Heterocyclic Compounds for the Treatment of Neurological and Psychological Disorders

A method of treating a neurological or psychiatric disorder by administering a compound of Formula I or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• Semicircle represents an optionally substituted cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl containing one, two or three rings;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl, —S—, —O—, —S(O)—, —S(O)2—, —S[C(R10)(R11)]u-, —S(O) [C(R10)(R11)]u-, S(O)2[C(R10)(R11)]u-, —O[C(R10)(R11)]u-, —N(R10)—, —N(R10)—[C(R10)(R11)]u-, —[C(R10)(R11)]u;
• wherein each u is independently 1, 2, 3, 4, 5, 6 or 7;
• wherein each R10 and R11 is independently absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• Cy1 is an optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or optionally substituted aryl;
• B is a linker or a direct bond;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• Each G1 and G2 is independently selected from absent, —S—, —O—, —S(O)—, —S(O)2—, —SC(R10)(R11)—, —S(O) C(R10)(R11)—, —S(O)2C(R10)(R11)—, —OC(R10)(R11)—, —N(R10)—, —C(R10)═C(R11)—, —N(R10)—C(R10)(R11)—, —[C(R10)(R11)]t-;
• wherein t is 1, 2 or 3;
• Each R1, R3 and R4 is independently selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• Alternatively, two R3 and R4 together form an optionally substituted ring;
• R5 is selected from —CH(R10)—OR20, —CH(R10)—OC(O)OR20, —CH(R10)—OC(O)R20, —CH(R10)—OC(O)NR20R21, —(CH(R10))—OPO3MY, —(CH(R10))—OP(O)(OR20)(OR21), —[CH(R10)O]z—R20, —[CH(R10)O]z—C(O)OR20, —[CH(R10)O]z—C(O)R20, —[CH(R10)O]z—C(O)NR20R21, —[CH(R10)O]z-OPO3MY, —[CH(R10)O]z—P(O)2(OR20)M and —[CH(R10)O]z—P(O)(OR20)(OR21);
• wherein z is 1, 2, 3, 4, 5, 6, or 7;
• each R20 and R21 is independently selected from hydrogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• Y and M are the same or different and each is a monovalent cation;
• or M and Y together is a divalent cation;
• and
• n, m and q are independently selected from 0, 1, and 2.

A method for sustained delivery of a compound of Formula XXIII:

• wherein A, B, D, R1, R2, R3, R4, Cy1, G1, G2, q and m are as defined above;
• comprising administering a compound of Formula I or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof;
• wherein represents a single or double bond;
• Semicircle represents an optionally substituted cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl containing one, two or three rings;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, —S—, —O—, —S(O)—, —S(O)2—, —S[C(R10)(R11)]u-, —S(O) [C(R10)(R11)]u-, —S(O)2[C(R10)(R11)]u-, —O[C(R10)(R11)]u-, —N(R10)—, —N(R10)—[C(R10)(R11)]u—, —[C(R10)(R11)]u;
• wherein each u is independently 1, 2, 3, 4, 5, 6 or 7;
• wherein each R10 and R11 is independently absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• Cy1 is an optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or optionally substituted aryl;
• B is a linker or a direct bond;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• Each G1 and G2 is independently selected from absent, —S—, —O—, —S(O)—, —S(O)2—, —SC(R10)(R11)—, —S(O)C(R10)(R11)—, —S(O)2C(R10)(R11)—, —OC(R10)(R11)—, —N(R10)—, —C(R10)═C(R11)—, —N(R10)—C(R10)(R11)—, —[C(R10)(R11)]t;
• wherein t is 1, 2 or 3;
• Each R1, R3 and R4 is independently selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10 optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• Alternatively, two R3 and R4 together form an optionally substituted ring;
• R5 is selected from —CH(R10)—OR20, —CH(R10)—OC(O)OR20, —CH(R10)—OC(O)R20, —CH(R10)—OC(O)NR20R21, —(CH(R10))—OPO3MY, —(CH(R10))—OP(O)(OR20)(OR21), —[CH(R10)O]z—R20, —[CH(R10)O]z—C(O)OR20, —[CH(R10)O]z—C(O)R20, —[CH(R10)O]z—C(O)NR20R21, —[CH(R10)O]z-OPO3MY, —[CH(R10)O]z—P(O)2(OR20)M and —[CH(R10)O]z—P(O)(OR20)(OR21);
• wherein z is 1, 2, 3, 4, 5, 6, or 7;
• each R20 and R21 is independently selected from hydrogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• Y and M are the same or different and each is a monovalent cation;
• or M and Y together is a divalent cation;
• and
• n, m and q are independently selected from 0, 1, and 2;
• wherein upon administration to the patient, release of the compound of Formula XXIII is sustained release.