halogen atom, etc., R2: hydrogen atom, halogen atom, etc., A: 5-membered or 6-membered heteroaromatic ring group containing 1 to 3 hetero atom(s) selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, and the heteroaromatic ring group, etc. may have halogen atom, nitrogen atom, etc. as substituent(s), B: formula; -CH=CH-, formula; -CH2O-, etc., Y: C1-C10 alkylene group which may have halogen atom, etc. as substituent(s), etc., Z: carboxyl group which may be protected, etc., m: an integer of 1 to 4, n: an integer of 1 to 3, ???------ represents a single bond or a double bond, or a pharmaceutically acceptable salt thereof and a medical composition containing the same as an effective ingredient which has leukotriene C4 antagonistic action and leukotriene E4 antagonistic action in addition to potent leukotriene D4 antagonistic action, and useful as antiasthmatic agent, antiallergic agent and anti-inflammatory agent.
Design of a versatile linker for solid phase peptide synthesis: Synthesis of C-terminal primary/seconary amides and hydrazides
Ramage,Irving,McInnes
, p. 6599 - 6602 (2007/10/02)
An efficient, versatile linker for solid phase peptide synthesis, based upon the dibenzocyclohepta-1,4-diene system, has been developed for the synthesis of C-terminal primary/secondary amides and hydrazides.
Photoinduced Electron Transfer in Porphyrin-Quinone Cyclophanes, 5. - Quinone-Porphyrin-Quinone and Quinone-Porphyrin-Donor Cyclophanes: Syntheses, Structures and Electron-Transfer-Related Properties
Staab, Heinz A.,Weiser, Juergen,Baumann, Ernst
, p. 2275 - 2284 (2007/10/02)
To study the structure dependence of photoinduced electron transfer between porphyrins and quinones the concept of a new family of porphyrin-quinone cyclophanes with vertical arrangements of porphyrin and quinone units is presented.The syntheses of the quinone-porphyrin-quinone cyclophane 1, the prototype of this series, and of the quinone-porphyrin-donor cyclophanes 12 and 14 are described.Spectroscopic data are discussed with regard to the structures involved and in relation to electron-transfer reactions occurring in these systems. Key Words: Photosynthesis models / Photoinduced electron transfer / Porphyrin-quinone cyclophanes
