CA3047287A1 - Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use - Google Patents

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Publication number

CA3047287A1

CA3047287A1 CA3047287A CA3047287A CA3047287A1 CA 3047287 A1 CA3047287 A1 CA 3047287A1 CA 3047287 A CA3047287 A CA 3047287A CA 3047287 A CA3047287 A CA 3047287A CA 3047287 A1 CA3047287 A1 CA 3047287A1

Authority

CA

Canada

Prior art keywords

thia

azabicyclo

amino

hept

ethynyl

Prior art date

2016-12-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

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• 238000000034 method Methods 0.000 title claims description 69
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 title claims description 4
• 239000002439 beta secretase inhibitor Substances 0.000 title description 2
• 150000004897 thiazines Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 313
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 74
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 42
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 26
• 238000011282 treatment Methods 0.000 claims abstract description 18
• 208000028698 Cognitive impairment Diseases 0.000 claims abstract description 11
• 238000002360 preparation method Methods 0.000 claims description 82
• 150000003839 salts Chemical class 0.000 claims description 74
• -1 2-propynyloxy Chemical group 0.000 claims description 59
• 229910052757 nitrogen Inorganic materials 0.000 claims description 43
• 206010012289 Dementia Diseases 0.000 claims description 34
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
• 210000004556 brain Anatomy 0.000 claims description 30
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims description 28
• 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 28
• 239000003814 drug Substances 0.000 claims description 19
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 14
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• 230000007505 plaque formation Effects 0.000 claims description 12
• 230000009467 reduction Effects 0.000 claims description 12
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 201000010374 Down Syndrome Diseases 0.000 claims description 9
• 208000012902 Nervous system disease Diseases 0.000 claims description 9
• 206010044688 Trisomy 21 Diseases 0.000 claims description 9
• 150000002367 halogens Chemical class 0.000 claims description 9
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 9
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 9
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
• 125000000335 thiazolyl group Chemical group 0.000 claims description 9
• 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 8
• 208000018737 Parkinson disease Diseases 0.000 claims description 8
• 206010048327 Supranuclear palsy Diseases 0.000 claims description 8
• 206010002022 amyloidosis Diseases 0.000 claims description 8
• 230000001054 cortical effect Effects 0.000 claims description 8
• 230000007850 degeneration Effects 0.000 claims description 8
• 230000003412 degenerative effect Effects 0.000 claims description 8
• 210000004558 lewy body Anatomy 0.000 claims description 8
• 125000001424 substituent group Chemical group 0.000 claims description 8
• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 5
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 2
• 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 2
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 3
• WRIHTLGFUKBBKQ-CEAUUGKZSA-N (1S,5S)-5-[5-[2-(5-chloro-3-methylpyridin-2-yl)ethynyl]-2-fluorophenyl]-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine Chemical compound ClC=1C=C(C(=NC=1)C#CC=1C=CC(=C(C=1)[C@]1(N=C(S[C@]2(CC12)COC)N)C)F)C WRIHTLGFUKBBKQ-CEAUUGKZSA-N 0.000 claims 2
