BR112013007685B1 - Compostos moduladores de receptor andrógeno seletivos, composição farmacêutica compreendendo os referidos compostos, método de identificação de um composto capaz de modular um receptor andrógeno, usos de um composto ou da composição e processo para a preparação de um composto - Google Patents
Compostos moduladores de receptor andrógeno seletivos, composição farmacêutica compreendendo os referidos compostos, método de identificação de um composto capaz de modular um receptor andrógeno, usos de um composto ou da composição e processo para a preparação de um composto Download PDFInfo
- Publication number
- BR112013007685B1 BR112013007685B1 BR112013007685-2A BR112013007685A BR112013007685B1 BR 112013007685 B1 BR112013007685 B1 BR 112013007685B1 BR 112013007685 A BR112013007685 A BR 112013007685A BR 112013007685 B1 BR112013007685 B1 BR 112013007685B1
- Authority
- BR
- Brazil
- Prior art keywords
- methyl
- trifluoro
- hydroxyethyl
- benzonitrile
- compound
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 225
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 31
- 108010080146 androgen receptors Proteins 0.000 title claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
- 230000008569 process Effects 0.000 title claims abstract description 9
- 102000001307 androgen receptors Human genes 0.000 title claims abstract 10
- 238000002360 preparation method Methods 0.000 title claims abstract 8
- 239000000849 selective androgen receptor modulator Substances 0.000 title abstract description 5
- -1 SUCH COMPOUNDS Chemical class 0.000 title description 22
- 229940083324 Selective androgen receptor modulator Drugs 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 14
- 208000035475 disorder Diseases 0.000 claims abstract description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 10
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 6
- 208000007502 anemia Diseases 0.000 claims abstract description 6
- 208000017169 kidney disease Diseases 0.000 claims abstract description 6
- 208000001076 sarcopenia Diseases 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 98
- 239000001257 hydrogen Substances 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 26
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 24
- 241000124008 Mammalia Species 0.000 claims description 23
- 206010006895 Cachexia Diseases 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 13
- 208000014674 injury Diseases 0.000 claims description 12
- 229960003604 testosterone Drugs 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- DCOLZOQRXPGYCC-PWSUYJOCSA-N 4-[(5r)-2-oxo-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1CCC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 DCOLZOQRXPGYCC-PWSUYJOCSA-N 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- 206010022489 Insulin Resistance Diseases 0.000 claims description 10
- 208000018631 connective tissue disease Diseases 0.000 claims description 10
- 208000029078 coronary artery disease Diseases 0.000 claims description 10
- 238000002657 hormone replacement therapy Methods 0.000 claims description 10
- 230000008733 trauma Effects 0.000 claims description 10
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 10
- 208000001132 Osteoporosis Diseases 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 7
- DCOLZOQRXPGYCC-ZYHUDNBSSA-N 4-[(5r)-2-oxo-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1CCC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 DCOLZOQRXPGYCC-ZYHUDNBSSA-N 0.000 claims description 7
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 7
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- 208000027418 Wounds and injury Diseases 0.000 claims description 7
- 206010000496 acne Diseases 0.000 claims description 7
- 210000003205 muscle Anatomy 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 208000030507 AIDS Diseases 0.000 claims description 6
- 208000010392 Bone Fractures Diseases 0.000 claims description 6
- 206010020112 Hirsutism Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 235000000346 sugar Nutrition 0.000 claims description 6
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 5
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 5
- 201000004384 Alopecia Diseases 0.000 claims description 5
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 5
- 206010053567 Coagulopathies Diseases 0.000 claims description 5
- 208000028698 Cognitive impairment Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 208000018035 Dental disease Diseases 0.000 claims description 5
- 206010013883 Dwarfism Diseases 0.000 claims description 5
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 5
- 206010014733 Endometrial cancer Diseases 0.000 claims description 5
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 5
- 201000009273 Endometriosis Diseases 0.000 claims description 5
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 5
- 208000036119 Frailty Diseases 0.000 claims description 5
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 5
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 206010060800 Hot flush Diseases 0.000 claims description 5
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 5
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 5
- 206010024264 Lethargy Diseases 0.000 claims description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
- 206010025323 Lymphomas Diseases 0.000 claims description 5
- 208000026139 Memory disease Diseases 0.000 claims description 5
- 206010027304 Menopausal symptoms Diseases 0.000 claims description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
- 208000029725 Metabolic bone disease Diseases 0.000 claims description 5
- 208000000112 Myalgia Diseases 0.000 claims description 5
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 5
- 208000008589 Obesity Diseases 0.000 claims description 5
- 208000010191 Osteitis Deformans Diseases 0.000 claims description 5
- 206010049088 Osteopenia Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 208000027868 Paget disease Diseases 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 206010036049 Polycystic ovaries Diseases 0.000 claims description 5
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 5
- 206010038389 Renal cancer Diseases 0.000 claims description 5
- 206010039792 Seborrhoea Diseases 0.000 claims description 5
- 208000020221 Short stature Diseases 0.000 claims description 5
- 206010040799 Skin atrophy Diseases 0.000 claims description 5
- 208000014151 Stomatognathic disease Diseases 0.000 claims description 5
- 208000013200 Stress disease Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 5
- 206010057644 Testis cancer Diseases 0.000 claims description 5
- 208000001435 Thromboembolism Diseases 0.000 claims description 5
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 5
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims description 5
- 206010052428 Wound Diseases 0.000 claims description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
- 230000036528 appetite Effects 0.000 claims description 5
- 235000019789 appetite Nutrition 0.000 claims description 5
- 206010003549 asthenia Diseases 0.000 claims description 5
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 5
- 208000015294 blood coagulation disease Diseases 0.000 claims description 5
- 230000037396 body weight Effects 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 230000009852 coagulant defect Effects 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 238000000502 dialysis Methods 0.000 claims description 5
- 230000003292 diminished effect Effects 0.000 claims description 5
- 208000026500 emaciation Diseases 0.000 claims description 5
- 208000010706 fatty liver disease Diseases 0.000 claims description 5
- 238000011010 flushing procedure Methods 0.000 claims description 5
- 208000024963 hair loss Diseases 0.000 claims description 5
- 230000003676 hair loss Effects 0.000 claims description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 5
- 201000008980 hyperinsulinism Diseases 0.000 claims description 5
- 201000001881 impotence Diseases 0.000 claims description 5
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 5
- 208000000509 infertility Diseases 0.000 claims description 5
- 231100000535 infertility Toxicity 0.000 claims description 5
- 230000036512 infertility Effects 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 201000010982 kidney cancer Diseases 0.000 claims description 5
