JP2019529443A5

JP2019529443A5 -

Download PDF

Info

Publication number: JP2019529443A5
Authority: JP; Japan
Prior art keywords: sulfonyl; hydroxy; pyrrolidine; hydroxymethyl; oxy
Prior art date: 2017-09-20
Legal status : Granted

Application number

JP2019515462A

Other languages

English (en)

Japanese (ja)

Other versions

JP2019529443A (ja

JP7025414B2 (ja

Filing date

2017-09-20

Publication date

2021-02-12

2017-09-20 Application filed filed Critical

2017-09-20 Priority claimed from PCT/IB2017/055700 external-priority patent/WO2018055524A1/en

2019-10-17 Publication of JP2019529443A publication Critical patent/JP2019529443A/ja

2021-02-12 Publication of JP2019529443A5 publication Critical patent/JP2019529443A5/ja

2022-02-24 Application granted granted Critical

2022-02-24 Publication of JP7025414B2 publication Critical patent/JP7025414B2/ja

Status Active legal-status Critical Current

2037-09-20 Anticipated expiration legal-status Critical

Links

125000000217 alkyl group Chemical group 0.000 claims description 82
-1 Hydroxy, amino Chemical group 0.000 claims description 43
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
125000001153 fluoro group Chemical group F* 0.000 claims description 32
150000001875 compounds Chemical class 0.000 claims description 22
125000004043 oxo group Chemical group O=* 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 17
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
SBUKLPSBNFWJCU-UHFFFAOYSA-N ClIBr Chemical compound ClIBr SBUKLPSBNFWJCU-UHFFFAOYSA-N 0.000 claims description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
239000002464 receptor antagonist Substances 0.000 claims description 6
229940044551 receptor antagonist Drugs 0.000 claims description 6
AWBOSXFRPFZLOP-UHFFFAOYSA-N 2,1,3-benzoxadiazole Chemical group C1=CC=CC2=NON=C21 AWBOSXFRPFZLOP-UHFFFAOYSA-N 0.000 claims description 5
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 5
229910021419 crystalline silicon Inorganic materials 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
125000002757 morpholinyl group Chemical group 0.000 claims description 5
229940125715 antihistaminic agent Drugs 0.000 claims description 4
239000000739 antihistaminic agent Substances 0.000 claims description 4
229940079593 drug Drugs 0.000 claims description 4
239000003112 inhibitor Substances 0.000 claims description 4
150000003222 pyridines Chemical class 0.000 claims description 4
108090000312 Calcium Channels Proteins 0.000 claims description 3
102000003922 Calcium Channels Human genes 0.000 claims description 3
229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 3
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
239000000674 adrenergic antagonist Substances 0.000 claims description 3
239000002170 aldosterone antagonist Substances 0.000 claims description 3
229940083712 aldosterone antagonist Drugs 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
239000002876 beta blocker Substances 0.000 claims description 3
229940097320 beta blocking agent Drugs 0.000 claims description 3
229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 claims description 3
239000000496 cardiotonic agent Substances 0.000 claims description 3
230000003177 cardiotonic effect Effects 0.000 claims description 3
239000002934 diuretic Substances 0.000 claims description 3
229940030606 diuretics Drugs 0.000 claims description 3
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 3
239000003149 muscarinic antagonist Substances 0.000 claims description 3
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 3
239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 3
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 3
239000002461 renin inhibitor Substances 0.000 claims description 3
229940086526 renin-inhibitors Drugs 0.000 claims description 3
230000003637 steroidlike Effects 0.000 claims description 3
102000003567 TRPV4 Human genes 0.000 claims description 2
101150098315 TRPV4 gene Proteins 0.000 claims description 2
102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 claims description 2
108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 claims description 2
239000005557 antagonist Substances 0.000 claims description 2
229940124599 anti-inflammatory drug Drugs 0.000 claims description 2
102000012740 beta Adrenergic Receptors Human genes 0.000 claims description 2
108010079452 beta Adrenergic Receptors Proteins 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
108091006073 receptor regulators Proteins 0.000 claims description 2
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 60
238000000034 method Methods 0.000 claims 19
125000004093 cyano group Chemical group *C#N 0.000 claims 18
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 17
206010011224 Cough Diseases 0.000 claims 16
125000001072 heteroaryl group Chemical group 0.000 claims 14
206010030113 Oedema Diseases 0.000 claims 12
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 12
208000002551 irritable bowel syndrome Diseases 0.000 claims 11
125000003118 aryl group Chemical group 0.000 claims 10
206010007559 Cardiac failure congestive Diseases 0.000 claims 8
125000003545 alkoxy group Chemical group 0.000 claims 8
206010019280 Heart failures Diseases 0.000 claims 6
208000002193 Pain Diseases 0.000 claims 6
208000003251 Pruritus Diseases 0.000 claims 6
230000000968 intestinal effect Effects 0.000 claims 6
208000005264 motor neuron disease Diseases 0.000 claims 6
208000004852 Lung Injury Diseases 0.000 claims 5
206010069363 Traumatic lung injury Diseases 0.000 claims 5
231100000515 lung injury Toxicity 0.000 claims 5
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 4
206010003445 Ascites Diseases 0.000 claims 4
206010048962 Brain oedema Diseases 0.000 claims 4
206010020772 Hypertension Diseases 0.000 claims 4
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 4
206010069351 acute lung injury Diseases 0.000 claims 4
201000000028 adult respiratory distress syndrome Diseases 0.000 claims 4
208000006752 brain edema Diseases 0.000 claims 4
208000013116 chronic cough Diseases 0.000 claims 4
208000024827 Alzheimer disease Diseases 0.000 claims 3
201000001320 Atherosclerosis Diseases 0.000 claims 3
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 3
208000015943 Coeliac disease Diseases 0.000 claims 3
206010010774 Constipation Diseases 0.000 claims 3
208000011231 Crohn disease Diseases 0.000 claims 3
201000004624 Dermatitis Diseases 0.000 claims 3
206010012735 Diarrhoea Diseases 0.000 claims 3
201000009273 Endometriosis Diseases 0.000 claims 3
206010016807 Fluid retention Diseases 0.000 claims 3
208000010412 Glaucoma Diseases 0.000 claims 3
206010062016 Immunosuppression Diseases 0.000 claims 3
206010021639 Incontinence Diseases 0.000 claims 3
206010061218 Inflammation Diseases 0.000 claims 3
201000010538 Lactose Intolerance Diseases 0.000 claims 3
208000019695 Migraine disease Diseases 0.000 claims 3
208000008589 Obesity Diseases 0.000 claims 3
206010033645 Pancreatitis Diseases 0.000 claims 3
208000017442 Retinal disease Diseases 0.000 claims 3
206010038923 Retinopathy Diseases 0.000 claims 3
206010040047 Sepsis Diseases 0.000 claims 3
208000005392 Spasm Diseases 0.000 claims 3
208000006011 Stroke Diseases 0.000 claims 3
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 3
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 3
