Inhibition of adenosine deaminase by analogues of adenosine and inosine, incorporating a common heterocyclic base, 4(7)-amino-6(5)H-imidazo[4,5-d]pyridazin-7(4)one.

abstract：:The mitotic spindle is a validated target for cancer chemotherapy. Drugs such as taxanes and vinca alkaloids specifically target microtubules and cause the mitotic spindle to collapse. However, toxicity and resistance are problems associated with these drugs. Thus, alternative approaches to inhibiting the mitotic spin...

journal_title：Journal of medicinal chemistry

authors： Kaan HY,Weiss J,Menger D,Ulaganathan V,Tkocz K,Laggner C,Popowycz F,Joseph B,Kozielski F

更新日期：2011-03-24 00:00:00

abstract：:Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthe...

journal_title：Journal of medicinal chemistry

authors： Audouze K,Nielsen EØ,Peters D

更新日期：2004-06-03 00:00:00

abstract：:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...

journal_title：Journal of medicinal chemistry

authors： Khanna S,Sobhia ME,Bharatam PV

更新日期：2005-04-21 00:00:00

abstract：:Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined ...

journal_title：Journal of medicinal chemistry

authors： Chen S,Lin CH,Kwon DS,Walsh CT,Coward JK

更新日期：1997-11-07 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：:The constitution of chlorpromazine has been studied in the context of its phototoxicity. Electron transfer from the side chain to the aromatic nucleus of the drug contributes to its instability to light. Even without the side chain, however, chlorophenothiazines appear to be very photolabile, so that it is unlikely th...

journal_title：Journal of medicinal chemistry

authors： Bunce NJ,Kumar Y,Ravanal L

更新日期：1979-02-01 00:00:00

abstract：:Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme that is involved in the de novo synthesis of purine nucleotides. Novel 2-aminooxazoles were synthesized and tested for inhibition of IMPDH catalytic activity. Multiple analogues based on this chemotype were found to inhibit IMPDH with low nanomolar potency. O...

journal_title：Journal of medicinal chemistry

authors： Dhar TG,Shen Z,Guo J,Liu C,Watterson SH,Gu HH,Pitts WJ,Fleener CA,Rouleau KA,Sherbina NZ,McIntyre KW,Shuster DJ,Witmer MR,Tredup JA,Chen BC,Zhao R,Bednarz MS,Cheney DL,MacMaster JF,Miller LM,Berry KK,Harper TW,

更新日期：2002-05-23 00:00:00

abstract：:The synthesis of four l-2'-deoxy-threose nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine, and guanosine has been performed. Especially the adenine containing analogue (PMDTA) was endowed with potent antiviral activity displaying an EC50 of 4.69 μM against HIV-1 and an EC50 value of 0.5 ...

journal_title：Journal of medicinal chemistry

authors： Liu C,Dumbre SG,Pannecouque C,Huang C,Ptak RG,Murray MG,De Jonghe S,Herdewijn P

更新日期：2016-10-27 00:00:00

abstract：:We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERRγ but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had com...

journal_title：Journal of medicinal chemistry

authors： Kim J,Woo SY,Im CY,Yoo EK,Lee S,Kim HJ,Hwang HJ,Cho JH,Lee WS,Yoon H,Kim S,Kwon OB,Hwang H,Kim KH,Jeon JH,Singh TD,Kim SW,Hwang SY,Choi HS,Lee IK,Kim SH,Jeon YH,Chin J,Cho SJ

更新日期：2016-11-23 00:00:00

abstract：:Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute the peptide pharmacophore i...

journal_title：Journal of medicinal chemistry

authors： Van der Poorten O,Knuhtsen A,Sejer Pedersen D,Ballet S,Tourwé D

更新日期：2016-12-22 00:00:00

abstract：:The effect of a variety of aryl substituents on the potency and selectivity of 19 analogues of 1,3-dipropyl-8-phenylxanthine as antagonists at A1- and A2-adenosine receptors in brain tissue was determined. The 4-sulfamoylphenyl and 4-carbamoylphenyl analogues are potent and somewhat selective for the A1 receptor. None...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Padgett WL,Shamim MT

