IP Library › Granted Patent US 11,046,686
Granted Patent B2
US 11,046,686 · App. 16/539,834 · Granted Jun 29, 2021

Thiadiazole IRAK4 compounds

Inventors: Stephen Ammann (Redwood City, CA); Elizabeth M. Bacon (Burlingame, CA); Gediminas Brizgys (San Carlos, CA); Elbert Chin (San Mateo, CA); Chienhung Chou (Dublin, CA); Jeromy J. Cottell (Redwood City, CA); Marilyn Ndukwe (Lebanon, NH); Marina Shatskikh (San Francisco, CA); James G. Taylor (Burlingame, CA); Nathan E. Wright (Foster City, CA); Zheng-Yu Yang (Palo Alto, CA); Sheila M. Zipfel (San Mateo, CA)
Assignee: Gilead Sciences, Inc.
C07D471/04C07D487/04
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Quick Facts
Patent No.
US 11,046,686
App. No.
16/539,834
Granted
Jun 29, 2021
Kind
B2
Abstract

A compound of Formula (I): pharmaceutically acceptable salts thereof, deuterated analogs thereof, compositions thereof, and methods of treating disease using a compound thereof are disclosed.

Claims (57)

1. A compound of Formula (I):

wherein “Het” is selected from:

X is selected from —H, —F, —Cl, —Br, and —CN;

R 1 and R 2 are each independently selected from:

C 1-10 alkyl optionally substituted with Z 1 ;

C 3-10 cycloalkyl optionally substituted with Z 1 ;

5-10 membered heteroaryl optionally substituted with Z 1 ;

C 6-10 aryl optionally substituted with Z 1 ;

4-12 membered heterocyclyl optionally substituted with Z 1 ; and

—H, —O—R 12 , —C(O)—R 12 , —C(O)O—R 12 , —C(O)—N(R 12 )(R 12 ), —N(R 12 )(R R 12 ), —N(R 12 ) 2 (R 12 ) + , —N(R 12 )C(O)—R 12 , —N(R 12 )C(O)O—R 12 , —N(R 12 )C(O)N(R 12 )(R 12 ), —N(R 12 )S(O) 2 (R 12 ), —NR 12 S(O) 2 N(R 12 )(R 12 ), —NR 12 S(O) 2 O(R 12 ), —OC(O)R 12 , —OC(O)OR 12 , —OC(O)—N(R 12 )(R 12 ), —Si(R 12 ) 3 , —S—R 12 , —S(O)R 12 , —S(O)(NH)R 12 , —S(O) 2 R 12 , —S(O) 2 N(R 12 )(R 12 ), or sulfoximine;

Z 1 is independently oxo, imino, sulfoximino, halo, —NO 2 , —N 3 , —CN, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, C 1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, —O—R 12 , —C(O)—R 12 , —C(O)O—R 12 , —C(O)—N(R 12 )(R 12 ), —N(R 12 )(R 12 ), —N(R 12 ) 2 (R 12 ) + , —N(R 12 )C(O)—R 12 , —N(R 12 )C(O)O—R 12 , —N(R 12 )C(O)N(R 12 )(R 12 ), —N(R 12 )S(O) 2 (R 12 ), —NR 12 S(O) 2 N(R 12 )(R 12 ), —NR 12 S(O) 2 O(R 12 ), —OC(O)R 12 , —OC(O)OR 12 , —OC(O)—N(R 12 )(R 12 ), —Si(R 12 ) 3 , —S—R 12 , —S(O)R 12 , —S(O)(NH)R 12 , —S(O) 2 R 12 or —S(O) 2 N(R 12 )(R 12 );

wherein any alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with Z 1a ;

