CA3062824A1 - Compounds and methods for treatment of visceral pain - Google Patents

Info

Publication number

CA3062824A1

CA3062824A1 CA3062824A CA3062824A CA3062824A1 CA 3062824 A1 CA3062824 A1 CA 3062824A1 CA 3062824 A CA3062824 A CA 3062824A CA 3062824 A CA3062824 A CA 3062824A CA 3062824 A1 CA3062824 A1 CA 3062824A1

Authority

CA

Canada

Prior art keywords

tetrahydro

cyclopropa

diaza

pentalene

carboxylic acid

Prior art date

2017-05-08

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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• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 1112
• 238000000034 method Methods 0.000 title claims abstract description 241
• 208000009935 visceral pain Diseases 0.000 title claims abstract description 88
• 238000011282 treatment Methods 0.000 title claims abstract description 38
• 208000002193 Pain Diseases 0.000 claims abstract description 146
• 230000036407 pain Effects 0.000 claims abstract description 137
• 208000005615 Interstitial Cystitis Diseases 0.000 claims abstract description 63
• 208000011231 Crohn disease Diseases 0.000 claims abstract description 57
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 53
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 51
• 201000007094 prostatitis Diseases 0.000 claims abstract description 36
• 208000004998 Abdominal Pain Diseases 0.000 claims abstract description 32
• 230000003187 abdominal effect Effects 0.000 claims abstract description 19
• 208000013507 chronic prostatitis Diseases 0.000 claims abstract description 18
• 210000001835 viscera Anatomy 0.000 claims abstract description 18
• 208000000450 Pelvic Pain Diseases 0.000 claims abstract description 17
• 208000000668 Chronic Pancreatitis Diseases 0.000 claims abstract description 16
• 201000009273 Endometriosis Diseases 0.000 claims abstract description 16
• 206010033645 Pancreatitis Diseases 0.000 claims abstract description 16
• 206010033649 Pancreatitis chronic Diseases 0.000 claims abstract description 16
• 230000003902 lesion Effects 0.000 claims abstract description 16
• 230000001684 chronic effect Effects 0.000 claims abstract description 13
• -1 ureyl Chemical group 0.000 claims description 328
• 125000003118 aryl group Chemical group 0.000 claims description 190
• 125000001072 heteroaryl group Chemical group 0.000 claims description 165
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 160
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 128
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 127
• 125000000623 heterocyclic group Chemical group 0.000 claims description 120
• 125000001424 substituent group Chemical group 0.000 claims description 120
• CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 claims description 101
• 229940126062 Compound A Drugs 0.000 claims description 88
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 88
• 239000000203 mixture Substances 0.000 claims description 87
• 150000003839 salts Chemical class 0.000 claims description 80
• 229910052736 halogen Inorganic materials 0.000 claims description 75
• 150000002367 halogens Chemical class 0.000 claims description 75
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 70
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 68
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 66
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 56
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 55
• 150000001204 N-oxides Chemical class 0.000 claims description 51
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 45
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 45
• 125000005549 heteroarylene group Chemical group 0.000 claims description 45
• 125000002947 alkylene group Chemical group 0.000 claims description 41
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 40
• 125000001769 aryl amino group Chemical group 0.000 claims description 40
• 125000004104 aryloxy group Chemical group 0.000 claims description 40
• 150000001602 bicycloalkyls Chemical group 0.000 claims description 40
• 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 40
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 35
• 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims description 30
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 30
• 239000003814 drug Substances 0.000 claims description 29
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 27
• 238000002411 thermogravimetry Methods 0.000 claims description 27
• 238000000113 differential scanning calorimetry Methods 0.000 claims description 25
• 238000001757 thermogravimetry curve Methods 0.000 claims description 25
• 230000004580 weight loss Effects 0.000 claims description 25
• 229940079593 drug Drugs 0.000 claims description 23
• 150000002148 esters Chemical class 0.000 claims description 23
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 20
