TWI766882B

TWI766882B - 新穎化合物類

新穎化合物類 Download PDF

Info

Publication number: TWI766882B
Authority: TW; Taiwan
Prior art keywords: mmol; cyano; ring; substituted; compound
Prior art date: 2016-09-29

Application number

TW106132939A

Other languages

English (en)

Chinese (zh)

Other versions

TW201825472A (zh

Inventor

馬丁史塔克利

馬克肯普

Original Assignee

英商使命醫療公司

Priority date

2016-09-29

Filing date

2017-09-26

Publication date

2022-06-11

2017-09-26 Application filed by 英商使命醫療公司 filed Critical 英商使命醫療公司

2018-07-16 Publication of TW201825472A publication Critical patent/TW201825472A/zh

2022-06-11 Application granted granted Critical

2022-06-11 Publication of TWI766882B publication Critical patent/TWI766882B/zh

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150000001875 compounds Chemical class 0.000 title claims description 167
230000004065 mitochondrial dysfunction Effects 0.000 claims abstract description 15
-1 oxazolopyridyl Chemical group 0.000 claims description 194
239000001257 hydrogen Substances 0.000 claims description 97
229910052739 hydrogen Inorganic materials 0.000 claims description 97
201000006417 multiple sclerosis Diseases 0.000 claims description 96
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 61
125000004093 cyano group Chemical group *C#N 0.000 claims description 36
229910052731 fluorine Inorganic materials 0.000 claims description 36
239000011737 fluorine Substances 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 34
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 29
208000024891 symptom Diseases 0.000 claims description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
230000002438 mitochondrial effect Effects 0.000 claims description 22
208000018737 Parkinson disease Diseases 0.000 claims description 21
238000011282 treatment Methods 0.000 claims description 18
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 14
230000007812 deficiency Effects 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
125000002971 oxazolyl group Chemical group 0.000 claims description 12
125000003226 pyrazolyl group Chemical group 0.000 claims description 12
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 11
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125000005945 imidazopyridyl group Chemical group 0.000 claims description 10
125000001715 oxadiazolyl group Chemical group 0.000 claims description 10
125000001425 triazolyl group Chemical group 0.000 claims description 10
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WMABMZXOIOIDRM-UHFFFAOYSA-N 3-[5-(3-cyanophenyl)-1H-imidazo[4,5-b]pyridin-2-yl]-3-fluoropiperidine-1-carbonitrile Chemical compound FC1(CCCN(C1)C#N)c1nc2nc(ccc2[nH]1)-c1cccc(c1)C#N WMABMZXOIOIDRM-UHFFFAOYSA-N 0.000 claims description 3
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MDHFPHDPIRYJFG-CQSZACIVSA-N 4-[5-[(3R)-1-cyano-3-fluoropiperidin-3-yl]-1,3,4-oxadiazol-2-yl]pyridine-2-carbonitrile Chemical compound C(#N)N1C[C@@](CCC1)(F)C1=NN=C(O1)C1=CC(=NC=C1)C#N MDHFPHDPIRYJFG-CQSZACIVSA-N 0.000 claims description 3
YRTYXUCVSHRVTO-GOSISDBHSA-N 6-[2-[(3R)-1-cyano-3-fluoropiperidin-3-yl]-1,3-benzoxazol-5-yl]pyrimidine-4-carbonitrile Chemical compound C(#N)N1C[C@@](CCC1)(F)C=1OC2=C(N=1)C=C(C=C2)C1=CC(=NC=N1)C#N YRTYXUCVSHRVTO-GOSISDBHSA-N 0.000 claims description 3
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CAJFCTOHBOXOFN-LJQANCHMSA-N 2-[2-[(3R)-1-cyano-3-fluoropiperidin-3-yl]-1,3-benzoxazol-5-yl]pyridine-4-carbonitrile Chemical compound C(#N)N1C[C@@](CCC1)(F)C=1OC2=C(N=1)C=C(C=C2)C=1C=C(C#N)C=CN=1 CAJFCTOHBOXOFN-LJQANCHMSA-N 0.000 claims description 2
JUYZCGUFQHIZRK-UHFFFAOYSA-N 3-[5-(3-cyanophenyl)-1,3-benzoxazol-2-yl]-3-fluoropiperidine-1-carbonitrile Chemical compound FC1(CCCN(C1)C#N)c1nc2cc(ccc2o1)-c1cccc(c1)C#N JUYZCGUFQHIZRK-UHFFFAOYSA-N 0.000 claims description 2
FQGIUHKVWDUNIX-UHFFFAOYSA-N 3-fluoro-3-[5-(4-phenylphenyl)-1,3,4-oxadiazol-2-yl]piperidine-1-carbonitrile Chemical compound C1(=CC=C(C=C1)C1=NN=C(O1)C1(CN(CCC1)C#N)F)C1=CC=CC=C1 FQGIUHKVWDUNIX-UHFFFAOYSA-N 0.000 claims description 2
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