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Sul principio della convenienza economica / Ulisse Gobbi Milano : Ulrico Hoepli, 1900
No full textSul principio della convenienza economica / Ulisse Gobbi
Milano : Ulrico Hoepli, 1900
31 p. ; 33 cm
Estratto da: Memorie del R. Istituto Lombardo di Scienze e Lettere, v. 21., 12. della 3. serie., fasc. 3
Paginato anche 174-20
Erratum: Patients with Severe Obesity during the COVID- 19 Pandemic: How to Maintain an Adequate Multidisciplinary Nutritional Rehabilitation Program? (Obes Facts. (2021) DOI: 10.1159/000513283)
No full textIn the article by De Amicis et al. entitled "Patients with Severe Obesity during the COVID- 19 Pandemic: How to Maintain an Adequate Multidisciplinary Nutritional Rehabilitation Program?" [Obes Facts. 2021, DOI: 10.1159/000513283], the author list is incorrect. The correct author list is: De Amicis R. Cancello R. Capodaglio P. Gobbi M. Brunani A. Gilardini L. Castelnuovo G. Molinari E. Barbieri V. Mambrini S.P. Battezzati A. Bertoli S
Caloapenesia diba Gobbi & Azevedo, sp. nov.
No full textCaloapenesia diba Gobbi & Azevedo, sp. nov. (Figs 3, 24, 44, 65, 66) Description. MALE. Body length 4.5 mm. LFW 2.9 mm. Color. Head and clypeus black; mesosoma dark castaneous with regions castaneous; antennae, mandible, metasoma castaneous; legs light castaneous; wings hyaline. Head (Fig. 3). Mandible with five apical teeth; angulate; uppermost and lower ones large, below uppermost and median small. Median clypeal lobe convex; apical margin strongly medially ventrad, with median tooth slightly conspicuous; carina high, arched in profile. Antennal torulus slightly prominent. Flagellomeres short; four first antennomeres in ratio about 16: 5: 6: 6; pedicel long, 1.25 × as long as wide; flagellomere I 1.50 × as long as wide; flagellomere IX 1.25 × as long as wide; flagellar pubescence erect, about half of diameter of flagellomeres. Frons polished; densely punctate. WH 0.91 × LH. WF 0.72 × WH. WF 1.71 × HE. Eye small, salient; pilosity abundant. Ocellus small. DAO 0.15 × WF; frontal angle of ocellar triangle acute. WOT 2.75 × DAO. OOL 1.20 × WOT. Distance of posterior ocellus to vertex crest 2.0 × DAO. VOL 1.07 × HE. Temple parallel. Vertex slightly convex. Occipital carina complete, not visible in dorsal view. Mesosoma (Fig. 24). Pronotal disc and mesonotum polished; densely punctate. Pronotal collar long. Pronotal declivity low. Pronotal disc 0.37 × as long as wide. Notauli strongly conspicuous; complete; convergent. Parapsidal furrow complete. Scutellar furrow long, slender, shallow, scrobiculate, posterior margin sinuous. Median region of scutellum not punctate. Median region of metanotum short, wide. Inner foveae of metanotal furrow not delimited. Propodeal disc 0.86 × as long as wide; 0.61 × as high as long; basal triangle conspicuous, rugulose, ototherwise disc strigulate; median carina absent; paramedian carina conspicuous, long; lateral carina conspicuous; sublateral carina conspicuous; transversal carina absent; declivity strigulate; side of propodeum coriaceous. Mesopleuron polished; callus absent; fovea deep; mesopleural pit absent. Metacarpus 0.41 × radial vein; discoidal vein strongly pigmented, not interstitial with median; first recurrent not pigmented; subdiscoidal vein slightly pigmented. Metasoma. Hypopygium (Fig. 44) 1.05 × as long