N-Benzyl/Aryl Substituted Tryptanthrin as Dual Inhibitors of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase.

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：:Membrane-bound aminopeptidase P (AP-P) participates in the degradation of bradykinin in several vascular beds. We have developed an inhibitor of AP-P called apstatin (1) (N-[(2S, 3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-prolyl-L-prolyl-L-al aninam ide); IC50,human = 2.9 microM. In the rat, apstatin can potentiate th...

journal_title：Journal of medicinal chemistry

authors： Maggiora LL,Orawski AT,Simmons WH

更新日期：1999-07-01 00:00:00

abstract：:Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs...

journal_title：Journal of medicinal chemistry

authors： Hagen H,Marzenell P,Jentzsch E,Wenz F,Veldwijk MR,Mokhir A

更新日期：2012-01-26 00:00:00

abstract：:Starting from the structure of the novel nonpeptidic angiotensin II antagonist DuP 753, a series of more rigid analogues was prepared by replacing the biphenyl part of DuP 753 with a naphthalene ring. Five different regioisomers (compounds 6a-e) were synthesized, and receptor binding in rat smooth muscle cell preparat...

journal_title：Journal of medicinal chemistry

authors： Bühlmayer P,Criscione L,Fuhrer W,Furet P,de Gasparo M,Stutz S,Whitebread S

更新日期：1991-10-01 00:00:00

abstract：:The delta-selective opioid peptide deltorphin C(H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) (DEL C) was modified by para-substitution of Phe3 with halogens (F, Cl, Br, I), amino, or nitro groups. The bioactive potencies in peripheral tissues and brain receptor selectivities of these analogues depended upon the particular sub...

journal_title：Journal of medicinal chemistry

authors： Salvadori S,Bianchi C,Lazarus LH,Scaranari V,Attila M,Tomatis R

更新日期：1992-12-11 00:00:00

abstract：:To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...

journal_title：Journal of medicinal chemistry

authors： Berardi F,Abate C,Ferorelli S,de Robertis AF,Leopoldo M,Colabufo NA,Niso M,Perrone R

更新日期：2008-12-11 00:00:00

abstract：:Certain structural similarities between prostaglandins with close-packed side chains and the perhydrocyclopentanophenanthrene nucleus of steroids prompted the synthesis and biological evaluation of 6beta, 17 beta-dihydroxy-5alpha-androstane-2alpha-carboxylic acid (30), its 6-deoxy derivative 28, and the corresponding ...

journal_title：Journal of medicinal chemistry

authors： Venton DL,Counsell RE,Sanner JH,Sierra K

更新日期：1975-01-01 00:00:00

abstract：:CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Å resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of C...

journal_title：Journal of medicinal chemistry

authors： Smith EW,Liu Y,Getschman AE,Peterson FC,Ziarek JJ,Li R,Volkman BF,Chen Y

更新日期：2014-11-26 00:00:00

abstract：:Protein tyrosine phosphatases (PTPs) constitute a diverse family of enzymes that, together with protein tyrosine kinases, control the level of intracellular tyrosine phosphorylation, thus regulating many cellular functions. PTP1B negatively regulates insulin signaling, in part, by dephosphorylating key tyrosine residu...

journal_title：Journal of medicinal chemistry

authors： Liljebris C,Larsen SD,Ogg D,Palazuk BJ,Bleasdale JE

更新日期：2002-04-25 00:00:00

abstract：:The dopamine D(3) receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D(3) versus D(2) receptor-preferring ligands, the partial agonist BP 897 was taken as a lead structure. Variations in the spacer and the aryl moie...

journal_title：Journal of medicinal chemistry

authors： Hackling A,Ghosh R,Perachon S,Mann A,Höltje HD,Wermuth CG,Schwartz JC,Sippl W,Sokoloff P,Stark H

更新日期：2003-08-28 00:00:00

abstract：:A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the co...

journal_title：Journal of medicinal chemistry

authors： Depreux P,Lesieur D,Mansour HA,Morgan P,Howell HE,Renard P,Caignard DH,Pfeiffer B,Delagrange P,Guardiola B

