NZ571793A - 2,6-substituted-4-monosubstituted amino-pyrimidine as prostaglandin D2 receptor antagonists - Google Patents
2,6-substituted-4-monosubstituted amino-pyrimidine as prostaglandin D2 receptor antagonistsInfo
- Publication number
- NZ571793A NZ571793A NZ571793A NZ57179307A NZ571793A NZ 571793 A NZ571793 A NZ 571793A NZ 571793 A NZ571793 A NZ 571793A NZ 57179307 A NZ57179307 A NZ 57179307A NZ 571793 A NZ571793 A NZ 571793A
- Authority
- NZ
- New Zealand
- Prior art keywords
- phenyl
- methoxy
- pyrimidin
- ethylamino
- dichloro
- Prior art date
Links
- 229940044551 receptor antagonist Drugs 0.000 title description 7
- 239000002464 receptor antagonist Substances 0.000 title description 7
- 102000009389 Prostaglandin D receptors Human genes 0.000 title description 4
- 108050000258 Prostaglandin D receptors Proteins 0.000 title description 4
- 150000005005 aminopyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 150000003839 salts Chemical class 0.000 claims abstract description 63
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 239000012453 solvate Substances 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 208000003251 Pruritus Diseases 0.000 claims abstract description 12
- 208000026935 allergic disease Diseases 0.000 claims abstract description 11
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 11
- 208000035475 disorder Diseases 0.000 claims abstract description 11
- XCJGLBWDZKLQCY-UHFFFAOYSA-N 2-methylpropane-2-sulfonic acid Chemical compound CC(C)(C)S(O)(=O)=O XCJGLBWDZKLQCY-UHFFFAOYSA-N 0.000 claims abstract description 7
- 201000004624 Dermatitis Diseases 0.000 claims abstract description 7
- 206010061218 Inflammation Diseases 0.000 claims abstract description 7
- 208000024780 Urticaria Diseases 0.000 claims abstract description 7
- 210000003630 histaminocyte Anatomy 0.000 claims abstract description 7
- 230000004054 inflammatory process Effects 0.000 claims abstract description 7
- 230000001684 chronic effect Effects 0.000 claims abstract description 6
- YZBNKRGGHAGNIQ-UHFFFAOYSA-N 1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]piperidine-3-carboxamide Chemical compound C=1C(N2CC(CCC2)C(N)=O)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl YZBNKRGGHAGNIQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 5
- 206010002198 Anaphylactic reaction Diseases 0.000 claims abstract description 4
- 206010008190 Cerebrovascular accident Diseases 0.000 claims abstract description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 4
- 206010063837 Reperfusion injury Diseases 0.000 claims abstract description 4
- 208000006011 Stroke Diseases 0.000 claims abstract description 4
- 201000008736 Systemic mastocytosis Diseases 0.000 claims abstract description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 4
- 230000036783 anaphylactic response Effects 0.000 claims abstract description 4
- 208000003455 anaphylaxis Diseases 0.000 claims abstract description 4
- 206010006451 bronchitis Diseases 0.000 claims abstract description 4
- 230000020411 cell activation Effects 0.000 claims abstract description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 4
- 230000000302 ischemic effect Effects 0.000 claims abstract description 4
- 208000008423 pleurisy Diseases 0.000 claims abstract description 4
- 230000035939 shock Effects 0.000 claims abstract description 4
- 230000009885 systemic effect Effects 0.000 claims abstract description 4
- LSGOBZJXRYUSIW-UHFFFAOYSA-N 1-[2-methoxy-6-[2-[4-(trifluoromethoxy)phenyl]ethylamino]pyrimidin-4-yl]-n-methylsulfonylpiperidine-3-carboxamide Chemical compound C=1C(N2CC(CCC2)C(=O)NS(C)(=O)=O)=NC(OC)=NC=1NCCC1=CC=C(OC(F)(F)F)C=C1 LSGOBZJXRYUSIW-UHFFFAOYSA-N 0.000 claims abstract description 3
