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排序方式: 共有464条查询结果,搜索用时 265 毫秒
61.
Patel MV Kolasa T Mortell K Matulenko MA Hakeem AA Rohde JJ Nelson SL Cowart MD Nakane M Miller LN Uchic ME Terranova MA El-Kouhen OF Donnelly-Roberts DL Namovic MT Hollingsworth PR Chang R Martino BR Wetter JM Marsh KC Martin R Darbyshire JF Gintant G Hsieh GC Moreland RB Sullivan JP Brioni JD Stewart AO 《Journal of medicinal chemistry》2006,49(25):7450-7465
The goal of this study was to identify a structurally distinct D(4)-selective agonist with superior oral bioavailability to our first-generation clinical candidate 1a (ABT-724) for the potential treatment of erectile dysfunction. Arylpiperazines such as (heteroarylmethyl)piperazine 1a, benzamide 2, and acetamides such as 3a,b exhibit poor oral bioavailability. Structure-activity relationship (SAR) studies with the arylpiperidine template provided potent partial agonists such as 4d and 5k that demonstrated no improvement in oral bioavailability. Further optimization with the (N-oxy-2-pyridinyl)piperidine template led to the discovery of compound 6b (ABT-670), which exhibited excellent oral bioavailability in rat, dog, and monkey (68%, 85%, and 91%, respectively) with comparable efficacy, safety, and tolerability to 1a. The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein. 相似文献
62.
Takashi Miyamoto Nicodème Sinzobahamvya Jutta Wetter Rolf Kallenberg Anne Marie Brecher Boulos Asfour Andreas E Urban 《European journal of cardio-thoracic surgery》2006,30(1):35-40
OBJECTIVE: To examine early and long-term results of surgical aortic valvotomy in neonates and infants aged less than 3 months. METHODS: A review of all 34 neonates (n=26) and young infants (n=8) aged 1-62 days undergoing primary open valvotomy for aortic valve stenosis between 1983 and 2003 was carried out. Associated major cardiac anomalies were endocardial fibroelastasis (n=8), aortic coarctation (n=3), subvalvular aortic stenosis (n=2), and ventricular septal defect (n=1). Risk factors for early mortality were estimated. Current information was available for 31 patients for a follow-up of 115+/-67 months. Kaplan-Meier method was used to estimate freedom from reintervention. RESULTS: Two neonates died early: operative mortality of 6% (2/34). Risk factors for early mortality were associated endocardial fibroelastosis, monocuspid aortic valve and impaired left ventricular function. No patient died late. Seven patients needed reintervention for re-aortic stenosis (n=5) or aortic insufficiency (n=2), i.e., re-valvotomy (n=3), valve replacement (n=2), Ross procedure (n=1), and balloon valvuloplasty (n=1). Freedom from reintervention was 85.1+/-6.9%, 78.0+/-9.35%, and 53.5+/-15.9% at 5, 10, and 15 years, respectively. CONCLUSIONS: Primary surgical aortic valvotomy in early infancy carries a low early and late mortality, a low occurrence of significant aortic regurgitation and a low early recurrence of aortic stenosis. In great majority of cases, reintervention can be delayed to allow implantation of an adult-sized prosthesis, when required. 相似文献
63.
64.
H. Delbrück H. C. Weichert G. Schmitt N. Firusian Prof. Dr. O. Wetter 《Journal of molecular medicine (Berlin, Germany)》1978,56(11):539-543
Zusammenfassung Anhand der klinischen Verläufe von 201 Patienten mit malignen Non-Hodgkin-Lymphomen wird der Zusammenhang zwischen der Prognose und der histologischen Einteilung nach der Kieler Klassifikation dargestellt.Die Fünfjahres-Überlebensrate bei 133 Patienten mit Lymphomen niedrigeren Malignitätsgrades lag bei 63% und bei 68 Patienten mit Lymphomen höheren Malignitätsgrades bei 23%, wobei Strahlen- und Chemotherapie in unterschiedlicher Weise eingesetzt wurden. Die günstigste Prognose hatten die Patienten mit zentrozytisch-zentroblastischen Lymphom, unabhängig vom Ausbreitungsstadium, während die Patienten mit lymphoblastischem Lymphom die ungünstigste Prognose hatten.Diese Ergebnisse unterstreichen die Bedeutung einer über rein morphologische Kriterien hinausgehenden Klassifikation der malignen Non-Hodgkin-Lymphome. 相似文献
65.