• MOAJIFLFRHPNCU-GPUOULLFSA-N (1S,5S,6S)-3-amino-5-[2-fluoro-5-[2-(5-prop-2-ynoxypyridin-2-yl)ethynyl]phenyl]-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(C)C1=C(C=CC(=C1)C#CC1=NC=C(C=C1)OCC#C)F)C(=O)N(C)C MOAJIFLFRHPNCU-GPUOULLFSA-N 0.000 claims 2
• RAHDYDYNSIAFMG-FDJWOJMMSA-N (1S,5S,6S)-3-amino-5-[2-fluoro-5-[2-[3-methyl-5-(1,3-oxazol-2-ylmethoxy)pyridin-2-yl]ethynyl]phenyl]-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(C)C1=C(C=CC(=C1)C#CC1=NC=C(C=C1C)OCC=1OC=CN=1)F)C(=O)N(C)C RAHDYDYNSIAFMG-FDJWOJMMSA-N 0.000 claims 2
• ASCVRCHPGUMCIB-ZTCOLXNVSA-N (1S,5S,6S)-3-amino-5-[5-[2-(5-cyano-3-methylpyridin-2-yl)ethynyl]-2-fluorophenyl]-5-(fluoromethyl)-N,N-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C1=C(C=CC(=C1)C#CC1=NC=C(C=C1C)C#N)F)C(=O)N(C)C ASCVRCHPGUMCIB-ZTCOLXNVSA-N 0.000 claims 2
• CBYOFAWUWAYPKP-KSEOMHKRSA-N (1S,5S,6S)-3-amino-5-[5-[2-(5-cyano-3-methylpyridin-2-yl)ethynyl]-2-fluorophenyl]-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(C)C1=C(C=CC(=C1)C#CC1=NC=C(C=C1C)C#N)F)C#N CBYOFAWUWAYPKP-KSEOMHKRSA-N 0.000 claims 2
• KEYGOCWGASLCFN-ZTCOLXNVSA-N (1S,5S,6S)-3-amino-5-[5-[2-(5-cyano-3-methylpyridin-2-yl)ethynyl]-2-fluorophenyl]-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(C)C1=C(C=CC(=C1)C#CC1=NC=C(C=C1C)C#N)F)C(=O)N(C)C KEYGOCWGASLCFN-ZTCOLXNVSA-N 0.000 claims 2
• FAQNBNVGHSOMNY-MISYRCLQSA-N (1S,5S,6S)-5-[5-[2-(5-chloropyridin-2-yl)ethynyl]-2-fluorophenyl]-1,5-bis(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine Chemical compound ClC=1C=CC(=NC=1)C#CC=1C=CC(=C(C=1)[C@]1(N=C(S[C@]2(C[C@@H]12)CF)N)CF)F FAQNBNVGHSOMNY-MISYRCLQSA-N 0.000 claims 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
• AOKKWUDSGZAXHM-HSWNYDEUSA-N (E)-3-[(1R,5S,6S)-3-amino-5-[5-[2-(5-cyanopyridin-2-yl)ethynyl]-2-fluorophenyl]-5-(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl]-N,N-dimethylprop-2-enamide Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C1=C(C=CC(=C1)C#CC1=NC=C(C=C1)C#N)F)/C=C/C(=O)N(C)C AOKKWUDSGZAXHM-HSWNYDEUSA-N 0.000 claims 2
• RMKIYSYQYMTKCY-STZQEDGTSA-N 2-[(1R,5S,6S)-3-amino-5-[5-[2-(5-cyanopyridin-2-yl)ethynyl]-2-fluorophenyl]-5-(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl]acetamide Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C1=C(C=CC(=C1)C#CC1=NC=C(C=C1)C#N)F)CC(=O)N RMKIYSYQYMTKCY-STZQEDGTSA-N 0.000 claims 2
• AFTWTRHAYWBSST-ONGRUHMKSA-N 2-[2-[3-[(1R,5S,6S)-3-amino-5-(fluoromethyl)-1-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyrimidine-5-carbonitrile Chemical compound NC1=N[C@@](CF)([C@@H]2C[C@@]2(S1)\C=C\C(=O)N1CCOCC1)c1cc(ccc1F)C#Cc1ncc(cn1)C#N AFTWTRHAYWBSST-ONGRUHMKSA-N 0.000 claims 2
• LTTMNBDRNFKKOY-ATZDWAIDSA-N 2-[2-[3-[(1S,5S,6S)-3-amino-1,5-bis(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]-1,3-thiazole-5-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC=1SC(=CN=1)C#N)CF LTTMNBDRNFKKOY-ATZDWAIDSA-N 0.000 claims 2
• HKMWURYHQXDLAG-NVAWJBEOSA-N 4-[2-[3-[(1R,5S,6S)-3-amino-5-(fluoromethyl)-1-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]benzonitrile Chemical compound NC1=N[C@@](CF)([C@@H]2C[C@@]2(S1)\C=C\C(=O)N1CCOCC1)c1cc(ccc1F)C#Cc1ccc(cc1)C#N HKMWURYHQXDLAG-NVAWJBEOSA-N 0.000 claims 2
• SFMCZNIJMMCWAL-MISYRCLQSA-N 5-[2-[3-[(1S,5S,6S)-3-amino-1,5-bis(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyrazine-2-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC=1N=CC(=NC=1)C#N)CF SFMCZNIJMMCWAL-MISYRCLQSA-N 0.000 claims 2
• RJOFQCKQEMAZEM-BAGYTPMASA-N 6-[2-[3-[(1R,5S,6S)-3-amino-1-(cyanomethyl)-5-(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)CC#N RJOFQCKQEMAZEM-BAGYTPMASA-N 0.000 claims 2
• KKRBCUDPEWDQPI-TUUZJDJFSA-N 6-[2-[3-[(1R,5S,6S)-3-amino-1-[(E)-2-cyanoethenyl]-5-(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)\C=C\C#N KKRBCUDPEWDQPI-TUUZJDJFSA-N 0.000 claims 2
