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Arvidsson, Per
Alternative names
Publications (10 of 32) Show all publications
Arvidsson, P. I., Sandberg, K. & Forsberg-Nilsson, K. (2016). Open for collaboration: an academic platform for drug discovery and development at SciLifeLab. Drug Discovery Today, 21(10), 1690-1698
Open this publication in new window or tab >>Open for collaboration: an academic platform for drug discovery and development at SciLifeLab
2016 (English)In: Drug Discovery Today, ISSN 1359-6446, E-ISSN 1878-5832, Vol. 21, no 10, p. 1690-1698Article, review/survey (Refereed) Published
Abstract [en]

The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform, and reflect on our first two years of operation, with the ambition to share learnings and best practice with academic drug discovery centers globally. We also discuss how the Swedish Teacher Exemption Law, an internationally unique aspect of the innovation system, has shaped the operation. Furthermore, we address how this investment in infrastructure and expertise can be utilized to facilitate international collaboration between academia and industry in the best interest of those ultimately benefiting the most from translational pharmaceutical research - the patients.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-311790 (URN)10.1016/j.drudis.2016.06.026 (DOI)000386401000014 ()27373760 (PubMedID)
Available from: 2017-01-02 Created: 2017-01-02 Last updated: 2018-01-13Bibliographically approved
Arvidsson, P. I., Domeij, B., Hansson, M. G., Landegren, U., Lind, A.-S. & Ullerås, E. (2015). Öppenheten förstör chansen till patent. Svenska dagbladet
Open this publication in new window or tab >>Öppenheten förstör chansen till patent
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2015 (Swedish)In: Svenska dagbladet, ISSN 2001-3868Article in journal, News item (Other (popular science, discussion, etc.)) Published
Place, publisher, year, edition, pages
Stockholm: Svenska Dagbladet AB & Co., 2015
National Category
Law (excluding Law and Society)
Identifiers
urn:nbn:se:uu:diva-256305 (URN)
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2017-02-08Bibliographically approved
Sawant, R. T., Stevenson, J., Odell, L. R. & Arvidsson, P. I. (2013). Organocatalytic asymmetric cross-aldol reaction of 2-chloroethoxy acetaldehyde: diversity-oriented synthesis of chiral substituted 1,4-dioxanes and morpholines. Tetrahedron: asymmetry, 24(2-3), 134-141
Open this publication in new window or tab >>Organocatalytic asymmetric cross-aldol reaction of 2-chloroethoxy acetaldehyde: diversity-oriented synthesis of chiral substituted 1,4-dioxanes and morpholines
2013 (English)In: Tetrahedron: asymmetry, ISSN 0957-4166, E-ISSN 1362-511X, Vol. 24, no 2-3, p. 134-141Article in journal (Refereed) Published
Abstract [en]

Herein we report a facile organocatalytic asymmetric direct cross-aldol reaction of 2-chloroethoxy acetaldehyde with aromatic aldehydes using (S)-(-)-alpha,alpha-diphenyl-2-pyrrolidinemethanol as an organocatalyst to afford anti-2-(2-chloroethoxy)-1-arylpropane-1,3-diols with excellent enantioselectivities (95-98%) and moderate diastereoselectivities (3.5-7:1). The 1,3-diols, obtained after the aldehyde reduction, represent highly functional intermediates that allow for further diversification into both chiral 1,4-dioxanes and morpholines, compounds that frequently display interesting biological activities.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-197659 (URN)10.1016/j.tetasy.2012.12.004 (DOI)000315550900007 ()
Available from: 2013-04-02 Created: 2013-04-02 Last updated: 2017-12-06Bibliographically approved
Makatini, M. M., Petzold, K., Alves, C. N., Arvidsson, P. I., Honarparvar, B., Govender, P., . . . Soliman, M. E. S. (2013). Synthesis, 2D-NMR and molecular modelling studies of pentacycloundecane lactam-peptides and peptoids as potential HIV-1 wild type C-SA protease inhibitors. Journal of enzyme inhibition and medicinal chemistry (Print), 28(1), 78-88
Open this publication in new window or tab >>Synthesis, 2D-NMR and molecular modelling studies of pentacycloundecane lactam-peptides and peptoids as potential HIV-1 wild type C-SA protease inhibitors
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2013 (English)In: Journal of enzyme inhibition and medicinal chemistry (Print), ISSN 1475-6366, E-ISSN 1475-6374, Vol. 28, no 1, p. 78-88Article in journal (Refereed) Published
Abstract [en]

