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Odell, Luke R.
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Publications (10 of 82) Show all publications
Schembri, L. S., Eriksson, J. & Odell, L. R. (2019). Palladium(0)-Catalyzed Carbonylative Synthesis of N-Acylsulfonamides via Regioselective Acylation. Journal of Organic Chemistry, 84(11), 6970-6981
Open this publication in new window or tab >>Palladium(0)-Catalyzed Carbonylative Synthesis of N-Acylsulfonamides via Regioselective Acylation
2019 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 84, no 11, p. 6970-6981Article in journal (Refereed) Published
Abstract [en]

N-Acylsulfonamides represent an important bioisostere of carboxylic acids that allow for greater molecular elaboration and enhanced hydrogen bonding capabilities. Herein, we present a mild and convenient palladium(0)-catalyzed synthesis of N-acylsulfonamides via the carbonylative coupling of sulfonyl azides and electron-rich heterocycles. The reaction proceeds via in situ generation of a sulfonyl isocyanate followed by regioselective acylation of an indole or pyrrole nucleophile. This approach has been used to synthesize 34 indole- and pyrrole-substituted N-acylsulfonamides in yields of up to 95%. Importantly, this process is ligand-free and compatible with an ex situ solid CO source and requires only slightly elevated temperatures, making it a highly attractive method for the preparation of this important class of compounds. This study further investigated the possibility of labeling N-acylsulfonamides with carbon-11 to facilitate biological evaluation and in vivo studies with positron emission tomography.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-389596 (URN)10.1021/acs.joc.9b00740 (DOI)000471212000042 ()31064177 (PubMedID)
Funder
Swedish Research Council, 2018-05133
Available from: 2019-07-24 Created: 2019-07-24 Last updated: 2019-07-24Bibliographically approved
Åkerbladh, L., Odell, L. R. & Larhed, M. (2019). Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions. Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, 30(2), 141-155
Open this publication in new window or tab >>Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions
2019 (English)In: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 30, no 2, p. 141-155Article in journal (Refereed) Published
Abstract [en]

This account summarizes Pd(0)-catalyzed Mo(CO) 6-mediated gas-free carbonylative reactions published in the period October 2011 to May 2018. Presented reactions include inter-and intramolecular carbonylations, carbonylative cross-couplings, and carbonylative multicomponent reactions using Mo(CO) 6 as a solid source of CO. The presented methodologies were developed mainly for small-scale applications, avoiding the problematic use of gaseous CO in a standard laboratory. In most cases, the reported Mo(CO) 6-mediated carbonylations were conducted in sealed vials or by using two-chamber solutions. 1 Introduction 2 Recent Developments 2.1 New CO Sources 2.2 Two-Chamber System for ex Situ CO Generation 2.3 Multicomponent Carbonylations 3 Carbonylations with N and O Nucleophiles 4 Carbonylative Cross-Coupling Reactions with Organometallics 5 Carbonylative Cascade Reactions 6 Carbonylative Cascade, Multistep Reactions 7 Summary and Outlook

Place, publisher, year, edition, pages
GEORG THIEME VERLAG KG, 2019
Keywords
carbonylation, molybdenum, multicomponent reactions, palladium, catalysis
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-375233 (URN)10.1055/s-0037-1610294 (DOI)000455224600005 ()
Funder
Knut and Alice Wallenberg Foundation
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29Bibliographically approved
Eriksson, J., Roy, T., Sawadjoon, S., Bachmann, K., Sköld, C., Larhed, M., . . . Odell, L. R. (2019). Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass. Nuclear Medicine and Biology, 71, 1-10
Open this publication in new window or tab >>Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass
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2019 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 71, p. 1-10Article in journal (Refereed) Published
Abstract [en]

Introduction: MK-7246 is a potent and selective antagonist for chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Within the pancreas CRTH2 is selectively expressed in pancreatic β-cells where it is believed to play a role in insulin release. Reduction in β-cell mass and insufficient insulin secretion in response to elevated blood glucose levels is a hallmark for type 1 and type 2 diabetes. Reported here is the synthesis of [11C]MK-7246 and initial preclinical evaluation towards CRTH2 imaging. The aim is to develop a method to quantify β-cell mass with PET and facilitate non-invasive studies of disease progression in individuals with type 2 diabetes.

Methods: The precursor N-desmethyl-O-methyl MK-7246 was synthesized in seven steps and subjected to methylation with [11C]methyl iodide followed by hydrolysis to obtain [11C]MK-7246 labelled in the N-methyl position. Preclinical evaluation included in vitro radiography and immune-staining performed in human pancreatic biopsies. Biodistribution studies were performed in rat by PET-MRI and in pig by PET-CT imaging. The specific tracer uptake was examined in pig by scanning before and after administration of MK-7246 (1 mg/kg). Predicted dosimetry of [11C]MK-7246 in human males was estimated based on the biodistribution in rat.

