Tài liệu Drugs: Photochemistry and Photostability doc

[...]... shortlived species in organic solvents, e g z ca 0.3 ps in ethanol, and is quite photoreactive via hydrogen abstraction under such conditions, and in general in an organic solution However, Photochemistry of Drugs: An Overview and Practical Problems b) ONO- - -NO2 3 0 ' RH / -N\ -W Products OH a \ 02 \ \ Sens Scheme 1 -\ 4 Drugs: Photochemistry and Photostabiliry the lifetime of this species increases by... analgesic and immunosuppressantdrugs; - drugs acting on the central nervous system; - cardiovascular, diuretic and hemotherapeutic drugs; - gonadotropic steroids and synthetic estrogens; - dermatologicals; - chemotherapeuticagents; - vitamins Photochemistry of Drugs:An Overview and Practical Problems 5 2.1 Anti-inflammatory, Analgesic and Immunosuppressant Drugs 2 I I Non-steroidal Anti-inflammatory and. .. transfer and, in part, ionisation.26 229 259 Drugs: Photochemistry and Photostability 6 C Y ~ ~ , N o ~ c H c O O R H M e H E 3 (7) Ph F M e IhCO Me H M e Scheme 4 PhCO%COO- HN+C(CH2OH)3 p w hv H20 or W H (12) PhCO X = CH2, CHOH, CH02H, CO Scheme 5 CHzCOOH I (13) COC~H,+C~ daylight COC&-4-C1 R = Me, CHO CH2COOMe + I c o c a-4-c 1 Scheme 6 ~ 0 ~ ~ ~14 - 4 c H 7 Photochemistry of Drugs:An Overview and Practical... rearrangement is a general reaction with aromatic esters and amides, and occurs via a radical mechanism, rather than via the ionic mechanism of the thermal reaction 5-Aminosalicylicacid (26), used for the treatment of 8 Drugs: Photochemistry and Photostability chronic inflammatory bowel polymerisation (Scheme 1l).40 diseases, undergoes light-accelerated oxidation and Scheme 10 HO H2N 02 hv _) HOO N HO N W O... state oxygen to a radical) photo-oxidation of the methyl group in position 5 This has been Drugs :Photochemistry and Photostability 10 attributed to the small distance between the methyl group of one molecule and the carbonyl group of a neighbouring molecule in the lattice This makes hydrogen abstraction easy and the resulting radical (31) adds oxygen to finally yield (32) (Scheme 13).52 Ph ”,O ’ Ph”,... and dehydration at the benzylic position, to give products (42) and (43) respectively, upon irradiation in aqueous solution (Scheme 17),55 and diphenylhydramine (44) suffers progressive N-dealkylation 56 The thiazine derivative promethazine (45) is N-dealkylated to phenothiazine (46) and this in turn oxidised to the sulfone (47) and to 3H-phenothiazin-3-one(48) (Scheme 18)s’ Ph2CHO(CH2)2NMe2 (44) Photochemistry. .. (56) and some of their acetates (see Scheme 20).65766 The primary photoproducts may undergo hrther transformation with cleavage of the three-membered ring, resulting in rearomatisation or cleavage of ring A or in expansion of ring B according to conditions R ' R" H H H H F a-Me F P-Me Scheme 20 Photochemistry of Drugs:An Overview and Practical Problems = 13 a + 0 0 xu + d llk ll X 0 0 n 00 W Drugs :Photochemistry. .. (path c), and this is the main path followed when one of the substituents is a stabilised alkyl group (secondary or Photochemistry of Drugs: An Overview and Practical Problems 15 allylic) This is the case with pentobarbital (59e, R=Et, R'=2-penty17R'=H)76 and secobarbital (59c R=allyl, Rt=2-pentyl,R"=H) (Scheme 22).77 This general scheme holds for the monoanion (the predominant species at pH lo), and the... or MeOH + Scheme 25 16 Drugs: Photochemistry and Photostability 2.2.2 Benzodiazepines Benzodiazepines are generally photolabile, but the path followed in the degradation depends on the structure of each derivative and on conditions Thus, diazepam (69) undergoes cleavage of the heterocyclic ring, the main products being the benzophenone (70) by irradiation at 320 mn in MeOH-H2O, and the dihydroquinazoline... the photochemistry, that is now dominated by reaction at that group (compare Scheme 1, b) As expected, this abstracts hydrogen and is reduced to the azoxy, azo, and amino knctions by irradiation in organic solvents under nitrogen (Scheme 27).85 In the presence of oxygen the molecule is rather photostable, but produces singlet oxygen.86 Analogously, the hypnotic Photochemistry of Drugs:An Overview and . x0 y0 w0 h1" alt="" Drugs: Photochemistry and Photostability