# US 8,785,434 B2 · Antiviral compounds

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- Number: US 8,785,434 B2
- Document ID: US8785434B2
- Status: Granted
- Kind: B2
- Application number: 13/099,006
- Filed: 2011-05-02
- Published: 2012-06-21
- Granted: 2014-07-22
- Earliest claimed: 2010-04-30
- Assignees: Prosetta Antiviral Inc.
- Applicants: Clarence R. Hurt; Vishwanath Lingappa; Beverly Freeman; Andy Atuegbu; Anatoliy Kitaygorodskyy
- Inventors: Clarence R. Hurt; Vishwanath Lingappa; Beverly Freeman; Andy Atuegbu; Anatoliy Kitaygorodskyy
- Web page: https://patentgrep.com/patent/US8785434B2

## CPC

- A61K 31/5415: ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/16: for influenza or rhinoviruses
- A61P 31/18: for HIV
- A61P 31/22: for herpes viruses
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Compounds and methods for preventing and treating viral infections are provided. In some embodiments, novel compounds broad-spectrum antiviral activity are provided. In more specific embodiments, the compounds and methods are effective against viruses such as Venezuelan Equine Encephalitis, West Nile Virus, and respiratory viruses including the common cold.

## Claims

### Claim 1

A compound having the structure:
and its pharmaceutically acceptable salts, hydrates, and coordination compounds, wherein:
R6 is halo or optionally substituted alkyl,
R1-R5 and R7a-R9b are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, thio, amino, carboxyl, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsuonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralkyloxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl;
R10 is hydrogen or optionally substituted alkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsufonyl, cycloalkylsulfonyl, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralkyloxycarbonyloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, and (cycloheteroalkyl)alkyloxycarbonyl;
X1 is (CR11R11′)m, wherein m is either 1 or 2 such that each of R11 and R11′, independently for each value of m, is selected independently from the group consisting of: hydrogen, halo, cyano, nitro, thio, amino, carboxyl, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl
Y is optionally present; and
when Y is present, Y is NR12, O, S, SO, or SO2, or a single or double bond between X2 and X3;
R12 is hydrogen or optionally substituted alkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsufonyl, cycloalkylsulfonyl, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralkyloxycarbonyloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, and (cycloheteroalkyl)alkyloxycarbonyl; and
X2 and X3 are (CR13R13′)n and (CR14R14′)o respectively, wherein each of n and o is independently either 1, 2, or 3 such that the sum n+o is either 3, 4, or 5, and independently for each value of the n and o methylene units of X2 and X3, each of R13, R13′, R14, and R14′ is selected independently from the group consisting of:
hydrogen, halo, cyano, nitro, thio, amino, carboxy, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl; and
when Y is not present X2 is R15 and X3 is R16, wherein
R15 and R16 are selected independently from the group consisting of: hydrogen and optionally substituted alkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsufonyl, cycloalkylsulfonyl, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheter-alkyloxycarbonyl, aralkyloxycarbonyloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, and (cycloheteroalkyl)alkyloxycarbonyl
wherein when said optionally substituted alkyl is substituted, said substitution is with a group which is hydrooxyl, nitro, amino, imino, cyano, halo, thio, thioamido, amidino, oxo, oxamidino, methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, lower alkyl, haloloweralkyl, loweralkoxy, haloloweralkoxy, lower alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, alkylthio, aminoalkyl, or cyanoalkyl.

### Claim 2 (depends on 1)

A compound of claim 1, wherein m is 1, such that X1 is (CR11′), thereby defining X1 as (CR11aR11b), said compound having the structure:
wherein R11a and R11b are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, thio, amino, carboxy, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl.

### Claim 3 (depends on 2)

A compound of claim 2, wherein Y is not present, said compound having the structure:

### Claim 4 (depends on 3)

A compound of claim 3, wherein each of R15 and R16 is hydrogen.

### Claim 5 (depends on 4)

A compound of claim 4, wherein each of R2-R5, R7a-R9b, R11a, and R11b is hydrogen, each of R1 and R6 independently is optionally substituted alkyl, and R10 is optionally substituted alkyl or alkylsulfonyl.

### Claim 6 (depends on 3)

A compound of claim 3, wherein each of R15 and R16 independently is alkyl or alkyloxyalkyl.

### Claim 7 (depends on 6)

A compound of claim 6, wherein each of R15 and R16 independently is alkyl.

