Substituted fused pyrimidine compounds, its preparation and uses thereof

A compound of formula I

• or a tautomer, polymorph, stereoisomer, solvate, or pharmaceutically acceptable salt thereof, wherein
• Y is selected from N or CR;
• R is selected from H, hydroxy, alkoxy, alkyl, aryl;
• R1 is selected from a group consisting of alkyl, alkenyl and alkynyl, wherein one or more methylene groups is optionally replaced by groups selected from —O—, —S(O)p—, NRaRa, or —C(O), and wherein the heteroatom is not adjacent to N in the ring;
• p is selected from 0, 1 or 2;
• wherein alkyl, alkenyl and alkynyl are unsubstituted or independently substituted with alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, —SO3H, aminocarbonylamino, hydroxyamino, alkoxyamino, or nitro;
• Z is selected from a bond, —O—, —S(O)p—, —NRa, —NRaC(O)— or —NRaS(O)2—;
• R2 is selected from a group consisting of alkyl, alkenyl, alkynyl, haloalkyl, aryl, arylalkyl, hydroxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl;
• wherein alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl are unsubstituted or independently substituted with alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, perhaloalkyl, CF3, OCF3, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, —SO3H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, —S(O)2NRbRb, —NRbS(O)2Rb or —S(O)pRc;
• wherein each substituent is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano or —S(O)pRd;
• R3 is selected from a group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl and arylalkyl;
• wherein alkyl, alkenyl, alkynyl, alkoxyalkyl and arylalkyl are unsubstituted or independently substituted with hydroxyl, alkyl, alkenyl, alkynyl or alkoxy;
• X is a (C3-C12)cycloalkyl;
• R4 is selected from hydrogen, cyano, hydroxyl, halogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carboxy, carboxyalkyl, alkoxy or haloalkoxy;
• A is selected from a bond, (C1-C6)alkyl, (C2-C6)alkenyl or (C2-C6)alkynyl group;
• wherein 1 to 4 methylene groups are optionally replaced by groups independently selected from 0, —S(O)p—, or —C(O)—;
• wherein A is optionally substituted with B;
• B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl or heteroaryl;
• wherein heterocyclyl, cycloalkyl, aryl and heteroaryl are unsubstituted or substituted independently with alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, —SO3H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NRbRb, —NRbS(O)2Rb or —S(O)pRc;
• wherein each substituent is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano or —S(O)pRd;
• each Ra is independently selected from the group consisting of hydrogen and alkyl;
• each Rb is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl;
• Rc is hydrogen, alkyl, aryl, heteroaryl or heterocyclyl;
• Rd is alkyl, aryl, or heteroaryl;
• n is 1 or 2;
• and p is 0, 1 or 2;
• with the proviso that—
• i. if A is bond, B and R4 are each hydrogen, then Z is not a bond;
• and
• ii. if Z is a bond, then R2 is not an alkyl, substituted with amino or substituted amino.