Christian Masaguer | University of Santiago de Compostela (original) (raw)

Papers by Christian Masaguer

Research paper thumbnail of CCDC 915941: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of Enantiospecific Recognition at the A2B Adenosine Receptor by Alkyl 2-Cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates

Journal of medicinal chemistry, Jan 3, 2017

A novel family of structurally simple, potent and selective non-xanthine A2BAR ligands was identi... more A novel family of structurally simple, potent and selective non-xanthine A2BAR ligands was identified and its antagonistic behavior was confirmed through functional experiments. The reported alkyl 2-cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahy-dropyrimidine-5-carboxylates (16) were designed by bioisosteric replacement of the carbonyl group at position 2 in a series of 3,4-dihydropyrimidin-2-ones. The scaffold (16) documented herein contains a chiral center at the heterocycle. Accordingly, the most attractive ligand of the series [(±)16b, Ki = 24.3 nM] was resolved into its two enantiomers by chiral HPLC and the absolute configuration was established by circular dichroism. The biological evaluation of both enantiomers demonstrated enantiospecific recognition at A2BAR, with the (S)-16b enantiomer retaining all the affinity (Ki = 15.1 nM), as predicted earlier by molecular modeling. This constitutes the first example of enantiospecific recognition at the A2B adenosine receptor and...

Research paper thumbnail of Synthesis of optically active �-benzyl-?-butyrolactone through lipase-catalyzed kinetic resolution

Tetrahedron Asymmetry, 2001

Research paper thumbnail of Synthesis and CNS Activity of Conformationally Restricted Butyrophenones. Part 27. New Synthetic Approaches to CNS Drugs. A Straightforward, Efficient Synthesis of Tetrahydroindol-4-ones and Tetrahydroquinolin-5-ones via Palladium-Catalyzed Oxidation of Hydroxyenaminones

Research paper thumbnail of Preparation of (R)-(−)- and (S)-(+)-3-hydroxymethyl-1-tetralone tosylates, key intermediates in the synthesis of new CNS drugs, via resolution of precursors

Tetrahedron: Asymmetry, 2003

The preparation of (R)-(−)-and (S)-(+)-3-hydroxymethyl-1-tetralone tosylates, key intermediates i... more The preparation of (R)-(−)-and (S)-(+)-3-hydroxymethyl-1-tetralone tosylates, key intermediates in the synthesis of new CNS drugs in the aminobutyrophenone family, has been developed via classical resolutions or lipase-catalyzed kinetic resolution of one of their precursors.

Research paper thumbnail of Synthesis of substituted tetralones as intermediates of CNS agents via palladium-catalyzed cross-coupling reactions

Tetrahedron Letters, 2007

A series of substituted tetralones as intermediates of CNS agents has been synthesized via Pd-cat... more A series of substituted tetralones as intermediates of CNS agents has been synthesized via Pd-catalyzed coupling reactions of 3-(methoxycarbonyl)-1,2,3,4-tetrahydro-1-oxonaphthalen-6-yl trifluoromethanesulfonate (5) with a variety of organometallic reagents.

Research paper thumbnail of Synthesis of optically active β-benzyl-γ-butyrolactone through lipase-catalyzed kinetic resolution

Tetrahedron: Asymmetry, 2001

The lipase-catalyzed kinetic resolution of the racemic g-hydroxy ester 2, coupled with subsequent... more The lipase-catalyzed kinetic resolution of the racemic g-hydroxy ester 2, coupled with subsequent acid-mediated cyclization, is an effective method for the synthesis of both enantiomers of b-benzyl-g-butyrolactone 1. This enzymatic process affords the product with high enantiomeric excess under mild reaction conditions and does not require optically active starting materials.

