CA2494367A1 - Methodes pour ameliorer la fonction respiratoire au moyen d'inhibiteurs du tgf-.beta. - Google Patents
Methodes pour ameliorer la fonction respiratoire au moyen d'inhibiteurs du tgf-.beta. Download PDFInfo
- Publication number
- CA2494367A1 CA2494367A1 CA002494367A CA2494367A CA2494367A1 CA 2494367 A1 CA2494367 A1 CA 2494367A1 CA 002494367 A CA002494367 A CA 002494367A CA 2494367 A CA2494367 A CA 2494367A CA 2494367 A1 CA2494367 A1 CA 2494367A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- lung
- phenyl
- compound
- tgf
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 61
- 230000004199 lung function Effects 0.000 title claims abstract description 47
- 230000006872 improvement Effects 0.000 title claims abstract description 26
- 239000003112 inhibitor Substances 0.000 title abstract description 21
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract description 21
- 150000003384 small molecules Chemical class 0.000 claims abstract description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 98
- 150000001875 compounds Chemical class 0.000 claims description 97
- 125000001424 substituent group Chemical group 0.000 claims description 84
- -1 cyano, phenyl Chemical group 0.000 claims description 71
- 210000004072 lung Anatomy 0.000 claims description 66
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
- 125000005843 halogen group Chemical group 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 201000010099 disease Diseases 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 208000004852 Lung Injury Diseases 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 231100000515 lung injury Toxicity 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 230000001404 mediated effect Effects 0.000 claims description 18
- 230000004071 biological effect Effects 0.000 claims description 17
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 15
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 108091000080 Phosphotransferase Proteins 0.000 claims description 12
- 102000020233 phosphotransferase Human genes 0.000 claims description 12
- 206010014561 Emphysema Diseases 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000000443 aerosol Substances 0.000 claims description 10
- 239000003053 toxin Substances 0.000 claims description 10
- 231100000765 toxin Toxicity 0.000 claims description 10
- 108700012359 toxins Proteins 0.000 claims description 10
- 230000001771 impaired effect Effects 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 206010006451 bronchitis Diseases 0.000 claims description 7
- 230000002452 interceptive effect Effects 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 7
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 6
- 208000019693 Lung disease Diseases 0.000 claims description 6
- 208000027418 Wounds and injury Diseases 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 208000007451 chronic bronchitis Diseases 0.000 claims description 6
- 230000006378 damage Effects 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 6
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 5
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 claims description 5
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 230000007812 deficiency Effects 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 230000002458 infectious effect Effects 0.000 claims description 5
- 229940002612 prodrug Drugs 0.000 claims description 5
- 239000000651 prodrug Chemical group 0.000 claims description 5
- 208000005333 pulmonary edema Diseases 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 5
- 230000000241 respiratory effect Effects 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 206010069351 acute lung injury Diseases 0.000 claims description 3
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 150000002460 imidazoles Chemical class 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 3
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 230000027455 binding Effects 0.000 abstract description 9
