Discovery of triazolo [1,5-a] pyridine derivatives as novel JAK1/2 inhibitors.

abstract：:Alkyl parabens are used as antimicrobial preservatives in cosmetics, food, and pharmaceutical products. However, the mode of action of these chemicals has not been assessed thoroughly. In this study, we determined the effects of alkyl parabens on plant pathogenic fungi. All the fungi tested, were susceptible to parabe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ito S,Yazawa S,Nakagawa Y,Sasaki Y,Yajima S

更新日期：2015-04-15 00:00:00

abstract：:A series of compounds based on a 4-phenyl-2-phenylaminopyridine scaffold that are potent and selective inhibitors of Traf2- and Nck-interacting kinase (TNIK) activity are described. These compounds were used as tools to test the importance of TNIK kinase activity in signaling and proliferation in Wnt-activated colorec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ho KK,Parnell KM,Yuan Y,Xu Y,Kultgen SG,Hamblin S,Hendrickson TF,Luo B,Foulks JM,McCullar MV,Kanner SB

更新日期：2013-01-15 00:00:00

abstract：:cis-4-Amino-L-proline derivatives 1 and 2 derived from quinazolinone and pyrazolo pyrimidone respectively were designed as novel lipid lowering agents. A preliminary in vivo screening indicates that 1b and 2a have moderate triglyceride lowering activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das SK,Narasimha Rao Krovvidi VL,Jagadheshan H,Iqbal J

更新日期：2002-12-16 00:00:00

abstract：:The first example of dual inhibitors for matrix metalloproteinase (MMP) and cathepsin is described. An appropriate alignment of peptide-parts and two different specific functional groups in one molecule led to the discovery of a potent dual inhibitor (3a). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamamoto M,Ikeda S,Kondo H,Inoue S

更新日期：2002-02-11 00:00:00

abstract：:Hypoxia is a characteristic feature of solid tumors. Herein, we have developed novel hypoxia-sensitive probes (IM-ACs) for Raman spectroscopic analysis, consisting of nitroimidazole as a hypoxia-targeting unit and acetylene group as the signal-emitting unit. Among IM-ACs synthesized in this study, IM-AC possessing a d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kurihara R,Ikemura Y,Tanabe K

更新日期：2016-10-15 00:00:00

abstract：:The affinity of a series of 2', 3'- and 5-modified thymidine analogues for Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) was evaluated. The affinities of several non-phosphorylated analogues are in the same order of magnitude as those of their phosphorylated congeners. In view of drug delivery pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vanheusden V,Van Rompaey P,Munier-Lehmann H,Pochet S,Herdewijn P,Van Calenbergh S

更新日期：2003-09-15 00:00:00

abstract：:A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Berger D,Dutia M,Powell D,Wissner A,DeMorin F,Raifeld Y,Weber J,Boschelli F

更新日期：2002-10-21 00:00:00

abstract：:The increase in the prevalence of multi drug-resistant and extensively drug-resistant strains of Mycobacteriumtuberculosis case demonstrates the urgent need of discovering new promising compounds with antimycobacterial activity. As part of our research program and with a aim of identifying new antitubercular drug cand...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alegaon SG,Alagawadi KR,Sonkusare PV,Chaudhary SM,Dadwe DH,Shah AS

更新日期：2012-03-01 00:00:00

abstract：:Structure-activity relationships (SAR) of fused 1,2,4-triazolo[1,5-c ]pyrimidine were performed. Various substituents were introduced into the heterocyclic ring to improve the potency of adenosine A(3) receptor binding affinity and A(3)-selectivity against other subtypes. Potent and selective A(3) receptor antagonists...

journal_title：Bioorganic & medicinal chemistry letters

authors： Okamura T,Kurogi Y,Hashimoto K,Sato S,Nishikawa H,Kiryu K,Nagao Y

更新日期：2004-07-16 00:00:00

abstract：:The synthesis, SAR, pharmacokinetic profile, and modeling studies of both monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4 moieties that are potent and selective factor Xa inhibitors will be discussed. Fused pyrazole analog 16a, with a 2'-methylsulfonylphenyl piperidine P4 group, was shown to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qiao JX,Cheng X,Smallheer JM,Galemmo RA,Drummond S,Pinto DJ,Cheney DL,He K,Wong PC,Luettgen JM,Knabb RM,Wexler RR,Lam PY

