P2-P3 conformationally constrained ketoamide-based inhibitors of cathepsin K.

abstract：:We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fox BM,Natero R,Richard K,Connors R,Roveto PM,Beckmann H,Haller K,Golde J,Xiao SH,Kayser F

更新日期：2011-04-15 00:00:00

abstract：:A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we rep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang W,Holyoke CW Jr,Barry J,Leighty RM,Cordova D,Vincent DR,Hughes KA,Tong MT,McCann SF,Xu M,Briddell TA,Pahutski TF,Lahm GP

更新日期：2016-11-15 00:00:00

abstract：:Vancomycin resistance is currently a major healthcare problem. The development of a catalytic monoclonal antibody (mAb) that hydrolyzes the D-Ala-D-Lac depsipeptide provides a potentially novel antibiotic strategy. A phosphonate hapten design was used to program antibody catalysis. The characteristics of the hapten we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Isomura S,Ashley JA,Wirsching P,Janda KD

更新日期：2002-03-25 00:00:00

abstract：:Catalytic disulfenylation reaction of alkenes by common Lewis acids has been investigated in detail. While reactions by FeCl(3) were feasible with cycloalkenes and other simple alkenes, much faster and excellent conversions were possible by AlCl(3) even with the substrates less reactive toward FeCl(3). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamagiwa N,Suto Y,Torisawa Y

更新日期：2007-11-15 00:00:00

abstract：:The relaxin family peptide receptors have been implicated in numerous physiological processes including energy homeostasis, cardiac function, wound healing, and reproductive function. Two family members, RXFP3 and RXFP4, are class A GPCRs with endogenous peptide ligands (relaxin-3 and insulin-like peptide 5 (INSL5), r...

journal_title：Bioorganic & medicinal chemistry letters

authors： DeChristopher B,Park SH,Vong L,Bamford D,Cho HH,Duvadie R,Fedolak A,Hogan C,Honda T,Pandey P,Rozhitskaya O,Su L,Tomlinson E,Wallace I

更新日期：2019-04-15 00:00:00

abstract：:Hsp90 represents a promising target for the development of both anti-cancer and neuroprotective agents. Structure-activity relationship studies on novobiocin and novobiocin analogues, led to the development of KU-32 and recently, KU-596, as lead compounds for the potential treatment of neurodegenerative diseases. Simi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao H,Anyika M,Girgis A,Blagg BS

更新日期：2014-08-01 00:00:00

abstract：:Chemical modifications are essential to improve metabolic stability and pharmacokinetic properties of siRNA to enable their systemic delivery. We investigated the effect of combing the phosphorothioate (PS) modification with metabolically stable phosphate analog (E)-5'-vinylphosphonate and GalNAc cluster conjugation o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prakash TP,Kinberger GA,Murray HM,Chappell A,Riney S,Graham MJ,Lima WF,Swayze EE,Seth PP

更新日期：2016-06-15 00:00:00

abstract：:A series of β-boswellic acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar A,Qayum A,Sharma PR,Singh SK,Shah BA

更新日期：2016-01-01 00:00:00

abstract：:Novel L- and D-configuration dioxolane 5-azacytosine and 6-azathymine nucleosides have been synthesized and evaluated for biological activity. (-)-(2S,4S)-1-[2-(Hydroxymethyl)-1,3-dioxolan-4-yl]-5-azacytosine (6) showed significant activity against HBV, whereas the D-configuration analogue (14) has been found to exhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Luo MZ,Liu MC,Mozdziesz DE,Lin TS,Dutschman GE,Gullen EA,Cheng YC,Sartorelli AC

更新日期：2000-09-18 00:00:00

abstract：:Aiming to develop selective anticancer drugs, we designed and synthesized three disulfides bearing a folic acid moiety as candidate folate receptor (FR)-targeted prodrugs of thiolate histone deacetylase inhibitors. Among them, compound 1 displayed growth-inhibitory activity toward folate receptor-positive MCF-7 breast...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suzuki T,Hisakawa S,Itoh Y,Suzuki N,Takahashi K,Kawahata M,Yamaguchi K,Nakagawa H,Miyata N