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 73
- 241000700159 Rattus Species 0.000 description 59
- 108010006654 Bleomycin Proteins 0.000 description 53
- 229960001561 bleomycin Drugs 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 53
- 229940126062 Compound A Drugs 0.000 description 39
- 229920000609 methyl cellulose Polymers 0.000 description 39
- 239000001923 methylcellulose Substances 0.000 description 39
- 235000010981 methylcellulose Nutrition 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 108020003175 receptors Proteins 0.000 description 32
- 102000005962 receptors Human genes 0.000 description 32
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 30
- 241001465754 Metazoa Species 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 239000011780 sodium chloride Substances 0.000 description 23
- 108010009583 Transforming Growth Factors Proteins 0.000 description 22
- 102000009618 Transforming Growth Factors Human genes 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 244000146510 Pereskia bleo Species 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 206010069363 Traumatic lung injury Diseases 0.000 description 15
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 14
- 238000010992 reflux Methods 0.000 description 12
- 238000010171 animal model Methods 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 125000002252 acyl group Chemical group 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 9
- 102000004889 Interleukin-6 Human genes 0.000 description 9
- 108090001005 Interleukin-6 Proteins 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 9
- 229960002591 hydroxyproline Drugs 0.000 description 9
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 230000035699 permeability Effects 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 7
- 125000002877 alkyl aryl group Chemical group 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 235000019504 cigarettes Nutrition 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 230000036387 respiratory rate Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 229920002307 Dextran Polymers 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 125000001041 indolyl group Chemical group 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 229960003299 ketamine Drugs 0.000 description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000000779 smoke Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 6
- 229960001600 xylazine Drugs 0.000 description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 5
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 5
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 5
- 125000003435 aroyl group Chemical group 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229960004979 fampridine Drugs 0.000 description 5
- 125000001183 hydrocarbyl group Chemical group 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000009325 pulmonary function Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- 206010002091 Anaesthesia Diseases 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 230000037005 anaesthesia Effects 0.000 description 4
- 230000003444 anaesthetic effect Effects 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000004761 fibrosis Effects 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000001543 one-way ANOVA Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 238000013222 sprague-dawley male rat Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 4
- 229960005294 triamcinolone Drugs 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000002238 attenuated effect Effects 0.000 description 3
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000004404 heteroalkyl group Chemical group 0.000 description 3
- 230000003116 impacting effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229940126586 small molecule drug Drugs 0.000 description 3
- 230000000391 smoking effect Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 2
- HJVAVGOPTDJYOJ-UHFFFAOYSA-N 2-amino-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(N)=C(C(O)=O)C=C1OC HJVAVGOPTDJYOJ-UHFFFAOYSA-N 0.000 description 2
