Piperazinylpyrazines with central serotoninmimetic activity.

abstract：:A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic ...

journal_title：Journal of medicinal chemistry

authors： Kaplánek R,Martásek P,Grüner B,Panda S,Rak J,Masters BS,Král V,Roman LJ

更新日期：2012-11-26 00:00:00

abstract：:4,6,6a,7,8,12b-Hexahydroindolo[4,3-ab]phenanthridines ("benzergolines") was the first structural class of potent and selective dopamine D1 agonists lacking a catechol group. In order to determine the enantioselectivity of the 7-methyl derivative in the adenylate cyclase assay, its 5,5a-dihydro precursor was resolved a...

journal_title：Journal of medicinal chemistry

authors： Seiler MP,Floersheim P,Markstein R,Widmer A

更新日期：1993-04-16 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：:We report the results of a three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modeling investigation of the interaction of the enzyme 3-phosphoglycerate kinase (PGK) with aryl and alkyl bisphosphonates. For the human enzyme, the IC50 values are predicted within a factor of 2 ove...

journal_title：Journal of medicinal chemistry

authors： Kotsikorou E,Sahota G,Oldfield E

更新日期：2006-11-16 00:00:00

abstract：:The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induce...

journal_title：Journal of medicinal chemistry

authors： Eda M,Takemoto T,Ono S,Okada T,Kosaka K,Gohda M,Matzno S,Nakamura N,Fukaya C

更新日期：1994-06-24 00:00:00

abstract：:The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents. The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP. In analogy with glutamine synthetase, we hypothesi...

journal_title：Journal of medicinal chemistry

authors： Chakravarty PK,Greenlee WJ,Parsons WH,Patchett AA,Combs P,Roth A,Busch RD,Mellin TN

更新日期：1989-08-01 00:00:00

abstract：:Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippoca...

journal_title：Journal of medicinal chemistry

authors： Scott JS,Bowker SS,Brocklehurst KJ,Brown HS,Clarke DS,Easter A,Ertan A,Goldberg K,Hudson JA,Kavanagh S,Laber D,Leach AG,MacFaul PA,Martin EA,McKerrecher D,Schofield P,Svensson PH,Teague J

更新日期：2014-11-13 00:00:00

abstract：:EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, the EGFR T790M secondary mutation has become a leading cause of clinically acquired resistance to these agents. Herein, on the basis of the previously reported irreversible EGFR i...

journal_title：Journal of medicinal chemistry

authors： Hao Y,Wang X,Zhang T,Sun D,Tong Y,Xu Y,Chen H,Tong L,Zhu L,Zhao Z,Chen Z,Ding J,Xie H,Xu Y,Li H

更新日期：2016-08-11 00:00:00

abstract：:The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms...

journal_title：Journal of medicinal chemistry

authors： Pirali T,Serafini M,Cargnin S,Genazzani AA

更新日期：2019-06-13 00:00:00

abstract：:UDP and UDP-glucose activate the P2Y14 receptor (P2Y14R) to modulate processes related to inflammation, diabetes, and asthma. A computational pipeline suggested alternatives to naphthalene of a previously reported P2Y14R antagonist (3, PPTN) using docking and molecular dynamics simulations on a hP2Y14R homology model ...

journal_title：Journal of medicinal chemistry

authors： Junker A,Balasubramanian R,Ciancetta A,Uliassi E,Kiselev E,Martiriggiano C,Trujillo K,Mtchedlidze G,Birdwell L,Brown KA,Harden TK,Jacobson KA

更新日期：2016-07-14 00:00:00

abstract：:Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed...

journal_title：Journal of medicinal chemistry

authors： Kees KL,Caggiano TJ,Steiner KE,Fitzgerald JJ Jr,Kates MJ,Christos TE,Kulishoff JM Jr,Moore RD,McCaleb ML

更新日期：1995-02-17 00:00:00

abstract：:A series of novel thiazolo[4,5- d]pyrimidin-7(6 H)-ones (3aa-3eq) were designed, synthesized, and evaluated as the type I positive allosteric modulators of human α7 nAChR expressed in Xenopus ooctyes by a two-electrode voltage clamp. The structure-activity relationship analysis identified the compound 3ea as a potent ...

