Prodrug esters of the indolocarbazole CEP-751 (KT-6587).

abstract：:Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous stud...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moreno L,Cabedo N,Ivorra MD,Sanz MJ,Castel AL,Carmen Álvarez M,Cortes D

更新日期：2013-09-01 00:00:00

abstract：:A series of 5-aminomethylquinoxaline-2,3-diones have been identified as potent and selective AMPA antagonists. Some of these compounds are also active at the glycine-binding site of the NMDA receptors. A number of these novel, water-soluble quinoxaline-2,3-dione derivatives display protective effects in the electrosho...

journal_title：Bioorganic & medicinal chemistry letters

authors： Auberson YP,Bischoff S,Moretti R,Schmutz M,Veenstra SJ

更新日期：1998-01-06 00:00:00

abstract：:The chemoenzymatic deacylation of ramoplanin A2 is described for the first time: ramoplanin A2 was Boc-protected and hydrogenated to Boc-protected tetrahydroramoplanin, which was subsequently deacylated using an acylase from Actinoplanes utahensis NRRL 12052. The chemoenzymatic process proceeded with 80% overall yield...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gandolfi R,Marinelli F,Ragg E,Romano D,Molinari F

更新日期：2012-08-15 00:00:00

abstract：:NAD(P)H-dependent oxidoreductases play important roles in biology. Recently, we reported that the luminescence lifetime of some Tb(3+) complexes is sensitive to NAD(P)H, and we used this phenomenon to detect activities of these enzymes. However, conventional time-resolved luminescence assays are susceptible to static ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Terai T,Ito H,Hanaoka K,Komatsu T,Ueno T,Nagano T,Urano Y

更新日期：2016-05-01 00:00:00

abstract：:Epothilone A reacted with hydrohalic acids to C12-C13 halohydrin regioisomers (ratios: 2:1-4:1), whereas epothilone B gave under the same conditions the isomerically pure C12 halo C13 hydroxy derivative. With non-nucleophilic Brønstedt acids and with Lewis acids a highly solvent dependent product distribution and some...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sefkow M,Kiffe M,Höfle G

更新日期：1998-11-03 00:00:00

abstract：:A series of 114 SIRT inhibitor candidates was assembled using 'click chemistry', by reacting two alkynes bearing 2-anilinobenzamide pharmacophore with 57 azide building blocks in the presence of Cu(I) catalyst. Screening identified two SIRT2-selective inhibitors, which were more SIRT2-selective than AGK2, a known SIRT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tatum PR,Sawada H,Ota Y,Itoh Y,Zhan P,Ieda N,Nakagawa H,Miyata N,Suzuki T

更新日期：2014-04-15 00:00:00

abstract：:4-(Substituted-benzylidine)-2-substituted-5,6-dihydrobenzo[h]quinazoline (5a-p) and 4-(substituted-benzylidine)-2-substituted-3, 4, 5, 6-tetrahydrobenzo[h]quinazoline (6a-p) have been synthesized from 2-(substituted-benzylidine)tetralone-1(3a-d) and several substituted guanidine sulfates(4a-d).These compounds were tes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agarwal KC,Sharma V,Shakya N,Gupta S

更新日期：2009-09-15 00:00:00

abstract：:Aspartic protease analogues synthesized by covering the surface of silica gel with carboxyl groups effectively hydrolyzed hemoglobin and gamma-globulin. It is proposed that the carboxyl group is involved in both complexation of the protein substrate and the catalytic cleavage of the peptide bonds of the complexed prot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim H,Chung YS,Paik H,Kim MS,Suh J

更新日期：2002-10-07 00:00:00

abstract：:We have developed two novel series of tetrasubstituted pyrazoles, embodying 1,3-diaryl-4,5-dialkyl or 3,5-diaryl-1,4-dialkyl substitution patterns. The scope of a regioselective method, developed by us earlier, was expanded to allow the synthesis of the first series of these tetrasubstituted pyrazoles directly from al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishiguchi GA,Rodriguez AL,Katzenellenbogen JA