Results: [11C]MK-7246 was obtained with activities sufficient for the current investigations (270±120 MBq) and a radiochemical purity of 93±2%. The tracer displayed focal binding in areas with insulin positive islet of Langerhans in human pancreas sections. Baseline uptake in pig was significantly reduced in CRTH2-rich areas after administration of MK-7246; pancreas (66% reduction) and spleen (88% reduction). [11C]MK-7246 exhibited a safe human predicted dosimetry profile as extrapolated from the rat biodistribution data.

Conclusions: Initial preclinical in vitro and in vivo evaluation of [11C]MK-7246 show binding and biodistribution properties suitable for PET imaging of CRTH2. Further studies are warranted to assess its potential in β-cell mass imaging and CRTH2 drug development.

National Category
Organic Chemistry Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-381559 (URN)10.1016/j.nucmedbio.2019.04.002 (DOI)000475837000001 ()
Funder
Swedish Research Council, 2018-05133Knut and Alice Wallenberg FoundationSwedish Child Diabetes FoundationGöran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2019-04-11 Created: 2019-04-11 Last updated: 2019-09-13Bibliographically approved
Odell, L. R., Åkerbladh, L., Schembri, L. S., Nordeman, P., Roslin, S. & Eriksson, J. (2018). Carbonylations beyond aryl-X: Development of new multicomponent reactions. Paper presented at 255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA. Abstract of Papers of the American Chemical Society, 255
Open this publication in new window or tab >>Carbonylations beyond aryl-X: Development of new multicomponent reactions
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2018 (English)In: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Article in journal, Meeting abstract (Other academic) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-367232 (URN)000435539901514 ()
Conference
255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2018-12-06Bibliographically approved
Sawant, R. T., Stevens, M. Y. & Odell, L. R. (2018). Microwave-Assisted aza-Friedel-Crafts Arylation of N-Acyliminium Ions: Expedient Access to 4 -Aryl 3,4-Dihydroquinazolinones. ACS OMEGA, 3(10), 14258-14265
Open this publication in new window or tab >>Microwave-Assisted aza-Friedel-Crafts Arylation of N-Acyliminium Ions: Expedient Access to 4 -Aryl 3,4-Dihydroquinazolinones
2018 (English)In: ACS OMEGA, ISSN 2470-1343, Vol. 3, no 10, p. 14258-14265Article in journal (Refereed) Published
Abstract [en]

A one-pot microwave-assisted aza-Friedel-Crafts arylation of N-acyliminium ions, generated in situ from o-formyl carbamates and different amines, is reported. This metal-free protocol provides rapid access to diverse 4-aryl 3,4-dihydroquinazolinones in excellent yield without any aqueous workup. A solvent-directed process for the selective aza-Friedel-Crafts arylation of electron-rich aryl/heteroaryl/butenyl-tethered N-acyliminium ions is also described.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-369754 (URN)10.1021/acsomega.8b02298 (DOI)000449026500209 ()
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Sawant, R. T., Stevens, M. Y. & Odell, L. R. (2017). Acetic acid-promoted cascade N-acyliminium ion/aza-Prins cyclization: stereoselective synthesis of functionalized fused tricyclic piperidines. Chemical Communications, 53(13), 2110-2113
Open this publication in new window or tab >>Acetic acid-promoted cascade N-acyliminium ion/aza-Prins cyclization: stereoselective synthesis of functionalized fused tricyclic piperidines
2017 (English)In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 53, no 13, p. 2110-2113Article in journal (Refereed) Published
Abstract [en]

A novel acetic acid-promoted metal-free cascade N-acyliminium ion/aza-Prins cyclization of o-formyl carbamates and homoallylamines is reported. This one-pot protocol provides efficient and rapid access to masked cis-hydroxyhexahydropyrido[1,2-c] quinazolin-6-ones with concomitant generation of two stereogenic centers, four C-C/C-O/C-N bonds and two new rings in good yield and excellent diastereoselectivity.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-319679 (URN)10.1039/c6cc09805c (DOI)000395625700006 ()28133651 (PubMedID)
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2018-01-13Bibliographically approved
Roslin, S. & Odell, L. R. (2017). Palladium and Visible-Light Mediated Carbonylative Suzuki-Miyaura Coupling of Unactivated Alkyl Halides and Aryl Boronic Acids. Chemical Communications, 53, 6895-6898
Open this publication in new window or tab >>Palladium and Visible-Light Mediated Carbonylative Suzuki-Miyaura Coupling of Unactivated Alkyl Halides and Aryl Boronic Acids
2017 (English)In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 53, p. 6895-6898Article in journal (Refereed) Published
Abstract [en]

