Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.

abstract：:Prothrombin is a vitamin K-dependent serine protease and plays pivotal roles in both procoagulant and anticoagulant pathway of hemostasis. In this study, prothrombin purified from porcine plasma was modified through PEGylation at N-terminal residue using 40 kDa PEG-phenyl-isothiocyanate (PIT-PEG40K). The monoPEGylated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou JG,Chen YM

更新日期：2011-06-01 00:00:00

abstract：:Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nabika R,Suyama TL,Hau AM,Misu R,Ohno H,Ishmael JE,McPhail KL,Oishi S,Fujii N

更新日期：2015-01-15 00:00:00

abstract：:Synthesis and biological evaluation of novel and potent cyclohexylamine-based histamine H3 receptor inverse agonists are described. Compounds in this newly identified series exhibited subnanomolar binding affinities for human receptor and no significant interaction with hERG channel. One derivative (10t) demonstrated ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Labeeuw O,Levoin N,Poupardin-Olivier O,Calmels T,Ligneau X,Berrebi-Bertrand I,Robert P,Lecomte JM,Schwartz JC,Capet M

更新日期：2011-09-15 00:00:00

abstract：:The first example of dual inhibitors for matrix metalloproteinase (MMP) and cathepsin is described. An appropriate alignment of peptide-parts and two different specific functional groups in one molecule led to the discovery of a potent dual inhibitor (3a). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamamoto M,Ikeda S,Kondo H,Inoue S

更新日期：2002-02-11 00:00:00

abstract：:Naturally occurring flavonoids co-exist as glycoside conjugates, which dominate aglycones in their content. To unveil the structure-activity relationship of a naturally occurring flavonoid, we investigated the effects of the glycosylation of naringenin on the inhibition of enzyme systems related to diabetes (protein t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jung HA,Paudel P,Seong SH,Min BS,Choi JS

更新日期：2017-06-01 00:00:00

abstract：:We previously identified the methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its obligate transcriptional coactivators and prevent thyroid hormone signaling. As part of our lead optimization work we demonstrated that sulfonylnitrophenylthiazoles (SNPTs), which repla...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hwang JY,Attia RR,Carrillo AK,Connelly MC,Guy RK

更新日期：2013-03-15 00:00:00

abstract：:This Letter details our ongoing efforts to develop selective positive allosteric modulators (PAMs) of the mGlu2/4 heterodimeric receptor that exists in the CNS and may represent a novel drug target to modulate the glutamatergic system. As multiple hit-to-lead campaigns from HTS hits failed to produce selective small m...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fulton MG,Loch MT,Rodriguez AL,Lin X,Javitch JA,Conn PJ,Niswender CM,Lindsley CW

更新日期：2020-07-01 00:00:00

abstract：:Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), which are activated by recognizing pathogen-associated molecular patterns (PAMPs). The activation of TLRs initiates innate immune responses and subsequently leads to adaptive immune responses. TLR agonists are effective immuomodulators in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baba A,Wakao M,Shinchi H,Chan M,Hayashi T,Yao S,Cottam HB,Carson DA,Suda Y

更新日期：2020-02-01 00:00:00

abstract：:The selective serotonin reuptake inhibitors (SSRI) fluoxetine, sertraline and citalopram have been investigated for their ability to activate two carbonic anhydrase (CA) isozymes, hCA I and hCA II, in parallel with two standard activators for which the X-ray structure (in complex with isozyme II) has been resolved: hi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Casini A,Caccia S,Scozzafava A,Supuran CT

更新日期：2003-08-18 00:00:00

abstract：:The synthesis of [1-[(5-hydroxy-4-(phenylmethyl)-3-oxazolidinyl)carbonyl]-2-ethylpropy lcarbamic acid phenylmethyl ester (2; MDL 104,903), a potent inhibitor of calpain, is described. Synthesis of related compounds, which offer insights into the mechanism of action for 2, are also described, as is an O-acetyl prodrug ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peet NP,Kim HO,Marquart AL,Angelastro MR,Nieduzak TR,White JN,Friedrich D,Flynn GA,Webster ME,Vaz RJ,Linnik MD,Koehl JR,Mehdi S,Bey P,Emary B,Hwang KK