230000001154 acute effect Effects 0.000 claims 3
230000002491 angiogenic effect Effects 0.000 claims 3
208000006673 asthma Diseases 0.000 claims 3
210000000988 bone and bone Anatomy 0.000 claims 3
230000001684 chronic effect Effects 0.000 claims 3
208000019425 cirrhosis of liver Diseases 0.000 claims 3
201000003146 cystitis Diseases 0.000 claims 3
206010012601 diabetes mellitus Diseases 0.000 claims 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
208000035475 disorder Diseases 0.000 claims 3
230000004064 dysfunction Effects 0.000 claims 3
208000003906 hydrocephalus Diseases 0.000 claims 3
230000001506 immunosuppresive effect Effects 0.000 claims 3
230000004054 inflammatory process Effects 0.000 claims 3
208000037805 labour Diseases 0.000 claims 3
201000010901 lateral sclerosis Diseases 0.000 claims 3
208000019423 liver disease Diseases 0.000 claims 3
208000030159 metabolic disease Diseases 0.000 claims 3
206010027599 migraine Diseases 0.000 claims 3
201000006417 multiple sclerosis Diseases 0.000 claims 3
230000003387 muscular Effects 0.000 claims 3
235000020824 obesity Nutrition 0.000 claims 3
201000008482 osteoarthritis Diseases 0.000 claims 3
239000000546 pharmaceutical excipient Substances 0.000 claims 3
230000002980 postoperative effect Effects 0.000 claims 3
208000005069 pulmonary fibrosis Diseases 0.000 claims 3
208000002815 pulmonary hypertension Diseases 0.000 claims 3
206010039083 rhinitis Diseases 0.000 claims 3
201000009890 sinusitis Diseases 0.000 claims 3
208000011580 syndromic disease Diseases 0.000 claims 3
230000009885 systemic effect Effects 0.000 claims 3
230000005760 tumorsuppression Effects 0.000 claims 3
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
208000024172 Cardiovascular disease Diseases 0.000 claims 2
206010011732 Cyst Diseases 0.000 claims 2
206010052139 Eye oedema Diseases 0.000 claims 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
208000035202 High altitude pulmonary edema Diseases 0.000 claims 2
241000282412 Homo Species 0.000 claims 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 2
230000003187 abdominal effect Effects 0.000 claims 2
125000005037 alkyl phenyl group Chemical group 0.000 claims 2
206010009887 colitis Diseases 0.000 claims 2
208000031513 cyst Diseases 0.000 claims 2
UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical group C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 claims 2
208000017169 kidney disease Diseases 0.000 claims 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
239000008194 pharmaceutical composition Substances 0.000 claims 2
208000007232 portal hypertension Diseases 0.000 claims 2
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 2
230000001568 sexual effect Effects 0.000 claims 2
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 2
229930192474 thiophene Natural products 0.000 claims 2
125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 2
QFNQYJOBGCIGHG-JKSUJKDBSA-N (3R,4S)-1-(2,4-dichlorophenyl)sulfonyl-3-(hydroxymethyl)-4-[6-(trifluoromethyl)pyridin-3-yl]oxypyrrolidin-3-ol Chemical compound ClC1=C(C=CC(=C1)Cl)S(=O)(=O)N1C[C@@]([C@H](C1)OC=1C=NC(=CC=1)C(F)(F)F)(O)CO QFNQYJOBGCIGHG-JKSUJKDBSA-N 0.000 claims 1
XPHDQKRQUQXAQU-DLBZAZTESA-N (3R,4S)-1-(2,4-dichlorophenyl)sulfonyl-4-(3,4-difluorophenoxy)-3-(hydroxymethyl)pyrrolidin-3-ol Chemical compound ClC1=C(C=CC(=C1)Cl)S(=O)(=O)N1C[C@@]([C@H](C1)OC1=CC(=C(C=C1)F)F)(O)CO XPHDQKRQUQXAQU-DLBZAZTESA-N 0.000 claims 1
VVUHDHVUWZEDRG-DLBZAZTESA-N (3R,4S)-4-(2,1,3-benzoxadiazol-5-yloxy)-1-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-3-(hydroxymethyl)pyrrolidin-3-ol Chemical compound N=1ON=C2C=1C=CC(=C2)O[C@@H]1[C@](CN(C1)S(=O)(=O)C1=C(C=C(C=C1)C(F)(F)F)F)(O)CO VVUHDHVUWZEDRG-DLBZAZTESA-N 0.000 claims 1
WBVNWZQWORYYJR-MAUKXSAKSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,3,4-trifluorophenoxy)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=C(C(=C(C=C1)F)F)F)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO WBVNWZQWORYYJR-MAUKXSAKSA-N 0.000 claims 1
UQEKJBKJDURGDP-ZWKOTPCHSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,4,5-trifluorophenoxy)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=C(C=C(C(=C1)F)F)F)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO UQEKJBKJDURGDP-ZWKOTPCHSA-N 0.000 claims 1
HFXNXMCKTXAEEH-FUHWJXTLSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(3,4,5-trifluorophenoxy)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=CC(=C(C(=C1)F)F)F)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO HFXNXMCKTXAEEH-FUHWJXTLSA-N 0.000 claims 1
QMLGGTCTALDWCI-RBUKOAKNSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-methoxyphenoxy)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=CC=C(C=C1)OC)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO QMLGGTCTALDWCI-RBUKOAKNSA-N 0.000 claims 1
JOMYYIYPFSKGHT-RBUKOAKNSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-methylphenoxy)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=CC=C(C=C1)C)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO JOMYYIYPFSKGHT-RBUKOAKNSA-N 0.000 claims 1
IHGUUOHXFRSNNX-GOEBONIOSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[2-(trifluoromethyl)pyrimidin-5-yl]oxypyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC=1C=NC(=NC=1)C(F)(F)F)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO IHGUUOHXFRSNNX-GOEBONIOSA-N 0.000 claims 1
CBRUVDPTKMLDST-ZWKOTPCHSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethoxy)phenoxy]pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=CC=C(C=C1)OC(F)(F)F)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO CBRUVDPTKMLDST-ZWKOTPCHSA-N 0.000 claims 1
VVWSNOSRMSLRHM-ZWKOTPCHSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethyl)phenoxy]pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=CC=C(C=C1)C(F)(F)F)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO VVWSNOSRMSLRHM-ZWKOTPCHSA-N 0.000 claims 1
CQQZDLVWCNKRPX-ZWKOTPCHSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethyl)phenoxy]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=CC=C(C=C1)C(F)(F)F)S(=O)(=O)C1=C(C#N)C=CC=C1)CO CQQZDLVWCNKRPX-ZWKOTPCHSA-N 0.000 claims 1
BGAGPKHQRQZTHM-DLBZAZTESA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[6-(trifluoromethyl)pyridin-3-yl]oxypyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC=1C=NC(=CC=1)C(F)(F)F)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO BGAGPKHQRQZTHM-DLBZAZTESA-N 0.000 claims 1
FGUYYSZEXSYFQA-ZWKOTPCHSA-N 2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-phenoxypyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound O[C@]1(CN(C[C@@H]1OC1=CC=CC=C1)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)CO FGUYYSZEXSYFQA-ZWKOTPCHSA-N 0.000 claims 1
BNAIFSCVWAYPDQ-ZWKOTPCHSA-N 2-[(3R,4S)-4-(2,1,3-benzoxadiazol-5-yloxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound N=1ON=C2C=1C=CC(=C2)O[C@@H]1[C@@](CN(C1)S(=O)(=O)C1=C(C#N)C=C(C=C1)C(F)(F)F)(CO)O BNAIFSCVWAYPDQ-ZWKOTPCHSA-N 0.000 claims 1
JTLJRBFDEMVPKX-ZWKOTPCHSA-N 2-[(3R,4S)-4-(3,4-difluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound FC=1C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC=1F JTLJRBFDEMVPKX-ZWKOTPCHSA-N 0.000 claims 1
GLWRWEKGRDAKNR-ZWKOTPCHSA-N 2-[(3R,4S)-4-(3-chloro-4-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound ClC=1C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC=1F GLWRWEKGRDAKNR-ZWKOTPCHSA-N 0.000 claims 1