Research paper thumbnail of Kinetic resolution of 3-hydroxymethylbenzocycloalkanols by selective asymmetric hydrogen-transfer oxidation

Tetrahedron: Asymmetry, 2003

Kinetic resolution of 3-hydroxymethylbenzocycloalkanols was performed by selective asymmetric hyd... more Kinetic resolution of 3-hydroxymethylbenzocycloalkanols was performed by selective asymmetric hydrogen-transfer oxidation using the Ru(II)-(S,S)-TsDPEN catalyst. Thus, several 3-hydroxymethyl-1-tetralols 7a-d afforded (1R,3R)-3-hydroxymethyl-1-tetralols (1R,3R)-7a-d and (S)-3-hydroxymethyl-1-tetralones (S)-9a-d, and 3-hydroxymethyl-1-indanol 7e gave (1R,3S)-3-hydroxymethyl-1-indanol (1R,3S)-7e and (R)-3-hydroxymethyl-1-indanone (R)-9e, with high enantioselectivities.

Research paper thumbnail of New CNS agent precursors. A simple and efficient route for synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as conformationally constrained butyrophenone analogues

Tetrahedron Letters, 1997

Starling from 3,4,5-trimethoxybenzoic acid, we described a practical and efficient five-step synt... more Starling from 3,4,5-trimethoxybenzoic acid, we described a practical and efficient five-step synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as new CNS agent precursors in an overall yield of 20%.

Research paper thumbnail of A practical and efficient route for synthesis of 6-aminomethyl-4-oxo-4,5,6,7-tetrahydroindoles as new CNS agent precursors

Tetrahedron Letters, 1996

Abstract Starting from 2,5-dimethoxybenzoic acid we described a practical and efficient route for... more Abstract Starting from 2,5-dimethoxybenzoic acid we described a practical and efficient route for synthesis of 6-aminomethyl-4-oxotetrahydroindoles with good to acceptable overall yields of 50-30%.

Research paper thumbnail of New synthetic approaches to CNS drugs. A straightforward, efficient synthesis of tetrahydroindol-4-ones and tetrahydroquinolin-5-ones via palladium-catalyzed oxidation of hydroxyenaminones

Tetrahedron Letters, 2002

We have developed a facile and efficient synthesis of new conformationally restricted butyropheno... more We have developed a facile and efficient synthesis of new conformationally restricted butyrophenones in the indole and quinoline series via palladium-catalyzed oxidation of hydroxyenaminones, and subsequent cyclization followed by spontaneous aromatization.

Research paper thumbnail of Alkylation of 3-Ethyl-2-methyl-4-oxo-4,5,6,7-tetrahydroindole with Bromoesters: Benzenesulfonyl as Convenient Nitrogen Protecting Group

HETEROCYCLES, 1992

a-Alkylation of 3-e t h y l-2-m e l h y l-4-o l l o-l H 4 , 5 , 6 , 7-t~i d o l e (3) with bromoe... more a-Alkylation of 3-e t h y l-2-m e l h y l-4-o l l o-l H 4 , 5 , 6 , 7-t~i d o l e (3) with bromoesters gives 3-e t h y l-2-m e t h y l-4-a x o-I H 4 , 5 , 6 , 7-t e l~ (Sa), 3e t h y l-2-m e t h y l 4-o x o-I H 4 , 5 , 6 , 7-t e t r a h y~p i o n a t e (Sb), and 3-ethyl-2-methyl4-oxo-1H4,5.6,7-tetr~ydro-5-indol-3-ppiae (6).

Research paper thumbnail of Synthesis, 3D-QSAR, and Structural Modeling of Benzolactam Derivatives with Binding Affinity for the D2 and D3 Receptors

ChemMedChem, 2010

Binding affinities are shown as pK i or percent displacement at 10 mm; all values are the mean of... more Binding affinities are shown as pK i or percent displacement at 10 mm; all values are the mean of two or three separate competition experiments, and the number of assays conducted for each compound is reported in parentheses.

