Serine protease inhibitors

A serine protease inhibitor compound of formula (I)

• 30
• wherein:
• R2 is a 5 or 6 membered aromatic carbon ring optionally interrupted by a nitrogen, oxygen or sulphur ring atom, optionally being substituted in the 3 and/or 4 position (in relation to the point of attachment of X—X) by halo, nitro, thiol, haloalkoxy, hydrazido, alkylhydrazido, amino, cyano, haloalkyl, alkylthio, alkenyl, alkynyl, acylamino, tri or difluoromethoxy, carboxy, acyloxy, MeSO2— or R1, or the substituents at the 3 and 4 positions taken together form a fused ring which is a 5 or 6 membered carbocyclic or heterocyclic ring optionally substituted by halo, haloalkoxy, haloalkyl, cyano, nitro, amino, hydrazido, alkylthio, alkenyl, alkynyl or R1j, and optionally substituted in the position alpha to the X—X group (i.e. 6 position for a six membered aromatic ring etc) by amino, hydroxy, halo, alkyl, carboxy, alkoxycarbonyl, cyano, amido, aminoalkyl, alkoxy or alkylthio with the proviso that R2 cannot be aminoisoquinolyl;
• each X independently is a C, N, O or S atom or a CO, CR1a, C(R1a)2 or NR1a group, at least one X being C, CO, CR1a or C(R1a)2;
• each R1a independently represents hydrogen or hydroxyl, alkoxy, alkyl, aminoalkyl, hydroxyalkyl alkoxyalkyl, alkoxycarbonyl, alkylaminocarbonyl, alkoxycarbonylamino, acyloxymethoxycarbonyl or alkylamino optionally substituted by hydroxy, alkylamino, alkoxy, oxo, aryl or cycloalkyl;
• R1 is as defined for R1a, provided that R1 is not unsubstituted aminoalkyl;
• Y (the α-atom) is a nitrogen atom or a CR1b group;
• Cy is a saturated or unsaturated, mono or poly cyclic, homo or heterocyclic group, optionally substituted by groups R3a or R3iXi;
• each R3a independently is R1c, amino, halo, cyano, nitro, thiol, alkylthio, alkylsulphonyl, alkylsulphenyl, triazolyl, imidazolyl, tetrazolyl, hydrazido, alkylimidazolyl, thiazolyl, alkylthiazolyl, alkyloxazolyl, oxazolyl, alkylsulphonamido, alkylaminosulphonyl, aminosulphonyl, haloalkoxy, haloalkyl, a group of the formula —C(X3)N(R11)R12 (wherein X3 is O or S;
• and R11 and R12 are independently selected from hydrogen, methyl or ethyl or together with the nitrogen atom to which they are attached form a pyrrolidin-1-yl, piperidin-1-yl or morpholino group), or —OCH2O— which is bonded to two adjacent ring atoms in Cy;
• Xi is a bond, O, NH or CH2;
• R3i is phenyl, pyridyl or pyrimidinyl optionally substituted by R3a;
• R1b, R1c and R1j are as defined for R1a;
• and
• -L-Lp(D)n is of the formula:
• 31
• in which Rr is —(CH2)c—Rc, —CHReRf, —CH2—CHReRf, —CH2—CH2—CHReRf, or Rg in which c is 1 or 2;
• Rc is thienyl, thiazolyl(which may bear an amino substituent), isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridyl (which may bear an alkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, alkylaminocarbonyl, amino, amido, (1-4C)alkoxycarbonyl, carboxy, acetylamino, chloro, fluoro, cyano, (1-3C)alkyl, trifluoromethyl, methoxy, ethoxy, nitro, hydroxy, alkylsulphonylamino, triazolyl or tetrazolyl substituent), pyrimidinyl, pyridazinyl, pyrazinyl or phenyl (which may bear a methyl, methylamino, dimethylamino, carboxy, dialkylaminosulphonyl, alkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, alkylaminocarbonyl, amino, amido, alkoxycarbonyl, acetylamino, chloro, fluoro, cyano, methoxy, ethoxy, nitro, hydroxy, alkylsulphonylamino, triazolyl or tetrazolyl substituent);
• each of Re and Rf independently is hydrogen or C1-3alkyl;
• or CHReRf is cyclopentyl (which may bear a hydroxy, amino, (1-3C)alkoxy, (1-3C)hydroxyalkyl, (1-3C)alkyl, carboxy, methoxycarbonyl or ethoxycarbonyl substituent at the 3- or 4-position), cyclohexyl (which may bear a hydroxy, amino, (1-3C)alkoxy, (1-3C)hydroxyalkyl, (1-3C)alkyl, carboxy, methoxycarbonyl or ethoxycarbonyl substituent at the 3- or 4-position), tetrahydropyran-4-yl, tetrahydrothiopyran-4-yl, pyrrolidin-3-yl (which may bear a hydroxy, amino, (1-3C)alkoxy, (1-3C)hydroxyalkyl, (1-3C)alkyl, carboxy, methoxycarbonyl or ethoxycarbonyl substituent at the 1-position), piperidin-4-yl (which may bear a hydroxy, amino, (1-3C)alkoxy, (1-3C)hydroxyalkyl, (1-3C)alkyl, carboxy, methoxycarbonyl or ethoxycarbonyl substituent at the 1-position), or indan-2-yl;
• and Rg is 2-methylsulphonylphenyl which may bear a 4-fluoro substituent or Rg is λ6-1,1-dioxobenzo[b]thiophen-7-yl;
• or a physiologically-tolerable salt thereof;
• provided that Lp(D)n is not of the formula (K):
• 32
• wherein X2 is fluoro or hydrogen.