Initial discovery

Classical Receptor Antagonists. Since the initial discovery of an anti-histaminic compound in 1933, a very high number of potent compounds were... 

Since the initial discovery[1,2] and subsequent development of large-scale synthesis of buckytubes[3], various methods for their synthesis, characterization, and potential applications have been pursued[4-12). Parallel to these experimental efforts, theoreticians have predicted that buckytubes may exhibit a variation in their electronic structure ranging from metallic to semiconducting, depending on the diameter of the tubes and the degree of helical arrangement[13-16]. Thus, careful characterization of buckytubes and their derivatives is essential for understanding the electronic properties of buckytubes. 

Since the initial discovery there have been several investigations that have examined the Grignard reaction with quinolinium and isoquinolinium salts... 

Over 100 years after the initial discovery, the Fischer indole synthesis remains the most commonly employed method for the preparation of indoles. ... 

After this initial discovery. Oersted waited three months, apparently for the construction of a more powerful current source. He then carried out sixty experiments to show that the magnetic field due to the current in a wire is circular around the wire. He showed that the effect is independent of the type of wire, and that it is independent of any intervening common materials. Later, he proved that the effect is proportional to the current in the wire. 

The ultimate model is the human in the clinical situation. Translational medicine with noninvasive imaging techniques and biomarkers is now able to furnish valuable information that can be used in the initial discovery process to produce better defined drugs. 

The synthesis of tetraalkyldipnictines of the type R4E2 (E = P, As, Sb, Bi), containing a central E—E bond, goes back to Cadet s initial discovery of the... 

The initial discoveries of the extension of the aromatic ring of the ortho-phthalaldehyde (OPA) to a naphthalene-2,3-dicarboxaldehyde (NBA) and the substitution of cyanide (CN ) for 2-ME as the nucleophile have provided the Center with a much more versatile reagent system (5,11), which maintains the sensitivity for primary aliphatic amines and amino acids, and now is known to form fluorescent products with oligopeptides, proteins, and other related analytes that possess a primary amine function (Equation 1). 

Figure 7.23 shows the prototype diazobenzo[Z ]fluorene-based natural products kinamycin A and prekinamycin. The kinamycin A-D family were first isolated from Streptomyces murayamaensis, but the structures were incorrectly characterized as having a cyanobenzo[Z ]carbazole ring. Since the initial discovery of the kinamycins, many new analogues have been discovered from natural sources.88-92... 

While the Medicinal Chemistry route was adequate for the initial discovery stage of drug development, viewed against the need to make multiple kilograms or much larger quantities of compound 1 efficiently, the original route suffered from a few obvious shortcomings. 

Since the initial discovery, much work has gone into improving the catalyst. The original zeolite contained small pores that limited oxidations to relatively small molecules with shapes that allowed them to move in and out of that pore system. One modification has been to isolate titanium in zeolites with larger pores so larger molecules can be oxidized. Another modification has been to incorporate other metal ions into the frameworks of different zeolites with... 

Because of this fortuitous coincidence, we decided early in the planning of the 2004 Course to set aside time in the program for a ceremony to commemorate the birthday of the laser, with the participation if possible of those who contributed to its initial discovery and development. Unfortunately, Profs. Basov and Prokhorov are no longer living however, Prof. Andrei Varlamov, on behalf of the Russian Academy of Sciences, agreed to attend the ceremony and give his recollections of these gentlemen and their early years of laser research. 

Background information on the initial discovery and uses of the catalysts discussed in this section are to be found in Reference l. 

Since its initial discovery by Michael Faraday in 1825,58 benzene (C6H6) has been recognized as an extraordinary substance. The spectacular properties of benzene and its derivatives (particularly the aniline dyes discovered by W. H. Perkin) initiated dramatic growth of the pharmaceutical, dyestuff, and munitions industries in the mid nineteenth century. The famous puzzle of the chemical structure of benzene was solved in 1865 by August Kekule in terms of two alternative six-membered-ring formulas ... 

RyRs do not exist as isolated SR ion channels, but as protein complexes subject to modulation by cellular metabolites, [Ca2+] , kinases and other factors (e.g. Marx et al 2000). Currently, very little is known with respect to the expression and localization of RyR isoforms, the regulatory factors underlying sensitivity of the complex to gating, and the effect of luminal (SR) Ca2+ on the probability of spontaneous or triggered release. A renewed focus on the role of RyRs in smooth muscle should help move the field from the initial discovery of these exciting phenomena to a clearer understanding of the function of this system in diverse smooth muscle tissues. 

Perhaps the one major drawback with DIPAMP is the long synthetic sequence required for its preparation, though shorter and cheaper methods are now available [12]. The ligand continues to be a player for the synthesis of amino acid derivatives at scale, including L-Dopa, as mentioned above [12, 25, 27-29]. Its continued use is a testament to the power of the initial discoveries, as well as showing that a chemical catalyst can achieve selectivities only previously seen with enzymes. 

More intricate and potentially more attractive are catalytic transmetallation processes involving Zr, which may be classified into three categories shown as Classes 3—5 in Scheme 1.21. This area was mainly initiated and developed by Negishi in the 1970s. The initial discovery of the Ni-catalyzed cross-coupling [10] was soon followed by that of the Pd-cat-... 

In the late 1970s, Kirchhoff at Dow Chemical Company developed the use of benzocyclobutenes in polymer synthesis and modification. These efforts culminated in 1985 with the issuance of the first patent describing the use of benzocyclobutene in the synthesis of high-molecular-weight polymer.27 Similar work that involved a thermosetting system based on Diels-Alder cycloaddition between terminal benzocyclobutene and alkyne groups,28,29 was reported separately and independently by Tan and Arnold.28 Since these initial discoveries, the field of benzocyclobutene polymers has expanded rapidly and benzocyclobutene chemistry constitutes the basis of a new and versatile approach to the synthesis of high-performance polymers for applications in the electronics and aerospace industries.30... 

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