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1.
J Dev Orig Health Dis ; : 1-10, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566171

RESUMO

Nonhuman primate (NHP) studies are crucial to biomedical research. NHPs are the species most similar to humans in lifespan, body size, and hormonal profiles. Planning research requires statistical power evaluation, which is difficult to perform when lacking directly relevant preliminary data. This is especially true for NHP developmental programming studies, which are scarce. We review the sample sizes reported, challenges, areas needing further work, and goals of NHP maternal nutritional programming studies. The literature search included 27 keywords, for example, maternal obesity, intrauterine growth restriction, maternal high-fat diet, and maternal nutrient reduction. Only fetal and postnatal offspring studies involving tissue collection or imaging were included. Twenty-eight studies investigated maternal over-nutrition and 33 under-nutrition; 23 involved macaques and 38 baboons. Analysis by sex was performed in 19; minimum group size ranged from 1 to 8 (mean 4.7 ± 0.52, median 4, mode 3) and maximum group size from 3 to 16 (8.3 ± 0.93, 8, 8). Sexes were pooled in 42 studies; minimum group size ranged from 2 to 16 (mean 5.3 ± 0.35, median 6, mode 6) and maximum group size from 4 to 26 (10.2 ± 0.92, 8, 8). A typical study with sex-based analyses had group size minimum 4 and maximum 8 per sex. Among studies with sexes pooled, minimum group size averaged 6 and maximum 8. All studies reported some significant differences between groups. Therefore, studies with group sizes 3-8 can detect significance between groups. To address deficiencies in the literature, goals include increasing age range, more frequently considering sex as a biological variable, expanding topics, replicating studies, exploring intergenerational effects, and examining interventions.

2.
J Dent Educ ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611257

RESUMO

The number of international students coming to the U.S. for post-secondary education has been steadily increasing. Prior research has found that international students encounter many barriers to academic success, but this topic has not been previously studied for the discipline of dental hygiene. The aims of this study were to investigate the barriers and challenges to academic success faced by international students in U.S. dental hygiene programs and to explore the students' thoughts on the value they bring to those programs. The overlapping qualitative methods of semi-structured focus groups and one-on-one interviews with 12 students in three U.S. dental hygiene programs were used for this phenomenological study. In the results, six themes emerged: language proficiency, communication challenges with faculty and patients, ability to adapt to a new educational system, adjusting to cultural differences, feelings of belonging, and the value of diversity. The most significant barrier for the participants was comprehension of the English language. Didactically, these students reported that they needed additional time to study and to process examination questions. This study found that these international students studying dental hygiene in the U.S. had academic challenges similar to international students studying in other disciplines. Dental hygiene educators may need to evaluate their didactic and test-taking strategies to ensure the academic success of international students.

3.
Eur J Dent Educ ; 23(3): 349-354, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31002204

RESUMO

INTRODUCTION: This study gathered information about life outside of the course for undergraduates studying at the School of Dentistry, Cardiff University. The aim was to explore how these external factors to the course may affect an individual's academic performance and well-being. MATERIALS AND METHODS: A cross-sectional study design was used. An online questionnaire designed for the purpose of the study was used to capture (quantitative and qualitative) data. Questions with dichotomous options, a range of statements with Likert scales (level of agreement) and open (free-text) questions were used. Data were analysed in SPSS using simple descriptive statistics and frequency distributions. Spearman's Rho was used to explore relationships for scaled categorical data. Content analysis was used for qualitative data. RESULTS: Two-thirds (n = 69, 63%) of participants reported being very stressed about their studies in the previous 12 months. The majority felt that external factors to their course (eg, lack of sleep, health issues, financial concerns, hobbies and issues with friends) had impacted on their academic lives with only 9% (n = 10) stating that their lives outside dentistry had no effect. DISCUSSION: Those who felt able to pursue hobbies and activities reported a better work-life balance and less stress. Questions about pursuing hobbies and sleep may help identify students at risk of being stressed or who may benefit from additional support in order to achieve a better work-life balance. CONCLUSION: This study has highlighted key areas for further investigation and opportunities for improving support to reduce student stress and improve well-being.


