Modeling of purine derivatives transport across cell membranes based on their partition coefficient determination and quantum chemical calculations.

abstract：:Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. The new tricyclic ligands are either angular, 2,3,3a,4,5,...

journal_title：Journal of medicinal chemistry

authors： Chidester CG,Lin CH,Lahti RA,Haadsma-Svensson SR,Smith MW

更新日期：1993-05-14 00:00:00

abstract：:(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride. ...

journal_title：Journal of medicinal chemistry

authors： Wu YJ,Boissard CG,Greco C,Gribkoff VK,Harden DG,He H,L'Heureux A,Kang SH,Kinney GG,Knox RJ,Natale J,Newton AE,Lehtinen-Oboma S,Sinz MW,Sivarao DV,Starrett JE Jr,Sun LQ,Tertyshnikova S,Thompson MW,Weaver D,Wong HS

更新日期：2003-07-17 00:00:00

abstract：:A series of pyrazolopyrimidine inhibitors of IRAK4 were developed from a high-throughput screen (HTS). Modification of an HTS hit led to a series of bicyclic heterocycles with improved potency and kinase selectivity but lacking sufficient solubility to progress in vivo. Structure-based drug design, informed by cocryst...

journal_title：Journal of medicinal chemistry

authors： Bryan MC,Drobnick J,Gobbi A,Kolesnikov A,Chen Y,Rajapaksa N,Ndubaku C,Feng J,Chang W,Francis R,Yu C,Choo EF,DeMent K,Ran Y,An L,Emson C,Huang Z,Sujatha-Bhaskar S,Brightbill H,DiPasquale A,Maher J,Wai J,McKenzi

更新日期：2019-07-11 00:00:00

abstract：:A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration o...

journal_title：Journal of medicinal chemistry

authors： Kale MG,Raichurkar A,P SH,Waterson D,McKinney D,Manjunatha MR,Kranthi U,Koushik K,Jena Lk,Shinde V,Rudrapatna S,Barde S,Humnabadkar V,Madhavapeddi P,Basavarajappa H,Ghosh A,Ramya VK,Guptha S,Sharma S,Vachaspati P,

更新日期：2013-11-14 00:00:00

abstract：:The transcription factor nuclear factor kappaB (NF-kappaB), which regulates expression of numerous antiinflammatory genes as well as genes that promote development of the prosurvival, antiapoptotic state is up-regulated in many cancer cells. The natural product resveratrol, a polyphenolic trans-stilbene, has numerous ...

journal_title：Journal of medicinal chemistry

authors： Heynekamp JJ,Weber WM,Hunsaker LA,Gonzales AM,Orlando RA,Deck LM,Jagt DL

更新日期：2006-11-30 00:00:00

abstract：:Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that t...

journal_title：Journal of medicinal chemistry

authors： Ghosh AK,Lee HY,Thompson WJ,Culberson C,Holloway MK,McKee SP,Munson PM,Duong TT,Smith AM,Darke PL

更新日期：1994-04-15 00:00:00

abstract：:The heretofore unknown gamma-(m-carboxyanilide) and gamma-(m-boronoanillide) derivatives of methotrexate (MTX) and the gamma-(m-carboxyanilide) derivatives of aminopterin (AMT) were prepared and tested as inhibitors of dihydrofolate reductase (DHFR) and as inhibitors of cell growth in culture with the aim of comparing...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Bader H,Freisheim JH

更新日期：1991-02-01 00:00:00

abstract：:Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivat...

journal_title：Journal of medicinal chemistry

authors： Tully WR,Gardner CR,Gillespie RJ,Westwood R

更新日期：1991-07-01 00:00:00

abstract：:In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C(23)(S)-methyl group in the side chain of bile acids such as chenodeoxycholic acid (CDCA) and 6-ethylchenodeoxycholic acid (6-ECDCA, INT-747) affords selectivity for TGR5. Herein we report further lead optimization...

journal_title：Journal of medicinal chemistry

authors： Pellicciari R,Gioiello A,Macchiarulo A,Thomas C,Rosatelli E,Natalini B,Sardella R,Pruzanski M,Roda A,Pastorini E,Schoonjans K,Auwerx J

更新日期：2009-12-24 00:00:00

abstract：:The natural abundance 13C magnetic resonance spectra of a series of sulfonamide drugs(sulfanilamide, sulfaguanidine,sulfathiazole, sulfasuxidine, sulfadiazine, sulfamerazine, sulfamethiazine, and sulfapyridine) have been determined at 25.15 MHz employing the pulse Fourier transform technique. The chemical shefts have ...