as wide; posterior margin strongly trilobate; median lobe convex, wide; lateral lobe convex, short; lateral margin slightly convex; anterior pigmented line ill-defined, slender; median stalk short; lateral stalk present, rectangular, conspicuous. Genitalia (Figs 65–66): aedeagus basally wide and narrowing apicad; apical margin of ventral paramere convex; dorsal paramere as wide as ventral one, glabrous; basivolsella not excavated; inner margin of cuspis convex; genital ring short. FEMALE unknown. Material examined. Holotype ♂. C. VIETNAM, Thua Thien Hue, Phong Dien N. P., nr. basecamp, 15 Km W Phong My, c 100 m, 22.III– 6.IV. 2001, Mal. trap 1–3, C. v. Achterberg & R. de Vries, RMNH’01. Paratypes. 2 ♂ THAILAND, Loei, Phu Kradueng NP, Koke Hin Ngam, 16 ° 51.817 ’N 101 ° 50.704 ’E, 270 m, Malaise trap, 23–30.viii. 2006, Sutin Khonglasae leg., T 489, QSBG. 1 ♂, C. VIETNAM, Thua Thien Hue, Phong Dién N. P., nr. base-camp, 15 Km W Phong My, 80–210 m, 23.III– 6.IV. 2001, Mal. traps, C. v. Achterberg & R. de Vries, RMNH’01. Distribution. Thailand (Loei); Vietnam (Thua Thien Hue). Remarks. Caloapenesia diba sp. nov. resembles C. rikawa sp. nov. by presents head rounded; clypeus rounded; ocellus small; eye small; flagellomeres short. But C. diba sp. nov. presents head elongate; eye smaller than in C. rikawa sp. nov.; ocelli separated; clypeus castaneous; antennae light castaneous; uppermost tooth not with upper margin forming cutting edge; hypopigial median lobe shorter than in C. rikawa sp. nov.; lateral stalk conspicuous and rectangular.Published as part of Gobbi, Fernanda T. & Azevedo, Celso O., 2014, Revision of Caloapenesia (Hymenoptera, Bethylidae), with description of sixteen new species, pp. 501-535 in Zootaxa 3860 (6) on pages 508-509, DOI: 10.11646/zootaxa.3860.6.1, http://zenodo.org/record/23144
Caloapenesia heira Gobbi & Azevedo, sp. nov.
No full textCaloapenesia heira Gobbi & Azevedo, sp. nov. (Figs 5, 26, 46, 69, 70) Description. MALE. Body length 3.5 mm. LFW 2.5 mm. Color. Head and clypeus black; mesosoma and scape dark castaneous; mandible, rest of antennae, pronotal collar, end of pronotum and legs castaneous; wings browish. Head (Fig. 5). Mandible with five apical teeth; uppermost convex, others angulate; large, subequal in length. Median clypeal lobe convex; apical margin slightly medially ventrad, with median tooth conspicuous; carina high, arched in profile. Antennal torulus slightly prominent. Flagellomeres median-sized; four first antennomeres in ratio about 9: 2: 3: 3; pedicel long, 1.25 × as long as wide; flagellomere I 1.65 × as long as wide; flagellomere IX 1.65 × as long as wide; flagellar pubescence suberect, about half of diameter of flagellomeres. Frons coriaceous; densely punctate. WH 0.92 × LH. WF 0.75 × WH. WF 1.81 × HE. Eye small, salient; pilosity sparse. Ocellus small. DAO 0.14 × WF; frontal angle of ocellar triangle acute. WOT 2.75 × DAO. OOL 1.18 × WOT. Distance of posterior ocellus to vertex crest 1.62 × DAO. VOL 1.06 × HE. Temple slightly divergent. Vertex straight. Occipital carina incomplete, not visible in dorsal view. Mesosoma (Fig. 26). Pronotal disc and mesonotum coriaceous; densely punctate. Pronotal collar long. Pronotal declivity high. Pronotal disc 0.41 × as long as wide. Notauli strongly conspicuous; complete; slightly convergent. Parapsidal furrow complete. Scutellar