40240-24-2Relevant academic research and scientific papers
Reactions of Aminopentadienal Derivatives with 5,6-Dihydropyridinium Salts as an Approach to Manzamine Alkaloids Based upon Biogenetic Considerations
Jakubowicz, Karine,Abdeljelil, Kamel Ben,Herdemann, Matthias,Martin, Marie-Therese,Gateau-Olesker, Alice,Mourabit, Ali Al,Marazano, Christian,Das, Bhupesh C.
, p. 7381 - 7387 (1999)
Recent results from our laboratory have prompted us to introduce a modification of the original Baldwin proposal for the biosynthesis of manzamine alkaloids. In this new model, aminopentadienal derivatives of general structures 2 or 3 can not only cyclize to give pyridinium salts such as cyclostellettamines but also react with 5,6-dihydropyridinium salts 1 leading to species such as 6 or 7, which would be key intermediates in the syntheses of manzamine A and halicyclamine B. On the basis of the chemistry depicted in Scheme 2, model reactions of dienes 9, 10, 12, and 13 with salts 1 have been investigated. Diene 9 gave an interesting rearrangement product 15a, while dienes 10 and 12 gave halicyclamine- and manzamine-type adducts 19 and 23, respectively. In addition, glutaconaldehyde derivative 13 gave adduct 32 possessing some characteristic features of sarain A.
Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of Lead Compound (3 R)-7-Hydroxy- N-[(1 S)-2-methyl-1-(piperidin-1-ylmethyl)propyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (PDTic)
Ondachi, Pauline W.,Kormos, Chad M.,Runyon, Scott P.,Thomas, James B.,Mascarella, S. Wayne,Decker, Ann M.,Navarro, Hernán A.,Fennell, Timothy R.,Snyder, Rodney W.,Carroll, F. Ivy
, p. 7525 - 7545 (2018/09/12)
Past studies have shown that it has been difficult to discover and develop potent and selective κ opioid receptor antagonists, particularly compounds having potential for clinical development. In this study, we present a structure-activity relationship (SAR) study of a recently discovered new class of tetrahydroisoquinoline κ opioid receptor antagonists which led to (3R)-7-hydroxy-N-{(1S)-2-methyl-1-[(-4-methylpiperidine-1-yl)methyl]propyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (12) (4-Me-PDTic). Compound 12 had a Ke = 0.37 nM in a [35S]GTPγS binding assay and was 645- and >8100-fold selective for the κ relative to the μ and δ opioid receptors, respectively. Calculated log BB and CNS (central nervous system) multiparameter optimization (MPO) and low molecular weight values all predict that 12 will penetrate the brain, and pharmacokinetic studies in rats show that 12 does indeed penetrate the brain.
Azaquinazoline Inhibitors Of Atypical Protein Kinase C
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, (2015/12/24)
The present application provides a compound of formula (I) and/or a salt thereof, wherein R1, G, and X are as defined herein. A compound of formula (I) and/or its salts have aPKC inhibitory activity, and may be used to treat proliferative disor
IMIDAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING PHARMACOKINETICS OF DRUG
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, (2015/01/06)
Imidazole derivatives of formula (I), pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising at least one imidazole derivative are disclosed. The imidazole derivatives are effective to inhibit CYP450 3A and can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.
IMIDAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG
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, (2015/01/06)
The present invention relates to Imidazole Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Y, R1 and R2 are as defined herein. The present invention also relates to compositions comprising at least one Imidazole Derivative, and and methods of using the Imidazole Derivatives for inhibiting CYP450 3A. Inhibition of CYP450 3A can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.
Further insight from model experiments into a possible scenario concerning the origin of manzamine alkaloids
Wypych, Jean-Charles,Nguyen, Tuan Minh,Nuhant, Philippe,Benechie, Michel,Marazano, Christian
supporting information; experimental part, p. 5418 - 5421 (2009/03/12)
(Chemical Equation Presented) Without the isolation of intermediates, 5,6-dihydropyridinium salts and their nitrile derivatives were prepared as shown in the scheme. Cyclization in the presence of an aminopentadienal led to the formation of the AB ring system of the halicyclamines, or, under alternative conditions, the fused AB ring system of the manzamines. Tf= trifluoromethanesulfonyl.
Synthesis of cis-3-methyl-4-aminopiperidine derivatives
Hilario, Flaviane Francisco,Santos, Daniela Cristina Dos,Gil, Laurent Frederic,Alves, Rosemeire Brondi,De Freitas, Rossimiriam Pereira
, p. 1184 - 1193 (2008/09/18)
A facile approach for the preparation of cis-3-methyl-4-aminopiperidine derivatives is described. The synthesis was carried out via regioselective ring opening of N-benzyl-3-methyl-3,4-epoxi-piperidine (8), which can be easily obtained in two steps from t
Stereoselectivity in Diels-Alder reactions of diene-substituted N-alkoxycarbonyl-1,2-dihydropyridines
Krow, Grant R.,Huang, Qiuli,Szczepanski, Steven W.,Hausheer, Fredrick H.,Carroll, Patrick J.
, p. 3458 - 3466 (2008/02/10)
(Chemical Equation Presented) Diene substituent effects on the regiochemical and stereochemical outcomes of uncatalyzed Diels-Alder reactions of N-alkoxycarbonyl-1,2-dihydropyridines with both styrene and methyl vinyl ketone (MVK) were studied. Alkyl subs
Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds
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Page/Page column 24, (2010/02/14)
The present invention relates to alkyne compounds of general formula I wherein the groups and radicals A, B, W, X, Y, Z, R1 and R2 have the meanings given in claim 1. Moreover the invention relates to pharmaceutical compositions containing at least one alkyne according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity and diabetes.
NOVEL ALKYNE COMPOUNDS WITH AN MCH-ANTAGONISTIC ACTION AND MEDICAMENTS CONTAINING SAID COMPOUNDS
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Page/Page column 65, (2010/02/14)
The invention relates to alkyne compounds of general formula (I), in which the groups and radicals A, B, W, X, Y, Z, R1 and R2 are defined as cited in claim 1. The invention also relates to medicaments containing at least one inventive alkyne. As a result of the antagonistic action against the MCH-receptor, the inventive medicaments are suitable for treating metabolic disorders and/or eating disorders, in particular adiposity and diabetes.
