IP Library › Granted Patent US 12,037,354

Granted Patent B2

US 12,037,354 · App. 17/298,658 · Granted Jul 16, 2024

Cyclic pantetheine derivatives and uses thereof

Inventors: Arthur George Taveras (Boston, MA); Enej Kuscer (Wassenaar, NL); Angelina Roberta Sekirnik (Leiden, NL); Dharini Shah (Boston, MA); Mercedes Valls Seron (Leiden, NL)

Assignee: VectivBio Comet AG

C07F9/65742 C07C327/22 C07C327/32 C07C327/34 C07D207/28 C07D307/33 C07D319/06 C07D491/113 C07D493/10 C07F7/081 C07F9/091 C07F9/12 C07F9/657154

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Quick Facts

Patent No.: US 12,037,354
App. No.: 17/298,658
Granted: Jul 16, 2024
Kind: B2

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Abstract

The present disclosure relates to compounds of Formula (P) or (II′-0): (Formulae (I′), (II′-0)), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.

Claims (73)

1. A compound of Formula (I′):

or a pharmaceutically acceptable salt or solvate thereof, wherein:

T is

R 1 is —C(═O)R 1b , —C(═O)R 1z ,

—C(═O)—(CH═CH) n —R 1a ,

—C(═O)CH 2 —[C(═O)CH 2 ] p —[CH 2 ] q —R 1a ,

—C(═O)CH(R 1a )—[C(═O)CH(R 1a )] p —[CH 2 ] q —R 1a ,

—C(═O)CH 2 —[CH(OR 1c )—CH 2 ] p —[CH 2 ] q —R 1a , —C(═O)CH 2 —[C(═O)CH 2 ] p —[CH(OR 1c )—CH 2 ] r —[CH 2 ] q —R 1a , —C(═O)CH 2 —[CH(OR 1c )—CH 2 ] r —[C(═O)CH 2 ] p —[CH 2 ] q —R 1a , —C(═O)OR 1c , C(═O)N(R 1c ) 2 , —C(═O)—CH═CH—C(═O)OR 1c , —C(═O)—[CH 2 ] q —C(═O)OR 1c , —C(═O)—CH 2 CH 2 —C(═O)OR 1c , —C(═O)CH 2 —[C(═O)CH 2 ] p —[CH 2 ] q — C(═O)OR 1c , —C(═O)—[CH 2 ] q —C(═O)R 1z , —C(═O)—CH 2 CH 2 —C(═O)R 1z , —C(═O)CH 2 —[C(═O)CH 2 ] p —[CH 2 ] q — C(═O)R 1z ,

each R 1a is independently H, oxo, halogen, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, —OR 1c , —C(═O)OR 1c , —C(═O)N(R 1c ) 2 , —N(R 1c ) 2 , —N(R 1c )C(═O)R 1b , —N(R 1c )C(═O)R 1z , —N(R 1c )C(═O)OR 1c , —OC(═O)R 1b , —OC(═O)R 1z , —OC(═O)OR 1c , —OSi(R 1g ) 3 , —SC(═O)R 1b , —SC(═O)R 1z , —SC(═O)OR 1c , —SC(═O)N(R 1c ) 2 , —C(═O)R 1b , —C(═O)R 1z , —SR 1a , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1e ;

each R 1b is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, —(CH 2 ) q —C(═O)OR 1c , —CH 2 —C(═O)—(CH 2 )q-C(═O)OR 1c , —CH 2 —[C(═O)CH 2 ] p —[CH 2 ] q —C(═O)OR 1c , —CH═CH—C(═O)OR 1c , —C(═O)OR 1c , —C(═O)N(R 1c ) 2 , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1e ;

each R 1c is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, C 3 -C 12 aryl, C 3 -C 12 heteroaryl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl), wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, C 3 -C 12 aryl, C 3 -C 12 heteroaryl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl) is optionally substituted with one or more R 1e ; or two R 1c together with the one or more intervening atoms to which they are connected, form C 3 -C 12 cycloalkyl or C 3 -C 12 heterocycloalkyl, wherein the C 3 -C 12 cycloalkyl or C 3 -C 12 heterocycloalkyl is optionally substituted with one or more R 1e ;

each R 1d is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 3 -C 10 cycloalkyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, C 3 -C 12 aryl, C 3 -C 12 heteroaryl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl), wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, C 3 -C 12 aryl, C 3 -C 12 heteroaryl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl) is optionally substituted with one or more R 1e ;

