Structure-activity relationships of 2'-fluoro-2',3'-unsaturated D-nucleosides as anti-HIV-1 agents.

abstract：:Malaria is still a leading cause of mortality among children in the developing world, and despite the immense progress made in reducing the global burden, further efforts are needed if eradication is to be achieved. In this context, targeting transmission is widely recognized as a necessary intervention toward that go...

journal_title：Journal of medicinal chemistry

authors： Rueda-Zubiaurre A,Yahiya S,Fischer OJ,Hu X,Saunders CN,Sharma S,Straschil U,Shen J,Tate EW,Delves MJ,Baum J,Barnard A,Fuchter MJ

更新日期：2020-03-12 00:00:00

abstract：:sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms was alternatively replaced by a methine or converted into an a...

journal_title：Journal of medicinal chemistry

authors： Berardi F,Abate C,Ferorelli S,Uricchio V,Colabufo NA,Niso M,Perrone R

更新日期：2009-12-10 00:00:00

abstract：:3',4'-Dihydroxynomifensine, 8-amino-1,2,3,4-tetrahydro-4-(3,4-dihydroxyphenyl)-2-methylisoquinoli ne (1a), is an agonist of dopamine receptors in central and peripheral systems. Since this dopamine receptor agonist bears an asymmetric center at position 4, its synthesis and resolution were undertaken as part of a stud...

journal_title：Journal of medicinal chemistry

authors： Dandridge PA,Kaiser C,Brenner M,Gaitanopoulos D,Davis LD,Webb RL,Foley JJ,Sarau HM

更新日期：1984-01-01 00:00:00

abstract：:A rapid, efficient procedure useful for the radiosynthesis of [Me-3H]-MPDP+ ([methyl-3H]-4-phenyl-2,3-dihydropyridinium species) is described. Hog liver microsomes or the highly purified flavin-containing monooxygenase from hog liver quantitatively biotransforms [Me-3H]-MPTP to its corresponding radiolabeled N-oxide. ...

journal_title：Journal of medicinal chemistry

authors： Cashman JR

更新日期：1988-06-01 00:00:00

abstract：:The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in an ACKR3-selective ligand, FC313 [ cyclo(-d-Tyr-l-Arg...

journal_title：Journal of medicinal chemistry

authors： Sekiguchi H,Kuroyanagi T,Rhainds D,Kobayashi K,Kobayashi Y,Ohno H,Heveker N,Akaji K,Fujii N,Oishi S

更新日期：2018-04-26 00:00:00

abstract：:Various 3'-deoxythymidine analogues with an heterocyclic five-membered ring in the 3'-erythro position have been synthesized. The pyrrol-1-yl (3) and the 1,2,4-triazol-4-yl (5) compounds were synthesized from 1-(3-amino-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine. The pyrazol-1-yl (16a), imidazol-1-yl (16b), and...

journal_title：Journal of medicinal chemistry

authors： Wigerinck P,Van Aerschot A,Janssen G,Claes P,Balzarini J,De Clercq E,Herdewijn P

更新日期：1990-02-01 00:00:00

abstract：:1 (MTC-220), a conjugate of paclitaxel and a muramyl dipeptide analogue, has been synthesized as a novel agent of dual antitumor growth and metastasis activities. In vitro and in vivo tests show that 1 retains its ability to inhibit tumor growth. It is superior to paclitaxel in its ability to prevent tumor metastasis ...

journal_title：Journal of medicinal chemistry

authors： Ma Y,Zhao N,Liu G

更新日期：2011-04-28 00:00:00

abstract：:A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-positi...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Du W,Hwang I,Rayl TJ,Kimball FS,Leung D,Hoover HS,Apodaca RL,Breitenbucher JG,Cravatt BF,Boger DL

更新日期：2007-03-08 00:00:00

abstract：:Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x) (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously reported biphenyl-based inhibitors that would provide additional interactions with the protein. These compounds were assayed for the ability to inhibit the binding of sialyl Le...

journal_title：Journal of medicinal chemistry

authors： Kogan TP,Dupré B,Bui H,McAbee KL,Kassir JM,Scott IL,Hu X,Vanderslice P,Beck PJ,Dixon RA

更新日期：1998-03-26 00:00:00

abstract：:The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C(2) symmetry element, we constructed symmetric dimers with ...

journal_title：Journal of medicinal chemistry

authors： Demmer O,Dijkgraaf I,Schumacher U,Marinelli L,Cosconati S,Gourni E,Wester HJ,Kessler H

