Cyclic sulfamide derivatives and methods of use

A compound of the formula

• 77
• wherein
• R1 is hydrogen, halogen, hydroxy, alkoxy, carboxy, cyano, nitro, trifluoromethyl, alkynyl, alkylthio, heteroaralkyl, heteroaralkoxy or heteroaryloxy provided that R1 is located at the 2-position when L3 is —(CHR)s— in which s is zero;
• or
• R1 is optionally substituted alkyl, alkenyl, optionally substituted amino, aralkyl, aralkoxy, aralkylthio, aryloxy, arylthio or cycloalkyl provided that a monocyclic aryl group which is substituted at the para position with a methylene or ethylene bridged nitrogen containing heterocycle does not constitute part of R1 when
• (i) R1 is located at the 2-position and L3 is —(CHR)s— in which s is zero;
• (ii) X and Y are CH;
• and
• (iii) Q2 is oxygen;
• or
• C—R1 may be replaced with nitrogen or N→O;
• or
• R1 and R2 combined together with the carbon atoms to which R1 and R2 are attached form an optionally substituted fused 5- to 6-membered aromatic or heteroaromatic ring provided that R1 and R2 are attached to carbon atoms adjacent to each other;
• or
• R2 is hydrogen, halogen, hydroxy, alkoxy, cyano, trifluoromethyl, nitro, optionally substituted amino, optionally substituted alkyl, alkylthio, aralkyl, heteroaralkyl, aralkoxy, heteroaralkoxy, aralkylthio, aryloxy, heteroaryloxy, arylthio or cycloalkyl;
• or
• R2 is —C(O)R3 wherein
• R3 is hydroxy or optionally substituted alkoxy;
• or
• R3 is —NR4R5 in which R4 and R5 are independently hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, aralkyl or heteroaralkyl;
• L1 is a single bond;
• or
• L1 is carbon which combined together with R2 and the carbon atoms to which L1 and R2 are attached form an optionally substituted fused 5- or 6-membered aromatic or heteroaromatic ring provided that L1 and R2 are attached to carbon atoms adjacent to each other;
• or
• L1 is CH or nitrogen which taken together with R2 and the carbon atoms to which L1 and R2 are attached form a fused 5- to 7-membered ring which may be interrupted with one or two heteroatoms selected from oxygen, nitrogen and sulfur provided that L1 and R2 are attached to carbon atoms adjacent to each other;
• or
• L1 is CH, oxygen, sulfur or nitrogen and L2 is carbon which combined together with L1, R2 and the carbon atoms to which L1 and R2 are attached form an optionally substituted fused 5- or 6-membered aromatic or heteroaromatic ring provided that L1 and R2 are attached to carbon atoms adjacent to each other;
• or
• L1 is —CH2—, oxygen, sulfur or —NR6— and L2 is CH which taken together with L1, R2 and the carbon atoms to which L1 and R2 are attached form a fused 5- to 7-membered ring which may be interrupted with one or two heteroatoms selected from oxygen, nitrogen and sulfur wherein
• R6 is hydrogen, optionally substituted alkyl, aralkyl, heteroaralkyl, alkoxycarbonyl, aryloxycarbonyl, carbamoyl, sulfonyl or acyl provided that L1 and R2 are attached to carbon atoms adjacent to each other;
• or
• L2 is —(CHR7)n— wherein
• R7 is hydrogen, hydroxy, alkoxy, carboxy, optionally substituted alkyl, cycloalkyl, aryl or heteroaryl;
• n is zero or an integer from 1 to 4;
• Z is —(CHR8)m—, —(CH2)mO(CHR8)r—, —(CH2)mS(CHR8)r— or —(CH2)mNR9(CHR8)r— wherein
• R8 is hydrogen, optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl;
• R9 is hydrogen, optionally substituted alkyl, cycloalkyl, aryl, heterocyclyl, aralkyl, heteroaralkyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, carbamoyl, sulfonyl, acyl or acylamino;
