# US 2025/0084094 A1 · Spirocyclic inhibitors of apol1 and methods of using same

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- Number: US 2025/0084094 A1
- Document ID: US20250084094A1
- Status: Published application
- Kind: A1
- Application number: 18/714,031
- Filed: 2022-11-29
- Published: 2025-03-13
- Earliest claimed: 2021-11-30
- Assignees: Vertex Pharmaceuticals Incorporated
- Applicants: Vertex Pharmaceuticals Incorporated
- Inventors: Timothy J. Senter; Leslie A. Dakin; Ming Chen; Steven D. Stone; Elena Dolgikh; Jessica H. Olsen; Haoxuan Wang
- Web page: https://patentgrep.com/patent/US20250084094A1

## CPC

- C07D 491/107: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- A61K 31/438: The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
- A61P 13/12: of the kidneys
- A61P 35/00: Antineoplastic agents
- C07D 221/20: Spiro-condensed ring systems
- C07D 471/10: Spiro-condensed systems
- C07D 495/10: Spiro-condensed systems
- C07F 5/025: {Boronic and borinic acid compounds}
- C07F 7/0816: {said ring comprising Si as a ring atom}
- C07F 7/0836: {Compounds with one or more Si-OH or Si-O-metal linkage}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The disclosure provides at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt chosen from compounds of Formula I, tautomers thereof, deuterated derivatives of those compounds or tautomers, and pharmaceutically acceptable salts of any of the foregoing, compositions comprising the same, and methods of using the same, including uses in treating APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and/or non-diabetic kidney disease (NDKD). (I)

