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US 9,067,905 B2Granted
Sulphone compounds and methods of making and using same
AssigneeZafgen, Inc.
InventorsHazel J. Dyke, Susan M. Cramp, Thomas D. Pallin, Janusz J. Kulagowski, John G. Montana, Robert Zahler
Life of this patent
Estimating the term…
Abstract
The invention provides sulphone compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various sulphone compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
Claims24
A compound represented by:
- and pharmaceutically acceptable salts, stereoisomers, esters and prodrugs thereof, wherein
- B is selected from the group consisting of a bond or (CR9R10)p, wherein p is 1 or 2;
- A is a ring selected from the group consisting of phenyl, a 5-6 membered heteroaryl having 1, 2 or 3 heteroatoms selected from S, N or O, a C3-6cycloalkyl, a 4-7 membered heterocycle, a bridged 6-10 membered heterocycle, and a bridged 6-10 membered cycloalkyl;
- R1 is selected from the group consisting of:
- hydrogen, halogen, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkoxy, C1-6alkyl-S(O)w— wherein w is 0, 1 or 2, C1-6 alkyl-N(Ra)-carbonyl, RfRgN—, RfRgN-carbonyl, RfRgN-carbonyl-N(Ra)—, RfRgNSO2—, C1-6alkyl-carbonyl-N(Ra)—, C1-6alkoxy-carbonyl-N(Ra)—, phenyl, phenyloxy, phenyl-C1-6alkyl-, phenyl-C1-6alkoxy, heteroaryl, heteroaryloxy, heteroaryl-C1-6alkyl, heteroaryl-C1-6alkoxy, heterocyclyl, heterocyclyloxy, heterocyclyl-C1-6alkyl, and heterocyclyl-C1-6alkoxy, wherein said heteroaryl is a 5-6 membered ring having one, two or three heteroatoms selected from O, S, or N, and wherein said phenyl or heteroaryl is optionally substituted with one or more substituents selected from Rb;
- wherein said heterocyclyl is a 4-7 membered ring optionally substituted by one or more substituents selected from Rc and wherein if said heterocyclyl contains a —NH moiety that nitrogen may be optionally substituted by one or more groups Rd;
- and wherein C2-6alkenyl, C2-6alkynyl, C3-6alkenyloxy, and C3-6alkynyloxy may be optionally substituted by one or more substituents selected from Rp, wherein C1-6alkyl and C1-6alkoxy may be optionally substituted by one or more substituents selected from Rp′ and wherein C3-6cycloalkyl and C3-6cycloalkoxy may be optionally substituted by one or more substituents selected from Rp″;
- R2 is selected from the group consisting of:
- hydrogen, halogen, hydroxyl, cyano, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6 alkynyloxy, C3-6cycloalkyloxy, C1-6alkyl-S(O)2—, C3-6cycloalkylC1-4alkyl-, C3-6cycloalkylC1-4alkoxy- , RfRgN-carbonyl, phenyl-C1-6alkyl-, phenyl, phenyoxy, phenyl-C1-6alkoxy-, heteroaryl, heteroaryloxy, heteroaryl-C1-6alkyl, heteroaryl-C1-6alkoxy, heterocyclylC1-6alkyl-, and heterocyclyl-C1-6alkoxy, wherein said heteroaryl is a 5-6 membered monocyclic ring having one, two or three heteroatoms selected from O, S, or N, and optionally substituted with one or more substituents selected from Rb;
- wherein said heterocyclyl is a 4-7 membered ring optionally substituted by one or more substituents selected from Re and wherein if said heterocyclyl contains a —NH moiety that nitrogen may be optionally substituted by one or more groups Rd, and wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C3-6alkenyloxy, or C3-6alkynyloxy may be optionally substituted by one or more substituents selected from halogen, hydroxyl, RaRa′N—, or cyano, and C3-6cycloalkyl and C3-6cycloalkoxy may be optionally substituted by one or more substituents selected from halogen, hydroxyl, RaRa′N—, cyano and C1-6alkyl;
- or
- R1 and R2 may be joined together with the carbons to which they are attached to form a 5-7 membered saturated, partially unsaturated, or unsaturated ring, optionally having 1, 2 or 3 heteroatoms selected from O, NRh, or S(O)r where r is 0, 1, or 2, wherein the formed 5-7 membered ring is optionally substituted on a carbon by one or more groups Re, and wherein the formed ring may be optionally bridged by a moiety selected from —O—, CH2, —(CH2)2—, cis-CH═CH—, NRh;
- or —CH2NRh—;
- and wherein if R1 is hydrogen, R2 may not be hydrogen;
- R3 is selected from the group consisting of hydrogen, hydroxyl, cyano, halogen, C1-6alkyl, or, C1-6alkoxy, wherein C1-6alkyl, and C1-6alkoxy may be optionally substituted by one or more halogens;
