Abstract：
:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. Compounds were synthesized by Michael addition of acrylonitrile to diphenylpyrazole followed by reductive alkylation of the resultant diphenylpyrazolepropionitriles. Compound 3 was equipotent with imipramine in standard antidepressant assays in animals but showed no significant anticholinergic action and did not antagonize the antihypertensive effects of clonidine and guanethidine.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Bailey DM,Hansen PE,Hlavac AG,Baizman ER,Pearl J,DeFelice AF,Feigenson MEdoi
10.1021/jm00380a020subject
Has Abstractpub_date
1985-02-01 00:00:00pages
256-60issue
2eissn
0022-2623issn
1520-4804journal_volume
28pub_type
杂志文章abstract：:Z-D-Phe-Pro-boroMpg-OPin (9a)1,2 has been shown previously to be a highly specific inhibitor of thrombin in spite of lacking an arginine-like guanidino group at the P1 site. A range of compounds have been synthesized based upon this lead compound, varying the neutral side chain at the P1 site. Of the 20 examples based...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00009a012
更新日期：1995-04-28 00:00:00
abstract：:The in vitro antineoplastic activity of many phosphorus-containing (e.g., phosphocholines) and non-phosphorus-containing (e.g., quaternary ammonium salts) ether lipids has been evaluated in the HL-60 promyelocytic cell line. These compounds are analogues of ET-18-OMe (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphochol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00066a011
更新日期：1993-07-09 00:00:00
abstract：:A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4-f]quinolines (2), was discovered, and a preliminary structure-activity relationship study around the 5-benzylidene ring generated several potent human progesterone receptor agonists (compounds 8, 16). These new progestins showed biologic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980366a
更新日期：1998-10-22 00:00:00
abstract：:Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00876
更新日期：2019-10-24 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis and limited therapeutic options. Therefore, there is an urgent need to identify new, safe, and targeted therapeutics for effective treatment of late as well as early stage disease. Plectin-1 (Plec-1) was recently identified as specifi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01571
更新日期：2016-06-09 00:00:00
abstract：:We have synthesized several 7alpha-fluoro (F) and 7alpha-iodo (I) analogues of 5alpha-dihydrotestosterone (5alpha-DHT) and 19-nor-5alpha-dihydrotestosterone (5alpha-NDHT) and tested them for binding to the androgen receptor and for their biological activity in an in vitro assay with cells that have been engineered to ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990064o
更新日期：1999-06-03 00:00:00
abstract：:Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991081g
更新日期：1999-10-07 00:00:00
abstract：:The chemical structures of sweet compounds are very different, ranging from sugars to amino acids and peptides or other compounds such as saccharin. The biological mechanism underlying the generation of sweet taste is still unknown, although in the past few years much research has provided evidence for the existence o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020833v
更新日期：2002-09-26 00:00:00
abstract：:The synthesis and testing of potential multisubstrate inhibitors of tyrosine-specific protein kinases are described. One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-[4-(fluorosulfonyl)benzoyl]adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics. The resulting mult...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00117a015
更新日期：1988-09-01 00:00:00
abstract：:In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-D...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00101a003
更新日期：1992-11-13 00:00:00
abstract：:Glycogen synthase kinase -3 (GSK-3) is a key enzyme involved in numerous physiological events and in major diseases, such as Alzheimer's disease, diabetes, and cardiac hypertrophy. Indirubins are bis-indoles that can be generated from various natural sources or chemically synthesized. While rather potent and selective...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800648y
更新日期：2008-10-23 00:00:00
abstract：:A series of 2,2-diarylethylamine derivatives has been examined for potential antidepressant activity in the tetrabenazine (TBZ) test. Diethanolamine 4 (McN-4187) was one of the more potent compounds despite its polar alcohol functionalities [ED50 values of 15 mg/kg (exploratory activity) and 1.5 mg/kg (ptosis)]. Struc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00374a022
更新日期：1984-08-01 00:00:00
abstract：:A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00225a023
更新日期：1976-03-01 00:00:00
abstract：:(+/-)-7-Aminosulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline (7) is one of the most potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) reported to date, but a blood-brain barrier (BBB) model indicates that it cannot penetrate the BBB. To increase the lipophilicity of 7 by addition ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0400653
更新日期：2004-08-26 00:00:00
abstract：:Thymidylate synthase X (ThyX) represents an attractive target for tuberculosis drug discovery. Herein, we selected 16 compounds through a virtual screening approach. We solved the first X-ray crystal structure of Thermatoga maritima (Tm) ThyX in complex with a nonsubstrate analog inhibitor. Given the active site simil...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00977
更新日期：2016-10-13 00:00:00
abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9804533
更新日期：1999-03-11 00:00:00
abstract：:The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Rep...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00127a041
更新日期：1989-07-01 00:00:00
abstract：:Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050408c
更新日期：2005-09-08 00:00:00
abstract：:A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists has been carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates, which contain 18 differe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00564
更新日期：2020-07-23 00:00:00
abstract：:We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030549j
更新日期：2004-06-03 00:00:00
abstract：:Long chain fatty acid elongase 6 (ELOVL6) catalyzes the elongation of long chain fatty acyl-CoAs and is a potential target for the treatment of metabolic disorders. The ultrahigh throughput screen of our corporate chemical collections resulted in the identification of a novel 3-sulfonyl-8-azabicyclo[3.2.1]octane class...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900488k
更新日期：2009-07-23 00:00:00
abstract：:The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401121k
更新日期：2013-09-12 00:00:00
abstract：:In a previous paper, we reported the N-hydroxyformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor. Despite its attraction as a potential therapeutic agent for cerebral diseases, the preparation of an injectable formulation of HET0016 was limited by its poor solubility under neutral cond...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020557k
更新日期：2003-12-04 00:00:00
abstract：:The melanocortin-3 (MC3) and melanocortin-4 (MC4) receptors regulate energy homeostasis, food intake, and associated physiological conditions. The melanocortin-4 receptor (MC4R) has been studied extensively. Less is known about specific physiological roles of the melanocortin-3 receptor (MC3R). A major obstacle to thi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301253y
更新日期：2013-04-11 00:00:00
abstract：:A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Co...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950644v
更新日期：1996-01-19 00:00:00
abstract：:The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00473
更新日期：2015-06-11 00:00:00
abstract：:On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenocepto...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a001
更新日期：1985-02-01 00:00:00
abstract：:The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyzes the transfer of ADP-ribose units onto substrate proteins by using nicotinamide adenine dinucleotide (NAD(+)) as a cosubstrate. They have a documented role in chromatin remodelling and DNA repair, and inhibitors of ARTD1 and 2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300746d
更新日期：2012-09-13 00:00:00
abstract：:Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00111a021
更新日期：1991-07-01 00:00:00
abstract：:Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CG...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01514
更新日期：2020-12-10 00:00:00
