Multicyclic compounds and methods of use thereof

A compound of formula (Ma):

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein
• R1 and R2 are each independently (i) hydrogen, alkyl, alkoxyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl, each of which is optionally substituted;
• or (ii) —(CH2)p—R8, wherein R8 is SO2alkyl or SO2aryl, each of which is optionally substituted;
• or (iii) R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted heterocyclyl or heteroaryl;
• R3 and R4 are each independently (i) hydrogen, alkyl, alkoxyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl, each of which is optionally substituted;
• or (ii) —(CH2)p—R9, wherein R9 is CF3, CN, nitro, amino, hydroxyl, or cycloalkoxyl, each of which is optionally substituted;
• or (iii) R3 and R4 together with the carbon atom to which they are attached form an optionally substituted cycloalkyl or heterocyclyl;
• or (iv) R3 and R1 together with the atoms to which they are attached form an optionally substituted heterocyclyl, and R4 is (i) or (ii);
• or (v) R3 and R4 are combined together to form a double bond and together with R1 and/or R2 and the atoms to which they are attached form an optionally substituted heteroaryl;
• R5 is (i) hydrogen, alkyl, alkoxyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl, each of which is optionally substituted;
• or (ii) —(CH2)p—R10, wherein R10 is CF3, CN, nitro, amino, hydroxyl, or cycloalkoxyl, each of which is optionally substituted;
• or (iii) R5 and R1 together with the atoms to which they are attached form an optionally substituted heterocyclyl;
• R6 and R7 are each independently (i) hydrogen, halo, alkyl, alkoxyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl, each of which is optionally substituted;
• or (ii) —(CH2)p—R11, wherein R11 is CF3, CN, nitro, amino (—NH2), hydroxyl, cycloalkoxyl, heteroaryl, or heterocyclyl, each of which is optionally substituted;
• or (iii) R6 and R7 together with the atoms to which they are attached form an optionally substituted aryl, heteroaryl, cycloalkyl or heterocyclyl ring;
• m is 0, 1, or 2;
• n is 0, 1, or 2;
• and
• each occurrence of p is independently 0, 1, or 2.

A method of preparing a compound of formula (IIIa):

• or a pharmaceutically acceptable salt or stereoisomer thereof, the method comprising:
• (a) treating a hydroxyalkyl thiophene of formula (i):
• with an amino-aldehyde acetal and an acid, to produce a compound of formula (IIIa), wherein:
• m is 0;
• n is 1;
• R1 and R2 are each independently hydrogen or C1-C4 alkyl;
• R3 and R4 are each independently hydrogen or C1-C4 alkyl;
• R5 is hydrogen;
• and
• R6 and R7 are each independently hydrogen, halo, or C1-C4 alkyl.