each Z 1a is independently oxo, imino, sulfoximino, halo, —NO 2 , —CN, —N 3 , C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, C 1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, —O—R 12 , —C(O)R 12 , —C(O)O—R 12 , —C(O)N(R 12 )(R 12 ), —N(R 12 )(R 12 ), —N(R 12 ) 2 (R 12 ) + , —N(R 12 )—C(O)R 12 , —N(R 12 )C(O)O(R 12 ), —N(R 12 )C(O)N(R 12 )(R 12 ), —N(R 12 )S(O) 2 (R 12 ), —N(R 12 )S(O) 2 —N(R 12 )(R 12 ), —N(R 12 )S(O) 2 O(R 12 ), —OC(O)R 12 , —OC(O)OR 12 , —OC(O)—N(R 12 )(R 12 ), —Si(R 12 ) 3 , —S—R 12 , —S(O)R 12 , —S(O)(NH)R 12 , —S(O) 2 R 12 or —S(O) 2 N(R 12 )(R 12 );

wherein any alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with Z 1b ;

each R 12 is independently H, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, aryl, heteroaryl or heterocyclyl;

wherein any alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with Z 1a ;

each Z 1b is independently oxo, imino, sulfoximino, hydroxy, halo, —NO 2 , —N 3 , —CN, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, C 1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, —O(C 1-9 alkyl), —O(C 2-6 alkenyl), —O(C 2-6 alkynyl), —O(C 3-15 cycloalkyl), —O(C 1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), —NH 2 , —NH(C 1-9 alkyl), —NH(C 2-6 alkenyl), —NH(C 2-6 alkynyl), —NH(C 3-15 cycloalkyl), —NH(C 1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C 1-9 alkyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 2-6 alkenyl) 2 , —N(C 2-6 alkynyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 1-8 haloalkyl) 2 , —N(aryl) 2 , —N(heteroaryl) 2 , —N(heterocyclyl) 2 , —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 2-6 alkenyl), —N(C 1-9 alkyl)(C 2-6 alkynyl), —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 1-8 haloalkyl), —N(C 1-9 alkyl)(aryl), —N(C 1-9 alkyl)(heteroaryl), —N(C 1-9 alkyl)(heterocyclyl), —C(O)(C 1-9 alkyl), —C(O)(C 2-6 alkenyl), —C(O)(C 2-6 alkynyl), —C(O)(C 3-15 cycloalkyl), —C(O)(C 1-8 haloalkyl), —C(O)(aryl), —C(O)(heteroaryl), —C(O)(heterocyclyl), —C(O)O(C 1-9 alkyl), —C(O)O(C 2-6 alkenyl), —C(O)O(C 2-6 alkynyl), —C(O)O(C 3-15 cycloalkyl), —C(O)O(Cis haloalkyl), —C(O)O(aryl), —C(O)O(heteroaryl), —C(O)O(heterocyclyl), —C(O)NH 2 , —C(O)NH(C 1-9 alkyl), —C(O)NH(C 2-6 alkenyl), —C(O)NH(C 2-6 alkynyl), —C(O)NH(C 3-15 cycloalkyl), —C(O)NH(C 1-8 haloalkyl), —C(O)NH(aryl), —C(O)NH(heteroaryl), —C(O)NH(heterocyclyl), —C(O)N(C 1-9 alkyl) 2 , —C(O)N(C 3-15 cycloalkyl) 2 , —C(O)N(C 2-6 alkenyl) 2 , —C(O)N(C 2-6 alkynyl) 2 , —C(O)N(C 3-15 cycloalkyl) 2 , —C(O)N(C 1-8 haloalkyl) 2 , —C(O)N(aryl) 2 , —C(O)N(heteroaryl) 2 , —C(O)N(heterocyclyl) 2 , —NHC(O)(C 1-9 alkyl), —NHC(O)(C 2-6 alkenyl), —NHC(O)(C 2-6 alkynyl), —NHC(O)(C 3-15 cycloalkyl), —NHC(O)(C 1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C 1-9 alkyl), —NHC(O)O(C 2-6 alkenyl), —NHC(O)O(C 2-6 alkynyl), —NHC(O)O(C 3-15 cycloalkyl), —NHC(O)O(C 1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C 1-9 alkyl), —NHC(O)NH(C 2-6 alkenyl), —NHC(O)NH(C 2-6 alkynyl), —NHC(O)NH(C 3-15 cycloalkyl), —NHC(O)NH(C 1-8 haloalkyl), —NHC(O)NH(aryl), —NHC(O)NH(heteroaryl), —NHC(O)NH(heterocyclyl), —SH, —S(C 1-9 alkyl), —S(C 2-6 alkenyl), —S(C 2-6 alkynyl), —S(C 3-15 cycloalkyl), —S(C 1-8 haloalkyl), —S(aryl), —S(heteroaryl), —S(heterocyclyl), —NHS(O)(C 1-9 alkyl), —N(C 1-9 alkyl)(S(O)(C 1-9 alkyl), —S(O)N(C 1-9 alkyl) 2 , —S(O)(C 1-9 alkyl), —S(O)(NH)(C 1-9 alkyl), —S(O)(C 2-6 alkenyl), —S(O)(C 2-6 alkynyl), —S(O)(C 3-15 cycloalkyl), —S(O)(C 1-8 haloalkyl), —S(O)(aryl), —S(O)(heteroaryl), —S(O)(heterocyclyl), —S(O) 2 (C 1-9 alkyl), —S(O) 2 (C 2-6 alkenyl), —S(O) 2 (C 2-6 alkynyl), —S(O) 2 (C 3-15 cycloalkyl), —S(O) 2 (C 1-8 haloalkyl), —S(O) 2 (aryl), —S(O) 2 (heteroaryl), —S(O) 2 (heterocyclyl), —S(O) 2 NH(C 1-9 alkyl), or —S(O) 2 N(C 1-9 alkyl) 2 ;

