IL282446B2 - Pyrrolo[2,3-d]pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates thereto - Google Patents
Pyrrolo[2,3-d]pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates theretoInfo
- Publication number
- IL282446B2 IL282446B2 IL282446A IL28244621A IL282446B2 IL 282446 B2 IL282446 B2 IL 282446B2 IL 282446 A IL282446 A IL 282446A IL 28244621 A IL28244621 A IL 28244621A IL 282446 B2 IL282446 B2 IL 282446B2
- Authority
- IL
- Israel
- Prior art keywords
- disease
- cancer
- pyrrolo
- autoimmune
- pyrimidin
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 12
- 239000000543 intermediate Substances 0.000 title description 5
- SDCVTUZMZOCTNV-UHFFFAOYSA-N 4-methylbenzenesulfonic acid 7H-pyrrolo[2,3-d]pyrimidine Chemical compound S(=O)(=O)(O)C1=CC=C(C)C=C1.N1C=NC=C2C1=NC=C2 SDCVTUZMZOCTNV-UHFFFAOYSA-N 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims description 55
- CBRJPFGIXUFMTM-WDEREUQCSA-N 1-[(2S,5R)-2-methyl-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl]prop-2-en-1-one Chemical compound N1=CN=C(C2=C1NC=C2)N[C@@H]2CC[C@@H](N(C2)C(C=C)=O)C CBRJPFGIXUFMTM-WDEREUQCSA-N 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 46
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 24
- 208000035475 disorder Diseases 0.000 claims description 22
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 21
- 230000001363 autoimmune Effects 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 206010023332 keratitis Diseases 0.000 claims description 12
- 201000004384 Alopecia Diseases 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 238000001069 Raman spectroscopy Methods 0.000 claims description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 9
- 231100000360 alopecia Toxicity 0.000 claims description 9
- 210000000056 organ Anatomy 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 8
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 8
- 201000004624 Dermatitis Diseases 0.000 claims description 8
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 8
- 206010013774 Dry eye Diseases 0.000 claims description 8
- 206010042742 Sympathetic ophthalmia Diseases 0.000 claims description 8
- 206010052779 Transplant rejections Diseases 0.000 claims description 8
- 206010046851 Uveitis Diseases 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 8
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 8
- 230000001684 chronic effect Effects 0.000 claims description 8
- 208000032839 leukemia Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 208000024799 Thyroid disease Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 206010047642 Vitiligo Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 206010025135 lupus erythematosus Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 238000002689 xenotransplantation Methods 0.000 claims description 5
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 claims description 4
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 claims description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 206010003571 Astrocytoma Diseases 0.000 claims description 4
- 208000004300 Atrophic Gastritis Diseases 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 claims description 4
- 208000023328 Basedow disease Diseases 0.000 claims description 4
- 208000009137 Behcet syndrome Diseases 0.000 claims description 4
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 4
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 4
- 208000018084 Bone neoplasm Diseases 0.000 claims description 4
- 208000014644 Brain disease Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010006895 Cachexia Diseases 0.000 claims description 4
- 208000015943 Coeliac disease Diseases 0.000 claims description 4
- 208000010007 Cogan syndrome Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010010904 Convulsion Diseases 0.000 claims description 4
- 206010066968 Corneal leukoma Diseases 0.000 claims description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- 208000032274 Encephalopathy Diseases 0.000 claims description 4
- 206010060742 Endocrine ophthalmopathy Diseases 0.000 claims description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 4
- 208000036495 Gastritis atrophic Diseases 0.000 claims description 4
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 4
- 206010018338 Glioma Diseases 0.000 claims description 4
- 208000024869 Goodpasture syndrome Diseases 0.000 claims description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 4
