6,7-dihydroxyisoquinoline-3-carboxylic acids are potent inhibitors on the binding of insulin-like growth factor (IGF) to IGF-binding proteins: optimization of the 1-position benzoyl side chain.

abstract：:Optimisation of affinity, chemical stability, metabolic stability and solubility led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with high affinity for the allosteric MPEP binding site, improved microsomal metabolic stability and anxiolytic-like activity in vivo as assessed by the Vogel co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Büttelmann B,Peters JU,Ceccarelli S,Kolczewski S,Vieira E,Prinssen EP,Spooren W,Schuler F,Huwyler J,Porter RH,Jaeschke G

更新日期：2006-04-01 00:00:00

abstract：:With the aim of finding more potential inhibitors against NADH-fumarate reductase (specific target for treating helminthiasis and cancer) from natural resources, Talaromyces wortmannii was treated with the epigenome regulatory agent suberoylanilide hydroxamic acid, which resulted in the isolation of four new wortmanni...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu WC,Wang YY,Liu JH,Ke AB,Zheng ZH,Lu XH,Luan YS,Xiu ZL,Dong YS

更新日期：2016-11-01 00:00:00

abstract：:The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang N,Wang QH,Wang WQ,Wang J,Li F,Tan SP,Cheng MS

更新日期：2012-01-01 00:00:00

abstract：:The selectivity and the binding affinity of previously reported carborane-containing ligands 2 and 3 toward ERβ remains to be optimized. To improve their biological profiles, a series of iodinated carboranyl phenol derivatives (4-6) were designed and synthesized as prospective ERβ-selective ligands with high affinity....

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Endo Y

更新日期：2017-09-01 00:00:00

abstract：:The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antag...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walters I,Austin C,Austin R,Bonnert R,Cage P,Christie M,Ebden M,Gardiner S,Grahames C,Hill S,Hunt F,Jewell R,Lewis S,Martin I,David Nicholls,David Robinson

更新日期：2008-01-15 00:00:00

abstract：:The structure-based design and synthesis of isothiazolidinone (IZD) inhibitors of PTP1B containing imidazoles and imidazolines and their modification to interact with the B site of PTP1B are described here. The X-ray crystal structures of 3I and 4I complexed with PTP1B were solved and revealed the inhibitors are inter...

journal_title：Bioorganic & medicinal chemistry letters

authors： Douty B,Wayland B,Ala PJ,Bower MJ,Pruitt J,Bostrom L,Wei M,Klabe R,Gonneville L,Wynn R,Burn TC,Liu PC,Combs AP,Yue EW

更新日期：2008-01-01 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：:The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhai W,Flynn N,Longhi DA,Tino JA,Murphy BJ,Slusarchyk D,Gordon DA,Pendri A,Shi S,Stoffel R,Ma B,Sofia MJ,Gerritz SW

更新日期：2008-09-15 00:00:00

abstract：:A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker DP,DeCrescenzo G,Freskos J,Getman DP,Hockerman SL,Li M,Mehta P,Munie GE,Swearingen C

更新日期：2001-10-22 00:00:00

abstract：:Structural features from the anticancer prodrug nemorubicin (MMDX) and the DNA-binding molecule DRAQ5™ were used to prepare anthraquinone-based compounds, which were assessed for their potential to interrogate cytochrome P450 (CYP) functional activity and localisation. 1,4-disubstituted anthraquinone 8 was shown to be...

journal_title：Bioorganic & medicinal chemistry letters

authors： Errington RJ,Sadiq M,Cosentino L,Wiltshire M,Sadiq O,Sini M,Lizano E,Pujol MD,Morais GR,Pors K

更新日期：2018-05-01 00:00:00

abstract：:Structure-activity relationship (SAR) efforts around our initial lead compound 1 led to the identification of potent P2X(7) receptor antagonists with improved pharmacokinetic profiles. These compounds were potent and selective at the P2X(7) receptor in both human and rodent. Compound (entry 31) exhibited oral efficacy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matasi JJ,Brumfield S,Tulshian D,Czarnecki M,Greenlee W,Garlisi CG,Qiu H,Devito K,Chen SC,Sun Y,Bertorelli R,Geiss W,Le VD,Martin GS,Vellekoop SA,Haber J,Allard ML