- 208000019423 liver disease Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 208000027202 mammary Paget disease Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 201000006938 muscular dystrophy Diseases 0.000 claims description 5
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 208000028169 periodontal disease Diseases 0.000 claims description 5
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 5
- 208000008742 seborrheic dermatitis Diseases 0.000 claims description 5
- 208000019116 sleep disease Diseases 0.000 claims description 5
- 201000003120 testicular cancer Diseases 0.000 claims description 5
- 201000003073 testicular leukemia Diseases 0.000 claims description 5
- 206010043554 thrombocytopenia Diseases 0.000 claims description 5
- 201000002510 thyroid cancer Diseases 0.000 claims description 5
- 206010046885 vaginal cancer Diseases 0.000 claims description 5
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 5
- 230000001457 vasomotor Effects 0.000 claims description 5
- YDGDWJFCZMDSDW-KOLCDFICSA-N 2-chloro-3-methyl-4-[(4r)-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound CC1=C(Cl)C(C#N)=CC=C1N1C(=O)OC[C@@H]1[C@H](O)C(F)(F)F YDGDWJFCZMDSDW-KOLCDFICSA-N 0.000 claims description 4
- AJSPBOQQLUICJK-BPTDKIDVSA-N 2-chloro-3-methyl-4-[(4s,5s)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C AJSPBOQQLUICJK-BPTDKIDVSA-N 0.000 claims description 4
- OCLUFVULSBZQOP-VHSXEESVSA-N 2-chloro-4-[(4s)-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@@H]1COC(=O)N1C1=CC=C(C#N)C(Cl)=C1 OCLUFVULSBZQOP-VHSXEESVSA-N 0.000 claims description 4
- GHAJKXVXLNSRDU-MQOMDTIOSA-N 2-chloro-4-[(4s,5s)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1 GHAJKXVXLNSRDU-MQOMDTIOSA-N 0.000 claims description 4
- GHAJKXVXLNSRDU-FZYJTZEISA-N 2-chloro-4-[(4s,5s)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1 GHAJKXVXLNSRDU-FZYJTZEISA-N 0.000 claims description 4
- DCTYIEQDJSQQKS-KOLCDFICSA-N 3-methyl-4-[(4r)-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)OC[C@@H]1[C@H](O)C(F)(F)F DCTYIEQDJSQQKS-KOLCDFICSA-N 0.000 claims description 4
- LPHQOQIPNPHGQA-ZJUUUORDSA-N 4-[(4r)-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1COC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 LPHQOQIPNPHGQA-ZJUUUORDSA-N 0.000 claims description 4
- CGPSIOMHVIIIGV-FZYJTZEISA-N 4-[(4s,5s)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 CGPSIOMHVIIIGV-FZYJTZEISA-N 0.000 claims description 4
- XELVPJGDFJHVCH-GHMZBOCLSA-N 4-[(5r)-3-methyl-2-oxo-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound O=C1N(C)C[C@H]([C@@H](O)C(F)(F)F)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 XELVPJGDFJHVCH-GHMZBOCLSA-N 0.000 claims description 4
- XELVPJGDFJHVCH-MNOVXSKESA-N 4-[(5r)-3-methyl-2-oxo-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound O=C1N(C)C[C@H]([C@H](O)C(F)(F)F)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 XELVPJGDFJHVCH-MNOVXSKESA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 206010051747 multiple endocrine neoplasia Diseases 0.000 claims description 4
- WTJSJWCRLSCIGQ-MWLCHTKSSA-N (5r)-1-(3,4-dichlorophenyl)-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-2-one Chemical compound FC(F)(F)[C@H](O)[C@H]1CCC(=O)N1C1=CC=C(Cl)C(Cl)=C1 WTJSJWCRLSCIGQ-MWLCHTKSSA-N 0.000 claims description 3
- WTJSJWCRLSCIGQ-KOLCDFICSA-N (5r)-1-(3,4-dichlorophenyl)-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-2-one Chemical compound FC(F)(F)[C@@H](O)[C@H]1CCC(=O)N1C1=CC=C(Cl)C(Cl)=C1 WTJSJWCRLSCIGQ-KOLCDFICSA-N 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- YDGDWJFCZMDSDW-MWLCHTKSSA-N 2-chloro-3-methyl-4-[(4r)-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound CC1=C(Cl)C(C#N)=CC=C1N1C(=O)OC[C@@H]1[C@@H](O)C(F)(F)F YDGDWJFCZMDSDW-MWLCHTKSSA-N 0.000 claims description 3
- AJSPBOQQLUICJK-NZXMKCKXSA-N 2-chloro-3-methyl-4-[(4s,5r)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C AJSPBOQQLUICJK-NZXMKCKXSA-N 0.000 claims description 3
- AJSPBOQQLUICJK-HFKOZYHYSA-N 2-chloro-3-methyl-4-[(4s,5r)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C AJSPBOQQLUICJK-HFKOZYHYSA-N 0.000 claims description 3
- AJSPBOQQLUICJK-UPZJHPNMSA-N 2-chloro-3-methyl-4-[(4s,5s)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C AJSPBOQQLUICJK-UPZJHPNMSA-N 0.000 claims description 3
- QHEPWISZBKIPMN-MFKMUULPSA-N 2-chloro-3-methyl-4-[(5r)-2-oxo-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]benzonitrile Chemical compound CC1=C(Cl)C(C#N)=CC=C1N1C(=O)CC[C@@H]1[C@H](O)C(F)(F)F QHEPWISZBKIPMN-MFKMUULPSA-N 0.000 claims description 3
- OCLUFVULSBZQOP-UWVGGRQHSA-N 2-chloro-4-[(4s)-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@@H]1COC(=O)N1C1=CC=C(C#N)C(Cl)=C1 OCLUFVULSBZQOP-UWVGGRQHSA-N 0.000 claims description 3
- GHAJKXVXLNSRDU-DIMCTHFVSA-N 2-chloro-4-[(4s,5r)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1 GHAJKXVXLNSRDU-DIMCTHFVSA-N 0.000 claims description 3
- GHAJKXVXLNSRDU-PFZYVWIYSA-N 2-chloro-4-[(4s,5r)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1 GHAJKXVXLNSRDU-PFZYVWIYSA-N 0.000 claims description 3
- GIPXIANWYFSQAU-PWSUYJOCSA-N 2-chloro-4-[(5r)-2-oxo-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1CCC(=O)N1C1=CC=C(C#N)C(Cl)=C1 GIPXIANWYFSQAU-PWSUYJOCSA-N 0.000 claims description 3
- DCTYIEQDJSQQKS-MWLCHTKSSA-N 3-methyl-4-[(4r)-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)OC[C@@H]1[C@@H](O)C(F)(F)F DCTYIEQDJSQQKS-MWLCHTKSSA-N 0.000 claims description 3
- CDCCUYIGQVCZGD-NZXMKCKXSA-N 3-methyl-4-[(4s,5r)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1C CDCCUYIGQVCZGD-NZXMKCKXSA-N 0.000 claims description 3
- CDCCUYIGQVCZGD-HFKOZYHYSA-N 3-methyl-4-[(4s,5r)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1C CDCCUYIGQVCZGD-HFKOZYHYSA-N 0.000 claims description 3
- CDCCUYIGQVCZGD-UPZJHPNMSA-N 3-methyl-4-[(4s,5s)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1C CDCCUYIGQVCZGD-UPZJHPNMSA-N 0.000 claims description 3
- CDCCUYIGQVCZGD-BPTDKIDVSA-N 3-methyl-4-[(4s,5s)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1C CDCCUYIGQVCZGD-BPTDKIDVSA-N 0.000 claims description 3
- GLGCTWNFYQFEIR-MFKMUULPSA-N 3-methyl-4-[(5r)-2-oxo-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)CC[C@@H]1[C@H](O)C(F)(F)F GLGCTWNFYQFEIR-MFKMUULPSA-N 0.000 claims description 3
- LPHQOQIPNPHGQA-NXEZZACHSA-N 4-[(4r)-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1COC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 LPHQOQIPNPHGQA-NXEZZACHSA-N 0.000 claims description 3
- CGPSIOMHVIIIGV-DIMCTHFVSA-N 4-[(4s,5r)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 CGPSIOMHVIIIGV-DIMCTHFVSA-N 0.000 claims description 3
- CGPSIOMHVIIIGV-PFZYVWIYSA-N 4-[(4s,5r)-5-methyl-2-oxo-4-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@@H](O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 CGPSIOMHVIIIGV-PFZYVWIYSA-N 0.000 claims description 3
- CGPSIOMHVIIIGV-MQOMDTIOSA-N 4-[(4s,5s)-5-methyl-2-oxo-4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 CGPSIOMHVIIIGV-MQOMDTIOSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 238000012544 monitoring process Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- YWXUYRCPRZSNBK-GZMMTYOYSA-N (5s)-1-(1,2,3-benzothiadiazol-6-yl)-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-2-one Chemical compound FC(F)(F)[C@H](O)[C@@H]1CCC(=O)N1C1=CC=C(N=NS2)C2=C1 YWXUYRCPRZSNBK-GZMMTYOYSA-N 0.000 claims description 2
- YWXUYRCPRZSNBK-KWQFWETISA-N (5s)-1-(1,2,3-benzothiadiazol-6-yl)-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-2-one Chemical compound FC(F)(F)[C@@H](O)[C@@H]1CCC(=O)N1C1=CC=C(N=NS2)C2=C1 YWXUYRCPRZSNBK-KWQFWETISA-N 0.000 claims description 2
- QHEPWISZBKIPMN-ZWNOBZJWSA-N 2-chloro-3-methyl-4-[(5r)-2-oxo-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]benzonitrile Chemical compound CC1=C(Cl)C(C#N)=CC=C1N1C(=O)CC[C@@H]1[C@@H](O)C(F)(F)F QHEPWISZBKIPMN-ZWNOBZJWSA-N 0.000 claims description 2
- GLGCTWNFYQFEIR-GWCFXTLKSA-N 3-methyl-4-[(5s)-2-oxo-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)CC[C@H]1[C@H](O)C(F)(F)F GLGCTWNFYQFEIR-GWCFXTLKSA-N 0.000 claims description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical group ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
- 125000005257 alkyl acyl group Chemical group 0.000 claims description 2
- 125000005251 aryl acyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000001282 organosilanes Chemical group 0.000 claims description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 6
- 208000019022 Mood disease Diseases 0.000 claims 4