- 208000015023 Graves' disease Diseases 0.000 claims description 4
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 4
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 4
- 208000005100 Herpetic Keratitis Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 206010022941 Iridocyclitis Diseases 0.000 claims description 4
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 4
- 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010027480 Metastatic malignant melanoma Diseases 0.000 claims description 4
- 208000024599 Mooren ulcer Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 208000002231 Muscle Neoplasms Diseases 0.000 claims description 4
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 4
- 201000002481 Myositis Diseases 0.000 claims description 4
- 206010029113 Neovascularisation Diseases 0.000 claims description 4
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 4
- 206010073938 Ophthalmic herpes simplex Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 206010034277 Pemphigoid Diseases 0.000 claims description 4
- 241000721454 Pemphigus Species 0.000 claims description 4
- 208000031845 Pernicious anaemia Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 4
- 206010036774 Proctitis Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 208000003251 Pruritus Diseases 0.000 claims description 4
- 208000033464 Reiter syndrome Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 206010039705 Scleritis Diseases 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 4
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 4
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 4
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 4
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 claims description 4
- 206010064996 Ulcerative keratitis Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 208000001445 Uveomeningoencephalitic Syndrome Diseases 0.000 claims description 4
- 206010047115 Vasculitis Diseases 0.000 claims description 4
- 208000034705 Vogt-Koyanagi-Harada syndrome Diseases 0.000 claims description 4
- 201000006966 adult T-cell leukemia Diseases 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 4
- 230000007815 allergy Effects 0.000 claims description 4
- 230000002491 angiogenic effect Effects 0.000 claims description 4
- 201000004612 anterior uveitis Diseases 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 4
- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 4
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 208000000594 bullous pemphigoid Diseases 0.000 claims description 4
- 230000002612 cardiopulmonary effect Effects 0.000 claims description 4
- 210000004027 cell Anatomy 0.000 claims description 4
- 208000016644 chronic atrophic gastritis Diseases 0.000 claims description 4
- 230000006720 chronic neuroinflammation Effects 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 201000001981 dermatomyositis Diseases 0.000 claims description 4
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 4
- 208000024558 digestive system cancer Diseases 0.000 claims description 4
- 230000004064 dysfunction Effects 0.000 claims description 4
- 206010014599 encephalitis Diseases 0.000 claims description 4
- 201000002491 encephalomyelitis Diseases 0.000 claims description 4
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 claims description 4
- 206010015037 epilepsy Diseases 0.000 claims description 4
- 208000030533 eye disease Diseases 0.000 claims description 4
- 201000010231 gastrointestinal system cancer Diseases 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 208000024908 graft versus host disease Diseases 0.000 claims description 4
- 208000006454 hepatitis Diseases 0.000 claims description 4
- 231100000283 hepatitis Toxicity 0.000 claims description 4
- 201000010884 herpes simplex virus keratitis Diseases 0.000 claims description 4
- 201000010666 keratoconjunctivitis Diseases 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 201000010901 lateral sclerosis Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 208000024714 major depressive disease Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000006512 mast cell neoplasm Diseases 0.000 claims description 4
- 208000008585 mastocytosis Diseases 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 201000008350 membranous glomerulonephritis Diseases 0.000 claims description 4
- 208000021039 metastatic melanoma Diseases 0.000 claims description 4
- 208000005264 motor neuron disease Diseases 0.000 claims description 4
