Dual Leucine Zipper Kinase Inhibitors for the Treatment of Neurodegeneration.

abstract：:Structure/activity studies on atrial natriuretic peptide ANP (1-28) have highlighted three portions of the native molecule as necessary for its biological responses. We have linked these three regions and excised the remaining segments to produce a family of small analogues (less than half the size of the parent) whic...

journal_title：Journal of medicinal chemistry

authors： von Geldern TW,Rockway TW,Davidsen SK,Budzik GP,Bush EN,Chu-Moyer MY,Devine EM Jr,Holleman WH,Johnson MC,Lucas SD

更新日期：1992-03-06 00:00:00

abstract：:In this article, we report the findings of a comprehensive structure-activity relationship study of N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters, in which novel analogues were designed, synthesized, and evaluated in vitro for antiproliferative effect. Two new compounds, 2 and 16, showed potent nanomolar activit...

journal_title：Journal of medicinal chemistry

authors： Mooney A,Tiedt R,Maghoub T,O'Donovan N,Crown J,White B,Kenny PT

更新日期：2012-06-14 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：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...

journal_title：Journal of medicinal chemistry

authors： Yahalom D,Rahimipour S,Koch Y,Ben-Aroya N,Fridkin M

更新日期：2000-07-27 00:00:00

abstract：:The modification of 3'-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and s...

journal_title：Journal of medicinal chemistry

authors： Dhanya RP,Sidique S,Sheffler DJ,Nickols HH,Herath A,Yang L,Dahl R,Ardecky R,Semenova S,Markou A,Conn PJ,Cosford ND

更新日期：2011-01-13 00:00:00

abstract：:A series of D-erythro- and L-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B(1) (FB(1)) on axonal growth in hippocampal neurons. The analogues contained either a C(7) side chain or a phenyl group substituted for the C(13) residue present in n...

journal_title：Journal of medicinal chemistry

authors： Van Overmeire I,Boldin SA,Dumont F,Van Calenbergh S,Slegers G,De Keukeleire D,Futerman AH,Herdewijn P

更新日期：1999-07-15 00:00:00

abstract：:Inhibition of the bromodomain of the transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed in vivo chemical tool 1 (GNE-272) for the bromodomain of CBP that was moderately potent and selective over BRD4(1). In pursuit of a more potent and selective ...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Murray J,Lai KW,Tsui V,Albrecht BK,An L,Beresini MH,de Leon Boenig G,Bronner SM,Chan EW,Chen KX,Chen Z,Choo EF,Clagg K,Clark K,Crawford TD,Cyr P,de Almeida Nagata D,Gascoigne KE,Grogan JL,Hatzivassiliou

更新日期：2017-11-22 00:00:00

abstract：:MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methylt...

journal_title：Journal of medicinal chemistry

authors： Karatas H,Townsend EC,Bernard D,Dou Y,Wang S

更新日期：2010-07-22 00:00:00

abstract：:In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use...

journal_title：Journal of medicinal chemistry

authors： Karlén A,Helander A,Kenne L,Hacksell U

更新日期：1989-04-01 00:00:00

abstract：:Continuing our search for vitamin D analogues, we explored the modification of the steroidal side chain and inserted a methylene moiety in position C-22 together with either lengthening the side chain or introducing a ring at the terminal end. Our conformational studies confirmed that the presence of a methylene group...

journal_title：Journal of medicinal chemistry

authors： Sibilska-Kaminski IK,Sicinski RR,Plum LA,DeLuca HF

更新日期：2020-07-09 00:00:00

abstract：:Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluate...

journal_title：Journal of medicinal chemistry

authors： Haadsma-Svensson SR,Svensson K,Duncan N,Smith MW,Lin CH

更新日期：1995-02-17 00:00:00

abstract：:The synthesis of analogues of the antipsychotic drug butaclamol bearing chloro substituents on the benzene rings is described. On the basis of a perceived topographical similarity of a putative chlorophenylethylamine pharmacophore present in these analogues and in VUFB-10032 and doclothepin, agents related to octoclot...

journal_title：Journal of medicinal chemistry

authors： Humber LG,Sideridis N,Asselin AA,Bruderlein FT,Voith K

更新日期：1978-12-01 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：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...

journal_title：Journal of medicinal chemistry

authors： Witiak DT,Kakodkar SV,Brunst GE,Baldwin JR,Rahwan RG

更新日期：1978-12-01 00:00:00

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：:A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT(2) receptor accommodating the "out-of-plane" substituent of MT(2)-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety ...

journal_title：Journal of medicinal chemistry

authors： Zlotos DP,Attia MI,Julius J,Sethi S,Witt-Enderby PA

更新日期：2009-02-12 00:00:00

abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...

journal_title：Journal of medicinal chemistry

authors： Nabuurs SB,Wagener M,de Vlieg J

更新日期：2007-12-27 00:00:00

abstract：:The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the redu...

