Design, synthesis and SAR of substituted indoles as selective TrkA inhibitors.

abstract：:Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide ...

journal_title：Bioorganic & medicinal chemistry letters

authors： El-Ayache NC,Li SH,Warnock M,Lawrence DA,Emal CD

更新日期：2010-02-01 00:00:00

abstract：:In the screening search for Hepatitis B virus inhibitory agents from medicinal plants, the ethanol extract of Piper longum Linn. was found to possess superior anti-HBV activity in vitro. Bioassay-guided fractionation coupled with repeated purification resulted in the isolation of four new compounds, involving two new ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang ZY,Liu WF,Zhang XM,Luo J,Ma YB,Chen JJ

更新日期：2013-04-01 00:00:00

abstract：:The addition of exogenous ent-cholesterol suppressed the antifungal activity of the amphotericin B when added to cultures of Candida albicans, but to a lesser extent than natural cholesterol. There were no detectable differences between added 2a or 2b on the antifungal activities of jaspamide or bengazole A, two unrel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Richter RK,Mickus DE,Rychnovsky SD,Molinski TF

更新日期：2004-01-05 00:00:00

abstract：:Nobiletin, a major component of polymethoxyflavones in citrus fruits, has a broad spectrum of health beneficial properties including anti-inflammatory and anti-carcinogenic activities. The metabolite identification of nobiletin in mouse urine has concluded that it undergoes mono-demethylation (3'- and 4'-demethylnobil...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li S,Sang S,Pan MH,Lai CS,Lo CY,Yang CS,Ho CT

更新日期：2007-09-15 00:00:00

abstract：:Depression is a serious illness that affects millions of patients. Current treatments are associated with a number of undesirable side effects. Neurokinin 1 receptor (NK1R) antagonists have recently been shown to potentiate the antidepressant effects of serotonin-selective reuptake inhibitors (SSRIs) in a number of an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Degnan AP,Tora GO,Han Y,Rajamani R,Bertekap R,Krause R,Davis CD,Hu J,Morgan D,Taylor SJ,Krause K,Li YW,Mattson G,Cunningham MA,Taber MT,Lodge NJ,Bronson JJ,Gillman KW,Macor JE

更新日期：2015-08-01 00:00:00

abstract：:Hitherto unknown protective effect of N,α-L-rhamnopyranosyl vincosamide (VR), isolated from Moringa oleifera leaves in isoproterenol (ISO)-induced cardiac toxicity was evaluated in rats. Oral administration of VR at 40 mg/kg for 7 days markedly reduced the ISO-induced increase in the levels of serum cardiac markers su...

journal_title：Bioorganic & medicinal chemistry letters

authors： Panda S,Kar A,Sharma P,Sharma A

更新日期：2013-02-15 00:00:00

abstract：:Here we report a number of novel JS-K structural analogues with sub-micromolar anti-proliferative activities against human leukemia cell lines HL-60 and U937; JS-K is the anti-cancer lead compound O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate. The ability of these compounds to g...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nandurdikar RS,Maciag AE,Citro ML,Shami PJ,Keefer LK,Saavedra JE,Chakrapani H

更新日期：2009-05-15 00:00:00

abstract：:The mechanism of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) to scavenge DPPH radical is clarified by density functional theory (DFT) calculations. It is revealed that H-atom-abstraction rather than electron-transfer reaction is involved in the radical-scavenging process of edaravone, and H-atom at position 4 is r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang LF,Zhang HY

更新日期：2003-11-03 00:00:00

abstract：:A variety of new prodrugs of 2'-methyl cytidine based on acyloxy ethylamino phosphoramidates have been synthesized and tested in vitro and in vivo for their biological activity. Compared with the parent drug a 10- to 20-fold increase in formation of nucleotide triphosphate in rat and human hepatocytes could be achieve...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donghi M,Attenni B,Gardelli C,Marco AD,Fiore F,Giuliano C,Laufer R,Leone JF,Pucci V,Rowley M,Narjes F

更新日期：2009-03-01 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：:Developing targeted validation probes that can interrogate biology is of interest for both chemists and biologists. The synthesis of suitable compounds provides a means for avoiding the costly labeling of cells with specific antibodies and the bias associated with the interpretation of biological validation experiment...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ho LA,Thomas E,McLaughlin RA,Flematti GR,Fuller RO

更新日期：2016-10-15 00:00:00

abstract：:On the search for anti-cancer compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the rhizomes of Acorus gramineus resulted in the isolation and identification of thirteen phenolic derivatives (1-13) including two new 8-O-4'-neolignans, n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim KH,Moon E,Kim HK,Oh JY,Kim SY,Choi SU,Lee KR

更新日期：2012-10-01 00:00:00

abstract：:A novel class of 2,3-tri- and tetrasubstituted γ-butyrolactones analogous to paraconic acids has been synthesized in one step using a straightforward three-component reaction among aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of representative compounds has been evaluated a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Le Floch C,Le Gall E,Léonel E,Martens T,Cresteil T

更新日期：2011-12-01 00:00:00

abstract：:GTP cyclohydrolase (GCYH-I) is an enzyme in the folate biosynthesis pathway that has not been previously exploited as an antibiotic target, although several pathogens including N. gonorrhoeae use a form of the enzyme GCYH-IB that is structurally distinct from the human homologue GCYH-IA. A comparison of the crystal st...

