Abstract:
:The synthesis of water-soluble, unsymmetrical, trisulfonated zinc phthalocyanines (ZnPcS3) as single products of the ring expansion of boron tri(4-sulfo)subphthalocyanine (SubPc) is reported. The novel, water-soluble trisulfo-SubPcB(OH) was prepared via hydrolysis of the tris(4-chlorosulfonyl)SubPcB(Br) which in turn was obtained from the condensation of 4-(chlorosulfonyl)phthalonitrile with BBr3 in 1-chlorobenzene. A number of ZnPcS3 analogues were prepared via the reaction of S3SubPcB (OH) with different diiminoisoindoline derivatives of increasing hydrophobicity. The reaction proceeds at relative low temperature with acceptable yields. Metalation of free base Pc's with zinc acetate dihydrate afforded the corresponding zinc complexes. Photodynamic activities were measured against the EMT-6 mouse mammary tumor cell line and compared to those of the known ZnPcS3 and ZnPcS4. Added (t-Bu)benzo and (t-Bu)naphtho groups increased the in vitro cell photoinactivation efficacy of the ZnPcS3, whereas addition of a fourth sulfobenzo or bulky diphenylpyrazino group decreased the activity of the parent molecule. The (t-Bu)naphthotrisulfobenzoporphyrazine induced the best in vivo photodynamic tumor control which, combined with its good solubility and broad absorption spectrum, renders this compound an interesting dye for photodynamic applications in medicine.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kudrevich S,Brasseur N,La Madeleine C,Gilbert S,van Lier JEdoi
10.1021/jm9702488subject
Has Abstractpub_date
1997-11-21 00:00:00pages
3897-904issue
24eissn
0022-2623issn
1520-4804pii
jm9702488journal_volume
40pub_type
杂志文章abstract::Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polya...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm701198s
更新日期:2008-01-24 00:00:00
abstract::The practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/acs.jmedchem.8b00180
更新日期:2018-08-09 00:00:00
abstract::A new, highly potent, selective, and water-soluble antagonist of the hA(3) adenosine receptor was synthesized and tested in binding and functional assays. Compound 4 (5-[[(4-pyridyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine hydrochloride) displayed high water solubility (...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm020974x
更新日期:2002-08-15 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::The academic setting provides an environment that may foster success in the discovery of certain types of small molecule tools while proving less suitable in others. For example, small molecule probes for poorly understood systems, those that exploit a specific resident expertise, and those whose commercial return is ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/jm400132d
更新日期:2013-09-26 00:00:00
abstract::(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride. ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm034073f
更新日期:2003-07-17 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
pub_type: 杂志文章
doi:10.1021/jm3004027
更新日期:2012-06-14 00:00:00
abstract::1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glyce...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00169a030
更新日期:1990-07-01 00:00:00
abstract::A new class of histamine analogues characterized by a 3, 3-diphenylpropyl substituent at the 2-position of the imidazole nucleus has been prepared outgoing from 4,4-diphenylbutyronitrile (4b) via cyclization of the corresponding methyl imidate 5b with 2-oxo-4-phthalimido-1-butyl acetate or 2-oxo-1,4-butandiol in liqui...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm991056a
更新日期:2000-03-23 00:00:00
abstract::The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneou...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9005912
更新日期:2010-01-14 00:00:00
abstract::Avermectins A2a, B1a, and B2a (1, 2, and 3) were acetylated to give 4"- and 23-acetates 4 and 5 and 4",23-diacetate 6 from 1, the 4"-and 5-acetates 7 and 8 and 4",5-diacetate 9 from 2, and triacetate 10 from 3. Structure proof by 300-MHz 1H NMR and mass spectral fragmentation is discussed for 10. Forcing acetylation c...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00348a010
更新日期:1982-06-01 00:00:00
abstract::Two routes for the synthesis of 6-substtituted 8-azaguanosine analogues are described. 2,5,6-Triamino-4(3H)-pyrimidinethione (1) was converted by methylation, nitrosation, and acetylation to -n-acetyl-7-(methylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-5-amine (5). The reaction of 5 with 2,3,5-tri-O-acetyl-D-ribofuranosy...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00232a004
更新日期:1976-10-01 00:00:00
