Antagonists of slow reacting substance of anaphylaxis. Synthesis of a series of chromone-2-carboxylic acids.

abstract：:1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the ...

journal_title：Journal of medicinal chemistry

authors： Batra S,Srivastava P,Roy K,Pandey VC,Bhaduri AP

更新日期：2000-09-07 00:00:00

abstract：:The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biolo...

journal_title：Journal of medicinal chemistry

authors： Kuo EA,Hambleton PT,Kay DP,Evans PL,Matharu SS,Little E,McDowall N,Jones CB,Hedgecock CJ,Yea CM,Chan AW,Hairsine PW,Ager IR,Tully WR,Williamson RA,Westwood R

更新日期：1996-11-08 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：:A series of analogues of streptonigrin, in which the quinoline of ring B is replaced by isoquinoline and the substituted pyridine of ring C is replaced by phenyl, nitrophenyl, aminophenyl, or benzyl functions, have been prepared. Thus, 1-substituted isoquinoline-5,8-diones with 7-amino or 6-(alkylamino) groups were pr...

journal_title：Journal of medicinal chemistry

authors： Rao KV,Beach JW

更新日期：1991-06-01 00:00:00

abstract：:Penicillin-binding proteins represent well-established, validated, and still very promising targets for the design and development of new antibacterial agents. The transglycosylase domain of penicillin-binding proteins is especially important, as it catalyzes polymerization of glycan chains, using the peptidoglycan pr...

journal_title：Journal of medicinal chemistry

authors： Sosič I,Anderluh M,Sova M,Gobec M,Mlinarič Raščan I,Derouaux A,Amoroso A,Terrak M,Breukink E,Gobec S

更新日期：2015-12-24 00:00:00

abstract：:A series of 3-acylbenzamidine (amidino)hydrazones 7a-h, the corresponding (hetero)aromatic congeners 7i-p, and 3,3'-bis-amidino-biaryls 25a-e were synthesized. The hydrazones 7a-p were prepared by conversion of the corresponding acyl nitriles 1a,c-d,i,n-p to the imido esters 3a,c-d,i and the amidines 5a,c-d,h-i, follo...

journal_title：Journal of medicinal chemistry

authors： Stanek J,Caravatti G,Capraro HG,Furet P,Mett H,Schneider P,Regenass U

更新日期：1993-01-08 00:00:00

abstract：:Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding m...

journal_title：Journal of medicinal chemistry

authors： Patel S,Cohen F,Dean BJ,De La Torre K,Deshmukh G,Estrada AA,Ghosh AS,Gibbons P,Gustafson A,Huestis MP,Le Pichon CE,Lin H,Liu W,Liu X,Liu Y,Ly CQ,Lyssikatos JP,Ma C,Scearce-Levie K,Shin YG,Solanoy H,Stark KL,Wa

更新日期：2015-01-08 00:00:00

abstract：:By screening an epigenetic compound library, we identified that UNC0638, a highly potent inhibitor of the histone methyltransferases G9a and GLP, was a weak inhibitor of SPIN1 (spindlin 1), a methyllysine reader protein. Our optimization of this weak hit resulted in the discovery of a potent, selective, and cell-activ...

journal_title：Journal of medicinal chemistry

authors： Xiong Y,Greschik H,Johansson C,Seifert L,Bacher J,Park KS,Babault N,Martini M,Fagan V,Li F,Chau I,Christott T,Dilworth D,Barsyte-Lovejoy D,Vedadi M,Arrowsmith CH,Brennan P,Fedorov O,Jung M,Farnie G,Liu J,Opperma

更新日期：2019-10-24 00:00:00

abstract：:Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed RT mutants and had an excellent pharmacokinetic profile in rats, dogs, and rhesus macaques. The compound als...

journal_title：Journal of medicinal chemistry

authors： Su DS,Lim JJ,Tinney E,Wan BL,Young MB,Anderson KD,Rudd D,Munshi V,Bahnck C,Felock PJ,Lu M,Lai MT,Touch S,Moyer G,DiStefano DJ,Flynn JA,Liang Y,Sanchez R,Perlow-Poehnelt R,Miller M,Vacca JP,Williams TM,Anthony

更新日期：2009-11-26 00:00:00

abstract：:Very few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In an attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of repres...

journal_title：Journal of medicinal chemistry

authors： Frantz MC,Rodrigo J,Boudier L,Durroux T,Mouillac B,Hibert M

更新日期：2010-02-25 00:00:00

abstract：:Comparative binding energy analysis, a technique to derive receptor-based three-dimensional quantitative structure-activity relationships (3D-QSAR), is herein extended to consider both affinity and selectivity in the derivation of the QSAR model. The extension is based on allowing multiple structurally related recepto...

journal_title：Journal of medicinal chemistry

authors： Murcia M,Morreale A,Ortiz AR

更新日期：2006-10-19 00:00:00

abstract：:A previously outlined general procedure for preparing various 3-substituted cephalosporins from the penicillin nucleus has been used, with modifications where required, to prepare a series of analogues of cephalexin with various substituents in the 3-methyl group. The 3-substituents most conducive to broad-spectrum an...

journal_title：Journal of medicinal chemistry

authors： Brain EG,Eglington AJ,James BG,Nayler JH,Osborne NF,Pearson MJ,Smale TC,Southgate R,Tolliday P,Basker MJ,Mizen LW,Sutherland R

