Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1) Antagonists Demonstrating Potent in Vivo Activity.

abstract：:A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulf...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Xu SP,Zhu LY,Cosby LA,Sartorelli AC

更新日期：1989-07-01 00:00:00

abstract：:Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex...

journal_title：Journal of medicinal chemistry

authors： Lemaire S,Yamashiro D,Li CH

更新日期：1976-03-01 00:00:00

abstract：:Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting ma...

journal_title：Journal of medicinal chemistry

authors： Kim HS,Begum K,Ogura N,Wataya Y,Tokuyasu T,Masuyama A,Nojima M,McCullough KJ

更新日期：2002-10-10 00:00:00

abstract：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...

journal_title：Journal of medicinal chemistry

authors： Xu Y,Jiang G,Tsukahara R,Fujiwara Y,Tigyi G,Prestwich GD

更新日期：2006-08-24 00:00:00

abstract：:A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeli...

journal_title：Journal of medicinal chemistry

authors： Pepe A,Pamment M,Kim YS,Lee S,Lee MJ,Beebe K,Filikov A,Neckers L,Trepel JB,Malhotra SV

更新日期：2013-11-14 00:00:00

abstract：:2-Alkylchromen-4-one 6-O-sulfamates, a new class of potent steroid sulfatase (STS) inhibitors, were evaluated for their estrogenic potential. Structure-activity relationships for estrogenic activity were identified; however, no correlation with STS inhibition was found. Estrogenicity is favored by bulky side chains an...

journal_title：Journal of medicinal chemistry

authors： Nussbaumer P,Winiski AP,Billich A

更新日期：2003-11-06 00:00:00

abstract：:In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable f...

journal_title：Journal of medicinal chemistry

authors： Pemberton N,Mogemark M,Arlbrandt S,Bold P,Cox RJ,Gardelli C,Holden NS,Karabelas K,Karlsson J,Lever S,Li X,Lindmark H,Norberg M,Perry MWD,Petersen J,Rodrigo Blomqvist S,Thomas M,Tyrchan C,Westin Eriksson A,Zlatoidsky

更新日期：2018-06-28 00:00:00

abstract：:Electron deficient, bivalent sulfur atoms have two areas of positive electrostatic potential, a consequence of the low-lying σ* orbitals of the C-S bond that are available for interaction with electron donors including oxygen and nitrogen atoms and, possibly, π-systems. Intramolecular interactions are by far the most ...

journal_title：Journal of medicinal chemistry

authors： Beno BR,Yeung KS,Bartberger MD,Pennington LD,Meanwell NA

更新日期：2015-06-11 00:00:00

abstract：:Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligo...

journal_title：Journal of medicinal chemistry

authors： Serby MD,Zhao H,Szczepankiewicz BG,Kosogof C,Xin Z,Liu B,Liu M,Nelson LT,Kaszubska W,Falls HD,Schaefer V,Bush EN,Shapiro R,Droz BA,Knourek-Segel VE,Fey TA,Brune ME,Beno DW,Turner TM,Collins CA,Jacobson PB,Sham H

更新日期：2006-04-20 00:00:00

abstract：:Several imidazolylphenyl sulfamate and (imidazolylphenoxy)alkyl sulfamate derivatives were synthesized and evaluated as topically active carbonic anhydrase inhibitors. Water solubility, pKa, carbonic anhydrase inhibition, and partition coefficient for the compounds were measured. Sulfamic acid 2-[4-(1H-imidazol-1-yl)p...

journal_title：Journal of medicinal chemistry

authors： Lo YS,Nolan JC,Maren TH,Welstead WJ Jr,Gripshover DF,Shamblee DA

更新日期：1992-12-25 00:00:00

abstract：:Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2-(298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex vi...

journal_title：Journal of medicinal chemistry

authors： Gaudreau P,Brazeau P,Richer M,Cormier J,Langlois D,Langelier Y

更新日期：1992-01-24 00:00:00

abstract：:Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...

journal_title：Journal of medicinal chemistry

authors： Devraj R,Barrett JF,Fernandez JA,Katzenellenbogen JA,Cushman M

更新日期：1996-08-16 00:00:00

abstract：:A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y2, P2Y4, and P2Y6 stably expressed in 1321N1 astrocytoma cells. Substituents at N3 of UTP were poorly tolerated by P2Y2 and P2Y4 receptors. In contrast, a large phenacyl substitue...

journal_title：Journal of medicinal chemistry

authors： El-Tayeb A,Qi A,Müller CE

更新日期：2006-11-30 00:00:00

abstract：:Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2-p53 protein-protein interaction has been pursued as a new cancer therapeutic strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early phase...

journal_title：Journal of medicinal chemistry

authors： Zhao Y,Aguilar A,Bernard D,Wang S

更新日期：2015-02-12 00:00:00

abstract：:A class of new pyrimidinyl peptidomimetic agents (compounds 1-6) were synthesized, and their in vitro antimalarial activities against Plasmodium falciparum were evaluated. The core structure of the new agents consists of a substituted 5-aminopyrimidone ring and a Michael acceptor side chain methyl 2-hydroxymethyl-but-...

journal_title：Journal of medicinal chemistry

authors： Zhu S,Hudson TH,Kyle DE,Lin AJ

更新日期：2002-08-01 00:00:00

abstract：:Partially hydrogenated derivatives of the new heterocyclic ring systems benz[d]indolo[2,3-g]azecine and bisindolo[3,2-d][2, 3-g]azecine were synthesized starting from lactones and amines via the described synthetic methods. In binding assays with rat striatal receptors, 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indol...

