Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications.

abstract：:We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized int...

journal_title：Journal of medicinal chemistry

authors： Kawakami M,Koya K,Ukai T,Tatsuta N,Ikegawa A,Ogawa K,Shishido T,Chen LB

更新日期：1998-01-01 00:00:00

abstract：:The synthesis and the X-ray structure of 16a-thiocamptothecin (TCPT), the thiopyridone analog of camptothecin (CPT), are accomplished. The crystal contains two structurally identical, yet independent molecules. Both of them are connected to other molecules via two intermolecular hydrogen bonds. S-methylation of TCPT l...

journal_title：Journal of medicinal chemistry

authors： Samorì C,Guerrini A,Varchi G,Zunino F,Beretta GL,Femoni C,Bombardelli E,Fontana G,Battaglia A

更新日期：2008-05-22 00:00:00

abstract：:A series of novel CCK tetrapeptide analogues of the general formula Boc-Trp-Lys(Tac)-N(R)-(CH2)nCON(R')Phe-NH2 (Tac = o-tolylaminocarbonyl), where R,R' = H or Me and n = 1-5, have been synthesized and tested. These analogues, which lack an acidic residue at the penultimate position, demonstrated surprisingly high CCK-...

journal_title：Journal of medicinal chemistry

authors： Elliott RL,Kopecka H,Tufano MD,Shue YK,Gauri AJ,Lin CW,Bianchi BR,Miller TR,Witte DG,Stashko MA

更新日期：1994-05-27 00:00:00

abstract：:We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterifi...

journal_title：Journal of medicinal chemistry

authors： McGuigan C,Madela K,Aljarah M,Bourdin C,Arrica M,Barrett E,Jones S,Kolykhalov A,Bleiman B,Bryant KD,Ganguly B,Gorovits E,Henson G,Hunley D,Hutchins J,Muhammad J,Obikhod A,Patti J,Walters CR,Wang J,Vernachio J,Ra

更新日期：2011-12-22 00:00:00

abstract：:Following the recent discoveries that some L-nucleosides are more or equal potent than their D-counterparts, we synthesized 2'-deoxy-2',2'-difluoro-L-erythro-pentofuranosyl nucleosides as potential antiviral agents. The target compounds were synthesized via the key intermediates 7a or 7b from L-gulono gamma-lactone. C...

journal_title：Journal of medicinal chemistry

authors： Kotra LP,Xiang Y,Newton MG,Schinazi RF,Cheng YC,Chu CK

更新日期：1997-10-24 00:00:00

abstract：:We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed aga...

journal_title：Journal of medicinal chemistry

authors： Pandey A,Volkots DL,Seroogy JM,Rose JW,Yu JC,Lambing JL,Hutchaleelaha A,Hollenbach SJ,Abe K,Giese NA,Scarborough RM

更新日期：2002-08-15 00:00:00

abstract：:In a previous study, we described affinity labeling of the lamb uterine estrogen receptor by 17 alpha-[(bromoacetoxy)alkyl/alkynyl]estradiols. However, the intrinsic receptor-alkylating activities of these compounds were probably very hampered by their poor hydrolytic stability in estrogen receptor-containing tissue e...

journal_title：Journal of medicinal chemistry

authors： el Garrouj D,Aliau S,Aumelas A,Borgna JL

更新日期：1995-06-23 00:00:00

abstract：:A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay...

journal_title：Journal of medicinal chemistry

authors： Bradbury RH,Allott CP,Dennis M,Fisher E,Major JS,Masek BB,Oldham AA,Pearce RJ,Rankine N,Revill JM

更新日期：1992-10-30 00:00:00

abstract：:The functional in vitro study of the enantiomers of imidazolines 4-7 highlighted the role played by the nature of the ortho phenyl substituent in determining the preferred α(2C)-AR configuration. Indeed, the (S) enantiomers of 4-6 or (R) enantiomer of 7 behave as eutomers and activate this subtype as full agonists; th...

journal_title：Journal of medicinal chemistry

authors： Del Bello F,Mattioli L,Ghelfi F,Giannella M,Piergentili A,Quaglia W,Cardinaletti C,Perfumi M,Thomas RJ,Zanelli U,Marchioro C,Dal Cin M,Pigini M

更新日期：2010-11-11 00:00:00

abstract：:Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore th...