更新日期：2011-06-15 00:00:00

abstract：:Protein-protein interactions (PPIs) are key elements of several important biological processes and have emerged as valuable targets in medicinal chemistry. Importantly, numerous specific protein-protein interactions (e.g., p53-HDM2 and Bcl-2-BH3 domains) were found to be involved in the development of several diseases...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wójcik P,Berlicki Ł

更新日期：2016-02-01 00:00:00

abstract：:A new series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates 1-3 were synthesized through an efficient conversion of 2-pivaloyl-4-oxo-6-ethynylpyrido[2,3-d]pyrimidine 5 to the corresponding 4-amino analog 7 via the activated 1,2,4-triazole intermediate 6. Compound 7 was used as the key intermediate for the pre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gossett LS,Habeck LL,Shackelford KA,Mendelsohn LG,Gates SB,Worzalla JF,Self TD,Theobald KS,Andis SL,Schultz RM,Shih C

更新日期：1999-01-04 00:00:00

abstract：:Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aoyama Y,Konoike T,Kanda A,Naya N,Nakajima M

更新日期：2001-07-09 00:00:00

abstract：:The use of chitosan as the wall of microcapsule designed for delivery of encapsulated celecoxib is reported. Microcapsules were characterised with respect to size and encapsulation efficiency of celecoxib. In vivo animals demonstrated that both free celecoxib administration and chitosan/celecoxib microcapsules adminis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheng SY,Yuen MC,Lam PL,Gambari R,Wong RS,Cheng GY,Lai PB,Tong SW,Chan KW,Lau FY,Kok SH,Lam KH,Chui CH

更新日期：2010-07-15 00:00:00

abstract：:SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved potency (K(i)( *)=15nM, EC 90=70nM) and pharmacokinetic properties...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nair LG,Sannigrahi M,Bogen S,Pinto P,Chen KX,Prongay A,Tong X,Cheng KC,Girijavallabhan V,George Njoroge F

更新日期：2010-01-15 00:00:00

abstract：:Over-expressions of miRNAs are being increasingly linked with many diseases including different types of cancer. In this study, the role of some known small molecular therapeutics has been investigated for their ability to bind with the pre-miRNA target (hsa-mir-155) and thereby to interfere with the Dicer catalyzed m...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maiti M,Nauwelaerts K,Herdewijn P

更新日期：2012-02-15 00:00:00

abstract：:In continuation of our efforts toward hit identification and optimization for a B-Raf kinase project, we have employed a scaffold hopping strategy. The original HTS hit scaffold pyrazolo[1,5-a]pyrimidine was replaced with different thienopyrimidine and thienopyridine scaffolds to append the optimal pharmacophore moiet...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gopalsamy A,Shi M,Hu Y,Lee F,Feldberg L,Frommer E,Kim S,Collins K,Wojciechowicz D,Mallon R

更新日期：2010-04-15 00:00:00

abstract：:β-carbolines from various natural and synthetic sources have been known to show diverse biological activities. As a part of our current ongoing project to search for potent natural product-derived anti-leishmanial compounds, we have synthesized a series of substituted 1-aryl-β-carboline derivatives. A total of 22 comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gohil VM,Brahmbhatt KG,Loiseau PM,Bhutani KK

更新日期：2012-06-15 00:00:00

abstract：:A series of 4,4-disubstituted cyclohexylamine NK(1) antagonists containing a lactam ring is described. The compounds are brain penetrant and activity is demonstrated in a ferret emesis model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hollingworth GJ,Carlson EJ,Castro JL,Chicchi GG,Clark N,Cooper LC,Dirat O,Salvo JD,Elliott JM,Kilburn R,Kurtz MM,Rycroft W,Tattersall FD,Tsao KL,Swain CJ

