Pierre Wyss - Academia.edu (original) (raw)
Papers by Pierre Wyss
ChemInform, 1990
myo‐Inositol phosphates are key mediators of cellular metabolism.
Chemischer Informationsdienst, 1972
ACS Symposium Series, 1991
Tetrahedron Letters, 1972
SYNTHESES OF HEPARIN SACCHARIDES Stereospecific synthesis of derivatives of 2-amino-2-deoxy-4-O-(... more SYNTHESES OF HEPARIN SACCHARIDES Stereospecific synthesis of derivatives of 2-amino-2-deoxy-4-O-(a-D-glucopyranuronosyl)-D-glucose
Neurotransmitter Actions and Interactions, 1990
This study describes the serendipitous discovery of moclobemide, a short-acting MAO-A inhibitor w... more This study describes the serendipitous discovery of moclobemide, a short-acting MAO-A inhibitor which is in an advanced stage of clinical development as an antidepressant. The short duration of action of this MAO inhibitor containing a morpholine ring moiety is due to the complete reversibility (probably by metabolism of the inhibitory molecular species) of MAO-A inhibition. Since moclobemide is much more effective in vivo than expected from its in vitro activity, investigations to identify a possible metabolite(s) more active as MAO-A inhibitor than the parent compound were carried out. The study of the MAO inhibitory characteristics of several known and putative moclobemide metabolites did not allow the identification of a potent MAO-A inhibitor but led to the discovery of Ro 16-6491, a potent MAO-B inhibitor of novel chemical structure. Systematic chemical modification of the aromatic ring system of Ro 16-6491 finally provided Ro 19-6327 and Ro 41-1049 which are highly selective and reversible inhibitors of MAO-B and MAO-A, respectively. Tritiated derivatives of Ro 19-6327 and Ro 41-1049 were used in binding studies to elucidate their mechanisms of action and to study their cellular distribution by quantitative enzyme radioautography.
Tetrahedron, 1976
Abstract Derivatives of the anomeric benzyl l -idopyranosides and l -idopyranosiduronates have be... more Abstract Derivatives of the anomeric benzyl l -idopyranosides and l -idopyranosiduronates have been synthesized from d -glucose as models for conformation studies. The two key reactions in the synthesis are: (a) inversion of configuration at C(5) of the d -glucofuranose derivative 4 , and (b) catalytic oxidation of the l -idopyranosides 19 , and 22 to uronic acids.
The Journal of pharmacology and experimental therapeutics, 1989
The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), prefer... more The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), preferentially of type A. Moclomide was active in three animal models considered predictive for antidepressant activity: 1) it prevented dose-dependently akinesia and blepharospasm induced in mice and rats by Ro 4-1284, a short-acting amine releasing agent. Prevention of akinesia by moclobemide also depended upon the dose of Ro 4-1284. For comparison also, effects of cimoxatone, harmaline, tranylcypromine and clorgyline are presented: 2) in cats, it selectively and dose-dependently suppressed rapid eye movement sleep without disturbing the sleep-wakefulness cycle; and 3) in the behavioral despair test in mice, it decreased the immobility score to a similar degree as amitriptyline or imipramine. In addition, moclobemide potentiated 5-hydroxytryptophan-induced stereotypies in rats with a potency similar to cimoxatone and with a duration of action of less than 24 hr. Moclobemide had almost no eff...