更新日期：2011-11-10 00:00:00

abstract：:The retinoid 6-[3'-(1-adamantyl)-4'-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN) and its active analogues induce cell-cycle arrest and programmed cell death (apoptosis) in cancer cells independently of retinoic acid receptor (RAR) interaction. Its analogue, (E)-4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-(3'-acetami...

journal_title：Journal of medicinal chemistry

authors： Dawson MI,Harris DL,Liu G,Hobbs PD,Lange CW,Jong L,Bruey-Sedano N,James SY,Zhang XK,Peterson VJ,Leid M,Farhana L,Rishi AK,Fontana JA

更新日期：2004-07-01 00:00:00

abstract：:4-(Phenylamino)-5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 1 and related compounds known as "diaryltubercidin" analogues are potent inhibitors of adenosine kinase (AK) and are orally active in animal models of pain such as the rat formalin paw model (GP3269 ED50= 6.4 mg/kg). However, the utility...

journal_title：Journal of medicinal chemistry

authors： Bookser BC,Ugarkar BG,Matelich MC,Lemus RH,Allan M,Tsuchiya M,Nakane M,Nagahisa A,Wiesner JB,Erion MD

更新日期：2005-12-01 00:00:00

abstract：:The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic...

journal_title：Journal of medicinal chemistry

authors： Gauthier JY,Jones T,Champion E,Charette L,Dehaven R,Ford-Hutchinson AW,Hoogsteen K,Lord A,Masson P,Piechuta H

更新日期：1990-10-01 00:00:00

abstract：:Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing p...

journal_title：Journal of medicinal chemistry

authors： Coxon GD,Furman BL,Harvey AL,McTavish J,Mooney MH,Arastoo M,Kennedy AR,Tettey JM,Waigh RD

更新日期：2009-06-11 00:00:00

abstract：:Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrat...

journal_title：Journal of medicinal chemistry

authors： Hampton A,Slotin LA,Kappler F,Sasaki T,Perini F

更新日期：1976-12-01 00:00:00

abstract：:A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 ade...

journal_title：Journal of medicinal chemistry

authors： Linden J,Patel A,Earl CQ,Craig RH,Daluge SM

更新日期：1988-04-01 00:00:00

abstract：:The AAA+ ATPase, p97, also referred to as VCP, plays an essential role in cellular homeostasis by regulating endoplasmic reticulum-associated degradation (ERAD), mitochondrial-associated degradation (MAD), chromatin-associated degradation, autophagy, and endosomal trafficking. Mutations in p97 have been linked to a nu...

journal_title：Journal of medicinal chemistry

authors： Huryn DM,Kornfilt DJP,Wipf P

更新日期：2020-03-12 00:00:00

abstract：:The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target o...

journal_title：Journal of medicinal chemistry

authors： Zhou HS,Hu LB,Zhang H,Shan WX,Wang Y,Li X,Liu T,Zhao J,You QD,Jiang ZY

更新日期：2020-10-08 00:00:00

abstract：:The synthesis of a series N-(4-piperidinyl)-1H-benzimidazol-2-amines and the preliminary evaluation of their in vitro and in vivo antihistaminic activity are described. Cyclodesulfurization of (2-aminophenyl)thioureas with mercury(II) oxide resulted in 2-aminobenzimidazole intermediates, which were monoalkylated on th...

journal_title：Journal of medicinal chemistry

authors： Janssens F,Torremans J,Janssen M,Stokbroekx RA,Luyckx M,Janssen PA

更新日期：1985-12-01 00:00:00

abstract：:Here we describe the design, synthesis, and pharmacological profile of 5-HT(1A) receptor ligands related to 1 (WAY-100635). The cyclohexyl moiety in 1 and its O-desmethylated analogue 3 were replaced by the bridgehead iodinated bridge-fused rings: adamantyl, cubyl, bicyclo[2.2.2]octyl, or bicyclo[2.2.1]heptyl. All ana...

journal_title：Journal of medicinal chemistry

authors： Al Hussainy R,Verbeek J,van der Born D,Braker AH,Leysen JE,Knol RJ,Booij J,Herscheid JK

更新日期：2011-05-26 00:00:00

abstract：:Conformational restriction of previously disclosed acyclic (diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 microM in a...

journal_title：Journal of medicinal chemistry

authors： Vaccaro W,Amore C,Berger J,Burrier R,Clader J,Davis H,Domalski M,Fevig T,Salisbury B,Sher R

更新日期：1996-04-12 00:00:00

abstract：:The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfh...

