KR20240000574A - 헤테로시클릭 화합물 - Google Patents
헤테로시클릭 화합물 Download PDFInfo
- Publication number
- KR20240000574A KR20240000574A KR1020237040339A KR20237040339A KR20240000574A KR 20240000574 A KR20240000574 A KR 20240000574A KR 1020237040339 A KR1020237040339 A KR 1020237040339A KR 20237040339 A KR20237040339 A KR 20237040339A KR 20240000574 A KR20240000574 A KR 20240000574A
- Authority
- KR
- South Korea
- Prior art keywords
- heptan
- azaspiro
- methanone
- triazol
- cyclopropyl
- 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.)
- Pending
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- 150000002391 heterocyclic compounds Chemical class 0.000 title abstract 2
- -1 cyano, hydroxy, amino Chemical group 0.000 claims description 803
- 150000001875 compounds Chemical class 0.000 claims description 327
- 229910052739 hydrogen Inorganic materials 0.000 claims description 300
- 239000001257 hydrogen Substances 0.000 claims description 298
- 150000003839 salts Chemical class 0.000 claims description 224
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 170
- 229910052736 halogen Inorganic materials 0.000 claims description 162
- 150000002367 halogens Chemical class 0.000 claims description 161
- 125000000623 heterocyclic group Chemical group 0.000 claims description 132
- 150000002431 hydrogen Chemical class 0.000 claims description 127
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 85
- 125000001072 heteroaryl group Chemical group 0.000 claims description 84
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 79
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 71
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 241000124008 Mammalia Species 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 49
- 238000011282 treatment Methods 0.000 claims description 47
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 43
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- 230000002265 prevention Effects 0.000 claims description 41
- 125000001153 fluoro group Chemical group F* 0.000 claims description 38
- 208000002193 Pain Diseases 0.000 claims description 34
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 30
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 29
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 28
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- 125000003545 alkoxy group Chemical group 0.000 claims description 21
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- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims description 21
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- 206010028980 Neoplasm Diseases 0.000 claims description 18
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 17
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- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 14
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- 208000004998 Abdominal Pain Diseases 0.000 claims description 12
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 12
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 12
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- 231100000228 neurotoxicity Toxicity 0.000 claims description 11
- 230000007135 neurotoxicity Effects 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 10
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- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 8
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 230000004736 colon carcinogenesis Effects 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- 201000001119 neuropathy Diseases 0.000 claims description 6
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- 208000033808 peripheral neuropathy Diseases 0.000 claims description 6
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 5
- 208000009935 visceral pain Diseases 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
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- 206010052904 Musculoskeletal stiffness Diseases 0.000 claims description 4
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- ABAQIAMYLCWBIP-UHFFFAOYSA-N O=C(N1CC(C2)(CC2N2N=C(C3CC3)N=C2)C1)N1CC(C2)(CC2OC2=NC(C(F)(F)F)=NC=C2)C1 Chemical compound O=C(N1CC(C2)(CC2N2N=C(C3CC3)N=C2)C1)N1CC(C2)(CC2OC2=NC(C(F)(F)F)=NC=C2)C1 ABAQIAMYLCWBIP-UHFFFAOYSA-N 0.000 claims description 4
- 208000005298 acute pain Diseases 0.000 claims description 4
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 4
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- RNOVGJWJVRESAA-UHFFFAOYSA-N 4-fluoro-2-(trifluoromethyl)phenol Chemical group OC1=CC=C(F)C=C1C(F)(F)F RNOVGJWJVRESAA-UHFFFAOYSA-N 0.000 claims description 3
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
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- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
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- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
