MX2013005454A - Inhibidores de nampt y rock. - Google Patents
Inhibidores de nampt y rock.Info
- Publication number
- MX2013005454A MX2013005454A MX2013005454A MX2013005454A MX2013005454A MX 2013005454 A MX2013005454 A MX 2013005454A MX 2013005454 A MX2013005454 A MX 2013005454A MX 2013005454 A MX2013005454 A MX 2013005454A MX 2013005454 A MX2013005454 A MX 2013005454A
- Authority
- MX
- Mexico
- Prior art keywords
- carboxamide
- dihydro
- phenyl
- carbamoyl
- isoindol
- Prior art date
Links
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 title abstract description 19
- 239000011435 rock Substances 0.000 title abstract 3
- 239000003112 inhibitor Substances 0.000 title description 15
- 102100033223 Nicotinamide phosphoribosyltransferase Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000000203 mixture Substances 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 10
- -1 thieno [3,2-c] pyridinyl Chemical group 0.000 claims description 2049
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 1277
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 713
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 267
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 182
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 152
- 125000000217 alkyl group Chemical group 0.000 claims description 127
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 113
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 110
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 103
- 125000003342 alkenyl group Chemical group 0.000 claims description 96
- 125000000304 alkynyl group Chemical group 0.000 claims description 96
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 82
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 76
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 72
- 125000003118 aryl group Chemical group 0.000 claims description 68
- 229910052794 bromium Inorganic materials 0.000 claims description 67
- 125000000623 heterocyclic group Chemical group 0.000 claims description 66
- 229910052801 chlorine Inorganic materials 0.000 claims description 65
- 229910052731 fluorine Inorganic materials 0.000 claims description 65
- 229910052740 iodine Inorganic materials 0.000 claims description 65
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 64
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 58
- 125000000565 sulfonamide group Chemical group 0.000 claims description 55
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 53
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 53
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 50
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 42
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 42
- 229910052799 carbon Inorganic materials 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- AHAAUUNDDOAEGE-UHFFFAOYSA-N isoindole-2-carboxamide Chemical compound C1=CC=CC2=CN(C(=O)N)C=C21 AHAAUUNDDOAEGE-UHFFFAOYSA-N 0.000 claims description 37
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 claims description 36
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 35
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 35
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 28
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 27
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 26
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 26
- IZFVDVUUMKZDCT-UHFFFAOYSA-N 1,3-dihydroisoindole-2-carboxamide Chemical compound C1=CC=C2CN(C(=O)N)CC2=C1 IZFVDVUUMKZDCT-UHFFFAOYSA-N 0.000 claims description 25
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 24
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 24
- 101100240519 Caenorhabditis elegans nhr-13 gene Proteins 0.000 claims description 23
- 101100240520 Caenorhabditis elegans nhr-14 gene Proteins 0.000 claims description 23
- 125000003386 piperidinyl group Chemical group 0.000 claims description 23
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 21
- MCTNCTSARWYYBF-UHFFFAOYSA-N pyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1=CN=CC2=CN(C(=O)N)C=C21 MCTNCTSARWYYBF-UHFFFAOYSA-N 0.000 claims description 20
- JUOYWJOZGLHNAK-UHFFFAOYSA-N 1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1=NC=C2CN(C(=O)N)CC2=C1 JUOYWJOZGLHNAK-UHFFFAOYSA-N 0.000 claims description 19
