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US 2004/0167188 A1Published application
Protein-tyrosine phosphatase inhibitors and uses thereof
OwnerZhili Xin, Gang Liu +4inventors
InventorsZhili Xin, Gang Liu, Zhonghua Pei, Bruce G. Szczepankiewicz, Michael D. Serby, Hongyu Zhao
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds of formula (I), 1 or a pharmaceutically suitable salt or prodrug thereof, which are useful for the selective inhibition of protein tyrosine phosphatase-1B (PTP1B), and are useful for the treatment of disorders caused by overexpressed or altered protein tyrosine phosphatase 1B.
Claims19
A compound of formula (I),
- 24
- or a pharmaceutically suitable salt or prodrug thereof, wherein
- A is a member selected from the group consisting of
- 25
- B and C are each independently a member selected from the group consisting of aryl, and heterocycle;
- R1 is a member a member selected from the group consisting of alkyl, alkoxy, alkylSO2, trifluoroalkylSO2, trifluoroalkylNH—, alkylSO2NH—, carboxy, cyano, HONHcarbonyl, RaONHcarbonyl, nitro, RaOC(O)—, HO3S—, H2NO2S—, RaNHO2S—, (HO)2(O)P—, (HO)2(O)PCH2—, (HO)2(O)PCHF—, (HO)2(O)PCF2— and heterocycle, wherein said heterocycle is a member selected from the group consisting of:
- 26
- R2, R3, R4, R5, R6 and R7 are each independently absent or are independently a member selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, aryl, arylcarbonyl, arylalkyl, carboxy, carboxyalkyl, cyano, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, heterocycle, heterocyclecarbonyl, heterocyclealkyl, hydroxy, hydroxyalkyl, nitro, trihaloalkyl, RaRbN, RaRbNalkyl, RaRbNcarbonyl, RaRbNcarbonylalkyl, RaRbNNsulfonyl, RaRbNNsulfonylalkyl, wherein Raand Rb are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, and heterocyclealkyl;
- L is -G-X1-J-X2-K- or a bond;
- G, J and K are independently a member selected from the group consisting of a bond, alkyl, alkenyl, aryl and cycloalkyl, wherein said alkyl, alkenyl, aryl and cycloalkyl may be optionally substituted with a group consisting of alkoxy, alkyl, halogen, hydroxy, hydroxyalkyl, carboxy and RdReN—, wherein Rd and Re are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl and arylalkyl;
- X1 and X2 are each independently a member selected from the group consisting of a bond, —O—, —N(Rc)—, —N(Rc)C(O)—, —C(O)N(Rc)—, —N(Rc)S(O)2—, —S(O)2N(Rc)—, and —C(O)—, wherein Rc is a member selected from the group consisting of hydrogen, alkyl and arylalkyl;
- and
- provided that if J is absent, then at least one of X1 and X2 must be absent.
10 more elements
A compound of formula (II),
- 27
- or a pharmaceutically suitable salt or prodrug thereof, wherein
- R1 is a member selected from the group consisting of alkyl, alkoxy, alkylSO2, trifluoroalkylSO2, trifluoroalkylNH—, alkylSO2NH—, carboxy, cyano, HONHcarbonyl, RaONHcarbonyl, nitro, RaOC(O)—, HO3S—, H2NO2S—, RaNHO2S—, (HO)2(O)P—, (HO)2(O)PCH2—, (HO)2(O)PCHF—, (HO)2(O)PCF2— and heterocycle, wherein said heterocycle is a member selected from the group consisting of:
- 28
- R2, R3, R4, R5, R6 and R7 are each independently absent or are independently a member selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, aryl, arylcarbonyl, arylalkyl, carboxy, carboxyalkyl, cyano, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, heterocycle, heterocyclecarbonyl, heterocyclealkyl, hydroxy, hydroxyalkyl, nitro, trihaloalkyl, RaRbN, RaRbNalkyl, RaRbNcarbonyl, RaRbNcarbonylalkyl, RaRbNNsulfonyl, RaRbNNsulfonylalkyl, wherein Raand Rb are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, and heterocyclealkyl;
- L is -G-X1-J-X2-K- or a bond;
- G, J and K are independently a member selected from the group consisting of a bond, alkyl, alkenyl, aryl and cycloalkyl, wherein said alkyl, alkenyl, aryl and cycloalkyl may be optionally substituted with a group consisting of alkoxy, alkyl, halogen, hydroxy, hydroxyalkyl, carboxy and RdReN—, wherein Rd and Re are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl and arylalkyl;
- X1 and X2 are each independently a member selected from the group consisting of a bond, —O—, —N(Rc)—, —N(Rc)C(O)—, —C(O)N(Rc)—, —N(Rc)S(O)2—, —S(O)2N(Rc)—, and —C(O)—, wherein Rc is a member selected from the group consisting of hydrogen, alkyl and arylalkyl;
- and
- provided that if J is absent, then at least one of X1 and X2 must be absent.
7 more elements
Dependencies are inferred from the claim text.