furrow long, slender, shallow, scrobiculate, posterior margin sinuous. Median region of scutellum polished, not punctate. Median region of metanotum short, wide. Inner foveae of metanotal furrow not delimited. Propodeal disc 1.10 × as long as wide; 0.52 × as high as long; basal triangle conspicuous, rugulose, rest of disc coriaceous; median carina absent; paramedian carina absent; lateral carina absent; sublateral carina absent; transversal carina absent; declivity medially strigulate, laterally punctate; side of propodeum slightly coriaceous. Mesopleuron slightly coriaceous; callus absent; fovea absent; mesopleural pit absent. Metacarpus 0.26 × radial vein; discoidal vein strongly pigmented, not interstitial with median; first recurrent slightly pigmented; subdiscoidal vein absent. Metasoma. Hypopygium (Fig. 46) 1.13 × as long as wide; posterior margin strongly trilobate; median lobe convex, slender; lateral lobe convex, long; lateral margin slightly convex; anterior pigmented line ill-defined, slender; median stalk long; lateral stalk absent. Genitalia (Figs 69–70): aedeagus uniformly wide; apical margin of ventral paramere convex; dorsal paramere as wide as ventral one, glabrous; basivolsella not excavated; inner margin of cuspis convex; genital ring long. FEMALE unknown. Material examined. Holotype, ♂. C. VIETNAM, Thua Thien Hué, Phong Dién N. P., nr. base-camp, 15 Km W Phong My, c 100 m, 22.III– 6.IV. 2001, Mal. trap 1–3, C. v. Achterberg & R. de Vries, RMNH’01. Distribution. Vietnam (Thua Thien Hué). Remarks. Caloapenesia heira sp. nov. resembles C. edas sp. nov. by present head elongate; eye and ocelli small; aedeagus uniformly wide. But C. heira sp. nov. presents median clypeal lobe rounded; scape shorter than in C. edas sp. nov.; occipital carina conspicuous; scutellum medialy polished; hypopygium strongly trilobate, with median lobe slender than in C. edas sp. nov.Published as part of Gobbi, Fernanda T. & Azevedo, Celso O., 2014, Revision of Caloapenesia (Hymenoptera, Bethylidae), with description of sixteen new species, pp. 501-535 in Zootaxa 3860 (6) on pages 510-511, DOI: 10.11646/zootaxa.3860.6.1, http://zenodo.org/record/23144
Nursing practice as bricoleur activity: a concept explored
No full textThe debates concerning the nature of nursing practice are often rooted in tensions between artistic, scientific and magical/mythical practice. It is within this context that the case is argued for considering that nursing practice involves bricoleur activity. This stance, which is derived from the work of Levi-Strauss, conceives elements of nursing practice as an embodied, bricoleur practice where practitioners draw on the 'shards and fragments' of the situation-at-hand to resolve the needs of the individual patient for whom they care. This conceptualisation of nursing practice will be analysed with a particular emphasis on its implication for nursing epistemology, pedagogy and praxis. The evidence to support this argument is drawn from empirical work that investigated nurses' use of intuition, the work of Levi-Strauss, and issues in nursing epistemology and ontology. The paper itself is written from the perspective of a bricoleur who uses 'bits and pieces' from the domains of nursing, philosophy, psychology, education, sociology and anthropology
Caloapenesia edas Gobbi & Azevedo, sp. nov.