• KJOFKJHARIZLRZ-ALCSNEQFSA-N 6-[2-[3-[(1R,5S,6S)-3-amino-5-(fluoromethyl)-1-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]-5-methylpyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1C)\C=C\C(=O)N1CCOCC1 KJOFKJHARIZLRZ-ALCSNEQFSA-N 0.000 claims 2
• FRVCLHJFWPHQDO-ACYVMRIUSA-N 6-[2-[3-[(1R,5S,6S)-3-amino-5-(fluoromethyl)-1-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)\C=C\C(=O)N1CCOCC1 FRVCLHJFWPHQDO-ACYVMRIUSA-N 0.000 claims 2
• OBBHGUFQORPJJT-JHRSTNGLSA-N 6-[2-[3-[(1S,5S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]-5-methylpyridine-3-carbonitrile Chemical compound NC=1S[C@]2(CC2[C@@](N=1)(C)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1C)COC OBBHGUFQORPJJT-JHRSTNGLSA-N 0.000 claims 2
• QFJKGLXJJDXVNA-CEAUUGKZSA-N 6-[2-[3-[(1S,5S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(CC2[C@@](N=1)(C)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)COC QFJKGLXJJDXVNA-CEAUUGKZSA-N 0.000 claims 2
• DYNPYLMDNBPLJS-DFQSSKMNSA-N 6-[2-[3-[(1S,5S,6R)-3-amino-7,7-difluoro-1-(hydroxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C([C@H]2[C@@](N=1)(C)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)(F)F)CO DYNPYLMDNBPLJS-DFQSSKMNSA-N 0.000 claims 2
• RGTGFOOOUNAWIC-CEMLEFRQSA-N 6-[2-[3-[(1S,5S,6S)-3-amino-1,5-bis(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]-5-methylpyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1C)CF RGTGFOOOUNAWIC-CEMLEFRQSA-N 0.000 claims 2
• SDRBUXDDHNLJGX-HMXCVIKNSA-N 6-[2-[3-[(1S,5S,6S)-3-amino-1,5-bis(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)CF SDRBUXDDHNLJGX-HMXCVIKNSA-N 0.000 claims 2
• GFZSQUSNLSAKTD-FQLPYIGMSA-N 6-[2-[3-[(1S,5S,6S)-3-amino-5-(fluoromethyl)-1-(3-morpholin-4-yl-3-oxopropyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]-5-methylpyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1C)CCC(=O)N1CCOCC1 GFZSQUSNLSAKTD-FQLPYIGMSA-N 0.000 claims 2
• GQUCJZKBSKTSBA-DURWQBQJSA-N 6-[2-[3-[(1S,5S,6S)-3-amino-5-(fluoromethyl)-1-(3-morpholin-4-yl-3-oxopropyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)CCC(=O)N1CCOCC1 GQUCJZKBSKTSBA-DURWQBQJSA-N 0.000 claims 2
• LVSIXOOZCSCCOL-GMKZXUHWSA-N 6-[2-[3-[(1S,5S,6S)-3-amino-5-(fluoromethyl)-1-(imidazol-1-ylmethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]pyridine-3-carbonitrile Chemical compound N1(C=NC=C1)C[C@]12SC(=N[C@]([C@@H]2C1)(CF)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1)N LVSIXOOZCSCCOL-GMKZXUHWSA-N 0.000 claims 2
• KGMQOELEPMRZJR-DFCKQENNSA-N 6-[2-[3-[(1S,5S,6S)-3-amino-5-methyl-1-(pyrrolidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl]ethynyl]-5-methylpyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(C)C=1C=C(C=CC=1F)C#CC1=NC=C(C#N)C=C1C)C(=O)N1CCCC1 KGMQOELEPMRZJR-DFCKQENNSA-N 0.000 claims 2
• QPLBYIGLUXTAPU-RQFYCUQDSA-N 6-[2-[5-[(1S,5S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-6-fluoropyridin-3-yl]ethynyl]-5-methylpyridine-3-carbonitrile Chemical compound NC=1S[C@]2(CC2[C@@](N=1)(C)C=1C=C(C=NC=1F)C#CC1=NC=C(C#N)C=C1C)C(=O)N1CCOCC1 QPLBYIGLUXTAPU-RQFYCUQDSA-N 0.000 claims 2
• KTNWHHMLWOVZTA-RQFYCUQDSA-N 6-[2-[5-[(1S,5S)-3-amino-5-methyl-1-(pyrrolidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-6-fluoropyridin-3-yl]ethynyl]-5-methylpyridine-3-carbonitrile Chemical compound NC=1S[C@]2(CC2[C@@](N=1)(C)C=1C=C(C=NC=1F)C#CC1=NC=C(C#N)C=C1C)C(=O)N1CCCC1 KTNWHHMLWOVZTA-RQFYCUQDSA-N 0.000 claims 2
• MYTZXYYCRAMPEU-PWIZWCRZSA-N 6-[2-[5-[(1S,5S,6S)-3-amino-1-(fluoromethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-6-fluoropyridin-3-yl]ethynyl]pyridine-3-carbonitrile Chemical compound NC=1S[C@]2(C[C@H]2[C@@](N=1)(C)C=1C=C(C=NC=1F)C#CC1=NC=C(C#N)C=C1)CF MYTZXYYCRAMPEU-PWIZWCRZSA-N 0.000 claims 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 2
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