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 derive propensities for intramolecular hydrogen bond formation of five- to eight-membered ring systems of relevance in drug discovery. A number of motifs, several of which are clearly underutilized in drug discovery, are analyzed in more detail by comparing small molecule and protein-ligand X-ray structures. To investigate effects on physicochemical properties, sets of closely related structures with and without the ability to form intramolecular hydrogen bonds were designed, synthesized, and characterized with respect to membrane permeability, water solubility, and lipophilicity. We find that changes in these properties depend on a subtle balance between the strength of the hydrogen bond interaction, geometry of the newly formed ring system, and the relative energies of the open and closed conformations in polar and unpolar environments. A number of general guidelines for medicinal chemists emerge from this study.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kuhn B,Mohr P,Stahl Mdoi
10.1021/jm100087ssubject
Has Abstractpub_date
2010-03-25 00:00:00pages
2601-11issue
6eissn
0022-2623issn
1520-4804journal_volume
53pub_type
杂志文章abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00193a011
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01116
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00357a023
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journal_title：Journal of medicinal chemistry
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doi：10.1021/acs.jmedchem.7b01588
更新日期：2018-08-23 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00216a021
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pub_type： 杂志文章
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00186a027
更新日期：1980-12-01 00:00:00
abstract：:A series of benzophenone derivatives has been synthesized and evaluated as inhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells. Through the use of the structure-activity relationships within this series of compounds and computational chemistry techniques, a binding conformation is prop...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00010a010
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00135a019
更新日期：1981-03-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00215a005
更新日期：1977-05-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9504870
更新日期：1996-03-29 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049137g
更新日期：2005-02-24 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01063
更新日期：2020-11-12 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00014a013
更新日期：1995-07-07 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00197a025
更新日期：1979-11-01 00:00:00
abstract：:A series of substituted benzenedisulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. One compound, 4-(4-methoxypiperidinosulfonyl)-2-chlorobenzenesulfonamide (19, UK-12130), was found to have anticonvulsant activity in animals at a dose level that gave only a minimal ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00207a001
更新日期：1978-09-01 00:00:00
abstract：:4,4-Ditritio-(-)-nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-)-nicotine via the readily prepared 4,4-dibromocotinine (3). Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a Ka of 4.7 X 10(6) M-1 and 13 fmol of binding sites/mg o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00182a028
更新日期：1980-08-01 00:00:00
abstract：:Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett's neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00405
更新日期：2018-06-28 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00760
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pub_type： 杂志文章
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更新日期：2013-04-25 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00017a011
更新日期：1995-08-18 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：2002-09-12 00:00:00
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journal_title：Journal of medicinal chemistry
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journal_title：Journal of medicinal chemistry
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journal_title：Journal of medicinal chemistry
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更新日期：1997-01-03 00:00:00
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更新日期：2008-02-14 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：2009-08-13 00:00:00
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journal_title：Journal of medicinal chemistry
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doi：10.1021/jm500660f
更新日期：2014-10-23 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：2016-07-14 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：2006-12-28 00:00:00