LEAZRIKBTMTVRA-RBUKOAKNSA-N 2-[(3R,4S)-4-(3-cyanophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C=1C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC=1 LEAZRIKBTMTVRA-RBUKOAKNSA-N 0.000 claims 1
PVKRKFKRLZZSQW-RBUKOAKNSA-N 2-[(3R,4S)-4-(3-fluoro-4-methoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound FC=1C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC=1OC PVKRKFKRLZZSQW-RBUKOAKNSA-N 0.000 claims 1
KVWQVLSYDNJLKD-RBUKOAKNSA-N 2-[(3R,4S)-4-(4-chloro-2-methoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound ClC1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)OC KVWQVLSYDNJLKD-RBUKOAKNSA-N 0.000 claims 1
KUNVDAVNFTWSQH-ZWKOTPCHSA-N 2-[(3R,4S)-4-(4-chloro-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound ClC1=C(C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)F KUNVDAVNFTWSQH-ZWKOTPCHSA-N 0.000 claims 1
CJPUHRPOFMSXTO-ZWKOTPCHSA-N 2-[(3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound ClC1=CC=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1 CJPUHRPOFMSXTO-ZWKOTPCHSA-N 0.000 claims 1
ALOQXGDVYINTRU-ZWKOTPCHSA-N 2-[(3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC1=CC=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=CC=C2)(CO)O)C=C1 ALOQXGDVYINTRU-ZWKOTPCHSA-N 0.000 claims 1
KXYLMSOURZWOMT-IWSJWDQHSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(1-hydroxyethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(C(C)O)O)OC1=CC(=C(C#N)C=C1)F KXYLMSOURZWOMT-IWSJWDQHSA-N 0.000 claims 1
GPCXZGZUBNNTTC-BJKOFHAPSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(2-trimethylsilylethynyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C#C[Si](C)(C)C)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F GPCXZGZUBNNTTC-BJKOFHAPSA-N 0.000 claims 1
RAYCYIKGBWRQBC-RBUKOAKNSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F RAYCYIKGBWRQBC-RBUKOAKNSA-N 0.000 claims 1
UNCHCGFSZQGKAS-LEWJYISDSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-ethylbenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)CC)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F UNCHCGFSZQGKAS-LEWJYISDSA-N 0.000 claims 1
ZWIIRLAGTIKTKA-LEWJYISDSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-ethynylbenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C#C)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F ZWIIRLAGTIKTKA-LEWJYISDSA-N 0.000 claims 1
CNAQFEJUMODUKO-VQTJNVASSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-methylbenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F CNAQFEJUMODUKO-VQTJNVASSA-N 0.000 claims 1
BOZNXQYTNRQBEB-LOSJGSFVSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-phenylbenzonitrile Chemical compound C(#N)C1=C(C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C=C(C=C2)C2=CC=CC=C2)C#N)(CO)O)C=C1)F BOZNXQYTNRQBEB-LOSJGSFVSA-N 0.000 claims 1
WPOKDPIUBKWKKU-RBUKOAKNSA-N 2-[(3R,4S)-4-(4-cyanophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=CC=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1 WPOKDPIUBKWKKU-RBUKOAKNSA-N 0.000 claims 1
NHKBFAYGDXXDIK-ZWKOTPCHSA-N 2-[(3R,4S)-4-(4-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1 NHKBFAYGDXXDIK-ZWKOTPCHSA-N 0.000 claims 1
FAMYKXAGXLCTTL-VQTJNVASSA-N 2-[(3R,4S)-4-[3-(cyanomethyl)phenoxy]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)CC=1C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC=1 FAMYKXAGXLCTTL-VQTJNVASSA-N 0.000 claims 1
MBMXYEKLVYNWEA-ZWKOTPCHSA-N 2-[(3R,4S)-4-[3-fluoro-4-(trifluoromethoxy)phenoxy]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound FC=1C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC=1OC(F)(F)F MBMXYEKLVYNWEA-ZWKOTPCHSA-N 0.000 claims 1
HKPVGEJLYISGTQ-ZWKOTPCHSA-N 2-[(3R,4S)-4-[3-fluoro-4-(trifluoromethyl)phenoxy]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound FC=1C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC=1C(F)(F)F HKPVGEJLYISGTQ-ZWKOTPCHSA-N 0.000 claims 1
NAHRWCKIZYCERC-VQTJNVASSA-N 2-[(3R,4S)-4-[4-(cyanomethyl)phenoxy]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)CC1=CC=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1 NAHRWCKIZYCERC-VQTJNVASSA-N 0.000 claims 1
AKJSOLMXGFOVRV-RBUKOAKNSA-N 2-[(3R,4S)-4-[4-cyano-3-(trifluoromethoxy)phenoxy]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)OC(F)(F)F AKJSOLMXGFOVRV-RBUKOAKNSA-N 0.000 claims 1
JSQLPSJOMUXHMZ-RBUKOAKNSA-N 2-[(3R,4S)-4-[4-cyano-3-(trifluoromethyl)phenoxy]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)C(F)(F)F JSQLPSJOMUXHMZ-RBUKOAKNSA-N 0.000 claims 1
CJPUHRPOFMSXTO-ROUUACIJSA-N 2-[(3S,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound ClC1=CC=C(O[C@@H]2[C@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1 CJPUHRPOFMSXTO-ROUUACIJSA-N 0.000 claims 1
NHBBJEBTHUFFCB-ROUUACIJSA-N 2-[(3S,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-fluorobenzonitrile Chemical compound ClC1=CC=C(O[C@@H]2[C@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)F)(CO)O)C=C1 NHBBJEBTHUFFCB-ROUUACIJSA-N 0.000 claims 1
KRMYDFGJHOCZAB-SFTDATJTSA-N 2-[(3S,4S)-4-(4-cyano-3-fluorophenoxy)-3-(ethylaminomethyl)-3-hydroxypyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@](C1)(O)CNCC)OC1=CC(=C(C#N)C=C1)F KRMYDFGJHOCZAB-SFTDATJTSA-N 0.000 claims 1
RAYCYIKGBWRQBC-OALUTQOASA-N 2-[(3S,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F RAYCYIKGBWRQBC-OALUTQOASA-N 0.000 claims 1
MBNKZKIVHNDIBP-PMACEKPBSA-N 2-[(3S,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(methylaminomethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CNC)O)OC1=CC(=C(C#N)C=C1)F MBNKZKIVHNDIBP-PMACEKPBSA-N 0.000 claims 1
MXXAORYJSYDSKI-VXKWHMMOSA-N 2-[(3S,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-[(propan-2-ylamino)methyl]pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CNC(C)C)O)OC1=CC(=C(C#N)C=C1)F MXXAORYJSYDSKI-VXKWHMMOSA-N 0.000 claims 1
HQGWLELEQNWXGA-RBUKOAKNSA-N 2-chloro-6-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C(=C(C=CC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C#N HQGWLELEQNWXGA-RBUKOAKNSA-N 0.000 claims 1
FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 claims 1
KUQATLJLKKKRGC-RBUKOAKNSA-N 2-fluoro-4-[(3S,4R)-1-(3-fluoro-4-methylphenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=CC(=C(C=C1)C)F KUQATLJLKKKRGC-RBUKOAKNSA-N 0.000 claims 1
YOLNBMSKLWGUJK-FUHWJXTLSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-(2,4,6-trichlorophenyl)sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=C(C=C(C=C1Cl)Cl)Cl YOLNBMSKLWGUJK-FUHWJXTLSA-N 0.000 claims 1
LKNKZEBUSSAXIV-ZWKOTPCHSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-(2-iodophenyl)sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=C(C=CC=C1)I LKNKZEBUSSAXIV-ZWKOTPCHSA-N 0.000 claims 1
PGVPUPCHNFGNAU-ZWKOTPCHSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-(4-iodophenyl)sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=CC=C(C=C1)I PGVPUPCHNFGNAU-ZWKOTPCHSA-N 0.000 claims 1
WKKRGMJLXNAWKT-DOTOQJQBSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-(5-iodopyridin-2-yl)sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=NC=C(C=C1)I WKKRGMJLXNAWKT-DOTOQJQBSA-N 0.000 claims 1
JCUSBFPKRDXQCI-PZJWPPBQSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-(6-methylpyridazin-3-yl)sulfonylpyrrolidin-3-yl]oxy-5-(2-methylpropoxy)benzonitrile Chemical compound FC1=C(C#N)C=C(C(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C=1N=NC(=CC=1)C)OCC(C)C JCUSBFPKRDXQCI-PZJWPPBQSA-N 0.000 claims 1
