Antiviral medicaments

US 6,372,883 B1
Filed: 03/10/1999
Issued: 04/16/2002
Est. Priority Date: 03/30/1998
Status: Expired due to Fees

First Claim

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1. A compound having the formula wherein:

E represents —

CHO or —

B(OH)₂;

R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;

R^2ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, aminocarbonyl-lower alkyl and lower cycloalkyl-lower alkyl;

R³represents hydrogen or lower alkyl;

or R^2aand R³together represent di-or trimethylene optionally substituted by hydroxy;

R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;

R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;

R⁶represents hydrogen or lower alkyl;

R^7bis selected from the group consisting of aryl-lower alkylthio-lower alkyl, aryl-lower alkoxy-aryl-lower alkyl, aryl-lower alkoxycarbonyl-lower alkyl, aryl-lower alkylcarbonyl-lower alkyl, nitroguanidino-lower alkyl, arylsulfonyl-guanidino-lower alkyl, lower alkylsulfonyl-lower alkyl, acetamidomethylthio-lower alkyl, aryl and heteroaryl-lower alkyl;

R^8ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl and aryl-lower alkyl; and

R^9bis selected from the group consisting of aryl-lower alkylcarbonyl, heteroaryl-lower alkylcarbonyl, arylaminocarbonyl-lower alkylcarbonyl, heteroarylthio-lower alkylcarbonyl, heteroarylcarbonyl, hydroxyfluorenylcarbonyl, heteroarylcarbonyl-lower alkylcarbonyl, lower alkoxy-lower alkylcarbonyl, aryl-carbonyl-lower alkylcarbonyl, lower alkoxy-lower alkoxy-lower alkoxy-lower alkylcarbonyl, arylcarbonylamino-lower alkylcarbonyl, lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonyl-lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonylamino-lower alkylcarbonyl, heterocyclylcarbonyl, lower alkylcarbonyloxy-lower alkylcarbonyl, lower alkoxycarbonyl-lower alkylcarbonyl, aryloxy-lower alkylcarbonyl, lower alkynylcarbonyl and lower cycloalkylcarbonyl.

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Abstract

The invention is concerned with amino acid derivatives of the formula embedded image

and salts of acidic compounds of formula I with bases, which are viral proteinase inhibitors useful as antiviral agents, especially for the treatment or prophylaxis of infections caused by Hepatitis C, Hepatitis G and human GB viruses.

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15 Claims

1. A compound having the formula wherein:
- E represents —
  
  CHO or —
  
  B(OH)₂;
  
  R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;
  
  R^2ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, aminocarbonyl-lower alkyl and lower cycloalkyl-lower alkyl;
  
  R³represents hydrogen or lower alkyl;
  
  or R^2aand R³together represent di-or trimethylene optionally substituted by hydroxy;
  
  R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;
  
  R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;
  
  R⁶represents hydrogen or lower alkyl;
  
  R^7bis selected from the group consisting of aryl-lower alkylthio-lower alkyl, aryl-lower alkoxy-aryl-lower alkyl, aryl-lower alkoxycarbonyl-lower alkyl, aryl-lower alkylcarbonyl-lower alkyl, nitroguanidino-lower alkyl, arylsulfonyl-guanidino-lower alkyl, lower alkylsulfonyl-lower alkyl, acetamidomethylthio-lower alkyl, aryl and heteroaryl-lower alkyl;
  
  R^8ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl and aryl-lower alkyl; and
  
  R^9bis selected from the group consisting of aryl-lower alkylcarbonyl, heteroaryl-lower alkylcarbonyl, arylaminocarbonyl-lower alkylcarbonyl, heteroarylthio-lower alkylcarbonyl, heteroarylcarbonyl, hydroxyfluorenylcarbonyl, heteroarylcarbonyl-lower alkylcarbonyl, lower alkoxy-lower alkylcarbonyl, aryl-carbonyl-lower alkylcarbonyl, lower alkoxy-lower alkoxy-lower alkoxy-lower alkylcarbonyl, arylcarbonylamino-lower alkylcarbonyl, lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonyl-lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonylamino-lower alkylcarbonyl, heterocyclylcarbonyl, lower alkylcarbonyloxy-lower alkylcarbonyl, lower alkoxycarbonyl-lower alkylcarbonyl, aryloxy-lower alkylcarbonyl, lower alkynylcarbonyl and lower cycloalkylcarbonyl.
- View Dependent Claims (2, 3)
- - 2. A compound of claim 1 wherein R¹is lower alkyl or halo-lower alkyl;
    - R²is lower alkyl;
      
      R³is hydrogen;
      
      R⁴is lower alkyl;
      
      R^5ais aryl-lower alkyl;
      
      R⁶is hydrogen;
      
      R^8ais carboxy-lower alkyl, hydroxy-lower alkyl or aryl-lower alkyl; and
      
      R^9bis heteroarylcarbonyl, hydroxyfluorenylcarbonyl, heterocyclylcarbonyl, heteroarylcarbonyl-lower alkylcarbonyl, heteroaryl-lower alkylcarbonyl or aryl-lower alkylcarbonyl.
  - 3. A compound of claim 2 which is 2(RS)-[[N-[N-[N-[N-[N-[(9-hydroxy-9-fluorenyl)carbonyl-L-seryl]-O-benzyl-D-seryl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde.