journal_title：Journal of medicinal chemistry

authors： Self CR,Barber WE,Machin PJ,Osbond JM,Smithen CE,Tong BP,Wickens JC,Bloxham DP,Bradshaw D,Cashin CH

更新日期：1991-02-01 00:00:00

abstract：:Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with t...

journal_title：Journal of medicinal chemistry

authors： Dong Y,Wang X,Kamaraj S,Bulbule VJ,Chiu FC,Chollet J,Dhanasekaran M,Hein CD,Papastogiannidis P,Morizzi J,Shackleford DM,Barker H,Ryan E,Scheurer C,Tang Y,Zhao Q,Zhou L,White KL,Urwyler H,Charman WN,Matile H,Witt

更新日期：2017-04-13 00:00:00

abstract：:A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of infection (EC₅₀ = 2.3 ± 0.8 μM) with marginal cy...

journal_title：Journal of medicinal chemistry

authors： Moore BP,Chung DH,Matharu DS,Golden JE,Maddox C,Rasmussen L,Noah JW,Sosa MI,Ananthan S,Tower NA,White EL,Jia F,Prisinzano TE,Aubé J,Jonsson CB,Severson WE

更新日期：2012-10-25 00:00:00

abstract：:The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water so...

journal_title：Journal of medicinal chemistry

authors： Weeks MS,Hill CL,Schinazi RF

更新日期：1992-04-03 00:00:00

abstract：:A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for activity against maximal electroshock-induced seizures in rodents. The most promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a purine anticonvulsant, has a profile in rodents that suggests 14 will be free of emes...

journal_title：Journal of medicinal chemistry

authors： Kelley JL,Koble CS,Davis RG,McLean EW,Soroko FE,Cooper BR

更新日期：1995-09-29 00:00:00

abstract：:The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conf...

journal_title：Journal of medicinal chemistry

authors： Borsari C,Rageot D,Dall'Asen A,Bohnacker T,Melone A,Sele AM,Jackson E,Langlois JB,Beaufils F,Hebeisen P,Fabbro D,Hillmann P,Wymann MP

更新日期：2019-09-26 00:00:00

abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...

journal_title：Journal of medicinal chemistry

authors： Yang X,Shi Q,Yang SC,Chen CY,Yu SL,Bastow KF,Morris-Natschke SL,Wu PC,Lai CY,Wu TS,Pan SL,Teng CM,Lin JC,Yang PC,Lee KH

更新日期：2011-07-28 00:00:00

abstract：:In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release ...

journal_title：Journal of medicinal chemistry

authors： Buckle DR,Outred DJ,Smith H,Spicer BA

更新日期：1984-11-01 00:00:00

abstract：:A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the alpha-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-tria...

journal_title：Journal of medicinal chemistry

authors： Ferreira SB,Sodero AC,Cardoso MF,Lima ES,Kaiser CR,Silva FP,Ferreira VF

更新日期：2010-03-25 00:00:00

abstract：:The synthesis and structure-activity relationships of C-terminal octapeptide analogues of anaphylatoxin C5a have been studied. The introduction of hydrophobic amino acids into the N-acetylated native octapeptide (N-Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) (1) has led to an analogue with 100 times more activity than the ...

journal_title：Journal of medicinal chemistry

authors： Kawai M,Quincy DA,Lane B,Mollison KW,Or YS,Luly JR,Carter GW

更新日期：1992-01-24 00:00:00

abstract：:Quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) have been applied to elucidate the mechanisms of genotoxicity (SOSIP) of nitrofuran derivatives on Escherichia coli PQ37. The following equation was developed: log SOSIP = -33.1qc2 + 1.00 log P - 1.50Isat - 1.19MR - 0....

journal_title：Journal of medicinal chemistry

authors： Debnath AK,Hansch C,Kim KH,Martin YC

更新日期：1993-04-16 00:00:00

abstract：:Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragm...

journal_title：Journal of medicinal chemistry

authors： Guillory X,Wolter M,Leysen S,Neves JF,Kuusk A,Genet S,Somsen B,Morrow JK,Rivers E,van Beek L,Patel J,Goodnow R,Schoenherr H,Fuller N,Cao Q,Doveston RG,Brunsveld L,Arkin MR,Castaldi P,Boyd H,Landrieu I,Chen H,O

更新日期：2020-07-09 00:00:00

abstract：:A new series of 11-[(aminoalkyl)carbonyl] derivatives of 6,11-dihydrodibenzo[c,f][1,2,5]thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) test. Effects on reserpine-induced hypothermia and toxicity for the most potent ...

journal_title：Journal of medicinal chemistry

authors： Giannotti D,Viti G,Sbraci P,Pestellini V,Volterra G,Borsini F,Lecci A,Meli A,Dapporto P,Paoli P

更新日期：1991-04-01 00:00:00