No full textCaloapenesia edas Gobbi & Azevedo, sp. nov. (Figs 4, 18, 25, 45, 67, 68) Description. MALE. Body length 6.4 mm. LFW 5.1 mm. Color. Head and mesosoma black; clypeus and propodeum dark castaneous; mandible, antennae and metasoma castaneous; legs light castaneous; wings brownish. Head (Figs 4, 18). Mandible with five apical teeth; uppermost convex, others angulate; large, subequal in length. Median clypeal lobe trapezoidal; apical margin strongly medially ventrad; carina high, arched in profile. Antennal torulus slightly prominent. Flagellomeres median-sized; four first antennomeres in ratio about 16: 5: 7: 6; pedicel short, 1.25 × as long as wide; flagellomere I 1.75 × as long as wide; flagellomere IX 1.50 × as long as wide; flagellar pubescence suberect and erect, about half of diameter of flagellomeres. Frons coriaceous; densely punctate. WH 1.03 × LH. WF 0.75 × WH. WF 1.90 × HE. Eye small, salient; pilosity very sparse. Ocellus small. DAO 0.14 × WF; frontal angle of ocellar triangle acute. WOT 2.7 × DAO. OOL 1.25 × WOT. Distance of posterior ocellus to vertex crest 1.7 × DAO. VOL 1.1 × HE. Temple slightly divergent. Vertex straight. Occipital carina illdefined. Mesosoma (Fig. 25). Pronotal disc and mesonotum slightly coriaceous; densely punctate. Pronotal collar long. Pronotal declivity high. Pronotal disc 0.35 × as long as wide. Notauli strongly conspicuous; complete; slightly convergent. Parapsidal furrow complete. Scutellar furrow long, slender, shallow, scrobiculate, posterior margin sinuous. Median region of scutellum polished, not punctate. Median region of metanotum short, wide. Inner foveae of metanotal furrow not delimited. Propodeal disc 1.20 × as long as wide; 0.57 × as high as long; basal triangle conspicuous, rugulose, rest of disc coriaceous; median carina absent; paramedian carina absent; lateral carina absent; sublateral carina absent; transversal carina absent; declivity strigulate; side of propodeum polished. Mesopleuron slightly coriaceous; callus absent; fovea shallow; mesopleural pit absent. Metacarpus 0.37 × radial vein; discoidal vein strongly pigmented, not interstitial with median; first recurrent strongly pigmented; subdiscoidal vein slightly pigmented. Metasoma. Hypopygium (Fig. 45) 1.15 × as long as wide; posterior margin slightly trilobate; median lobe convex, wide; lateral lobe convex, very short; lateral margin straight; anterior pigmented line not defined; median stalk long; lateral stalk present, rectangular, inconspicuous. Genitalia (Figs 67–68): aedeagus uniformly wide; apical margin of ventral paramere convex; dorsal paramere as wide as ventral one, glabrous; basivolsella not excavated; inner margin of cuspis convex; genital ring long. FEMALE unknown. Material examined. Holotype, ♂. S. VIETNAM, Lam Gong, Bidoup Nuiba N. P., nr. Da Lat, Mal. Trap 1 –12, 1650– 1700 m, 11–19.X. 2005, C. v. Achterberg & R. de Vries, RMNH’05. Distribution. Vietnam (Lam Gong). Remarks. Caloapenesia edas sp. nov. is very similar to C. heira sp. nov. by presents head elongate; eye and ocelli small; aedeagus uniformly wide. But C. edas sp. nov. presents median clypeal lobe trapezoidal; occipital carina inconspicuous; scutellum totally polished; hypopygium slightly trilobate, with median lobe wider than in C. heira sp. nov. Caloapenesia edas sp. nov. resembles C. paruwa sp. nov. by presents head elongate; eye and ocelli small; aedeagus uniformly wide; hypopygium slightly trilobate. But C. edas sp. nov. presents uppermost tooth of mandible convex; hypopigial lateral lobe more conspicuous than in C. paruwa sp. nov. Caloapenesia edas sp. nov. resembles too C. launeci sp. nov. by median clypeal lobe trapezoidal. But C. edas sp. nov. presents clypeus trapezoidal with corners convex.Published as part of Gobbi, Fernanda T. & Azevedo, Celso O., 2014, Revision of Caloapenesia (Hymenoptera, Bethylidae), with description of sixteen new species, pp. 501-535 in Zootaxa 3860 (6) on pages 509-510, DOI: 10.11646/zootaxa.3860.6.1, http://zenodo.org/record/23144
Caloapenesia jailuna Gobbi & Azevedo, sp. nov.
