AMINO-9,10-SECOSTEROIDS

Abstract: The amino-9,10-secosteroids of formula (I) of the present invention contain an amino group attached to the terminal carbon atom of the C17-side chain and are useful as pharmaceutical agents for treating a number of conditions including spinal trauma, mild and/or moderate to severe head injury, etc.

Description: AMINO-9.10-SECOSTEROIDS BACKGROUND OF THE INVENTION 1. Field of the Invention Disclosed are 9,10-secosteroids substituted at Z_η 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 Tetrahed¬ ron 2, 80 (1958). However, none of the prior art secosteroids contain an amine functionality at the ^ter xmal position of the C_ side chain. Further, none of these secosteroids is useful in treating, head injury, spinal cord trauma or stroke. Published PCT patent application Serial No 86/01797 discloses amino steroids where the- amine portion includes acyclic, aromatic and heterocyclic amine functionality very similar to the amino sub- stituents of the present invention. In published PCT patent applica¬ tion Serial No 86/01797, the amino substituent was attached to the terminal carbon atom of the steroidal C_ side chain. The present invention differs from Published PCT patent application Serial No 86/01797 in that the non-amine portion is not a steroid. Published PCT patent application Serial No 86/01797 also disclosed numerous references involving various amines and amino substituents which are incorporated here by reference. Published PCT patent application Serial No 86/01797 is the reference which discloses amino sub¬ stituents most similar to those of the present invention. German Patent 1,087,598 and US Patent 2,920,999 disclose simple 21-amino derivatives of Δ -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 (mor- pholine, 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-me hyl-N-phenyl were exemplified. SUMMARY OF INVENTION Disclosed is an amino-9,10-secosteroid of formula (I) where: R3 is -H or -CO-R3.1 where R_. is C 1 -C alkyl or phenyl optionally substituted with 1 or 2 R3.2 where ^-2 is ~ CH 3> -OCH3, -F and -Cl; (C-I) R9 is R9-i:R9-2 and R ll is R ll-l :R ll-2' wnere one of R 9-l and R9-2 is " H and the ot ^ er taken together with one of __ι_ι and R__ .2 to form a second bond between C9 and C__ and the other of χι__ and ^χ.2 s ~H; (C-II) R9 is -H:-H and K. is -0; (C-III) Rg is -H: -H and ^ is --R\\-2'β-Rl\-k where one of χi_3 and .4 is -H or -OH and the other is -H; (D-I) ^g is i6-l ; Rl6-2 an 17 - s 17-l : 17-2' w ^er one of 16-l an 16-2 - s "^ or "CH3 and the other taken together with one of 17-X and χ7_2 forms a second bond between C__ and C_ , and the other of yj-i and χ7„2 is - G( ~ z) " (CH 2 ) n" NR 21A R 2lB' where z i s "°. -CH2 or 20-1 : "H where 20-I s "^ or "CH3, where n is 0 through 6, where (1) -(CH 2 ) m -NR 2 ι.ι-heteroaryl, where m is 2, 3 or 4, where 2I-I is -H or C -C3 alkyl, where heteroaryl is: (a) pyridin-2- (F-l) , 3- (F-2) or 4-yl (F-3) or the N-oxide thereof optionally substituted by 1 or 2 R21-2' De i n tne same or different, where 2I-2 ^ s (i) -F, (ϋ) -Cl, (ϋi) -Br, (iv) C C 5 alkyl, (vi) -aryl, where aryl is phenyl optionally substituted with 1 through 2 -F, -Cl, -Br, C;L-C3 alkoxy, -C00H, -NH2, C_' c 3 alkylamino, di(C- L -C3)alkylamino, where the alkyl groups are the same or different, 1-pyrrolidinyl-, 1-piperidinyl, 1-hexa- methylenimino- , 1-hep amethylenimino- , C2-C acylamino