4. A compound of the formula whereinE is —
- CHO or —
  
  B(OH)₂;
  
  R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;
  
  R^2ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, aminocarbonyl-lower alkyl and lower cycloalkyl-lower alkyl;
  
  R³is hydrogen or lower alkyl;
  
  or taken together with R^2aform di-or trimethylene optionally substituted by hydroxy;
  
  R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;
  
  R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;
  
  R⁶is hydrogen or lower alkyl;
  
  R^7bis selected from the group consisting of aryl-lower alkylthio-lower alkyl, aryl-lower alkoxy-aryl-lower alkyl, aryl-lower alkoxycarbonyl-lower alkyl, aryl-lower alkylcarbonyl-lower alkyl, nitroguanidino-lower alkyl, arylsulfonyl-guanidino-lower alkyl, lower alkylsulfonyl-lower alkyl, acetamidomethylthio-lower alkyl, aryl and heteroaryl-lower alkyl;
  
  R^8ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl and aryl-lower alkyl; and
  
  R^9ais selected from the group consisting of lower alkylcarbonyl, carboxy-lower alkyl-carbonyl, arylcarbonyl, lower alkylsulfonyl, arylsulfonyl, lower alkoxycarbonyl and aryl-lower alkoxycarbonyl;
  
  or basic salts of acidic compounds thereof.
- View Dependent Claims (5)
- - 5. The compound of claim 4 wherein said compound is selected from the group consisting of:

6. A compound having the formula whereinE is —
- CHO or —
  
  B(OH)₂;
  
  R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;
  
  R^2ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, aminocarbonyl-lower alkyl and lower cycloalkyl-lower alkyl;
  
  R³is hydrogen or lower alkyl;
  
  or taken together with R^2ato form di- or trimethylene optionally substituted by hydroxy;
  
  R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;
  
  R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;
  
  R⁶is hydrogen or lower alkyl;
  
  R^7bis selected from the group consisting of aryl-lower alkylthio-lower alkyl, aryl-lower alkoxy-aryl-lower alkyl, aryl-lower alkoxycarbonyl-lower alkyl, aryl-lower alkylcarbonyl-lower alkyl, nitroguanidino-lower alkyl, arylsulfonyl-guanidino-lower alkyl, lower alkylsulfonyl-lower alkyl, acetamidomethylthio-lower alkyl, aryl and heteroaryl-lower alkyl;
  
  R^8bis selected from the group consisting of mercapto-lower alkyl, lower alkylsulfonyl-lower alkyl, aryl-lower alkoxy-lower alkyl and aryl-heteroaryl-lower alkyl;
  
  R^9ais selected from the group consisting of lower alkylcarbonyl, carboxy-lower alkyl-carbonyl, arylcarbonyl, lower alkylsulfonyl, arylsulfonyl, lower alkoxycarbonyl and aryl-lower alkoxycarbonyl;
  
  or basic salts of acidic compounds thereof.
- View Dependent Claims (7)
- - 7. The compound of claim 6, wherein said compound is selected from the group consisting of:

8. A compound having the formula whereinE is —
- CHO or —
  
  B(OH)₂;
  
  R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;
  
  R^2ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, aminocarbonyl-lower alkyl and lower cycloalkyl-lower alkyl;
  
  R³is hydrogen or lower alkyl;
  
  or taken together with R^2aform di- or trimethylene optionally substituted by hydroxy;
  
  R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;
  
  R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;
  
  R⁶is hydrogen or lower alkyl;
  
  R^7bis selected from the group consisting of aryl-lower alkylthio-lower alkyl, aryl-lower alkoxy-aryl-lower alkyl, aryl-lower alkoxycarbonyl-lower alkyl, aryl-lower alkylcarbonyl-lower alkyl, nitroguanidino-lower alkyl, arylsulfonyl-guanidino-lower alkyl, lower alkylsulfonyl-lower alkyl, acetamidomethylthio-lower alkyl, aryl and heteroaryl-lower alkyl;
  
  R^8ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl and aryl-lower alkyl; and
  