更新日期：2006-03-01 00:00:00

abstract：:A novel series of oxadiazole EP1 receptor antagonists was identified by replacing the amide of a known glycine sulfonamide derivative with a 1,3,4-oxadiazole. Optimization of the substitution patterns on the three aromatic rings led to the identification of high affinity EP1 receptor antagonists. The derivative with h...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hall A,Brown SH,Chowdhury A,Giblin GM,Gibson M,Healy MP,Livermore DG,Wilson RJ,Naylor A,Rawlings DA,Roman S,Ward E,Willay C

更新日期：2007-08-15 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：:A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng DM,Wai JM,Kuduk SD,Ng C,Murphy KL,Ransom RW,Reiss D,Chang RS,Harrell CM,MacNeil T,Tang C,Prueksaritanont T,Freidinger RM,Pettibone DJ,Bock MG

更新日期：2005-05-02 00:00:00

abstract：:The synthesis and structure-activity relationships of zygosporamide, a known potent and selective cytotoxic natural product against SF-268 and RXF 393 cell lines, are described. The potencies of the synthetic zygosporamide are similar to those reported for the natural product toward all cancer cell lines examined with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Zhang F,Zhang Y,Liu JO,Ma D

更新日期：2008-08-01 00:00:00

abstract：:In continuation of our program aimed at the discovery and development of compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, 21N-arylsulfonyl-3-acetylindole analogs (2a-u) were synthesized and preliminarily evaluated as HIV-1 inhibitors in vitro. Among of all the analogs, several compoun...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ran JQ,Huang N,Xu H,Yang LM,Lv M,Zheng YT

更新日期：2010-06-15 00:00:00

abstract：:Pd(II), Cu(II) and Zn(II) complexes (1-3) based on 4'-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2':6',2″-terpyridine were synthesized and characterized by UV, IR, NMR, EPR, HRMS, elemental analyses, and molar conductivity measurements. The cytotoxicity of these complexes against HL-60, BGC-823, KB, Bel-7402, A549, Hela, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu W,Wang Y,Liu S,Yang X,Wang S,Li S,Zhou G,Qin X,Zhou C,Zhang J

更新日期：2013-09-15 00:00:00

abstract：:A new cytotoxic β-carboline alkaloid, 1-methyl-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-β-carbolin-1-yl)-cyclopentanol (1), was isolated from roots of Galianthe thalictroides, together with the alkaloid 1-(hydroxymethyl)-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-β-carbolin-1-yl)-cyclopentanol (2), the anthraquinones 1-...

journal_title：Bioorganic & medicinal chemistry letters

authors： de Oliveira Figueiredo P,Perdomo RT,Garcez FR,de Fatima Cepa Matos M,de Carvalho JE,Garcez WS

更新日期：2014-03-01 00:00:00

abstract：:Investigation of hydrophobic extract of Dichondra repens (Convolvulaceae) led to the isolation of three new resin glycosides dichondrins A-C (1-3), and three known resin glycosides cus-1, cus-2, and cuse 3. All the isolated resin glycosides with an acyclic core were evaluated for their multidrug resistance reversal ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song WB,Wang WQ,Zhang SW,Xuan LJ

更新日期：2015-02-15 00:00:00

abstract：:We herein report the discovery of four series of fused 5,6-bicyclic heterocycles as γ-secretase modulators. Synthesis and SAR of these series are discussed. These compounds represent a new class of γ-secretase modulators that demonstrate moderate to good in vitro potency in inhibiting Aβ(42) production. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qin J,Dhondi P,Huang X,Mandal M,Zhao Z,Pissarnitski D,Zhou W,Aslanian R,Zhu Z,Greenlee W,Clader J,Zhang L,Cohen-Williams M,Jones N,Hyde L,Palani A

更新日期：2011-01-15 00:00:00

abstract：:S1P receptors (S1PR1-5) are a group of GPCRs activated by a high affinity binding with S1P that have important roles in the regulation of the immune system. A potent S1PR agonist FTY720 is an immunomodulator used to treat multiple sclerosis and several 'second generation' drugs are under clinical development. Subtype-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hur W,Rosen H,Gray NS

更新日期：2017-01-01 00:00:00