- 201000002077 muscle cancer Diseases 0.000 claims description 4
- 206010028417 myasthenia gravis Diseases 0.000 claims description 4
- 201000008383 nephritis Diseases 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 230000000414 obstructive effect Effects 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 201000006292 polyarteritis nodosa Diseases 0.000 claims description 4
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 4
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 claims description 4
- 230000001823 pruritic effect Effects 0.000 claims description 4
- 230000002685 pulmonary effect Effects 0.000 claims description 4
- 208000002574 reactive arthritis Diseases 0.000 claims description 4
- 208000023504 respiratory system disease Diseases 0.000 claims description 4
- 201000000306 sarcoidosis Diseases 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 201000000849 skin cancer Diseases 0.000 claims description 4
- 208000020431 spinal cord injury Diseases 0.000 claims description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 206010043778 thyroiditis Diseases 0.000 claims description 4
- 230000009529 traumatic brain injury Effects 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 201000005539 vernal conjunctivitis Diseases 0.000 claims description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 3
- 208000004631 alopecia areata Diseases 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 57
- 239000007787 solid Substances 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 32
- 239000000843 powder Substances 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 17
- 239000000523 sample Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- 239000002002 slurry Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 150000003016 phosphoric acids Chemical class 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- 229940079593 drug Drugs 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 238000001237 Raman spectrum Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- -1 (2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl Chemical group 0.000 description 6
- 238000004922 13C solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 230000007170 pathology Effects 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000005384 cross polarization magic-angle spinning Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000001144 powder X-ray diffraction data Methods 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 201000006474 Brain Ischemia Diseases 0.000 description 3
- YOZLVAFWYLSRRN-VZXYPILPSA-N C[C@H]1CC[C@H](CN1C(=O)C=C)NC2=NC=NC3=C2C=CN3.CC1=CC=C(C=C1)S(=O)(=O)O Chemical compound C[C@H]1CC[C@H](CN1C(=O)C=C)NC2=NC=NC3=C2C=CN3.CC1=CC=C(C=C1)S(=O)(=O)O YOZLVAFWYLSRRN-VZXYPILPSA-N 0.000 description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 description 3
- IHGVGTOGBYHPLW-DZGCQCFKSA-N ClC=1N=C(C2=C(N1)NC=C2)N[C@@H]2CC[C@@H](N(C2)C(=O)OCC2=CC=CC=C2)C Chemical compound ClC=1N=C(C2=C(N1)NC=C2)N[C@@H]2CC[C@@H](N(C2)C(=O)OCC2=CC=CC=C2)C IHGVGTOGBYHPLW-DZGCQCFKSA-N 0.000 description 3
- 238000005079 FT-Raman Methods 0.000 description 3
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 3
- 208000003084 Graves Ophthalmopathy Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 229960004592 isopropanol Drugs 0.000 description 3
- 150000002690 malonic acid derivatives Chemical class 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 201000005737 orchitis Diseases 0.000 description 3
- 208000015385 phacoanaphylactic uveitis Diseases 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 3
- GLNZGGFNQUSLIJ-UHFFFAOYSA-N tert-butyl n-(6-methylpyridin-3-yl)carbamate Chemical compound CC1=CC=C(NC(=O)OC(C)(C)C)C=N1 GLNZGGFNQUSLIJ-UHFFFAOYSA-N 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- QMPMPSGDPRHZCG-VZXYPILPSA-N 1-[(2S,5R)-2-methyl-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl]prop-2-en-1-one propanedioic acid Chemical compound OC(=O)CC(O)=O.C[C@H]1CC[C@H](CN1C(=O)C=C)Nc1ncnc2[nH]ccc12 QMPMPSGDPRHZCG-VZXYPILPSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 238000004566 IR spectroscopy Methods 0.000 description 2
- 102000015617 Janus Kinases Human genes 0.000 description 2
- 108010024121 Janus Kinases Proteins 0.000 description 2