  R^9bis selected from the group consisting of aryl-lower alkylcarbonyl, heteroaryl-lower alkylcarbonyl, arylaminocarbonyl-lower alkylcarbonyl, heteroarylthio-lower alkylcarbonyl, heteroarylcarbonyl, hydroxyfluorenylcarbonyl, heteroarylcarbonyl-lower alkylcarbonyl, lower alkoxy-lower alkylcarbonyl, aryl-carbonyl-lower alkylcarbonyl, lower alkoxy-lower alkoxy-lower alkoxy-lower alkylcarbonyl, arylcarbonylamino-lower alkylcarbonyl, lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonyl-lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonylamino-lower alkylcarbonyl, heterocyclylcarbonyl, lower alkylcarbonyloxy-lower alkylcarbonyl, lower alkoxycarbonyl-lower alkylcarbonyl, aryloxy-lower alkylcarbonyl, lower alkynylcarbonyl and lower cycloalkylcarbonyl;
  
  or basic salts of acidic compounds thereof.
- View Dependent Claims (9)
- - 9. The compound of claim 8, wherein said compound is selected from the group consisting of:

10. A compound of the formula whereinE is —
- CHO or —
  
  B(OH)₂;
  
  R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;
  
  R²is R^2aor R^2b;
  
  R^2ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, aminocarbonyl-lower alkyl and lower cycloalkyl-lower alkyl;
  
  R^2bis aryl-lower alkoxy-aryl-lower alkyl or heteroaryl-lower alkyl;
  
  R³is hydrogen or lower alkyl;
  
  or taken together with R²form di- or trimethylene optionally substituted by hydroxy;
  
  R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;
  
  R⁵is R^5aor R^5b;
  
  R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;
  
  R^5bis lower cycloalkyl-lower alkyl;
  
  R⁶is hydrogen or lower alkyl;
  
  R⁷is selected from the group consisting of nitroguanidino-lower alkyl, lower alkylsulfonyl-lower alkyl and acetamidomethylthio-lower alkyl;
  
  R^8ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl and aryl-lower alkyl;
  
  R^8bis selected from the group consisting of mercapto-lower alkyl, lower alkylsulfonyl-lower alkyl, aryl-lower alkoxy-lower alkyl and aryl-heteroaryl-lower alkyl;
  
  R⁹is R^9aor R^9b;
  
  R^9ais selected from the group consisting of lower alkylcarbonyl, carboxy-lower alkyl-carbonyl, arylcarbonyl, lower alkylsulfonyl, arylsulfonyl, lower alkoxycarbonyl and aryl-lower alkoxycarbonyl;
  
  R^9bis selected from the group consisting of aryl-lower alkylcarbonyl, heteroaryl-lower alkylcarbonyl, arylaminocarbonyl-lower alkylcarbonyl, heteroarylthio-lower alkylcarbonyl, heteroarylcarbonyl, hydroxyfluorenylcarbonyl, heteroarylcarbonyl-lower alkylcarbonyl, lower alkoxy-lower alkylcarbonyl, aryl-carbonyl-lower alkylcarbonyl, lower alkoxy-lower alkoxy-lower alkoxy-lower alkylcarbonyl, arylcarbonylamino-lower alkylcarbonyl, lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonyl-lower cycloalkyl-lower alkylcarbonyl, lower alkylcarbonylamino-lower alkylcarbonyl, heterocyclylcarbonyl, lower alkylcarbonyloxy-lower alkylcarbonyl, lower alkoxycarbonyl-lower alkylcarbonyl, aryloxy-lower alkylcarbonyl, lower alkynylcarbonyl and lower cycloalkylcarbonyl;
  
  or basic salts of acidic compounds thereof.

11. A compound of the formula whereinE is —
- CHO or —
  
  B(OH)₂;
  
  R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;
  
  R^2bis aryl-lower alkoxy-aryl-lower alkyl or heteroaryl-lower alkyl;
  
  R³is hydrogen or lower alkyl;
  
  or taken together with R^2bform di- or trimethylene optionally substituted by hydroxy;
  
  R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;
  
  R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;
  
  R⁶is hydrogen or lower alkyl;
  
  R^7ais carboxy-lower alkyl;
  
  R^8ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl and aryl-lower alkyl;
  
  R^9ais selected from the group consisting of lower alkylcarbonyl, carboxy-lower alkyl-carbonyl, arylcarbonyl, lower alkylsulfonyl, arylsulfonyl, lower alkoxycarbonyl and aryl-lower alkoxycarbonyl;
  
  or basic salts of acidic compounds thereof.
- View Dependent Claims (12)
- - 12. The compound of claim 11, wherein said compound is selected from the group consisting of:

13. A compound having the formula whereinE is —
- CHO or —
  
  B(OH)₂;
  