and -NH-CH0 or with 1 -F or -CF3; (vii) - R2 _3 2i_3 where the 2l-3 S are the same or different and are -H, C_-C_ alkyl or -CH2-CH-CH2, (viiiα) *CH 2 -(CH 2 ) q -CH 2 -N*- where the atoms marked with an asterisk (*) are bonded to each other resulting in th formation of a ring, where q is 1 through 5, (vIIi5) *CH2-CH2-(CH2) c -G-(CH 2 ) -CH2-CH2-N* where the atoms marked with an asterisk (*) are bonded to each othe resulting in the formation of a ring (F-4) , where G is -0- , -S-, -SO-, -SO2- or -NHR21.4, where 21-4 is -H, ^-03 alkyl, or aryl a defined above, where c and d are the same or different and are through 2 with the proviso that the total number of ring carbon atom is 4, 5 or 6, (ix) 3-ρyrrolin-l-yl, (F-5) (x) pyrrol-1-yl optionally substituted wit C1-C3 alkyl, (F-6) (xi) piperidin-1-yl optionally substitute with 1 or 2 C ] _-C3 alkyl, (F-7) (xii) 1,2,3,6-tetrahydropyridin-l-yl, (F-8) (xiii) 1-hexamethyleneimino containing a 3- or 4- double bond or 3- and 5- double bonds, (F-9) (xiv) 1,4-dihydro-l-pyridinyl substituted i the 4 position by two C1-C3 alkyl being the same or different, (F-10) (xv) -OH, (xvi) C1-C3 alkoxy, (xvii) -NR2i_7-(CH 2 ) e -Q where Q is 2-pyridi- nyl where R2I-7 s -H or C_-C_ alkyl and e is 0 through 3, (xviii) pyridin-2-, 3- or 4-yl, (xix) -CF3 (xx) -CCI3 (b) 1,3,5-triazin-2-yl or the N-oxide thereof optionally substituted at the 4- and/or 6- position with R2I-2 where 21-2 - s as e fi ne above, (F-ll) (c) pyrimidin-4-yl or the N-oxide thereof optionally substituted at the 2- and/or 6- and 5- and/or 6- position with 21-2 where 2I-2 i as defined above, (F-12) (d) pyrimidin-2-yl optionally substituted at 4- and/or 6- position with 1 or 2 2I-2 as is defined above, (F-13) (e) pyrazin-2-yl optionally substituted with 1 or 2 i-2 as defined above, (F-14) (f) imidazol-2-yl optionally substituted in the 1 position with C ] _-C_ alkyl or -aryl, where aryl is as defined above, and further optionally substituted with 1 or 2 21-2 as defined above, (F-15) (g) l,3,4-triazol-2-yl optionally substituted in the 1 position with C1-C3 alkyl or -aryl, where aryl is as defined above, and further optionally substituted with 21-2 as defined above, (F-16) (h) imidazol-4- or 5-yl optionally- substituted in the 1 position with C -C alkyl or -aryl, where aryl is as defined above, and further optionally substituted with 1 or 2 21-2 as defined above, (F-17) (i) benzo[b]thien-2-yl, (F-18) (j) indol-2-yl, (F-19) (k) benzo[b]thiazol-2-yl, (F-20) (1) benzimidazol-2-yl, (F-21) (m) 4-[2-[4-[2,6-bis(l-pyrrolidinyl)-4- pyrimidinyl] -l-piperazinyl]ethyl]piperazinyl, (F-22) (n) l,2,4-triazin-3-yl optionally substituted at the 5- and/or 6- position with 2I-2 as ^ s defined above, (F-23) (2) (l-piperazinyl)-(C2-C4)alkyl optionally sub¬ stituted in the 4- position with -aryl or -heteroaryl as defined above, (F-24) (3) -heteroaryl, as defined above, (4) -(CH2 m - 4 where m is as defined above and where X4 is (a) -0-CH 2 CH2-Y, where Y is Cχ-C 3 alkylamino, di(C -C3)alkylamino where the alkyl groups are the same or different, C3-C5 alkyleneimino , optionally substituted with 1 or 2 C -C3 alkyl, (b) -NR21.5CH2CH2-Y, where 21-5 is -H or C1-C3 alkyl and Y is as defined above, (c) -(CH 2 ) g -N( 2i_ 5) -heteroaryl, where g is 2, 3 or 4, and where 2I-5 and heteroaryl are as defined above, (5) -(CH2) m -NR 21 _ 6 R 21 _ 8 , where R 21 _ 6 is -H or Cχ-C3 alkyl and 21-8 ^ s -aryl or -heteroaryl as defined above, or 21-6 an 21-8 are taken together with the attached nitrogen atom to form a saturated mono-nitrogen C3-C6 heterocyclic ring and where is as defined above, (6) -(CHCH 3 ) b -(CH 2 )f-R2i.9 I where b is 0 and f is 1 through 3 or b is one and f is 0 through 3, where R 2 χ_g is phenyl substituted with 1 through 3 -OH, C-_-C_ alkoxy, -NR 2 _ o R 21-ll where R 21-10 an 21-ll are t * ιe same or different and are -H, C -C3 alkyl or are taken together with the attached nitrogen atom to form a C4.C cyclicarαino ring, (7) -(CH2>i-heteroaryl, where i is 1 through 4 an heteroaryl is as defined above, (8) (l-piperazinyl)acetyl substituted in the 4- position by heteroaryl where heteroaryl is as defined above, (F-25) (9) (l-piperazinyl)carbonylmethyl substituted in the 4- positionby -heteroarylwhereheteroaryl is as definedabove, and(F-26) (B) R 2 IB s (1) -H, (2) Cχ-03 alkyl, (3) C5-C7 cycloalkyl, (4) -(CH2) m -NR 2 .χ-heteroaryl, where m, 21-1 and heteroaryl are as defined above, (5) (l-piperazinyl)-(C 2 -C4)alkyl optionally sub¬ stituted in the 4- position with -aryl or -heteroaryl as defined above, (F-24) (6) - CH2) m - 4, where m and X4 are as defined above, (7) -(CH 2 ) m -NR21-6 R 21-8> where m, 21-6 and R 21-8 are as defined above, (8) -(CHCH 3 ) -(CH 2 )f-R2i_9, where b, f and R 2 ι_9 are as defined above, (C) 2IA and R 21B are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of (1) 2-(carboxy)-l-pyrrolidinyl optionally as the C1-C3 alkyl ester or as a pharmaceutically acceptable salt, (F-27) (2) 2-(carboxy)-l-piperidinyl optionally as the C -C3 alkyl ester or as a pharmaceutically acceptable salt, (F-28) (3) 2-(carboxy)-l-hexamethyleneimino optionally as the C1-C3 alkyl ester or as a pharmaceutically acceptable salt, (F-29) (4) 2-(carboxy)-l-heptamethyleneimino optionally as the C1-C3 alkyl ester or as a pharmaceutically acceptable salt,(F-30) (5) 1-piperazinyl substituted in the 4- position with R2i_i2"CO-(CH2) - where 2I-12 is -heteroaryl, -NR 2 l-13heteroaryl and 2-furanyl, where 21-13 is -H or C1-C3 alkyl, where j is 0 through 3 and aryl is as defined above, (F-31) (6) 1-piperazinyl substituted in the 4- position with heteroaryl-(CH2)ή-, where heteroaryl and j are as defined above, (F-32) (7) 1-piperazinyl substituted in the 4- position with aryl-(CH2) - , where aryl and j are as defined above, (F-33) (8) 4-hydroxy-l-piperidinyl substituted in the 4- position with aryl as defined above, (F-34) (9) 1-piperazinyl substituted in the 4- position with heteroaryl-NR21-13" C0_ ( CH 2^i" > where heteroaryl, R21-I3 and i are as defined above; (F-35) (D-II) R g is α-Ri6-3 : ^-Ri6-4 where one of Rχg_3 and Rχg_4 is -H and the other is -H, -F, -CH3 or -OH, and R 17 is -CH-(CH 2 ) p - 2iA- 21B > where p is 1 or 2, where 2 IA and 21B re as defined above; (D-III) R 16 is α-R 16 _ 5 :y9-R 16 _ 6 and R 17 is o-R 17 _ 5 :0-R 17 _ 6 , where R 16-5 is " H » " 0H > " F or " CH 3 and R 16-6 is ~ H > "0H ' ~ F « or "CH 3> with the proviso that at least one of χg.5 and Rχg.g i s "^ > where R17.5 is -H, -OH, -GH3, -CH2CH3, C2-C7 alkanoyloxy or -0-CO-aryl, where aryl is as defined above, and χ7. is -C( « Z -(CH2) n - 2i A 2iB» where Z, n, 2 1A an R 21B are as defined above; (D-IV) the 16,17-acetonide of a compound where χ _5 "OH, R 16 . 6 is -H, R 17 . 