SK77298A3 - Nonpeptide derivatives, pharmaceutical composition containing them and their use - Google Patents

Info

Publication number

SK77298A3

SK77298A3 SK772-98A SK77298A SK77298A3 SK 77298 A3 SK77298 A3 SK 77298A3 SK 77298 A SK77298 A SK 77298A SK 77298 A3 SK77298 A3 SK 77298A3

Authority

SK

Slovakia

Prior art keywords

pyridyl

substituted

alkyl

aryl

ethyl

Prior art date

1995-12-14

Links

• Espacenet
• Global Dossier
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• 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
• 150000001875 compounds Chemical class 0.000 claims abstract description 113
• 238000011282 treatment Methods 0.000 claims abstract description 55
• 150000003839 salts Chemical class 0.000 claims abstract description 16
• 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims abstract description 13
• 239000003163 gonadal steroid hormone Substances 0.000 claims abstract description 12
• 239000000203 mixture Substances 0.000 claims description 120
• -1 C (O) OR 11 Chemical group 0.000 claims description 117
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 69
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 42
• 125000003118 aryl group Chemical group 0.000 claims description 39
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 36
• 125000003107 substituted aryl group Chemical group 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 30
• 125000000623 heterocyclic group Chemical group 0.000 claims description 24
• 125000005842 heteroatom Chemical group 0.000 claims description 21
• 125000004429 atom Chemical group 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• 125000002837 carbocyclic group Chemical group 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 102000018997 Growth Hormone Human genes 0.000 claims description 15
• 108010051696 Growth Hormone Proteins 0.000 claims description 15
• 239000000122 growth hormone Substances 0.000 claims description 15
• 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims description 14
• 238000004519 manufacturing process Methods 0.000 claims description 14
• 125000004432 carbon atom Chemical group C* 0.000 claims description 13
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
• XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims description 12
• 229940035638 gonadotropin-releasing hormone Drugs 0.000 claims description 12
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 11
• 150000002367 halogens Chemical class 0.000 claims description 11
• 206010046798 Uterine leiomyoma Diseases 0.000 claims description 9
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 230000001419 dependent effect Effects 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 201000010260 leiomyoma Diseases 0.000 claims description 8
• 230000001817 pituitary effect Effects 0.000 claims description 7
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 229920001774 Perfluoroether Polymers 0.000 claims description 6
• 208000035475 disorder Diseases 0.000 claims description 6
• 230000003287 optical effect Effects 0.000 claims description 6
• 210000002307 prostate Anatomy 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 201000009273 Endometriosis Diseases 0.000 claims description 5
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
• 230000001456 gonadotroph Effects 0.000 claims description 4
• 206010025135 lupus erythematosus Diseases 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 4
• 230000002028 premature Effects 0.000 claims description 4
• 208000003200 Adenoma Diseases 0.000 claims description 3
• 206010020880 Hypertrophy Diseases 0.000 claims description 3
• 206010036618 Premenstrual syndrome Diseases 0.000 claims description 3
• 206010038669 Respiratory arrest Diseases 0.000 claims description 3
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000002619 bicyclic group Chemical group 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000001153 fluoro group Chemical group F* 0.000 claims description 2
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
• 125000004043 oxo group Chemical group O=* 0.000 claims description 2
• 230000035935 pregnancy Effects 0.000 claims description 2
• 208000019116 sleep disease Diseases 0.000 claims description 2
• 125000003545 alkoxy group Chemical group 0.000 claims 3
• 201000011510 cancer Diseases 0.000 claims 2
• 206010001233 Adenoma benign Diseases 0.000 claims 1
• 125000000304 alkynyl group Chemical group 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 125000000547 substituted alkyl group Chemical group 0.000 claims 1
• 210000004291 uterus Anatomy 0.000 claims 1
• 239000005557 antagonist Substances 0.000 abstract description 5
• NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 155
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 140
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 137
• 239000000243 solution Substances 0.000 description 91
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 53
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
• 235000019439 ethyl acetate Nutrition 0.000 description 47
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 47
• 238000006243 chemical reaction Methods 0.000 description 45
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
• 239000000741 silica gel Substances 0.000 description 32
• 229910002027 silica gel Inorganic materials 0.000 description 32
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
• 238000003818 flash chromatography Methods 0.000 description 30
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 29
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
• 239000000460 chlorine Substances 0.000 description 25
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
• 229910052938 sodium sulfate Inorganic materials 0.000 description 21
• 235000011152 sodium sulphate Nutrition 0.000 description 21