• 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 20
• 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 20
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 20
• 150000003857 carboxamides Chemical class 0.000 claims description 20
• 125000005363 dialkylsulfonamide group Chemical group 0.000 claims description 20
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
• 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 claims description 18
• 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 claims description 18
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
• CHODSSFYKUSDHG-UHFFFAOYSA-N 1-fluoro-2-methylpropan-2-amine Chemical compound CC(C)(N)CF CHODSSFYKUSDHG-UHFFFAOYSA-N 0.000 claims description 15
• 239000013078 crystal Chemical group 0.000 claims description 15
• 125000005724 cycloalkenylene group Chemical group 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 125000001153 fluoro group Chemical group F* 0.000 claims description 15
• 238000002483 medication Methods 0.000 claims description 15
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
• YFBWGBFWVFEGEZ-UHFFFAOYSA-N 1,1,1-trifluoro-2-methylpropan-2-amine Chemical compound CC(C)(N)C(F)(F)F YFBWGBFWVFEGEZ-UHFFFAOYSA-N 0.000 claims description 14
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 14
• 239000003937 drug carrier Substances 0.000 claims description 14
• 208000025865 Ulcer Diseases 0.000 claims description 12
• 239000002671 adjuvant Substances 0.000 claims description 12
• 230000001363 autoimmune Effects 0.000 claims description 12
• 238000002512 chemotherapy Methods 0.000 claims description 11
• DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 claims description 10
• 239000013543 active substance Substances 0.000 claims description 10
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
• 229960004391 lorazepam Drugs 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 239000000014 opioid analgesic Substances 0.000 claims description 10
• 229960002870 gabapentin Drugs 0.000 claims description 7
• BLILOWUXFRXWQN-IUCAKERBSA-N (1as,5as)-2-pyrazin-2-yl-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (2,2,2-trifluoro-1,1-dimethyl-ethyl)-amide Chemical compound C([C@@H]1C[C@@H]1C=12)C=1C(C(=O)NC(C)(C)C(F)(F)F)=NN2C1=CN=CC=N1 BLILOWUXFRXWQN-IUCAKERBSA-N 0.000 claims description 6
• QBXHZDXUNZGSFL-NXEZZACHSA-N (1ar,5ar)-2-pyrazin-2-yl-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid tert-butylamide Chemical compound C([C@H]1C[C@H]1C=12)C=1C(C(=O)NC(C)(C)C)=NN2C1=CN=CC=N1 QBXHZDXUNZGSFL-NXEZZACHSA-N 0.000 claims description 5
• GITVPBOHDLIKRA-UMVBOHGHSA-N (2R,4R)-N-[(1S)-2-hydroxy-1-(oxan-4-yl)ethyl]-9-pyrazin-2-yl-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxamide Chemical compound N([C@H](CO)C1CCOCC1)C(=O)C(C=1C[C@H]2C[C@H]2C=11)=NN1C1=CN=CC=N1 GITVPBOHDLIKRA-UMVBOHGHSA-N 0.000 claims description 5
• GBBSUAFBMRNDJC-MRXNPFEDSA-N (5R)-zopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-MRXNPFEDSA-N 0.000 claims description 5
• ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 claims description 5
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 5
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 5
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 5
• GNXFOGHNGIVQEH-UHFFFAOYSA-N 2-hydroxy-3-(2-methoxyphenoxy)propyl carbamate Chemical compound COC1=CC=CC=C1OCC(O)COC(N)=O GNXFOGHNGIVQEH-UHFFFAOYSA-N 0.000 claims description 5
• 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
• KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 claims description 5
• 108030001720 Bontoxilysin Proteins 0.000 claims description 5
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 5
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
• 239000005977 Ethylene Substances 0.000 claims description 5
• PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 claims description 5
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 5
• 208000005298 acute pain Diseases 0.000 claims description 5
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 claims description 5
• 229960004538 alprazolam Drugs 0.000 claims description 5
• KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 claims description 5
• 229960000836 amitriptyline Drugs 0.000 claims description 5
• 239000000730 antalgic agent Substances 0.000 claims description 5
• 230000000049 anti-anxiety effect Effects 0.000 claims description 5
• 230000000573 anti-seizure effect Effects 0.000 claims description 5
• 239000000935 antidepressant agent Substances 0.000 claims description 5
• 229940005513 antidepressants Drugs 0.000 claims description 5
• 239000003472 antidiabetic agent Substances 0.000 claims description 5
• 239000002249 anxiolytic agent Substances 0.000 claims description 5
• 229960000794 baclofen Drugs 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 229940053031 botulinum toxin Drugs 0.000 claims description 5