- R4 is selected from the group consisting of hydrogen, hydroxyl, cyano, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkoxy, C1-6alkyl-S(O), wherein w is 0, 1 or 2, RfRgN—, RfRgN-carbonyl, RfRgN-carbonyl-N(Ra)—, RfRgN—SO2—, C1-6alkyl-carbonyl-N(Ra)—, and C1-6alkoxy-carbonyl-N(Ra)—, wherein C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C3-6alkenyloxy, or C3-6alkynyloxy may be optionally substituted by one or more substituents selected from Rp;
- wherein C1-6alkyl and C1-6alkoxy may be optionally substituted by one or more substituents selected from Rp′, and wherein C3-6cycloalkyl may be optionally substituted by one or more substituents selected from Rp″;
- m is 1 or 2;
- R5 is selected, independently for each occurrence, from the group consisting of hydrogen, hydroxyl, cyano, halogen, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C3-6cycloalkyl, or C1-6alkoxy, or RfRgN—, wherein C1-6alkyl, C2-6alkenyl, C3-6 alkynyl, C3-6cycloalkyl, or C1-6alkoxy may be optionally substituted with one or more halogens;
- R6 is selected from the group consisting of hydrogen, hydroxyl, cyano, halogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkoxy, C1-6alkyl-S(O)w— wherein w is 0, 1 or 2, RfRgN—, RfRgN-carbonyl-, RfRgN-carbonyl-N(Ra)—, RfRgN—SO2—, C1-6alkyl-carbonyl-N(Ra)—, C1-6alkylsulphonylN(Ra)—, C1-6alkoxycarbonyl-N(Ra)—, phenyl, phenoxy, phenyl-C1-6alkoxy, heteroaryl, heteroaryloxy, heterocycloxy, heteroaryl-C1-6alkyl, heteroaryl-C1-6alkoxy-, heterocyclyl-C1-6alkyl-, and heterocyclyl-C1-6alkoxy-, wherein said heteroaryl is a 5-6 membered monocyclic ring having one, two or three heteroatoms selected from O, S, or N, and optionally substituted with one or more substituents selected from Rb;
- wherein said heterocyclyl is a 4-7 membered ring optionally substituted by one or more substituents selected from Rc and wherein if said heterocyclyl contains a —NH moiety that nitrogen may be optionally substituted by one or more groups Rd, and, wherein C1-6alkyl and C1-6alkoxy may be optionally substituted by Rp′, wherein C2-6alkenyl, and C2-6 alkynyl may be optionally substituted by one or more substituents selected from Rp;
- and wherein C3-6cycloalkyl or C3-6 cycloalkoxy may be optionally substituted by one or more substituents selected from Rp″;
- R7 and R8 are independently selected from the group consisting of hydrogen, halogen, C1-6alkoxy, C2-6alkenyl, C3-6alkynyl, and C3-6cycloalkyl wherein C2-6alkenyl, C3-6alkynyl is optionally substituted by Rp, wherein C1-6alkyl is optionally substituted by Rp′;
- and wherein C3-6 cycloalkyl is optionally substituted by Rp″;
- or R7 and R8 taken together with the carbon to which they are attached form a cyclopropyl ring or 4-6 membered ring which may optionally have one group selected from N(Rh), O or S(O)r wherein r is 0, 1, or 2;
- R9 and R10 are independently selected from the group consisting of hydrogen, C1-6alkoxy, halogen, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, and C3-6cycloalkyl wherein C2-6alkenyl, C3-6alkynyl is optionally substituted by Rp, C1-6alkyl and C1-6alkoxy is optionally substituted by Rp′;
- and C3-6cycloalkyl is optionally substituted by Rp″;
- or R9 and R10 taken together with the carbon to which they are attached form a cyclopropyl ring or 4-6 membered ring which may optionally have one group selected from N(Rh), O or S(O)r wherein r is 0, 1, or 2;
- W is —S(O)n—, or —S(O)(NR11)—;
- n is 1 or 2;
- R11 is selected from the group consisting of H, C1-3alkyl, CN;
- q is 0, 1, 2, or 3;
- Ra and Ra′ are independently selected, for each occurrence, from the group consisting of hydrogen and C1-6alkyl, or Ra and Ra′ when they occur together may form a 4-6 membered heterocyclic ring, wherein C1-6alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, oxo and hydroxyl, and wherein the heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, alkyl, oxo or hydroxyl;
- Rb is independently selected, for each occurrence, from the group consisting of halogen, hydroxyl, cyano, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkoxy, C1-6alkyl-S(O)w— wherein w is 0, 1 or 2, C1-6alkylN(Ra)—, C1-6alkyl-N(Ra)carbonyl, RaRa′N—, RaRa′N-carbonyl-, RaRa′N-carbonyl-N(Ra)—;