IFTQJCIZESUWDG-GOEBONIOSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[2-(trifluoromethyl)pyrimidin-5-yl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C=1C=NC(=NC=1)C(F)(F)F IFTQJCIZESUWDG-GOEBONIOSA-N 0.000 claims 1
RBKPBIMDFZDKAG-RBUKOAKNSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[2-methyl-4-(trifluoromethyl)phenyl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=C(C=C(C=C1)C(F)(F)F)C RBKPBIMDFZDKAG-RBUKOAKNSA-N 0.000 claims 1
YPSQKUXGRYPZMP-FCHUYYIVSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[4-(trifluoromethyl)phenyl]sulfonylpyrrolidin-3-yl]oxy-5-(2-methylpropoxy)benzonitrile Chemical compound FC1=C(C#N)C=C(C(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=CC=C(C=C1)C(F)(F)F)OCC(C)C YPSQKUXGRYPZMP-FCHUYYIVSA-N 0.000 claims 1
VXWNRMAUQHKNHT-ZWKOTPCHSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[4-(trifluoromethyl)phenyl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=CC=C(C=C1)C(F)(F)F VXWNRMAUQHKNHT-ZWKOTPCHSA-N 0.000 claims 1
PAIBGHXMSPVDPA-UKILVPOCSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[5-(2-phenylethynyl)pyridin-2-yl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=NC=C(C=C1)C#CC1=CC=CC=C1 PAIBGHXMSPVDPA-UKILVPOCSA-N 0.000 claims 1
PLIRXCTWUNSBPV-DOTOQJQBSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[5-(trifluoromethoxy)pyridin-2-yl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=NC=C(C=C1)OC(F)(F)F PLIRXCTWUNSBPV-DOTOQJQBSA-N 0.000 claims 1
QSPPCQZBPSEOHB-DOTOQJQBSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[5-(trifluoromethyl)pyridin-2-yl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=NC=C(C=C1)C(F)(F)F QSPPCQZBPSEOHB-DOTOQJQBSA-N 0.000 claims 1
WWIFABLYOMFZBP-XJKSGUPXSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[5-(trifluoromethyl)thiophen-2-yl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C=1SC(=CC=1)C(F)(F)F WWIFABLYOMFZBP-XJKSGUPXSA-N 0.000 claims 1
SXZFUDIXPJKQFR-WMLDXEAASA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[6-(trifluoromethoxy)pyridin-2-yl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C1=NC(=CC=C1)OC(F)(F)F SXZFUDIXPJKQFR-WMLDXEAASA-N 0.000 claims 1
OAYXWPXRHKQBTA-ZWKOTPCHSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[6-(trifluoromethyl)pyridin-3-yl]sulfonylpyrrolidin-3-yl]oxy-5-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound FC1=C(C#N)C=C(C(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C=1C=NC(=CC=1)C(F)(F)F)OCC(F)(F)F OAYXWPXRHKQBTA-ZWKOTPCHSA-N 0.000 claims 1
FAFREWBOGVGLDU-LEWJYISDSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[6-(trifluoromethyl)pyridin-3-yl]sulfonylpyrrolidin-3-yl]oxy-5-(2-methylpropoxy)benzonitrile Chemical compound FC1=C(C#N)C=C(C(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C=1C=NC(=CC=1)C(F)(F)F)OCC(C)C FAFREWBOGVGLDU-LEWJYISDSA-N 0.000 claims 1
GZNVWSHNMVIORD-DLBZAZTESA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-[6-(trifluoromethyl)pyridin-3-yl]sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1(CO)O)S(=O)(=O)C=1C=NC(=CC=1)C(F)(F)F GZNVWSHNMVIORD-DLBZAZTESA-N 0.000 claims 1
NITLHDRMZNGSBZ-ZUSMLRIVSA-N 2-fluoro-4-[(3S,4R)-4-hydroxy-4-[(1R)-1-hydroxyethyl]-1-(4-iodophenyl)sulfonylpyrrolidin-3-yl]oxybenzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)O[C@H]1CN(C[C@]1([C@@H](C)O)O)S(=O)(=O)C1=CC=C(C=C1)I NITLHDRMZNGSBZ-ZUSMLRIVSA-N 0.000 claims 1
CGQUJTXVZBQBTL-DLBZAZTESA-N 3-[(3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound ClC1=CC=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C=2C(=NC=CC=2)C#N)(CO)O)C=C1 CGQUJTXVZBQBTL-DLBZAZTESA-N 0.000 claims 1
LVLFFXSNOUTCQO-ZWKOTPCHSA-N 3-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound C(#N)C1=C(C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C=2C(=NC=CC=2)C#N)(CO)O)C=C1)F LVLFFXSNOUTCQO-ZWKOTPCHSA-N 0.000 claims 1
LTAZQCAKTONOJS-YXKWSERDSA-N 3-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-[(1S)-1-hydroxyethyl]pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound C(#N)C1=C(C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C=2C(=NC=CC=2)C#N)([C@H](C)O)O)C=C1)F LTAZQCAKTONOJS-YXKWSERDSA-N 0.000 claims 1
QHZNBVCRJNQCMI-VQTJNVASSA-N 3-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-4-methoxybenzonitrile Chemical compound C(#N)C=1C=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=1)OC QHZNBVCRJNQCMI-VQTJNVASSA-N 0.000 claims 1
LVLFFXSNOUTCQO-ROUUACIJSA-N 3-[(3S,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound C(#N)C1=C(C=C(O[C@@H]2[C@](CN(C2)S(=O)(=O)C=2C(=NC=CC=2)C#N)(CO)O)C=C1)F LVLFFXSNOUTCQO-ROUUACIJSA-N 0.000 claims 1
CHOOTPDQSWZUFB-ZWKOTPCHSA-N 3-bromo-4-[(3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound BrC=1C=C(C#N)C=CC=1S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC=C(C=C1)Cl)(CO)O CHOOTPDQSWZUFB-ZWKOTPCHSA-N 0.000 claims 1
ZFPPZLYAGQEEOM-XZOQPEGZSA-N 3-butoxy-4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxybenzonitrile Chemical compound C(CCC)OC1=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC(=C1)C#N ZFPPZLYAGQEEOM-XZOQPEGZSA-N 0.000 claims 1
TYWHEJMBWGVFEW-ZWKOTPCHSA-N 3-chloro-4-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethyl)phenoxy]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=C(C#N)C=CC=1S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC=C(C=C1)C(F)(F)F)(CO)O TYWHEJMBWGVFEW-ZWKOTPCHSA-N 0.000 claims 1
WTAZKBZVUKNROS-ZWKOTPCHSA-N 3-chloro-4-[(3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=C(C#N)C=CC=1S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC=C(C=C1)Cl)(CO)O WTAZKBZVUKNROS-ZWKOTPCHSA-N 0.000 claims 1
TZFPRBYLOKPOLA-RBUKOAKNSA-N 3-chloro-4-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC1=C(C=CC(=C1)C#N)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F TZFPRBYLOKPOLA-RBUKOAKNSA-N 0.000 claims 1
BLOAUDWOPBYPMR-OCCQLPPTSA-N 3-chloro-4-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-[(1S)-1-hydroxyethyl]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC1=C(C=CC(=C1)C#N)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@H](C)O)O)OC1=CC(=C(C#N)C=C1)F BLOAUDWOPBYPMR-OCCQLPPTSA-N 0.000 claims 1
UNBDCUUJLUFWTD-RBUKOAKNSA-N 3-chloro-4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxybenzonitrile Chemical compound ClC1=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=CC(=C1)C#N UNBDCUUJLUFWTD-RBUKOAKNSA-N 0.000 claims 1
TZFPRBYLOKPOLA-OALUTQOASA-N 3-chloro-4-[(3S,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC1=C(C=CC(=C1)C#N)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F TZFPRBYLOKPOLA-OALUTQOASA-N 0.000 claims 1
LOPGPWHFAXBCDR-RBUKOAKNSA-N 4-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-3-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C(F)(F)F LOPGPWHFAXBCDR-RBUKOAKNSA-N 0.000 claims 1
LMVHKGPFEDQJIX-RBUKOAKNSA-N 4-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-3-fluorobenzonitrile Chemical compound C(#N)C1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)F LMVHKGPFEDQJIX-RBUKOAKNSA-N 0.000 claims 1
XBWSVBQFTXFZKT-VQTJNVASSA-N 4-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-3-methoxybenzonitrile Chemical compound C(#N)C1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)OC XBWSVBQFTXFZKT-VQTJNVASSA-N 0.000 claims 1
RXNBROCPNDBIDE-VQTJNVASSA-N 4-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-3-methylbenzonitrile Chemical compound C(#N)C1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C RXNBROCPNDBIDE-VQTJNVASSA-N 0.000 claims 1
