Process Development of 4-[N-Methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline Dihydrochloride:  A Key Intermediate for TAK-779, a Small-Molecule Nonpeptide CCR5 Antagonist

2002 ◽  
Vol 6 (1) ◽  
pp. 70-73 ◽  
Author(s):  
Hideo Hashimoto ◽  
Tomomi Ikemoto ◽  
Tatsuya Itoh ◽  
Hideaki Maruyama ◽  
Tadashi Hanaoka ◽  
...  
Keyword(s):  
Small Molecule ◽  
Process Development ◽  
Ccr5 Antagonist

ChemInform Abstract: Process Development of 4-[N-Methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline Dihydrochloride (VI): A Key Intermediate for TAK-779 (VII), a Small-Molecule Nonpeptide CCR5 Antagonist.

ChemInform ◽  
2010 ◽  
Vol 33 (23) ◽  
pp. no-no
Author(s):  
Hideo Hashimoto ◽  
Tomomi Ikemoto ◽  
Tatsuya Itoh ◽  
Hideaki Maruyama ◽  
Tadashi Hanaoka ◽  
...  
Keyword(s):  
Small Molecule ◽  
Process Development ◽  
Ccr5 Antagonist

scholarly journals Analysis of Binding Sites for the New Small-Molecule CCR5 Antagonist TAK-220 on Human CCR5

2005 ◽  
Vol 49 (11) ◽  
pp. 4708-4715 ◽  
Author(s):  
Masao Nishikawa ◽  
Katsunori Takashima ◽  
Toshiya Nishi ◽  
Rika A. Furuta ◽  
Naoyuki Kanzaki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Small Molecule ◽  
Conformational Changes ◽  
Binding Pocket ◽  
Inhibitory Effect ◽  
Ccr5 Antagonist ◽  
Amino Acid Residues ◽  
Ccr5 Antagonists ◽  
Human Ccr5 ◽  
Hiv 1

ABSTRACT G protein-coupled receptor CCR5 is the main coreceptor for macrophage-tropic human immunodeficiency virus type 1 (HIV-1), and various small-molecule CCR5 antagonists are being developed to treat HIV-1 infection. It has been reported that such CCR5 antagonists, including TAK-779, bind to a putative binding pocket formed by transmembrane domains (TMs) 1, 2, 3 and 7 of CCR5, indicating the importance of the conformational changes of the TMs during virus entry. In this report, using a single-round infection assay with human CCR5 and its substitution mutants, we demonstrated that a new CCR5 antagonist, TAK-220, shares the putative interacting amino acid residues Asn252 and Leu255 in TM6 with TAK-779 but also requires the distinct residues Gly163 and Ile198 in TMs 4 and 5, respectively, for its inhibitory effect. We suggested that, together with molecular models of the interactions between the drugs and CCR5, the inhibitory activity of TAK-220 could involve direct interactions with amino acid residues in TMs 4, 5, and 6 in addition to those in the previously postulated binding pocket. The possible interaction of drugs with additional regions of the CCR5 molecule would help to develop a new small-molecule CCR5 antagonist.

scholarly journals A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity

1999 ◽  
Vol 96 (10) ◽  
pp. 5698-5703 ◽  
Author(s):  
M. Baba ◽  
O. Nishimura ◽  
N. Kanzaki ◽  
M. Okamoto ◽  
H. Sawada ◽  
...  
Keyword(s):  
Small Molecule ◽  
Ccr5 Antagonist ◽  
Anti Hiv ◽  
Hiv 1

Leveraging an Industrial–Academic Partnership To Optimize Small Molecule Process Development within the Pharmaceutical Industry

2015 ◽  
Vol 19 (2) ◽  
pp. 344-346 ◽  
Author(s):  
Rebecca E. Deasy ◽  
Catherine N. Slattery ◽  
Marie Kissane ◽  
Orla A. McNamara ◽  
Denis Lynch ◽  
...  
Keyword(s):  
Pharmaceutical Industry ◽  
Small Molecule ◽  
Process Development

Quality by design in formulation and process development for a freeze-dried, small molecule parenteral product: a case study

2011 ◽  
Vol 16 (6) ◽  
pp. 549-576 ◽  
Author(s):  
Linas N. Mockus ◽  
Timothy W. Paul ◽  
Nathan A. Pease ◽  
Nancy J. Harper ◽  
Prabir K. Basu ◽  
...  
Keyword(s):  
Small Molecule ◽  
Quality By Design ◽  
Process Development ◽  
Freeze Dried ◽  
Parenteral Product

scholarly journals Potential of small-molecule fungal metabolites in antiviral chemotherapy

2017 ◽  
Vol 25 (2) ◽  
pp. 20-52 ◽  
Author(s):  
Biswajit G Roy
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Process Development ◽  
Antiviral Treatment ◽  
Fungal Species ◽  
Viral Diseases ◽  
Mechanistic Study ◽  
Fungal Metabolites ◽  
New Drug ◽  
Novel Therapeutic Strategies

Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5–10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure–activity relationship of some common and important classes of fungal metabolites.

Advanced TEM sample preparation techniques for submicron Si devices

1995 ◽  
Vol 53 ◽  
pp. 516-517 ◽  
Author(s):  
P. B. Basham ◽  
H. L. Tsai
Keyword(s):  
Sample Preparation ◽  
Process Development ◽  
Light Transmission ◽  
Specific Area ◽  
Turnaround Time ◽  
Small Hole ◽  
Area Of Interest ◽  
Transmission Electron ◽  
Polished Side ◽  
Preparation Techniques

The use of transmission electron microscopy (TEM) to support process development of advanced microelectronic devices is often challenged by a large amount of samples submitted from wafer fabrication areas and specific-spot analysis. Improving the TEM sample preparation techniques for a fast turnaround time is critical in order to provide a timely support for customers and improve the utilization of TEM. For the specific-area sample preparation, a technique which can be easily prepared with the least amount of effort is preferred. For these reasons, we have developed several techniques which have greatly facilitated the TEM sample preparation.For specific-area analysis, the use of a copper grid with a small hole is found to be very useful. With this small-hole grid technique, TEM sample preparation can be proceeded by well-established conventional methods. The sample is first polished to the area of interest, which is then carefully positioned inside the hole. This polished side is placed against the grid by epoxy Fig. 1 is an optical image of a TEM cross-section after dimpling to light transmission.

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