- RaRa′N—SO2—, and C1-6alkyl-carbonyl-N(Ra)—, wherein C2-6alkenyl, C3-6alkynyl, or C1-6alkoxy may be optionally substituted by one or more substituents selected from Rp;
- wherein C3-6cycloalkyl and C3-6cycloalkoxy may be optionally substituted by one or more substituents selected from Rp ″, and wherein C1-6alkyl may be optionally substituted by one or more substituents selected from Rp′;
- Rc for each occurrence is independently selected from the group consisting of, hydroxyl, cyano, oxo, halogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C1-6alkyl-S(O)w—, wherein w is 0, 1 or 2, C1-6alkyl-NRa—, C1-6alkylC3-6cycloalkyl-, C3-6cycloalkylC1-6alkyl, RaRa′N—, C1-6alkylcarbonyl-N(Ra)—;
- C1-6alkoxycarbonyl-N(Ra)—, RaRa′N—SO2—, RaRa′N-carbonyl-, RaRa′N-carbony-N(Ra), wherein C1-6alkenyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, or C1-6alkoxy may be optionally substituted by Rt;
- Rd is independently selected for each occurrence from the group consisting of C1-6alkyl, C1-6alkylcarbonyl or C1-6alkylsulphonyl, wherein C1-6alkyl is optionally substituted by one or more substituents selected from halogen, hydroxyl, and RaRa′N—;
- Re is independently selected for each occurrence from the group consisting of hydroxyl, cyano, halogen, oxo, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl, C1-4alkoxy, C3-6alkenyloxy, C3-6allcynyloxy, C3-6cycloalkoxy, C3-6cycloalkyl-C1-4alkyloxy-, C1-4alkyl-S(O)w—wherein w is 0, 1 or 2, RaRa′N—, RaRa′N- carbonyl, RaRa′N-carbonyl-N(Ra)—, RaRa′N—SO2—, C1-6alkyl-carbonyl-N(Ra)—, C1-6alkyl-SO2—N(Ra)—, C1-6alkoxycarbonyl-, C1-4alkoxycarbonyl-N(Ra)—, wherein C2-4alkenyl, and C2-4alkynyl may be optionally substituted by one or more substituents selected from Rp;
- wherein C1-4alkyl and C1-4alkoxy may optionally substituted by one or more substituents selected from Rp′;
- and wherein C3-6cycloalkyl or C3-6cycloalkoxy may be optionally substituted by Rp″;
- Rfand Rg, independently for each occurrence, are selected from group consisting of hydrogen, C1-4alkyl optionally substituted by one or more substituents selected from Rp′, and C3-6cycloalkyl optionally substituted by one or more substituents selected from Rp″,
- or Rfand Rgtaken together with the nitrogen to which they are attached form a 4-7 membered heterocyclyl, optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxyl, oxo, cyano, C1-6alkyl, C1-6alkoxy, RaRa′N—, C1-6alkylcarbonyl-N(Ra)—;
- C1-6alkoxycarbonyl-N(Ra)—, RaRa′N—SO2—, RaRa′N-carbonyl-, RaRa′N-carbonyl-N(Ra), and wherein C1-6alkyl or C1-6alkoxy may be optionally substituted by at least one or more substituent selected from the group consisting of RaRa′N—, halogen, hydroxy, cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, C1-4alkylS(O)w—, wherein w is 0, 1 or 2;
- Rp is independently selected, for each occurrence, from the group consisting of RaRa′N—, halogen, hydroxy, cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, and C1-4alkylS(O)w—, wherein w is 0, 1 or 2;
- Rp′ is independently selected, for each occurrence, from the group consisting of RaRa′N—, halogen, hydroxy, cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, C1-4alkylS(O)w— and C3-6cycloalkyl, wherein w is 0, 1 or 2 and wherein C3-6cycloalkyl is optionally substituted with Rp″;
- Rp″ is independently selected, for each occurrence, from the group consisting of RaRa′N—, halogen, hydroxy, cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, C1-4alkylS(O)w and C1-6alkyl, wherein w is 0, 1 or 2 and C1-6alkyl is optionally substituted by one or more substituents selected from Rp;
- Rt is independently selected from the group consisting of RaRa′N—, halogen, cyano, hydroxyl and C1-6alkoxy;
- Rh is independently selected from the group consisting of hydrogen, C1-6alkyl, C3-6alkenyl (wherein any unsaturated bond is not directly attached to a nitrogen), C3-6alkynyl(wherein any unsaturated bond is not directly attached to a nitrogen), C3-6cycloalkyl, C1-6alkyl-S(O)2—, and C1-6alkyl-N(Ra)carbonyl, wherein C1-6alkyl is optionally substituted by one or more substituents selected from Rp′;
- wherein C3-6alkenyl and C3-6alkynyl are optionally substituted by at least one substituent selected from Rp, and wherein C3-6cycloalkyl is optionally substituted by at least one substituent selected from Rp″.
