CA2635232A1 - Inhibiteurs de l'amide hydrolase d'acides gras - Google Patents
Inhibiteurs de l'amide hydrolase d'acides gras Download PDFInfo
- Publication number
- CA2635232A1 CA2635232A1 CA002635232A CA2635232A CA2635232A1 CA 2635232 A1 CA2635232 A1 CA 2635232A1 CA 002635232 A CA002635232 A CA 002635232A CA 2635232 A CA2635232 A CA 2635232A CA 2635232 A1 CA2635232 A1 CA 2635232A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- optionally substituted
- pharmaceutically acceptable
- group
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108010046094 fatty-acid amide hydrolase Proteins 0.000 title claims abstract description 116
- 102100029111 Fatty-acid amide hydrolase 1 Human genes 0.000 title claims abstract description 114
- 239000003112 inhibitor Substances 0.000 title abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 280
- 239000000203 mixture Substances 0.000 claims abstract description 131
- 238000000034 method Methods 0.000 claims abstract description 85
- 230000000694 effects Effects 0.000 claims abstract description 75
- -1 heterocycloalkoxy Chemical group 0.000 claims description 283
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 247
- 125000000217 alkyl group Chemical group 0.000 claims description 106
- 125000003118 aryl group Chemical group 0.000 claims description 81
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 70
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 64
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 125000000623 heterocyclic group Chemical class 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 58
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 51
- 239000000651 prodrug Substances 0.000 claims description 48
- 229940002612 prodrug Drugs 0.000 claims description 48
- 239000002207 metabolite Substances 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 39
- 150000001204 N-oxides Chemical class 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims description 36
- 208000035475 disorder Diseases 0.000 claims description 34
- 208000002193 Pain Diseases 0.000 claims description 32
- 125000004122 cyclic group Chemical group 0.000 claims description 32
- 239000012453 solvate Substances 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
- 230000005764 inhibitory process Effects 0.000 claims description 23
- 208000030159 metabolic disease Diseases 0.000 claims description 22
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
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- 239000011230 binding agent Substances 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000003107 substituted aryl group Chemical group 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 16
- 125000002947 alkylene group Chemical group 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000004011 3 membered carbocyclic group Chemical group 0.000 claims description 14
- 125000001845 4 membered carbocyclic group Chemical group 0.000 claims description 14
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
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- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims description 12
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- 150000003973 alkyl amines Chemical class 0.000 claims description 12
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- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
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- 125000000842 isoxazolyl group Chemical group 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 12
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 12
- 125000002971 oxazolyl group Chemical group 0.000 claims description 12
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 12
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- 125000002098 pyridazinyl group Chemical group 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 12
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 12
- 125000004306 triazinyl group Chemical group 0.000 claims description 12
- 125000001425 triazolyl group Chemical group 0.000 claims description 12
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 11
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 11
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 11
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 11
- 125000004988 dibenzothienyl group Chemical group C1(=CC=CC=2SC3=C(C21)C=CC=C3)* 0.000 claims description 11
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 11
- 125000002757 morpholinyl group Chemical group 0.000 claims description 11
- 125000003386 piperidinyl group Chemical group 0.000 claims description 11
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 11
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 11
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 11
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 10
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000005493 quinolyl group Chemical group 0.000 claims description 10
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000005390 cinnolyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 8
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- 208000026935 allergic disease Diseases 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000005945 imidazopyridyl group Chemical group 0.000 claims description 8
