IL305165A

IL305165A - Tyk2 inhibitors and uses thereof

Tyk2 inhibitors and uses thereof

Info

Publication number: IL305165A
Authority: IL; Israel
Prior art keywords: substituted; unsubstituted; methyl; amino; dihydro
Prior art date: 2021-02-19

Application number

IL305165A

Other languages

English (en)

Hebrew (he)

Original Assignee

Sudo Biosciences Ltd

Priority date

2021-02-19

Filing date

2022-02-16

Publication date

2023-10-01

2022-02-16 Application filed by Sudo Biosciences Ltd filed Critical Sudo Biosciences Ltd

2023-10-01 Publication of IL305165A publication Critical patent/IL305165A/en

Links

229940123371 Tyrosine kinase 2 inhibitor Drugs 0.000 title description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 464
239000001257 hydrogen Substances 0.000 claims description 464
150000001875 compounds Chemical class 0.000 claims description 348
150000002431 hydrogen Chemical group 0.000 claims description 345
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 223
125000005345 deuteroalkyl group Chemical group 0.000 claims description 208
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 193
125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 140
150000003839 salts Chemical class 0.000 claims description 136
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 116
229910052736 halogen Inorganic materials 0.000 claims description 115
239000012453 solvate Substances 0.000 claims description 109
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 107
125000000623 heterocyclic group Chemical group 0.000 claims description 107
150000002367 halogens Chemical group 0.000 claims description 103
125000004093 cyano group Chemical group *C#N 0.000 claims description 101
-1 C3-Ccycloalkyl Chemical group 0.000 claims description 98
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 94
125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 81
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 78
125000004433 nitrogen atom Chemical group N* 0.000 claims description 75
229910052799 carbon Inorganic materials 0.000 claims description 74
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 73
238000000034 method Methods 0.000 claims description 72
229910052757 nitrogen Inorganic materials 0.000 claims description 59
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 58
125000004429 atom Chemical group 0.000 claims description 57
201000010099 disease Diseases 0.000 claims description 56
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 54
125000003709 fluoroalkyl group Chemical group 0.000 claims description 50
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 44
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 44
229910052805 deuterium Inorganic materials 0.000 claims description 44
125000002950 monocyclic group Chemical group 0.000 claims description 44
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
125000001072 heteroaryl group Chemical group 0.000 claims description 41
DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 claims description 41
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 38
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 37
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 37
125000003566 oxetanyl group Chemical group 0.000 claims description 35
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 32
239000008194 pharmaceutical composition Substances 0.000 claims description 32
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
125000000753 cycloalkyl group Chemical group 0.000 claims description 29
125000001620 monocyclic carbocycle group Chemical group 0.000 claims description 27
235000005152 nicotinamide Nutrition 0.000 claims description 27
239000011570 nicotinamide Substances 0.000 claims description 27
229960003966 nicotinamide Drugs 0.000 claims description 27
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 26
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 26
208000027866 inflammatory disease Diseases 0.000 claims description 24
125000004404 heteroalkyl group Chemical group 0.000 claims description 22
125000002393 azetidinyl group Chemical group 0.000 claims description 20
239000007788 liquid Substances 0.000 claims description 20
125000002619 bicyclic group Chemical group 0.000 claims description 18
125000001309 chloro group Chemical group Cl* 0.000 claims description 18
