132194-30-0Relevant articles and documents
Identification of HUHS190, a human naftopidil metabolite, as a novel anti-bladder cancer drug
Fukuhara, Hiroshi,Gotoh, Akinobu,Kino, Yukari,Kurioka, Rina,Mabuchi, Miyuki,Matsunaga, Wataru,Nakao, Syuhei,Shimizu, Tadashi,Tanaka, Akito,Yamaguchi, Keiko,Yamamoto, Momoka
, (2020)
We carried out structure-activity relationship study on anti-cancer effects of naftopidil (1) and its metabolites, resulted in identification of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190), a major human metabolite of 1, which exhibited the most selective toxicities between against normal and cancer cells (Table 1). 2 was more hydrophilic compared to 1, was enough to be prepared in high concentration solution of more than 100 μM in saline for an intravesical instillation drug. Moreover, serum concentration of 2 was comparable to that of 1, an oral preparation drug, after oral administration at 32 mg/kg (Fig. 3). Both of 1 and 2 showed broad-spectrum anti-cancer activities in vitro, for example, 1 and 2 showed inhibitory activity IC50 = 21.1 μM and 17.2 μM for DU145, human prostate cancer cells, respectively, and IC50 = 18.5 μM and 10.5 μM for T24 cells, human bladder cancer cells. In this study, we estimated anticancer effects of 2 in a bladder cancer model after intravesical administration similar to clinical cases. A single intravesical administration of 2 exhibited the most potent inhibitory activities among the clinical drugs for bladder cancers, BCG and Pirarubicin, without obvious side effects and toxicity (Fig. 4). Thus, HUHS190 (2) can be effective for patients after post-TURBT therapy of bladder cancer without side effects, unlike the currently available clinical drugs.
Synthesis of potential Naftopidil metabolites
Kutscher,Engel,Fleischhauer,Niebch
, p. 803 - 806 (2007/10/02)
The synthesis of four proposed metabolites 1-4 of Naftopidil, a selective α1-antagonist, is reported. These compounds comprise hydroxylated and demethylated derivatives and a cleavage product of Naftopidil.
Metabolic fate of the novel antihypertensive drug naftopidil
Niebch,Locher,Peter,Borbe
, p. 1027 - 1032 (2007/10/02)
The metabolism of 14C-naftopidil ((R,S)-1-(2-methoxyphenyl)-1-piperazinyl-3-(1-naphthyl-oxy)-2-propanol , CAS 57149-07-2) and the pharmacodynamic action of the metabolites was investigated. The metabolic pathway in rat, dog, mouse and man was qualitatively similar, with preference for the hydroxylation of the phenyl or naphthyl moiety of naftopidil ((phenyl)hydroxy-metabolite, (naphthyl)hydroxy-metabolite). Cleavage of the parent compound and production of the propylene glycol metabolite was a further important reaction especially for rat and man. In all species investigated, demethylation of naftopidil occurs to a minor extent. O-desmethyl-naftopidil, (phenyl)hydroxy-naftopidil and (naphthyl)hydroxy-naftopidil were found to have similar affinities for the α1-adrenoceptors as the parent compound (IC50(nmol/l): 433.0; 585.0; 52.7; respectively; naftopidil: 235.0). The naftopidil metabolites, like the parent compound showed no α2- or β-adrenoceptor affinity.
Piperazine derivatives, uses thereof and pharmaceutical compositions containing them
-
, (2008/06/13)
The present invention provides compounds of the general formula: STR1 wherein R1 is a hydroxyl group or a methoxy radical, R2 is a hydrogen atom or a hyroxyl group and R3 is a hydrogen atom or a hydroxyl group, with the proviso that R2 and R3 are not simultaneously hydrogen atoms when R1 is a methoxy radical; and the pharmacologically acceptable salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them.
