Design and synthesis of tetracyclic nonpeptidic biaryl nitrile inhibitors of cathepsin K.

abstract：:Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen C,Chen Y,Pontillo J,Guo Z,Huang CQ,Wu D,Madan A,Chen T,Wen J,Xie Q,Tucci FC,Rowbottom M,Zhu YF,Wade W,Saunders J,Bozigian H,Struthers RS

更新日期：2008-06-01 00:00:00

abstract：:Five-coordinated oxovanadium(IV) complexes with ciprofloxacin and various uninegative bidentate amino acids have been prepared. The structure of complexes has been investigated using spectral, physicochemical, mass spectroscopy, and elemental analyses. The antimicrobial activities (MIC) of the complexes, ligands, meta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel MN,Patel SH,Chhasatia MR,Parmar PA

更新日期：2008-12-15 00:00:00

abstract：:SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishii H,Koyama H,Hagiwara K,Miura T,Xue G,Hashimoto Y,Kitahara G,Aida Y,Suzuki M

更新日期：2012-02-01 00:00:00

abstract：:Macrocyclic bis(bibenzyl)-type phenolic natural products, found exclusively in bryophytes, exhibit potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Here, in order to identify the minimum essential structure for cell membrane leakage-mediated anti-MRSA activity of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujii K,Morita D,Onoda K,Kuroda T,Miyachi H

更新日期：2016-05-01 00:00:00

abstract：:To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Horio T,Hamasaki T,Inoue T,Wakayama T,Itou S,Naito H,Asaki T,Hayase H,Niwa T

更新日期：2007-05-15 00:00:00

abstract：:A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF. W-68 and other DNA topoisomerase II inhibitors are prepare...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamal A,Laxman N,Ramesh G

更新日期：2000-09-18 00:00:00

abstract：:Eight peptoids have been synthesized as peptidomimetics of the cytostatic Dolastatin 15, a depsipeptide isolated from the Indian sea hare Dolabella auricularia. The compounds have been tested against several human cancer cell lines and did not show any cytostatic properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schmitt J,Bernd M,Kutscher B,Kessler H

更新日期：1998-02-17 00:00:00

abstract：:Bisubstrate analog inhibitors in which a nicotinamide mimic is attached to a series of structurally diversified guanidines (arginine mimics) were synthesized and evaluated for inhibition of cholera toxin. The mechanism-based bisubstrate inhibitors were up to 1400-fold more potent than the natural substrate NAD+ and 40...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang G

更新日期：2008-07-01 00:00:00

abstract：:A new class of benzimidazole-5-sulfonamides has been identified as nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Initial structure-activity relationships are presented resulting in compounds 19 and 28 with submicromolar dual functional activity on human and rat receptors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto K,Tatsuta M,Kataoka M,Yasoshima K,Shogase Y,Shimazaki M,Yura T,Li Y,Yamamoto N,Gupta JB,Urbahns K

更新日期：2005-02-01 00:00:00

abstract：:An efficient synthesis of [D-lysine](8)cyclosporin A has been developed. Several analogs of [D-lysine](8)cyclosporin A have been synthesized and show promising anti-HCV activity, particularly compounds 39 and 43, which each exhibit an anti-HCV EC(50)<200 nM, and are each ≥50-fold less immunosuppressive than cyclospori...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scribner A,Houck D,Huang Z,Mosier S,Peel M,Scorneaux B

更新日期：2010-11-15 00:00:00

abstract：:Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crys...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang X,Cheng CC,Fischmann TO,Duca JS,Richards M,Tadikonda PK,Reddy PA,Zhao L,Siddiqui MA,Parry D,Davis N,Seghezzi W,Wiswell D,Shipps GW Jr

更新日期：2013-05-01 00:00:00

abstract：:Mannose-6-phosphate (M6P)-containing N-linked glycans are essential signaling molecules for sorting hydrolases in eukaryotic cells. Their receptors, especially the cation-independent M6P receptors (CI-MPRs), have emerged as promising protein targets for targeted drug delivery for the treatment of lysosomal storage dis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu Y,Marshall J,Li Q,Edwards N,Chen G

更新日期：2013-04-15 00:00:00

abstract：:N6-Substituted adenosine analogues containing cyclic hydrazines or chiral hydroxy (ar)alkyl groups, designed to interact with the S2 and S3 receptor subregions, have been synthesized and their binding to the adenosine A1 and A2A receptors have been investigated. Examples of both types of compounds were found to exhibi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ha SB,Melman N,Jacobson KA,Nair V

更新日期：1997-12-16 00:00:00

abstract：:A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hattori K,Kohchi Y,Oikawa N,Suda H,Ura M,Ishikawa T,Miwa M,Endoh M,Eda H,Tanimura H,Kawashima A,Horii I,Ishitsuka H,Shimma N

更新日期：2003-03-10 00:00:00

abstract：:A series of new 9-O-substituted berberine derivatives (4a-j) as telomeric quadruplex ligands was synthesized and evaluated. The results from biophysical and biochemical assay indicated that introducing of positive charged aza-aromatic terminal group into the side chain of 9-position of berberine significantly improved...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma Y,Ou TM,Tan JH,Hou JQ,Huang SL,Gu LQ,Huang ZS

更新日期：2009-07-01 00:00:00

abstract：:Damage to DNA is caused by ionizing radiation, genotoxic chemicals or collapsed replication forks. When DNA is damaged or cells fail to respond, a mutation that is associated with breast or ovarian cancer may occur. Mammalian cells control and stabilize the genome using a cell cycle checkpoint to prevent damage to DNA...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang YL,Lin CY,Shih KC,Huang JW,Tang CY

