Discovery of 2-[5-(4-Fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic Acid (SX-517): Noncompetitive Boronic Acid Antagonist of CXCR1 and CXCR2.

abstract：:Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and...

journal_title：Journal of medicinal chemistry

authors： Moormann AE,Pitzele BS,Jones PH,Gullikson GW,Albin D,Yu SS,Bianchi RG,Sanguinetti EL,Rubin B,Grebner M

更新日期：1990-02-01 00:00:00

abstract：:N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 A showed that the N-piperidinopropyl group in 2 is not stretched along t...

journal_title：Journal of medicinal chemistry

authors： Bartolucci C,Haller LA,Jordis U,Fels G,Lamba D

更新日期：2010-01-28 00:00:00

abstract：:A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed s...

journal_title：Journal of medicinal chemistry

authors： Nielsen SF,Thastrup O,Pedersen R,Olsen CE,Christensen SB

更新日期：1995-01-20 00:00:00

abstract：:Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. The new tricyclic ligands are either angular, 2,3,3a,4,5,...

journal_title：Journal of medicinal chemistry

authors： Chidester CG,Lin CH,Lahti RA,Haadsma-Svensson SR,Smith MW

更新日期：1993-05-14 00:00:00

abstract：:The cytotoxic complex, [PtCl(Am)2(ACRAMTU)](NO3)2 (1) ((Am)2 = ethane-1,2-diamine, en; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea), is a dual platinating/intercalating DNA binder that, unlike clinical platinum agents, does not induce DNA cross-links. Here, we demonstrate that substitution of the thi...

journal_title：Journal of medicinal chemistry

authors： Ma Z,Choudhury JR,Wright MW,Day CS,Saluta G,Kucera GL,Bierbach U

更新日期：2008-12-11 00:00:00

abstract：:A series of substituted 3-aryl- and hydroxy-3-aryloctahydropyrido[2,1-c][1,4]oxazines has been synthesized for purposes of investigating potentially useful CNS pharmacological actions of this novel heterocyclic system. The preferred conformation of the bicyclic system of the parent compounds, 1 and 2, has been shown t...

journal_title：Journal of medicinal chemistry

authors： Rankin GO,Riley TN,Murphy JC

更新日期：1978-05-01 00:00:00

abstract：:Various lines of evidence, including molecular modeling studies, imply that the endoethylenic bridge of 3,8-diazabicyclo[3.2. 1]octanes (DBO, 1) plays an essential role in modulating affinity toward mu opioid receptors. This hypothesis, together with the remarkable analgesic properties observed for N(3) propionyl, N(8...

journal_title：Journal of medicinal chemistry

authors： Vianello P,Albinati A,Pinna GA,Lavecchia A,Marinelli L,Borea PA,Gessi S,Fadda P,Tronci S,Cignarella G

更新日期：2000-06-01 00:00:00

abstract：:Protein arginine methyltransferase 1 (PRMT1) is involved in many biological activities, such as gene transcription, signal transduction, and RNA processing. Overexpression of PRMT1 is related to cardiovascular diseases, kidney diseases, and cancers; therefore, selective PRMT1 inhibitors serve as chemical probes to inv...

journal_title：Journal of medicinal chemistry

authors： Hu H,Owens EA,Su H,Yan L,Levitz A,Zhao X,Henary M,Zheng YG

更新日期：2015-02-12 00:00:00

abstract：:Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...

journal_title：Journal of medicinal chemistry

authors： Devraj R,Barrett JF,Fernandez JA,Katzenellenbogen JA,Cushman M

更新日期：1996-08-16 00:00:00

abstract：:There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrat...

journal_title：Journal of medicinal chemistry

authors： Douat-Casassus C,Borbulevych O,Tarbe M,Gervois N,Jotereau F,Baker BM,Quideau S

更新日期：2010-10-14 00:00:00

abstract：:The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors ...

journal_title：Journal of medicinal chemistry

authors： Huang KW,Hsu KC,Chu LY,Yang JM,Yuan HS,Hsiao YY

更新日期：2016-09-08 00:00:00

abstract：:The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from bone marrow to peripheral circulation. We have discovered a novel series of ...

