HRP20030298A2 - Bridged piperazine derivatives - Google Patents

Info

Publication number

HRP20030298A2

HRP20030298A2 HR20030298A HRP20030298A HRP20030298A2 HR P20030298 A2 HRP20030298 A2 HR P20030298A2 HR 20030298 A HR20030298 A HR 20030298A HR P20030298 A HRP20030298 A HR P20030298A HR P20030298 A2 HRP20030298 A2 HR P20030298A2

Authority

HR

Croatia

Prior art keywords

alkyl

alkylamino

alkylcarbonylamino

amino

aryl

Prior art date

2000-10-19

Links

• Espacenet
• Global Dossier
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• 150000004885 piperazines Chemical class 0.000 title description 2
• 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 339
• 150000001875 compounds Chemical class 0.000 claims description 265
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 165
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 144
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 109
• -1 hydroxy, hydroxysulfonyl Chemical group 0.000 claims description 83
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 82
• 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 81
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 80
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 74
• 125000005281 alkyl ureido group Chemical group 0.000 claims description 70
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 67
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 63
• 238000000034 method Methods 0.000 claims description 63
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 62
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 52
• 125000001072 heteroaryl group Chemical group 0.000 claims description 52
• 150000003839 salts Chemical class 0.000 claims description 46
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 44
• 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 40
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 36
• 125000001475 halogen functional group Chemical group 0.000 claims description 35
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 31
• 125000003545 alkoxy group Chemical group 0.000 claims description 31
• 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 30
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 28
• 239000001257 hydrogen Substances 0.000 claims description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
• 206010061218 Inflammation Diseases 0.000 claims description 27
• 208000015181 infectious disease Diseases 0.000 claims description 27
• 230000004054 inflammatory process Effects 0.000 claims description 27
• 239000002253 acid Substances 0.000 claims description 23
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims description 22
• 208000035475 disorder Diseases 0.000 claims description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 230000002265 prevention Effects 0.000 claims description 19
• 102000004127 Cytokines Human genes 0.000 claims description 18
• 108090000695 Cytokines Proteins 0.000 claims description 18
• 241000701022 Cytomegalovirus Species 0.000 claims description 18
• 206010014561 Emphysema Diseases 0.000 claims description 18
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 18
• 230000001684 chronic effect Effects 0.000 claims description 18
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 18
• 230000001154 acute effect Effects 0.000 claims description 17
• 238000004519 manufacturing process Methods 0.000 claims description 17
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
• 241000124008 Mammalia Species 0.000 claims description 16
• 150000001412 amines Chemical class 0.000 claims description 16
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 16
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 16
• 102000004500 CCR1 Receptors Human genes 0.000 claims description 15
• 108010017319 CCR1 Receptors Proteins 0.000 claims description 15
• 108010002352 Interleukin-1 Proteins 0.000 claims description 15
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 15
• 239000001301 oxygen Substances 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 125000006719 (C6-C10) aryl (C1-C6) alkyl group Chemical group 0.000 claims description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 239000000651 prodrug Substances 0.000 claims description 12
• 229940002612 prodrug Drugs 0.000 claims description 12
• 230000002829 reductive effect Effects 0.000 claims description 12
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 11
• 201000010099 disease Diseases 0.000 claims description 11
• 230000002757 inflammatory effect Effects 0.000 claims description 11
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 10
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 10
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 10
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 10
• 125000001769 aryl amino group Chemical group 0.000 claims description 10
• 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 10
• 239000007787 solid Substances 0.000 claims description 10
• 210000001519 tissue Anatomy 0.000 claims description 10
• 208000007788 Acute Liver Failure Diseases 0.000 claims description 9
• 206010000804 Acute hepatic failure Diseases 0.000 claims description 9
• 206010027654 Allergic conditions Diseases 0.000 claims description 9
• 201000001320 Atherosclerosis Diseases 0.000 claims description 9
• 208000023275 Autoimmune disease Diseases 0.000 claims description 9
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 9
