BRPI0611966B1 - Composto ou sal farmaceuticamente aceitável do mesmo e composição farmacêutica os compreendendo - Google Patents
Composto ou sal farmaceuticamente aceitável do mesmo e composição farmacêutica os compreendendo Download PDFInfo
- Publication number
- BRPI0611966B1 BRPI0611966B1 BRPI0611966-2A BRPI0611966A BRPI0611966B1 BR PI0611966 B1 BRPI0611966 B1 BR PI0611966B1 BR PI0611966 A BRPI0611966 A BR PI0611966A BR PI0611966 B1 BRPI0611966 B1 BR PI0611966B1
- Authority
- BR
- Brazil
- Prior art keywords
- phenyl
- chloro
- adamantane
- amide
- carboxylic acid
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 313
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 47
- 150000003839 salts Chemical class 0.000 title claims abstract description 35
- ZDRVLAOYDGQLFI-UHFFFAOYSA-N 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol;hydrochloride Chemical compound Cl.C1=CC(O)=CC=C1NC1=NC(C=2C=CC(Cl)=CC=2)=CS1 ZDRVLAOYDGQLFI-UHFFFAOYSA-N 0.000 claims abstract description 184
- 108010035597 sphingosine kinase Proteins 0.000 claims abstract description 184
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 114
- 201000010099 disease Diseases 0.000 claims abstract description 85
- 230000005764 inhibitory process Effects 0.000 claims abstract description 25
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 22
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 17
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 16
- 210000004027 cell Anatomy 0.000 claims description 101
- -1 -OH Chemical group 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 74
- 206010028980 Neoplasm Diseases 0.000 claims description 60
- 238000011282 treatment Methods 0.000 claims description 55
- 230000004913 activation Effects 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 33
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 claims description 28
- 208000035475 disorder Diseases 0.000 claims description 28
- 201000011510 cancer Diseases 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 230000002757 inflammatory effect Effects 0.000 claims description 23
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000001188 haloalkyl group Chemical group 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 19
- 230000001404 mediated effect Effects 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 201000001320 Atherosclerosis Diseases 0.000 claims description 18
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 18
- 201000004681 Psoriasis Diseases 0.000 claims description 17
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 17
- 208000006673 asthma Diseases 0.000 claims description 17
- 206010003246 arthritis Diseases 0.000 claims description 16
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 14
- 230000002159 abnormal effect Effects 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 108091000080 Phosphotransferase Proteins 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 102000020233 phosphotransferase Human genes 0.000 claims description 10
- 230000002062 proliferating effect Effects 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
- OECLPECEPAYMGH-UHFFFAOYSA-N 3-(4-chlorophenyl)adamantane-1-carboxylic acid Chemical compound C1C(C(=O)O)(C2)CC(C3)CC1CC32C1=CC=C(Cl)C=C1 OECLPECEPAYMGH-UHFFFAOYSA-N 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 210000003584 mesangial cell Anatomy 0.000 claims description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- 208000026935 allergic disease Diseases 0.000 claims description 5
- 230000007815 allergy Effects 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- CAOTVXGYTWCKQE-UHFFFAOYSA-N 3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)-1-adamantanecarboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCC=4C=CN=CC=4)CC2CC3C1 CAOTVXGYTWCKQE-UHFFFAOYSA-N 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 4