journal_title：Journal of medicinal chemistry

authors： Wu CH,Song JS,Kuan HH,Wu SH,Chou MC,Jan JJ,Tsou LK,Ke YY,Chen CT,Yeh KC,Wang SY,Yeh TK,Tseng CT,Huang CL,Wu MH,Kuo PC,Lee CJ,Shia KS

更新日期：2018-02-08 00:00:00

abstract：:Brr2 is an RNA helicase belonging to the Ski2-like subfamily and an essential component of spliceosome. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step for spliceosomal activation. An HTS campaign using an RNA-dependent ATPase assay and initial SAR study identified two diffe...

journal_title：Journal of medicinal chemistry

authors： Iwatani-Yoshihara M,Ito M,Klein MG,Yamamoto T,Yonemori K,Tanaka T,Miwa M,Morishita D,Endo S,Tjhen R,Qin L,Nakanishi A,Maezaki H,Kawamoto T

更新日期：2017-07-13 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：:Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compoun...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Lin S,Aung TT,Lim F,Zou H,Bai Y,Li J,Lin H,Pang LM,Koh WL,Salleh SM,Lakshminarayanan R,Zhou L,Qiu S,Pervushin K,Verma C,Tan DT,Cao D,Liu S,Beuerman RW

更新日期：2015-01-22 00:00:00

abstract：:A three-dimensional model of the AT1 receptor was constructed by means of a homology modeling procedure, using the X-ray structure of bovine rhodopsin as the initial template and taking into account the available site-directed mutagenesis data. The docking of losartan and its active metabolite EXP3174, followed by 1 n...

journal_title：Journal of medicinal chemistry

authors： Tuccinardi T,Calderone V,Rapposelli S,Martinelli A

更新日期：2006-07-13 00:00:00

abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase ...

journal_title：Journal of medicinal chemistry

authors： Irwin N,O'Harte FP,Gault VA,Green BD,Greer B,Harriott P,Bailey CJ,Flatt PR

更新日期：2006-02-09 00:00:00

abstract：:The constitution of chlorpromazine has been studied in the context of its phototoxicity. Electron transfer from the side chain to the aromatic nucleus of the drug contributes to its instability to light. Even without the side chain, however, chlorophenothiazines appear to be very photolabile, so that it is unlikely th...

journal_title：Journal of medicinal chemistry

authors： Bunce NJ,Kumar Y,Ravanal L

更新日期：1979-02-01 00:00:00

abstract：:A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3K...

journal_title：Journal of medicinal chemistry

authors： Thakur A,Tawa GJ,Henderson MJ,Danchik C,Liu S,Shah P,Wang AQ,Dunn G,Kabir M,Padilha EC,Xu X,Simeonov A,Kharbanda S,Stone R,Grewal G

更新日期：2020-04-23 00:00:00

abstract：:A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant a...

journal_title：Journal of medicinal chemistry

authors： van Acker FA,Hageman JA,Haenen GR,van Der Vijgh WJ,Bast A,Menge WM

更新日期：2000-10-05 00:00:00

abstract：:Three derivatives of angelicin (1) [4'-methyl-, 4,4'-dimethyl-, and 4',5-dimethylangelicin (2a-c)] have been prepared with the aim of obtaining new agents for the photochemotherapy of psoriasis. These compounds form a complex in the dark with DNA that shows an affinity for the macromolecule higher than that of the par...

journal_title：Journal of medicinal chemistry

authors： Dall'Acqua F,Vedaldi D,Bordin F,Baccichetti F,Carlassare F,Tamaro M,Rodighiero P,Pastorini G,Guiotto A,Recchia G,Cristofolini M

更新日期：1983-06-01 00:00:00

abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...