更新日期：1977-08-01 00:00:00

abstract：:The synthesis and bioactivity of the retinoid X receptor (RXR) antagonist 4-[(3'-n-butyl-5',6',7',8'-tetrahydro-5',5',8',8'-tetramethyl-2'-naphthalenyl)(cyclopropylidene)methyl]benzoic acid and several heteroatom-substituted analogues are described. Ligand design was based on the scaffold of the 3'-methyl RXR-selectiv...

journal_title：Journal of medicinal chemistry

authors： Cavasotto CN,Liu G,James SY,Hobbs PD,Peterson VJ,Bhattacharya AA,Kolluri SK,Zhang XK,Leid M,Abagyan R,Liddington RC,Dawson MI

更新日期：2004-08-26 00:00:00

abstract：:A new 1,4-dihydropyridine 5a, containing a cyano group at the C3 position, was recently reported to possess excellent mineralocorticoid receptor (MR) antagonist in vitro potency and no calcium channel-blocker (CCB) activity. In the present study, we report the structure-activity relationships of this novel series of c...

journal_title：Journal of medicinal chemistry

authors： Arhancet GB,Woodard SS,Iyanar K,Case BL,Woerndle R,Dietz JD,Garland DJ,Collins JT,Payne MA,Blinn JR,Pomposiello SI,Hu X,Heron MI,Huang HC,Lee LF

更新日期：2010-08-26 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

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：:Because of the ambiguities of how to treat ionization in empirical equations which relate biological activity to partition coefficient by use of a (log P)2 term, a theoretical approach to the problem is proposed. Based on a simplified view of assays of potency following in vitro or continuous infusion administration o...

journal_title：Journal of medicinal chemistry

authors： Martin YC,Hackbarth JJ

更新日期：1976-08-01 00:00:00

abstract：:From a micromolar high throughput screening hit 7, the successful complementary application of a chemogenomic approach and of a scaffold hopping exercise rapidly led to a low single digit nanomolar human vasopressin 1a (hV1a) receptor antagonist 38. Initial optimization of the mouse V1a activities delivered suitable t...

journal_title：Journal of medicinal chemistry

authors： Ratni H,Rogers-Evans M,Bissantz C,Grundschober C,Moreau JL,Schuler F,Fischer H,Alvarez Sanchez R,Schnider P

更新日期：2015-03-12 00:00:00

abstract：:A series of N,N-dialkyltryptamines with methylthio or methylenedioxy substituents in the 4, 5, and 6 positions and methyl or isopropyl on the side-chain nitrogen has been synthesized. The behavioral pharmacology of these compounds showed them to possess Bovet-Gatti profiles characteristic of hallucinogens, and the 5-m...

journal_title：Journal of medicinal chemistry

authors： Kline TB,Benington F,Morin RD,Beaton JM

更新日期：1982-08-01 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：: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：: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：:The (E)- and (Z)-m-(trifluoromethyl)-alpha, beta-dimethylcinnamamides and some of their N-alkyl derivatives were prepared and pharmacologically tested as anticonvulsant agents in order to verify if a ring substituent, like the m-CF3 group, different from a halogen but possessing the same electronic effect could lead t...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Cuttica A,Passerini N

更新日期：1981-05-01 00:00:00

abstract：:A series of regioisomeric substituted 6-O-benzyl ethers of 6 beta-naltrexol (12) in which isothiocyanate groups were attached directly to or one carbon removed from the aromatic ring of the benzyl group were prepared. These agents were prepared to obtain electrophilic opioid ligands potentially useful in the character...

journal_title：Journal of medicinal chemistry

authors： Davis RD,Nelson WL

更新日期：1995-02-03 00:00:00

abstract：:Short peptide-based inhibition of fusion remains an attractive goal in antihuman immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report the use of the dithiol bisalkylation reaction to generate a series of m-xylene ...

journal_title：Journal of medicinal chemistry

authors： Meng G,Pu J,Li Y,Han A,Tian Y,Xu W,Zhang T,Li X,Lu L,Wang C,Jiang S,Liu K

更新日期：2019-10-10 00:00:00

abstract：:In a search for improved multiple drug resistance (MDR) modulators, we identified a novel series of substituted pyrroloquinolines that selectively inhibits the function of P-glycoprotein (Pgp) without modulating multidrug resistance-related protein 1 (MRP1). These compounds were evaluated for their toxicity toward dru...

journal_title：Journal of medicinal chemistry

authors： Lee BD,Li Z,French KJ,Zhuang Y,Xia Z,Smith CD

更新日期：2004-03-11 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：:The mechanism of action of a general class of mechanism-based inhibitors of serine proteases, including human neutrophil elastase (HNE), has been elucidated by determining the X-ray crystal structure of an enzyme-inhibitor complex. The captured intermediate indicates that processing of inhibitor by the enzyme generate...

journal_title：Journal of medicinal chemistry

authors： Huang W,Yamamoto Y,Li Y,Dou D,Alliston KR,Hanzlik RP,Williams TD,Groutas WC

更新日期：2008-04-10 00:00:00

abstract：:With the aim of up-regulating antitumor efficacy and down-regulating adverse effects, three types of aromatic imide and diimides were designed to couple with different polyamines. The in vitro assays revealed that two naphthalene diimide-polyamine conjugates could inhibit the growth of multiple cancer cell lines more ...

journal_title：Journal of medicinal chemistry

authors： Wang Y,Zhang X,Zhao J,Xie S,Wang C

更新日期：2012-04-12 00:00:00

abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00