Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis.

abstract：:The structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds incorporate various Michael acceptor moieties and are shown to irreversibly bind to HRV serotype 14 3CP with inhibition activities (kobs/[I]) r...

journal_title：Journal of medicinal chemistry

authors： Dragovich PS,Webber SE,Babine RE,Fuhrman SA,Patick AK,Matthews DA,Lee CA,Reich SH,Prins TJ,Marakovits JT,Littlefield ES,Zhou R,Tikhe J,Ford CE,Wallace MB,Meador JW 3rd,Ferre RA,Brown EL,Binford SL,Harr JE,DeLisle

更新日期：1998-07-16 00:00:00

abstract：:The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induce...

journal_title：Journal of medicinal chemistry

authors： Eda M,Takemoto T,Ono S,Okada T,Kosaka K,Gohda M,Matzno S,Nakamura N,Fukaya C

更新日期：1994-06-24 00:00:00

abstract：:Acetylcholinesterase (AChE), a key enzyme in the central and peripheral nervous systems, is the principal target of organophosphorus nerve agents. Quaternary oximes can regenerate AChE activity by displacing the phosphyl group of the nerve agent from the active site, but they are poorly distributed in the central nerv...

journal_title：Journal of medicinal chemistry

authors： Santoni G,de Sousa J,de la Mora E,Dias J,Jean L,Sussman JL,Silman I,Renard PY,Brown RCD,Weik M,Baati R,Nachon F

更新日期：2018-09-13 00:00:00

abstract：:In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the abil...

journal_title：Journal of medicinal chemistry

authors： Khalil EM,Ojala WH,Pradhan A,Nair VD,Gleason WB,Mishra RK,Johnson RL

更新日期：1999-02-25 00:00:00

abstract：:The 5'-phosphate (1) of the antiviral nucleoside 5-cyano-2'-deoxyuridine was synthesized and evaluated for inhibition of thymidylate synthetase purified from methotrexate-resistant Lactobacillus casei. Compound 1 was a potent competitive inhibitor with a K1 of 0.55 microns. Irreversible enzyme inhibition by this compo...

journal_title：Journal of medicinal chemistry

authors： Chang CT,Edwards MW,Torrence PF,Mertes MP

更新日期：1979-09-01 00:00:00

abstract：:Small molecule protein kinase inhibitors are widely employed as biological reagents and as leads in the design of drugs for a variety of diseases. One of the hardest challenges in kinase inhibitor design is achieving target selectivity. By utilizing X-ray structural information for four promiscuous inhibitors, we prop...

journal_title：Journal of medicinal chemistry

authors： Aronov AM,Murcko MA

更新日期：2004-11-04 00:00:00

abstract：:5-Alkoxy-3-(N-substituted carbamoly)-1-phenylpyrazoles were prepared and tested for antiinflammatory and hypnotic activity. Four compounds showed antiinflammatory activity and three possessed hypnotic properties. ...

journal_title：Journal of medicinal chemistry

authors： Sugiura S,Ohno S,Ohtani O,Izumi K,Kitamikado T,Asai H,Kato K

更新日期：1977-01-01 00:00:00

abstract：:PABA/NO is a diazeniumdiolate of structure Me(2)NN(O)=NOAr (where Ar is a 5-substituted-2,4-dinitrophenyl ring whose 5-substituent is N-methyl-p-aminobenzoic acid). It has shown activity against human ovarian cancer xenografts in mice rivaling that of cisplatin, but it is poorly soluble and relatively unstable in wate...

journal_title：Journal of medicinal chemistry

authors： Saavedra JE,Srinivasan A,Buzard GS,Davies KM,Waterhouse DJ,Inami K,Wilde TC,Citro ML,Cuellar M,Deschamps JR,Parrish D,Shami PJ,Findlay VJ,Townsend DM,Tew KD,Singh S,Jia L,Ji X,Keefer LK

更新日期：2006-02-09 00:00:00

abstract：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Del Tacca M,Mazzanti L,Ceserani R