journal_title：Journal of medicinal chemistry

authors： Chang C,Floss HG,Peck GE

更新日期：1975-05-01 00:00:00

abstract：:The synthesis and biological evaluation of the two known phenolic metabolites of paclitaxel are described. The C3'-phenolic metabolite 2 of paclitaxel was prepared from 7-(triethylsilyl)-baccatin III (8) and enantioenriched N-benzoyl-2-azetidinone 7. The C2-phenolic metabolite 3 was synthesized from paclitaxel (1a) vi...

journal_title：Journal of medicinal chemistry

authors： Park H,Hepperle M,Boge TC,Himes RH,Georg GI

更新日期：1996-07-05 00:00:00

abstract：:Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains the major obstacle for successful treatment of cancer. Inhibition of Pgp transport is important for higher efficacy of anticancer drugs. Lipophilic cationogenic amines with at least one tertiary N atom, such as verapamil, are classical PgP-blocking ag...

journal_title：Journal of medicinal chemistry

authors： Sidorova TA,Nigmatov AG,Kakpakova ES,Stavrovskaya AA,Gerassimova GK,Shtil AA,Serebryakov EP

更新日期：2002-11-21 00:00:00

abstract：:Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The α4β2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid dis...

journal_title：Journal of medicinal chemistry

authors： Wu J,Zhang Y,Maida LE,Santos RG,Welmaker GS,LaVoi TM,Nefzi A,Yu Y,Houghten RA,Toll L,Giulianotti MA

更新日期：2013-12-27 00:00:00

abstract：:Squalestatins without either the hydroxy group at C-4 or the carboxylic acid at C-3 or C-4 were prepared and evaluated for their ability to inhibit rat liver microsomal squalene synthase (SQS) in vitro. These modifications were well tolerated for compounds with the 4,6-dimethyloctenoate ester at C-6 (S1 series). Howev...

journal_title：Journal of medicinal chemistry

authors： Chan C,Andreotti D,Cox B,Dymock BW,Hutson JL,Keeling SE,McCarthy AD,Procopiou PA,Ross BC,Sareen M,Scicinski JJ,Sharratt PJ,Snowden MA,Watson NS

更新日期：1996-01-05 00:00:00

abstract：:Hydroxy-2-phenylindoles carrying substituted benzyl groups and similar substituents at the nitrogen were synthesized and tested for their ability to displace estradiol from its receptor. All of the derivatives tested exhibited high binding affinities for the calf uterine estrogen receptor, with RBA values ranging from...

journal_title：Journal of medicinal chemistry

authors： von Angerer E,Strohmeier J

更新日期：1987-01-01 00:00:00

abstract：:We have identified RWJ-671818 (8) as a novel, low molecular weight, orally active inhibitor of human alpha-thrombin (K(i) = 1.3 nM) that is potentially useful for the acute and chronic treatment of venous and arterial thrombosis. In a rat deep venous thrombosis model used to assess antithrombotic efficacy, oral admini...

journal_title：Journal of medicinal chemistry

authors： Lu T,Markotan T,Ballentine SK,Giardino EC,Spurlino J,Crysler CS,Brown K,Maryanoff BE,Tomczuk BE,Damiano BP,Shukla U,End D,Andrade-Gordon P,Bone RF,Player MR

更新日期：2010-02-25 00:00:00

abstract：:A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted-N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Cheng JC,Ishiguro K,Sartorelli AC

更新日期：1985-09-01 00:00:00

abstract：:The pharmaceutical industry has recognized that many drug-like molecules can self-aggregate in aqueous media and have physicochemical properties that skew experimental results and decisions. Herein, we introduce the use of a simple NMR strategy for detecting the formation of aggregates using dilution experiments that ...

journal_title：Journal of medicinal chemistry

authors： LaPlante SR,Carson R,Gillard J,Aubry N,Coulombe R,Bordeleau S,Bonneau P,Little M,O'Meara J,Beaulieu PL

更新日期：2013-06-27 00:00:00

abstract：:The tetrapeptide sequence His-Phe-Arg-Trp, derived from melanocyte-stimulating hormone (alphaMSH) and its analogs, causes a decrease in food intake and elevates energy utilization upon binding to the melanocortin-4 receptor (MC4R). To utilize this sequence as an effective agent for treating obesity, we improved its me...

journal_title：Journal of medicinal chemistry

authors： Hess S,Linde Y,Ovadia O,Safrai E,Shalev DE,Swed A,Halbfinger E,Lapidot T,Winkler I,Gabinet Y,Faier A,Yarden D,Xiang Z,Portillo FP,Haskell-Luevano C,Gilon C,Hoffman A

更新日期：2008-02-28 00:00:00

abstract：:The subject compounds were prepared as a part of a continuing structure-activity study of the contrasting actions (agonism-antagonism) of (+)- and (-)-11-hydroxy-10-methylaporphine at serotonin (5-HT1A) receptors. None of the targeted nonoxygenated aporphine derivatives demonstrated significant activity in assays for ...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Raghupathi R,Moe ST,Johnson AK,Long JP