• m and r are independently zero or an integer of 1 or 2;
• Q1 is hydrogen, optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl provided that
• (i) Q1 is not 2-phenyloxazol-4-yl when
• R1 and R2 are hydrogen;
• X and Y are CH;
• L1 is a single bond located at the 4-position;
• L2 is —(CHR7)n— wherein n is zero;
• L3 is —(CHR)s— wherein s is zero;
• Z is —(CH2)m—O(CHR8)r— wherein R8 is hydrogen, m is zero and r is 2;
• and
• Q2 is oxygen;
• or
• (ii) Q1 is not hydrogen when
• R1 and R2 are hydrogen;
• X and Y are CH;
• L1 is a single bond;
• L2 is —(CHR7)n— wherein n is zero;
• L3 is —(CHR)s— wherein R is hydrogen and s is 1;
• Z is —(CHR8)m— wherein m is zero;
• and
• Q2 is oxygen;
• or
• Q1 is —C(O)NR4aR5a, —C(O)R10, —C(O)OR10 or —S(O)qR10 wherein R4a and R5a are as defined for R4 and R5;
• R10 is optionally substituted alkyl, cycloalkyl, aryl, heterocyclyl, aralkyl or heteroaralkyl;
• q is an integer of 1 or 2;
• or
• Q1is a radical of the formula
• 78
• wherein
• W1 is aryl, heteroaryl, aralkyl or heteroaralkyl;
• or
• W1 is —C(O)R3a in which R3a is hydroxy or optionally substituted alkoxy;
• or
• R3a is —NR4aR5a in which R4a and R5a are as defined for R4 and R5;
• R11 is hydrogen, alkyl or aryl;
• U1 is —C(O)—, —S(O)2— or —(CH2)r— in which r is as defined for Z;
• V1 is hydroxy, alkoxy, aryl, heteroaryl, optionally substituted alkyl or cycloalkyl;
• or
• V1 is —NR4bR5b in which R4b and R5b are as defined for R4 and R5 provided that
• (i) L2 is —(CHR7)n— in which n is an integer of 1 or 2;
• and
• (ii) Z is —(CHR8)m— in which m is zero;
• or
• Q1 is a radical of the formula
• 79
• wherein
• W2 is —C(O)R3a in which R3a is hydroxy or optionally substituted alkoxy;
• or
• R3a is —NR4aR5a in which R4a and R5a are as defined for R4 and R5;
• R11 is hydrogen, alkyl or aryl;
• U2 is —(CH2)p— in which p is zero or 1;
• V2 is —NR4bC(O)R5b, —NR4bC(O)OR5b, —NR4bC(O)NR4cR5b or —NR4bS(O)2R5b in which R4b and R4c are as defined for R4, and R5b has a meaning as defined for R5 provided that
• (i) L2 is —(CHR7)n— in which n is an integer of 1 or 2;
• and
• (ii) Z is —(CHR8)m— in which m is zero;
• or
• Q1 is a radical of the formula
• 80
• wherein
• W3 is —C(O)R3a in which R3a is hydroxy or optionally substituted alkoxy;
• or
• R3a is —NR4aR5a in which R4a and R5a are as defined for R4 and R5;
• R11 is hydrogen, alkyl or aryl;
• U3 is —(CH2)p— in which p is zero or 1;
• V3 is —NHC(O)CHR4bNHC(O)R12 wherein R4b is as defined for R4;
• R12 is hydrogen, aryl, heterocyclyl, aralkyl, heteroaralkyl, optionally substituted alkyl, alkoxy or cycloalkyl;
• or
• R12 is —NR4cR5b, in which R4c and R5b are as defined for R4 and R5 provided that
• (i) L2 is —(CHR7)n— in which n is an integer of 1 or 2;
• and
• (ii) Z is —(CHR8)m— in which m is zero;
• L3 is —(CHR)s— wherein
• R is hydrogen, carboxy, optionally substituted alkyl, cycloalkyl, aryl or heteroaryl;
• s is zero or an integer from 1 to 3;
• Q2 is oxygen, sulfur or NR13 wherein
• R13 is hydrogen, hydroxy or lower alkyl;
• X and Y are independently CH or nitrogen;
• or
• —X═Y— is sulfur, oxygen or —NR14— wherein
• R14 is hydrogen, optionally substituted alkyl, alkoxycarbonyl, acyl, aryloxycarbonyl, heteroaryloxycarbonyl, carbamoyl or sulfonyl;
• or a pharmaceutically acceptable salt thereof;
• or a prodrug derivative thereof.