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US5340828A Expired / Lapsed US ⏱️ 0.0 years remaining

Inhibitors of farnesyl protein transferase

Assignee: Merck and Co Inc
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Filing: 1991-09-30
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Granted: 1994-08-23
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Expires: 2011-09-30
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Abstract

Abstract The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Inventors

  • 👤 Samuel L. Graham
  • 👤 S. Jane deSolms

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-08 13:01
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06008; C07K5/06017; C07K5/06034; A; A61; A61P; A61P35/00; C07K5/08; C07K5/0802; C07K5/0804; C07K5/0808; A61K; A61K38/00

Claims Analysis

Total Claims: 10
Claim 1
Independent Claim 150 words
A compound which inhibits farnesyl-protein transferase of the formula: ##STR9## wherein: X or Y are independently H 2 or O, provided that at least one of these is H 2 ; R 1 is H, an alkyl group, an acyl group, an alkylsulfonyl group or arylsulfonyl group, wherein alkyl and acyl groups comprise straight chain or branched chain hydrocarbons of 1 to 6 carbon atoms, or in the alternative R 1 NH may be absent; R 2 and R 3 are the side chains of naturally occurring amino acids, or in the alternative may be substituted or unsubstituted aliphatic, aromatic or heterocyclic groups, which comprise allyl, cyclohexyl, phenyl, pyridyl, imidazolyl or saturated chains of 2 to 8 carbon atoms, wherein the aliphatic substitutents may be substituted with an aromatic or heteroaromatic ring; Z is O or S; and n is 0, 1, or 2; or the pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim 150 words
A compound which inhibits farnesyl-protein transferase of the formula: ##STR9## wherein: X or Y are independently H 2 or O, provided that at least one of these is H 2 ; R 1 is H, an alkyl group, an acyl group, an alkylsulfonyl group or arylsulfonyl group, wherein alkyl and acyl groups comprise straight chain or branched chain hydrocarbons of 1 to 6 carbon atoms, or in the alternative R 1 NH may be absent; R 2 and R 3 are the side chains of naturally occurring amino acids, or in the alternative may be substituted or unsubstituted aliphatic, aromatic or heterocyclic groups, which comprise allyl, cyclohexyl, phenyl, pyridyl, imidazolyl or saturated chains of 2 to 8 carbon atoms, wherein the aliphatic substitutents may be substituted with an aromatic or heteroaromatic ring; Z is O or S; and n is 0, 1, or 2; or the pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim 23 words
A compound which inhibits farnesyl-protein transferase which is: N-(2(R)-amino-3-mercaptopropyl)isoleucyl-phenylalanylhomoserine, N-(2(R)-amino-3-mercaptopropyl)isoleucyl-isoleucyl-homoserine, N-[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)-methyl pentyl]isoleucyl-homoserine, N-[N'-(2(R)-amino-3-mercaptopropyl)isoleucyl-phenyl-alanyl]-3(S)-amino-4-hydroxypentanoic acid, or N-[N'-(2(R)-amino-3-mercaptopropyl)isoleucyl-isoleucyl]-3(S)-amino-4-hydroxypentanoic acid, or the pharmaceutically acceptable salts thereof.
Claim 4
Dependent Claim 23 words
A compound which inhibits farnesyl-protein transferase which is: N-(2(R)-amino-3-mercaptopropyl)isoleucyl-phenylalanylhomoserine, N-(2(R)-amino-3-mercaptopropyl)isoleucyl-isoleucyl-homoserine, N-[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)-methyl pentyl]isoleucyl-homoserine, N-[N'-(2(R)-amino-3-mercaptopropyl)isoleucyl-phenyl-alanyl]-3(S)-amino-4-hydroxypentanoic acid, or N-[N'-(2(R)-amino-3-mercaptopropyl)isoleucyl-isoleucyl]-3(S)-amino-4-hydroxypentanoic acid, or the pharmaceutically acceptable salts thereof.
Claim 5
Dependent Claim 10 words
A compound of claim 2 which is: N-[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)-methyl pentyl]isoleucyl-homoserine ##STR10##
Claim 6
Dependent Claim 9 words
A compound of claim 2 is: N-[N'-(2(R)-amino-3-mercaptopropyl)isoleucyl-isoleucyl]-3(S)-amino-4-hydroxy-pentanoic acid ##STR11##
Claim 7
Dependent Claim 20 words
A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 1.
Claim 8
Dependent Claim 19 words
A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of compound of claim 2.
Claim 9
Dependent Claim 19 words
A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of compound of claim 3.
Claim 10
Dependent Claim 19 words
A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of compound of claim 4.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1997-08-22 1998-02-21 1998-08-23 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2001-08-22 2002-02-21 2002-08-23 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2005-08-22 2006-02-21 2006-08-23 $7700.00 Window Closed / Lapsed

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