journal_title：Journal of medicinal chemistry

authors： Ehrt C,Brinkjost T,Koch O

更新日期：2016-05-12 00:00:00

abstract：:In a recent paper (Colotta et al. J. Med. Chem. 2000, 43, 1158-1164) we reported the synthesis and adenosine receptor binding activity of two sets of 2-aryl-1,2,4-triazolo[4,3-a]quinoxalines (A and B) some of which were potent and selective A(1) or A(3) antagonists. In this paper the synthesis of a set of 2-arylpyrazo...

journal_title：Journal of medicinal chemistry

authors： Colotta V,Catarzi D,Varano F,Cecchi L,Filacchioni G,Martini C,Trincavelli L,Lucacchini A

更新日期：2000-08-10 00:00:00

abstract：:Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed...

journal_title：Journal of medicinal chemistry

authors： Kees KL,Caggiano TJ,Steiner KE,Fitzgerald JJ Jr,Kates MJ,Christos TE,Kulishoff JM Jr,Moore RD,McCaleb ML

更新日期：1995-02-17 00:00:00

abstract：:The availability of peptide and non-peptide Ang II receptor antagonists has permitted the study of Ang II receptor heterogeneity. It is now widely recognized that there are at least two distinct Ang II receptor subtypes. AT1 receptors are selective in their recognition of agents such as losartan, DuP 532, L-158,809, S...

journal_title：Journal of medicinal chemistry

authors： VanAtten MK,Ensinger CL,Chiu AT,McCall DE,Nguyen TT,Wexler RR,Timmermans PB

更新日期：1993-12-10 00:00:00

abstract：:Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compound...

journal_title：Journal of medicinal chemistry

authors： Gurney ME,Nugent RA,Mo X,Sindac JA,Hagen TJ,Fox D 3rd,O'Donnell JM,Zhang C,Xu Y,Zhang HT,Groppi VE,Bailie M,White RE,Romero DL,Vellekoop AS,Walker JR,Surman MD,Zhu L,Campbell RF

更新日期：2019-05-23 00:00:00

abstract：:The synthesis, stability, and antitumor activity of a series of water-soluble third generation platinum(II) complexes have been described. Among these complexes, [2,2-bis(aminomethyl)-1,3- propanediol-N,N'] [1,1-cyclobutanedicarboxylato(2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylate(2-)-O,O'](tetrahydro-4H-py...

journal_title：Journal of medicinal chemistry

authors： Bitha P,Carvajal SG,Citarella RV,Child RG,Delos Santos EF,Dunne TS,Durr FE,Hlavka JJ,Lang SA Jr,Lindsay HL

更新日期：1989-08-01 00:00:00

abstract：:A pair of enantiomeric Pt(II) complexes, [Pt(R-ahaz)Cl2] and [Pt(S-ahaz)Cl2] (ahaz = 3-aminohexahydroazepine), has been investigated for their ability to bind enantioselectively to DNA. Improved synthetic procedures were developed for preparing both the ligands and the Pt complexes. The structure of the complex of the...

journal_title：Journal of medicinal chemistry

authors： Fenton RR,Easdale WJ,Er HM,O'Mara SM,McKeage MJ,Russell PJ,Hambley TW

更新日期：1997-03-28 00:00:00

abstract：:4-(Phenylamino)-5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 1 and related compounds known as "diaryltubercidin" analogues are potent inhibitors of adenosine kinase (AK) and are orally active in animal models of pain such as the rat formalin paw model (GP3269 ED50= 6.4 mg/kg). However, the utility...

journal_title：Journal of medicinal chemistry

authors： Bookser BC,Ugarkar BG,Matelich MC,Lemus RH,Allan M,Tsuchiya M,Nakane M,Nagahisa A,Wiesner JB,Erion MD

更新日期：2005-12-01 00:00:00

abstract：:Comparative binding energy analysis, a technique to derive receptor-based three-dimensional quantitative structure-activity relationships (3D-QSAR), is herein extended to consider both affinity and selectivity in the derivation of the QSAR model. The extension is based on allowing multiple structurally related recepto...

journal_title：Journal of medicinal chemistry

authors： Murcia M,Morreale A,Ortiz AR

更新日期：2006-10-19 00:00:00