Self-organizing maps for identification of new inhibitors of P-glycoprotein.

abstract：:The bromodomain and extra-terminal (BET) family proteins have recently emerged as promising drug targets for cancer therapy. In this study, identification of an 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one fragment (47) as a new binder to the BET bromodomains and the subsequent incorporation of fragment 47 to the scaffold...

journal_title：Journal of medicinal chemistry

authors： Li Z,Xiao S,Yang Y,Chen C,Lu T,Chen Z,Jiang H,Chen S,Luo C,Zhou B

更新日期：2020-04-23 00:00:00

abstract：:The programmed cell death or apoptosis plays both physiological and pathological roles in biology. Anomalous activation of apoptosis has been associated with malignancies. The intrinsic mitochondrial pathway of apoptosis activation occurs through a multiprotein complex named the apoptosome. We have discovered molecule...

journal_title：Journal of medicinal chemistry

authors： Mondragón L,Orzáez M,Sanclimens G,Moure A,Armiñán A,Sepúlveda P,Messeguer A,Vicent MJ,Pérez-Payá E

更新日期：2008-02-14 00:00:00

abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Rizzo A,Trotta R,Pagano B,Iachettini S,De Tito S,Lauri I,Fotticchia I,Giustiniano M,Marinelli L,Giancola C,Novellino E,Biroccio A,Randazzo A

更新日期：2012-11-26 00:00:00

abstract：:From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...

journal_title：Journal of medicinal chemistry

authors： Smits RA,de Esch IJ,Zuiderveld OP,Broeker J,Sansuk K,Guaita E,Coruzzi G,Adami M,Haaksma E,Leurs R

更新日期：2008-12-25 00:00:00

abstract：:Accumulation of beta-amyloid aggregates (Abeta) in the brain is linked to the pathogenesis of Alzheimer's disease (AD). We report a novel approach for producing 1,4-diphenyltriazoles as probes for targeting Abeta aggregates in the brain. The imaging probes, a series of substituted tricyclic 1,4-diphenyltriazoles showi...

journal_title：Journal of medicinal chemistry

authors： Qu W,Kung MP,Hou C,Oya S,Kung HF

更新日期：2007-07-12 00:00:00

abstract：:Sepsis is characterized by a systemic inflammatory response syndrome. Derivatives of indole have been reported to exhibit diverse biological activities. This study reports on the design and synthesis of a new series of indole-2-carboxamide derivatives, which are screened for their anti-inflammatory activities in RAW 2...

journal_title：Journal of medicinal chemistry

authors： Liu Z,Tang L,Zhu H,Xu T,Qiu C,Zheng S,Gu Y,Feng J,Zhang Y,Liang G

更新日期：2016-05-26 00:00:00

abstract：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...

journal_title：Journal of medicinal chemistry

authors： Yahalom D,Rahimipour S,Koch Y,Ben-Aroya N,Fridkin M

更新日期：2000-07-27 00:00:00

abstract：:The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Rep...

journal_title：Journal of medicinal chemistry

authors： Allen MC,Fuhrer W,Tuck B,Wade R,Wood JM

更新日期：1989-07-01 00:00:00

abstract：:Spiropyrimidinetriones are a novel class of antibacterial agents that target the bacterial type II topoisomerase via a new mode of action. Compound ETX0914 is thus far the only drug from this class that is being evaluated in clinical trials. To improve the antibacterial activity and pharmacokinetic properties of ETX09...

journal_title：Journal of medicinal chemistry

authors： Shi C,Zhang Y,Wang T,Lu W,Zhang S,Guo B,Chen Q,Luo C,Zhou X,Yang Y

更新日期：2019-03-28 00:00:00

abstract：:Histone lysine methyltransferases (HKMTs) are an important class of targets for epigenetic therapy. 1 (chaetocin), an epidithiodiketopiperazine (ETP) natural product, has been reported to be a specific inhibitor of the SU(VAR)3-9 class of HKMTs. We have studied the inhibition of the HKMT G9a by 1 and functionally rela...

journal_title：Journal of medicinal chemistry

authors： Cherblanc FL,Chapman KL,Reid J,Borg AJ,Sundriyal S,Alcazar-Fuoli L,Bignell E,Demetriades M,Schofield CJ,DiMaggio PA Jr,Brown R,Fuchter MJ