In this study, eight non-natural peptides and peptoids incorporating the pentacycloundecane (PCU) lactam were designed and synthesized as potential inhibitors of the wild type C-SA HIV-protease. Five of these inhibitors gave IC50 values ranging from 0.5 up to 0.75 mu M against the resistance-prone wild type C-South African HIV-protease. NMR EASY-ROESY studies enabled us to describe the secondary structure of three of these compounds in solution. The 3D structures of the selected cage peptides were also modelled in solution using QM/MM/MD simulations. Satisfactory agreement between the NMR observations and the low energy calculated structures exists. Only one of these inhibitors (11 peptoid), which showed the best IC50 (0.5 mu M), exhibited a definable 3-D structure in solution. Autodock4 and AutodockVina were used to model the potential interaction between these inhibitors and the HIV-PR. It appears that the docking results are too crude to be correlated with the relative narrow range of experimental IC50 values (0.5-10 mu M). The PCU-peptides and peptoides were several orders less toxic (145 mu M for 11 and 102 mu M for 11 peptoid) to human MT-4 cells than lopinavir (0.025 mu M). This is the first example of a polycyclic cage framework to be employed as an HIV-PR transition state analogue inhibitor and can potentially be utilized for other diseases related proteases.

Keywords
pentacycloundecane lactam-peptides, peptoids, HIV-1 wild type C-SA protease, QM/MM/MD simulations, molecular docking
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-196021 (URN)10.3109/14756366.2011.633907 (DOI)000313663400010 ()
Available from: 2013-03-04 Created: 2013-03-04 Last updated: 2017-12-06Bibliographically approved
Borhade, S. R., Sandström, A. & Arvidsson, P. I. (2013). Synthesis of Novel Aryl and Heteroaryl Acyl Sulfonimidamides via Pd-Catalyzed Carbonylation Using a Nongaseous Precursor. Organic Letters, 15(5), 1056-1059
Open this publication in new window or tab >>Synthesis of Novel Aryl and Heteroaryl Acyl Sulfonimidamides via Pd-Catalyzed Carbonylation Using a Nongaseous Precursor
2013 (English)In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 15, no 5, p. 1056-1059Article in journal (Refereed) Published
Abstract [en]

Hitherto unexplored aryl and heteroaryl acyl sulfonimidamides have been prepared through the development of a new Pd-catalyzed carbonylation protocol. This novel methodology, employing sulfonimidamides as nucleophiles and CO gas ex situ released from solid Mo(CO)(6) in a sealed two-chamber system, yields a wide range of carbamate protected acyl sulfonimidamides in good to excellent yields.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-197992 (URN)10.1021/ol400049m (DOI)000315707400021 ()
Available from: 2013-04-08 Created: 2013-04-08 Last updated: 2017-12-06Bibliographically approved
Yngve, U., Paulsen, K., Macsari, I., Sundstrom, M., Santangelo, E., Linde, C., . . . Arvidsson, P. I. (2013). Triazolopyrimidinones as gamma-secretase modulators: structure-activity relationship, modulator profile, and in vivo profiling. MedChemComm, 4(2), 422-431
Open this publication in new window or tab >>Triazolopyrimidinones as gamma-secretase modulators: structure-activity relationship, modulator profile, and in vivo profiling
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2013 (English)In: MedChemComm, ISSN 2040-2503, E-ISSN 2040-2511, Vol. 4, no 2, p. 422-431Article in journal (Refereed) Published
Abstract [en]