each R 1e is independently H, halogen, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, —OR 1g , —C(═O)OR 1g , —C(═O)N(R 1g ) 2 , —N(R 1g ) 2 , —N(R 1g )C(═O)R 1f , —N(R 1g )C(═O)R 1z , —N(R 1g )C(═O)OR 1g , —OC(═O)R 1f , —OC(═O)R 1z , —OC(═O)OR 1g , —OSi(R 1g ) 3 , —SR 1g , —N + (R 1g ) 3 , —SC(═O)R 1f , —SC(═O)R 1z , —SC(═O)OR 1g , —SC(═O)N(R 1g ) 2 , —C(═O)R 1f , —C(═O)R 1z , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1z ;

each R 1f is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, —OSi(R 1g ) 3 , —CH 2 C(═O)OR 1g , —CH═CH—C(═O)OR 1g , —C(═O)OR 1g , —C(═O)N(R 1g ) 2 , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1z ;

each R 1g is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, C 3 -C 12 aryl, C 3 -C 12 heteroaryl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl), wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, C 3 -C 12 aryl, C 3 -C 12 heteroaryl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl) is optionally substituted with one or more R 1z ;

each R 1z is independently

each n is independently an integer ranging from 0 to 20;

each p is independently an integer ranging from 0 to 20;

each q is independently an integer ranging from 0 to 20; and

each r is independently an integer ranging from 0 to 20.

2. The compound of claim 1 , wherein the compound is of Formula (I′):

or a pharmaceutically acceptable salt or solvate thereof, wherein:

each T is independently

each R t is independently R 1 , R 1a , or R 1b ; or

two R t , together with the one or more intervening atoms they are attached to, form a C 3 -C 12 cycloalkyl or C 3 -C 12 heterocycloalkyl, wherein C 3 -C 12 cycloalkyl or C 3 -C 12 heterocycloalkyl is optionally substituted with one or more Ria;

t is an integer ranging from 0 to 5;

each R 1a is independently H, oxo, halogen, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, —OR 1c , —C(═O)OR 1c , —C(═O)N(R 1c ) 2 , —N(R 1c ) 2 , —N(R 1c )C(═O)R 1b , —N(R 1c )C(═O)R 1z , —N(R 1c )C(═O)OR 1c , —OC(═O)R 1b , —OC(═O)R 1z , —OC(═O)OR 1c , —SC(═O)R 1b , —SC(═O)R 1z , —SC(═O)OR 1c , —SC(═O)N(R 1c ) 2 , —C(═O)R 1b , —C(═O)R 1z , —SR 1a , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1e ;

each R 1b is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, —(CH 2 ) q —C(═O)OR 1c , —CH 2 —C(═O)—(CH 2 ) q —C(═O)OR 1c , —CH 2 —[C(═O)CH 2 ] p —[CH 2 ] q —C(═O)OR 1c , —CH═CH—C(═O)OR 1c , —C(═O)OR 1c , —C(═O)N(R 1c ) 2 , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1e ;

each R 1e is independently H, halogen, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, —OR 1g , —C(═O)OR 1g , —C(═O)N(R 1g ) 2 , —N(R 1g ) 2 , —N(R 1g )C(═O)R 1f , —N(R 1g )C(═O)R 1z , —N(R 1g )C(═O)OR 1g , —OC(═O)R 1f , —OC(═O)R 1z , —OC(═O)OR 1g , —SR 1g , —N + (R 1g ) 3 , —SC(═O)R 1f , —SC(═O)R 1z , —SC(═O)OR 1g , —SC(═O)N(R 1g ) 2 , —C(═O)R 1f , —C(═O)R 1z , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1z ;

each R 1f is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, —CH 2 C(═O)OR 1g , —CH═CH—C(═O)OR 1g , —C(═O)OR 1g , —C(═O)N(R 1g ) 2 , or R 1z , wherein the C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl is optionally substituted with one or more R 1z ;

each R 1z is independently

each n is independently an integer ranging from 0 to 20;

each p is independently an integer ranging from 0 to 20;

each q is independently an integer ranging from 0 to 20; and

each r is independently an integer ranging from 0 to 20.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

each R 12 is independently

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1a is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, —OR 1c , —C(═O)OR 1c , —C(═O)R 1b , —C(═O)R 1z , or R 1z .

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1b is independently C 1 -C 20 alkyl, C 2 -C 20 alkenyl, —(CH 2 ) q —C(═O)OR 1c , —CH 2 —C(═O)—(CH 2 ) q —C(═O)OR 1c , —CH 2 —[C(═O)CH 2 ] p —[CH 2 ] q —C(═O)OR 1c , —CH═CH—C(═O)OR 1c , or R 1z .

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1c is independently H, C 1-20 alkyl, C 2-20 alkenyl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl).

