Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors.

abstract：:In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei L,Steiner JP,Hamilton GS,Wu YQ

更新日期：2004-09-06 00:00:00

abstract：:We designed and synthesized a small series of 2-aryl-imidazo[2,1-b]benzothiazole, representing a combination of motifs from the two most potent amyloid imaging agents, PIB and IMPY. The binding affinity of the new compounds ranged from 6 to 133 nM. Among the best compounds, 3b (K(i)=6 nM) can be labeled with (11)CH(3)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alagille D,DaCosta H,Baldwin RM,Tamagnan GD

更新日期：2011-05-15 00:00:00

abstract：:Radioligands are powerful tools for examining the pharmacological profiles of chemical leads and thus facilitate drug discovery. In this study, we identified and characterized 3-([1,1,1-(3)H]methyl)-2-(4-{[3-(1-pyrrolidinyl)propyl]oxy} phenyl)-4(3H)-quinazolinone ([(3)H]1) as a potent and selective radioligand for his...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mitobe Y,Ito S,Mizutani T,Nagase T,Sato N,Tokita S

更新日期：2009-08-01 00:00:00

abstract：:Clinically relevant Lys103Asn (K103N) mutant frequently observed in HIV-1 reverse transcriptase (RT) confers drug resistance. To obtain useful structural information necessary for targeted-inhibitor design, molecular docking combined with 3D-QSAR CoMFA and CoMSIA was applied to a set of 53 structurally diverse HIV-RT ...

journal_title：Bioorganic & medicinal chemistry letters

authors： San Juan AA

更新日期：2008-02-01 00:00:00

abstract：:The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kessler U,Castagnolo D,Pagano M,Deodato D,Bernardini M,Pilger B,Ranadheera C,Botta M

更新日期：2013-10-15 00:00:00

abstract：:A novel series of imidazo[1,5-a]pyrazines was synthesized and evaluated as corticotropin releasing hormone (CRH) receptor ligands. SAR studies focused primarily on dialkylamino side chain optimization. SAR of the aryl and small alkyl substituents was also explored. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hartz RA,Gilligan PJ,Nanda KK,Tebben AJ,Fitzgerald LW,Miller K

更新日期：2002-02-11 00:00:00

abstract：:Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH(2) were synthesized either by esterifying the Glu side-chain of the parent peptide in solution with alcohols in the presence of resin-bound dicyclohexylcarbodiimide or by solid-phase peptide chemistry. Affinities of these ester prodrugs to lipid membranes ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prokai-Tatrai K,Nguyen V,Zharikova AD,Braddy AC,Stevens SM,Prokai L

更新日期：2003-03-24 00:00:00

abstract：:A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta) has proven to be effective in clinical trials for the treatment of depression. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bymaster FP,Beedle EE,Findlay J,Gallagher PT,Krushinski JH,Mitchell S,Robertson DW,Thompson DC,Wallace L,Wong DT

更新日期：2003-12-15 00:00:00

abstract：:A new class of selective nonsteroidal glucocorticoid receptor modulators typified by N-[3-[benzyl-(4-chloro-2-fluoro-benzyl)-amino]-2-methyl-phenyl]-methanesulfonamide 19 has been discovered. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Link JT,Sorensen BK,Patel J,Emery M,Grynfarb M,Goos-Nilsson A

更新日期：2004-05-03 00:00:00

abstract：:We describe the synthesis and binding affinities on D(2), 5-HT(2A) and 5-HT(2C) receptors of 6-aminomethyl-6,7-dihydro-1H-indazol-4(5H)-ones and 6-aminomethyl-6,7-dihydro-3-methyl-benzo[d]isoxazol-4(5H)-ones, as conformationally constrained butyrophenone analogues. One of the new compounds showed good in vitro binding...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barceló M,Raviña E,Masaguer CF,Domínguez E,Areias FM,Brea J,Loza MI

更新日期：2007-09-01 00:00:00

abstract：:RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat cau...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guan L,Luo Y,Ja WW,Disney MD