Research paper thumbnail of Synthesis and Affinities for Dopamine (D2) and 5-Hydroxytryptamine (5-HT2A Receptors of 1-(Benzoylpropyl)-4-(1-oxocycloalkyl-2-ethyl)- piperazines as Cyclic Butyrophenone Derivatives

Chemical and Pharmaceutical Bulletin, 1996

Research paper thumbnail of Synthesis and binding affinity of novel 3-aminoethyl-1-tetralones, potential atypical antipsychotics

Bioorganic & Medicinal Chemistry Letters, 2005

Pyridine derivatives R 0380 Synthesis and Binding Affinity of Novel 3-Aminoethyl-1-tetralones, Po... more Pyridine derivatives R 0380 Synthesis and Binding Affinity of Novel 3-Aminoethyl-1-tetralones, Potential Atypical Antipsychotics.-Compound (VII) shows the highest antipsychotic activity off all tested compounds.-(

Research paper thumbnail of Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

Bioorganic & Medicinal Chemistry Letters, 2009

Research paper thumbnail of Chemoenzymatic synthesis and binding affinity of novel (R)- and (S)-3-aminomethyl-1-tetralones, potential atypical antipsychotics

Bioorganic & Medicinal Chemistry Letters, 2004

A series of (R)-and (S)-3-aminomethyl-1-tetralones, conformationally constrained analogues of hal... more A series of (R)-and (S)-3-aminomethyl-1-tetralones, conformationally constrained analogues of haloperidol, have been obtained by enzymatic resolution of the corresponding racemic 3-hydroxymethyl-1-tetralones using Pseudomonas fluorescens lipase. Their binding affinities at dopamine D 2 and serotonin 5-HT 2A and 5-HT 2C receptors were determined showing in some cases an atypical antipsychotic profile with Meltzer's ratio higher than 1.30.

Research paper thumbnail of Pyridazine Derivatives, VIII1): Synthesis and Antihypertensive Activity of 6-(2-Thienyl)-5-aminomethyl-3-hydrazino-pyridazines

Archiv der Pharmazie, 1991

... h ydrazino-p yr idazines Enrique Ravina*, Carmen Teran, Neftali G. Dominguez, and Christian F... more ... h ydrazino-p yr idazines Enrique Ravina*, Carmen Teran, Neftali G. Dominguez, and Christian F. Masaguer Dpt. ... References Part VII: C. Teran, E. Ravina, L. Santana, N. Garcia Dominguez, G. Garcia Men, JA Fontenla, F. Orallo, and JM Calleja, Arch. Pharm. ...

Research paper thumbnail of Aromatic ring functionalization of benzolactam derivatives: New potent dopamine D3 receptor ligands

Bioorganic & Medicinal Chemistry Letters, 2011

Since the discovery of the dopamine D(3) receptor, an intensive effort has been directed toward t... more Since the discovery of the dopamine D(3) receptor, an intensive effort has been directed toward the development of potent and selective ligands in order to elucidate the function and potential therapeutic advantages of targeting D(3) receptors. As a part of our efforts, a novel series of substituted benzolactams derivatives was synthesized mostly through palladium-catalyzed reactions. Their affinities on D(1)-D(4) receptors were evaluated and the data led us to highly potent D(3) ligands, some of them highly selective for D(3) receptor, compared to the related dopamine receptor subtypes. Functional D(3) activity assays of the most relevant compounds have been carried out revealing antagonist as well as partial agonist activity.

Research paper thumbnail of Integrated Ugi-Based Assembly of Functionally, Skeletally, and Stereochemically Diverse 1,4-Benzodiazepin-2-ones

The Journal of Organic Chemistry, 2015

A practical, integrated and versatile U-4CR-based assembly of 1,4benzodiazepin-2-ones exhibiting ... more A practical, integrated and versatile U-4CR-based assembly of 1,4benzodiazepin-2-ones exhibiting functional, skeletal and stereochemically diverse substitution patterns is described. By virtue of its convergence, atom economy and bond-forming efficiency herein documented methodology exemplify the reconciliation of structural complexity and experimental simplicity in the context of medicinal chemistry projects.