journal_title：Journal of medicinal chemistry

authors： Huddle BC,Grimley E,Buchman CD,Chtcherbinine M,Debnath B,Mehta P,Yang K,Morgan CA,Li S,Felton J,Sun D,Mehta G,Neamati N,Buckanovich RJ,Hurley TD,Larsen SD

更新日期：2018-10-11 00:00:00

abstract：:A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimetho...

journal_title：Journal of medicinal chemistry

authors： Dillard RD,Yen TT,Stark P,Pavey DE

更新日期：1980-07-01 00:00:00

abstract：:We previously have reported four possible binding conformation of dynorphin A (Dyn A) for the central kappa opioid receptors, induced by the address sequence, using a molecular mechanics energy minimization approach. The lowest energy conformation was found to exhibit an alpha-helical conformation in the cyclized addr...

journal_title：Journal of medicinal chemistry

authors： Lung FD,Collins N,Stropova D,Davis P,Yamamura HI,Porreca F,Hruby VJ

更新日期：1996-03-01 00:00:00

abstract：:cKIT kinase inhibitors, e.g., imatinib, could induce drug-acquired mutations such as cKIT T670I that rendered drug resistance after chronic treatment. Through a type II kinase inhibitor design approach we discovered a highly potent type II cKIT kinase inhibitor compound 35 (CHMFL-KIT-8140), which potently inhibited bo...

journal_title：Journal of medicinal chemistry

authors： Li B,Wang A,Liu J,Qi Z,Liu X,Yu K,Wu H,Chen C,Hu C,Wang W,Wu J,Hu Z,Ye L,Zou F,Liu F,Wang B,Wang L,Ren T,Zhang S,Bai M,Zhang S,Liu J,Liu Q

更新日期：2016-09-22 00:00:00

abstract：:(6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydropteroic acid was synthesized in several steps from 4,4-(ethylenedioxy)-cyclohexanone and [4-(tert-butyloxycarbonyl)benzyl]triphenylphosphonium bromide and was elaborated to (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid and (6R,6S)-5,8,10-trideaza-5,6,7,8-te...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Moran RG

更新日期：1989-03-01 00:00:00

abstract：:A new class of acyclic adenosine analogues is described which exhibit broad-spectrum antiviral activity and are apparently targeted at S-adenosyl-L-homocysteine hydrolase. The compounds are all alkyl (i.e., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, tert-butyl, 1-pentyl, 3-methylbutyl, 1-octy...

journal_title：Journal of medicinal chemistry

authors： De Clercq E,Holý A

更新日期：1985-03-01 00:00:00

abstract：:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we...

journal_title：Journal of medicinal chemistry

authors： Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

更新日期：2004-01-29 00:00:00

abstract：:Structural genomics will yield an immense number of protein three-dimensional structures in the near future. Automated theoretical methodologies are needed to exploit this information and are likely to play a pivotal role in drug discovery. Here, we present a fully automated, efficient docking methodology that does no...

journal_title：Journal of medicinal chemistry

authors： Glick M,Grant GH,Richards WG

更新日期：2002-10-10 00:00:00

abstract：:1, 8-Disubstituted derivatives of adenosine cyclic 3', 5'-phosphate (cAMP) were synthesized by N-oxidation or N-methylation of previously reported 8-substituted cAMP derivatives to yield 8-bromoadenosine cyclic 3', 5'-phosphate 1-oxide and 8-(benzylthio)-1-methyladenosine cyclic 3', 5'-phosphate. Substituents were int...

journal_title：Journal of medicinal chemistry

authors： Uno H,Meyer RB,Shuman DA,Robins RK,Simon LN,Miller JP

更新日期：1976-03-01 00:00:00

abstract：:Sepsis, which is a systemic inflammatory response that follows a bacterial infection, has a high mortality rate and limited therapeutic options. Here we show that the antimicrobial peptide OH-CATH30, which naturally occurs in snake, selectively regulates the innate immune response to protect mice from lethal sepsis. T...

journal_title：Journal of medicinal chemistry

authors： Li SA,Xiang Y,Wang YJ,Liu J,Lee WH,Zhang Y

更新日期：2013-11-27 00:00:00

abstract：:In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist 0 (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized....

