Chem pharm bull

Chem pharm bull

Originally, Chemical & Pharmaceutical Bulletin (CPB) covered all aspects of the pharmaceutical sciences, however, since the topics covered by the above journal became increasingly diverse, as a new sister journal, Biological & Pharmaceutical Bulletin was created in 1993.

Now CPB covers physical and inorganic chemistry, organic chemistry, natural products chemistry, medicinal chemistry, analytical chemistry, pharmacognosy and physical pharmacy.

Language: English
Abbreviation Title: Chem. Pharm. Bull.
Journal Coden: CPBTAL
ISSN: 0009-2363 (print), 1347-5223 (web)
Journal homepage: Chemical & Pharmaceutical Bulletin website

Open access articles are available for this journal from the year 1958 to 2008.

To browse substances from the Chemical & Pharmaceutical Bulletin please use the following links:

Discriminatory drug delivery into target cells is essential to effectively elicit the drug activity and to avoid off-target side effects; however, transporting drugs across the cell membrane is difficult due to factors such as molecular size, hydrophilicity, intercellular adhesiveness, and efflux transporters, particularly, in the brain capillary endothelial cells. Drug delivery into the brain is blocked by the blood–brain barrier (BBB). Thus, developing drugs for the central nervous system (CNS) diseases remains a challenge. The approach based on receptor-mediated transcytosis (RMT) can overcome this impassable problem at the BBB. Well-designed molecules for RMT form conjugates with the ligand and drugs via linkers or nanoparticles. Cell penetrating peptides (CPPs), receptor-targeting peptides, and monoclonal antibodies (mAbs) are often used as ligands. The binding of ligand to the receptor on the endothelial cell surface induces endocytosis. Existing exosomes comprising the conjugates move in the cytoplasm and fuse with the opposite plasma membrane to release them. Subsequently, the transcytosed conjugate-loaded drugs or released drugs from the conjugates elicit activity in the brain. As receptors, transferrin receptor (TfR), low-density lipoprotein receptor (LDLR), and insulin receptor (InsR) have been used to intendedly induce transcytosis. Presently, several clinical trials on CNS drugs for Alzheimer’s and Parkinson disease are hindered due to poor drug distribution into the brain. Therefore, this strategy based on RMT is a promising method for CNS drugs to be transported into the brain. In this review, I introduce the practicality and possibility of drug delivery into brain across the BBB using RMT.

Читайте также:  Now foods цитрат магния

In drug development, drug delivery into brain across the blood-brain barrier (BBB) is a serious problem. Particularly, the BBB is impermeable to large and medium-sized molecules. Accordingly, drugs for diseases of the central nervous system (CNS) are unable to elicit their activity in brain. However, receptor-mediated transcytosis can solve such impermeability. Actually, using receptors such as transferrin receptor (TfR), low-density lipoprotein receptor (LDLR), and insulin receptor (InsR), that express on the surface of brain capillary endothelial cells, delivered well-designed drugs into brain through endocytosis and exocytosis. This methodology will be a promising approach to cure patients suffering from CNS diseases.

Herein, we describe a novel synthetic method for 2,5-disubstituted tetrazoles from 5-substituted tetrazoles using cobalt-catalyzed intermolecular hydroamination reaction of nonactivated olefins. Owing to its mild conditions, the method enabled the use of substrates having acid-labile functional groups, such as silyloxy and methoxymethyloxy groups. By using optically active cobalt complexes, asymmetric intermolecular hydroamination of nonactivated olefins, a longstanding challenge in synthetic organic chemistry, was developed to produce optically active disubstituted tetrazoles.

An efficient synthetic method for 2,5-disubstituted tetrazoles from 5-substituted tetrazoles is developed. In this paper, the authors established a cobalt-catalyzed site-selective alkylation of tetrazoles via atom-economic hydroamination reaction between tetrazoles and non-activated olefins. The authors also applied the developed reaction to an asymmetric intermolecular hydroamination of non-activated olefins, which is one of the longstanding problems in synthetic organic chemistry.

Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections and a significant pathogen for both adults and children. Although two drugs have been approved for the treatment of RSV infections, the low therapeutic index of these drugs have led pharmaceutical companies to develop safe and effective small-molecule anti-RSV drugs. The pyrazolo[1,5-a]pyrimidine series of compounds containing a piperidine ring at the 2-position of the pyrazolo[1,5-a]pyrimidine scaffold are known as candidate RSV fusion (F) protein inhibitor drugs, such as presatovir and P3. The piperidine ring has been revealed to facilitate the formation of an appropriate dihedral angle between the pyrazolo[1,5-a]pyrimidine scaffold and the plane of the amide bond for exertion of anti-RSV activity. A molecular-dynamic study on newly designed compounds with an acyclic chain instead of the piperidine ring proposed and demonstrated a new series of pyrazolo[1,5-a]pyrimidine derivatives, such as 9c with a 1-methyaminopropyl moiety, showing similar dihedral angle distributions to those in presatovir. Compound 9c exhibited potent anti-RSV activity with an EC50 value of below 1 nM, which was similar to that of presatovir. A subsequent optimization study on the benzene ring of 9c led to the potent RSV F protein inhibitor 14f with an EC50 value of 0.15 nM. The possibility of improving the biological properties of anti-RSV agents by modification at the 7-position of pyrazolo[1,5-a]pyrimidine is also discussed.