- 206010039966 Senile dementia Diseases 0.000 claims 4
- 238000002054 transplantation Methods 0.000 claims 4
- 208000033830 Hot Flashes Diseases 0.000 claims 3
- 102000004877 Insulin Human genes 0.000 claims 3
- 108090001061 Insulin Proteins 0.000 claims 3
- 229940125396 insulin Drugs 0.000 claims 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 2
- 208000019622 heart disease Diseases 0.000 claims 2
- GIPXIANWYFSQAU-ZYHUDNBSSA-N 2-chloro-4-[(5r)-2-oxo-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]benzonitrile Chemical compound FC(F)(F)[C@H](O)[C@H]1CCC(=O)N1C1=CC=C(C#N)C(Cl)=C1 GIPXIANWYFSQAU-ZYHUDNBSSA-N 0.000 claims 1
- 208000035269 cancer or benign tumor Diseases 0.000 claims 1
- 230000002124 endocrine Effects 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 11
- 210000002307 prostate Anatomy 0.000 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 330
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 250
- 235000019439 ethyl acetate Nutrition 0.000 description 165
- 239000011541 reaction mixture Substances 0.000 description 159
- 239000000243 solution Substances 0.000 description 131
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 124
- 239000000284 extract Substances 0.000 description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- 238000005160 1H NMR spectroscopy Methods 0.000 description 85
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 76
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 67
- 239000007832 Na2SO4 Substances 0.000 description 67
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 67
- 229910052938 sodium sulfate Inorganic materials 0.000 description 67
- 235000011152 sodium sulphate Nutrition 0.000 description 67
- 238000004440 column chromatography Methods 0.000 description 56
- 239000007787 solid Substances 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 239000000460 chlorine Substances 0.000 description 48
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
- 239000013058 crude material Substances 0.000 description 39
- 238000000746 purification Methods 0.000 description 33
- 239000011734 sodium Substances 0.000 description 30
- 239000012299 nitrogen atmosphere Substances 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
- 150000001299 aldehydes Chemical class 0.000 description 26
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 26
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 26
- 239000003098 androgen Substances 0.000 description 24
- 238000004128 high performance liquid chromatography Methods 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 14
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical group C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000006188 syrup Substances 0.000 description 13
- 235000020357 syrup Nutrition 0.000 description 13
- 239000003039 volatile agent Substances 0.000 description 13
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 12
- 102100032187 Androgen receptor Human genes 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 11
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 10
- ZRKWMRDKSOPRRS-UHFFFAOYSA-N N-Methyl-N-nitrosourea Chemical compound O=NN(C)C(N)=O ZRKWMRDKSOPRRS-UHFFFAOYSA-N 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 9
- 235000015165 citric acid Nutrition 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 229940030486 androgens Drugs 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 235000015320 potassium carbonate Nutrition 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- 230000002354 daily effect Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 6
- GPMLYTBRZINDFP-MUUNZHRXSA-N 3-methyl-4-[(5r)-2-oxo-5-(trityloxymethyl)pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)CC[C@@H]1COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 GPMLYTBRZINDFP-MUUNZHRXSA-N 0.000 description 6
- LCCPQUYXMFXCAC-UHFFFAOYSA-N 4-fluoro-2-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=C(C#N)C(C(F)(F)F)=C1 LCCPQUYXMFXCAC-UHFFFAOYSA-N 0.000 description 6
- TXLASMPYJZSRON-UHFFFAOYSA-N 4-fluoro-3-methyl-2-(trifluoromethyl)benzonitrile Chemical compound CC1=C(F)C=CC(C#N)=C1C(F)(F)F TXLASMPYJZSRON-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 229960003473 androstanolone Drugs 0.000 description 6
- 239000000051 antiandrogen Substances 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- DOTFDVJUHLEXJF-UHFFFAOYSA-N n-[4-chloro-2-methyl-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide Chemical compound CC1=C(NC(=O)C(C)(C)C)C=CC(Cl)=C1C(F)(F)F DOTFDVJUHLEXJF-UHFFFAOYSA-N 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- UJDSRXSZJCJVCS-UHFFFAOYSA-N 2-amino-5-nitrobenzenethiol Chemical compound NC1=CC=C([N+]([O-])=O)C=C1S UJDSRXSZJCJVCS-UHFFFAOYSA-N 0.000 description 5
- FGBKSQXFNVUCEN-UHFFFAOYSA-N 4-amino-3-methyl-2-(trifluoromethyl)benzonitrile Chemical compound CC1=C(N)C=CC(C#N)=C1C(F)(F)F FGBKSQXFNVUCEN-UHFFFAOYSA-N 0.000 description 5
- UKEXDPWRCYZDHX-UHFFFAOYSA-N 6-nitro-1,2,3-benzothiadiazole Chemical compound [O-][N+](=O)C1=CC=C2N=NSC2=C1 UKEXDPWRCYZDHX-UHFFFAOYSA-N 0.000 description 5
- 206010065687 Bone loss Diseases 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- GXYXQQRSSGXCDL-LLVKDONJSA-N methyl (4r)-3-[4-cyano-3-(trifluoromethyl)phenyl]-1-methyl-2-oxoimidazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1CN(C)C(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 GXYXQQRSSGXCDL-LLVKDONJSA-N 0.000 description 5
- BTRKFJPZEKOSMJ-WRWORJQWSA-N methyl (4r,5s)-3-[4-cyano-3-(trifluoromethyl)phenyl]-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 BTRKFJPZEKOSMJ-WRWORJQWSA-N 0.000 description 5
- RHFURLKTQHDNSK-UHFFFAOYSA-N n-[4-cyano-2-methyl-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide Chemical compound CC1=C(NC(=O)C(C)(C)C)C=CC(C#N)=C1C(F)(F)F RHFURLKTQHDNSK-UHFFFAOYSA-N 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- XLHVFSYMOBPJBR-SNVBAGLBSA-N (4r)-3-[4-cyano-3-(trifluoromethyl)phenyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid Chemical compound O=C1N(C)C[C@H](C(O)=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 XLHVFSYMOBPJBR-SNVBAGLBSA-N 0.000 description 4
- FHADHGAXUKFKHY-UHFFFAOYSA-N 1,2,3-benzothiadiazol-6-amine Chemical compound NC1=CC=C2N=NSC2=C1 FHADHGAXUKFKHY-UHFFFAOYSA-N 0.000 description 4
- PGKPNNMOFHNZJX-UHFFFAOYSA-N 2-chloro-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(Cl)=C1 PGKPNNMOFHNZJX-UHFFFAOYSA-N 0.000 description 4
- AQQRMFAGRPUMMD-SNVBAGLBSA-N 4-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound OC[C@H]1CCC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 AQQRMFAGRPUMMD-SNVBAGLBSA-N 0.000 description 4
- VFMAEOZNCMUBNH-MUUNZHRXSA-N 4-[(5r)-2-oxo-5-(trityloxymethyl)pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=C(C#N)C(C(F)(F)F)=CC(N2C(CC[C@@H]2COC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=O)=C1 VFMAEOZNCMUBNH-MUUNZHRXSA-N 0.000 description 4
- RNKWVMABVAOUJN-CYBMUJFWSA-N 5-o-benzyl 1-o-tert-butyl (5r)-3-methyl-2-oxoimidazolidine-1,5-dicarboxylate Chemical compound CC(C)(C)OC(=O)N1C(=O)N(C)C[C@@H]1C(=O)OCC1=CC=CC=C1 RNKWVMABVAOUJN-CYBMUJFWSA-N 0.000 description 4
- HRDFWZRRQDWWAB-UHFFFAOYSA-N 6-bromo-1,2,3-benzothiadiazole Chemical compound BrC1=CC=C2N=NSC2=C1 HRDFWZRRQDWWAB-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 4
- 229930195711 D-Serine Natural products 0.000 description 4
- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 description 4
- 229930182822 D-threonine Natural products 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- SXTMXSXWPZPIFG-SNVBAGLBSA-N benzyl (4r)-1-methyl-2-oxoimidazolidine-4-carboxylate Chemical compound N1C(=O)N(C)C[C@@H]1C(=O)OCC1=CC=CC=C1 SXTMXSXWPZPIFG-SNVBAGLBSA-N 0.000 description 4
- RYSIXQJLUUCDHP-QGZVFWFLSA-N benzyl (4r)-3-[4-cyano-3-(trifluoromethyl)phenyl]-1-methyl-2-oxoimidazolidine-4-carboxylate Chemical compound N1([C@H](CN(C1=O)C)C(=O)OCC=1C=CC=CC=1)C1=CC=C(C#N)C(C(F)(F)F)=C1 RYSIXQJLUUCDHP-QGZVFWFLSA-N 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- JIKXSDDPRBYTMI-SNVBAGLBSA-N methyl (2r)-2-(3-chloro-4-cyano-2-methylanilino)-3-hydroxypropanoate Chemical compound COC(=O)[C@@H](CO)NC1=CC=C(C#N)C(Cl)=C1C JIKXSDDPRBYTMI-SNVBAGLBSA-N 0.000 description 4
- PPUGAXOEADSMFP-SNVBAGLBSA-N methyl (2r)-2-[4-cyano-3-(trifluoromethyl)anilino]-3-hydroxypropanoate Chemical compound COC(=O)[C@@H](CO)NC1=CC=C(C#N)C(C(F)(F)F)=C1 PPUGAXOEADSMFP-SNVBAGLBSA-N 0.000 description 4