Assuntos
Amigos , Estudantes , Estudos Transversais , Humanos , Inquéritos e Questionários
4.
J Med Primatol ; 48(4): 226-235, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31025367

RESUMO

BACKGROUND: Non-human primate models of developmental programing by maternal mismatch between pregnancy and lactation diets are needed for translation to human programing outcomes. We present baboon offspring morphometry from birth to 3 years, and blood cortisol and adrenocorticotropin (ACTH) from 2 to 24 months. METHODS: Control mothers ate chow; mismatch mothers ate 30% less than controls during pregnancy and high-fat high-energy diet through lactation. RESULTS: Mismatch mothers lost weight during pregnancy. At birth, there were trends toward lower weight in mismatch offspring of both sexes (P = 0.06). From 0-3 years, catch-up growth occurred. Mismatch offspring male and female body weight increased faster than controls (P < 0.001). Mismatch female offspring showed greater increase in BMI (P < 0.001) and abdominal circumference (P = 0.008) vs controls. ACTH and cortisol slopes from 2 to 24 months of age were similar between groups in both sexes. Cortisol and ACTH increased after weaning in all groups. CONCLUSIONS: Mismatch produces sexually dimorphic post-natal growth phenotypes.

5.
J Med Chem ; 62(7): 3553-3574, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30938524

RESUMO

Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared and evaluated to address solubility and absorption limitations. While the phosphate prodrug failed to release 1 in rats, the introduction of a methylene spacer facilitated prodrug activation, but parent exposure was lower than that following direct administration of 1. Val amino acid and Val-Val dipeptides imparted low plasma exposure of the parent, although the exposure of the prodrugs was high, reflecting good absorption. Screening of additional amino acids resulted in the identification of an l-Phe ester that offered an improved exposure of 1 and reduced levels of the circulating prodrug. Further molecular editing focusing on the linker design culminated in the discovery of the self-immolative l-Phe-Sar dipeptide derivative 74 that gave four-fold improved AUC and eight-fold higher Ctrough values of 1 compared with oral administration of the drug itself, demonstrating a successful prodrug approach to the oral delivery of 1.

6.
Br Dent J ; 226(5): 342-348, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30850791

RESUMO

Aims To establish what work a sample of Overseas Registration Examination (ORE) registrants were undertaking and understand what had facilitated or impeded them from finding suitable employment as dentists. Method An online questionnaire, consisting of both closed and open questions, was used to capture data from a population of 1,106 former ORE candidates who passed the examination between 2009 and 2014 and were registered by the General Dental Council (GDC). The data were analysed and presented in the form of tables, figures and a presentation of the major themes that emerged from the responses. Results There was a 42% response rate. Seventy-one percent of respondents were employed as dentists in the UK, with the majority providing a mixture of private and NHS patient treatment. Most who were not working as dentists were actively seeking training places. Additional themes that were identified included: the availability of Dental Foundation/Vocational Training places; poor employment practices; perceptions of the strengths and weaknesses of the ORE; and some ideas about the future responsibilities of the GDC. Conclusions This survey has highlighted some difficulties that many ORE registrants face finding suitable work as dentists. Stakeholders should be aware of these challenges.

7.
Physiol Rep ; 7(6): e14024, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30912236

RESUMO

Poor nutrition during pregnancy is a worldwide public health problem. Maternal nutrient reduction (MNR) is associated with maternal and fetal stress and a sex-dependent decrease in nonhuman primate (NHP) cognitive performance. Early life stress potentiates epileptogenesis in a sex-specific manner, and temporal lobe (TL) epilepsy is associated with neurocognitive disorders. The endogenous cannabinoid system (ECS) demonstrates remarkable developmental changes and plays a key role in aging-related diseases (e.g., dementia). Baboons have been studied as a natural model of epilepsy and express all ECS system components. We therefore evaluated baboon fetal temporal cortex ECS ontogenic and MNR-dependent changes. At 120 days gestational age (dGA) (term 185 days), maternal, fetal, and placental morphometry were similar between control and MNR pregnancies. MNR maternal weight gain was decreased compared with controls at 165 dGA independent of fetal sex. In male fetuses, expression of ECS synthesizing and degrading enzymes was gestational age-dependent, with the exception of fatty acid amide hydrolase (FAAH). MNR had a sex-specific effect on the protein expression of CB1R during development: CB1R protein expression was decreased in fetal temporal cortex of male fetuses at 120 and 140 dGA. Our data reveal that the MNR has sex-specific effects on temporal cortical expression of the ECS in baboon offspring and shows vulnerability of ECS in male fetuses during gestation.

8.
J Med Chem ; 62(3): 1348-1361, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30609350

RESUMO

A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for activity against HIV-1 infection in cell culture. Small molecules that bind within the LEDGF/p75-binding site promote aberrant multimerization of the integrase enzyme and are of significant interest as HIV-1-replication inhibitors. Structure-activity-relationship studies and rat pharmacokinetic studies of lead compounds are presented.

