TW201200518A - Heterocyclic inhibitors of histamine receptors for the treatment of disease - Google Patents

Info

Publication number

TW201200518A

TW201200518A TW100107575A TW100107575A TW201200518A TW 201200518 A TW201200518 A TW 201200518A TW 100107575 A TW100107575 A TW 100107575A TW 100107575 A TW100107575 A TW 100107575A TW 201200518 A TW201200518 A TW 201200518A

Authority

TW

Taiwan

Prior art keywords

group

compound

optionally substituted

alkyl

heteroaryl

Prior art date

2010-03-10

Links

• Espacenet
• Global Dossier
• Discuss

• 238000011282 treatment Methods 0.000 title claims abstract description 45
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 40
• 201000010099 disease Diseases 0.000 title claims description 36
• 125000000623 heterocyclic group Chemical group 0.000 title claims description 25
• 239000003112 inhibitor Substances 0.000 title abstract description 8
• 102000000543 Histamine Receptors Human genes 0.000 title description 14
• 108010002059 Histamine Receptors Proteins 0.000 title description 14
• 150000001875 compounds Chemical class 0.000 claims abstract description 258
• 238000000034 method Methods 0.000 claims abstract description 74
• 230000000172 allergic effect Effects 0.000 claims abstract description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 5
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 5
• -1 amidino, carboxy, fluorenyl Chemical group 0.000 claims description 175
• 125000000217 alkyl group Chemical group 0.000 claims description 120
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 102
• 125000003118 aryl group Chemical group 0.000 claims description 100
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 92
• 125000001072 heteroaryl group Chemical group 0.000 claims description 73
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 67
• 150000003839 salts Chemical class 0.000 claims description 67
• 239000001257 hydrogen Substances 0.000 claims description 65
• 229910052739 hydrogen Inorganic materials 0.000 claims description 65
• 125000002950 monocyclic group Chemical group 0.000 claims description 63
• 125000003545 alkoxy group Chemical group 0.000 claims description 56
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 51
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 49
• 150000001412 amines Chemical class 0.000 claims description 49
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 48
• 239000005557 antagonist Substances 0.000 claims description 48
• 239000003814 drug Substances 0.000 claims description 48
• 150000002431 hydrogen Chemical class 0.000 claims description 45
• 125000001188 haloalkyl group Chemical group 0.000 claims description 40
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 36
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 35
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 35
• 229910052736 halogen Inorganic materials 0.000 claims description 35
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 33
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 32
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 29
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
• 230000000694 effects Effects 0.000 claims description 28
• 150000002367 halogens Chemical class 0.000 claims description 28
• 125000000304 alkynyl group Chemical group 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 125000003342 alkenyl group Chemical group 0.000 claims description 25
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 25
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 25
• 229940124597 therapeutic agent Drugs 0.000 claims description 25
• 229960001340 histamine Drugs 0.000 claims description 24
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 21
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 21
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 21
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 21
• 206010061218 Inflammation Diseases 0.000 claims description 19
• 230000004054 inflammatory process Effects 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 229930192474 thiophene Chemical group 0.000 claims description 19
• 125000005842 heteroatom Chemical group 0.000 claims description 18
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 17
• 125000003277 amino group Chemical group 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 125000005843 halogen group Chemical group 0.000 claims description 16
• 208000003251 Pruritus Diseases 0.000 claims description 15
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 15
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 14
• 208000006673 asthma Diseases 0.000 claims description 14
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 14
• 230000005764 inhibitory process Effects 0.000 claims description 14
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 13
• 206010039083 rhinitis Diseases 0.000 claims description 13
• 239000000126 substance Substances 0.000 claims description 13
• 230000000699 topical effect Effects 0.000 claims description 13
• 208000002193 Pain Diseases 0.000 claims description 12
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 12
• 206010036790 Productive cough Diseases 0.000 claims description 11
• 208000010668 atopic eczema Diseases 0.000 claims description 11
• 210000003802 sputum Anatomy 0.000 claims description 11
• 208000024794 sputum Diseases 0.000 claims description 11
• 206010010741 Conjunctivitis Diseases 0.000 claims description 10
• 201000010105 allergic rhinitis Diseases 0.000 claims description 10
• 210000003491 skin Anatomy 0.000 claims description 10
• 206010028735 Nasal congestion Diseases 0.000 claims description 9
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 9
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 9
• 210000003630 histaminocyte Anatomy 0.000 claims description 9
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 8
• 201000004624 Dermatitis Diseases 0.000 claims description 8
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 8
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• 230000009467 reduction Effects 0.000 claims description 8
• 230000009885 systemic effect Effects 0.000 claims description 8
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 8
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 7
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical group C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical group C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 7
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 7
• 150000003852 triazoles Chemical group 0.000 claims description 7
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical group C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 6
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical group C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 6
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical group C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 claims description 6
• 229910021529 ammonia Inorganic materials 0.000 claims description 6
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 6
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 6
• 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 6
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 6
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical group C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 6
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Chemical group C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 6
• 208000024891 symptom Diseases 0.000 claims description 6
• 206010027654 Allergic conditions Diseases 0.000 claims description 5
• ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims description 5
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 5
• JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 claims description 5
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 5
• 208000024998 atopic conjunctivitis Diseases 0.000 claims description 5
• 201000008937 atopic dermatitis Diseases 0.000 claims description 5
• 239000003246 corticosteroid Substances 0.000 claims description 5
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 5
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 5
• JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 claims description 5
• 208000037916 non-allergic rhinitis Diseases 0.000 claims description 5
• 229960004114 olopatadine Drugs 0.000 claims description 5
• 150000002923 oximes Chemical class 0.000 claims description 5
• 230000001105 regulatory effect Effects 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 238000001356 surgical procedure Methods 0.000 claims description 5
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
• 102000015696 Interleukins Human genes 0.000 claims description 4
• 108010063738 Interleukins Proteins 0.000 claims description 4
• ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 claims description 4
• 239000002671 adjuvant Substances 0.000 claims description 4
• 229960001803 cetirizine Drugs 0.000 claims description 4
• SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 claims description 4
• 229960003291 chlorphenamine Drugs 0.000 claims description 4
• 229960001271 desloratadine Drugs 0.000 claims description 4
• 229960000520 diphenhydramine Drugs 0.000 claims description 4
• 229940047122 interleukins Drugs 0.000 claims description 4
• 206010023332 keratitis Diseases 0.000 claims description 4
• 201000010666 keratoconjunctivitis Diseases 0.000 claims description 4
• 229960004958 ketotifen Drugs 0.000 claims description 4
• 229960003088 loratadine Drugs 0.000 claims description 4
• 210000001595 mastoid Anatomy 0.000 claims description 4
