US 5,175,281 AGranted

Pharmaceutically active pyrimidinylpiperazinylsterioids

AssigneeThe Upjohn Company

InventorsJohn M. McCall, Donald E. Ayer, E. Jonathan Jacobsen, Frederick J. VanDoornik, John R. Palmer, Harold A. Karnes

Life of this patent

Estimating the term…

Abstract

Disclosed are .DELTA..sup.9(11) -steroids (VI) and amino substituted steroids (XI) which contain an amino group attached to the terminal carbon atom of the C.sub.17 -side chain, more particularly amino steroids (Ia and Ib), aromatic steroids (II), .DELTA..sup.16 -steroids (IIIa and IIIb), reduced A-ring steroids (IV), .DELTA..sup.17(20) -steroids (Va and Vb) and .DELTA..sup.9(11) -steroids (VI) which are useful as pharmaceutical agents for treating a number of conditions.

Claims23

Dependent claims

An amino substituted steroid of formula (XI) ##STR37## where:

(A-I) R.sub.6 is.alpha.-R.sub.61 :.beta.-R.sub.62, R.sub.10 is .alpha.-R.sub.101 :.beta.-R.sub.102 and R.sub.7 is .alpha.-H:.beta.-H, where one of R.sub.61 and R.sub.62 is --H, and the other is --H, --F, or C.sub.1 -C.sub.3 alkyl, R.sub.102 is --CH.sub.3, R.sub.101 and R.sub.5 taken together are --(CH.sub.2).sub.2 --C(.dbd.R.sub.33)--CH.dbd. or --CH.dbd.CH--CO--CH.dbd., where R.sub.33 is .dbd.O or .alpha.-H:.beta.-OR.sub.34 or .alpha.-OR.sub.34 :.beta.-H, where R.sub.34 is --H, --CO--CH.sub.3, --CO--C.sub.2 H.sub.5, --CO--C.sub.6 H.sub.5, --CO--O--CH.sub.3 or --CO--O--C.sub.2 H.sub.5 ;
(A-II) R.sub.5 is .alpha.-R.sub.53 :.beta.-R.sub.54, R.sub.6 is .alpha.-R.sub.63 :.beta.-R.sub.64, R.sub.10 is .alpha.-R.sub.103 :.beta.-R.sub.104 and R.sub.7 is .alpha.-H:.beta.-H, where one of R.sub.63 and R.sub.64 is --H, and the other taken together with one of R.sub.53 and R.sub.54 forms a second bond between C.sub.5 and C.sub.6 , R .sub.104 is -CH.sub.3 R.sub.103 and the other of R.sub.53 and R.sub.54 taken together is --(CH.sub.2).sub.2 --C(H)(OH)--CH.sub.2 --;
(A-III) R.sub.10 and R.sub.5 taken together are .dbd.CH--CH.dbd.C(OR.sub.3)--CH.dbd. where R.sub.3 is --H, C.sub.1 -C.sub.3 alkyl, --CO--H, C.sub.2 -C.sub.4 alkanoyl or benzyl, R.sub.6 is .alpha.-R.sub.65 :.beta.-R.sub.66 where one of R.sub.65 and R.sub.66 is --H, and the other is --H, --F, or C.sub.1 -C.sub.3 alkyl and R.sub.7 is .alpha.-H:.beta.-H;
(A-IV) R.sub.5 is .alpha.-R.sub.57 :.beta.-R.sub.58, R.sub.6 is .alpha.-R.sub.67 :.beta.R.sub.68, R.sub.7 is .alpha.-H:.beta.=H and R.sub.10 is .alpha.-R.sub.107 :.beta.-R.sub.108, where one of R.sub.57 and R.sub.58 is --H, R.sub.107 and the other of R.sub.57 and R.sub.58 taken together are --(CH.sub.2).sub.2 --C(.dbd.R.sub.33)--CH.sub.2, where R.sub.33 is as defined above, R.sub.108 is --CH.sub.3, where one of R.sub.67 and R.sub.68 is --H and the other is --H, --F, or C.sub.1 -C.sub.3 alkyl;
(A-V) R.sub.6 is R.sub.69 :R.sub.610, R.sub.7 is R.sub.79 R.sub.710, R.sub.10 is .alpha.-R.sub.109 R.sub.1010, where one of R.sub.69 and R.sub.610 is --H and the other taken together with one of R.sub.79 and R.sub.710 forms a second bond of R.sub.79 and R.sub.710 is --H, R.sub.1010 is --CH.sub.3, R.sub.109 and R.sub.5 taken together are --(CH.sub.2).sub.2 --C(.dbd.R.sub.33)--CH.dbd. or --CH.dbd.CH--CO--CH.dbd., where R.sub.33 is as defined above;