- UOYBOOHWEOPXGD-QPUJVOFHSA-N methyl (2r,3s)-2-(3-chloro-4-cyano-2-methylanilino)-3-hydroxybutanoate Chemical compound COC(=O)[C@@H]([C@H](C)O)NC1=CC=C(C#N)C(Cl)=C1C UOYBOOHWEOPXGD-QPUJVOFHSA-N 0.000 description 4
- YOFOJRITXZMDFL-QPUJVOFHSA-N methyl (2r,3s)-2-[4-cyano-2-methyl-3-(trifluoromethyl)anilino]-3-hydroxybutanoate Chemical compound COC(=O)[C@@H]([C@H](C)O)NC1=CC=C(C#N)C(C(F)(F)F)=C1C YOFOJRITXZMDFL-QPUJVOFHSA-N 0.000 description 4
- BHCNSICIHKLSQO-SNVBAGLBSA-N methyl (4r)-3-(3-chloro-4-cyanophenyl)-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1COC(=O)N1C1=CC=C(C#N)C(Cl)=C1 BHCNSICIHKLSQO-SNVBAGLBSA-N 0.000 description 4
- ZGTICVCNXQDVED-SNVBAGLBSA-N methyl (4r)-3-[4-cyano-2-methyl-3-(trifluoromethyl)phenyl]-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1COC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1C ZGTICVCNXQDVED-SNVBAGLBSA-N 0.000 description 4
- IWTWTMKDECVOET-SNVBAGLBSA-N methyl (4r)-3-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1COC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 IWTWTMKDECVOET-SNVBAGLBSA-N 0.000 description 4
- DKBVYJBHCXECQP-PRHODGIISA-N methyl (4r,5r)-3-(3-chloro-4-cyano-2-methylphenyl)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C DKBVYJBHCXECQP-PRHODGIISA-N 0.000 description 4
- PBVCSEASIYSIDH-UHFFFAOYSA-N n-[4-chloro-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=C(Cl)C(C(F)(F)F)=C1 PBVCSEASIYSIDH-UHFFFAOYSA-N 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 230000009469 supplementation Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- JRNKGRQJJWAOGP-SECBINFHSA-N (2r)-2-(3-chloro-4-cyano-2-methylanilino)-3-hydroxypropanoic acid Chemical compound CC1=C(Cl)C(C#N)=CC=C1N[C@H](CO)C(O)=O JRNKGRQJJWAOGP-SECBINFHSA-N 0.000 description 3
- JBIIAOFYJBVTIW-SECBINFHSA-N (2r)-2-[4-cyano-2-methyl-3-(trifluoromethyl)anilino]-3-hydroxypropanoic acid Chemical compound CC1=C(N[C@H](CO)C(O)=O)C=CC(C#N)=C1C(F)(F)F JBIIAOFYJBVTIW-SECBINFHSA-N 0.000 description 3
- BRTOIMFIMYCKQG-SECBINFHSA-N (2r)-2-[4-cyano-3-(trifluoromethyl)anilino]-3-hydroxypropanoic acid Chemical compound OC[C@H](C(O)=O)NC1=CC=C(C#N)C(C(F)(F)F)=C1 BRTOIMFIMYCKQG-SECBINFHSA-N 0.000 description 3
- PNUMYQLEKOFXSG-QUBYGPBYSA-N (2r,3s)-2-(3-chloro-4-cyanoanilino)-3-hydroxybutanoic acid Chemical compound C[C@H](O)[C@H](C(O)=O)NC1=CC=C(C#N)C(Cl)=C1 PNUMYQLEKOFXSG-QUBYGPBYSA-N 0.000 description 3
- BIHQESNPPMUMCA-WRWORJQWSA-N (2r,3s)-2-[4-cyano-2-methyl-3-(trifluoromethyl)anilino]-3-hydroxybutanoic acid Chemical compound C[C@H](O)[C@H](C(O)=O)NC1=CC=C(C#N)C(C(F)(F)F)=C1C BIHQESNPPMUMCA-WRWORJQWSA-N 0.000 description 3
- KIXUDDJBUMRCHZ-QUBYGPBYSA-N (2r,3s)-2-[4-cyano-3-(trifluoromethyl)anilino]-3-hydroxybutanoic acid Chemical compound C[C@H](O)[C@H](C(O)=O)NC1=CC=C(C#N)C(C(F)(F)F)=C1 KIXUDDJBUMRCHZ-QUBYGPBYSA-N 0.000 description 3
- FQSSRLVFPQIRJK-JOCHJYFZSA-N (5r)-5-(trityloxymethyl)pyrrolidin-2-one Chemical compound N1C(=O)CC[C@@H]1COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 FQSSRLVFPQIRJK-JOCHJYFZSA-N 0.000 description 3
- PSGHPVALZJYHFO-VIFPVBQESA-N 2-chloro-4-[(4s)-4-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-3-methylbenzonitrile Chemical compound CC1=C(Cl)C(C#N)=CC=C1N1C(=O)OC[C@@H]1CO PSGHPVALZJYHFO-VIFPVBQESA-N 0.000 description 3
- BIOOMKAXWCGWKJ-KCJUWKMLSA-N 2-chloro-4-[(4s,5r)-4-(hydroxymethyl)-5-methyl-2-oxo-1,3-oxazolidin-3-yl]-3-methylbenzonitrile Chemical compound OC[C@H]1[C@@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C BIOOMKAXWCGWKJ-KCJUWKMLSA-N 0.000 description 3
- BIOOMKAXWCGWKJ-KWQFWETISA-N 2-chloro-4-[(4s,5s)-4-(hydroxymethyl)-5-methyl-2-oxo-1,3-oxazolidin-3-yl]-3-methylbenzonitrile Chemical compound OC[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C BIOOMKAXWCGWKJ-KWQFWETISA-N 0.000 description 3
- IOKBJSAKTZEMBR-UHFFFAOYSA-N 2-chloro-4-fluoro-3-methylbenzonitrile Chemical compound CC1=C(F)C=CC(C#N)=C1Cl IOKBJSAKTZEMBR-UHFFFAOYSA-N 0.000 description 3
- ZYEAFDYYVGFSFO-VIFPVBQESA-N 4-[(4s)-4-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-3-methyl-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)OC[C@@H]1CO ZYEAFDYYVGFSFO-VIFPVBQESA-N 0.000 description 3
- MKOKHHPGMPUTHI-CPCISQLKSA-N 4-[(4s,5s)-4-(hydroxymethyl)-5-methyl-2-oxo-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound OC[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 MKOKHHPGMPUTHI-CPCISQLKSA-N 0.000 description 3
- CPGWTELAVMWXSK-UHFFFAOYSA-N 4-bromo-3-methyl-2-(trifluoromethyl)benzonitrile Chemical compound CC1=C(Br)C=CC(C#N)=C1C(F)(F)F CPGWTELAVMWXSK-UHFFFAOYSA-N 0.000 description 3
- UMAKBVHIKMYIGQ-GFCCVEGCSA-N 5-o-benzyl 1-o-tert-butyl (5r)-2-oxoimidazolidine-1,5-dicarboxylate Chemical compound C1NC(=O)N(C(=O)OC(C)(C)C)[C@H]1C(=O)OCC1=CC=CC=C1 UMAKBVHIKMYIGQ-GFCCVEGCSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 230000001195 anabolic effect Effects 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- IXFPZURTMHZHLV-SNVBAGLBSA-N methyl (2r)-2-[4-cyano-2-methyl-3-(trifluoromethyl)anilino]-3-hydroxypropanoate Chemical compound COC(=O)[C@@H](CO)NC1=CC=C(C#N)C(C(F)(F)F)=C1C IXFPZURTMHZHLV-SNVBAGLBSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000001625 seminal vesicle Anatomy 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 201000010653 vesiculitis Diseases 0.000 description 3
- JRSZVNVJBOAUDD-SECBINFHSA-N (2r)-2-(3-chloro-4-cyanoanilino)-3-hydroxypropanoic acid Chemical compound OC[C@H](C(O)=O)NC1=CC=C(C#N)C(Cl)=C1 JRSZVNVJBOAUDD-SECBINFHSA-N 0.000 description 2
- QDUXEUWZKSXNSH-WRWORJQWSA-N (2r,3s)-2-(3-chloro-4-cyano-2-methylanilino)-3-hydroxybutanoic acid Chemical compound C[C@H](O)[C@H](C(O)=O)NC1=CC=C(C#N)C(Cl)=C1C QDUXEUWZKSXNSH-WRWORJQWSA-N 0.000 description 2
- YKJWZPPBBBYUOX-AREMUKBSSA-N (5r)-1-(1,2,3-benzothiadiazol-6-yl)-5-(trityloxymethyl)pyrrolidin-2-one Chemical compound C([C@H]1CCC(N1C=1C=C2SN=NC2=CC=1)=O)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 YKJWZPPBBBYUOX-AREMUKBSSA-N 0.000 description 2
- CCCIJQPRIXGQOE-XWSJACJDSA-N 17beta-hydroxy-17-methylestra-4,9,11-trien-3-one Chemical compound C1CC2=CC(=O)CCC2=C2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C=C2 CCCIJQPRIXGQOE-XWSJACJDSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
- GZMZTDVQJNSCIL-VIFPVBQESA-N 4-[(4s)-4-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound OC[C@H]1COC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 GZMZTDVQJNSCIL-VIFPVBQESA-N 0.000 description 2
- WHXZJFXRYFGDSH-SNVBAGLBSA-N 4-[(5r)-5-(hydroxymethyl)-3-methyl-2-oxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound O=C1N(C)C[C@H](CO)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 WHXZJFXRYFGDSH-SNVBAGLBSA-N 0.000 description 2
- PMDYLCUKSLBUHO-UHFFFAOYSA-N 4-amino-2-(trifluoromethyl)benzonitrile Chemical compound NC1=CC=C(C#N)C(C(F)(F)F)=C1 PMDYLCUKSLBUHO-UHFFFAOYSA-N 0.000 description 2
- XZZVLHLYHDELAI-UHFFFAOYSA-N 4-bromo-2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC(Br)=CC=C1C#N XZZVLHLYHDELAI-UHFFFAOYSA-N 0.000 description 2
- ASPDJZINBYYZRU-UHFFFAOYSA-N 5-amino-2-chlorobenzotrifluoride Chemical compound NC1=CC=C(Cl)C(C(F)(F)F)=C1 ASPDJZINBYYZRU-UHFFFAOYSA-N 0.000 description 2
- QLUFBCVWKTWKBF-UHFFFAOYSA-N 6-nitro-1,3-benzothiazole Chemical compound [O-][N+](=O)C1=CC=C2N=CSC2=C1 QLUFBCVWKTWKBF-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 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 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 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 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 230000001548 androgenic effect Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 230000010287 polarization Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000036299 sexual function Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- KIEXGUUJAYEUSM-UHFFFAOYSA-N trifluoromethylsilane Chemical compound FC(F)(F)[SiH3] KIEXGUUJAYEUSM-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- QDUXEUWZKSXNSH-RDDDGLTNSA-N (2r,3r)-2-(3-chloro-4-cyano-2-methylanilino)-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@H](C(O)=O)NC1=CC=C(C#N)C(Cl)=C1C QDUXEUWZKSXNSH-RDDDGLTNSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- LDRWTKQWSXGSTM-GFCCVEGCSA-N (3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](CC(O)=O)C(=O)OCC1=CC=CC=C1 LDRWTKQWSXGSTM-GFCCVEGCSA-N 0.000 description 1
- NNIDIQNZSWDURK-MRVPVSSYSA-N (5r)-1-(1,2,3-benzothiadiazol-6-yl)-5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OC[C@H]1CCC(=O)N1C1=CC=C(N=NS2)C2=C1 NNIDIQNZSWDURK-MRVPVSSYSA-N 0.000 description 1