9.
J Med Primatol ; 48(2): 90-98, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30569595

RESUMO

BACKGROUND: Non-human primate models of developmental programming by maternal obesity (MO) are needed for translation to human programming outcomes. We present baboon offspring (F1) morphometry, blood cortisol, and adrenocorticotropic hormone (ACTH) from 0.9 gestation to 0-2 years. METHODS: Control mothers ate chow; MO mothers ate high-fat high-energy diet pre-pregnancy through lactation. RESULTS: Maternal obesity mothers weighed more than controls pre-pregnancy. Maternal obesity gestational weight gain was lower with no correlation with fetal or placenta weights. At 0.9 gestation, MO and control F1 morphometry and ACTH were similar. MO-F1 0.9 gestation male cortisol was lower, rising slower from 0-2 years vs control-F1. At birth, male MO-F1 and control-F1 weights were similar, but growth from 0-2 years was steeper in MO-F1; newborn female MO-F1 weighed more than control-F1 but growth from 0-2 years was similar. ACTH did not change in either sex. CONCLUSIONS: Maternal obesity produced sexually dimorphic fetal and postnatal growth and hormonal phenotypes.

10.
J Med Chem ; 61(16): 7289-7313, 2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30067361

RESUMO

GSK3532795, formerly known as BMS-955176 (1), is a potent, orally active, second-generation HIV-1 maturation inhibitor (MI) that advanced through phase IIb clinical trials. The careful design, selection, and evaluation of substituents appended to the C-3 and C-17 positions of the natural product betulinic acid (3) was critical in attaining a molecule with the desired virological and pharmacokinetic profile. Herein, we highlight the key insights made in the discovery program and detail the evolution of the structure-activity relationships (SARs) that led to the design of the specific C-17 amine moiety in 1. These modifications ultimately enabled the discovery of 1 as a second-generation MI that combines broad coverage of polymorphic viruses (EC50 <15 nM toward a panel of common polymorphisms representative of 96.5% HIV-1 subtype B virus) with a favorable pharmacokinetic profile in preclinical species.

11.
J Med Primatol ; 47(6): 427-429, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29956833

RESUMO

We investigated menstrual cycles in intrauterine growth restricted (IUGR, 7-10 years, n = 8) and age-matched control (n = 10) baboons. Cycle duration and plasma anti-Mullerian hormone were similar. IUGR spent more days per cycle swollen and had elevated early morning fasted serum cortisol, suggesting normal fertility in the presence of increased psychosocial stress.

12.
Reprod Sci ; : 1933719118778794, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29871548

RESUMO

INTRODUCTION: Women threatening premature delivery receive synthetic glucocorticoids (sGC) to accelerate fetal lung maturation, reducing neonatal mortality and morbidity. Few investigations have explored potential long-term offspring side effects. We previously reported increased pericardial fat and liver lipids in 10-year-old (human equivalent 40 years) male baboons exposed to 3 antenatal sGC courses. We hypothesized middle-aged sGC male offspring show obesity-related morphometric changes. METHODS: Pregnant baboons received courses of 2 betamethasone injections (175 µg·kg-1·d-1 intramuscular) at 0.6, 0.64, and 0.68 gestation. At 10 to 12.5 years, we measured morphometrics and serum lipids in 5 sGC-exposed males and 10 age-matched controls. We determined whether morphometric parameters predicted amount of pericardial fat or lipids. Life-course serum lipids were measured in 25 males (7-23 years) providing normal regression formulas to compare sGC baboons' lipid biological and chronological age. RESULTS: Birth weights were similar. When studied, sGC-exposed males showed a steeper weight increase from 8 to 12 years and had increased waist and hip circumferences, neck and triceps skinfolds, and total and low-density lipoprotein cholesterol. Triceps skinfold correlated with apical and midventricular pericardial fat thickness, hip and waist circumferences with insulin. CONCLUSIONS: Triceps skinfold and waist and hip circumferences are useful biomarkers for identifying individuals at risk for obesity and metabolic dysregulation following fetal sGC exposure. Prenatal sGC exposure predisposes male offspring to internal adiposity, greater body size, and increased serum lipids. Results provide further evidence for developmental programming by fetal sGC exposure and call attention to potential emergence of adverse life-course effects.

13.
J Med Chem ; 61(9): 4176-4188, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29693401

RESUMO

HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug-drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug in rats. This strategy was refined by conjugating the amine with a promoiety designed to undergo bio-activation, as a means of modulating the subsequent chemo-activation. This culminated in a lead prodrug that (1) yielded substantially better oral drug delivery of 1 when compared to the parent itself, the simple acyl migration-based prodrug, and the corresponding simple l-Val prodrug, (2) acted as a depot which resulted in a sustained release of the parent drug in vivo, and (3) offered the benefit of mitigating the pH-dependent absorption associated with 1, thereby potentially reducing the risk of decreased bioavailability with concurrent use of stomach-acid-reducing drugs.