更新日期：2007-08-01 00:00:00

abstract：:Pyrido[1,2-a]indole-1,4-diones and benzo[f]pyrido[1,2-a]indole-6,11-diones were synthesized and tested for in vitro antifungal activity against two pathogenic strains of fungi. Among them tested, many compounds showed good antifungal activity. The results suggest that pyrido[1,2-a]indole-1,4-diones and benzo[f]pyrido[...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ryu CK,Yoon JH,Song AL,Im HA,Kim JY,Kim A

更新日期：2012-01-01 00:00:00

abstract：:SB-216763 is a novel, potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor with an IC(50) value of 34 nM. [(11)C]SB-216763 (3-(2,4-dichlorophenyl)-4-(1-[(11)C]methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of GSK-3, was first designed and synthesized in 20-30% decay cor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Hutchins GD,Zheng QH

更新日期：2011-01-01 00:00:00

abstract：:A series of 2-phenylbenzofuran derivatives with a diphenylmethylcarbamoyl group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. They had inhibitory activities against both enzymes and the 6-carbamoyl derivativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishibashi K,Nakajima K,Sugioka Y,Sugiyama M,Hamada T,Horikoshi H,Nishi T

更新日期：1998-03-17 00:00:00

abstract：:Vismodegib is the first FDA approved cancer therapy based on inhibition of aberrant hedgehog signaling. Like most cancer therapies, vismodegib suffered from resistance, even during clinical development. Numerous reports demonstrated that simultaneous blockage of hedgehog and PI3K/AKT/mTOR pathways resulted in signific...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang Z,Ma H,Sun Z,Luo L,Tian S,Zheng J,Zhang X

更新日期：2015-09-01 00:00:00

abstract：:A range of 3,4-alkylated five-membered ring derivatives of gabapentin were synthesised. One compound (21) had an excellent level of potency against alpha(2)delta and was profiled in in vivo models of pain and anxiety. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blakemore DC,Bryans JS,Carnell P,Field MJ,Kinsella N,Kinsora JK,Meltzer LT,Osborne SA,Thompson LR,Williams SC

更新日期：2010-01-01 00:00:00

abstract：:The affinity of a series of 2', 3'- and 5-modified thymidine analogues for Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) was evaluated. The affinities of several non-phosphorylated analogues are in the same order of magnitude as those of their phosphorylated congeners. In view of drug delivery pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vanheusden V,Van Rompaey P,Munier-Lehmann H,Pochet S,Herdewijn P,Van Calenbergh S

更新日期：2003-09-15 00:00:00

abstract：:A series of novel nikkomycin analogue inhibitors of the chitin synthase of fungal cell wall was synthesized and evaluated for their inhibitory activities. Among them, the compound having a phenanthrene group at the terminal amino acid was found to possess strong anti-chitin synthase activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Obi K,Uda J,Iwase K,Sugimoto O,Ebisu H,Matsuda A

更新日期：2000-07-03 00:00:00

abstract：:Several recent reports have highlighted the feasibility of the use of penfluridol, a well-known antipsychotic agent, as a chemotherapeutic agent. In vivo experiments have confirmed the cytotoxic activity of penfluridol in triple-negative breast cancer model, lung cancer model, and further studies have been proposed to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ashraf-Uz-Zaman M,Sajib MS,Cucullo L,Mikelis CM,German NA

更新日期：2018-12-15 00:00:00

abstract：:Preclinical studies suggest that compounds with dual norepinephrine reuptake inhibitor (NRI) and 5-HT(1A) partial agonist properties may provide an important new therapeutic approach to ADHD, depression, and anxiety. Reported herein is the discovery of a novel chemical series with a favorable NRI and 5-HT(1A) partial ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dounay AB,Barta NS,Campbell BM,Coleman C,Collantes EM,Denny L,Dutta S,Gray DL,Hou D,Iyer R,Maiti SN,Ortwine DF,Probert A,Stratman NC,Subedi R,Whisman T,Xu W,Zoski K

更新日期：2010-02-01 00:00:00

abstract：:The reduced activation of PPARs has a positive impact on cancer cell growth and viability in multiple preclinical tumor models, suggesting a new therapeutic potential for PPAR antagonists. In the present study, the benzothiazole amides 2a-g were synthesized and their activities on PPARs were investigated. Transactivat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ammazzalorso A,De Lellis L,Florio R,Laghezza A,De Filippis B,Fantacuzzi M,Giampietro L,Maccallini C,Tortorella P,Veschi S,Loiodice F,Cama A,Amoroso R

