Hemisuccinate

As a low molecular weight compound DAS is not significantly immunogenic, ie, it is a hapten and thus requires conjugation to a suitable antigenic carrier in order to eUcit a successfiil antibody response in animals. DAS treated with succinic anhydride results in the D AS—hemisuccinate (DAS—HMS) shown. 

As shown in Table 2, free DAS, as expected, is its own best displacing agent, whereas only DAS—HMS showed any appreciable displacing capabiUty. This can be expected because the hemisuccinate linker is also immunogenic and leads to the production of antibodies specific for the linker in the polyclonal antibody population. AH the other toxins had at least lOOx less the avidity for the antibody, illustrating the specificity of the aDAS for DAS. 

In Older to improve the poor oral absorption of carbenicillin [4697-36-3] a bpophilic rndanyl ester has been formulated, Geocillin [33331-88-3] (5). Prednisolone [30-24-8] a steroid, is derivatized to its C-21 hemisuccinate sodium salt (6) to make it extremely water-soluble (108). 

Benfurodil hemisuccinate Benzbromarone Mexiletine HCI Chloroacetonitrile Bendazac... 

C2H3CIO 75-36-5) see Acebutolol Acetiamine Acetylcholine chloride L-Alanine Benfurodil hemisuccinate . Chlorprothixene Flumetasone Ibuprofen lotalamic acid loxitalamic acid Levodopa Methestrol dipropionate Midecamycin acetate Naproxen Nimesulide Paclitaxel Paramethasone Phensuximide Retinol Rocuronium bromide Rofecoxib Ropinirole Tazarotene Thiopropazate Tiracizine Vecuronium bromide... 

C3H3CIO 78-95-5) see Befunolol Benfurodil hemisuccinate Benzarone Mexiletine Ofloxacin Secnidazole Sertaconazole Zoraepirac chloroacetonitrile... 

CifiHpNO, 33522-95-1) see Nalbuphine Naloxone 2 -hydroxy-4 -(2,5-dihydro-5-oxo-3-furyl)acetophenone (C12H10O4 3447-63-0) see Benfurodil hemisuccinate 0-(4-hydroxy-3,5-diiodophenyl)-3,S-diiodo-a-methyl-tyrosine... 

Hydrocortisone hemisuccinate Ibuprofen Indomethacin Ketoprofen Mefenamic acid Naproxen Noramidopyrine Oxyphenbutazone Phenylbutazone Piroxicam Sulindac Sulfinpyrazone Tartrazine Tolmetin... 

Dartanol, 24 536 Dart impact strength, 20 429 Darzens-Claisen condensation, 14 570 Darzens condensation, 10 505 DAS antibody, 14 145, 147 DAS-hemisuccinate (DAS-HMS), 14 144 DASH-Sodium Study, 22 813 Data, growth of, 21 612-613. See also Decay data... 

Propranolol-Hemisuccinate-Bovine-Serum-Albumin (BSA) Conjugate... 

It is also interesting to note that the three hemiesters of metronidazole are good substrates of pig liver esterases. The ty2 values for hydrolysis of the hemisuccinate, hemiglutarate, and hemimaleinate were 0.2, 2.3, and 2.0 h, respectively, in 5% pig liver homogenate at 37° and pH 7.4. 

Figure 4.4. The chemical synthesis of dexamethaso-ne-HSA. Dexamethasone hemisuccinate is first converted to a reactive intermediate with isobutylchlorocarbonate and is then coupled to the free E-NH2 of the lysine residues in human serum albumin (HSA).

The synthesis of letrozole (3) is quite simple (Scheme 3.5). An Sn2 displacement of 4-bromomethyl-benzonitrile (25) with imidazole was carried out in methylene chloride at room temperature to produce adduct 26. Deprotonation of 26 in DMF using potassium t-butoxide was followed by addition of para-fluorobenzonitrile. The S Ar reaction afforded letrozole (3) as an oil. In order to make the crystalline drug, a hemisuccinate was prepared, which has a melting point of 149-150°C. 

S)-N-(tert-butoxycarbonyl)-hydroxymethylpiperidine (8) is a key intermediate in the synthesis of a potent tryptase inhibitor (Scheme 7.5). It was synthesized from (R,.S)-3-hydroxyrnethylpiperidine via fractional crystallization of the corresponding L(-)dibenzoyl tartrate salt followed by hydrolysis and acylation [17]. The lipase from Pseudomonas cepacia (PS-30) immobilized on polypropylene accurel PP catalyzed the esterification of racemic 6 with succinic anhydride and toluene, giving the (S)-hemisuccinate ester (7). This was easily separated and hydrolyzed by base to the (S)-Boc-protected 3-hydroxymethylpiperidine (8). Using this repeated esterification procedure gave a 32% yield (maximum theoretical yield = 50%) and 98.9% . 

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