Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.

abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...

journal_title：Journal of medicinal chemistry

authors： Bamford MJ,Coe PL,Walker RT

更新日期：1990-09-01 00:00:00

abstract：:Because of the double-edged nature of NO, the development of isoform-selective NOS substrates is a highly desirable goal. Given the striking similarity in the heme active sites of the three NOS isoforms, it presents an challenging problem. Several N-aryl-N'-hydroxyguanidines have recently been shown as substrates that...

journal_title：Journal of medicinal chemistry

authors： Jia Q,Cai T,Huang M,Li H,Xian M,Poulos TL,Wang PG

更新日期：2003-06-05 00:00:00

abstract：:HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal struc...

journal_title：Journal of medicinal chemistry

authors： Grasberger BL,Lu T,Schubert C,Parks DJ,Carver TE,Koblish HK,Cummings MD,LaFrance LV,Milkiewicz KL,Calvo RR,Maguire D,Lattanze J,Franks CF,Zhao S,Ramachandren K,Bylebyl GR,Zhang M,Manthey CL,Petrella EC,Pantoliano MW

更新日期：2005-02-24 00:00:00

abstract：:Etoxadrol (2a), one of the eight possible optical isomers of 2-ethyl-2-phenyl-4-(2-piperidyl)-1,3-dioxolane, was synthesized from (S,S)-1-(2-piperidyl)-1,2-ethanediol, which was obtained from cleavage of dexoxadrol (1a, (S,S)-2,2-diphenyl-4-(2-piperidyl)-1,3-dioxolane). The absolute configuration of etoxadrol hydrochl...

journal_title：Journal of medicinal chemistry

authors： Thurkauf A,Zenk PC,Balster RL,May EL,George C,Carroll FI,Mascarella SW,Rice KC,Jacobson AE,Mattson MV

更新日期：1988-12-01 00:00:00

abstract：:Novel classical antifolates (3 and 4) and 17 nonclassical antifolates (11-27) were synthesized as antitumor and/or antiopportunistic infection agents. Intermediates for the synthesis of 3, 4, and 11-27 were 2,4-diamino-5-alkylsubstituted-7H-pyrrolo[2,3-d]pyrimidines, 31 and 38, prepared by a ring transformation/ring a...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Jain HD,Queener SF,Kisliuk RL

更新日期：2008-08-14 00:00:00

abstract：:A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine resid...

journal_title：Journal of medicinal chemistry

authors： Plattner JJ,Marcotte PA,Kleinert HD,Stein HH,Greer J,Bolis G,Fung AK,Bopp BA,Luly JR,Sham HL

更新日期：1988-12-01 00:00:00

abstract：:Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic target or biomarker for several diseases including aggressive cancer, arthritis, and parasitic infections. The development of probes capable of assessing CTB activity in cell lysates, living cells, and animal models of disease are needed ...

journal_title：Journal of medicinal chemistry

authors： Chowdhury MA,Moya IA,Bhilocha S,McMillan CC,Vigliarolo BG,Zehbe I,Phenix CP

更新日期：2014-07-24 00:00:00

abstract：:5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated ...

journal_title：Journal of medicinal chemistry

authors： De Croos PZ,Sangdee P,Stockwell BL,Kar L,Thompson EB,Johnson ME,Currie BL

更新日期：1990-12-01 00:00:00

abstract：:A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3) dual and selective inhibitors into the putative binding sites of alpha(IIb)beta(3...

journal_title：Journal of medicinal chemistry

authors： Feuston BP,Culberson JC,Hartman GD

更新日期：2003-12-04 00:00:00

abstract：:A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1),...

journal_title：Journal of medicinal chemistry

authors： Asano N,Nishida M,Kato A,Kizu H,Matsui K,Shimada Y,Itoh T,Baba M,Watson AA,Nash RJ,Lilley PM,Watkin DJ,Fleet GW

更新日期：1998-07-02 00:00:00

abstract：:Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal chemistry practice. To examine the recent state-of-the-art in lead-like drug discovery, we surveyed recent drug approvals from 2011 to 2017 and top 200 prescr...

journal_title：Journal of medicinal chemistry

authors： Raymer B,Bhattacharya SK

更新日期：2018-12-13 00:00:00

abstract：:Screening of our internal chemical collection against the neuropeptide Y5 (NPY Y5) receptor allowed the identification of a benzoxazine derivative 5f as a hit that showed moderate affinity (IC(50) = 300 nM). With the aim of improving the in vitro potency, a series of 2-benzoxazinone derivatives have been synthesized a...

journal_title：Journal of medicinal chemistry

authors： Torrens A,Mas J,Port A,Castrillo JA,Sanfeliu O,Guitart X,Dordal A,Romero G,Fisas MA,Sánchez E,Hernández E,Pérez P,Pérez R,Buschmann H

更新日期：2005-03-24 00:00:00

abstract：:New efficient antifungal agents are urgently needed to treat drug-resistant fungal infections. Here, we designed and synthesized a series of cationic xanthone amphiphilics as antifungal agents from natural α-mangostin to combat fungal resistance. The attachment of cationic residues on the xanthone scaffold of α-mangos...

journal_title：Journal of medicinal chemistry

authors： Lin S,Sin WLW,Koh JJ,Lim F,Wang L,Cao D,Beuerman RW,Ren L,Liu S

更新日期：2017-12-28 00:00:00

abstract：:A series of 1-R-5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones was prepared and evaluated for central nervous system depressant activity. Several of these compounds, in particular, 7-chloro-5-ethoxy-1-methyl-3H-1,4-benzodiazepin-2(1H)-one (2), gave a profile and activity level similar to diazepam when measured in mice. ...

