Discovery of ligands for ADP-ribosyltransferases via docking-based virtual screening.

abstract：:A pharmacophore model, Hypo1, was built on the basis of 21 training-set indole compounds with varying levels of antiproliferative activity. Hypo1 possessed important chemical features required for the inhibitors and demonstrated good predictive ability for biological activity, with high correlation coefficients of 0.9...

journal_title：Journal of medicinal chemistry

authors： Chiang YK,Kuo CC,Wu YS,Chen CT,Coumar MS,Wu JS,Hsieh HP,Chang CY,Jseng HY,Wu MH,Leou JS,Song JS,Chang JY,Lyu PC,Chao YS,Wu SY

更新日期：2009-07-23 00:00:00

abstract：:A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H 3 receptor inverse agonists. 2-Methyl-3-(4-[[3-(1-pyrrolidinyl)propyl]oxy]phenyl)-5-(trifluoromethyl)-4(3 H)-quinazolinone ( 1) was identified as a promising derivative for further evaluation following optimization of key paramet...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Mizutani T,Ishikawa S,Sekino E,Sasaki T,Fujimura T,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Fukami T,Sato N

更新日期：2008-08-14 00:00:00

abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...

journal_title：Journal of medicinal chemistry

authors： Rivier JE,Hoeger C,Erchegyi J,Gulyas J,DeBoard R,Craig AG,Koerber SC,Wenger S,Waser B,Schaer JC,Reubi JC

更新日期：2001-06-21 00:00:00

abstract：:A novel cytochrome P450, CYP53A15, was identified in the pathogenic filamentous ascomycete Cochliobolus lunatus. The protein, classified into the CYP53 family, was capable of para hydroxylation of benzoate. Benzoate is a key intermediate in the metabolism of aromatic compounds in fungi and yet basically toxic to the o...

journal_title：Journal of medicinal chemistry

authors： Podobnik B,Stojan J,Lah L,Krasevec N,Seliskar M,Rizner TL,Rozman D,Komel R

更新日期：2008-06-26 00:00:00

abstract：:Quantitative structure-activity studies were carried out on a series of N-isopropylaryl hydrazides which inhibits monoamine oxidase (MAO). The inhibitory potencies of these compounds of MAO were found to correlate with the electron-withdrawing capacity of the aryl ring substituents as estimated by both empirical Hamme...

journal_title：Journal of medicinal chemistry

authors： Johnson CL

更新日期：1976-05-01 00:00:00

abstract：:Opical antipodes of the axial phenyl analgetic, alpha-promedol hydrochloride (3), were prepared and the absolute stereochemistry wasd determined by relating one of the enantiomers to its gamme diastereomer having the 2S, 4S,5R configuration. The analegetic potency of (+)-(2R,4S,5S)-3 is 20 times that of morphine, whil...

journal_title：Journal of medicinal chemistry

authors： Fries DF,Portoghese PS

更新日期：1976-09-01 00:00:00

abstract：:On-line affinity capillary electrophoresis-electrospray ionization-mass spectrometry (ACE-MS) was used for the simultaneous measurement of multiple binding constants of an all-D-tetrapeptide library to the model receptor, vancomycin. Determination of Kd values for the 19 peptides of the form Fmoc-DXYA is demonstrated....

journal_title：Journal of medicinal chemistry

authors： Dunayevskiy YM,Lyubarskaya YV,Chu YH,Vouros P,Karger BL

更新日期：1998-03-26 00:00:00

abstract：:A structure-activity analysis of peptides containing backbone C alpha-methyl modification at the P4 site of the angiotensinogen sequence led to the discovery of potent renin inhibitors with apparent in vitro metabolic stability. Boc-alpha-MePro-Phe-His-Leu psi[CHOHCH2]Val-Ile-Amp dicitrate (Va) is a potent inhibitor o...

journal_title：Journal of medicinal chemistry

authors： Thaisrivongs S,Pals DT,Lawson JA,Turner SR,Harris DW

更新日期：1987-03-01 00:00:00

abstract：:1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glyce...

journal_title：Journal of medicinal chemistry

authors： Sochacka E,Nawrot B,Pankiewicz KW,Watanabe KA

更新日期：1990-07-01 00:00:00

abstract：:The enantiomers of two isosteric phosphonate analogs of the ether-linked antitumor agent 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OMe) were synthesized and evaluated for their cytotoxicity against various mouse leukemic cell lines in vitro and in vivo. The key step in the synthesis of the alkyloxy a...

journal_title：Journal of medicinal chemistry

authors： Bittman R,Byun HS,Mercier B,Salari H

更新日期：1994-02-04 00:00:00

abstract：:Kadsurenone, a specific receptor antagonist of platelet-activating factor (PAF), and its analogues were prepared from derivatives of cinnamyl alcohol and (allyloxy)phenol. Racemic kadsurenone, resolvable by a Chiralpak column at low temperatures, has an IC50 value of 2 X 10(-7) M, which is about 50% of the activity of...

