- Beta-thiopropionyl-amino acid derivatives and their use as beta-lactamase inhibitors
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PCT No. PCT/EP97/05709 Sec. 371 Date Apr. 7, 1999 Sec. 102(e) Date Apr. 7, 1999 PCT Filed Oct. 10, 1997 PCT Pub. No. WO98/17639 PCT Pub. Date Apr. 30, 1998Mercapto amino acid derivatives of formula (I), wherein R is hydrogen, a salt-forming cation of a in vivo hydrolysable ester-forming group; R1 is selected from (a) and (b) in which A is a monocyclic aryl or heteroaryl ring and B is a monocyclic aryl, alicyclic or heterocyclic ring, C and D are independently -Zp-(CR8CR9)q- or -(CR8CR9)q-Zp- where p is 0 or 1, q is 0 to 3 provided that p+q in C is not 0, R8 and R9 are independently hydrogen or (C1-6)alkyl or together represent oxo and Z is O, NR10 or S(O)x where R10 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl and x is 0-2, and wherein C and D are linked ortho to one another on each of the rings A and B in formula (b); R2 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl; R3 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms, (C3-7)cycloalkyl, fused aryl(C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl-(CH2)m-X-(CH2)n, heterocyclyl or heterocyclyl-(CH2)m-X-(CH2)n, where m is 0 to 3, n is 1 to 3 and X is O or S(O)x where x is 0-2 or a bond; R4 is hydrogen or an in vivo hydrolysable acyl group; and R5 and R6 are independently hydrogen and (C1-6)alkyl or together represent (CH2)r, where r is 2 to 5; for use in treatment of bacterial infections in humans or animals by administration in combination with a beta -lactam antiobiotic.
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- Pyrrolidine and thiazole derivatives with antibacterial and metallo- beta -lactamase inhibitory properties
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PCT No. PCT/EP96/04014 Sec. 371 Date Jun. 10, 1998 Sec. 102(e) Date Jun. 10, 1998 PCT Filed Sep. 9, 1996 PCT Pub. No. WO97/10225 PCT Pub. Date Mar. 20, 1997This invention relates to a method of treating bacterial infections in humans or animals comprising
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- beta -thiopropionyl-aminoacid derivatives and their use as beta -lactamase inhibitors
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PCT No. PCT/EP97/00516 Sec. 371 Date Jan. 13, 1999 Sec. 102(e) Date Jan. 13, 1999 PCT Filed Feb. 3, 1997 PCT Pub. No. WO97/30027 PCT Pub. Date Aug. 21, 1997A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a beta -lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R1 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C1-6)alkylcarbonyloxy, (C1-6)alkoxycarbonyl, formyl or (C1-6)alkylcarbonyl group, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl(C1-6)alkyl, heterocyclyl or heterocyclyl(C1-6)alkyl; R2 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl; R3 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms, (C3-7)cycloalkyl, fused aryl(C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl-(CHR10)m-X-(CHR11)n, heterocyclyl or heterocyclyl-(CHR10)m-X-(CHR11)n, where m is 0 to 3, n is 1 to 3, each R10 and R11 is independently hydrogen or (C1-4)alkyl and X is O, S(O)x where x is 0-2, or a bond; R4 is hydrogen, or an in vivo hydrolysable acyl group; and R5 and R6 are independently hydrogen and (C1-6)alkyl or together represent (CH2)p where p is 2 to 5. Some compounds are claimed per se.
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- N-(MERCAPTOACYL) PEPTIDYL DERIVATIVES AS ANTIDEGENERATIVE AGENTS
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Novel N-(mercaptoacyl)peptidyl compounds are useful as inhibitors of matrix metalloendoproteinases which degrade major components of articular cartilage and basement membranes causing degenerative diseases such as arthritis, periodontal disease, corneal ulceration, are described. For example, N-(2-thiomethyl-4-phenyl-butanoyl)-L-leucinamide was prepared and its inhibitory activity against stromelysin was tested in vitro.
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- Mercaptoacyl amino acid inhibitors of atriopeptidase. 1. Structure- activity relationship studies of methionine and S-alkylcysteine derivatives
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A broad series of N-(3-mercaptoacyl) amino acid derivatives was evaluated for their ability to inhibit atriopeptidase (neutral endopeptidase, EC 3.4.24.11) in vitro and in vivo. Structural parameters studied were (i) the substituent on the 2-position of the 3-mercaptopropionyl moiety, (ii) the amino acid component, (iii) the S-terminal derivative, and (iv) the C- terminal derivative. Optimum activity was observed for derivatives of methionine and S-alkylcysteines. N-[3-Mercapto-2(S)-[(2- methylphenyl)methyl]-1-oxopropyl]-L-methionine was identified as a highly effective inhibitor of atriopeptidase meriting evaluation as a potential cardiovascular therapeutic agent.
- Neustadt,Smith,Nechuta,Bronnenkant,Haslanger,Watkins,Foster,Sybertz
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p. 2461 - 2476
(2007/10/02)
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- Aminobenzoic and aminocyclohexanecarboylic acid compounds, compositions, and their method of use
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Compounds of the formula inhibit the action of neutral endopeptidase. As a result, such compounds produce diuresis, natriuresis, and lower blood pressure as well as being useful in the treatment of congestive heart failure, relieving pain, and diarrhea when administered to a mammalian host.
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