Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions

A method of treating short bowel syndrome in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound of Formula (I),

• wherein,
• D is selected from the group consisting of O, S, and NR8,
• X, Y, and Z is
• J, K, T, and U are each independently selected from the group consisting of C, CH, and N;
• the subscript p is an integer of from 0 to 4;
• the subscript q is an integer of from 0 to 4;
• R1 is a member selected from the group consisting of H, C1-10alkyl, C1-10substituted alkyl, C3-7cycloalkyl, C2-10alkenyl, C2-10 alkynyl, —X1—CORa, —X1—CO2Ra, —X1—CONRaRb, —SO2Ra, a 4- to 7-membered heterocyclo group, aryl and a 5- to 10-membered heteroaryl group, wherein each of said cycloalkyl group, heterocyclo group, aryl group and heteroaryl group is optionally substituted with from 1 to 4 substituents independently selected from halo, C1-10alkyl, C1-10substituted alkyl, C3-7cycloalkyl, C2-10alkenyl, C2-10 alkynyl, aryl, heteroaryl, —CN, —NRaCORb, —NRaCONRaRb, —NO2, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —S(O)mRa, —NRaS(O)2Rb, and SO2NRaRb, or optionally Ra and Rb are combined to form a 4-, 5- or 6-membered ring, and X1 is selected from the group consisting of a bond, C2-6alkene, C2-6alkyne, —C(O)—, and —C(O)—(CH2)1-4-, wherein the aliphatic portions of X1 are optionally substituted with one to three members selected from halogen, C1-4alkyl, C1-4substituted alkyl and C1-4haloalkyl;
• each R2 is a member independently selected from the group consisting of halogen, C1-5 alkyl, C1-5substituted alkyl, C3-7cycloalkyl, —CORa, —CO2Ra, —CONRaRb, —ORa, —NRaRb, —NRaCORb, —SORaRb, —SO2Ra and —SO2NRaRb, and wherein when the subscript q is 2 and R2 is alkyl or substituted alkyl, the two R2 members can optionally cyclize to form a ring;
• each R7 is independently selected from the group consisting of halo, C1-10alkyl, C1-10 substituted alkyl, C3,7cycloalkyl, C2-10alkenyl, C2-10 alkynyl, —CN, —NO2, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —NRaCORb, —NRaCO2Rb, —NRaCONRaRb, —S(O)mRa, —NRaS(O)mRb, —SO2NRaRb, a 4- to 7-membered heterocyclo group, aryl and a 5- to 10-membered heteroaryl group, wherein each of said heterocyclo groups, said aryl and heteroaryl groups are optionally substituted with from one to four substituents independently selected from halo, oxo, C1-4 alkyl, C1-4haloalkyl, C3-7 cycloalkyl, —CN, —NO2, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —NRaCORb, —NRaCO2Rb, —NRaCONRaRb, —S(O)mRa, —NRaSO2Rb, and —SO2NRaRb and wherein the subscript m is an integer of from 0 to 2, or optionally Ra and Rb are combined to form a 4-, 5- or 6-membered ring;
• R8 is a member independently selected from the group consisting of hydrogen, C1-4alkyl, and C1-4haloalkyl;
• and each Ra and Rb is independently selected from the group consisting of hydrogen, C1-10 alkyl, C1-10haloalkyl, C3-10 cycloalkyl, heterocyclyl, C2-10 alkenyl, C2-10 alkynyl, aryl, 5- to 6-membered heteroaryl and arylC1-4alkyl;
• and wherein the aliphatic portions of each of said Ra and Rb is optionally substituted with from one to three members selected from the group consisting of halo, —ORn, —OCORn, —OC(O)N(Rn)2, —SRn, —S(O)Rn, —S(O)2Rn, —S(O)2N(Rn)2, —NRnS(O)2Rn, —C(O)N(Rn)2, —C(O)Rn, —NRnC(O)Rn, —NRnC(O)N(Rn)2, —CO2Rn, —NRnCO2Rn, —CN, —NO2, —N(Rn)2 and —NRnS(O)2N(Rn)2, wherein each Rn is independently hydrogen or an unsubstituted C1-6 alkyl;
• and wherein the aryl and heteroaryl portions are optionally substituted with from one to three members selected from halogen, —ORm, —OC(O)N(Rm)2, —SRm, —S(O)Rm, —S(O)2Rm, —S(O)2N(Rm)2, —NRmS(O)2Rm, —C(O)N(Rm)2, —C(O)Rm, —NRmC(O)Rm, —NRmC(O)N(Rm)2, —CO2Rm, —NRmCO2Rm, —CN, —NO2, —N(Rm)2 and —NRmS(O)2N(Rm)2, wherein each Rm is independently hydrogen or an unsubstituted C1-6 alkyl;
• or a pharmaceutically acceptable salt or ester thereof;
• and
• wherein the molecular weight of said compound is less than 1200.