• 210000002850 nasal mucosa Anatomy 0.000 claims description 4
• JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 claims description 4
• 238000011200 topical administration Methods 0.000 claims description 4
• ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 claims description 3
• MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 claims description 3
• 208000002177 Cataract Diseases 0.000 claims description 3
• LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 claims description 3
• 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 3
• 206010013774 Dry eye Diseases 0.000 claims description 3
• 206010015958 Eye pain Diseases 0.000 claims description 3
• PVLJETXTTWAYEW-UHFFFAOYSA-N Mizolastine Chemical compound N=1C=CC(=O)NC=1N(C)C(CC1)CCN1C1=NC2=CC=CC=C2N1CC1=CC=C(F)C=C1 PVLJETXTTWAYEW-UHFFFAOYSA-N 0.000 claims description 3
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
• 230000001668 ameliorated effect Effects 0.000 claims description 3
• 229940120638 avastin Drugs 0.000 claims description 3
• 125000001309 chloro group Chemical class Cl* 0.000 claims description 3
• 229960003728 ciclesonide Drugs 0.000 claims description 3
• 229960001971 ebastine Drugs 0.000 claims description 3
• MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 claims description 3
• 208000030533 eye disease Diseases 0.000 claims description 3
• 229960000890 hydrocortisone Drugs 0.000 claims description 3
• ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 claims description 3
• 229960000930 hydroxyzine Drugs 0.000 claims description 3
• 210000004969 inflammatory cell Anatomy 0.000 claims description 3
• 230000007803 itching Effects 0.000 claims description 3
• ZCGOMHNNNFPNMX-KYTRFIICSA-N levocabastine Chemical compound C1([C@@]2(C(O)=O)CCN(C[C@H]2C)[C@@H]2CC[C@@](CC2)(C#N)C=2C=CC(F)=CC=2)=CC=CC=C1 ZCGOMHNNNFPNMX-KYTRFIICSA-N 0.000 claims description 3
• 229960001120 levocabastine Drugs 0.000 claims description 3
• 229960001508 levocetirizine Drugs 0.000 claims description 3
• 229960001144 mizolastine Drugs 0.000 claims description 3
• QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 claims description 3
• 229960001664 mometasone Drugs 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical group C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 3
• 238000006748 scratching Methods 0.000 claims description 3
• 230000002393 scratching effect Effects 0.000 claims description 3
• 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims description 2
• BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 2
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 2
• 101100240528 Caenorhabditis elegans nhr-23 gene Proteins 0.000 claims description 2
• 206010015943 Eye inflammation Diseases 0.000 claims description 2
• 206010028741 Nasal inflammation Diseases 0.000 claims description 2
• 208000005141 Otitis Diseases 0.000 claims description 2
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 2
• 229960004574 azelastine Drugs 0.000 claims description 2
• 150000003431 steroids Chemical class 0.000 claims description 2
• CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 claims 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims 1
• QMEQBOSUJUOXMX-UHFFFAOYSA-N 2h-oxadiazine Chemical compound N1OC=CC=N1 QMEQBOSUJUOXMX-UHFFFAOYSA-N 0.000 claims 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-O Pyrazolium Chemical compound C1=CN[NH+]=C1 WTKZEGDFNFYCGP-UHFFFAOYSA-O 0.000 claims 1
• JZFICWYCTCCINF-UHFFFAOYSA-N Thiadiazin Chemical compound S=C1SC(C)NC(C)N1CCN1C(=S)SC(C)NC1C JZFICWYCTCCINF-UHFFFAOYSA-N 0.000 claims 1
• SHWNNYZBHZIQQV-UHFFFAOYSA-L calcium;disodium;2-[2-[bis(carboxylatomethyl)azaniumyl]ethyl-(carboxylatomethyl)azaniumyl]acetate Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-L 0.000 claims 1
• 230000012292 cell migration Effects 0.000 claims 1
• 208000026935 allergic disease Diseases 0.000 abstract description 6
• 230000002265 prevention Effects 0.000 abstract description 5
• 208000027866 inflammatory disease Diseases 0.000 abstract description 3
• 208000022873 Ocular disease Diseases 0.000 abstract description 2
• 230000001363 autoimmune Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 247
• 239000000203 mixture Substances 0.000 description 146
• 235000019439 ethyl acetate Nutrition 0.000 description 131
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
• 239000000243 solution Substances 0.000 description 73
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• 238000010626 work up procedure Methods 0.000 description 64
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 59
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• 238000009472 formulation Methods 0.000 description 55
• 239000011541 reaction mixture Substances 0.000 description 49
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
• 238000005481 NMR spectroscopy Methods 0.000 description 45
• 239000002904 solvent Substances 0.000 description 45
• 238000005160 1H NMR spectroscopy Methods 0.000 description 42
• 239000007787 solid Substances 0.000 description 38
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 34
• 239000012044 organic layer Substances 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 32
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
• 101150041968 CDC13 gene Proteins 0.000 description 26
• 206010057190 Respiratory tract infections Diseases 0.000 description 26
• 239000002585 base Substances 0.000 description 25
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 24
• 239000011734 sodium Substances 0.000 description 24
• 239000004480 active ingredient Substances 0.000 description 22
• ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 22
• 238000001914 filtration Methods 0.000 description 21
• 238000003818 flash chromatography Methods 0.000 description 21
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 20
• 210000004027 cell Anatomy 0.000 description 20
• 239000003795 chemical substances by application Substances 0.000 description 20
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
• 101710166940 Histamine H3 receptor Proteins 0.000 description 18
• 102100032508 Histamine H3 receptor Human genes 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 17
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 17
• 150000003840 hydrochlorides Chemical class 0.000 description 17
• 102000005962 receptors Human genes 0.000 description 17
• 108020003175 receptors Proteins 0.000 description 17
• 239000002253 acid Substances 0.000 description 16
• 229940079593 drug Drugs 0.000 description 16
• 239000000651 prodrug Substances 0.000 description 16
• 229940002612 prodrug Drugs 0.000 description 16
• 239000000725 suspension Substances 0.000 description 15
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 14
• 229920006395 saturated elastomer Polymers 0.000 description 14
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 13
• 241001465754 Metazoa Species 0.000 description 13
• 239000007864 aqueous solution Substances 0.000 description 13
• 238000003556 assay Methods 0.000 description 13
• 125000004432 carbon atom Chemical group C* 0.000 description 13
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 13
• 210000001508 eye Anatomy 0.000 description 13
• 239000000843 powder Substances 0.000 description 13
• 230000001225 therapeutic effect Effects 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
• 239000000556 agonist Substances 0.000 description 12
• CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• 229910052717 sulfur Inorganic materials 0.000 description 11
• 239000003826 tablet Substances 0.000 description 11
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
• QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 208000024780 Urticaria Diseases 0.000 description 10
• 230000008901 benefit Effects 0.000 description 10
• 229910000024 caesium carbonate Inorganic materials 0.000 description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• 238000000338 in vitro Methods 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 9
• 125000004429 atom Chemical group 0.000 description 9
• 230000001684 chronic effect Effects 0.000 description 9
• 239000006196 drop Substances 0.000 description 9
• 239000004615 ingredient Substances 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
• 230000001154 acute effect Effects 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 239000000499 gel Substances 0.000 description 8
• 235000011187 glycerol Nutrition 0.000 description 8
• 239000007924 injection Substances 0.000 description 8
• 238000002347 injection Methods 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• 210000001331 nose Anatomy 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 239000000546 pharmaceutical excipient Substances 0.000 description 8
• 239000013641 positive control Substances 0.000 description 8
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
• 206010020751 Hypersensitivity Diseases 0.000 description 7
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 7
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000012267 brine Substances 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 239000003208 petroleum Substances 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 239000003755 preservative agent Substances 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• 229910052707 ruthenium Inorganic materials 0.000 description 7
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 6
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 6
• 229910020889 NaBH3 Inorganic materials 0.000 description 6
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
• 239000001768 carboxy methyl cellulose Substances 0.000 description 6