66.
Sixteen groups of plant viruses 总被引:2,自引:0,他引:2
B D Harrison J T Finch A J Gibbs M Hollings R J Shepherd V Valenta C Wetter 《Virology》1971,45(2):356-363
Sixteen groups of plant viruses are described. The type members and main characteristics of each group are listed. The extension of this system to other plant viruses is discussed, and it is recommended that only well studied viruses should be grouped. Names are proposed for twelve of the groups: bromovirus, carlavirus, caulimovirus, comovirus, cucumovirus, nepovirus, potexvirus, potyvirus, tobamovirus, tobravirus, tombusvirus, and tymovirus. We suggest that the value of these names should be tested by using them for an experimental period. 相似文献
67.
68.
L A Wetter J H Payne G Kirshenbaum E F Podoll T Bachinsky L W Way 《Archives of surgery (Chicago, Ill. : 1960)》1992,127(10):1195-8; discussion 1198-9
The ultrasonic dissector disrupts tissues in proportion to their fluid content by ultrasonically induced cavitational forces. Since sturdy tissues are spared, the instrument tends to follow tissue planes and to dissect fat and other soft tissues selectively. We performed a prospective, randomized, controlled trial in 73 patients comparing the safety and efficacy of a prototype ultrasonic dissector with that of electrosurgery and laser during laparoscopic cholecystectomy. Randomization was as follows: ultrasonic dissector, 37 patients; electrosurgery, 21 patients; and laser, 15 patients. The results were not different with respect to patient characteristics, amount of blood loss, technical difficulties, length of hospital stay, or return to work. Subjectively, the ultrasonic dissector was thought to be of special value in isolating the hilar structures, particularly when they were edematous or embedded in fat. The ultrasonic dissector disintegrated the fat, which was rapidly cleared up the suction channel, allowing the cystic duct and artery to be bared with less risk of injury. We concluded that the ultrasonic dissector has unique attributes that contribute to the ease and safety of laparoscopic cholecystectomy. 相似文献
69.
70.
Gomtsyan A Bayburt EK Schmidt RG Zheng GZ Perner RJ Didomenico S Koenig JR Turner S Jinkerson T Drizin I Hannick SM Macri BS McDonald HA Honore P Wismer CT Marsh KC Wetter J Stewart KD Oie T Jarvis MF Surowy CS Faltynek CR Lee CH 《Journal of medicinal chemistry》2005,48(3):744-752
Novel transient receptor potential vanilloid 1 (TRPV1) receptor antagonists with various bicyclic heteroaromatic pharmacophores were synthesized, and their in vitro activity in blocking capsaicin activation of TRPV1 was assessed. On the basis of the contribution of these pharmacophores to the in vitro potency, they were ranked in the order of 5-isoquinoline > 8-quinoline = 8-quinazoline > 8-isoquinoline > or = cinnoline approximately phthalazine approximately quinoxaline approximately 5-quinoline. The 5-isoquinoline-containing compound 14a (hTRPV1 IC50 = 4 nM) exhibited 46% oral bioavailability and in vivo activity in animal models of visceral and inflammatory pain. Pharmacokinetic and pharmacological properties of 14a are substantial improvements over the profile of the high-throughput screening hit 1 (hTRPV1 IC50 = 22 nM), which was not efficacious in animal pain models and was not orally bioavailable. 相似文献