- 230000005796 circulatory shock Effects 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 208000028169 periodontal disease Diseases 0.000 claims description 4
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 4
- FCQYHSJMJJEGAE-UHFFFAOYSA-N 1-[1-[3-(4-chlorophenyl)-1-adamantyl]ethyl]-3-[4-chloro-3-(trifluoromethyl)phenyl]urea Chemical compound C1C(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC2CC13C(C)NC(=O)NC1=CC=C(Cl)C(C(F)(F)F)=C1 FCQYHSJMJJEGAE-UHFFFAOYSA-N 0.000 claims description 3
- 206010000830 Acute leukaemia Diseases 0.000 claims description 3
- 201000000274 Carcinosarcoma Diseases 0.000 claims description 3
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 3
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 3
- 208000017604 Hodgkin disease Diseases 0.000 claims description 3
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 3
- 208000005410 Mediastinal Neoplasms Diseases 0.000 claims description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 3
- 208000000160 Olfactory Esthesioneuroblastoma Diseases 0.000 claims description 3
- 208000002774 Paraproteinemias Diseases 0.000 claims description 3
- 206010039491 Sarcoma Diseases 0.000 claims description 3
- 206010042658 Sweat gland tumour Diseases 0.000 claims description 3
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 3
- 208000006593 Urologic Neoplasms Diseases 0.000 claims description 3
- 208000018234 adnexal spiradenoma/cylindroma of a sweat gland Diseases 0.000 claims description 3
- 239000012752 auxiliary agent Substances 0.000 claims description 3
- 201000011529 cardiovascular cancer Diseases 0.000 claims description 3
- 208000024207 chronic leukemia Diseases 0.000 claims description 3
- 208000032099 esthesioneuroblastoma Diseases 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000008585 mastocytosis Diseases 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 230000002071 myeloproliferative effect Effects 0.000 claims description 3
- VNDHLVBKQCOMFN-UHFFFAOYSA-N n-[1-[3-(4-chlorophenyl)-1-adamantyl]ethyl]-1-methylpiperidin-4-amine Chemical compound C1C(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC2CC13C(C)NC1CCN(C)CC1 VNDHLVBKQCOMFN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 230000000926 neurological effect Effects 0.000 claims description 3
- 208000007312 paraganglioma Diseases 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 201000009571 retroperitoneal cancer Diseases 0.000 claims description 3
- 201000007416 salivary gland adenoid cystic carcinoma Diseases 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 2
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 2
- YTJSYIDTZUEQNC-UHFFFAOYSA-N 1-(4-bromophenyl)-n-[1-[3-(4-chlorophenyl)-1-adamantyl]ethyl]ethanamine Chemical compound C=1C=C(Br)C=CC=1C(C)NC(C)C(C1)(C2)CC(C3)CC1CC32C1=CC=C(Cl)C=C1 YTJSYIDTZUEQNC-UHFFFAOYSA-N 0.000 claims description 2
- ULBNIUROMLDOJN-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-1-adamantyl]-n-(1h-imidazol-5-ylmethyl)ethanamine Chemical compound C1C(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC2CC13C(C)NCC1=CN=CN1 ULBNIUROMLDOJN-UHFFFAOYSA-N 0.000 claims description 2
- BOHCPAZXXDWFOJ-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-1-adamantyl]-n-(2-pyridin-4-ylethyl)ethanamine Chemical compound C1C(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC2CC13C(C)NCCC1=CC=NC=C1 BOHCPAZXXDWFOJ-UHFFFAOYSA-N 0.000 claims description 2
- BPAJZNYYVQTLHM-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-1-adamantyl]-n-[(4-phenylthiophen-2-yl)methyl]ethanamine Chemical compound C1C(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC2CC13C(C)NCC(SC=1)=CC=1C1=CC=CC=C1 BPAJZNYYVQTLHM-UHFFFAOYSA-N 0.000 claims description 2
