Patent ID: 8283344
Filing Date: 2012-10-09
Classification: A61K,A61P

Abstract:
1. A method of treating cyclic or severe congenital neutropenia, in a patient in need of such treatment comprising administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R M is (1) hydrogen, (2) C (3) hydroxy C (4) halo C (5) C (6) C Ra and Rb are each individually (1) hydrogen, (2) C (3) halo, (4) carboxy, (5) C (6) phenyl, (7) C (8) di-(C (9) hydroxy; R (1) hydrogen, (2) C (3) halo, (4) carboxy, (5) C (6) phenyl, (7) C (8) aminoC (9) aminoC (10) hydroxy, (11) aminocarbonyl wherein the amino is optionally mono or di-substituted with C (12) hydroxymethyl, (13) aminocarbonyloxy C (14) cyano, (15) morpholinocarbonylphenyl, (16) amino wherein the amino is optionally mono or di-substituted with C (17) morpholinocarbonyl; R4 is (a) Q-C(O)—Y—N(R7)(R8), or (b) Q-C(O)—ORx, where Rx is carboxyC-16alkyl, benzyloxycarbonylC wherein Q is a covalent bond or —C(R wherein R 5 and R 6 are each individually C 1-3 alkyl or hydrogen, Y is or a covalent bond; R R (a) hydrogen, (b) C (c) C (d) hydroxy C (e) polyhydroxyC (f) carboxamido C (g) polyacyloxyC (h) C (i) substituted phenyl or phenyl C (j) C (k) C (l) heteroaryl C (m) carboxy C (n) carbo C (o) phenylsulfonyl, (p) C (q) benzyloxy, (r) morpholinyl C (s) tetrahydropyranyl, (t) aminoC (u) aminocarbonyl wherein the amino is optionally mono or di-substituted with C (v) aminocarbonyloxyC (w) azabicyclo of 7 to 12 atoms, (x) di C (y) bicycloalkyl of 7 to 12 atoms, (z) C (aa) pyrazolidinyl, (bb) substituted piperidinyl or pyrrolidinyl wherein the substitutent is hydrogen, C (cc) substituted pyrrolidinyl wherein the substitutent is carboxamido or amino wherein the amino is optionally mono or di-substituted with C (dd) pyrimidinyl, (ee) N-cyano-N′-phenylamidino, (ff) phosphonoC (gg) α-C wherein X (1) hydrogen, (2) halo, (3) C (4) halo-C (5) C (6) hydroxy-C (7) C (8) C (9) CN, (10) CF (11) CH (12) amino wherein the amino is optionally mono or di-substituted with C (13) carboxy, or (14) phenylsulfonylaminocarbonyl; X n is 1, 2, 3, 4 or 5; R R wherein R 7 and R 8 are joined together to form mono or di-substituted ring of 4, 5, 6, or 7 atoms or 7 to 12 atoms such as (1) piperidinyl or homopiperidinyl, (2) piperazinyl, (3) morpholinyl, thiomorpholinyl or 1,1-dioxo-4-thiomorpholinyl, (4) pyrroylidinyl, (5) pyrryl, (6) imidazolyl, (7) triazolyl, (8) saturated azabicyclo of 7 to 12 atoms, (9) azaspiro having 3 to 9 carbon atoms, said ring being saturated, (10) tetrazolyl, (11) pyrazolidinyl, (12) dihydrodimethozyisoquinolyl, (13) azetidinyl, or (14) diazabicyclo ring of 7-12 atoms, wherein the substituents are each selected from the group consisting of hydrogen and C 1-3 alkyl, benzyloxycarbonyl, carboxy, phenyl C 1-3 alkyl amino carbonyl, pyrrolidinylmethyl, hydroxy C 1-3 alkyl, C 1-6 alkyloxy, C 1-4 -alkyloxy carbonyl, aminocarbonyl wherein the amino is optionally mono or di-substituted with C 1-6 alkyl, and oxo; or —N(R7)R8 may be an amino acid residue including natural amino acids such as lysine; or R said rings to include piperazinyl and homopiperazinyl; or R form a mono or di-substituted monocyclic saturated ring of 5 to 7 atoms and having one hetero atom which is the nitrogen to which R wherein R 9 and R 12 are joined together to form a mono or di-substituted saturated monocyclic ring of 5, 6; or 7 atoms, said ring having one hetero atom which is the nitrogen to which R 9 is attached; or wherein R 10 and R 12 are joined together to form a mono or di-substituted saturated monocyclic ring of 5, 6, or 7 carbon atoms; or wherein R 8 and R 11 are joined together to form a mono or di-substituted saturated monocyclic ring of 5, 6, or 7 atoms, said ring having one hetero atom which is the nitrogen to which R 8 is attached; and the substituents are independently selected from Hydrogen and C 1-3 alkyl, thereby treating cyclic or severe congenital neutropenia in a patient in need of such treatment.