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 2
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 2
- 101001010513 Homo sapiens Leukocyte elastase inhibitor Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102100020870 La-related protein 6 Human genes 0.000 description 2
- 108050008265 La-related protein 6 Proteins 0.000 description 2
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 2
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 2
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 2
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 239000000168 bronchodilator agent Substances 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 108700016226 indium-bleomycin Proteins 0.000 description 2
- 230000003434 inspiratory effect Effects 0.000 description 2
- 230000004068 intracellular signaling Effects 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 125000005544 phthalimido group Chemical group 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- GSNAAJMDJKCIAM-UHFFFAOYSA-N 2-(2-fluorophenyl)-5-nitro-n-pyridin-4-ylquinazolin-4-amine Chemical compound C=12C([N+](=O)[O-])=CC=CC2=NC(C=2C(=CC=CC=2)F)=NC=1NC1=CC=NC=C1 GSNAAJMDJKCIAM-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- RAAGZOYMEQDCTD-UHFFFAOYSA-N 2-fluorobenzoyl chloride Chemical compound FC1=CC=CC=C1C(Cl)=O RAAGZOYMEQDCTD-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- VDULOAUXSMYUMG-UHFFFAOYSA-N 2-phenyl-1h-quinazolin-4-one Chemical compound N=1C2=CC=CC=C2C(O)=NC=1C1=CC=CC=C1 VDULOAUXSMYUMG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- MGWGWNFMUOTEHG-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-1,3-thiazol-2-amine Chemical compound CC1=CC(C)=CC(C=2N=C(N)SC=2)=C1 MGWGWNFMUOTEHG-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- RUCHWTKMOWXHLU-UHFFFAOYSA-N 5-nitroanthranilic acid Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C(O)=O RUCHWTKMOWXHLU-UHFFFAOYSA-N 0.000 description 1
- 238000013296 A/J mouse Methods 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 102000005606 Activins Human genes 0.000 description 1
- 208000000884 Airway Obstruction Diseases 0.000 description 1
- 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 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108010005853 Anti-Mullerian Hormone Proteins 0.000 description 1
- 238000011719 B6C3F1 mouse Methods 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 238000011767 DBA/2J (JAX™ mouse strain) Methods 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 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 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 description 1
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- YUENFNPLGJCNRB-UHFFFAOYSA-N anthracen-1-amine Chemical compound C1=CC=C2C=C3C(N)=CC=CC3=CC2=C1 YUENFNPLGJCNRB-UHFFFAOYSA-N 0.000 description 1
- 239000000868 anti-mullerian hormone Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000005251 aryl acyl group Chemical group 0.000 description 1
- 150000003975 aryl alkyl amines Chemical class 0.000 description 1
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000003857 carboxamides Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000002849 elastaseinhibitory effect Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000035992 intercellular communication Effects 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 230000010262 intracellular communication Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000007040 lung development Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- HTYIXCKSEQQCJO-UHFFFAOYSA-N phenaglycodol Chemical compound CC(C)(O)C(C)(O)C1=CC=C(Cl)C=C1 HTYIXCKSEQQCJO-UHFFFAOYSA-N 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000002206 pro-fibrotic effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004291 sulphur dioxide Substances 0.000 description 1
- 235000010269 sulphur dioxide Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- 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