更新日期：2002-03-25 00:00:00

abstract：:The structure-activity relationships of 5,6-positions of aminopyridine carboxamide-based c-Jun N-terminal Kinase (JNK) inhibitors were explored to expand interaction with the kinase specificity and ribose-binding pockets. The syntheses of analogues and the impact of structural modification on in vitro potency and cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu G,Zhao H,Liu B,Xin Z,Liu M,Kosogof C,Szczepankiewicz BG,Wang S,Clampit JE,Gum RJ,Haasch DL,Trevillyan JM,Sham HL

更新日期：2006-11-15 00:00:00

abstract：:Twenty 13,28-epoxy and related triterpenoid saponins from Ardisia japonica were evaluated for their anti-proliferative activity on human liver cancer cells and normal liver cells. Eight saponins selectively inhibited the growth of liver cancer Bel-7402 and HepG-2 cells without affecting the survival of normal liver HL...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Q,Li W,Hui LP,Zhao CY,He L,Koike K

更新日期：2012-10-01 00:00:00

abstract：:The chemical resolution, using N-tosyl-L-proline as a chiral auxiliary, of a racemate of the pyrazole analog (+/-)-N-Boc-CPzI of the left hand segment (CPI) of the antitumor agent CC-1065, and the cytotoxic evaluation of both enantiomers are described. The reported results further validate the direct relationship betw...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baraldi PG,Cacciari B,Romagnoli R,Spalluto G,Boyce CW,Boger DL

更新日期：1999-11-01 00:00:00

abstract：:A novel fluorescein-based fluorescent probe for nitroxyl (HNO) based on the reductive Staudinger ligation of HNO with an aromatic phosphine was prepared. This probe reacts with HNO derived from Angeli's salt and 4-bromo Piloty's acid under physiological conditions without interference by other biological redox species...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miao Z,Reisz JA,Mitroka SM,Pan J,Xian M,King SB

更新日期：2015-01-01 00:00:00

abstract：:The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P = 2.153 +/- 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cingolani GM,Di Stefano A,Mosciatti B,Napolitani F,Giorgioni G,Ricciutelli M,Claudi F

更新日期：2000-06-19 00:00:00

abstract：:Distamycin and nitrogen mustard conjugates, in which the nitrogen mustard unit was coupled to the C-terminus of the pyrrole, were synthesized. The switching of the nitrogen mustard unit from the N-terminus to the C-terminus did not compromise the compound's cytotoxicity. Compound 3, bearing three pyrrole units, was hi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Wright SC,Larrick JW

更新日期：2003-02-10 00:00:00

abstract：:We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, whic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang LX,Zhou XB,Xiao ML,Jiang N,Liu F,Zhou WX,Wang XK,Zheng ZB,Li S

更新日期：2014-08-15 00:00:00

abstract：:A novel series of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R) is reported. Members of this series have been identified, which exhibit sub-micromolar binding affinity for the MC4-R, functional potency <100nM, and good oral exposure in rat. Antagonists of the MC4-R are potentially u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marsilje TH,Roses JB,Calderwood EF,Stroud SG,Forsyth NE,Blackburn C,Yowe DL,Miao W,Drabic SV,Bohane MD,Daniels JS,Li P,Wu L,Patane MA,Claiborne CF

更新日期：2004-07-16 00:00:00

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：:In HEK293 cells stably expressing alpha4beta2 nAChRs, naltrexone, but not naloxone, blocked alpha4beta2 nAChRs via an open-channel blocking mechanism. In primary hippocampal cultures, naltrexone inhibited alpha7 nAChRs up-regulated by nicotine, and in organotypic hippocampal cultures naltrexone caused a time-dependent...

