Other Analogs

4-Phenyl-2-azabicyclo[2.2.1]heptanes (27) have been synthesized via conventional routes by Takeda s group(21) as an extension of their arylmorphan and arylazabicyclo[3.2.1]octane studies. When R = H no analgesic activity was exhibited in the MW test however, curiously, the corresponding methyl ethers [e.g., 27 (R = Me)] were about x pentazocine as agonists. Some derivatives were moderate antagonists (— pentazocine). 

4-Aryl-2-azabicyclo[2.2.2]octanes (28) show a similar pattern of activities.(19) Although these compounds are not analgesic in the MW test, some of them (28, R and R1 = H andR = H. andR1 = Me) have pentazocinelike antagonist properties. 

Displacement of the nitrogen from its morphan position, as in the 1-phenyl-3-azabicyclo[3.3.1]nonanes (29), afforded compounds without MW analgesic activity, but where, again, some antagonist activity was detected.(22) 

Although isomorphans with bridgehead nitrogens (30) have been synthesized,(23) none have appropriately positioned aryl substituents. 

The necessity for having an appropriately positioned aromatic ring on a morphan nucleus for narcotic analgesic activity has been demonstrated.(25) 2-Methylmorphan (32) and the corresponding 6- and 7-enes were found to be devoid of MHP activity. Several substituted analogs of 31 have been reported more recently. (38 40) Some of these were synthetic precursors ofbenzomorphan-like compounds with a heterocyclic A-ring. 

---

This discussion refers to external plasticization only. Several theories, varyiag ia detail and complexity, have been proposed ia order to explain plasticizer action. Some theories iavolve detailed analysis of polarity, solubiHty, and iateraction parameters and the thermodynamics of polymer behavior, whereas others treat plasticization as a simple lubrication of chains of polymer from each other, analogous to the lubrication of metal parts by oil. Although each theory is not exhaustive, an understanding of the plasticization process can be gained by combining ideas from each theory, and an overall theory of plasticization must include all these aspects. 

Generally these derivatives are rather unstable and behave as oxidizing and halogenating agents. 1-Iodoimidazoles are more stable than other analogs. 

The example shown in Eq. (6.5) was conducted using 0.5 mole of bis-(2-mer-captoethyl) ether and 0.5 mole of 1,8-dichloro-3,6-dioxaoctane. The base was sodium hydroxide (1 mole) and between 900 and 2,000 mL of ethanol were used. The exact quantity of ethanol used in this synthesis is not clear from the experimental description. The reaction time was somewhere between 7 and 14 hours (again, unspecified), after which time the product (6) was isolated by vacuum distillation, as a viscous oil, in 27% yield. Similar approaches were utilized by this group for the synthesis of other analogs ". ... 

Other analogs give yields of approximately 25%. been employed. ... 

In addition to flnoroacetate, consider whether other analogs of TCA cycle metabolites or intermediates might be introduced to inhibit other, specific reactions of the cycle. Explain your reasoning. 

Another point for structural diversification is the sulfonamide group. Imai had already shown that a wide variety of groups could be introduced at this position to optimize the reaction. Since a wide variety of sulfonyl chlorides are commercially available, a number of different types of groups could be examined (Scheme 3.34). Testing of a variety of aryl and alkyl groups on the 1,2-cyclohexanediamine backbone demonstrates that the simple methanesulfonamide 122 is clearly superior or equal to many other analogs in the cyclopropanation of cinnamyl alcohol (Table 3.11). Another concern which was directly addressed by this survey was the question of catalyst solubility. 

Besides the aldol reaction in the true sense, there are several other analogous reactions, where some enolate species adds to a carbonyl compound. Such reactions are often called aldol-type reactions the term aldol reaction is reserved for the reaction of aldehydes and ketones. 

Several of these oxadiazoloquinoxaline 5-oxides have been converted into quinoxaline 1,4-dioxides. For example, 2-oxo-2//-[l,2,4]oxadiazolo[2,3-a]quinoxa-line-4-carbonitrile 5-oxide (572) in refluxing ethanol or 2-propanol for 2 h gave 3-ethoxycarbonylamino- (573, R = Et) or 3-isopropoxycarbonylamino-2-quinoxa-linecarbonitrile 1,4-dioxide (573, R = Pr ) in 61% or 74% yield, respectively 10 other analogous products with 6- and/or 7-substituents were made unambiguously in a similar way. ... 

H2O, 60°C, 30 min 34% after separation from several other products) 2-p-chlorophenylquinoxaline (67%) and other analogs were made similarly, and a possible mechanism was suggested. " ... 

Phenyl-6-trifluoromethylquinoxaline (229) gave 2-phenyl-6-trifluoromethyl-quinoxaline 4-oxide (230) (HCO2H, 30% H2O2, 50°C, 12 h 85% homologs similarly)6-methoxy- (231, R = OMe) and 6-nitro-3-phenylquinoxaline 1-oxide (231, R = N02), as well as other analogs, were made similarly in... 

Each of these compounds, 53-56, was shown to be a very effective competitive inhibitor of the enzyme with respect to the fructose 1,6-diphosphate, whereas several other analogs, including acyclic structures, had no effect. These and other results suggest that the furanose form of the sugar diphosphate is the active form in the enzymatic reaction (105). More recent studies using rapid quenching techniques and C-nmr measurements have confirmed this hypothesis and indicate that the enzyme uses the a anomer 52 much more rapidly than the 3 anomer 50 and probably uses the a anomer exclusively (106). 

Carbonylation of CpFe(CO)2Me at 125°C and 2000 psi of CO has afforded CpFe(CO)2COMe [Eq. (2)] (70), which, unlike CpMo(CO)3CO-Me, is stable. No other analogous acyls have been prepared by this method, almost certainly because of the availability of a more convenient synthesis from Na[CpFe(CO)2] and RCOCl. 

Perkin WH (1877) Formation of coumarin and of cinnamic and of other analogous acids from the aromatic aldehydes. J Chem Soc 31 388—427... 

Photoelimination of carbon dioxide from the 2-oxazolin-5-one 474 in the presence of methyl acrylate affords the cis- and frans-l-pyrrolines 475 and 476.394 A nitrile ylid is believed to be involved in this and other analogous transformations.395... 

The conjugated dienone 82 reacts with Et3SiH/TiCl4 to yield the nonconju-gated product 83 shown in Eq. 280.449 Other analogous dienones behave similarly with triethylsilane, but TMDO gives the best yields.458... 

Other analogs of CA-4, 7 have been developed and are also in clinical trials. These include AVE8062 (formerly known as AC-7700,10), a water soluble analog [33]. 

---