- ONJOLWLTTNQBFD-UHFFFAOYSA-N 2-[1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]piperidin-3-yl]acetic acid Chemical compound C=1C(N2CC(CC(O)=O)CCC2)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl ONJOLWLTTNQBFD-UHFFFAOYSA-N 0.000 claims abstract description 3
- 206010006482 Bronchospasm Diseases 0.000 claims abstract description 3
- 230000007885 bronchoconstriction Effects 0.000 claims abstract description 3
- MGHZKNFIOQBZTR-UHFFFAOYSA-N 5-[2-methoxy-6-[2-[4-(trifluoromethoxy)phenyl]ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C=1C(C=2SC(=CC=2)C(O)=O)=NC(OC)=NC=1NCCC1=CC=C(OC(F)(F)F)C=C1 MGHZKNFIOQBZTR-UHFFFAOYSA-N 0.000 claims abstract 3
- KTRNNQBBPZPDFO-UHFFFAOYSA-N 2-[3-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]phenyl]-2-methyl-1-thiomorpholin-4-ylpropan-1-one Chemical compound C=1C(C=2C=C(C=CC=2)C(C)(C)C(=O)N2CCSCC2)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl KTRNNQBBPZPDFO-UHFFFAOYSA-N 0.000 claims abstract 2
- AVJUTAMMINWDOQ-UHFFFAOYSA-N 2-[3-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]phenyl]-2-methylpropanamide Chemical compound C=1C(C=2C=C(C=CC=2)C(C)(C)C(N)=O)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl AVJUTAMMINWDOQ-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000004519 manufacturing process Methods 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims description 87
- -1 3-carboxy-pyrrolidinyl Chemical group 0.000 claims description 56
- 208000006673 asthma Diseases 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 12
- 201000010105 allergic rhinitis Diseases 0.000 claims description 12
- 201000008937 atopic dermatitis Diseases 0.000 claims description 12
- 210000004027 cell Anatomy 0.000 claims description 12
- 125000004494 ethyl ester group Chemical group 0.000 claims description 12
- BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 claims description 12
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 11
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 claims description 11
- 101000988802 Homo sapiens Hematopoietic prostaglandin D synthase Proteins 0.000 claims description 11
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 11
- 239000005557 antagonist Substances 0.000 claims description 11
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 7
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 6
- ULRPISSMEBPJLN-UHFFFAOYSA-N 2h-tetrazol-5-amine Chemical compound NC1=NN=NN1 ULRPISSMEBPJLN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 4
- 208000002177 Cataract Diseases 0.000 claims description 4
- 206010038848 Retinal detachment Diseases 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 229940047889 isobutyramide Drugs 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 230000004264 retinal detachment Effects 0.000 claims description 4
- XEOVLKHUDVRVLK-UHFFFAOYSA-N 1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]-n-methylsulfonylpiperidine-3-carboxamide Chemical compound C=1C(N2CC(CCC2)C(=O)NS(C)(=O)=O)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl XEOVLKHUDVRVLK-UHFFFAOYSA-N 0.000 claims description 3
- 208000004262 Food Hypersensitivity Diseases 0.000 claims description 3
- 206010016946 Food allergy Diseases 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 3
- 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 claims description 3
- 229960003592 fexofenadine Drugs 0.000 claims description 3
- 235000020932 food allergy Nutrition 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 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 3
- 229960003088 loratadine Drugs 0.000 claims description 3
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 2