(C-I) R.sub.11 is .alpha.-R.sub.111 :.beta.R.sub.112, where one of R.sub.111 and R.sub.112 is taken together with R.sub.9 to form a second bond between C.sub.9 and C.sub.11 and the other of R.sub.111 and R.sub.112 is --H;
(C-II) R.sub.9 is --Cl and R.sub.11 is .dbd.O or .alpha.-H:.beta.-R.sub.114 where R.sub.114 is --Cl or --OH;
(C-III) R.sub.9 is --H or --F and R.sub.11 is .dbd.O or .alpha.-R.sub.115 :.beta.-R.sub.116, where one of R.sub.115 and R.sub.116 is --H, and the between C.sub.6 C.sub.7, and the other of R.sub.115 and R.sub.116 is --H, --OH or C.sub.1 -C.sub.12 alkoxy;
(C-IV) R.sub.9 is --H or --F and R.sub.11 is .alpha.-O-CO-R.sub.117 :.beta.-H, where R.sub.117 is
(A) C.sub.1 -C.sub.3 alkyl,
(B) C.sub.1 -C.sub.12 alkoxy,
(C) furanyl,
(D) --NR.sub.122 R.sub.123, where one of R.sub.122 and R.sub.123 is --H, methyl or ethyl and the other is --H, C.sub.1 -C.sub.4 alkyl or phenyl,
(E) --X.sub.3 --X.sub.1, where X.sub.3 is --O-- or a valence bond, where X.sub.1 is phenyl optionally substituted with 1 through 2 --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 carboxylic acid acylamino and --NH--CHO or with 1 --F or --CF.sub.3 ;
(D-I) R.sub.16 is R.sub.161 :R.sub.162 and R.sub.17 is R.sub.171 :R.sub.172, where one of R.sub.161 and R.sub.162 is --H or --CH.sub.3 and the other taken together with one of R.sub.171 and R.sub.172 forms a second bond between C.sub.16 and C.sub.17, and the other of R.sub.171 and R.sub.172 is --C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, where Z is .dbd.O, .dbd.CH.sub.2 or R.sub.179 :--H where R.sub.179 is --H or --CH.sub.3, where n is 1 through 6, where R.sub.21 and R.sub.210 are taken together with the attached nitrogen atom to form 1-piperazinyl substituted in the 4-- position with X.sub.2 --(CH.sub.2).sub.j --, where j is 0 through 3 and X.sub.2 is
(1) pyrimidin-4-yl or the N-oxide thereof optionally substituted at the 2- and/or 6-position with R.sub.212 where R.sub.212 is:
(i) -F,
(ii) -Cl,
(iii) -Br,
(iv) C.sub.1 -C.sub.5 alkyl,
(v) -CH.sub.2 --CH.dbd.CH.sub.2,
(vi) -X.sub.1, where X.sub.1 is as defined above,
(vii) -NR.sub.213 R.sub.213 where the R.sub.213 's are the same or different and are -H, C.sub.1 -C.sub.3 alkyl or -CH.sub.2 --CH.dbd.CH.sub.2,
(viii.alpha.) *CH.sub.2 -(CH.sub.2).sub.q --CH.sub.2 --N*-- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, where q is 1 through 5,
(viii.beta.) *CH.sub.2 --CH.sub.2 --(CH.sub.2).sub.c --G--(CH.sub.2).sub.d --CH.sub.2 --CH.sub.2 --N*-- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, where G is --O--, --S--, --SO--, --SO.sub.2 --, or --NHR.sub.214, where R.sub.214 is --H, C.sub.1 -C.sub.3 alkyl, or X.sub.1 as defined above, where c and d are the same or different and are 0 through 2 with the proviso that the total number of ring carbon atoms is 4, 5 or 6,