OOBQVYSGIVJKLB-ZWKOTPCHSA-N 4-[(3S,4R)-1-(2,1,3-benzoxadiazol-5-ylsulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound N=1ON=C2C=1C=CC(=C2)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F OOBQVYSGIVJKLB-ZWKOTPCHSA-N 0.000 claims 1
GLNANLDDBGBFDP-FUHWJXTLSA-N 4-[(3S,4R)-1-(2,3-dichlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC=C1Cl)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F GLNANLDDBGBFDP-FUHWJXTLSA-N 0.000 claims 1
VEKPUFJACSQBMV-ZWKOTPCHSA-N 4-[(3S,4R)-1-(2,4-dichlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F VEKPUFJACSQBMV-ZWKOTPCHSA-N 0.000 claims 1
NSUFPNUHKUSOCN-KQPNJSLMSA-N 4-[(3S,4R)-1-(2,4-dichlorophenyl)sulfonyl-4-hydroxy-4-[(1S)-1-hydroxyethyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@H](C)O)O)OC1=CC(=C(C#N)C=C1)F NSUFPNUHKUSOCN-KQPNJSLMSA-N 0.000 claims 1
HYTGDWSVNKFFIJ-WMLDXEAASA-N 4-[(3S,4R)-1-(2,6-dichloropyridin-3-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=NC(=CC=C1S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)Cl HYTGDWSVNKFFIJ-WMLDXEAASA-N 0.000 claims 1
URUJVHKAFLBDAT-ZWKOTPCHSA-N 4-[(3S,4R)-1-(2-bromo-4-chlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=C(C=CC(=C1)Cl)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F URUJVHKAFLBDAT-ZWKOTPCHSA-N 0.000 claims 1
INGOBCPNEFHRQJ-RBUKOAKNSA-N 4-[(3S,4R)-1-(2-bromo-4-methoxyphenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=C(C=CC(=C1)OC)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F INGOBCPNEFHRQJ-RBUKOAKNSA-N 0.000 claims 1
VYWTVROAADDMNC-ZWKOTPCHSA-N 4-[(3S,4R)-1-(2-bromophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F VYWTVROAADDMNC-ZWKOTPCHSA-N 0.000 claims 1
ANIVMSHAMOFVPS-ZWKOTPCHSA-N 4-[(3S,4R)-1-(2-chloro-4-iodophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC(=C1)I)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F ANIVMSHAMOFVPS-ZWKOTPCHSA-N 0.000 claims 1
OTUZYPFEWVLDAR-RBUKOAKNSA-N 4-[(3S,4R)-1-(2-chloro-4-methylphenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC(=C1)C)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F OTUZYPFEWVLDAR-RBUKOAKNSA-N 0.000 claims 1
UDACHGNOHQZQAE-ZWKOTPCHSA-N 4-[(3S,4R)-1-(2-chlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F UDACHGNOHQZQAE-ZWKOTPCHSA-N 0.000 claims 1
DINXOINIVYKLRH-OCCQLPPTSA-N 4-[(3S,4R)-1-(2-cyano-4-fluorophenyl)sulfonyl-4-hydroxy-4-[(1S)-1-hydroxyethyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)F)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@H](C)O)O)OC1=CC(=C(C#N)C=C1)F DINXOINIVYKLRH-OCCQLPPTSA-N 0.000 claims 1
QXGDAKGHFGPQIN-RBUKOAKNSA-N 4-[(3S,4R)-1-(2-cyano-4-iodophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)I)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F QXGDAKGHFGPQIN-RBUKOAKNSA-N 0.000 claims 1
FUIZWTYPRZUPCR-SKOKVVANSA-N 4-[(3S,4R)-1-(2-cyano-4-methoxyphenyl)sulfonyl-4-hydroxy-4-[(1S)-1-hydroxyethyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)OC)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@H](C)O)O)OC1=CC(=C(C#N)C=C1)F FUIZWTYPRZUPCR-SKOKVVANSA-N 0.000 claims 1
XJGYLMWPNKXXNM-VQTJNVASSA-N 4-[(3S,4R)-1-(2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound C(#N)C1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(F)(F)F)F XJGYLMWPNKXXNM-VQTJNVASSA-N 0.000 claims 1
IMPVWSDQRRBQBI-XZOQPEGZSA-N 4-[(3S,4R)-1-(2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2-methylpropoxy)benzonitrile Chemical compound C(#N)C1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(C)C)F IMPVWSDQRRBQBI-XZOQPEGZSA-N 0.000 claims 1
NMMLXSMBLJSNCM-RBUKOAKNSA-N 4-[(3S,4R)-1-(2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F NMMLXSMBLJSNCM-RBUKOAKNSA-N 0.000 claims 1
HXCDWGMPZUSPKO-QTJFZDIUSA-N 4-[(3S,4R)-1-(2-cyanophenyl)sulfonyl-4-hydroxy-4-[(1S)-1-hydroxyethyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@H](C)O)O)OC1=CC(=C(C#N)C=C1)F HXCDWGMPZUSPKO-QTJFZDIUSA-N 0.000 claims 1
JSYVUWQUXKEOCX-VQTJNVASSA-N 4-[(3S,4R)-1-(2-ethynylphenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#C)C1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F JSYVUWQUXKEOCX-VQTJNVASSA-N 0.000 claims 1
OYRPQZSFKXVMIW-RBUKOAKNSA-N 4-[(3S,4R)-1-(4-bromo-2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C#N OYRPQZSFKXVMIW-RBUKOAKNSA-N 0.000 claims 1
CRFSCDPIVJTOKY-ZWKOTPCHSA-N 4-[(3S,4R)-1-(4-bromophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F CRFSCDPIVJTOKY-ZWKOTPCHSA-N 0.000 claims 1
FQOIRZPBDPSXMK-RBUKOAKNSA-N 4-[(3S,4R)-1-(4-chloro-2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C#N FQOIRZPBDPSXMK-RBUKOAKNSA-N 0.000 claims 1
MTOSZFBIYRBZHX-OCCQLPPTSA-N 4-[(3S,4R)-1-(4-chloro-2-cyanophenyl)sulfonyl-4-hydroxy-4-[(1S)-1-hydroxyethyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@H](C)O)O)OC1=CC(=C(C#N)C=C1)F)C#N MTOSZFBIYRBZHX-OCCQLPPTSA-N 0.000 claims 1
VLACCUVXIIMGKV-LEWJYISDSA-N 4-[(3S,4R)-1-(4-chloro-2-cyanophenyl)sulfonyl-4-hydroxy-4-[(2-hydroxyethylamino)methyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@](C1)(CNCCO)O)OC1=CC(=C(C#N)C=C1)F)C#N VLACCUVXIIMGKV-LEWJYISDSA-N 0.000 claims 1
XUQOKJTXAWHPIG-GOEBONIOSA-N 4-[(3S,4R)-1-(4-chloro-2-methylpyrazol-3-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=NN(C=1S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C XUQOKJTXAWHPIG-GOEBONIOSA-N 0.000 claims 1
ZNGHMFZWPHGPCS-ZWKOTPCHSA-N 4-[(3S,4R)-1-(4-chlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F ZNGHMFZWPHGPCS-ZWKOTPCHSA-N 0.000 claims 1
MGPLXTXAOKOIGS-VQTJNVASSA-N 4-[(3S,4R)-1-(4-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound C(#N)C1=CC=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(F)(F)F)F MGPLXTXAOKOIGS-VQTJNVASSA-N 0.000 claims 1
BOMBLDAGOMRXFU-XZOQPEGZSA-N 4-[(3S,4R)-1-(4-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2-methylpropoxy)benzonitrile Chemical compound C(#N)C1=CC=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(C)C)F BOMBLDAGOMRXFU-XZOQPEGZSA-N 0.000 claims 1
GNUSVHQKJZLIPF-RBUKOAKNSA-N 4-[(3S,4R)-1-(4-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=CC=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F GNUSVHQKJZLIPF-RBUKOAKNSA-N 0.000 claims 1
MLBIDNNNCSDRHY-DOTOQJQBSA-N 4-[(3S,4R)-1-(5-bromopyridin-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F MLBIDNNNCSDRHY-DOTOQJQBSA-N 0.000 claims 1
QSEVQKCQMPOXMH-ULHBIWDBSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-(1-hydroxyethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(C(C)O)O)OC1=CC(=C(C#N)C=C1)F QSEVQKCQMPOXMH-ULHBIWDBSA-N 0.000 claims 1
UHNWQHOCPOIRNP-FUHWJXTLSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(F)(F)F)F UHNWQHOCPOIRNP-FUHWJXTLSA-N 0.000 claims 1
FXSPGILSUUJZOG-DOTOQJQBSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F FXSPGILSUUJZOG-DOTOQJQBSA-N 0.000 claims 1
CGCBPQPQZUEBIO-PZJWPPBQSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxynaphthalene-1-carbonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC=C(C2=CC=CC=C12)C#N CGCBPQPQZUEBIO-PZJWPPBQSA-N 0.000 claims 1
YUJAPESAGAZAHG-WSTZPKSXSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-[(1R)-1-hydroxybutyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@@H](CCC)O)O)OC1=CC(=C(C#N)C=C1)F YUJAPESAGAZAHG-WSTZPKSXSA-N 0.000 claims 1
NRLLNAACZNKZCA-ZIFCJYIRSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-[(1R)-1-hydroxypropyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@@H](CC)O)O)OC1=CC(=C(C#N)C=C1)F NRLLNAACZNKZCA-ZIFCJYIRSA-N 0.000 claims 1
