Nonpeptide oxytocin antagonists: potent, orally bioavailable analogs of L-371,257 containing a 1-R-(pyridyl)ethyl ether terminus.

abstract：:Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. In the preceding letter, we detailed the discovery of clinical candidate PF-04693627, a potent mPGES-1 inhibitor possessing a novel benzoxazole structure. While PF-04693627 was undergoing furthe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walker DP,Arhancet GB,Lu HF,Heasley SE,Metz S,Kablaoui NM,Franco FM,Hanau CE,Scholten JA,Springer JR,Fobian YM,Carter JS,Xing L,Yang S,Shaffer AF,Jerome GM,Baratta MT,Moore WM,Vazquez ML

更新日期：2013-02-15 00:00:00

abstract：:Optically active tetrahydroisoquinoline alkaloids, (R)-(+)-higenamine (1R) and (S)-(-)-higenamine (1 S), and their optically active 1-naphthylmethyl analogues (2 and 3), were synthesized by enantioselective hydrogenation of the corresponding dihydroisoquinoline intermediates 7 as a key step. The evaluation of the plat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pyo MK,Lee DH,Kim DH,Lee JH,Moon JC,Chang KC,Yun-Choi HS

更新日期：2008-07-15 00:00:00

abstract：:A series of acetylcholine carbamoyl analogues, cyclised at the carbamate moiety or at the cationic head or at both, were tested for binding affinity at muscarinic and neuronal nicotinic receptors (nAChRs). While no muscarinic affinity was found, submicromolar Ki values, similar to that of carbachol, were measured at α...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bolchi C,Valoti E,Binda M,Fasoli F,Ferrara R,Fumagalli L,Gotti C,Matucci R,Vistoli G,Pallavicini M

更新日期：2013-12-01 00:00:00

abstract：:Selective antagonism of the platelet GPIIb/IIIa receptor represents an attractive mechanism for the prevention and treatment of a number of thrombotic disease states. The antiplatelet activity of the oral GPIIb/IIIa receptor antagonists DMP 754 and DMP 802 have been disclosed. In this paper, the synthesis and biologic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sielecki TM,Liu J,Mousa SA,Racanelli AL,Hausner EA,Wexler RR,Olson RE

更新日期：2001-08-20 00:00:00

abstract：:A reliable and efficient synthesis of a Ni(II) salen complex useful in probing nucleic acid structure is described and illustrates a general approach for constructing cis diamines suitable for assembly into N2O2 Schiff base complexes. Two equivalents of an aryllithium reacted with 1,4-dimethylpiperazine-2,3-dione to f...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shearer JM,Rokita SE

更新日期：1999-02-08 00:00:00

abstract：:In plant biology, calcium ions are involved in a variety of intriguing biological phenomena as a secondary messenger. However, most conventional calcium indicators are not applicable for plant cells because of the difficulty with their localization control in plant cells. We here introduce a method to monitor spatiote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takaoka Y,Shigenaga M,Imai M,Nukadzuka Y,Ishimaru Y,Saito K,Yokoyama R,Nishitani K,Ueda M

更新日期：2016-01-01 00:00:00

abstract：:Analogues of the tetrahydroisoquinoline family of antitumor antibiotics, 3-epi-jorumycin (3) and 3-epi-renieramycin G (4), in addition to their respective parent natural products (-)-jorumycin (1) and (-)-renieramycin G (2) were evaluated against both human colon (HCT-116) and human lung (A549) cancer cell lines. (-)-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lane JW,Estevez A,Mortara K,Callan O,Spencer JR,Williams RM

更新日期：2006-06-15 00:00:00

abstract：:Based on previous SAR studies on N-benzylindole and barbituric acid hybrid molecules, we have synthesized a series of aromatic substituted 5-((1-benzyl-1H-indol-3-yl)methylene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione analogs (3a-i) and evaluated them for their in vitro growth inhibition and cytotoxicity against ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Madadi NR,Penthala NR,Janganati V,Crooks PA

更新日期：2014-01-15 00:00:00

abstract：:Bromofluoroacetophenone derivatives which produce fluorine substituted phenyl radicals that cleave DNA upon excitation were investigated as a novel photonuclease. Pyrrolecarboxamide-conjugated bromofluoroacetophenones; 4'-bromo-2'-fluoroacetophenone and 2'-bromo-4'-fluoroacetophenone were synthesized and their DNA cle...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wender PA,Jeon R