• 210000003169 central nervous system Anatomy 0.000 description 6
• 210000003979 eosinophil Anatomy 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 230000008020 evaporation Effects 0.000 description 6
• 125000004438 haloalkoxy group Chemical group 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
• 238000011068 loading method Methods 0.000 description 6
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 6
• 229940016286 microcrystalline cellulose Drugs 0.000 description 6
• 239000008108 microcrystalline cellulose Substances 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 239000000600 sorbitol Substances 0.000 description 6
• 229960002920 sorbitol Drugs 0.000 description 6
• 235000010356 sorbitol Nutrition 0.000 description 6
• 239000003381 stabilizer Substances 0.000 description 6
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 6
• DSDCDMKASWVZHI-UHFFFAOYSA-M zinc;2-methanidylpropane;bromide Chemical compound Br[Zn+].CC(C)[CH2-] DSDCDMKASWVZHI-UHFFFAOYSA-M 0.000 description 6
• GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 description 5
• 244000215068 Acacia senegal Species 0.000 description 5
• IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 5
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 5
• 108010010803 Gelatin Proteins 0.000 description 5
• 229920000084 Gum arabic Polymers 0.000 description 5
• 229920002125 Sokalan® Polymers 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
• 229930006000 Sucrose Natural products 0.000 description 5
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
• IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 5
• 235000010489 acacia gum Nutrition 0.000 description 5
• 239000000205 acacia gum Substances 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 230000008485 antagonism Effects 0.000 description 5
• 239000012911 assay medium Substances 0.000 description 5
• 125000002619 bicyclic group Chemical group 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 229940095074 cyclic amp Drugs 0.000 description 5
• 230000006870 function Effects 0.000 description 5
• 239000008273 gelatin Substances 0.000 description 5
• 229920000159 gelatin Polymers 0.000 description 5
• 235000019322 gelatine Nutrition 0.000 description 5
• 235000011852 gelatine desserts Nutrition 0.000 description 5
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 5
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
• 239000006210 lotion Substances 0.000 description 5
• 239000000314 lubricant Substances 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 239000001301 oxygen Substances 0.000 description 5
• 235000018102 proteins Nutrition 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• NIPZZXUFJPQHNH-UHFFFAOYSA-M pyrazine-2-carboxylate Chemical compound [O-]C(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-M 0.000 description 5
• 230000011664 signaling Effects 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 5
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 5
• 229940032147 starch Drugs 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 229960004793 sucrose Drugs 0.000 description 5
• 239000005720 sucrose Substances 0.000 description 5
• 239000004094 surface-active agent Substances 0.000 description 5
• 208000011580 syndromic disease Diseases 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• MLCNOCRGSBCAGH-UHFFFAOYSA-N 2,3-dichloropyrazine Chemical compound ClC1=NC=CN=C1Cl MLCNOCRGSBCAGH-UHFFFAOYSA-N 0.000 description 4
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 4
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
• 241000416162 Astragalus gummifer Species 0.000 description 4
• BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 229920002307 Dextran Polymers 0.000 description 4
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
• 241000699670 Mus sp. Species 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 239000007832 Na2SO4 Substances 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• 229920001615 Tragacanth Polymers 0.000 description 4
• 208000027418 Wounds and injury Diseases 0.000 description 4
• 239000000443 aerosol Substances 0.000 description 4
• 230000000844 anti-bacterial effect Effects 0.000 description 4
• 206010006451 bronchitis Diseases 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910001424 calcium ion Inorganic materials 0.000 description 4
• 150000001721 carbon Chemical group 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 238000000423 cell based assay Methods 0.000 description 4
• 229960002086 dextran Drugs 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 4
• 230000002496 gastric effect Effects 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 229960001375 lactose Drugs 0.000 description 4
• 239000007937 lozenge Substances 0.000 description 4
• 239000011777 magnesium Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• 238000002156 mixing Methods 0.000 description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 4
• 125000004076 pyridyl group Chemical group 0.000 description 4
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 4
• 239000002464 receptor antagonist Substances 0.000 description 4
• 229940044551 receptor antagonist Drugs 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• 230000000638 stimulation Effects 0.000 description 4
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 4
• 239000011593 sulfur Substances 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 0.000 description 4
• 229940033134 talc Drugs 0.000 description 4
• 235000012222 talc Nutrition 0.000 description 4
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 4
• DBXVDQXATVVFGM-UHFFFAOYSA-N tert-butyl 4-(3-amino-5-bromopyrazin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(Br)N=C1N DBXVDQXATVVFGM-UHFFFAOYSA-N 0.000 description 4
• 125000004149 thio group Chemical group *S* 0.000 description 4
• 235000010487 tragacanth Nutrition 0.000 description 4
• 239000000196 tragacanth Substances 0.000 description 4
• 229940116362 tragacanth Drugs 0.000 description 4
• 238000011269 treatment regimen Methods 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical group NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 3
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
• ABQYSTWSLKDOGY-UHFFFAOYSA-N 3-chloro-1h-pyrazine-2-thione Chemical compound SC1=NC=CN=C1Cl ABQYSTWSLKDOGY-UHFFFAOYSA-N 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 229920002907 Guar gum Polymers 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
• 229920000881 Modified starch Polymers 0.000 description 3
• HVRLZEKDTUEKQH-NOILCQHBSA-N Olopatadine hydrochloride Chemical compound Cl.C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 HVRLZEKDTUEKQH-NOILCQHBSA-N 0.000 description 3
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 3
• 208000036284 Rhinitis seasonal Diseases 0.000 description 3
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
• 235000010443 alginic acid Nutrition 0.000 description 3
• 229920000615 alginic acid Polymers 0.000 description 3
• 150000001345 alkine derivatives Chemical group 0.000 description 3
• 125000002947 alkylene group Chemical group 0.000 description 3
• 230000007815 allergy Effects 0.000 description 3
• 239000007900 aqueous suspension Substances 0.000 description 3
• FDPKMJDUXJFKOI-UHFFFAOYSA-N azetidin-3-amine Chemical compound NC1CNC1 FDPKMJDUXJFKOI-UHFFFAOYSA-N 0.000 description 3
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• 239000002738 chelating agent Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 238000002648 combination therapy Methods 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 210000004443 dendritic cell Anatomy 0.000 description 3
• 239000008121 dextrose Substances 0.000 description 3
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
• 125000004494 ethyl ester group Chemical group 0.000 description 3
• 229960003592 fexofenadine Drugs 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 208000007565 gingivitis Diseases 0.000 description 3
• 229960001031 glucose Drugs 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 235000010417 guar gum Nutrition 0.000 description 3
• 239000000665 guar gum Substances 0.000 description 3
• 229960002154 guar gum Drugs 0.000 description 3
• 150000002391 heterocyclic compounds Chemical class 0.000 description 3
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 230000033001 locomotion Effects 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• 230000005012 migration Effects 0.000 description 3
• 238000013508 migration Methods 0.000 description 3
• 125000002757 morpholinyl group Chemical group 0.000 description 3
• 239000002736 nonionic surfactant Substances 0.000 description 3
• 239000008183 oral pharmaceutical preparation Substances 0.000 description 3
• 239000006072 paste Substances 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• 125000003386 piperidinyl group Chemical group 0.000 description 3
• 229920001983 poloxamer Polymers 0.000 description 3
• 229960000502 poloxamer Drugs 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
• 229920000053 polysorbate 80 Polymers 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 230000002335 preservative effect Effects 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 239000003380 propellant Substances 0.000 description 3
• NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 3
• JVANLUCASVHWEW-UHFFFAOYSA-N pyridazine Chemical compound N1=C=C=C=C=N1 JVANLUCASVHWEW-UHFFFAOYSA-N 0.000 description 3
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 3
• 150000003254 radicals Chemical class 0.000 description 3
• 208000017022 seasonal allergic rhinitis Diseases 0.000 description 3