- YWXUYRCPRZSNBK-KCJUWKMLSA-N (5r)-1-(1,2,3-benzothiadiazol-6-yl)-5-[(1s)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-2-one Chemical compound FC(F)(F)[C@@H](O)[C@H]1CCC(=O)N1C1=CC=C(N=NS2)C2=C1 YWXUYRCPRZSNBK-KCJUWKMLSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- KYRPHTMAIOFGRP-VIFPVBQESA-N 2-chloro-4-[(4s)-4-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]benzonitrile Chemical compound OC[C@H]1COC(=O)N1C1=CC=C(C#N)C(Cl)=C1 KYRPHTMAIOFGRP-VIFPVBQESA-N 0.000 description 1
- MNUSYJUTKBPUMG-CPCISQLKSA-N 2-chloro-4-[(4s,5s)-4-(hydroxymethyl)-5-methyl-2-oxo-1,3-oxazolidin-3-yl]benzonitrile Chemical compound OC[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1 MNUSYJUTKBPUMG-CPCISQLKSA-N 0.000 description 1
- GIPXIANWYFSQAU-RWANSRKNSA-N 2-chloro-4-[(5r)-2-oxo-5-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl]benzonitrile Chemical compound FC(F)(F)C(O)[C@H]1CCC(=O)N1C1=CC=C(C#N)C(Cl)=C1 GIPXIANWYFSQAU-RWANSRKNSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- GLGCTWNFYQFEIR-ZWNOBZJWSA-N 3-methyl-4-[(5r)-2-oxo-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)CC[C@@H]1[C@@H](O)C(F)(F)F GLGCTWNFYQFEIR-ZWNOBZJWSA-N 0.000 description 1
- GLGCTWNFYQFEIR-GXFFZTMASA-N 3-methyl-4-[(5s)-2-oxo-5-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)CC[C@H]1[C@@H](O)C(F)(F)F GLGCTWNFYQFEIR-GXFFZTMASA-N 0.000 description 1
- WOUCPDZSHFXNMZ-SNVBAGLBSA-N 4-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]-3-methyl-2-(trifluoromethyl)benzonitrile Chemical compound C1=CC(C#N)=C(C(F)(F)F)C(C)=C1N1C(=O)CC[C@@H]1CO WOUCPDZSHFXNMZ-SNVBAGLBSA-N 0.000 description 1
- GZMZTDVQJNSCIL-SECBINFHSA-N 4-[(4r)-4-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-(trifluoromethyl)benzonitrile Chemical compound OC[C@@H]1COC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 GZMZTDVQJNSCIL-SECBINFHSA-N 0.000 description 1
- HDUWFMNUYWQGRQ-KWQFWETISA-N 4-[(4s,5s)-4-(hydroxymethyl)-5-methyl-2-oxo-1,3-oxazolidin-3-yl]-3-methyl-2-(trifluoromethyl)benzonitrile Chemical compound OC[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1C HDUWFMNUYWQGRQ-KWQFWETISA-N 0.000 description 1
- 229940113178 5 Alpha reductase inhibitor Drugs 0.000 description 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102000014654 Aromatase Human genes 0.000 description 1
- 108010078554 Aromatase Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229940126650 Compound 3f Drugs 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010014486 Elevated triglycerides Diseases 0.000 description 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 description 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000011327 Increased bone mineral density Diseases 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 241001602876 Nata Species 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 101150071808 PTHLH gene Proteins 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010051482 Prostatomegaly Diseases 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000001744 Sodium fumarate Substances 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108010049264 Teriparatide Proteins 0.000 description 1
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 206010047486 Virilism Diseases 0.000 description 1
- 208000010399 Wasting Syndrome Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940124325 anabolic agent Drugs 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000002402 anti-lipaemic effect Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 230000000123 anti-resoprtive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- BXBOMORKYGQSFX-SECBINFHSA-N benzyl (5r)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C([C@@H]1OC(=O)NC1)OCC1=CC=CC=C1 BXBOMORKYGQSFX-SECBINFHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 208000021863 corticosteroid-induced osteoporosis Diseases 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- MSJMDZAOKORVFC-SEPHDYHBSA-L disodium fumarate Chemical compound [Na+].[Na+].[O-]C(=O)\C=C\C([O-])=O MSJMDZAOKORVFC-SEPHDYHBSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 231100000794 masculinization Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- UJLMEDAGIVVXHS-SNVBAGLBSA-N methyl (2r)-2-(3-chloro-4-cyanoanilino)-3-hydroxypropanoate Chemical compound COC(=O)[C@@H](CO)NC1=CC=C(C#N)C(Cl)=C1 UJLMEDAGIVVXHS-SNVBAGLBSA-N 0.000 description 1
- UOYBOOHWEOPXGD-PRHODGIISA-N methyl (2r,3r)-2-(3-chloro-4-cyano-2-methylanilino)-3-hydroxybutanoate Chemical compound COC(=O)[C@@H]([C@@H](C)O)NC1=CC=C(C#N)C(Cl)=C1C UOYBOOHWEOPXGD-PRHODGIISA-N 0.000 description 1
- GYJCRHFLWFHSSR-WRWORJQWSA-N methyl (2r,3s)-2-(3-chloro-4-cyanoanilino)-3-hydroxybutanoate Chemical compound COC(=O)[C@@H]([C@H](C)O)NC1=CC=C(C#N)C(Cl)=C1 GYJCRHFLWFHSSR-WRWORJQWSA-N 0.000 description 1
- LZAJQTQRQPHHNE-SNVBAGLBSA-N methyl (4r)-3-(3-chloro-4-cyano-2-methylphenyl)-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1COC(=O)N1C1=CC=C(C#N)C(Cl)=C1C LZAJQTQRQPHHNE-SNVBAGLBSA-N 0.000 description 1
- DKBVYJBHCXECQP-QPUJVOFHSA-N methyl (4r,5s)-3-(3-chloro-4-cyano-2-methylphenyl)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1C DKBVYJBHCXECQP-QPUJVOFHSA-N 0.000 description 1
- IRDNGDNYNLXAFL-WRWORJQWSA-N methyl (4r,5s)-3-(3-chloro-4-cyanophenyl)-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(Cl)=C1 IRDNGDNYNLXAFL-WRWORJQWSA-N 0.000 description 1
- GECURNGHOADLQU-QPUJVOFHSA-N methyl (4r,5s)-3-[4-cyano-2-methyl-3-(trifluoromethyl)phenyl]-5-methyl-2-oxo-1,3-oxazolidine-4-carboxylate Chemical compound COC(=O)[C@H]1[C@H](C)OC(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1C GECURNGHOADLQU-QPUJVOFHSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000004300 potassium benzoate Substances 0.000 description 1
- 235000010235 potassium benzoate Nutrition 0.000 description 1
- 229940103091 potassium benzoate Drugs 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035946 sexual desire Effects 0.000 description 1
- 230000036301 sexual development Effects 0.000 description 1
- 230000035938 sexual maturation Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940005573 sodium fumarate Drugs 0.000 description 1
- 235000019294 sodium fumarate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
- 229960005460 teriparatide Drugs 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960001712 testosterone propionate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- 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
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P17/10—Anti-acne agents
-
- 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
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/30—Oxygen or sulfur atoms
- C07D233/32—One oxygen atom
- C07D233/36—One oxygen atom with hydrocarbon radicals, substituted by nitrogen atoms, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70567—Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Molecular Biology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Gynecology & Obstetrics (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38744010P | 2010-09-28 | 2010-09-28 | |
| US61/387,440 | 2010-09-28 | ||
| PCT/US2011/053375 WO2012047617A1 (en) | 2010-09-28 | 2011-09-27 | Selective androgen receptor modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112013007685A2 BR112013007685A2 (pt) | 2016-08-09 |
| BR112013007685B1 true BR112013007685B1 (pt) | 2021-11-09 |
Family
ID=44773172
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112013007685-2A BR112013007685B1 (pt) | 2010-09-28 | 2011-09-27 | Compostos moduladores de receptor andrógeno seletivos, composição farmacêutica compreendendo os referidos compostos, método de identificação de um composto capaz de modular um receptor andrógeno, usos de um composto ou da composição e processo para a preparação de um composto |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US9133182B2 (https=) |
| EP (1) | EP2621901B1 (https=) |
| JP (1) | JP5965909B2 (https=) |
| AU (1) | AU2011312490B2 (https=) |
| BR (1) | BR112013007685B1 (https=) |
| ES (1) | ES2550319T3 (https=) |
| WO (1) | WO2012047617A1 (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX338831B (es) | 2010-02-04 | 2016-05-03 | Radius Health Inc | Moduladores selectivos de receptores de androgenos. |
| EP2568806B1 (en) | 2010-05-12 | 2016-05-11 | Radius Health, Inc. | Therapeutic regimens |
| US9133182B2 (en) | 2010-09-28 | 2015-09-15 | Radius Health, Inc. | Selective androgen receptor modulators |
