Moderately potent steroids

Examples of group I, i.e. weak or low efficacy topical steroids, are hydrocortisone acetate in various concentrations, methylprednisolone 1.0% and prednisolone 0.5%. Group II, the moderately potent steroids, includes alclometasone dipropionate 0.05%, hydrocortisone butyrate 0.1%, triamcinolone acetonide 0.025% and fluocinolone ace-tonide 0.01%. Group III, the potent steroids, contains among others betamethasone valerate 0.1%, betamethasone dipropionate 0.05%, budesonide 0.025%, desoximetasone 0.05%, fluticasone propionate 0.05%, amcinonide 0.1%, fluocinonide 0.05% and mometasone furoate 0.1%. Group IV comprises the very potent agents such as clobetasol propionate 0.05% and halobetasol propionate 0.05%. 

In the work by Forsatz and Snow, three APIs and one excipient were determined by HPLC-UV and HPLC-CAD .22 The APIs were mometasone furorate, a moderately potent glucocorticoid steroid used in the treatment of inflammatory skin disorders, albuterol, a short-acting /32-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma, and Loratadine, a drug used to treat allergies. The excipient evaluated was lactose. In this work, the signal-to-noise ratio was compared at 10 ng for each of the APIs. Sensitivity was comparable for both albuterol and loratadine when compared to HPLC-UV, while CAD offered... 

Miscellaneous - As a consequence of the wide-spread search for anti-inflammatory agents several novel structures with a variety of activity-profiles have been discovered. A pyrazolo(3. 4-c) pyridine derivative (Su 15336) (XXI), possessing the partial structure of a family of very potent steroids, has been reported to be one of the most active nonsteroidal agents. 5-n-Butyl-l-cyclohexyl-2, 4, 6-trioxoperhydro-pyrimidine (XXII) (TBA 300) is a moderately active compound comparable to phenylbutazone. 

Pancuronium bromide (Pavulon) is a synthetic bis-quaternary agent containing a steroid nucleus (amino steroid), as denoted by the -curonium suffix. It is five times as potent as d-tubocurarine. Unlike d-tubocu-rarine, it does not release histamine or block ganglionic transmission. Like d-tubocurarine, it has a moderately long onset (2.9 minutes) and duration of action (110 minutes). Pancuronium and its metabolite are eliminated in the urine. 

The steroidal a-(isocyanomethyl)phosphonates (130) and (133) have been synthesized by methylation of the carbanions (129) and (132), respectively.66 Compounds (130) and (133) behave as N,P-ketals in that they can be hydrolysed to the corresponding ketones (131) and (134) (Scheme 10). A range of a-substituted a-aminophosphonic acids (136) have been prepared in moderate to excellent yield by the alkylation of the protected a-aminophosphonate (135) with alkyl and aryl halides and Michael acceptors under phase transfer catalysis (Scheme 11).67 The reactions of the lithium carbanion of diethyl prop-2-enyIphosphonate (137) with a,P-unsaturated ketones and esters have been investigated.6S Attack can be at the a- or y-positions in the phosphonate although in all cases Michael addition to the a, p-unsaturated carbonyl is preferred to attack at carbonyl carbon. In some examples simple adducts (138) are formed, but in more complex cases addition is followed by cyclisation to give (139) (Scheme 12). The bisphosphonate (141), which is a potent inhibitor of myo-inositol monophosphatase, has been prepared with the phosphonylation of the carbanion of (140) as a key step.6 9... 

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