- QGWDIVZNAVTCTM-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-1-adamantyl]-n-[(6-chloropyridin-3-yl)methyl]ethanamine Chemical compound C1C(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC2CC13C(C)NCC1=CC=C(Cl)N=C1 QGWDIVZNAVTCTM-UHFFFAOYSA-N 0.000 claims description 2
- UQQYBGHIKSIJHD-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-1-adamantyl]-n-[(9-ethylcarbazol-3-yl)methyl]ethanamine Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1CNC(C)C(C1)(C2)CC(C3)CC1CC32C1=CC=C(Cl)C=C1 UQQYBGHIKSIJHD-UHFFFAOYSA-N 0.000 claims description 2
- OTDRGXKKAVUHRC-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(1-methylpiperidin-4-yl)adamantane-1-carboxamide Chemical compound C1CN(C)CCC1NC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 OTDRGXKKAVUHRC-UHFFFAOYSA-N 0.000 claims description 2
- FOGUTKLPKIFAAY-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(2,4-dihydroxyphenyl)adamantane-1-carboxamide Chemical compound OC1=CC(O)=CC=C1NC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 FOGUTKLPKIFAAY-UHFFFAOYSA-N 0.000 claims description 2
- PDHWTCIBPDYFPU-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(2-morpholin-4-ylethyl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCN4CCOCC4)CC2CC3C1 PDHWTCIBPDYFPU-UHFFFAOYSA-N 0.000 claims description 2
- IEGQBFMMSKUZFB-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(2-phenylethyl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCC=4C=CC=CC=4)CC2CC3C1 IEGQBFMMSKUZFB-UHFFFAOYSA-N 0.000 claims description 2
- TUNOMCQVHVVXBC-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(2-piperazin-1-ylethyl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCN4CCNCC4)CC2CC3C1 TUNOMCQVHVVXBC-UHFFFAOYSA-N 0.000 claims description 2
- MCFZBWFOBKXVPI-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(2-pyridin-4-ylethyl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCC=4C=CN=CC=4)CC2CC3C1 MCFZBWFOBKXVPI-UHFFFAOYSA-N 0.000 claims description 2
- JQWJVPZFSPABGC-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(2h-tetrazol-5-yl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NC=4NN=NN=4)CC2CC3C1 JQWJVPZFSPABGC-UHFFFAOYSA-N 0.000 claims description 2
- VVEQHTNBYLWPTI-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(3-imidazol-1-ylpropyl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCCN4C=NC=C4)CC2CC3C1 VVEQHTNBYLWPTI-UHFFFAOYSA-N 0.000 claims description 2
- HFEVWSNMPDVMMR-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(3-phenylpropyl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCCC=4C=CC=CC=4)CC2CC3C1 HFEVWSNMPDVMMR-UHFFFAOYSA-N 0.000 claims description 2
- WGPFHEAFOUMERK-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(3-pyrrolidin-1-ylpropyl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCCN4CCCC4)CC2CC3C1 WGPFHEAFOUMERK-UHFFFAOYSA-N 0.000 claims description 2
- FLJWPZLQSHTEQL-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(4-hydroxyphenyl)adamantane-1-carboxamide Chemical compound C1=CC(O)=CC=C1NC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 FLJWPZLQSHTEQL-UHFFFAOYSA-N 0.000 claims description 2
- SSMHCUUPXFFQFG-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(4-methylpiperazin-1-yl)adamantane-1-carboxamide Chemical compound C1CN(C)CCN1NC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 SSMHCUUPXFFQFG-UHFFFAOYSA-N 0.000 claims description 2
- KYDGZXHLXPTZNJ-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(7h-purin-6-yl)adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NC=4C=5N=CNC=5N=CN=4)CC2CC3C1 KYDGZXHLXPTZNJ-UHFFFAOYSA-N 0.000 claims description 2
