Hydrocodone structure

Hydrocodone is an opium analgesic (pain reliever) and antitussive (cough suppressant). It is related in structure to other alkaloids used as drugs, such as morphine and codeine (see Section 8). It increased 20% in number of prescriptions for one year. Its synthesis from codeine is by simple reactions. 

The gold standard of opiate pain relievers is morphine. It was one of the first compounds extracted, isolated, and purified from the opium poppy, and it continues to be one of the most widely used pain relievers today. Morphine and other opiate drugs such as heroin, codeine, oxycodone, and hydrocodone have very similar chemical structures (Figure 3.2). However, other opiates such as fentanyl and meperidine (Demerol) have a slightly different structure (Figure 3.3). 

Figure 3.2 This diagram illustrates the chemical structures of morphine, codeine, oxycodone, hydrocodone, and heroin. Notice how each molecule differs from the others by only a few atoms.

The correct structure of morphine was proposed in 1925. Ultimate proof of its correct structure had to await its total synthesis, accomplished three decades later. The lack of the correct structure of morphine did not discourage the synthesis of several morphine congeners and derivatives by chemical reaction with the known peripheral functional groups, specifically the phenolic hydroxyl (C-3), and allylic alcohol (C-6), and the double bond (C-7-8) (Fig. 5-8). Among the derivatives introduced before 1930 and still in common usage today are codeine,6 ethylmorphine (Dionin), diacetylmorphine (heroin), hydromor-phone (Dilaudid), hydrocodone (Dicodid), and methyldihydromorphinone (Metopon). 

As shown in Figure 8, the total stabilization energy of the model hydration of hydromorphone base is 4.1 kcal mole compared to 9.4 kcal mole for oxymorphone base, with similar energies for hydrocodone and oxycodone. Since the models in Figure 7 are considered to represent the hydration of the fragments by which the two molecules differ structurally, this result indicates that the free base of oxymorphone... 

Chemical Structures hydrocodone, see Figure 20.1 oxycodone, see Figure 20.2 ibuprofen, see Figure 20.3... 

Opioids can be classified according to stractural similarity with morphine in semisynthetic and synthetic derivatives. Structurally similar, semisynthetic morphinelike derivatives as well as stracturally distinct opioids have been synthesized to search for compounds able to improve analgesic effects that minimize side effects. Semisynthetic derivatives include morphine-related agonists (hydromorphone, hydrocodone, oxycodone, oxymorphone, and codeine), and moiphine-related partial agonist and antagonists (buprenorphine, naloxone, and naltrexone). Synthetic derivatives include phenylpiperidines (meperidine and loperamide), diphenylpropylamines (methadone and propoxyphene), and piperidines (fentaityl, alfentanyl, sufentanil, and remifen-tanil) (Dumas and Pollack, 2008). 

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