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 19
- JBUPIUUZCPCWIP-UHFFFAOYSA-N 1-[4-(3-methylbutylcarbamoyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound CC(CCNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N)C JBUPIUUZCPCWIP-UHFFFAOYSA-N 0.000 claims description 18
- OZICCGREQCQJKP-UHFFFAOYSA-N 1-[4-(3-phenylpropylcarbamoyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1(=CC=CC=C1)CCCNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N OZICCGREQCQJKP-UHFFFAOYSA-N 0.000 claims description 18
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 18
- 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 18
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 18
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 17
- 201000011510 cancer Diseases 0.000 claims description 17
- 101100079984 Caenorhabditis elegans nhr-9 gene Proteins 0.000 claims description 16
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 16
- 201000001320 Atherosclerosis Diseases 0.000 claims description 13
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- DLICCRWEQRSYNH-UHFFFAOYSA-N pyrrolo[3,4-b]pyridine-6-carboxamide Chemical compound C1=CC=NC2=CN(C(=O)N)C=C21 DLICCRWEQRSYNH-UHFFFAOYSA-N 0.000 claims description 13
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 108020004021 3-ketosteroid receptors Proteins 0.000 claims description 12
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 12
- 208000006673 asthma Diseases 0.000 claims description 12
- 125000000532 dioxanyl group Chemical group 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000002971 oxazolyl group Chemical group 0.000 claims description 12
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 12
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 12
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 12
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- HHSXKHODJRRGHF-UHFFFAOYSA-N 1-[6-(pyridine-3-carbonylamino)hexyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound N1=CC(=CC=C1)C(=O)NCCCCCCC1N(CC2=CC=CC=C12)C(=O)N HHSXKHODJRRGHF-UHFFFAOYSA-N 0.000 claims description 11
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 11
- 208000024827 Alzheimer disease Diseases 0.000 claims description 11
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 230000002757 inflammatory effect Effects 0.000 claims description 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 11
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 10
- 125000000070 5-oxo-L-proline group Chemical group [H]N1[C@@](C(=O)[*])([H])C([H])([H])C([H])([H])C1=O 0.000 claims description 10
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims description 10
- 201000006417 multiple sclerosis Diseases 0.000 claims description 10
- 208000011580 syndromic disease Diseases 0.000 claims description 10
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 101100240518 Caenorhabditis elegans nhr-12 gene Proteins 0.000 claims description 9
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 9
- 201000004681 Psoriasis Diseases 0.000 claims description 9
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- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 9
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 208000037803 restenosis Diseases 0.000 claims description 9
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 208000030507 AIDS Diseases 0.000 claims description 8
- IPUFBBSEFIOIKD-UHFFFAOYSA-N C1COCC1CNC(=O)C2=CC=C(C=C2)C3C4=CC=CC=C4CN3C(=O)N Chemical compound C1COCC1CNC(=O)C2=CC=C(C=C2)C3C4=CC=CC=C4CN3C(=O)N IPUFBBSEFIOIKD-UHFFFAOYSA-N 0.000 claims description 8
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 8
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims description 8
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 8
- 241001139947 Mida Species 0.000 claims description 8
- 108091008648 NR7C Proteins 0.000 claims description 8
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- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 8
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 7
- KTSBCNUXOPPNQD-UHFFFAOYSA-N O1C(CCC1)CNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N Chemical compound O1C(CCC1)CNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N KTSBCNUXOPPNQD-UHFFFAOYSA-N 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