5 is -OH and R 17 _g is -C(-Z)-(C3^) n -HR 2 _A R 21B» where Z, n, - 2IA and R 21B are as defined above; (D-V) R 16 is α- R i6-7 : 0- R 16-8 and R 17 is α-C(-Z)-(CH 2 ) n -N- 2lA R 21B : ^" where Z, n, 2IA an R 21B are as defined above, where 16-7 ls ° H ' ■ ° H ' " F or _CH 3 and R 16-8 is " H > _0H ' _F ' or " CH 3» v til the proviso that at least one of χg_5 an R 16-6 s "^ and pharmaceutically acceptable salts thereof, and hydrates and solvates thereof. Further disclosed are amino-9,10-secosteroids (I) where R^g and 7 are (D-II) R-χg is --R_ -3 '-β-^-16-^ where one of χg_3 and χ _4 is -H and the other is -H, -F, -CH 3 or -OH, and R 17 is -CH-(CH 2 ) p - R2iA- R 2IB; (D-III) R 16 is a-R 16 . 5 :β-R 16 . 6 and R 17 is α-R 17 _ 5 : / S-R 17 .g, where R 16-5 is _H > -° H > " F or "CH 3 and R 16-6 is _H > ' 0H ' _F > or _CH 3> vith the proviso that at least one of Rχg_5 and Rχg_g is -H, where Rχ _5 is -H, -OH, -CH3, -CH2CH3, C 2 -C 7 alkanoyloxy or -0-CO-aryl, and where R 17-6 is -C(-Z)-(CH 2 ) n -NR 21A R2iB; (D-IV) the 16,17-acetonide of a compound where Rχg.5 is -OH, R 16 .g is -H, R 17 _5 is -OH and R 17 _ is -C(-Z)-(CH 2 ) n -NR 2lA R 2 iB; (D-V) R 16 is -R 16 . 7 :/9-R 16 . 8 and R 17 is α-C(-Z) - (CH 2 ) n -N- R 21A R 21B : ^" H where Z, n, 2IA and R 21B are as defined above, where R 16-7 is •H ' ■ ° H > ' F or "CH 3 and R 16-8 is 'H > -° H > _F - or "CH 3- with the proviso that at least one of χ .5 and Rχg_g is -H. Also disclosed are amino-9,10-secosteroids (I) where 7 is α-R 17 _ 5 :/3-Rι .g, where 17.5 is -H, -OH, -CH3, -CH 2 CH 3 , C 2 -C 7 alkanoyloxy or -O-CO-aryl, and where Rχ 7 .g is -C(-Z)-(CH 2 ) n - N^IA^IB- Additionally disclosed are amino-9,10-secosteroids (I) where R 7 is -CH-(CH 2 ) p -NR 2lA R 21B . Further disclosed are amino-9,10-secosteroids (I) 1 where R- is =0. Also disclosed are amino-9,10-secosteroids (I) where R9 is 9-l :R 9-2 an ll i s R ll-l :R ll-2' where one of Rg.χ and Rg_ 2 i -H and the other taken together with one of n_ι and R__.2 to form a second bond between C9 and C__ and the other of χi-1 and R__ .2 is -H. DETAILED DESCRIPTION OF THE INVENTION The amino-9,10-secosteroids (I), also known as octahydro indenones or indenes, of the present invention can be thought of as being made of two parts, an amine portion and a secosteroid portion. The desired amino-9,10-secosteroids (I) are preferably prepared by condensing the desired amine portion with the desired secosteroid portion. The preferred amino-9,10-secosteroids (I) have a keto func¬ tionality at what is C__ of a steroid. Therefore, one either starts with a 11-keto steroid (corticoid or non-corticoid) or the cor¬ responding llα- or 110-hydroxy steroid, and oxidizes it to the cor¬ responding 11-keto steroid by methods well known to those skilled in the art, preferably pyridinium chlorochromate/sodium acetate in a solvent such as methylene chloride; see, EXAMPLE 2. EXAMPLE 1 demonstrates one convenient method to protect the 17α- and 21-hydroxy groups during the oxidation of the secondary alcohol at C\ . The intact Δ 1, -3-keto steroid starting material is then converted to a secosteroid by methods well known to those skilled in the art, see for example J. Chem. Soc. Chem. Commun., 709 (1982), ibid 1096 (1983) and Tetrahedron 2, 80 (1958). Preferred is the process using lithium and ammonia in THF; see, EXAMPLE 3. The free hydroxyl groups of the C 7 -side chain may be appropriately protected as determined and by procedures known to those skilled in the art. If a "Δ^CH)"-secosteroid is desired