HUP0103143A2 - A fruktóz-1,6-biszfoszfatáz új heteroaromás inhibitorai, eljárás az előállításukra és alkalmazásuk - Google Patents

A fruktóz-1,6-biszfoszfatáz új heteroaromás inhibitorai, eljárás az előállításukra és alkalmazásuk

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Publication number
HUP0103143A2
HUP0103143A2 HU0103143A HUP0103143A HUP0103143A2 HU P0103143 A2 HUP0103143 A2 HU P0103143A2 HU 0103143 A HU0103143 A HU 0103143A HU P0103143 A HUP0103143 A HU P0103143A HU P0103143 A2 HUP0103143 A2 HU P0103143A2
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HU
Hungary
Prior art keywords
group
alkyl
atom
aryl
diseases
Prior art date
Application number
HU0103143A
Other languages
English (en)
Inventor
Atul Agarwal
Qun Dang
Mark D. Erion
Srinivas Rao Kasibhatla
K. Raja Reddy
M. Rami Reddy
Original Assignee
Metabasis Therapeutics, Inc.
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Publication date
Application filed by Metabasis Therapeutics, Inc. filed Critical Metabasis Therapeutics, Inc.
Publication of HUP0103143A2 publication Critical patent/HUP0103143A2/hu
Publication of HUP0103143A3 publication Critical patent/HUP0103143A3/hu

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    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
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  • Enzymes And Modification Thereof (AREA)

Abstract

A tal lm ny t rgya az új, (I) és a (X) ltal nos képletű, heteroarom s,egy foszfon tcsoportot tartalmazó vegyületek, amelyek a fruktóz-1,6-biszfoszfat z hat sos inhibitorai. Ugyancsak a tal lm ny oltalmik"rébe tartoznak az (I) és (X) ltal nos képletű vegyületek prodrugjaiis. M srészt a tal lm ny t rgya ezen vegyületek elő llít sa, valaminta vegyületek in vitro és in vivo FBP z-g tló aktivit sa. A tal lm nymég tov bbi t rgya az ilyen FBP z-inhibitorok klinikai alkalmaz sa azolyan betegségek kezelésére vagy megelőzésére, amelyekben aglükoneogenezis g tl sa és/vagy a vércukorszint cs"kkentése ter pi seredményt hoz. A tal lm ny szerinti vegyületek ugyancsak alkalmasak aglikogénfelesleg t rol s val j ró betegségek, egyes kardiovaszkul risbetegségek (atheroszklerózis, miokardi lis iszkémi s k rosod sok), ésanyagcsere-betegségek (péld ul hiperkoleszterinémia, hiperlipidémia)kezelésére vagy megelőzésére, amelyeket a hiperinzulinémia éshiperglikémia súlyosbítani képes. Az (I) és (X) ltal nos képletekben aszubsztituensek jelentése az al bbiakban megadott: R5 jelentése az albbi csoportok egyike amelyekben minden G jelentése egym stólfüggetlenül szén-, nitrogén-, oxigén-, kén- vagy szelénatom, ahol csakegyetlen G lehet oxigén-, kén- vagy szelénatom, és legfeljebb egy Glehet nitrogénatom; minden G' jelentése egym stól függetlenül szén-vagy nitrogénatom, ahol kettőnél nem t"bb G' lehet nitrogénatom; Ajelentése hidrogénatom, halogénatom, alkil-, alkenil-, alkinil-,halogénezett alkil-, perhalogénezett alkil- vagy arilcsoport, vagy egy-NR42, -CONR42, -CO2R3, -S(O)R3, -SO2R3, -CH2OH, -CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR42 vagy -NHAc képletű csoport,vagy semmi; minden egyes B és D jelentése egym stól függetlenülhidrogénatom, halogénatom, alkil-, alkenil-, alkinil-, aril-,aliciklusos, aralkil-, alkoxi-alkil- vagy perhalogénezett alkil-csoport, ciano- vagy nitrocsoport vagy egy -C(O)R11, -C(O)SR3, -SO2R11, -S(O)R3, -NR92, -OR3 vagy -SR3 ltal nos képletű csoport(amelyek k"zül az arra alkalmas csoportok szubsztitu lva lehetnek),vagy semmi; E jelentése hidrogénatom, halogénatom, alkil-, alkenil-,alkinil-, aril-, aliciklusos, alkoxi-alkil- vagy perhalogénezettalkilcsoport, ciano- vagy nitrocsoport, vagy egy -C(O)OR3, -CONR42, -NR9, -OR3 vagy -SR3 ltal nos képletű csoport, (amelyek k"zül az arraalkalmasak szubsztitu lva lehetnek), vagy semmi; J jelentésehidrogénatom vagy semmi; X jelentése egy adott esetben szubsztitu lt"sszek"tő csoport, Y jelentése oxicsoport vagy egy -NR6- ltal nosképletű csoport; ha Y jelentése oxicsoport, akkor a hozz csatlakozó R1csoport jelentése hidrogénatom, alkil-, adott esetben szubsztitu ltaril-, adott esetben szubsztitu lt aliciklusos (ahol a ciklus egykarbon t- vagy tiokarbon tcsoportot tartalmaz), adott esetbenszubsztitu lt alkil-aril-, -alkil-S-S-alkil-hidroxi- vagy
HU0103143A 1998-09-09 1999-09-03 Novel heteroaromatic inhibitors of fructose 1,6-bisphosphatase, process for their preparation and their use HUP0103143A3 (en)

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US7312219B2 (en) 2007-12-25
US20070232571A1 (en) 2007-10-04
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