wherein any alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more halo, C 1-9 alkyl, C 1-8 haloalkyl, —OH, —NH 2 , —NH(C 1-9 alkyl), —NH(C 3-15 cycloalkyl), —NH(C 1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C 1-9 alkyl) 2 , —N(C 3-15 cycloalkyl) 2 , —NHC(O)(C 3-15 cycloalkyl), —NHC(O)(C 1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C 1-9 alkyl), —NHC(O)O(C 2-6 alkynyl), —NHC(O)O(C 3-15 cycloalkyl), —NHC(O)O(C 1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C 1-9 alkyl), —S(O)(NH)(C 1-9 alkyl), S(O) 2 (C 1-9 alkyl), —S(O) 2 (C 3-15 cycloalkyl), —S(O) 2 (C 1-8 haloalkyl), —S(O) 2 (aryl), —S(O) 2 (heteroaryl), —S(O) 2 (heterocyclyl), —S(O) 2 NH(C 1-9 alkyl), —S(O) 2 N(C 1-9 alkyl) 2 , —O(C 3-15 cycloalkyl), —O(C 1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), or —O(C 1-9 alkyl);

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is C 3-10 cycloalkyl optionally substituted with Z 1 .

3. The compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is C 3-8 cycloalkyl optionally substituted with —OH, —N(R 12 )C(O)(R 12 ), —N(R 12 )C(O)O(R 12 ), or —C(O)N(R 12 ) (R 12 ).

4. The compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is a 4-8 membered heterocyclyl optionally substituted with Z 1 .

5. The compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is a 4-8 membered heterocyclyl substituted with —OH, —N(R 12 )C(O)(R 12 ), —N(R 12 )C(O)O(R 12 ), or —C(O)N(R 12 ) (R 12 ).

