Abstract：
:A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4-halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic acid group. Compound 13j (UK-356,202) combines excellent potency and selectivity, and has been selected as a candidate for clinical evaluation.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Barber CG,Dickinson RP,Fish PVdoi
10.1016/j.bmcl.2004.03.094subject
Has Abstractpub_date
2004-06-21 00:00:00pages
3227-30issue
12eissn
0960-894Xissn
1464-3405pii
S0960894X04004688journal_volume
14pub_type
杂志文章abstract：:Gram positive (Bacillus cereus, B. subtilis), Gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, and Candida albicans as a representative of fungi were used for screening the in vitro antimicrobial activity of diarylamines in the 2,3,5-trimethylbenzo[b]thiophene series bearing different substituents, s...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.09.038
更新日期：2004-12-06 00:00:00
abstract：:In this study, 5-methylmellein (5-MM) loaded bovine serum albumin nanoparticles (BSA NPs) were developed using desolvation technique. The developed nanoparticles were characterized for their mean particle size, polydispersity, zeta potential, loading efficiency, X-ray diffractometry (XRD), differential scanning calori...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2017.10.064
更新日期：2017-12-01 00:00:00
abstract：:To develop more valuable and effective fungicide candidates, a novel series of 3,4-dichloroisothioxazole-based cycloalkylsulfonamides were synthesized and their structures were identified by 1H NMR, 13C NMR, MS and elemental analysis. Compound 3k was further confirmed by X-ray single crystal diffraction. The in vitro ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2019.03.047
更新日期：2019-06-01 00:00:00
abstract：:Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compo...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.06.071
更新日期：2007-09-15 00:00:00
abstract：:A novel class of 1-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-ureas are described as potent inhibitors of heparanase. Among them are 1,3-bis-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea (7a) and 1,3-bis-[4-(5,6-dimethyl-1H-benzoimidazol-2-yl)-phenyl]-urea (7d), which displayed good heparanase i...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2005.09.069
更新日期：2006-01-15 00:00:00
abstract：:A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (3...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2015.08.075
更新日期：2015-10-15 00:00:00
abstract：:Two types of P1-P3-linked macrocyclic renin inhibitors containing the hydroxyethylene isostere (HE) scaffold just outside the macrocyclic ring have been synthesized. An aromatic or aliphatic substituent (P3sp) was introduced in the macrocyclic ring aiming at the S3 subpocket (S3sp) in order to optimize the potency. A ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.10.140
更新日期：2011-01-01 00:00:00
abstract：:The synthesis and inhibitory activities of 10 potential inhibitors of Pfmrk, a Plasmodium falciparum cyclin-dependent protein kinase, are described. The most potent inhibitor is a 3-phenyl-quinolinone compound with an IC(50) value of 18 microM. It is the first compound reported to inhibit Pfmrk at the micro molar rang...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(01)00578-9
更新日期：2001-11-05 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
pub_type： 杂志文章
doi：10.1016/j.bmcl.2009.10.026
更新日期：2010-01-01 00:00:00
abstract：:A new series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structure-activity relationships (S...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(02)00746-1
更新日期：2002-12-02 00:00:00
abstract：:A series of 6-hydroxy-7-methoxy-4-chromanone- (2a-e) and chroman-2-carboxamides (3a-e) were synthesized and their antioxidant activities were evaluated. While compounds 2a-e were less active, compounds 3a-e exhibited more potent inhibition of lipid peroxidation initiated by Fe(2+) and ascorbic acid in rat brain homoge...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2005.03.118
更新日期：2005-06-02 00:00:00
abstract：:A high throughput screening campaign revealed compound 1 as a potent antagonist of the human CCK(1) receptor. Here, we report the syntheses and SAR studies of 1,5-diarylpyrazole analogs with various structural modifications of the alkane side chain of the molecule. The difference in affinity between the two enantiomer...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.09.093
更新日期：2007-12-01 00:00:00
abstract：:To design artificial restriction enzymes, synthetic catalytic centers that effectively hydrolyze linear double-stranded polydeoxyribonucleotides are needed. The Co(III) complex of cyclen (CoCyc) attached to polystyrene derivatives hydrolyzes linearized pUC18 DNA with half-lives as short as 30 min at 25 degrees C. The ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(01)00615-1
更新日期：2001-12-03 00:00:00
abstract：:Novel (E)-N(1)-(benzyl)cinnamamidines were prepared and evaluated as NR2B subtype NMDA receptor ligands. Excellent affinity was achieved by appropriate substitution of either phenyl ring. The 2-methoxybenzyl compound 1h had approximately 1,000-fold lower IC(50) in NR2B than NR2A-containing cells. Replacement of the st...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(02)01060-0
更新日期：2003-02-24 00:00:00