## Claims

### Claim 1

A compound represented by the following structural formula:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
Ring A is chosen from 6-membered aryl and 6-membered heteroaryl groups;
X is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Y is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Z is chosen from a bond, —CH2—, —NH—, —C(O)—, —S(O)2—, and —O—, wherein:
at least one of X and Y is chosen from —CH2— and —C(O)—; and
for each of X, Y, and Z, a hydrogen atom in each instance of —CH2— or —NH— is optionally replaced by R1;
R1, for each occurrence, is independently chosen from halogen, —OH, cyano, phenyl, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 carbocyclyl, 4- to 6-membered heterocyclyl, —C(═O)ORc, —C(═O)N(Rc)2, and —OS(═O)2Rc groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl groups;
the 4- to 6-membered heterocyclyl of R1 comprises one heteroatom chosen from nitrogen and oxygen;
the C1-C6 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, and C1-C4 alkoxy groups;
the C1-C6 alkoxy of R1 is optionally substituted with 1 to 3 groups independently chosen from —OH, cyano, and halogen groups;
the C3-C6 carbocyclyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups; and
the phenyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
R2 is chosen from cyano, C1-C6 alkyl, —C(═O)O(C1-C4 alkyl), C2-C6 alkynyl, and
wherein:
the C1-C6 alkyl of R2 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), —C(═O)N(C1-C4 alkyl)2, C3-C6 carbocyclyl, 5- to 10-membered heterocyclyl, C6 aryl, and 5- to 10-membered heteroaryl groups;
Ring B is chosen from C3-C12 carbocyclyl, 3- to 12-membered heterocyclyl, C6 and C10 aryl, and 5- to 10-membered heteroaryl groups, wherein Ring B is optionally substituted with 1, 2, 3, 4, or 5 Ra groups, wherein:
Ra, for each occurrence, is independently chosen from halogen, cyano, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, —C(═O)NRhRi, —NRhi, —NRhC(O)Rk, —NRhC(O)ORk, —NRhC(═O)NRiRj, —NRhS(═O)pRk, —ORk, —OC(═O)Rk, —OC(═O)ORk, —OC(═O)NRhRi, —[O(CH2)q]rO(C1-C6 alkyl), —S(═O)pRk, —S(═O)pNRhRi, —C(═O)ORk, C3-C12 carbocyclyl, 3- to 12-membered heterocyclyl, C6 and C10 aryl, and 5- to 10-membered heteroaryl groups, wherein:
the C1-C6 alkyl, C1-C6 alkoxy, and the C2-C6 alkenyl of Ra are each optionally substituted with 1 to 3 groups independently chosen from C6 to C10 aryl (optionally substituted with 1 to 3 Rm groups), 5- to 10-membered heterocyclyl (optionally substituted with 1 to 3 Rm groups), 5-to 10-membered heteroaryl (optionally substituted with 1 to 3 Rm groups), cyano, —C(═O)Rk, —C(═O)ORk, —C(═O)NRhRi, —NRhRi, —NRhC(═O)Rk, —NRhC(═O)ORk, —NRhC(═O)NRiRj, —NRhS(═O)pRk, —ORk, —OC(═O)Rk, —OC(═O)ORk, —OC(═O)NRhRi, —S(═O)pRk, —S(═O)pNRhRi, —O(C6 aryl) (optionally substituted with 1 to 3 Rm groups), and C3-C6 carbocyclyl groups (optionally substituted with 1 to 3 Rm groups);
the C3-C12 carbocyclyl, the 3- to 12-membered heterocyclyl, the C6 and C10 aryl, and the 5- to 10-membered heteroaryl of Ra are each optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, C1-C4 alkyl, —NRhRi, and —ORk groups, wherein:
Rh,Ri, and Rj, for each occurrence, are each independently chosen from hydrogen, C1-C4 alkyl, C6-C10 aryl, and C3-C6 cycloalkyl groups, wherein:
the C1-C4 alkyl of any one of Rh, Ri, and Rj is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, and —OH groups;
Rk, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, 5- to 10-membered heterocyclyl, and C3-C6 carbocyclyl groups, wherein:
the C1-C4 alkyl of any one of Rk is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, and —OH groups;
Rm, for each occurrence, is independently chosen from halogen, cyano, oxo, C1-C6 alkyl, C1-C6 alkoxy, —S(═O)pRk, and —ORk groups, wherein:
the C1-C6 alkyl of Rm is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, and —O(C1-C4 alkyl) groups;
R3 is chosen from C1-C6 alkyl, —C(═O)O(C1-C4 alkyl), C3-C12 carbocyclyl, 3- to 12-membered heterocyclyl, C6 and C10 aryl, and 5- to 10-membered heteroaryl groups, wherein:
the C1-C6 alkyl of R3 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
the C3-C12 carbocyclyl, the 3- to 12-membered heterocyclyl, the C6 and C10 aryl, and the 5- to 10-membered heteroaryl of R3 are each optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl) (optionally substituted with —OH), —N(C1-C4 alkyl)2, C1-C5 alkyl (optionally substituted with —OH or —S(═O)2(C1-C4 alkyl)), C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), —NHC(═O)(C1-C4 alkyl), —C(═O)(C1-C4 alkoxy), and —C(═O)N(C1-C4 alkyl)2 groups;
m is an integer chosen from 0, 1, 2, 3, 4, and 5;
p, for each occurrence, is an integer independently chosen from 1 and 2; and
q and r, for each occurrence, are each an integer independently chosen from 1, 2, 3, and 4.