A method of treating inflammatory bowel disease in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound of Formula (I),

• wherein,
• D is selected from the group consisting of O, S, and NR8,
• X, Y, and Z is
• J, K, T, and U are each independently selected from the group consisting of CH, and N;
• the subscript p is an integer of from 0 to 4;
• the subscript q is an integer of from 0 to 4;
• R1 is a member selected from the group consisting of H, C1-10alkyl, C1-10substituted alkyl, C3-7cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, —X1—CORa, —X1—CO2Ra, —X1—CONRaRb, —SO2Ra, a 4- to 7-membered heterocyclo group, aryl and a 5- to 10-membered heteroaryl group, wherein each of said cycloalkyl group, heterocyclo group, aryl group and heteroaryl group is optionally substituted with from 1 to 4 substituents independently selected from halo, C1-10alkyl, C1-10substituted alkyl, C3-7cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, —CN, —NRaCORb, —NRaCONRaRb, —NO2, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —S(O)mRa, —NRaS(O)2Rb, and SO2NRaRb, or optionally Ra and Rb are combined to form a 4-, 5- or 6-membered ring, and X1 is selected from the group consisting of a bond, C2-6alkene, C2-6alkyne, —C(O)—, and —C(O)—(CH2)1-4—, wherein the aliphatic portions of X1 are optionally substituted with one to three members selected from halogen, C1-4alkyl, C1-4substituted alkyl and C1-4haloalkyl;
• each R2 is a member independently selected from the group consisting of halogen, C1-5 alkyl, C1-5substituted alkyl, C3-7cycloalkyl, —CORa, —CO2Ra, —CONRaRb, —ORa, —NRaRb, —NRaCORb, —SORaRb, —SO2Ra and —SO2NRaRb, and wherein when the subscript q is 2 and R2 is alkyl or substituted alkyl, the two R2 members can optionally cyclize to form a ring;
• each R7 is independently selected from the group consisting of halo, C1-10alkyl, C1-10 substituted alkyl, C3,7cycloalkyl, C2-10alkenyl, C2-10 alkynyl, —CN, —NO2, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —NRaCORb, —NRaCO2Rb, —NRaCONRaRb, —S(O)mRa, —NRaS(O)mRb, —SO2NRaRb, a 4- to 7-membered heterocyclo group, aryl and a 5- to 10-membered heteroaryl group, wherein each of said heterocyclo groups, said aryl and heteroaryl groups are optionally substituted with from one to four substituents independently selected from halo, oxo, C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, —CN, —NO2, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —NRaCORb, —NRaCO2Rb, —NRaCONRaRb, —S(O)mRa, —NRaSO2Rb, and —SO2NRaRb and wherein the subscript m is an integer of from 0 to 2, or optionally Ra and Rb are combined to form a 4-, 5- or 6-membered ring;
• R8 is a member independently selected from the group consisting of hydrogen, C1-4alkyl, and C1-4haloalkyl;
• and each Ra and Rb is independently selected from the group consisting of hydrogen, C1-10 alkyl, C1-10haloalkyl, C3-10 cycloalkyl, heterocyclyl, C2-10alkenyl, C2-10 alkynyl, aryl, 5- to 6-membered heteroaryl and arylC1-4alkyl;
• and wherein the aliphatic portions of each of said Ra and Rb is optionally substituted with from one to three members selected from the group consisting of halo, —ORn, —OCORn, —OC(O)N(Rn)2, —SRn, —S(O)Rn, —S(O)2Rn, —S(O)2N(Rn)2, —NRnS(O)2Rn, —C(O)N(Rn)2, —C(O)Rn, —NRnC(O)Rn, —NRnC(O)N(Rn)2, —CO2Rn, —NRnCO2Rn, —CN, —NO2, —N(Rn)2 and —NRnS(O)2N(Rn)2, wherein each Rn is independently hydrogen or an unsubstituted C1-6 alkyl;
• and wherein the aryl and heteroaryl portions are optionally substituted with from one to three members selected from halogen, —ORm, —OC(O)N(Rm)2, —SRm, —S(O)Rm, —S(O)2Rm, —S(O)2N(Rm)2, —NRmS(O)2Rm, —C(O)N(Rm)2, —C(O)Rm, —NRmC(O)Rm, —NRmC(O)N(Rm)2, —CO2Rm, —NRmCO2Rm, —CN, —NO2, —N(Rm)2 and —NRmS(O)2N(Rm)2, wherein each Rm is independently hydrogen or an unsubstituted C1-6 alkyl;
• or a pharmaceutically acceptable salt or ester thereof;
• and
• wherein the molecular weight of said compound is less than 1200.