• 125000001246 bromo group Chemical group Br* 0.000 claims description 5
• 229960000623 carbamazepine Drugs 0.000 claims description 5
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 229960003572 cyclobenzaprine Drugs 0.000 claims description 5
• JURKNVYFZMSNLP-UHFFFAOYSA-N cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 claims description 5
• 229960003529 diazepam Drugs 0.000 claims description 5
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 5
• 229960002866 duloxetine Drugs 0.000 claims description 5
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 5
• 125000006343 heptafluoro propyl group Chemical group 0.000 claims description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• 230000001939 inductive effect Effects 0.000 claims description 5
• 229960001848 lamotrigine Drugs 0.000 claims description 5
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 229960002330 methocarbamol Drugs 0.000 claims description 5
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
• 229940035363 muscle relaxants Drugs 0.000 claims description 5
• 239000003158 myorelaxant agent Substances 0.000 claims description 5
• 229960001158 nortriptyline Drugs 0.000 claims description 5
• SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 claims description 5
• 229960001233 pregabalin Drugs 0.000 claims description 5
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 5
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
• 229960004394 topiramate Drugs 0.000 claims description 5
• PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 claims description 5
• 229960004688 venlafaxine Drugs 0.000 claims description 5
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• 229940125708 antidiabetic agent Drugs 0.000 claims description 4
• 230000003213 activating effect Effects 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 230000000007 visual effect Effects 0.000 claims description 3
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 42
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 36
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 15
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 9
• ACSQLTBPYZSGBA-GMXVVIOVSA-N olorinab Chemical compound C([C@@H]1C[C@@H]1C=12)C=1C(C(=O)N[C@H](CO)C(C)(C)C)=NN2C1=C[N+]([O-])=CC=N1 ACSQLTBPYZSGBA-GMXVVIOVSA-N 0.000 claims 7
• VRDXDROAZSDMSA-UHFFFAOYSA-N (1-aminocyclobutyl)methanol Chemical compound OCC1(N)CCC1 VRDXDROAZSDMSA-UHFFFAOYSA-N 0.000 claims 3
• KJNZJSIOABLVBK-MWLCHTKSSA-N (1ar,5ar)-2-(2,4-dichloro-phenyl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (1-hydroxymethyl-cyclopropyl)-amide Chemical compound C([C@H]1C[C@H]1C=1N(N=2)C=3C(=CC(Cl)=CC=3)Cl)C=1C=2C(=O)NC1(CO)CC1 KJNZJSIOABLVBK-MWLCHTKSSA-N 0.000 claims 3
• SFZNWMHZWDDKDL-MWLCHTKSSA-N (1ar,5ar)-2-(4-chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (cyano-dimethyl-methyl)-amide Chemical compound C([C@H]1C[C@H]1C=12)C=1C(C(=O)NC(C)(C)C#N)=NN2C1=CC(Cl)=CC=N1 SFZNWMHZWDDKDL-MWLCHTKSSA-N 0.000 claims 3
• VXHUHYVFORNNJX-VXGBXAGGSA-N (1ar,5ar)-2-(4-cyano-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide Chemical compound C([C@H]1C[C@H]1C=12)C=1C(C(=O)NC(CO)(CO)C)=NN2C1=CC(C#N)=CC=N1 VXHUHYVFORNNJX-VXGBXAGGSA-N 0.000 claims 3
• IXMKFODNZUOYIW-MWLCHTKSSA-N (1ar,5ar)-2-(4-fluoro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide Chemical compound C([C@H]1C[C@H]1C=12)C=1C(C(=O)NC(C)(CO)C)=NN2C1=CC(F)=CC=N1 IXMKFODNZUOYIW-MWLCHTKSSA-N 0.000 claims 3
• KKFNSSOSJAWXJS-MWLCHTKSSA-N (1ar,5ar)-2-(5-cyano-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide Chemical compound C([C@H]1C[C@H]1C=12)C=1C(C(=O)NC(C)(CO)C)=NN2C1=CN=C(C#N)C=N1 KKFNSSOSJAWXJS-MWLCHTKSSA-N 0.000 claims 3
• NRNFYIOXSKULCO-MWLCHTKSSA-N (1ar,5ar)-2-(5-fluoro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide Chemical compound C([C@H]1C[C@H]1C=12)C=1C(C(=O)NC(C)(CO)C)=NN2C1=CC=C(F)C=N1 NRNFYIOXSKULCO-MWLCHTKSSA-N 0.000 claims 3
• TVCYLBQVKJBKGA-NQBHXWOUSA-N (1ar,5ar)-2-pyrazin-2-yl-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((s)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide Chemical compound C([C@H]1C[C@H]1C=12)C=1C(C(=O)N[C@H](CO)C(C)(C)C)=NN2C1=CN=CC=N1 TVCYLBQVKJBKGA-NQBHXWOUSA-N 0.000 claims 3
• PPXLCGDEKRKXGU-ONGXEEELSA-N (1as,5as)-2-(4-chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (2-fluoro-1,1-dimethyl-ethyl)-amide Chemical compound C([C@@H]1C[C@@H]1C=12)C=1C(C(=O)NC(C)(CF)C)=NN2C1=CC(Cl)=CC=N1 PPXLCGDEKRKXGU-ONGXEEELSA-N 0.000 claims 3
• SDASTXGOZXJKBD-ONGXEEELSA-N (1as,5as)-2-(4-chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1h-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (2-fluoro-1-fluoro methyl-1-hydroxymethyl-ethyl)-amide Chemical compound C([C@@H]1C[C@@H]1C=12)C=1C(C(=O)NC(CF)(CF)CO)=NN2C1=CC(Cl)=CC=N1 SDASTXGOZXJKBD-ONGXEEELSA-N 0.000 claims 3
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