48 more elements
A compound represented by Formula IV:
- or pharmaceutically acceptable salts, esters, stereoisomers, or prodrugs thereof, wherein
- R1 is selected from the group consisting of:
- hydrogen, halogen, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkoxy, C1-6alkyl-S(O),— wherein w is 0, 1 or 2, C1-6alkyl-N(Ra)-carbonyl, RfRgN—, RfRgN-carbonyl, RfRgN-carbonyl-N(Ra)—, RfRgNSO2—, C1-6alkyl-carbonyl-N(Ra)—, C1-6 alkoxy-carbonyl-N(Ra)—, phenyl, phenyloxy, phenyl-C1-6alkyl-, phenyl-C1-6alkoxy, heteroaryl, heteroaryloxy, heteroaryl-C1-6alkyl, heteroaryl-C1-6alkoxy, heterocyclyl, heterocyclyloxy, heterocyclyl-C1-6alkyl, and heterocyclyl-C1-6alkoxy, wherein said heteroaryl is a 5-6 membered ring having one, two or three heteroatoms selected from O, S, or N, and wherein said phenyl or heteroaryl is optionally substituted with one or more substituents selected from Rb;
- wherein said heterocyclyl is a 4-7 membered ring optionally substituted by one or more substituents selected from Rcand wherein if said heterocyclyl contains a —NH moiety that nitrogen may be optionally substituted by one or more groups Rd;
- and wherein C2-6alkenyl, C2-6alkynyl, C3-6alkenyloxy, and C3-6alkynyloxy may be optionally substituted by one or more substituents selected from RP, and wherein C1-6alkyl and C1-6alkoxy may be optionally substituted by one or more substituents selected from Rp′ and wherein C3-6cycloalkyl and C3-6cycloalkoxy may be optionally substituted by one or more substituents selected from Rp″;
- R2 is selected from the group consisting of:
- halogen, hydroxyl, cyano, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C2-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkyloxy, C1-6alkyl-S(O)2—, C3-6cycloalkylC1-4alkyl-, C3-6cycloalkylC1-4alkoxy- , RfRgN-carbonyl, phenyl-C1-6alkyl-, phenyl, phenyoxy, phenyl-C1-6alkoxy-, heteroaryl, heteroaryloxy, heteroaryl-C1-6alkyl, heteroaryl-C1-6alkoxy, heterocyclylC1-6alkyl-, and heterocyclyl-C1-6alkoxy, wherein said heteroaryl is a 5-6 membered monocyclic ring having one, two or three heteroatoms selected from O, S, or N, and optionally substituted with one or more substituents selected from Rb;
- wherein said heterocyclyl is a 4-7 membered ring optionally substituted by one or more substituents selected from Rc and wherein if said heterocyclyl contains a —NH moiety that nitrogen may be optionally substituted by one or more groups Rd, and wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C3-6alkenyloxy, or C3-6alkynyloxy may be optionally substituted by one or more substituents selected from halogen, hydroxyl, RaRa′N—, or cyano, and wherein C3-6cycloalkyl and C3-6cycloalkoxy may be optionally substituted by one or more substituents selected from halogen, hydroxyl, RaRa′N—, cyano and C1-6alkyl;
- or
- R1 and R2 may be joined together with the carbons to which they are attached to form a 5-7 membered saturated, partially unsaturated, or unsaturated ring, optionally having 1, 2 or 3 heteroatom groups selected from O, NRh, or S(O)r where r is 0, 1, or 2, wherein the formed 5-7 membered ring is optionally substituted on a carbon by one or more groups Re, and wherein the formed ring may be optionally bridged by a moiety selected from CH2, —(CH2)2—, cis-CH═CH—, NRh;
- or —CH2NRh—;
- and wherein if R1 is hydrogen, R2 may not be hydrogen;
- R5 is selected, independently for each occurrence, from the group consisting of hydrogen, hydroxyl, cyano, halogen, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C3-6cycloalkyl, or C1-6alkoxy, or RfRgN—, wherein C1-6alkyl, C2-6alkenyl, C3-6 alkynyl, C3-6cycloalkyl, or C1-6alkoxy may be optionally substituted with one or more halogens;