更新日期：1986-08-01 00:00:00

abstract：:A series of O-alkylated analogs of 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO) were synthesized and characterized as ligands for muscarinic acetylcholine receptors (mAChRs). O-Methyl-THAO (4a), O-ethyl-THAO (4b), O-isopropyl-THAO (4c), and O-propargyl-THAO (4d) were shown to be potent inhibitors of the bi...

journal_title：Journal of medicinal chemistry

authors： Bräuner-Osborne H,Ebert B,Brann MR,Falch E,Krogsgaard-Larsen P

更新日期：1995-06-09 00:00:00

abstract：:2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...

journal_title：Journal of medicinal chemistry

authors： van Wijngaarden I,Kruse CG,van Hes R,van der Heyden JA,Tulp MT

更新日期：1987-11-01 00:00:00

abstract：:G-protein coupled receptor (GPCR) GPR109a is a molecular target for nicotinic acid and is expressed in adipocytes, spleen, and immune cells. Nicotinic acid has long been used for the treatment of dyslipidemia due to its capacity to positively affect serum lipids to a greater extent than other currently marketed drugs....

journal_title：Journal of medicinal chemistry

authors： Boatman PD,Lauring B,Schrader TO,Kasem M,Johnson BR,Skinner P,Jung JK,Xu J,Cherrier MC,Webb PJ,Semple G,Sage CR,Knudsen J,Chen R,Luo WL,Caro L,Cote J,Lai E,Wagner J,Taggart AK,Carballo-Jane E,Hammond M,Collett

更新日期：2012-04-26 00:00:00

abstract：:n-Octyl, n-dodecyl, and n-hexadecyl alpha- and gamma-esters of methotrexate (MTX) were compared with the previously described alpha- and gamma-n-butyl esters and with MTX as inhibitors of dihydrofolate reductase (DHFR) and human leukemic lymphoblasts (CEM cells) in culture. The overall order of activity in both test s...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Yu CS,Lazarus H,Beardsley GP

更新日期：1984-05-01 00:00:00

abstract：:Three rationally designed pyrrolobenzodiazepine (PBD) drug-linkers have been synthesized via intermediate 19 for use in antibody-drug conjugates (ADCs). They lack a cleavable trigger in the linker and consist of a maleimide for cysteine antibody conjugation, a hydrophilic spacer, and either an alkyne (6), triazole (7)...

journal_title：Journal of medicinal chemistry

authors： Gregson SJ,Masterson LA,Wei B,Pillow TH,Spencer SD,Kang GD,Yu SF,Raab H,Lau J,Li G,Lewis Phillips GD,Gunzner-Toste J,Safina BS,Ohri R,Darwish M,Kozak KR,Dela Cruz-Chuh J,Polson A,Flygare JA,Howard PW

更新日期：2017-12-14 00:00:00

abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...

journal_title：Journal of medicinal chemistry

authors： Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm K

更新日期：1994-10-28 00:00:00

abstract：:A number of fluorenyl and diphenylmethane analogues of verapamil, chosen as having the same substituents arranged in different ways around the quaternary carbon, were synthesized in order to evaluate the importance of the stereoisomerism at that point of the molecule. The compounds were tested with the Langendorff tec...

journal_title：Journal of medicinal chemistry

authors： Gualtieri F,Teodori E,Bellucci C,Pesce E,Piacenza G

更新日期：1985-11-01 00:00:00

abstract：:The dihydrochalcone derivatives of the bitter flavonoids naringin and neohesperedin are intensely sweet. Phyllodulcin is as sweet as the dihydrochalcones with similar taste properties although its structure apparently resembles that of bitter flavanone or flavone. Multifaceted approaches, including X-ray crystal struc...

