Synthesis and beta-adrenergic blocking activity of new aliphatic oxime ethers.

abstract：:Bifunctional quinolinonyl DKA derivatives were first described as nonselective inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions of HIV-1 integrase (IN), while 7-aminosubstituted quinolinonyl derivatives were proven IN strand transfer inhibitors (INSTIs) that also displayed activity against ribonuc...

journal_title：Journal of medicinal chemistry

authors： Pescatori L,Métifiot M,Chung S,Masoaka T,Cuzzucoli Crucitti G,Messore A,Pupo G,Madia VN,Saccoliti F,Scipione L,Tortorella S,Di Leva FS,Cosconati S,Marinelli L,Novellino E,Le Grice SF,Pommier Y,Marchand C,Costi R,Di

更新日期：2015-06-11 00:00:00

abstract：:alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Ou...

journal_title：Journal of medicinal chemistry

authors： Zembower DE,Gilbert JA,Ames MM

更新日期：1993-02-05 00:00:00

abstract：:New drugs and molecular targets are urgently needed to address the emergence and spread of drug-resistant tuberculosis. Mycobacterium tuberculosis ( Mtb) inosine 5'-monophosphate dehydrogenase 2 ( MtbIMPDH2) is a promising yet controversial potential target. The inhibition of MtbIMPDH2 blocks the biosynthesis of guani...

journal_title：Journal of medicinal chemistry

authors： Chacko S,Boshoff HIM,Singh V,Ferraris DM,Gollapalli DR,Zhang M,Lawson AP,Pepi MJ,Joachimiak A,Rizzi M,Mizrahi V,Cuny GD,Hedstrom L

更新日期：2018-06-14 00:00:00

abstract：:Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or ary...

journal_title：Journal of medicinal chemistry

authors： von Geldern TW,Kester JA,Bal R,Wu-Wong JR,Chiou W,Dixon DB,Opgenorth TJ

更新日期：1996-02-16 00:00:00

abstract：:As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42), anilinopyrimidines I were identified as potent antagonists of corticotropin-releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing factor, CRF1-R). Our next goal was to understand the receptor-bound conformation o...

journal_title：Journal of medicinal chemistry

authors： Hodge CN,Aldrich PE,Wasserman ZR,Fernandez CH,Nemeth GA,Arvanitis A,Cheeseman RS,Chorvat RJ,Ciganek E,Christos TE,Gilligan PJ,Krenitsky P,Scholfield E,Strucely P

更新日期：1999-03-11 00:00:00

abstract：:The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC(50) = 6.1 ± 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallo...

journal_title：Journal of medicinal chemistry

authors： Lawrence HR,Martin MP,Luo Y,Pireddu R,Yang H,Gevariya H,Ozcan S,Zhu JY,Kendig R,Rodriguez M,Elias R,Cheng JQ,Sebti SM,Schonbrunn E,Lawrence NJ

更新日期：2012-09-13 00:00:00

abstract：:A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 ade...

journal_title：Journal of medicinal chemistry

authors： Linden J,Patel A,Earl CQ,Craig RH,Daluge SM

更新日期：1988-04-01 00:00:00

abstract：:We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed aga...

journal_title：Journal of medicinal chemistry

authors： Pandey A,Volkots DL,Seroogy JM,Rose JW,Yu JC,Lambing JL,Hutchaleelaha A,Hollenbach SJ,Abe K,Giese NA,Scarborough RM

更新日期：2002-08-15 00:00:00

abstract：:A series of 3-acylbenzamidine (amidino)hydrazones 7a-h, the corresponding (hetero)aromatic congeners 7i-p, and 3,3'-bis-amidino-biaryls 25a-e were synthesized. The hydrazones 7a-p were prepared by conversion of the corresponding acyl nitriles 1a,c-d,i,n-p to the imido esters 3a,c-d,i and the amidines 5a,c-d,h-i, follo...

journal_title：Journal of medicinal chemistry

authors： Stanek J,Caravatti G,Capraro HG,Furet P,Mett H,Schneider P,Regenass U

更新日期：1993-01-08 00:00:00

abstract：:The tetrapeptide H-Arg-Gly-Asp-Ser-OH (1) (RGDS), representing a recognition sequence of fibrinogen for its platelet receptor GP IIb-IIIa (integrin alpha IIb beta 3), served as lead compound for the development of highly potent and selective fibrinogen receptor antagonists. Replacement of the N-terminal arginine by p-...