更新日期：2003-05-19 00:00:00

abstract：:1-((Substituted)methyl)quinoxaline-2,3(1H,4H)-dione (2a-e) and 1-((substituted)acryloyl)quinoxaline-2,3(1H,4H)-dione (4a-c) were synthesized from quinoxaline-2,3(1H,4H)-dione 1 and evaluated for their antimicrobial activities. Results of the antitubercular screening against Mycobacterium tuberculosis H(37)Rv showed th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramalingam P,Ganapaty S,Rao ChB

更新日期：2010-01-01 00:00:00

abstract：:A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Berger D,Dutia M,Powell D,Wissner A,DeMorin F,Raifeld Y,Weber J,Boschelli F

更新日期：2002-10-21 00:00:00

abstract：:In our ongoing search for new anti-invasive chemotypes, we have made an excursion from previously reported potent 1,3-diarylpropenones (chalcones) to congeners bearing longer linkers between the aromatic moieties. Nine 1,ω-diarylalkenones, including curcumin and bisdemethoxycurcumin, were evaluated in the chick heart ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roman BI,De Ryck T,Verhasselt S,Bracke ME,Stevens CV

更新日期：2015-03-01 00:00:00

abstract：:A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and th...

journal_title：Bioorganic & medicinal chemistry letters

authors： McNulty J,Nair JJ,Singh M,Crankshaw DJ,Holloway AC,Bastida J

更新日期：2009-06-15 00:00:00

abstract：:New, non-natural dinucleotide 5'-monophosphates, with a surrogate isonucleoside component of l-related stereochemistry at the 'terminal' position, have been synthesized. Structures of 2a-c were confirmed by multinuclear NMR spectra ((1)H, (13)C, (31)P, COSY), UV hypochromicity and FAB HRMS data. These compounds are to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chi G,Neamati N,Nair V

更新日期：2004-10-04 00:00:00

abstract：:The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II with a topically acting antiglaucoma sulfonamide (the 2-N,N-diethylaminoethylamide of 5-(4-carboxybenzenesulfonamido-1,3,4-thiadiazole-2-sulfonamide), has been resolved at a resolution of 1.6A. This compound is a very potent inhibitor of t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abbate F,Casini A,Scozzafava A,Supuran CT

更新日期：2004-05-03 00:00:00

abstract：:Distamycin and nitrogen mustard conjugates, in which the nitrogen mustard unit was coupled to the C-terminus of the pyrrole, were synthesized. The switching of the nitrogen mustard unit from the N-terminus to the C-terminus did not compromise the compound's cytotoxicity. Compound 3, bearing three pyrrole units, was hi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Wright SC,Larrick JW

更新日期：2003-02-10 00:00:00

abstract：:In this paper, we describe the synthesis of N-(6-cyano-1,3-dimethyl-2,4-dioxo-5-substituted-1,3-dihydropyridino[2,3-d] pyrimidin-7-yl)imides 1. We will show the synthesis of 1 using both conventional heating and microwave techniques. In addition, the imide was attached to polystyrene and this immobilized imide was equ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nicewonger RB,Ditto L,Kerr D,Varady L

更新日期：2002-07-22 00:00:00

abstract：:Selective σ2 ligands continue to be an active target for medications to attenuate the effects of psychostimulants. In the course of our studies to determine the optimal substituents in the σ2-selective phenyl piperazines analogues with reduced activity at other neurotransmitter systems, we discovered that 1-(3-chlorop...

journal_title：Bioorganic & medicinal chemistry letters

authors： Motel WC,Healy JR,Viard E,Pouw B,Martin K,Matsumoto RR,Coop A

更新日期：2013-12-15 00:00:00

abstract：:Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a defect in pancreatic beta-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARalpha, PPARgamma and PPARbeta/(d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Parmenon C,Guillard J,Caignard DH,Hennuyer N,Staels B,Audinot-Bouchez V,Boutin JA,Dacquet C,Ktorza A,Viaud-Massuard MC

更新日期：2008-03-01 00:00:00

abstract：:Nanometer-scale architectures assembled on cell surface receptors from smaller macromolecular constituents generated a large amplification of fluorescence. A targeted dendrimer was synthesized from a cystamine-core G4 PAMAM dendrimer, and contained an anti-BrE3 monoclonal antibody as the targeting group, several fluor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Isaacman S,Buckley M,Wang X,Wang EY,Liebes L,Canary JW