### Claim 2 (depends on 1)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein:
Ring A is chosen from 6-membered aryl and 6-membered heteroaryl groups;
X is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Y is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Z is chosen from a bond, —CH2—, —NH—, —C(O)—, —S(O)2—, and —O—, wherein:
at least one of X and Y is chosen from —CH2— and —C(O)—; and
for each of X, Y, and Z, a hydrogen atom in each instance of —CH2— or —NH— is optionally replaced by R1;
R1, for each occurrence, is independently chosen from halogen, —OH, cyano, phenyl, C1-C6 alkyl, C1-C6 alkoxy, —C(═O)ORc, —C(═O)N(Rc)2, and —OS(═O)2Rc groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl groups;
the C1-C6 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, and C1-C4 alkoxy groups;
the C1-C6 alkoxy of R1 is optionally substituted with 1 to 3 groups independently chosen from —OH, cyano, and halogen groups;
the phenyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
R2 is chosen from C1-C6 alkyl and
wherein:
the C1-C6 alkyl of R2 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), —C(═O)N(C1-C4 alkyl)2, C3-C6 carbocyclyl, 5- to 10-membered heterocyclyl, C6 aryl, and 5- to 10-membered heteroaryl groups;
Ring B is chosen from 3- to 12-membered heterocyclyl, C6 aryl, and 5- to 10-membered heteroaryl groups, wherein Ring B is optionally substituted with 1, 2, 3, 4, or 5 Ra groups, wherein:
Ra, for each occurrence, is independently chosen from halogen, cyano, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, —C(═O)NRhRi, —NRhRi, —NRhC(═O)Rk, —NRhC(═O)ORk, —NRhC(═O)NRiRj, —NRhS(═O)pRk, —ORk, —OC(═O)Rk, —OC(═O)ORk, —OC(═O)NRhRi, —[O(CH2)q]rO(C1-C6 alkyl), —S(═O)pRk, —S(═O)pNRhRi, —C(═O)ORk, C3-C12 carbocyclyl, 3- to 12-membered heterocyclyl, C6 and C10 aryl, and 5- to 10-membered heteroaryl groups, wherein:
the C1-C6 alkyl, C1-C6 alkoxy, and the C2-C6 alkenyl of Ra are each optionally substituted with 1 to 3 groups independently chosen from C6 to C10 aryl (optionally substituted with 1 to 3 Rm groups), 5- to 10-membered heterocyclyl (optionally substituted with 1 to 3 Rm groups), 5-to 10-membered heteroaryl (optionally substituted with 1 to 3 Rmgroups), cyano, —C(═O)Rk, —C(═O)ORk, —C(═O)NRhRi, —NRhi, —NRhC(═O)Rk,
—NRhC(═O)ORk, —NRhC(═O)NRiRj, —NRhS(═O)pRk, —ORk, —OC(═O)Rk, —OC(═O)ORk, —OC(═O)NRhRi, —S(═O)pRk, —S(═O)pNRhRi, and C3-C6 carbocyclyl groups (optionally substituted with 1 to 3 Rm groups);
the C3-C12 carbocyclyl, the 3- to 12-membered heterocyclyl, the C6 and C10 aryl, and the 5- to 10-membered heteroaryl of Ra are each optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, C1-C4 alkyl, —NRhRi, and —ORk groups, wherein:
Rh, Ri, and Rj, for each occurrence, are each independently chosen from hydrogen, C1-C4 alkyl, C6-C10 aryl, and C3-C6 cycloalkyl groups, wherein:
the C1-C4 alkyl of any one of Rh, Ri, and Rj is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, and —OH groups;
Rk, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, 5- to 10-membered heterocyclyl, and C3-C6 carbocyclyl groups, wherein:
the C1-C4 alkyl of any one of Rk is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, and —OH groups;
Rm, for each occurrence, is independently chosen from halogen, cyano, oxo, C1-C6 alkyl, C1-C6 alkoxy, —S(═O)pRk, and —ORk groups, wherein:
the C1-C6 alkyl of Rm is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, and —OH groups;
R3 is chosen from C1-C6 alkyl groups, wherein:
the C1-C6 alkyl of R3 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
m is an integer chosen from 0, 1, 2, and 3;
p, for each occurrence, is an integer independently chosen from 1 and 2; and
q and r, for each occurrence, are each an integer independently chosen from 1, 2, 3, and 4.

### Claim 3 (depends on 1, 2)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1 or 2, wherein:
Ring A is chosen from 6-membered aryl and 6-membered heteroaryl groups;
X is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Y is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Z is chosen from a bond, —CH2—, —NH—, —C(O)—, —S(O)2—, and —O—, wherein:
at least one of X and Y is chosen from —CH2— and —C(O)—; and
for each of X, Y, and Z, a hydrogen atom in each instance of —CH2— or —NH— is optionally replaced by R1;
R1, for each occurrence, is independently chosen from halogen, —OH, cyano, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)ORc, —C(═O)N(Rc)2, and —OS(═O)2Rc groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl groups;
the C1-C6 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH groups;
R2 is
wherein:
Ring B is chosen from 5-membered heterocyclyl and 5-membered heteroaryl groups, wherein Ring B is optionally substituted with 1 or 2 Ra groups, wherein:
Ra, for each occurrence, is independently chosen from C1-C6 alkyl groups optionally substituted with 1 group independently chosen from —S(═O)pRk groups, wherein:
Rk, for each occurrence, is independently chosen from C1-C4 alkyl groups;
R3 is chosen from C1-C3 alkyl groups;
m is an integer chosen from 0, 1, 2, and 3; and
p, for each occurrence, is an integer independently chosen from 1 and 2.

