Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors.

abstract：:Based on the structures of aminopyridine thrombin inhibitors (1), a series of aminoalkyl- and guanidinoalkyl-substituted diarylsulfonamides were prepared. The most potent derivative, N-[3-(4-guanidinobutoxy)-5-methyl-phenyl]-benzenesulfonamide (6c) had Ki = 0.18 microM for thrombin and did not inhibit trypsin, plasmin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weber IR,Neidlein R,von der Saal W,Grams F,Leinert H,Strein K,Engh RA,Kucznierz R

更新日期：1998-07-07 00:00:00

abstract：:Novel and artificial anthraquinone-carbohydrate hybrids were designed and synthesized, and found to effectively cleave DNA under irradiation with a long wavelength UV light and also exhibit cytotoxicity against HeLa S3 cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Toshima K,Maeda Y,Ouchi H,Asai A,Matsumura S

更新日期：2000-10-02 00:00:00

abstract：:The investigation of the Vietnamese marine sponge Spongia sp. led to the isolation of three new sesquiterpene phenols, langconols A-C (1-3), and one new sesquiterpene hydroxyquinone, langcoquinone C (4), together with two known meroterpenoids (5 and 6). Their structures were determined on the basis of spectroscopic an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nguyen HM,Ito T,Kurimoto SI,Ogawa M,Win NN,Hung VQ,Nguyen HT,Kubota T,Kobayashi J,Morita H

更新日期：2017-07-15 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：:A novel series of non-nucleoside HCV NS5B polymerase inhibitors was prepared from a (2Z)-2-benzoylamino-3-(4-phenoxy-phenyl)-acrylic acid template. Solution and solid phase analog synthesis focused on the northern region of the template combined with structure based design led to the discovery of several potent and or...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pfefferkorn JA,Nugent R,Gross RJ,Greene M,Mitchell MA,Reding MT,Funk LA,Anderson R,Wells PA,Shelly JA,Anstadt R,Finzel BC,Harris MS,Kilkuskie RE,Kopta LA,Schwende FJ

更新日期：2005-06-02 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer's and substance abuse. Presently, (123)I-5-IA-85380 is used in human studies and requires over 6h of scanning time, thus increases patient discomfort. We have designed and synthesized 3-iodo-5-[2-(S)-3-pyrrolinylmethox...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pandey SK,Pan S,Kant R,Kuruvilla SA,Pan ML,Mukherjee J

更新日期：2012-12-15 00:00:00

abstract：:A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the protease-bound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clarke MO,Byun D,Chen X,Doerffler E,Leavitt SA,Sheng XC,Yang CY,Kim CU

更新日期：2012-01-15 00:00:00

abstract：:New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sasaki S,Hashimoto T,Obana N,Yasuda H,Uehara Y,Maeda M

更新日期：1998-05-05 00:00:00

abstract：:A series of alpha1a receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nantermet PG,Barrow JC,Selnick HG,Homnick CF,Freidinger RM,Chang RS,O'Malley SS,Reiss DR,Broten TP,Ransom RW,Pettibone DJ,Olah T,Forray C

更新日期：2000-08-07 00:00:00

abstract：:Four new steroids, namely klyflaccisteroids G-J (1-4) were isolated from the Formosan soft coral Klyxum flaccidum. The structures of compounds 1-4 were established by spectral data analysis (IR, MS, 1D and 2D NMR) and comparison of spectral data with those of the related known compounds. Cytotoxicity assay revealed th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tseng WR,Huang CY,Tsai YY,Lin YS,Hwang TL,Su JH,Sung PJ,Dai CF,Sheu JH

更新日期：2016-07-15 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：:Cyclic imides are well known to be very important antitumor agents such as mitonafide and amonafide etc. Based on this fact, we have synthesized two series of cyclic imide derivatives containing two cyclic imide moiety in their structures (bis-cyclic imides) and screened them for in vitro anticancer activity against f...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar A,Banerjee S,Roy P,Sondhi SM,Sharma A

更新日期：2017-02-01 00:00:00

abstract：:The syntheses and biological profiles of sulfoximine-based Vioxx analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx (1). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SJ,Buschmann H,Bolm C

更新日期：2011-08-15 00:00:00

abstract：:The enzyme ATP citrate lyase (ACL) catalyzes the formation of cytosolic acetyl CoA, the starting material for de novo lipid and cholesterol biosynthesis. The dysfunction and upregulation of ACL in numerous cancers makes it an attractive target for developing anticancer therapies. ACL inhibition by shRNA knockdown limi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jernigan FE,Hanai JI,Sukhatme VP,Sun L

更新日期：2017-02-15 00:00:00

abstract：:The synthesis of a 20 member 2-aminoimidazole/triazole pilot library is reported. Each member of the library was screened for its ability to inhibit or promote biofilm development of either Escherichia coli and Acinetobacter baumannii. From this screen, E. coli-selective 2-aminoimidazoles were discovered, with the bes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Reed CS,Huigens RW 3rd,Rogers SA,Melander C

更新日期：2010-11-01 00:00:00

abstract：:Arenobufagin is a naturally occurring bufadienolide showing promising antitumor activity accompanied however with apparent cardiac toxicity. Following the recent discovery that oxidative damage possibly be an important cause of the cardiac toxicity of cardenolides, a strategy fusing the antitumor agent arenobufagin wi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hou W,Huang ZX,Xu HG,Lin J,Zhang DM,Peng QL,Lin H,Chang YQ,Wang LH,Yao Z,Sun PH,Chen WM