### Claim 8 (depends on 7)

A compound of claim 7, wherein each of R15 and R16 independently is methyl or ethyl.

### Claim 9 (depends on 8)

A compound of claim 8, wherein each of R2-R5, R7a-R9b, R11a, and R11b is hydrogen, and R10 is hydrogen, or optionally substituted alkyl, alkyloxycarbonyl, alkylsulfonyl, cycloalkylsulfonyl, and alkylaminosulfonyl.

### Claim 10 (depends on 2)

A compound of claim 2, wherein Y is present, said compound having the structure:

### Claim 11 (depends on 10)

A compound of claim 10, wherein each of n and o is 2, such that X2 and X3 have the form (CR13R13′)2 and (CR14R14b)2 respectively defining thereby X2 as (CR13aR13b)(CR13cR13d) and X3 as (CR14aR14b) (CR14cR14d), said compound having the structure:
wherein R13a-R14d are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, thio, amino, carboxy, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl.

### Claim 12 (depends on 11)

A compound of claim 11, wherein each of R2-R5, R7a-R9b, R11a, R11b, and R13a-R14d is hydrogen.

### Claim 13 (depends on 12)

A compound of claim 12, wherein Y is NR12 or O.

### Claim 14 (depends on 13)

A compound of claim 13, wherein Y is NR12, and R10 and R12 are selected independently from the group consisting of: hydrogen, or optionally substituted alkyl, alkyloxycarbonyl, alkylsulfonyl, cycloalkylsulfonyl, and alkylaminosulfonyl.

### Claim 15 (depends on 13)

A compound of claim 13, wherein Y is O.

### Claim 16 (depends on 1)

A compound of claim 1, wherein m is 2, such that X1 is (CR11R11′)2, thereby defining X1 as (CR11aR11b)(CR11cR11d), said compound having the structure:
wherein R11a-R11d are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, thio, amino, carboxy, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl.

### Claim 17 (depends on 16)

A compound of claim 16, wherein Y is not present, said compound having the structure:
wherein R11a-R11d selected independently from the group consisting of: hydrogen, halo, cyano, nitro, thio, amino, carboxy, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl.

### Claim 18 (depends on 16)

A compound of claim 16, wherein Y is present, said compound having the structure:
wherein R11a-R11d are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, thio, amino, carboxy, formyl, and optionally substituted alkyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkylcarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, cycloheteroalkylcarbonyl, aralkylcarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, dialkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, aralkylcarbonylthiooxy, carbonylthio, heteroaralkylcarbonylthio, (cycloalkyloxy)carbonylthio, (cycloheteroalkyl)alkylcarbonylthio, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoalkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl.

### Claim 19 (depends on 1)

A method for treating a viral disease in a mammal afflicted with such disease, comprising administering to such mammal a therapeutically effective amount of the compound of claim 1 wherein said viral disease is influenza, Adenovirus, Human Corona Virus, Herpes Simplex Virus, Rhinovirus, Respiratory Syntactical Virus, Hepatitis C Virus, Human Immunodeficiency Virus, Monkey Pox Virus, Rabies Virus, Dengue Virus, Easter Equine Encephalitis Virus, Venezuelan Equine Encephalitis Virus, Wester Equine Encephalitis Virus, West Nile Virus, Chikungunya Virus, Ebola Virus, or Marburg Virus.

### Claim 20 (depends on 19)

The method of claim 19, wherein said viral disease is an etiological component of a respiratory syndrome selected from the group consisting of: bronchiolitis, the common cold, croup, influenza, and pneumonia.

### Claim 21 (depends on 1)

A compound of claim 1, which is 3-(diethylamino)-1-ethyl-7-(piperazin-1-yl)phenothiazin-5-ium.

### Claim 22 (depends on 1)

A compound of claim 1, which is 3-(1,4-diazepan-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium.

### Claim 23 (depends on 1)

A compound of claim 1, which is 3-(4-(cyclopropylsulfonyl)piperazin-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium.

### Claim 24 (depends on 1)

A compound of claim 1, which is 3,7-di(4-methylpiperazin-1-yl)-1-t-butylphenothiazin-5-ium.

### Claim 25 (depends on 1)

A compound of claim 1, which is 1,9-dichloro-3-(piperazin-1-yl)-7-(pyrrolidin-1-yl)phenothiazin-5-ium.

### Claim 26 (depends on 1)

A compound of claim 1, which is 3,7-(di(4-methylpiperazin-1-yl))-1-ethyl-9-methylphenothiazin-5-ium.