journal_title：Bioorganic & medicinal chemistry letters

authors： Samaan GN,Paranagama N,Haque A,Hecht DA,Swairjo MA,Purse BW

更新日期：2020-01-15 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：:The synthesis and biological activities of a series of new 1beta-methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of pyrrolidine were described. Among these compounds, 1,2,3-thiadiazole derivative 1h showed the most potent antibacterial activity and advanced pharmacokinetics in comparison ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shin KJ,Koo KD,Yoo KH,Kang YK,Park SW,Kim DJ

更新日期：2001-09-03 00:00:00

abstract：:A urokinase targeting conjugate of 2'-deoxy-5-fluorouridine (5-FUdr) was synthesized and tested for tumor-cell selective cytotoxicity in vitro. The 5-FUdr prodrug 2'-deoxy-5-fluoro-3'-O-(3-carboxypropanoyl)uridine (5-FUdrsuccOH) containing an ester-labile succinate linker was attached to the specific urokinase inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vine KL,Locke JM,Bremner JB,Pyne SG,Ranson M

更新日期：2010-05-01 00:00:00

abstract：:A novel series of aminopyrimidine IKK2 inhibitors have been developed which show excellent in vitro inhibition of this enzyme and good selectivity over the IKK1 isoform. The relative potency and selectivity of these compounds has been rationalized using QSAR and structure-based modelling. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bingham AH,Davenport RJ,Gowers L,Knight RL,Lowe C,Owen DA,Parry DM,Pitt WR

更新日期：2004-01-19 00:00:00

abstract：:Oxidation of 4-methylcatechol previously exposed to aqueous calcium chloride was shown by ion chromatography to be associated with release of calcium ions. The catechol was oxidised to the corresponding orthoquinone by the use of tyrosinase from Agaricus bisporus. The oxidative release of calcium from the catechol is ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Riley PA,Stratford MR

更新日期：2015-04-01 00:00:00

abstract：:Vitamin D receptor (VDR) ligands are therapeutic agents for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. VDR ligands also show immense potential as therapeutic agents for autoimmune diseases and cancers of the skin, prostate, colon, and breast as well as leukemia. LG190178 is a novel no...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hakamata W,Sato Y,Okuda H,Honzawa S,Saito N,Kishimoto S,Yamashita A,Sugiura T,Kittaka A,Kurihara M

更新日期：2008-01-01 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 7-acyloxymethylcamptothecin and 20-O-acyl-7-acyloxymethylcamptothecin derivatives were regioselectively prepared on different solvents. 7-Acyloxymethylcamptothecins possess more efficacy than 20-O-acyl-7-acyloxymethylcamptothecins against six human cancer cell lines in vitro. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pan XD,Han R,Sun PY

更新日期：2003-11-03 00:00:00

abstract：:Piperazinyl benzamidines were prepared and found to bind to the rat delta (delta) opioid receptor. The most active compounds had a N,N-diethylcarboxamido group and a N-benzyl piperazine. The most potent among these was N,N-diethyl-4-[4-(phenylmethyl)-1-piperazinyl][2-(trifluoromethyl)phenyl]iminomethyl]benzamide (27) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nortey SO,Baxter EW,Codd EE,Zhang SP,Reitz AB

更新日期：2001-07-09 00:00:00

abstract：:In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent eff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan X,Wang Z,Sudom A,Cardozo M,DeGraffenreid M,Di Y,Fan P,He X,Jaen JC,Labelle M,Liu J,Ma J,McMinn D,Miao S,Sun D,Tang L,Tu H,Ursu S,Walker N,Ye Q,Powers JP

更新日期：2010-12-01 00:00:00

abstract：:Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DS,Pezzuto JM,Pisha E

更新日期：1998-07-07 00:00:00

abstract：:A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the structure of hit compound VII obtained by virtual screening approach. Their in vitro anti-proliferative activity was evaluated against three human cancer cell lines rich in HSP90 namely; colorectal carcinoma (HCT-116), and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： El-Shafey HW,Gomaa RM,El-Messery SM,Goda FE

更新日期：2020-08-01 00:00:00

abstract：:A series of pyridine-linked indanone derivatives were designed and synthesized to discover new small molecules for the treatment of inflammatory bowel disease (IBD). Compounds 5b and 5d exhibited strongest inhibitory activity against TNF-α-induced monocyte adhesion to colon epithelial cells (an in vitro model of colit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kadayat TM,Banskota S,Bist G,Gurung P,Magar TBT,Shrestha A,Kim JA,Lee ES

更新日期：2018-08-01 00:00:00

abstract：:The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Buckman BO,Mohan R,Koovakkat S,Liang A,Trinh L,Morrissey MM

更新日期：1998-08-18 00:00:00

abstract：:A novel series of readily water soluble 8-methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]++ +pyrazines were synthesized. The -10-yl acetic acid ((+)-3) and -10-carboxylidene (4) derivatives exhibit potent affinities (IC50=4 and 19 nM, respectively) and antagonist properties (IC50 = 2 and 3 nM, respectiv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mignani S,Bohme GA,Boireau A,Cheve M,Damour D,Debono MW,Genevois-Borella A,Imperato A,Jimonet P,Pratt J,Randle JC,Ribeill Y,Vuilhorgne M,Stutzmann JM

更新日期：2000-03-20 00:00:00

abstract：:The inhibition of ribonuclease Bi by 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is enhanced by 30-fold in the presence of Zn(2+). Thus, an N-hydroxyurea nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of a ribonuclease. This result engenders a general strategy for the inhibition of non-metalloenzy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Higgin JJ,Yakovlev GI,Mitkevich VA,Makarov AA,Raines RT

更新日期：2003-02-10 00:00:00