更新日期：2018-09-01 00:00:00

abstract：:A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P(1) hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P(1) moiety. Replacement of the benzothiophene with different heterocyclic sy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lo HY,Nemoto PA,Kim JM,Hao MH,Qian KC,Farrow NA,Albaugh DR,Fowler DM,Schneiderman RD,Michael August E,Martin L,Hill-Drzewi M,Pullen SS,Takahashi H,De Lombaert S

更新日期：2011-08-01 00:00:00

abstract：:Starting from compound 1, we utilized biostructural data to successfully evolve an existing series into a new chemotype with a promising overall profile, exemplified by 19. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jamieson C,Maclean JK,Brown CI,Campbell RA,Gillen KJ,Gillespie J,Kazemier B,Kiczun M,Lamont Y,Lyons AJ,Moir EM,Morrow JA,Pantling J,Rankovic Z,Smith L

更新日期：2011-01-15 00:00:00

abstract：:The iridium(III)-catalyzed ortho-C-H amidation of benzoic acids with sulfonyl azides is described. These transformations allow the facile generation of N-sulfonyl anthranilic acids, which are known as crucial scaffolds found in biologically active molecules. In addition, all synthetic products were evaluated for in vi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Han SH,Suh HS,Jo H,Oh Y,Mishra NK,Han S,Kim HS,Jung YH,Lee BM,Kim IS

更新日期：2017-05-15 00:00:00

abstract：:To develop more valuable and effective fungicide candidates, a novel series of 3,4-dichloroisothioxazole-based cycloalkylsulfonamides were synthesized and their structures were identified by 1H NMR, 13C NMR, MS and elemental analysis. Compound 3k was further confirmed by X-ray single crystal diffraction. The in vitro ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Y,Wang M,Ahmed M,He L,Ji M,Qi Z,Li X

更新日期：2019-06-01 00:00:00

abstract：:Synthesis of novel 1,2,3-triazole-linked beta-lactam-bile acid conjugates 17-24 using 1,3-dipolar cycloaddition reaction of azido beta-lactam and terminal alkyne of bile acids in the presence of Cu(I) catalyst (click chemistry) have been realized. These molecules were evaluated in vitro for their antifungal and antiba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vatmurge NS,Hazra BG,Pore VS,Shirazi F,Chavan PS,Deshpande MV

更新日期：2008-03-15 00:00:00

abstract：:Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen ZZ,Xie YD,Shao LH,Wang QT,Xu YH,Bian XL

更新日期：2018-12-15 00:00:00

abstract：:The HIV-1 envelope glycoprotein gp41 fusion intermediate is a promising drug target for inhibiting viral entry. However, drug development has been impeded by challenges inherent in mediating the underlying protein-protein interaction. Here we report on the identification of fragments that bind to a C-terminal sub-pock...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu S,Gochin M

更新日期：2013-09-15 00:00:00

abstract：:The discovery of a novel series of 2-(4-pyridyl)thienopyridinone GSK-3β inhibitors is reported. X-ray crystallography reveals its binding mode and enables rationalization of the SAR. The initial optimization of the template for improved cellular activity and predicted CNS penetration is also presented. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gentile G,Bernasconi G,Pozzan A,Merlo G,Marzorati P,Bamborough P,Bax B,Bridges A,Brough C,Carter P,Cutler G,Neu M,Takada M

更新日期：2011-08-15 00:00:00

abstract：:Mismatch binding protein MutS binding to bulge structure in DNA duplexes was controlled by UV irradiation. 4-O-(2-Nitrobenzyl)thymidine or 4-O-[2-(2-nitrophenyl)propyl]thymidine was incorporated into DNA duplexes a bulged position. The MutS did not bind to the caged DNA duplexes but bound after removing the 2-nitroben...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seio K,Ohno Y,Ohno K,Takeshita L,Kanamori T,Masaki Y,Sekine M