• 239000007921 spray Substances 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• AKFFNGSKBWBPMI-UHFFFAOYSA-N tert-butyl 4-(5-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(Br)N2C1=NN=C2 AKFFNGSKBWBPMI-UHFFFAOYSA-N 0.000 description 3
• 150000003573 thiols Chemical class 0.000 description 3
• 239000000052 vinegar Substances 0.000 description 3
• 235000021419 vinegar Nutrition 0.000 description 3
• HUQJRYMLJBBEDO-UHFFFAOYSA-N (5-chloro-1h-indol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC2=CC(Cl)=CC=C2N1 HUQJRYMLJBBEDO-UHFFFAOYSA-N 0.000 description 2
• FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 2
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• NRMCJKAOFFFLFH-UHFFFAOYSA-N 1-(5-thiophen-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)azetidin-3-amine Chemical compound C1C(N)CN1C(C1=NN=CN11)=NC=C1C1=CC=CS1 NRMCJKAOFFFLFH-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
• MGTUVUVRFJVHAL-UHFFFAOYSA-N 2,8-dibenzyl-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3-ol Chemical compound Oc1c(Cc2ccccc2)nc2c(Cc3ccccc3)nc(cn12)-c1ccc(O)cc1 MGTUVUVRFJVHAL-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• OPGFHAPWUDKGHK-UHFFFAOYSA-N 2-methyl-6-(4-methylpiperazin-1-yl)pyrazine Chemical compound C1CN(C)CCN1C1=CN=CC(C)=N1 OPGFHAPWUDKGHK-UHFFFAOYSA-N 0.000 description 2
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
• DODAPRNRDPTFIT-UHFFFAOYSA-N 3,5-dibromo-2-methoxypyrazine Chemical compound COC1=NC=C(Br)N=C1Br DODAPRNRDPTFIT-UHFFFAOYSA-N 0.000 description 2
• DTLBKXRFWUERQN-UHFFFAOYSA-N 3,5-dibromopyrazin-2-amine Chemical compound NC1=NC=C(Br)N=C1Br DTLBKXRFWUERQN-UHFFFAOYSA-N 0.000 description 2
• SMJWSYDXAHYIKL-UHFFFAOYSA-N 5-bromo-2,4-dichloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=C(Cl)N=CC(Br)=C1Cl SMJWSYDXAHYIKL-UHFFFAOYSA-N 0.000 description 2
• IAOONUZRICRTIM-UHFFFAOYSA-N 5-bromo-2-(4-methylpiperazin-1-yl)pyridine-3,4-diamine Chemical compound C1CN(C)CCN1C1=NC=C(Br)C(N)=C1N IAOONUZRICRTIM-UHFFFAOYSA-N 0.000 description 2
• SIFNHCBGPOJHHZ-UHFFFAOYSA-N 5-bromo-2-chloro-3-nitropyridin-4-amine Chemical compound NC1=C(Br)C=NC(Cl)=C1[N+]([O-])=O SIFNHCBGPOJHHZ-UHFFFAOYSA-N 0.000 description 2
• QOWALNIZDHZTSM-UHFFFAOYSA-N 5-bromo-2-chloropyrimidin-4-amine Chemical compound NC1=NC(Cl)=NC=C1Br QOWALNIZDHZTSM-UHFFFAOYSA-N 0.000 description 2
• PUAJVHSNEHQMNU-UHFFFAOYSA-N 5-bromo-4-hydroxy-3-nitro-1h-pyridin-2-one Chemical compound OC=1NC=C(Br)C(=O)C=1[N+]([O-])=O PUAJVHSNEHQMNU-UHFFFAOYSA-N 0.000 description 2
• FAZNGFFMXPNDTQ-UHFFFAOYSA-N 5-bromo-8-methoxy-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound COC1=NC=C(Br)N2C=NN=C12 FAZNGFFMXPNDTQ-UHFFFAOYSA-N 0.000 description 2
• WXVMLTWAMFIODZ-UHFFFAOYSA-N 8-chloro-5-thiophen-2-yl-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound N12C=NN=C2C(Cl)=NC=C1C1=CC=CS1 WXVMLTWAMFIODZ-UHFFFAOYSA-N 0.000 description 2
• NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
• 108010000239 Aequorin Proteins 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
• 108010006654 Bleomycin Proteins 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 206010006458 Bronchitis chronic Diseases 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• 206010009137 Chronic sinusitis Diseases 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 102000005889 Cysteine-Rich Protein 61 Human genes 0.000 description 2
• 108010019961 Cysteine-Rich Protein 61 Proteins 0.000 description 2
• 201000003883 Cystic fibrosis Diseases 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• 239000004375 Dextrin Substances 0.000 description 2
• 229920001353 Dextrin Polymers 0.000 description 2
• XYWDPYKBIRQXQS-UHFFFAOYSA-N Diisopropyl sulfide Chemical compound CC(C)SC(C)C XYWDPYKBIRQXQS-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• 108091006027 G proteins Proteins 0.000 description 2
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
• 102000030782 GTP binding Human genes 0.000 description 2
• 108091000058 GTP-Binding Proteins 0.000 description 2
• 208000007514 Herpes zoster Diseases 0.000 description 2
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
• 206010020565 Hyperaemia Diseases 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 229920002774 Maltodextrin Polymers 0.000 description 2
• 239000005913 Maltodextrin Substances 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
• 208000000592 Nasal Polyps Diseases 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 235000019483 Peanut oil Nutrition 0.000 description 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 206010035664 Pneumonia Diseases 0.000 description 2
• 208000037062 Polyps Diseases 0.000 description 2
• 239000004372 Polyvinyl alcohol Substances 0.000 description 2
• 206010036376 Postherpetic Neuralgia Diseases 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 206010070834 Sensitisation Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 238000006619 Stille reaction Methods 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 206010042674 Swelling Diseases 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• 241000534944 Thia Species 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• NVSPJDGXKBDYIZ-UHFFFAOYSA-N [1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1=NC=CN2C=NN=C21 NVSPJDGXKBDYIZ-UHFFFAOYSA-N 0.000 description 2
• ZATXVRSLQDRAHZ-UHFFFAOYSA-N [1,3]oxazolo[4,5-c]pyridine Chemical compound N1=CC=C2OC=NC2=C1 ZATXVRSLQDRAHZ-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 150000001242 acetic acid derivatives Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
• 125000004450 alkenylene group Chemical group 0.000 description 2
• 125000003282 alkyl amino group Chemical group 0.000 description 2
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
• 125000005011 alkyl ether group Chemical group 0.000 description 2
• 125000004419 alkynylene group Chemical group 0.000 description 2
• 239000013566 allergen Substances 0.000 description 2
• OYTKINVCDFNREN-UHFFFAOYSA-N amifampridine Chemical compound NC1=CC=NC=C1N OYTKINVCDFNREN-UHFFFAOYSA-N 0.000 description 2
• 229960004012 amifampridine Drugs 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 2
• 239000000739 antihistaminic agent Substances 0.000 description 2
• 229940125715 antihistaminic agent Drugs 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• 125000005018 aryl alkenyl group Chemical group 0.000 description 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
• 125000005015 aryl alkynyl group Chemical group 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• 239000003899 bactericide agent Substances 0.000 description 2
• 125000005605 benzo group Chemical group 0.000 description 2
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 230000029918 bioluminescence Effects 0.000 description 2
• 238000005415 bioluminescence Methods 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 235000010290 biphenyl Nutrition 0.000 description 2
• 229960001561 bleomycin Drugs 0.000 description 2
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• ZDIGNSYAACHWNL-UHFFFAOYSA-N brompheniramine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Br)C=C1 ZDIGNSYAACHWNL-UHFFFAOYSA-N 0.000 description 2
• 229960000725 brompheniramine Drugs 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 229960001631 carbomer Drugs 0.000 description 2
• 150000007942 carboxylates Chemical class 0.000 description 2
• 239000004359 castor oil Substances 0.000 description 2
• 235000019438 castor oil Nutrition 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• CETPSERCERDGAM-UHFFFAOYSA-N ceric oxide Chemical compound O=[Ce]=O CETPSERCERDGAM-UHFFFAOYSA-N 0.000 description 2
• 229910000422 cerium(IV) oxide Inorganic materials 0.000 description 2
• 150000001805 chlorine compounds Chemical class 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 208000007451 chronic bronchitis Diseases 0.000 description 2
• 208000027157 chronic rhinosinusitis Diseases 0.000 description 2
• 208000024376 chronic urticaria Diseases 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 229960001334 corticosteroids Drugs 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
• 235000019425 dextrin Nutrition 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 125000004982 dihaloalkyl group Chemical group 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 150000002009 diols Chemical class 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
• 210000005069 ears Anatomy 0.000 description 2
• 239000003974 emollient agent Substances 0.000 description 2
• 230000003203 everyday effect Effects 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 239000010685 fatty oil Substances 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 239000000417 fungicide Substances 0.000 description 2
• PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 2
• 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
• 239000003349 gelling agent Substances 0.000 description 2
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
• 229920001519 homopolymer Polymers 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 230000028709 inflammatory response Effects 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 206010022437 insomnia Diseases 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000000865 liniment Substances 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 210000004698 lymphocyte Anatomy 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 229940035034 maltodextrin Drugs 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 125000006682 monohaloalkyl group Chemical group 0.000 description 2
• 238000000465 moulding Methods 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 239000013642 negative control Substances 0.000 description 2