更新日期：2013-11-14 00:00:00

abstract：:A variety of N-(phenylsulfonyl)-N-phenylglycines 5, N-(phenylsulfonyl)-2-phenylglycines 6, and N-(phenylsulfonyl)anthranilic acids 7 were prepared as analogues of the N-(phenylsulfonyl)glycine 1 aldose reductase inhibitors. In the rat lens assay, several derivatives of 5 display greater inhibitory activity than the co...

journal_title：Journal of medicinal chemistry

authors： DeRuiter J,Borne RF,Mayfield CA

更新日期：1989-01-01 00:00:00

abstract：:A number of novel alpha-melanotropin (alpha-MSH) analogues have been designed, synthesized, and assayed for bioactivity at the melanocortin-1 (MC1) receptor from Xenopus frog skin, and selected potent analogues were examined at recombinant human MC1, MC3, and MC4 receptors expressed in human embryonic kidney (HEK) cel...

journal_title：Journal of medicinal chemistry

authors： Han G,Quillan JM,Carlson K,Sadée W,Hruby VJ

更新日期：2003-02-27 00:00:00

abstract：:A series of 4-amino[1,2,4]triazolo[4,3-a]quinoxalines has been prepared. Many compounds from this class reduce immobility in Porsolt's behavioral despair model in rats upon acute administration and may therefore have therapeutic potential as novel and rapid acting antidepressant agents. Optimal activity in this test i...

journal_title：Journal of medicinal chemistry

authors： Sarges R,Howard HR,Browne RG,Lebel LA,Seymour PA,Koe BK

更新日期：1990-08-01 00:00:00

abstract：:We have synthesized a set of bis-pyranobenzoquinones through a direct and highly efficient approach based on a double intramolecular domino Knoevenagel hetero Diels-Alder reaction. These bis-pyranobenzoquinone derivatives are compounds whose skeletons have similarities to those of some anticancerous and leishmanicidal...

journal_title：Journal of medicinal chemistry

authors： Jiménez-Alonso S,Pérez-Lomas AL,Estévez-Braun A,Muñoz Martinez F,Chávez Orellana H,Ravelo AG,Gamarro F,Castanys S,López M

更新日期：2008-11-27 00:00:00

abstract：:An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to unders...

journal_title：Journal of medicinal chemistry

authors： Snow RJ,Cardozo MG,Morwick TM,Busacca CA,Dong Y,Eckner RJ,Jacober S,Jakes S,Kapadia S,Lukas S,Panzenbeck M,Peet GW,Peterson JD,Prokopowicz AS 3rd,Sellati R,Tolbert RM,Tschantz MA,Moss N

更新日期：2002-08-01 00:00:00

abstract：:With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the ...

journal_title：Journal of medicinal chemistry

authors： Yu Q,Holloway HW,Flippen-Anderson JL,Hoffman B,Brossi A,Greig NH

更新日期：2001-11-22 00:00:00

abstract：:The synthesis and biological evaluation of novel prodrugs for use in the antibody directed enzyme prodrug therapy (ADEPT) of cancer based on the cytotoxic antibiotic duocarmycin SA (1) are described. In this approach, we investigated the influence of the sugar moiety of the glycosidic prodrug on the QIC(50) values as ...

journal_title：Journal of medicinal chemistry

authors： Tietze LF,Schuster HJ,Krewer B,Schuberth I

更新日期：2009-01-22 00:00:00

abstract：:A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibit...

journal_title：Journal of medicinal chemistry

authors： Patel V,Mazitschek R,Coleman B,Nguyen C,Urgaonkar S,Cortese J,Barker RH,Greenberg E,Tang W,Bradner JE,Schreiber SL,Duraisingh MT,Wirth DF,Clardy J

更新日期：2009-04-23 00:00:00

abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...

journal_title：Journal of medicinal chemistry

authors： Matharu SS,Rowlands DA,Taylor JB,Westwood R

更新日期：1977-02-01 00:00:00

abstract：:8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell ...

journal_title：Journal of medicinal chemistry

authors： Jesus AR,Dias C,Matos AM,de Almeida RF,Viana AS,Marcelo F,Ribeiro RT,Macedo MP,Airoldi C,Nicotra F,Martins A,Cabrita EJ,Jiménez-Barbero J,Rauter AP

更新日期：2014-11-26 00:00:00

abstract：:The synthesis of 5-heteroaryl-substituted 2'-deoxyuridines is described. The heteroaromatics were obtained from three different 5-substituted 2'-deoxyuridines. Cycloaddition reaction of nitrile oxides on the 5-ethynyl derivative 1 gave the isoxazoles 4a-e. The thiazole derivatives 14a-c were obtained from the 5-thioca...