- R6 is selected from the group consisting of hydrogen, hydroxyl, cyano, halogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkoxy, C1-6alkyl-S(O)w— wherein w is 0, 1 or 2, RfRgN—, RfRgN-carbonyl-, RfRgN—carbonyl-N(Ra)—, RfRgN—SO2—, C1-6alkyl-carbonyl-N(Ra)—, C1-6alkylsulphonylN(Ra)—, C1-6alkoxycarbonyl-N(Ra)—, phenyl, phenoxy, phenyl-C1-6alkyl-, phenyl-C1-6alkyoxy, heteroaryl, heteroaryloxy, heterocycloxy, heteroaryl-C1-6alkyl, heteroaryl-C1-6alkoxy-, heterocyclyl-C1-6alkyl-, and heterocyclyl-C1-6alkoxy-, wherein said heteroaryl is a 5-6 membered monocyclic ring having one, two or three heteroatoms selected from O, S, or N, and optionally substituted with one or more substituents selected from Rb;
- wherein said heterocyclyl is a 4-7 membered ring optionally substituted by one or more substituents selected from Rc and wherein if said heterocyclyl contains a —NH moiety that nitrogen may be optionally substituted by one or more groups Rd, and, wherein C1-6alkyl and C1-6alkoxy may be optionally substituted by Rp′, wherein C2-6alkenyl, and C2-6 alkynyl may be optionally substituted by one or more substituents selected from Rp;
- and wherein C3-6cycloalkyl or C3-6 cycloalkoxy may be optionally substituted by one or more substituents selected from Rp″;
- Ra and Ra′ are independently selected, for each occurrence, from the group consisting of hydrogen and C1-6alkyl, or Ra and Ra′ when they occur together may form a 4-6 membered heterocyclic ring, wherein C1-6alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, oxo and hydroxyl, and wherein the heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, alkyl, oxo or hydroxyl;
- Rb is independently selected, for each occurrence, from the group consisting of halogen, hydroxyl, cyano, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C3-6alkenyloxy, C3-6 alkynyloxy, C3-6cycloalkoxy, C3-6cycloalkyl, C1-6alkyl-S(O)w—wherein w is 0, 1 or 2, C1-6alkylN(Ra)—, C1-6alkyl-N(Ra)carbonyl, RaRa′N—, RaRa′N-carbonyl-, RaRa′N-carbonyl-N(Ra)—;
- RaRa′N—SO2—, and C1-6alkyl-carbonyl-N(Ra)—, wherein C2-6alkenyl, C2-6alkynyl, or C1-6alkoxy may be optionally substituted by one or more substituents selected from Rp;
- wherein C3-6cycloalkyl may be optionally substituted by one or more substituents selected from Rp″, and wherein C1-6alkyl may be optionally substituted by one or more substituents selected from Rp′;
- Rc for each occurrence is independently selected from the group consisting of, hydroxyl, cyano, oxo, halogen, C1-6alkyl, C2-6alkenyl, C3-6 alkynyl, C3-6cycloalkyl, C1-6alkoxy, C1-6alkyl-S(O)w—, wherein w is 0, 1 or 2, C1-6alkyl-NRa—, C1-6alkylC3-6cycloalkyl-, C3-6cycloalkylC1-6alkyl, RaRa′N—, C1-6alkylcarbonyl-N(Ra)—;
- C1-6alkoxycarbonyl-N(Ra)—, RaRa′N—SO2—, RaRa′N-carbonyl-, RaRa′N—carbonyl-N(Ra)—,wherein C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C3-6cycloalkyl, or C1-6alkoxy may be optionally substituted by Rt;
- Rd is independently selected for each occurrence from the group consisting of C1-6alkyl, C1-6alkylcarbonyl or C1-6alkylsulphonyl, wherein C1-6alkyl is optionally substituted by one or more substituents selected from halogen, hydroxyl, and RaRa′N—;
- Re is independently selected for each occurrence from the group consisting of hydroxyl, cyano, halogen, oxo, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl, C1-4alkoxy, C3-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkoxy, C3-6cycloalkyl-C1-4alkoxy-, C1-4alkyl-S(O )w—wherein w is 0, 1 or 2, RaRa'N—, RaRa′N-carbonyl, RaRa′N-carbonyl-N(Ra)—, RaRa′N—SO2—, C1-6alkyl-carbonyl-N(Ra)—, C1-6alkyl-SO2—N(Ra)—, C1-6alkoxycarbonyl-, C1-4alkoxycarbonyl-N(Ra)—, wherein C2-4alkenyl, and C2-4alkynyl may be optionally substituted by one or more substituents selected from Rp;
- wherein C1-4alkyl and C1-4alkoxy may optionally substituted by one or more substituents selected from Rp′;