Research paper thumbnail of CCDC 915941: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of Enantiospecific Recognition at the A2B Adenosine Receptor by Alkyl 2-Cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates

Journal of medicinal chemistry, Jan 3, 2017

A novel family of structurally simple, potent and selective non-xanthine A2BAR ligands was identi... more A novel family of structurally simple, potent and selective non-xanthine A2BAR ligands was identified and its antagonistic behavior was confirmed through functional experiments. The reported alkyl 2-cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahy-dropyrimidine-5-carboxylates (16) were designed by bioisosteric replacement of the carbonyl group at position 2 in a series of 3,4-dihydropyrimidin-2-ones. The scaffold (16) documented herein contains a chiral center at the heterocycle. Accordingly, the most attractive ligand of the series [(±)16b, Ki = 24.3 nM] was resolved into its two enantiomers by chiral HPLC and the absolute configuration was established by circular dichroism. The biological evaluation of both enantiomers demonstrated enantiospecific recognition at A2BAR, with the (S)-16b enantiomer retaining all the affinity (Ki = 15.1 nM), as predicted earlier by molecular modeling. This constitutes the first example of enantiospecific recognition at the A2B adenosine receptor and...

Research paper thumbnail of Synthesis of optically active �-benzyl-?-butyrolactone through lipase-catalyzed kinetic resolution

Tetrahedron Asymmetry, 2001

Research paper thumbnail of Synthesis and CNS Activity of Conformationally Restricted Butyrophenones. Part 27. New Synthetic Approaches to CNS Drugs. A Straightforward, Efficient Synthesis of Tetrahydroindol-4-ones and Tetrahydroquinolin-5-ones via Palladium-Catalyzed Oxidation of Hydroxyenaminones

Research paper thumbnail of Preparation of (R)-(−)- and (S)-(+)-3-hydroxymethyl-1-tetralone tosylates, key intermediates in the synthesis of new CNS drugs, via resolution of precursors

Tetrahedron: Asymmetry, 2003

The preparation of (R)-(−)-and (S)-(+)-3-hydroxymethyl-1-tetralone tosylates, key intermediates i... more The preparation of (R)-(−)-and (S)-(+)-3-hydroxymethyl-1-tetralone tosylates, key intermediates in the synthesis of new CNS drugs in the aminobutyrophenone family, has been developed via classical resolutions or lipase-catalyzed kinetic resolution of one of their precursors.

Research paper thumbnail of Synthesis of substituted tetralones as intermediates of CNS agents via palladium-catalyzed cross-coupling reactions

Tetrahedron Letters, 2007

A series of substituted tetralones as intermediates of CNS agents has been synthesized via Pd-cat... more A series of substituted tetralones as intermediates of CNS agents has been synthesized via Pd-catalyzed coupling reactions of 3-(methoxycarbonyl)-1,2,3,4-tetrahydro-1-oxonaphthalen-6-yl trifluoromethanesulfonate (5) with a variety of organometallic reagents.

Research paper thumbnail of Synthesis of optically active β-benzyl-γ-butyrolactone through lipase-catalyzed kinetic resolution

Tetrahedron: Asymmetry, 2001

The lipase-catalyzed kinetic resolution of the racemic g-hydroxy ester 2, coupled with subsequent... more The lipase-catalyzed kinetic resolution of the racemic g-hydroxy ester 2, coupled with subsequent acid-mediated cyclization, is an effective method for the synthesis of both enantiomers of b-benzyl-g-butyrolactone 1. This enzymatic process affords the product with high enantiomeric excess under mild reaction conditions and does not require optically active starting materials.