journal_title：Journal of medicinal chemistry

authors： Wigerinck P,Snoeck R,Claes P,De Clercq E,Herdewijn P

更新日期：1991-06-01 00:00:00

abstract：:A novel class of biphenyl analogues containing a benzoic acid moiety based on lead compound 8i have been identified as potent and selective human beta 3 adrenergic receptor (beta 3-AR) agonists with good oral bioavailability and long plasma half-life. After further substituent effects were investigated at the terminal...

journal_title：Journal of medicinal chemistry

authors： Imanishi M,Tomishima Y,Itou S,Hamashima H,Nakajima Y,Washizuka K,Sakurai M,Matsui S,Imamura E,Ueshima K,Yamamoto T,Yamamoto N,Ishikawa H,Nakano K,Unami N,Hamada K,Matsumura Y,Takamura F,Hattori K

更新日期：2008-03-27 00:00:00

abstract：:High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identify...

journal_title：Journal of medicinal chemistry

authors： Pike KG,Morris J,Ruston L,Pass SL,Greenwood R,Williams EJ,Demeritt J,Culshaw JD,Gill K,Pass M,Finlay MR,Good CJ,Roberts CA,Currie GS,Blades K,Eden JM,Pearson SE

更新日期：2015-03-12 00:00:00

abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...

journal_title：Journal of medicinal chemistry

authors： Nabuurs SB,Wagener M,de Vlieg J

更新日期：2007-12-27 00:00:00

abstract：:The poor solubility of the thymidylate synthase (TS) inhibiting antifolate 10-propargyl-5,8-dideazafolic acid has posed problems for its clinical use and is probably responsible for its renal toxicity. The insolubility is caused by the 2-amino-3,4-dihydro-4-oxopyrimidine moiety of the drug which stabilizes the solid s...

journal_title：Journal of medicinal chemistry

authors： Jones TR,Thornton TJ,Flinn A,Jackman AL,Newell DR,Calvert AH

更新日期：1989-04-01 00:00:00

abstract：:The construction of bioactive peptides using β-amino acid-containing sequence patterns is a very promising strategy to obtain analogues that exhibit properties of high interest for medicinal chemistry applications. β-Amino acids have been shown to modulate the conformation, dynamics, and proteolytic susceptibility of ...

journal_title：Journal of medicinal chemistry

authors： Cabrele C,Martinek TA,Reiser O,Berlicki Ł

更新日期：2014-12-11 00:00:00

abstract：:The melanocortin-3 (MC3) and melanocortin-4 (MC4) receptors regulate energy homeostasis, food intake, and associated physiological conditions. The melanocortin-4 receptor (MC4R) has been studied extensively. Less is known about specific physiological roles of the melanocortin-3 receptor (MC3R). A major obstacle to thi...

journal_title：Journal of medicinal chemistry

authors： Singh A,Dirain M,Witek R,Rocca JR,Edison AS,Haskell-Luevano C

更新日期：2013-04-11 00:00:00

abstract：:A series of 3-(alkoxymethyl)-alpha-(N-substituted aminomethyl)-4-hydroxybenzyl alcohols was synthesized as potential bronchodilators. The ability to prevent effects against histamine-induced bronchoconstriction in guinea pigs was studied to determine their bronchodilating activity. Introduction of a methoxymethyl grou...

journal_title：Journal of medicinal chemistry

authors： Sohda S,Fujimoto M,Tamegai T,Hirose N

更新日期：1979-03-01 00:00:00

abstract：:The modulation of the endocannabinoid system is emerging as a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neur...

journal_title：Journal of medicinal chemistry

authors： Montanari S,Scalvini L,Bartolini M,Belluti F,Gobbi S,Andrisano V,Ligresti A,Di Marzo V,Rivara S,Mor M,Bisi A,Rampa A

更新日期：2016-07-14 00:00:00

abstract：:We recently discovered the isoform selective RAR beta 2 ligand 4'-octyl-4-biphenylcarboxylic acid (3, AC-55649). Although 3 is highly potent at RAR beta 2 and displays excellent selectivity, solubility issues make it unsuitable for drug development. Herein we describe the exploration of the SAR in a biphenyl and a phe...

journal_title：Journal of medicinal chemistry

authors： Lund BW,Knapp AE,Piu F,Gauthier NK,Begtrup M,Hacksell U,Olsson R

更新日期：2009-03-26 00:00:00