Endothelin antagonists: search for surrogates of methylendioxyphenyl by means of a Kohonen neural network.

abstract：:We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu-catalyz...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zou Y,Albohy A,Sandbhor M,Cairo CW

更新日期：2010-12-15 00:00:00

abstract：:A series of dehydroabietic acid (DHAA, 2) derivatives was synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBKalpha channels. Systematic modifications of the peripheral functionality of ring C of DHAA showed that the introduction of a nitro or (thio)urea group in ring C gre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cui YM,Yasutomi E,Otani Y,Yoshinaga T,Ido K,Sawada K,Ohwada T

更新日期：2008-10-01 00:00:00

abstract：:A novel series of N,N'-bis[2-oxo-2H-1-benzopyran]-3-carboxamide derivatives have been synthesized and investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO). Some of the synthesized compounds show good selective inhibitory activity against the MAO-A isoform. Both the MA...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chimenti F,Secci D,Bolasco A,Chimenti P,Granese A,Carradori S,Befani O,Turini P,Alcaro S,Ortuso F

更新日期：2006-08-01 00:00:00

abstract：:A new family of photonuclease, thiadiazole-naphthalimide were synthesized and evaluated. Thiadiazole group was incorporated for the first time. These compounds intercalated into DNA efficiently and damaged DNA as low as 10 microM photochemically. Mechanism experiment showed that electron transfer and radicals were inv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Y,Xu Y,Qian X,Qu B

更新日期：2003-10-20 00:00:00

abstract：:A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high pu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dickerson TJ,Reed NN,Janda KD

更新日期：2001-06-18 00:00:00

abstract：:Three new iridoid glycosides, 6"-O-trans-caffeoylgenipin gentiobioside (1), genipin 1-O-β-D-apiofuranosyl (1→6)-β-D-glucopyranoside (2), genipin 1-O-α-D-xylopyranosyl (1→6)-β-D-glucopyranoside (3), three new monocyclic monoterpenoids, jasminoside R (4), jasminoside S (5), jasminoside T (6), together with nine known ir...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peng K,Yang L,Zhao S,Chen L,Zhao F,Qiu F

更新日期：2013-02-15 00:00:00

abstract：:In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Som...

journal_title：Bioorganic & medicinal chemistry letters

authors： Luo G,Chen L,Civiello R,Pin SS,Xu C,Kostich W,Kelley M,Conway CM,Macor JE,Dubowchik GM

更新日期：2012-04-15 00:00:00

abstract：:Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shah K,Patel D,Jadav P,Sheikh M,Sairam KV,Joharapurkar A,Jain MR,Bahekar R

更新日期：2012-09-15 00:00:00

abstract：:The 2',6'-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH(3) showed the highest affinity (K(i)mu=7.45 n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujita Y,Tsuda Y,Motoyama T,Li T,Miyazaki A,Yokoi T,Sasaki Y,Ambo A,Niizuma H,Jinsmaa Y,Bryant SD,Lazarus LH,Okada Y

更新日期：2005-02-01 00:00:00

abstract：:Heterocyclic substituted derivatives of the antipsoriatic anthralin were synthesized and evaluated in vitro for their antiproliferative action against keratinocytes and their ability to induce keratinocyte differentiation. The indole-2-carboxylic acid analogue 2e exhibited the same excellent antiproliferative activity...

journal_title：Bioorganic & medicinal chemistry letters

authors： Müller K,Reindl H,Breu K

更新日期：2001-01-08 00:00:00

abstract：:Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-l) and l-[(2-hydroxy-ethoxy)methyl]-4(1H)quinolone-3-carboxylic acids (3a-j and 3l) were synthesized and 2a-j, 2l and 3a-j, 3l were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: silylation of the desired quinol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lucero Bd,Gomes CR,Frugulhetti IC,Faro LV,Alvarenga L,de Souza MC,de Souza TM,Ferreira VF