更新日期：1993-05-14 00:00:00

abstract：:Details of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors (NNRTIs) have been elucidated using a biosensor-based approach. This initial study was performed with HIV-1 reverse transcriptase mutant K103N, the phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs lice...

journal_title：Journal of medicinal chemistry

authors： Geitmann M,Unge T,Danielson UH

更新日期：2006-04-20 00:00:00

abstract：:Effective and safe analgesics represent an unmet medical need for the treatment of acute and chronic pain. A series of N-cyclopropylmethyl-7α-phenyl-6,14-endoethanotetrahydronorthebaines were designed, synthesized, and assayed, leading to the discovery of a benzylamine derivative (compound 4, SLL-039) as a highly sele...

journal_title：Journal of medicinal chemistry

authors： Xiao L,Wang Y,Zhang M,Wu W,Kong L,Ma Y,Xu X,Liu X,He Q,Qian Y,Sun H,Wu H,Lin C,Huang H,Ye R,Jiang S,Ye RF,Yuan C,Fang S,Xue D,Yang X,Chen H,Zheng Y,Yu L,Xie Q,Zheng L,Fu W,Li W,Qiu Z,Liu J,Shao

更新日期：2019-12-26 00:00:00

abstract：:A series of cis- and trans-dihydroxycotahydrobenzo[f]quinoline congeners of dopamine has been prepared, in which the N substitutent is H, ethyl, or n-propyl. The trans isomers include the dopamine moiety held rigidly in an antiperiplanar diposition which is believed to be necessary for certian central and peripheral d...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Suarez-Gutierrez C,Lee T,Long JP,Costall B,Fortune DH,Naylor RJ

更新日期：1979-04-01 00:00:00

abstract：:Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4'-thioadenosines. Hydrophobic N(6) and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high...

journal_title：Journal of medicinal chemistry

authors： Nayak A,Chandra G,Hwang I,Kim K,Hou X,Kim HO,Sahu PK,Roy KK,Yoo J,Lee Y,Cui M,Choi S,Moss SM,Phan K,Gao ZG,Ha H,Jacobson KA,Jeong LS

更新日期：2014-02-27 00:00:00

abstract：:The first synthesis of the tamoxifen metabolite norendoxifen is reported. This included syntheses of (E)-norendoxifen, (Z)-norendoxifen, and (E,Z)-norendoxifen isomers. (Z)-Norendoxifen displayed affinity for aromatase (Ki 442 nM), estrogen receptor-α (EC50 17 nM), and estrogen receptor-β (EC50 27.5 nM), while the cor...

journal_title：Journal of medicinal chemistry

authors： Lv W,Liu J,Lu D,Flockhart DA,Cushman M

更新日期：2013-06-13 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：:In 1869, Crum Brown discovered the first structure-activity link by showing that alkaloids, even convulsive ones, were converted by N-methylation to muscle relaxants resembling curarine (itself a quaternary amine). This led to an attempt to link every type of drug action to its own cluster of atoms. This quest was jol...

journal_title：Journal of medicinal chemistry

authors： Albert A

更新日期：1982-01-01 00:00:00

abstract：:A metabolism-based approach toward the optimization of a series of N-arylsulfonamide-based γ-secretase inhibitors is reported. The lead cyclohexyl analogue 6 suffered from extensive oxidation on the cycloalkyl motif by cytochrome P450 3A4, translating into poor human liver microsomal stability. Knowledge of the metabo...

journal_title：Journal of medicinal chemistry

authors： Stepan AF,Karki K,McDonald WS,Dorff PH,Dutra JK,Dirico KJ,Won A,Subramanyam C,Efremov IV,O'Donnell CJ,Nolan CE,Becker SL,Pustilnik LR,Sneed B,Sun H,Lu Y,Robshaw AE,Riddell D,O'Sullivan TJ,Sibley E,Capetta S,Atch

更新日期：2011-11-24 00:00:00

abstract：:The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC(50) (72 h) values against a panel of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to nonmalign...

journal_title：Journal of medicinal chemistry

authors： Schobert R,Seibt S,Mahal K,Ahmad A,Biersack B,Effenberger-Neidnicht K,Padhye S,Sarkar FH,Mueller T

更新日期：2011-09-22 00:00:00

abstract：:Class A-class C mechanism-based beta-lactamase inhibitors were designed on the basis of the intermediacy of an oxycarbenium species capable of cross-linking with amino acids residues in the active site. Penams 24 and 27 were very potent against AmpC in vitro. The MIC values of 24 in combination with piperacillin again...

journal_title：Journal of medicinal chemistry

authors： Sandanayaka VP,Prashad AS,Yang Y,Williamson RT,Lin YI,Mansour TS

更新日期：2003-06-19 00:00:00