Research paper thumbnail of Kinetic resolution of 3-hydroxymethylbenzocycloalkanols by selective asymmetric hydrogen-transfer oxidation

Tetrahedron: Asymmetry, 2003

Kinetic resolution of 3-hydroxymethylbenzocycloalkanols was performed by selective asymmetric hyd... more Kinetic resolution of 3-hydroxymethylbenzocycloalkanols was performed by selective asymmetric hydrogen-transfer oxidation using the Ru(II)-(S,S)-TsDPEN catalyst. Thus, several 3-hydroxymethyl-1-tetralols 7a-d afforded (1R,3R)-3-hydroxymethyl-1-tetralols (1R,3R)-7a-d and (S)-3-hydroxymethyl-1-tetralones (S)-9a-d, and 3-hydroxymethyl-1-indanol 7e gave (1R,3S)-3-hydroxymethyl-1-indanol (1R,3S)-7e and (R)-3-hydroxymethyl-1-indanone (R)-9e, with high enantioselectivities.

Research paper thumbnail of New CNS agent precursors. A simple and efficient route for synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as conformationally constrained butyrophenone analogues

Tetrahedron Letters, 1997

Starling from 3,4,5-trimethoxybenzoic acid, we described a practical and efficient five-step synt... more Starling from 3,4,5-trimethoxybenzoic acid, we described a practical and efficient five-step synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as new CNS agent precursors in an overall yield of 20%.

Research paper thumbnail of A practical and efficient route for synthesis of 6-aminomethyl-4-oxo-4,5,6,7-tetrahydroindoles as new CNS agent precursors

Tetrahedron Letters, 1996

Abstract Starting from 2,5-dimethoxybenzoic acid we described a practical and efficient route for... more Abstract Starting from 2,5-dimethoxybenzoic acid we described a practical and efficient route for synthesis of 6-aminomethyl-4-oxotetrahydroindoles with good to acceptable overall yields of 50-30%.

Research paper thumbnail of New synthetic approaches to CNS drugs. A straightforward, efficient synthesis of tetrahydroindol-4-ones and tetrahydroquinolin-5-ones via palladium-catalyzed oxidation of hydroxyenaminones

Tetrahedron Letters, 2002

We have developed a facile and efficient synthesis of new conformationally restricted butyropheno... more We have developed a facile and efficient synthesis of new conformationally restricted butyrophenones in the indole and quinoline series via palladium-catalyzed oxidation of hydroxyenaminones, and subsequent cyclization followed by spontaneous aromatization.

Research paper thumbnail of Alkylation of 3-Ethyl-2-methyl-4-oxo-4,5,6,7-tetrahydroindole with Bromoesters: Benzenesulfonyl as Convenient Nitrogen Protecting Group

HETEROCYCLES, 1992

a-Alkylation of 3-e t h y l-2-m e l h y l-4-o l l o-l H 4 , 5 , 6 , 7-t~i d o l e (3) with bromoe... more a-Alkylation of 3-e t h y l-2-m e l h y l-4-o l l o-l H 4 , 5 , 6 , 7-t~i d o l e (3) with bromoesters gives 3-e t h y l-2-m e t h y l-4-a x o-I H 4 , 5 , 6 , 7-t e l~ (Sa), 3e t h y l-2-m e t h y l 4-o x o-I H 4 , 5 , 6 , 7-t e t r a h y~p i o n a t e (Sb), and 3-ethyl-2-methyl4-oxo-1H4,5.6,7-tetr~ydro-5-indol-3-ppiae (6).

Research paper thumbnail of Synthesis, 3D-QSAR, and Structural Modeling of Benzolactam Derivatives with Binding Affinity for the D2 and D3 Receptors

ChemMedChem, 2010

Binding affinities are shown as pK i or percent displacement at 10 mm; all values are the mean of... more Binding affinities are shown as pK i or percent displacement at 10 mm; all values are the mean of two or three separate competition experiments, and the number of assays conducted for each compound is reported in parentheses.