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- YEAGHQMMDVSVJX-UHFFFAOYSA-N CCC(COC)NC(C1=CC=C(C(C2=CC=CC=C2C2)N2C(N)=O)C=C1)=O Chemical compound CCC(COC)NC(C1=CC=C(C(C2=CC=CC=C2C2)N2C(N)=O)C=C1)=O YEAGHQMMDVSVJX-UHFFFAOYSA-N 0.000 claims description 6
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- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- VCKRKHVOASUOMA-UHFFFAOYSA-N O1CCC(CC1)CNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N Chemical compound O1CCC(CC1)CNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N VCKRKHVOASUOMA-UHFFFAOYSA-N 0.000 claims description 6
- MLQVRTQYQQFTPA-UHFFFAOYSA-N OC(CNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N)(C)C Chemical compound OC(CNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N)(C)C MLQVRTQYQQFTPA-UHFFFAOYSA-N 0.000 claims description 6
- VYPKLCNXDFHATP-UHFFFAOYSA-N OCCCCNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N Chemical compound OCCCCNC(=O)C1=CC=C(C=C1)C1N(CC2=CC=CC=C12)C(=O)N VYPKLCNXDFHATP-UHFFFAOYSA-N 0.000 claims description 6
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- 125000004122 cyclic group Chemical group 0.000 claims description 6
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 6
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- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 6
- DMFSPVRZNNUHMU-UHFFFAOYSA-N n-[4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C(=O)C(C)C)CCC1C(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 DMFSPVRZNNUHMU-UHFFFAOYSA-N 0.000 claims description 6
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- PDRJERCIMDBJHK-UHFFFAOYSA-N n-[4-(1-benzyl-3,6-dihydro-2h-pyridin-4-yl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(CC1)=CCN1CC1=CC=CC=C1 PDRJERCIMDBJHK-UHFFFAOYSA-N 0.000 claims description 2
- UYOCQGZXQURYMC-UHFFFAOYSA-N n-[4-(1-benzylpyrazol-4-yl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=C1)C=NN1CC1=CC=CC=C1 UYOCQGZXQURYMC-UHFFFAOYSA-N 0.000 claims description 2
- IETDFCSFOLLCJH-UHFFFAOYSA-N n-[4-(1-butanoyl-3,6-dihydro-2h-pyridin-4-yl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1N(C(=O)CCC)CCC(C=2C=CC(NC(=O)N3CC4=CC=CC=C4C3)=CC=2)=C1 IETDFCSFOLLCJH-UHFFFAOYSA-N 0.000 claims description 2
- DNMLESRNFLMWDM-UHFFFAOYSA-N n-[4-(1-butylsulfonylpiperidin-4-yl)oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(S(=O)(=O)CCCC)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 DNMLESRNFLMWDM-UHFFFAOYSA-N 0.000 claims description 2
- OMIBIXSVWNKTDP-UHFFFAOYSA-N n-[4-(1-cyclopropylsulfonylpiperidin-4-yl)oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(CC1)CCN1S(=O)(=O)C1CC1 OMIBIXSVWNKTDP-UHFFFAOYSA-N 0.000 claims description 2
- XGZJVJPWXRFRKT-UHFFFAOYSA-N n-[4-(1-methylpyrazol-4-yl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1=NN(C)C=C1C(C=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 XGZJVJPWXRFRKT-UHFFFAOYSA-N 0.000 claims description 2
- NNYQMZRRROXOSO-UHFFFAOYSA-N n-[4-(1-oxa-4,8-diazaspiro[5.5]undecane-4-carbonyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(C1)CCOC21CCCNC2 NNYQMZRRROXOSO-UHFFFAOYSA-N 0.000 claims description 2
- VUWDCMUNOHVZHZ-UHFFFAOYSA-N n-[4-(1-oxa-4,8-diazaspiro[5.5]undecane-4-carbonyl)phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(C1)CCOC21CCCNC2 VUWDCMUNOHVZHZ-UHFFFAOYSA-N 0.000 claims description 2
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- ASGOFYZSXRHCGE-UHFFFAOYSA-N n-[4-(1-oxo-2h-pyrrolo[1,2-d][1,2,4]triazin-4-yl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC1=CC=C(C=2N3C=CC=C3C(=O)NN=2)C=C1 ASGOFYZSXRHCGE-UHFFFAOYSA-N 0.000 claims description 2
- VLVNQPIWFZLUMV-UHFFFAOYSA-N n-[4-(1-oxo-2h-pyrrolo[1,2-d][1,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-1-ylmethyl)-1,3-dihydroisoindole-2-carboxamide Chemical compound C=1C=C(C=2N3C=CC=C3C(=O)NN=2)C=CC=1NC(=O)N(CC1=C2)CC1=CC=C2CN1CCCC1 VLVNQPIWFZLUMV-UHFFFAOYSA-N 0.000 claims description 2
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- RTAKSYIEOZRYHZ-UHFFFAOYSA-N n-[4-(2,5-diazaspiro[3.5]nonane-2-carbonyl)phenyl]-5-fluoro-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC(F)=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(C1)CC21CCCCN2 RTAKSYIEOZRYHZ-UHFFFAOYSA-N 0.000 claims description 2
