JP2011515396A5 - - Google Patents
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- JP2011515396A5 JP2011515396A5 JP2011500799A JP2011500799A JP2011515396A5 JP 2011515396 A5 JP2011515396 A5 JP 2011515396A5 JP 2011500799 A JP2011500799 A JP 2011500799A JP 2011500799 A JP2011500799 A JP 2011500799A JP 2011515396 A5 JP2011515396 A5 JP 2011515396A5
- Authority
- JP
- Japan
- Prior art keywords
- fluorophenyl
- methyl
- carboxy
- phenyl
- methoxy
- 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.)
- Granted
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- -1 1-carboxyethylamino, 1-carboxy-4-guanidinobutylamino, 3-amino- 1-carboxy-3-oxopropylamino, 1,2-dicarboxyethylamino, 1-carboxy-2-mercaptoethylamino, 4-amino-1-carboxy-4-oxobutylamino Chemical group 0.000 claims description 1374
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 594
- 150000001875 compounds Chemical class 0.000 claims description 536
- 150000003839 salts Chemical class 0.000 claims description 276
- 239000012453 solvate Substances 0.000 claims description 276
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 236
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 232
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 232
- 238000011282 treatment Methods 0.000 claims description 225
- 125000003118 aryl group Chemical group 0.000 claims description 223
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 167
- 125000001072 heteroaryl group Chemical group 0.000 claims description 128
- 229910052799 carbon Inorganic materials 0.000 claims description 107
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 106
- 229910052739 hydrogen Inorganic materials 0.000 claims description 105
- 239000003814 drug Substances 0.000 claims description 104
- 239000008194 pharmaceutical composition Substances 0.000 claims description 96
- 125000001424 substituent group Chemical group 0.000 claims description 96
- 238000004519 manufacturing process Methods 0.000 claims description 91
- 150000004677 hydrates Chemical class 0.000 claims description 90
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 88
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 86
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 81
- 229910052736 halogen Inorganic materials 0.000 claims description 77
- 150000002367 halogens Chemical class 0.000 claims description 77
- 239000000126 substance Substances 0.000 claims description 76
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 71
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 62
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 61
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 56
- 102000009079 Epoprostenol Receptors Human genes 0.000 claims description 49
- 108010073099 Epoprostenol Receptors Proteins 0.000 claims description 49
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 45
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 44
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 44
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 44
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 44
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 44
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 44
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 44
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 44
- 208000035475 disorder Diseases 0.000 claims description 42
- 208000006673 asthma Diseases 0.000 claims description 34
- 208000014777 Pulmonary venoocclusive disease Diseases 0.000 claims description 31
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 31
- 208000031467 Pulmonary capillary hemangiomatosis Diseases 0.000 claims description 30
- 201000001320 Atherosclerosis Diseases 0.000 claims description 29
- 206010063837 Reperfusion injury Diseases 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 29
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 29
- 208000035478 Interatrial communication Diseases 0.000 claims description 28
- 208000001910 Ventricular Heart Septal Defects Diseases 0.000 claims description 28
- 208000013914 atrial heart septal defect Diseases 0.000 claims description 28
- 206010003664 atrial septal defect Diseases 0.000 claims description 28
- 208000037803 restenosis Diseases 0.000 claims description 28
