EA032794B1 - (2s)-n-[(1s)-1-циано-2-фенилэтил]-1,4-оксазепан-2-карбоксамиды в качестве ингибиторов дипептидилпептидазы i - Google Patents

Info

Publication number

EA032794B1

EA032794B1 EA201691375A EA201691375A EA032794B1 EA 032794 B1 EA032794 B1 EA 032794B1 EA 201691375 A EA201691375 A EA 201691375A EA 201691375 A EA201691375 A EA 201691375A EA 032794 B1 EA032794 B1 EA 032794B1

Authority

EA

Eurasian Patent Office

Prior art keywords

ethyl

cyano

carboxamide

oxazepan

phenyl

Prior art date

2014-01-24

Links

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• 102100029921 Dipeptidyl peptidase 1 Human genes 0.000 title abstract description 34
• 101710087078 Dipeptidyl peptidase 1 Proteins 0.000 title abstract description 32
• 239000003112 inhibitor Substances 0.000 title description 17
• 150000001875 compounds Chemical class 0.000 claims abstract description 249
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• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 10
• -1 3,7-dimethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl Chemical group 0.000 claims description 251
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 109
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 101
• 206010039083 rhinitis Diseases 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 30
• 230000001154 acute effect Effects 0.000 claims description 29
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• 229910052731 fluorine Inorganic materials 0.000 claims description 20
• 210000004072 lung Anatomy 0.000 claims description 20
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• 229910052801 chlorine Inorganic materials 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 201000010105 allergic rhinitis Diseases 0.000 claims description 16
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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
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• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 12
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• 229910052794 bromium Inorganic materials 0.000 claims description 10
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
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• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 8
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• 239000003085 diluting agent Substances 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 5
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• 241000315672 SARS coronavirus Species 0.000 claims description 5
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 5
• 230000000118 anti-neoplastic effect Effects 0.000 claims description 5
• 208000013116 chronic cough Diseases 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 239000000428 dust Substances 0.000 claims description 5
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• 125000001424 substituent group Chemical group 0.000 claims description 5
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• 208000001319 vasomotor rhinitis Diseases 0.000 claims description 5
• VCVCFYIPGOTDMC-UHFFFAOYSA-N (3-phenylphenyl) methanesulfonate Chemical compound CS(=O)(=O)OC1=CC=CC(C=2C=CC=CC=2)=C1 VCVCFYIPGOTDMC-UHFFFAOYSA-N 0.000 claims description 4
• 208000018569 Respiratory Tract disease Diseases 0.000 claims description 4
• 241000725643 Respiratory syncytial virus Species 0.000 claims description 4
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 230000035882 stress Effects 0.000 claims description 4
• FCRODBUNBQJNPU-SFTDATJTSA-N (2S)-N-[(1S)-1-cyano-2-[4-(4-cyanophenyl)phenyl]ethyl]-1,4-oxazepane-2-carboxamide Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C1=CC=C(C=C1)C#N)NC(=O)[C@H]1OCCCNC1 FCRODBUNBQJNPU-SFTDATJTSA-N 0.000 claims description 3
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
• 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
• 230000003637 steroidlike Effects 0.000 claims description 3
• QCTYSVBOKIUUFU-UGKGYDQZSA-N (2S)-N-[(1S)-1-cyano-2-[4-(3-methyl-1,2-benzoxazol-5-yl)phenyl]ethyl]-1,4-oxazepane-2-carboxamide Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C=1C=CC2=C(C(=NO2)C)C1)NC(=O)[C@H]1OCCCNC1 QCTYSVBOKIUUFU-UGKGYDQZSA-N 0.000 claims description 2
• BVHRFMZXVRJZAF-URXFXBBRSA-N (2S)-N-[(1S)-1-cyano-2-[4-[3-[2-(dimethylamino)ethyl]-2-oxo-1,3-benzoxazol-5-yl]phenyl]ethyl]-1,4-oxazepane-2-carboxamide Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C=1C=CC2=C(N(C(O2)=O)CCN(C)C)C1)NC(=O)[C@H]1OCCCNC1 BVHRFMZXVRJZAF-URXFXBBRSA-N 0.000 claims description 2
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
• AEXFXNFMSAAELR-RXVVDRJESA-N brensocatib Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C=1C=CC2=C(N(C(O2)=O)C)C1)NC(=O)[C@H]1OCCCNC1 AEXFXNFMSAAELR-RXVVDRJESA-N 0.000 claims 2
• BQIZWZAQEICNDG-GMAHTHKFSA-N (2S)-N-[(1S)-1-cyano-2-[4-(1-methyl-2-oxoquinolin-7-yl)phenyl]ethyl]-1,4-oxazepane-2-carboxamide Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C1=CC=C2C=CC(N(C2=C1)C)=O)NC(=O)[C@H]1OCCCNC1 BQIZWZAQEICNDG-GMAHTHKFSA-N 0.000 claims 1
• PYXGGJVWIVBQRO-PMACEKPBSA-N (2S)-N-[(1S)-1-cyano-2-[4-(4-fluorophenyl)phenyl]ethyl]-1,4-oxazepane-2-carboxamide Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C1=CC=C(C=C1)F)NC(=O)[C@H]1OCCCNC1 PYXGGJVWIVBQRO-PMACEKPBSA-N 0.000 claims 1
• KFOHIWSKADTAQW-OZXSUGGESA-N (2S)-N-[(1S)-1-cyano-2-[4-[3-(oxan-4-ylmethyl)-2-oxo-1,3-benzoxazol-5-yl]phenyl]ethyl]-1,4-oxazepane-2-carboxamide Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C=1C=CC2=C(N(C(O2)=O)CC2CCOCC2)C1)NC(=O)[C@H]1OCCCNC1 KFOHIWSKADTAQW-OZXSUGGESA-N 0.000 claims 1
• USBDHHJQNTYSNJ-PMACEKPBSA-N (2S)-N-[(1S)-1-cyano-2-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]-1,4-oxazepane-2-carboxamide Chemical compound C(#N)[C@H](CC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)NC(=O)[C@H]1OCCCNC1 USBDHHJQNTYSNJ-PMACEKPBSA-N 0.000 claims 1
• CBWWXOUBSQCMHB-GMAHTHKFSA-N (2S)-N-[(1S)-2-[4-[4-(azetidin-1-ylsulfonyl)phenyl]phenyl]-1-cyanoethyl]-1,4-oxazepane-2-carboxamide Chemical compound N1(CCC1)S(=O)(=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C#N)NC(=O)[C@H]1OCCCNC1 CBWWXOUBSQCMHB-GMAHTHKFSA-N 0.000 claims 1
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 110
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