IL123560A

IL123560A - Transformed tetracyclic compounds (by converted to phenyl in position 4), their preparation and medicinal preparations containing them

Transformed tetracyclic compounds (by converted to phenyl in position 4), their preparation and medicinal preparations containing them

Info

Publication number: IL123560A
Authority: IL; Israel
Prior art keywords: compound; formula; alkyl; piperidinyl; mmol
Prior art date: 1995-09-08

Application number

IL12356096A

Other languages

English (en)

Hebrew (he)

Other versions

IL123560A0 (en

Original Assignee

Lilly Co Eli

Priority date

1995-09-08

Filing date

1996-08-26

Publication date

2002-02-10

1996-08-26 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1996-08-26 Priority to IL14016296A priority Critical patent/IL140162A0/xx

1998-10-30 Publication of IL123560A0 publication Critical patent/IL123560A0/xx

2002-02-10 Publication of IL123560A publication Critical patent/IL123560A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 256
-1 4-substituted phenyl Chemical group 0.000 title claims abstract description 57
239000008194 pharmaceutical composition Substances 0.000 title claims description 10
238000002360 preparation method Methods 0.000 title description 81
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 35
150000003839 salts Chemical class 0.000 claims abstract description 21
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 7
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 7
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 5
239000000262 estrogen Substances 0.000 claims description 49
229940011871 estrogen Drugs 0.000 claims description 48
125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 23
206010028980 Neoplasm Diseases 0.000 claims description 22
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 11
KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims description 9
230000001419 dependent effect Effects 0.000 claims description 8
239000003085 diluting agent Substances 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
206010006187 Breast cancer Diseases 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
238000009806 oophorectomy Methods 0.000 claims description 6
SHZOSHQRQXBBKE-UHFFFAOYSA-N 6H-[1]benzothiolo[3,2-c]chromene Chemical compound C1=CC=CC2=C1C1=C(CO2)C2=C(S1)C=CC=C2 SHZOSHQRQXBBKE-UHFFFAOYSA-N 0.000 claims description 5
206010065687 Bone loss Diseases 0.000 claims description 5
201000011510 cancer Diseases 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
208000006386 Bone Resorption Diseases 0.000 claims description 4
230000024279 bone resorption Effects 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 4
230000009245 menopause Effects 0.000 claims description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 3
208000026310 Breast neoplasm Diseases 0.000 claims description 3
239000007818 Grignard reagent Substances 0.000 claims description 3
230000002152 alkylating effect Effects 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 2
RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 claims 2
JINGWVVDIREDBI-UHFFFAOYSA-N 1-[2-[4-(3,9-dihydroxy-6h-[1]benzothiolo[3,2-c]chromen-6-yl)phenoxy]ethyl]pyrrolidin-2-one Chemical compound O1C2=CC(O)=CC=C2C=2SC3=CC(O)=CC=C3C=2C1C(C=C1)=CC=C1OCCN1CCCC1=O JINGWVVDIREDBI-UHFFFAOYSA-N 0.000 claims 1
CLCBSJRLQJPRGN-UHFFFAOYSA-N 2,8-dimethoxy-5-[4-(2-piperidin-1-ylethoxy)phenyl]-11,12-dihydrobenzo[c]phenanthridin-6-one Chemical compound C=1C(OC)=CC=C2C=1CCC(C1=CC=C(OC)C=C1C1=O)=C2N1C(C=C1)=CC=C1OCCN1CCCCC1 CLCBSJRLQJPRGN-UHFFFAOYSA-N 0.000 claims 1
WDHIYKZHKBKYCY-UHFFFAOYSA-N 5-[4-(2-piperidin-1-ylethoxy)phenyl]-6h-benzo[c]phenanthridine-2,8-diol Chemical compound C=1C(O)=CC=C(C2=C3C4=CC=C(O)C=C4C=C2)C=1CN3C(C=C1)=CC=C1OCCN1CCCCC1 WDHIYKZHKBKYCY-UHFFFAOYSA-N 0.000 claims 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims 1
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
150000004795 grignard reagents Chemical class 0.000 claims 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 43
206010027304 Menopausal symptoms Diseases 0.000 abstract description 11
206010067269 Uterine fibrosis Diseases 0.000 abstract description 9
230000004663 cell proliferation Effects 0.000 abstract description 9
210000000329 smooth muscle myocyte Anatomy 0.000 abstract description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract 1
XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 169
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 123
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 120
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 114
239000000203 mixture Substances 0.000 description 94
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
238000000034 method Methods 0.000 description 71
239000000047 product Substances 0.000 description 71
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
239000000243 solution Substances 0.000 description 60
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 57
229940093499 ethyl acetate Drugs 0.000 description 56
235000019439 ethyl acetate Nutrition 0.000 description 56
239000007787 solid Substances 0.000 description 48
238000005481 NMR spectroscopy Methods 0.000 description 47
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
238000006243 chemical reaction Methods 0.000 description 40
238000004587 chromatography analysis Methods 0.000 description 39
239000000741 silica gel Substances 0.000 description 39