- 201000003130 ventricular septal defect Diseases 0.000 claims description 28
- DVMILACIDBEACH-UHFFFAOYSA-N 6-fluoropyridine Chemical compound FC1=C=CC=C[N]1 DVMILACIDBEACH-UHFFFAOYSA-N 0.000 claims description 26
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 25
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 22
- 208000029147 Collagen-vascular disease Diseases 0.000 claims description 22
- 206010020772 Hypertension Diseases 0.000 claims description 22
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 22
- 230000035602 clotting Effects 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 20
- 208000024891 symptom Diseases 0.000 claims description 20
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 19
- 206010040047 Sepsis Diseases 0.000 claims description 19
- 208000021076 Pulmonary arterial hypertension associated with congenital heart disease Diseases 0.000 claims description 18
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 17
- 238000002411 thermogravimetry Methods 0.000 claims description 17
- 201000004681 Psoriasis Diseases 0.000 claims description 16
- 206010012601 diabetes mellitus Diseases 0.000 claims description 16
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 15
- 206010002383 Angina Pectoris Diseases 0.000 claims description 15
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 15
- 208000011231 Crohn disease Diseases 0.000 claims description 15
- 208000031886 HIV Infections Diseases 0.000 claims description 15
- 208000037357 HIV infectious disease Diseases 0.000 claims description 15
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 0.000 claims description 15
- 208000020875 Idiopathic pulmonary arterial hypertension Diseases 0.000 claims description 15
- 206010061218 Inflammation Diseases 0.000 claims description 15
- 208000019693 Lung disease Diseases 0.000 claims description 15
- 208000006011 Stroke Diseases 0.000 claims description 15
- 206010052779 Transplant rejections Diseases 0.000 claims description 15
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 15
- 230000002159 abnormal effect Effects 0.000 claims description 15
- 206010000496 acne Diseases 0.000 claims description 15
- 230000007214 atherothrombosis Effects 0.000 claims description 15
- 230000001684 chronic effect Effects 0.000 claims description 15
- 208000029078 coronary artery disease Diseases 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 15
- 230000004054 inflammatory process Effects 0.000 claims description 15
- 230000004410 intraocular pressure Effects 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 208000010125 myocardial infarction Diseases 0.000 claims description 15
- 230000000414 obstructive effect Effects 0.000 claims description 15
- 238000010911 splenectomy Methods 0.000 claims description 15
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 15
- 239000003053 toxin Substances 0.000 claims description 15
- 231100000765 toxin Toxicity 0.000 claims description 15
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 15
- 201000002829 CREST Syndrome Diseases 0.000 claims description 14
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 14
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 14
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 14
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 14
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 14
- 206010039710 Scleroderma Diseases 0.000 claims description 14
- 208000001106 Takayasu Arteritis Diseases 0.000 claims description 14
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 14
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 14
- 201000006417 multiple sclerosis Diseases 0.000 claims description 14
- 208000003278 patent ductus arteriosus Diseases 0.000 claims description 14
- 208000005987 polymyositis Diseases 0.000 claims description 14
- 210000003492 pulmonary vein Anatomy 0.000 claims description 14
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 13
- 208000021068 Pulmonary arterial hypertension associated with portal hypertension Diseases 0.000 claims description 13
- 208000030533 eye disease Diseases 0.000 claims description 13
- 201000001981 dermatomyositis Diseases 0.000 claims description 12