(ix) 3-pyrrolin-1-yl,
(x) pyrrol-1-yl optionally substituted with C.sub.1 -C.sub.3 alkyl,
(xi) piperidin-1-yl optionally substituted with 1 or 2 C.sub.1 -C.sub.3 alkyl,
(xii) 1,2,3,6-tetrahydropyridin-1-yl,
(xiii) 1-hexamethyleneimino containing a 3- or 4- double bond or 3- and 5-double bonds,
(xiv) 1,4-dihydro-1-pyridinyl substituted in the 4 position by two C.sub.1 -C.sub.3 alkyl being the same or different,
(xv) --OH,
(xvi) C.sub.1 -C.sub.3 alkoxy,
(xvii) --NR.sub.217 --(CH.sub.2).sub.e --Q where Q is 2-pyridinyl where R.sub.217 is --H or C.sub.1 -C.sub.3 alkyl and e is 0 through 3,
(xviii) pyridin-2-, 3-, or 4-yl,
(2) 4-[2-[4-[2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazinyl]ethyl]-piper azinyl, (13)
(D-II) R.sub.16 is .alpha.--R.sub.163 :.beta.13 R.sub.164 where one of R.sub.163 and R.sub.164 is --H and the other is --H, --F, --CH.sub.3 or --OH, and R.sub.17 is .dbd.CH--(CH.sub.2).sub.p --NR.sub.21 R.sub.210, where p is 1 or 2, where R.sub.21 and R.sub.210 are as defined above;
(D-III) R.sub.16 is .alpha.--R.sub.165 :.beta.--R.sub.166 and R.sub.17 is .alpha.--R.sub.175 :.beta.--R.sub.176, where R.sub.165 is --H, --OH, --F or --CH.sub.3 and R.sub.166 is --H, --OH, --F, or --CH.sub.3, with the proviso that at least one of R.sub.165 and R.sub.166 is --H, where R.sub.175 is --H, --OH, --CH.sub.3, --CH.sub.2 CH.sub.3, C.sub.2 -C.sub.7 alkanolyloxy or --O--CO--X.sub.1, where X.sub.1 is as defined above, and where R.sub.176 is --C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, where Z, n, R.sub.21 and R.sub.210 are as defined above;
(D-IV) the 16,17-acetonide of a compound where R.sub.165 is --OH, R.sub.166 is --H, R.sub.175 is --OH and R.sub.176 is --C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, where Z, n, R.sub.21 and R.sub.210 are as defined above;
and pharmaceutically acceptable salts, hydrates and solvates thereof;
with the following overall provisos that:
(I) one of R.sub.161 or R.sub.162 is taken together with one of R.sub.171 or R.sub.172 to form a second bond between C.sub.16 and C.sub.17, only when R.sub.10 is .alpha.-R.sub.101 :.beta.-R.sub.102, .alpha.-R.sub.103 :.beta.-R.sub.104, .alpha.-R.sub.107 :.beta.-R.sub.108 or .alpha.-R.sub.109 :.beta.-R.sub.1010,
(II) R.sub.17 is .dbd.CH--(CH.sub.2).sub.p --NR.sub.21 R.sub.210, only when R.sub.10 is .alpha.-R.sub.101 :.beta.-R.sub.102, .alpha.-R.sub.103 :.beta.-R.sub.104, .alpha.-R.sub.107 :.beta.-R.sub.108 or .alpha.-R.sub.109 :.beta.-R.sub.1010,
(III) R.sub.5 and R.sub.10 taken together are .dbd.CH--CH.dbd.C(OR.sub.3)--CH.dbd., only when R.sub.17 is .alpha.-R.sub.175 :.beta.-R.sub.176 or the 16,17-acetonide of a compound where R.sub.16 is .alpha.-OH:.beta.--H and R.sub.17 is .alpha.--OH:.beta.--C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, and
(IV) R.sub.5 is .alpha.--R.sub.57 :.beta.--R.sub.58, only when R.sub.17 is .alpha.--R.sub.175 :.beta.--R.sub.176 or .alpha.--OH:.beta.--C--(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, or the 16,17-acetonide thereof.