更新日期：2006-02-15 00:00:00

abstract：:Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gomez R,Jolly S,Williams T,Tucker T,Tynebor R,Vacca J,McGaughey G,Lai MT,Felock P,Munshi V,DeStefano D,Touch S,Miller M,Yan Y,Sanchez R,Liang Y,Paton B,Wan BL,Anthony N

更新日期：2011-12-15 00:00:00

abstract：:Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, its high expression is associated with prostate cancer progression, and has been becoming an active target for imaging or therapeutic applications for prostate cancer. On the other hand, streptavidin-biotin system has been successfully employe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu T,Nedrow-Byers JR,Hopkins MR,Wu LY,Lee J,Reilly PT,Berkman CE

更新日期：2012-06-15 00:00:00

abstract：:Two series of 1-alkyl-2-aryl-4-(1-naphthoyl)pyrroles were synthesized and their affinities for the cannabinoid CB(1) and CB(2) receptors were determined. In the 2-phenyl series (5) the N-alkyl group was varied from n-propyl to n-heptyl. A second series of 23 1-pentyl-2-aryl-4-(1-naphthoyl)-pyrroles (6) was also prepar...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huffman JW,Padgett LW,Isherwood ML,Wiley JL,Martin BR

更新日期：2006-10-15 00:00:00

abstract：:The synthesis and biological evaluation of novel cycloheptaquinoline antagonists of the human H(3) receptor are described. Two series of compounds, bearing either an amino substituent or an alkyne linker at the 11-position, were investigated. Modifications of the amino substituents, optimization of chain length and th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Turner SC,Esbenshade TA,Bennani YL,Hancock AA

更新日期：2003-07-07 00:00:00

abstract：:A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide derivatives were synthesized via converting the readily available 4-hydroxy coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate followed by hydrolysis and then reacting with different substituted amines. The molecular struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rambabu D,Mulakayala N,Ismail,Kumar KR,Kumar GP,Mulakayala C,Kumar CS,Kalle AM,Rao MV,Oruganti S,Pal M

更新日期：2012-11-01 00:00:00

abstract：:Pyridone-based peptidomimetic inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with an aminomethylene ketone activating group in the P1' position are described. Several analogues with sub-nanomolar Ki's versus ICE and improved aqueous solubility are reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Semple G,Ashworth DM,Batt AR,Baxter AJ,Benzies DW,Elliot LH,Evans DM,Franklin RJ,Hudson P,Jenkins PD,Pitt GR,Rooker DP,Yamamoto S,Isomura Y

更新日期：1998-04-21 00:00:00

abstract：:Janus kinases (JAKs) including JAK1, JAK2, JAK3, and TYK2 are members of a family of intracellular nonreceptor tyrosine kinases, which have been demonstrated to be critical in the cell signaling pathway and involved in inflammatory diseases and cancer. V617F mutation in JAK2 has been implicated in polycythaemia vera (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma X,Diao Y,Ge H,Xu F,Zhu L,Zhao Z,Li H

更新日期：2020-04-15 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：:Based on the favorable antiviral profiles of 4'-substituted nucleosides, novel 1-(2'-deoxy-2'-fluoro-4'-C-ethynyl-beta-D-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC(50) values of 86 and 1.34 nM, respectively, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Q,Li Y,Song C,Qian K,Chen CH,Lee KH,Chang J

更新日期：2010-07-15 00:00:00

abstract：:A novel series of benzenesulfonamides that contain ferrocenyl or ruthenocenyl moieties were synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant carbonic anhydrase (CA) isozymes: hCA I, II and tumour-associated IX (h=human). This manuscript describes the regiosel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Salmon AJ,Williams ML,Innocenti A,Vullo D,Supuran CT,Poulsen SA

更新日期：2007-09-15 00:00:00

abstract：:A novel conjugate of Hoechst 33258, pyrene and neomycin was synthesized and examined for its binding and stabilization of A-T rich DNA duplexes using spectroscopic and viscometric techniques. The conjugate, containing three well known ligands that bind nucleic acids albeit in different binding modes, was found to sign...

