ES2756580T3 - Procedimiento para la preparación del compuesto N-(3,5-dimetilfenil)-N'-(2-trifluorometilfenil) guanidina - Google Patents
Procedimiento para la preparación del compuesto N-(3,5-dimetilfenil)-N'-(2-trifluorometilfenil) guanidina Download PDFInfo
- Publication number
- ES2756580T3 ES2756580T3 ES16756641T ES16756641T ES2756580T3 ES 2756580 T3 ES2756580 T3 ES 2756580T3 ES 16756641 T ES16756641 T ES 16756641T ES 16756641 T ES16756641 T ES 16756641T ES 2756580 T3 ES2756580 T3 ES 2756580T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- compound
- crystalline solid
- solid form
- dimethylphenyl
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 112
- 238000000034 method Methods 0.000 title claims abstract description 50
- DVIJFJSZZNOTLP-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-2-[2-(trifluoromethyl)phenyl]guanidine Chemical compound CC1=CC(C)=CC(NC(=N)NC=2C(=CC=CC=2)C(F)(F)F)=C1 DVIJFJSZZNOTLP-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- -1 cyanamide compound Chemical class 0.000 claims abstract description 15
- 239000003495 polar organic solvent Substances 0.000 claims abstract description 12
- 239000007787 solid Substances 0.000 claims description 61
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 40
- 230000008569 process Effects 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 20
- 230000001413 cellular effect Effects 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 108010033674 rho GTP-Binding Proteins Proteins 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 102000007268 rho GTP-Binding Proteins Human genes 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 6
- 230000008018 melting Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- 125000003158 alcohol group Chemical group 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 17
- 101150058540 RAC1 gene Proteins 0.000 description 14
- 102100022122 Ras-related C3 botulinum toxin substrate 1 Human genes 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 201000010099 disease Diseases 0.000 description 13
- 239000000243 solution Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000000113 differential scanning calorimetry Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000002062 proliferating effect Effects 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 230000000704 physical effect Effects 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 102100025051 Cell division control protein 42 homolog Human genes 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 102100027609 Rho-related GTP-binding protein RhoD Human genes 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102000042463 Rho family Human genes 0.000 description 3
- 108091078243 Rho family Proteins 0.000 description 3
- 229940125846 compound 25 Drugs 0.000 description 3
- 239000010779 crude oil Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- XOAYHDJRYDSPJZ-UHFFFAOYSA-N (3,5-dimethylphenyl)thiourea Chemical compound CC1=CC(C)=CC(NC(N)=S)=C1 XOAYHDJRYDSPJZ-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 2
- RQBHTTDLFFGKJR-UHFFFAOYSA-N 3,5-dimethylaniline;hydrochloride Chemical compound Cl.CC1=CC(C)=CC(N)=C1 RQBHTTDLFFGKJR-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 102000016914 ras Proteins Human genes 0.000 description 2
- 108010014186 ras Proteins Proteins 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000011477 surgical intervention Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- ZFQMSPFLYBUSLE-UHFFFAOYSA-N Cc1cc(NC#N)cc(C)c1 Chemical compound Cc1cc(NC#N)cc(C)c1 ZFQMSPFLYBUSLE-UHFFFAOYSA-N 0.000 description 1
- 102000011068 Cdc42 Human genes 0.000 description 1