更新日期：1994-09-30 00:00:00

abstract：:Four subtypes of adenosine receptors are currently known, that is, A(1), A(2A), A(2B), and A(3) receptors. Interestingly, quite substantial species differences exist especially between human and rat A(3) receptors. As a result, ligands such as CCPA, which are very selective for the rat A(1) receptor versus the human A...

journal_title：Journal of medicinal chemistry

authors： Beukers MW,Wanner MJ,Von Frijtag Drabbe Künzel JK,Klaasse EC,IJzerman AP,Koomen GJ

更新日期：2003-04-10 00:00:00

abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds w...

journal_title：Journal of medicinal chemistry

authors： Ali A,Reddy GS,Nalam MN,Anjum SG,Cao H,Schiffer CA,Rana TM

更新日期：2010-11-11 00:00:00

abstract：:The synthesis and antihypertensive activity of a series of novel 3-[(substituted-carbonyl)amino]-2H-1-benzopyran-4-ols, administered orally to spontaneously hypertensive rats, are described. Optimum activity in this series was observed for compounds with branched alkyl or branched alkylamino groups flanking the carbon...

journal_title：Journal of medicinal chemistry

authors： Cassidy F,Evans JM,Hadley MS,Haladij AH,Leach PE,Stemp G

更新日期：1992-05-01 00:00:00

abstract：:TYK2 is an emerging drug target for various human autoimmune diseases. However, discovery of selective TYK2 inhibitor over other JAK family members (i.e., JAK1, 2, 3) by targeting the catalytically active site (Janus Homologue 1 (JH1) domain) is challenging. This Viewpoint discusses the discovery of a series of N-meth...

journal_title：Journal of medicinal chemistry

authors： Chang Y,Xu S,Ding K

更新日期：2019-10-24 00:00:00

abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...

journal_title：Journal of medicinal chemistry

authors： Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

更新日期：2003-05-22 00:00:00

abstract：:Fourteen structurally diverse Annonaceous acetogenins, representing the three main classes of bis-adjacent, bis-nonadjacent, and single-THF ring(s), were tested for their ability to inhibit the growth of adriamycin resistant human mammary adenocarcinoma (MCF-7/Adr) cells. This cell line is resistant to treatment with ...

journal_title：Journal of medicinal chemistry

authors： Oberlies NH,Chang CJ,McLaughlin JL

更新日期：1997-06-20 00:00:00

abstract：:Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in the cytosolic solubilization of fatty acids during fat absorption. In the current studies, the interaction of L-FABP with a range of lipophilic drugs has been evaluated to explore the potential for L-FABP to provide an ...

journal_title：Journal of medicinal chemistry

authors： Chuang S,Velkov T,Horne J,Porter CJ,Scanlon MJ

更新日期：2008-07-10 00:00:00

abstract：:A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the ...

journal_title：Journal of medicinal chemistry

authors： Xu H,Baidoo K,Gunn AJ,Boswell CA,Milenic DE,Choyke PL,Brechbiel MW

更新日期：2007-09-20 00:00:00

abstract：:Quantitative structure-activity studies were carried out on a series of N-isopropylaryl hydrazides which inhibits monoamine oxidase (MAO). The inhibitory potencies of these compounds of MAO were found to correlate with the electron-withdrawing capacity of the aryl ring substituents as estimated by both empirical Hamme...

journal_title：Journal of medicinal chemistry

authors： Johnson CL

更新日期：1976-05-01 00:00:00

abstract：:A series of esters of 6beta-hydroxynortropane and the N-methyl analogue 6beta-tropanol were synthesized and screened versus binding of an antagonist (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)-, m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and on native...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Gupta TH,Padgett WL,Pei XF

更新日期：2000-06-29 00:00:00

abstract：:Polymeric nanoparticles (PNPs) may efficiently deliver in vivo therapeutics to tumors when conjugated to specific targeting agents. Gint4.T aptamer specifically recognizes platelet-derived growth factor receptor β and can cross the blood-brain barrier (BBB). We synthesized Gint4.T-conjugated PNPs able of high uptake i...