更新日期：1999-08-16 00:00:00

abstract：:Herein we report the synthesis of a series of bicyclo[3.2.1]octanes and their binding characteristics at the dopamine and serotonin transporters. The data confirm that a heteroatom at position 8 of the tropane nucleus is not a prerequisite for binding since the bicyclo[3.2.1]octanes prove potent inhibitors of both tra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meltzer PC,Blundell P,Chen Z,Yong YF,Madras BK

更新日期：1999-03-22 00:00:00

abstract：:Analogues of the benzazepine dopamine D1 receptor antagonist SCH-23390 incorporating the cyclo-pentadienyltricarbonyl-rhenium (CPTR) moiety were synthesized and evaluated pharmacologically. The CPTR derivatives retained affinity (0.3-2.9 nM) and D1 selectivity of the parent compound, supporting their use as neuropharm...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tamagnan G,Baldwin RM,Kula NS,Baldessarini RJ,Innis RB

更新日期：2000-05-15 00:00:00

abstract：:The structure-activity relationships of 5,6-positions of aminopyridine carboxamide-based c-Jun N-terminal Kinase (JNK) inhibitors were explored to expand interaction with the kinase specificity and ribose-binding pockets. The syntheses of analogues and the impact of structural modification on in vitro potency and cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu G,Zhao H,Liu B,Xin Z,Liu M,Kosogof C,Szczepankiewicz BG,Wang S,Clampit JE,Gum RJ,Haasch DL,Trevillyan JM,Sham HL

更新日期：2006-11-15 00:00:00

abstract：:We report herein the synthesis and stereochemical structure-activity relationships of novel morpholine analogues 12 and 13 with regards to NK1, NK2 and NK3 tachykinin receptor binding affinity. An essential requirement for more potent binding affinities was controlled by absolute configuration. (S,R)-12 and (S,R)-13 e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishi T,Ishibashi K,Takemoto T,Nakajima K,Fukazawa T,Iio Y,Itoh K,Mukaiyama O,Yamaguchi T

更新日期：2000-08-07 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：:Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between...

journal_title：Bioorganic & medicinal chemistry letters

authors： Edink E,Akdemir A,Jansen C,van Elk R,Zuiderveld O,de Kanter FJ,van Muijlwijk-Koezen JE,Smit AB,Leurs R,de Esch IJ

更新日期：2012-02-01 00:00:00

abstract：:A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 microM as an inhibi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cushman M,Insaf S,Ruell JA,Schaeffer CA,Rice WG

更新日期：1998-04-07 00:00:00

abstract：:In an effort to better understand the conformational preferences that inform the biological activity of naltrexone and related naltrexol derivatives, a new synthesis of the restricted analog 3-OBn-6β,14-epoxymorphinan 4 is described. 4 was synthesized starting from naltrexone in 50% overall yield, proceeding through t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Martin DJ,FitzMorris PE,Li B,Ayestas M,Sally EJ,Dersch CM,Rothman RB,Deveau AM

更新日期：2012-11-15 00:00:00

abstract：:From a readily available 5-C-Me ribofuranoside, we have realized a reliable route to valuable 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives at gram scale with confirmed stereochemistry. These adenosine derivatives are useful starting materials for the preparation of 5'-deoxy-5'-amino-5'-C-methyl adenosine deriva...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu T,Xie W,Li C,Ren H,Mao Y,Chen G,Cheng M,Zhao D,Shen J,Li J,Zhou Y,Xiong B,Chen YL