### Claim 4 (depends on 1, 2, 3)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-3, wherein:
Ring A is chosen from 6-membered aryl and 6-membered heteroaryl groups;
X is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Y is chosen from —CH2—, —C(O)—, —S(O)2—, —NH—, and —O—;
Z is chosen from a bond, —CH2—, —NH—, —C(O)—, —S(O)2—, and —O—, wherein:
at least one of X and Y is chosen from —CH2— and —C(O)—; and
for each of X, Y, and Z, a hydrogen atom in each instance of —CH2— or —NH— is optionally replaced by R1;
R1, for each occurrence, is independently chosen from halogen, —OH, cyano, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)ORc, —C(═O)N(Rc)2, and —OS(═O)2Rc groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl groups;
the C1-C6 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH groups;
R2 is
wherein:
Ring B is chosen from pyrazole and triazole groups, wherein Ring B is optionally substituted with 1 or 2 Ra groups, wherein:
Ra, for each occurrence, is independently chosen from C1-C6 alkyl groups optionally substituted with 1 group independently chosen from —S(═O)pRk groups, wherein:
Rk, for each occurrence, is independently chosen from C1-C4 alkyl groups;
R3 is methyl;
m is an integer chosen from 0, 1, 2, and 3; and
p, for each occurrence, is an integer independently chosen from 1 and 2.

### Claim 5 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-4, wherein Ring A is chosen from phenyl, pyrimidinyl, and pyridinyl, and all other variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 6 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-4, wherein Ring A is phenyl, and all other variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 7 (depends on 1, 5)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, 5, or 6, wherein R1, for each occurrence, is independently chosen from hydrogen, halogen, cyano, —OH, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)N(Rc)2, and C3-C6 cycloalkyl groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen and C1-C2 alkyl groups;
the C1-C4 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, and C1-C2 alkoxy groups;
the C1-C4 alkoxy of R1 is optionally substituted with 1 to 3 independently chosen from halogen groups; and
the C3-C6 cycloalkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, and C1-C2 alkoxy groups;
and all other variables not specifically defined herein are as defined in claim 1, 5, or 6.

### Claim 8 (depends on 1, 5)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, 5, or 6, wherein R1, for each occurrence, is independently chosen from F, Cl, Br, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)N(Rc)2, and C3-C6 cycloalkyl groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen and C1-C2 alkyl groups;
the C1-C4 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH;
the C1-C4 alkoxy of R1 is optionally substituted with 1 to 3 independently chosen from halogen groups; and
the C3-C6 cycloalkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH;
and all other variables not specifically defined herein are as defined in claim 1, 5, or 6.

### Claim 9 (depends on 1, 5)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, 5, or 6, wherein R1, for each occurrence, is independently chosen from F, Cl, Br, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)N(Rc)2, and C3-C6 cycloalkyl groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen and C1-C2 alkyl groups;
the C1-C4 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH; and
the C1-C4 alkoxy of R1 is optionally substituted with 1 to 3 independently chosen from halogen groups;
and all other variables not specifically defined herein are as defined in claim 1, 5, or 6.

### Claim 10 (depends on 1, 5)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, 5, or 6, wherein R1, for each occurrence, is independently chosen from F, Cl, Br, —CH3, —CH(CH3)2, —CF3, —OCH3, —OCF3, —C(═O)N(CH3)2, and cyclopropyl;
and all other variables not specifically defined herein are as defined in claim 1, 5, or 6.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-10, wherein m is 1; and all other variables not specifically defined herein are as defined in any one of claims 1-10.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-10, wherein m is 2; and all other variables not specifically defined herein are as defined in any one of claims 1-10.

### Claim 13 (depends on 1, 5, 6, 7, 8, 9, 10, 11, 12)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 and 5-12, wherein Ring B is chosen from cyclopropyl, 5- to 10-membered heterocyclyl, phenyl, and 5- to 9-membered heteroaryl groups; each of which is optionally substituted with 1, 2, 3, 4, or 5 Ra groups; and all other variables not specifically defined herein are as defined in any one of claims 1 and 5-12.