then it is preferable to use samarium iodide or n-tributyl tin hydride on the xanthate ester of an 11-hydroxy steroid. Next, the hydroxyl group at the C5 position of the secosteroid (C3 of a steroid) is optionally protected by methods well known to those skilled in the art, for example as the benzyl ether; see, EXAMPLE 4. Next, the protecting groups on the C_ j side chain are removed by methods well known to those skilled in the art appropriate for the particular protecting group. For example, if there are hydroxy groups at 17 and 21 of the corticoid type starting material, and they are protected as the ace onide, this group is readily removed by acid as is well known to those skilled in the art, see EXAMPLE 5. This is done so as to be able to functionalize the position to which the amine will attach with a good leaving group such as tosylate, mesylate, chloride, bromide, iodide, and equivalents thereof, see EXAMPLE 6. Next what corresponds to the "21-position B of the parent steroid is converted from a hydroxy functionality to a good leaving group such as chloride and/or tosylate. The use of p-toluenesulfonyl chloride produces both the chloro and tosyl derivatives. This mixture can be separated if desired. However, since both react with the amines to produce the desired amino-9,10-secosteroids (I), it is preferred to react the mixture of chloro and tosyl derivatives. Alternatively and preferably the leaving group, when chloride, can be introduced by use of triphenylphosphine and carbon tetrachloride, see EXAMPLE 15. The desired secosteroid with a good leaving group in the position to which it is desired to attach the amine, and the desired amine are condensed in an aprotic solvent such as acetonitrile, DMF, THF, methylene chloride, DMA, ether and the like containing a base. It is preferred that the solvent be DMF or if a mixture, contain a high % of DMF. It is further preferred that the condensation take place in the presence of an iodide, such as sodium or potassium. Suitable bases include carbonate, bicarbonate, triethylamine, diisopropylethylamine and the like. Last, any remaining protecting groups removable by hydrogenoly¬ sis are removed by methods well known to those skilled in the art; see EXAMPLES 8, 10 and 12 to produce the desired amino-9,10-seco¬ steroid (I) . Alternatively, cyclohexadiene can be used in place o cyclohexene. If it is desired that R^χ be α-H: ?-0H or α-0H: -H, the compoun where R^χ is -0 is reduced with sodium borohydride or lithiu selectride. Further, if it is desired that there be a double bond in the position C9 to C__ of the parent steroid (one of R9.1 or R9.2 are taken together with one of n- ] _ and n-2 to form a second bond between C9 and C__) the 11-hydroxy form is dehydrated by means well known to those skilled in the art or preferably one forms the Δ 'H' double bond when one transforms the steroid to the secosteroid by the process disclosed in J. Chem. Soc. Chem. Commun., 709 (1982). If it is desired that the substituent at C_ a be -H rather than -OH, the hydroxyl group can be removed by reaction with TMS-I (trimeth lsil l iodide). This can be done before or after the steroid is converted to the secosteroid, preferably before. It is preferred that the condensation of the amine and secos- teroid be the desired amine and desired secosteroid with the excep¬ tion of readily removable protecting groups. Alternatively, in principle, a (derivative) form of the secosteroid not necessarily desired as the final product (I) , can be reacted in its c terminal 21-halo, 21mesylate or 21- osylate form with the appropriate amine to afford an amino-9,10-secosteroid. Following this, the secosteroid nucleus itself can be modified to produce the desired amino-9,10- secosteroid (I). While this is an alternative process, in principle, to produce the amino-9,10-secosteroids (I) of the present invention, in practice it is an undesirable method compared to the preferred process of reacting the C term χ na halo, tosyl or mesyl analog corre¬ sponding to the secosteroid portion of desired amino-9,10-seco¬ steroids (I) , with an amine corresponding to the amine portion of the desired amino-9,10-secosteroids (I) as is apparent to one skilled in the art. Yet another alternative procedure, in principle, to produce some of the amino-9,10-secosteroids (I) of the invention which involve amino substituents which can be thought of as having 2 or more components, can be produced by first reacting the halo, tosyl or mesyl secosteroid with a portion of the desired amine substituent to form an aminosecosteroid in which there is an amine substituent at the C termj _ na -position followed by further reaction of the amino portion of the amino-9,10-secosteroid to produce the complete amine substituent at the C term χ na position. While this is an alternative process in principle, in practice it is usually undesirable compared to the preferred process. It is preferred that the R3 group is -H, acetyl or benzyl. It is more preferred that R3 be -H. In what is known to those skilled in the art as the C-ring of a steroid, the substitution includes 11-keto, Δ' ϋ), and 11- (a/β) - hydroxy. It is preferred that the substitution be 11-keto. With the Δ^°-9,10-secos eroid (I), it is preferred that the sub¬ stituent at C__ be -H. With the other 9,10-secosteroids (I) having two substituents at C s it is preferred that the substituent be either two -H's or a -H and a -CH3. If -CH3, it is preferred that it be in the a configuration. It is preferred that the side chain at C_η be -C(-Z)-(CH2) n -N- 21A 21B- c s preferred that Z is -0 or -H,-H, it is more prefer- red that Z is -0. It is preferred that n is 1. It is preferred that 21A and 21B ^ e taken together with the attached nitrogen atom to form a heterocyclic ring. It is preferred that the heterocyclic ring be 1-piperazinyl substituted in the 4- position with -(CH2)-ϊ-hetero¬ aryl (F-32) or 1-piperazinyl substituted in the 4- position with -(CH2>j-aryl (F-33) . It is more preferred that the heterocyclic ring be 1-piperazinyl substituted in the -position with - (CR_) -hetero¬ aryl. It is preferred that j is 0. With the substituent - CH2)j- heteroaryl, it is preferred that heteroaryl be selected from the group consisting of l,3,5-triazin-4-yl substituted in the 2- and/or 6- position with 2-pyridinyl, pyrimidin-4-yl substituted in the 2- and/or 6- position with 1-pyrrolidinyl, pyrimidin-4-yl substituted in the 2- and/or 6- position with 4-morpholin l, l,3,5-triazin-4-yl substituted in the 2- and 6- position with 1-pyrrolidinyl and pyridinyl substituted in the 3- position with - R21.3 2I-3 where one of 2I-3 i -H and the other is C2 alkyl. It is preferred that the compounds not be the N-oxide. It is also preferred that heteroaryl be selected from the group consisting of (a) l,3,5-triazin-4-yl optionally