Abstract：
:Studies of molecular structure-carcinogenicity relations for a set of 157 aromatic amines are reported. A computer-assisted approach using pattern-recognition methods was used to develop a series of discriminants for aromatic amino carcinogenic potential. The 157 compounds were divided into subsets according to tumor site, route of administration, and activity. Sets of calculated molecular structure descriptors were generated that could support linear discriminant functions able to separate sets of active carcinogens from inactive compounds. Prominent among the important structural descriptors were those coding sizes and shapes of the amines. The pattern-recognition results were not strongly affected by differences in active site, and the study showed that mixed data sets could be used in computer-assisted structure-carcinogenicity studies.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Yuta K,Jurs PCdoi
10.1021/jm00135a003subject
Has Abstractpub_date
1981-03-01 00:00:00pages
241-51issue
3eissn
0022-2623issn
1520-4804journal_volume
24pub_type
杂志文章abstract：:The protoberberine alkaloids berberine (1), palmatine (2), jatrorrhizine (3), and several berberine derivatives (4-10) were tested for antimalarial activity in vitro against Plasmodium falciparum and in vivo against Plasmodium berghei. The berberine derivatives 4-10 were designed and synthesized to maximize structural...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00401a006
更新日期：1988-06-01 00:00:00
abstract：:Tipifarnib (R115777), an inhibitor of human protein farnesyltransferase (PFT), is shown to be a highly potent inhibitor of Trypanosoma cruzi growth (ED(50) = 4 nM). Surprisingly, this is due to the inhibition of cytochrome P450 sterol 14-demethylase (CYP51, EC 1.14.13.70). Homology models of the T. cruzi CYP51 were us...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050441z
更新日期：2005-08-25 00:00:00
abstract：:The ever-growing risk of bacterial resistance is a critical concern. Among the various antimicrobial resistant bacterial strains, methicillin and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the basis of the hypothesis that microbes have reduced ability to d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01433
更新日期：2018-11-21 00:00:00
abstract：:The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we de...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100087s
更新日期：2010-03-25 00:00:00
abstract：:A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00093a011
更新日期：1992-07-24 00:00:00
abstract：:The objective of this study is the measurement of the rates of hydrolysis of a series of chloroethyl sulfide derivatives, under stimulated physiological conditions. Interferences encountered with the conventional spectrophotometric method prompted the use of a rapid-response, chloride selective electrode. This probe w...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00222a037
更新日期：1977-12-01 00:00:00
abstract：:Treatment with HIV-1 protease inhibitors, a component of highly active antiretroviral therapy (HAART), often results in viral resistance. Structural and biochemical characterization of a 6X protease mutant arising from in vitro selection with compound 1, a C 2-symmetric diol protease inhibitor, has been previously des...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800149m
更新日期：2008-10-23 00:00:00
abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00171a024
更新日期：1990-09-01 00:00:00
abstract：:Methodology is presented for assembling fluorescently labeled bivalent molecules from monovalent constituents, without side chain protection or coupling agents. To illustrate the procedure, a series of bivalent peptidomimetics directed toward the Trk receptors were prepared and screened via fluorescent activated cell ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm034103e
更新日期：2003-08-14 00:00:00
abstract：:To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two compounds, where C-2 position of the antimalarial drug primaquine is blocked by metabolically stable bulky alkyl group are synthesized. Compound 2 [R = C(CH(3))(3)] of the series has produced excellent antimalarial efficacy against P. be...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304562
更新日期：2004-01-15 00:00:00
abstract：:Cysteine proteases play an important role in cell migration and tumor metastasis. Therefore, their inhibitors are of colossal interest, having potential to be developed as effective antimetastatic drugs for tumor chemotherapy. Traditionally, secondary metabolites from streptomyces show a wide range of diversity with r...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9014179
更新日期：2010-07-22 00:00:00
abstract：:Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a m...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm7009233
更新日期：2007-12-13 00:00:00