- and wherein C3-6cycloalkyl or C3-6cycloalkoxy may be optionally substituted by Rp″;
- Rf and Rg, independently for each occurrence, are selected from group consisting of hydrogen, C1-4alkyl optionally substituted by one or more substituents selected from Rp′, and C3-6cycloalkyl optionally substituted by one or more substituents selected from Rp″,
- or Rf and Rg taken together with the nitrogen to which they are attached form a 4-7 membered heterocyclyl, optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxyl, oxo, cyano, C1-6alkyl, C1-6alkoxy, RaRa′N—, C1-6alkylcarbonyl-N(Ra)—;
- C1-6alkoxycarbonyl-N(Ra)—, RaRa′N—SO2—, RaRa′N-carbonyl-, RaRa′N-carbonyl-N(Ra), and wherein C1-6alkyl or C1-6alkoxy may be optionally substituted by at least one or more substituent selected from the group consisting of RaRa′N, halogen, hydroxy, and cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, C1-4alkylS(O)w—, wherein w is 0, 1 or 2;
- Rp is independently selected, for each occurrence, from the group consisting of RaRa′N—, halogen, hydroxy, cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, and C1-4alkylS(O)w—, wherein w is 0, 1 or 2;
- Rp′ is independently selected, for each occurrence, from the group consisting of RaRa′N—, halogen, hydroxy, cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, C1-4alkylS(O)w— and C3-6cycloalkyl, wherein w is 0, 1 or 2 and wherein C3-6cycloalkyl is optionally substituted with Rp″;
- Rp″ is independently selected, for each occurrence, from the group consisting of RaRa′N—, halogen, hydroxy, cyano, C1-4alkoxycarbonyl, RaRa′N-carbonyl, RaRa′N—SO2—, C1-4alkoxy, C1-4alkylS(O)w and C1-6alkyl, wherein w is 0, 1 or 2 and wherein C1-6alkyl is optionally substituted by one or more substituents selected from Rp;
- Rt is independently selected from the group consisting of RfRgN—, halogen, cyano, hydroxyl and C1-6alkoxy;
- Rh is independently selected from the group consisting of hydrogen, C1-6alkyl, C3-6alkenyl (wherein any unsaturated bond is not directly attached to a nitrogen), C3-6alkynyl(wherein any unsaturated bond is not directly attached to a nitrogen), C3-6cycloalkyl, C1-6alkyl-S(O)2—, and C1-6alkyl-N(Ra)carbonyl, wherein C1-6alkyl is optionally substituted by one or more substituents selected from Rp′;
- wherein C3-6alkenyl and C3-6alkynyl are optionally substituted by at least one substituent selected from Rp, and wherein C3-6cycloalkyl is optionally substituted by at least one substituent selected from Rp″.
32 more elements
A compound selected from the group consisting of:
- 2-(Benzenesulphonylmethyl)-5-ethylbenzoic acid;
- 6-(Benzenesulphonylmethyl)-3-ethyl-2-methoxy-benzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-propyl-benzoic acid;
- 6-(Benzenesulphinylmethyl)-3-ethyl-2-methoxy-benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-cyclopropyl-2-methoxy-benzoic acid;
- 6-(4-Chlorobenzenesulphonylmethyl)-3-ethyl-2-methoxy-benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-bromo-2-methoxy-benzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-methyl-benzoic acid;
- 3-Ethyl-2-methoxy-6-(2-methylbenzenesulphonyl-methyl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxy-benzoic acid;
- 6-(1-Benzenesulphonylethyl)-3-ethyl-2-methoxy-benzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-(oxazol-5-yl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(isothiazol-5-yl)-2-methoxy-benzoic acid;
- 2-(Benzenesulphonylmethyl)-5-furan-3-yl)benzoic acid;
- 2-(Benzenesulphonylmethyl)-5-(oxazol-5-yl)benzoic acid;
- 3-(Furan-3-yl)-2-methoxy-6-(2-methyl-benzenesulphonylmethyl)benzoic acid;
- 6-(3-Chlorobenzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(oxazol-4-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl-3-(isothiazol-4-yl)-2-methoxybenzoic acid;
