Rationalization alternative

Raloxifene is a SERM devoid of stimulating effects on the uterus as is known from the initial studies (Delmas et al. 1997). Eliminating one of the major concerns raised by the experience gained with tamoxifen studies, both in prevention and adjuvant treatments, puts raloxifene in a place of privilege to be a rational alternative agent. At the same time it improves bone density, prevents osteoporosis and vertebral fracture, and reduces cardiovascular events in a subset of high-risk patients (Silverman et al. 2004). The evidences on the effects of raloxifene on the uterus are explained in detail in Chap. 10 of this book. 

Next in our response to EPA s proposals was to present a detailed critique of the particular proposal which the Agency was bringing forth, and in addition --and this is most important -- to offer a constructive, rational alternative to that proposal, which not only met the goals of the Act, but was within the limits and the scope prescribed by Congress. 

MacGregor, R.R. and Graziani, A.L. (1997) Oral adminstration of antibiotics A rational alternative to the parenteral route. Clin. Infect. Diseases, 24 457 167. 

If the oral route is unsuccessful, a rational alternative is to use suppositories of diclofenac 100 mg for pain and domperidone 30 mg for vomiting, although the diarrhoea that may accompany migraine would compromise their efficacy. Efficient use of an analgesic and an antiemetic is adequate for the majority of acute attacks. 

Attempted peroxy acid epoxidation of the bicyclic ketone (31 equation 13) gave the lactone (33), instead of several possible rational alternatives. The epoxide (32) was implicated as an intermediate when it was independently synthesized from the epoxy alcohol, and shown to give (33) on treatment with aqueous acid.- A mechanism involving scission of the acyl bridgehead bond via the hydrated 1,1 -diol form of the ketone was proposed to account for the formation of this unexpected product. The rearrangement of the isolongifolene derivative (34 equation 14) appears to be mechanistically related. The product (35) is formed by brief treatment with dilute HCIO4 in dioxane as a mixture of isomers believed to arise by acid-catalyzed epimerization of the carbinol center. ... 

The use ofLt in early pregnancy may be associated with an increase in the incidence of cardiovascular anomalies of the newborn, especially Ebstein s malformation. The antimanic anticonvulsants valproic acid and probably carbamazepine have an associated risk of irreversible spina bifida that may exceed 1/100, and so do not represent a rational alternative for pregnant women. In balancing the risk versus benefit of using LG in pregnancy, it is important to evaluate the risk of untreated manic-depressive disorder and to consider conservative measures, such as deferring intervention until symptoms arise or using a safer treatment, such as a neuroleptic or ECT... 

An important goal of studying chemical descriptors for their ability to predict aqueous solubility was to provide a rational alternative to the intuitive bias that tended to dominate the descriptor selection in this area of research. Many scientists had included in their studies descriptors that... 

The purpose of this chapter is to present a rational alternative for those instances when laboratory data do not exist or, if it is desirable, to extrapolate field experience. 

Looking a bit further in time, probably new APAs possessing higher therapeutic effect will be described. In that case, the actually accessible lipases may not be sufficiently effective to resolve the racemic mixtures, so that the screening of new lipase-producing microorganisms appears to be a rational alternative for obtaining biocatalysts with improved efficiency. 

One may rationalize emulsion type in terms of interfacial tensions. Bancroft [20] and later Clowes [21] proposed that the interfacial film of emulsion-stabilizing surfactant be regarded as duplex in nature, so that an inner and an outer interfacial tension could be discussed. On this basis, the type of emulsion formed (W/O vs. O/W) should be such that the inner surface is the one of higher surface tension. Thus sodium and other alkali metal soaps tend to stabilize O/W emulsions, and the explanation would be that, being more water- than oil-soluble, the film-water interfacial tension should be lower than the film-oil one. Conversely, with the relatively more oil-soluble metal soaps, the reverse should be true, and they should stabilize W/O emulsions, as in fact they do. An alternative statement, known as Bancroft s rule, is that the external phase will be that in which the emulsifying agent is the more soluble [20]. A related approach is discussed in Section XIV-5. 