- 239000007836 KH2PO4 Substances 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- XLNZCMLTICDRBR-VZXYPILPSA-N P(=O)(O)(O)O.N1=CN=C(C2=C1NC=C2)N[C@@H]2CC[C@@H](N(C2)C(C=C)=O)C Chemical compound P(=O)(O)(O)O.N1=CN=C(C2=C1NC=C2)N[C@@H]2CC[C@@H](N(C2)C(C=C)=O)C XLNZCMLTICDRBR-VZXYPILPSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000013583 drug formulation Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- MIVUDAUOXJDARR-CYBMUJFWSA-N (2r)-2-[(3,5-dinitrobenzoyl)amino]-2-phenylacetic acid Chemical compound N([C@@H](C(=O)O)C=1C=CC=CC=1)C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 MIVUDAUOXJDARR-CYBMUJFWSA-N 0.000 description 1
- 238000004482 13C cross polarization magic angle spinning Methods 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical class CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 101001110286 Homo sapiens Ras-related C3 botulinum toxin substrate 1 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 238000005004 MAS NMR spectroscopy Methods 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102100022122 Ras-related C3 botulinum toxin substrate 1 Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 101150012828 UPC2 gene Proteins 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- RAFKCLFWELPONH-UHFFFAOYSA-N acetonitrile;dichloromethane Chemical compound CC#N.ClCCl RAFKCLFWELPONH-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- QDXRLZBFPKVDHC-STEACBGWSA-N benzyl (2S,5R)-5-amino-2-methylpiperidine-1-carboxylate hydrochloride Chemical compound Cl.C[C@H]1CC[C@@H](N)CN1C(=O)OCC1=CC=CC=C1 QDXRLZBFPKVDHC-STEACBGWSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 239000010431 corundum Substances 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 238000005388 cross polarization Methods 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000000048 melt cooling Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 238000010966 qNMR Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000010996 solid-state NMR spectroscopy Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- NNMBHCRWGGSRBE-UHFFFAOYSA-N tert-butyl n-(6-methylpiperidin-3-yl)carbamate Chemical compound CC1CCC(NC(=O)OC(C)(C)C)CN1 NNMBHCRWGGSRBE-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862748628P | 2018-10-22 | 2018-10-22 | |
| PCT/IB2019/058940 WO2020084435A1 (en) | 2018-10-22 | 2019-10-21 | Pyrrolo[2,3-d]pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates thereto |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IL282446A IL282446A (en) | 2021-06-30 |
| IL282446B1 IL282446B1 (en) | 2024-02-01 |
| IL282446B2 true IL282446B2 (en) | 2024-06-01 |
Family
ID=68343187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL282446A IL282446B2 (en) | 2018-10-22 | 2019-10-21 | Pyrrolo[2,3-d]pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates thereto |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US12116368B2 (enExample) |
| EP (1) | EP3870584A1 (enExample) |
| JP (1) | JP6944496B2 (enExample) |
| KR (1) | KR102629132B1 (enExample) |
| CN (1) | CN112888691B (enExample) |
| AR (1) | AR116797A1 (enExample) |
| AU (1) | AU2019363840B2 (enExample) |
| BR (1) | BR112021007568A2 (enExample) |
| CA (1) | CA3059000A1 (enExample) |
| IL (1) | IL282446B2 (enExample) |
| MX (1) | MX2021003241A (enExample) |
| SG (1) | SG11202103667QA (enExample) |
| TW (1) | TWI729530B (enExample) |
| WO (1) | WO2020084435A1 (enExample) |
| ZA (1) | ZA202101735B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4021452B1 (en) * | 2019-08-26 | 2023-12-20 | Chemwerth Inc | Substituted (7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino compounds useful as jak1 inhibitors |
| CN113121539A (zh) * | 2019-12-31 | 2021-07-16 | 江苏艾立康医药科技有限公司 | 一种pf06651600的制备方法 |
| KR20220123271A (ko) * | 2019-12-31 | 2022-09-06 | 화이자 알앤디 유케이 리미티드 | 1-((2S,5R)-5-((7H-피롤로[2,3-d]피리미딘-4-일)아미노)-2-메틸피페리딘-1-일)프로프-2-엔-1-온의 안정한 즉시 방출형 정제 및 캡슐 제형 |
| CN111620880B (zh) * | 2020-06-15 | 2022-06-10 | 江苏艾立康医药科技有限公司 | Pf-06651600 dl-酒石酸盐，晶型及其制备方法 |
| CN111732591B (zh) * | 2020-06-15 | 2022-06-10 | 江苏艾立康医药科技有限公司 | Pf-06651600 l-酒石酸盐，晶型及其制备方法 |
| CN111620879B (zh) * | 2020-06-15 | 2022-06-10 | 江苏艾立康医药科技有限公司 | Pf-06651600马来酸盐，晶型及其制备方法 |
| WO2022012587A1 (zh) * | 2020-07-14 | 2022-01-20 | 苏州晶云药物科技股份有限公司 | 丙烯酮类化合物的丙二酸盐晶型及其制备方法 |
| KR102473645B1 (ko) * | 2020-08-28 | 2022-12-05 | (주)부흥산업사 | (2S,5R)-벤질 5-(t-부톡시카르보닐아미노)-2-메틸피페리딘-1-카르복실레이트의 제조방법 |
| CN112877379B (zh) * | 2021-01-18 | 2023-09-01 | 华南理工大学 | 一种化学酶法合成n-[(3r,6r)-6-甲基哌啶-3-基]氨基甲酸叔丁酯的方法 |
| WO2025144783A1 (en) * | 2023-12-28 | 2025-07-03 | Aclaris Therapeutics, Inc. | Methods of synthesizing substituted pyrrolopyrimidine compounds |
