Synthesis of novel pyrazolo[3,4-b]quinolinebisphosphonic acids and an unexpected intramolecular cyclization and phosphonylation reaction.

Novel pyrazolo[3,4-b]quinoline α-ketophosphonic and hydroxymethylenebisphosphonic acid compounds were synthesized using different methodologies, starting from 2-chloro-3-formylquinoline 1. New phosphonic acid compounds were obtained as N-1 derivatives with a side chain with 1 or 3 (n = 1 or 3) methylene groups. All phosphonic acid compounds and their corresponding ester and carboxylic acid precursors were fully characterized, and their structures elucidated by spectroscopic data, using NMR techniques and infrared and high-resolution mass spectroscopy. During the process to obtain the N-1 substituted derivative with two methylene groups (n = 2) in the side chain, an unexpected addition-cyclization cascade reaction was observed, involving the phosphonylation of an aromatic ring and the formation of a new six-member lactam ring to afford a tetracyclic ring system. This was an unexpected result since other pyrazolo[3,4-b]quinoline derivatives and all corresponding pyrazolo[3,4-b]pyridine derivatives already prepared, under similar experimental conditions, did not undergo this reaction. This domino reaction occurs with different phosphite reagents but only affords the six-member ring. The spectroscopic data allowed the identification of the new synthesized tetracyclic compounds and the X-ray diffraction data of compound 11 enabled the confirmation of the proposed structures.

Validation of the Comprehensive ICF Core Set for obstructive pulmonary diseases from the patient's perspective.

This study aimed to validate the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for obstructive pulmonary diseases (OPDs) from the perspective of patients with chronic obstructive pulmonary disease. A cross-sectional qualitative study was carried out with outpatients with chronic obstructive pulmonary disease using focus groups with an ICF-based approach. Qualitative data were analysed using the meaning condensation procedure by two researchers with expertise in the ICF. Thirty-two participants (37.5% women; 63.8 ± 11.3 years old) were included in six focus groups. A total of 61 (86%) ICF categories of the Comprehensive ICF Core Set for OPD were confirmed. Thirty-nine additional second-level categories not included in the Core Set were identified: 15 from the body functions component, four from the body structures, nine from the activities and participation and 11 from the environmental factors. The majority of the categories included in the Comprehensive ICF Core Set for OPD were confirmed from the patients' perspective. However, additional categories, not included in the Core Set, were also reported. The categories included in the Core Set were not confirmed and the additional categories need to be investigated further to develop an instrument tailored to patients' needs. This will promote patient-centred assessments and rehabilitation interventions.