6. The compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is —C(O)—N(R 12 )(R 12 ).

7. A compound of Formula (Ia):

wherein R 1 and R 2 are each independently selected from:

C 1-10 alkyl optionally substituted with Z 1 ;

C 3-10 cycloalkyl optionally substituted with Z 1 ;

5-10 membered heteroaryl optionally substituted with Z 1 ;

C 6-10 aryl optionally substituted with Z 1 ;

4-12 membered heterocyclyl optionally substituted with Z 1 ; and

—H, —O—R 12 , —C(O)—R 12 , —C(O)O—R 12 , —C(O)—N(R 12 )(R 12 ), —N(R 12 )(R 12 ), —N(R 12 ) 2 (R 12 ) + , —N(R 12 )C(O)—R 12 , —N(R 12 )C(O)O—R 12 , —N(R 12 )C(O)N(R 12 )(R 12 ), —N(R 12 )S(O) 2 (R 12 ), —NR 12 S(O) 2 N(R 12 )(R 12 ), —NR 12 S(O) 2 O(R 12 ), —OC(O)R 12 , —OC(O)OR 12 , —OC(O)—N(R 12 )(R 12 ), —Si(R 12 ) 3 , —S—R 12 , —S(O)R 12 , —S(O)(NH)R 12 , —S(O) 2 R 12′ —S(O) 2 N(R 12 )(R 12 ), or sulfoximino;

and wherein Z 1 is independently oxo, imino, sulfoximino, halo, —NO 2 , —N 3 , —CN, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, Cis haloalkyl, aryl, heteroaryl, heterocyclyl, —O—R 12 , —C(O)—R 12 , —C(O)O—R 12 , —C(O)—N(R 12 )(R 12 ), —N(R 12 )(R 12 ), —N(R 12 ) 2 (R 12 ) + , —N(R 12 )C(O)—R 12 , —N(R 12 )C(O)O—R 12 , —N(R 12 )C(O)N(R 12 )(R 12 ), —N(R 12 )S(O) 2 (R 12 ), —NR 12 S(O) 2 N(R 12 )(R 12 ), —NR 12 S(O) 2 O(R 12 ), —OC(O)R 12 , —OC(O)OR 12 , —OC(O)—N(R 12 )(R 12 ), —Si(R 12 ) 3 , —S—R 12 , —S(O)R 12 , —S(O)(NH)R 12 , —S(O) 2 R 12 or —S(O) 2 N(R 12 )(R 12 );

wherein any alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with Z 1a ;

each Z 1a is independently oxo, imino, sulfoximino, halo, —NO 2 , —CN, —N 3 , C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, C 1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, —O—R 12 , —C(O)R 12 , —C(O)O—R 12 , —C(O)N(R 12 )(R 12 ), —N(R 12 )(R 12 ), —N(R 12 ) 2 (R 12 ) + , —N(R 12 )—C(O)R 12 , —N(R 12 )C(O)O(R 12 ), —N(R 12 )C(O)N(R 12 )(R 12 ), —N(R 12 )S(O) 2 (R 12 ), —N(R 12 )S(O) 2 —N(R 12 )(R 12 ), —N(R 12 )S(O) 2 O(R 12 ), —OC(O)R 12 , —OC(O)OR 12 , —OC(O)—N(R 12 )(R 12 ), —Si(R 12 ) 3 , —S—R 12 , —S(O)R 12 , —S(O)(NH)R 12 , —S(O) 2 R 12 or —S(O) 2 N(R 12 )(R 12 );

wherein any alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with Z 1b ;

each R 12 is independently H, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, aryl, heteroaryl or heterocyclyl;

wherein any alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with Z 1a ;

