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.
Derivatives of alphaphenylacrylic acid and their use in agriculture
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, (2008/06/13)
Compounds of formula: STR1 and stereoisomers thereof, wherein R1 and R2, which are the same or different, are optionally substituted alkyl; W, X, Y and Z, which are the same or different, are hydrogen, halogen, hydroxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aralkyl, optionally substituted aryloxyalkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted alkynyl, optionally substituted amino, optionally substituted arylazo, optionally substituted heteroarylalkyl, optionally substituted heteroaryloxyalkyl, optionally substituted acylamino, nitro, cyano, --OR3, --SR3, --CO2 R4, --CONR5 R6, --COR7, --CR8 =NR9, --N=CR10 R11, --SOR12 or --SO2 R13, or any two of W, X, Y, and Z, in adjacent positions on the phenyl ring, optionally join to form an optionally substituted fused ring, either aromatic or aliphatic, optionally containing one or more heteroatoms; R3 is optionally substituted alkyl, or cycloalkyl optionally containing a hetero atom in the cycloalkyl ring, optionally substituted alkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted acyl, or optionally substituted heteroaryl; R4, R5, R6, R7, R8, R10 and R11, which are the same or different, are hydrogen or optionally substituted alkyl, optionally substituted cycloalkyl, cycloalkylalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted aralkyl; and R9, R12 and R13 are optionally substituted aryl or optionally substituted heteroaryl. The compounds are useful in agriculture as fungicides, plant growth regulators and insecticides.