journal_title：Bioorganic & medicinal chemistry letters

authors： Almeida LE,Pereira EF,Camara AL,Maelicke A,Albuquerque EX

更新日期：2004-04-19 00:00:00

abstract：:This report details a search for alternative strains that produce the diterpenoid sphaeropsidin A (SphA) among A. candidus strains from the USDA Northern Regional Research Laboratories Culture Collection. We identified two strains that produced SphA using a limited set of test media. An initial scaled-up fermentation ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Y,Scott R,Hooper AR,Bartholomeusz GA,Kornienko A,Bills GF

更新日期：2017-12-15 00:00:00

abstract：:Building on our initial work, we have identified additional novel inhibitors of sphingosine kinase-1 (SK1). These new analogs address the shortcomings found in our previously reported compounds. Inhibitors 51 and 54 demonstrated oral bioavailability in a rat PK study. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiang Y,Hirth B,Kane JL Jr,Liao J,Noson KD,Yee C,Asmussen G,Fitzgerald M,Klaus C,Booker M

更新日期：2010-08-01 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 novel 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives was designed, and synthesized based on our previous studies. Also their activities were evaluated as competitive inhibitors of protein tyrosine phosphatase 1B (PTP1B). Compounds 6d-6g, 7b, 7c, 7e, 7j, 7k, 7m, 14b and 14e-14f showed potent ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Z,Liu Z,Lee W,Kim SN,Yoon G,Cheon SH

更新日期：2014-08-01 00:00:00

abstract：:Novel imidazole frameworks have been identified as potent partial agonists of the alpha(1A) adrenergic receptor, with good selectivity over the alpha(1B), alpha(1D) and alpha(2A) receptor sub-types. Nitrile 28 possessed attractive CNS drug-like properties with good membrane permeability and no P-pg mediated efflux. 28...

journal_title：Bioorganic & medicinal chemistry letters

authors： Whitlock GA,Brennan PE,Roberts LR,Stobie A

更新日期：2009-06-01 00:00:00

abstract：:The induction of conformationally restricted N-(aryl or heteroaryl)-3-azabicyclo[3.1.0]hexane derivatives at P(2) region of compounds of 2-cyanopyrrolidine class was explored to develop novel DPP-IV inhibitors. The synthesis, structure-activity relationship, and selectivity against related proteases are delineated. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sattigeri JA,Andappan MM,Kishore K,Thangathirupathy S,Sundaram S,Singh S,Sharma S,Davis JA,Chugh A,Bansal VS

更新日期：2008-07-15 00:00:00

abstract：:Twenty three side chain analogs of the crambescidin alkaloids were prepared from the corresponding pentacyclic zwitterionic core acid. In the crambescidin 800 and 657 series, potency increased with increasing chain length. In addition, substantial variations in tumor selectivity with structure were seen. Crambescidin ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aron ZD,Pietraszkiewicz H,Overman LE,Valeriote F,Cuevas C

更新日期：2004-07-05 00:00:00

abstract：:New carbon-11 and fluorine-18 labeled N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were designed and synthesized as potential positron emission tomography AMPA (2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid) receptor ligands to image brain diseases. The single crystal structure ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao M,Kong D,Clearfield A,Zheng QH

更新日期：2006-04-15 00:00:00

abstract：:A series of monocyclic thiophenes was designed and synthesized as PTP1B inhibitors. Guided by X-ray co-crystal structural information and computational modeling, rational design led to key interactions with Asp48 and improved inhibitory potency against PTP1B. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wan ZK,Lee J,Xu W,Erbe DV,Joseph-McCarthy D,Follows BC,Zhang YL

更新日期：2006-09-15 00:00:00

abstract：:The discovery of PPAR antagonists is emerging as an useful tool for elucidating the biological role of the receptor. Here we report the identification of N-(phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of potent PPARα antagonists obtained from chemical modification of carboxylic acid agon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ammazzalorso A,Giancristofaro A,D'Angelo A,Filippis BD,Fantacuzzi M,Giampietro L,Maccallini C,Amoroso R

更新日期：2011-08-15 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