6-Alkoxyisoindolin-1-one based dopamine D2 partial agonists as potential antipsychotics.

abstract：:In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei L,Steiner JP,Hamilton GS,Wu YQ

更新日期：2004-09-06 00:00:00

abstract：:The stereochemistry of the tubulin inhibitors taltobulin HTI-286 (2) and HTI-042 (3) was determined by utilizing the DPFGSE 1D NOE experiment. Single crystal X-ray diffraction analysis further confirmed the absolute configuration of these two compounds, which carry the (S,S,S)-configuration necessary for biological ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niu C,Ho DM,Williamson RT,Zask A,Ayral-Kaloustian S

更新日期：2010-03-01 00:00:00

abstract：:A series of competitive, reversible cathepsin S (CatS) inhibitors was investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4-arylpiperazin-1-yl group found in our screening hit. Continued investigation into replacement...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grice CA,Tays K,Khatuya H,Gustin DJ,Butler CR,Wei J,Sehon CA,Sun S,Gu Y,Jiang W,Thurmond RL,Karlsson L,Edwards JP

更新日期：2006-04-15 00:00:00

abstract：:PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker drugs for antibody dr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holte D,Lyssikatos JP,Valdiosera AM,Swinney Z,Sisodiya V,Sandoval J,Lee C,Aujay MA,Tchelepi RB,Hamdy OM,Gu C,Lin B,Sarvaiya H,Pysz MA,Laysang A,Williams S,Jun Lee D,Holda MK,Purcell JW,Gavrilyuk J

更新日期：2020-12-15 00:00:00

abstract：:Constraining the catechol aryl ether moiety of bastadins by incorporation into a macrocyle is not necessary in order to mimic the effects of these marine natural products on neuronal calcium homeostasis. Simple, acyclic analogs that embody the 'western' or 'eastern' parts of bastadins were found to evoke comparable re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zieminska E,Lazarewicz JW,Couladouros EA,Moutsos VI,Pitsinos EN

更新日期：2008-11-01 00:00:00

abstract：:Bioassay-guided fractionation of an active fraction from an extract of a marine starfish, Novodinia antillensis, led to the isolation and identification of two new saponins, Sch 725737 (1) and Sch 725739 (2). Compound 1 was identified as the NaV1.8 inhibitor with IC(50) of approximately 9 microM. The purification and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang SW,Chan TM,Buevich A,Priestley T,Crona J,Reed J,Wright AE,Patel M,Gullo V,Chen G,Pramanik B,Chu M

更新日期：2007-10-15 00:00:00

abstract：:In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yasuno T,Ohe T,Takahashi K,Nakamura S,Mashino T

更新日期：2015-08-15 00:00:00

abstract：:The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kessler U,Castagnolo D,Pagano M,Deodato D,Bernardini M,Pilger B,Ranadheera C,Botta M

更新日期：2013-10-15 00:00:00

abstract：:The in vitro and in vivo activities of a series of (2R,3R)-2-(2,4-difluorophenyl)-3-(substituted indazol-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol as potential antifungal agents are described. In particular, the analog 12j having 5-bromo substitution on the indazole ring exhibited significant antifungal activity again...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park JS,Yu KA,Kang TH,Kim S,Suh YG

更新日期：2007-06-15 00:00:00

abstract：:Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen ZZ,Xie YD,Shao LH,Wang QT,Xu YH,Bian XL

更新日期：2018-12-15 00:00:00

abstract：:The X-ray crystallographic structure for the adduct of an activator with human carbonic anhydrase isozyme I (hCA I) is reported. L-Histidine binds deep within the enzyme active site, participating in a network of hydrogen bonds involving its carboxylate moiety and the zinc-bound water molecule, as well as the imidazol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Temperini C,Scozzafava A,Supuran CT

更新日期：2006-10-01 00:00:00

abstract：:Regiospecific synthesis of 2,3-disubstituted-L-histidines and 2,3-disubstituted histamines starting from L-histidine methyl ester and histamine is reported. The key step involves homolytic free radical alkylation via silver catalyzed oxidative decarboxylation of alkylcarboxylic acids with ammonium persulfate. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Narayanan S,Vangapandu S,Jain R

更新日期：2001-05-07 00:00:00

abstract：:Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jervis PJ,Graham LM,Foster EL,Cox LR,Porcelli SA,Besra GS

更新日期：2012-07-01 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 variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (K(i)< or =2 nM) with improved in vitro anticoagulant activity (2xTG< or =1 microM) a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jia ZJ,Wu Y,Huang W,Zhang P,Clizbe LA,Goldman EA,Sinha U,Arfsten AE,Edwards ST,Alphonso M,Hutchaleelaha A,Scarborough RM,Zhu BY