- PEABYJUNQJJDFL-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[(3,4,5-trifluorophenyl)methyl]adamantane-1-carboxamide Chemical compound FC1=C(F)C(F)=CC(CNC(=O)C23CC4CC(CC(C4)(C3)C=3C=CC(Cl)=CC=3)C2)=C1 PEABYJUNQJJDFL-UHFFFAOYSA-N 0.000 claims description 2
- OXSKXGXUEXMSOU-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[(3,4-difluorophenyl)methyl]adamantane-1-carboxamide Chemical compound C1=C(F)C(F)=CC=C1CNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 OXSKXGXUEXMSOU-UHFFFAOYSA-N 0.000 claims description 2
- KNZHUAFGWMRPPB-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[(3,4-dihydroxyphenyl)methyl]adamantane-1-carboxamide Chemical compound C1=C(O)C(O)=CC=C1CNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 KNZHUAFGWMRPPB-UHFFFAOYSA-N 0.000 claims description 2
- KDVLMDUZMLTVCC-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[(3,5-difluorophenyl)methyl]adamantane-1-carboxamide Chemical compound FC1=CC(F)=CC(CNC(=O)C23CC4CC(CC(C4)(C3)C=3C=CC(Cl)=CC=3)C2)=C1 KDVLMDUZMLTVCC-UHFFFAOYSA-N 0.000 claims description 2
- YSXVOAGBYOVPCE-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[(4-methylsulfonylphenyl)methyl]adamantane-1-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 YSXVOAGBYOVPCE-UHFFFAOYSA-N 0.000 claims description 2
- DZEWWAOQHPWXFD-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[(4-phenoxyphenyl)methyl]adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCC=4C=CC(OC=5C=CC=CC=5)=CC=4)CC2CC3C1 DZEWWAOQHPWXFD-UHFFFAOYSA-N 0.000 claims description 2
- HJRLZOFSIKSWRY-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[(4-phenylphenyl)methyl]adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCC=4C=CC(=CC=4)C=4C=CC=CC=4)CC2CC3C1 HJRLZOFSIKSWRY-UHFFFAOYSA-N 0.000 claims description 2
- VBPBIIMTWLNHMF-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[1-(4-chlorophenyl)ethyl]adamantane-1-carboxamide Chemical compound C=1C=C(Cl)C=CC=1C(C)NC(=O)C(C1)(C2)CC(C3)CC1CC32C1=CC=C(Cl)C=C1 VBPBIIMTWLNHMF-UHFFFAOYSA-N 0.000 claims description 2
- MKNDEXRNJHZKAW-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[2-(1-methylpyrrolidin-2-yl)ethyl]adamantane-1-carboxamide Chemical compound CN1CCCC1CCNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 MKNDEXRNJHZKAW-UHFFFAOYSA-N 0.000 claims description 2
- NEOXEHZXYBCPRQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[2-(3,4-dihydroxyphenyl)ethyl]adamantane-1-carboxamide Chemical compound C1=C(O)C(O)=CC=C1CCNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 NEOXEHZXYBCPRQ-UHFFFAOYSA-N 0.000 claims description 2
- YHSMOWBWEKXCOH-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[2-(3-phenoxyphenyl)ethyl]adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCC=4C=C(OC=5C=CC=CC=5)C=CC=4)CC2CC3C1 YHSMOWBWEKXCOH-UHFFFAOYSA-N 0.000 claims description 2
- DDKQPYDADCHNAC-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[2-(4-fluorophenyl)ethyl]adamantane-1-carboxamide Chemical compound C1=CC(F)=CC=C1CCNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 DDKQPYDADCHNAC-UHFFFAOYSA-N 0.000 claims description 2
- JXODZLJNLRSHAQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[2-(4-hydroxyphenyl)ethyl]adamantane-1-carboxamide Chemical compound C1=CC(O)=CC=C1CCNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 JXODZLJNLRSHAQ-UHFFFAOYSA-N 0.000 claims description 2
- FTSWULOWYOIFNH-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[2-(4-phenoxyphenyl)ethyl]adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCC=4C=CC(OC=5C=CC=CC=5)=CC=4)CC2CC3C1 FTSWULOWYOIFNH-UHFFFAOYSA-N 0.000 claims description 2
- CGNFWPOGZWLXGM-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[3-(2-oxopyrrolidin-1-yl)propyl]adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C2)CC(C3)(C(=O)NCCCN4C(CCC4)=O)CC2CC3C1 CGNFWPOGZWLXGM-UHFFFAOYSA-N 0.000 claims description 2