Journal of Medicinal Chemistry, 2003
Journal of Carbohydrate Chemistry, 1985
Reaction of methyl [benzyl 2-[(benzyloxycarbonyl)-amino]-3-chloro-2,3,4-trideoxy-β-L-threo-hex-4-... more Reaction of methyl [benzyl 2-[(benzyloxycarbonyl)-amino]-3-chloro-2,3,4-trideoxy-β-L-threo-hex-4-enopyrano-sid]uronate,3,4-trideoxy-β-L-threo-hex-4-enopyranosidjuronate (7) with silver fluoride gave the 5-fluoro, 3,4-unsaturated uronate derivative 8, which, on treatment with methanolic ammonia, afforded the corresponding 5-meth-oxy, uronamide 9. The structures of 8 and 9 were confirmed by spectral data and by x-ray crystallographic analysis of 8. H NMR spectroscopy parameters for 9 and its diastercomen 11 have been used to
Helvetica Chimica Acta, 1980
Synthesis of 2‐Substituted Imidazole NucleosidesCondensation of the trimethylsilyl derivatives of... more Synthesis of 2‐Substituted Imidazole NucleosidesCondensation of the trimethylsilyl derivatives of 2‐substituted diethyl and dimethyl imidazole‐4,5‐dicarboxylates (3–5 and 7–9) with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose (2) in the presence of trimethysilyl trifluoromethanesulfonate provided the 2‐substituted diethyl and dimethyl 1‐(2′,3′, 5′‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)imidazole‐4, 5‐dicarboxylates 10–15. These were treated with ammonia to afford the 2‐substituted 1‐(β‐D‐ribofuranosyl)imidazole‐4,5‐dicarboxamides 16–21. Treatment of 2‐methyl‐(16) and 2‐ethyl‐1‐(β‐D‐ribofuranosyl)imidazole‐4,5‐dicarboxamide (17) with fuming nitric acid in oleum at −30° yielded the nitric acid esters 23 and 24. Besides the esterification of the sugar hydroxyl groups one H‐atom of the imidazolecarboxamide function at C(5) in these nucleosides was also substituted by the NO2 group.The conformations in solution of 16 and 23 have been determined by 1H‐ and 13C‐NMR. spectroscopy. These studies...
Helvetica Chimica Acta, 1978
Synthesis of Imidazole NucleosidesThe acid‐catalyzed fusion of dimethyl imidazole‐4,5‐dicarboxyla... more Synthesis of Imidazole NucleosidesThe acid‐catalyzed fusion of dimethyl imidazole‐4,5‐dicarboxylate (7) with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose (6) provided dimethyl 1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)imidazole‐4,5‐dicarboxylate (11) as the major product together with some β‐anomer (13). The β‐anomer (11) was obtained as the only product when the trimethylsilyl derivative (9) of 7 was condensed with 6 in the presence of stannic chloride. Nucleoside 11 was treated with ammonia, and various primary amines to provide 1‐β‐D‐ribofuranosylimidazole‐4, 5‐dicarbox‐amide (5) and N, N'‐disubstitued dicarboxamides (18‐26) respectively. The synthesis of 1‐β‐(33) and 1‐β‐D‐arabinofuranosylimidazole‐4,5‐dicarboxamide (34), is also described. The conformation of 5, as studied by 1H‐and 13C‐NMR.‐spectroscopy, was shown to be very similar to that of adenosine.The oxidation of the 2′,3′‐O′‐isopropylidene derivative (15) of 5 with potassium permanganate or chromic oxide, followe...
Helvetica Chimica Acta, 1975
Derivatives of benzyl 2‐[1‐(benzyloxy)formamido]‐2‐deoxy‐α‐D‐glucopyranoside with various protect... more Derivatives of benzyl 2‐[1‐(benzyloxy)formamido]‐2‐deoxy‐α‐D‐glucopyranoside with various protecting groups at C(3) (benzoyl, benzyl and N‐phenylcarbamoyl) and C(6) (benzoyl, benzylsulfonyl, N‐phenylcarbamoyl and tosyl) have been synthesized as starting materials for disaccharides. The C(4) and C(6) hydroxyl groups of the amino sugar were initially blocked by an acetal group. After introduction of the protecting group at C(3), the acetal group was removed by acid hydrolysis, and the C(6) hydroxyl group was selectively acylated or sulfonylated. The 3,6‐di‐O‐benzoate has also been prepared by dimolar benzoylation of the amino sugar, whereby the 4,6‐isomer was obtained as a by‐product.
