Pancreatic lipase inhibitor compounds, their synthesis and use

A process of manufacturing a compound having the structure:

• wherein,
• XR2 is
• —N([CH2]7CH3)C(O)NH(CH2)7CH3,
• —N([CH2]6CH3)C(O)NH(CH2)6CH3,
• —NH(CH2)qCH3,
• —NH(C6H4)O(C6H5),
• —N(CH3)(CH2)5CH3,
• —NHCH[(CH2)3CH3]2,
• —NHCH(CH3)[CH2]5CH3, or
• —N([CH2]7CH3)2;
• q is an integer from 6 to 15;
• R1 is H, substituted or unsubstituted C1-C15 alkyl, or unsubstituted C2-C15 alkyl, C1-C8 alkylaryl, —C(O)OR4, —C(O)NR4R5, —CR6R6′OR4, —CR6R6′OC(O)R4, —CR6R6′OC(O)NHR7, —C(O)NR8R9, —C(O)NR8R9NR8R9, —N(R5)C(O)NHR5, or CH2R4;
• R2 is a substituted or unsubstituted, straight chain C1-C30 alkyl or branched C3-C30 alkyl, aryl, alkylaryl, arylalkyl, heteroarylalkyl or cycloalkyl;
• R3 is H or substituted or unsubstituted C1-C6 alkyl-CH3, —CH2OCH3 or cycloalkyl;
• R4 is H or a substituted or unsubstituted, straight chain or branched, C6-C30 alkyl, aryl, —CH2-aryl, arylalkyl, heteroarylalkyl or cycloalkyl;
• R5 is H or a substituted or unsubstituted, straight chain or branched, C6-C30 alkyl, aryl, arylalkyl, heteroarylalkyl or cycloalkyl;
• R6 and R6′ are each independently H, substituted or unsubstituted C1-C6 alkyl, dialkyl or cycloalkyl or together form a 3-7 membered cycloalkyl or aryl group ring system;
• R7 is H or substituted or unsubstituted C1-C12 alkyl or cycloalkyl;
• R8 and R9 are each independently H, substituted or unsubstituted C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylaryl, or NR8R9 together form a substituted piperazine or piperidine ring or a dihydro-1H-isoquinoline ring system,
• comprising
• (a) reacting
• in the presence of sulfur, a base and solvent to produce:
• (b) reacting the product of step (a) with
• in the presence of a base to produce:
• (c) reacting the product of step (b) with trifluoroacetic acid (TFA) in the presence of solvent to produce:
• (d) reacting the product of step (c) with SOCl2 in the presence of solvent to produce the compound.

A compound having the structure:

• wherein,
• X is O, S, or CH2;
• Y is O;
• R1 is H, substituted C1-C15 alkyl, unsubstituted C2-C15 alkyl, C1-C8 alkylaryl, —C(O)OR4, —C(O)NR4R5, —CR6R6′OR4, —CR6R6′OC(O)R4, —CR6R6′OC(O)NHR7, —C(O)NR8R9 NR8R9, —N(R5)C(O)NHR5, or CH2R4;
• R2 is a substituted or unsubstituted, straight chain C1-C30 alkyl or branched C3-C30 alkyl, aryl, alkylaryl, arylalkyl, heteroarylalkyl or cycloalkyl;
• and
• R3 is H, —CH3, —CH2OCH3 or C3-C10 cycloalkyl,
• wherein
• R4 is H or a substituted or unsubstituted, straight chain or branched, C6-C30 alkyl, aryl, —CH2-aryl, aryl —C1-C30 alkyl, heteroaryl-C1-C30 alkyl or C3-C10 cycloalkyl;
• R5 is H or a substituted or unsubstituted, straight chain or branched, C6-C30 alkyl, aryl C1-C30 alkyl, heteroarylalkyl or cycloalkyl;
• R6 and R6′ are each independently H, substituted or unsubstituted C1-C6 alkyl, dialkyl or C3-C10 cycloalkyl or together form a 3-7 membered cycloalkyl or aryl group;
• R7 is H or substituted or unsubstituted C1-C12 alkyl or C3-C10 cycloalkyl;
• and
• R8 and R9 are each independently H, substituted or unsubstituted C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylaryl, or NR8R9 together form a substituted piperazine or piperidine ring or a dihydro-1H-isoquinoline ring system,
• or a specific enantiomer thereof, or a specific tautomer, or a pharmaceutically acceptable salt thereof.

A process of manufacturing a compound having the structure:

• wherein,
• X is O, S, or CH2;
• R1 is H, substituted C1-C15 alkyl, unsubstituted C2-C15 alkyl, C1-C8 alkylaryl, —C(O)OR4, —C(O)NR4R5, —CR6R6′OR4,
• CR6R6′OC(O)R4, —CR6R6′OC(O)NHR7, —C(O)NR8R9, —C(O)NR8R9NR8R9, —N(R5)C(O)NHR5, or CH2R4;
• R2 is a substituted or unsubstituted, straight chain C1-C30 alkyl or branched C3-C30 alkyl, aryl, alkylaryl, arylalkyl, heteroarylalkyl or cycloalkyl;
• R3 is H, —CH3, —CH2OCH3 or cycloalkyl;
• R4 is H or a substituted or unsubstituted, straight chain or branched, C6-C30 alkyl, aryl, —CH2-aryl, arylalkyl, heteroarylalkyl or cycloalkyl;
• R5 is H or a substituted or unsubstituted, straight chain or branched, C6-C30 alkyl, arylalkyl, heteroarylalkyl or cycloalkyl;
• R6 and R6′ are each independently H, substituted or unsubstituted C1-C6 alkyl, dialkyl or cycloalkyl or together form a 3-7 membered cycloalkyl or aryl group;
• R7 is H or substituted or unsubstituted C1-C12 alkyl or cycloalkyl;
• R8 and R9 are each independently H, substituted or unsubstituted C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylaryl, or NR8R9 together form a substituted piperazine or piperidine ring or a dihydro-1H-isoquinoline ring system,
• comprising
• (a) reacting
• in the presence of sulfur, a base and solvent to produce:
• (b) reacting the product of step (a) with
• in the presence of a base to produce:
• c) reacting the product of step (b) with trifluoroacetic acid (TFA) in the presence of solvent to produce:
• (d) reacting the product of step (c) with SOCl2 in the presence of solvent to produce the compound.