TW200811104A - Crystalline forms of a dimethylphenyl compound - Google Patents

Info

Publication number

TW200811104A

TW200811104A TW096114174A TW96114174A TW200811104A TW 200811104 A TW200811104 A TW 200811104A TW 096114174 A TW096114174 A TW 096114174A TW 96114174 A TW96114174 A TW 96114174A TW 200811104 A TW200811104 A TW 200811104A

Authority

TW

Taiwan

Prior art keywords

crystalline free

acid

ethyl

methyl

free

Prior art date

2006-04-25

Links

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• -1 dimethylphenyl compound Chemical class 0.000 title description 87
• 238000000034 method Methods 0.000 claims abstract description 55
• 239000012458 free base Substances 0.000 claims abstract description 11
• 239000000203 mixture Substances 0.000 claims description 140
• 150000001875 compounds Chemical class 0.000 claims description 103
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 101
• 239000002253 acid Substances 0.000 claims description 92
• 238000012360 testing method Methods 0.000 claims description 69
• 239000003814 drug Substances 0.000 claims description 64
• 239000002585 base Substances 0.000 claims description 56
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
• 239000000243 solution Substances 0.000 claims description 51
• 229940124597 therapeutic agent Drugs 0.000 claims description 49
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 33
• 239000002904 solvent Substances 0.000 claims description 33
• 150000002148 esters Chemical class 0.000 claims description 29
• 238000010521 absorption reaction Methods 0.000 claims description 24
• 239000000843 powder Substances 0.000 claims description 21
• 239000004305 biphenyl Substances 0.000 claims description 19
• 239000003795 chemical substances by application Substances 0.000 claims description 19
• 235000010290 biphenyl Nutrition 0.000 claims description 18
• 238000011282 treatment Methods 0.000 claims description 17
• 239000013078 crystal Substances 0.000 claims description 14
• 108060003345 Adrenergic Receptor Proteins 0.000 claims description 13
• 102000017910 Adrenergic receptor Human genes 0.000 claims description 13
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 13
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 12
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 12
• 150000003431 steroids Chemical class 0.000 claims description 12
• 239000003513 alkali Substances 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 9
• 229940079593 drug Drugs 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 9
• 239000007864 aqueous solution Substances 0.000 claims description 8
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 7
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims description 6
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims description 6
• 239000007789 gas Substances 0.000 claims description 6
• 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 239000002689 soil Substances 0.000 claims description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 5
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 4
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 150000003254 radicals Chemical class 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 239000012466 permeate Substances 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 35
• 239000012453 solvate Substances 0.000 abstract description 17
• 208000019693 Lung disease Diseases 0.000 abstract description 11
• 230000008569 process Effects 0.000 abstract description 6
• 239000000543 intermediate Substances 0.000 abstract description 4
• ABKYKPJDWBZALL-QNGWXLTQSA-N [1-[3-[4-[[[(2r)-2-(3-formamido-4-hydroxyphenyl)-2-hydroxyethyl]amino]methyl]-2,5-dimethylanilino]-3-oxopropyl]piperidin-4-yl] n-(2-phenylphenyl)carbamate Chemical compound CC=1C=C(CNC[C@H](O)C=2C=C(NC=O)C(O)=CC=2)C(C)=CC=1NC(=O)CCN(CC1)CCC1OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 ABKYKPJDWBZALL-QNGWXLTQSA-N 0.000 abstract 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
• 210000004027 cell Anatomy 0.000 description 50
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
• 239000007787 solid Substances 0.000 description 30
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 26
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
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• 238000003556 assay Methods 0.000 description 21
• 238000002360 preparation method Methods 0.000 description 21
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 20
• 239000007788 liquid Substances 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 19
• 239000002002 slurry Substances 0.000 description 19
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 238000001514 detection method Methods 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
• 239000011541 reaction mixture Substances 0.000 description 17
• 239000000872 buffer Substances 0.000 description 16
• 210000000170 cell membrane Anatomy 0.000 description 16
• 230000002829 reductive effect Effects 0.000 description 15
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 14
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
• MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 14
• 239000002245 particle Substances 0.000 description 14
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 13
• 206010057190 Respiratory tract infections Diseases 0.000 description 13
• 230000000694 effects Effects 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
• 235000019439 ethyl acetate Nutrition 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• 229910052757 nitrogen Inorganic materials 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• 239000000052 vinegar Substances 0.000 description 12
• 235000021419 vinegar Nutrition 0.000 description 12
• TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical compound NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 11
• 239000000556 agonist Substances 0.000 description 11
• 238000009739 binding Methods 0.000 description 11
• 239000012267 brine Substances 0.000 description 11
• 238000001914 filtration Methods 0.000 description 11
• 229940071648 metered dose inhaler Drugs 0.000 description 11
• 239000012071 phase Substances 0.000 description 11
• 208000024891 symptom Diseases 0.000 description 11
• 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 10
• 201000010099 disease Diseases 0.000 description 10
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• 239000008101 lactose Substances 0.000 description 10
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• 239000000706 filtrate Substances 0.000 description 9
• 239000004615 ingredient Substances 0.000 description 9
• 239000008188 pellet Substances 0.000 description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• 238000002411 thermogravimetry Methods 0.000 description 9
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
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• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
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• 238000005481 NMR spectroscopy Methods 0.000 description 7
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• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
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