# US 2017/0283429 A1 · Compounds for the treatment of paramyxovirus viral infections

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- Number: US 2017/0283429 A1
- Document ID: US20170283429A1
- Status: Published application
- Kind: A1
- Application number: 15/627,757
- Filed: 2017-06-20
- Published: 2017-10-05
- Earliest claimed: 2012-08-23
- Assignees: Alios BioPharma, Inc.
- Applicants: Alios BioPharma, Inc.
- Inventors: Guangyi Wang; Leonid Beigelman; Anh Truong; Carmela Napolitano; Daniele Andreotti; Haiying He
- Web page: https://patentgrep.com/patent/US20170283429A1

## CPC

- C07D 495/04: Ortho-condensed systems
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/277: having a ring, e.g. verapamil
- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A61K 31/381: having five-membered rings
- A61K 31/382: having six-membered rings, e.g. thioxanthenes (thiothixene A61K31/496)
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/4025: not condensed and containing further heterocyclic rings, e.g. cromakalim
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61K 31/4155: non condensed and containing further heterocyclic rings
- A61K 31/4164: 1,3-Diazoles
- A61K 31/4196: 1,2,4-Triazoles
- A61K 31/423: condensed with carbocyclic rings
- A61K 31/426: 1,3-Thiazoles
- A61K 31/427: not condensed and containing further heterocyclic rings
- A61K 31/428: condensed with carbocyclic rings
- A61K 31/4365: the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
- A61K 31/4375: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A61K 31/4418: having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
- A61K 31/4427: containing further heterocyclic ring systems
- A61K 31/4436: containing a heterocyclic ring having sulfur as a ring hetero atom
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/4704: 2-Quinolinones, e.g. carbostyril
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/4725: containing further heterocyclic rings
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/497: containing further heterocyclic rings
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/538: ortho- or peri-condensed with carbocyclic ring systems
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- C07C 243/18: containing rings
- C07C 243/34: to carbon atoms of a carbon skeleton further substituted by nitrogen atoms
- C07C 251/80: the carbon skeleton containing rings
- C07C 251/84: having doubly-bound carbon atoms of hydrazone groups being part of rings other than six-membered aromatic rings
- C07C 255/34: with cyano groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by unsaturated carbon chains
- C07C 255/66: having cyano groups and nitrogen atoms being part of hydrazine or hydrazone groups bound to the same carbon skeleton
- C07D 207/335: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D 209/08: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- C07D 209/14: Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D 209/20: substituted additionally by nitrogen atoms, e.g. tryptophane
- C07D 209/86: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
- C07D 213/42: having hetero atoms attached to the substituent nitrogen atom (nitro radicals C07D213/26)
- C07D 213/50: Ketonic radicals
- C07D 213/65: attached in position 3 or 5
- C07D 213/68: attached in position 4
- C07D 215/12: with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D 215/14: Radicals substituted by oxygen atoms
- C07D 215/38: Nitrogen atoms (nitro radicals C07D215/18)
- C07D 215/42: attached in position 4
- C07D 217/24: Oxygen atoms
- C07D 233/38: with acyl radicals or hetero atoms directly attached to ring nitrogen atoms
- C07D 233/60: with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
- C07D 233/61: with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C07D 233/88: Nitrogen atoms, e.g. allantoin
- C07D 261/20: condensed with carbocyclic rings or ring systems
- C07D 277/56: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D 277/64: with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C07D 307/40: Radicals substituted by oxygen atoms
- C07D 307/52: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D 307/81: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D 307/91: Dibenzofurans; Hydrogenated dibenzofurans
- C07D 311/68: with nitrogen atoms directly attached in position 4
- C07D 333/16: by oxygen atoms
- C07D 333/20: by nitrogen atoms (nitro, nitroso radicals C07D333/12)
- C07D 333/50: condensed with carbocyclic rings or ring systems
- C07D 333/54: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D 333/58: Radicals substituted by nitrogen atoms
- C07D 333/62: 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 carbon atoms of the hetero ring
- C07D 333/66: Nitrogen atoms not forming part of a nitro radical
- C07D 333/68: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D 333/76: Dibenzothiophenes
- C07D 335/06: Benzothiopyrans; Hydrogenated benzothiopyrans
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/10: linked by a carbon chain containing aromatic rings
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 409/04: directly linked by a ring-member-to-ring-member bond
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 409/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 413/14: containing three or more hetero rings
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 495/14: Ortho-condensed systems
- C07C 2602/08: the other ring being five-membered, e.g. indane
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Disclosed herein are new antiviral compounds, together with pharmaceutical compositions that include one or more antiviral compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection with one or more small molecule compounds. Examples of paramyxovirus infection include an infection caused by human respiratory syncytial virus (RSV).