  R¹is selected from the group consisting of lower alkyl, halo-lower alkyl, cyano-lower alkyl, lower-alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, aryl-lower alkyl, heteroaryl-lower alkyl, lower alkenyl and lower alkynyl;
  
  R^2ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, aminocarbonyl-lower alkyl and lower cycloalkyl-lower alkyl;
  
  R³is hydrogen or lower alkyl;
  
  or taken together with R^2aform di- or trimethylene optionally substituted by hydroxy;
  
  R⁴is selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower cyclo-alkyl-lower alkyl, carboxy-lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl, aryl-lower alkylthio-lower alkyl, lower alkenyl, aryl and lower cycloalkyl;
  
  R^5ais selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, aryl-lower alkyl, aryl-lower alkylthio-lower alkyl, cyano-lower alkylthio-lower alkyl and lower cycloalkyl;
  
  R⁶is hydrogen or lower alkyl;
  
  R^7ais selected from the group consisting of isopropyl and cyclohexyl;
  
  R^8bis selected from the group consisting of mercapto-lower alkyl, lower alkylsulfonyl-lower alkyl, aryl-lower alkoxy-lower alkyl and aryl-heteroaryl-lower alkyl;
  
  R^9ais selected from the group consisting of lower alkylcarbonyl, carboxy-lower alkyl-carbonyl, arylcarbonyl, lower alkylsulfonyl, arylsulfonyl, lower alkoxycarbonyl and aryl-lower alkoxycarbonyl;
  
  or basic salts of acidic compounds thereof.
- View Dependent Claims (14)
- - 14. The compound of claim 13, wherein said compound is selected from the group consisting of:

15. The compound selected from the group consisting of:
- 2(RS)-[[N-[N-[N-[N-[N-[4-(4-Methylphenyl)butyryl]-L-α
  
  -aspartyl]-L-(α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-[3-(4-methylbenzoyl)propionyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[-[N-[N-[N-[N-[2-[2-(2-methoxyethoxy)ethoxyacetyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[2-(4-oxo-2-thioxo-3-thiazolidinyl)acetyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-[3-(2-methyl-4-nitro-1-imidazolyl)propionyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-(5-hexynoyl)-L-α
  
  -aspartyl]-L-(α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[-[N-[-N-[N-(6-quinolyl)carbonyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[-N-[N-[-[N -[N-(6-oxo-3-pyranyl)carbonyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-[2-(1,3-benzodioxol-5-yl)acetyl]-L-α
  
  -aspartyl]-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[-N[N-[(5,6-dihydro-6,6-dimethyl-4-oxo-4H-pyran-2-yl)carbonyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-[2-(2-naphthyl)acetyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-(3-benzamidopropionyl)-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-[(1,2,3,4-tetrahydro-2,4-dioxo-5-pyrimidinyl)carbonyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-(3-methyl-2-thenoyl)-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-(2-cyclohexylacetyl)-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  2(RS)-[[N-[N-[N-[N-[N-[2(RS)-(4-nitrophenyl)propionyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-4,4,4-trifluorobutyraldehyde;
  
  1(RS)-[[N-[N-[N-[N-[N-[(6-oxo-6H-pyran-3-yl)carbonyl]-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]propylboronic acid;
  
  1(RS)-[[N-[N-[N-[N-[N-(4-acetamidobutyryl)-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]propylboronic acid; and
  
  1(RS)-[[N-[N-[N-[N-[N-(2-acetoxyacetyl)-L-α
  
  -aspartyl]-L-α
  
  -glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]propylboronic acid.

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Current Assignee
Hoffmann-La Roche Incorporated (Roche Holding AG)
Original Assignee
Hoffmann-La Roche Incorporated (Roche Holding AG)
Inventors
Wilson, Francis Xavier, Raynham, Tony Michael, Attwood, Michael Richard, Jones, Philip Stephen, Hurst, David Nigel, Kay, Paul Brittain
Primary Examiner(s)
CELSA, BENNETT M

Application Number

US09/265,617
Time in Patent Office

1,133 Days
Field of Search

514/2, 514/17, 514/18, 530/329, 530/330, 424/189.1
US Class Current

530/329
CPC Class Codes

A61K 38/00   Medicinal preparations cont...

A61P 31/00   Antiinfectives, i.e. antibi...

A61P 31/12   Antivirals

A61P 31/14   for RNA viruses

C07K 7/06   having 5 to 11 amino acids

Y02P 20/55   Design of synthesis routes,...

Antiviral medicaments

First Claim

3 Assignments

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Accused Products

Abstract

69 Citations

15 Claims

Specification

Solutions

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Antiviral medicaments

First Claim

3 Assignments

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

69 Citations

15 Claims

Specification

Subscription Required

Solutions

Use Cases

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