journal_title：Journal of medicinal chemistry

authors： Li Y,Sun L,Yang T,Jiao W,Tang J,Huang X,Huang Z,Meng Y,Luo L,Wang X,Bian X,Zhang F,Wang K,Sun Q

更新日期：2019-01-10 00:00:00

abstract：:Several norindenoisoquinolines substituted with methoxy or methylenedioxy groups have been prepared and their anticancer properties evaluated in cancer cell cultures and in topoisomerase I inhibition assays. 2,3-Dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride (14) is a strong topoisomerase I i...

journal_title：Journal of medicinal chemistry

authors： Ioanoviciu A,Antony S,Pommier Y,Staker BL,Stewart L,Cushman M

更新日期：2005-07-28 00:00:00

abstract：:A number of 7-benzoylbenzofuran-5-ylacetic acids and 7-benzoylbenzothiophene-5-ylacetic acids were synthesized. The compounds were generally only 1/2 to 3 times as potent as phenylbutazone in the rat paw edema antiinflammatory assay. However, they show greater activity as analgetic agents. The most active compound is ...

journal_title：Journal of medicinal chemistry

authors： Dunn JP,Ackerman NA,Tomolonis AJ

更新日期：1986-11-01 00:00:00

abstract：:The interaction between β-catenin and B-cell CLL/lymphoma 9 (BCL9), critical for the transcriptional activity of β-catenin, is mediated by a helical segment from BCL9 and a large binding groove in β-catenin. Design of potent, metabolically stable BCL9 peptides represents an attractive approach to inhibit the activity ...

journal_title：Journal of medicinal chemistry

authors： Kawamoto SA,Coleska A,Ran X,Yi H,Yang CY,Wang S

更新日期：2012-02-09 00:00:00

abstract：:The protein kinase C (PKC) family of serine/threonine kinases is implicated in a wide variety of cellular processes. The PKC theta (PKCtheta) isoform is involved in TCR signal transduction and T cell activation and regulates T cell mediated diseases, including lung inflammation and airway hyperresponsiveness. Thus inh...

journal_title：Journal of medicinal chemistry

authors： Cole DC,Asselin M,Brennan A,Czerwinski R,Ellingboe JW,Fitz L,Greco R,Huang X,Joseph-McCarthy D,Kelly MF,Kirisits M,Lee J,Li Y,Morgan P,Stock JR,Tsao DH,Wissner A,Yang X,Chaudhary D

更新日期：2008-10-09 00:00:00

abstract：:2,9beta-Dimethyl-2'-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereoc...

journal_title：Journal of medicinal chemistry

authors： Inoue H,O-ishi T,May EL

更新日期：1975-08-01 00:00:00

abstract：:(3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple f...

journal_title：Journal of medicinal chemistry

authors： Wu ES,Cole TE,Davidson TA,Dailey MA,Doring KG,Fedorchuk M,Loch JT 3rd,Thomas TL,Blosser JC,Borrelli AR

更新日期：1989-01-01 00:00:00

abstract：:The sea anemone peptide APETx2 is a potent and selective blocker of acid-sensing ion channel 3 (ASIC3). APETx2 is analgesic in a variety of rodent pain models, but the lack of knowledge of its pharmacophore and binding site on ASIC3 has impeded development of improved analogues. Here we present a detailed structure-ac...

journal_title：Journal of medicinal chemistry

authors： Jensen JE,Cristofori-Armstrong B,Anangi R,Rosengren KJ,Lau CH,Mobli M,Brust A,Alewood PF,King GF,Rash LD

更新日期：2014-11-13 00:00:00

abstract：:Phenacyl-riphenylphosphorane (1a) and several analogs substituted in the meta position of the phenacyl group lowered blood glucose levels in 48-hr fasted rats. The corresponding phosphonium salts had comparable hypoglycemic activity. Two compounds (1a and 1b) were also hypoglycemic in fed rats, but hypoglycemia could ...

journal_title：Journal of medicinal chemistry

authors： Blank B,DiTullio NW,Deviney L,Roberts JT,Saunders HL

更新日期：1975-09-01 00:00:00

abstract：:Although there are many estrogen receptor antagonists with improved tissue selectivity profiles compared with tamoxifen, optimal tissue selectivity has not yet been demonstrated. As such there is still a need for additional diversity and new chemical scaffolds to allow for exploration of improved tissue selectivity. H...