| US9682960B2 (en) | 2013-12-19 | 2017-06-20 | Endorecherche, Inc. | Non-steroidal antiandrogens and selective androgen receptor modulators with a pyridyl moiety |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| FI3834824T3 (fi) | 2014-03-28 | 2025-12-05 | Univ Duke | Estrogeenireseptoripositiivisen rintasyövän hoito selektiivisellä estrogeenireseptorin modulaattorilla |
| KR101597327B1 (ko) * | 2014-04-24 | 2016-02-24 | 동아에스티 주식회사 | 옥사졸리딘계 화합물 및 이를 포함하는 선택적 안드로겐 수용체 효능제 |
| US9682933B2 (en) * | 2014-05-30 | 2017-06-20 | British Columbia Cancer Agency Branch | Androgen receptor modulators and methods for their use |
| LT3474841T (lt) | 2016-06-22 | 2022-06-10 | Ellipses Pharma Ltd | Ar+ krūties vėžio gydymo būdai |
| KR102707399B1 (ko) | 2017-01-05 | 2024-09-13 | 래디어스 파마슈티컬스, 인코포레이티드 | Rad1901-2hcl의 다형 형태 |
| CN107311960A (zh) * | 2017-08-11 | 2017-11-03 | 温州大学 | 1,2,3‑苯并噻二唑类化合物的合成方法 |
| WO2019055687A1 (en) | 2017-09-13 | 2019-03-21 | Ohio State Innovation Foundation | METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA |
| IL279853B2 (en) | 2018-07-04 | 2025-01-01 | Radius Pharmaceuticals Inc | Polymorphic forms of RAD 1901-2HCL |
| CN113348163B (zh) | 2019-02-12 | 2024-10-08 | 雷迪厄斯制药公司 | 方法和化合物 |
| CN114746400A (zh) * | 2019-11-20 | 2022-07-12 | 南京明德新药研发有限公司 | 用作选择性雄激素受体调节剂的化合物 |
| US12552806B2 (en) | 2020-03-20 | 2026-02-17 | University Of Southern California | Androgen receptor regulation by small molecule enantiomers |
| WO2024046605A1 (en) * | 2022-09-02 | 2024-03-07 | National Center For Scientific Research "Demokritos" | Compounds for the detection of ligandrol |
Family Cites Families (158)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1547758A (en) | 1975-07-29 | 1979-06-27 | Shell Int Research | Herbicidal composition |
| JPH01261381A (ja) | 1988-04-12 | 1989-10-18 | Nippon Soda Co Ltd | オキサ(チア)ジアゾール誘導体、その製造方法及び殺ダニ剤 |
| US5411981A (en) | 1991-01-09 | 1995-05-02 | Roussel Uclaf | Phenylimidazolidines having antiandrogenic activity |
| FR2693461B1 (fr) | 1992-07-08 | 1994-09-02 | Roussel Uclaf | Nouvelles phénylimidazolidines substituées, leur procédé de préparation, leur application comme médicaments et les compositions pharmaceutiques les renfermant. |
| US5589452A (en) | 1992-07-14 | 1996-12-31 | Syntex (U.S.A.) Inc. | Analogs of parathyroid hormone and parathyroid hormone related peptide: synthesis and use for the treatment of osteoporosis |
| GB9310635D0 (en) | 1993-05-21 | 1993-07-07 | Glaxo Group Ltd | Chemical compounds |
| DE19517430A1 (de) | 1995-05-12 | 1996-11-14 | Boehringer Mannheim Gmbh | Pharmazeutische Darreichungsform von Parathormon mit einer zwei- bis sechsstündigen Wirkstoff-Freisetzungsperiode |
| UA51652C2 (uk) | 1995-06-08 | 2002-12-16 | Новартіс Аг | Спосіб гідрування імінів |
| US7410948B2 (en) | 1995-07-13 | 2008-08-12 | Societe De Conseils De Recherches Et D'applications Scientifiques, Sas | Analogs of parathyroid hormone |
| US6544949B1 (en) | 1995-07-13 | 2003-04-08 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Analogs of parathyroid hormone |
| US5969095A (en) | 1995-07-13 | 1999-10-19 | Biomeasure, Inc. | Analogs of parathyroid hormone |
| US5723577A (en) | 1995-07-13 | 1998-03-03 | Biomeasure Inc. | Analogs of parathyroid hormone |
| US5955574A (en) | 1995-07-13 | 1999-09-21 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A. | Analogs of parathyroid hormone |
| JP2000513362A (ja) | 1996-06-27 | 2000-10-10 | リガンド・ファーマスーティカルス・インコーポレーテッド | アンドロゲン受容体モジュレーター化合物及び方法 |
| US20090264534A1 (en) | 1996-11-27 | 2009-10-22 | Dalton James T | Selective androgen receptor modulators |
| FR2770842B1 (fr) * | 1997-11-13 | 1999-12-17 | Oreal | Nouveaux composes derives de n-aryl 2-hydroxy alkylamides |
| EP0922467A3 (en) | 1997-12-12 | 2000-05-24 | Takeda Chemical Industries, Ltd. | Iontophoretic drug delivery |
| JP4154017B2 (ja) | 1997-12-30 | 2008-09-24 | 久光製薬株式会社 | イオントフォレーシス装置および薬物ユニット |
| US6159959A (en) | 1999-05-06 | 2000-12-12 | American Home Products Corporation | Combined estrogen and antiestrogen therapy |
| US6566372B1 (en) * | 1999-08-27 | 2003-05-20 | Ligand Pharmaceuticals Incorporated | Bicyclic androgen and progesterone receptor modulator compounds and methods |
| AU1280701A (en) | 1999-11-17 | 2001-05-30 | Novartis Ag | Iontophoretic transdermal delivery of peptides |
| US6544553B1 (en) | 1999-12-28 | 2003-04-08 | Watson Pharmaceuticals, Inc. | Dosage forms and methods for oral delivery of progesterone |
| PT1246814E (pt) | 1999-12-30 | 2005-07-29 | Signal Pharm Llc | Compostos e metodos para a modulacao de receptores de estrgenio |
| BR0111298A (pt) | 2000-06-28 | 2005-05-10 | Bristol Myers Squibb Co | Moduladores seletivos dos receptores de andrógenos e métodos para identificação, projeto e uso dos mesmos |
| ATE355854T1 (de) | 2000-08-03 | 2007-03-15 | Antares Pharma Ipl Ag | Neue zusammensetzung zur transdermalen und/oder transmukosalen wirkstoffanwendung mit geeignetem therapeutischen spiegel |
| AU2006201538B2 (en) | 2000-08-24 | 2008-02-21 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| EP1401801B1 (en) | 2000-08-24 | 2006-11-02 | The University Of Tennessee Research Corporation | Selective androgen receptor modulators and methods of use thereof |
| US7371721B2 (en) | 2000-09-18 | 2008-05-13 | Sanos Bioscience A/S | Use of GLP-2 and related compounds for the treatment, prevention, diagnosis, and prognosis of bone-related disorders and calcium homeostasis related syndromes |
| US7186683B2 (en) | 2000-09-18 | 2007-03-06 | Sanos Bioscience A/S | Use of GLP for the treatment, prevention, diagnosis, and prognosis of bone-related and nutrition-related disorders |
| BR0114909A (pt) | 2000-10-26 | 2004-02-03 | Alza Corp | Dispositivos de distribuição de drogas transdérmicas possuindo microprotuberâncias revestidas |
| WO2003011824A1 (en) | 2001-07-31 | 2003-02-13 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| WO2003015761A1 (en) | 2001-08-13 | 2003-02-27 | Merck & Co., Inc. | Selective estrogen receptor modulators |
| US8853266B2 (en) | 2001-12-06 | 2014-10-07 | University Of Tennessee Research Foundation | Selective androgen receptor modulators for treating diabetes |
| EP1465619A1 (en) | 2002-01-14 | 2004-10-13 | Nordic Bioscience A/S | Suppression of cartilage degradation via the estrogen receptor |
| MXPA04007870A (es) | 2002-02-15 | 2005-06-20 | Endorech Inc | Derivados de bifenilo y su uso como agentes antiandrogenicos. |
| US7772433B2 (en) | 2002-02-28 | 2010-08-10 | University Of Tennessee Research Foundation | SARMS and method of use thereof |
| ATE481397T1 (de) | 2002-04-24 | 2010-10-15 | Merck Sharp & Dohme | Modulatoren des östrogenrezeptors |
| ITMI20020934A1 (it) * | 2002-05-03 | 2003-11-03 | Danimite Dipharma S P A | Processo per la sintesi di benazepril cloridrato |
| TW200407324A (en) | 2002-05-17 | 2004-05-16 | Bristol Myers Squibb Co | Bicyclic modulators of androgen receptor function |
| TW200307553A (en) | 2002-05-24 | 2003-12-16 | Akzo Nobel Nv | Treatment of post-menopausal complaints in breast cancer patients |
| AU2003248052A1 (en) | 2002-07-12 | 2004-02-02 | Yamanouchi Pharmaceutical Co., Ltd. | N-phenyl-(2r,5s)dimethylpiperadine derivative |
| BR0313405A (pt) | 2002-08-12 | 2005-07-12 | Takeda Pharmaceutical | Compostos, métodos para preparar um composto e para prevenir e/ou tratar câncer, prodroga, medicamento, modulador do receptor de androgênio, agente para prevenir e/ou tratar hipogonadismo ou pertubação climatérica masculina, osteoporose e câncer, e, uso de um composto |
| US7383084B2 (en) | 2002-10-31 | 2008-06-03 | Transpharma Medical Ltd. | Transdermal delivery system for dried particulate or lyophilized medications |
| IL152574A (en) | 2002-10-31 | 2009-09-22 | Transpharma Medical Ltd | A system for passing through the skin of dry items or dried medicines |
| US7662404B2 (en) | 2002-10-31 | 2010-02-16 | Transpharma Medical Ltd. | Transdermal delivery system for dried particulate or lyophilized peptides and polypeptides |
| US8133505B2 (en) | 2002-10-31 | 2012-03-13 | Transpharma Medical Ltd. | Transdermal delivery system for dried particulate or lyophilized medications |
| EP1581217A4 (en) | 2002-11-01 | 2007-07-11 | Merck & Co Inc | CARBONYLAMINO-BENZIMIDAZOLE DERIVATIVES AS MODULATORS OF ANDROGENIC RECEPTORS |
| UA79504C2 (en) | 2002-11-07 | 2007-06-25 | Organon Nv | Indols for treating diseases associated with androgen receptors |
| US7632858B2 (en) | 2002-11-15 | 2009-12-15 | Bristol-Myers Squibb Company | Open chain prolyl urea-related modulators of androgen receptor function |