- FUJSJWRORKKPAI-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)acetyl chloride Chemical compound ClC(=O)COC1=CC=C(Cl)C=C1Cl FUJSJWRORKKPAI-UHFFFAOYSA-N 0.000 claims description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical group CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 229960002052 salbutamol Drugs 0.000 claims description 2
- 229960000195 terbutaline Drugs 0.000 claims description 2
- 230000006399 behavior Effects 0.000 claims 3
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims 2
- LDXDSHIEDAPSSA-OAHLLOKOSA-N Ramatroban Chemical group N([C@@H]1CCC=2N(C3=CC=CC=C3C=2C1)CCC(=O)O)S(=O)(=O)C1=CC=C(F)C=C1 LDXDSHIEDAPSSA-OAHLLOKOSA-N 0.000 claims 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims 2
- 230000001387 anti-histamine Effects 0.000 claims 2
- 239000002876 beta blocker Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 150000002617 leukotrienes Chemical class 0.000 claims 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 2
- 229950004496 ramatroban Drugs 0.000 claims 2
- VMLHPGXVJSKWHY-UHFFFAOYSA-N 1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]-n-ethylsulfonylpiperidine-3-carboxamide Chemical compound C1C(C(=O)NS(=O)(=O)CC)CCCN1C1=CC(NCCC=2C(=CC(Cl)=CC=2)Cl)=NC(OC)=N1 VMLHPGXVJSKWHY-UHFFFAOYSA-N 0.000 claims 1
- IYJLGFKDKLUCRP-UHFFFAOYSA-N 1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methylpyrimidin-4-yl]pyrrolidine-3-carboxylic acid Chemical compound C=1C(N2CC(CC2)C(O)=O)=NC(C)=NC=1NCCC1=CC=C(Cl)C=C1Cl IYJLGFKDKLUCRP-UHFFFAOYSA-N 0.000 claims 1
- YDEULJMWFOJROS-UHFFFAOYSA-N 2-[1-[2-methoxy-6-[2-[4-(trifluoromethoxy)phenyl]ethylamino]pyrimidin-4-yl]piperidin-3-yl]-2-methylpropanoic acid Chemical compound C=1C(N2CC(CCC2)C(C)(C)C(O)=O)=NC(OC)=NC=1NCCC1=CC=C(OC(F)(F)F)C=C1 YDEULJMWFOJROS-UHFFFAOYSA-N 0.000 claims 1
- AGUDOSNOSGSAPX-UHFFFAOYSA-N 2-[3-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]phenyl]-n,n,2-trimethylpropanamide Chemical compound C=1C(C=2C=C(C=CC=2)C(C)(C)C(=O)N(C)C)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl AGUDOSNOSGSAPX-UHFFFAOYSA-N 0.000 claims 1
- DADRKLXYGIHKDF-UHFFFAOYSA-N 6-(4-aminopiperidin-1-yl)-n-[2-(2,4-dichlorophenyl)ethyl]-2-methoxypyrimidin-4-amine Chemical compound C=1C(N2CCC(N)CC2)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl DADRKLXYGIHKDF-UHFFFAOYSA-N 0.000 claims 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical group CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 claims 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 claims 1
- 229950001653 cilomilast Drugs 0.000 claims 1
- AZFDTSPRXQHCPI-UHFFFAOYSA-N ethyl 5-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]-1-methyl-2,3-dihydroindole-2-carboxylate Chemical compound C=1C=C2N(C)C(C(=O)OCC)CC2=CC=1C(N=C(OC)N=1)=CC=1NCCC1=CC=C(Cl)C=C1Cl AZFDTSPRXQHCPI-UHFFFAOYSA-N 0.000 claims 1
- 229960005127 montelukast Drugs 0.000 claims 1
- ZTKQZYQPZSJIDK-UHFFFAOYSA-N n-tert-butylsulfonyl-2-[3-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]phenyl]-2-methylpropanamide Chemical compound C=1C(C=2C=C(C=CC=2)C(C)(C)C(=O)NS(=O)(=O)C(C)(C)C)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl ZTKQZYQPZSJIDK-UHFFFAOYSA-N 0.000 claims 1
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical group FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 claims 1
- 229960002586 roflumilast Drugs 0.000 claims 1
- 229960004764 zafirlukast Drugs 0.000 claims 1
- TWCVFANBWVBQJJ-UHFFFAOYSA-N 1-[2-methoxy-6-[2-[4-(trifluoromethoxy)phenyl]ethylamino]pyrimidin-4-yl]piperidine-3-carboxylic acid Chemical compound C=1C(N2CC(CCC2)C(O)=O)=NC(OC)=NC=1NCCC1=CC=C(OC(F)(F)F)C=C1 TWCVFANBWVBQJJ-UHFFFAOYSA-N 0.000 abstract description 2
- MAAOYSWBZXNTOB-UHFFFAOYSA-N ethyl 2-[1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]piperidin-3-yl]acetate Chemical compound C1C(CC(=O)OCC)CCCN1C1=CC(NCCC=2C(=CC(Cl)=CC=2)Cl)=NC(OC)=N1 MAAOYSWBZXNTOB-UHFFFAOYSA-N 0.000 abstract description 2