42 more elements

Dependencies are inferred from the claim text.

Facts

Application: 07/749,830Filed 26 Aug 1991 · division
Priority: 12 Sep 1985
Granted: 29 Dec 1992
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07D 213/74
Nitrogen atoms: amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 213/65
One oxygen atom: attached in position 3 or 5
C07D 239/50
Two or more oxygen, sulphur or nitrogen atoms: three nitrogen atoms
C07D 249/14
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…

Family

Serial775,204Parent of this continuation-in-part · filed 12 Sep 1985
Serial811,058Parent of this continuation-in-part · filed 19 Dec 1985
Serial877,287Parent of this continuation-in-part · filed 23 Jun 1986
Serial888,231Parent of this continuation-in-part · filed 29 Jul 1986
Serial121,822Parent of this continuation-in-part · filed 11 May 1987
Serial227,812Parent of this continuation-in-part · filed 3 Aug 1988
Serial229,675Parent of this division · filed 8 Aug 1988
US 5,099,019 AParent of this division
US 5,175,281 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

An amino substituted steroid of formula (XI) ##STR37## where:

(A-I) R.sub.6 is.alpha.-R.sub.61 :.beta.-R.sub.62, R.sub.10 is .alpha.-R.sub.101 :.beta.-R.sub.102 and R.sub.7 is .alpha.-H:.beta.-H, where one of R.sub.61 and R.sub.62 is --H, and the other is --H, --F, or C.sub.1 -C.sub.3 alkyl, R.sub.102 is --CH.sub.3, R.sub.101 and R.sub.5 taken together are --(CH.sub.2).sub.2 --C(.dbd.R.sub.33)--CH.dbd. or --CH.dbd.CH--CO--CH.dbd., where R.sub.33 is .dbd.O or .alpha.-H:.beta.-OR.sub.34 or .alpha.-OR.sub.34 :.beta.-H, where R.sub.34 is --H, --CO--CH.sub.3, --CO--C.sub.2 H.sub.5, --CO--C.sub.6 H.sub.5, --CO--O--CH.sub.3 or --CO--O--C.sub.2 H.sub.5 ;
(A-II) R.sub.5 is .alpha.-R.sub.53 :.beta.-R.sub.54, R.sub.6 is .alpha.-R.sub.63 :.beta.-R.sub.64, R.sub.10 is .alpha.-R.sub.103 :.beta.-R.sub.104 and R.sub.7 is .alpha.-H:.beta.-H, where one of R.sub.63 and R.sub.64 is --H, and the other taken together with one of R.sub.53 and R.sub.54 forms a second bond between C.sub.5 and C.sub.6 , R .sub.104 is -CH.sub.3 R.sub.103 and the other of R.sub.53 and R.sub.54 taken together is --(CH.sub.2).sub.2 --C(H)(OH)--CH.sub.2 --;
(A-III) R.sub.10 and R.sub.5 taken together are .dbd.CH--CH.dbd.C(OR.sub.3)--CH.dbd. where R.sub.3 is --H, C.sub.1 -C.sub.3 alkyl, --CO--H, C.sub.2 -C.sub.4 alkanoyl or benzyl, R.sub.6 is .alpha.-R.sub.65 :.beta.-R.sub.66 where one of R.sub.65 and R.sub.66 is --H, and the other is --H, --F, or C.sub.1 -C.sub.3 alkyl and R.sub.7 is .alpha.-H:.beta.-H;
(A-IV) R.sub.5 is .alpha.-R.sub.57 :.beta.-R.sub.58, R.sub.6 is .alpha.-R.sub.67 :.beta.R.sub.68, R.sub.7 is .alpha.-H:.beta.=H and R.sub.10 is .alpha.-R.sub.107 :.beta.-R.sub.108, where one of R.sub.57 and R.sub.58 is --H, R.sub.107 and the other of R.sub.57 and R.sub.58 taken together are --(CH.sub.2).sub.2 --C(.dbd.R.sub.33)--CH.sub.2, where R.sub.33 is as defined above, R.sub.108 is --CH.sub.3, where one of R.sub.67 and R.sub.68 is --H and the other is --H, --F, or C.sub.1 -C.sub.3 alkyl;
(A-V) R.sub.6 is R.sub.69 :R.sub.610, R.sub.7 is R.sub.79 R.sub.710, R.sub.10 is .alpha.-R.sub.109 R.sub.1010, where one of R.sub.69 and R.sub.610 is --H and the other taken together with one of R.sub.79 and R.sub.710 forms a second bond of R.sub.79 and R.sub.710 is --H, R.sub.1010 is --CH.sub.3, R.sub.109 and R.sub.5 taken together are --(CH.sub.2).sub.2 --C(.dbd.R.sub.33)--CH.dbd. or --CH.dbd.CH--CO--CH.dbd., where R.sub.33 is as defined above;