- (Z)-6-((2-(3-(Diethylamino)prop-1-enyl)benzenesulfonyl)methyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- (E)-6-((2-(3-(diethylamino)prop-1-enyl)benzenesulfonyl)methyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-2-ethoxy-3-(furan-3-yl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-hydroxy-benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-(2-hydroxyethoxy)benzoic acid;
- 6-(2-(3-Diethylaminopropyl)benzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 3-(3-Furan-3-yl)-2-methoxy-6-(pyridin-3-ylsulphonylmethyl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(isoxazol-3-yl)-2-methoxybenzoic acid;
- 3-(Furan-3-yl)-2-methoxy-6-(2-methoxybenzenesulphonylmethyl) benzoic acid;
- 3-(Furan-3-yl)-2-methoxy-6-(pyridin-2-ylsulphonylmethyl)benzoic acid;
- 3-Ethyl-6-(4-fluorobenzenesulphonylmethyl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-3-cyano-2-methoxy-benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(furan-2-yl)-2-methoxy-benzoic acid;
- 2-(2-Aminoethoxy)-6-(benzenesulphonylmethyl)-3-(furan-3-yl)benzoic acid hydrochloride;
- 2-(2-Aminoethoxy)-6-(3-chlorobenzenesulphonylmethyl)-3-(furan-3-yl)benzoic acid hydrochloride;
- 2-(2-Aminoethoxy)-6-(4-fluorobenzenesulphonylmethyl)-3-(furan-3-yl)benzoic acid hydrochloride;
- 2-(2-Aminoethoxy)-3-(furan-3-yl)-6-(2-methoxybenzenesulphonylmethyl)benzoic acid hydrochloride;
- 6-(2-Chlorobenzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(3-Fluorobenzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(2-Fluorobenzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 3-(Furan-3-yl)-6-(3-methoxybenzenesulphonylmethyl)-2-methoxybenzoic acid;
- 2-(2-Aminoethoxy)-3-ethyl-6-benzenesulphonylmethylbenzoic acid hydrochloride;
- 2-(3-Aminopropoxy)-6-benzenesulphonylmethyl-3-(furan-3-yl)benzoic acid hydrochloride;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-(thien-2-yl)benzoic acid;
- 6-(4-Fluorobenzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-phenylbenzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-(3-pyridyl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-(pyrazol-3-yl)benzoic acid;
- 2-Methoxy-6-(2-methylbenzenesulphonylmethyl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-(thiazol-2-yl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-(2-methoxyethoxy)-benzoic acid;
- 6-Benzenesulphonylmethyl-2-(2-dimethylaminoethoxy)-3-(furan-3-yl)benzoic acid hydrochloride;
- 6-(Benzenesulphonylmethyl)-2-methyoxy-3-(thien-3-yl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-2-(cyanomethoxy)-3-(furan-3-yl)benzoic acid;
- 2-(2-Aminoethylamino)-6-benzenesulphonylmethyl-3-(furan-3-yl)-benzoic acid hydrochloride;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-[2-(methylamino)-ethoxy]benzoic acid hydrochloride;
- 6-(Benzenesulphonylmethyl)-3-ethyl-2-(2-methyl-2H-pyrazol-3-yl)-benzoic acid;
- 2-(2-Aminopropoxy)-6-(benzenesulphonylmethyl)-3-(furan-3-yl)-benzoic acid hydrochloride;
- 6-Benzenesulphonylmethyl-3-ethyl-2-(1-methyl-1H-pyrazol-3-yl)-benzoic acid;
- 2-(3-Aminopropyl)-6-(benzenesulphonylmethyl)-3-(furan-3-yl)-benzoic acid hydrochloride;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-(pyrazol-1-yl)benzoic acid;
- 2-(Benzenesulphonylmethyl)-5-(2-methyl-2H-pyrazol-3-yl)benzoic acid;
- 2-(Benzenesulphonylmethyl)naphthalene-l-carboxylic acid;
- 3-(Furan-3-yl)-6-(2-hydroxybenzenesulphonylmethyl)-2-methoxybenzoic acid;
- 3-(Furan-3-yl)-6-(3-hydroxybenzenesulphonylmethyl)-2-methoxy-benzoic acid;
- 2-(Benzenesulphonylmethyl)-5-(2-methylfuran-3-yl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-ethyl-2-(1H-pyrazol-3-yl)benzoic acid;
- 3-(Furan-3-yl)-2-methoxy-6-(piperidine-1-ylsulphonylmethyl)benzoic acid;
- 3-(Furan-3-yl)-2-methoxy-6-(pyrrolidin-1-ylsulphonylmethyl)-benzoic acid;