journal_title：Journal of medicinal chemistry

authors： Schmidt JM,Mercure J,Tremblay GB,Pagé M,Kalbakji A,Feher M,Dunn-Dufault R,Peter MG,Redden PR

更新日期：2003-04-10 00:00:00

abstract：:A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The ...

journal_title：Journal of medicinal chemistry

authors： Bodor N,Shek E,Higuchi T

更新日期：1976-01-01 00:00:00

abstract：:4,4-Ditritio-(-)-nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-)-nicotine via the readily prepared 4,4-dibromocotinine (3). Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a Ka of 4.7 X 10(6) M-1 and 13 fmol of binding sites/mg o...

journal_title：Journal of medicinal chemistry

authors： Vincek WC,Martin BR,Aceto MD,Bowman ER

更新日期：1980-08-01 00:00:00

abstract：:Three monomethylated derivatives of 4'-hydroxyacetanilide (acetaminophen) were prepared in order to compare their cytotoxic potential and analgesic activity with that of acetaminophen. Only 4'-hydroxy-N-methylacetanilide (N-methylacetaminophen) was devoid of cytotoxic effects to hepatic tissue of mice. Results of comp...

journal_title：Journal of medicinal chemistry

authors： Harvison PJ,Forte AJ,Nelson SD

更新日期：1986-09-01 00:00:00

abstract：:Novel 3,5-bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones (3a-e) display potent cytotoxicity and a preferential lethality toward various neoplasms compared to some normal cells. The corresponding sulfonic acid analogues 5a-e and an isostere 4 demonstrated substantially lower activity. The leads 3d...

journal_title：Journal of medicinal chemistry

authors： Das U,Pati HN,Sakagami H,Hashimoto K,Kawase M,Balzarini J,De Clercq E,Dimmock JR

更新日期：2011-05-12 00:00:00

abstract：:Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a...

journal_title：Journal of medicinal chemistry

authors： Kánai K,Arányi P,Böcskei Z,Ferenczy G,Harmat V,Simon K,Bátori S,Náray-Szabo G,Hermecz I

更新日期：2008-12-11 00:00:00

abstract：:Protein kinase B (PKB)-selective inhibitors were designed, synthesized, and cocrystallized using the AGC kinase family protein kinase A (PKA, often called cAMP-dependent protein kinase); PKA has been used as a surrogate for other members of this family and indeed for protein kinases in general. The high homology betwe...

journal_title：Journal of medicinal chemistry

authors： Breitenlechner CB,Friebe WG,Brunet E,Werner G,Graul K,Thomas U,Künkele KP,Schäfer W,Gassel M,Bossemeyer D,Huber R,Engh RA,Masjost B

更新日期：2005-01-13 00:00:00

abstract：:Osteoclast-mediated bone matrix resorption has been attributed to cathepsin K, a cysteine protease of the papain family that is abundantly and selectively expressed in osteoclast. Inhibition of cathepsin K could potentially be an effective method to prevent osteoporosis. Structure-activity studies on a series of rever...

journal_title：Journal of medicinal chemistry

authors： Tavares FX,Boncek V,Deaton DN,Hassell AM,Long ST,Miller AB,Payne AA,Miller LR,Shewchuk LM,Wells-Knecht K,Willard DH Jr,Wright LL,Zhou HQ

更新日期：2004-01-29 00:00:00

abstract：:A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K(i) values ranged from 0.05 nM to >100 nM. (R)-N-(2-Fluoroethyl)-3-pi...

journal_title：Journal of medicinal chemistry

authors： Skaddan MB,Kilbourn MR,Snyder SE,Sherman PS,Desmond TJ,Frey KA

更新日期：2000-11-16 00:00:00

abstract：:New 2-[2'-(dimethylamino)ethyl]-3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at the 6- and 7-positions were prepared. Nucleophilic aromatic displacement was a key reaction in the syntheses. Ten of the new compounds were more potent than the unsubstituted compound, azonafide, in a panel of tumor cells inclu...

journal_title：Journal of medicinal chemistry

authors： Sami SM,Dorr RT,Sòlyom AM,Alberts DS,Iyengar BS,Remers WA

更新日期：1996-04-12 00:00:00