更新日期：1979-06-01 00:00:00

abstract：:Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been validated as an attractive therapeutic target for cancer therapy. To stop both STAT3 activation and dimerization, a viable strategy is to design inhibitors blocking its SH2 domain phosphotyrosine binding site that is respons...

journal_title：Journal of medicinal chemistry

authors： Yu W,Xiao H,Lin J,Li C

更新日期：2013-06-13 00:00:00

abstract：:New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cycl...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Tolman RL,Greenlee WJ,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-07-24 00:00:00

abstract：:A broad screening program previously identified phenprocoumon (1) as a small molecule template for inhibition of HIV protease. Subsequent modification of this lead through iterative cycles of structure-based design led to the activity enhancements of pyrone and dihydropyrone ring systems (II and V) and amide-based sub...

journal_title：Journal of medicinal chemistry

authors： Turner SR,Strohbach JW,Tommasi RA,Aristoff PA,Johnson PD,Skulnick HI,Dolak LA,Seest EP,Tomich PK,Bohanon MJ,Horng MM,Lynn JC,Chong KT,Hinshaw RR,Watenpaugh KD,Janakiraman MN,Thaisrivongs S

更新日期：1998-08-27 00:00:00

abstract：:Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resist...

journal_title：Journal of medicinal chemistry

authors： Skepper CK,Armstrong D,Balibar CJ,Bauer D,Bellamacina C,Benton BM,Bussiere D,De Pascale G,De Vicente J,Dean CR,Dhumale B,Fisher LM,Fuller J,Fulsunder M,Holder LM,Hu C,Kantariya B,Lapointe G,Leeds JA,Li X,Lu P,Lv

更新日期：2020-07-23 00:00:00

abstract：:A novel, simple, and efficient method for the chemical resolution of epidithiodioxopiperazines is reported, which is based upon covalent formation of diastereomers. This method might be a general one for the resolution of chiral cyclic disulfides. Dithiol 5, prepared from 2 by reduction with NaBH4, was allowed to reac...

journal_title：Journal of medicinal chemistry

authors： Ottenheijm HC,Herscheid JD,Tijhuis MW,Nivard RJ,De Clercq E,Prick PA

更新日期：1978-08-01 00:00:00

abstract：:The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute corona...

journal_title：Journal of medicinal chemistry

authors： Chackalamannil S,Wang Y,Greenlee WJ,Hu Z,Xia Y,Ahn HS,Boykow G,Hsieh Y,Palamanda J,Agans-Fantuzzi J,Kurowski S,Graziano M,Chintala M

更新日期：2008-06-12 00:00:00

abstract：:Following erythrocyte invasion, malaria parasites export a catalogue of remodeling proteins into the infected cell that enable parasite development in the human host. Export is dependent on the activity of the aspartyl protease, plasmepsin V (PMV), which cleaves proteins within the Plasmodium export element (PEXEL; Rx...

journal_title：Journal of medicinal chemistry

authors： Sleebs BE,Gazdik M,O'Neill MT,Rajasekaran P,Lopaticki S,Lackovic K,Lowes K,Smith BJ,Cowman AF,Boddey JA

更新日期：2014-09-25 00:00:00

abstract：:A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio ...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Meurer LC,Tolman RL,Greenlee WJ,Patchett AA,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-05-29 00:00:00

abstract：:Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length ...

journal_title：Journal of medicinal chemistry

authors： Abiru T,Miyashita T,Watanabe Y,Yamaguchi T,Machida H,Matsuda A

更新日期：1992-06-12 00:00:00

abstract：:Introduction of a nitrogen atom into the cyclohexane ring of 2-(4-phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-azavesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less pote...

journal_title：Journal of medicinal chemistry

authors： Efange SM,Khare A,Parsons SM,Bau R,Metzenthin T

更新日期：1993-04-16 00:00:00

abstract：:A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints ...

