DK3186268T3 - Estere af steroide lactam og bis(2-chlorethyl)-aminophenoxy propionsyre-derivater - Google Patents
Estere af steroide lactam og bis(2-chlorethyl)-aminophenoxy propionsyre-derivater Download PDFInfo
- Publication number
- DK3186268T3 DK3186268T3 DK16739424.6T DK16739424T DK3186268T3 DK 3186268 T3 DK3186268 T3 DK 3186268T3 DK 16739424 T DK16739424 T DK 16739424T DK 3186268 T3 DK3186268 T3 DK 3186268T3
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- DK
- Denmark
- Prior art keywords
- lactam
- mmol
- bis
- mixture
- vol
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- -1 STEROID LACTAM Chemical class 0.000 title description 11
- QVHYXLRIRSZISL-UHFFFAOYSA-N 2-amino-5-chloro-3-(2-chloroethyl)-2-phenoxypentanoic acid Chemical class ClCCC(C(C(=O)O)(OC1=CC=CC=C1)N)CCCl QVHYXLRIRSZISL-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 40
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- 150000003839 salts Chemical class 0.000 claims description 20
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- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 46
- 150000003951 lactams Chemical class 0.000 description 41
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
- 230000003637 steroidlike Effects 0.000 description 32
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108010085012 Steroid Receptors Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002295 alkylating antineoplastic agent Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001589 lymphoproliferative effect Effects 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
- 230000036210 malignancy Effects 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000247 oncostatic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 231100000188 sister chromatid exchange Toxicity 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
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- 230000000699 topical effect Effects 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/005—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by nitrogen as hetero atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (12)
1. Forbindelse af formel (I) eller et farmaceutisk acceptabelt salt deraf
hvor Ri er valgt fra gruppen bestående af
R2 er valgt fra gruppen bestående af H, -CH3, -CH=CH2, -CH2-CH3, - CH2CH2CH3,
R3 er valgt fra gruppen bestående af H, -OH, -NH2.
2. Forbindelse ifølge krav 1, eller et farmaceutisk acceptabelt salt deraf, hvor Ri er valgt fra gruppen bestående af
3. Forbindelse ifølge krav 2 eller et farmaceutisk acceptabelt salt deraf, hvor Ri er valgt fra gruppen bestående af
4. Forbindelse ifølge krav 2 eller et farmaceutisk acceptabelt salt deraf, hvor Ri er valgt fra gruppen bestående af
5. Forbindelse ifølge et hvilket som helst af kravene 1-4 eller et farmaceutisk acceptabelt salt deraf, hvor R2 er valgt fra gruppen bestående af H, -CH3, -CH=CH2, - CH2-CH3, -CH2CH2CH3.
6. Forbindelse ifølge krav 5 eller et farmaceutisk acceptabelt salt deraf, hvor R2 er H.
7. Forbindelse ifølge et hvilket som helst af kravene 1-6 eller et farmaceutisk acceptabelt salt deraf, hvor R3 er H.
8. Forbindelse ifølge et hvilket som helst af kravene 1-6 eller et farmaceutisk acceptabelt salt deraf, hvor R3 er -NH2.
9. Forbindelse ifølge et hvilket som helst af kravene 1-8 eller et farmaceutisk acceptabelt salt deraf til anvendelse i medicin.
10. Forbindelse ifølge et hvilket som helst af kravene 1-8 eller et farmaceutisk acceptabelt salt deraf til anvendelse i behandlingen af kræft.
11. Forbindelse ifølge et hvilket som helst af kravene 1-8 eller et farmaceutisk acceptabelt salt deraf til anvendelse i behandlingen af kræft i æggestokkene, brystkræft, prostatakræft eller leukæmi.