journal_title：Journal of medicinal chemistry

authors： Shin W,Kim SJ,Shin JM,Kim SH

更新日期：1995-10-13 00:00:00

abstract：:By modification of key carboxylate, hydrophobic, and zinc-binding groups projected from a sterically restricted terphenyl scaffold, a series of simple and nonpeptide mimetics of the Cys-Val-Ile-Met tetrapeptide substrate of protein farnesyltransferase (FTase) have been designed and synthesized. A crystal structure of ...

journal_title：Journal of medicinal chemistry

authors： Ohkanda J,Lockman JW,Kothare MA,Qian Y,Blaskovich MA,Sebti SM,Hamilton AD

更新日期：2002-01-03 00:00:00

abstract：:The preparation and plasma lipid altering characteristics of a series of 4H-3,1-benzoxazin-4-ones are described. Hypocholesterolemic, hypotriglyceridemic, and high-density-lipoprotein elevating properties are found for derivatives bearing a 4-(1,1-dimethylethyl)phenyl group at the 2-position, and this activity is disp...

journal_title：Journal of medicinal chemistry

authors： Fenton G,Newton CG,Wyman BM,Bagge P,Dron DI,Riddell D,Jones GD

更新日期：1989-01-01 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：:Multidrug-resistant Staphylococcus aureus, including MRSA (methicillin-resistant) and VRSA (vancomycin-resistant), causes serious healthcare-associated infections, even sepsis and death. Here, we identified six novel cathelicidins (CATHPb1-6) from Python bivittatu, and CATHPb1 displayed the best in vitro pharmacologic...

journal_title：Journal of medicinal chemistry

authors： Cai S,Qiao X,Feng L,Shi N,Wang H,Yang H,Guo Z,Wang M,Chen Y,Wang Y,Yu H

更新日期：2018-03-08 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：:The mixed topoisomerase I/II inhibitor N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is currently in clinical trial as an anticancer drug. A series of acridine-substituted analogues were prepared, using a new synthetic route to substituted acridine-4-carboxylic acids (conversion of substituted diphenylamine ...

journal_title：Journal of medicinal chemistry

authors： Spicer JA,Gamage SA,Atwell GJ,Finlay GJ,Baguley BC,Denny WA

更新日期：1997-06-06 00:00:00

abstract：:Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemist...

journal_title：Journal of medicinal chemistry

authors： Pryde DC,Maw GN,Planken S,Platts MY,Sanderson V,Corless M,Stobie A,Barber CG,Russell R,Foster L,Barker L,Wayman C,Van Der Graaf P,Stacey P,Morren D,Kohl C,Beaumont K,Coggon S,Tute M

更新日期：2006-07-13 00:00:00

abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...

journal_title：Journal of medicinal chemistry

authors： Ishiguro M,Tanaka R,Namikawa K,Nasu T,Inoue H,Nakatsuka T,Oyama Y,Imajo S

更新日期：1997-07-04 00:00:00

abstract：:Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragm...

journal_title：Journal of medicinal chemistry

authors： Guillory X,Wolter M,Leysen S,Neves JF,Kuusk A,Genet S,Somsen B,Morrow JK,Rivers E,van Beek L,Patel J,Goodnow R,Schoenherr H,Fuller N,Cao Q,Doveston RG,Brunsveld L,Arkin MR,Castaldi P,Boyd H,Landrieu I,Chen H,O

更新日期：2020-07-09 00:00:00

abstract：:A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(...

journal_title：Journal of medicinal chemistry

authors： Learmonth DA,Vieira-Coelho MA,Benes J,Alves PC,Borges N,Freitas AP,da-Silva PS

更新日期：2002-01-31 00:00:00

abstract：:Metallocene-derived bioisosteres lead to exceptionally strong binding G-protein-coupled receptor ligands, indicating substantial plasticity of the receptor excluded volume. Novel binding profiles of ferrocenylcarboxamides combining subnanomolar Ki values for the dopamine D4 receptor (1a, 0.52 nM; 1b, 0.63 nM) with sup...

journal_title：Journal of medicinal chemistry

authors： Schlotter K,Boeckler F,Hübner H,Gmeiner P

更新日期：2005-06-02 00:00:00