(C-I) R.sub.11 is .alpha.-R.sub.111 :.beta.R.sub.112, where one of R.sub.111 and R.sub.112 is taken together with R.sub.9 to form a second bond between C.sub.9 and C.sub.11 and the other of R.sub.111 and R.sub.112 is --H;
(C-II) R.sub.9 is --Cl and R.sub.11 is .dbd.O or .alpha.-H:.beta.-R.sub.114 where R.sub.114 is --Cl or --OH;
(C-III) R.sub.9 is --H or --F and R.sub.11 is .dbd.O or .alpha.-R.sub.115 :.beta.-R.sub.116, where one of R.sub.115 and R.sub.116 is --H, and the between C.sub.6 C.sub.7, and the other of R.sub.115 and R.sub.116 is --H, --OH or C.sub.1 -C.sub.12 alkoxy;
(C-IV) R.sub.9 is --H or --F and R.sub.11 is .alpha.-O-CO-R.sub.117 :.beta.-H, where R.sub.117 is
(A) C.sub.1 -C.sub.3 alkyl,
(B) C.sub.1 -C.sub.12 alkoxy,
(C) furanyl,
(D) --NR.sub.122 R.sub.123, where one of R.sub.122 and R.sub.123 is --H, methyl or ethyl and the other is --H, C.sub.1 -C.sub.4 alkyl or phenyl,
(E) --X.sub.3 --X.sub.1, where X.sub.3 is --O-- or a valence bond, where X.sub.1 is phenyl optionally substituted with 1 through 2 --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 carboxylic acid acylamino and --NH--CHO or with 1 --F or --CF.sub.3 ;
(D-I) R.sub.16 is R.sub.161 :R.sub.162 and R.sub.17 is R.sub.171 :R.sub.172, where one of R.sub.161 and R.sub.162 is --H or --CH.sub.3 and the other taken together with one of R.sub.171 and R.sub.172 forms a second bond between C.sub.16 and C.sub.17, and the other of R.sub.171 and R.sub.172 is --C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, where Z is .dbd.O, .dbd.CH.sub.2 or R.sub.179 :--H where R.sub.179 is --H or --CH.sub.3, where n is 1 through 6, where R.sub.21 and R.sub.210 are taken together with the attached nitrogen atom to form 1-piperazinyl substituted in the 4-- position with X.sub.2 --(CH.sub.2).sub.j --, where j is 0 through 3 and X.sub.2 is
(1) pyrimidin-4-yl or the N-oxide thereof optionally substituted at the 2- and/or 6-position with R.sub.212 where R.sub.212 is:
(i) -F,
(ii) -Cl,
(iii) -Br,
(iv) C.sub.1 -C.sub.5 alkyl,
(v) -CH.sub.2 --CH.dbd.CH.sub.2,
(vi) -X.sub.1, where X.sub.1 is as defined above,
(vii) -NR.sub.213 R.sub.213 where the R.sub.213 's are the same or different and are -H, C.sub.1 -C.sub.3 alkyl or -CH.sub.2 --CH.dbd.CH.sub.2,
(viii.alpha.) *CH.sub.2 -(CH.sub.2).sub.q --CH.sub.2 --N*-- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, where q is 1 through 5,
(viii.beta.) *CH.sub.2 --CH.sub.2 --(CH.sub.2).sub.c --G--(CH.sub.2).sub.d --CH.sub.2 --CH.sub.2 --N*-- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, where G is --O--, --S--, --SO--, --SO.sub.2 --, or --NHR.sub.214, where R.sub.214 is --H, C.sub.1 -C.sub.3 alkyl, or X.sub.1 as defined above, where c and d are the same or different and are 0 through 2 with the proviso that the total number of ring carbon atoms is 4, 5 or 6,
(ix) 3-pyrrolin-1-yl,
(x) pyrrol-1-yl optionally substituted with C.sub.1 -C.sub.3 alkyl,
(xi) piperidin-1-yl optionally substituted with 1 or 2 C.sub.1 -C.sub.3 alkyl,
(xii) 1,2,3,6-tetrahydropyridin-1-yl,
(xiii) 1-hexamethyleneimino containing a 3- or 4- double bond or 3- and 5-double bonds,
(xiv) 1,4-dihydro-1-pyridinyl substituted in the 4 position by two C.sub.1 -C.sub.3 alkyl being the same or different,
(xv) --OH,
(xvi) C.sub.1 -C.sub.3 alkoxy,
(xvii) --NR.sub.217 --(CH.sub.2).sub.e --Q where Q is 2-pyridinyl where R.sub.217 is --H or C.sub.1 -C.sub.3 alkyl and e is 0 through 3,
(xviii) pyridin-2-, 3-, or 4-yl,
