A Simple Route to 2‐Vinylimidazoles

Rothenberg, Alan S.; Dauplaise, David L.; Panzer, Hans P.

doi:10.1002/anie.198305601

Cited by 14 publications

(7 citation statements)

References 4 publications

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“…16 Subsequent oxidation into aldehyde 58 under Swern's conditions 26 and then reaction with ammonia and glyoxal 27 gave the final product. Significance and Validity of Pharmacological Parameters.…”

Section: Chemistrymentioning

confidence: 99%

Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 2. Syntheses and Biological Activities of 1,4-Dialkyl-, 1,4-Dibenzyl, and 1-Benzyl-4-alkyl-2-(4‘,5‘-dihydro-1‘H- imidazol-2‘-yl)piperazines and Isosteric Analogues of Imidazoline

et al. 1999

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Piperazine derivatives have been identified as new antidiabetic compounds. Structure-activity relationship studies in a series of 1-benzyl-4-alkyl-2-(4′,5′-dihydro-1′H-imidazol-2′-yl)piperazines resulted in the identification of 1-methyl-4-(2′,4′-dichlorobenzyl)-2-(4′,5′-dihydro-1′H-imidazol-2′-yl)piperazine, PMS 812 (S-21663), as a highly potent antidiabetic agent on a rat model of diabetes, mediated by an important increase of insulin secretion independently of R 2 adrenoceptor blockage. These studies were extended to find additional compounds in these series with improved properties. In such a way, substitution of both piperazine N atoms was first optimized by using various alkyl, branched or not, and benzyl groups. Second, some modifications of the imidazoline ring and its replacement by isosteric heterocycles were carried out, proceeding from PMS 812, to evaluate their influence on the antidiabetic activity. The importance of the distance between the imidazoline ring and the piperazine skeleton was studied third. Finally, the influence of the N-benzyl moiety was also analyzed compared to a direct N-phenyl substitution. The pharmacological evaluation was performed in vivo using glucose tolerance tests on a rat model of type II diabetes. The most active compounds were 1,4-diisopropyl-2-(4′,5′-dihydro-1′H-imidazol-2′-yl)piperazine (41a), PMS 847 (S-22068), and 1,4-diisobutyl-2-(4′,5′-dihydro-1′H-imidazol-2′-yl)piperazine (41b), PMS 889 (S-22575), which strongly improved glucose tolerance without any side event or hypoglycemic effect. More particularly, PMS 847 proved to be as potent after po (100 µmol/kg) as after ip administration and appears as a good candidate for clinical investigations.

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Section: Chemistrymentioning

confidence: 99%

Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 2. Syntheses and Biological Activities of 1,4-Dialkyl-, 1,4-Dibenzyl, and 1-Benzyl-4-alkyl-2-(4‘,5‘-dihydro-1‘H- imidazol-2‘-yl)piperazines and Isosteric Analogues of Imidazoline

et al. 1999

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“…Compounds 34 and 35 have already been described in the literature and their identities were checked by 1 H and 13 C NMR and by GC-MS.…”

Section: -Substituted Pyrazinesmentioning

confidence: 99%

“…Compounds 24-27 have already been described [13] and were identified by their NMR spectra and GC-MS analysis.…”

Section: -Substituted 1h-imidazolesmentioning

confidence: 99%

“…[13] The 2-substituted oxazoles C (Table 3) and the 2-substituted oxazolines D (Table 4) were synthesized from the corresponding carboxylic acids by using published procedures. [14,15] The 2-substituted pyrazines E were also prepared as described in the literature.…”

Section: Synthesis Of the Inhibitorsmentioning

confidence: 99%

“…[29] 1-Substituted 1H-imidazoles: The preparation of the 1-substituted 1H-imidazoles was performed by the procedure exemplified by compound 11. Most of them have already been described [30,31] and their identities were checked by 1 H and 13 C NMR and by GC-MS.…”

mentioning

confidence: 99%

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Synthesis and in vitro Activity of Heterocyclic Inhibitors of CYP2A6 and CYP2A13, Two Cytochrome P450 Enzymes Present in the Respiratory Tract

et al. 2009

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The synthesis of several heterocyclic compounds (1- or 2-substituted 1H-imidazoles and 2-substituted oxazoles, oxazolines and pyrazines) has been achieved. These compounds were tested as inhibitors of CYP2A6 and CYP2A13--two cytochrome P450 enzymes present in the respiratory tract--with a view to preventing the formation of carcinogenic metabolites of nicotine and inhibiting the metabolism of fragrances. 1-Substituted imidazoles bearing short alkyl chains displayed IC(50) values of around 2 microM for both enzymes, together with high vapour pressures.