abstract::A series of analogues of Pro-Leu-Gly-NH2 (PLG) in which the leucine residue has been replaced with the aliphatic amino acids L-isoleucine, L-2-aminohexanoic acid (Ahx), L-2-aminopentanoic acid, and L-2-aminobutanoic acid and the aromatic amino acids L-phenylalanine, L-phenylglycine, L- and D-2-amino-4-phenylbutanoic a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00168a045
更新日期:1990-06-01 00:00:00
abstract::Structural modifications requiring novel synthetic chemistry were made to the morpholine acetal human neurokinin-1 (hNK-1) receptor antagonist 4, and this resulted in the discovery of 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-ox o-1 ,2,4-triazol-5-yl)methyl morpholine (17). This m...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm980299k
更新日期:1998-11-05 00:00:00
abstract::Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short (15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attrac...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0606591
更新日期:2006-11-16 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::We recently described the discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure-activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm101181u
更新日期:2011-02-24 00:00:00
abstract::Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminometh...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049917p
更新日期:2004-10-07 00:00:00
abstract::From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800876b
更新日期:2008-12-25 00:00:00
abstract::The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT1B-like receptors is described. Several important auxiliary binding sites of the 5HT1B-like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9605849
更新日期:1997-07-18 00:00:00
abstract::The problem of structure-activity relationships in sulfonamide type compounds is tackled on the ground that both bacteriostatic activities and structural indices must be referred to the specific individual forms assumed by sulfa drugs in the active solutions. The frequency value of the symmetric stretching mode of the...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00244a002
更新日期:1975-10-01 00:00:00
abstract::USP7 is a promising target for cancer therapy as its inhibition is expected to decrease function of oncogenes, increase tumor suppressor function, and enhance immune function. Using a structure-based drug design strategy, a new class of reversible USP7 inhibitors has been identified that is highly potent in biochemica...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00245
更新日期:2020-05-28 00:00:00
abstract::Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly les...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b01170
更新日期:2015-11-12 00:00:00
abstract::The spread of antibiotic-resistant pathogens is a growing concern, and new families of antibacterials are desperately needed. Odilorhabdins are a new class of antibacterial compounds that bind to the bacterial ribosome and kill bacteria through inhibition of the translation. NOSO-95C, one of the first member of this f...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b00790
更新日期:2018-09-13 00:00:00
abstract::Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b00166
更新日期:2016-05-26 00:00:00
abstract::Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. We describe the synthesis and PR binding affinities of a series of bromine- and iodine-substituted 16alpha,17alpha-dioxolane progestins, some of which, when appropriately radiolabeled, are pot...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm060348q
更新日期:2006-07-27 00:00:00
abstract::Extensions and refinements of the receptor mapping method as originally developed by Crippen are presented. In a set of newly developed algorithms measures are taken to reduce the number of required energy parameters to a statistically acceptable degree. The most important measure is the incorporation of lipophilicity...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00152a017
更新日期:1986-02-01 00:00:00
abstract::Methyllycaconitine (MLA, 1) is a novel, potent probe for mammalian and insect nicotinic acetylcholine receptors (nAChR) and displays remarkable selectivity toward neuronal [125I]-alpha-bungarotoxin (alpha BgTX) binding sites that correspond to alpha 7-type nAChR in mammalian brain. We have shown that, among a number o...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9604991
更新日期:1996-11-22 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::Electron deficient, bivalent sulfur atoms have two areas of positive electrostatic potential, a consequence of the low-lying σ* orbitals of the C-S bond that are available for interaction with electron donors including oxygen and nitrogen atoms and, possibly, π-systems. Intramolecular interactions are by far the most ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501853m
更新日期:2015-06-11 00:00:00