journal_title：Journal of medicinal chemistry

authors： Alig L,Edenhofer A,Hadváry P,Hürzeler M,Knopp D,Müller M,Steiner B,Trzeciak A,Weller T

更新日期：1992-11-13 00:00:00

abstract：:A series of benzyl-substituted phthalonitriles, substituted at the 3-, 4-, and 4,5-positions, underwent varied condensations with phthalonitrile to give a series of protected (monohydroxy- and polyhydroxyphthalocyaninato)zinc(II) derivatives which were readily cleaved to give several hydroxyphthalocyanines (ZnPc) (pht...

journal_title：Journal of medicinal chemistry

authors： Hu M,Brasseur N,Yildiz SZ,van Lier JE,Leznoff CC

更新日期：1998-05-21 00:00:00

abstract：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...

journal_title：Journal of medicinal chemistry

authors： Witiak DT,Kakodkar SV,Brunst GE,Baldwin JR,Rahwan RG

更新日期：1978-12-01 00:00:00

abstract：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...

journal_title：Journal of medicinal chemistry

authors： Clark RL,Pessolano AA,Shen TY,Jacobus DP,Jones H,Lotti VJ,Flataker LM

更新日期：1978-09-01 00:00:00

abstract：:The mechanism of action of a general class of mechanism-based inhibitors of serine proteases, including human neutrophil elastase (HNE), has been elucidated by determining the X-ray crystal structure of an enzyme-inhibitor complex. The captured intermediate indicates that processing of inhibitor by the enzyme generate...

journal_title：Journal of medicinal chemistry

authors： Huang W,Yamamoto Y,Li Y,Dou D,Alliston KR,Hanzlik RP,Williams TD,Groutas WC

更新日期：2008-04-10 00:00:00

abstract：:Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high sele...

journal_title：Journal of medicinal chemistry

authors： Liu G,Xin Z,Pei Z,Hajduk PJ,Abad-Zapatero C,Hutchins CW,Zhao H,Lubben TH,Ballaron SJ,Haasch DL,Kaszubska W,Rondinone CM,Trevillyan JM,Jirousek MR

更新日期：2003-09-25 00:00:00

abstract：:The dynorphin (Dyn) A analogue zyklophin ([N-benzyl-Tyr(1)-cyclo(d-Asp(5),Dap(8))]dynorphin A(1-11)NH2) is a kappa opioid receptor (KOR)-selective antagonist in vitro, is active in vivo, and antagonizes KOR in the CNS after systemic administration. Hence, we synthesized zyklophin analogues to explore the structure-act...

journal_title：Journal of medicinal chemistry

authors： Joshi AA,Murray TF,Aldrich JV

更新日期：2015-11-25 00:00:00

abstract：:In humans, bitter taste is mediated by 25 TAS2Rs. Many compounds, including certain active pharmaceutical ingredients, excipients, and nutraceuticals, impart their bitter taste (or in part) through TAS2R8 activation. However, effective TAS2R8 blockers that can either suppress or reduce the bitterness of these compound...

journal_title：Journal of medicinal chemistry

authors： Fotsing JR,Darmohusodo V,Patron AP,Ching BW,Brady T,Arellano M,Chen Q,Davis TJ,Liu H,Servant G,Zhang L,Williams M,Saganich M,Ditschun T,Tachdjian C,Karanewsky DS

更新日期：2020-05-14 00:00:00

abstract：:We report the activities of 62 bisphosphonates as inhibitors of the Leishmania major mevalonate/isoprene biosynthesis pathway enzyme, farnesyl pyrophosphate synthase. The compounds investigated exhibit activities (IC(50) values) ranging from approximately 100 nM to approximately 80 microM (corresponding to K(i) values...

journal_title：Journal of medicinal chemistry

authors： Sanders JM,Gómez AO,Mao J,Meints GA,Van Brussel EM,Burzynska A,Kafarski P,González-Pacanowska D,Oldfield E

更新日期：2003-11-20 00:00:00

abstract：:The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors with high affinity (Ki = 14 nM), while it lacks affinity at rat A3 receptors. Acylated derivatives of the 5-amino group and other modifications were prepared in an effort to provide A3 subtype...

