Some content of this application is unavailable at the moment.
If this situation persists, please contact us atFeedback&Contact
1. (WO1997017363) THROMBIN INHIBITORS
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/1997/017363 International Application No.: PCT/EP1996/004785
Publication Date: 15.05.1997 International Filing Date: 30.10.1996
Chapter 2 Demand Filed: 25.04.1997
IPC:
C07C 237/22 (2006.01) ,C07D 207/16 (2006.01) ,C07D 277/28 (2006.01) ,C07D 417/12 (2006.01) ,C07K 5/02 (2006.01) ,C07K 5/065 (2006.01) ,C07K 5/078 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
237
Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
02
having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
22
having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
207
Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
02
with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
04
having no double bonds between ring members or between ring members and non-ring members
10
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 ring carbon atoms
16
Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
277
Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
02
not condensed with other rings
20
having two or three double bonds between ring members or between ring members and non-ring members
22
with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
28
Radicals substituted by nitrogen atoms
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
417
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/196
02
containing two hetero rings
12
linked by a chain containing hetero atoms as chain links
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
5
Peptides having up to four amino acids in a fully defined sequence; Derivatives thereof
02
containing at least one abnormal peptide link
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
5
Peptides having up to four amino acids in a fully defined sequence; Derivatives thereof
04
containing only normal peptide links
06
Dipeptides
065
the side chain of the first amino acid containing carbocyclic rings, e.g. Phe, Tyr
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
5
Peptides having up to four amino acids in a fully defined sequence; Derivatives thereof
04
containing only normal peptide links
06
Dipeptides
078
the first amino acid being heterocyclic, e.g. Pro, His, Trp
Applicants:
AKZO NOBEL N.V. [NL/NL]; Velperweg 76 NL-6824 BM Arnhem, NL (AllExceptUS)
ADANG, Anton, Egbert, Peter [NL/NL]; NL (UsOnly)
VAN BOECKEL, Constant, Adriaan, Anton [NL/NL]; NL (UsOnly)
GROOTENHUIS, Peter, Diederik, Jan [NL/NL]; NL (UsOnly)
PETERS, Jacobus, Albertus, Maria [NL/NL]; NL (UsOnly)
Inventors:
ADANG, Anton, Egbert, Peter; NL
VAN BOECKEL, Constant, Adriaan, Anton; NL
GROOTENHUIS, Peter, Diederik, Jan; NL
PETERS, Jacobus, Albertus, Maria; NL
Agent:
HERMANS, F., G., M.; Postbus 20 NL-5340 BH Oss, NL
Priority Data:
95202982.503.11.1995EP
95203554.119.12.1995EP
Title (EN) THROMBIN INHIBITORS
(FR) INHIBITEURS DE LA THROMBINE
Abstract:
(EN) The invention relates to non-slow-binding thrombin inhibitors of the formula: A-B-C-Lys-D wherein A is H, 2-hydroxy-3-cyclohexyl-propionyl-, R1, R1-O-CO-, R1-CO-, R1-SO2-, -(CHR2)nCOOR3, or an N-protecting group, wherein R1 is selected from -(1-6C)alkylene-COOH, (1-12C)alkyl, (2-12C)alkenyl, (6-14C)aryl, (7-15C)aralkyl and (8-16C)aralkenyl, the aryl group of which may be substituted with (1-6C)alkyl, (2-12C)alkoxy, hydroxy, or halogen; R2 is H or has the same meaning as R1, R3 is selected from H, (1-12C)alkyl, (2-12C)alkenyl, (6-14C)aryl, (7-15C)aralkyl and (8-16C)aralkenyl, the aryl group of which may be substituted with (1-6C)alkyl, (2-12C)alkoxy, hydroxy or halogen; n is an integer of 1 to 3; B is a bond, L-Asp or an ester derivative thereof, Leu, norLeu, -N(benzyl)-CH2-CO-, -N(2-indane)-CH2-CO-, D-1-Piq, D-3-Piq, D-Tiq, Atc or a D-amino acid having a hydrophobic aromatic side chain; C is Azt, Pro, Pec, norLeu(cyclo)Gly, an amino acid of one of the formulae -N[(3-8C)cycloalkyl]-CH2-CO- or -N(benzyl)-CH2-CO-, D is selected from COOH, tetrazole, oxazole, thiazole and benzothiazole, or A and C have the aforesaid meanings, B is D-(3-8C)cycloalkylalanine, and D is tetrazole, oxazole, thiazole or benzothiazole; or a prodrug thereof; or a pharmaceutically acceptable salt thereof; with the exception of the compound Me-D-Phe-Pro-Lys-COOH. The compounds can be used as antithrombotic agents.
(FR) L'invention concerne des inhibiteurs de la thrombine, à fixation non lente et répondant à la formule A-B-C-Lys-D dans laquelle A représente H, 2-hydroxy-3-cyclohexyl-propionyle-, R1, R1-O-CO-, R1-CO-, R1-SO2-, -(CHR2)nCOOR3, ou un groupe N-protecteur, dans lesquels R1 est choisi parmi -alkylène C1-6-COOH, alkyle C1-12, alcényle C2-12, aryle C6-14, aralkyle C7-15 et aralcényle C8-16, dont le groupe aryle peut être substitué par alkyle C1-6, alcoxy C2-12, hydroxy ou halogène, R2 représente H ou possède la même notation que R1, R3 est choisi parmi H, alkyle C1-12, alcényle C2-12, acyle C6-14, aralkyle C7-15 et aralcényle C8-16, dont le groupe aryle peut être substitué par alkyle C1-6, alcoxy C2-12, hydroxy ou halogène, n étant un nombre entier compris entre 1 et 3, B représente une liaison, L-Asp ou un dérivé ester de celui-ci, Leu, norLeu, -N(benzyl)-CH2-CO-, -N(2-indane)-CH2-CO-, D-1-Piq, D-3-Piq, D-Tiq, ATC ou un acide aminé D possédant une chaîne latérale aromatique hydrophobe, C représente Azt, Pro, Pec, norLeu(cyclo)Gly, un acide aminé répondant à l'une des formules -N(cycloalkyle C3-8)-CH2-CO- ou -N(benzyle)-CH2-CO-, D est choisi parmi COOH, tétrazole, oxazole, thiazole et benzothiazole, ou bien A et C possèdent les notations ci-dessus, B représente D-cycloalkylalanine C3-8, et D représente tétrazole, oxazole, thiazole ou benzothiazole. L'invention concerne également un promédicament de ces composés, ou un sel de ceux-ci, acceptable sur le plan pharmacologique, à l'exception du composé Me-D-Phe-Pro-Lys-COOH. On peut utiliser ces composés en tant qu'agents antithrombotiques.
Designated States: AU, BR, CA, CN, CZ, HU, JP, KR, MX, NO, PL, RU, TR, US
European Patent Office (AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE)
Publication Language: English (EN)
Filing Language: English (EN)
Also published as:
CZPV1998-1339NO19981965TR1998/00773MXPA/a/1998/003479EP0858464RU02178796
US20010007764JPH11515033 CN1202902CA2235586KR1019990067219AU1996074975