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US 11,958,873 B2Granted
Proteasome activity enhancing compounds
AssigneeKineta, Inc.
InventorsMatthew Cullen, Sheila Hauck, Bolin Geng, Megan Foley, Cecilia M. Bastos, Benito Munoz, Markus Haeberlein, Bradley Tait
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds having the Formula (I), (II), (III), (IV), and (V), compositions thereof, and methods for the treatment of a condition associated with a dysfunction in proteostasis.
Claims35
A compound having a structure of Formula (II), or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof:
- wherein:
- Q1 is C(Ra) or nitrogen;
- Q2 is selected from the group consisting of C(R3) and N;
- Q6 and Q7 are each CH;
- R1, R2, R3b, R3e, R3g, and Rg are each independently selected from the group consisting of hydrogen and optionally substituted C1-C10 alkyl;
- R3 is independently selected from the group consisting of hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted aryl, halo, ORc, N3, NRdRd, C(O)ORc, NO2, CN, C(O)Rc, C(O)C(O)Rc, C(O)NRdRd, NRdC(O)Rc, NRdS(O)nRc, N(Rd)(COORc), NRdC(O)C(O)Rc, NRdC(O)NRdRd, NRdS(O)nNRdRd, NRdS(O)nRc, S(O)nRc, S(O)nNRdRd, OC(O)ORc, (C═NRd)Rc, OC(O)Rc, optionally substituted heterocyclic and optionally substituted heteroaryl;
- R3c is selected from the group consisting of hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted aryl, halo, N3, ORc, NRdRd, C(O)ORc, NO2, CN, C(O)Rc, C(O)C(O)Rc, C(O)NRdRd, NRdC(O)Rc, NRdS(O)nRc, N(Rd)(COORc), NRdC(O)C(O)Rc, NRdC(O)NRdRd, NRdS(O)nNRdRd, NRdS(O)nRc, S(O)nRc, S(O)nNRdRd, OC(O)ORc, (C═NRd)Rc, OC(O)Rc, optionally substituted heterocyclic, and optionally substituted heteroaryl;
- R3f is halo or CN;
- Z is selected from the group consisting of NRbRb, optionally substituted aryl, optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, and ORc;
- each Ra is independently selected from the group consisting of hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted aryl, halo, N3, ORc, NRdRd, C(O)ORC, NO2, CN, C(O)Rc, C(O)C(O)RC, C(O)NRdRd, NRdC(O)RC, NRdS(O)nRc, N(Rd)(COORc), NRdC(O)C(O)Rc, NRdC(O)NRdRd, NRdS(O)nNRdRd, NRdS(O)nRc, S(O)nRc, S(O)nNRdRd, OC(O)ORc, (C═NRd)Rc, OC(O)Rc, optionally substituted heterocyclic, and optionally substituted heteroaryl;
- each Rb is independently selected from the group consisting of hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C1-C10 alkoxy, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl;
- each Rc is independently selected from the group consisting of hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl;
- each Rd is independently selected from the group consisting of hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C1-C10 alkoxy, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl;
- or two geminal Rd groups are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclic or an optionally substituted heteroaryl;
- each Re is independently selected from the group consisting of hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted heterocyclic, optionally substituted aryl and optionally substituted heteroaryl;
- and
- each n is independently 0, 1 or 2.
14 more elements
A compound, or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein the compound is selected from the group consisting of:
Dependencies are inferred from the claim text.