Patent NZ229649A successfully refreshed from Google Patents.
NZ229649A
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NZ
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Estramustine derivatives and pharmaceutical compositions
Assignee: Pharmacia Ab
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Filing: 1989-06-21
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Granted: —
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Expires: 2009-06-21
Abstract
Abstract The present invention concerns novel compounds having the general formula wherein R<1>, R<2> and R<3> are selected from the group consisting of hydrogen or lower alkyl having 1-4 carbon atoms, wherein R<2> and R<3> together with the N atom can also form a ring having 2-5 carbon atoms and wherein n is 0, 1 or 2, and pharmaceutically acceptable salts thereof. The compounds according to the invention are useful as anticancer agents.
Inventors
- 👤 Bertil Valdemar Hansen
- 👤 Per-Olov Gunnar Gunnarsson
- 👤 Henri Rene Mollberg
- 👤 Sven-Ake Johansson
Bibliographic Details
Application Number
—
Jurisdiction
NZ
Data Source
google_patents
Last Synchronized
2026-11-02 20:52
CPC Classifications
C; C07; C07C; C07C271/00; C07C271/06; C07C271/40; C07C271/42; C07C271/46; C07J; C07J41/00; C07J41/0033; C07J41/0072; A; A61; A61P; A61P35/00; A61P43/00
Claims Analysis
Total Claims: 5
Claim 1
Independent Claim
243 words
/ n 10 22 9 6 4 9 TABLE 1 Oral bioavailability of estramustine 1n dogs. AUC-values after administration of solutions of the estramustine esters Dog No. Estramustine ^ j .. „ „ „ J , 0 phosphate Compound No. 6:2 Compound No. 4:2 disodium salt 8727 147 100 - 8729 16.4 140 94.0 8731 34.0 45.8 79.8 8733 19.5 184.8 - 8735 - - 2.6 8742 - - 153.4 Mean±S.D. 54.3 ± 62.4 118 ± 59 82.6 t Example 12 Formulation, plain tablets I Compound No. 6:2, mg 160 Corn starch, mg 15 II Polyvidone, mg 8 Ethanol q.s. III Corn starch, mg 15 Magnesium stearate, mg 2 I 1s mixed and granulated with solution II. After drying and milling through 1 mm sieve III 1s added. The mixture 1s compressed to tablets with a weight of 200 mg. Example 13 Formulation, capsules The mixture from example 12 1s filled into hard capsules, size No. 1. . ■ ■■ j- n WHAT HE CLAIM IS: 22UVAU 1. Compounds having the general formula C1CH,CH, 0 2 2 \ II ^ N-C-0 C1CH2CH2' 0 R1 R2 II I / 0-C-CH-(CH_) -N CH-1 V wherein R1, R2 and R3 are selected from the group consisting of hydrogen and lower alkyl having 1-4 carbon atoms, wherein R2 and R3 together with the N atom can also form a ring having 2-5 carbon atoms and wherein n 1s 0, 1 or 2, and pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim
11 words
Compounds according to claim 1 characterized 1n that n 1s 0.
Claim 3
Dependent Claim
13 words
Compounds according to claim 1 or 2 characterized 1n that R1 1s hydrogen.
Claim 4
Dependent Claim
26 words
Compounds according to any of the claims 1-3, characterized 1n that R2 and R3 are equal or different and consist of hydrogen, 'J methyl or ethyl.
Claim 5
Dependent Claim
318 words
A compound according to claim 1 selected from the following group: 17-estramustine N,N-d1ethyl aminoacetate (3 17-estramustine 4-(N,N-d1methylam1no)butyrate 17-estramustine N-methyl ami noacetate 17-estramustine aminoacetate •• v \ 17-estramustine 2-am1noprop1onate ' 29 0CTI99l£j 17-estramustine N-ethylaminoacetate J ^ y'f' 17-estramustine N-(2-propyl)am1 noacetate ." f r' 17-estramustine 3-am1noprop1onate 17-estramustine N-(l-propyl)am1noacetate . - 12 22iH'M A compound according to claim 1 selected from the following group: 17-estramustine N-methylaminoacetate, hydrochloride 17-estramustine aminoacetate, hydrochloride 17-estramustine N-methylaminoacetate, methanesulfonate 17-estramustine aminoacetate, methanesulfonate 17-estramustine N-methyl aminoacetate, ethanesulfonate 17-estramustine aminoacetate, ethanesulfonate . Method of preparing compounds having the general formula I defined in claim 1 characterized by a) esterlfylng estramustine with an acid having a reactive subs-tltuent giving a compound having the formula II: J C1CH2CH2- 0 ^ N-C-0 C1CH2CH2 0-C-CH-(CH2)n-R / 290CTl99, Vv o'\ II O wherein R4 Is a reactive substltuent and then reacting compound II with an amine having the general formula HNR2R3, or b) esterlfylng estramustine with an amino add having the general formula H00C-CH-(CH2)n-NR2R5, wherein R5 1s R3 or optio-R1 nally a protecting group, giving an intermediate having the general formula II, wherein R4 1s -NR2R5, from which the protecting group 1s afterwards removed for the preparation of compounds having the general formula I. Method according to claim 7 characterized in that compounds wherein n 1s 0 are prepared. — \ 29OCT|»9|£ v- f|i|t - Method according to claim 7 or 8 characterized 1n that compounds wherein R1 1s hydrogen are prepared. Method according to any of the claims 7-9 characterized 1n that compounds wherein R2 and R3 are equal or different and are selected from the group consisting of hydrogen, methyl or ethyl are prepared. Pharmaceutical compositions containing as an active Ingredient one or more of the compounds having the general formula I defined in claim 1, preferably together with a pharmaceutical ly acceptable carrier and, 1f desired, other pharmacologically active agents. JATED. THIS <^7 DAY OF OcXM^Aq^) A. J. PARK & SON
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