• 230000002981 neuropathic effect Effects 0.000 description 2
• 239000002858 neurotransmitter agent Substances 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 239000000312 peanut oil Substances 0.000 description 2
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
• 208000033808 peripheral neuropathy Diseases 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 125000005561 phenanthryl group Chemical group 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• 229940067107 phenylethyl alcohol Drugs 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 239000000049 pigment Substances 0.000 description 2
• RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 2
• 125000006684 polyhaloalkyl group Polymers 0.000 description 2
• 229920005862 polyol Polymers 0.000 description 2
• 150000003077 polyols Chemical class 0.000 description 2
• 229920000137 polyphosphoric acid Polymers 0.000 description 2
• 229920002451 polyvinyl alcohol Polymers 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000002685 pulmonary effect Effects 0.000 description 2
• 208000002815 pulmonary hypertension Diseases 0.000 description 2
• XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 2
• NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical compound NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 description 2
• 125000001453 quaternary ammonium group Chemical group 0.000 description 2
• 210000003370 receptor cell Anatomy 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000036387 respiratory rate Effects 0.000 description 2
• 208000023504 respiratory system disease Diseases 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 230000008313 sensitization Effects 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 201000009890 sinusitis Diseases 0.000 description 2
• 230000007958 sleep Effects 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• 229960001922 sodium perborate Drugs 0.000 description 2
• YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 2
• 239000007901 soft capsule Substances 0.000 description 2
• 239000012265 solid product Substances 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 239000011877 solvent mixture Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 230000008961 swelling Effects 0.000 description 2
• 230000002195 synergetic effect Effects 0.000 description 2
• 238000007910 systemic administration Methods 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• OPNDHVIWESXZFB-UHFFFAOYSA-N tert-butyl 4-(4-amino-5-bromopyrimidin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(Br)C(N)=N1 OPNDHVIWESXZFB-UHFFFAOYSA-N 0.000 description 2
• ANKKEWNPPJQFNI-UHFFFAOYSA-N tert-butyl 4-(5-bromo-3-chloropyrazin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(Br)N=C1Cl ANKKEWNPPJQFNI-UHFFFAOYSA-N 0.000 description 2
• NQWPWJXHYKJORT-UHFFFAOYSA-N tert-butyl 4-(6-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC(Br)=CN2C1=NN=C2 NQWPWJXHYKJORT-UHFFFAOYSA-N 0.000 description 2
• PJFXJXCGBYHRTQ-UHFFFAOYSA-N tert-butyl 4-[5-bromo-4-(dimethylaminomethylideneamino)pyrimidin-2-yl]piperazine-1-carboxylate Chemical compound C1=C(Br)C(N=CN(C)C)=NC(N2CCN(CC2)C(=O)OC(C)(C)C)=N1 PJFXJXCGBYHRTQ-UHFFFAOYSA-N 0.000 description 2
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 2
• 230000000451 tissue damage Effects 0.000 description 2
• 231100000827 tissue damage Toxicity 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 150000003648 triterpenes Chemical class 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 230000008728 vascular permeability Effects 0.000 description 2
• 230000024883 vasodilation Effects 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• WYRSGXAIHNMKOL-UHFFFAOYSA-N $l^{1}-sulfanylethane Chemical compound CC[S] WYRSGXAIHNMKOL-UHFFFAOYSA-N 0.000 description 1
• QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 1
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• DYWNLSQWJMTVGJ-UHFFFAOYSA-N (1-hydroxy-1-phenylpropan-2-yl)azanium;chloride Chemical compound Cl.CC(N)C(O)C1=CC=CC=C1 DYWNLSQWJMTVGJ-UHFFFAOYSA-N 0.000 description 1
• RRCMGJCFMJBHQC-UHFFFAOYSA-N (2-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1Cl RRCMGJCFMJBHQC-UHFFFAOYSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
• SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 1
• NGZYRKGJWYJGRS-RXMQYKEDSA-N (3r)-n-methylpyrrolidin-3-amine Chemical compound CN[C@@H]1CCNC1 NGZYRKGJWYJGRS-RXMQYKEDSA-N 0.000 description 1
• CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
• XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 1
• JFCLNCVCDFUJPO-UHFFFAOYSA-N (5-chlorothiophen-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)S1 JFCLNCVCDFUJPO-UHFFFAOYSA-N 0.000 description 1
• DKYYLYWTTBGVKE-UHFFFAOYSA-N (5-chlorothiophen-3-yl)boronic acid Chemical compound OB(O)C1=CSC(Cl)=C1 DKYYLYWTTBGVKE-UHFFFAOYSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
• IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• POPHMOPNVVKGRW-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydronaphthalene Chemical compound C1CCC2CCCCC2=C1 POPHMOPNVVKGRW-UHFFFAOYSA-N 0.000 description 1
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
• KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
• HKPUZZOQHBYMPZ-UHFFFAOYSA-N 1-$l^{1}-sulfanylpropane Chemical compound CCC[S] HKPUZZOQHBYMPZ-UHFFFAOYSA-N 0.000 description 1
• IQRAGNMEYWPLKC-UHFFFAOYSA-N 1-(diaminomethylidene)-3-methylideneguanidine Chemical compound NC(=N)NC(=N)N=C IQRAGNMEYWPLKC-UHFFFAOYSA-N 0.000 description 1
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• PTTHBZMGHRDZCV-UHFFFAOYSA-N 1h-indol-3-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CNC2=C1 PTTHBZMGHRDZCV-UHFFFAOYSA-N 0.000 description 1
• FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 1
• LXFQSRIDYRFTJW-UHFFFAOYSA-M 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S([O-])(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-M 0.000 description 1
• ZEZJPIDPVXJEME-UHFFFAOYSA-N 2,4-Dihydroxypyridine Chemical compound OC=1C=CNC(=O)C=1 ZEZJPIDPVXJEME-UHFFFAOYSA-N 0.000 description 1
• BLDFSDCBQJUWFG-UHFFFAOYSA-N 2-(methylamino)-1,2-diphenylethanol Chemical compound C=1C=CC=CC=1C(NC)C(O)C1=CC=CC=C1 BLDFSDCBQJUWFG-UHFFFAOYSA-N 0.000 description 1
• YANGEESWIGIKOP-UUWRZZSWSA-N 2-[[(2r)-1-[4-[4-[3-(azepan-1-yl)propoxy]phenyl]butyl]pyrrolidin-2-yl]methyl]-4-[(4-chlorophenyl)methyl]phthalazin-1-one Chemical compound C1=CC(Cl)=CC=C1CC(C1=CC=CC=C1C1=O)=NN1C[C@@H]1N(CCCCC=2C=CC(OCCCN3CCCCCC3)=CC=2)CCC1 YANGEESWIGIKOP-UUWRZZSWSA-N 0.000 description 1
• LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
• IEBAOPMEYUWQPD-UHFFFAOYSA-N 2-butan-2-ylsulfanylbutane Chemical compound CCC(C)SC(C)CC IEBAOPMEYUWQPD-UHFFFAOYSA-N 0.000 description 1
• CKUVSPQGYLELRG-UHFFFAOYSA-N 2-chloro-6-methylpyrazine Chemical compound CC1=CN=CC(Cl)=N1 CKUVSPQGYLELRG-UHFFFAOYSA-N 0.000 description 1
• GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 1
• JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• LNMBCRKRCIMQLW-UHFFFAOYSA-N 2-tert-butylsulfanyl-2-methylpropane Chemical compound CC(C)(C)SC(C)(C)C LNMBCRKRCIMQLW-UHFFFAOYSA-N 0.000 description 1
• YKSQPGLJCBOZNG-UHFFFAOYSA-N 2-thiophen-2-yl-1h-indole Chemical compound C1=CSC(C=2NC3=CC=CC=C3C=2)=C1 YKSQPGLJCBOZNG-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• KUZXQXCWRNFIHK-UHFFFAOYSA-N 3,3-diethyldodecane Chemical compound CCCCCCCCCC(CC)(CC)CC KUZXQXCWRNFIHK-UHFFFAOYSA-N 0.000 description 1
• JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
• FUQNVLVKZFXFNI-UHFFFAOYSA-N 3-[4-[4-[4-[4-(3,3-dimethylpiperidin-1-yl)butoxy]phenyl]piperidine-1-carbonyl]naphthalen-1-yl]propanoic acid Chemical compound C1C(C)(C)CCCN1CCCCOC1=CC=C(C2CCN(CC2)C(=O)C=2C3=CC=CC=C3C(CCC(O)=O)=CC=2)C=C1 FUQNVLVKZFXFNI-UHFFFAOYSA-N 0.000 description 1
• OCNBSSLDAIWTKS-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-8-methylquinolin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)=CC=CC2=CC=1CN(C1=NN(C)N=N1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OCNBSSLDAIWTKS-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• XCMISAPCWHTVNG-UHFFFAOYSA-N 3-bromothiophene Chemical compound BrC=1C=CSC=1 XCMISAPCWHTVNG-UHFFFAOYSA-N 0.000 description 1
• 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 1
• BKYGVGWYPFVKTK-UHFFFAOYSA-N 4-hydroxy-3-nitro-1h-pyridin-2-one Chemical compound OC=1NC=CC(=O)C=1[N+]([O-])=O BKYGVGWYPFVKTK-UHFFFAOYSA-N 0.000 description 1
• 150000005168 4-hydroxybenzoic acids Chemical class 0.000 description 1
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
• XQWZEFVEVXRCTQ-UHFFFAOYSA-N 5-(4-methylpiperazin-1-yl)-8-thiophen-2-yltetrazolo[1,5-c]pyrimidine Chemical compound C1CN(C)CCN1C(N1N=NN=C11)=NC=C1C1=CC=CS1 XQWZEFVEVXRCTQ-UHFFFAOYSA-N 0.000 description 1
• DZOABTLSEKDCJW-UHFFFAOYSA-N 5-(5-chlorothiophen-2-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1CN(C)CCN1C(C1=NN=CN11)=NC=C1C1=CC=C(Cl)S1 DZOABTLSEKDCJW-UHFFFAOYSA-N 0.000 description 1
• XPFKHZFVULZCRH-UHFFFAOYSA-N 5-(5-chlorothiophen-3-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1CN(C)CCN1C(C1=NN=CN11)=NC=C1C1=CSC(Cl)=C1 XPFKHZFVULZCRH-UHFFFAOYSA-N 0.000 description 1
• WIEPVFRTSGHWNE-UHFFFAOYSA-N 5-(5-chlorothiophen-3-yl)-8-piperazin-1-yl-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound S1C(Cl)=CC(C=2N3C=NN=C3C(N3CCNCC3)=NC=2)=C1 WIEPVFRTSGHWNE-UHFFFAOYSA-N 0.000 description 1
• FJDSTHATOWTHRG-UHFFFAOYSA-N 5-(furan-2-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1CN(C)CCN1C(C1=NN=CN11)=NC=C1C1=CC=CO1 FJDSTHATOWTHRG-UHFFFAOYSA-N 0.000 description 1
• KAPYGSUXANDQEE-UHFFFAOYSA-N 5-(furan-3-yl)-8-piperazin-1-yl-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1CNCCN1C(C1=NN=CN11)=NC=C1C1=COC=C1 KAPYGSUXANDQEE-UHFFFAOYSA-N 0.000 description 1