Research paper thumbnail of Synthesis and Affinities for Dopamine (D2) and 5-Hydroxytryptamine (5-HT2A Receptors of 1-(Benzoylpropyl)-4-(1-oxocycloalkyl-2-ethyl)- piperazines as Cyclic Butyrophenone Derivatives

Chemical and Pharmaceutical Bulletin, 1996

Research paper thumbnail of Synthesis and binding affinity of novel 3-aminoethyl-1-tetralones, potential atypical antipsychotics

Bioorganic & Medicinal Chemistry Letters, 2005

Pyridine derivatives R 0380 Synthesis and Binding Affinity of Novel 3-Aminoethyl-1-tetralones, Po... more Pyridine derivatives R 0380 Synthesis and Binding Affinity of Novel 3-Aminoethyl-1-tetralones, Potential Atypical Antipsychotics.-Compound (VII) shows the highest antipsychotic activity off all tested compounds.-(

Research paper thumbnail of Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

Bioorganic & Medicinal Chemistry Letters, 2009

Research paper thumbnail of Chemoenzymatic synthesis and binding affinity of novel (R)- and (S)-3-aminomethyl-1-tetralones, potential atypical antipsychotics

Bioorganic & Medicinal Chemistry Letters, 2004

A series of (R)-and (S)-3-aminomethyl-1-tetralones, conformationally constrained analogues of hal... more A series of (R)-and (S)-3-aminomethyl-1-tetralones, conformationally constrained analogues of haloperidol, have been obtained by enzymatic resolution of the corresponding racemic 3-hydroxymethyl-1-tetralones using Pseudomonas fluorescens lipase. Their binding affinities at dopamine D 2 and serotonin 5-HT 2A and 5-HT 2C receptors were determined showing in some cases an atypical antipsychotic profile with Meltzer's ratio higher than 1.30.

Research paper thumbnail of Pyridazine Derivatives, VIII1): Synthesis and Antihypertensive Activity of 6-(2-Thienyl)-5-aminomethyl-3-hydrazino-pyridazines

Archiv der Pharmazie, 1991

... h ydrazino-p yr idazines Enrique Ravina*, Carmen Teran, Neftali G. Dominguez, and Christian F... more ... h ydrazino-p yr idazines Enrique Ravina*, Carmen Teran, Neftali G. Dominguez, and Christian F. Masaguer Dpt. ... References Part VII: C. Teran, E. Ravina, L. Santana, N. Garcia Dominguez, G. Garcia Men, JA Fontenla, F. Orallo, and JM Calleja, Arch. Pharm. ...

Research paper thumbnail of Aromatic ring functionalization of benzolactam derivatives: New potent dopamine D3 receptor ligands

Bioorganic & Medicinal Chemistry Letters, 2011

Since the discovery of the dopamine D(3) receptor, an intensive effort has been directed toward t... more Since the discovery of the dopamine D(3) receptor, an intensive effort has been directed toward the development of potent and selective ligands in order to elucidate the function and potential therapeutic advantages of targeting D(3) receptors. As a part of our efforts, a novel series of substituted benzolactams derivatives was synthesized mostly through palladium-catalyzed reactions. Their affinities on D(1)-D(4) receptors were evaluated and the data led us to highly potent D(3) ligands, some of them highly selective for D(3) receptor, compared to the related dopamine receptor subtypes. Functional D(3) activity assays of the most relevant compounds have been carried out revealing antagonist as well as partial agonist activity.

Research paper thumbnail of Integrated Ugi-Based Assembly of Functionally, Skeletally, and Stereochemically Diverse 1,4-Benzodiazepin-2-ones

The Journal of Organic Chemistry, 2015

A practical, integrated and versatile U-4CR-based assembly of 1,4benzodiazepin-2-ones exhibiting ... more A practical, integrated and versatile U-4CR-based assembly of 1,4benzodiazepin-2-ones exhibiting functional, skeletal and stereochemically diverse substitution patterns is described. By virtue of its convergence, atom economy and bond-forming efficiency herein documented methodology exemplify the reconciliation of structural complexity and experimental simplicity in the context of medicinal chemistry projects.