Abstract：
:In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have led to steroidal and nonsteroidal drugs in numerous preclinical and clinical trials, with promising results in oncology and women's health, including endometriosis. Drugs have been designed to inhibit STS, e.g., Irosustat, as innovative dual-targeting aromatase-steroid sulfatase inhibitors (DASIs) and as multitargeting agents for hormone-independent tumors, such as the steroidal STX140 and nonsteroidal counterparts, acting inter alia through microtubule disruption. The aryl sulfamate pharmacophore is highly versatile, operating via three distinct mechanisms of action, and imbues attractive pharmaceutical properties. This Perspective gives a personal view of the work leading both to the therapeutic concepts and these drugs, their current status, and how they might develop in the future.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Thomas MP,Potter BVdoi
10.1021/acs.jmedchem.5b00386subject
Has Abstractpub_date
2015-10-08 00:00:00pages
7634-58issue
19eissn
0022-2623issn
1520-4804journal_volume
58pub_type
杂志文章abstract：:Although there are many estrogen receptor antagonists with improved tissue selectivity profiles compared with tamoxifen, optimal tissue selectivity has not yet been demonstrated. As such there is still a need for additional diversity and new chemical scaffolds to allow for exploration of improved tissue selectivity. H...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2003-04-10 00:00:00
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journal_title：Journal of medicinal chemistry
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doi：10.1021/jm1015507
更新日期：2012-02-09 00:00:00
abstract：:The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the redu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00106a044
更新日期：1991-02-01 00:00:00
abstract：:The dynorphin (Dyn) A analogue zyklophin ([N-benzyl-Tyr(1)-cyclo(d-Asp(5),Dap(8))]dynorphin A(1-11)NH2) is a kappa opioid receptor (KOR)-selective antagonist in vitro, is active in vivo, and antagonizes KOR in the CNS after systemic administration. Hence, we synthesized zyklophin analogues to explore the structure-act...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501827k
更新日期：2015-11-25 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01183
更新日期：2016-12-22 00:00:00
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journal_title：Journal of medicinal chemistry
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doi：10.1021/jm501853m
更新日期：2015-06-11 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401325r
更新日期：2013-10-24 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0302039
更新日期：2003-12-18 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00086a002
更新日期：1992-04-17 00:00:00
abstract：:The effect of aromatic nitro compounds on the oxidative metabolism of representative type I (hexobarbital and aminopyrene) and type II (aniline and zoxazolamine) substrates by cytochrome P-450 dependent liver enzymes was studied. Nitro compounds (nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00223a034
更新日期：1976-01-01 00:00:00
abstract：:We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the 4-keto-1,2-oxathiole-2,2-dioxide (beta-keto-gamma-sultone) heterocyclic system. Several 4- and 5-substituted-5H-1,2-oxathiole-2,2-dioxide derivatives were found to have a selective inhibitory activity against ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8014662
更新日期：2009-03-26 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020955n
更新日期：2003-01-02 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4014357
更新日期：2013-11-27 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070721+
更新日期：2007-10-04 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 synthesis and biological evaluation of a series of novel 1-(aryloxy)-2-propanolamines and several related deshydroxy analogues are described. Compounds 4-29 were prepared and investigated for their class III electrophysiological activity in isolated canine Purkinje fibers and in anesthetized open-chest dogs. None ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00115a010
更新日期：1991-11-01 00:00:00
abstract：:4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieti...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0201114
更新日期：2002-09-26 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm50001a012
更新日期：1985-05-01 00:00:00
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pub_type： 杂志文章
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doi：10.1021/jm00087a018
更新日期：1992-05-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：1998-05-21 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00343a015
更新日期：1982-01-01 00:00:00
abstract：:3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9703348
更新日期：1997-07-04 00:00:00
abstract：:In this study we describe an extension of our previous studies on cis-benzylidenemalononitrile tyrphostins. We have introduced S-aryl substituents in the 5 position (meta vis-a-vis the malononitrile moiety). We find that these compounds are potent blockers of EGFR kinase and its homolog HER-2 kinase. Interestingly, we...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00075a010
更新日期：1993-11-12 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a013
更新日期：1985-10-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2017-05-11 00:00:00
abstract：:The identification of centrally efficacious β-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease (AD) has historically been thwarted by an inability to maintain alignment of potency, brain availability, and desired absorption, distribution, metabolism, and excretion (ADME) properties. In this paper,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501833t
更新日期：2015-03-26 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