• QGFYFOHMBDMGBZ-UHFFFAOYSA-N 5-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol Chemical compound C1=C(O)C(CN(CC)CC)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 QGFYFOHMBDMGBZ-UHFFFAOYSA-N 0.000 description 1
• BQDRPPKMRJSPEU-UHFFFAOYSA-N 5-[8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazin-5-yl]-1,3-thiazole Chemical compound C1CN(C)CCN1C(C1=NN=CN11)=NC=C1C1=CN=CS1 BQDRPPKMRJSPEU-UHFFFAOYSA-N 0.000 description 1
• SIKXIUWKPGWBBF-UHFFFAOYSA-N 5-bromo-2,4-dichloropyrimidine Chemical compound ClC1=NC=C(Br)C(Cl)=N1 SIKXIUWKPGWBBF-UHFFFAOYSA-N 0.000 description 1
• HWJXNXSRBIYASQ-UHFFFAOYSA-N 5-bromo-2-(4-methylpiperazin-1-yl)-3-nitropyridin-4-amine Chemical compound C1CN(C)CCN1C1=NC=C(Br)C(N)=C1[N+]([O-])=O HWJXNXSRBIYASQ-UHFFFAOYSA-N 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• MBFFBGDJUTWNSJ-UHFFFAOYSA-N 5-piperazin-1-yl-8-thiophen-2-yltetrazolo[1,5-c]pyrimidine Chemical compound C1CNCCN1C(N1N=NN=C11)=NC=C1C1=CC=CS1 MBFFBGDJUTWNSJ-UHFFFAOYSA-N 0.000 description 1
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
• 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
• ZLJLYILYSDGQLY-UHFFFAOYSA-N 6-bromo-8-chloro-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound ClC1=NC(Br)=CN2C=NN=C12 ZLJLYILYSDGQLY-UHFFFAOYSA-N 0.000 description 1
• MBIVXTZRISLZLY-UHFFFAOYSA-N 6-methyl-8-(4-methylpiperazin-1-yl)-5-thiophen-2-yltetrazolo[1,5-a]pyrazine Chemical compound C1CN(C)CCN1C(C1=NN=NN11)=NC(C)=C1C1=CC=CS1 MBIVXTZRISLZLY-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• 125000001960 7 membered carbocyclic group Chemical group 0.000 description 1
• AZIXOGQCOAHTBZ-UHFFFAOYSA-N 7-chloro-4-(4-methylpiperazin-1-yl)-[1]benzofuro[3,2-d]pyrimidin-2-amine Chemical compound C1CN(C)CCN1C1=NC(N)=NC2=C1OC1=CC(Cl)=CC=C12 AZIXOGQCOAHTBZ-UHFFFAOYSA-N 0.000 description 1
• RRHZYQDMFPKPDT-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-5-(thiophen-2-ylmethyl)-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1CN(C)CCN1C(C1=NN=CN11)=NC=C1CC1=CC=CS1 RRHZYQDMFPKPDT-UHFFFAOYSA-N 0.000 description 1
• CMAJSSVAOLSINK-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-5-phenyl-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1CN(C)CCN1C(C1=NN=CN11)=NC=C1C1=CC=CC=C1 CMAJSSVAOLSINK-UHFFFAOYSA-N 0.000 description 1
• WJNARRKPUCPDSE-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-5-thiophen-2-ylimidazo[1,5-a]pyrazine Chemical compound C1CN(C)CCN1C(C1=CN=CN11)=NC=C1C1=CC=CS1 WJNARRKPUCPDSE-UHFFFAOYSA-N 0.000 description 1
• ARBUQDRMEQRJHP-UHFFFAOYSA-N 8-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-5-thiophen-2-ylimidazo[1,2-a]pyrazine-2-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(C1=NC(=CN11)C(O)=O)=NC=C1C1=CC=CS1 ARBUQDRMEQRJHP-UHFFFAOYSA-N 0.000 description 1
• DTPSSXONCXLEJS-UHFFFAOYSA-N 8-methoxy-5-thiophen-2-yl-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound N12C=NN=C2C(OC)=NC=C1C1=CC=CS1 DTPSSXONCXLEJS-UHFFFAOYSA-N 0.000 description 1
• CXZAOGVDWOEJPK-UHFFFAOYSA-N 8-piperazin-1-yl-5-(thiophen-2-ylmethyl)-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C=1N=C(N2CCNCC2)C2=NN=CN2C=1CC1=CC=CS1 CXZAOGVDWOEJPK-UHFFFAOYSA-N 0.000 description 1
• CBRFKTRLMQJUSK-UHFFFAOYSA-N 8-piperazin-1-yl-5-[3-(trifluoromethyl)phenyl]-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound FC(F)(F)C1=CC=CC(C=2N3C=NN=C3C(N3CCNCC3)=NC=2)=C1 CBRFKTRLMQJUSK-UHFFFAOYSA-N 0.000 description 1
• RUHPIILQGQXAJJ-UHFFFAOYSA-N 8-piperazin-1-yl-5-thiophen-2-ylimidazo[1,2-a]pyrazine Chemical compound C1CNCCN1C(C1=NC=CN11)=NC=C1C1=CC=CS1 RUHPIILQGQXAJJ-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 241000208140 Acer Species 0.000 description 1
• 206010001029 Acute pulmonary oedema Diseases 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 208000000884 Airway Obstruction Diseases 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
• 208000035939 Alveolitis allergic Diseases 0.000 description 1
• 206010053555 Arthritis bacterial Diseases 0.000 description 1
• 206010003557 Asthma exercise induced Diseases 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 201000008283 Atrophic Rhinitis Diseases 0.000 description 1
• 102000007527 Autoreceptors Human genes 0.000 description 1
• 108010071131 Autoreceptors Proteins 0.000 description 1
• 238000011725 BALB/c mouse Methods 0.000 description 1
• 208000027496 Behcet disease Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
• 229940123208 Biguanide Drugs 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• YJPIPNOLHGPDEY-UHFFFAOYSA-N BrC1C(=O)NC(C1)=O.NN Chemical compound BrC1C(=O)NC(C1)=O.NN YJPIPNOLHGPDEY-UHFFFAOYSA-N 0.000 description 1
• SEFXAEFHHAAWSI-UHFFFAOYSA-N BrC=1N=C(C(=NC1)C=1NC2=CC=CC=C2C1)Cl Chemical compound BrC=1N=C(C(=NC1)C=1NC2=CC=CC=C2C1)Cl SEFXAEFHHAAWSI-UHFFFAOYSA-N 0.000 description 1
• 206010006482 Bronchospasm Diseases 0.000 description 1
• 206010006811 Bursitis Diseases 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• RDUFOKNFOWTTAU-UHFFFAOYSA-N CC(C)C[S] Chemical compound CC(C)C[S] RDUFOKNFOWTTAU-UHFFFAOYSA-N 0.000 description 1
• WAUHABGEEBVFTF-UHFFFAOYSA-N CCCC[S] Chemical compound CCCC[S] WAUHABGEEBVFTF-UHFFFAOYSA-N 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 241000723346 Cinnamomum camphora Species 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 241000272201 Columbiformes Species 0.000 description 1
• 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
• 206010012434 Dermatitis allergic Diseases 0.000 description 1
• 206010012442 Dermatitis contact Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014561 Emphysema Diseases 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 206010014950 Eosinophilia Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 208000004657 Exercise-Induced Asthma Diseases 0.000 description 1
• 208000027445 Farmer Lung Diseases 0.000 description 1
• 208000003241 Fat Embolism Diseases 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• XYZZKVRWGOWVGO-UHFFFAOYSA-N Glycerol-phosphate Chemical compound OP(O)(O)=O.OCC(O)CO XYZZKVRWGOWVGO-UHFFFAOYSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 206010018634 Gouty Arthritis Diseases 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 102000003710 Histamine H2 Receptors Human genes 0.000 description 1
• 108090000050 Histamine H2 Receptors Proteins 0.000 description 1
• 102000004384 Histamine H3 receptors Human genes 0.000 description 1
• 108090000981 Histamine H3 receptors Proteins 0.000 description 1
• 101000887490 Homo sapiens Guanine nucleotide-binding protein G(z) subunit alpha Proteins 0.000 description 1
• 101100455054 Homo sapiens LTA4H gene Proteins 0.000 description 1
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
• 208000004454 Hyperalgesia Diseases 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 206010020852 Hypertonia Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 208000004575 Infectious Arthritis Diseases 0.000 description 1
• 206010065390 Inflammatory pain Diseases 0.000 description 1
• 208000006877 Insect Bites and Stings Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• 150000000994 L-ascorbates Chemical class 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 239000004166 Lanolin Substances 0.000 description 1
• 102100022118 Leukotriene A-4 hydrolase Human genes 0.000 description 1
• 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 201000005505 Measles Diseases 0.000 description 1
• 241000361919 Metaphire sieboldi Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• WKSXRWSOSLGSTN-UHFFFAOYSA-N Methoxypyrazine Chemical compound COC1=CN=CC=N1 WKSXRWSOSLGSTN-UHFFFAOYSA-N 0.000 description 1
• 208000034388 Mountain sickness acute Diseases 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• FHQDWPCFSJMNCT-UHFFFAOYSA-N N(tele)-methylhistamine Chemical compound CN1C=NC(CCN)=C1 FHQDWPCFSJMNCT-UHFFFAOYSA-N 0.000 description 1
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 229930192627 Naphthoquinone Natural products 0.000 description 1
• 208000028389 Nerve injury Diseases 0.000 description 1
• 201000009053 Neurodermatitis Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 206010061323 Optic neuropathy Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 108010058846 Ovalbumin Proteins 0.000 description 1
• 229910019213 POCl3 Inorganic materials 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 244000055346 Paulownia Species 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 208000008469 Peptic Ulcer Diseases 0.000 description 1
• 241000577218 Phenes Species 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 206010034960 Photophobia Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 206010037437 Pulmonary thrombosis Diseases 0.000 description 1
• ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038910 Retinitis Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 206010039088 Rhinitis atrophic Diseases 0.000 description 1
• 241000208422 Rhododendron Species 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 101100075025 Scheffersomyces stipitis (strain ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL Y-11545) LTA4 gene Proteins 0.000 description 1
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
• 206010039897 Sedation Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 206010040742 Sinus congestion Diseases 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 208000006045 Spondylarthropathies Diseases 0.000 description 1
• MKRNVBXERAPZOP-UHFFFAOYSA-N Starch acetate Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OC(C)=O)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 MKRNVBXERAPZOP-UHFFFAOYSA-N 0.000 description 1
