Abstract：
:Extensive quantum chemical calculations have been made of the electronic distribution and conformational behavior of meperidine and desmethyl-, (+)-alpha, and (+)-beta-prodine using PCILO, a semiempirical molecular orbital method. For this series of opiates, a phenyl equatorial conformation was preferred over a phenyl axial one, with the equatorial conformer most favored in the most potent compounds. Using the low-energy equatorial conformer obtained for each compound, together with calculated net atomic charges, their observed potency variation could successfully be explained. From the results, these compounds appear to act at the morphine receptor with an identical piperidine rather than phenyl ring site.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Loew GH,Jester JRdoi
10.1021/jm00245a001keywords:
subject
Has Abstractpub_date
1975-11-01 00:00:00pages
1051-6issue
11eissn
0022-2623issn
1520-4804journal_volume
18pub_type
杂志文章abstract：:Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-base...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00077
更新日期：2020-09-10 00:00:00
abstract：:A series of 2-aryldopamine analogues were synthesized and evaluated for their effects on D1 and D2 dopamine receptors. The 2-phenyldopamine and 6-phenylbenzazepine analogues exhibited weak binding to both D1 and D2 receptors. The 9-(aminomethyl)fluorenes also exhibited weak D2 binding; however, 2,5,6-trihydroxy-9H-flu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00160a018
更新日期：1986-10-01 00:00:00
abstract：:In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4016137
更新日期：2013-12-27 00:00:00
abstract：:9,10-Didehydro-6-methyl-8beta-arylergolines 2, in which the carboxyl group of lysergic acid and isolysergic acid is replaced by various aryl groups, were prepared in two steps by alkylation of aromatic substrates with the tetracyclic allylic alcohol 3, followed by aromatization with MnO2. The new ergolines 2 have mode...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00218a025
更新日期：1977-08-01 00:00:00
abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0702478
更新日期：2007-09-20 00:00:00
abstract：:Hydroxy-2-phenylindoles carrying substituted benzyl groups and similar substituents at the nitrogen were synthesized and tested for their ability to displace estradiol from its receptor. All of the derivatives tested exhibited high binding affinities for the calf uterine estrogen receptor, with RBA values ranging from...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00384a022
更新日期：1987-01-01 00:00:00
abstract：:A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 ade...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00399a010
更新日期：1988-04-01 00:00:00
abstract：:This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00166a017
更新日期：1990-04-01 00:00:00
abstract：:The understanding of the physiological role of the G-protein coupled serotonin 5-HT(7) receptor is largely rudimentary. Therefore, selective and potent pharmacological tools will add to the understanding of serotonergic effects mediated through this receptor. In this report, we describe two compound classes, chromans ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0498102
更新日期：2004-07-29 00:00:00
abstract：:A series of 2-(2-nitrobenzoyl)cyclohexane-1,3-dione analogues (1-9) were designed, synthesized, and evaluated for inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), a key enzyme involved in the catabolism of tyrosine which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. The correlations ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010568y
更新日期：2002-05-23 00:00:00
abstract：:Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00068a001
更新日期：1993-08-06 00:00:00
abstract：:Metastin/kisspeptin is an endogenous ligand of KISS1 Receptor (KISS1R). Metastin and KISS1R are suggested to play crucial roles in regulating the secretion of gonadotropin-releasing hormone (GnRH), and continuous administration of metastin derivatives attenuated the plasma testosterone levels in male rats. Our optimiz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00379
更新日期：2016-10-13 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
pub_type： 杂志文章
doi：10.1021/jm300612z
更新日期：2012-10-25 00:00:00
abstract：:Proteasomes of pathogenic microbes have become attractive targets for anti-infectives. Coevolving with its human host, Mycobacterium tuberculosis (Mtb) has developed mechanisms to resist host-imposed nitrosative and oxidative stresses. Genetic deletion or pharmacological inhibition of the Mtb proteasome (Mtb20S) rende...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01187
更新日期：2019-10-24 00:00:00
abstract：:The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously been identified as the most interesting member of a series of selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 1 (R1 = OH)....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00088a010
更新日期：1992-05-15 00:00:00
abstract：:The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00218a009
更新日期：1977-08-01 00:00:00
abstract：:Overexpression of myeloid cell leukemia-1 (Mcl-1) in cancers correlates with high tumor grade and poor survival. Additionally, Mcl-1 drives intrinsic and acquired resistance to many cancer therapeutics, including B cell lymphoma 2 family inhibitors, proteasome inhibitors, and antitubulins. Therefore, Mcl-1 inhibition ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01991
更新日期：2019-04-25 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
pub_type： 信件
doi：10.1021/jm034107j
更新日期：2003-10-09 00:00:00
abstract：:Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040103i
更新日期：2004-08-12 00:00:00
abstract：:The concept of molecular hybridization led us to discover a novel series of coumarin-dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301281e
更新日期：2013-01-10 00:00:00
abstract：:Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding m...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01160
更新日期：2020-10-22 00:00:00
abstract：:Acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF) are both serious public health problems with high incidence and mortality rate in adults, and with few drugs available for the efficient treatment in clinic. In this study, we identified that two known histone deacetylase (HDAC) inhibitors, suberanilohydr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01507
更新日期：2017-03-09 00:00:00
abstract：:A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy as...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501601b
更新日期：2015-03-26 00:00:00
abstract：:A series of 5-substituted tetrahydroisoquinolines was synthesized via a 10-step linear synthesis to assess whether replacement of noscapine's southern isobenzofuranone with other moieties resulted in retained cytotoxic activity. One such molecule, 18g, bearing a para-methoxybenzyl functionality with N-ethylcarbamoyl s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00986
更新日期：2018-09-27 00:00:00
abstract：:Eleven new 12-amino-6,7,10,11-tetrahydro-7, 11-methanocycloocta[b]quinoline derivatives [tacrine (THA)-huperzine A hybrids, rac-21-31] have been synthesized as racemic mixtures and tested as acetylcholinesterase (AChE) inhibitors. For derivatives unsubstituted at the benzene ring, the highest activity was obtained for...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980620z
更新日期：1999-08-26 00:00:00
abstract：:Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990418b
更新日期：1999-12-16 00:00:00
abstract：:As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980058c
更新日期：1998-08-13 00:00:00
abstract：:Novel 3,5-bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones (3a-e) display potent cytotoxicity and a preferential lethality toward various neoplasms compared to some normal cells. The corresponding sulfonic acid analogues 5a-e and an isostere 4 demonstrated substantially lower activity. The leads 3d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101595p
更新日期：2011-05-12 00:00:00
abstract：:The hPepT1-mediated transport properties of a series of 11 synthesized beta- and gamma-peptides have been studied in Caco-2 cells. The results show that several of the compounds interact with the peptide transporter, but only two beta-dipeptides act as substrates and are transported across the cell monolayers. These t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070148u
更新日期：2007-10-18 00:00:00
abstract：:Studies indicate that MAO-B is induced in peripheral inflammatory diseases. To target peripheral tissues using MAO-B inhibitors that do not permeate the blood-brain barrier (BBB) the MAO-B-selective inhibitor deprenyl was remodeled by replacing the terminal acetylene with a CO2H function, and incorporating a para-OCH2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01588
更新日期：2018-08-23 00:00:00