### Claim 27 (depends on 1)

A compound of claim 1, which is 3,7-di(1,4-diazepan-1-yl)-1-ethyl-9-methylphenothiazin-5-ium.

### Claim 28 (depends on 1)

A compound of claim 1, which is 3-(dimethylamino)-1-ethyl-9-methyl-7-(4-(trifluoromethylsulfonyl)piperazin-1-yl)phenothiazin-5-ium.

### Claim 29 (depends on 1)

A compound of claim 1, which is 3,7-di(1,4-diazepan-1-yl)-1-trifluoromethylphenothiazin-5-ium.

### Claim 30 (depends on 1)

A compound of claim 1, which is a member selected from 3-amino-7-(4-isopropylpiperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 3-amino-1,9-dimethyl-7-(4-(methylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, 3-amino-1,9-dimethyl-7-(4-(trifluoromethylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, and 3-amino-7-(4-(isopropylsulfonyl)piperazin-1-yl)-1,9-dimethylphenothiazin-5-ium.

### Claim 31 (depends on 1)

A compound of claim 1, which is a member selected from 7-(4-(tert-butoxycarbonyl)piperazin-1-yl)-1-chloro-3-(diethylamino)phenothiazin-5-ium, 1-chloro-3-(diethylamino)-7-(piperazin-1-yl)phenothiazin-5-ium, 7-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(diethylamino)-1-ethylphenothiazin-5-ium, 3-(diethylamino)-1-ethyl-7-(piperazin-1-yl)phenothiazin-5-ium, 3-(bis(2-methoxyethyl)amino)-7-(4-(tertbutoxycarbonyl)piperazin-1-yl)-1-ethylphenothiazin-5-ium, and 3-(bis(2-methoxyethyl)amino)-1,9-dichloro-7-(piperazin-1-yl)phenothiazin-5-ium.

### Claim 32 (depends on 1)

A compound of claim 1, which is a member selected from 1,9-dichloro-3,7-di(piperazin-1-yl)phenothiazin-5-ium, 1-trifluoromethyl-3,7-di(4-methylpiperazin-1-yl)phenothiazin-5-ium, 3,7-(di(4-Boc-piperazin-1-yl))-1-trifluoromethylphenothiazin-5-ium, 3,7-dipiperazinyl-1-trifluoromethylphenothiazin-5-ium, 3,7-di(4-methylpiperazin-1-yl)-1-n-butylphenothiazin-5-ium, 3,7-di(4-methylpiperazin-1-yl)-1-methylphenothiazin-5-ium, 1-(tert-butyl)-3,7-bis(4-methylpiperazin-1-yl)phenothiazin-5-ium, and 3,7-di(4-methylpiperazin-1-yl)-1-isopropylphenothiazin-5-ium.