- 108050001278 Cdc42 Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241000282620 Hylobates sp. Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101150111584 RHOA gene Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 238000010913 antigen-directed enzyme pro-drug therapy Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 208000018554 digestive system carcinoma Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 201000011523 endocrine gland cancer Diseases 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 201000008298 histiocytosis Diseases 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000008172 membrane trafficking Effects 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000031539 regulation of cell division Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/02—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of guanidine from cyanamide, calcium cyanamide or dicyandiamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/06—Purification or separation of guanidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ARP150102582A AR101498A1 (es) | 2015-08-11 | 2015-08-11 | Procedimiento para la preparación del compuesto n-(3,5-dimetilfenil)-n-(2-trifluorometilfenil)guanidina y su forma cristalina a |
| EP15382424 | 2015-08-11 | ||
| PCT/EP2016/069033 WO2017025560A1 (en) | 2015-08-11 | 2016-08-10 | A process for the preparation of the compound n-(3,5-dimethylphenyl)-n'-(2-trifluoromethylphenyl) guanidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2756580T3 true ES2756580T3 (es) | 2020-04-27 |
Family
ID=56799434
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16756641T Active ES2756580T3 (es) | 2015-08-11 | 2016-08-10 | Procedimiento para la preparación del compuesto N-(3,5-dimetilfenil)-N'-(2-trifluorometilfenil) guanidina |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US10343984B2 (enExample) |
| EP (1) | EP3334707B1 (enExample) |
| JP (1) | JP6748188B2 (enExample) |
| CN (1) | CN107922322B (enExample) |
| AR (1) | AR101498A1 (enExample) |
| BR (1) | BR112018002614B1 (enExample) |
| CA (1) | CA2994781A1 (enExample) |
| CY (1) | CY1122481T1 (enExample) |
| DK (1) | DK3334707T3 (enExample) |
| ES (1) | ES2756580T3 (enExample) |
| HR (1) | HRP20192301T1 (enExample) |
| HU (1) | HUE046959T2 (enExample) |
| LT (1) | LT3334707T (enExample) |
| MX (1) | MX383481B (enExample) |
| PL (1) | PL3334707T3 (enExample) |
| PT (1) | PT3334707T (enExample) |
| RS (1) | RS59759B1 (enExample) |
| RU (1) | RU2737430C2 (enExample) |
| SI (1) | SI3334707T1 (enExample) |
| SM (1) | SMT201900747T1 (enExample) |
| WO (1) | WO2017025560A1 (enExample) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN172842B (enExample) * | 1990-05-17 | 1993-12-11 | Boots Pharmaceuticals Limited | |
| AU2962297A (en) * | 1996-05-24 | 1998-01-05 | Neurosearch A/S | Phenyl derivatives useful as blockers of chloride channels |
| US8283370B2 (en) * | 2008-10-03 | 2012-10-09 | The United States Of America As Represented By The Secretary Of The Army | Imidazolidinedione derivatives as antimalarial agents, preparation thereof, and methods of use |
| EP2766342B1 (en) * | 2011-10-11 | 2016-02-10 | Universidad Nacional de Quilmes | Phenyl-guanidine derivatives |
-
2015
- 2015-08-11 AR ARP150102582A patent/AR101498A1/es not_active Application Discontinuation
-
2016
- 2016-08-10 SI SI201630561T patent/SI3334707T1/sl unknown
- 2016-08-10 LT LTEP16756641.3T patent/LT3334707T/lt unknown
- 2016-08-10 ES ES16756641T patent/ES2756580T3/es active Active
- 2016-08-10 PL PL16756641T patent/PL3334707T3/pl unknown
- 2016-08-10 RU RU2018107840A patent/RU2737430C2/ru active
- 2016-08-10 JP JP2018506997A patent/JP6748188B2/ja not_active Expired - Fee Related
- 2016-08-10 CA CA2994781A patent/CA2994781A1/en active Pending
- 2016-08-10 HR HRP20192301TT patent/HRP20192301T1/hr unknown
- 2016-08-10 RS RS20191669A patent/RS59759B1/sr unknown
- 2016-08-10 EP EP16756641.3A patent/EP3334707B1/en active Active
- 2016-08-10 DK DK16756641.3T patent/DK3334707T3/da active
