Derivatives piperidin-4-IL azetidine as inhibitors of JAK1

a compound of Formula (I): ** ** Formula or pharmaceutically acceptable salt thereof; where: X is N or CR2; Y is N or CR3; Z is H, cyano, halo, C1-3 alkyl or C1-3 haloalkyl; L is C (R4) 2, C (> = O), C (> = O) N (R4a), C (> = O) C (R4b) 2, S (> = O) 2, C (> = O) O, C (> = O) OC (R4b) 2 OC (> = O) N (R4a) C (R4b) 2); A is C1-6 alkyl, C3-14 cycloalkyl, C2-13 heterocycloalkyl, C6-14 aryl or C1-14 heteroaryl; wherein said C1-6 alkyl, C3-14 cycloalkyl, C2-13 heterocycloalkyl, C6-14 aryl and C1-14 heteroaryl individually replaced and optionally 1, 2, 3, 4, 5 or 6 groups independently selected R5; or each R1 is independently C1-4 alkyl, hydroxy, C1-4 alkoxy, fluorine, hydroxyl- C1-4alkyl or C1-4 alkoxy C1-4 alkyl; two R1 groups together form a bridge of 3-2- carbons or a bridge of the formula -CH2-O-CH2; R2 is H, halo, hydroxy, cyano, C1-4 alkyl, C1-4 haloalkoxy or C1-4 alkoxy; R3 is H, cyano, amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-6 alkylamino, C1-6 alkylsulfonyl, carbamoyl, C1-6 alkylcarbamyl, di-C1-6 alkylcarbamyl, caboxi, C1-6 alkoxycarbonyl or C1-6 alquilcabonilo; each R4 is independently H or C1-4 alkyl; or two R4 groups together with the carbon atom to which they are attached form a ring cicloaqluilo 3, 4, 5 or 6 members; R4a is H or C1-4 alkyl; each R4b is independently H or C1-4 alkyl; or two groups R4b together with the carbon atom to which they are attached forms a cycloalkyl ring with 3, 4, 5 or 6 members; each R5 is independently halo, cyano, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-3 alkyl, C2 -10 heterocycloalkyl, C2-10 heteroaryl-C1-3 alkyl, C6-10 aryl, C6-10 aryl-C3-10 alkyl, C1-10 heteroaryl, C1-10 heteroaryl-C1-3 alkyl, ORa, SRa, C ( O) Rb, C (O) NRcRd, C (O) ORa, OC (O) Rb, OC (O) NRcRd, NRcRd, NR c C (O) Rb, NR c C (O) ORa, NR c C (O) NRcRd, C ( > = NRe) Rb, C (> = NRe) NRcRd, NR c C (> = NRe) NRcRd, NRcS (O) Rb, NRcS (O) 2 R b, NRcS (O) 2NRcRd, S (O) Rb, S (O) NRcRd, S (O) 2 R d, S (O) 2 R d, S (O) 2 R b or S (O) 2NRcRd; where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 ciclooalquilo, C3-10 cycloalkyl-C1-3 alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl- C1-3alkyl , C6-10 aryl, C6-10 aryl-C1-3 alkyl, C1-10 heteroaryl, C1-10 heteroaryl and-C1-3alkyl and optionally substituted individually by 1, 2, 3, 4 or 5 groups independently selected R6 ; each R6 is independently halo, cyano, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-3 alkyl, C2 -10 heterocycloalkyl, C2-10 heterocycloalkyl- C1-3 alkyl, C6-10 aryl, C6-10 aryl-C1-3 alkyl, C1-10 heteroaryl, C1-10 heteroaryl-C1-3 alkyl, OR a1, SR a1, C ( O) Rb1, C (O) NRc1Rd1, C (O) OR a1, OC (O) R b1, OC (O) NRc1Rd1, C (> = NRe1) NRe1Rd1, NR c1 C (> = NRe1) NRc1Rd1, NRc1Rd1, NR c1 C (O) Rb1, NR c1 C (O) OR a1, NR c1 C (O) NRc1Rd1, NR c1 (O) R b1, NR c1 S (O) 2Rb1, NR c1 (O) 2NRc1Rd1, S (O) R b1, S (O) NRc1Rd1, S (O) 2Rb1, or S (O) 2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-3 alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-3 alkyl, C6-10 aryl, C6-10 aryl-C1-3 alkyl, C1-10 heteroaryl C1-10 heteroaryl and-C1-3alkyl and optionally substituted individually by 1, 2, 3, 4 or 5 groups independently selected Rh ; each Ra, Rb, Rc and Rd is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3- 10 cycloalkyl, C3-10 cycloalkyl-C1-3 alkyl, C2 -10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-3 alkyl, C6-10 aryl, C6-10 aryl-C1-3 alkyl, C1-10 heteroaryl, or C1-10 heteroaryl-C1-3 alkyl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-3 alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-3 alkyl, C6-10 aryl, C6-10 aryl-C1-3 alkyl, C1-10 heteroaryl, C1-10 heteroaryl-and C1-3alkyl is optionally individually and replaced by 1, 2, 3, 4 or 5 groups independently Rg selected; or Rc and Rd together with the N atom to which they are attached form a group or, each optionally substituted by 1, 2, 3 or 4 substituents independently selected heteroaryl group 3, 4, 5, 6 or 7 members halo, cyano, nitro, hydroxyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3- 7 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-6 alkylamino, thio, C1- 6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamoyl, C1-6 alquilocarbamilo, di-C1-6 alquilocarbamilo, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl and ; each Re is independently H, C1-6 alkyl, CN, hydroxy, C1-6 alkoxy, C1-6 alkylsulfonyl, carboxy, C1-6 alkylcarbonyl, aminosulphonyl, C1-6 alquiloaminosulfonilo, di-C1-6 alquiloaminosulfonilo, carbamyl, C1-6 alquilocarbamilo or di-C1-6 alquilocarbamilo; each Ra1, Rb1, Rc1, Rd1 and is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-3 alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-3 alkyl, C6-10 aryl, C6-10 aryl-C1-3 alkyl, C1-10 heteroaryl, or C1-10 heteroaryl-C1-3 alkyl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-3 alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-3 alkyl, C6-10 aryl, C6-10 aryl-C1-3 alkyl, C1-10 heteroaryl, C1-10 heteroaryl-and C1-3alkyl optionally individually and replaced by 1, 2, 3, 4 or 5 groups Rg ' independently selected; or Rc1 and Rd1 together with the N atom to which they are attached form a group or, each optionally substituted by 1, 2, 3 or 4 substituents independently selected heteroaryl group 3, 4, 5, 6 or 7 members halo, cyano, nitro, hydroxyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3- 7 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-6 alkylamino, thio, C1- 6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamoyl, C1-6 alquilocarbamilo, di-C1-6 alquilocarbamilo, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, and C1-6 alquilocarboniloamino; Re1 each independently is H, C1-6 alkyl, CN, hydroxy, C1-6 alkoxy, C1-6 alkylsulfonyl, carboxy, C1-6 alkylcarbonyl, aminosulphonyl, C1-6 alquiloaminosulfonilo, di-C1-6 alquiloaminosulfonilo, carbamyl, C1-6 alquilocarbamilo or di-C1-6 alquilocarbamilo; each Rg, Rg ', Rh and is independently halo, cyano, nitro, hydroxyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-6 alkylamino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamoyl, C1-6 alquilocarbamilo, di- C1-6 alquilocarbamilo, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, or C1-6 alquilocarboniloamino; n is 0, 1, 2, 3 or 4.