### Claim 33 (depends on 1)

A compound of claim 1, which is a member selected from 3-(dimethylamino)-1,9-dimethyl-7-(4-methylpiperazin-1-yl)phenothiazin-5-ium, 3-(4-(tert-butoxycarbonyl)piperazin-1-yl)-7-(dimethylamino)-1,9-dimethylphenothiazin-5-ium, 3-(dimethylamino)-1,9-dimethyl-7-(piperazin-1-yl)phenothiazin-5-ium, 3,7-bis(4-(tert-butoxycarbonyl)piperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 3-(butyl(methyl)amino)-7-(4-(2-methoxyethyl)piperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 3-(4-(cyclopropylsulfonyl)piperazin-1-yl)-7-(dimethylamino)-1,9-dimethylphenothiazin-5-ium, 3-(dimethylamino)-7-(4-(isopropylsulfonyl)piperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 3-(dimethylamino)-1,9-dimethyl-7-(4-(2,2,2-trifluoroethylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, 4-carboxy-3-(dimethylamino)-1,9-dimethyl-7-(4-methylpiperazin-1-yl)phenothiazin-5-ium, 4-carboxy-7-(dimethylamino)-1,9-dimethyl-3-(4-methylpiperazin-1-yl)phenothiazin-5-ium, 3-(4-(cyclopropylsulfonyl)piperazin-1-yl)-7-(dimethylamino)-1-isopropyl-9-methylphenothiazin-5-ium, 3-(diethylamino)-1,9-dimethyl-7-(4-(methylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, 3-(diethylamino)-1,9-dimethyl-7-(piperazin-1-yl)phenothiazin-5-ium, 3-(diethylamino)-7-(4-isopropylpiperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 3-(diethylamino)-7-(4-isopropylpiperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 1,9-diethyl-3-dimethylamino-7-[4-isopropylpiperazinyl]-phenothiazinium, 3-(butyl(methyl)amino)-1,9-dimethyl-7-(4-methylpiperazin-1-yl)phenothiazin-5-ium, 3-(dimethylamino)-1,9-diethyl-7-((4-trifluoromethylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, 3-(4-(cyclopentylsulfonyl)piperazin-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, 3-(dimethylamino)-9-ethyl-1-isopropyl-7-(4-isopropylpiperazin-1-yl)phenothiazin-5-ium, 3-(butyl(methyl)amino)-7-((4-cyclopropylsulfonyl)piperazin-1-yl)-1,9-diethylphenothiazin-5-ium, 3-(4-cyclopentylpiperazin-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, 3-(dimethylamino)-1,9-diethyl-7-(4-(2-methoxyethyl)piperazin-1-yl)phenothiazin-5-ium, 3-(4-(cyclopropylsulfonyl)piperazin-1-yl)-7-(dimethylamino)-1-ethyl-9-isopropylphenothiazin-5-ium, 3-(dimethylamino)-9-ethyl-1-isopropyl-7-((4-trifluoromethylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, 3-(dimethylamino)-7-(4-(N,N-dimethylsulfamoyl)piperazin-1-yl)-1,9-diethylphenothiazin-5-ium, 3-(4-(cyclopropylsulfonyl)piperazin-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, 3-((4-tert-butylcarbamoyl)piperazin-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, 3-(4-butylpiperazin-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, 3-(4-acetylpiperazin-1-yl)-7-(methyl(n-butyl)amino)-1,9-dimethylphenothiazin-5-ium, 3-(4-boc-piperazin-1-yl)-7-(methyl(n-butyl)amino)-1,9-dimethylphenothiazin-5-ium, 3-(piperazin-1-yl)-7-(methyl(n-butyl)amino)-1,9-dimethylphenothiazin-5-ium, 3-(dimethylamino)-1-ethyl-9-methyl-7-(4-methylpiperazin-1-yl)-phenothiazin-5-ium, 3-(dimethylamino)-1-ethyl-9-methyl-7-(4-(trifluoromethylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, 3-(4-(cyclopropylsulfonyl)piperazin-1-yl)-7-(dimethylamino)-9-ethyl-1-methyl-phenothiazin-5-ium, and 3-(bis(2-methoxyethyl)amino)-1-ethyl-9-methyl-7-(4-methylpiperazin-1-yl)phenothiazin-5-ium.

### Claim 34 (depends on 1)

A compound of claim 1, which is a member selected from 1,9-dimethyl-3,7-bis(4-methylpiperazin-1-yl)phenothiazin-5-ium, 3,7-bis(4-(tert-butoxycarbonyl)piperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 3,7-bis[4-(2-methoxyethyl)piperazin-1-yl]-1,9-dimethyl-phenothiazin-5-ium, 1,9-dimethyl-3,7-bis(4-sulfamoylpiperazin-1-yl)phenothiazin-5-ium, 3,7-bis(4-isopropylpiperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 3, 7 bis(4(cyclopropanecarbonyl)piperazin-1-yl)-1,9-diethylphenothiazin-5-ium, 3,7-bis(4-(cyclopropylsulfonyl)piperazin-1-yl)-1,9-diethyl-phenothiazin-5-ium, 3,7-di(4-acetylpiperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, and 3,7-(di(4-methylpiperazin-1-yl))-1-ethyl-9-methylphenothiazin-5-ium.

### Claim 35 (depends on 1)

A compound of claim 1, which is a member selected from 1,9-dimethyl-3-morpholino-7-(4-sulfamoylpiperazin-1-yl)phenothiazin-5-ium, 3-((2R,6S)-2,6-dimethylmorpholino)-1,9-dimethyl-7-(4-sulfamoylpiperazin-1-yl)phenothiazin-5-ium, 3-((2R,6R)-2,6-dimethylmorpholino)-1,9-dimethyl-7-(4-sulfamoylpiperazin-1-yl)phenothiazin-5-ium, 1,9-diethyl-3-morpholino-7-(4-sulfamoylpiperazin-1-yl)phenothiazin-5-ium, 3-(4-(tert-butoxycarbonyl)-3-(methoxycarbonyl)-piperazin-1-yl)-1,9-diethyl-7-morpholinophenothiazin-5-ium, 3-(4-boc-piperazin-1-yl)-1-ethyl-9-methyl-7-morpholino-phenothiazin-5-ium, and 1-ethyl-9-methyl-7-morpholino-3-(piperazin-1-yl)-phenothiazin-5-ium.