- 2016-08-10 SM SM20190747T patent/SMT201900747T1/it unknown
- 2016-08-10 MX MX2018001548A patent/MX383481B/es unknown
- 2016-08-10 US US15/751,437 patent/US10343984B2/en active Active
- 2016-08-10 HU HUE16756641A patent/HUE046959T2/hu unknown
- 2016-08-10 PT PT167566413T patent/PT3334707T/pt unknown
- 2016-08-10 BR BR112018002614-0A patent/BR112018002614B1/pt not_active IP Right Cessation
- 2016-08-10 WO PCT/EP2016/069033 patent/WO2017025560A1/en not_active Ceased
- 2016-08-10 CN CN201680045772.4A patent/CN107922322B/zh not_active Expired - Fee Related
-
2019
- 2019-12-27 CY CY20191101359T patent/CY1122481T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK1256253A1 (en) | 2019-09-20 |
| DK3334707T3 (da) | 2020-01-06 |
| HUE046959T2 (hu) | 2020-04-28 |
| MX2018001548A (es) | 2018-06-22 |
| JP6748188B2 (ja) | 2020-08-26 |
| RU2737430C2 (ru) | 2020-11-30 |
| HRP20192301T1 (hr) | 2020-03-20 |
| SMT201900747T1 (it) | 2020-03-13 |
| JP2018525393A (ja) | 2018-09-06 |
| US10343984B2 (en) | 2019-07-09 |
| LT3334707T (lt) | 2020-01-27 |
| RU2018107840A3 (enExample) | 2019-12-18 |
| CY1122481T1 (el) | 2021-01-27 |
| BR112018002614A2 (enExample) | 2018-10-02 |
| MX383481B (es) | 2025-03-14 |
| CN107922322A (zh) | 2018-04-17 |
| RS59759B1 (sr) | 2020-02-28 |
| EP3334707B1 (en) | 2019-10-09 |
| BR112018002614B1 (pt) | 2023-04-11 |
| EP3334707A1 (en) | 2018-06-20 |
| SI3334707T1 (sl) | 2020-03-31 |
| US20180244608A1 (en) | 2018-08-30 |
| WO2017025560A1 (en) | 2017-02-16 |
| PL3334707T3 (pl) | 2020-05-18 |
| PT3334707T (pt) | 2020-01-14 |
| RU2018107840A (ru) | 2019-09-12 |
| CN107922322B (zh) | 2023-11-03 |
| CA2994781A1 (en) | 2017-02-16 |
| AR101498A1 (es) | 2016-12-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2881395T3 (es) | Composiciones y métodos para inhibir la actividad de la arginasa | |
| ES2975263T3 (es) | Formas cristalinas de un compuesto triazolopirimidínico | |
| ES2960953T3 (es) | Forma de sal de clorhidrato para la inhibición de EZH2 | |
| TWI597282B (zh) | ６，７-不飽合-７-胺甲醯基嗎啡喃衍生物之結晶及其製造方法 | |
| JP5596680B2 (ja) | 経口抗がん製剤 | |
| ES3040587T3 (en) | Fenfluramine compositions and methods of preparing the same | |
| CN103140512B (zh) | 聚合物缀合的MetAP2抑制剂及其应用的治疗方法 | |
| ES2714100T3 (es) | Compuestos de quinolina fusionados como inhibidores de mTor, pi3k | |
| ES2347185T3 (es) | Nuevos derivados de imidazoles, su preparacion y su utilizacion como medicamento. | |
| CN106478502B (zh) | 1,2,3,4-四氢异喹啉衍生物、其制备方法和应用 | |
| WO2023061406A1 (zh) | 含三并环结构的parp抑制剂、及其制备方法和医药用途 | |
| JP2024160326A (ja) | Ｅａａｔ２活性化因子およびその使用方法 | |
| KR20090122218A (ko) | ５-(２,４-디히드록시-５-이소프로필-페닐)-４-(４-모르폴린-４-일메틸-페닐)-이속사졸-３-카르복실산 에틸아미드의 산 부가염, 수화물 및 다형체, 및 이들 형태를 포함하는 제제 | |
| ES2969887T3 (es) | Derivados de ácido sulfopropanoico para tratar trastornos neurodegenerativos | |
| ES2756580T3 (es) | Procedimiento para la preparación del compuesto N-(3,5-dimetilfenil)-N'-(2-trifluorometilfenil) guanidina | |
| CN104334530A (zh) | N-((s)-2,3-二羟基-丙基)-3-(2-氟-4-碘-苯基氨基)-异烟酰胺的固态形式 | |
| ES2844425T3 (es) | Forma polimórfica cristalina de 3-hidroxi-4,5-bis-benciloxi-6-benciloximetil-2-fenil-2-oxo-2lambda5-[1,2]oxafosfinano | |
| TW201922690A (zh) | 環－amp反應元素結合蛋白的抑制劑 | |
| JP2025509950A (ja) | Ｐｉ３ｋ阻害剤の結晶形態及び塩ならびにその製造方法及びその使用方法 | |
| HK1256253B (en) | A process for the preparation of the compound n-(3,5-dimethylphenyl)-n'-(2-trifluoromethylphenyl) guanidine | |
| WO2022063197A1 (zh) | 一种嘧啶甲酰胺类化合物及其应用 | |
| RU2802964C2 (ru) | Твердые формы 2-(5-(4-(2-морфолиноэтокси)фенил)пиридин-2-ил)-n-бензилацетамида | |
| ES2354286T3 (es) | Cristal de un compuesto de indol que contiene sulfonamida y procedimiento de producción del mismo. | |
| JP6165816B2 (ja) | 非常に速い皮膚浸透率を有するアセトアミノフェン及び関連化合物の正荷電水溶性プロドラッグ | |
| WO2024249820A2 (en) | Neuroplastigen modulators for the treatment of pain, itch and nerve injury |