SIOXICFSGALSME-JLBUNGTFSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-[(1R)-1-methoxyethyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@@H](C)OC)O)OC1=CC(=C(C#N)C=C1)F SIOXICFSGALSME-JLBUNGTFSA-N 0.000 claims 1
YUJAPESAGAZAHG-CMKODMSKSA-N 4-[(3S,4R)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-[(1S)-1-hydroxybutyl]pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)([C@H](CCC)O)O)OC1=CC(=C(C#N)C=C1)F YUJAPESAGAZAHG-CMKODMSKSA-N 0.000 claims 1
IVALWPTVORKCDD-XJKSGUPXSA-N 4-[(3S,4R)-1-(5-chlorothiophen-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC=C(S1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F IVALWPTVORKCDD-XJKSGUPXSA-N 0.000 claims 1
RJLZQVMPPZFBEO-PKOBYXMFSA-N 4-[(3S,4R)-1-(5-ethynylpyridin-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#C)C=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F RJLZQVMPPZFBEO-PKOBYXMFSA-N 0.000 claims 1
KJCIAEYCZMXCHI-DOTOQJQBSA-N 4-[(3S,4R)-1-(6-bromopyridin-3-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=CC=C(C=N1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F KJCIAEYCZMXCHI-DOTOQJQBSA-N 0.000 claims 1
QAOGGNPOPWZSKZ-DOTOQJQBSA-N 4-[(3S,4R)-1-(6-chloropyridin-3-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC=C(C=N1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F QAOGGNPOPWZSKZ-DOTOQJQBSA-N 0.000 claims 1
QGCIGIMOZYBELR-XHDPSFHLSA-N 4-[(3S,4R)-1-[(2,4-dichloro-1,3-thiazol-5-yl)sulfonyl]-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1SC(=C(N=1)Cl)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F QGCIGIMOZYBELR-XHDPSFHLSA-N 0.000 claims 1
HKVNZULQFVWSLB-MAUKXSAKSA-N 4-[(3S,4R)-1-[(4-chloro-2,1,3-benzoxadiazol-7-yl)sulfonyl]-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC=C(C=2C1=NON=2)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F HKVNZULQFVWSLB-MAUKXSAKSA-N 0.000 claims 1
WQQJHVORKBOCPF-FUHWJXTLSA-N 4-[(3S,4R)-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C(=CC(=C1)C(F)(F)F)Cl)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F WQQJHVORKBOCPF-FUHWJXTLSA-N 0.000 claims 1
RSRAIHHHVIBEHS-MAUKXSAKSA-N 4-[(3S,4R)-1-[2-(difluoromethoxy)pyridin-3-yl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound FC(OC1=NC=CC=C1S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)F RSRAIHHHVIBEHS-MAUKXSAKSA-N 0.000 claims 1
MSIAHBPHGRHRRA-ZWKOTPCHSA-N 4-[(3S,4R)-1-[2-bromo-4-(trifluoromethoxy)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=C(C=CC(=C1)OC(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F MSIAHBPHGRHRRA-ZWKOTPCHSA-N 0.000 claims 1
JKJSOMHQISEAFC-ZWKOTPCHSA-N 4-[(3S,4R)-1-[2-chloro-4-(trifluoromethoxy)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC(=C1)OC(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F JKJSOMHQISEAFC-ZWKOTPCHSA-N 0.000 claims 1
JIMXWIUFUQBTRJ-ZWKOTPCHSA-N 4-[(3S,4R)-1-[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F JIMXWIUFUQBTRJ-ZWKOTPCHSA-N 0.000 claims 1
ITPKBJACSNLTSW-ZWKOTPCHSA-N 4-[(3S,4R)-1-[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxybenzonitrile Chemical compound ClC1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC=C(C#N)C=C1 ITPKBJACSNLTSW-ZWKOTPCHSA-N 0.000 claims 1
UPQIVFUHQOZMPS-DOTOQJQBSA-N 4-[(3S,4R)-1-[2-chloro-6-(trifluoromethyl)pyridin-3-yl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=NC(=CC=C1S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C(F)(F)F UPQIVFUHQOZMPS-DOTOQJQBSA-N 0.000 claims 1
VGJNSYJWHIVHEJ-RBUKOAKNSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethoxy)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)OC(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F VGJNSYJWHIVHEJ-RBUKOAKNSA-N 0.000 claims 1
RXHDNLAFZYZACM-QFBILLFUSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2,3-difluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=C(C(=C(C#N)C=C1)F)F RXHDNLAFZYZACM-QFBILLFUSA-N 0.000 claims 1
QMMAVNBFFODRNM-RBUKOAKNSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2,5-difluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1F)F QMMAVNBFFODRNM-RBUKOAKNSA-N 0.000 claims 1
NSOKZCAAIFWIFO-RBUKOAKNSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2,6-difluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C(=C1)F)F NSOKZCAAIFWIFO-RBUKOAKNSA-N 0.000 claims 1
OVJKEYHSUXMOJY-VQTJNVASSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(F)(F)F)F OVJKEYHSUXMOJY-VQTJNVASSA-N 0.000 claims 1
CUCYZAPLEHPOJR-XZOQPEGZSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2-methylpropoxy)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(C)C)F CUCYZAPLEHPOJR-XZOQPEGZSA-N 0.000 claims 1
SLINGTBXDDBVPA-RBUKOAKNSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-hydroxybenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1O)F SLINGTBXDDBVPA-RBUKOAKNSA-N 0.000 claims 1
SQLLIYDKJYEGMU-VQTJNVASSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-methoxybenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OC)F SQLLIYDKJYEGMU-VQTJNVASSA-N 0.000 claims 1
SEOAWYNQQPRNAJ-FCHUYYIVSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-propan-2-yloxybenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OC(C)C)F SEOAWYNQQPRNAJ-FCHUYYIVSA-N 0.000 claims 1
UJJGUSVHXJYFRK-FCHUYYIVSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-propoxybenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCCC)F UJJGUSVHXJYFRK-FCHUYYIVSA-N 0.000 claims 1
YLVLOTPWDLVGEL-XZOQPEGZSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-(2-methylpropoxy)benzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)OCC(C)C YLVLOTPWDLVGEL-XZOQPEGZSA-N 0.000 claims 1
WEDOWLLJOAINJP-RBUKOAKNSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)C(F)(F)F WEDOWLLJOAINJP-RBUKOAKNSA-N 0.000 claims 1
RVHPSDFKHBDMAN-FCHUYYIVSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-cyclopropyloxybenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)OC1CC1 RVHPSDFKHBDMAN-FCHUYYIVSA-N 0.000 claims 1
FLXROIFEVZQXIZ-LEWJYISDSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-ethoxybenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)OCC FLXROIFEVZQXIZ-LEWJYISDSA-N 0.000 claims 1
GPWPVGZKMNYBCK-RBUKOAKNSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-fluorobenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)F GPWPVGZKMNYBCK-RBUKOAKNSA-N 0.000 claims 1
XABZUWSMJXKIRT-RBUKOAKNSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-hydroxybenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)O XABZUWSMJXKIRT-RBUKOAKNSA-N 0.000 claims 1
ZCYUSHDKUAIRCI-VQTJNVASSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-methoxybenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)OC ZCYUSHDKUAIRCI-VQTJNVASSA-N 0.000 claims 1
FYFFIGHPVHVHCJ-VQTJNVASSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-methylbenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)C FYFFIGHPVHVHCJ-VQTJNVASSA-N 0.000 claims 1
CICBFBCGGCWNCK-FCHUYYIVSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-propan-2-yloxybenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)OC(C)C CICBFBCGGCWNCK-FCHUYYIVSA-N 0.000 claims 1
VFUKCXSNKBBHIY-FCHUYYIVSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-3-propoxybenzonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=C(C#N)C=C(C=C2)C(F)(F)F)(CO)O)C=C1)OCCC VFUKCXSNKBBHIY-FCHUYYIVSA-N 0.000 claims 1
QUKDXZNFJVORAD-LEWJYISDSA-N 4-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-5-ethoxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC)F QUKDXZNFJVORAD-LEWJYISDSA-N 0.000 claims 1