| WO2025146702A1 (en) * | 2024-01-03 | 2025-07-10 | Msn Laboratories Private Limited, R&D Center | Solid state forms of 1-{(2s,5r)-2-methyl-5-[(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino] piperidine-1-yl}prop-2-en-1-one 4-methylbenzene-1-sulfonic acid |
| WO2025244944A1 (en) * | 2024-05-20 | 2025-11-27 | Opna Bio SA | Crystal forms of an agent |
| WO2025257773A1 (en) | 2024-06-11 | 2025-12-18 | Assia Chemical Industries Ltd. | Processes for the preparation of ritlecitinib and intermediates thereof |
| CN119060059B (zh) * | 2024-08-21 | 2025-10-28 | 武汉九州钰民医药科技有限公司 | 一种甲苯磺酸利特昔替尼的制备工艺 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3318565A1 (en) * | 2013-12-05 | 2018-05-09 | Pfizer Inc | Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1087970B1 (en) | 1998-06-19 | 2004-04-28 | Pfizer Products Inc. | PYRROLO 2,3-d]PYRIMIDINE COMPOUNDS |
| MA41350A (fr) * | 2015-01-14 | 2017-11-21 | Janssen Pharmaceutica Nv | Synthèse d'un inhibiteur de la tyrosine kinase de bruton |
| CN105859721B (zh) * | 2015-01-22 | 2018-04-17 | 浙江京新药业股份有限公司 | 一种伊布鲁替尼的制备方法 |
-
2019
- 2019-10-16 JP JP2019189151A patent/JP6944496B2/ja active Active
- 2019-10-17 TW TW108137470A patent/TWI729530B/zh active
- 2019-10-17 CA CA3059000A patent/CA3059000A1/en active Pending
- 2019-10-21 US US17/286,018 patent/US12116368B2/en active Active
- 2019-10-21 IL IL282446A patent/IL282446B2/en unknown
- 2019-10-21 EP EP19794259.2A patent/EP3870584A1/en active Pending
- 2019-10-21 WO PCT/IB2019/058940 patent/WO2020084435A1/en not_active Ceased
- 2019-10-21 AU AU2019363840A patent/AU2019363840B2/en active Active
- 2019-10-21 CN CN201980069164.0A patent/CN112888691B/zh active Active
- 2019-10-21 MX MX2021003241A patent/MX2021003241A/es unknown
- 2019-10-21 BR BR112021007568-2A patent/BR112021007568A2/pt unknown
- 2019-10-21 SG SG11202103667QA patent/SG11202103667QA/en unknown
- 2019-10-21 KR KR1020217015125A patent/KR102629132B1/ko active Active
- 2019-10-22 AR ARP190103015A patent/AR116797A1/es unknown
-
2021
- 2021-03-15 ZA ZA2021/01735A patent/ZA202101735B/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3318565A1 (en) * | 2013-12-05 | 2018-05-09 | Pfizer Inc | Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides |
Non-Patent Citations (1)
| Title |
|---|
| ATLI THORARENSEN ET AL,, DESIGN OF A JANUS KINASE 3 (JAK3) SPECIFIC INHIBITOR 1-((2 S ,5 R )-5-((7 H -PYRROLO[2,3- D ]PYRIMIDIN-4-YL)AMINO)-2-METHYLPIPERIDIN-1-YL)PROP-2-EN-1-ONE (PF-06651600) ALLOWING FOR THE INTERROGATION OF JAK3 SIGNALING IN HUMANS, 16 February 2017 (2017-02-16) * |
Also Published As
| Publication number | Publication date |
|---|---|
| US20210387989A1 (en) | 2021-12-16 |
| AR116797A1 (es) | 2021-06-16 |
| KR102629132B1 (ko) | 2024-01-29 |
| BR112021007568A2 (pt) | 2021-07-27 |
| IL282446A (en) | 2021-06-30 |
| CN112888691A (zh) | 2021-06-01 |
| US12116368B2 (en) | 2024-10-15 |
| EP3870584A1 (en) | 2021-09-01 |
| AU2019363840A1 (en) | 2021-04-01 |
| TW202033525A (zh) | 2020-09-16 |
| ZA202101735B (en) | 2022-07-27 |
| CA3059000A1 (en) | 2020-04-22 |
| KR20210080468A (ko) | 2021-06-30 |
| MX2021003241A (es) | 2021-05-12 |
| TWI729530B (zh) | 2021-06-01 |
| CN112888691B (zh) | 2023-10-31 |
| JP2020066629A (ja) | 2020-04-30 |
| AU2019363840B2 (en) | 2021-12-09 |
| WO2020084435A1 (en) | 2020-04-30 |
| IL282446B1 (en) | 2024-02-01 |
| JP6944496B2 (ja) | 2021-10-06 |
| SG11202103667QA (en) | 2021-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2019363840B2 (en) | Pyrrolo(2,3-d)pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates thereto | |
| US10723730B2 (en) | Solid forms of a selective CDK4/6 inhibitor | |
| EP3687535B1 (en) | Crystalline hydrochloride salt of lumateperone | |
| JP2025183304A (ja) | Ｒｈｏ関連タンパク質キナーゼ阻害剤の塩、その固体形態、その調製方法およびその使用 | |
| US20250282789A1 (en) | Crystalline pyrimidinyl-3,8-diazabicyclo[3.2.1]octanylmethanone compound and use thereof | |
| RU2849555C2 (ru) | Тозилат пирроло[2,3-d]пиримидина, его кристаллическая форма и способ получения и промежуточные продукты для этой цели | |
| HK40054619B (zh) | 吡咯并[2，3-d]嘧啶甲苯磺酸盐、其结晶形式以及有关的制备方法和中间体 | |
| HK40054619A (en) | Pyrrolo[2,3-d]pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates thereto | |
| TWI873326B (zh) | (1R,3R)-3-(氰甲基)-3-(4-(6-(1-甲基-1H-吡唑-4-基)吡唑并[1,5-a]吡-4-基)-1H-吡唑-1-基)環丁烷-1-甲腈之結晶型及其製備方法與用途 | |
| US20230399331A1 (en) | Solid forms of jak inhibitor and process of preparing the same | |
| TWI904227B (zh) | Rho相關蛋白激酶抑制劑的鹽、其固體形式及其製備方法和用途 | |
| HK40023529A (en) | Solid forms of a selective cdk4/6 inhibitor |