### Claim 14 (depends on 1, 5, 6, 7, 8, 9, 10, 11, 12)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 and 5-12, wherein Ring B is chosen from cyclopropyl, 5- to 10-membered heterocyclyl comprising 1 to 3 heteroatoms chosen from N and O, phenyl, and 5-to 9-membered heteroaryl comprising 1 to 3 heteroatoms chosen from N and O; each of which is optionally substituted with 1, 2, 3, 4, or 5 Ra groups; and all other variables not specifically defined herein are as defined in any one claims of 1 and 5-12.

### Claim 15 (depends on 1, 5, 6, 7, 8, 9, 10, 11, 12)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 and 5-12, wherein Ring B is chosen from cyclopropyl, 5-membered heterocyclyl comprising 1 to 3 heteroatoms chosen from N and O, 6-membered heterocyclyl comprising 1 to 3 heteroatoms chosen from N and O, 9-membered heterocyclyl comprising 1 to 3 heteroatoms chosen from N and O, 10-membered heterocyclyl comprising 1 to 3 heteroatoms chosen from N and O, phenyl, 5-membered heteroaryl comprising 1 to 3 heteroatoms chosen from N and O, 6-membered heteroaryl comprising 1 to 3 heteroatoms chosen from N and O, and 9-membered heteroaryl comprising 1 to 3 heteroatoms chosen from N and O; each of which is optionally substituted with 1, 2, 3, 4, or 5 Ra groups; and all other variables not specifically defined herein are as defined in any one of claims 1 and 5-12.

### Claim 16 (depends on 1, 5, 6, 7, 8, 9, 10, 11, 12)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 and 5-12, wherein Ring B is chosen from
each of which is optionally substituted with 1, 2, 3, 4, or 5 Ra groups; and all other variables not specifically defined herein are as defined in any one of claims 1 and 5-12.

### Claim 17 (depends on 1, 5, 6, 7, 8, 9, 10, 11, 12)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 and 5-12, wherein Ring B is chosen from
each of which is optionally substituted with 1, 2, 3, 4, or 5 Ra groups; and all other variables not specifically defined herein are as defined in any one of claims 1 and 5-12.

### Claim 18 (depends on 1, 5, 6, 7, 8, 9, 10, 11, 12)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 and 5-12, wherein Ring B is
which is optionally substituted with 1 Ra group; and all other variables not specifically defined herein are as defined in any one of claims 1 and 5-12.

### Claim 19 (depends on 13, 14, 15, 16, 17, 18)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 13-18, wherein Ra, for each occurrence, is independently chosen from halogen, cyano, C1-C6 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, —C(═O)NRhRi, —NRhRi, —NRhC(O)Rk, —ORk, —[O(CH2)q]rO(C1-C6 alkyl), —S(═O)2Rk, —S(═O)2NRhRi, C3-C6 cycloalkyl, 5 to 10-membered heterocyclyl, phenyl, and 5- to 8-membered heteroaryl groups, wherein:
the C1-C6 alkyl of Ra is optionally substituted with 1 to 3 groups independently chosen from cyano, —C(═O)NRhRi, —NRhRi, —NRhC(═O)Rk, —NRhC(═O)ORk, —NRhC(═O)NRiRj, —NRhS(═O)pRk, —ORk, —S(═O)2Rk, —S(═O)pNRhRi, and C3-C6 cycloalkyl groups;
the C3-C6 cycloalkyl, the 5- to 10-membered heterocyclyl, the phenyl, and the 5- to 8-membered heteroaryl of Ra are each optionally substituted with 1 to 3 groups independently chosen from halogen, C1-C2 alkyl, and —ORk groups, wherein:
Rh, Ri, and Rj, for each occurrence, are each independently chosen from hydrogen, C1-C2 alkyl, cyclopropyl, and cyclobutyl groups, wherein:
the C1-C2 alkyl of any one of Rh, Ri, and Rj is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH;
Rk, for each occurrence, is each independently chosen from hydrogen and C1-C4 alkyl groups, wherein:
the C1-C4 alkyl of Rk is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH; and
q and r are each an integer chosen from 1, 2, and 3;
and all other variables not specifically defined herein are as defined in any one of claims 13-18.