- 230000001404 mediated effect Effects 0.000 claims description 12
- 230000001052 transient effect Effects 0.000 claims description 11
- 230000002490 cerebral effect Effects 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 230000000302 ischemic effect Effects 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 206010012667 Diabetic glaucoma Diseases 0.000 claims description 7
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000003944 tolyl group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000004892 2-methylpropylamino group Chemical group CC(CN*)C 0.000 claims description 4
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 claims description 4
- 238000001179 sorption measurement Methods 0.000 claims description 4
- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 4
- NPDKXVKJRHPDQT-UHFFFAOYSA-N 2-[[4-[[(4-chlorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid Chemical compound C1CC(COCC(=O)O)CCC1COC(=O)N(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 NPDKXVKJRHPDQT-UHFFFAOYSA-N 0.000 claims description 3
- XCIVGPGSJPAWCB-UHFFFAOYSA-N 2-[[4-[[(4-fluorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid Chemical compound C1CC(COCC(=O)O)CCC1COC(=O)N(C=1C=CC(F)=CC=1)C1=CC=CC=C1 XCIVGPGSJPAWCB-UHFFFAOYSA-N 0.000 claims description 3
- CMXRZQLTIHQYPZ-UHFFFAOYSA-N 2-[[4-[[[(3-chlorophenyl)-phenylcarbamoyl]amino]methyl]cyclohexyl]methoxy]acetic acid Chemical compound C1CC(COCC(=O)O)CCC1CNC(=O)N(C=1C=C(Cl)C=CC=1)C1=CC=CC=C1 CMXRZQLTIHQYPZ-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- 208000013223 septicemia Diseases 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- BXMBDSIYGOKPJM-UHFFFAOYSA-L C(C)(C)O.C(C)(=O)[O-].[Ca+2].C(C)(=O)[O-] Chemical compound C(C)(C)O.C(C)(=O)[O-].[Ca+2].C(C)(=O)[O-] BXMBDSIYGOKPJM-UHFFFAOYSA-L 0.000 claims description 2
- XGULNLBDYZNHDJ-UHFFFAOYSA-L C(C)(C)O.C(C)(=O)[O-].[Mg+2].C(C)(=O)[O-] Chemical compound C(C)(C)O.C(C)(=O)[O-].[Mg+2].C(C)(=O)[O-] XGULNLBDYZNHDJ-UHFFFAOYSA-L 0.000 claims description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 2
- 239000001639 calcium acetate Substances 0.000 claims description 2
- 235000011092 calcium acetate Nutrition 0.000 claims description 2
- 229960005147 calcium acetate Drugs 0.000 claims description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 2
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 2
- 239000011654 magnesium acetate Substances 0.000 claims description 2
- 235000011285 magnesium acetate Nutrition 0.000 claims description 2
- 229940069446 magnesium acetate Drugs 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 208000020193 Pulmonary artery hypoplasia Diseases 0.000 claims 22
- JPQUDQIQRLMROB-UHFFFAOYSA-N [K].CC(C)O Chemical compound [K].CC(C)O JPQUDQIQRLMROB-UHFFFAOYSA-N 0.000 claims 1
- 230000036571 hydration Effects 0.000 claims 1
- 238000006703 hydration reaction Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 175
- 239000013078 crystal Substances 0.000 description 23
- 229940126208 compound 22 Drugs 0.000 description 17
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 16
- 125000001188 haloalkyl group Chemical group 0.000 description 16
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- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 12
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- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 9
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 7
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- PRRDEJJYDQAWMQ-UHFFFAOYSA-N 2-[[4-(aminomethyl)cyclohexyl]methoxy]acetic acid Chemical compound NCC1CCC(COCC(O)=O)CC1 PRRDEJJYDQAWMQ-UHFFFAOYSA-N 0.000 description 2
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 2
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Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6985708P | 2008-03-18 | 2008-03-18 | |
| US61/069,857 | 2008-03-18 | ||
| US12362108P | 2008-04-09 | 2008-04-09 | |
| US61/123,621 | 2008-04-09 | ||
| US20722009P | 2009-02-09 | 2009-02-09 | |
| US61/207,220 | 2009-02-09 | ||
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Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101903324B (zh) | 2007-12-17 | 2013-07-03 | 联合治疗公司 | 一种制备Remodulin中的活性成分曲前列素的改良方法 |