## Claims

### Claim at position 1

-81. (canceled)

### Claim 82

A compound of Formula (II), or a pharmaceutically acceptable salt thereof, having the structure:
Ab-Lb-Yb (II)
wherein: Lb is selected from the group consisting of:
Ab is an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted aryl(C1-2 alkyl), an optionally substituted heteroaryl or an optionally substituted heterocyclyl;
Yb is an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl or an optionally substituted heterocyclyl;
when Lb is Formula (IIc), between X2b and X3b represents a single or double bond between X2b and X3b, when between X2b and X3b is a double bond, then X1b is independently NR3b or CR3b1R3b2, X2b is N (nitrogen) or CR7b1, and X3b is N (nitrogen) or CR4b; when between X2b and X3b is a single bond, then X1b is independently NR3b or CR3b1R3b2, X2b is O (oxygen), NR7b or C(R7b2)(R7b3), and X3b is NR4b, C(═O) or CR4bR8b; or
X1b, X2b and X3b are each independently C (carbon), N (nitrogen), O (oxygen) or C(═O), and form a ring or ring system selected from the group consisting of an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted heterocyclyl by joining X1b and X3b together; with the proviso that the valencies of X1b, X2b and X3b are satisfied with a substituent selected from the group consisting of hydrogen and an optionally substituted C1-4 alkyl, and X1b, X2b and X3b are uncharged;
X4b is NR6b1 or C(R6b2)2;
X5b is NR6b3 or C(R6b4)2;
X6b is NR6b5 or C(═O);
X7b is NR6b6CH2 or —C(═O)— an optionally substituted pyridinyl-;
Zb is N or CH;
R1b is hydrogen or an unsubstituted C1-4 alkyl;
R1b2 is hydrogen or an unsubstituted C1-4 alkyl;
when Lb is Formula (IIg), then Yb is absent;
when of Formula (IIl) is a single bond, then R1b3 is hydroxy; when of Formula (IIl) is a double bond, then R1b3 is O (oxygen);
R2b and R2b1 are each independently hydrogen or an optionally substituted C1-4 alkyl, and when more than one R2b and/or more than one R2b1 are present, each R2b and each R2b1 is the same or different;
R3b, R3b1 and R3b2 are each independently hydrogen or an unsubstituted C1-4 alkyl;
R4b is hydrogen, an optionally substituted C1-4 alkyl or an optionally substituted alkoxyalkyl;
R5b and R5b1 are each independently hydrogen or hydroxy;
R6b1, each R6b2, R6b3, each R6b4, R6b5 and R6b6 are each independently hydrogen or an unsubstituted C1-4 alkyl;
R7b and R7b1 are each independently be hydrogen or an unsubstituted C1-4 alkyl;
R7b2 and R7b3 are each independently hydrogen or an unsubstituted C1-4 alkyl; or R7b2 and R7b3 together form ═O;
R8b is hydrogen or an unsubstituted C1-4 alkyl;
R9b and R10b are each independently an unsubstituted C1-4 alkyl, an unsubstituted C1-4 alkenyl or an unsubstituted C1-4 alkoxy; or
R9b and R10b are taken together to form an unsubstituted aryl, an unsubstituted heteroaryl or an optionally substituted heterocyclyl;
ring B is an optionally substituted
or an optionally substituted
ring B1 is an optionally substituted mono-cyclic cycloalkyl, an optionally substituted phenyl, an optionally substituted mono-cyclic heteroaryl or an optionally substituted mono-cyclic heterocyclyl;
ring B2 is an optionally substituted heteroaryl;
ring B3 is an optionally substituted pyridinyl;
ring B4 is an optionally substituted heteroaryl or an optionally substituted heterocyclyl;
ring B5 is an optionally substituted pyridinyl;
ring B6 is an optionally substituted pyridinyl;
ring B7 is an optionally substituted heterocyclyl;
m1b and m2b are each independently 0 or 1; provided that at least one of m1b and m2b is 1;
m3b is 0 or 1; and
nb is 2 or 3.

### Claim 83 (depends on 82)

The compound of claim 82, wherein Lb is Formula (IIa).

### Claim 84

(canceled)

### Claim 85

(canceled)

### Claim 86

(canceled)

### Claim 87 (depends on 83)

The compound of claim 83, wherein the compound is selected from the group consisting of

### Claim 88 (depends on 82)

The compound of claim 82, wherein Lb is Formula (IIb).

### Claim 89

(canceled)

### Claim 90

(canceled)

### Claim 91

(canceled)

### Claim 92 (depends on 88)

The compound of claim 88, wherein the compound is selected from the group consisting of

### Claim 93 (depends on 82)

The compound of claim 82, wherein Lb is Formula (IIc).