• 208000005279 Status Asthmaticus Diseases 0.000 description 1
• PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
• 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 206010042496 Sunburn Diseases 0.000 description 1
• 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
• AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 101150049278 US20 gene Proteins 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 206010049590 Upper respiratory tract inflammation Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 206010047139 Vasoconstriction Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
• 229920002494 Zein Polymers 0.000 description 1
• 244000126002 Ziziphus vulgaris Species 0.000 description 1
• PHVIJPGOLHMERM-UHFFFAOYSA-N [2-amino-2-(methylamino)hydrazinyl]methane Chemical compound CNN(N)NC PHVIJPGOLHMERM-UHFFFAOYSA-N 0.000 description 1
• WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 1
• NQCBQFBHEQDGNB-UHFFFAOYSA-I [Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]S([O-])(=O)=O Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]S([O-])(=O)=O NQCBQFBHEQDGNB-UHFFFAOYSA-I 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
• 229960005339 acitretin Drugs 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 230000009692 acute damage Effects 0.000 description 1
• 208000018315 acute mountain sickness Diseases 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 102000030621 adenylate cyclase Human genes 0.000 description 1
• 108060000200 adenylate cyclase Proteins 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 230000008484 agonism Effects 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000005055 alkyl alkoxy group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 125000001118 alkylidene group Chemical group 0.000 description 1
• IHUNBGSDBOWDMA-AQFIFDHZSA-N all-trans-acitretin Chemical compound COC1=CC(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1C IHUNBGSDBOWDMA-AQFIFDHZSA-N 0.000 description 1
• 229940008201 allegra Drugs 0.000 description 1
• 201000009961 allergic asthma Diseases 0.000 description 1
• 208000002029 allergic contact dermatitis Diseases 0.000 description 1
• 201000010435 allergic urticaria Diseases 0.000 description 1
• 230000003281 allosteric effect Effects 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001414 amino alcohols Chemical class 0.000 description 1
• CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 239000003945 anionic surfactant Substances 0.000 description 1
• PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
• 150000004056 anthraquinones Chemical class 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000003266 anti-allergic effect Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 238000011861 anti-inflammatory therapy Methods 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 206010003230 arteritis Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
• 230000002238 attenuated effect Effects 0.000 description 1
• 230000003416 augmentation Effects 0.000 description 1
• 208000029407 autoimmune urticaria Diseases 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 239000000022 bacteriostatic agent Substances 0.000 description 1
• 230000003385 bacteriostatic effect Effects 0.000 description 1
• 210000003651 basophil Anatomy 0.000 description 1
• 230000003796 beauty Effects 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 229960004217 benzyl alcohol Drugs 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• XKXHCNPAFAXVRZ-UHFFFAOYSA-N benzylazanium;chloride Chemical compound [Cl-].[NH3+]CC1=CC=CC=C1 XKXHCNPAFAXVRZ-UHFFFAOYSA-N 0.000 description 1
• MKCBRYIXFFGIKN-UHFFFAOYSA-N bicyclo[1.1.1]pentane Chemical group C1C2CC1C2 MKCBRYIXFFGIKN-UHFFFAOYSA-N 0.000 description 1
• LPCWKMYWISGVSK-UHFFFAOYSA-N bicyclo[3.2.1]octane Chemical compound C1C2CCC1CCC2 LPCWKMYWISGVSK-UHFFFAOYSA-N 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000000035 biogenic effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 150000001621 bismuth Chemical class 0.000 description 1
• 230000000740 bleeding effect Effects 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 229960003166 bromazine Drugs 0.000 description 1
• ZQDJSWUEGOYDGT-UHFFFAOYSA-N bromazine hydrochloride Chemical compound [Cl-].C=1C=C(Br)C=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 ZQDJSWUEGOYDGT-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 210000000621 bronchi Anatomy 0.000 description 1
• 230000007885 bronchoconstriction Effects 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 239000007975 buffered saline Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 230000003139 buffering effect Effects 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 229960000846 camphor Drugs 0.000 description 1
• 229930008380 camphor Natural products 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
• 229940049638 carbomer homopolymer type c Drugs 0.000 description 1
• 229940043234 carbomer-940 Drugs 0.000 description 1
• 229940031663 carbomer-974p Drugs 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 229960004424 carbon dioxide Drugs 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 239000003093 cationic surfactant Substances 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 229910000420 cerium oxide Inorganic materials 0.000 description 1
• SXMBKHYDZOCBMT-PPUGGXLSSA-N chembl2151197 Chemical compound C1[C@@H](C(=O)NCC)C[C@@]1(F)C(C=C1F)=CC=C1CN1CCCC1 SXMBKHYDZOCBMT-PPUGGXLSSA-N 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 230000035605 chemotaxis Effects 0.000 description 1
• 235000015111 chews Nutrition 0.000 description 1
• 229960002152 chlorhexidine acetate Drugs 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 208000030949 chronic idiopathic urticaria Diseases 0.000 description 1
• 206010072757 chronic spontaneous urticaria Diseases 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 229940119122 clarinex Drugs 0.000 description 1
• 229940088529 claritin Drugs 0.000 description 1
• UCAIEVHKDLMIFL-UHFFFAOYSA-N clobenpropit Chemical compound C1=CC(Cl)=CC=C1CNC(=N)SCCCC1=CNC=N1 UCAIEVHKDLMIFL-UHFFFAOYSA-N 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 206010009869 cold urticaria Diseases 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 150000001924 cycloalkanes Chemical class 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 230000002354 daily effect Effects 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229940119743 dextran 70 Drugs 0.000 description 1
• 229960002380 dibutyl phthalate Drugs 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
• 125000006003 dichloroethyl group Chemical group 0.000 description 1
• 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000032625 disorder of ear Diseases 0.000 description 1
• 229960003638 dopamine Drugs 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 229940112573 elestat Drugs 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 239000002532 enzyme inhibitor Substances 0.000 description 1
• 229940125532 enzyme inhibitor Drugs 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
• VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 1
• MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 210000002388 eustachian tube Anatomy 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 208000024695 exercise-induced bronchoconstriction Diseases 0.000 description 1
• 238000013401 experimental design Methods 0.000 description 1
• 210000000744 eyelid Anatomy 0.000 description 1
• 208000022195 farmer lung disease Diseases 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000004634 feeding behavior Effects 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 239000008098 formaldehyde solution Substances 0.000 description 1
• 230000000855 fungicidal effect Effects 0.000 description 1
• 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
• 230000027119 gastric acid secretion Effects 0.000 description 1
• 210000001914 gastric parietal cell Anatomy 0.000 description 1
• 229940114119 gentisate Drugs 0.000 description 1
• 239000003292 glue Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 125000000262 haloalkenyl group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 230000000423 heterosexual effect Effects 0.000 description 1
• 102000034345 heterotrimeric G proteins Human genes 0.000 description 1
• 108091006093 heterotrimeric G proteins Proteins 0.000 description 1
• SELIRUAKCBWGGE-UHFFFAOYSA-N hexadecanoic acid;octadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O SELIRUAKCBWGGE-UHFFFAOYSA-N 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000003453 histamine agonist Substances 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 102000052301 human GNAZ Human genes 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 150000005828 hydrofluoroalkanes Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 239000001341 hydroxy propyl starch Substances 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
• 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
• 230000035874 hyperreactivity Effects 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 229960003943 hypromellose Drugs 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• SHTYVPZQTIYWOJ-UHFFFAOYSA-N imidazo[1,2-a]pyrazin-2-amine Chemical compound C1=CN=CC2=NC(N)=CN21 SHTYVPZQTIYWOJ-UHFFFAOYSA-N 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000004968 inflammatory condition Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 239000011147 inorganic material Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 229940125425 inverse agonist Drugs 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 230000037427 ion transport Effects 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 239000002563 ionic surfactant Substances 0.000 description 1
