Discovery of a β-Hairpin Octapeptide, c[Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro], Mimetic of Agouti-Related Protein(87-132) [AGRP(87-132)] with Equipotent Mouse Melanocortin-4 Receptor (mMC4R) Antagonist Pharmacology.

abstract：:Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selectiv...

journal_title：Journal of medicinal chemistry

authors： Lin J,Deng H,Jin L,Pandey P,Quinn J,Cantin S,Rynkiewicz MJ,Gorga JC,Bibbins F,Celatka CA,Nagafuji P,Bannister TD,Meyers HV,Babine RE,Hayward NJ,Weaver D,Benjamin H,Stassen F,Abdel-Meguid SS,Strickler JE

更新日期：2006-12-28 00:00:00

abstract：:Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have...

journal_title：Journal of medicinal chemistry

authors： Chu CY,Chang CP,Chou YT,Handoko,Hu YL,Lo LC,Lin JJ

更新日期：2013-04-11 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：:An enzymatically activated liposome-based drug-delivery concept involving masked antitumor ether lipids (AELs) has been investigated. This concept takes advantage of the cytotoxic properties of AEL drugs as well as the membrane permeability enhancing properties of these molecules, which can lead to enhanced drug diffu...

journal_title：Journal of medicinal chemistry

authors： Andresen TL,Davidsen J,Begtrup M,Mouritsen OG,Jørgensen K

更新日期：2004-03-25 00:00:00

abstract：:Learning and memory deficits in Alzheimer's disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described that uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4-Methylthiazole (M...

journal_title：Journal of medicinal chemistry

authors： Qin Z,Luo J,VandeVrede L,Tavassoli E,Fa' M,Teich AF,Arancio O,Thatcher GR

更新日期：2012-08-09 00:00:00

abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...

journal_title：Journal of medicinal chemistry

authors： Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo R

更新日期：2012-11-26 00:00:00

abstract：:A number of 7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3d-d]pyrimidine derivatives that are structurally related to toyocamycin and sangivamycin and the seco nucleosides of tubercidin, toyocamycin, and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-brom...

journal_title：Journal of medicinal chemistry

authors： Gupta PK,Daunert S,Nassiri MR,Wotring LL,Drach JC,Townsend LB

更新日期：1989-02-01 00:00:00

abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...

journal_title：Journal of medicinal chemistry

authors： Chern JW,Tao PL,Wang KC,Gutcait A,Liu SW,Yen MH,Chien SL,Rong JK

更新日期：1998-08-13 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 use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological inte...

journal_title：Journal of medicinal chemistry

authors： Reis J,Gaspar A,Milhazes N,Borges F

更新日期：2017-10-12 00:00:00

abstract：:Several norindenoisoquinolines substituted with methoxy or methylenedioxy groups have been prepared and their anticancer properties evaluated in cancer cell cultures and in topoisomerase I inhibition assays. 2,3-Dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride (14) is a strong topoisomerase I i...

journal_title：Journal of medicinal chemistry

authors： Ioanoviciu A,Antony S,Pommier Y,Staker BL,Stewart L,Cushman M

更新日期：2005-07-28 00:00:00

abstract：:Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant ...

journal_title：Journal of medicinal chemistry

authors： Wu T,Nagle A,Kuhen K,Gagaring K,Borboa R,Francek C,Chen Z,Plouffe D,Goh A,Lakshminarayana SB,Wu J,Ang HQ,Zeng P,Kang ML,Tan W,Tan M,Ye N,Lin X,Caldwell C,Ek J,Skolnik S,Liu F,Wang J,Chang J,Li C,Hollenbe

更新日期：2011-07-28 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 CXC chemokine receptor 7 (CXCR7)/ACKR3 is a chemokine receptor that recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and interferon-inducible T-cell α chemoattractant (I-TAC)/CXCL11. Here, we report the development of novel CXCR7-selective ligands with a cyclic pentapeptide scaffold through an SAR study of ...

journal_title：Journal of medicinal chemistry

authors： Oishi S,Kuroyanagi T,Kubo T,Montpas N,Yoshikawa Y,Misu R,Kobayashi Y,Ohno H,Heveker N,Furuya T,Fujii N

更新日期：2015-07-09 00:00:00

abstract：:Recently described biphenyl analogues of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying poten...

journal_title：Journal of medicinal chemistry

authors： Sutherland HS,Blaser A,Kmentova I,Franzblau SG,Wan B,Wang Y,Ma Z,Palmer BD,Denny WA,Thompson AM

更新日期：2010-01-28 00:00:00

abstract：:An efficient and general method has been developed for fluorine-18 labeling of beta-blockers that possess the propanolamine moiety. A new synthetically versatile intermediate, 3-(1-(benzyloxy)propan-2-yl)-2-oxooxazolidin-5-yl)methyl 4-methylbenzenesulfonate (13), was prepared and can be conjugated to any phenoxy core....

