# US 2014/0194505 A1 · Neuraminidase Inhibitors

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0194505 A1
- Document ID: US20140194505A1
- Status: Published application
- Kind: A1
- Application number: 14/177,713
- Filed: 2014-02-11
- Published: 2014-07-10
- Earliest claimed: 2010-04-02
- Assignees: SineVir Therapeutics LLC
- Applicants: SineVir Therapeutics LLC
- Inventors: John Hilfinger; Wei Shen
- Web page: https://patentgrep.com/patent/US20140194505A1

## CPC

- C07C 233/41: with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
- A61P 31/12: Antivirals
- A61P 31/16: for influenza or rhinoviruses
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 279/16: having nitrogen atoms of guanidine groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07D 309/28: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 309/30: Oxygen atoms, e.g. delta-lactones
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Disclosed are neuraminidase inhibitor compounds and pharmaceutical compositions with improved bioavailability and/or improved efficacy and methods of treating influenza using the compounds and pharmaceuticals compositions.

## Claims

### Claim 1

A compound of formula (I):
wherein: L1 is —(CRoRo)mC(R4)2(CRoRo)nO(CRoRo)o—;
R1 is —C(O)(CRoRo)rC(RoR′)(CRoRo)sNH2, —C(O)(CRoRo)rC(RoR′)(CRoRo)sN(H)C(O)(CRoRo)wC(RoR″)(CRoRo)x—NH2, or —C(O)(CRoRo)C(RoR′)(CRoRo)sN(H)C(O)(CRoRo)wC(RoR″)(CRoRo)xN(H)C(O)(CRoRo)yC(RoR″′)(CRoRo)zNH2;
each occurrence of m, n, o, r, s, w, x, y, or z is independently zero, one, or two;
each occurrence of Ro is independently H, optionally substituted alkyl, optionally, substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
R2 is NH2 or —NHC(NH2)NH;
R3 is H, —OR*, or —CHR*R**;
R′, R″ and R′″ are each independently an amino acid side chain;
each occurrence of R4 is independently hydrogen or an optionally substituted group selected from a C1-C6 alkyl group, a 3-7 membered saturated, partially saturated or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen or oxygen or two occurrences of R4 are taken together with the atom(s) to which they are bound to form an optionally substituted 3-7 membered ring, wherein if one occurrence of R4 is H, then the other occurrence of R4 is not H or —CH3;
R* and R** are independently, H, OH, —OR5, or optionally substituted C1-C12 alkyl;
R5 is optionally substituted C1-C6 alkyl, or —C(O)NRoRo;
X1 is O or CH wherein if X1 is O, then there is a single bond between X1 and X2 and a double bond between X2 and X3; and wherein X1 is CH then there is a double bond between X1 and X2 and a single bond between X2 and X3;
X2 is C; and
X3 is CH or CH2;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, having the structure of formula (II) or formula (III):
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein R* and R** are independently, H, —OH, —OR5, or C1-C12 alkyl optionally substituted with one or more substituent each independently selected from —OH, —OR5, or —OC(O)(C1-C8 alkyl).

### Claim 4 (depends on 1)

The compound according to claim 1, wherein R3 is —CH(OR5)CH(OR5)CH2(OR5), —CH(OCH3)CH2(OH)CH2OC(O)(CH2)6CH3.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein R2 is —NHC(NH2)NH.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein R1 is —C(O)(CRoRo)rC(RoR′)(CRoRo)sNH2; and r and s are each independently zero, one or two.

### Claim 7 (depends on 6)

The compound according to claim 6, wherein R1 is —C(O)C(RoR′)NH2.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein L1 is —C(R4)2O—.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein and R′, R″ and R′″ are each independently H, —CH3, —CH(CH3)CH2CH3, —CH2CH(CH3)2, —CH2OH, —CH(CH3)2, —CH2C(O)OH, —CH2CH2C(O)OH, —CH2CH2CH2CH2NH2, —CH2CH2CH2NHC(═NH)NH2, —CH2SH, —CH2C(O)NH2, —CH2CH2C(O)NH2, —CH(OH)CH3, —CH2CH2SCH3,
or the side chain that is comprised by proline.

### Claim 10 (depends on 9)

The compound according to claim 9, wherein and R′, R″ and R″ are each independently H, —CH3, —CH(CH3)CH2CH3, —CH2CH(CH3)2, CH(CH3)2—CH2OH, or —CH2CH2CH2CH2NH2.

