Patent ID: 6683078
Filing Date: 2004-01-27
Classification: A61K,A61P

Abstract:
A process for treating a condition associated with aggrecanase activity in a host animal, wherein:the process comprises administering a compound or a pharmaceutically-acceptable salt thereof to the host animal in an amount effective to treat the condition; the compound corresponds in structure to Formula A: the ring structure W is a 5- or 6-member aromatic or heteroaromatic ring; X is â€”CH2â€” or â€”N(R9)â€”; R9 is selected from the group consisting of hydrogen, aryl, alkyl, and arylalkyl; y and z are each zero or one and the sum of x and y is either zero or 1; R1 is a substituent that: contains a 5- or 6-member a cyclohydrocarbyl, heterocyclo, aryl, or heteroaryl bonded directly to the depicted SO2 group, and has a length greater than about that of a hexyl group and less than about that of an eicosyl group; where R1 contains a 6-member ring bonded directly to the depicted SO2 group, R1 has geometrical dimensions such that if R1 were to be rotated about an axis drawn through the SO2-bonded 1-position and the 4-position of the SO2-bonded R1 6-member ring, the 3-dimensional volume defined by the rotation would have a widest dimension in a direction transverse to the axis of rotation of about that of a furanyl ring to about that of 2 phenyl rings; where R1 contains a 5-member ring bonded directly to the depicted SO2 group, R1 has geometric dimensions such that if the R1 substituent were to be rotated about an axis drawn through the SO2-bonded 1-position and the center of the 3,4-bond of the SO2-bonded R1 5-member ring, the 3-dimensional volume defined by the rotation would have a widest dimension in a direction transverse to the axis of rotation of about that of a furanyl ring to about that of 2 phenyl rings; as to R2 and R3: R2 and R3 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, Ra-oxyalkyl, hydroxy, thiol, Ra-thioalkyl, haloalkyl, â€”N(Rb)(Rc), N(Rb)(Rc)-alkyl, N(Rd)(Re)-alkanoyl-N(Rb)-alkyl, N(Rb)(Rc)-alkoxy, N(Rb)(Rc)-alkoxyalkyl, heterocyclo, heterocycloalkyl, heterocyclooxy, heterocyclothio, heteroaryl, heteroarylalkyl, heteroaryloxy, and heteroarylthio, or R2 and R3, together with the carbon to which they are both bonded, form a 4- to 8-member carbocyclic or heterocyclic ring; as to R5 and R6: R5 and R6 are independently selected from the group consisting of hydrogen, halogen, nitro, hydroxy, carboxy, cyano, â€”N(Rb)(Rc), alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, acylalkyl, cycloalkyl, thiol, alkylthio, arylthio, cycloalkylthio, hydroxyalkylthio, alkoxy, haloalkoxy, cycloalkoxy, alkoxyalkyl, alkoxyalkoxy, heterocyclooxy, N(Rb)(Rc)-alkyl, N(Rb)(Rc)-alkoxy, N(Rb)(Rc)-carbonyl, N(Rb)(Rc)-alkylthio, and N(Rb)(Rc)-sulfonyl, or R5 and R6, together with the atoms to which R5 and R6 are both bonded, for an aliphatic or aromatic carbocyclic or heterocyclic ring having from 5 to 7 members; R20 is: â€”Oâ€”R21, wherein R21 is hydrogen, C1-C6-alkyl, aryl, aryl-C1-C6-alkyl, or a pharmaceutically acceptable cation, â€”NR13â€”Oâ€”R22, wherein R22 is a selectively removable protecting group, and R13 is hydrogen, C1-C6-alkyl, or benzyl, â€”NR13â€”Oâ€”R14, wherein R13 is hydrogen, C1-C6-alkyl, or benzyl, and R14 is hydrogen, a pharmaceutically acceptable cation, or â€”C(V)R15, wherein: V is O or S, and R15 is C1-C6-alkyl, aryl, C1-C6-alkoxy, heteroaryl-C1-C6-alkyl, C3-C8-cycloalkyl-C1-C6-alkyl, aryloxy, aryl-C1-C6-alkoxy, aryl-C1-C6-alkyl, heteroaryl, or amino-C1-C6-alkyl, wherein: â€ƒthe amino-C1-C6-alkyl nitrogen is unsubstituted, â€ƒthe amino-C1-C6-alkyl nitrogen is substituted with 1 or 2 substituents independently selected from the group consisting of C1-C6-alkyl, aryl, aryl-C1-C6-alkyl, C3-C8-cycloalkyl-C1-C6-alkyl, aryl-C1-C6-alkoxycarbonyl, C1-C6-alkoxycarbonyl, and C1-C6-alkanoyl, or â€ƒthe amino-C1-C6-alkyl nitrogen, together with the 2 substituents bonded thereto, form a 5- to 8-member heterocyclo or heteroaryl ring, or â€”NR23R24, wherein either: R23 and R24 are independently selected from the group consisting of hydrogen, C1-C6-alkyl, amino-C1-C6-alkyl, hydroxy-C1-C6-alkyl, aryl, and aryl-C1-C6-alkyl, or R23 and R24, together with the nitrogen to which they are both bonded, form a 5- to 8-member ring optionally containing an additional heteroatom that is oxygen, nitrogen, or sulfur; Rb and Rc are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, carboxyalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, alkoxyalkyl, bisalkoxyalkyl, perfluoroalkoxyalkyl, alkanoyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkoxycarbonyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, aryloxyalkyl, aryloxycarbonyl, arylsulfonyl, aralkanoyl, aroyl, aryliminocarbonyl, heterocyclo, heterocycloalkyl, heterocycloalkylcarbonyl, heteroaryl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, alkylsulfonyl, heteroarylsulfonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, aminoalkylcarbonyl, aminosulfonyl, and aminoalkylsulfonyl, wherein any amino nitrogen of Rb or Rc is: unsubstituted, substituted with 1 or 2 Rd substituents, or substituted with substituents such that the substituents, taken together with the amino nitrogen, form either: a saturated or partially saturated heterocyclo optionally substituted with 1, 2, or 3 Rd substituents, or a heteroaryl optionally substituted with 1, 2, or 3 Rf substituents; each Rd and Re is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl; each Rf is independently selected from the group consisting of halogen, cyano, nitro, hydroxy, alkyl, alkoxy, aryl, and â€”N(Rd)(Re).