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- 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
- A61P11/06—Antiasthmatics
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
L'invention concerne des méthodes pour améliorer la fonction respiratoire par administration de petites molécules non peptidiques agissant en tant qu'inhibiteurs du TGF-.beta., se liant de manière spécifique au récepteur TGF-.beta. de type 1 (TGF.beta.-R1). De préférence, lesdits inhibiteurs sont des dérivés de quinazoline.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39936902P | 2002-07-25 | 2002-07-25 | |
| US60/399,369 | 2002-07-25 | ||
| PCT/US2003/023240 WO2004010929A2 (fr) | 2002-07-25 | 2003-07-23 | Methodes pour ameliorer la fonction respiratoire au moyen d'inhibiteurs du tgf-$g(b) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2494367A1 true CA2494367A1 (fr) | 2004-02-05 |
Family
ID=31188573
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002494367A Abandoned CA2494367A1 (fr) | 2002-07-25 | 2003-07-23 | Methodes pour ameliorer la fonction respiratoire au moyen d'inhibiteurs du tgf-.beta. |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1575506A4 (fr) |
| AU (1) | AU2003256783A1 (fr) |
| CA (1) | CA2494367A1 (fr) |
| WO (1) | WO2004010929A2 (fr) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004048930A2 (fr) * | 2002-11-22 | 2004-06-10 | Scios, Inc. | METHODE PERMETTANT DE CONTRER UN CHANGEMENT PATHOLOGIQUE DANS LA VOIE ss-ADRENERGIQUE |
| DE602004014347D1 (de) | 2003-03-12 | 2008-07-24 | Millennium Pharm Inc | Chinazolin-derivate als tgf-beta-inhibitoren |
| ES2279441T3 (es) | 2003-09-19 | 2007-08-16 | Astrazeneca Ab | Derivados de quinazolina. |
| AU2006261607A1 (en) | 2005-06-24 | 2006-12-28 | Gilead Sciences, Inc. | Pyrido(3,2-d)pyrimidines and pharmaceutical compositions useful for treating hepatitis C. |
| EP2862867A3 (fr) * | 2005-10-25 | 2015-08-05 | The Johns Hopkins University | Procédés et compositions pour le traitement du syndrome de Marfan et troubles associés |
| US8338435B2 (en) | 2006-07-20 | 2012-12-25 | Gilead Sciences, Inc. | Substituted pyrido(3,2-D) pyrimidines and pharmaceutical compositions for treating viral infections |
| MX2009003518A (es) | 2006-10-03 | 2009-08-25 | Genzyme Corp | Uso de antagonistas de tgf-beta para tratar a los infantes en riesgo de desarrollar displasia brocopulmonar. |
| WO2008071605A2 (fr) * | 2006-12-15 | 2008-06-19 | F. Hoffmann-La Roche Ag | Méthodes de traitement de maladies inflammatoires |
| TW200840584A (en) | 2006-12-26 | 2008-10-16 | Gilead Sciences Inc | Pyrido(3,2-d)pyrimidines useful for treating viral infections |
| WO2010002998A1 (fr) | 2008-07-03 | 2010-01-07 | Gilead Sciences, Inc. | Pyrido(3,2-d)pyrimidines trisubstituées en position 2,4,6 utiles pour traiter des infections virales |
| JP2012513464A (ja) | 2008-12-23 | 2012-06-14 | ザ トラスティーズ オブ コロンビア ユニヴァーシティ イン ザ シティ オブ ニューヨーク | ホスホジエステラーゼ阻害剤及びその使用 |
| AU2011273931B2 (en) | 2010-06-28 | 2015-04-23 | Merck Patent Gmbh | 2,4- diaryl - substituted [1,8] naphthyridines as kinase inhibitors for use against cancer |
| US8609672B2 (en) | 2010-08-27 | 2013-12-17 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
| ES2542647T3 (es) | 2011-03-09 | 2015-08-07 | Merck Patent Gmbh | Derivados de pirido[2,3 b]pirazina y sus usos terapéuticos |
| US20140308275A1 (en) | 2011-07-27 | 2014-10-16 | Inserm (Institut National De La Sante Et De La Recherche Medicale | Methods for diagnosing and treating myhre syndrome |
| AU2011379972B2 (en) | 2011-10-26 | 2016-05-12 | Seattle Children's Research Institute | Cysteamine in the treatment of fibrotic disease |
| TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| BR112020006677A2 (pt) | 2017-10-05 | 2020-10-06 | Fulcrum Therapeutics, Inc. | uso de inibidores p38 para reduzir a expressão de dux4 |
| CN109053597B (zh) * | 2018-06-14 | 2021-03-19 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | 一种炎症抑制化合物及其制备方法 |
| CN108727283B (zh) * | 2018-06-14 | 2021-03-02 | 温州医科大学附属第一医院 | 一种苯磺酰氨类抗炎化合物的合成方法 |
