Inhibitors of complement factors and uses thereof
AssigneeAnnexon, Inc.
InventorsDean R. Artis, Colin P. Leslie, Luca B. Mileo, Claudia Beato, Federico Sorana, Bruno Di Guglielmo, Chiara Padroni
Life of this patent
Estimating the term…
Abstract
Disclosed are compounds of formula I and II and pharmaceutically acceptable salts thereof. Also disclosed are methods of treating a neurodegenerative disorder, an inflammatory disease, an autoimmune disease, an ophthalmic disease or a metabolic disorder using the compounds disclosed herein.
Claims36
A method of treating a disease or condition selected from myasthenia gravis, rheumatoid arthritis, dermatomyositis, chronic idiopathic demyelinating polyneuropathy, autoimmune hemolytic anemia, warm autoimmune hemolytic anemia, and cold agglutinin disease in an individual in need thereof, comprising administering a compound represented by formula I or II:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is hydrogen, halogen, amino, hydroxyl, alkoxy, or alkylthio;
- W is N;
- V and X are selected such that either V is CRa and X is N, or V is N and X is CRb;
- Ra is hydrogen, halogen, nitro, cyano, amino, hydroxyl, alkoxy, alkylthio, or alkyl;
- Rb is hydrogen, halogen, nitro, cyano, amino, hydroxyl, alkoxy, alkylthio, alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- each U independently is N or CRc;
- each Rc independently is hydrogen, halogen, alkyl, or alkoxy;
- ring Z1 is a five- or six-membered aryl or heteroaryl;
- ring Z2 is a five- or six-membered heterocycle;
- each R2 independently is halogen, nitro, cyano, amino, acylamino, amido, hydroxyl, alkoxy, alkylthio, acyl, amidino, azido, carbamoyl, carboxyl, carboxyester, guanidine, haloalkyl, haloalkoxy, heteroalkyl, imino, oxime, phosphonate, dialkylphosphine oxide, sulfonyl, sulfonamido, sulfonyl urea, sulfinyl, sulfinic acid, sulfonic acid, thiocyanate, thiocarbonyl, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- or two vicinal R2, together with the intervening carbon atoms to which they attach, combine to form a 5- or 6-membered carbocycle, 5- or 6-membered heterocycle, 5- or 6-membered aryl, or 5- or 6-membered heteroaryl;
- n is 0 or an integer selected from 1-4, as valency permits;
- each R6 independently is halogen, nitro, cyano, amino, acylamino, amido, hydroxyl, oxo, carboxyl, alkoxy, alkylthio, acyl, amidino, azido, carbamoyl, carboxyl, carboxyester, guanidine, haloalkyl, haloalkoxy, heteroalkyl, imino, oxime, phosphonate, dialkylphosphine oxide, sulfonyl, sulfonamido, sulfonyl urea, sulfinyl, sulfinic acid, sulfonic acid, thiocyanate, thiocarbonyl, alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- or any two R6, together with the intervening carbon atom(s) to which they attach, combine to form a carbocycle or heterocycle;
- q is 0 or an integer selected from 1-4, as valency permits;
- R3 is
- or
- M is N(R8)3, N(R8)2, OR8 or SR8;
- each R8 is independently hydrogen, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- and
- R3a and R3b independently are hydrogen, alkyl, acyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- or R3a and R3b, together with the boron atom and the two intervening oxygen atoms that separate them, combine to form a monocyclic or polycyclic heterocyclyl;
- or R3a, R3b, and M, together with the boron atom and the intervening oxygen atoms, combine to form a polycyclic heterocycle.
A method of treating a disease or condition selected from myasthenia gravis, rheumatoid arthritis, dermatomyositis, chronic idiopathic demyelinating polyneuropathy, autoimmune hemolytic anemia, warm autoimmune hemolytic anemia, and cold agglutinin disease in an individual in need thereof, comprising administering a compound represented by formula I-c-1 or I-c-2:
- or a pharmaceutically acceptable salt thereof, wherein
- R2a is alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- each R2 independently is halogen, nitro, cyano, amino, acylamino, amido, hydroxyl, alkoxy, alkylthio, acyl, amidino, azido, carbamoyl, carboxyl, carboxyester, guanidine, haloalkyl, haloalkoxy, heteroalkyl, imino, oxime, phosphonate, dialkylphosphine oxide, sulfonyl, sulfonamido, sulfonyl urea, sulfinyl, sulfinic acid, sulfonic acid, thiocyanate, thiocarbonyl, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- or two vicinal R2, together with the intervening carbon atoms to which they attach, combine to form a 5- or 6-membered carbocycle, 5- or 6-membered heterocycle, 5- or 6-membered aryl, or 5- or 6-membered heteroaryl;
- n is 0 or an integer selected from 1-2;
- R3 is
- M is N(R8)3, N(R8)2, OR8 or SR8;
- each R8 is independently hydrogen, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- and
- R3a and R3b independently are hydrogen, alkyl, acyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
- or R3a and R3b, together with the boron atom and the two intervening oxygen atoms that separate them, combine to form a monocyclic or polycyclic heterocyclyl;
- or R3a, R3b, and M, together with the boron atom and the intervening oxygen atoms, combine to form a polycyclic heterocycle.
A method of treating a disease or condition selected from myasthenia gravis, rheumatoid arthritis, dermatomyositis, chronic idiopathic demyelinating polyneuropathy, autoimmune hemolytic anemia, warm autoimmune hemolytic anemia, and cold agglutinin disease in an individual in need thereof, comprising administering a compound selected from:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.