# US 2019/0167651 A1 · Heteroaryl sulfonamides and ccr2/ccr9

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- Number: US 2019/0167651 A1
- Document ID: US20190167651A1
- Status: Published application
- Kind: A1
- Application number: 16/272,401
- Filed: 2019-02-11
- Published: 2019-06-06
- Earliest claimed: 2006-07-14
- Assignees: ChemoCentryx, Inc.
- Applicants: ChemoCentryx, Inc.
- Inventors: Solomon Ungashe; Zheng Wei; Arindrajit Basak; Trevor T. Charvat; Wei Chen; Jeff Jin; Jimmie Moore; Yibin Zeng; Sreenivas Punna; Daniel Dairaghi; Derek Hansen; Andrew M.K. Pennell; John J. Wright; Antoni Krasinski; Qiang Wang
- Web page: https://patentgrep.com/patent/US20190167651A1

## CPC

- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 37/00: Drugs for immunological or allergic disorders
- C07C 311/21: having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07D 213/75: Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C07D 241/22: Benzenesulfonamido pyrazines
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 407/04: directly linked by a ring-member-to-ring-member bond
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 498/04: Ortho-condensed systems
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds are provided that act as potent antagonists of the CCR2 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR2. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases, and as controls in assays for the identification of CCR2 antagonists.

## Claims

### Claim 1

A method of preparing a compound of Formula A, comprising:
(a) reacting a compound of Formula B with a Grignard reagent to produce a compound of Formula C; and
(b) deprotecting the compound of Formula C to produce the compound of Formula A,
wherein
Ar is selected from the group consisting of substituted or unsubstituted C6-10 aryl and substituted or unsubstituted 5- to 10-membered heteroaryl;
Y6 is halogen or substituted or unsubstituted C1-8 alkyl;
R is a protecting group;
R100 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocycle; and
Z3 and Z7 are each independently —CR67—;
R67 is independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, —CN, ═O, —NO2, —OR68, —OC(O)R68, —CO2R68, —C(O)R68, —C(O)NR69R68, —OC(O)NR69R68, —NR70C(O)R68, —NR70C(O)NR69R68, —NR69R68, —NR70CO2R68, —SR68, —S(O)R68, —S(O)2R68, —S(O)2NR69R68, —NR70S(O)2R68, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl;
R68, R69, and R70 are independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, aryl, and heteroaryl; or
R69 and R68 or R70 and R68, together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring.

### Claim 2 (depends on 1)

The method of claim 1, wherein Y6 is unsubstituted C1-8 alkyl.

### Claim 3 (depends on 1)

The method of claim 1, wherein Z3 and Z7 are —CH—.

### Claim 4 (depends on 1)

The method of claim 1, wherein R100 is hydrogen.

### Claim 5 (depends on 1)

The method of claim 1, wherein Ar is substituted or unsubstituted C6-10 aryl.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound of Formula A is

### Claim 7 (depends on 1)

The method of claim 1, wherein the Grignard reagent is formed by reacting an iodoheterocycle with an alkyl- or aryl-magnesium chloride in a solvent.

### Claim 8 (depends on 7)

The method of claim 7, wherein the alkyl-magnesium chloride is isopropylmagnesium chloride.

### Claim 9 (depends on 7)

The method of claim 7, wherein the iodoheterocycle is a protected or unprotected 4-iodo-1H-pyrrolo[2,3-b]pyridine.

### Claim 10 (depends on 7)

The method of claim 7, wherein iodoheterocycle is 1-(tert-butyl-dimethyl-silanyl)-4-iodo-1H-pyrrolo[2,3-b]pyridine.

### Claim 11 (depends on 7)

The method of claim 7, wherein the solvent is tetrahydrofuran.

### Claim 12 (depends on 1)

The method of claim 1, wherein the compound of Formula C is deprotected in the presence of an acid.

### Claim 13 (depends on 12)

The method of claim 12, wherein the acid is hydrochloric acid.

### Claim 14

A method of preparing a compound of Formula A, comprising:
reacting a compound of Formula B with Grignard reagent to produce a compound of Formula A; and
wherein
Ar is selected from the group consisting of substituted or unsubstituted C6-10 aryl and substituted or unsubstituted 5- to 10-membered heteroaryl;
Y6 is halogen or substituted or unsubstituted C1-8 alkyl;
R100 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocycle; and
Z3 and Z7 are each independently —CR67—;
R67 is independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, —CN, ═O, —NO2, —OR68, —OC(O)R68, —CO2R68, —C(O)R68, —C(O)NR69R68, —OC(O)NR69R68, —NR70C(O)R68, —NR70C(O)NR69R68, —NR69R68, —NR70CO2R68, —SR68, —S(O)R68, —S(O)2R68, —S(O)2NR69R68, —NR70S(O)2R68, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl;
R68, R69, and R70 are independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, aryl, and heteroaryl; or
R69 and R68 or R70 and R68, together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring.

### Claim 15 (depends on 14)

The method of claim 14, wherein Y6 is unsubstituted C1-8 alkyl.

### Claim 16 (depends on 14)

The method of claim 14, wherein Z3 and Z7 are —CH—.

### Claim 17 (depends on 14)

The method of claim 14, wherein R100 is hydrogen.

### Claim 18 (depends on 14)

The method of claim 14, wherein Ar is substituted or unsubstituted C6-10 aryl.

### Claim 19 (depends on 14)

The method of claim 14, wherein the compound of Formula A is

### Claim 20 (depends on 14)

The method of claim 14, wherein the Grignard reagent is formed by reacting an iodoheterocycle with an alkyl- or aryl-magnesium chloride in a solvent.