### Claim 36 (depends on 1)

A compound of claim 1, which is a member selected from 3-(azetidin-1-yl)-7-(4-(isopropylsulfonyl)piperazin-1-yl)-1,9-dimethylphenothiazin-5-ium, 1,9-dimethyl-3-(pyrrolidin-1-yl)-7-(4-(2,2,2-trifluoroethylsulfonyl)piperazin-1-yl)phenothiazin-5-ium, and 3-(4-(cyclopropylsulfonyl)piperazin-1-yl)-9-ethyl-1-methyl-7-(pyrrolidin-1-yl)-phenothiazin-5-ium.

### Claim 37 (depends on 1)

A compound of claim 1, which is a member selected from 3-(4-(cyclopropylsulfonyl)-1,4-diazepan-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, 3-(dimethylamino)-1,9-diethyl-7-((methylsulfonyl)-1,4-diazepan-1-yl)phenothiazin-5-ium, 3-(dimethylamino)-1,9-diethyl-7-(4-(ethylsulfonyl)-1,4-diazepan-1-yl)phenothiazin-5-ium, 3-(4-(tert-butylcarbamoyl)-1,4-′diazepan-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, 3-(dimethylamino)-1,9-diethyl-7-(4-sulfamoyl-1,4-diazepan-1-yl)phenothiazin-5-ium, 3-(dimethylamino)-1,9-diethyl-7-(4-(isopropylsulfonyl)-1,4-diazepan-1-yl)phenothiazin-5-ium, 3-(dimethylamino)-1,9-diethyl-7-(4-(methylbut-2-enyl)-1,4-diazepan-1-yl)phenothiazin-5-ium, 3-(4-(tert-butoxycarbonyl)-1,4-diazepan-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium, and 3-(1,4-diazepan-1-yl)-7-(dimethylamino)-1,9-diethylphenothiazin-5-ium.

### Claim 38 (depends on 1)

A compound of claim 1, which is a member selected from 3,7-di(1,4-diazepan-1-yl)-1,9-dimethylphenothiazin-5-ium, 3-(1,4-diazepan-1-yl)-1,9-diethyl-7-(4-ureidopiperidin-1-yl)phenothiazin-5-ium, 3,7-di(1,4-diazepan-1-yl)-1,9-diethylphenothiazin-5-ium, 3-(4-(tert-butoxycarbonyl)-1,4-diazepan-1-yl)-1,9-diethyl-7-(2-methylpyrrolidin-1-yl)phenothiazin-5-ium, 3-(1,4-diazepan-1-yl)-1,9-diethyl-7-(2-methylpyrrolidin-1-yl)phenothiazin-5-ium, 3,7-bis(4-(tert-butoxycarbonyl)-1,4-diazepan-1-yl)-1,9-diethylphenothiazin-5-ium, 1-ethyl-9-methyl-7-((4-m ethylsulfonyl)-1,4-diazepan-1-yl)-3-(pyrrolidin-1-yl)-phenothiazin-5-ium, 3,7-bis(4-boc-1,4-diazepan-1-yl)-1-ethyl-9-methyl-phenothiazin-5-ium, 3-(4-boc-1,4-diazepan-1-yl)-1-ethyl-9-methyl-7-(pyrrolidin-1-yl)-phenothiazin-5-ium, 3,7-di(1,4-diazepan-1-yl)-1-ethyl-9-methyl-phenothiazin-5-ium, and 3-(1,4-diazepan-1-yl)-1-ethyl-9-methyl-7-(pyrrolidin-1-yl)-phenothiazin-5-ium.

### Claim 39 (depends on 19)

The method of claim 19, wherein said viral disease is influenza.

### Claim 40 (depends on 19)

The method of claim 19, wherein said viral disease is Human Immunodeficiency Virus.

### Claim 41 (depends on 1)

A compound of claim 1, which is 7-(4-methylpiperazin-1-yl)-3-(pyrrolidin-1-yl)-1-(trifluoromethyl)phenothiazin-5-ium.