更新日期：2013-12-01 00:00:00

abstract：:We have discovered that phenyltriazolinone is a novel and potent P1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S1 binding pocket which is larger in size to accommodate the p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Quan ML,Pinto DJ,Rossi KA,Sheriff S,Alexander RS,Amparo E,Kish K,Knabb RM,Luettgen JM,Morin P,Smallwood A,Woerner FJ,Wexler RR

更新日期：2010-02-15 00:00:00

abstract：:Serine racemase, the enzyme responsible for d-serine synthesis in the central nervous system, has been identified as a potential therapeutic target to treat N-methyl-d-aspartate receptors-related pathologies. The search for specific inhibitors of the enzyme has revealed that serine racemase is a difficult target, with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dellafiora L,Marchetti M,Spyrakis F,Orlandi V,Campanini B,Cruciani G,Cozzini P,Mozzarelli A

更新日期：2015-10-01 00:00:00

abstract：:A series of 4,4-disubstituted cyclohexylamine based CCR5 antagonists has been designed and synthesized. Their antiviral structure-activity relationship has been extensively explored. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan M,Aquino C,Dorsey GF Jr,Ferris R,Kazmierski WM

更新日期：2009-09-01 00:00:00

abstract：:A series of cis-3,4-disubstituted piperidines was synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. Compound 24 emerged with an attractive profile, possessing excellent binding (CCR2 IC(50)=3.4 nM) and functional antagonism (calcium flux IC(50)=2.0 nM and chemotaxis IC(50)=5.4 nM). Studies to ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cherney RJ,Nelson DJ,Lo YC,Yang G,Scherle PA,Jezak H,Solomon KA,Carter PH,Decicco CP

更新日期：2008-09-15 00:00:00

abstract：:Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipide...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu P,Liu W,Ren J,Wang Y,Ning Y,Huang M,Hu X,Wei L,Ji M,Cai J

更新日期：2019-08-15 00:00:00

abstract：:Novel 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives have been prepared and their synthesis described herein. In vitro affinities for delta-, micro-, and kappa-opioid receptors are reported. Evaluation of some representative compounds from this series in the mouse neonatal ultrasonic vocalization test and the mo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trabanco AA,Aerts N,Alvarez RM,Andrés JI,Boeckx I,Fernández J,Gómez A,Janssens FE,Leenaerts JE,De Lucas AI,Matesanz E,Steckler T,Pullan S

更新日期：2007-07-15 00:00:00

abstract：:New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Michellys PY,Boehm MF,Chen JH,Grese TA,Karanewsky DS,Leibowitz MD,Liu S,Mais DA,Mapes CM,Reifel-Miller A,Ogilvie KM,Rungta D,Thompson AW,Tyhonas JS,Yumibe N,Ardecky RJ

更新日期：2003-11-17 00:00:00

abstract：:We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fuchi N,Iura Y,Kaneko H,Nitta A,Suyama K,Ueda H,Yamaguchi S,Nishimura K,Fujii S,Sekiya Y,Yamada M,Takahashi T

更新日期：2012-07-01 00:00:00

abstract：:Ubiquitin-dependent proteolysis of cellular proteins is one of the major pathways to regulate protein function posttranslationally. Here we demonstrate a potentially general method of degrading any targeted proteins by the ubiquitin-dependent proteolysis in living cells, using small-molecule proteolysis inducer (SMPI)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang D,Baek SH,Ho A,Kim K

更新日期：2004-02-09 00:00:00

abstract：:Compound DNSTT-Cu2+, a novel chelate of Cu2+ with DOTA conjugated to a fluorescent dansyl fragment, is developed for imaging cell apoptosis. Apoptotic U-87MG cells could be selectively visualized by the fluorescence of DNSTT-Cu2+ from cytoplasm of cells, confirmed by the fluorescence of apoptosis cells co-labeled with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Han J,Wang X,Yu M

更新日期：2016-11-15 00:00:00

abstract：:Inhibition of histone deacetylases class I/II enzymes is a new, promising approach for cancer therapy. In the present study, we disclose a new structural class of HDAC inhibitors with the trithiocarbonate motif. A clear structure-activity-relationship was obtained for the cap-linker motif and the putative Zn(2+) compl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dehmel F,Ciossek T,Maier T,Weinbrenner S,Schmidt B,Zoche M,Beckers T

更新日期：2007-09-01 00:00:00

abstract：:α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2-17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evalua...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang JJ,Zhang ZH,He F,Liu XW,Xu XJ,Dai LJ,Liu QM,Yuan M

更新日期：2018-02-15 00:00:00

abstract：:Casein kinase 2 catalytic subunit (CK2α) is classified into two subtypes CK2α1 and CK2α2. CK2α1 is a drug discovery target, whereas CK2α2 is an off-target of CK2α1 inhibitors. High amino acid sequence homology between these subtypes hampers efforts to produce ATP competitive inhibitors that are highly selective to CK2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tsuyuguchi M,Nakaniwa T,Hirasawa A,Nakanishi I,Kinoshita T

更新日期：2020-01-15 00:00:00

abstract：:The present studies have identified a series of diaminopyrimidines and diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes of pyrimidines and four regioisomeric classes of pyridines were synthesized and analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of differen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Denhart DJ,Purandare AV,Catt JD,King HD,Gao A,Deskus JA,Poss MA,Stark AD,Torrente JR,Johnson G,Mattson RJ

更新日期：2004-08-16 00:00:00