229910002027 silica gel Inorganic materials 0.000 description 39
239000012044 organic layer Substances 0.000 description 35
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
229910052938 sodium sulfate Inorganic materials 0.000 description 32
235000011152 sodium sulphate Nutrition 0.000 description 32
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 31
210000004027 cell Anatomy 0.000 description 29
239000010410 layer Substances 0.000 description 29
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 28
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 28
210000001519 tissue Anatomy 0.000 description 28
241001465754 Metazoa Species 0.000 description 27
238000012360 testing method Methods 0.000 description 26
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 25
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
238000009472 formulation Methods 0.000 description 21
230000000694 effects Effects 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
239000004480 active ingredient Substances 0.000 description 17
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 17
230000012010 growth Effects 0.000 description 17
210000004291 uterus Anatomy 0.000 description 17
239000003795 chemical substances by application Substances 0.000 description 16
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 16
239000000583 progesterone congener Substances 0.000 description 16
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
239000012298 atmosphere Substances 0.000 description 15
239000012267 brine Substances 0.000 description 15
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
229910021529 ammonia Inorganic materials 0.000 description 14
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 14
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 14
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 14
239000006260 foam Substances 0.000 description 14
239000004615 ingredient Substances 0.000 description 14
208000037803 restenosis Diseases 0.000 description 14
239000002904 solvent Substances 0.000 description 14
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 13
239000000908 ammonium hydroxide Substances 0.000 description 13
230000002357 endometrial effect Effects 0.000 description 13
241000700159 Rattus Species 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
210000000988 bone and bone Anatomy 0.000 description 12
201000010099 disease Diseases 0.000 description 12
201000010260 leiomyoma Diseases 0.000 description 12
238000010992 reflux Methods 0.000 description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
201000009273 Endometriosis Diseases 0.000 description 11
208000001132 Osteoporosis Diseases 0.000 description 11
239000002253 acid Substances 0.000 description 11
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
238000000746 purification Methods 0.000 description 11
230000004044 response Effects 0.000 description 11
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
238000002560 therapeutic procedure Methods 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
239000007858 starting material Substances 0.000 description 10
239000003826 tablet Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
229960002568 ethinylestradiol Drugs 0.000 description 9
230000009467 reduction Effects 0.000 description 9
210000002966 serum Anatomy 0.000 description 9
238000001356 surgical procedure Methods 0.000 description 9
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
206010046798 Uterine leiomyoma Diseases 0.000 description 8
QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 8
238000000338 in vitro Methods 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000000843 powder Substances 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
ZMXDDKWLCZADIW-YYWVXINBSA-N N,N-dimethylformamide-d7 Chemical compound [2H]C(=O)N(C([2H])([2H])[2H])C([2H])([2H])[2H] ZMXDDKWLCZADIW-YYWVXINBSA-N 0.000 description 7
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 7
238000010790 dilution Methods 0.000 description 7
239000012895 dilution Substances 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 7
DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
229920002472 Starch Polymers 0.000 description 6
102000004887 Transforming Growth Factor beta Human genes 0.000 description 6
108090001012 Transforming Growth Factor beta Proteins 0.000 description 6
239000002775 capsule Substances 0.000 description 6
239000001768 carboxy methyl cellulose Substances 0.000 description 6
239000012043 crude product Substances 0.000 description 6
230000001076 estrogenic effect Effects 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
150000002632 lipids Chemical class 0.000 description 6
239000012280 lithium aluminium hydride Substances 0.000 description 6
239000012452 mother liquor Substances 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
239000008107 starch Substances 0.000 description 6
235000019698 starch Nutrition 0.000 description 6
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
208000024891 symptom Diseases 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 6
ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 6
208000010579 uterine corpus leiomyoma Diseases 0.000 description 6
201000007954 uterine fibroid Diseases 0.000 description 6
230000002792 vascular Effects 0.000 description 6
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
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