journal_title：Journal of medicinal chemistry

authors： Kim YC,Ji XD,Jacobson KA

更新日期：1996-10-11 00:00:00

abstract：:Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]p...

journal_title：Journal of medicinal chemistry

authors： Ryu H,Jin MK,Kim SY,Choi HK,Kang SU,Kang DW,Lee J,Pearce LV,Pavlyukovets VA,Morgan MA,Tran R,Toth A,Lundberg DJ,Blumberg PM

更新日期：2008-01-10 00:00:00

abstract：:(E)-5-(2-Bromovinyl)isodideoxyuridine (BVisoDDU), synthesized on the basis of molecular modeling, is selectively active against HSV-1 (three different strains) but inactive against HSV-2. Unlike BVDU, BVisoDDU is completely resistant to cleavage by thymidine phosphorylase. BVisoDDU is also the first nucleoside analogu...

journal_title：Journal of medicinal chemistry

authors： Guenther S,Balzarini J,De Clercq E,Nair V

更新日期：2002-12-05 00:00:00

abstract：:The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...

journal_title：Journal of medicinal chemistry

authors： Azevedo CM,Watterson KR,Wargent ET,Hansen SV,Hudson BD,Kępczyńska MA,Dunlop J,Shimpukade B,Christiansen E,Milligan G,Stocker CJ,Ulven T

更新日期：2016-10-13 00:00:00

abstract：:We report herein the discovery of the human immunodeficiency virus type-1 (HIV-1) integrase inhibitors dolutegravir (S/GSK1349572) (3) and S/GSK1265744 (4). These drugs stem from a series of carbamoyl pyridone analogues designed using a two-metal chelation model of the integrase catalytic active site. Structure-activi...

journal_title：Journal of medicinal chemistry

authors： Johns BA,Kawasuji T,Weatherhead JG,Taishi T,Temelkoff DP,Yoshida H,Akiyama T,Taoda Y,Murai H,Kiyama R,Fuji M,Tanimoto N,Jeffrey J,Foster SA,Yoshinaga T,Seki T,Kobayashi M,Sato A,Johnson MN,Garvey EP,Fujiwara T

更新日期：2013-07-25 00:00:00

abstract：:A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11- oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochem...

journal_title：Journal of medicinal chemistry

authors： Kurokawa M,Uno H,Nakamura H,Sato F,Naruto S

更新日期：1990-02-01 00:00:00

abstract：:Quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) have been applied to elucidate the mechanisms of genotoxicity (SOSIP) of nitrofuran derivatives on Escherichia coli PQ37. The following equation was developed: log SOSIP = -33.1qc2 + 1.00 log P - 1.50Isat - 1.19MR - 0....

journal_title：Journal of medicinal chemistry

authors： Debnath AK,Hansch C,Kim KH,Martin YC

更新日期：1993-04-16 00:00:00

abstract：:We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequen...

journal_title：Journal of medicinal chemistry

authors： Wiles JA,Hashimoto A,Thanassi JA,Cheng J,Incarvito CD,Deshpande M,Pucci MJ,Bradbury BJ

更新日期：2006-01-12 00:00:00

abstract：:The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MR...

journal_title：Journal of medicinal chemistry

authors： Ma Z,Chu DT,Cooper CS,Li Q,Fung AK,Wang S,Shen LL,Flamm RK,Nilius AM,Alder JD,Meulbroek JA,Or YS

更新日期：1999-10-07 00:00:00

abstract：:Starting from a known inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase (IN); caffeic acid phenethyl ester (CAPE), a putative three-point pharmacophore for binding of inhibitors to IN was derived. This pharmacophore was used to search the National Cancer Institute three-dimensional (3D) structural dat...

journal_title：Journal of medicinal chemistry

authors： Nicklaus MC,Neamati N,Hong H,Mazumder A,Sunder S,Chen J,Milne GW,Pommier Y

更新日期：1997-03-14 00:00:00

abstract：:Analogues of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives (3, 3') were prepared to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against t...

journal_title：Journal of medicinal chemistry

authors： Gomez-Monterrey I,Campiglia P,Carotenuto A,Stiuso P,Bertamino A,Sala M,Aquino C,Grieco P,Morello S,Pinto A,Ianelli P,Novellino E

更新日期：2008-05-22 00:00:00

abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...

journal_title：Journal of medicinal chemistry

authors： Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

更新日期：2003-05-22 00:00:00