### Claim 94

(canceled)

### Claim 95

(canceled)

### Claim 96

(canceled)

### Claim 97

(canceled)

### Claim 98

(canceled)

### Claim 99

(canceled)

### Claim 100 (depends on 93)

The compound of claim 93, wherein the compound is selected from the group consisting of

### Claim 101 (depends on 82)

The compound of claim 82, wherein Lb is selected from the group consisting of Formula (IId), Formula (IIf), Formula (IIh) and Formula (IIj).

### Claim 102

(canceled)

### Claim 103

(canceled)

### Claim 104

(canceled)

### Claim 105

(canceled)

### Claim 106

(canceled)

### Claim 107

(canceled)

### Claim 108

(canceled)

### Claim 109 (depends on 101)

The compound of claim 101, wherein the compound is selected from the group consisting of

### Claim 110 (depends on 82)

The compound of claim 82, wherein Lb is selected from the group consisting of Formula (IIe) and Formula (IIm).

### Claim 111

(canceled)

### Claim 112

(canceled)

### Claim 113

(canceled)

### Claim 114

(canceled)

### Claim 115 (depends on 110)

The compound of claim 110, wherein the compound is selected from the group consisting of

### Claim 116 (depends on 82)

The compound of claim 82, wherein Lb is Formula (IIg).

### Claim 117

(canceled)

### Claim 118

(canceled)

### Claim 119

(canceled)

### Claim 120

(canceled)

### Claim 121 (depends on 116)

The compound of claim 116, wherein the compound is selected from the group consisting of:

### Claim 122 (depends on 82)

The compound of claim 82, wherein Lb is selected from the group consisting of Formula (IIi), Formula (IIk) and Formula (IIl).

### Claim 123

(canceled)

### Claim 124

(canceled)

### Claim 125

(canceled)

### Claim 126

(canceled)

### Claim 127 (depends on 122)

The compound of claim 122, wherein the compound is selected from the group consisting of

### Claim 128

(canceled)

### Claim 129

(canceled)

### Claim 130

(canceled)

### Claim 131

(canceled)

### Claim 132

(canceled)

### Claim 133

(canceled)

### Claim 134

(canceled)

### Claim 135

(canceled)

### Claim 136 (depends on 82)

The compound of claim 82, Ab is an optionally substituted aryl.

### Claim 137

(canceled)

### Claim 138

(canceled)

### Claim 139

(canceled)

### Claim 140 (depends on 82)

The compound of claim 82, wherein Ab is an optionally substituted aryl(C1-2 alkyl).

### Claim 141 (depends on 82)

The compound of claim 82, wherein Ab is an optionally substituted cycloalkyl or an optionally substituted cycloalkenyl.

### Claim 142 (depends on 82)

The compound of claim 82, wherein Ab is an optionally substituted heteroaryl or an optionally substituted heterocyclyl.

### Claim 143 (depends on 82)

The compound of claim 82, wherein Yb is an optionally substituted aryl.

### Claim 144

(canceled)

### Claim 145 (depends on 82)

The compound of claim 82, wherein Yb is an optionally substituted cycloalkyl or an optionally substituted cycloalkenyl.

### Claim 146 (depends on 82)

The compound of claim 82, wherein Yb is an optionally substituted mono-cyclic heteroaryl.

### Claim 147 (depends on 82)

The compound of claim 82, wherein Yb is an optionally substituted bi-cyclic heteroaryl.

### Claim 148 (depends on 82)

The compound of claim 82, wherein Yb is an optionally substituted heterocyclyl.

### Claim 149

(canceled)

### Claim 150 (depends on 82)

A pharmaceutical composition comprising an effective amount of a compound of claim 82, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.

### Claim 151 (depends on 82)

A method of ameliorating or treating a paramyxovirus infection comprising contacting a cell infected with a paramyxovirus in a subject suffering from a paramyxovirus infection with an effective amount of a compound of claim 82, or a pharmaceutically acceptable salt thereof.

### Claim 152 (depends on 82)

A method of inhibiting replication of a paramyxovirus comprising contacting a cell infected with a paramyxovirus with an effective amount of a compound of claim 82, or a pharmaceutically acceptable salt thereof.

### Claim 153

(canceled)

### Claim 154 (depends on 151)

The method of claim 151, wherein the paramyxovirus infection is a human respiratory syncytial virus infection.

### Claim 155 (depends on 151)

The method of claim 151, wherein the paramyxovirus infection is a human respiratory syncytial virus infection; and further comprising contacting the cell with one or more anti-RSV agents.

### Claim 156 (depends on 155)

The method of claim 155, wherein the one or more anti-RSV agents is selected from the group consisting of ribavirin, palivizumab, RSV-IGIV, ALN-RSV01, BMS-433771, RFI-641, RSV604, MDT-637, BTA9881, TMC-353121, MBX-300 and YM-53403.