each Z 1b is independently oxo, imino, sulfoximino, hydroxy, halo, —NO 2 , —N 3 , —CN, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, C 1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, —O(C 1-9 alkyl), —O(C 2-6 alkenyl), —O(C 2-6 alkynyl), —O(C 3-15 cycloalkyl), —O(C 1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), —NH 2 , —NH(C 1-9 alkyl), —NH(C 2-6 alkenyl), —NH(C 2-6 alkynyl), —NH(C 3-15 cycloalkyl), —NH(C 1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C 1-9 alkyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 2-6 alkenyl) 2 , —N(C 2-6 alkynyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 1-8 haloalkyl) 2 , —N(aryl) 2 , —N(heteroaryl) 2 , —N(heterocyclyl) 2 , —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 2-6 alkenyl), —N(C 1-9 alkyl)(C 2-6 alkynyl), —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 1-8 haloalkyl), —N(C 1-9 alkyl)(aryl), —N(C 1-9 alkyl)(heteroaryl), —N(C 1-9 alkyl)(heterocyclyl), —C(O)(C 1-9 alkyl), —C(O)(C 2-6 alkenyl), —C(O)(C 2-6 alkynyl), —C(O)(C 3-15 cycloalkyl), —C(O)(C 1-8 haloalkyl), —C(O)(aryl), —C(O)(heteroaryl), —C(O)(heterocyclyl), —C(O)O(C 1-9 alkyl), —C(O)O(C 2-6 alkenyl), —C(O)O(C 2-6 alkynyl), —C(O)O(C 3-15 cycloalkyl), —C(O)O(C 1-8 haloalkyl), —C(O)O(aryl), —C(O)O(heteroaryl), —C(O)O(heterocyclyl), —C(O)NH 2 , —C(O)NH(C 1-9 alkyl), —C(O)NH(C 2-6 alkenyl), —C(O)NH(C 2-6 alkynyl), —C(O)NH(C 3-15 cycloalkyl), —C(O)NH(C 1-8 haloalkyl), —C(O)NH(aryl), —C(O)NH(heteroaryl), —C(O)NH(heterocyclyl), —C(O)N(C 1-9 alkyl) 2 , —C(O)N(C 3-15 cycloalkyl) 2 , —C(O)N(C 2-6 alkenyl) 2 , —C(O)N(C 2-6 alkynyl) 2 , —C(O)N(C 3-15 cycloalkyl) 2 , —C(O)N(C 1-8 haloalkyl) 2 , —C(O)N(aryl) 2 , —C(O)N(heteroaryl) 2 , —C(O)N(heterocyclyl) 2 , —NHC(O)(C 1-9 alkyl), —NHC(O)(C 2-6 alkenyl), —NHC(O)(C 2-6 alkynyl), —NHC(O)(C 3-15 cycloalkyl), —NHC(O)(C 1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C 1-9 alkyl), —NHC(O)O(C 2-6 alkenyl), —NHC(O)O(C 2-6 alkynyl), —NHC(O)O(C 3-15 cycloalkyl), —NHC(O)O(C 1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C 1-9 alkyl), —NHC(O)NH(C 2-6 alkenyl), —NHC(O)NH(C 2-6 alkynyl), —NHC(O)NH(C 3-15 cycloalkyl), —NHC(O)NH(C 1-8 haloalkyl), —NHC(O)NH(aryl), —NHC(O)NH(heteroaryl), —NHC(O)NH(heterocyclyl), —SH, —S(C 1-9 alkyl), —S(C 2-6 alkenyl), —S(C 2-6 alkynyl), —S(C 3-15 cycloalkyl), —S(C 1-8 haloalkyl), —S(aryl), —S(heteroaryl), —S(heterocyclyl), —NHS(O)(C 1-9 alkyl), —N(C 1-9 alkyl)(S(O)(C 1-9 alkyl), —S(O)N(C 1-9 alkyl) 2 , —S(O)(C 1-9 alkyl), —S(O)(NH)(C 1-9 alkyl), —S(O)(C 2-6 alkenyl), —S(O)(C 2-6 alkynyl), —S(O)(C 3-15 cycloalkyl), —S(O)(C 1-8 haloalkyl), —S(O)(aryl), —S(O)(heteroaryl), —S(O)(heterocyclyl), —S(O) 2 (C 1-9 alkyl), —S(O) 2 (C 2-6 alkenyl), —S(O) 2 (C 2-6 alkynyl), —S(O) 2 (C 3-15 cycloalkyl), —S(O) 2 (C 1-8 haloalkyl), —S(O) 2 (aryl), —S(O) 2 (heteroaryl), —S(O) 2 (heterocyclyl), —S(O) 2 NH(C 1-9 alkyl), or —S(O) 2 N(C 1-9 alkyl) 2 ;