journal_title：Journal of medicinal chemistry

authors： Gogerty JH,Griot RG,Habeck D,Iorio LC,Houlihan WJ

更新日期：1977-07-01 00:00:00

abstract：:2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial properties that are selective for Helicobacter spp., but they also have an inherent susceptibility to metabolic oxidation to furnish 2-[[(2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump inhibitors (PPIs). We ha...

journal_title：Journal of medicinal chemistry

authors： Kühler TC,Swanson M,Christenson B,Klintenberg AC,Lamm B,Fägerhag J,Gatti R,Olwegård-Halvarsson M,Shcherbuchin V,Elebring T,Sjöström JE

更新日期：2002-09-12 00:00:00

abstract：:A series of 3-thioindolamidines (and 3-indolamidines) related to mixidine (1) was studied for cardiac-slowing properties, following the discovery of activity for prototype thioindole 2. Structure-activity relationships were explored, leading to many potent antitachycardiac agents (6-9, 12, 13, 15-17, 20, 23, 24, 30, 3...

journal_title：Journal of medicinal chemistry

authors： Zelesko MJ,McComsey DF,Hageman WE,Nortey SO,Baker CA,Maryanoff BE

更新日期：1983-02-01 00:00:00

abstract：:Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated agai...

journal_title：Journal of medicinal chemistry

authors： Gamage SA,Figgitt DP,Wojcik SJ,Ralph RK,Ransijn A,Mauel J,Yardley V,Snowdon D,Croft SL,Denny WA

更新日期：1997-08-01 00:00:00

abstract：:The discovery of BMS-605339 (35), a tripeptidic inhibitor of the NS3/4A enzyme, is described. This compound incorporates a cyclopropylacylsulfonamide moiety that was designed to improve the potency of carboxylic acid prototypes through the introduction of favorable nonbonding interactions within the S1' site of the pr...

journal_title：Journal of medicinal chemistry

authors： Scola PM,Wang AX,Good AC,Sun LQ,Combrink KD,Campbell JA,Chen J,Tu Y,Sin N,Venables BL,Sit SY,Chen Y,Cocuzza A,Bilder DM,D'Andrea S,Zheng B,Hewawasam P,Ding M,Thuring J,Li J,Hernandez D,Yu F,Falk P,Zhai G,S

更新日期：2014-03-13 00:00:00

abstract：:A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimu...

journal_title：Journal of medicinal chemistry

authors： Nilsson BM,Vargas HM,Hacksell U

更新日期：1992-07-24 00:00:00

abstract：:1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was res...

journal_title：Journal of medicinal chemistry

authors： Yasumoto M,Moriyama A,Unemi N,Hashimoto S,Suzue T

更新日期：1977-12-01 00:00:00

abstract：:(N)-Methanocarba nucleosides containing bicyclo[3.1.0]hexane replacement of the ribose ring previously demonstrated selectivity as A(3) adenosine receptor (AR) agonists (5'-uronamides) or antagonists (5'-truncated). Here, these two series were modified in parallel at the adenine C2 position. N(6)-3-Chlorobenzyl-5'-N-m...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Chinn M,Ivanov AA,Klutz AM,Gao ZG,Jacobson KA

更新日期：2009-12-10 00:00:00

abstract：:With the emergence of oseltamivir-resistant influenza viruses and in view of a highly pathogenic flu pandemic, it is important to develop new anti-influenza agents. Here, the development of neuraminidase (NA) inhibitors that were designed to overcome resistance mechanisms along with unfavorable pharmacokinetic (PK) pr...

journal_title：Journal of medicinal chemistry

authors： Schade D,Kotthaus J,Riebling L,Kotthaus J,Müller-Fielitz H,Raasch W,Koch O,Seidel N,Schmidtke M,Clement B

更新日期：2014-02-13 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 synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the redu...

journal_title：Journal of medicinal chemistry

authors： Self CR,Barber WE,Machin PJ,Osbond JM,Smithen CE,Tong BP,Wickens JC,Bloxham DP,Bradshaw D,Cashin CH

更新日期：1991-02-01 00:00:00

abstract：:The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in anima...

journal_title：Journal of medicinal chemistry

authors： Cao J,Slack RD,Bakare OM,Burzynski C,Rais R,Slusher BS,Kopajtic T,Bonifazi A,Ellenberger MP,Yano H,He Y,Bi GH,Xi ZX,Loland CJ,Newman AH

更新日期：2016-12-08 00:00:00

abstract：:p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-e...

journal_title：Journal of medicinal chemistry

authors： Cheeseright TJ,Holm M,Lehmann F,Luik S,Göttert M,Melville JL,Laufer S

更新日期：2009-07-23 00:00:00

abstract：:Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid cycle. However, mutant IDH1/2 (mIDH1/2) reduces α-KG to the oncometabolite 2-hydroxyglutarate (2-HG). High levels of 2-HG competitively inhibit the α-KG-depe...

journal_title：Journal of medicinal chemistry

authors： Ma T,Zou F,Pusch S,Xu Y,von Deimling A,Zha X

更新日期：2018-10-25 00:00:00

abstract：:The need for drugs that lack the obtrusive and limiting side effects of the tricyclic antidepressants has prompted the search for agents with greatly enhanced selectivity for specific mechanisms believed to be essential for antidepressant efficacy. The potential role of derangements of 5-HT pathways in the etiology of...

journal_title：Journal of medicinal chemistry

authors： Welch WM,Kraska AR,Sarges R,Koe BK

更新日期：1984-11-01 00:00:00

abstract：:The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be...

journal_title：Journal of medicinal chemistry

authors： Mungall WS,Lemmen LJ,Lemmen KL,Dethmers JK,Norling LL

更新日期：1978-07-01 00:00:00

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