Abstract：
:The levo and dextro isomers of 2,5-dimethyl-2'-hydroxy-9alpha- and -9beta-propyl-6,7-benzomorphans have been prepared. The analgesic potency and physical dependence capacity of the optical isomers and their racemic parents were determined. The 9alpha-propyl levo isomer was analgesically equipotent with morphine; the 9beta-propyl levo isomer was considerably more potent subcutaneously and equipotent orally. None of the optical isomers suppressed the withdrawal syndrome; the 9beta-propyl levo isomer exacerbated the withdrawal syndrome.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Rice KC,Jacobson AEdoi
10.1021/jm00225a021subject
Has Abstractpub_date
1976-03-01 00:00:00pages
430-2issue
3eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract：:Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061078e
更新日期：2007-04-19 00:00:00
abstract：:Alpha-glucosidases play important roles in the digestion of carbohydrates and biosynthesis of viral envelope glycoproteins. Inhibitors of alpha-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs. Here, we report the synthesis and alpha-glucosidase inhibitory activity ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800621x
更新日期：2008-10-09 00:00:00
abstract：:Fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design were used to identify novel inhibitors for BACE-1. A rapid optimization of an initial NMR hit was achieved by a combination of NMR and a functional assay, resulting in the identification of an isothiourea h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901472u
更新日期：2010-02-11 00:00:00
abstract：:N6-isopentenyladenosine (i6A), a modified nucleoside belonging to the cytokinin family, has shown in humans many biological actions, including antitumoral effects through the modulation of the farnesyl pyrophosphate synthase (FPPS) activity. To investigate the relationship between i6A and FPPS, we undertook an inverse...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500869x
更新日期：2014-09-25 00:00:00
abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501792c
更新日期：2015-02-26 00:00:00
abstract：:The synthesis, stability, and antitumor activity of a series of water-soluble third generation platinum(II) complexes have been described. Among these complexes, [2,2-bis(aminomethyl)-1,3- propanediol-N,N'] [1,1-cyclobutanedicarboxylato(2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylate(2-)-O,O'](tetrahydro-4H-py...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a052
更新日期：1989-08-01 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 variation in amino acid sequence within sets of peptides is described by three principal properties, z1, z2, and z3, per varied amino acid position. These principal properties are derived from a principal components analysis of a matrix of 29 physicochemical variables for the 20 coded (in mRNA) amino acids. The sc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00390a003
更新日期：1987-07-01 00:00:00
abstract：:The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00205a024
更新日期：1978-07-01 00:00:00
abstract：:The in vitro pharmacological properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00051a016
更新日期：1994-12-09 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
pub_type： 杂志文章
doi：10.1021/jm021074j
更新日期：2003-04-10 00:00:00
abstract：:The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00360a002
更新日期：1983-06-01 00:00:00
abstract：:Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x) (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously reported biphenyl-based inhibitors that would provide additional interactions with the protein. These compounds were assayed for the ability to inhibit the binding of sialyl Le...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9704917
更新日期：1998-03-26 00:00:00
abstract：:Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tubercu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00432
更新日期：2016-06-23 00:00:00
abstract：:Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflamm...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5010539
更新日期：2014-10-09 00:00:00
abstract：:Several polynuclear Pt(II) chelates with biogenic polyamines were synthesized and screened for their potential antiproliferative and cytotoxic activity in different human cancer cell lines. To gather information regarding the structure-activity relationships underlying their biological activity, the complexes studied ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0311238
更新日期：2004-05-20 00:00:00
abstract：:A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-conf...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00052a009
更新日期：1994-12-23 00:00:00
abstract：:Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, the use of nonantibiotic molecules to block resistance mechanisms is a powerful alternative. Bacterial efflux pumps exert an early step in AMR development by allowing bacteria to grow at subinhibitor...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00791
更新日期：2018-09-13 00:00:00
abstract：:The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/prot...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01234
更新日期：2016-11-23 00:00:00
abstract：:The 2,3-bis[[(N-methylcarbamoyl)oxy]methyl]-3-pyrroline 1-oxide 5 was synthesized and tested in the murine P388 lymphocytic leukemia model. The compound showed significant reproducible activity and was more potent than indicine N-oxide. 1-Methyl-2-phenyl-3,4-bis[[(N-2- propylcarbamoyl)oxy]methyl]-3-pyrroline N-oxide (...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00394a036
更新日期：1987-11-01 00:00:00
abstract：:Nine representatives of the title series of compounds [(ClCH2CH2)2NP(O)(NH2)ON = CRR'] were synthesized as potential anticancer prodrugs, based on the possibility of enzymatic reduction of the N-O bond to release the known cytotoxic agent phosphoramide mustard [1, (ClCH2CH2)2NP(O)(NH2)OH]. The dimethyl derivative (2, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00366a029
更新日期：1983-12-01 00:00:00
abstract：:We present a novel method to better investigate adverse drug reactions in chemical space. By integrating data sources about adverse drug reactions of drugs with an established cheminformatics modeling method, we generate a data set that is then visualized with a systems biology tool. Thereby new insights into undesire...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801546k
更新日期：2009-05-14 00:00:00
abstract：:This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301226a
更新日期：2012-11-26 00:00:00
abstract：:The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0494873
更新日期：2004-12-02 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：:To improve the biological profile of 20(S)-camptothecin, a novel class of 20-O-linked camptothecin glycoconjugates has been designed for preferential cellular uptake into tumor cells by an active transport mechanism. Such conjugates have been optimized for enhanced solubility, stabilization of the camptothecin lactone...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010893l
更新日期：2001-11-22 00:00:00
abstract：:Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,3-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990965x
更新日期：2000-11-30 00:00:00
abstract：:In an attempt to synthesize pentamidine-aplysinopsin hybrid molecule 25, a lead molecule 8 (containing Z-configured aplysinopsin moiety) was identified for antileishmanial activity. Optimization of lead 8 provided 24 (containing E-configured aplysinopsin) possessing 10 times more activity and 401-fold less toxicity th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900564x
更新日期：2009-10-08 00:00:00
abstract：:Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401685f
更新日期：2014-05-08 00:00:00
abstract：:A series of commercial phenyl-, heteroaryl-, alkyl-, and alkenylboronic acids were evaluated for their FAAH and MGL inhibitory activities. The compounds were generally selective for FAAH, with IC50 in the nanomolar or low-micromolar range. Eight of these compounds inhibited MGL with IC50 in the micromolar range. The m...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801051t
更新日期：2008-11-27 00:00:00
