Abstract：
:The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c] pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-pyrrolidinol analogue 17 (IC50 = 2.7 nM) was found to be approximately 5-fold more potent than the corresponding pyrrolidine analogue 16 (IC50 = 15 nM). In the rat and hamster vasa deferentia (mu-specific and delta-specific tissues, respectively), 17 showed only weak antagonist activity (pKB > 5.5), underlining its selectivity for the kappa-opioid receptor. The major activity for 17 is resident in the 4S,3'S-isomer 26 (rabbit vas deferens IC50 = 1.1 nM). Compound 26 displays excellent antinociceptive activity, as determined in the mouse acetylcholine-induced abdominal constriction test (ED50 = 0.001 mg/kg, sc).
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Naylor A,Judd DB,Scopes DI,Hayes AG,Birch PJdoi
10.1021/jm00040a004subject
Has Abstractpub_date
1994-07-08 00:00:00pages
2138-44issue
14eissn
0022-2623issn
1520-4804journal_volume
37pub_type
杂志文章abstract：:The solid-phase reductive alkylation of the Lys side chain in positions 6 (D) and 8 (L) and position 8 alone of the LH-RH antagonist [N-Ac-D-Nal,D-Ph2,3,D-Arg6,Phe7,D-Ala10]LH-RH was investigated in an attempt to reduce the histamine-releasing activity inherent to most potent antagonists while retaining high antiovula...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00393a038
更新日期：1987-10-01 00:00:00
abstract：:A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC(50) = 8.98 +/- 0.90 microM) which was used as a lead compo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2001-05-10 00:00:00
abstract：:Nitric oxide synthases (NOSs) comprise three closely related isoforms that catalyze the oxidation of L-arginine to L-citrulline and the important second messenger nitric oxide (NO). Pharmacological selective inhibition of neuronal NOS (nNOS) has the potential to be therapeutically beneficial in various neurodegenerati...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2013-04-11 00:00:00
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journal_title：Journal of medicinal chemistry
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doi：10.1021/jm00111a009
更新日期：1991-07-01 00:00:00
abstract：:The delta-selective opioid peptide deltorphin C(H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) (DEL C) was modified by para-substitution of Phe3 with halogens (F, Cl, Br, I), amino, or nitro groups. The bioactive potencies in peripheral tissues and brain receptor selectivities of these analogues depended upon the particular sub...
journal_title：Journal of medicinal chemistry
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doi：10.1021/jm00103a001
更新日期：1992-12-11 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm00197a025
更新日期：1979-11-01 00:00:00
abstract：:The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsew...
journal_title：Journal of medicinal chemistry
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abstract：:Tumor-associated macrophages (TAMs) have a significant presence in the tumor stroma across multiple human malignancies and are believed to be beneficial to tumor growth. Targeting CSF1R has been proposed as a potential therapy to reduce TAMs, especially the protumor, immune-suppressive M2 TAMs. Additionally, the high ...
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更新日期：2006-05-04 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00101
更新日期：2016-04-14 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00746
更新日期：2015-09-10 00:00:00
abstract：:We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 (5), the derivative of MS I, potentiates ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01511
更新日期：2019-11-14 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01357
更新日期：2019-02-28 00:00:00
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doi：10.1021/jm800791f
更新日期：2009-02-26 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00257
更新日期：2015-05-28 00:00:00
abstract：:The adenovirus serotype Ad37 binds to and infects human corneal epithelial (HCE) cells through attachment to cellular glycoproteins carrying terminal sialic acids. By use of the crystallographic structure of the sialic acid-interacting domain of the Ad37 fiber protein in complex with sialyllactose, a set of N-acyl mod...
journal_title：Journal of medicinal chemistry
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doi：10.1021/jm801609s
更新日期：2009-06-25 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：2011-06-23 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：1984-05-01 00:00:00
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更新日期：2019-02-28 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：1996-01-19 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00167a018
更新日期：1990-05-01 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：2005-06-16 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：2008-08-28 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：1998-01-15 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：2013-09-12 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：2005-10-20 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00396
更新日期：2017-08-24 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801220a
更新日期：2009-02-12 00:00:00