journal_title：Journal of medicinal chemistry

authors： Stephenson KA,Wilson AA,Meyer JH,Houle S,Vasdev N

更新日期：2008-08-28 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...

journal_title：Journal of medicinal chemistry

authors： Yu LF,Zhang HK,Caldarone BJ,Eaton JB,Lukas RJ,Kozikowski AP

更新日期：2014-10-23 00:00:00

abstract：:Fragment-based drug discovery has become a powerful method for the generation of drug leads against therapeutic targets. Beyond the identification of novel and effective starting points for drug design, fragments have emerged as reliable tools for assessing protein druggability and identifying protein hot spots. Here,...

journal_title：Journal of medicinal chemistry

authors： Krimm I,Lancelin JM,Praly JP

更新日期：2012-02-09 00:00:00

abstract：:Catechol O-methyltransferase (COMT) is the enzyme responsible for the O-methylation of endogenous neurotransmitters and of xenobiotic substances and hormones incorporating catecholic structures. COMT is a druggable biological target for the treatment of various central and peripheral nervous system disorders, includin...

journal_title：Journal of medicinal chemistry

authors： Kiss LE,Soares-da-Silva P

更新日期：2014-11-13 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：:Spiropyrimidinetriones are a novel class of antibacterial agents that target the bacterial type II topoisomerase via a new mode of action. Compound ETX0914 is thus far the only drug from this class that is being evaluated in clinical trials. To improve the antibacterial activity and pharmacokinetic properties of ETX09...

journal_title：Journal of medicinal chemistry

authors： Shi C,Zhang Y,Wang T,Lu W,Zhang S,Guo B,Chen Q,Luo C,Zhou X,Yang Y

更新日期：2019-03-28 00:00:00

abstract：:Extension of the structure-activity relationship studies that led to the discovery of the nonsedating potent muscle relaxant, antiinflammatory, and analgesic agent (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 1, has given rise to (E)-2-(4-chloro-6-fluoro-1-indanylidene)-N-methylacetamide, 2. Compound 2 is a potent an...

journal_title：Journal of medicinal chemistry

authors： Musso DL,Orr GF,Cochran FR,Kelley JL,Selph JL,Rigdon GC,Cooper BR,Jones ML

更新日期：2003-01-30 00:00:00

abstract：:We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more p...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Zou H,Lin S,Lin H,Soh RT,Lim FH,Koh WL,Li J,Lakshminarayanan R,Verma C,Tan DT,Cao D,Beuerman RW,Liu S

更新日期：2016-01-14 00:00:00

abstract：:The tetrapeptide sequence His-Phe-Arg-Trp, derived from melanocyte-stimulating hormone (alphaMSH) and its analogs, causes a decrease in food intake and elevates energy utilization upon binding to the melanocortin-4 receptor (MC4R). To utilize this sequence as an effective agent for treating obesity, we improved its me...

journal_title：Journal of medicinal chemistry

authors： Hess S,Linde Y,Ovadia O,Safrai E,Shalev DE,Swed A,Halbfinger E,Lapidot T,Winkler I,Gabinet Y,Faier A,Yarden D,Xiang Z,Portillo FP,Haskell-Luevano C,Gilon C,Hoffman A

更新日期：2008-02-28 00:00:00

abstract：:New analogues of flavone-8-acetic acid were synthesized, bearing an alkoxy group in position 3 and different substituents on the benzene ring in position 2 of the flavone nucleus. The compounds were tested for direct cytotoxicity against four human tumor cell lines and for indirect antitumor effects by measuring their...

journal_title：Journal of medicinal chemistry

authors： Gobbi S,Rampa A,Bisi A,Belluti F,Piazzi L,Valenti P,Caputo A,Zampiron A,Carrara M

更新日期：2003-08-14 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：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...

journal_title：Journal of medicinal chemistry

authors： Clark RL,Pessolano AA,Shen TY,Jacobus DP,Jones H,Lotti VJ,Flataker LM

更新日期：1978-09-01 00:00:00

abstract：:N-Methylation of two retinoidal amide compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (3, Am80) and 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carbonyl]amino]benzoic acid (5, Am580), resulted in the disappearance of their potent differentiation-inducing act...

journal_title：Journal of medicinal chemistry

authors： Kagechika H,Himi T,Kawachi E,Shudo K

更新日期：1989-10-01 00:00:00

abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of 14 camptothecin derivatives of polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A) camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43 are descri...

journal_title：Journal of medicinal chemistry

authors： Zhao R,al-Said NH,Sternbach DL,Lown JW

更新日期：1997-01-17 00:00:00

abstract：:The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structu...

journal_title：Journal of medicinal chemistry

authors： Wade RC,Clark KJ,Goodford PJ

更新日期：1993-01-08 00:00:00