- 6-[2-(2-Diethylaminoethylamino)benzenesulphonylmethyl]-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-2-ethyl-3-(furan-3-yl)benzoic acid;
- 6-[2-(2-Diethylaminoethoxy)benzenesulphonylmethyl]-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-(prop-1-yn-1-yl)benzoic acid;
- 2-(Benzenesulphonylmethyl)-6-methoxybenzoic acid;
- 6-(Cyclohexanesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-2-(carbamoylmethoxy)-3-(furan-3-yl)-benzoic acid;
- (Z)-6-((2-(3-(Diethylamino)prop-1-enyl)-4-fluorobenzenesulfonyl)methyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 3-(Furan-3-yl)-6-(3-hydroxypyrrolidine-1-ylsulphonylmethyl)-2-methoxybenzoic acid;
- 2-(Azetidin-3-yloxy)-6-(benzenesulphonylmethyl)-3-(furan-3-yl)-benzoic acid hydrochloride;
- 6-(Bicyclo[2.2.2]octane-2-ylsulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Bicyclo[2.2.2]octane-2-ylsulphonylmethyl)-2-methoxy-3-(tetrahydrofuran-3-yl)benzoic acid;
- 6-(7-Azabicyclo[2.2.1]heptane-7-ylsulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(4,4-Difluoropiperidine-1-ylsulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Bicyclo[2.2.1]heptane-7-ylsulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-methylamino benzoic acid;
- 6-(8-Azabicyclo[3.2.1]octane-8-ylsulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid;
- 2-(Benzenesulphonylmethyl)-8-methoxynaphthalene-1-carboxylic acid;
- 6-[2-(3-Diethylaminopropylamino)benzenesulphonylmethyl]-3-(furan-3-yl)-2-methoxybenzoic acid;
- (Z)-2-(Cyanomethoxy)-6-((2-(3-(diethylamino)prop-1-enyl)-4-fluorobenzenesulfonyl)methyl)-3-(furan-3-yl)benzoic acid;
- (Z)-3-(Furan-3-yl)-2-methoxy-6-((2-(3-(piperidin-l-yl)prop-1-enyl)benzenesulfonyl)methyl)benzoic acid ;
- 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2,4-dimethoxybenzoic acid;
- 6-[2-(2-Diethylaminomethylazetidin-1-yl)-benzenesulphonylmethyl]-3-(furan-3-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-2-(cyanomethylamino)-3-(furan-3-yl)benzoic acid;
- 6-(Benzenesulphonylmethyl)-3-(imidazol-1-yl)-2-methoxybenzoic acid;
- 6-(Benzenesulphonylmethyl)-2-methoxy-3-(thiazol-5-yl)benzoic acid;
- 3-(Furan-3-yl)-2-methoxy-6-[(S-phenylsulphonimidoyl)methyl]benzoic acid;
- 3-(Furan-3-yl)-2-methoxy-6-[(N-methyl-S-phenylsulphonimidoyl)methyl]benzoic acid;
- and 6-[(N-cyano-S-phenylsulphonimidoyl)methyl]-3-(furan-3-yl)-2-methoxybenzoic acid;
- and pharmaceutically acceptable salts and stereoisomers thereof.
95 more elements
A compound selected from the group consisting of 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid, 2-(2-Aminoethoxy)-6-(benzenesulphonylmethyl)-3-(furan-3-yl)benzoic acid hydrochloride, 6-(4-Fluorobenzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid, 6-(3-Fluorobenzenesulphonylmethyl)-3-(furan-3-yl)-2-methoxybenzoic acid, 6-(Benzenesulphonylmethyl)-2-(cyanomethoxy)-3-(furan-3-yl)benzoic acid, 6-(Benzenesulphonylmethyl)-3-(furan-3-yl)-2-methylamino benzoic acid, 6-(Benzenesulphonylmethyl)-2-(cyanomethylamino)-3-(furan-3-yl)benzoic acid, and 6-(Benzenesulphonylmethyl)-3-(isothiazol-5-yl)-2-methoxy-benzoic acid.
A compound selected from the group consisting of (Z)-6-((2-(3-(Diethylamino)prop-1-enyl)benzenesulfonyl)methyl)-3-(furan-3-yl)-2-methoxybenzoic acid 6-[2-(3-Diethylaminopropyl)benzenesulphonylmethyl]-3-(furan-3-yl)-2-methoxybenzoic acid, (Z)-6-((2-(3-(Diethylamino)prop-1-enyl)-4-fluorobenzenesulfonyl)methyl)-3-(furan-3-yl)-2-methoxybenzoic acid, 6-[2-(3-Diethylaminopropylamino)benzenesulphonylmethyl]-3-(furan-3-yl)-2-methoxybenzoic acid, (Z)-2-(Cyanomethoxy)-6-((2-(3-(diethylamino)prop-1-enyl)-4-fluorobenzenesulfonyl)methyl)-3-(furan-3-yl)benzoic acid, and (Z)-3-(Furan-3-yl)-2-methoxy-6-((2-(3-(piperidin-1-yl)prop-1-enyl)benzenesulfonyl)methyl)benzoic acid.
Dependencies are inferred from the claim text.