No full textCaloapenesia jailuna Gobbi & Azevedo, sp. nov. (Figs 7, 19, 28, 48, 73, 74) Description. MALE. Body length 3.7 mm. LFW 2.5 mm. Color. Head, clypeus and mesosoma black; antennae and metasoma castaneous; mandible and legs light castaneous; wings subhyaline. Head (Figs 7, 19). Mandible with five apical teeth; angulate; small, subequal in length. Median clypeal lobe convex; apical margin not medially ventrad, with median tooth conspicuous; carina high, straight in profile. Antennal torulus slightly prominent. Flagellomeres median-sized; four first antennomeres in ratio about 16: 5: 6: 7; pedicel long, 1.25 × as long as wide; flagellomere I 1.5 × as long as wide; flagellomere IX 1.70 × as long as wide; flagellar pubescence suberect and erect, about half of diameter of flagellomeres. Frons polished; densely punctate. WH 1.0 × LH. WF 0.72 × WH. WF 1.60 × HE. Eye small, salient; pilosity abundant. Ocellus small. DAO 0.16 × WF; frontal angle of ocellar triangle acute. WOT 2.5 × DAO. OOL 1.1 × WOT. Distance of posterior ocellus to vertex crest 1.15 × DAO. VOL 0.77 × HE. Temple parallel. Vertex straight. Occipital carina complete, not visible in dorsal view. Mesosoma (Fig. 28). Pronotal disc coriaceous, mesonotum polished; densely punctate. Pronotal collar short. Pronotal declivity low. Pronotal disc 0.44 × as long as wide. Notauli strongly conspicuous; complete; slightly convergent. Parapsidal furrow complete. Scutellar furrow long, slender, shallow, scrobiculate, posterior margin straight. Median region of scutellum not punctate. Median region of metanotum short, wide. Inner foveae of metanotal furrow not delimited. Propodeal disc 0.90 × as long as wide; 0.60 × as high as long; basal triangle conspicuous, rugulose, rest of disc coriaceous; median carina absent; paramedian carina conspicuous, long; lateral carina present, inconspicuous; sublateral carina absent; transversal carina absent; declivity strigulate; side of propodeum polished. Mesopleuron polished; callus present; fovea shallow; mesopleural pit absent. Metacarpus 0.35 × radial vein; discoidal vein strongly pigmented, interstitial with median; first recurrent slightly pigmented; subdiscoidal vein slightly pigmented. Metasoma. Hypopygium (Fig. 48) 1.12 × as long as wide; posterior margin slightly trilobate; median lobe angulate, slender; lateral lobe rectangular, very short; lateral margin straight; anterior pigmented line ill-defined, slender; median stalk short; lateral stalk absent. Genitalia (Figs 73–74): aedeagus basally wide and fining at the top; apical margin of ventral paramere convex; dorsal paramere wider than ventral paramere, glabrous; basivolsella not excavated; inner margin of cuspis sinuous; genital ring short. FEMALE unknown. Material examined. Holotype, ♂. INDONESIA, S. Halmahera, 20 Km S. Payahe, Sagutora, Mal. Trap 11, c 125 m, 18.II– 18.III. 1995, C. v. Achterberg, R. de Vries & Y. Yasir, RMNH’ 95. Distribution. Indonesia (Halmahera). Remarks. Caloapenesia jailuna sp. nov. resembles C. philippinensis and C. leptata sp. nov. by head wider than long, excluding length of clypeus. But C. jailuna sp. nov. presents head quadrangular; ocellus and eye small; median clypeal lobe rounded, without median region ventrad, with a median tooth well conspicuous; lateral lobe of posterior margin of hypopygium very short and rectangular.Published as part of Gobbi, Fernanda T. & Azevedo, Celso O., 2014, Revision of Caloapenesia (Hymenoptera, Bethylidae), with description of sixteen new species, pp. 501-535 in Zootaxa 3860 (6) on page 512, DOI: 10.11646/zootaxa.3860.6.1, http://zenodo.org/record/23144
Caloapenesia inyara Gobbi & Azevedo, sp. nov.