更新日期：2004-03-08 00:00:00

abstract：:A series of novel 5-trans-hydroxyadamantan-2-yl-5,6,7,8-tetrahydropyrazolo[4,3-c]azepin-4(1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described. We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Udagawa S,Sakami S,Takemura T,Sato M,Arai T,Nitta A,Aoki T,Kawai K,Iwamura T,Okazaki S,Takahashi T,Kaino M

更新日期：2013-03-15 00:00:00

abstract：:The first biological target for the natural product complanadine A has been determined. The pseudosymmetric alkaloid functions as a selective agonist for the Mas-related G protein-coupled receptor X2 (MrgprX2), a G protein-coupled receptor that is highly expressed in neurons. Given the potential of MrgprX2 to function...

journal_title：Bioorganic & medicinal chemistry letters

authors： Johnson T,Siegel D

更新日期：2014-08-01 00:00:00

abstract：:Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Snead AN,Miyakawa M,Tan ES,Scanlan TS

更新日期：2008-11-15 00:00:00

abstract：:Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha7 NNR...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li T,Bunnelle WH,Ryther KB,Anderson DJ,Malysz J,Helfrich R,Grønlien JH,Håkerud M,Peters D,Schrimpf MR,Gopalakrishnan M,Ji J

更新日期：2010-06-15 00:00:00

abstract：:A novel series of potent DGAT-1 inhibitors was developed originating from the lactam-based clinical candidate PF-04620110. Incorporation of a dioxino[2,3-d]pyrimidine-based core afforded good alignment of pharmacophore features and resulted in improved passive permeability. Development of an efficient, homochiral synt...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dow RL,Andrews M,Aspnes GE,Balan G,Michael Gibbs E,Guzman-Perez A,Karki K,Laperle JL,Li JC,Litchfield J,Munchhof MJ,Perreault C,Patel L

更新日期：2011-10-15 00:00:00

abstract：:A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Na...

journal_title：Bioorganic & medicinal chemistry letters

authors： Danho W,Swistok J,Cheung AW,Kurylko G,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-02-24 00:00:00

abstract：:N6-Substituted adenosine analogues containing cyclic hydrazines or chiral hydroxy (ar)alkyl groups, designed to interact with the S2 and S3 receptor subregions, have been synthesized and their binding to the adenosine A1 and A2A receptors have been investigated. Examples of both types of compounds were found to exhibi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ha SB,Melman N,Jacobson KA,Nair V

更新日期：1997-12-16 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：: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：:Through a systematic modification of the novel angiogenesis inhibitor 4-senecioyloxymethyl-6,7-dimethoxycoumarin (1) we found that a 6,7-dimethoxy moiety is important for bioactivity of 1. Replacement of the lactone functionality in coumarin 1 by an amide decreased its activity. By substitution of the senecioyl chain ...

journal_title：Bioorganic & medicinal chemistry letters

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

更新日期：2002-09-02 00:00:00

abstract：:A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure-activity relationships (SARs) of this novel class of arylthiourea derivatives that show...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang IJ,Wang LW,Hsu SJ,Lee CC,Lee YC,Wu YS,Yueh A,Wang JC,Hsu TA,Chao YS,Chern JH

更新日期：2009-11-01 00:00:00

abstract：:Conformationally restricted analogues of the central linker unit of bacterial methionyl tRNA synthetase (MRS) inhibitors have been prepared. The (1S,2R)-cyclopentylmethyl moiety was identified as the preferred cyclic linker, with significant diastereo- and enantioselectivity of activity. Combination of this linker wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jarvest RL,Berge JM,Brown P,Houge-Frydrych CS,O'Hanlon PJ,McNair DJ,Pope AJ,Rittenhouse S

更新日期：2003-04-07 00:00:00

abstract：:The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n=15), shows the most potent promotion of axonal growth in the pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Vela-Ruiz M,Bagnard D,Luu B

更新日期：2006-05-15 00:00:00

abstract：:A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC50 = 0.2 microM) and activity against ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tran TP,Ellsworth EL,Sanchez JP,Watson BM,Stier MA,Showalter HD,Domagala JM,Shapiro MA,Joannides ET,Gracheck SJ,Nguyen DQ,Bird P,Yip J,Sharadendu A,Ha C,Ramezani S,Wu X,Singh R

更新日期：2007-03-01 00:00:00

abstract：:A series of pethidine analogs were synthesized and their affinities for the [(3)H]N-methyl-scopolamine (NMS) binding site on muscarinic acetylcholine receptors (mAChRs) were determined using M1, M3 or M5 human mAChRs expressed by Chinese hamster ovary (CHO) cell membranes. Compound 6b showed the highest binding affini...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee NR,Zhang X,Darna M,Dwoskin LP,Zheng G

更新日期：2015-11-15 00:00:00