- UKDFCFRWPVYUIR-UHFFFAOYSA-N 1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]-n,n-dimethylpiperidine-3-carboxamide Chemical compound C=1C(N2CC(CCC2)C(=O)N(C)C)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl UKDFCFRWPVYUIR-UHFFFAOYSA-N 0.000 abstract 1
- NEXSRFDRKBDAPJ-UHFFFAOYSA-N 2-[3-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]-5-(2-hydroxypropan-2-yl)phenyl]propan-2-ol Chemical compound C=1C(C=2C=C(C=C(C=2)C(C)(C)O)C(C)(C)O)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl NEXSRFDRKBDAPJ-UHFFFAOYSA-N 0.000 abstract 1
- RTJZFAGJGHSINY-UHFFFAOYSA-N 5-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]-2,3-dihydro-1-benzofuran-2-carboxylic acid Chemical compound C=1C(C=2C=C3CC(OC3=CC=2)C(O)=O)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl RTJZFAGJGHSINY-UHFFFAOYSA-N 0.000 abstract 1
- QDMSZPBZDLAHMH-UHFFFAOYSA-N C(C)S(=O)(=O)O.ClC1=C(C=CC(=C1)Cl)CCNC1=CC(=NC(=N1)OC)N1CC(CCC1)C(=O)NS(=O)(=O)C Chemical compound C(C)S(=O)(=O)O.ClC1=C(C=CC(=C1)Cl)CCNC1=CC(=NC(=N1)OC)N1CC(CCC1)C(=O)NS(=O)(=O)C QDMSZPBZDLAHMH-UHFFFAOYSA-N 0.000 abstract 1
- 208000019693 Lung disease Diseases 0.000 abstract 1
- RLKLTDOTIXEKFE-UHFFFAOYSA-N n-[1-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound C=1C(N2CCC(CC2)NC(C)=O)=NC(OC)=NC=1NCCC1=CC=C(Cl)C=C1Cl RLKLTDOTIXEKFE-UHFFFAOYSA-N 0.000 abstract 1
- KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
- 239000000203 mixture Substances 0.000 description 66
- 239000000243 solution Substances 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- 238000001819 mass spectrum Methods 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 27
- 238000000034 method Methods 0.000 description 27
- 239000007787 solid Substances 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 239000002585 base Substances 0.000 description 19
- 229940002612 prodrug Drugs 0.000 description 19
- 239000000651 prodrug Substances 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000004480 active ingredient Substances 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 239000007788 liquid Substances 0.000 description 15
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 14
- 150000002148 esters Chemical class 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 150000003180 prostaglandins Chemical class 0.000 description 9
- 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 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 230000006978 adaptation Effects 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 239000012139 lysis buffer Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 238000002821 scintillation proximity assay Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 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 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 206010012434 Dermatitis allergic Diseases 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
- 238000010521 absorption reaction Methods 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 230000005587 bubbling Effects 0.000 description 5
- 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 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 150000004677 hydrates Chemical class 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 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
- 206010020751 Hypersensitivity Diseases 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
- 229920002472 Starch Polymers 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003925 fat Substances 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000008101 lactose 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
- 239000002609 medium Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 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 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 241001024304 Mino Species 0.000 description 3