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 9
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 9
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 9
• 208000000059 Dyspnea Diseases 0.000 claims description 9
• 206010013975 Dyspnoeas Diseases 0.000 claims description 9
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 9
• 206010018691 Granuloma Diseases 0.000 claims description 9
• 208000031886 HIV Infections Diseases 0.000 claims description 9
• 206010020164 HIV infection CDC Group III Diseases 0.000 claims description 9
• 206010019280 Heart failures Diseases 0.000 claims description 9
• 206010019663 Hepatic failure Diseases 0.000 claims description 9
• 208000009889 Herpes Simplex Diseases 0.000 claims description 9
• 208000007514 Herpes zoster Diseases 0.000 claims description 9
• 241000725303 Human immunodeficiency virus Species 0.000 claims description 9
• 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 9
• 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 9
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 9
• 208000016604 Lyme disease Diseases 0.000 claims description 9
• 206010027202 Meningitis bacterial Diseases 0.000 claims description 9
• 206010027236 Meningitis fungal Diseases 0.000 claims description 9
• 208000034578 Multiple myelomas Diseases 0.000 claims description 9
• 208000003435 Optic Neuritis Diseases 0.000 claims description 9
• 241001111421 Pannus Species 0.000 claims description 9
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 9
• 208000007048 Polymyalgia Rheumatica Diseases 0.000 claims description 9
• 201000004681 Psoriasis Diseases 0.000 claims description 9
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 9
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 9
• 206010063837 Reperfusion injury Diseases 0.000 claims description 9
• 206010040070 Septic Shock Diseases 0.000 claims description 9
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 9
• 206010046851 Uveitis Diseases 0.000 claims description 9
• 206010047115 Vasculitis Diseases 0.000 claims description 9
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
• 231100000836 acute liver failure Toxicity 0.000 claims description 9
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 9
• 208000006673 asthma Diseases 0.000 claims description 9
• 201000008937 atopic dermatitis Diseases 0.000 claims description 9
• 201000009904 bacterial meningitis Diseases 0.000 claims description 9
• 206010006451 bronchitis Diseases 0.000 claims description 9
• 208000007451 chronic bronchitis Diseases 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 9
• 201000010056 fungal meningitis Diseases 0.000 claims description 9
• 208000006454 hepatitis Diseases 0.000 claims description 9
• 231100000283 hepatitis Toxicity 0.000 claims description 9
• 150000002431 hydrogen Chemical class 0.000 claims description 9
• 206010020718 hyperplasia Diseases 0.000 claims description 9
• 230000008595 infiltration Effects 0.000 claims description 9
• 238000001764 infiltration Methods 0.000 claims description 9
• 230000004968 inflammatory condition Effects 0.000 claims description 9
• 206010022000 influenza Diseases 0.000 claims description 9
• 208000014674 injury Diseases 0.000 claims description 9
• 210000005067 joint tissue Anatomy 0.000 claims description 9
• 231100000835 liver failure Toxicity 0.000 claims description 9
• 208000007903 liver failure Diseases 0.000 claims description 9
• 206010025135 lupus erythematosus Diseases 0.000 claims description 9
• 201000004792 malaria Diseases 0.000 claims description 9
• 201000006417 multiple sclerosis Diseases 0.000 claims description 9
• 208000010125 myocardial infarction Diseases 0.000 claims description 9
• 210000000056 organ Anatomy 0.000 claims description 9
• 201000008482 osteoarthritis Diseases 0.000 claims description 9
• 208000037803 restenosis Diseases 0.000 claims description 9
• 201000000306 sarcoidosis Diseases 0.000 claims description 9
• 230000036303 septic shock Effects 0.000 claims description 9
• 208000011580 syndromic disease Diseases 0.000 claims description 9
• 230000000451 tissue damage Effects 0.000 claims description 9
• 231100000827 tissue damage Toxicity 0.000 claims description 9
• 230000008733 trauma Effects 0.000 claims description 9
• 241000701161 unidentified adenovirus Species 0.000 claims description 9
• 241001529453 unidentified herpesvirus Species 0.000 claims description 9
• 230000003612 virological effect Effects 0.000 claims description 9
• 238000002689 xenotransplantation Methods 0.000 claims description 9
• 208000006386 Bone Resorption Diseases 0.000 claims description 8
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
• 102000019034 Chemokines Human genes 0.000 claims description 8
• 108010012236 Chemokines Proteins 0.000 claims description 8
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 8
• 206010024229 Leprosy Diseases 0.000 claims description 8
• 229910019142 PO4 Inorganic materials 0.000 claims description 8
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 8
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 8
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 8
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 8
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 8
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 8
• 230000015572 biosynthetic process Effects 0.000 claims description 8
• 230000024279 bone resorption Effects 0.000 claims description 8