### Claim 11 (depends on 1)

The compound according to claim 1, wherein each occurrence of R4 is independently H or a C1-C6 alkyl group, wherein if one occurrence of R4 is H, then the other occurrence of R4 is not H or CH3.

### Claim 12 (depends on 1)

The compound according to claim 1, wherein each occurrence of R4 is independently H, —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CH2CH2CH3, —CH(CH3)CH2CH3, —CH2CH(CH3)2, —C(CH3)3, —CH2(CH2)3CH3, —CH(CH3)(CH2)2CH3, —CH(CH3)CH(CH3)2, —C(CH3)2CH2CH3, —CH(CH2CH3)2, —CH2CH(CH3)CH2CH3, —CH2CH2CH(CH3)2, —CH2C(CH3)3, CH2(CH2)CH3, —CH(CH3)(CH2)3CH3, —CH2CH(CH3)(CH2)2CH3, —CH2CH2CH(CH3)CH2CH3, —CH2(CH2)2CH(CH3)2, —CH(CH3)CH(CH3)CH2CH3, —CH(CH3)CH2CH(CH3)2, —CH2CH(CH3)CH(CH3)2, —CH2CH2CH2CH(CH3)2, —C(CH3)2CH2CH2CH3, —C(CH3)2CH(CH3)2, —C(CH2CH3)2CH3, or —CH2CH(CH2CH3)2,
wherein if one occurrence of R4 is H, then the other occurrence of R4 is not H or CH3.

### Claim 13 (depends on 2)

The compound according to claim 2, wherein L1 is —CH(CH(CH3)2)O—, R1 is —C(O)CH(C(CH3)2)NH2, R2 is —NHC(NH2)NH and R3 is —CH(OH)CH(OH)CH2(OH); L1 is —CH(CH(CH3)2)O—, R1 is —C(O)CH(C(CH3)2)NH2, R2 is —NHC(NH2)NH and R3 is —CH(OCH3)CH(OH)CH2(OH); L1 is —CH(CH(CH3)2)O—, R1 is —C(O)CH(C(CH3)2)NH2, R2 is —NHC(NH2)NH and R3 is —CH(OCH3)CH2(OH)CH2OC(O)(CH2)6CH3; or L1 is —CH(CH(CH3)2)O—, R1 is —C(O)CH(C(CH3)2)NH2, R2 is —NHC(NH2)NH and R3 is —OCH(CH2CH3)2.

### Claim 14

A compound which is:

### Claim 15 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1.

### Claim 16 (depends on 1)

A method of treating a viral infection in a subject, comprising: administering a compound according to claim 1, to a subject in need thereof.

### Claim 17 (depends on 16)

The method according to claim 16, wherein the viral infection is an influenza virus infection.

### Claim 18

A compound of formula (IV):
wherein: L1 is —(CRoRo)mC(R4)2(CRoRo)nO(CRoRo)o—;
R1 is —C(O)(CRoRo)rC(RoR′)(CRoRo)sNH2, —C(O)(CRoRo)rC(RoR′)(CRoRo)sN(H)C(O)(CRoRo)wC(RoR″)(CRoRo)xNH2, or —C(O)(CRoRo)rC(RoR′)(CRoRo)sN(H)C(O)(CRoRo)wC(RoR″)(CRoRo)xN(H)C(O)(CRoRo)yC(RoR″′)(CRoRo)zNH2;
each occurrence of m, n, o, r, s, w, x, y, or z is independently zero, one, or two;
each occurrence of Ro is independently alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl;
each occurrence of R4 is independently hydrogen or an optionally substituted group selected from a C1-C6 alkyl group, a 3-7 membered saturated, partially saturated or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen or oxygen or two occurrences of R4 are taken together with the atom(s) to which they are bound to form an optionally substituted 3-7 membered ring, wherein if one occurrence of R4 is H, then the other occurrence of R4 is not H or CH3;
R5 is optionally substituted C1-C4 alkyl, —C(O)NRoRo;
R6 is C1-C10 alkyl; and
R7 is —OH, —OR5, C1-C6 alkyl or —NRoRo;
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 18)

The compound according to claim 18, wherein R6 is —C(CH2CH3)2.

### Claim 20 (depends on 18)

The compound according to claim 18, wherein R7 is —OH or —OR5.