No full textCaloapenesia inyara Gobbi & Azevedo, sp. nov. (Figs 6, 27, 47, 71, 72) Description. MALE. Body length 4.7 mm. LFW 2.8 mm. Color. Head, clypeus and mesosoma black; antennae, mandible and metasoma castaneous; legs ligth castaneous; wings subhyaline. Head (Fig. 6). Mandible with five apical teeth; angulate; small, subequal in length. Median clypeal lobe subrectangular; apical margin strongly medially ventrad, with median tooth conspicuous; carina high, arched in profile. Antennal torulus slightly prominent. Flagellomeres short; four first antennomeres in ratio about 15: 5: 6: 6; pedicel long, 1.25 × as long as wide; flagellomere I 1.50 × as long as wide; flagellomere IX 1.25 × as long as wide; flagellar pubescence suberect and erect, about half of diameter of flagellomeres. Frons polished; densely punctate. WH 1.0 × LH. WF 0.74 × WH. WF 1.61 × HE. Eye small, salient; pilosity sparse. Ocellus small. DAO 0.15 × WF; frontal angle of ocellar triangle nearly right. WOT 3.0 × DAO. OOL 1.0 × WOT. Distance of posterior ocellus to vertex crest 1.70 × DAO. VOL 0.83 × HE. Temple subparallel. Vertex straight. Occipital carina complete, not visible in dorsal view. Mesosoma (Fig. 27). Pronotal disc and mesonotum polished; densely punctate. Pronotal collar long. Pronotal declivity high. Pronotal disc 0.34 × as long as wide. Notauli strongly conspicuous; complete; slightly convergent. Parapsidal furrow complete. Scutellar furrow long, slender, shallow, scrobiculate, posterior margin straight. Median region of scutellum not punctate. Median region of metanotum short, wide. Inner foveae of metanotal furrow not delimited. Propodeal disc 0.91 × as long as wide; 0.52 × as high as long; basal triangle conspicuous, rugulose, rest of disc coriaceous; median carina absent; paramedian carina inconspicuous, long; lateral carina present, inconspicuous; sublateral carina present, inconspicuous; transversal carina absent; declivity slightly strigulate; side of propodeum polished, or slightly coriaceous. Mesopleuron polished; callus present; fovea shallow; mesopleural pit absent. Metacarpus 0.22 × radial vein; discoidal vein slightly pigmented, not interstitial with median; first recurrent slightly pigmented; subdiscoidal vein slightly pigmented. Metasoma. Hypopygium (Fig. 47) 1.02 × as long as wide; posterior margin strongly trilobate; median lobe convex, wide; lateral lobe subangulate, short; lateral margin slightly convex; anterior pigmented line ill-defined, slender; median stalk short; lateral stalk present, spiniform, inconspicuous. Genitalia (Figs 71–72): aedeagus basally wide and narrowing apicad; dorsal paramere as wide as ventral one, glabrous; basivolsella slightly excavated; inner margin of cuspis convex; genital ring short. FEMALE unknown. Material examined. Holotype, ♂. S. VIETNAM, Dông Nai, Càt Tiên N. P., Ficus trial, Mal. traps, c. 100 m, 9–30.IV. 2007, M. P. Quy & N. T. Manh, RMNH’07. Paratypes. S. VIETNAM, Dông Nai, Càt Tiên N. P., Ficus trial, Mal. traps, c. 100 m, 2 ♂, 9–30.IV. 2007, M. P. Quy & N. T. Manh, RMNH’07; 1 ♂, 1–9.X. 2005, C. v. Achterberg & R. de Vries, RMNH’05. Distribution. Vietnam (Dông Nai). Remarks. Caloapenesia inyara sp. nov. resembles C. rikawa sp. nov. by presents head rounded; clypeus rounded; ocellus and eye small; flagellomeres short; aedeagus basally wide. But C. inyara sp. nov. presents head slightly shorter than in C. rikawa sp. nov.; antennae light castaneous; carina paramedian absent; hypopigial median lobe convex and shorter than in C. rikawa sp. nov.; lateral margin of hypopygium convex; lateral stalk spiniform.Published as part of Gobbi, Fernanda T. & Azevedo, Celso O., 2014, Revision of Caloapenesia (Hymenoptera, Bethylidae), with description of sixteen new species, pp. 501-535 in Zootaxa 3860 (6) on pages 511-512, DOI: 10.11646/zootaxa.3860.6.1, http://zenodo.org/record/23144
Virtual interactive practice™: A strategy to enhance learning and competence in health care students