The structure-activity relationship for a series of potent g-secretase modulators based on the 6,7-dihydro4H-[1,2,4]triazolo[1,5-a]pyrimidin-5-one scaffold is described. Furthermore, we report details regarding the modulator profile on A beta processing, as well as in vivo efficacy, for the optimized compounds.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-196029 (URN)10.1039/c2md20312j (DOI)000314311600019 ()
Available from: 2013-03-04 Created: 2013-03-04 Last updated: 2017-12-06
Macsari, I., Besidski, Y., Csjernyik, G., Nilsson, L. I., Sandberg, L., Yngve, U., . . . Arvidsson, P. I. (2012). 3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na(V)1.7 with Efficacy in Rat Pain Models. Journal of Medicinal Chemistry, 55(15), 6866-6880
Open this publication in new window or tab >>3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na(V)1.7 with Efficacy in Rat Pain Models
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2012 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 55, no 15, p. 6866-6880Article in journal (Refereed) Published
Abstract [en]

The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure activity relationships, and in vitro and in vivo characterization of a novel series of Na(V)1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na(V)1.7 potency, selectivity over Na(V)1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity versus Na(V)1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclinical behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-179901 (URN)10.1021/jm300623u (DOI)000307264100019 ()
Available from: 2012-08-28 Created: 2012-08-27 Last updated: 2017-12-07
Borgegård, T., Gustavsson, S., Nilsson, C., Parpal, S., Klintenberg, R., Berg, A.-L., . . . Lundkvist, J. (2012). Alzheimer's Disease: Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy. Journal of Neuroscience, 32(48), 17297-17305
Open this publication in new window or tab >>Alzheimer's Disease: Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
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2012 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, no 48, p. 17297-17305Article in journal (Refereed) Published
Abstract [en]

γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-187798 (URN)10.1523/JNEUROSCI.1451-12.2012 (DOI)000311794700025 ()23197721 (PubMedID)
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2017-12-07Bibliographically approved
Chakka, S. K., Francis, V., Cele, Z. E. D., Sosibo, S. C., Arvidsson, P. I., Kruger, H. G., . . . Govender, T. (2012). Asymmetric conjugate addition of thioglycolate to a range of chalcones using tetrahydroisoquinoline (TIQ) N,N '-dioxide ligands. Tetrahedron: asymmetry, 23(8), 616-622
Open this publication in new window or tab >>Asymmetric conjugate addition of thioglycolate to a range of chalcones using tetrahydroisoquinoline (TIQ) N,N '-dioxide ligands
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2012 (English)In: Tetrahedron: asymmetry, ISSN 0957-4166, E-ISSN 1362-511X, Vol. 23, no 8, p. 616-622Article in journal (Refereed) Published
Abstract [en]

A series of novel TIQ based N,N'-oxide ligands were synthesised and screened for their catalytic activity in the enantioselective conjugate addition of thioglycolate to chalcones. Bulky groups on the side chain of the TIQ backbone provided the highest enantioselectivity of up to 88% with 10 mol % catalyst loading. It was also observed that these reactions proceeded optimally in the presence of dichloromethane as a solvent. Screening of various metals emphasized La(OTf)(3) as the ideal pre-catalyst for this particular reaction.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-187794 (URN)10.1016/j.tetasy.2012.04.010 (DOI)000306304200014 ()
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2017-12-07Bibliographically approved
Yngve, U., Söderman, P., Svensson, M., Rosqvist, S. & Arvidsson, P. I. (2012). Imidazopyridine-based inhibitors of glycogen synthase kinase 3: synthesis and evaluation of amide isostere replacements of the carboxamide scaffold. Chemistry and Biodiversity, 9(11), 2442-2452
Open this publication in new window or tab >>Imidazopyridine-based inhibitors of glycogen synthase kinase 3: synthesis and evaluation of amide isostere replacements of the carboxamide scaffold
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2012 (English)In: Chemistry and Biodiversity, ISSN 1612-1872, E-ISSN 1612-1880, Vol. 9, no 11, p. 2442-2452Article in journal (Refereed) Published
Abstract [en]

In this study, we explored the effect of bioisostere replacement in a series of glycogen synthase kinase 3 (GSK3) inhibitors based on the imidazopyridine core. The synthesis and biological evaluation of a number of novel sulfonamide, 1,2,4-oxadiazole, and thiazole derivates as amide bioisosteres, as well as a computational rationalization of the obtained results are reported.

National Category
Medical and Health Sciences Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-187797 (URN)10.1002/cbdv.201200308 (DOI)000311299400006 ()23161627 (PubMedID)
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2018-01-12
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