abstract：:The synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated to discover SAR at P(1') and P(3') positions, and most of these derivatives exhibit better in vitro antibacterial activity than existing drug...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.11.102
更新日期：2011-02-01 00:00:00
abstract：:A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar K(i)'s against SYK and potent inhibition in mast cell degranulation assays. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.09.106
更新日期：2008-12-01 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
pub_type： 杂志文章
doi：10.1016/j.bmcl.2015.01.027
更新日期：2015-03-01 00:00:00
abstract：:Hippuristanol is a natural product that has recently been shown to inhibit eukaryotic translation initiation and tumor cell proliferation. To investigate the structure and activity relationship of hippuristanol, we synthesized a series of analogs by expanding the size of its F ring and determined their effects on the ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.03.093
更新日期：2010-05-15 00:00:00
abstract：:In the search for spin labelled intercalators of general use to construct DNA-binding conjugates, 6-chloro-2-[(1-oxyl-2,2,5,5-tetramethyl- pyrrolin-3-yl)methyloxy]-9-phenoxy-acridine 5, has been prepared. This key-intermediate reacts with amines to give the corresponding labelled 9-amino substituted acridines. Compara...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(98)00089-4
更新日期：1998-03-17 00:00:00
abstract：:A novel synthetic method was developed for the synthesis of venlafaxine using inexpensive reagents. An improvement in the method, in the yield was achieved for the conversion of the venlafaxine. This is an improved version, simple and efficient method for the large-scale synthesis of venlafaxine. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.03.098
更新日期：2004-06-21 00:00:00
abstract：:The shift in apparent IC(50) that attends addition of serum proteins to in vitro cellular, enzymatic, and receptor binding assays can be used to determine the dissociation constant for compound-serum protein complexes. We show here that a simple linear relationship exists between the apparent IC(50) in the presence of...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.01.103
更新日期：2004-05-03 00:00:00
abstract：:The structure-activity relationship (SAR) of the lactone ring of himbacine derived thrombin receptor (PAR-1) antagonists (e.g., 2-5) is described. The effect of the lactone carbonyl group on binding to PAR-1 is dependent on the substitution pattern of the pyridine ring. A stereoselective intramolecular Michael additio...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2006.06.042
更新日期：2006-09-15 00:00:00
abstract：:A new series of polyhydroxylated N-benzylbenzamide derivatives containing an adamantyl moiety has been synthesized, and the depigmenting and tyrosinase inhibitory activities of the molecules were evaluated. The lipophilic character of the adamantyl moiety appeared to confer greater depigmentation power on the benzamid...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.12.144
更新日期：2012-03-01 00:00:00
abstract：:New polyphenol classes have been tested against amyloid-beta peptide aggregation. We have identified four novel polyphenols which could be efficient fibril inhibitors in Alzheimer's disease: malvidin and its glucoside and curculigosides B and D. We suggest that molecules with the particular C(6)-linkers-C(6) structure...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.11.028
更新日期：2008-01-15 00:00:00
abstract：:Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC(50) approximately 5.5...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2006.05.065
更新日期：2006-08-15 00:00:00
abstract：:A series of carboxamide derivatives of 5'-amino-2',5'-dideoxy-5-ethyluridine has been prepared as inhibitors of HSV-TK (herpes simplex virus thymidine kinase). The most potent compounds were derived from xanthene, thioxanthene and dihydroanthracene carboxylic acids. The lead compounds show subnanomolar IC(50) values a...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(01)00256-6
更新日期：2001-07-09 00:00:00
abstract：:A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC(50) values in the range of 10-150 nM and selectivity over the L-type channels up to nearly...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.01.008
更新日期：2010-02-15 00:00:00
abstract：:Inhibition of Rho kinase (ROCK) is an attractive strategy for the treatment of diseases such as hypertension, glaucoma, and cancer. Here we report chroman-3-amides as highly potent ROCK inhibitors with sufficient kinase selectivity, excellent cell activity, good microsomal stability, and desirable pharmacokinetic prop...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.10.080
更新日期：2008-12-15 00:00:00
abstract：:Two sesterterpene sulfates (1-2) were isolated from tropical sponge Hippospongia sp. and their inhibitory activities against isocitrate lyase (ICL) from the rice blast fungus Mgnaporthe grisea were evaluated. Compound 3 was obtained by hydrolysis of compound 1. Compounds 1 and 3 were found to be potent ICL inhibitors,...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.02.027
更新日期：2007-05-01 00:00:00
abstract：:VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of s...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.10.094
更新日期：2012-01-01 00:00:00