Читайте также:  Atlet hard mass

This report describes the design, synthesis, and evaluation of a new series of pyrazolo[1,5-a]pyrimidine derivatives for treatment against respiratory syncytial virus (RSV). The pyrazolo[1,5-a]pyrimidine series of compounds containing a piperidine ring at the 2-position of the pyrazolo[1,5-a]pyrimidine scaffold are known as candidate RSV fusion (F) protein inhibitor drugs. The piperidine ring has been revealed to facilitate the formation of an appropriate dihedral angle between the pyrazolo[1,5-a]pyrimidine scaffold and the plane of the amide bond for exertion of anti-RSV activity. A molecular-dynamic study on pyrazolo[1,5-a]pyrimidine derivatives focusing on the dihedral angles proposed and demonstrated potent anti-RSV inhibitors with an acyclic chain instead of a piperidine ring. A subsequent optimization study on pyrazolo[1,5-a]pyrimidine derivatives containing 1-methylaminopropyl group led to a highly potent anti-RSV agent with an EC50 value of less than 1 nM.

The cryptolactones A1, A2, B1, and B2 isolated from a Cryptomyzus sp. aphid were synthesized via the Mukaiyama aldol reaction and olefin metathesis. Their antipodes and derivatives were also synthesized by the same strategy to investigate structure–activity relationships. These compounds exhibited cytotoxic activity against human promyelocytic leukemia HL-60 cells with IC50 values of 2.1–42 µM.

Aphids have unique polyketide pigments, which possess interesting biological activities such as cytotoxicity. In this article, the authors have focused on cryptolactone A1, A2, B1, and B2, colorless polyketide lactones, isolated from a colorless aphid, Cryptomyzus sp., and accomplished the asymmetric total syntheses of these compounds, their analogs bearing shorter carbon chains, and their antipodes. The investigation of structure-activity relationships among these compounds was carried out and revealed that both enantiomers exhibited similar cytotoxic properties towards HL-60 cell lines. However, compounds with shorter carbon chains were less cytotoxic than the others.

Читайте также:  25 Метров под водой в бассейне

Various aromatic lactones have been synthesized and their regioselectivity (1,2-addition vs. 1,4- or 1,6-addition) investigated in reactions with organolithium species, particularly n-BuLi and sec-BuLi. The regioselectivity varied greatly depending on various factors, such as the bulkiness of both substrates and organolithium species, and types of solvent and cosolvent. In particular, 1,4-addition with dearomatization occurred preferentially using sec-BuLi as the nucleophile in tetrahydrofuran (THF) with hexamethylphosphoramide (HMPA) or N,N′-dimethylpropyleneurea (DMPU) as cosolvent. For sec-BuLi, the reaction was estimated to proceed through a single-electron transfer mechanism.

Organic reactions using dearomatization have attracted much attention as a new approach to constructing complicated cyclic molecules. This paper describes the regioselectivity of nucleophilic addition of organolithium species (in particular, n-BuLi and sec-BuLi) to various aromatic lactones. The results of many experiments indicated that the regioselectivity varied greatly depending on various factors, such as the bulkiness of both substrates and organolithium species, and types of solvent and cosolvent. It is particularly interesting that the reactions mechanism of the addition of organolithium species differed between n — BuLi (via ionic process) and sec -BuLi (via one electron transfer process).

Journal Abbreviation: CHEM PHARM BULL
Journal ISSN: 0009-2363

About Chemical & Pharmaceutical Bulletin

    Originally, Chemical & Pharmaceutical Bulletin (CPB) covered all aspects of the pharmaceutical sciences, however, since the topics covered by the above journal became increasingly diverse, as a new sister journal, Biological & Pharmaceutical Bulletin was created in 1993.

Now CPB covers physical and inorganic chemistry, organic chemistry, natural products chemistry, medicinal chemistry, analytical chemistry, pharmacognosy and physical pharmacy.

Ссылка на основную публикацию
Bcaa влияние на печень
Научные исследования подтверждают важность аминокислот BCAA как для поддержания мышечной массы и её роста в бодибилдинге и спорте в целом,...
125 Грамм воды это сколько
15 Октября, 2018 Напитки Анна Кирницкая Стакан по всем своим критериям лучше других емкостей подходит для измерения объемов и веса...
13 Дневная японская диета меню
Японскую диету можно сравнить со сложным экзаменом, который требует проявить самурайскую силу воли у худеющего. После сдачи которого, будет заметна...
Bcaa инструкция по применению
Среди поклонников силовых тренировок со стажем практически каждый пробовал пищевые добавки под общим названием «BCAA». Многие знают, что они «помогают...
Adblock detector