ChemInform, 1990
myo‐Inositol phosphates are key mediators of cellular metabolism.
Chemischer Informationsdienst, 1972
ACS Symposium Series, 1991
Tetrahedron Letters, 1972
SYNTHESES OF HEPARIN SACCHARIDES Stereospecific synthesis of derivatives of 2-amino-2-deoxy-4-O-(... more SYNTHESES OF HEPARIN SACCHARIDES Stereospecific synthesis of derivatives of 2-amino-2-deoxy-4-O-(a-D-glucopyranuronosyl)-D-glucose
Neurotransmitter Actions and Interactions, 1990
This study describes the serendipitous discovery of moclobemide, a short-acting MAO-A inhibitor w... more This study describes the serendipitous discovery of moclobemide, a short-acting MAO-A inhibitor which is in an advanced stage of clinical development as an antidepressant. The short duration of action of this MAO inhibitor containing a morpholine ring moiety is due to the complete reversibility (probably by metabolism of the inhibitory molecular species) of MAO-A inhibition. Since moclobemide is much more effective in vivo than expected from its in vitro activity, investigations to identify a possible metabolite(s) more active as MAO-A inhibitor than the parent compound were carried out. The study of the MAO inhibitory characteristics of several known and putative moclobemide metabolites did not allow the identification of a potent MAO-A inhibitor but led to the discovery of Ro 16-6491, a potent MAO-B inhibitor of novel chemical structure. Systematic chemical modification of the aromatic ring system of Ro 16-6491 finally provided Ro 19-6327 and Ro 41-1049 which are highly selective and reversible inhibitors of MAO-B and MAO-A, respectively. Tritiated derivatives of Ro 19-6327 and Ro 41-1049 were used in binding studies to elucidate their mechanisms of action and to study their cellular distribution by quantitative enzyme radioautography.
Tetrahedron, 1976
Abstract Derivatives of the anomeric benzyl l -idopyranosides and l -idopyranosiduronates have be... more Abstract Derivatives of the anomeric benzyl l -idopyranosides and l -idopyranosiduronates have been synthesized from d -glucose as models for conformation studies. The two key reactions in the synthesis are: (a) inversion of configuration at C(5) of the d -glucofuranose derivative 4 , and (b) catalytic oxidation of the l -idopyranosides 19 , and 22 to uronic acids.
The Journal of pharmacology and experimental therapeutics, 1989
The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), prefer... more The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), preferentially of type A. Moclomide was active in three animal models considered predictive for antidepressant activity: 1) it prevented dose-dependently akinesia and blepharospasm induced in mice and rats by Ro 4-1284, a short-acting amine releasing agent. Prevention of akinesia by moclobemide also depended upon the dose of Ro 4-1284. For comparison also, effects of cimoxatone, harmaline, tranylcypromine and clorgyline are presented: 2) in cats, it selectively and dose-dependently suppressed rapid eye movement sleep without disturbing the sleep-wakefulness cycle; and 3) in the behavioral despair test in mice, it decreased the immobility score to a similar degree as amitriptyline or imipramine. In addition, moclobemide potentiated 5-hydroxytryptophan-induced stereotypies in rats with a potency similar to cimoxatone and with a duration of action of less than 24 hr. Moclobemide had almost no eff...