- DDYNSGDAPDBOET-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]adamantane-1-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1=CSC(NC(=O)C23CC4CC(CC(C4)(C3)C=3C=CC(Cl)=CC=3)C2)=N1 DDYNSGDAPDBOET-UHFFFAOYSA-N 0.000 claims description 2
- IGOFOIZMFDPXFX-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]adamantane-1-carboxamide Chemical compound FC1=CC(C(F)(F)F)=CC=C1CNC(=O)C1(CC(C2)(C3)C=4C=CC(Cl)=CC=4)CC3CC2C1 IGOFOIZMFDPXFX-UHFFFAOYSA-N 0.000 claims description 2
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Families Citing this family (55)
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| AU2008276512A1 (en) * | 2007-07-17 | 2009-01-22 | Amgen Inc. | Thiadiazole modulators of PKB |
| US7897619B2 (en) | 2007-07-17 | 2011-03-01 | Amgen Inc. | Heterocyclic modulators of PKB |
| US8372888B2 (en) * | 2008-04-29 | 2013-02-12 | Enzo Therapeutics, Inc. | Sphingosine kinase type 1 inhibitors, compositions and processes for using same |
| US8314151B2 (en) | 2008-04-29 | 2012-11-20 | Enzo Therapeutics, Inc. | Sphingosine kinase type 1 inhibitors, and processes for using same |
| US20110275673A1 (en) * | 2008-09-19 | 2011-11-10 | Yibin Xiang | Inhibitors of sphingosine kinase 1 |
| EP2166094A1 (en) | 2008-09-23 | 2010-03-24 | Ecole Normale Superieure De Lyon | Methods for prolonging the health benefits triggered by a dietary restriction using a sphingosine kinase inhibitor |
| CA2742866C (en) | 2008-11-06 | 2017-10-24 | Musc Foundation For Research Development | Lysosomotropic inhibitors of acid ceramidase |
| PL2405751T3 (pl) | 2009-03-12 | 2016-01-29 | Apogee Biotechnology Corp | Proleki inhibitorów kinazy sfingozyny |
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| US9062015B2 (en) * | 2009-12-14 | 2015-06-23 | Merck Patent Gmbh | Inhibitors of sphingosine kinase |
| JPWO2012121168A1 (ja) * | 2011-03-04 | 2014-07-17 | 国立大学法人京都大学 | キナーゼ阻害剤 |
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| EP2822548B1 (en) | 2012-02-08 | 2019-04-24 | University of Virginia Patent Foundation | Long chain base sphingosine kinase inhibitors |
| RU2524216C1 (ru) * | 2013-04-09 | 2014-07-27 | Федеральное государственное бюджетное учреждение "Научно-исследовательский институт вирусологии им. Д.И. Ивановского" Министерства здравоохранения Российской Федерации | Пептидные производные 1-(1-адамантил)этиламина и их противовирусное действие |
| RU2529201C1 (ru) * | 2013-06-18 | 2014-09-27 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Волгоградский государственный технический университет" (ВолгГТУ) | Способ получения n-(2-гетероциклоалкил-1-илэтил)адамантан-2-аминов |
| EP3201181B1 (en) | 2014-10-01 | 2020-12-02 | Virginia Tech Intellectual Properties, Inc. | Sphingosine kinase inhibitors |
| CN107106525B (zh) * | 2014-10-24 | 2021-03-19 | 红山生物医药有限公司 | 用于抑制单链rna病毒复制的治疗 |
| EP3223807B1 (en) | 2014-11-24 | 2021-09-15 | The Board of Trustees of the University of Illinois | Method of preventing or treating a pulmonary disease or condition |
| WO2016110595A1 (en) * | 2015-01-09 | 2016-07-14 | Atonomics A/S | A UNIVERSAL ASSAY FOR DETERMINING THE QUANTITY OF TNFα INHIBITORY DRUGS AND THEIR CORRESPONDING ANTI-DRUG-ANTIBODIES |
| CN104529859B (zh) * | 2015-01-13 | 2016-08-17 | 佛山市赛维斯医药科技有限公司 | 含苯胺和二烯氟代金刚烷结构的化合物、其制备方法和用途 |
| CA2997671A1 (en) * | 2015-10-06 | 2017-04-13 | Redhill Biopharma Ltd. | Combination therapies for treating cancer |
| RU2605698C1 (ru) * | 2015-12-23 | 2016-12-27 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Волгоградский государственный технический университет" (ВолгГТУ) | Производные 2-(адамант-2-ил)этиламина, обладающие потенциальной противовирусной активностью |
| AU2017208970A1 (en) * | 2016-01-18 | 2018-08-02 | Arisan Therapeutics | Adamatane derivatives for the treatment of filovirus infection |