- 206010028735 Nasal congestion Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 201000009961 allergic asthma Diseases 0.000 description 3
- 230000009285 allergic inflammation Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 150000004760 silicates Chemical class 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 2
- 239000005631 2,4-Dichlorophenoxyacetic acid Substances 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000206672 Gelidium Species 0.000 description 2
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 101150003085 Pdcl gene Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 229940122913 Prostaglandin D2 receptor antagonist Drugs 0.000 description 2
- 206010041235 Snoring 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 239000013566 allergen Substances 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 230000001668 ameliorated effect Effects 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 238000010009 beating Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 210000000795 conjunctiva Anatomy 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000013024 dilution buffer Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 150000002690 malonic acid derivatives Chemical class 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003883 ointment base Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000000700 radioactive tracer Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 150000003873 salicylate salts Chemical class 0.000 description 2
- 238000006748 scratching Methods 0.000 description 2
- 230000002393 scratching effect Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004809 thin layer chromatography Methods 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
- 239000012588 trypsin Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical class O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IBDIPBWIXJRJQM-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-n-ethylpropan-2-amine;hydron;chloride Chemical compound Cl.CCNC(C)CC1=CC=C2OCOC2=C1 IBDIPBWIXJRJQM-UHFFFAOYSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical class OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- JVLFMTZUPSBCNJ-UHFFFAOYSA-N 3,5-difluoropyridin-2-amine Chemical compound NC1=NC=C(F)C=C1F JVLFMTZUPSBCNJ-UHFFFAOYSA-N 0.000 description 1
- MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical group [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus 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
- 241000725101 Clea Species 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 241001507939 Cormus domestica Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 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
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 1
- 101100456896 Drosophila melanogaster metl gene Proteins 0.000 description 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 102100038636 FYVE, RhoGEF and PH domain-containing protein 2 Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 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
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 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 1
- 241001245789 Goodea atripinnis Species 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 1
- 101001031749 Homo sapiens FYVE, RhoGEF and PH domain-containing protein 2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241001233242 Lontra Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241001314546 Microtis <orchid> Species 0.000 description 1
- 102000015728 Mucins Human genes 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101000890749 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) F420-dependent hydroxymycolic acid dehydrogenase Proteins 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 101000800755 Naja oxiana Alpha-elapitoxin-Nno2a Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102000015433 Prostaglandin Receptors Human genes 0.000 description 1