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- YBDCFBDWZWTOHA-UHFFFAOYSA-N n-[4-(6,8-dihydro-5h-imidazo[1,5-a]pyrazine-7-carbonyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC1=CC=C(C(=O)N2CC3=CN=CN3CC2)C=C1 YBDCFBDWZWTOHA-UHFFFAOYSA-N 0.000 claims description 2
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- AKACVGYZNQTMHA-OAQYLSRUSA-N n-[4-[(3r)-1-(cyclobutanecarbonyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C([C@H](C1)OC2=CC=C(C=C2)NC(=O)N2CC3=CN=CC=C3C2)CN1C(=O)C1CCC1 AKACVGYZNQTMHA-OAQYLSRUSA-N 0.000 claims description 2
- BIZKTPKQPKRZMM-NRFANRHFSA-N n-[4-[(3s)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)CC(C)C)CC[C@@H]1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 BIZKTPKQPKRZMM-NRFANRHFSA-N 0.000 claims description 2
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- VZDZSLMHVUAMOZ-UHFFFAOYSA-N n-[4-[1-(1h-pyrrole-2-carbonyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(CC1)CCN1C(=O)C1=CC=CN1 VZDZSLMHVUAMOZ-UHFFFAOYSA-N 0.000 claims description 2
- DRJHEGUTUUUQDJ-UHFFFAOYSA-N n-[4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]oxyphenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1CN(C(=O)C(C)C(C)C)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 DRJHEGUTUUUQDJ-UHFFFAOYSA-N 0.000 claims description 2
- LGXPTIFQNBTPQV-UHFFFAOYSA-N n-[4-[1-(2,5-dimethylpyrazole-3-carbonyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound CN1N=C(C)C=C1C(=O)N1CC=C(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CC1 LGXPTIFQNBTPQV-UHFFFAOYSA-N 0.000 claims description 2
- PUVGPMLTNLHWBB-UHFFFAOYSA-N n-[4-[1-(2-cyclobutylacetyl)piperidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CCC(OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CN1C(=O)CC1CCC1 PUVGPMLTNLHWBB-UHFFFAOYSA-N 0.000 claims description 2
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- HUMHIGARYZRRHW-UHFFFAOYSA-N n-[4-(4-pyridazin-3-ylpiperazine-1-carbonyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(CC1)CCN1C1=CC=CN=N1 HUMHIGARYZRRHW-UHFFFAOYSA-N 0.000 claims 1
- BRHFZSLOUHSJFI-UHFFFAOYSA-N n-[4-(4-pyrimidin-2-ylpiperazine-1-carbonyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(CC1)CCN1C1=NC=CC=N1 BRHFZSLOUHSJFI-UHFFFAOYSA-N 0.000 claims 1
- MBXBOHPHTMUPPY-UHFFFAOYSA-N n-[4-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(C1)CC21CCCO2 MBXBOHPHTMUPPY-UHFFFAOYSA-N 0.000 claims 1
- RBWJYGNVJJQEDZ-UHFFFAOYSA-N n-[4-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(C1)CC21CCCO2 RBWJYGNVJJQEDZ-UHFFFAOYSA-N 0.000 claims 1
- WQJINVMVEZQUHU-UHFFFAOYSA-N n-[4-(6-oxa-2-azaspiro[3.5]nonane-2-carbonyl)phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N(C1)CC21CCCOC2 WQJINVMVEZQUHU-UHFFFAOYSA-N 0.000 claims 1
- MOVOYOUMHJPPQC-UHFFFAOYSA-N n-[4-(butylcarbamoyl)phenyl]-5-fluoro-1,3-dihydroisoindole-2-carboxamide Chemical compound C1=CC(C(=O)NCCCC)=CC=C1NC(=O)N1CC2=CC(F)=CC=C2C1 MOVOYOUMHJPPQC-UHFFFAOYSA-N 0.000 claims 1
- FDLODAGTJBJJQI-UHFFFAOYSA-N n-[4-(cyclohexylcarbamoyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)NC1CCCCC1 FDLODAGTJBJJQI-UHFFFAOYSA-N 0.000 claims 1
- GRKCUIQVKUTEAY-UHFFFAOYSA-N n-[4-(cyclopentylcarbamoyl)phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)NC1CCCC1 GRKCUIQVKUTEAY-UHFFFAOYSA-N 0.000 claims 1
- MJBHHDHNUQHFIW-UHFFFAOYSA-N n-[4-(morpholine-4-carbonyl)phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)N1CCOCC1 MJBHHDHNUQHFIW-UHFFFAOYSA-N 0.000 claims 1
- SXGHKSKWGJUPDT-UHFFFAOYSA-N n-[4-(prop-2-ynylcarbamoyl)phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC1=CC=C(C(=O)NCC#C)C=C1 SXGHKSKWGJUPDT-UHFFFAOYSA-N 0.000 claims 1
- SBCBKQFYWJVDEO-UHFFFAOYSA-N n-[4-[(2-methyl-2-morpholin-4-ylbutyl)carbamoyl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C=1C=C(NC(=O)N2CC3=CC=CC=C3C2)C=CC=1C(=O)NCC(C)(CC)N1CCOCC1 SBCBKQFYWJVDEO-UHFFFAOYSA-N 0.000 claims 1
- UXRHXEZPYSUSRN-NRFANRHFSA-N n-[4-[(2s)-2-(2-hydroxyethyl)piperidine-1-carbonyl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound OCC[C@@H]1CCCCN1C(=O)C(C=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 UXRHXEZPYSUSRN-NRFANRHFSA-N 0.000 claims 1
- GBTOJPNLSXLKPU-OAQYLSRUSA-N n-[4-[(3r)-1-(2-cyclopropylacetyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C([C@@H](CC1)OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)N1C(=O)CC1CC1 GBTOJPNLSXLKPU-OAQYLSRUSA-N 0.000 claims 1