wherein any alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more halo, C 1-9 alkyl, C 1-8 haloalkyl, —OH, —NH 2 , —NH(C 1-9 alkyl), —NH(C 3-15 cycloalkyl), —NH(C 1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C 1-9 alkyl) 2 , —N(C 3-15 cycloalkyl) 2 , —NHC(O)(C 3-15 cycloalkyl), —NHC(O)(C 1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C 1-9 alkyl), —NHC(O)O(C 2-6 alkynyl), —NHC(O)O(C 3-15 cycloalkyl), —NHC(O)O(C 1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C 1-9 alkyl), —S(O)(NH)(C 1-9 alkyl), S(O) 2 (C 1-9 alkyl), —S(O) 2 (C 3-15 cycloalkyl), —S(O) 2 (C 1-8 haloalkyl), —S(O) 2 (aryl), —S(O) 2 (heteroaryl), —S(O) 2 (heterocyclyl), —S(O) 2 NH(C 1-9 alkyl), —S(O) 2 N(C 1-9 alkyl) 2 , —O(C 3-15 cycloalkyl), —O(C 1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), or —O(C 1-9 alkyl);

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof.

8. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is C 1-10 alkyl optionally substituted with Z 1 .

9. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is C 1-5 alkyl optionally substituted with —F, —OH, or —CN.

10. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is 4-8 membered heterocycle optionally substituted with Z 1 .

11. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is oxetane, tetrahydrofuran or tetrahydropyran optionally substituted with Z 1 .

12. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is C 3-10 cycloalkyl optionally substituted with Z 1 .

13. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is C 3-10 cycloalkyl substituted with 5-10 membered heteroaryl wherein said 5-10 membered heteroaryl is optionally substituted with Z 1a .

14. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is C 3-10 cycloalkyl substituted with C 1-3 alkyl and said C 1-3 alkyl is further substituted with Z 1a .

15. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 1 is 5-10 membered heteroaryl optionally substituted with Z 1 .

16. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is C 1-10 alkyl optionally substituted with Z 1 .

17. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is C 1-10 alkyl optionally substituted with one or more —F, —OH or combinations thereof.

18. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is C 3-10 cycloalkyl optionally substituted with Z 1 .

19. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is C 3-8 cycloalkyl optionally substituted with —OH, —N(R 12 )C(O)(R 12 ), —N(R 12 )C(O)O(R 12 ), or —C(O)N(R 12 ) (R 12 ).

20. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is a 4-8 membered heterocyclyl optionally substituted with Z 1 .

21. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein R 2 is —C(O)—N(R 12 )(R 12 ).

22. A method of treating an inflammatory condition, in a patient in need thereof, the method comprising administering to said patient a compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers or deuterated analog thereof, wherein the inflammatory condition is selected from IBD, SLE, Psoriasis and Rheumatoid Arthritis.

23. A method of treating an inflammatory condition, in a patient in need thereof, the method comprising administering to said patient a pharmaceutical composition comprising a compound of claim 1 , wherein the inflammatory condition is selected from IBD, SLE, Psoriasis and Rheumatoid Arthritis.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2019
From: AMMANN, STEPHEN; BACON, ELIZABETH M.; BRIZGYS, GEDIMINAS; CHIN, ELBERT; CHOU, CHIENHUNG; COTTELL, JEROMY J.; NDUKWE, MARILYN; SHATSKIKH, MARINA; TAYLOR, JAMES G.; WRIGHT, NATHAN E.; YANG, ZHENG-YU; ZIPFEL, SHEILA M.
To: GILEAD SCIENCES, INC.
Reel/Frame 051106/0087 →
Continuity (2)
Provisional Application 62718262 · Aug 13, 2018
Related Publication 20200079769A1 · Mar 12, 2020
Cited By (2)
US 12,528,814 US 12,570,662