| CA2512000C (en) | 2002-12-26 | 2011-08-09 | Eisai Co., Ltd. | Selective estrogen receptor modulator |
| EP1603858A2 (en) | 2003-03-11 | 2005-12-14 | NeuroSearch A/S | Kcnq channel modulating compounds and their pharmaceutical use |
| JP2007500245A (ja) | 2003-06-10 | 2007-01-11 | スミスクライン ビーチャム コーポレーション | 化合物 |
| US20060142387A1 (en) | 2003-06-10 | 2006-06-29 | Rodolfo Cadilla | Chemical compounds |
| FI20030958A0 (fi) | 2003-06-27 | 2003-06-27 | Orion Corp | Uusia yhdisteitä |
| WO2005000309A2 (en) | 2003-06-27 | 2005-01-06 | Ionix Pharmaceuticals Limited | Chemical compounds |
| MXPA06000281A (es) | 2003-06-30 | 2006-07-03 | Johnson & Johnson | Formulaciones para microproyecciones revestidas que contienen contraiones no volatiles. |
| US20070155664A1 (en) | 2003-07-04 | 2007-07-05 | Nycomed Danmark A/S | Parathyroid hormone (pth) containing pharmaceutical compositions for oral use |
| MXPA06001751A (es) * | 2003-08-22 | 2006-05-12 | Ligand Pharm Inc | Derivados de 6-cicloamino-2-quinolinona como compuestos moduladores de receptor de androgeno. |
| AU2004272007B2 (en) | 2003-09-10 | 2009-05-28 | Merck Sharp & Dohme Corp. | 17-heterocyclic-4-azasteroid derivatives as androgen receptor modulators |
| GB0324551D0 (en) | 2003-10-21 | 2003-11-26 | Karobio Ab | Novel compounds |
| US20050124625A1 (en) | 2003-10-21 | 2005-06-09 | Salvati Mark E. | Piperazine derivatives and their use as modulators of nuclear hormone receptor function |
| CA2543641A1 (en) | 2003-10-31 | 2005-05-19 | Alza Corporation | Self-actuating applicator for microprojection array |
| US7256208B2 (en) | 2003-11-13 | 2007-08-14 | Bristol-Myers Squibb Company | Monocyclic N-Aryl hydantoin modulators of androgen receptor function |
| BRPI0416042A (pt) | 2003-11-13 | 2007-01-02 | Alza Corp | composição e aparelho para suprimento transdérmico |
| CA2545048A1 (en) | 2003-11-20 | 2005-06-02 | Warner-Lambert Company Llc | Androgen receptor modulators |
| IL159273A0 (en) | 2003-12-09 | 2004-06-01 | Transpharma Medical Ltd | Transdermal delivery system for sustained release of polypeptides |
| WO2005060956A1 (en) | 2003-12-12 | 2005-07-07 | University Of Maryland, Baltimore | IMMUNOMODULATORY COMPOUNDS THAT TARGET AND INHIBIT THE pY+3 BINDING SITE OF TYROSENE KINASE p56 LCK SH2 DOMAIN |
| KR101536701B1 (ko) | 2004-01-07 | 2015-07-14 | 앙도르쉐르슈 인코포레이티드 | 헬릭스 12 배향형 스테로이드계 약학 제품 |
| EP1709021B1 (en) | 2004-01-22 | 2010-08-04 | Eli Lilly And Company | Selective estrogen receptor modulators for the treatment of vasomotor symptoms |
| IL160033A0 (en) | 2004-01-25 | 2004-06-20 | Transpharma Medical Ltd | Transdermal delivery system for polynucleotides |
| US20050182105A1 (en) | 2004-02-04 | 2005-08-18 | Nirschl Alexandra A. | Method of using 3-cyano-4-arylpyridine derivatives as modulators of androgen receptor function |
| US7820702B2 (en) | 2004-02-04 | 2010-10-26 | Bristol-Myers Squibb Company | Sulfonylpyrrolidine modulators of androgen receptor function and method |
| JP4805909B2 (ja) | 2004-03-03 | 2011-11-02 | スミスクライン ビーチャム コーポレーション | 選択的アンドロゲン受容体モジュレーターとしてのアニリン誘導体 |
| US7625923B2 (en) | 2004-03-04 | 2009-12-01 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| US7696241B2 (en) | 2004-03-04 | 2010-04-13 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
| US7388027B2 (en) | 2004-03-04 | 2008-06-17 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
| GB0405033D0 (en) | 2004-03-05 | 2004-04-07 | Karobio Ab | Novel pharmaceutical compositions |
| US8519158B2 (en) | 2004-03-12 | 2013-08-27 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds and methods |
| JP2007223901A (ja) | 2004-03-24 | 2007-09-06 | Takeda Chem Ind Ltd | 複素環化合物およびその用途 |
| CA2562132A1 (en) | 2004-04-08 | 2005-10-27 | Merck & Co., Inc. | 17 beta-acetamide-4-azasteroids as androgen receptor modulators |
| TW200602317A (en) | 2004-04-23 | 2006-01-16 | Akzo Nobel Nv | Novel androgens |
| CN1980917B (zh) | 2004-05-03 | 2014-02-12 | 詹森药业有限公司 | 作为选择性雄激素受体调节剂(sarms)的新的吲哚衍生物 |
| CN1980891B (zh) | 2004-05-03 | 2011-03-09 | 詹森药业有限公司 | 作为选择性雄激素受体调节剂(sarms)的吲哚、苯并呋喃和苯并噻吩衍生物 |
| EP1747193A1 (en) | 2004-05-11 | 2007-01-31 | Pfizer Products Incorporated | Benzonitrile derivatives to treat musculoskeletal frailty |
| MXPA06013168A (es) | 2004-05-13 | 2007-05-15 | Johnson & Johnson | Aparato y metodo para el suministro transdermico de agentes de la hormona paratiroidea. |
| CA2566942A1 (en) | 2004-05-17 | 2005-12-08 | Acadia Pharmaceuticals Inc. | Androgen receptor modulators and method of treating disease using the same |
| US20080119456A1 (en) | 2004-05-29 | 2008-05-22 | Trond Ulven | Substituted Thiazoleacetic Acid as Crth2 Ligands |
| ATE552235T1 (de) | 2004-06-07 | 2012-04-15 | Univ Tennessee Res Foundation | Selektive androgen-rezeptor-modulator und anwendungsverfahren dafür |
| EP1791821B1 (en) | 2004-09-10 | 2013-06-05 | Janssen Pharmaceutica NV | Novel imidazolidin-2-one derivatives as selective androgen receptor modulators (sarms) |
| ATE514700T1 (de) | 2004-09-20 | 2011-07-15 | Janssen Pharmaceutica Nv | Neues tetrazyklisches heteroatom mit als sexualsteroidhormon-rezeptormodulatoren geeigneten derivaten |
| EP1805147B1 (en) | 2004-09-30 | 2014-08-13 | Janssen Pharmaceutica NV | Novel benzimidazole derivatives useful as selective androgen receptor modulators (sarms) |
| US8143425B2 (en) | 2004-10-12 | 2012-03-27 | Bristol-Myers Squibb Company | Heterocyclic aromatic compounds useful as growth hormone secretagogues |
| EP1809275A1 (en) | 2004-10-13 | 2007-07-25 | Smithkline Beecham Corporation | Chemical compounds |
| JP2008518968A (ja) | 2004-10-29 | 2008-06-05 | メルク エンド カムパニー インコーポレーテッド | アンドロゲン受容体モジュレーターとしてのn−(ピリジン−3−イル)−2−フェニルブタンアミド |
| CN104803916B (zh) | 2004-11-16 | 2017-08-11 | 詹森药业有限公司 | 用作选择性雄激素受体调节剂(sarms)的杂环衍生物 |
| CA2587780A1 (en) | 2004-11-18 | 2006-05-26 | Transpharma Medical Ltd. | Combined micro-channel generation and iontophoresis for transdermal delivery of pharmaceutical agents |
| US8143257B2 (en) | 2004-11-23 | 2012-03-27 | Ptc Therapeutics, Inc. | Substituted phenols as active agents inhibiting VEGF production |
| NZ555974A (en) | 2005-01-10 | 2010-11-26 | Acadia Pharm Inc | Aminophenyl derivatives as selective androgen receptor modulators |
| WO2006113552A2 (en) | 2005-04-15 | 2006-10-26 | Smithkline Beecham Corporation | Cyanoarylamines |
| DK1891038T3 (da) | 2005-05-13 | 2009-01-19 | Lilly Co Eli | Substituerede n-arylpyrrolidiner som selektive androgenreceptormodulatorer |
| EP1888512A2 (en) | 2005-06-06 | 2008-02-20 | Smithkline Beecham Corporation | Chemical compounds |
| US7829589B2 (en) | 2005-06-10 | 2010-11-09 | Elixir Pharmaceuticals, Inc. | Sulfonamide compounds and uses thereof |
| US7709516B2 (en) | 2005-06-17 | 2010-05-04 | Endorecherche, Inc. | Helix 12 directed non-steroidal antiandrogens |
| CN101203491A (zh) | 2005-06-24 | 2008-06-18 | 伊莱利利公司 | 可用作雄激素受体调节剂的四氢咔唑衍生物(sarm) |
| WO2007005887A2 (en) | 2005-07-01 | 2007-01-11 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds, compositions and uses thereof |
| EP1911743B8 (en) * | 2005-08-01 | 2013-01-16 | Takeda Pharmaceutical Company Limited | Cyclic amine compound |
| JP2008303145A (ja) | 2005-09-22 | 2008-12-18 | Takeda Chem Ind Ltd | Grk阻害剤からなる強心薬 |
| US7776859B2 (en) | 2005-10-14 | 2010-08-17 | Bristol-Myers Squibb Company | Hexahydroimidazopyrazin-3-one compounds useful as modulators of androgen receptor function |
| CA2629193C (en) | 2005-11-18 | 2016-03-29 | 3M Innovative Properties Company | Coatable compositions, coatings derived therefrom and microarrays having such coatings |
| TW200730505A (en) | 2005-12-07 | 2007-08-16 | Merck & Co Inc | Polymorphs of an androgen receptor modulator |
| ES2551305T3 (es) | 2005-12-28 | 2015-11-17 | Alza Corporation | Formulaciones terapéuticas estables |
| ES2402305T3 (es) | 2006-01-24 | 2013-04-30 | Janssen Pharmaceutica N.V. | Benzimidazolas 2-sustituidas nuevas como moduladores del receptor de andrógeno selectivo (SARMS) |
| CA2642598C (en) | 2006-03-03 | 2014-05-27 | Orion Corporation | Selective androgen receptor modulators |
| AU2007225056A1 (en) | 2006-03-15 | 2007-09-20 | Alza Corporation | Apparatus and method for transdermal delivery of parathyroid hormone agents to prevent or treat osteopenia |
| US9119945B2 (en) | 2006-04-20 | 2015-09-01 | 3M Innovative Properties Company | Device for applying a microneedle array |
| CA2656067C (en) | 2006-06-23 | 2014-08-12 | Radius Health, Inc. | Treatment of vasomotor symptoms with selective estrogen receptor modulators |