abstract：:Rexinoids are ligands for the retinoid X receptor (RXR) that have great promise for both the prevention and treatment of cancer and metabolic diseases. In this regard, synthetic, functional, and structural investigations into the structure-activity relationships of derivatives of the potent RXR agonist (E)-3-[3-(3,5,5...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900096q
更新日期：2009-05-28 00:00:00
abstract：:Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070307+
更新日期：2007-09-06 00:00:00
abstract：:Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codepe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040215+
更新日期：2005-09-08 00:00:00
abstract：:A novel class of artemisinin analogs, N-alkyl-11-aza-9-desmethylartemisinins 17-29, were synthesized via ozonolysis and acid-catalyzed cyclization of precursor amides 5-16. These amides were prepared through condensation of an activated ester of the known intermediate acid 2 with the corresponding primary amine. The a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00026a011
更新日期：1995-12-22 00:00:00
abstract：:1-(2-Phenoxyethyl)-1H-imidazole was found to be an inhibitor of thromboxane (TxA2) synthetase, but it also inhibited the adrenal cytochrome P-450 enzyme steroid 11 beta-hydroxylase. The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a009
更新日期：1985-10-01 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：:Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitro for inhibition of human carbonic anhydrase II (CA II) and ex vivo for their ability to inhibit Ca II in the albino rabbit eye after topical administration. Compound 11a was found to lower intraocular pressure (IOP) in bo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00094a016
更新日期：1992-08-07 00:00:00
abstract：:We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterifi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2011673
更新日期：2011-12-22 00:00:00
abstract：:A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the targe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00049a019
更新日期：1994-11-11 00:00:00
abstract：:Enantiomerically pure (+)- and (-)-carbocyclic thymidine, (-)-carbocyclic 3'-epi-thymidine, (+)-carbocyclic 3'-deoxy-3'-azidothymidine, (+)-carbocyclic 2,3'-O-anhydrothymidine, (+)-carbocyclic 3'-O,6'-methylenethymidine, and (+)-(6'S)-carbocyclic 6'-methylthymidine were synthesized in a stereospecific manner from comm...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00167a011
更新日期：1990-05-01 00:00:00
abstract：:Dicarba analogues of the cyclic opioid peptides H-Tyr-c[d-Cys-Gly-Phe-d(or l)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061294n
更新日期：2007-03-22 00:00:00
abstract：:ACTIBIND and its human homologue RNASET2 are T2 ribonucleases (RNases). RNases are ubiquitous and efficient enzymes that hydrolyze RNA to 3' mononucleotides and also possess antitumorigenic and antiangiogenic activities. Previously, we have shown that ACTIBIND and RNASET2 bind actin and interfere with the cytoskeletal...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1015507
更新日期：2012-02-09 00:00:00
abstract：:A series of pyridine-2-carboxaldehyde N-oxide and pyridine-2-carboxaldehyde (thio)phosphoric hydrazones and two cupric chelates was synthesized. The hydrazones, chelates, and combinations of hydrazones and cupric chloride were tested against mice bearing P388 lymphocytic leukemia, Sarcoma 180, or Ehrlich carcinoma asc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00209a011
更新日期：1978-11-01 00:00:00
abstract：:Four novel steroidal alpha-methylene delta-lactones have been synthesized and shown to be active against human nasopharyngeal carcinoma (KB) cells in culture. The syntheses involved the use of known alpha-methylenation procedures. In addition, the lactone 6 was directly methylenated by reaction with CH2O/KOH or Et2NH/...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00175a019
更新日期：1980-01-01 00:00:00
abstract：:Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a linking group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00096a001
更新日期：1992-09-04 00:00:00
abstract：:Pharmacophore, two-dimensional (2D), and three-dimensional (3D) quantitative structure-activity relationship (QSAR) modeling techniques were used to develop and test models capable of rationalizing and predicting human UDP-glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity and binding affinity (as K(m,app)). T...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020397c
更新日期：2003-04-24 00:00:00
abstract：:Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401389u
更新日期：2013-11-14 00:00:00
abstract：:A series of tetramisole derivatives was synthesized and tested for inhibitory activity against alkaline phosphatase which was partially purified from a murine ascitic neoplasm resistant to 6-thiopurines (Sarcoma 180/TG). These agents included derivatives substituted with halogens, CH3, or NO2 groups at either the meta...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00214a021
更新日期：1977-04-01 00:00:00