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 8
• 239000010452 phosphate Substances 0.000 claims description 8
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
• 201000008827 tuberculosis Diseases 0.000 claims description 8
• 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 7
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 7
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 6
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 6
• 150000007513 acids Chemical class 0.000 claims description 6
• 230000003042 antagnostic effect Effects 0.000 claims description 6
• 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 claims description 6
• 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 6
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
• 230000000670 limiting effect Effects 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• 125000003342 alkenyl group Chemical group 0.000 claims description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
• 230000002401 inhibitory effect Effects 0.000 claims description 5
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
• FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 claims description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
• DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 claims description 4
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims description 4
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
• 229910002651 NO3 Inorganic materials 0.000 claims description 4
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
• 229910052783 alkali metal Inorganic materials 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 4
• 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 4
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 4
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
• 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 4
• 229940050410 gluconate Drugs 0.000 claims description 4
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 4
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 4
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 4
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 4
• 229940095064 tartrate Drugs 0.000 claims description 4
• 150000001447 alkali salts Chemical class 0.000 claims description 3
• 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
• 125000000304 alkynyl group Chemical group 0.000 claims description 3
• 125000003118 aryl group Chemical group 0.000 claims description 3
• 229940077388 benzenesulfonate Drugs 0.000 claims description 3
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 3
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 3
• 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 3
• NDQQRRVKUBPTHQ-QBIQUQHTSA-N (2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO NDQQRRVKUBPTHQ-QBIQUQHTSA-N 0.000 claims description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
• 125000005091 alkenylcarbonylamino group Chemical group 0.000 claims description 2
• 150000003973 alkyl amines Chemical class 0.000 claims description 2
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 2
• 125000003368 amide group Chemical group 0.000 claims description 2
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
• 125000005419 heteroarylsulfonylamino group Chemical group 0.000 claims description 2
• 125000000623 heterocyclic group Chemical group 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 230000000302 ischemic effect Effects 0.000 claims description 2
• 201000009961 allergic asthma Diseases 0.000 claims 3
• 210000000988 bone and bone Anatomy 0.000 claims 1
• 102000005962 receptors Human genes 0.000 claims 1
• 108020003175 receptors Proteins 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
• 239000011541 reaction mixture Substances 0.000 description 91
• 238000006243 chemical reaction Methods 0.000 description 85
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• 239000000243 solution Substances 0.000 description 57
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
• 238000002360 preparation method Methods 0.000 description 34
• 239000000203 mixture Substances 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 29
• 229910002027 silica gel Inorganic materials 0.000 description 29
• 210000004027 cell Anatomy 0.000 description 27
• 238000004587 chromatography analysis Methods 0.000 description 27
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 27
• 235000019341 magnesium sulphate Nutrition 0.000 description 27
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• 235000019441 ethanol Nutrition 0.000 description 24
• 239000002585 base Substances 0.000 description 23
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• 239000000010 aprotic solvent Substances 0.000 description 18
• 239000000706 filtrate Substances 0.000 description 16
• 239000005416 organic matter Substances 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 15
• 238000010992 reflux Methods 0.000 description 14
• 239000012065 filter cake Substances 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• 235000017557 sodium bicarbonate Nutrition 0.000 description 12
• 239000003880 polar aprotic solvent Substances 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
• 239000012312 sodium hydride Substances 0.000 description 9
• 229910000104 sodium hydride Inorganic materials 0.000 description 9
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