Fluorine in health care: Organofluorine containing blockbuster drugs

O’Hagan, David

doi:10.1016/j.jfluchem.2010.03.003

Cited by 761 publications

(320 citation statements)

References 30 publications

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“…The effects of fluorination on molecular properties are well established, and their use in compound property optimisation in many fields like material 1, 2 and medicinal chemistry, [3][4][5][6] as well as crystal engineering 7,8 and agrochemistry 9,10 benefit from this strong influence. After the debate about the effective ability of fluorine to act as a hydrogen-bond (H-bond, HB) acceptor, [11][12][13][14][15] the occurrence of intermolecular OHF H-bonding is now clearly established through experimental and theoretical evidences.…”

Section: Introductionmentioning

confidence: 99%

α‐Fluoro‐o‐cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen‐Bond Acidity

et al. 2016

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The conformational preferences of o-cresols driven by fluorination have been thoroughly investigated from a theoretical point of view with quantum chemical methods and compared to those recently reported for benzyl alcohols. Key conformers of both families exhibit a 6-membered intramolecular hydrogen-bond (IMHB) interaction. A significant enhancement of IMHB strength is observed in -fluoro-o-cresols, owing to the simultaneous increase of the aliphatic fluorine hydrogen-bond (HB) basicity and of the aromatic hydroxyl HB acidity, compared to o-fluorobenzyl alcohols, which are characterized by aromatic fluorine atoms and aliphatic hydroxyl groups. In the case of di-and trifluorinated derivatives, the occurrence of a three-centre hydrogen-bond is emphasised and its features discussed. The impact of these structural predilections on ocresol HB properties has been characterised from the estimation of the HB acidity parameter, pKAHY, weighted according to their conformational populations. We find that -fluorination leads to an HB acidity decrease of the hydroxyl group (in contrast with o-fluorination of benzyl alcohols), whereas ,-difluorination results in no significant variation of pKAHY. Finally, an increase of HB acidity is predicted upon methyl perfluorination, which has been confirmed experimentally. Theoretical descriptors based on AIM, NCI and NBO analyses allows rationalizing the predicted trends, and reveal a relationship with the strength of the established OHF IMHB.

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Section: Introductionmentioning

confidence: 99%

α‐Fluoro‐o‐cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen‐Bond Acidity

et al. 2016

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“…1 In particular, fluorinated molecules have lately gained extraordinary importance as drug candidates. 2 Special attention has been recently devoted to the preparation of chiral molecules featuring stereocenters bearing directly a fluorine atom or a trifluoromethyl group. 3 Despite the great interest in the last years in the topic, the highly stereochemically efficient synthesis of chiral organofluorine compounds still represents a challenge for synthetic chemists.…”

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confidence: 99%

Stereoselective metal-free catalytic synthesis of chiral trifluoromethyl aryl and alkyl amines

et al. 2013

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The enantioselective organocatalytic reduction of trifluoromethyl aryl and alkyl ketoimines afforded the corresponding fluorinated amines with high chemical and stereochemical efficiency. The Lewis base catalyzed reaction with trichlorosilane led to chiral products with a trifluoromethyl group directly linked to the newly generated stereocenter typically in >90% yield and up to 98% e.e.Organofluorine compounds find applications in several fields of scientific research, like pharmaceuticals, agrochemicals and veterinary, but also in materials science.

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“…Because of the high importance of fluorinated biomolecules in drug design, the introduction of one or more fluorine atoms into an organic molecule has attracted high interest over the past ten years [6][7][8][9][10]. In view of the significance of a fluorine atom in an organic molecule, epoxide opening with fluoride, without doubt, is a highly useful approach for the introduction of a fluorine atom into a certain molecule [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Fluorination of some functionalized cycloalkenes through epoxidation and oxirane opening with Deoxofluor or XtalFluor-E

Remete¹,

Fülöp²,

Kiss³

2017

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Fluorine in health care: Organofluorine containing blockbuster drugs

Cited by 761 publications

References 30 publications

α‐Fluoro‐o‐cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen‐Bond Acidity

α‐Fluoro‐o‐cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen‐Bond Acidity

Stereoselective metal-free catalytic synthesis of chiral trifluoromethyl aryl and alkyl amines

Fluorination of some functionalized cycloalkenes through epoxidation and oxirane opening with Deoxofluor or XtalFluor-E

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