21971-23-3Relevant academic research and scientific papers
Development of potent and selective inhibitors of aldo-keto reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase) based on N -phenyl-aminobenzoates and their structure-activity relationships
Adeniji, Adegoke O.,Twenter, Barry M.,Byrns, Michael C.,Jin, Yi,Chen, Mo,Winkler, Jeffrey D.,Penning, Trevor M.
supporting information; experimental part, p. 2311 - 2323 (2012/05/04)
Aldo-keto reductase 1C3 (AKR1C3; type 5 17β-hydroxysteroid dehydrogenase) is overexpressed in castration resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5α-dihydrotestosterone. Selective AKR1C3 inhibitors are required because compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of 5α-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular, are potent but nonselective AKR1C3 inhibitors. Using flufenamic acid, 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid, as lead compound, five classes of structural analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure-activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC.
QUINAZOLINE POTASSIUM CHANNEL INHIBITORS
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Page/Page column 28, (2008/06/13)
The present invention relates to compounds having the structure (I) useful as potassium channel inhibitors to treat cardiac arrhythmias, and the like.
Integrin receptor antagonists
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, (2008/06/13)
Compounds of formula (I) STR1 wherein A1 is C or N; E is a five- or six-membered heteroaromatic or six-membered aromatic ring optionally substituted by R3 or R4 ; X1 --X2 is CHR1 --CH, CR1 =CH, NR1 --CH, S(O)u --CH or O--CH; X3 is CR5 R5 ', NR5, S(O)u or O; R2 is --OR', --NR'R", --NR'SO2 R'", --NR'OR', --OCR'2 C(O)OR', --OCR'2 OC(O)--R', --OCR'2 C(O)NR'2, CF3 or --COCR'2 R2 '; R3, R4 and R7 are independently H, halo, --OR12, --SR12, --CN, --NR'R12, --NO2, --CF3, CF3 S(O)r --, --CO2 R', --CONR'2, R14 --C0-6 alky-, R14 --C1-6 oxoalkyl-, R14 --C2-6 alkenyl-, R14 --C2-6 alkynyl-, R14 --C0-6 alkyloxy-, R14 --C0-6 alkylamino- or R14 --C0-6 alkyl--S(O)r --; R6 is W--(CR'2)q --Z--(CR'R10)--U--(CR'2)s --V-- or W'--(CR'2)q --U--(CR'2)s -- U and V are absent or CO, CR'2, C(=CR152), S(O)n, O, NR15, CR15 'OR15, CR'(OR")CR'2, CR'2 CR'(OR") C(O)CR'2, CR152 C(O), CONR15, NR15 CO, OC(O), C(O)O, C(S)O, OC(S), C(S)NR15, NR15 C(S), SO2 NR15, NR15 SO2, N=N, NR15 NR15, NR15 CR152, NR15 CR152, CR152 O, OCR152, C$(m)ZC, CR15 =CR15, Het, or Ar, provided that U and V are not simultaneously absent, and W and W' are a nitrogen-containing substituent, and integrin receptor antagonists.