| JP6902040B2 (ja) | 2016-01-28 | 2021-07-14 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 免疫チェックポイント阻害剤の効力を増強する方法 |
| US11180489B2 (en) | 2016-03-30 | 2021-11-23 | U niversity of Virginia Patent Foundation | Sphingosine kinase inhibitor amidoxime prodrugs |
| WO2017218421A1 (en) * | 2016-06-13 | 2017-12-21 | Meharry Medical College | Modulation of the nitric oxide synthase pathway for oral health |
| EP3482199A1 (en) * | 2016-07-08 | 2019-05-15 | Atonomics A/S | A universal assay for determining the quantity of therapeutic monoclonal antibodies and their corresponding anti-drug-antibodies in samples |
| WO2018237379A2 (en) | 2017-06-23 | 2018-12-27 | Enzo Biochem, Inc. | Sphingosine pathway modulating compounds for the treatment of cancers |
| US10660879B2 (en) | 2017-06-23 | 2020-05-26 | Enzo Biochem, Inc. | Sphingosine pathway modulating compounds for the treatment of cancers |
| WO2019018185A1 (en) * | 2017-07-15 | 2019-01-24 | Arisan Therapeutics Inc. | ENANTIOMERICALLY PURE ADAMATANE DERIVATIVES FOR THE TREATMENT OF FILOVIRUS INFECTIONS |
| WO2019140254A1 (en) * | 2018-01-12 | 2019-07-18 | President And Fellows Of Harvard College | Multicyclic compounds and use of same for treating tuberculosis |
| US11261201B2 (en) | 2018-01-12 | 2022-03-01 | President And Fellows Of Harvard College | TRNA synthetase inhibitors |
| US20210080467A1 (en) | 2018-02-21 | 2021-03-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of sk1 as biomarker for predicting response to immunecheckpoint inhibitors |
| AU2019101780A4 (en) * | 2018-05-02 | 2021-04-15 | Sun Yat-Sen University | Use of SPHK2 inhibitor as drug for repairing bone marrow hematopoietic system injury or treating bone marrow hematopoietic dysfunction |
| RU2732297C2 (ru) * | 2018-11-14 | 2020-09-15 | Общество с ограниченной ответственностью "Гурус БиоФарм" | Производные нестероидных противовоспалительных средств |
| CN111233887A (zh) * | 2018-11-28 | 2020-06-05 | 武汉武药科技有限公司 | 一种盐酸多佐胺中间体的合成工艺 |
| KR102887366B1 (ko) * | 2019-01-04 | 2025-11-14 | (주)아모레퍼시픽 | 아다만탄 카르복실산 벤질 아마이드 유도체 화합물 및 그를 포함하는 피부 미백용 조성물 |
| KR20210118101A (ko) * | 2019-01-16 | 2021-09-29 | 아포지 바이오테크놀로지 코포레이션 | 항암 면역 반응을 유도하는 방법 |
| RU2697409C1 (ru) * | 2019-04-30 | 2019-08-14 | Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | 1-Адамантил-3-(((1R,4aS,10aR)-7-изопропил-1,4а-диметил-1,2,3,4,4а,9,10,10а-октагидрофенантрен-1-ил)метил)мочевина, проявляющая ингибирующее действие в отношении фермента тирозил-ДНК-фосфодиэстеразы 1 человека и увеличивающая активность темозоломида в отношении клеток глиобластомы |
| CN110330452A (zh) * | 2019-06-12 | 2019-10-15 | 山东省医学科学院药物研究所(山东省抗衰老研究中心、山东省新技术制药研究所) | 四氢吡咯烷类化合物或其药学上可接受的盐及其制备方法和应用 |
| CN110483284B (zh) * | 2019-08-26 | 2022-05-13 | 浙江工业大学 | 一种1-金刚烷甲酸-2-(取代苯甲酰氧基)乙酯类化合物及其合成方法和应用 |
| EP4117630A4 (en) | 2020-03-10 | 2024-07-03 | RedHill Biopharma Ltd. | TREATMENT OF CORONAVIRUS INFECTIONS |
| US20230218644A1 (en) | 2020-04-16 | 2023-07-13 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
| CN112336863A (zh) * | 2020-11-26 | 2021-02-09 | 中山大学附属第八医院(深圳福田) | S1p受体抑制剂在制备防治强直性脊柱炎产品中的应用 |
| US11471448B2 (en) | 2020-12-15 | 2022-10-18 | Redhill Biopharma Ltd. | Sphingosine kinase 2 inhibitor for treating coronavirus infection in moderately severe patients with pneumonia |
| CN116217468A (zh) * | 2023-02-22 | 2023-06-06 | 天津民祥药业有限公司 | 一种奥帕尼布的新型合成方法 |
| WO2026035293A1 (en) | 2024-08-06 | 2026-02-12 | Apogee Biotechnology Corporation | Compositions and methods for the prevention and treatment of obesity and obesity-induced disease |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3352912A (en) * | 1963-07-24 | 1967-11-14 | Du Pont | Adamantanes and tricyclo[4. 3. 1. 1 3.8] undecanes |