journal_title：Journal of medicinal chemistry

authors： Witt T,Hock FJ,Lehmann J

更新日期：2000-05-18 00:00:00

abstract：:Somatostatin-14 (somatostatin) and its clinically available analogues octreotide, lanreotide, and vapreotide are potent inhibitors of growth hormone, insulin, and glucagon release. Recently, a novel backbone cyclic somatostatin analogue c(GABA-Phe-Trp-(D)Trp-Lys-Thr-Phe-GlyC3-NH(2)) (analogue 1, PTR 3173) that possess...

journal_title：Journal of medicinal chemistry

authors： Gazal S,Gelerman G,Ziv O,Karpov O,Litman P,Bracha M,Afargan M,Gilon C

更新日期：2002-04-11 00:00:00

abstract：:The synthesis of a series of 2-, 3-, and 4-substituted benzylamine derivatives is described. These compounds were studied for their effect on experimental cardiac arrhythmias. Many of the derivatives, but in particular 2-(p-methoxyphenylethynyl)benzylamine (3d), alpha,alpha-dimethyl-4y(phenylethynyl)benzylamine (7a), ...

journal_title：Journal of medicinal chemistry

authors： Remy DC,Van Saun WA Jr,Engelhardt EL

更新日期：1975-02-01 00:00:00

abstract：:Recruitment of suppressive CD4+ FOXP3+ regulatory T cells (Treg) to the tumor microenvironment (TME) has the potential to weaken the antitumor response in patients receiving treatment with immuno-oncology (IO) agents. Human Treg express CCR4 and can be recruited to the TME through the CC chemokine ligands CCL17 and CC...

journal_title：Journal of medicinal chemistry

authors： Jackson JJ,Ketcham JM,Younai A,Abraham B,Biannic B,Beck HP,Bui MHT,Chian D,Cutler G,Diokno R,Hu DX,Jacobson S,Karbarz E,Kassner PD,Marshall L,McKinnell J,Meleza C,Okal A,Pookot D,Reilly MK,Robles O,Shunatona HP

更新日期：2019-07-11 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：:Several compounds having portions of the camptothecin ring system were prepared. These compounds were screened against L1210 lymphoid leukemia with negative results. Two of the analogs which contained the pyridine and hydroxylactone D and E rings were also screened for inhibition of DNA and RNA syntheses in HeLa cells...

journal_title：Journal of medicinal chemistry

authors： Horwitz SB,Bristol JA,Comins DL,Davenport RW,Kane MJ,Lyle RE,Maloney JR,Portlock DE

更新日期：1975-05-01 00:00:00

abstract：:To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated produ...

journal_title：Journal of medicinal chemistry

authors： Huang GF,Okada M,De Clercq E,Torrence PF

更新日期：1981-04-01 00:00:00

abstract：:A new 1,4-dihydropyridine 5a, containing a cyano group at the C3 position, was recently reported to possess excellent mineralocorticoid receptor (MR) antagonist in vitro potency and no calcium channel-blocker (CCB) activity. In the present study, we report the structure-activity relationships of this novel series of c...

journal_title：Journal of medicinal chemistry

authors： Arhancet GB,Woodard SS,Iyanar K,Case BL,Woerndle R,Dietz JD,Garland DJ,Collins JT,Payne MA,Blinn JR,Pomposiello SI,Hu X,Heron MI,Huang HC,Lee LF

更新日期：2010-08-26 00:00:00

abstract：:Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes 1 and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC(50) values in the nanomolar range. The phe...

journal_title：Journal of medicinal chemistry

authors： Salem OI,Frotscher M,Scherer C,Neugebauer A,Biemel K,Streiber M,Maas R,Hartmann RW

更新日期：2006-01-26 00:00:00

abstract：:A series of analogues of the potent and selective sigma receptor ligand 1,3-ditolylguanidine (DTG) were synthesized and demonstrated to have high affinity for the sigma receptor as measured by in vitro [3H]DTG displacement studies using guinea pig brain tissue. Three of these 1-aryl-3-(1-adamantyl)guanidines were radi...

journal_title：Journal of medicinal chemistry

authors： Wilson AA,Dannals RF,Ravert HT,Sonders MS,Weber E,Wagner HN Jr

更新日期：1991-06-01 00:00:00

abstract：:The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromo...

journal_title：Journal of medicinal chemistry

authors： Buonsanti MF,Bertinaria M,Stilo AD,Cena C,Fruttero R,Gasco A

更新日期：2007-10-04 00:00:00

abstract：:In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds that mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular ...

journal_title：Journal of medicinal chemistry

authors： Thaker HD,Sgolastra F,Clements D,Scott RW,Tew GN

更新日期：2011-04-14 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：:The bromodomain and extra-terminal (BET) family proteins have recently emerged as promising drug targets for cancer therapy. In this study, identification of an 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one fragment (47) as a new binder to the BET bromodomains and the subsequent incorporation of fragment 47 to the scaffold...

journal_title：Journal of medicinal chemistry

authors： Li Z,Xiao S,Yang Y,Chen C,Lu T,Chen Z,Jiang H,Chen S,Luo C,Zhou B

更新日期：2020-04-23 00:00:00

abstract：:There is compelling evidence that Bax channel activity stimulates cytochrome c release leading ultimately to cell death, which is a key event in ischemic injuries and neurodegenerative diseases. Here 3,6-dibromocarbazole piperazine derivatives of 2-propanol are described as the first small and potent modulators of the...

journal_title：Journal of medicinal chemistry

authors： Bombrun A,Gerber P,Casi G,Terradillos O,Antonsson B,Halazy S

更新日期：2003-10-09 00:00:00