This genera] scheme could be used to explain hydrogen exchange in the 5-position, providing a new alternative for the reaction (466). This leads us also to ask whether some reactions described as typically electrophilic cannot also be rationalized by a preliminary hydration of the C2=N bond. The nitration reaction of 2-dialkylaminothiazoles could occur, for example, on the enamine-like intermediate (229) (Scheme 141). This scheme would explain why alkyl groups on the exocyclic nitrogen may drastically change the reaction pathway (see Section rV.l.A). Kinetic studies and careful analysis of by-products would enable a check of this hypothesis. 

Quantitative risk analysis (QRA) is a powerful analysis approach used to help manage risk and improve safety in many industries. When properly performed with appropriate respect for its theoretical and practical limitations, QRA provides a rational basis for evaluating process safety and comparing improvement alternatives. However, QRA is not a panacea that can solve all problems, make decisions for a manager, or substitute for existing safety assurance and loss prevention activities. Even when QRA is preferred, qualitative results, which always form the foundation for QRA, should be used to verify and support any conclusions drawn from QRA. 

Examination of the data given in Table 2 shows a rational fit of the experimental data to the equations of Van Deemter, Giddings and Knox. Both the Huber and Horvath equations, however, gave alternating positive and negative values for the constant (D)... 

Young and Wilcock [7] have recently provided an alternative to this simple approach. They also follow step (a), but rather than obtaining as in (b) they determine the constituent entropy increa.ses (due to the various irreversible thermal and mixing effects). Essentially, they determine the downstream state from the properties To and the entropy. v, rather than T), and po- This approach is particularly convenient if the rational efficiency of the plant is sought. The lost work or the irreversibility ( f = "lay be subtracted... 

The anomalous iodoacetamide-fluoride reaction violates this rule, in that a less stable -halonium complex (18) must be involved, which then opens to (19) in the Markownikoff sense. This has been rationalized in the following way estimates of nonbonded destabilizing interactions in the possible products suggest that the actual product (16) is more stable than the alternative 6)5-fluoro-5a-iodo compound, so the reaction may be subject to a measure of thermodynamic control in the final attack of fluoride ion on the iodonium intermediate. To permit this, the a- and -iodonium complexes would have to exist in equilibrium with the original olefin, product formation being determined by a relatively high rate of attack upon the minor proportion of the less stable )9-iodonium ion. 

Which nitrogen in each molecule is more basic Compare energies of the alternative conjugate acids (Nprotonated imidazole, NH protonated imidazole, N protonated pyrazole and NH protonated pyrazole). Which compound, imidazole or pyrazole, is more basic Compare the energies of protonation (leading to the favored conjugate acid in each case). Rationalize your result. 

Assignment of the l,2,4-triazolo[l,5-c]pyrimidine structures to the products obtained from the previously described cyclizations and not the alternative [4,3-c] structures has been rationalized and corroborated on the basis of (a) preference of cyclization at the more nucleophilic triazole ring N2 rather than at its less nucleophilic N4 (65JOC3601 88JMC1014), (b) inability of the obtained products to undergo acid- or base-catalyzed Dimroth rearrangement, a property characteristic of the thermodynamically less stable [4,3-c] isomers (91JMC281), (c) comparison with unequivocally prepared... 

It is not obvious how the adsorbed 2,2 -dihydro-2,2 -bipyridine (14) could leave the catalyst without undergoing dehydrogenation either simultaneously or before desorption. This second alternative could however be rationalized if it is assumed that in the preparation of 2,2 -bipyridine the two molecules of pyridine are bonded to one atom of nickel (15). The formation of the carbon-carbon bond could... 

In his original paper,2 Cram disclosed an alternative model that rationalizes the preferred stereochemical course of nucleophilic additions to chiral carbonyl compounds containing an a heteroatom that is capable of forming a complex with the organometallic reagent. This model, known as the Cram cyclic or Cram chelate model, has been extensively studied by Cram9 and by others,410... 

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