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- SLBGAAXUJGPVSV-UHFFFAOYSA-N spiro[3.3]heptan-2-ol Chemical compound C1C(O)CC11CCC1 SLBGAAXUJGPVSV-UHFFFAOYSA-N 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- KVOUHLVOTMOJBS-UHFFFAOYSA-N tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC11CNC1 KVOUHLVOTMOJBS-UHFFFAOYSA-N 0.000 description 1
- XPDIKRMPZNLBAC-UHFFFAOYSA-N tert-butyl 3-iodoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(I)C1 XPDIKRMPZNLBAC-UHFFFAOYSA-N 0.000 description 1
- HQHRAGXKFOTSQE-UHFFFAOYSA-N tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC21CC(=O)C2 HQHRAGXKFOTSQE-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
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- 239000003440 toxic substance Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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- 238000000844 transformation Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- HILRAMQWKMIWCB-UHFFFAOYSA-N tributyl(cyanomethyl)phosphanium Chemical compound CCCC[P+](CCCC)(CCCC)CC#N HILRAMQWKMIWCB-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- SCHZCUMIENIQMY-UHFFFAOYSA-N tris(trimethylsilyl)silicon Chemical compound C[Si](C)(C)[Si]([Si](C)(C)C)[Si](C)(C)C SCHZCUMIENIQMY-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
- C07D405/14—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 three or more hetero rings
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- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
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- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP21170090.1 | 2021-04-23 | ||
| EP21170090 | 2021-04-23 | ||
| CNPCT/CN2022/083125 | 2022-03-25 | ||
| CN2022083125 | 2022-03-25 | ||
| PCT/EP2022/060644 WO2022223750A1 (en) | 2021-04-23 | 2022-04-22 | Heterocyclic compounds |
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| KR20240000574A true KR20240000574A (ko) | 2024-01-02 |
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| ES2986417T3 (es) | 2018-08-13 | 2024-11-11 | Hoffmann La Roche | Nuevos compuestos heterocíclicos como inhibidores de la monoacilglicerol lipasa |
| ES2955037T3 (es) | 2018-11-22 | 2023-11-28 | Hoffmann La Roche | Nuevos compuestos heterocíclicos |
| WO2023130043A1 (en) * | 2021-12-29 | 2023-07-06 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment of anxiety |
| WO2023130050A1 (en) * | 2021-12-29 | 2023-07-06 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment and management of pain |
| CA3242372A1 (en) * | 2021-12-29 | 2023-07-06 | Psy Therapeutics, Inc. | Inhibiting monoacylglycerol lipase (magl) |
| WO2023144160A1 (en) * | 2022-01-25 | 2023-08-03 | F. Hoffmann-La Roche Ag | New heterocyclic compounds |
| JP2025525350A (ja) * | 2022-06-24 | 2025-08-05 | エフ. ホフマン-ラ ロシュ アーゲー | Magl阻害剤としての新規複素環-カルボニル-環式化合物 |
| CA3261681A1 (en) | 2022-08-05 | 2024-02-08 | Kumquat Biosciences Inc. | HETEROCYCLIC COMPOUNDS AND THEIR USES |
| WO2024215863A2 (en) * | 2023-04-13 | 2024-10-17 | Psy Therapeutics, Inc. | Inhibiting monoacylglycerol lipase (magl) |
| WO2025010392A2 (en) * | 2023-07-06 | 2025-01-09 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment of neurological disorders |
| WO2025010394A2 (en) * | 2023-07-06 | 2025-01-09 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment and management of inflammatory conditions |
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| PE20171057A1 (es) * | 2014-10-08 | 2017-07-21 | Hoffmann La Roche | Derivados espirodiamina como inhibidores de la aldosterona sintasa |
| UA125171C2 (uk) * | 2015-07-02 | 2022-01-26 | Янссен Саєнсиз Айрленд Юсі | Антибактеріальні сполуки |
| KR102765806B1 (ko) * | 2017-09-05 | 2025-02-10 | 블랙손 테라퓨틱스, 인크. | 바소프레신 수용체 길항제 및 그와 관련된 제품 및 방법 |
| JP2021516229A (ja) * | 2018-02-28 | 2021-07-01 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 低親和性ポリ(ad−リボース)ポリメラーゼ1依存性細胞毒性剤 |
| WO2019209962A1 (en) * | 2018-04-25 | 2019-10-31 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
| ES2955037T3 (es) * | 2018-11-22 | 2023-11-28 | Hoffmann La Roche | Nuevos compuestos heterocíclicos |
| CN111793064B (zh) * | 2019-04-02 | 2023-06-23 | 上海美悦生物科技发展有限公司 | 一种作为irak抑制剂的化合物及其制备方法和用途 |
| MX2023003240A (es) * | 2020-09-22 | 2023-06-16 | Janssen Pharmaceutica Nv | Moduladores de monoacilglicerol lipasa de ciclobutilamida. |
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| MX2023012477A (es) | 2023-11-03 |
| CO2023014721A2 (es) | 2023-11-20 |
| JP2024521618A (ja) | 2024-06-04 |
| US20240199587A1 (en) | 2024-06-20 |
| AR125401A1 (es) | 2023-07-12 |
| IL306126A (en) | 2023-11-01 |
| EP4326714A1 (en) | 2024-02-28 |
| WO2022223750A1 (en) | 2022-10-27 |
| AU2022260537A1 (en) | 2023-09-21 |
| CN117295726A (zh) | 2023-12-26 |
| CL2023003154A1 (es) | 2024-04-12 |
| PE20240239A1 (es) | 2024-02-16 |
| CA3215260A1 (en) | 2022-10-27 |
| CR20230496A (es) | 2023-11-15 |
| TW202309010A (zh) | 2023-03-01 |
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