### Claim 20 (depends on 13, 14, 15, 16, 17, 18)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 13-18, wherein Ra, for each occurrence, is independently chosen from halogen, cyano, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, —C(═O)NRhRi, —NRhRi, —NRhC(═O)Rk, ORk, —[O(CH2)q]rO(C1-C4 alkyl), —S(═O)2Rk, —S(═O)2NRhRi, cyclopropyl, cyclobutyl, 5- to 6-membered heterocyclyl, phenyl, and 5- to 6-membered heteroaryl, wherein:
the C1-C6 alkyl of Ra is optionally substituted with 1 to 3 groups independently chosen from cyano, —C(═O)NRhRi, —S(═O)2Rk, —NRhRi, —ORk, cyclopropyl, and cyclobutyl groups, wherein:
the cyclopropyl, the cyclobutyl, the 5- to 6-membered heterocyclyl, the phenyl, and the 5 to 6-membered heteroaryl of Ra are each optionally substituted with 1 to 3 groups independently chosen from halogen, —CH3, —OH, and —OCH3; wherein:
Rh and Ri, for each occurrence, are each independently chosen from hydrogen, —CH3, cyclopropyl, and cyclobutyl groups, wherein:
the —CH3 of any one of Rh and Ri is optionally substituted with 1 to 3 groups independently chosen from F, Cl, and —OH;
Rk, for each occurrence, is each independently chosen from hydrogen and —CH3, wherein:
the —CH3 of Rk is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH;
and all other variables not specifically defined herein are as defined in any one of claims 13-18.

### Claim 21 (depends on 13, 14, 15, 16, 17, 18)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 13-18, wherein Ra, for each occurrence, is independently chosen from F, Cl, Br, cyano, C1-C6 alkyl, C1-C2 alkoxy, C1-C2 haloalkyl, —C(═O)NRhRi, —NRhRi, —NRhC(═O)Rk, ORk, —[O(CH2)q]rO(C1-C2 alkyl), —S(═O)2Rk, —S(═O)2NRhRi, cyclopropyl, cyclobutyl, 5-membered heterocyclyl, phenyl, and 6-membered heteroaryl groups, wherein:
the C1-C6 alkyl of Ra is optionally substituted with 1 to 3 groups independently chosen from cyano, —C(═O)NRhRi, —ORk, —S(═O)2Rk, and cyclopropyl;
the cyclopropyl, the cyclobutyl, the 5- to 6-membered heterocyclyl, the phenyl, and the 5- to 6-membered heteroaryl of Ra are each optionally substituted with 1 to 3 groups independently chosen from halogen, —CH3, —OH, and —OCH3, wherein:
Rh and Ri, for each occurrence, are each independently chosen from hydrogen, —CH3, and cyclopropyl; wherein:
the —CH3 of any one of Rh and Riis optionally substituted with 1 to 3 groups independently chosen from F, Cl, and —OH;
Rk, for each occurrence, is each independently chosen from hydrogen and —CH3; and
q and r are each an integer independently chosen from 1 and 2;
and all other variables not specifically defined herein are as defined in any one of claims 13-18.

### Claim 22 (depends on 13, 14, 15, 16, 17, 18)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 13-18, wherein Ra, for each occurrence, is independently chosen from F, cyano, —OH, —CH3, —CF3, —CH(CH3)2, —(CH2)2OH, —(CH2)2OCH3, —CH2CH(OH)C2H5,
—CH2C(CH3)(CH2OH)2, —OCH3, —OCH2CH3, —O(CH2)2]2OCH3, —CH2C(═O)NHCH3, —(CH2)2SO2CH3, —CH2C(═O)N(CH3)2, —CH2(cyclopropyl), —C(═O)NH2, —C(═O)NH(cyclopropyl), —NH2, —NHCH3, —N(CH3)2, —NHC(CH3)2CH2OH, —NHC(═O)CH3, —SO2CH3, —SO2NH2, cyclopropyl, 2-methoxyphenyl, N-methylpiperazinyl, tetrahydro-2H-pyranyl, methylpyrazolyl, pyridinyl, and tetrahydrothiophenyl 1,1-dioxide; and all other variables not specifically defined herein are as defined in any one of claims 13-18.

### Claim 23 (depends on 13, 14, 15, 16, 17, 18)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 13-18, wherein Ra, for each occurrence, is independently chosen from —CH3 and —(CH2)2SO2CH3; and all other variables not specifically defined herein are as defined in any one of claims 13-18.

### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by the following structural formula:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein all variables not specifically defined herein are as defined in any one of claims 1-23.