• 238000005481 NMR spectroscopy Methods 0.000 description 20
• 239000003921 oil Substances 0.000 description 18
• 235000019198 oils Nutrition 0.000 description 18
• 229920006395 saturated elastomer Polymers 0.000 description 18
• 239000003960 organic solvent Substances 0.000 description 17
• 239000007787 solid 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
• 238000001819 mass spectrum Methods 0.000 description 16
• 238000000034 method Methods 0.000 description 16
• 238000004809 thin layer chromatography Methods 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
• 239000002253 acid Substances 0.000 description 15
• 238000000746 purification Methods 0.000 description 15
• 239000000725 suspension Substances 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• 239000004480 active ingredient Substances 0.000 description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• 150000001412 amines Chemical class 0.000 description 13
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 description 12
• 239000011541 reaction mixture Substances 0.000 description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• 235000017557 sodium bicarbonate Nutrition 0.000 description 10
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 102000009151 Luteinizing Hormone Human genes 0.000 description 9
• 108010073521 Luteinizing Hormone Proteins 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 239000012267 brine Substances 0.000 description 9
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• 235000008504 concentrate Nutrition 0.000 description 9
• 239000012141 concentrate Substances 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 239000003112 inhibitor Substances 0.000 description 9
• 229940040129 luteinizing hormone Drugs 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 150000007513 acids Chemical class 0.000 description 8
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
• 229940122361 Bisphosphonate Drugs 0.000 description 7
• 150000004663 bisphosphonates Chemical class 0.000 description 7
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• JHFAEUICJHBVHB-UHFFFAOYSA-N 1h-indol-2-ol Chemical compound C1=CC=C2NC(O)=CC2=C1 JHFAEUICJHBVHB-UHFFFAOYSA-N 0.000 description 6
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• 206010065687 Bone loss Diseases 0.000 description 6
• 206010062767 Hypophysitis Diseases 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• 150000001408 amides Chemical class 0.000 description 6
• 239000000908 ammonium hydroxide Substances 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 239000000796 flavoring agent Substances 0.000 description 6
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 6
• 239000012442 inert solvent Substances 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 210000003635 pituitary gland Anatomy 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 6
• YHYICNMHQHRSAN-UHFFFAOYSA-N 2-[2-(1h-indol-3-yl)ethylamino]isoindole-1,3-dione Chemical class O=C1C2=CC=CC=C2C(=O)N1NCCC1=CNC2=CC=CC=C12 YHYICNMHQHRSAN-UHFFFAOYSA-N 0.000 description 5
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 5
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
• 206010056438 Growth hormone deficiency Diseases 0.000 description 5
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 239000003098 androgen Substances 0.000 description 5
• 229940030486 androgens Drugs 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 239000011575 calcium Substances 0.000 description 5
• 229910052791 calcium Inorganic materials 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 235000003599 food sweetener Nutrition 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• NSECJXCOETXUHS-UHFFFAOYSA-N 1-methylsulfonylspiro[2h-indole-3,4'-piperidine] Chemical compound C12=CC=CC=C2N(S(=O)(=O)C)CC21CCNCC2 NSECJXCOETXUHS-UHFFFAOYSA-N 0.000 description 4
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 4
• WZEAFDRGKYFRED-UHFFFAOYSA-N 4-chloro-1-(3,5-dimethylphenyl)butan-1-one Chemical compound CC1=CC(C)=CC(C(=O)CCCCl)=C1 WZEAFDRGKYFRED-UHFFFAOYSA-N 0.000 description 4
• 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 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
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• 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 4
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• 239000005909 Kieselgur Substances 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• 229910019142 PO4 Inorganic materials 0.000 description 4
• 239000007900 aqueous suspension Substances 0.000 description 4
• 229910000085 borane Inorganic materials 0.000 description 4
• 125000006309 butyl amino group Chemical group 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 229940124558 contraceptive agent Drugs 0.000 description 4
• 239000003433 contraceptive agent Substances 0.000 description 4
• 235000014113 dietary fatty acids Nutrition 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 229940011871 estrogen Drugs 0.000 description 4
• 239000000262 estrogen Substances 0.000 description 4
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
• 239000000194 fatty acid Substances 0.000 description 4
• 229930195729 fatty acid Natural products 0.000 description 4
• 229940028334 follicle stimulating hormone Drugs 0.000 description 4
• 235000013355 food flavoring agent Nutrition 0.000 description 4
• 239000003324 growth hormone secretagogue Substances 0.000 description 4
• 238000011534 incubation Methods 0.000 description 4
• 239000000787 lecithin Substances 0.000 description 4
• 235000010445 lecithin Nutrition 0.000 description 4
• 229940067606 lecithin Drugs 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 4
• 230000036961 partial effect Effects 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
• 239000010452 phosphate Substances 0.000 description 4
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