| PT2038252T (pt) | 2006-07-12 | 2016-12-16 | Univ Tennessee Res Found | Acilanilidos substituidos e métodos de utilização dos mesmos |
| CA2658098A1 (en) | 2006-07-19 | 2008-01-24 | Osurf | Selective androgen receptor modulators, analogs and derivatives thereof and uses thereof |
| TW200815428A (en) * | 2006-08-15 | 2008-04-01 | Wyeth Corp | Oxazolidone derivatives as PR modulators |
| CN101528214B (zh) | 2006-08-24 | 2013-06-05 | 田纳西大学研究基金会 | 取代的n-酰基苯胺及其使用方法 |
| ES2452343T3 (es) | 2006-09-29 | 2014-04-01 | Glaxosmithkline Llc | Compuestos de indol sustituidos |
| US7803770B2 (en) | 2006-10-03 | 2010-09-28 | Radius Health, Inc. | Method of treating osteoporosis comprising administration of PTHrP analog |
| KR101512377B1 (ko) | 2006-10-03 | 2015-04-28 | 라디우스 헬쓰, 인코포레이티드 | 골 아나볼릭 단백질을 위한 약물 전달 방법 |
| WO2008044033A1 (en) | 2006-10-11 | 2008-04-17 | Astrazeneca Ab | Amide derivatives |
| UA98777C2 (en) | 2006-11-20 | 2012-06-25 | Эли Лилли Энд Компани | Tetrahydrocyclopenta[b]indole compounds as androgen receptor modulators |
| WO2008121602A1 (en) | 2007-03-29 | 2008-10-09 | Smithkline Beecham Corporation | Chemical compounds |
| WO2008124000A2 (en) | 2007-04-02 | 2008-10-16 | Ligand Pharmaceuticals Incorporated | Thiazole derivatives as androgen receptor modulator compounds |
| US9284345B2 (en) | 2007-04-12 | 2016-03-15 | Endorecherche, Inc. | 17alpha-substituted steroids as systemic antiandrogens and selective androgen receptor modulators |
| WO2008128100A1 (en) | 2007-04-13 | 2008-10-23 | The Regents Of The University Of California | Small-molecule inhibitors of the androgen receptor |
| AU2008241470B2 (en) | 2007-04-16 | 2013-11-07 | Corium Pharma Solutions, Inc. | Solvent-cast microneedle arrays containing active |
| GB0712099D0 (en) | 2007-06-22 | 2007-08-01 | Wivenhoe Technology Ltd | Transmission Of Audio Information |
| PL2176220T3 (pl) | 2007-08-07 | 2013-08-30 | Takeda Pharmaceuticals Co | Pochodne pirolidyn-2-onu jako modulatory receptora androgenowego |
| WO2009054988A1 (en) | 2007-10-23 | 2009-04-30 | Alza Corporation | Transdermal sustained release drug delivery |
| WO2009065600A2 (en) | 2007-11-21 | 2009-05-28 | Technische Universität Dresden | Means for treating myosin-related diseases |
| KR101595238B1 (ko) | 2007-12-21 | 2016-02-18 | 리간드 파마슈티칼스 인코포레이티드 | 선택적 안드로겐 수용체 조절제(sarm) 및 이의 용도 |
| BRPI0821676A2 (pt) | 2007-12-21 | 2015-06-16 | Astrazeneca Ab | Composto, composição farmacêutica, e, processo para a preparação dos compostos. |
| US8268872B2 (en) | 2008-02-22 | 2012-09-18 | Radius Health, Inc. | Selective androgen receptor modulators |
| ES2488990T3 (es) | 2008-02-22 | 2014-09-01 | Radius Health, Inc. | Moduladores selectivos del receptor de andrógenos |
| WO2009133861A1 (ja) * | 2008-04-28 | 2009-11-05 | 武田薬品工業株式会社 | 環状アミン化合物 |
| US20110124617A1 (en) | 2008-05-09 | 2011-05-26 | Lyttle C Richard | Combination Therapy for BreastCancer Comprising an Antiestrogenic Agent |
| BRPI0912394A2 (pt) | 2008-05-16 | 2016-07-26 | Lilly Co Eli | moduladores do receptor de androgênio à base de tetra-hidrociclopenta[b]indol |
| WO2010022176A1 (en) | 2008-08-19 | 2010-02-25 | Ferring International Center S.A. | Methods of treatment for skeletal conditons |
| EP2383013A4 (en) | 2008-12-26 | 2012-11-28 | Hisamitsu Pharmaceutical Co | MICRO NEEDLE DEVICE |
| US8629157B2 (en) * | 2009-01-05 | 2014-01-14 | Boehringer Ingelheim International Gmbh | Pyrrolidine compounds which modulate the CB2 receptor |
| US20100226966A1 (en) | 2009-03-03 | 2010-09-09 | Daddona Peter E | Method for transdermal controlled release drug delivery |
| WO2010118287A1 (en) | 2009-04-10 | 2010-10-14 | Radius Health, Inc. | Selective androgen receptor modulators |
| JP5671453B2 (ja) * | 2009-04-28 | 2015-02-18 | 中外製薬株式会社 | スピロイミダゾロン誘導体 |
| US20110172609A1 (en) | 2010-01-08 | 2011-07-14 | Ratio, Inc. | Microneedle component assembly for drug delivery device |
| MX338831B (es) | 2010-02-04 | 2016-05-03 | Radius Health Inc | Moduladores selectivos de receptores de androgenos. |
| IE20100174A1 (en) | 2010-03-25 | 2012-02-29 | Trinity College Dublin | Transdermal administration of peptides |
| WO2011140274A2 (en) | 2010-05-04 | 2011-11-10 | Corium International, Inc. | Method and device for transdermal delivery of parathyroid hormone using a microprojection array |
| EP2568806B1 (en) | 2010-05-12 | 2016-05-11 | Radius Health, Inc. | Therapeutic regimens |
| CA2800253C (en) | 2010-05-28 | 2022-07-12 | 3M Innovative Properties Company | Aqueous formulations for coating microneedle arrays |
| US8642632B2 (en) | 2010-07-02 | 2014-02-04 | Radius Health, Inc. | Selective androgen receptor modulators |
| US9133182B2 (en) | 2010-09-28 | 2015-09-15 | Radius Health, Inc. | Selective androgen receptor modulators |
| WO2012075375A1 (en) | 2010-12-02 | 2012-06-07 | Lanco Biosciences, Inc. | Delivery of parathyroid hormones by microinjection systems |
| BR112013027153A2 (pt) | 2011-04-22 | 2016-11-29 | 3M Innovative Properties Co | método de aplicação de fármaco para pth, pthrp e peptídeos relacionados |
| EP2785406A4 (en) | 2011-11-30 | 2015-10-21 | 3M Innovative Properties Co | MICRONADEL DEVICE WITH A PEPTIDE THERAPEUTIC AND AN AMINO ACID AND METHOD FOR THE PRODUCTION AND USE THEREOF |
-
2011
- 2011-09-27 US US13/876,809 patent/US9133182B2/en active Active
- 2011-09-27 EP EP11767355.8A patent/EP2621901B1/en active Active
- 2011-09-27 BR BR112013007685-2A patent/BR112013007685B1/pt active IP Right Grant
- 2011-09-27 ES ES11767355.8T patent/ES2550319T3/es active Active
- 2011-09-27 WO PCT/US2011/053375 patent/WO2012047617A1/en not_active Ceased
- 2011-09-27 AU AU2011312490A patent/AU2011312490B2/en active Active
- 2011-09-27 JP JP2013530412A patent/JP5965909B2/ja active Active
-
2015
- 2015-07-22 US US14/806,360 patent/US9920044B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| BR112013007685A2 (pt) | 2016-08-09 |
| EP2621901B1 (en) | 2015-07-29 |
| AU2011312490B2 (en) | 2015-06-25 |
| JP2013537919A (ja) | 2013-10-07 |
| US9133182B2 (en) | 2015-09-15 |
| US9920044B2 (en) | 2018-03-20 |
| WO2012047617A1 (en) | 2012-04-12 |
| US20130217732A1 (en) | 2013-08-22 |
| ES2550319T3 (es) | 2015-11-06 |
| AU2011312490A1 (en) | 2013-04-11 |
| EP2621901A1 (en) | 2013-08-07 |
| US20150322059A1 (en) | 2015-11-12 |
| JP5965909B2 (ja) | 2016-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BR112013007685B1 (pt) | Compostos moduladores de receptor andrógeno seletivos, composição farmacêutica compreendendo os referidos compostos, método de identificação de um composto capaz de modular um receptor andrógeno, usos de um composto ou da composição e processo para a preparação de um composto | |
| JP5308458B2 (ja) | 選択的アンドロゲン受容体調節物質 | |
| CA2817784C (en) | Method of treating contrast-induced nephropathy | |
| US8268872B2 (en) | Selective androgen receptor modulators | |
| US8642632B2 (en) | Selective androgen receptor modulators | |
| BR112013026466B1 (pt) | Derivados de ácido 3-fenilpropiônico ramificados e o seu uso | |
| BR112014010576B1 (pt) | Compostos inibidores de neprilisina (nep), seus usos, processo de preparação dos compostos e composição farmacêutica compreendendo os compostos | |
| JP2010195799A (ja) | アンドロゲン受容体モジュレーター化合物としての6−シクロアミノ−2−キノリノン誘導体 | |
| BRPI0613943A2 (pt) | composto, composição farmacêutica, enantiÈmeros (+) e (-) isolados de um composto, método para produzir um composto, composição neurobiologicamente ativa, usos de um composto, de uma composição farmacêutica, e de uma composiçãoneurobiologicamente ativa | |
| JP2012514630A5 (https=) | ||
| TW201536794A (zh) | Dgat1抑制劑及其製備方法和用途 | |
| CN111372928B (zh) | 用作钾通道抑制剂的苯并咪唑衍生物 | |
| KR20140059202A (ko) | 피라졸린 유도체 및 선택적 안드로겐 수용체 조절제로서의 그의 용도 | |
| FR2992645A1 (fr) | Nouveaux derives de pyrrolidine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] | ||
| B25G | Requested change of headquarter approved |
Owner name: RADIUS HEALTH, INC. (US) |
|
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B25A | Requested transfer of rights approved |
Owner name: RADIUS PHARMACEUTICALS, INC. (US) |
|
| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] |
Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI |
|
| B06T | Formal requirements before examination [chapter 6.20 patent gazette] | ||
| B25G | Requested change of headquarter approved |
Owner name: RADIUS PHARMACEUTICALS, INC. (US) |
|
| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 27/09/2011, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO. |