• 208000001875 irritant dermatitis Diseases 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001261 isocyanato group Chemical group *N=C=O 0.000 description 1
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000004922 lacquer Substances 0.000 description 1
• 229960001021 lactose monohydrate Drugs 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 208000002741 leukoplakia Diseases 0.000 description 1
• UFPQIRYSPUYQHK-WAQVJNLQSA-N leukotriene A4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(O)=O UFPQIRYSPUYQHK-WAQVJNLQSA-N 0.000 description 1
• VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
• 238000000670 ligand binding assay Methods 0.000 description 1
• 229940059904 light mineral oil Drugs 0.000 description 1
• 229940040145 liniment Drugs 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229960001855 mannitol Drugs 0.000 description 1
• 208000008585 mastocytosis Diseases 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000015654 memory Effects 0.000 description 1
• JABGXPCRNXUENL-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1N=CNC2=NC=N[C]12 JABGXPCRNXUENL-UHFFFAOYSA-N 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 1
• JHAFPCUTESQLDZ-UHFFFAOYSA-N methyl 8-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxylate Chemical compound C12=NN=CN2C(C(=O)OC)=CN=C1N1CCN(C(=O)OC(C)(C)C)CC1 JHAFPCUTESQLDZ-UHFFFAOYSA-N 0.000 description 1
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 235000019426 modified starch Nutrition 0.000 description 1
• 239000007932 molded tablet Substances 0.000 description 1
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 210000004400 mucous membrane Anatomy 0.000 description 1
• 230000003843 mucus production Effects 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• OXKUGIFNIUUKAW-UHFFFAOYSA-N n,n-dimethylformamide;hydrazine Chemical compound NN.CN(C)C=O OXKUGIFNIUUKAW-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• FQZVHBZZHHLEPE-UHFFFAOYSA-N n-methyl-1-(5-thiophen-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)azetidin-3-amine Chemical compound C1C(NC)CN1C(C1=NN=CN11)=NC=C1C1=CC=CS1 FQZVHBZZHHLEPE-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 150000002791 naphthoquinones Chemical class 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 239000000133 nasal decongestant Substances 0.000 description 1
• 201000009240 nasopharyngitis Diseases 0.000 description 1
• 229920001206 natural gum Polymers 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000008764 nerve damage Effects 0.000 description 1
• 208000013315 neuromuscular junction disease Diseases 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
• 230000006959 non-competitive inhibition Effects 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 229920001542 oligosaccharide Polymers 0.000 description 1
• 150000002482 oligosaccharides Chemical class 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 208000020911 optic nerve disease Diseases 0.000 description 1
• 229940061037 optivar Drugs 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 229940092253 ovalbumin Drugs 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 229940090118 patanase Drugs 0.000 description 1
• 229940097078 patanol Drugs 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 229960000292 pectin Drugs 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 239000003961 penetration enhancing agent Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 208000000689 peptic esophagitis Diseases 0.000 description 1
• 208000011906 peptic ulcer disease Diseases 0.000 description 1
• 125000001151 peptidyl group Chemical group 0.000 description 1
• 208000022719 perennial allergic rhinitis Diseases 0.000 description 1
• 230000009984 peri-natal effect Effects 0.000 description 1
• 208000028169 periodontal disease Diseases 0.000 description 1
• 210000000578 peripheral nerve Anatomy 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 238000009521 phase II clinical trial Methods 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000002165 photosensitisation Effects 0.000 description 1
• 239000003504 photosensitizing agent Substances 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229920001993 poloxamer 188 Polymers 0.000 description 1
• 229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
• 239000004584 polyacrylic acid Substances 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920000193 polymethacrylate Polymers 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229940068968 polysorbate 80 Drugs 0.000 description 1
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
• 230000002980 postoperative effect Effects 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229940069328 povidone Drugs 0.000 description 1
• 229920003124 powdered cellulose Polymers 0.000 description 1
• 235000019814 powdered cellulose Nutrition 0.000 description 1
• 238000012910 preclinical development Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
• MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
• 229940048914 protamine Drugs 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 238000010926 purge Methods 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
• IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 238000007830 receptor-based assay Methods 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 230000002207 retinal effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 201000003068 rheumatic fever Diseases 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 208000008742 seborrheic dermatitis Diseases 0.000 description 1
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 230000036280 sedation Effects 0.000 description 1
• 230000020341 sensory perception of pain Effects 0.000 description 1
• 201000001223 septic arthritis Diseases 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 230000037380 skin damage Effects 0.000 description 1
• 208000019116 sleep disease Diseases 0.000 description 1
• 239000000779 smoke Substances 0.000 description 1
• 230000016160 smooth muscle contraction Effects 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• 239000000344 soap Substances 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000017550 sodium carbonate Nutrition 0.000 description 1
• UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
• 229960002218 sodium chlorite Drugs 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
• 230000000392 somatic effect Effects 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 201000005671 spondyloarthropathy Diseases 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 229960004274 stearic acid Drugs 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
• 235000021286 stilbenes Nutrition 0.000 description 1
• 230000001300 stimulation of adenylate cyclase Effects 0.000 description 1
• 239000004575 stone Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• MBQHDWOTUOFUNO-UHFFFAOYSA-N tert-butyl 10-(1H-pyridazin-2-yl)decanoate Chemical compound N1(NC=CC=C1)CCCCCCCCCC(=O)OC(C)(C)C MBQHDWOTUOFUNO-UHFFFAOYSA-N 0.000 description 1
• FYUVLZRRIRGSTE-UHFFFAOYSA-N tert-butyl 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1NCC2CN(C(=O)OC(C)(C)C)CC21 FYUVLZRRIRGSTE-UHFFFAOYSA-N 0.000 description 1
• IJINSJSWDSHUBL-UHFFFAOYSA-N tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=CN=C1Cl IJINSJSWDSHUBL-UHFFFAOYSA-N 0.000 description 1
• PLKZQHIFFXTATF-UHFFFAOYSA-N tert-butyl 4-(8-bromotetrazolo[1,5-c]pyrimidin-5-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(Br)C2=NN=NN12 PLKZQHIFFXTATF-UHFFFAOYSA-N 0.000 description 1
• DGPPETAGKWNJPU-UHFFFAOYSA-N tert-butyl 4-(tetrazolo[1,5-a]pyrazin-8-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=CN2C1=NN=N2 DGPPETAGKWNJPU-UHFFFAOYSA-N 0.000 description 1
• PVVMIUNIKGUADF-UHFFFAOYSA-N tert-butyl 4-[5-(hydroxymethyl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(CO)N2C1=NN=C2 PVVMIUNIKGUADF-UHFFFAOYSA-N 0.000 description 1
• DRLJHMDELRERQB-UHFFFAOYSA-N tert-butyl 4-[5-[hydroxy(thiophen-2-yl)methyl]-[1,2,4]triazolo[4,3-a]pyrazin-8-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(C1=NN=CN11)=NC=C1C(O)C1=CC=CS1 DRLJHMDELRERQB-UHFFFAOYSA-N 0.000 description 1
• IZUZIVIUDTZPFE-UHFFFAOYSA-N tert-butyl decanoate Chemical compound CCCCCCCCCC(=O)OC(C)(C)C IZUZIVIUDTZPFE-UHFFFAOYSA-N 0.000 description 1
• YKSGTKAVVPSEIW-UHFFFAOYSA-N tert-butyl phthalazine-1-carboxylate Chemical compound C1(=NN=CC2=CC=CC=C12)C(=O)OC(C)(C)C YKSGTKAVVPSEIW-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
• 125000000858 thiocyanato group Chemical group *SC#N 0.000 description 1
• 125000000101 thioether group Chemical group 0.000 description 1
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 239000003860 topical agent Substances 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 229940066528 trichloroacetate Drugs 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 230000025033 vasoconstriction Effects 0.000 description 1
• 208000001319 vasomotor rhinitis Diseases 0.000 description 1
• PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 230000003313 weakening effect Effects 0.000 description 1
• 210000004885 white matter Anatomy 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1
• 239000000811 xylitol Substances 0.000 description 1
• HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
• 229960002675 xylitol Drugs 0.000 description 1
• 235000010447 xylitol Nutrition 0.000 description 1
• 229940093612 zein Drugs 0.000 description 1
• 239000005019 zein Substances 0.000 description 1
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
• 229940057977 zinc stearate Drugs 0.000 description 1
• 229940036139 zyrtec Drugs 0.000 description 1