| US3663565A (en) | 1969-07-02 | 1972-05-16 | Searle & Co | Esters and amides of 3-phenyladamantane-1-carboxylic acid |
| US3657273A (en) * | 1970-05-01 | 1972-04-18 | Searle & Co | Adamantane-1 3-dicarboxamides |
| BE791392A (fr) * | 1971-11-15 | 1973-05-14 | Scherico Ltd | Aryl- et aralcoylamides substitues |
| US4053509A (en) * | 1971-11-15 | 1977-10-11 | Schering Corporation | Substituted aryl and aralkyl amides |
| SU451691A1 (ru) * | 1973-03-27 | 1974-11-30 | Киевский Ордена Ленина Политехнический Институт Им.50-Летия Великой Октябрьской Социалистической Революции | Способ получени -метилстеариламидов адамантанкарбоновых кислот |
| US4349552A (en) * | 1978-10-30 | 1982-09-14 | Fujisawa Pharmaceutical Company, Ltd. | 5-Fluorouracil derivatives, and their pharmaceutical compositions |
| JPS5671075A (en) * | 1979-11-12 | 1981-06-13 | Sumitomo Chem Co Ltd | Novel imidazole derivative |
| CA1228346A (en) * | 1983-10-07 | 1987-10-20 | George M. Kramer | Adamantylamine/long chain alkylamine catalysts and use in paraffin-olefin alkylation process |
| SU1367194A1 (ru) * | 1984-03-16 | 1996-04-10 | В.Ю. Ковтун | Литиевая соль 1-адамантанкарбоновой кислоты, обладающая психостимулирующей активностью |
| SU1574586A1 (ru) * | 1988-06-20 | 1990-06-30 | Институт Биоорганической Химии Ан Усср | Способ получени замещенных бромом адамантан-1-карбоновых кислот |
| DE58905637D1 (de) * | 1989-04-14 | 1993-10-21 | Merz & Co Gmbh & Co | Verwendung von Adamantan-Derivaten zur Prävention und Behandlung der cerebralen Ischämie. |
| JP2511573B2 (ja) * | 1990-11-29 | 1996-06-26 | 川崎製鉄株式会社 | 1―エチルアダマンタンの製造方法 |
| JPH04322743A (ja) * | 1991-04-24 | 1992-11-12 | Kawasaki Steel Corp | アルキルアダマンタン類の製造用触媒およびこれを用いたアルキルアダマンタン類の製造方法 |
| JPH04330947A (ja) * | 1991-05-02 | 1992-11-18 | Kawasaki Steel Corp | 1−ビニルアダマンタン製造用触媒およびこれを用いた1−ビニルアダマンタンの製造方法 |
| NZ252717A (en) * | 1992-05-15 | 1996-05-28 | British Tech Group | Adamantane-pyridine derivatives and medicaments |
| JP2001524468A (ja) * | 1997-11-21 | 2001-12-04 | エヌピーエス ファーマシューティカルズ インコーポレーテッド | 中枢神経系疾患を治療するための代謝調節型グルタミン酸受容体アンタゴニスト |
| CN100390178C (zh) * | 1999-11-12 | 2008-05-28 | 拜奥根Idec马萨诸塞公司 | 作为腺苷受体拮抗剂的多环烷基嘌呤 |
| JP4271348B2 (ja) * | 2000-06-16 | 2009-06-03 | 出光興産株式会社 | 1,3−アダマンタンジカルボン酸ジ−tert−ブチルの製造方法 |
| RU2197467C2 (ru) * | 2000-11-09 | 2003-01-27 | Институт нефтехимии и катализа АН РБ и УНЦ РАН | Способ получения 1-хлор-3-ацетил- и 1,3-дихлор-5-ацетиладамантанов |
| AU2003245555A1 (en) * | 2002-06-17 | 2003-12-31 | The Pennsylvania State Research Foundation | Sphingosine kinase inhibitors |
| US20040116479A1 (en) * | 2002-10-04 | 2004-06-17 | Fortuna Haviv | Method of inhibiting angiogenesis |
| EP1615667A2 (en) * | 2003-04-11 | 2006-01-18 | Novo Nordisk A/S | Combinations of an 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist |
| ATE467616T1 (de) * | 2003-04-11 | 2010-05-15 | High Point Pharmaceuticals Llc | Verbindungen mit aktivität an der 11beta- hydroxasteroiddehydrogenase |
| JP2008518903A (ja) * | 2004-11-02 | 2008-06-05 | ファイザー・インク | 置換および非置換アダマンチルアミドの新規化合物 |
| GB0506133D0 (en) * | 2005-03-24 | 2005-05-04 | Sterix Ltd | Compound |
| US8324237B2 (en) * | 2005-05-20 | 2012-12-04 | Smith Charles D | Methods for the treatment and prevention of inflammatory diseases |
| US20060270631A1 (en) * | 2005-05-26 | 2006-11-30 | Smith Charles D | Methods for the treatment and prevention of angiogenic diseases |
| CN101248041B (zh) * | 2005-06-17 | 2013-11-20 | 艾宝奇生物工艺有限公司 | 鞘氨醇激酶抑制剂 |
| PL2405751T3 (pl) * | 2009-03-12 | 2016-01-29 | Apogee Biotechnology Corp | Proleki inhibitorów kinazy sfingozyny |
| WO2010129954A1 (en) * | 2009-05-08 | 2010-11-11 | Apogee Biotechnology Corporation | Treatment of ischemia-reperfusion injury |
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