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The Retro–Diels–Alder Reaction PartI.CCDienophiles

Rickborn

1998

Organic Reactions

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The Diels–Alder (“DA”) reaction is so familiar to organic chemists that the retro‐Diels–Alder or retro‐diene reaction (hereafter “rDA”) requires no conceptual introduction. However, a working definition is needed to indicate the coverage of this review. The intent is to include all reported examples of the general skeletal process excluded in this chapter. Any of the atoms in the starting material (cycloadduct) may be carbon or heteroatom, and substituents on all positions are allowed. In addition, any bond order available to the element in any oxidation state is included, as well as bonding to non‐nearest neighbor atoms (bicyclics, etc.). The volume of literature required separation of this review into two parts. Part I covers all expelled C–C dienophiles, i.e. those reactions that generate a new carbon‐carbon double or triple bond in the dienophile that is formed. Part II, to appear later, covers those expelled dienophiles in which one or both atoms is a heteroatom. Certain specific topics are intentionally omitted. These are: rDA reactions invoked under mass spectral conditions; rDA reactions of polymeric substrates; Electrocyclic processes, some of which are arguably very similar to rDA reactions (these are not addressed unless needed for clarification of an rDA sequence); and a thorough discussion of homo‐rDA reactions. CAS‐Online searches resulted in ca. 1,300 references, of which ca. 900 proved pertinent to the rDA topic as defined and delimited above. Active literature searching was halted in April 1995, but occasional more recent articles are included. Over 2,500 pertinent references were eventually found. Most were obtained by perusal of primary literature (articles) and secondary sources (books and reviews). Computer based search success was limited mainly by the failure of authors or abstractors to key‐word this topic, an especially common occurrence when the expelled dienophile was a simple substance such as N 2 or CO 2 . Overall, approximately 3,500 books, chapters, reviews, articles, and abstracts were consulted in an effort to make this review as comprehensive as possible. This was done with the certainty that some pertinent literature would be missed, tempered by the view that these omissions are probably also lost to any future rational search method. Many secondary sources proved valuable not only for in‐depth discussion of certain rDA reaction types, but also for providing comparisons with related topics. To assist the reader, these secondary sources are referenced (alphabetically by first author within broad subject areas) with a title or brief note on the topic(s) addressed. The first group lists earlier reviews with primary focus on rDA reactions, followed by items of Historical/General Interest, reviews that deal with Experimental Methods, DA reactions (general and specific), reviews of Related Topics (these impinge in more or less significant ways on rDA reactions), and general treatments of Theory and Mechanism.

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A Simple Route to 2‐Vinylimidazoles

Abstract: Table 2 (selected data). 'H-NMR chemical shifts [a] of la, b and 2a, b [b, c].

Cited by 14 publications

References 4 publications

Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 2. Syntheses and Biological Activities of 1,4-Dialkyl-, 1,4-Dibenzyl, and 1-Benzyl-4-alkyl-2-(4‘,5‘-dihydro-1‘H- imidazol-2‘-yl)piperazines and Isosteric Analogues of Imidazoline

Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 2. Syntheses and Biological Activities of 1,4-Dialkyl-, 1,4-Dibenzyl, and 1-Benzyl-4-alkyl-2-(4‘,5‘-dihydro-1‘H- imidazol-2‘-yl)piperazines and Isosteric Analogues of Imidazoline

Synthesis and in vitro Activity of Heterocyclic Inhibitors of CYP2A6 and CYP2A13, Two Cytochrome P450 Enzymes Present in the Respiratory Tract

The Retro–Diels–Alder Reaction PartI.CCDienophiles

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