更新日期：2017-11-15 00:00:00

abstract：:Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester as a potent and selective mGluR1 non-competitive antagonist, the use of a doubly (13)C-labeled analogue to identify, and consequently prevent, metabolically labile positions is reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Micheli F,Cavanni P,Di Fabio R,Donati D,Hamdan M,Provera S,Tranquillini ME,Vitulli G

更新日期：2007-02-15 00:00:00

abstract：:In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the treatment of acute respiratory failure, we rationally designed and synthesized a series of peptide-based carboxylic acid-containing transition-state inhibitors. The presence of valyl moiety is found to be essential for potent in vitro in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sato F,Inoue Y,Omodani T,Imano K,Okazaki H,Takemura T,Komiya M

更新日期：2002-02-25 00:00:00

abstract：:Novel dihydroalkoxybenzyloxopyrimidine (S-DABO) derivatives targeting the non-nucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been synthesized using a novel computer model for the NNI binding pocket and tested for their RT inhibitory activity in cell-free a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vig R,Mao C,Venkatachalam TK,Tuel-Ahlgren L,Sudbeck EA,Uckun FM

更新日期：1998-06-16 00:00:00

abstract：:A simple and versatile method for preparation of (D)-Phe-Pro peptidomimetic bicyclic thiazolidine lactams is presented. These bicyclic lactams have chemical diversity alpha to the lactam carbonyl and, when linked to electrophilic arginines, provide potent thrombin inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bachand B,DiMaio J,Siddiqui MA

更新日期：1999-04-05 00:00:00

abstract：:We report the results of our study into a series of simple phenyl and alkyl sulfamates and alkyl methanesulfonates as potential inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that the substituted phenyl sulfamates are good irreversible inhibitors; the alkyl sulfamate compounds were foun...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahmed S,James K,Owen CP,Patel CK,Sampson L

更新日期：2002-05-06 00:00:00

abstract：:Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy for improving stability both in vitro and in vivo. This led to t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morrison AJ,Adam JM,Baker JA,Campbell RA,Clark JK,Cottney JE,Deehan M,Easson AM,Fields R,Francis S,Jeremiah F,Keddie N,Kiyoi T,McArthur DR,Meyer K,Ratcliffe PD,Schulz J,Wishart G,Yoshiizumi K

更新日期：2011-01-01 00:00:00

abstract：:Different types of heterogenized catalysts were involved in asymmetric reactions. Hydrogen transfer reduction was performed with amino alcohols derived from poly((S)-(GMA-co-EGDMA or DVB)) and hydrogenation with BINAP grafted onto PEG or copolymerized with isocyanates as ligands. Attempts of catalysts recycling are re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Saluzzo C,Lamouille T,Hérault D,Lemaire M

更新日期：2002-07-22 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：:Utilizing a combination of high-throughput and multi-step synthesis, SAR in a novel series of M(1) acetylcholine receptor antagonists was rapidly established. The efforts led to the discovery the highly potent M(1) antagonists 6 (VU0431263), and 8f (VU0433670). Functional Schild analysis and radioligand displacement e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Poslusney MS,Sevel C,Utley TJ,Bridges TM,Morrison RD,Kett NR,Sheffler DJ,Niswender CM,Daniels JS,Conn PJ,Lindsley CW,Wood MR

更新日期：2012-11-15 00:00:00

abstract：:Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barnes-Seeman D,Boiselle C,Capacci-Daniel C,Chopra R,Hoffmaster K,Jones CT,Kato M,Lin K,Ma S,Pan G,Shu L,Wang J,Whiteman L,Xu M,Zheng R,Fu J

更新日期：2014-08-15 00:00:00

abstract：:(-)-Renieramycin G and fifteen C-22 analogs were prepared employing l-tyrosine as the chiral starting material. These analogs, along with (-)-renieramycin G itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, A2780, MCF-7, A549, BGC-823, Ketr3, KB, Hela cells. The IC(50) values of most of these a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu W,Dong W,Liao X,Yan Z,Guan B,Wang N,Liu Z

更新日期：2011-03-01 00:00:00