LQYHLWVJQINMKQ-VQTJNVASSA-N 4-[(3S,4R)-1-[2-ethynyl-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#C)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F LQYHLWVJQINMKQ-VQTJNVASSA-N 0.000 claims 1
VILBXAQZVSFLLC-PKOBYXMFSA-N 4-[(3S,4R)-1-[4-(difluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound FC(C1=CC=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)F VILBXAQZVSFLLC-PKOBYXMFSA-N 0.000 claims 1
SQCXZHFCVCBBHI-ZWKOTPCHSA-N 4-[(3S,4R)-1-[4-bromo-2-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C(F)(F)F SQCXZHFCVCBBHI-ZWKOTPCHSA-N 0.000 claims 1
YFWWHOUJKUORRR-ZWKOTPCHSA-N 4-[(3S,4R)-1-[4-chloro-3-(trifluoromethoxy)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)OC(F)(F)F YFWWHOUJKUORRR-ZWKOTPCHSA-N 0.000 claims 1
IUYPYNJJDVSDEU-FCHUYYIVSA-N 4-[(3S,4R)-1-[6-(2-cyclopropylethynyl)pyridin-3-yl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C1(CC1)C#CC1=CC=C(C=N1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F IUYPYNJJDVSDEU-FCHUYYIVSA-N 0.000 claims 1
APJGXHUVYIUWAT-KBXCAEBGSA-N 4-[(3S,4R)-1-[6-(difluoromethoxy)pyridin-2-yl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound FC(OC1=CC=CC(=N1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)F APJGXHUVYIUWAT-KBXCAEBGSA-N 0.000 claims 1
VIEIJAIASWSNJQ-MAUKXSAKSA-N 4-[(3S,4R)-1-[6-(difluoromethoxy)pyridin-3-yl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound FC(OC1=CC=C(C=N1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)F VIEIJAIASWSNJQ-MAUKXSAKSA-N 0.000 claims 1
UGWWKMJMRKCMRR-RBUKOAKNSA-N 4-[(3S,4R)-4-(aminomethyl)-1-(4-chloro-2-cyanophenyl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@@]1([C@H](CN(C1)S(=O)(=O)C1=C(C=C(C=C1)Cl)C#N)OC1=CC(=C(C#N)C=C1)F)O UGWWKMJMRKCMRR-RBUKOAKNSA-N 0.000 claims 1
IQEGRQYYSXOUJI-DOTOQJQBSA-N 4-[(3S,4R)-4-(aminomethyl)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)Cl)OC1=CC(=C(C#N)C=C1)F)O IQEGRQYYSXOUJI-DOTOQJQBSA-N 0.000 claims 1
PEKJQVCUESHMTN-DPZKZMLUSA-N 4-[(3S,4R)-4-[(1R)-1-aminoethyl]-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound N[C@H](C)[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)Cl)OC1=CC(=C(C#N)C=C1)F)O PEKJQVCUESHMTN-DPZKZMLUSA-N 0.000 claims 1
PEKJQVCUESHMTN-SDDDUWNISA-N 4-[(3S,4R)-4-[(1S)-1-aminoethyl]-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound N[C@@H](C)[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)Cl)OC1=CC(=C(C#N)C=C1)F)O PEKJQVCUESHMTN-SDDDUWNISA-N 0.000 claims 1
VEKPUFJACSQBMV-ROUUACIJSA-N 4-[(3S,4S)-1-(2,4-dichlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F VEKPUFJACSQBMV-ROUUACIJSA-N 0.000 claims 1
JEJCVOBORGLBAV-ROUUACIJSA-N 4-[(3S,4S)-1-(2-bromo-4-fluorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=C(C=CC(=C1)F)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F JEJCVOBORGLBAV-ROUUACIJSA-N 0.000 claims 1
KXSURIBYDVPHDH-OALUTQOASA-N 4-[(3S,4S)-1-(2-cyano-4-fluorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)F)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F KXSURIBYDVPHDH-OALUTQOASA-N 0.000 claims 1
BTAYQMNXFRBPII-PMACEKPBSA-N 4-[(3S,4S)-1-(2-cyano-4-methoxyphenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)OC)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F BTAYQMNXFRBPII-PMACEKPBSA-N 0.000 claims 1
NMMLXSMBLJSNCM-OALUTQOASA-N 4-[(3S,4S)-1-(2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound C(#N)C1=C(C=CC=C1)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F NMMLXSMBLJSNCM-OALUTQOASA-N 0.000 claims 1
OYRPQZSFKXVMIW-OALUTQOASA-N 4-[(3S,4S)-1-(4-bromo-2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound BrC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C#N OYRPQZSFKXVMIW-OALUTQOASA-N 0.000 claims 1
FQOIRZPBDPSXMK-OALUTQOASA-N 4-[(3S,4S)-1-(4-chloro-2-cyanophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C#N FQOIRZPBDPSXMK-OALUTQOASA-N 0.000 claims 1
SQQYIVZFMYFKMS-LPHOPBHVSA-N 4-[(3S,4S)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-(2-hydroxypropan-2-yl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@@](C1)(C(C)(C)O)O)OC1=CC(=C(C#N)C=C1)F SQQYIVZFMYFKMS-LPHOPBHVSA-N 0.000 claims 1
UHNWQHOCPOIRNP-WMZOPIPTSA-N 4-[(3S,4S)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1OCC(F)(F)F)F UHNWQHOCPOIRNP-WMZOPIPTSA-N 0.000 claims 1
FXSPGILSUUJZOG-RDJZCZTQSA-N 4-[(3S,4S)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound ClC=1C=CC(=NC=1)S(=O)(=O)N1C[C@@H]([C@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F FXSPGILSUUJZOG-RDJZCZTQSA-N 0.000 claims 1
UGWWKMJMRKCMRR-OALUTQOASA-N 4-[(3S,4S)-4-(aminomethyl)-1-(4-chloro-2-cyanophenyl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=C(C=C(C=C1)Cl)C#N)OC1=CC(=C(C#N)C=C1)F)O UGWWKMJMRKCMRR-OALUTQOASA-N 0.000 claims 1
VYTPAKCIAYHXPF-HOCLYGCPSA-N 4-[(3S,4S)-4-(aminomethyl)-1-(4-chloro-2-methylpyrazol-3-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=C(C=NN1C)Cl)OC1=CC(=C(C#N)C=C1)F)O VYTPAKCIAYHXPF-HOCLYGCPSA-N 0.000 claims 1
LDFMTXHBXGYSSV-RDJZCZTQSA-N 4-[(3S,4S)-4-(aminomethyl)-1-(5-bromopyridin-2-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)Br)OC1=CC(=C(C#N)C=C1)F)O LDFMTXHBXGYSSV-RDJZCZTQSA-N 0.000 claims 1
IQEGRQYYSXOUJI-RDJZCZTQSA-N 4-[(3S,4S)-4-(aminomethyl)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)Cl)OC1=CC(=C(C#N)C=C1)F)O IQEGRQYYSXOUJI-RDJZCZTQSA-N 0.000 claims 1
GJTQFZUKBQMBOD-RDJZCZTQSA-N 4-[(3S,4S)-4-(aminomethyl)-1-(5-chloropyridin-2-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxybenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)Cl)OC1=CC=C(C#N)C=C1)O GJTQFZUKBQMBOD-RDJZCZTQSA-N 0.000 claims 1
FSUVBKQFJJXWPI-RDJZCZTQSA-N 4-[(3S,4S)-4-(aminomethyl)-1-(5-fluoropyridin-2-yl)sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)F)OC1=CC(=C(C#N)C=C1)F)O FSUVBKQFJJXWPI-RDJZCZTQSA-N 0.000 claims 1
XZAQHIADPRKFBU-YJBOKZPZSA-N 4-[(3S,4S)-4-(aminomethyl)-1-[5-(difluoromethoxy)pyridin-2-yl]sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)OC(F)F)OC1=CC(=C(C#N)C=C1)F)O XZAQHIADPRKFBU-YJBOKZPZSA-N 0.000 claims 1
YPQJZVOIYLLURE-YJBOKZPZSA-N 4-[(3S,4S)-4-(aminomethyl)-1-[5-(difluoromethyl)pyridin-2-yl]sulfonyl-4-hydroxypyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)C(F)F)OC1=CC(=C(C#N)C=C1)F)O YPQJZVOIYLLURE-YJBOKZPZSA-N 0.000 claims 1
QBOCPJZKIRNVAQ-RDJZCZTQSA-N 4-[(3S,4S)-4-(aminomethyl)-4-hydroxy-1-(5-iodopyridin-2-yl)sulfonylpyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)I)OC1=CC(=C(C#N)C=C1)F)O QBOCPJZKIRNVAQ-RDJZCZTQSA-N 0.000 claims 1
FHHVTOGIRDJOOI-RDJZCZTQSA-N 4-[(3S,4S)-4-(aminomethyl)-4-hydroxy-1-[5-(trifluoromethoxy)pyridin-2-yl]sulfonylpyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C1=NC=C(C=C1)OC(F)(F)F)OC1=CC(=C(C#N)C=C1)F)O FHHVTOGIRDJOOI-RDJZCZTQSA-N 0.000 claims 1
TXJRDRQBDKNGFG-RDJZCZTQSA-N 4-[(3S,4S)-4-(aminomethyl)-4-hydroxy-1-[6-(trifluoromethoxy)pyridin-3-yl]sulfonylpyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C=1C=NC(=CC=1)OC(F)(F)F)OC1=CC(=C(C#N)C=C1)F)O TXJRDRQBDKNGFG-RDJZCZTQSA-N 0.000 claims 1
BFLRKBYCHRDPOW-IRXDYDNUSA-N 4-[(3S,4S)-4-(aminomethyl)-4-hydroxy-1-[6-(trifluoromethyl)pyridin-3-yl]sulfonylpyrrolidin-3-yl]oxy-2-fluorobenzonitrile Chemical compound NC[C@]1([C@H](CN(C1)S(=O)(=O)C=1C=NC(=CC=1)C(F)(F)F)OC1=CC(=C(C#N)C=C1)F)O BFLRKBYCHRDPOW-IRXDYDNUSA-N 0.000 claims 1
