Sequenced Treatment

Rush, A. J., Fava, M., Wisniewski, S. R. et al. (2004). Sequenced treatment alternatives to relieve depression (STAR D) rationale and design. Controlled Clinical Trials, 25(1), 119-42. 

Secondary allylic amines 184 have been prepared from aldehydes 181 (R1 = H, Me or Ph R2 = Me, Et or H) by the following sequence treatment with an amine R3NH2 (R3 = i-Pr, t-Bu, cyclohexyl or PhCH2) yields an imine 182, which is chlorinated by N-chlorosuccinimide. Dehydrochlorination of the resulting chloro compound with potassium t-butoxide gives an allylic imine 183, which is reduced to the product by means of methanolic sodium borohydride191. 

The term preconditioning here is reserved for between-runs steps. Treatment of new capillaries is described in the Section II b, and pre-sequence treatment is described in the Section II d. 

The conversion of the iodide 1481 to the olefin 1482 was achieved by a conventional four-step sequence. Treatment of 1482 with iodine, potassium iodide. 

The interpretation of the pharmacokinetic variables Cmax, AUCs and MRT of insulin glulisine was based on 95 % confidence intervals, after ln-transformation of the data. These 95 % confidence intervals were calculated for the respective mean ratios of pair-wise treatment comparisons. In addition, the test treatment was compared to the reference treatment with respect to the pharmacokinetic variables using an ANOVA with subject, treatment and period effects, after ln-transformation of the data. The subject sum of squares was partitioned to give a term for sequence (treatment by period interaction) and a term for subject within sequence (a residual term). Due to the explorative nature of the study, no adjustment of the a-level was made for the multiple testing procedure. 

In a similar sequence, treatment of (684) with 3-bromopropionic acid produced (685), which cyclized to imidazo[2,l-6][l,3]thiazine (686) upon heating with acetic anhydride (74JPR147). 

Isoamijiol (159 Scheme 52), a linear 5,7,6-ring-fused member of the dolastane group of diterpenes, is the principal secondary metabolite in the brown seaweed Dictyota linearis. In the course of the synthesis of (159), Pattenden also used a photocycloaddition-fragmentation sequence. Treatment of (157) with HF as mentioned above yields the hydroazulenone portion (158) of (159), which then was elaborated to isoamijiol. This is the first example of a C=C bond and an Si—-O bond being used as push-i)uU partners in a fragmentation. 

AUC(0—oo) and Cmax are presented in Table 6.5. Two subjects did not return to the clinic and did not complete the study. Hence, these subjects had only data from Period 1. Natural-log transformed AUC(0—oo) and Cmax were used as the dependent variables. The analysis of variance consisted of sequence, treatment, and period as fixed effects. Subjects nested within sequence were treated as a random effect using a random intercept model. The model was fit using REML. Table 6.6 presents the results. The 90% Cl for the ratio of treatment means for both AUC(0—oo) and Cmax were entirely contained within the interval 80-125%. Hence, it was concluded that food had no effect on the pharmacokinetics of the drug. 

A solid-phase submonomer approach to A-substituted j8-aminopro-pionic acid oligomers or )8-peptoids has been developed by Hamper et al. [63]. It is based on a simple two-step acylation and Michael addition reaction sequence. Treatment of Wang resin with 2 equiv. of acryloyl chloride in the presence of triethylamine in excess afforded the corresponding acrylate resin 86 (Scheme 23) [63]. Michael addition of a 6- to 10-fold excess of a given primary amine in DMSO afforded polymer-bound A-substituted -alanines (87). Trimeric A-benzyl-j8-aminopropionic acid (88) was prepared in 67% overall yield by repetition of this two-step sequence. 

Tables CXXXIX to CXLVH show the results of sequence treatment for resorcinoU vanillin and salicylic acid.

V. Chemical oxidatioa entoa s leageot), carbon adsoiption and bioangmentadon sequence treatment of vanillin... 

Table CXXXIX Carbon adsorpiton, cbemtcal oxidation and bloaugmentatlon sequence treatment of resorcinol... 

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