journal_title：Journal of medicinal chemistry

authors： Blankley CJ,Kaltenbronn JS,DeJohn DE,Werner A,Bennett LR,Bobowski G,Krolls U,Johnson DR,Pearlman WM,Hoefle ML

更新日期：1987-06-01 00:00:00

abstract：:A series of tetrahydropyranyl (THP) derivatives has been developed as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT) for use as anticancer agents. Structural modification of the submicromolar hit compound 3 led to the potent 3-methoxy substituted analogue 27. Further SAR development around th...

journal_title：Journal of medicinal chemistry

authors： Judd WR,Slattum PM,Hoang KC,Bhoite L,Valppu L,Alberts G,Brown B,Roth B,Ostanin K,Huang L,Wettstein D,Richards B,Willardsen JA

更新日期：2011-07-28 00:00:00

abstract：:Rexinoids are ligands for the retinoid X receptor (RXR) that have great promise for both the prevention and treatment of cancer and metabolic diseases. In this regard, synthetic, functional, and structural investigations into the structure-activity relationships of derivatives of the potent RXR agonist (E)-3-[3-(3,5,5...

journal_title：Journal of medicinal chemistry

authors： Pérez Santín E,Germain P,Quillard F,Khanwalkar H,Rodríguez-Barrios F,Gronemeyer H,de Lera AR,Bourguet W

更新日期：2009-05-28 00:00:00

abstract：:NF-κB-inducing kinase (NIK) is a protein kinase central to the noncanonical NF-κB pathway downstream from multiple TNF receptor family members, including BAFF, which has been associated with B cell survival and maturation, dendritic cell activation, secondary lymphoid organ development, and bone metabolism. We report ...

journal_title：Journal of medicinal chemistry

authors： Blaquiere N,Castanedo GM,Burch JD,Berezhkovskiy LM,Brightbill H,Brown S,Chan C,Chiang PC,Crawford JJ,Dong T,Fan P,Feng J,Ghilardi N,Godemann R,Gogol E,Grabbe A,Hole AJ,Hu B,Hymowitz SG,Alaoui Ismaili MH,Le H,Lee

更新日期：2018-08-09 00:00:00

abstract：:A noninvasive topical ocular therapy for the treatment of neovascular or "wet" age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in v...

journal_title：Journal of medicinal chemistry

authors： Adams CM,Anderson K,Artman G 3rd,Bizec JC,Cepeda R,Elliott J,Fassbender E,Ghosh M,Hanks S,Hardegger LA,Hosagrahara VP,Jaffee B,Jendza K,Ji N,Johnson L,Lee W,Liu D,Liu F,Long D,Ma F,Mainolfi N,Meredith EL,Miran

更新日期：2018-02-22 00:00:00

abstract：:Sepsis is characterized by a systemic inflammatory response syndrome. Derivatives of indole have been reported to exhibit diverse biological activities. This study reports on the design and synthesis of a new series of indole-2-carboxamide derivatives, which are screened for their anti-inflammatory activities in RAW 2...

journal_title：Journal of medicinal chemistry

authors： Liu Z,Tang L,Zhu H,Xu T,Qiu C,Zheng S,Gu Y,Feng J,Zhang Y,Liang G

更新日期：2016-05-26 00:00:00

abstract：:Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A ...

journal_title：Journal of medicinal chemistry

authors： Liu YA,Jin Q,Zou Y,Ding Q,Yan S,Wang Z,Hao X,Nguyen B,Zhang X,Pan J,Mo T,Jacobsen K,Lam T,Wu TY,Petrassi HM,Bursulaya B,DiDonato M,Gordon WP,Liu B,Baaten J,Hill R,Nguyen-Tran V,Qiu M,Zhang YQ,Kamireddy A,

更新日期：2020-03-26 00:00:00

abstract：:The melanocortin-3 (MC3) and melanocortin-4 (MC4) receptors regulate energy homeostasis, food intake, and associated physiological conditions. The melanocortin-4 receptor (MC4R) has been studied extensively. Less is known about specific physiological roles of the melanocortin-3 receptor (MC3R). A major obstacle to thi...

journal_title：Journal of medicinal chemistry

authors： Singh A,Dirain M,Witek R,Rocca JR,Edison AS,Haskell-Luevano C

更新日期：2013-04-11 00:00:00

abstract：:sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2...

journal_title：Journal of medicinal chemistry

authors： Nakazato A,Ohta K,Sekiguchi Y,Okuyama S,Chaki S,Kawashima Y,Hatayama K

更新日期：1999-03-25 00:00:00