125000000547 substituted alkyl group Chemical group 0.000 claims description 17
208000023275 Autoimmune disease Diseases 0.000 claims description 16
125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 15
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
125000001153 fluoro group Chemical group F* 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 13
125000006413 ring segment Chemical group 0.000 claims description 12
125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
AKHLYRVPWDJMKZ-UHFFFAOYSA-N CC1=CC(NC2=NC=C(C(NC)=O)C(NC3=CC=CC4=C3N(C)CC3=CN(C)N=C43)=C2)=NC(C)=N1 Chemical compound CC1=CC(NC2=NC=C(C(NC)=O)C(NC3=CC=CC4=C3N(C)CC3=CN(C)N=C43)=C2)=NC(C)=N1 AKHLYRVPWDJMKZ-UHFFFAOYSA-N 0.000 claims description 10
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125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 10
230000001404 mediated effect Effects 0.000 claims description 9
VJDPXYTXHGSONN-UHFFFAOYSA-N CNC(C(C(NC1=CC=CC2=C1N(C)CC1=CN(C)N=C21)=C1)=CN=C1NC(C=C1)=NC=C1F)=O Chemical compound CNC(C(C(NC1=CC=CC2=C1N(C)CC1=CN(C)N=C21)=C1)=CN=C1NC(C=C1)=NC=C1F)=O VJDPXYTXHGSONN-UHFFFAOYSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
201000004681 Psoriasis Diseases 0.000 claims description 7
125000004428 fluoroalkoxy group Chemical group 0.000 claims description 7
239000000499 gel Substances 0.000 claims description 7
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 7
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
206010012438 Dermatitis atopic Diseases 0.000 claims description 6
201000008937 atopic dermatitis Diseases 0.000 claims description 6
201000006417 multiple sclerosis Diseases 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
125000002098 pyridazinyl group Chemical group 0.000 claims description 6
125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
208000011580 syndromic disease Diseases 0.000 claims description 6
201000004384 Alopecia Diseases 0.000 claims description 5
208000011231 Crohn disease Diseases 0.000 claims description 5
208000003556 Dry Eye Syndromes Diseases 0.000 claims description 5
206010013774 Dry eye Diseases 0.000 claims description 5
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208000036824 Psoriatic arthropathy Diseases 0.000 claims description 5
206010046851 Uveitis Diseases 0.000 claims description 5
206010047642 Vitiligo Diseases 0.000 claims description 5
239000006071 cream Substances 0.000 claims description 5
208000002557 hidradenitis Diseases 0.000 claims description 5
201000007162 hidradenitis suppurativa Diseases 0.000 claims description 5
206010025135 lupus erythematosus Diseases 0.000 claims description 5
239000002674 ointment Substances 0.000 claims description 5
206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
208000015943 Coeliac disease Diseases 0.000 claims description 4
206010009900 Colitis ulcerative Diseases 0.000 claims description 4
206010039710 Scleroderma Diseases 0.000 claims description 4
208000021386 Sjogren Syndrome Diseases 0.000 claims description 4
201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
231100000360 alopecia Toxicity 0.000 claims description 4
230000000968 intestinal effect Effects 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 claims description 3
BFBQORVFQMFQKL-UHFFFAOYSA-N CNC(C(N=NC(NC(C1CC1)=O)=C1)=C1NC1=CC=CC2=C1OCC1=CN(C3COC3)N=C21)=O Chemical compound CNC(C(N=NC(NC(C1CC1)=O)=C1)=C1NC1=CC=CC2=C1OCC1=CN(C3COC3)N=C21)=O BFBQORVFQMFQKL-UHFFFAOYSA-N 0.000 claims description 3
201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 3
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206010042953 Systemic sclerosis Diseases 0.000 claims description 3
208000036971 interstitial lung disease 2 Diseases 0.000 claims description 3
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YZSRQEDWPXNUCB-UHFFFAOYSA-N CC1=CC(NC2=CC(NC3=CC=CC4=C3N(C)CC3=CN(C)N=C43)=C(C(NC)=O)N=N2)=NC(C)=N1 Chemical compound CC1=CC(NC2=CC(NC3=CC=CC4=C3N(C)CC3=CN(C)N=C43)=C(C(NC)=O)N=N2)=NC(C)=N1 YZSRQEDWPXNUCB-UHFFFAOYSA-N 0.000 claims description 2
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MDQPHWXNDZIBLK-UHFFFAOYSA-N CC1OC(C(NC2=C(C(NC)=O)N=NC(NC(C=C3)=NC=C3F)=C2)=CC=C2)=C2C2=NN(C)C=C12 Chemical compound CC1OC(C(NC2=C(C(NC)=O)N=NC(NC(C=C3)=NC=C3F)=C2)=CC=C2)=C2C2=NN(C)C=C12 MDQPHWXNDZIBLK-UHFFFAOYSA-N 0.000 claims description 2
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