- Predictable stereoselective and chemoselective hydroxylations and epoxidations with P450 3A4
-
Enantioselective hydroxylation of one specific methylene in the presence of many similar groups is debatably the most challenging chemical transformation. Although chemists have recently made progress toward the hydroxylation of inactivated C-H bonds, enzymes such as P450s (CYPs) remain unsurpassed in specificity and scope. The substrate promiscuity of many P450s is desirable for synthetic applications; however, the inability to predict the products of these enzymatic reactions is impeding advancement. We demonstrate here the utility of a chemical auxiliary to control the selectivity of CYP3A4 reactions. When linked to substrates, inexpensive, achiral theobromine directs the reaction to produce hydroxylation or epoxidation at the fourth carbon from the auxiliary with pro-R facial selectivity. This strategy provides a versatile yet controllable system for regio-, chemo-, and stereoselective oxidations at inactivated C-H bonds and demonstrates the utility of chemical auxiliaries to mediate the activity of highly promiscuous enzymes.
- Larsen, Aaron T.,May, Erin M.,Auclair, Karine
-
supporting information; experimental part
p. 7853 - 7858
(2011/06/26)
-
- Combination preparation for use in dementia
-
The invention relates to a composition which is a pharmaceutical combination preparation comprising a compound which has an acetylcholinesterase-inhibitory action or exhibits muscarinergic action and a compound which increases the endogenous extracellular adenosine level, wherein the combination preparation is suitable for the treatment of dementia. The invention further relates to a process for the production of the combination preparation. The invention additionally relates to a process for treating patients in need of suitable therapy with the combination preparation.
- -
-
-
- Use of antibodies to TNF or fragments derived thereof and xanthine derivatives for combination therapy and compositions therefor
-
A combined preparation for simultaneous combined, simultaneous separate, or sequential use in the therapy of prophylaxis of disorders associated with undesirable high levels of TNF, e.g. septic or endotoxic shock and immunoregulatory and inflammatory disorders, which comprises an antibody to TNF or a TNF binding fragment thereof and a xanthine derivative. Particular preferred xanthine derivatives are 3,7-dimethyl-1(5-oxo-hexyl)xanthine (known as Pentoxifylline or TRENTAL) and 1-(5-hydroxy-5-methylhexyl)-3-methylxanthine and similar compounds. The anti-TNF antibody or fragment is preferably monospecific especially a humanized recombinant antibody or fragment.
- -
-
-
- Xanthine derivatives for the treatment of secondary nerve cell damage and functional disorders after cranio-cerebral traumas
-
The use of xanthine derivatives for the treatment of secondary nerve cell damage and functional disorders after cranio-cerebral traumas (CCT) The use of xanthine derivatives of the formula I STR1 and of their physiologically tolerable salts, in which R1 is oxoalkyl, hydroxyalkyl or alkyl, R2 is hydrogen or alkyl and R3 is hydrogen, alkyl, oxoalkyl or an alkyl having up to 6 carbon atoms, whose carbon chain is interrupted by an oxygen atom, for the production of pharmaceuticals for the treatment of disorders which can occur after cranio-cerebral traumas is described.
- -
-
-