| CN108727282B (zh) * | 2018-06-14 | 2021-03-02 | 温州医科大学附属第一医院 | 一种含苯磺酰氨基的抗炎化合物及其合成方法 |
| CN108912060B (zh) * | 2018-06-14 | 2021-03-19 | 温州医科大学 | 一种喹唑啉类抗炎化合物及其合成方法 |
| CN108912059B (zh) * | 2018-06-14 | 2021-03-02 | 温州医科大学附属第一医院 | 一种含氮杂环炎症抑制化合物的合成方法 |
| CN108912061B (zh) * | 2018-06-14 | 2021-03-19 | 温州医科大学 | 一种喹唑啉类炎症抑制化合物的合成方法 |
| EP3947737A2 (fr) | 2019-04-02 | 2022-02-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Méthodes de prédiction et de prévention du cancer chez des patients ayant des lésions prémalignes |
| CN112568188B (zh) * | 2021-02-24 | 2021-05-25 | 澎立生物医药技术(上海)有限公司 | 一种制作Brown Norway大鼠肺纤维化模型的方法 |
| TW202309022A (zh) | 2021-04-13 | 2023-03-01 | 美商努法倫特公司 | 用於治療具egfr突變之癌症之胺基取代雜環 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4366189A (en) * | 1979-12-21 | 1982-12-28 | Ciba-Geigy Corporation | 4-Heterocyclyl-4'-vinylstilbenes |
| JP2657760B2 (ja) * | 1992-07-15 | 1997-09-24 | 小野薬品工業株式会社 | 4−アミノキナゾリン誘導体およびそれを含有する医薬品 |
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| US6492497B1 (en) * | 1999-04-30 | 2002-12-10 | Cambridge Antibody Technology Limited | Specific binding members for TGFbeta1 |
| CO5271680A1 (es) * | 2000-02-21 | 2003-04-30 | Smithkline Beecham Corp | Compuestos |
| WO2002022605A1 (fr) * | 2000-09-15 | 2002-03-21 | Vertex Pharmaceuticals Incorporated | Composes de pyrazole utiles comme inhibiteurs de proteine kinase |
| AU2002225730A1 (en) * | 2000-11-16 | 2002-05-27 | Smith Kline Beecham Corporation | Compounds |
| EP1351691A4 (fr) * | 2000-12-12 | 2005-06-22 | Cytovia Inc | 2-aryl-4-arylaminopyrimidines substituees et analogues en tant qu'activateurs de caspases et qu'inducteurs d'apoptose, et utilisation associee |
| GB0102672D0 (en) * | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| AU2003229305A1 (en) * | 2002-05-17 | 2003-12-02 | Scios, Inc. | TREATMENT OF FIBROPROLIFERATIVE DISORDERS USING TGF-Beta INHIBITORS |
| WO2004048930A2 (fr) * | 2002-11-22 | 2004-06-10 | Scios, Inc. | METHODE PERMETTANT DE CONTRER UN CHANGEMENT PATHOLOGIQUE DANS LA VOIE ss-ADRENERGIQUE |
-
2003
- 2003-07-23 EP EP03771821A patent/EP1575506A4/fr not_active Withdrawn
- 2003-07-23 WO PCT/US2003/023240 patent/WO2004010929A2/fr not_active Ceased
- 2003-07-23 CA CA002494367A patent/CA2494367A1/fr not_active Abandoned
- 2003-07-23 AU AU2003256783A patent/AU2003256783A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004010929A2 (fr) | 2004-02-05 |
| EP1575506A4 (fr) | 2008-04-23 |
| AU2003256783A1 (en) | 2004-02-16 |
| WO2004010929A3 (fr) | 2005-12-01 |
| EP1575506A2 (fr) | 2005-09-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2494367A1 (fr) | Methodes pour ameliorer la fonction respiratoire au moyen d'inhibiteurs du tgf-.beta. | |
| EP1107959B1 (fr) | Derives de quinazoline utilisables comme medicaments | |
| US20190134033A1 (en) | Pharmaceutical combinations | |
| CA2501932C (fr) | Utilisation des quinolinones de benzimidazole pour le traitement du cancer | |
| RU2660354C2 (ru) | Комбинированные продукты, содержащие ингибиторы тирозинкиназ, и их применение | |
| JP2001316267A (ja) | ドーパミンアゴニスト療法に付随するジスキネジーを処置するためにampaレセプターアンタゴニストを投与する方法 | |
| KR20160061911A (ko) | 최적하 투여된 화학 화합물의 치료 효과 | |
| US11117865B2 (en) | Inhibitors of bromodomain-containing protein 4 (BRD4) | |
| US20040192583A1 (en) | Treatment of obesity and associated conditions with TGF-beta inhibitors | |
| CN115485027A (zh) | 冠状病毒感染引起的化学感觉功能障碍的治疗 | |
| US20040146509A1 (en) | Methods for improvement of lung function using TGF-beta inhibitors | |
| US20040127575A1 (en) | Method for counteracting a pathologic change in the beta-adrenergic pathway | |
| CN112237579B (zh) | 药物组合及其用途 | |
| TW202126305A (zh) | 使用egfr及cdk4/6抑制劑之組合以治療egfr突變體相關癌症 | |
| WO2025137710A1 (fr) | Méthodes de traitement du cancer à l'aide de combinaisons de modulateurs de gcn2 et de belzutifan | |
| CA3024976C (fr) | Traitement de la maladie de parkinson | |
| HK40082665A (en) | Treatment for parkinson s disease | |
| HK1035897B (en) | Quinazoline derivatives as medicaments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |