Pyrrolidine derivatives as prostaglandin modulators

A compound of the following Formula X, or a pharmaceutically acceptable salt thereof:

• wherein
• A is selected from O and CH2;
• B is CR2R3 or absent wherein R2 and R3 are independently selected from H and C1-C6 alkyl;
• or A and B taken in combination form a 1,2-vinylene group;
• G is oxo;
• L is C(O)Z;
• Q is (CR2R3)q which may include 0 or 1 C═C double bond;
• U is —CR6R7—W, wherein R6 and R7 are independently selected from H and C1-C6 alkyl;
• or R6 and R7 can form a C3-C6 cycloalkyl with the carbon they are attached to;
• V is selected from aryl and heteroaryl;
• or V is (CR2R3)m when A and B taken in combination form a 1,2-vinylene group or an ethynyl group;
• W is selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl C1-C6 alkyl, aryl and heteroaryl;
• Z is hydroxy;
• q is an integer selected from 0, 1, 2, 3, 4 and 5;
• m is an integer selected from 1, 2, 3, 4, 5 and 6.

A compound of the following Formula X′, or a pharmaceutically acceptable salt thereof:

• wherein
• A is CH2;
• B is CR2R3 or absent wherein R2 and R3 are independently selected from H and C1-C6 alkyl;
• G is oxo;
• L is C(O)Z;
• Q is (CR2R3)q which may include 0 or 1 C═C double bond;
• U is —CR6R7—W, wherein R6 and R7 form a C3-C6 cycloalkyl with the carbon they are attached to;
• V is selected from (CR2R3)m, aryl and heteroaryl;
• W is selected from hydrogen, C3-C6 cycloalkyl and C1-C6 alkyl C3-C6cycloalkyl;
• Z is hydroxy;
• q is an integer selected from 0, 1, 2, 3 and 4;
• m is an integer selected from 1, 2, 3, 4, 5 and 6.

A compound of the following Formula XI, or a pharmaceutically acceptable salt thereof:

• wherein
• G is oxo;
• L is C(O)Z;
• Q is (CR2R3)q wherein R2 and R3 are independently selected from H and C1-C6 alkyl;
• U is —CR6R7—W, wherein R6 and R7 are independently selected from H and C1-C6 alkyl;
• or R6 and R7 can form a C3-C6 cycloalkyl with the carbon they are attached to;
• V is selected from aryl and heteroaryl;
• W is selected from hydrogen, C1-C6 alkyl and C3-C6 cycloalkyl C1-C6 alkyl;
• Z is hydroxy;
• m is an integer selected from 1, 2 and 3;
• q is selected from 1 and 2.

A compound of following Formula XII, or a pharmaceutically acceptable salt thereof:

• wherein
• G is oxo;
• L is C(O)Z;
• Q is (CR2R3)q wherein R2 and R3 are independently selected from H and C1-C6 alkyl,
• U is —CR6R7—W, wherein R6 and R7 are independently selected from H and C1-C6 alkyl;
• or
• R6 and R7 can form a C3-C6 cycloalkyl with the carbon they are attached to;
• V is (CR2R3)m;
• W is selected from aryl and heteroaryl;
• Z is hydroxy,
• q is an integer selected from 1 and 2;
• m is an integer selected from 1, 2 and 3.

A compound of the following Formula XIII, or a pharmaceutically acceptable salt thereof:

• wherein A is O, S, or CR2R3;
• B is (CR2R3) m, or absent;
• or
• A and B taken in combination form an optionally substituted 1,2-vinylene group or an ethynyl group;
• V is (CR2R3)m, optionally substituted divalent aryl, or optionally substituted divalent heteroaryl;
• L is C(O)Z;
• G is oxo (═O), hydroxyl, or optionally substituted alkoxy;
• Q is (CR2R3)q which may include 0 or 1 C═C double bonds;
• U is an optionally substituted alkyl group;
• Z is hydroxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl optionally substituted heteroalkynyl, amino, NR4R5, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted carbocyclic aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, or optionally substituted heteroarylalkyl;
• n is an integer selected from 0-3;
• m is an integer selected from 1-6;
• q is an integer selected from 0-5;
• and
• R2 and R3 are independently hydroxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl, optionally substituted heteroalkynyl;
• R4 and R5 are independently are independently selected at each occurrence from the group consisting of hydrogen optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl, optionally substituted heteroalkynyl, optionally substituted carbocyclic aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl,
• or R4 and R5 taken in combination is an optionally substituted heterocycloalkyl.

A compound of the following Formula XIV, or a pharmaceutically acceptable salt thereof:

• wherein
• q is an integer from 1-3;
• q′ is an integer from 2-4;
• G is oxo or methoxy;
• Z is hydroxy, C1-6 alkoxy, amino or mono C1-6 alkylamino or di-C1-6 alkylamino;
• and
• U is a —(CR2R3)s—W, wherein R2 and R3 are independently hydrogen, hydroxy, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl, or optionally substituted heteroalkynyl;
• s is an integer from 0-6;
• W is hydrogen or C3-7 cycloalkyl.

A compound of the following Formula XV, or a pharmaceutically acceptable salt thereof:

• wherein A is O or CH2;
• B is CH2 or absent
• V is divalent phenyl, divalent furan, or divalent thiophene;
• q is an integer from 1-3;
• G is oxo or methoxy;
• Z is hydroxy, C1-C6 alkoxy, amino or mono C1-6 alkylamino or di C1-6 alkylamino;
• and
• U is a —(CR2R3)s—W, wherein R2 and R3 are independently hydrogen, hydroxy, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl;
• optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl, or optionally substituted heteroalkynyl;
• s is an integer from 0-6;
• and W is hydrogen or C3-7cycloalkyl.