- 108010050183 Prostaglandin Receptors Proteins 0.000 description 1
- 229940122144 Prostaglandin receptor antagonist Drugs 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-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
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 241000862969 Stella Species 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 102100036704 Thromboxane A2 receptor Human genes 0.000 description 1
- 108090000300 Thromboxane Receptors Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 101100407705 Zinnia violacea POD2 gene Proteins 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- IMIDOCRTMDIQIJ-UHFFFAOYSA-N aminocarb Chemical compound CNC(=O)OC1=CC=C(N(C)C)C(C)=C1 IMIDOCRTMDIQIJ-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 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 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- QTPGEBNYYFYLFS-UHFFFAOYSA-N butane-1,3-diol;propane-1,2-diol Chemical group CC(O)CO.CC(O)CCO QTPGEBNYYFYLFS-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000013262 cAMP assay Methods 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 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
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- RNOJZAYWQCKGRK-UHFFFAOYSA-N diazene hydrochloride Chemical compound Cl.N=N RNOJZAYWQCKGRK-UHFFFAOYSA-N 0.000 description 1
- 229960003887 dichlorophen Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- PJFXDPZWCVXNQZ-UHFFFAOYSA-N ethyl 3-oxo-1,2-dihydropyrazole-4-carboxylate Chemical group CCOC(=O)C1=CNNC1=O PJFXDPZWCVXNQZ-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012909 foetal bovine serum Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 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 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000011554 guinea pig model Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 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
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000035515 penetration Effects 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
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000002089 prostaglandin antagonist Substances 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000001533 respiratory mucosa Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Otolaryngology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74467606P | 2006-04-12 | 2006-04-12 | |
| PCT/US2007/066481 WO2007121280A1 (en) | 2006-04-12 | 2007-04-12 | 2,6-substituted-4-monosubstituted amino-pyrimidine as prostaglandin d2 receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ571793A true NZ571793A (en) | 2011-08-26 |
Family
ID=38294040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ571793A NZ571793A (en) | 2006-04-12 | 2007-04-12 | 2,6-substituted-4-monosubstituted amino-pyrimidine as prostaglandin D2 receptor antagonists |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US20090036469A1 (enExample) |
| EP (1) | EP2010503A1 (enExample) |
| JP (1) | JP2009533473A (enExample) |
| KR (1) | KR20080108287A (enExample) |
| CN (1) | CN101421252B (enExample) |
| AR (1) | AR060403A1 (enExample) |
| AU (1) | AU2007238052B2 (enExample) |
| BR (1) | BRPI0710710A2 (enExample) |
| CA (1) | CA2649083C (enExample) |
| CR (1) | CR10249A (enExample) |
| DO (1) | DOP2007000068A (enExample) |
| EC (1) | ECSP088813A (enExample) |
| HN (1) | HN2008001530A (enExample) |
| MA (1) | MA30409B1 (enExample) |
| MX (1) | MX2008011369A (enExample) |
| NO (1) | NO20084291L (enExample) |
| NZ (1) | NZ571793A (enExample) |
| PE (1) | PE20080186A1 (enExample) |