更新日期：2018-11-01 00:00:00

abstract：:Eight esters of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone with melphalan were prepared and tested for their antitumor activity (S-180) and cytotoxicity. 2-[1-[4-(p-Bis(2-chloroethyl)-aminophenyl)-butanoyloxy]methyl]-1,4-dihydroxy-9,10-anthraquinone and 2-[1-[4-(p-bis(2-chloroethyl)-aminophenyl)-butanoyloxy]e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin G,You Y,Ahn B

更新日期：2001-06-04 00:00:00

abstract：:Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen C,Chen Y,Pontillo J,Guo Z,Huang CQ,Wu D,Madan A,Chen T,Wen J,Xie Q,Tucci FC,Rowbottom M,Zhu YF,Wade W,Saunders J,Bozigian H,Struthers RS

更新日期：2008-06-01 00:00:00

abstract：:Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D(3)/D(2) compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D(3) and D(2) receptors. Several members of this group showed excellent pharmacokinetic and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agai-Csongor E,Domány G,Nógrádi K,Galambos J,Vágó I,Keserű GM,Greiner I,Laszlovszky I,Gere A,Schmidt E,Kiss B,Vastag M,Tihanyi K,Sághy K,Laszy J,Gyertyán I,Zájer-Balázs M,Gémesi L,Kapás M,Szombathelyi Z

更新日期：2012-05-15 00:00:00

abstract：:Aminoglycoside antibiotics target an internal RNA loop within the bacterial ribosomal decoding site. Here, we describe the synthesis and SAR of novel 3,5-diamino-piperidine derivatives as aminoglycoside mimetics, and show they act as inhibitors of bacterial translation and growth. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou Y,Gregor VE,Ayida BK,Winters GC,Sun Z,Murphy D,Haley G,Bailey D,Froelich JM,Fish S,Webber SE,Hermann T,Wall D

更新日期：2007-03-01 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 high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si S

更新日期：2015-11-15 00:00:00

abstract：:N-Aryl derivatives of edaravone were identified as potentially effective small molecule inhibitors of tau and beta-amyloid aggregation in the context of developing disease-modifying therapeutics for Alzheimer's disease (AD). Palladium-catalyzed hydrazine monoarylation protocols were then employed as an expedient means...

journal_title：Bioorganic & medicinal chemistry letters

authors： MacLean MA,Diez-Cecilia E,Lavery CB,Reed MA,Wang Y,Weaver DF,Stradiotto M

更新日期：2016-01-01 00:00:00

abstract：:High potency pyrazole-based noncovalent inhibitors of human cathepsin S (CatS) were developed by modification of the benzo-fused 5-membered ring heterocycles found in earlier series of CatS inhibitors. Although substitutions on this heterocyclic framework had a moderate impact on enzymatic potency, dramatic effects on...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei J,Pio BA,Cai H,Meduna SP,Sun S,Gu Y,Jiang W,Thurmond RL,Karlsson L,Edwards JP

更新日期：2007-10-15 00:00:00

abstract：:A series of flavonoid analogues were synthesized and screened for the in vitro antioxidant activity through their ability to quench 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. The activity of these compounds, measured in comparison to the well-known standard antioxidants (29-32), their precursors (38-42) and other ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das S,Mitra I,Batuta S,Niharul Alam M,Roy K,Begum NA

更新日期：2014-11-01 00:00:00

abstract：:Oridonin (1) is a complex ent-kaurane diterpenoid with unique antitumor profile, which is isolated from Isodon rubescens. In order to develop novel derivatives of oridonin with improved potency, a series of nitric oxide (NO)-releasing oridonin derivatives were synthesized by coupling diazeniumdiolates with oridonin an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu S,Wang G,Lin Y,Zhang Y,Pei L,Yao H,Hu M,Qiu Y,Huang Z,Zhang Y,Xu J

更新日期：2016-06-15 00:00:00

abstract：:A series of 5,6-diaryl-2-amino-pyrazines were prepared and found to have antagonist-like properties at the CB1 receptor. Subsequent SAR studies optimized both receptor potency and drug-like properties including solubility and Cytochrome-P450 inhibition potential. Optimized compounds were demonstrated to be inverse ago...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wustrow DJ,Maynard GD,Yuan J,Zhao H,Mao J,Guo Q,Kershaw M,Hammer J,Brodbeck RM,Near KE,Zhou D,Beers DS,Chenard BL,Krause JE,Hutchison AJ

更新日期：2008-06-01 00:00:00

abstract：:Several newer isosteric analogues of glycosyl phosphates, namely of glycosyl phosphoramidates, were synthesized in good yields using Staudinger reaction of their corresponding azides with trimethyl phosphite followed by de-O-acetylation. The structure and conformation of the fully protected analogue synthesized, namel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kannan T,Vinodhkumar S,Varghese B,Loganathan D

更新日期：2001-09-17 00:00:00

abstract：:To make full use both of optical properties of quantum dots (QDs) and of specific interactions between aptamers and their ligands of interest, we employed QD-conjugated RNA aptamer interactions with histidine tag. QDs offer revolutionary fluorescence performance due to their long-term photostability, brilliant colors,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shin S,Kim IH,Kang W,Yang JK,Hah SS

更新日期：2010-06-01 00:00:00

abstract：:A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and sel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sutton JC,Bolton SA,Hartl KS,Huang MH,Jacobs G,Meng W,Ogletree ML,Pi Z,Schumacher WA,Seiler SM,Slusarchyk WA,Treuner U,Zahler R,Zhao G,Bisacchi GS

更新日期：2002-11-04 00:00:00