journal_title：Bioorganic & medicinal chemistry letters

authors： Willis B,Arya DP

更新日期：2009-09-01 00:00:00

abstract：:A polyphemusin peptide analogue, T22 ([Tyr(5,12), Lys7]-polyphemusin II), and its shortened potent analogues, T134 (des-[Cys(8,13), Tyr(9,12)]-[D-Lys10, Pro11, L-citrulline16]-T22 without C-terminal amide) and T140 [[L-3-(2-naphthyl)alanine3]-T134], strongly inhibit the T-cell line-tropic (T-tropic) HIV-1 infection th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tamamura H,Omagari A,Oishi S,Kanamoto T,Yamamoto N,Peiper SC,Nakashima H,Otaka A,Fujii N

更新日期：2000-12-04 00:00:00

abstract：:Antagonists of the integrin receptor alpha(v)beta(3) are expected to have utility in the treatment of osteoporosis through inhibition of bone resorption. A series of potent, chain-shortened, pyrrolidinone-containing alpha(v)beta(3) receptor antagonists is described. Two sets of diasteromeric pairs of high-affinity ant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perkins JJ,Duong LT,Fernandez-Metzler C,Hartman GD,Kimmel DB,Leu CT,Lynch JJ,Prueksaritanont T,Rodan GA,Rodan SB,Duggan ME,Meissner RS

更新日期：2003-12-15 00:00:00

abstract：:A large database of chemical structures was screened for potential inhibitors of beta-secretase was carried out using in silico multi-filter techniques. Substructure screening, computer-aided ligand docking, binding free energy calculations, and partial interaction energy analyses were performed successively to identi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujimoto T,Matsushita Y,Gouda H,Yamaotsu N,Hirono S

更新日期：2008-05-01 00:00:00

abstract：:7-Methoxy-8-decynyl-benzolactam-V8 4 is synthesized using a catalytic asymmetric alkylation reaction as a key step. This compound shows potent activity to three PKC isozymes tested (Ki =45.6, 91.1, and 121.3 nM to PKCalpha, delta, and epsilon, respectively), indicating that introduction of a suitable substituent at th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma D,Zhang T,Wang G,Kozikowski AP,Lewin NE,Blumberg PM

更新日期：2001-01-22 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：:A series of 3-aryl-2-propenoates including cinnamates, (E)-methyl/ethyl 3-[2-(1,4-dimethoxy-5,8-dione)naphthalenyl]-2-propenoates (8ba, 8bb) and (E)-methyl/ethyl 3-[2-(1,4-dihydroxy-9,10-dione)anthracenyl]-2-propenoates (9aa,9ab) was synthesized and evaluated for antitumor cytotoxicity. It was found that the ortho- or...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nam NH,You YJ,Kim Y,Hong DH,Kim HM,Ahn BZ

更新日期：2001-05-07 00:00:00

abstract：:The synthesis of two separable isomeric testosterone dimers is reported. The dimers are made from testosterone in a 5 step sequence and with 36% overall yield. The key dimerization step was performed using Hoveyda-Grubb's metathesis catalysts on 7alpha-allyltestosterone with 75% yield. The synthesis led to separable i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bastien D,Leblanc V,Asselin E,Bérubé G

更新日期：2010-04-01 00:00:00

abstract：:The same two major CYP mediated metabolites of DG-051 were produced in the presence of rat, dog, monkey and human liver microsomes. Their respective structures were hypothesized based on mass spectrometry data correlated with the parent structure and confirmed by comparison with authentic synthetic samples. The number...

journal_title：Bioorganic & medicinal chemistry letters

authors： Enache LA,Zhang J,Sullins DW,Kennedy I,Onua E,Zembower DE,Muellner FW,Singh J,Kiselyov AS

更新日期：2009-11-15 00:00:00