journal_title：Journal of medicinal chemistry

authors： Zhang M,Xu B,Li N,Liu H,Shi X,Zhang Q,Shi Y,Xu K,Xiao J,Chen D,Zhu H,Sun Y,Zhang T,Zhang R,Fang Q

更新日期：2020-12-24 00:00:00

abstract：:NAD+ has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Although the beneficial effects of boosting NAD+ on mitochondrial fitness, metabolism, and li...

journal_title：Journal of medicinal chemistry

authors： Pellicciari R,Liscio P,Giacchè N,De Franco F,Carotti A,Robertson J,Cialabrini L,Katsyuba E,Raffaelli N,Auwerx J

更新日期：2018-02-08 00:00:00

abstract：:Glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) are proglucagon derived peptides that are released from gut endocrine cells in response to nutrient intake. These molecules are rapidly inactivated by the action of dipeptidyl peptidase IV (DPP-4) which limits their use as therapeutic agents. The rece...

journal_title：Journal of medicinal chemistry

authors： Suzuki R,Brown GA,Christopher JA,Scully CCG,Congreve M

更新日期：2020-02-13 00:00:00

abstract：:In drug discovery, it is essential to identify binding sites on protein surfaces that drug-like molecules could exploit to exert a biological effect. Both X-ray crystallography and NMR experiments have demonstrated that organic solvents bind precisely at these locations. We show that this effect is reproduced using mo...

journal_title：Journal of medicinal chemistry

authors： Seco J,Luque FJ,Barril X

更新日期：2009-04-23 00:00:00

abstract：:While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improv...

journal_title：Journal of medicinal chemistry

authors： Chen X,Giraldes J,Sprague ER,Shakya S,Chen Z,Wang Y,Joud C,Mathieu S,Chen CH,Straub C,Duca J,Hurov K,Yuan Y,Shao W,Touré BB

更新日期：2017-03-09 00:00:00

abstract：:Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form,...

journal_title：Journal of medicinal chemistry

authors： Primofiore G,Marini AM,Da Settimo F,Martini C,Bardellini A,Giannaccini G,Lucacchini A

更新日期：1989-12-01 00:00:00

abstract：:In previous reports illustrating the effects of conformational restriction of the N-terminal region of human pancreatic growth hormone releasing factor, we demonstrated that D-amino acid substitutions in either of positions 1, 2, or 3 resulted in greatly increased growth hormone releasing activity both in vivo and in ...

journal_title：Journal of medicinal chemistry

authors： Coy DH,Murphy WA,Sueiras-Diaz J,Coy EJ,Lance VA

更新日期：1985-02-01 00:00:00

abstract：:The clinical use of anticancer lipids is severely limited by their ability to cause lysis of red blood cells prohibiting intravenous injection. Novel delivery systems are therefore required in order to develop anticancer ether lipids (AELs) into clinically useful anticancer drugs. In a recent article (J. Med. Chem. 20...

journal_title：Journal of medicinal chemistry

authors： Andresen TL,Jensen SS,Madsen R,Jørgensen K

更新日期：2005-11-17 00:00:00

abstract：:A series of tetrahydrobenzofuranyl and tetrahydrobenzothienyl propenoic acids that showed potent agonist activity against RXRalpha were synthesized via a structure-based design approach. Among the compounds studied, 46a,b showed not only very good potency against RXRalpha (K(i) = 6 nM) but was also found to be greater...

journal_title：Journal of medicinal chemistry

authors： Haffner CD,Lenhard JM,Miller AB,McDougald DL,Dwornik K,Ittoop OR,Gampe RT Jr,Xu HE,Blanchard S,Montana VG,Consler TG,Bledsoe RK,Ayscue A,Croom D

更新日期：2004-04-08 00:00:00

abstract：:The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examine...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Dickinson RP,Parry MJ,Randall MJ

更新日期：1986-09-01 00:00:00

abstract：:Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the development of a selective JAK2 inhibitor. A program to optimize select...

journal_title：Journal of medicinal chemistry

authors： Dugan BJ,Gingrich DE,Mesaros EF,Milkiewicz KL,Curry MA,Zulli AL,Dobrzanski P,Serdikoff C,Jan M,Angeles TS,Albom MS,Mason JL,Aimone LD,Meyer SL,Huang Z,Wells-Knecht KJ,Ator MA,Ruggeri BA,Dorsey BD

更新日期：2012-06-14 00:00:00