- VEASUYIINLQDCM-RTWAWAEBSA-N n-[4-[(3r)-1-[(2s)-oxolane-2-carbonyl]pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C([C@H](C1)OC2=CC=C(C=C2)NC(=O)N2CC3=CN=CC=C3C2)CN1C(=O)[C@@H]1CCCO1 VEASUYIINLQDCM-RTWAWAEBSA-N 0.000 claims 1
- GBTOJPNLSXLKPU-NRFANRHFSA-N n-[4-[(3s)-1-(2-cyclopropylacetyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C([C@H](CC1)OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)N1C(=O)CC1CC1 GBTOJPNLSXLKPU-NRFANRHFSA-N 0.000 claims 1
- AKACVGYZNQTMHA-NRFANRHFSA-N n-[4-[(3s)-1-(cyclobutanecarbonyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C([C@@H](C1)OC2=CC=C(C=C2)NC(=O)N2CC3=CN=CC=C3C2)CN1C(=O)C1CCC1 AKACVGYZNQTMHA-NRFANRHFSA-N 0.000 claims 1
- RHJNXBUJMLXATA-UHFFFAOYSA-N n-[4-[1-(1-methylcyclopropanecarbonyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=CCN1C(=O)C1(C)CC1 RHJNXBUJMLXATA-UHFFFAOYSA-N 0.000 claims 1
- BWYCODMFUCJIGW-UHFFFAOYSA-N n-[4-[1-(1-methylpyrazole-4-carbonyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1=NN(C)C=C1C(=O)N1CC=C(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CC1 BWYCODMFUCJIGW-UHFFFAOYSA-N 0.000 claims 1
- JTWWPIDGCWJMOL-UHFFFAOYSA-N n-[4-[1-(1-methylpyrrole-2-carbonyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound CN1C=CC=C1C(=O)N1CC=C(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CC1 JTWWPIDGCWJMOL-UHFFFAOYSA-N 0.000 claims 1
- CYRMNXSQOKRJSP-UHFFFAOYSA-N n-[4-[1-(1-methylpyrrolidine-3-carbonyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1N(C)CCC1C(=O)N1CC=C(C=2C=CC(NC(=O)N3CC4=CC=CC=C4C3)=CC=2)CC1 CYRMNXSQOKRJSP-UHFFFAOYSA-N 0.000 claims 1
- ASJRKGNYRIKKLY-UHFFFAOYSA-N n-[4-[1-(1-methylpyrrolidine-3-carbonyl)piperidin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C)CCC1C(=O)N1CCC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CC1 ASJRKGNYRIKKLY-UHFFFAOYSA-N 0.000 claims 1
- PAPZZYCWTHGANS-UHFFFAOYSA-N n-[4-[1-(2,2-difluorocyclopropanecarbonyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound FC1(F)CC1C(=O)N1CC=C(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CC1 PAPZZYCWTHGANS-UHFFFAOYSA-N 0.000 claims 1
- MHQDAHDVHMNGTI-UHFFFAOYSA-N n-[4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)C(C)(C)CC)CC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 MHQDAHDVHMNGTI-UHFFFAOYSA-N 0.000 claims 1
- ZSFJDQMBDPSGLU-UHFFFAOYSA-N n-[4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)C(C)(C)C)CC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 ZSFJDQMBDPSGLU-UHFFFAOYSA-N 0.000 claims 1
- CDGRQOUEKZQAFV-UHFFFAOYSA-N n-[4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C(=O)C(C)(C)C)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 CDGRQOUEKZQAFV-UHFFFAOYSA-N 0.000 claims 1
- WUTGXSCXJOVZQC-UHFFFAOYSA-N n-[4-[1-(2,5-dimethyl-1h-pyrrole-3-carbonyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound N1C(C)=CC(C(=O)N2CC=C(CC2)C=2C=CC(NC(=O)N3CC4=CC=CC=C4C3)=CC=2)=C1C WUTGXSCXJOVZQC-UHFFFAOYSA-N 0.000 claims 1
- NHCVLNCQYLWPLK-UHFFFAOYSA-N n-[4-[1-(2-cyclohexylacetyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C(OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CN1C(=O)CC1CCCCC1 NHCVLNCQYLWPLK-UHFFFAOYSA-N 0.000 claims 1
- INDKCPHMHHKBSK-UHFFFAOYSA-N n-[4-[1-(2-cyclopentylacetyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CCN1C(=O)CC1CCCC1 INDKCPHMHHKBSK-UHFFFAOYSA-N 0.000 claims 1
- DUVRUDUMUPFBPT-UHFFFAOYSA-N n-[4-[1-(2-cyclopropylacetyl)piperidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CCC(OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CN1C(=O)CC1CC1 DUVRUDUMUPFBPT-UHFFFAOYSA-N 0.000 claims 1
- SKKBHNUQSAPEFR-UHFFFAOYSA-N n-[4-[1-(2-cyclopropylacetyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CCN1C(=O)CC1CC1 SKKBHNUQSAPEFR-UHFFFAOYSA-N 0.000 claims 1
- VOIIKRKFPFYMOV-UHFFFAOYSA-N n-[4-[1-(2-ethylbutanoyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)C(CC)CC)CC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 VOIIKRKFPFYMOV-UHFFFAOYSA-N 0.000 claims 1
- PTPQPADJFFVIJB-UHFFFAOYSA-N n-[4-[1-(2-ethylbutanoyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C(=O)C(CC)CC)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 PTPQPADJFFVIJB-UHFFFAOYSA-N 0.000 claims 1