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, each R 1d is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, C 3 -C 12 aryl, C 3 -C 12 heteroaryl, —(C 1 -C 20 alkyl)-(C 3 -C 12 cycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 heterocycloalkyl), —(C 1 -C 20 alkyl)-(C 3 -C 12 aryl), or —(C 1 -C 20 alkyl)-(C 3 -C 12 heteroaryl).

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1e is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, —OR 1g , —C(═O)OR 1g , —C(═O)OR 1f , —C(═O)R 1z , —N(R 1g )C(═O)R 1z , —OC(═O)R 1z , —N + (R 1g ) 3 , or R 1z .

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1f is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, —CH 2 C(═O)OR 1g , —CH═CH—C(═O)OR 1g , or —C(═O)OR 1g , R 1z .

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1z is independently

11. The compound of claim 1 , being of Formula (I′-1) or (I′-2):

or a pharmaceutically acceptable salt or solvate thereof.

12. The compound of claim 1 , wherein T is

and R 1 is —C(═O)—R 1a , —C(═O)—CH 2 —R 1a , —C(═O)—CH 2 CH 2 —R 1a or —C(═O)—CH═CH—R 1a , wherein R 1a is C 1 -C 20 alkyl, —C(═O)R 1b , or —C(═O)OR 1c , wherein the C 1 -C 20 alkyl is optionally substituted with one or more R 1e .

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein T is

and R 1 is —C(═O)—CH 3 , —C(═O)—CH 2 —CH(OH)—CH 3 , —C(═O)—CH 2 —C(═O)—CH 3 , —C(═O)—CH 2 CH 2 —C(═O)OH, —C(═O)—CH 2 CH 2 —C(═O)OCH 3 , —C(═O)—CH═CH—CH 3 , —C(═O)—CH═CH—C(═O)OH, or —C(═O)—CH═CH—C(═O)OCH 3 .

14. The compound of claim 1 , wherein the compound is of Formula (II-1), (II-2), (IIaa), (IIab), (IIac), (Had), (IIaa-1), (IIaa-2), (IIab-1), (IIab-2), (IIac-1), (IIac-2), (IIad-1), (IIad-2), (IIae), (IIaf), (IIag), (IIah), (IIae-1), (IIae-2), (IIaf-1), (IIaf-2), (IIag-1), (IIag-2), (IIah-1), (IIah-2), (IIai), (IIaj), (IIak), (IIal), (IIam), (IIan), (IIai-1), (IIai-2), (IIaj-1), (IIaj-2), (IIak-1), (IIak-2), (IIal-1), (IIal-2), (IIam-1), (IIam-2), (IIan-1), or (IIan-2):

or a pharmaceutically acceptable salt or solvate thereof.

15. The compound of claim 1 , wherein the compound is of Formula (IIaa), (IIab), (IIac), or (Had):

or a pharmaceutically acceptable salt or solvate thereof.

16. The compound of claim 1 , wherein the compound is selected from Compound Nos. 1, 3, 5, 21, 36, 39, 42, 61, 447, 448, 451 and 485, and pharmaceutically acceptable salts thereof:

447

448

451

485

17. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.

18. A method of treating or preventing a disease characterized by and/or associated with decreased concentrations of one or more of free CoA, acetyl-CoA, acyl-CoA, a precursor of free CoA, an active metabolite of free CoA, an active metabolite of a free CoA precursor, a precursor of acetyl-CoA, an active metabolite of acetyl-CoA, an active metabolite of an acetyl-CoA precursor, a precursor of acyl-CoA, an active metabolite of acyl-CoA, and/or an active metabolite of an acyl-CoA precursor in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignments (5)

RELEASE OF SECURITY INTEREST Recorded Aug 24, 2023

From: KREOS CAPITAL VI (UK) LIMITED

To: VECTIVBIO COMET AG, F/K/A COMET THERAPEUTICS, INC.

Reel/Frame 064702/0362 →

CORRECTIVE ASSIGNMENT TO CORRECT THE NATURE OF CONVEYANCE SHOULD BE MERGER WITH AN EFFECTIVE DATE OF 07/07/2022 PREVIOUSLY RECORDED AT REEL: 061123 FRAME: 0627. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Oct 7, 2022

From: COMET THERAPEUTICS, INC.

To: VECTIVBIO COMET AG

Reel/Frame 061705/0038 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 16, 2022

From: TAVERAS, ARTHUR GEORGE; SEKIRNIK, ANGELINA ROBERTA; VALLS SERON, MERCEDES; KUSCER, ENEJ; SHAH, DHARINI

To: COMET THERAPEUTICS, INC.

Reel/Frame 061123/0553 →

CHANGE OF NAME Recorded Sep 16, 2022

From: COMET THERAPEUTICS, INC.

To: VECTIVBIO COMET AG

Reel/Frame 061123/0627 →

SECURITY INTEREST Recorded Mar 29, 2022