14.
Bioorg Med Chem Lett ; 28(9): 1550-1557, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29631960

RESUMO

The design and synthesis of a series of C28 amine-based betulinic acid derivatives as HIV-1 maturation inhibitors is described. This series represents a continuation of efforts following on from previous studies of C-3 benzoic acid-substituted betulinic acid derivatives as HIV-1 maturation inhibitors (MIs) that were explored in the context of C-28 amide substituents. Compared to the C-28 amide series, the C-28 amine derivatives exhibited further improvements in HIV-1 inhibitory activity toward polymorphisms in the Gag polyprotein as well as improved activity in the presence of human serum. However, plasma exposure of basic amines following oral administration to rats was generally low, leading to a focus on moderating the basicity of the amine moiety distal from the triterpene core. The thiomorpholine dioxide (TMD) 20 emerged from this study as a compound with the optimal antiviral activity and an acceptable pharmacokinetic profile in the C-28 amine series. Compared to the C-28 amide 3, 20 offers a 2- to 4-fold improvement in potency towards the screening viruses, exhibits low shifts in the EC50 values toward the V370A and ΔV370 viruses in the presence of human serum or human serum albumin, and demonstrates improved potency towards the polymorphic T371A and V362I virus variants.

15.
J Med Primatol ; 46(6): 293-303, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28744866

RESUMO

BACKGROUND: Most developmental programming studies on maternal nutrient reduction (MNR) are in altricial rodents whose maternal nutritional burden and offspring developmental trajectory differ from precocial non-human primates and humans. METHODS: Control (CTR) baboon mothers ate ad libitum; MNR mothers ate 70% global control diet in pregnancy and lactation. RESULTS: We present offspring morphometry, blood cortisol, and adrenocorticotropin (ACTH) during second half of gestation (G) and first three postnatal years. Moderate MNR produced intrauterine growth restriction (IUGR). IUGR males (n=43) and females (n=28) were smaller than CTR males (n=50) and females (n=47) in many measurements at many ages. In CTR, fetal ACTH increased 228% and cortisol 48% between 0.65G and 0.9G. IUGR ACTH was elevated at 0.65G and cortisol at 0.9G. 0.9G maternal gestational weight gain, fetal weight, and placenta weight were correlated. CONCLUSIONS: Moderate IUGR decreased body weight and morphometric measurements at key time points and altered hypothalamo-pituitary-adrenal function.


Assuntos
Dieta , Retardo do Crescimento Fetal/fisiopatologia , Feto/fisiologia , Doenças dos Macacos/fisiopatologia , Estado Nutricional , Papio hamadryas , Fenótipo , Hormônio Adrenocorticotrópico/sangue , Fenômenos Fisiológicos da Nutrição Animal , Animais , Feminino , Retardo do Crescimento Fetal/etiologia , Hidrocortisona/sangue , Lactação , Masculino , Doenças dos Macacos/etiologia , Papio hamadryas/crescimento & desenvolvimento , Gravidez
16.
Bioorg Med Chem Lett ; 27(4): 1089-1093, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28089701

RESUMO

A series of potent and novel acylsulfonamide-bearing triazines were synthesized and the structure-activity relationships (SARs) as HCV entry inhibitors were evaluated. This acylsulfonamide series was derived from an early lead, 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoic acid wherein the carboxylic acid was replaced with an acylsulfonamide moiety. This structural modification provided a class of compounds which projected an additional vector off the terminus of the acylsulfonamide functionality as a means to drive activity. This effort led to the discovery of potent analogues within this series that demonstrated sub-nanomolar EC50 values in the HCV pseudotype particle (HCVpp) assay.


Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Fusão de Membrana/efeitos dos fármacos , Triazinas/farmacologia , Animais , Antivirais/química , Antivirais/farmacocinética , Hepacivirus/fisiologia , Humanos , Ratos , Relação Estrutura-Atividade , Triazinas/química , Triazinas/farmacocinética
17.
Disabil Health J ; 9(4): 575-83, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27461727

RESUMO

BACKGROUND: Survival for many individuals with paralysis is increasing, making this population a larger subset of the aging population (Molton, & Jensen, 2010). Yet little is known about the demographics and health of this population (Freedman, 2014). OBJECTIVE: This study is one of the first evaluations of the differences in etiology, sociodemographic and health characteristics (i.e., health status, chronic, and secondary and medical conditions) of adults aging with versus into disability. METHODS: A cross sectional epidemiological study was performed using secondary data from a nationally representative sample of adults with paralysis. The National Paralysis Survey is a random digit-dial survey of over 70,000 households. Weighted descriptive and regression analyses were conducted. RESULTS: Eighty percent of those aging with paralysis had disabilities for 40+ years. They showed significantly better self-reported health status, and a trend for more secondary and medical conditions. Those aging into paralysis had more chronic diseases. CONCLUSIONS: Differences are evident between those aging with vs. into paralysis. These findings suggest that differentiating subgroups of older adults with disabilities by onset of disability makes disability and health information more actionable for programs and policies. Additional studies to explore the intersection of aging and disability onset across adulthood could increase our understanding of the dynamics of aging in persons with early and later onset disabilities.