更新日期：2016-10-01 00:00:00

abstract：:Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Iserloh U,Wu Y,Cumming JN,Pan J,Wang LY,Stamford AW,Kennedy ME,Kuvelkar R,Chen X,Parker EM,Strickland C,Voigt J

更新日期：2008-01-01 00:00:00

abstract：:A novel series of benzothiophene derivatives was discovered as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity relationship studies on high-throughput screening hit compound 1 led to the identification of 7-acetyl-3-methyl-N-(quinolin-2-yl)-1-benzothiophene-2-carboxamide (16), with potent inhibitory acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kawamoto Y,Tomino M,Hiramatsu K,Oyama Y,Hayashi Y

更新日期：2019-06-01 00:00:00

abstract：:To discover new natural-product-based insecticidal agents, a series of novel oxime derivatives of podophyllotoxin-based phenazines modified in the C, D and E rings of podophyllotoxin were prepared and tested as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhi X,Yang C,Yu X,Xu H

更新日期：2014-12-15 00:00:00

abstract：:Horner-Emmons reaction of 4"-dehydro-5-O-TBDMS-avermectin B(1a) with a variety of phosphorus ylides using LHMDS gave novel 4"-alkylidene avermectin derivatives in high yields. Further modifications led to derivatives bearing diverse functional groups. The new avermectin derivatives showed potent growth inhibitory acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagai K,Sunazuka T,Shiomi K,Harder A,Turberg A,Omura S

更新日期：2003-11-17 00:00:00

abstract：:The synthesis and anti-angiogenic activities of linomide and its analogues are reported. Three of the analogues are 3.3-69 times more potent than linomide at inhibiting blood vessel formation in the CAM angiogenesis assay. These compounds possessed considerable anti-proliferative activity against isolated HUVEC cells ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi J,Xiao Z,Ihnat MA,Kamat C,Pandit B,Hu Z,Li PK

更新日期：2003-03-24 00:00:00

abstract：:Two series of 5-phenyl furocoumarin derivatives were designed and prepared based on our previous research. All new compounds were characterized by (1)H NMR, (13)C NMR and mass spectra. Furthermore, they were screened for their vasodilatory activity on the mesenteric artery of Sprague-Dawley rats, and they all presente...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang C,Wang T,Huang L,Lu W,Zhang J,He H

更新日期：2016-01-15 00:00:00

abstract：:A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory a...

journal_title：Bioorganic & medicinal chemistry letters

authors： He H,Wang X,Shi L,Yin W,Yang Z,He H,Liang Y

更新日期：2016-07-15 00:00:00

abstract：:The design and profile of a series of adamantyl-containing long acting beta(2)-adrenoreceptor agonists are described. An optimal pharmacokinetic profile of low oral bioavailability was combined with a strong pharmacology profile when assessed using a guinea pig trachea tissue model. A focus was then placed on developi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brown AD,Bunnage ME,Glossop PA,James K,Jones R,Lane CA,Lewthwaite RA,Mantell S,Perros-Huguet C,Price DA,Trevethick M,Webster R

更新日期：2008-02-15 00:00:00

abstract：:The highly selective agonists of the A(3) adenosine receptor (AR), Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine), and its 4'-thio analogue, were successfully converted into selective antagonists simply by appending a second N-methyl group on the 5'-uronamide position. The 2-chloro-5'-(N,N-d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao ZG,Joshi BV,Klutz AM,Kim SK,Lee HW,Kim HO,Jeong LS,Jacobson KA

更新日期：2006-02-01 00:00:00

abstract：:A series of N-8 substituted analogs based upon the spiropiperidine core of the original lead compound 1 was synthesized. This lead has been elaborated to compounds to give compounds 2 and 3 (R=H) that exhibited high NOP binding affinity as well as selectivity against other known opioid receptors. These two series have...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldwell JP,Matasi JJ,Fernandez X,McLeod RL,Zhang H,Fawzi A,Tulshian DB

更新日期：2009-02-15 00:00:00