| RU (1) | RU2431631C2 (enExample) |
| TN (1) | TNSN08339A1 (enExample) |
| TW (1) | TW200815395A (enExample) |
| UA (1) | UA95950C2 (enExample) |
| UY (1) | UY30283A1 (enExample) |
| WO (1) | WO2007121280A1 (enExample) |
| ZA (1) | ZA200807380B (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5039594B2 (ja) * | 2008-02-08 | 2012-10-03 | 株式会社日立ハイテクノロジーズ | レビュー装置，検査領域設定支援システム、および、欠陥の画像得方法 |
| AR074776A1 (es) * | 2008-12-18 | 2011-02-09 | Sanofi Aventis | Metodo para tratar la degeneracion macular; modulando el sistema inmunitario del paciente |
| TW201204708A (en) * | 2010-03-16 | 2012-02-01 | Aventis Pharma Inc | A substituted pyrimidine as a prostaglandin D2 receptor antagonist |
| EP2547672A1 (en) * | 2010-03-16 | 2013-01-23 | Aventis Pharmaceuticals Inc. | Substituted pyrimidines as prostaglandin d2 receptor antagonists |
| EP2590944B1 (en) | 2010-07-05 | 2015-09-30 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin d2 receptor modulators |
| US8785467B2 (en) * | 2010-09-30 | 2014-07-22 | Merck Sharp & Dohme Corp. | Alkoxy pyrimidine PDE10 inhibitors |
| US9255090B2 (en) | 2011-12-21 | 2016-02-09 | Actelion Pharmaceuticals Ltd. | Heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| US9169270B2 (en) | 2012-07-05 | 2015-10-27 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| EP2912458B1 (en) | 2012-10-24 | 2018-07-18 | NYU Winthrop Hospital | Non-invasive biomarker to identify subjects at risk of preterm delivery |
| RU2673084C2 (ru) * | 2013-11-08 | 2018-11-22 | Киссеи Фармасьютикал Ко., Лтд. | Производное карбоксиметилпиперидина |
| SG11201700777VA (en) | 2014-08-04 | 2017-02-27 | Nuevolution As | Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| WO2018210992A1 (en) | 2017-05-18 | 2018-11-22 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives |
| AU2018268311B2 (en) | 2017-05-18 | 2022-02-10 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives as PGE2 receptor modulators |
| US11325899B2 (en) | 2017-05-18 | 2022-05-10 | Idorsia Pharmaceuticals Ltd | Benzofurane and benzothiophene derivatives as PGE2 receptor modulators |
| WO2018210994A1 (en) | 2017-05-18 | 2018-11-22 | Idorsia Pharmaceuticals Ltd | Phenyl derivatives as pge2 receptor modulators |
| US20200264188A1 (en) | 2017-09-13 | 2020-08-20 | Progenity, Inc. | Preeclampsia biomarkers and related systems and methods |
| US20220408745A1 (en) * | 2019-09-13 | 2022-12-29 | Meiji Co., Ltd. | Solid food and solid milk having hole penetrating first face and second face |
| EP4070113A4 (en) | 2019-12-04 | 2023-12-20 | Biora Therapeutics, Inc. | ASSESSMENT OF PREECAMPSIA USING FREE AND DISSOCIATE PLACENTAL GROWTH FACTOR ASSAYS |
| EP4076661A1 (en) | 2019-12-20 | 2022-10-26 | Nuevolution A/S | Compounds active towards nuclear receptors |
| EP4076657A1 (en) | 2019-12-20 | 2022-10-26 | Nuevolution A/S | Compounds active towards nuclear receptors |
| EP4126875A1 (en) | 2020-03-31 | 2023-02-08 | Nuevolution A/S | Compounds active towards nuclear receptors |
| WO2021198955A1 (en) | 2020-03-31 | 2021-10-07 | Nuevolution A/S | Compounds active towards nuclear receptors |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3644799A1 (de) * | 1986-06-04 | 1987-12-10 | Hoechst Ag | Neue pyrimidin-derivate, deren herstellung und verwendung |
| US5047554A (en) * | 1989-04-18 | 1991-09-10 | Pfizer Inc. | 3-substituted-2-oxindole derivatives |
| SE0200411D0 (sv) * | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
| HN2005000795A (es) * | 2004-10-15 | 2010-08-19 | Aventis Pharma Inc | Pirimidinas como antagonistas del receptor de prostaglandina d2 |
| GT200600457A (es) * | 2005-10-13 | 2007-04-27 | Aventis Pharma Inc | Sal de fosfato dihidrogeno como antagonistas del receptor de prostaglandina d2 |
-
2007