| WO2009117095A1 (en) * | 2008-03-18 | 2009-09-24 | Arena Pharmaceuticals, Inc. | Modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto |
| US20110224262A1 (en) | 2008-11-26 | 2011-09-15 | Arena Pharmaceuticals, Inc. | Pyrazolyl substituted carbonic acid derivatives as modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto |
| ES2548882T3 (es) | 2008-12-08 | 2015-10-21 | Arena Pharmaceuticals, Inc. | Moduladores del receptor de prostaciclina (PGl2) útiles para el tratamiento de trastornos relacionados con los mismos |
| WO2011037613A1 (en) * | 2009-09-23 | 2011-03-31 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of pgi2 receptor agonists |
| JP6046034B2 (ja) | 2010-06-03 | 2016-12-14 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニルの製造 |
| US20130345471A1 (en) | 2011-03-02 | 2013-12-26 | United Therapeutics Corporation | Synthesis of intermediate for treprostinil production |
| RU2016149812A (ru) | 2014-06-06 | 2018-07-17 | Флексус Байосайенсиз, Инк. | Иммунорегулирующие средства |
| US9593061B2 (en) | 2014-10-20 | 2017-03-14 | United Therapeutics Corporation | Synthesis of intermediates for producing prostacyclin derivatives |
| US10537546B2 (en) | 2014-10-23 | 2020-01-21 | Arena Pharmaceuticals, Inc. | Method of treating conditions related to the PGI2 receptor |
| UY36391A (es) | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido1), sus métodos de síntesis y composiciones farmacèuticas que las contienen |
| UY36390A (es) | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen |
| BR112017008809A2 (pt) | 2014-11-05 | 2017-12-19 | Flexus Biosciences Inc | agentes imunorreguladores |
| RU2632449C1 (ru) * | 2016-04-26 | 2017-10-04 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Уральский государственный медицинский университет Министерства здравоохранения Российской Федерации" (ГБОУ ВПО УГМУ Минздрава России) | Способ оптимизации лечения мужчин кардиотропной терапией и заместительной гормональной терапией при андрогенодефиците с артериальной гипертензией |
| US12377067B2 (en) * | 2016-11-10 | 2025-08-05 | Arena Pharmaceuticals, Inc. | Methods of treating PAH with combinations of ralinepag and other agents |
| MX2019006938A (es) | 2016-12-14 | 2019-09-06 | Respira Therapeutics Inc | Metodos y composiciones para trataminto de hipertension pulmonar y otros trastornos del pulmon. |
| IL268997B2 (en) | 2017-03-01 | 2023-09-01 | Arena Pharm Inc | Preparations containing pgi2 receptor agonists and processes for their preparation |
| BR112020001748A2 (pt) * | 2017-07-27 | 2020-07-21 | Allergan, Inc. | agonistas de receptor de prostaciclina para redução de gordura corporal |
| CA3072079A1 (en) | 2017-08-07 | 2019-02-14 | Arena Pharmaceuticals, Inc. | Methods of treatment |
| JP2021512902A (ja) * | 2018-02-07 | 2021-05-20 | メッドシャイン ディスカバリー インコーポレイテッド | プロスタサイクリン受容体アゴニスト |
| EP3796902A1 (en) | 2018-05-16 | 2021-03-31 | Arena Pharmaceuticals, Inc. | Compositions comprising pgi2-receptor agonists and processes for the preparation thereof |
| WO2020048299A1 (zh) * | 2018-09-06 | 2020-03-12 | 广东东阳光药业有限公司 | 药物共晶体及其制备方法 |
| CN110903219A (zh) * | 2018-09-18 | 2020-03-24 | 广东东阳光药业有限公司 | 酰胺衍生物的盐及其制备方法 |
| CN114213256B (zh) * | 2021-12-27 | 2025-03-25 | 维思普新材料（苏州）有限公司 | 一种二(4-联苯基)胺的制备方法 |
| WO2023158634A1 (en) * | 2022-02-15 | 2023-08-24 | United Therapeutics Corporation | Crystalline prostacyclin (ip) receptor agonist and uses thereof |
| AU2023236147A1 (en) * | 2022-03-17 | 2024-09-19 | United Therapeutics Corporation | Ralinepag prodrugs and uses thereof |
| US20250282716A1 (en) | 2024-03-11 | 2025-09-11 | United Therapeutics Corporation | Methods of making ip-receptor agonists |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2945530A1 (de) * | 1979-11-10 | 1981-06-04 | Chemische Werke Hüls AG, 4370 Marl | Harnstoffe mit cyclischen substituenten, ihre herstellung und verwendung als herbizide |
| JPS5686417A (en) * | 1979-12-17 | 1981-07-14 | Nissan Motor | Contact discriminating circuit |
| JPH03160438A (ja) | 1989-11-20 | 1991-07-10 | Konica Corp | ハロゲン化銀カラー写真感光材料 |
| EP0442448A3 (en) | 1990-02-13 | 1992-08-12 | Bristol-Myers Squibb Company | Heterocyclic carboxylic acids and esters |
| CA2085844A1 (en) * | 1991-12-27 | 1993-06-28 | Nobuyuki Hamanaka | Fused benzeneoxyacetic acid derivatives |