Assuntos
Envelhecimento , Pessoas com Deficiência , Nível de Saúde , Paralisia , Atividades Cotidianas , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/epidemiologia , Estudos Transversais , Características da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Inquéritos e Questionários
18.
ACS Med Chem Lett ; 7(6): 568-72, 2016 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-27326328

RESUMO

HIV-1 maturation inhibition (MI) has been clinically validated as an approach to the control of HIV-1 infection. However, identifying an MI with both broad polymorphic spectrum coverage and good oral exposure has been challenging. Herein, we describe the design, synthesis, and preclinical characterization of a potent, orally active, second generation HIV-1 MI, BMS-955176 (2), which is currently in Phase IIb clinical trials as part of a combination antiretroviral regimen.

19.
J Dent Hyg ; 90(3): 181-91, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27340184

RESUMO

PURPOSE: The purpose of this descriptive study was to assess data pertinent to the Permit L local anesthesia license among practicing dental hygienists in Massachusetts, providing an overview of characteristics, practice behaviors, barriers for obtaining the permit and self-perceived competency. METHODS: A convenience sample of dental hygienists (n=6,167) identified through a publically available data base were invited to participate in a web-based survey. The survey consisted of demographic and Permit L specific questions. Items regarding opinions were rated using a 5-point Likert scale while frequencies and percentiles were used to evaluate demographics and practice-based information. Spearman's Rank correlation was performed to determine association between variables. RESULTS: A 10% (n=615) response rate was attained with (n=245) non-Permit L holders and (n=370) Permit L holders. Respondents reported significant differences in demographics and opinions between non-Permit L holders and Permit L holders (p<0.01) and between those certified through continuing education or curriculum based programs (p<0.01). Significant relationships were found in demographics (p<0.01) and practice (p<0.05) items in relation to the length of time the Permit L has been held. Themes from the data and comments indicate multiple factors influencing obtaining or not obtaining the Permit L. CONCLUSION: The results of this study provide an overview of Permit L local anesthesia administration that is generally comparable to previous studies and offers new insights into why some Massachusetts dental hygienists choose not to pursue certification. This study highlights the potential to increase the prevalence of the Permit L, address barriers to pursuing the Permit L, and further evaluate self-perceived barriers.


Assuntos
Anestesia Local/métodos , Higienistas Dentários/legislação & jurisprudência , Licenciamento em Odontologia/legislação & jurisprudência , Higiene Bucal/métodos , Adulto , Idoso , Certificação , Estudos Transversais , Currículo , Educação Continuada/legislação & jurisprudência , Feminino , Humanos , Masculino , Massachusetts , Pessoa de Meia-Idade , Inquéritos e Questionários
20.
ChemMedChem ; 11(14): 1517-30, 2016 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-27310202

RESUMO

The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in many disease states, including tumor cells, either by growth factor receptor tyrosine kinases or by the genetic mutation and amplification of key pathway components. A variety of PI3K isoforms play differential roles in cancers. As such, the development of PI3K inhibitors from novel compound classes should lead to differential pharmacological and pharmacokinetic profiles and allow exploration in various indications, combinations, and dosing regimens. A screening effort aimed at the identification of PI3Kγ inhibitors for the treatment of inflammatory diseases led to the discovery of the novel 2,3-dihydroimidazo[1,2-c]quinazoline class of PI3K inhibitors. A subsequent lead optimization program targeting cancer therapy focused on inhibition of PI3Kα and PI3Kß. Herein, initial structure-activity relationship findings for this class and the optimization that led to the identification of copanlisib (BAY 80-6946) as a clinical candidate for the treatment of solid and hematological tumors are described.


Assuntos
Imidazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe Ib de Fosfatidilinositol 3-Quinase/antagonistas & inibidores , Classe Ib de Fosfatidilinositol 3-Quinase/química , Descoberta de Drogas , Humanos , Ligações de Hidrogênio , Imidazóis/síntese química , Imidazóis/química , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirimidinas/síntese química , Pirimidinas/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade
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