- 210000000987 immune system Anatomy 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000005022 packaging material Substances 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 7
- 206010063897 Renal ischaemia Diseases 0.000 claims description 7
- 101100495911 Arabidopsis thaliana CHR10 gene Proteins 0.000 claims description 6
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- 235000014632 disordered eating Nutrition 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
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- 239000001257 hydrogen Substances 0.000 claims description 5
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims 1
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 1
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- 238000009472 formulation Methods 0.000 description 60
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
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- Chemical & Material Sciences (AREA)
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Applications Claiming Priority (17)
Application Number | Priority Date | Filing Date | Title |
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US75503505P | 2005-12-29 | 2005-12-29 | |
US60/755,035 | 2005-12-29 | ||
US82287706P | 2006-08-18 | 2006-08-18 | |
US60/822,877 | 2006-08-18 | ||
US82307606P | 2006-08-21 | 2006-08-21 | |
US60/823,076 | 2006-08-21 | ||
US82488706P | 2006-09-07 | 2006-09-07 | |
US60/824,887 | 2006-09-07 | ||
US82786106P | 2006-10-02 | 2006-10-02 | |
US60/827,861 | 2006-10-02 | ||
US82875306P | 2006-10-09 | 2006-10-09 | |
US60/828,753 | 2006-10-09 | ||
US86656806P | 2006-11-20 | 2006-11-20 | |
US60/866,568 | 2006-11-20 | ||
US11/561,774 | 2006-11-20 | ||
US11/561,774 US20070155707A1 (en) | 2005-12-29 | 2006-11-20 | Ionizable inhibitors of fatty acid amide hydrolase |
PCT/US2006/049485 WO2007079180A2 (fr) | 2005-12-29 | 2006-12-28 | Inhibiteurs de l’amide hydrolase d’acides gras |
Publications (1)
Publication Number | Publication Date |
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CA2635232A1 true CA2635232A1 (fr) | 2007-07-12 |
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Family Applications (1)
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CA002635232A Abandoned CA2635232A1 (fr) | 2005-12-29 | 2006-12-28 | Inhibiteurs de l'amide hydrolase d'acides gras |
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EP (1) | EP1969051A2 (fr) |
JP (1) | JP2009522287A (fr) |
KR (1) | KR20080091132A (fr) |
AU (1) | AU2006332675A1 (fr) |
CA (1) | CA2635232A1 (fr) |
IL (1) | IL191819A0 (fr) |
MX (1) | MX2008008529A (fr) |
WO (1) | WO2007079180A2 (fr) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9101160B2 (en) | 2005-11-23 | 2015-08-11 | The Coca-Cola Company | Condiments with high-potency sweetener |
WO2008042892A2 (fr) * | 2006-10-02 | 2008-04-10 | N.V. Organon | Procédé de traitement de troubles du métabolisme énergétique en empêchant l'activité d'un amide hydrolase d'acide gras |
ES2357340T3 (es) | 2006-10-18 | 2011-04-25 | Pfizer Products Inc. | Compuestos de biaril éter urea. |
US8017168B2 (en) | 2006-11-02 | 2011-09-13 | The Coca-Cola Company | High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith |
EP2632912A4 (fr) * | 2010-10-28 | 2014-05-07 | Scripps Research Inst | Carbamates inhibiteurs de sérine hydrolases pour lutter contre le cancer |
WO2014023325A1 (fr) * | 2012-08-06 | 2014-02-13 | Fondazione Istituto Italiano Di Tecnologia | Inhibiteurs de faah et de cox multicibles et leurs utilisations thérapeutiques |
ITMI20131180A1 (it) * | 2013-07-15 | 2015-01-16 | Fond Istituto Italiano Di Tecnologia | O-alchil triazolil carbammati come inibitori di idrolasi delle ammidi degli acidi grassi (faah) |
EP3529245A4 (fr) | 2016-10-24 | 2020-12-23 | Yumanity Therapeutics, Inc. | Composés et utilisations de ces derniers |
EP3700934A4 (fr) | 2017-10-24 | 2021-10-27 | Yumanity Therapeutics, Inc. | Composés et utilisations de ces composés |
JP2022520930A (ja) | 2019-01-24 | 2022-04-04 | ユマニティ セラピューティクス,インコーポレーテッド | 化合物及びその使用 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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EP1558591B1 (fr) * | 2002-10-07 | 2014-05-07 | The Regents of The University of California | Modulation de l'anxiete par blocage de l'hydrolyse de l'anandamide |
-
2006
- 2006-12-28 WO PCT/US2006/049485 patent/WO2007079180A2/fr active Application Filing
- 2006-12-28 CA CA002635232A patent/CA2635232A1/fr not_active Abandoned
- 2006-12-28 EP EP06848278A patent/EP1969051A2/fr not_active Withdrawn
- 2006-12-28 MX MX2008008529A patent/MX2008008529A/es not_active Application Discontinuation
- 2006-12-28 AU AU2006332675A patent/AU2006332675A1/en not_active Abandoned
- 2006-12-28 JP JP2008548741A patent/JP2009522287A/ja not_active Withdrawn
- 2006-12-28 KR KR1020087016335A patent/KR20080091132A/ko not_active Application Discontinuation
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2008
- 2008-05-29 IL IL191819A patent/IL191819A0/en unknown
Also Published As
Publication number | Publication date |
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IL191819A0 (en) | 2008-12-29 |
MX2008008529A (es) | 2008-09-26 |
JP2009522287A (ja) | 2009-06-11 |
WO2007079180A3 (fr) | 2007-11-29 |
AU2006332675A1 (en) | 2007-07-12 |
KR20080091132A (ko) | 2008-10-09 |
WO2007079180A2 (fr) | 2007-07-12 |
EP1969051A2 (fr) | 2008-09-17 |
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