更新日期：2007-03-01 00:00:00

abstract：:Polymyxin B (1) monohydrochloride was converted to the tetra-BOC derivatives 1b and 1c by reaction with di-tert-butyl dicarbonate. The structures of these protected intermediates were established utilizing a degradative sequence that afforded 3 and 5. A method for the deprotection 2,4-dinitrophenylamines to the free a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weinstein J,Afonso A,Moss E Jr,Miller GH

更新日期：1998-12-01 00:00:00

abstract：:Gynostemma pentaphyllum has been widely used as a traditional herb for its antioxidant and immunostimulatory activities. We have previously reported several useful dammarane-type saponins with cytotoxicity against A549 human lung cancer cells from heat-processed G. pentaphyllum. In this study, a new dammarane-type sap...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xing SF,Jang M,Wang YR,Piao XL

更新日期：2016-04-01 00:00:00

abstract：:(2S)-2-(3-Chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (1b) has been identified as a potent CCR5 antagonist having an IC50=10 nM. Herein, structure-activity relationship studies of non-spiro piperidines are described, which led to the disco...

journal_title：Bioorganic & medicinal chemistry letters

authors： Finke PE,Oates B,Mills SG,MacCoss M,Malkowitz L,Springer MS,Gould SL,DeMartino JA,Carella A,Carver G,Holmes K,Danzeisen R,Hazuda D,Kessler J,Lineberger J,Miller M,Schleif WA,Emini EA

更新日期：2001-09-17 00:00:00

abstract：:Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shiomi S,Wada K,Umeda Y,Kato H,Tsukamoto S,Ishikawa H

更新日期：2018-09-01 00:00:00

abstract：:Menin functions as an oncogenic cofactor of mixed lineage leukaemia (MLL) fusion proteins in leukaemogenesis. The menin-MLL interface is a potential therapeutic target in acute leukaemia cases. In this study, approximately 900 clinical compounds were evaluated and ranked using pharmacophore-based virtual screening, th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li L,Zhou R,Geng H,Yue L,Ye F,Xie Y,Liu J,Kong X,Jiang H,Huang J,Luo C

更新日期：2014-05-01 00:00:00

abstract：:A series of structurally novel aryl ureas was derived from optimization of the HTS lead as selective histamine H3 receptor (H3R) antagonists. The SAR was explored and the data obtained set up the starting point and foundation for further optimization. The most potent tool compounds, as exemplified by compounds 2l, 5b,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao Z,Hurst WJ,Guillot E,Czechtizky W,Lukasczyk U,Nagorny R,Pruniaux MP,Schwink L,Sanchez JA,Stengelin S,Tang L,Winkler I,Hendrix JA,George PG

更新日期：2013-06-01 00:00:00

abstract：:PIM1 is a proto-oncogene encoding the serine/threonine PIM1 kinase. PIM1 kinase plays important roles in regulating aspects of cell cycle progression, apoptosis resistance, and has been implicated in the development of such malignancies as prostate cancer and acute myeloid leukemia among others. Knockout of PIM1 kinas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schroeder RL,Goyal N,Bratton M,Townley I,Pham NA,Tram P,Stone T,Geathers J,Nguyen K,Sridhar J

更新日期：2016-07-01 00:00:00

abstract：:Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the trea...

journal_title：Bioorganic & medicinal chemistry letters

authors： May-Dracka TL,Arduini R,Bertolotti-Ciarlet A,Bhisetti G,Brickelmaier M,Cahir-McFarland E,Enyedy I,Fontenot JD,Hesson T,Little K,Lyssikatos J,Marcotte D,McKee T,Murugan P,Patterson T,Peng H,Rushe M,Silvian L,Spilker K

更新日期：2018-06-01 00:00:00

abstract：:A series of derivatives of the new ring system pyrrolo[2,3-h]quinoline-2-one was synthesized and evaluated as photoreagents toward cultured human tumor cells. Remarkable phototoxycity resulted for some derivatives, especially those bearing the phenyl group at the 7-position. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barraja P,Diana P,Lauria A,Montalbano A,Almerico AM,Dattolo G,Cirrincione G,Viola G,Dall'Acqua F