| JPH06329598A (ja) | 1993-05-19 | 1994-11-29 | Daicel Chem Ind Ltd | エステルの製造方法 |
| DE4318889A1 (de) | 1993-06-07 | 1994-12-08 | Bayer Ag | Verfahren zur Herstellung von organischen Carbamaten |
| JP3160438B2 (ja) | 1993-09-29 | 2001-04-25 | 株式会社東芝 | 交通流予測装置 |
| TW282456B (https=) | 1994-03-10 | 1996-08-01 | Fujisawa Yakusin Kogyo Kk | |
| JPH11269138A (ja) | 1998-03-20 | 1999-10-05 | Mitsubishi Paper Mills Ltd | 有機塩基発生剤 |
| US6335459B1 (en) | 1998-12-23 | 2002-01-01 | Syntex (U.S.A.) Llc | Aryl carboxylic acid and aryl tetrazole derivatives as IP receptor modulators |
| EP1046631A1 (en) | 1999-04-19 | 2000-10-25 | Rolic AG | Liquid crystalline compounds |
| GB9908934D0 (en) * | 1999-04-19 | 1999-06-16 | Rolic Ag | Liquid crystalline compounds |
| US20040048844A1 (en) * | 1999-10-20 | 2004-03-11 | Bristol-Myers Squibb Pharma Company | Acylsemicarbazides as cyclin dependent kinase inhibitors useful as anti-cancer and anti-proliferative agents |
| KR100523119B1 (ko) * | 2000-03-16 | 2005-10-20 | 에프. 호프만-라 로슈 아게 | Ｉｐ 길항제로서의 카복실산 유도체 |
| WO2002055484A1 (en) | 2001-01-12 | 2002-07-18 | Takeda Chemical Industries, Ltd. | Biaryl compound, process for producing the same, and agent |
| EP1357908A4 (en) * | 2001-01-30 | 2009-07-15 | Merck & Co Inc | "ACYLSULFAMIDES FOR THE TREATMENT OF FATIBILITY, DIABETES AND LIPID DISORDERS" |
| TWI316055B (https=) * | 2001-04-26 | 2009-10-21 | Nippon Shinyaku Co Ltd | |
| WO2003007888A2 (en) * | 2001-07-20 | 2003-01-30 | Adipogenix, Inc. | Fat accumulation-modulating compounds |
| CN101284773A (zh) * | 2001-08-09 | 2008-10-15 | 小野药品工业株式会社 | 羧酸衍生物及以它为活性成分的药剂 |
| TW200307539A (en) * | 2002-02-01 | 2003-12-16 | Bristol Myers Squibb Co | Cycloalkyl inhibitors of potassium channel function |
| TWI293715B (en) * | 2002-10-10 | 2008-02-21 | Sipix Imaging Inc | A method for inducing or enhancing the threshold of an electrophoretic display, an electrophoretic fluid and an electrophoretic display |
| CN1735598A (zh) * | 2002-11-11 | 2006-02-15 | 拜耳医药保健股份公司 | 作为ip受体拮抗剂的苯基或杂芳基氨基烷烃衍生物 |
| RU2351590C2 (ru) * | 2003-02-10 | 2009-04-10 | Вертекс Фармасьютикалз Инкорпорейтед | Способ получения диариламина |
| GB0317498D0 (en) * | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Compounds |
| JP4339890B2 (ja) * | 2003-09-22 | 2009-10-07 | エフ．ホフマン−ラ ロシュ アーゲー | アミノアルキルアミド置換シクロヘキシル誘導体 |
| JP4402413B2 (ja) | 2003-09-29 | 2010-01-20 | 財団法人２１あおもり産業総合支援センター | Ｕ字型化合物およびこれを含む液晶組成物 |
| DE102004006785A1 (de) | 2004-02-11 | 2005-09-08 | Mayr, Herbert, Prof. Dr. | Verfahren zur CC-Bindungsknüpfung zwischen elektrophilen Substraten und TT-Verbindungen in neutralen bis basischen wässrigen oder alkoholischen Lösungsmitteln ohne den Einsatz einer Lewis- oder Protonensäure |
| JP2008510726A (ja) * | 2004-08-20 | 2008-04-10 | エントレメッド インコーポレイテッド | プロテイナーゼ活性化受容体アンタゴニストを含む組成物および方法 |
| JP2006083085A (ja) | 2004-09-15 | 2006-03-30 | Kyowa Hakko Kogyo Co Ltd | 二環性ピリミジン誘導体の製造法およびその合成中間体 |
| JP4792731B2 (ja) | 2004-11-12 | 2011-10-12 | Ｄｉｃ株式会社 | 重合性液晶組成物及び当該組成物の硬化物 |
| WO2007051255A1 (en) | 2005-11-04 | 2007-05-10 | The University Of Sydney | Process for the preparation of compounds containing an azacyclic ring system |
| JP2007161867A (ja) | 2005-12-14 | 2007-06-28 | Toyo Ink Mfg Co Ltd | インキ組成物 |
| WO2007106721A2 (en) * | 2006-03-10 | 2007-09-20 | Jenrin Discovery | Cannabinoid receptor antagonists/inverse agonists useful for treating obesity |
| US20080075692A1 (en) | 2006-05-09 | 2008-03-27 | Perrine Susan P | Methods for treating blood disorders |
| WO2009117095A1 (en) * | 2008-03-18 | 2009-09-24 | Arena Pharmaceuticals, Inc. | Modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto |
| US20110224262A1 (en) * | 2008-11-26 | 2011-09-15 | Arena Pharmaceuticals, Inc. | Pyrazolyl substituted carbonic acid derivatives as modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto |
| ES2548882T3 (es) | 2008-12-08 | 2015-10-21 | Arena Pharmaceuticals, Inc. | Moduladores del receptor de prostaciclina (PGl2) útiles para el tratamiento de trastornos relacionados con los mismos |
| WO2011037613A1 (en) | 2009-09-23 | 2011-03-31 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of pgi2 receptor agonists |
| JP3160438U (ja) | 2010-04-14 | 2010-06-24 | 孝枝 袴田 | 弦楽器演奏練習補助具 |
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