- INQDIJMKEBEUFH-UHFFFAOYSA-N n-[4-[1-(2-methoxyacetyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C(=O)COC)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 INQDIJMKEBEUFH-UHFFFAOYSA-N 0.000 claims 1
- GRKBRUQQJDPCCN-UHFFFAOYSA-N n-[4-[1-(2-methylbutanoyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)C(C)CC)CC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 GRKBRUQQJDPCCN-UHFFFAOYSA-N 0.000 claims 1
- KVRSDPLGCNPGRH-UHFFFAOYSA-N n-[4-[1-(2-methylbutanoyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C(=O)C(C)CC)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 KVRSDPLGCNPGRH-UHFFFAOYSA-N 0.000 claims 1
- NTWCVRSXRCEMPQ-UHFFFAOYSA-N n-[4-[1-(2-methylpentanoyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C(=O)C(C)CCC)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 NTWCVRSXRCEMPQ-UHFFFAOYSA-N 0.000 claims 1
- KONWNNYUEMJZFS-UHFFFAOYSA-N n-[4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)C(C)C)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 KONWNNYUEMJZFS-UHFFFAOYSA-N 0.000 claims 1
- FQPYQMCCLMOTCG-UHFFFAOYSA-N n-[4-[1-(2-morpholin-4-ylacetyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C(OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CN1C(=O)CN1CCOCC1 FQPYQMCCLMOTCG-UHFFFAOYSA-N 0.000 claims 1
- LDMGTCGWYWNQGC-UHFFFAOYSA-N n-[4-[1-(2-morpholin-4-ylacetyl)piperidin-4-yl]oxyphenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1CC(OC=2C=CC(NC(=O)N3CC4=CC=CC=C4C3)=CC=2)CCN1C(=O)CN1CCOCC1 LDMGTCGWYWNQGC-UHFFFAOYSA-N 0.000 claims 1
- KRHPSKLOCYKBAQ-UHFFFAOYSA-N n-[4-[1-(3,3,3-trifluoropropanoyl)piperidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)CC(F)(F)F)CCCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 KRHPSKLOCYKBAQ-UHFFFAOYSA-N 0.000 claims 1
- GYSIJEOPFJWSSJ-UHFFFAOYSA-N n-[4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C(=O)CC(F)(F)F)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 GYSIJEOPFJWSSJ-UHFFFAOYSA-N 0.000 claims 1
- RCSLMXCTVQEQKJ-UHFFFAOYSA-N n-[4-[1-(3-ethoxypropanoyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)CCOCC)CCC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=C1 RCSLMXCTVQEQKJ-UHFFFAOYSA-N 0.000 claims 1
- WCMQLJKBMNEQBG-UHFFFAOYSA-N n-[4-[1-(3-methylbutanoyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)CC(C)C)CCC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=C1 WCMQLJKBMNEQBG-UHFFFAOYSA-N 0.000 claims 1
- VHCZNBKXHGQPOY-UHFFFAOYSA-N n-[4-[1-(3-methylbutanoyl)piperidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)CC(C)C)CCCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 VHCZNBKXHGQPOY-UHFFFAOYSA-N 0.000 claims 1
- UFUJZFQOXFRIQF-UHFFFAOYSA-N n-[4-[1-(3-piperidin-1-ylpropanoyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C(OC=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CN1C(=O)CCN1CCCCC1 UFUJZFQOXFRIQF-UHFFFAOYSA-N 0.000 claims 1
- HECMHVAEXIWMDT-UHFFFAOYSA-N n-[4-[1-(3-pyrrol-1-ylpropanoyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=CCN1C(=O)CCN1C=CC=C1 HECMHVAEXIWMDT-UHFFFAOYSA-N 0.000 claims 1
- SCJCNTNQRFZBIM-UHFFFAOYSA-N n-[4-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)CCC(F)(F)F)CCC1OC(C=C1)=CC=C1NC(=O)N1CC2=CN=CC=C2C1 SCJCNTNQRFZBIM-UHFFFAOYSA-N 0.000 claims 1
- BWBZRUYICNPDHX-UHFFFAOYSA-N n-[4-[1-(cyclobutanecarbonyl)piperidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(C1)CCCN1C(=O)C1CCC1 BWBZRUYICNPDHX-UHFFFAOYSA-N 0.000 claims 1
- VSHQUTIHAMAHNH-UHFFFAOYSA-N n-[4-[1-(cyclobutanecarbonyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(CC1)CCN1C(=O)C1CCC1 VSHQUTIHAMAHNH-UHFFFAOYSA-N 0.000 claims 1
- SWVMBWLDIOWBSV-UHFFFAOYSA-N n-[4-[1-(cyclopentanecarbonyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(CC1)CCN1C(=O)C1CCCC1 SWVMBWLDIOWBSV-UHFFFAOYSA-N 0.000 claims 1
- FJPUKRFFWAIXJV-UHFFFAOYSA-N n-[4-[1-(cyclopentanecarbonyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(C1)CCN1C(=O)C1CCCC1 FJPUKRFFWAIXJV-UHFFFAOYSA-N 0.000 claims 1
- LZFGPRDUWGLCMB-UHFFFAOYSA-N n-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(CC1)CCN1C(=O)C1CC1 LZFGPRDUWGLCMB-UHFFFAOYSA-N 0.000 claims 1
- SLHUTUPTISMNHP-UHFFFAOYSA-N n-[4-[1-(cyclopropanecarbonyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(C1)CCN1C(=O)C1CC1 SLHUTUPTISMNHP-UHFFFAOYSA-N 0.000 claims 1
- AFFJNJLJNOWCFB-UHFFFAOYSA-N n-[4-[1-(furan-2-carbonyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(C1)CN1C(=O)C1=CC=CO1 AFFJNJLJNOWCFB-UHFFFAOYSA-N 0.000 claims 1