### Claim 25 (depends on 1, 24)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1 or 24, wherein Z is chosen from —CH2—, —NH—, —C(O)—, —S(O)2—, and —O—; and all other variables not specifically defined herein are as defined in claim 1 or 24.

### Claim 26 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by one of the following structural formulae:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein all variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 27 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by one of the following structural formulae:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein all variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 28 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by one of the following structural formulae:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein all variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 29 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by one of the following structural formulae:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
R1a is chosen from hydrogen, halogen, —OH, and phenyl groups, wherein:
the phenyl of R1a is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
R1b and R1c are each independently chosen from hydrogen, halogen, —OH, cyano, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)ORc, —C(═O)N(Rc)2, and —OS(═O)2Rc groups, wherein:
Rc, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl groups; and
the C1-C6 alkyl of R1b and/or R1c is optionally substituted with 1 to 3 groups independently chosen from halogen and —OH groups; and
all variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 30 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by one of the following structural formulae:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
R1a is chosen from hydrogen, phenyl, and C(═O)N(Rc1)2 groups, wherein:
the phenyl of R1a is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 alkoxy,
—C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
Rc1, for each occurrence, is independently chosen from hydrogen and C1-C4 alkyl groups;
R1b and R1c are each independently chosen from hydrogen and halogen groups; and
all variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 31 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by one of the following structural formulae:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
R1a and R1b are each independently chosen from hydrogen, halogen, C1-C4 alkyl, and C1-C4 haloalkyl groups; and
all variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 32 (depends on 1, 2, 3, 4)

The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, wherein the compound is represented by one of the following structural formulae:
a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
R1a and R1b are each independently chosen from hydrogen, halogen, C1-C4 alkyl, and C1-C4 haloalkyl groups; and
all variables not specifically defined herein are as defined in any one of claims 1-4.

### Claim 33

A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt chosen from the compounds of Table 1, tautomers thereof, deuterated derivatives of those compounds and tautomers, and pharmaceutically acceptable salts of any of the foregoing.

### Claim 34

A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt chosen from the compounds of Table 2, tautomers thereof, deuterated derivatives of those compounds and tautomers, and pharmaceutically acceptable salts of any of the foregoing.

### Claim 35 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)

A pharmaceutical composition comprising at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-34 and a pharmaceutically acceptable carrier.

### Claim 36 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A method of treating focal segmental glomerulosclerosis and/or non-diabetic kidney disease comprising administering to a patient in need thereof at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-34 or a pharmaceutical composition according to claim 35.

### Claim 37 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A method of inhibiting APOL1 activity comprising contacting said APOL1 with at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-34 or a pharmaceutical composition according to claim 35.

### Claim 38 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)

A silicon derivative of the at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-34.

### Claim 39 (depends on 38)

A pharmaceutical composition comprising a silicon derivative according to claim 38.

### Claim 40 (depends on 38, 39)

A method of treating focal segmental glomerulosclerosis and/or non-diabetic kidney disease comprising administering to a patient in need thereof a silicon derivative according to claim 38 or a pharmaceutical composition according to claim 39.

### Claim 41 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)

A boron derivative of the at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-34.

### Claim 42 (depends on 41)

A pharmaceutical composition comprising a boron derivative according to claim 41.

### Claim 43 (depends on 41, 42)

A method of treating focal segmental glomerulosclerosis and/or non-diabetic kidney disease comprising administering to a patient in need thereof a boron derivative according to claim 41 or a pharmaceutical composition according to claim 42.

### Claim 44 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)

A phosphorus derivative of at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-34.

### Claim 45 (depends on 44)

A pharmaceutical composition comprising a phosphorus derivative according to claim 44.

### Claim 46 (depends on 44, 45)

A method of treating focal segmental glomerulosclerosis and/or non-diabetic kidney disease comprising administering to a patient in need thereof a phosphorus derivative according to claim 44 or a pharmaceutical composition according to claim 45.

### Claim 47 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A method of treating an APOL1-mediated disease comprising administering to a patient in need thereof at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1-34 or a pharmaceutical composition according to claim 35.

### Claim 48 (depends on 47)

The method according to claim 47, wherein the APOL1-mediated disease is cancer.

### Claim 49 (depends on 47, 48)

The method according to claim 47 or claim 48, wherein the APOL1-mediated disease is pancreatic cancer.