- 2007-04-10 AR ARP070101501A patent/AR060403A1/es not_active Application Discontinuation
- 2007-04-10 DO DO2007000068A patent/DOP2007000068A/es unknown
- 2007-04-12 EP EP07760526A patent/EP2010503A1/en not_active Withdrawn
- 2007-04-12 MX MX2008011369A patent/MX2008011369A/es active IP Right Grant
- 2007-04-12 WO PCT/US2007/066481 patent/WO2007121280A1/en not_active Ceased
- 2007-04-12 NZ NZ571793A patent/NZ571793A/en not_active IP Right Cessation
- 2007-04-12 BR BRPI0710710-2A patent/BRPI0710710A2/pt not_active IP Right Cessation
- 2007-04-12 AU AU2007238052A patent/AU2007238052B2/en not_active Expired - Fee Related
- 2007-04-12 KR KR1020087024764A patent/KR20080108287A/ko not_active Withdrawn
- 2007-04-12 TW TW096112790A patent/TW200815395A/zh unknown
- 2007-04-12 PE PE2007000450A patent/PE20080186A1/es not_active Application Discontinuation
- 2007-04-12 CN CN2007800127354A patent/CN101421252B/zh not_active Expired - Fee Related
- 2007-04-12 UY UY30283A patent/UY30283A1/es not_active Application Discontinuation
- 2007-04-12 CA CA2649083A patent/CA2649083C/en not_active Expired - Fee Related
- 2007-04-12 JP JP2009505615A patent/JP2009533473A/ja not_active Abandoned
- 2007-04-12 UA UAA200813109A patent/UA95950C2/ru unknown
- 2007-04-12 RU RU2008144578/04A patent/RU2431631C2/ru not_active IP Right Cessation
-
2008
- 2008-08-26 CR CR10249A patent/CR10249A/es not_active Application Discontinuation
- 2008-08-27 TN TNP2008000339A patent/TNSN08339A1/en unknown
- 2008-08-27 ZA ZA200807380A patent/ZA200807380B/xx unknown
- 2008-10-07 US US12/246,918 patent/US20090036469A1/en not_active Abandoned
- 2008-10-09 EC EC2008008813A patent/ECSP088813A/es unknown
- 2008-10-10 HN HN2008001530A patent/HN2008001530A/es unknown
- 2008-10-14 NO NO20084291A patent/NO20084291L/no not_active Application Discontinuation
- 2008-11-10 MA MA31375A patent/MA30409B1/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PE20080186A1 (es) | 2008-04-15 |
| MA30409B1 (fr) | 2009-05-04 |
| AU2007238052A1 (en) | 2007-10-25 |
| CA2649083A1 (en) | 2007-10-25 |
| UY30283A1 (es) | 2007-11-30 |
| US20090036469A1 (en) | 2009-02-05 |
| AU2007238052B2 (en) | 2011-12-22 |
| JP2009533473A (ja) | 2009-09-17 |
| HK1131975A1 (en) | 2010-02-12 |
| RU2008144578A (ru) | 2010-05-20 |
| HN2008001530A (es) | 2012-01-17 |
| DOP2007000068A (es) | 2007-10-31 |
| ZA200807380B (en) | 2009-05-27 |
| BRPI0710710A2 (pt) | 2011-08-16 |
| AR060403A1 (es) | 2008-06-11 |
| KR20080108287A (ko) | 2008-12-12 |
| WO2007121280A1 (en) | 2007-10-25 |
| ECSP088813A (es) | 2008-11-27 |
| NO20084291L (no) | 2008-11-11 |
| CR10249A (es) | 2008-11-26 |
| MX2008011369A (es) | 2008-09-18 |
| TW200815395A (en) | 2008-04-01 |
| TNSN08339A1 (en) | 2009-12-29 |
| RU2431631C2 (ru) | 2011-10-20 |
| CN101421252B (zh) | 2011-10-12 |
| EP2010503A1 (en) | 2009-01-07 |
| CA2649083C (en) | 2011-06-28 |
| CN101421252A (zh) | 2009-04-29 |
| UA95950C2 (en) | 2011-09-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NZ571793A (en) | 2,6-substituted-4-monosubstituted amino-pyrimidine as prostaglandin D2 receptor antagonists | |
| EP2066628B1 (en) | 2-phenyl-indoles as prostaglandin d2 receptor antagonists | |
| US20070265278A1 (en) | 2-phenyl-indoles as prostaglandin d2 receptor antagonists | |
| WO2008039882A1 (en) | A combination of niacin and a prostaglandin d2 receptor antagonist | |
| SG183533A1 (en) | Substituted pyrimidines as prostaglandin d2 receptor antagonists | |
| US20130005741A1 (en) | Substituted pyrimidine as a prostaglandin d2 receptor antagonist | |
| ES2352725T3 (es) | 2-fenil-indoles como antagonistas del receptor de la prostaglandina d2. | |
| HK1131975B (en) | 2,6-substituted-4-monosubstituted amino-pyrimidine as prostaglandin d2 receptor antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| LAPS | Patent lapsed |