(2) 4-[2-[4-[2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazinyl]ethyl]-piper azinyl, (13)
(D-II) R.sub.16 is .alpha.--R.sub.163 :.beta.13 R.sub.164 where one of R.sub.163 and R.sub.164 is --H and the other is --H, --F, --CH.sub.3 or --OH, and R.sub.17 is .dbd.CH--(CH.sub.2).sub.p --NR.sub.21 R.sub.210, where p is 1 or 2, where R.sub.21 and R.sub.210 are as defined above;
(D-III) R.sub.16 is .alpha.--R.sub.165 :.beta.--R.sub.166 and R.sub.17 is .alpha.--R.sub.175 :.beta.--R.sub.176, where R.sub.165 is --H, --OH, --F or --CH.sub.3 and R.sub.166 is --H, --OH, --F, or --CH.sub.3, with the proviso that at least one of R.sub.165 and R.sub.166 is --H, where R.sub.175 is --H, --OH, --CH.sub.3, --CH.sub.2 CH.sub.3, C.sub.2 -C.sub.7 alkanolyloxy or --O--CO--X.sub.1, where X.sub.1 is as defined above, and where R.sub.176 is --C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, where Z, n, R.sub.21 and R.sub.210 are as defined above;
(D-IV) the 16,17-acetonide of a compound where R.sub.165 is --OH, R.sub.166 is --H, R.sub.175 is --OH and R.sub.176 is --C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, where Z, n, R.sub.21 and R.sub.210 are as defined above;
and pharmaceutically acceptable salts, hydrates and solvates thereof;
with the following overall provisos that:
(I) one of R.sub.161 or R.sub.162 is taken together with one of R.sub.171 or R.sub.172 to form a second bond between C.sub.16 and C.sub.17, only when R.sub.10 is .alpha.-R.sub.101 :.beta.-R.sub.102, .alpha.-R.sub.103 :.beta.-R.sub.104, .alpha.-R.sub.107 :.beta.-R.sub.108 or .alpha.-R.sub.109 :.beta.-R.sub.1010,
(II) R.sub.17 is .dbd.CH--(CH.sub.2).sub.p --NR.sub.21 R.sub.210, only when R.sub.10 is .alpha.-R.sub.101 :.beta.-R.sub.102, .alpha.-R.sub.103 :.beta.-R.sub.104, .alpha.-R.sub.107 :.beta.-R.sub.108 or .alpha.-R.sub.109 :.beta.-R.sub.1010,
(III) R.sub.5 and R.sub.10 taken together are .dbd.CH--CH.dbd.C(OR.sub.3)--CH.dbd., only when R.sub.17 is .alpha.-R.sub.175 :.beta.-R.sub.176 or the 16,17-acetonide of a compound where R.sub.16 is .alpha.-OH:.beta.--H and R.sub.17 is .alpha.--OH:.beta.--C(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, and
(IV) R.sub.5 is .alpha.--R.sub.57 :.beta.--R.sub.58, only when R.sub.17 is .alpha.--R.sub.175 :.beta.--R.sub.176 or .alpha.--OH:.beta.--C--(.dbd.Z)--(CH.sub.2).sub.n --NR.sub.21 R.sub.210, or the 16,17-acetonide thereof.

42 more elements

Facts

Application

07/749,830Filed 26 Aug 1991 · division

Priority

12 Sep 1985

Granted

29 Dec 1992

Term ends

Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07D 213/74
Nitrogen atoms: amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 213/65
One oxygen atom: attached in position 3 or 5
C07D 239/50
Two or more oxygen, sulphur or nitrogen atoms: three nitrogen atoms
C07D 249/14
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…

Family

Serial775,204Parent of this continuation-in-part · filed 12 Sep 1985

Serial811,058Parent of this continuation-in-part · filed 19 Dec 1985

Serial877,287Parent of this continuation-in-part · filed 23 Jun 1986

Serial888,231Parent of this continuation-in-part · filed 29 Jul 1986

Serial121,822Parent of this continuation-in-part · filed 11 May 1987

Serial227,812Parent of this continuation-in-part · filed 3 Aug 1988

Serial229,675Parent of this division · filed 8 Aug 1988

US 5,099,019 AParent of this division

US 5,175,281 AThis patent

From the US filing history. Foreign family members aren’t listed.