12. Farmaceutisk forbindelse omfattende en forbindelse ifølge et hvilket som helst af kravene 1-8 eller et farmaceutisk acceptabelt salt deraf og en farmaceutisk acceptabel bærer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15386022 | 2015-06-29 | ||
| PCT/EP2016/065071 WO2017001439A1 (en) | 2015-06-29 | 2016-06-28 | Esters of steroidal lactam and bis(2-chloroethyl) aminophenoxy propanoic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3186268T3 true DK3186268T3 (da) | 2019-03-18 |
Family
ID=53716416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK16739424.6T DK3186268T3 (da) | 2015-06-29 | 2016-06-28 | Estere af steroide lactam og bis(2-chlorethyl)-aminophenoxy propionsyre-derivater |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US10208083B2 (da) |
| EP (1) | EP3186268B1 (da) |
| JP (1) | JP6708670B2 (da) |
| KR (1) | KR102647748B1 (da) |
| CN (1) | CN107835817B (da) |
| AU (1) | AU2016286205B8 (da) |
| BR (1) | BR112017027850B1 (da) |
| CA (1) | CA2990307C (da) |
| CY (1) | CY1121264T1 (da) |
| DK (1) | DK3186268T3 (da) |
| ES (1) | ES2712429T3 (da) |
| HK (1) | HK1248241A1 (da) |
| HR (1) | HRP20190327T1 (da) |
| HU (1) | HUE043468T2 (da) |
| IL (1) | IL256456B (da) |
| LT (1) | LT3186268T (da) |
| MX (1) | MX369930B (da) |
| PL (1) | PL3186268T3 (da) |
| PT (1) | PT3186268T (da) |
| RS (1) | RS58630B1 (da) |
| RU (1) | RU2719457C2 (da) |
| SI (1) | SI3186268T1 (da) |
| TR (1) | TR201902369T4 (da) |
| WO (1) | WO2017001439A1 (da) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1527161A (en) * | 1976-02-19 | 1978-10-04 | Leo A | Enol esters of steroids |
| SU1361152A1 (ru) * | 1983-07-08 | 1987-12-23 | Всесоюзный онкологический научный центр АМН СССР | Сложные моноэфиры 5 @ -андростандиола-3 @ ,17 @ ,про вл ющие противоопухолевую и гормональную активность |
| WO2013142873A2 (en) * | 2012-03-23 | 2013-09-26 | The Board Of Trustees Of The University Of Illinois | Complex and structurally diverse compounds |
-
2016
- 2016-06-28 US US15/738,328 patent/US10208083B2/en active Active
- 2016-06-28 LT LTEP16739424.6T patent/LT3186268T/lt unknown
- 2016-06-28 CN CN201680038078.XA patent/CN107835817B/zh active Active
- 2016-06-28 RS RS20190229A patent/RS58630B1/sr unknown
- 2016-06-28 KR KR1020187002060A patent/KR102647748B1/ko active Active
- 2016-06-28 HK HK18105389.8A patent/HK1248241A1/zh unknown
- 2016-06-28 SI SI201630188T patent/SI3186268T1/sl unknown
- 2016-06-28 PT PT16739424T patent/PT3186268T/pt unknown
- 2016-06-28 HU HUE16739424A patent/HUE043468T2/hu unknown
- 2016-06-28 JP JP2017567610A patent/JP6708670B2/ja active Active
- 2016-06-28 HR HRP20190327TT patent/HRP20190327T1/hr unknown
- 2016-06-28 ES ES16739424T patent/ES2712429T3/es active Active
- 2016-06-28 MX MX2017016679A patent/MX369930B/es active IP Right Grant
- 2016-06-28 RU RU2018103071A patent/RU2719457C2/ru active
- 2016-06-28 DK DK16739424.6T patent/DK3186268T3/da active
- 2016-06-28 TR TR2019/02369T patent/TR201902369T4/tr unknown
- 2016-06-28 AU AU2016286205A patent/AU2016286205B8/en active Active
- 2016-06-28 BR BR112017027850-2A patent/BR112017027850B1/pt active IP Right Grant
- 2016-06-28 WO PCT/EP2016/065071 patent/WO2017001439A1/en not_active Ceased
- 2016-06-28 EP EP16739424.6A patent/EP3186268B1/en active Active
- 2016-06-28 CA CA2990307A patent/CA2990307C/en active Active
- 2016-06-28 PL PL16739424T patent/PL3186268T3/pl unknown
-
2017
- 2017-12-20 IL IL25645617A patent/IL256456B/en active IP Right Grant
-
2019
- 2019-02-13 CY CY20191100191T patent/CY1121264T1/el unknown
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