journal_title：Journal of medicinal chemistry

authors： Ponpipom MM,Bugianesi RL,Brooker DR,Yue BZ,Hwang SB,Shen TY

更新日期：1987-01-01 00:00:00

abstract：:The DNA-intercalating agent amsacrine is an effective drug for the treatment of human leukemias and lymphomas but has minimal solid tumor activity. As a first step in identifying analogues with a wider spectrum of activity, a comparison was made of the in vivo antileukemic (P-388) activity of amsacrine analogues given...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Atwell GJ,Baguley BC

更新日期：1984-03-01 00:00:00

abstract：:A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza-analogues were prepared and screened at selected dopamine, serotonin, and adrenergic receptor subtypes. 2-Substituted imidazopyridines and pyridazines presented high affinities and selectivities for D4 dopamine receptors. Whereas functional expe...

journal_title：Journal of medicinal chemistry

authors： Enguehard-Gueiffier C,Hübner H,El Hakmaoui A,Allouchi H,Gmeiner P,Argiolas A,Melis MR,Gueiffier A

更新日期：2006-06-29 00:00:00

abstract：:The steroidal sulfonylpyrazole 1 bound to the rat ventral prostate androgen receptor in vitro; it inhibited testosterone propionate induced increases in ventral prostate weight in vivo in the castrated, immature male rat with an ED50 of 15 mg/kg po. Compound 1 lacked androgenic activity in vivo in contrast to the pare...

journal_title：Journal of medicinal chemistry

authors： Christiansen RG,Bell MR,D'Ambra TE,Mallamo JP,Herrmann JL,Ackerman JH,Opalka CJ,Kullnig RK,Winneker RC,Snyder BW

更新日期：1990-08-01 00:00:00

abstract：:Rotigaptide (3) is an antiarrhythmic peptide that improves cardiac conduction by modifying gap-junction communication. Small molecule gap-junction modifiers with improved physical properties were identified from a Zealand Pharma peptide library using pharmaceutical profiling, established SAR around 3, and a putative p...

journal_title：Journal of medicinal chemistry

authors： Butera JA,Larsen BD,Hennan JK,Kerns E,Di L,Alimardanov A,Swillo RE,Morgan GA,Liu K,Wang Q,Rossman EI,Unwalla R,McDonald L,Huselton C,Petersen JS

更新日期：2009-02-26 00:00:00

abstract：:Conjugates of curcumin to two differently sized poly(ethylene glycol) molecules were synthesized in an attempt to overcome the low aqueous solubility of this natural product with cytotoxic activity against some human cancer cell lines. The soluble conjugates exhibited enhanced cytotoxicity as compared to that of the p...

journal_title：Journal of medicinal chemistry

authors： Safavy A,Raisch KP,Mantena S,Sanford LL,Sham SW,Krishna NR,Bonner JA

更新日期：2007-11-29 00:00:00

abstract：:We have previously shown that the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA, 2), binds to AMPA receptors in a manner different from that of AMPA (1) itself and that 2, in contrast to 1, also binds to kainic acid re...

journal_title：Journal of medicinal chemistry

authors： Bang-Andersen B,Ahmadian H,Lenz SM,Stensbøl TB,Madsen U,Bøgesø KP,Krogsgaard-Larsen P

更新日期：2000-12-14 00:00:00

abstract：:CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the h...

journal_title：Journal of medicinal chemistry

authors： Ortiz Zacarías NV,van Veldhoven JPD,den Hollander LS,Dogan B,Openy J,Hsiao YY,Lenselink EB,Heitman LH,IJzerman AP

更新日期：2019-12-26 00:00:00

abstract：:Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butylproline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both...

journal_title：Journal of medicinal chemistry

authors： Bélec L,Slaninova J,Lubell WD

更新日期：2000-04-20 00:00:00

abstract：:The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited and incurable neurodegenerative disorders primarily afflicting the pediatric population. Current treatment regimens offer only symptomatic relief and do not target the underlying cause of the disease. Although the underlying pathophysiology that drives...

journal_title：Journal of medicinal chemistry

authors： Kinarivala N,Trippier PC

更新日期：2016-05-26 00:00:00

abstract：:Aberrant activation of S6 kinase 1 (S6K1) is found in many diseases, including diabetes, aging, and cancer. We developed ATP competitive organometallic kinase inhibitors, EM5 and FL772, which are inspired by the structure of the pan-kinase inhibitor staurosporine, to specifically inhibit S6K1 using a strategy previous...

journal_title：Journal of medicinal chemistry

authors： Qin J,Rajaratnam R,Feng L,Salami J,Barber-Rotenberg JS,Domsic J,Reyes-Uribe P,Liu H,Dang W,Berger SL,Villanueva J,Meggers E,Marmorstein R