更新日期：2014-03-01 00:00:00

abstract：:In search of effective antidiabetic agents having therapeutic effect by inhibiting α-glucosidase and preventive effect by scavenging free radicals, Horsfieldia macrobotrys showed promising bioactivity required for the proposed criteria. Bioassay-guided isolation of the stem bark extract resulted in two new arylalkanon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramadhan R,Phuwapraisirisan P

更新日期：2015-10-15 00:00:00

abstract：:A novel solid-phase synthesis of 5'-radiolabeled oligonucleotides is described. The labeling reaction is carried out by the phosphoramidite method with the aid of [4,6-di-14C]-5'-dimethoxytritylthymidine building block 1. The feasibility of the method is demonstrated by preparation of 3'-phosphorylated dodecathymidyla...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guzaev A,Boyode B,Balow G,Tivel KL,Manoharan M

更新日期：1998-05-05 00:00:00

abstract：:The synthesis and antibacterial activity of 2,5-dihydropyrrole formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated, and some of these derivatives showed better in vitro antibacterial activity than existing drugs, including penicillin, ciprofloxacin, vancomycin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi W,Duan Y,Qian Y,Li M,Yang L,Hu W

更新日期：2010-06-15 00:00:00

abstract：:New N-(1,2-diphenylethyl)piperazines 6 are disclosed as dual serotonin and noradrenaline reuptake inhibitors (SNRI) which may have potential in treating stress urinary incontinence (SUI). In this Letter, we present new data for SNRI PF-526014 (4) including performance in a canine in vivo model of SUI, cardiovascular a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fray MJ,Fish PV,Allan GA,Bish G,Clarke N,Eccles R,Harrison AC,Le Net JL,Phillips SC,Regan N,Sobry C,Stobie A,Wakenhut F,Westbrook D,Westbrook SL,Whitlock GA

更新日期：2010-06-15 00:00:00

abstract：:The first non-substrate like inhibitors of human cytosolic phosphoenolpyruvate carboxykinase (PEPCK) competitive with GTP are reported. An effort to discover orally active compounds that improve glucose homeostasis in Type 2 diabetics by reversibly inhibiting PEPCK led to the discovery of 1-allyl-3-butyl-8-methylxanth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Foley LH,Wang P,Dunten P,Ramsey G,Gubler ML,Wertheimer SJ

更新日期：2003-10-20 00:00:00

abstract：:A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin CH,Krishnaiah M,Sreenu D,Subrahmanyam VB,Rao KS,Mohan AV,Park CY,Son JY,Sheen YY,Kim DK

更新日期：2011-10-15 00:00:00

abstract：:Inhibition of 11beta-HSD1 has demonstrated potential in the treatment of various components of metabolic syndrome. We wish to report herein the discovery of novel azabicyclic sulfonamide based 11beta-HSD1 inhibitors. Highly potent compounds exhibiting inhibitory activities at both human and mouse 11beta-HSD1 were iden...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shah U,Boyle CD,Chackalamannil S,Baker H,Kowalski T,Lee J,Terracina G,Zhang L

更新日期：2010-03-01 00:00:00

abstract：:Here we report identification of new lead compounds based on quinoline and indenoquinolines with variable side chains as antiprotozoal agents. Quinolines 32, 36 and 37 (Table 1) and indenoquinoline derivatives 14 and 23 (Table 2) inhibit the in vitro growth of the Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma bru...

journal_title：Bioorganic & medicinal chemistry letters

authors： Upadhayaya RS,Dixit SS,Földesi A,Chattopadhyaya J

更新日期：2013-05-01 00:00:00

abstract：:In a continuing study of hybrid compounds containing the alpha-bromoacryloyl moiety as potential anticancer drugs, we synthesized a novel series of hybrids 4a-h, in which this moiety was linked to a 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (4b, 4c, 4e and 4g) demonstrated pronounced, subm...

journal_title：Bioorganic & medicinal chemistry letters

authors： Romagnoli R,Baraldi PG,Cruz-Lopez O,Lopez Cara C,Carrion MD,Balzarini J,Hamel E,Basso G,Bortolozzi R,Viola G

更新日期：2010-05-01 00:00:00

abstract：:Bruton's Tyrosine Kinase (BTK) is one of the crucial kinases for the B cell maturation and mast cell activation, and specific inhibitors of BTK are considered to be attractive targets in drug discovery research. In this Letter, we have designed and synthesized a new fluorescent probe for TR-FRET-based high-throughput ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Asami T,Kawahata W,Sawa M

更新日期：2015-01-01 00:00:00