journal_title：Journal of medicinal chemistry

authors： Monaco I,Camorani S,Colecchia D,Locatelli E,Calandro P,Oudin A,Niclou S,Arra C,Chiariello M,Cerchia L,Comes Franchini M

更新日期：2017-05-25 00:00:00

abstract：:The gold(I) complexes of the general formula [Au(L(n))(PPh(3))]·xH(2)O (1-8; n = 1-8 and x = 0-1.5), where L(n) stands for a deprotonated form of the benzyl-substituted derivatives of 6-benzylaminopurine, were prepared, thoroughly characterized (elemental analyses, FT-IR, Raman and multinuclear NMR spectroscopy, ESI+ ...

journal_title：Journal of medicinal chemistry

authors： Trávníček Z,Starha P,Vančo J,Silha T,Hošek J,Suchý P Jr,Pražanová G

更新日期：2012-05-24 00:00:00

abstract：:Neuropeptide S (NPS) is the endogenous ligand of the previously orphan G-protein coupled receptor now named NPSR. The NPS-NPSR receptor system regulates important biological functions such as sleep/waking, locomotion, anxiety and food intake. Recently, exhaustive Ala scan and d-amino acid scan studies, together with s...

journal_title：Journal of medicinal chemistry

authors： Tancredi T,Guerrini R,Marzola E,Trapella C,Calo G,Regoli D,Reinscheid RK,Camarda V,Salvadori S,Temussi PA

更新日期：2007-09-06 00:00:00

abstract：:A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and ...

journal_title：Journal of medicinal chemistry

authors： Hirose N,Kuriyama S,Kato Y,Toyoshima S

更新日期：1976-02-01 00:00:00

abstract：:The mitotic kinesin Eg5 is critical for the assembly of the mitotic spindle and is a promising chemotherapy target. Previously, we identified S-trityl-L-cysteine as a selective inhibitor of Eg5 and developed triphenylbutanamine analogues with improved potency, favorable drug-like properties, but moderate in vivo activ...

journal_title：Journal of medicinal chemistry

authors： Good JA,Wang F,Rath O,Kaan HY,Talapatra SK,Podgórski D,MacKay SP,Kozielski F

更新日期：2013-03-14 00:00:00

abstract：:Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, ...

journal_title：Journal of medicinal chemistry

authors： Sham HL,Bolis G,Stein HH,Fesik SW,Marcotte PA,Plattner JJ,Rempel CA,Greer J

更新日期：1988-02-01 00:00:00

abstract：:A structure-guided design approach using a homology model of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was used to improve the potency of a series of imidazopyridazine inhibitors as potential antimalarial agents. This resulted in high affinity compounds with PfCDPK1 enzyme IC50 values less tha...

journal_title：Journal of medicinal chemistry

authors： Chapman TM,Osborne SA,Wallace C,Birchall K,Bouloc N,Jones HM,Ansell KH,Taylor DL,Clough B,Green JL,Holder AA

更新日期：2014-04-24 00:00:00

abstract：:Homologous recombination repair (HRR), a crucial approach in DNA damage repair, is an attractive target in cancer therapy and drug design. The Bloom syndrome protein (BLM) is a 3'-5' DNA helicase that performs an important role in HRR regulation. However, limited studies about BLM inhibitors and their biological effec...

journal_title：Journal of medicinal chemistry

authors： Yin QK,Wang CX,Wang YQ,Guo QL,Zhang ZL,Ou TM,Huang SL,Li D,Wang HG,Tan JH,Chen SB,Huang ZS

更新日期：2019-03-28 00:00:00

abstract：:A weak, nonselective G protein-coupled receptor 120 (GPR120) agonist 10 was found by screening a series of carboxylic acids derived from the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist 3. Modification based on the homology model of GPR120 led to the first GPR120-selective agonist 12. These res...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Igari S,Hirasawa A,Hata M,Ishiguro M,Fujieda H,Itoh Y,Hirano T,Nakagawa H,Ogura M,Makishima M,Tsujimoto G,Miyata N

更新日期：2008-12-11 00:00:00