更新日期：2019-08-15 00:00:00

abstract：:New bis-pyridinium oxime reactivators connected with CH2O(CH2)n OCH2 linkers between two pyridinium rings were designed and synthesized, and their reactivation potency was evaluated for AChE inhibited by organophosphorus VX agent. Among the prepared compounds, 1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichlor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Oh KA,Yang GY,Jun D,Kuca K,Jung YS

更新日期：2006-09-15 00:00:00

abstract：:A series of prenylflavonoids with multiple hydroxyl groups were synthesized and evaluated for their vasorelaxant activities against rat aorta rings pre-contracted by phenylephrine (PE), as well as their neuroprotective effects against OGD induced PC12 cell injury. The results indicated that the prenyl group at A-ring ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dong X,Qi L,Jiang C,Chen J,Wei E,Hu Y

更新日期：2009-06-15 00:00:00

abstract：:The title compound (4A) was synthesized and tested as a mechanism-based inactivator of the sterol methyl transferase (SMT) enzyme from Prototheca wickerhamii. Using cycloartenol as substrate, 4A was found to exhibit time-dependent inactivation kinetics, generating a Ki value of 30 microM and Kinact value of 0.30 min-1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nes WD,He L,Mangla AT

更新日期：1998-12-15 00:00:00

abstract：:The design and syntheses of new fluoroquinolone antibacterial agents having pyrrolidine ring at C-7 position are described. The pyrrolidine ring is optically active and possesses methyloxime functional group. Two of them have excellent in vitro antibacterial activities and pharmacokinetic profiles. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi DR,Shin JH,Yang J,Yoon SH,Jung YH

更新日期：2004-03-08 00:00:00

abstract：:Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA performs the fundamental biological functions such as regulation and protection of chromosome ends. This digest highlights the human telomere RNA G-quadruplex structures, telomere RNA functions, G-quadruplex-binding small molecules, and futu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y

更新日期：2018-08-15 00:00:00

abstract：:Several substituted quinolin-4-amines and heteroaromatic analogs were synthesized and evaluated for interaction with triplex polydA.2polydT and duplex polydA.polydT by using UV-thermal melting experiments. Excellent triple-helix DNA ligands with high affinity toward T.A.T triplets and triple/duplex selectivity were de...

journal_title：Bioorganic & medicinal chemistry letters

authors： Strekowski L,Hojjat M,Wolinska E,Parker AN,Paliakov E,Gorecki T,Tanious FA,Wilson WD

更新日期：2005-02-15 00:00:00

abstract：:4-Thiazolidinone derivatives were synthesized using T3P®-DMSO media as a cyclodehydrating agent. All the molecules were tested for their cytotoxicity against leukemic cell lines. The compound 3-(4-bromophenyl)-2-(4-(dimethylamino)phenyl)thiazolidin-4-one (4e) with electron donating substituent at para position of phen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharath Kumar KS,Hanumappa A,Vetrivel M,Hegde M,Girish YR,Byregowda TR,Rao S,Raghavan SC,Rangappa KS

更新日期：2015-09-01 00:00:00

abstract：:Structure-activity studies on the oxytocin antagonist 1 (L-371,257; Ki = 9.3 nM) have led to the identification of a related series of compounds containing an ortho-trifluoroethoxyphenylacetyl core which are orally bioavailable and have significantly improved potency in vitro and in vivo, e.g., compound 8 (L-374,943; ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Williams PD,Bock MG,Evans BE,Freidinger RM,Gallicchio SN,Guidotti MT,Jacobson MA,Kuo MS,Levy MR,Lis EV,Michelson SR,Pawluczyk JM,Perlow DS,Pettibone DJ,Quigley AG,Reiss DR,Salvatore C,Stauffer KJ,Woyden CJ

更新日期：1999-05-03 00:00:00

abstract：:The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Raubo P,Andrews DM,McKelvie JC,Robb GR,Smith JM,Swarbrick ME,Waring MJ

更新日期：2015-08-15 00:00:00

abstract：:AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin EC,Hu Y,Amantea CM,Pham LM,Cajica J,Okerberg E,Brown HE,Fraser A,Du L,Kohno Y,Ishiyama J,Kozarich JW,Shreder KR

更新日期：2012-01-15 00:00:00