Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1989-09-19
1991-02-26
Shen, Cecilia
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
540450, 540596, 540597, 540598, 540601, 544 59, 544 60, 544 82, 544111, 544129, 544130, 544182, 544211, 544212, 544217, 544219, 544309, 544310, 544311, 544312, 544313, 544314, 544331, 544332, 544336, 544357, 544360, 544364, 544405, 546194, 546268, 546275, 546276, 546280, 546281, 546306, 546312, 546345, 548100, 548190, 548194, 548195, 548325, 548333, 548336, 548337, 548469, 549 57, 564180, 564342, 564345, C07D40500, C07D40300, C07D27912, C07D41300, C07D25300, C07D23902, C07D24100, C07D24102, C07D41300, C07D2
Patent
active
049963180
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
Disclosed are 9,10-secosteroids substituted at C.sub.17 with a substituent which has an amino group. These compounds are useful pharmaceutical agents in treating head injury, spinal cord trauma or stroke.
2. Description of the Related Art
Secosteroids are well known to those skilled in the art, see J. Chem. Soc. Chem. Commun., 709 (1982), ibid 1096 (1983) and Tetrahedron 2, 80 (1958). However, none of the prior art secosteroids contain an amine functionality at the C.sub.terminal position of the C.sub.17 side chain. Further, none of these secosteroids is useful in treating, head injury, spinal cord trauma or stroke.
Published PCT patent application Ser. No. 86/01797 discloses amino steroids where the amine portion includes acyclic, aromatic and heterocyclic amine functionality very similar to the amino substituents of the present invention. In published PCT patent application Ser. No. 86/01797, the amino substituent was attached to the terminal carbon atom of the steroidal C.sub.17 side chain. The present invention differs from Published PCT patent application Ser. No. 86/01797 in that the non-amine portion is not a steroid. Published PCT patent application Ser. NO. 86/01797 also disclosed numerous references involving various amines and amino substituents which are incorporated here by reference. Published PCT patent application Ser. No. 86/01797 is the reference which discloses amino substituents most similar to those of the present invention.
German Patent No. 1,087,598 and U.S. Pat. No. 2,920,999 disclose simple 21-amino derivatives of .DELTA..sup.4 -3-keto steroids. The amines include both mono and bis substituted amines. In the cases where the amino group is disubstituted, the two substituents can be cyclized with the attached nitrogen atom to form a heterocyclic amino group (morpholine, pyrrolidine, piperidine, pyridine). The amines were chosen from the group consisting of amino, monoalkylamino, dialkylamino, phenylamino, pyridylamino, benzylamino, picolinylamino, N-alkyl-N-phenylamino, N-alkyl-N-pyridylamino, morpholinyl, pyrryl, pyrrolidyl, piperidino and C-alkylated piperidino, though only N-piperidino, N,N-diethyl and N-methyl-N-phenyl were exemplified.
SUMMARY OF INVENTION
Disclosed is an amino-9,10-secosteroid of formula (I) where:
R.sub.3 is --H or --CO-R.sub.3-1 is C.sub.1 -C.sub.4 alkyl or phenyl optionally substituted with 1 or 2 R.sub.3-2 where R.sub.3-2 is --CH.sub.3, --OCH.sub.3, --F and --Cl;
(C-I) R.sub.9 is R.sub.9-1 :R.sub.9-2 and R.sub.11 is R.sub.11-1 :R.sub.11-2, where one of R.sub.9-1 and R.sub.9-2 is --H and the other taken together with one of R.sub.11-1 and R.sub.11-2 to form a second bond between C.sub.9 and C.sub.11 and the other of R.sub.11-1 and R.sub.11-2 is --H;
(C-II) R.sub.9 is --H:--H and R.sub.11 is .dbd.O;
(C-III) R.sub.9 is --H:--H and R.sub.11 is .alpha.-R.sub.11-3 :.beta.-R.sub.11-4 where one of R.sub.11-3 and R.sub.11-4 is --H or --OH and the other is --H;
(D-I) R.sub.16 is R.sub.16-1 :R.sub.16-2 and R.sub.17 is R.sub.17-1 :R.sub.17-2, where one of R.sub.16-1 and R.sub.16-2 is --H or --CH.sub.3 and the other taken together with one of R.sub.17-1 and R.sub.17-2 forms a second bond between C.sub.16 and C.sub.17, and the other of R.sub.17-1 and R.sub.17-2 is --C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21A R.sub.21B, where Z is .dbd.O, .dbd.CH.sub.2 or R.sub.20-1 :--H where R.sub.20-1 is --H or --CH.sub.3, where n is 0 through 6, where where R.sub.21-1 is --H or C.sub.1 -C.sub.3 alkyl, where heteroaryl is: optionally substituted by 1 or 2 R.sub.21-2, being the same or different, where R.sub.21-2 is --F, --Cl, --Br, C.sub.1 -C.sub.3 alkoxy, --COOH, --NH.sub.2, C.sub.1 -C.sub.3 alkylamino, di(C.sub.1 -C.sub.3)alkylamino, where the alkyl groups are the same or different, 1-pyrrolidinyl-, 1-piperidinyl, 1-hexamethylenimino-, 1-heptamethylenimino-, C.sub.2 -C.sub.4 acylamino and --NH--CHO; different and are --H, C.sub.1 -C.sub.3 alkyl or --CH.sub.2 --CH.dbd.CH.sub.2, atoms marked with an asterisk (*) are bonded to eac
REFERENCES:
patent: 2920999 (1960-01-01), Agnello
Oh-kita et al., Chem. Abst., 105-115530b, abst. of WO86/01797.
J. Chem. Soc. Chem. Commun., 709, (1982).
J. Chem. Soc. Chem. Commun., 1096, (1983).
Tetrahedron 2:80, (1958).
Gall Martin
Higuchi Robert I.
Shen Cecilia
Stein Bruce
The Upjohn Company
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