No full textThis paper reports the processes and initial outcomes of a pilot study which investigated a week long ‘virtual’ children’s ward experience for nursing students. Providing sufficient and meaningful experiences which enable students to quickly and effectively achieve competence in diverse areas of practice is often frustrated by the realities of available clinical experiences. Our response to this challenge was to more fully exploit and evaluate technologies which can be used to provide these learning experiences. Students experienced ‘real time’ scenario based work involving SIM-MAN; interactive information technology scenarios, critical incidents, master classes, video conferencing, and observational skill development exercises. Evaluation methodologies included observation of student performance, competence self rating scales; analysis of videotaped performance episodes and other data generated through the learning activities and lived experience accounts of participants. Initial findings indicate(1) statistically significant improvements in student competence measured through self reports; and (2) evidence of improvement gleaned from observed accounts, video analysis and qualitative evaluative comments. The final outcomes, including work with a control group, will be available for Conference
SEARCH FOR SELECTIVE ANTAGONISTS AT α1-ADRENORECEPTOR SUBTYPES: WB-4101 RELATED COMPOUNDS
No full textThe development of subtype selective α1 ligands is intensively pursued in order to obtain more effective and safer agents for the treatment of cardiovascular pathologies such as hypertension and arrhythmia, but also and particularly of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).
One of the oldest and most potent α1 antagonists is represented by WB-4101, a 2-aminomethyl-1,4-benzodioxane derivative which is slightly selective for α1A and, to a minor extent, for α1D-ARs with respect to α1B-AR and 5-HT1A serotoninergic receptor. Many structural modifications of WB-4101 have been done to improve both affinity and selectivity.1-4 Some evidences, resulting from mutagenesis and docking studies, suggest that the benzodioxane moiety and the 2,6-dimethoxyphenoxy residue of WB-4101 are, respectively, involved in conferring α1a selectivity and high α1 affinity. Consistently with these findings, our recent researches have demonstrated that removal of one or both ortho-methoxy substituents adversely affects the affinity for the three α1-AR subtypes, but not that for the 5-HT1A receptor.3
On the basis of these indications, we synthesized a number of S and R analogues of WB-4101, characterized by different substitutions at the benzodioxane and/or phenoxy fragment, in order to modulate and, hopefully, to improve the activity and selectivity profile of the parent compound. In particular, we considered derivatives with benzodioxane 8-substituted with F,4 Cl, OH or OMe 4 or fused with a cyclohexane to give a tetrahydronaphthodioxane polycycle.2 On the other hand, 2,6-dimethoxyphenyl residue was replaced by ortho methoxy substituted 1-naphthyl 2 or biphenyl systems. Finally, hybrid structures were designed combining some of the above modifications. After binding assays, which demonstrated the better α1a, α1b, α1d and 5-HT1A affinity of the S enantiomers, these latter were tested in functional assays on isolated tissues, finding that almost all were able to discriminate among the α1-AR subtypes.
1. Bolognesi M.L., Budriesi R., Cavalli A., Chiarini A., Gotti R., Leonardi A., Minarini A., Poggesi E., Recanatini M., Rosini M., Tumiatti V., Melchiorre C. J.Med.Chem. 1999, 42, 4214-4224.
2. Bolchi C., Catalano P., Fumagalli L., Gobbi M., Pallavicini M., Pedretti A., Villa L., Vistoli G., Valoti E. Bioorg.Med.Chem. 2004, 12, 4937-51.
3. Fumagalli L., Bolchi C., Colleoni S., Gobbi M., Moroni B., Pallavicini M., Pedretti A., Villa L., Vistoli G., Valoti E. Bioorg.Med.Chem. 2005, 13, 2547-2559.
4. Valoti E., Pallavicini M., Villa L., Pezzetta D. J.Org.Chem. 2001, 66, 1018-1025
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