Journal of Medicinal Chemistry, 2003
Journal of Carbohydrate Chemistry, 1985
Reaction of methyl [benzyl 2-[(benzyloxycarbonyl)-amino]-3-chloro-2,3,4-trideoxy-β-L-threo-hex-4-... more Reaction of methyl [benzyl 2-[(benzyloxycarbonyl)-amino]-3-chloro-2,3,4-trideoxy-β-L-threo-hex-4-enopyrano-sid]uronate,3,4-trideoxy-β-L-threo-hex-4-enopyranosidjuronate (7) with silver fluoride gave the 5-fluoro, 3,4-unsaturated uronate derivative 8, which, on treatment with methanolic ammonia, afforded the corresponding 5-meth-oxy, uronamide 9. The structures of 8 and 9 were confirmed by spectral data and by x-ray crystallographic analysis of 8. H NMR spectroscopy parameters for 9 and its diastercomen 11 have been used to
Helvetica Chimica Acta, 1980
Synthesis of 2‐Substituted Imidazole NucleosidesCondensation of the trimethylsilyl derivatives of... more Synthesis of 2‐Substituted Imidazole NucleosidesCondensation of the trimethylsilyl derivatives of 2‐substituted diethyl and dimethyl imidazole‐4,5‐dicarboxylates (3–5 and 7–9) with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose (2) in the presence of trimethysilyl trifluoromethanesulfonate provided the 2‐substituted diethyl and dimethyl 1‐(2′,3′, 5′‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)imidazole‐4, 5‐dicarboxylates 10–15. These were treated with ammonia to afford the 2‐substituted 1‐(β‐D‐ribofuranosyl)imidazole‐4,5‐dicarboxamides 16–21. Treatment of 2‐methyl‐(16) and 2‐ethyl‐1‐(β‐D‐ribofuranosyl)imidazole‐4,5‐dicarboxamide (17) with fuming nitric acid in oleum at −30° yielded the nitric acid esters 23 and 24. Besides the esterification of the sugar hydroxyl groups one H‐atom of the imidazolecarboxamide function at C(5) in these nucleosides was also substituted by the NO2 group.The conformations in solution of 16 and 23 have been determined by 1H‐ and 13C‐NMR. spectroscopy. These studies...
Helvetica Chimica Acta, 1978
Synthesis of Imidazole NucleosidesThe acid‐catalyzed fusion of dimethyl imidazole‐4,5‐dicarboxyla... more Synthesis of Imidazole NucleosidesThe acid‐catalyzed fusion of dimethyl imidazole‐4,5‐dicarboxylate (7) with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose (6) provided dimethyl 1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)imidazole‐4,5‐dicarboxylate (11) as the major product together with some β‐anomer (13). The β‐anomer (11) was obtained as the only product when the trimethylsilyl derivative (9) of 7 was condensed with 6 in the presence of stannic chloride. Nucleoside 11 was treated with ammonia, and various primary amines to provide 1‐β‐D‐ribofuranosylimidazole‐4, 5‐dicarbox‐amide (5) and N, N'‐disubstitued dicarboxamides (18‐26) respectively. The synthesis of 1‐β‐(33) and 1‐β‐D‐arabinofuranosylimidazole‐4,5‐dicarboxamide (34), is also described. The conformation of 5, as studied by 1H‐and 13C‐NMR.‐spectroscopy, was shown to be very similar to that of adenosine.The oxidation of the 2′,3′‐O′‐isopropylidene derivative (15) of 5 with potassium permanganate or chromic oxide, followe...
Helvetica Chimica Acta, 1975
Derivatives of benzyl 2‐[1‐(benzyloxy)formamido]‐2‐deoxy‐α‐D‐glucopyranoside with various protect... more Derivatives of benzyl 2‐[1‐(benzyloxy)formamido]‐2‐deoxy‐α‐D‐glucopyranoside with various protecting groups at C(3) (benzoyl, benzyl and N‐phenylcarbamoyl) and C(6) (benzoyl, benzylsulfonyl, N‐phenylcarbamoyl and tosyl) have been synthesized as starting materials for disaccharides. The C(4) and C(6) hydroxyl groups of the amino sugar were initially blocked by an acetal group. After introduction of the protecting group at C(3), the acetal group was removed by acid hydrolysis, and the C(6) hydroxyl group was selectively acylated or sulfonylated. The 3,6‐di‐O‐benzoate has also been prepared by dimolar benzoylation of the amino sugar, whereby the 4,6‐isomer was obtained as a by‐product.