- MTEQEPOXRJULDJ-UHFFFAOYSA-N n-[4-[1-(furan-3-carbonyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(C1)CN1C(=O)C=1C=COC=1 MTEQEPOXRJULDJ-UHFFFAOYSA-N 0.000 claims 1
- JHAWTTVVQHCFFQ-UHFFFAOYSA-N n-[4-[1-(oxane-2-carbonyl)pyrrolidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(C1)CCN1C(=O)C1CCCCO1 JHAWTTVVQHCFFQ-UHFFFAOYSA-N 0.000 claims 1
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- WBFDGGAXQVQQSC-UHFFFAOYSA-N n-[4-[1-(pyridazine-3-carbonyl)piperidin-4-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(CC1)CCN1C(=O)C1=CC=CN=N1 WBFDGGAXQVQQSC-UHFFFAOYSA-N 0.000 claims 1
- QCBHQONELXKVSJ-UHFFFAOYSA-N n-[4-[1-(pyrimidine-4-carbonyl)azetidin-3-yl]oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1C2=CC=NC=C2CN1C(=O)NC(C=C1)=CC=C1OC(C1)CN1C(=O)C1=CC=NC=N1 QCBHQONELXKVSJ-UHFFFAOYSA-N 0.000 claims 1
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- CDJMMAQEDPBEGO-UHFFFAOYSA-N n-[4-[1-[2-[(2-methylpropan-2-yl)oxy]acetyl]-3,6-dihydro-2h-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1N(C(=O)COC(C)(C)C)CCC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=C1 CDJMMAQEDPBEGO-UHFFFAOYSA-N 0.000 claims 1
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- ZOTWYVIKQGTOSC-UHFFFAOYSA-N n-[4-[4-(2-methylpropanoyl)piperazin-1-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1CN(C(=O)C(C)C)CCN1C(C=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 ZOTWYVIKQGTOSC-UHFFFAOYSA-N 0.000 claims 1
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- VZXNRXCCBRFQHT-JFGZAKSSSA-N n-[4-[4-[[(2r)-oxolane-2-carbonyl]amino]cyclohexen-1-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=CCC1NC(=O)[C@H]1CCCO1 VZXNRXCCBRFQHT-JFGZAKSSSA-N 0.000 claims 1
- VZXNRXCCBRFQHT-YANBTOMASA-N n-[4-[4-[[(2s)-oxolane-2-carbonyl]amino]cyclohexen-1-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=CCC1NC(=O)[C@@H]1CCCO1 VZXNRXCCBRFQHT-YANBTOMASA-N 0.000 claims 1
- XEGPHYHQGBJCTD-PSDZMVHGSA-N n-[4-[4-[[(3r)-oxolane-3-carbonyl]amino]cyclohexen-1-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=CCC1NC(=O)[C@@H]1CCOC1 XEGPHYHQGBJCTD-PSDZMVHGSA-N 0.000 claims 1
- XEGPHYHQGBJCTD-AIBWNMTMSA-N n-[4-[4-[[(3s)-oxolane-3-carbonyl]amino]cyclohexen-1-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CC(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)=CCC1NC(=O)[C@H]1CCOC1 XEGPHYHQGBJCTD-AIBWNMTMSA-N 0.000 claims 1
- NBQIQYXUPSTLIQ-UHFFFAOYSA-N n-[4-[4-[[2-(4-methylpiperazin-1-yl)acetyl]amino]cyclohexen-1-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide Chemical compound C1CN(C)CCN1CC(=O)NC1CC=C(C=2C=CC(NC(=O)N3CC4=CN=CC=C4C3)=CC=2)CC1 NBQIQYXUPSTLIQ-UHFFFAOYSA-N 0.000 claims 1
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- ZXTFFDCOTONYSH-UHFFFAOYSA-N n-[4-[[1-(3-methylbutyl)pyrazol-4-yl]carbamoyl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1=NN(CCC(C)C)C=C1NC(=O)C(C=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 ZXTFFDCOTONYSH-UHFFFAOYSA-N 0.000 claims 1
- ROVKZKSUKSIJRM-UHFFFAOYSA-N n-[4-[[2-(furan-2-yl)-2-pyrrolidin-1-ylethyl]carbamoyl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(C=C1)=CC=C1C(=O)NCC(C=1OC=CC=1)N1CCCC1 ROVKZKSUKSIJRM-UHFFFAOYSA-N 0.000 claims 1
- KXSVZLXHBVIQLL-UHFFFAOYSA-N n-[4-[[2-[(dimethylamino)methyl]phenyl]methylcarbamoyl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound CN(C)CC1=CC=CC=C1CNC(=O)C(C=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 KXSVZLXHBVIQLL-UHFFFAOYSA-N 0.000 claims 1
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- DTJKKBKPHPRHPY-UHFFFAOYSA-N n-[4-[[4-(trifluoromethoxy)phenyl]carbamoyl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)C(C=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 DTJKKBKPHPRHPY-UHFFFAOYSA-N 0.000 claims 1
- JGUWGIBPZLFKKR-UHFFFAOYSA-N n-[4-[methyl(oxolan-2-ylmethyl)carbamoyl]phenyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C=1C=C(NC(=O)N2CC3=CC=CC=C3C2)C=CC=1C(=O)N(C)CC1CCCO1 JGUWGIBPZLFKKR-UHFFFAOYSA-N 0.000 claims 1
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- YOYXRERXIHRXBN-UHFFFAOYSA-N n-[6-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxypyridin-3-yl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1CN(C(=O)CCC(F)(F)F)CCC1OC(N=C1)=CC=C1NC(=O)N1CC2=CC=CC=C2C1 YOYXRERXIHRXBN-UHFFFAOYSA-N 0.000 claims 1