HAJIQKDAYSTMBH-SFTDATJTSA-N 4-[[(4S,5S)-2-(4-chloro-2-cyanophenyl)sulfonyl-6-oxa-2,9-diazaspiro[4.5]decan-4-yl]oxy]-2-fluorobenzonitrile Chemical compound ClC1=CC(=C(C=C1)S(=O)(=O)N1C[C@@]2([C@H](C1)OC1=CC(=C(C#N)C=C1)F)OCCNC2)C#N HAJIQKDAYSTMBH-SFTDATJTSA-N 0.000 claims 1
ZCHLIXGIGMZMMA-DLBZAZTESA-N 5-[(3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound ClC1=CC=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C=2C=CC(=NC=2)C#N)(CO)O)C=C1 ZCHLIXGIGMZMMA-DLBZAZTESA-N 0.000 claims 1
SZLCLXSFLBZYLC-ZWKOTPCHSA-N 5-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound C(#N)C1=C(C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C=2C=CC(=NC=2)C#N)(CO)O)C=C1)F SZLCLXSFLBZYLC-ZWKOTPCHSA-N 0.000 claims 1
UVEGKAIFYYUKPX-FCHUYYIVSA-N 5-[(3R,4S)-4-[4-cyano-5-fluoro-2-(2-methylpropoxy)phenoxy]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound C(#N)C1=CC(=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C=2C=CC(=NC=2)C#N)(CO)O)C=C1F)OCC(C)C UVEGKAIFYYUKPX-FCHUYYIVSA-N 0.000 claims 1
IJZSXZSALULAFF-DLBZAZTESA-N 5-[(3S,4R)-1-(2,4-dichlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxypyridine-2-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC=1C=CC(=NC=1)C#N IJZSXZSALULAFF-DLBZAZTESA-N 0.000 claims 1
LXZMWEHWRKIKAE-ZWKOTPCHSA-N 5-[(3S,4R)-1-(2-chloro-4-methylphenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxypyridine-2-carbonitrile Chemical compound ClC1=C(C=CC(=C1)C)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC=1C=CC(=NC=1)C#N LXZMWEHWRKIKAE-ZWKOTPCHSA-N 0.000 claims 1
NHXYOGAQVFPIDR-DLBZAZTESA-N 5-[(3S,4R)-1-[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxypyridine-2-carbonitrile Chemical compound ClC1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC=1C=CC(=NC=1)C#N NHXYOGAQVFPIDR-DLBZAZTESA-N 0.000 claims 1
AHLSZGBIDJIVEW-ZWKOTPCHSA-N 5-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxypyridine-2-carbonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC=1C=CC(=NC=1)C#N AHLSZGBIDJIVEW-ZWKOTPCHSA-N 0.000 claims 1
ZMSVIWDOIUSPQA-DOTOQJQBSA-N 5-[(3S,4R)-1-[2-cyano-4-(trifluoromethyl)phenyl]sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]oxypyrimidine-2-carbonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC=1C=NC(=NC=1)C#N ZMSVIWDOIUSPQA-DOTOQJQBSA-N 0.000 claims 1
GXFAAHNBXMVYAN-DOTOQJQBSA-N 5-[(3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-(2,4,6-trichlorophenyl)sulfonylpyrrolidin-3-yl]oxypyridine-2-carbonitrile Chemical compound O[C@@]1([C@H](CN(C1)S(=O)(=O)C1=C(C=C(C=C1Cl)Cl)Cl)OC=1C=CC(=NC=1)C#N)CO GXFAAHNBXMVYAN-DOTOQJQBSA-N 0.000 claims 1
OXHAEQVNFPDJMM-ROUUACIJSA-N 5-[(3S,4S)-3-(aminomethyl)-4-(4-cyano-3-fluorophenoxy)-3-hydroxypyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile Chemical compound NC[C@@]1(CN(C[C@@H]1OC1=CC(=C(C=C1)C#N)F)S(=O)(=O)C=1C=CC(=NC=1)C#N)O OXHAEQVNFPDJMM-ROUUACIJSA-N 0.000 claims 1
WSZDSTZMGOLMKN-LEWJYISDSA-N 5-acetyl-2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound C(C)(=O)C1=CC(=C(C=C1)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F)C#N WSZDSTZMGOLMKN-LEWJYISDSA-N 0.000 claims 1
XLEDOOPTHGDFBM-MAUKXSAKSA-N 5-chloro-2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,3,4-trifluorophenoxy)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@]([C@H](C1)OC1=C(C(=C(C=C1)F)F)F)(CO)O XLEDOOPTHGDFBM-MAUKXSAKSA-N 0.000 claims 1
JTOZCQYBNHBBRU-ZWKOTPCHSA-N 5-chloro-2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,4,5-trifluorophenoxy)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@]([C@H](C1)OC1=C(C=C(C(=C1)F)F)F)(CO)O JTOZCQYBNHBBRU-ZWKOTPCHSA-N 0.000 claims 1
NFNPBLFKICNGGE-FUHWJXTLSA-N 5-chloro-2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(3,4,5-trifluorophenoxy)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC(=C(C(=C1)F)F)F)(CO)O NFNPBLFKICNGGE-FUHWJXTLSA-N 0.000 claims 1
NMLACHJIUCXAQG-ZWKOTPCHSA-N 5-chloro-2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethyl)phenoxy]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC=C(C=C1)C(F)(F)F)(CO)O NMLACHJIUCXAQG-ZWKOTPCHSA-N 0.000 claims 1
ZZFKDPXRRZGRRM-ZWKOTPCHSA-N 5-chloro-2-[(3R,4S)-4-(3,4-difluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC(=C(C=C1)F)F)(CO)O ZZFKDPXRRZGRRM-ZWKOTPCHSA-N 0.000 claims 1
ASHAHKVYLRHMGO-ZWKOTPCHSA-N 5-chloro-2-[(3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC=C(C=C1)Cl)(CO)O ASHAHKVYLRHMGO-ZWKOTPCHSA-N 0.000 claims 1
NMLACHJIUCXAQG-ROUUACIJSA-N 5-chloro-2-[(3S,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethyl)phenoxy]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@@]([C@H](C1)OC1=CC=C(C=C1)C(F)(F)F)(CO)O NMLACHJIUCXAQG-ROUUACIJSA-N 0.000 claims 1
ASHAHKVYLRHMGO-ROUUACIJSA-N 5-chloro-2-[(3S,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound ClC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@@]([C@H](C1)OC1=CC=C(C=C1)Cl)(CO)O ASHAHKVYLRHMGO-ROUUACIJSA-N 0.000 claims 1
SPWWNFPEVFBWFI-ZWKOTPCHSA-N 5-fluoro-2-[(3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethyl)phenoxy]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound FC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@]([C@H](C1)OC1=CC=C(C=C1)C(F)(F)F)(CO)O SPWWNFPEVFBWFI-ZWKOTPCHSA-N 0.000 claims 1
SPWWNFPEVFBWFI-ROUUACIJSA-N 5-fluoro-2-[(3S,4S)-3-hydroxy-3-(hydroxymethyl)-4-[4-(trifluoromethyl)phenoxy]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound FC=1C=CC(=C(C#N)C=1)S(=O)(=O)N1C[C@@]([C@H](C1)OC1=CC=C(C=C1)C(F)(F)F)(CO)O SPWWNFPEVFBWFI-ROUUACIJSA-N 0.000 claims 1
ZXDMAMYQGVGABG-FUHWJXTLSA-N 6-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-3-carbonitrile Chemical compound C(#N)C1=C(C=C(O[C@@H]2[C@@](CN(C2)S(=O)(=O)C2=NC=C(C#N)C=C2)(CO)O)C=C1)F ZXDMAMYQGVGABG-FUHWJXTLSA-N 0.000 claims 1
208000026372 Congenital cystic kidney disease Diseases 0.000 claims 1
208000026292 Cystic Kidney disease Diseases 0.000 claims 1
208000019693 Lung disease Diseases 0.000 claims 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 1
229940049706 benzodiazepine Drugs 0.000 claims 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
230000000694 effects Effects 0.000 claims 1
125000006005 fluoroethoxy group Chemical group 0.000 claims 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical group C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 claims 1
229960002449 glycine Drugs 0.000 claims 1
230000002401 inhibitory effect Effects 0.000 claims 1
210000000936 intestine Anatomy 0.000 claims 1
150000002617 leukotrienes Chemical class 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
229940095102 methyl benzoate Drugs 0.000 claims 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
230000001575 pathological effect Effects 0.000 claims 1
125000003226 pyrazolyl group Chemical group 0.000 claims 1
150000003230 pyrimidines Chemical group 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
208000019553 vascular disease Diseases 0.000 claims 1
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 4
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 4
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 4
239000003199 leukotriene receptor blocking agent Substances 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
UCTWMZQNUQWSLP-UHFFFAOYSA-N Adrenaline Natural products CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 1
102000004136 Vasopressin Receptors Human genes 0.000 description 1
108090000643 Vasopressin Receptors Proteins 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1

JP2019515462A 2016-09-20 2017-09-20 Ｔｒｐｖ４拮抗薬 Active JP7025414B2 (ja)