- Preparation of tritium-labeled PF-622, a novel fatty acid amide hydrolase inhibitor
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To make a detailed characterization of the mechanism of inhibition and selectivity of a novel fatty acid amide hydrolase inhibitor PF-622, 3 tritium isotopomers were prepared. [3H]PF-622a labeled at the piperazine ring B and [3H]PF-622b labeled at both the ring B and phenyl ring A were synthesized via catalytic H(hydrogen)-T(tritium) exchange, utilizing 1 equiv and excess of Crabtree's catalyst, respectively. The preparation of [3H]PF-622c labeled only at the phenyl ring A was achieved via tritiodebromination of the bromide precursor, using Pd(PPh3)4 as a catalyst. The observations from these tritiation reactions might open a new perspective in the labeling for the targets having a similar moiety.
- Zhang, Yinsheng
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- PIPERAZINYL AND PIPERIDINYL UREAS AS MODULATORS OF FATTY ACID AMIDE HYDROLASE
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Compounds of formula (I) : wherein, Z is -N-or>CH; R1 is -H or -C1-4alkyl; Ar1 is 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-primidinyl, 5-pyrimidinyl, or phenyl, each unsubstituted or substituted at a carbon ring member with one or two Ra moieties; Wher each Ra moiety is independently selected from the group consisting of -C1-4alkyl, -C2-4alkenyl, -OH, -OC1-4alkyl, halo, -CF3, -OCF3, -SCF3, -SH, -S(O)0-2C1-4alkyl, -OSO2C1-4alkyl, -CO2C1-4alkyl, -CO2H, -COC1-4alkyl, -N(Rb)Rc, -SO2NRbRc, -NRbSO2Rc, -C(=O)NRbRc, -NO2, and -CN, wherein Rb and Rc are each independently -H or -C1-4alkyl; and Ar2 is defined in the claims are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).
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(2008/06/13)
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