journal_title：Journal of medicinal chemistry

authors： D de Araujo A,Lim J,Wu KC,Xiang Y,Good AC,Skerlj R,Fairlie DP

更新日期：2018-04-12 00:00:00

abstract：:Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage in the place of the pyrophosphate have been synthesized from nicotinamide adenine dinucleotide analogues enzymatically using Aplysia californica ADP-ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (cADPR[CH(2)]) and methy...

journal_title：Journal of medicinal chemistry

authors： Xu L,Walseth TF,Slama JT

更新日期：2005-06-16 00:00:00

abstract：:A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT(2) receptor accommodating the "out-of-plane" substituent of MT(2)-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety ...

journal_title：Journal of medicinal chemistry

authors： Zlotos DP,Attia MI,Julius J,Sethi S,Witt-Enderby PA

更新日期：2009-02-12 00:00:00

abstract：:A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but wer...

journal_title：Journal of medicinal chemistry

authors： van Vliet LA,Tepper PG,Dijkstra D,Damsma G,Wikström H,Pugsley TA,Akunne HC,Heffner TG,Glase SA,Wise LD

更新日期：1996-10-11 00:00:00

abstract：:A series of analogues of the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester having hydroxy and/or methoxy substitution on the aromatic ring was synthesized and tasted. The introduction of a methoxy group in the para position of the aromatic ring of the peptide sweetener is crucial to the reduction or dest...

journal_title：Journal of medicinal chemistry

authors： Kawai M,Chorev M,Marin-Rose J,Goodman M

更新日期：1980-04-01 00:00:00

abstract：:The ortho hydroxy/methyl, hydroxy/hydroxymethyl, hydroxy/formyl, and hydroxy/carboxy substitution patterns, some of which confer dopaminergic agonist effects upon 2-aminotetralin ring systems, have been incorporated into beta-phenethylamine, 2-aminoindan, and trans-octahydrobenzo[f]quinoline rings. Certain of the 2-am...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Furlano DC,Dushin RG,Chang YA,Baird SR,Soliman LN,Flynn JR,Long JP,Bhatnagar RK

更新日期：1986-10-01 00:00:00

abstract：:The bioavailability of aromatic azaheterocyclic drugs can be affected by the activity of aldehyde oxidase (AO). Susceptibility to AO metabolism is difficult to predict computationally and can be complicated in vivo by differences between species. Here we report the use of bis(((difluoromethyl)sulfinyl)oxy)zinc (DFMS) ...

journal_title：Journal of medicinal chemistry

authors： O'Hara F,Burns AC,Collins MR,Dalvie D,Ornelas MA,Vaz AD,Fujiwara Y,Baran PS

更新日期：2014-02-27 00:00:00

abstract：:A theoretically rigorous and computationally tractable methodology for the prediction of the free energies of binding of protein-ligand complexes is presented. The method formulated involves developing molecular dynamics trajectories of the enzyme, the inhibitor, and the complex, followed by a free energy component an...

journal_title：Journal of medicinal chemistry

authors： Kalra P,Reddy TV,Jayaram B

更新日期：2001-12-06 00:00:00

abstract：:Bridging chemical and biological space is the key to drug discovery and development. Typically, cheminformatics methods operate under the assumption that similar chemicals have similar biological activity. Ideally then, one could predict a drug's biological function(s) given only its chemical structure by similarity s...

journal_title：Journal of medicinal chemistry

authors： Nettles JH,Jenkins JL,Bender A,Deng Z,Davies JW,Glick M

更新日期：2006-11-16 00:00:00

abstract：:A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of s...

journal_title：Journal of medicinal chemistry

authors： Kim HK,Kang MK,Jung KH,Kang SH,Kim YH,Jung JC,Lee GH,Chang Y,Kim TJ

更新日期：2013-10-24 00:00:00

abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...

journal_title：Journal of medicinal chemistry

authors： Ishiguro M,Tanaka R,Namikawa K,Nasu T,Inoue H,Nakatsuka T,Oyama Y,Imajo S

更新日期：1997-07-04 00:00:00