更新日期：2015-01-08 00:00:00

abstract：:Although the illness malaria is caused by the asexual blood stages, the presence of gametocytes is directly responsible for the infection of the vector Anopheles, thus perpetuating the plasmodial cycle. Fight against malaria is more than ever a current problem, and the solution will probably go through the development...

journal_title：Journal of medicinal chemistry

authors： Dechy-Cabaret O,Benoit-Vical F

更新日期：2012-12-13 00:00:00

abstract：:The E and Z isomers of 2-[2-(3-chlorophenyl)-1-phenyl-1-propenyl]pyridine (2a,b) and 2-[2-(3-chlorophenyl)-1-(4-hydroxyphenyl)-1-propenyl]pyridine (4a,b) were synthesized and separated as possible metabolites of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1a). Following administration of 1a to rats, a ...

journal_title：Journal of medicinal chemistry

authors： Kokosa JM,Sinsheimer JE,Wade DR,Drach JC,Burckhalter JH

更新日期：1978-02-01 00:00:00

abstract：:A series of novel nitroheterocyclic phosphoramidates has been evaluated for antitumor activity in murine and xenograft tumor models and for toxicity in mice. Significant increases in lifespan and long-term survivors were noted in L1210 leukemia and B16 melanoma models, and both complete and partial tumor regressions w...

journal_title：Journal of medicinal chemistry

authors： Borch RF,Liu J,Joswig C,Baggs RB,Dexter DL,Mangold GL

更新日期：2001-01-04 00:00:00

abstract：:We previously discovered an orally active human gonadotropin-releasing hormone (GnRH) receptor antagonist, thieno[2,3-d]pyrimidine-2,4-dione derivative 1 (sufugolix). To reduce the cytochrome P450 (CYP) inhibitory activity and improve in vivo GnRH antagonistic activity, further optimization of this scaffold was carrie...

journal_title：Journal of medicinal chemistry

authors： Miwa K,Hitaka T,Imada T,Sasaki S,Yoshimatsu M,Kusaka M,Tanaka A,Nakata D,Furuya S,Endo S,Hamamura K,Kitazaki T

更新日期：2011-07-28 00:00:00

abstract：:A series of substituted benzenedisulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. One compound, 4-(4-methoxypiperidinosulfonyl)-2-chlorobenzenesulfonamide (19, UK-12130), was found to have anticonvulsant activity in animals at a dose level that gave only a minimal ...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Gadsby B

更新日期：1978-09-01 00:00:00

abstract：:The synthesis of chiral 1,5-benzothiazepines 2a-c, 14a-c, 15c, and 16a prepared from cysteine is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound. Compound 2c was the most potent in vitro having an IC50 of 2.95 nM. The ester of 2c, i.e. 14c, was found to inhibit the A...

journal_title：Journal of medicinal chemistry

authors： Slade J,Stanton JL,Ben-David D,Mazzenga GC

更新日期：1985-10-01 00:00:00

abstract：:The N-2 atoms of phosphorus 2,2-dimethylhydrazides, contrary to a previous report, can be methylated by iodomethane. Treatment of the resulting dihydrazinium iodides with aqueous sodium hydroxide results in mono- instead of didehydroiodination, apparently due to resonance stabilization of the inner salt form. The phos...

journal_title：Journal of medicinal chemistry

authors： Cates LA,Li VS,Saddawi BH,Alkadhi KA

更新日期：1985-05-01 00:00:00

abstract：:(N)-Methanocarba adenosine 5'-methyluronamides containing known A(3) AR (adenosine receptor)-enhancing modifications, i.e., 2-(arylethynyl)adenine and N(6)-methyl or N(6)-(3-substituted-benzyl), were nanomolar full agonists of human (h) A(3)AR and highly selective (K(i) ∼0.6 nM, N(6)-methyl 2-(halophenylethynyl) analo...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Deflorian F,Phan K,Gao ZG,Wan TC,Gizewski E,Auchampach JA,Jacobson KA

更新日期：2012-05-24 00:00:00

abstract：:As a continuation of our efforts to develop innovative ligands for D(3), 5-HT(1A), and 5-HT(2A) receptors with low propensity to block hERG channels, we propose a series bishetero(homo)arylpiperazines 5a-m as novel and potent multifunctional ligands characterized by low occupancy at D(2) and 5-HT(2C) receptors. ...

journal_title：Journal of medicinal chemistry

authors： Butini S,Campiani G,Franceschini S,Trotta F,Kumar V,Guarino E,Borrelli G,Fiorini I,Novellino E,Fattorusso C,Persico M,Orteca N,Sandager-Nielsen K,Jacobsen TA,Madsen K,Scheel-Kruger J,Gemma S

更新日期：2010-06-24 00:00:00