Herein, a simple and efficient method for the palladium-catalyzed carbonylation of aryl boronic acids with unactivated alkyl iodides and bromides under visible-light irradiation, ambient temperature and low CO-pressure is presented. Notably, the procedure uses readily available equipment and an inexpensive palladium catalyst to generate the key alkyl radical intermediate. These mild conditions enabled the synthesis of a range of functionalized aryl alkyl ketones including the antipsychotic drug, melperone.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-329634 (URN)10.1039/c7cc02763j (DOI)000404282900021 ()
Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2017-10-26
Åkerbladh, L., Schembri, L. S., Larhed, M. & Odell, L. R. (2017). Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N-Acylguanidines. Journal of Organic Chemistry, 82(23), 12520-12529
Open this publication in new window or tab >>Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N-Acylguanidines
2017 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 82, no 23, p. 12520-12529Article in journal (Refereed) Published
Abstract [en]

A convenient synthetic strategy toward N-acylguanidines via a sequential one-pot multicomponent carbonylation/amination reaction has been developed. The compounds were readily obtained via an N-cyanobenzamide intermediate formed from the Pd(0)-catalyzed carbonylative coupling of cyanamide and aryl iodides or bromides. Subsequent amination with a large variety of amines provided the final N-acylguanidines, with the overall formation of one C-C and two C-N bonds, in moderate to excellent yields. The substrate scope was found to be wide and the methodology was used to produce over 50 compounds, including 29 novel molecules. Furthermore, three separate nitrogen-containing heterocycles were prepared from the N-acylguanidines synthesized using the developed multicomponent, carbonylative method.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-343509 (URN)10.1021/acs.joc.7b02294 (DOI)000417342300056 ()29027801 (PubMedID)
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-03-08Bibliographically approved
Nordeman, P., Chow, S. Y., Odell, A. F., Antoni, G. & Odell, L. R. (2017). Palladium-mediated C-11-carbonylations using aryl halides and cyanamide. Organic and biomolecular chemistry, 15(22), 4875-4881
Open this publication in new window or tab >>Palladium-mediated C-11-carbonylations using aryl halides and cyanamide
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2017 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 15, no 22, p. 4875-4881Article in journal (Refereed) Published
Abstract [en]

A robust and high-yielding radiochemical synthesis of C-11-N-cyanobenzamides using a palladium-mediated aminocarbonylation with C-11-CO, aryl halides and cyanamide is described. The bidentate ligand 1,1'-bis(diphenylphosphino)ferrocene provided C-11-N-cyanobenzamides from aryl-iodides, bromides, triflates and even chlorides in 28-79% radiochemical yield after semi-preparative HPLC. To further highlight the utility of this method, novel C-11-N-cyanobenzamide analogs of flufenamic acid, meflanamic acid, dazoxiben and tamibarotene were synthesized in 34-71% radiochemical yields.

National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-327370 (URN)10.1039/c7ob01064h (DOI)000403005500018 ()28537303 (PubMedID)
Available from: 2017-08-11 Created: 2017-08-11 Last updated: 2018-01-13Bibliographically approved
Odell, L. R., Abdel-Hamid, M. K., Hill, T. A., Chau, N., Young, K. A., Deane, F. M., . . . McCluskey, A. (2017). Pyrimidine-Based Inhibitors of Dynamin I GTPase Activity: Competitive Inhibition at the Pleckstrin Homology Domain. Journal of Medicinal Chemistry, 60(1), 349-361
Open this publication in new window or tab >>Pyrimidine-Based Inhibitors of Dynamin I GTPase Activity: Competitive Inhibition at the Pleckstrin Homology Domain
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2017 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 60, no 1, p. 349-361Article in journal (Refereed) Published
Abstract [en]

The large GTPase dynamin mediates membrane fission during clathrin-mediated endocytosis (CME). The aminopyrimidine compounds, were reported to disrupt clynamin localization to the plasina membrane via the PH domain and,iniplicate this mechanism in the inhibition of CME. We have used a computational approach of binding site identification, docking, and interaction energy calculations to design and synthesize a new library of aminopyrimidine analogues targeting site-2 of the pleckstrin homology (PH) domain. The optimized analogues showed low micromolar inhibition against both dynamin I (IC50 = 10.6 +/- 1.3 to 1.6 +/- 0.3 mu M) and CME (IC50(CME) = 65.9 +/- 7.7 to 17 +/- 1.1 mM), which makes this. series among The more potent inhibitors of dynamin.and CME yet reported. In:CME and growth inhibition cell-based assays, the data obtained Was consistent with dynamin inhibition. CEREP ExpresS profiling identified off-.target effects at the cholecystokinin, dopamine D-2, histamine H-1 and H-2, melanocortin, rnelatonin, muscarir* M-1 and M-3 neurokinin, opioid KOP and serotonin receptors.

National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-316033 (URN)10.1021/acs.jmedchem.6b01422 (DOI)000392035100023 ()27997171 (PubMedID)
Funder
Australian Research Council
Available from: 2017-02-24 Created: 2017-02-24 Last updated: 2018-01-13Bibliographically approved
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