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- ITPOQLRDCMWKNX-UHFFFAOYSA-N n-[5-(4-pyridin-2-ylpiperazine-1-carbonyl)pyridin-2-yl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1C2=CC=CC=C2CN1C(=O)NC(N=C1)=CC=C1C(=O)N(CC1)CCN1C1=CC=CC=N1 ITPOQLRDCMWKNX-UHFFFAOYSA-N 0.000 description 1
- REDZAVQGVBHEFF-UHFFFAOYSA-N n-[6-[[4-(dimethylamino)benzoyl]amino]hexyl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1=CC(N(C)C)=CC=C1C(=O)NCCCCCCNC(=O)N1CC2=CC=CC=C2C1 REDZAVQGVBHEFF-UHFFFAOYSA-N 0.000 description 1
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- 210000002241 neurite Anatomy 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- JOUIQRNQJGXQDC-ZYUZMQFOSA-L nicotinate D-ribonucleotide(2-) Chemical compound O1[C@H](COP([O-])([O-])=O)[C@@H](O)[C@@H](O)[C@@H]1[N+]1=CC=CC(C([O-])=O)=C1 JOUIQRNQJGXQDC-ZYUZMQFOSA-L 0.000 description 1
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- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 230000005731 poly ADP ribosylation Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
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- 238000011069 regeneration method Methods 0.000 description 1
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- 108010041788 rho-Associated Kinases Proteins 0.000 description 1
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- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41372210P | 2010-11-15 | 2010-11-15 | |
| US201161474015P | 2011-04-11 | 2011-04-11 | |
| US201161525405P | 2011-08-19 | 2011-08-19 | |
| PCT/US2011/060425 WO2012067965A1 (en) | 2010-11-15 | 2011-11-11 | Nampt and rock inhibitors |
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| MX2013005454A true MX2013005454A (es) | 2013-06-24 |
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| MX2013005454A MX2013005454A (es) | 2010-11-15 | 2011-11-11 | Inhibidores de nampt y rock. |
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2011
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- 2011-11-11 SG SG2013037643A patent/SG190819A1/en unknown
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- 2011-11-11 WO PCT/US2011/060425 patent/WO2012067965A1/en not_active Ceased
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- 2011-11-11 PH PH1/2013/500975A patent/PH12013500975A1/en unknown
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- 2011-11-11 US US13/294,303 patent/US9302989B2/en active Active
- 2011-11-11 EP EP11787996.5A patent/EP2640698A1/en not_active Withdrawn
- 2011-11-11 TW TW100141323A patent/TW201238950A/zh unknown
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- 2011-11-11 KR KR1020137015348A patent/KR20140009251A/ko not_active Ceased
- 2011-11-11 BR BR112013012078A patent/BR112013012078A2/pt not_active IP Right Cessation
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- 2011-11-11 JP JP2013538943A patent/JP6117104B2/ja active Active
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2013
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2015
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2017
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| PE20140913A1 (es) | 2014-08-22 |
| CN103313968A (zh) | 2013-09-18 |
| EP2640698A1 (en) | 2013-09-25 |
| US10093624B2 (en) | 2018-10-09 |
| PH12013500975A1 (en) | 2013-07-08 |
| US20120122842A1 (en) | 2012-05-17 |
| SG10202010119TA (en) | 2020-11-27 |
| TW201238950A (en) | 2012-10-01 |
| CO6761389A2 (es) | 2013-09-30 |
| RU2013126657A (ru) | 2014-12-27 |
| CR20130267A (es) | 2013-10-04 |
| US20160031880A1 (en) | 2016-02-04 |
| CL2013001340A1 (es) | 2013-09-06 |
| DOP2013000106A (es) | 2013-10-15 |
| WO2012067965A1 (en) | 2012-05-24 |
| US9302989B2 (en) | 2016-04-05 |
| JP2013542265A (ja) | 2013-11-21 |
| BR112013012078A2 (pt) | 2019-09-24 |
| JP2017132792A (ja) | 2017-08-03 |
| AU2017200079A1 (en) | 2017-02-02 |
| IL225862A0 (en) | 2013-06-27 |
| GT201300124A (es) | 2014-12-12 |
| KR20140009251A (ko) | 2014-01-22 |
| JP6117104B2 (ja) | 2017-04-19 |
| AU2011329233A1 (en) | 2013-05-23 |
| ECSP13012993A (es) | 2014-01-31 |
| SG10201602857UA (en) | 2016-05-30 |
| SG190819A1 (en) | 2013-07-31 |
| AR083855A1 (es) | 2013-03-27 |
| UY33726A (es) | 2012-06-29 |
| CA2816594A1 (en) | 2012-05-24 |
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