更新日期：2003-08-18 00:00:00

abstract：:A number of compounds bearing a quaternary ammonium moiety were found to be antagonists with nanomolar binding affinity for the chemokine receptor-2. The structure-activity relationships in the series are described herein along with some detailed characterization of the interesting compounds. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lagu B,Gerchak C,Pan M,Hou C,Singer M,Malaviya R,Matheis M,Olini G,Cavender D,Wachter M

更新日期：2007-08-01 00:00:00

abstract：:The structure-activity relationship of various N-acyl-Gly-, N-acyl-Sar-, and N-blocked-boroPro derivatives against three prolyl peptidases was explored. Several N-acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory activity against fibroblast activation protein (FAP) and prolyl oligopeptidase (PO...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tran T,Quan C,Edosada CY,Mayeda M,Wiesmann C,Sutherlin D,Wolf BB

更新日期：2007-03-01 00:00:00

abstract：:A series of 14-deoxy-11,12-didehydroandrographolide analogues were synthesized from naturally occurring andrographolide and their cytotoxicity evaluated against nine cancer cell lines including cholangiocarcinoma. Analogues 5a and 5b exhibited the most potent cytotoxicity with ED50s of 3.37 and 3.08 μM on KKU-M213 cel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sombut S,Bunthawong R,Sirion U,Kasemsuk T,Piyachaturawat P,Suksen K,Suksamrarn A,Saeeng R

更新日期：2017-12-01 00:00:00

abstract：:The selectivity and the binding affinity of previously reported carborane-containing ligands 2 and 3 toward ERβ remains to be optimized. To improve their biological profiles, a series of iodinated carboranyl phenol derivatives (4-6) were designed and synthesized as prospective ERβ-selective ligands with high affinity....

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Endo Y

更新日期：2017-09-01 00:00:00

abstract：:A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross-coupling reactions provided an array of compounds with a range of in vitro activities. In particular, compound 9e, 4(3,5-difluorophenyl)-N-(6-methylpyridin-1-yl)picolin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kulkarni SS,Newman AH

更新日期：2007-04-01 00:00:00

abstract：:Fibronectin contains the active sequence Arg-Gly-Asp (RGD), along with its synergic site Pro-His-Ser-Arg-Asn (PHSRN). However, the PHSRN peptide does not show synergic activity when it is mixed with the RGD peptide, indicating that a spatial array between RGD and PHSRN in fibronectin may be necessary for synergic acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hojo K,Susuki Y,Maeda M,Okazaki I,Nomizu M,Kamada H,Yamamoto Y,Nakagawa S,Mayumi T,Kawasaki K

更新日期：2001-06-04 00:00:00

abstract：:An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (>100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wilson KJ,Witter DJ,Grimm JB,Siliphaivanh P,Otte KM,Kral AM,Fleming JC,Harsch A,Hamill JE,Cruz JC,Chenard M,Szewczak AA,Middleton RE,Hughes BL,Dahlberg WK,Secrist JP,Miller TA

更新日期：2008-03-15 00:00:00

abstract：:A total of 106 nitric oxide-releasing derivatives of oleanolic acid were synthesized and their effects on the inhibition of anti-Fas-mediated HepG2 cell apoptosis were evaluated in vitro. Several compounds inhibited anti-Fas-mediated HepG2 cell apoptosis in a dose-dependent manner. Within this series of compounds, 8b ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen L,Zhang Y,Kong X,Peng S,Tian J

更新日期：2007-06-01 00:00:00

abstract：:Benz[b]oxepines 4a-g and 12-oxobenzo[c]phenanthridines 5a-d were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular radical cyclization reaction. Radical cyclization of O-vinyl compounds preferentially led to the 7-endo-trig cyclization pathway to the benz[b]oxepines and 12-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee SH,Van HT,Yang SH,Lee KT,Kwon Y,Cho WJ

更新日期：2009-05-01 00:00:00

abstract：:GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Zheng QH

更新日期：2012-02-15 00:00:00

abstract：:Structure-activity relationships for a recently discovered thiazolyl phenyl ether series of acetyl-CoA carboxylase (ACC) inhibitors were investigated. Preliminary efforts to optimize the series through modification of the distal aryl ether moiety of the lead scaffold resulted in the identification of compounds exhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clark RF,Zhang T,Xin Z,Liu G,Wang Y,Hansen TM,Wang X,Wang R,Zhang X,Frevert EU,Camp HS,Beutel BA,Sham HL,Gu YG

更新日期：2006-12-01 00:00:00