substituted in the 2- and/or 6- position with 2i-2> (b) pyrimidin-2-yl optionally substituted at 4- and/or 6 position with 1 or 2 2X-2> (c) pyrimidin-4-yl optionally substituted at the 2- and/or 6- position with R 2 χ-2 and (d) pyridin-2-yl optionally substituted by 1 or 2 R2X-2- bein the same or different. It is further preferred that heteroaryl b selected from the group consisting of (a) l,3,5-triazin-4-yl substituted at the 2- and 6- positio with pyrrolidine or diethylamine, (b) pyrimidin-2-yl optionally substituted at the 4- and 6- position with pyrrolidine, (c) pyrimidin-4-yl optionally substituted at the 2- and 6- position with pyrrolidine" or diethylamine, (d) pyridin-2-yl and (e) pyridin-2-yl substituted with pyrrolidine, ethylamine or diethylamine. It is preferred that the heterocyclic ring be selected from the group consisting of 4-(2-pyridinyl)-l-piperazinyl, 4- [4,6-bis(2-propenylamino)-l,3,5-triazin-2-yl]-1-piperazinyl, 4- [2,6-bis(l-pyrrolidinyl)-4-pyrimidinyl] -1-piperazinyl, 4- [2,6-bis(morpholino)-4-pyrimidinyl] -1-piperazinyl, 4-[4,6-bis(die hylamino)-2-pyrimidinyl] -1-piperazinyl, 4- [4,6-bis(l-pyrrolidinyl)-l,3,5-triazin-2-yl] -1-piperazinyl, 4- [3,6-bis(diethylamino)-2-pyridinyl]-1-piperazinyl, 4- [3-(ethylamino)-2-pyridinyl] -1-piperazinyl, 4- [6-(diethylamino)-2-pyridinyl] -1-piperazinyl, 4-[4,6-bis(2-ρyridinyl)-l,3,5-triazin-2-yl]-1-piperazinyl and 4- [2,6-bis(2-pyridinyl)-4-pyrimidinyl] -1-piperazinyl. It is preferred that the amino-9,10-secosteroid (I) be selected from the group consisting of 3a-methyl-3 -hydroxy-7- [2- (5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- (2 ,6-bis(1-pyrrolidinyl)-4-pyrimidinyl)-1-piperazinylj cetyl] - octahydro-5H-inden-5-one, 3a-methyl-3α-hydroxy-7- [2-(5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- (2-pyridinyl) -l-piperazinyl]acetyl]octahydro-5H-inden-5-one, 3a-methyl-3α-hydroxy-7- [2- (5-hydroxy-2-me hylphenyl)-ethyl] -3- [2- [4- [3- (ethylamino) -2 -pyridinyl] -1-piperazinyl] acetyl] -octahydro- 5H- inden- 5 - one , 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl]-3-[2-[4-(2,6- bis(l-pyrrolidinyl) -4-pyrimidinyl) -1 -piperazinyl] ethyl] -3α- octahydro - 5H- inden- 5 -one, 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl]-3-[2-[4-[3- (ethylamino) -2-pyridinyl] -1-piperazinyl] ethyl] -3α- octahydro -5H- inden-5-one, 3a-Methyl- 3α-hydroxy-7- [2- (5-hydroxy-2-methylphenyl) -ethyl] -3- [2- [4- [2 , 6-bis(2-pyridinyl) -4-pyrimidinyl]-l-piperazinyl]acetyl] - octahydro - 5H - inden- 5 - one , 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl]-3-[2-[4-[3- (ethylamino) -2-pyridinyl] -1-piperazinyl] ethylidene] -3α-octahydro-5H- inden-5-one, 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl]-3-[2-[4-[3- (ethyla ino) -2-pyridinyl] -1-piperazinyl] acetyl] -3α-octahydro-5H- inden-5-one, 3a-methyl-7- [2- (5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4-(2,6- bis(l-pyrrolidinyl) -4-pyrimidinyl) -1 -piperazinyl] ethyl] -3α- octahydro - 5H- inden- 5 -one, 3a-methyl-7- [2- (5-hydroxy-2-methylphenyl)ethyl] -3α- [2- [4-(2,6- bis(l-pyrrolidinyl) -4-pyrimidinyl) -l-piperazinyl]acetyl] -3/5-octa- hydro - 5H- inden- 5 - one , 3a-methyl = 7-[2-(5-hydroxy-2-methylphenyl)ethyl]-3α-[2-[4-[3- (ethylamino) -2-pyridinyl] -1-piperazinyl] acetyl] - 3β -octahydro -5H - inden- 5 -one, 3a-methyl- 3 / 5- [2- [4- [3, 6-bis (diethylamino) -2-pyridinyl] -1-piper- azinyl] cetyl] -7- [2- (5-hydroxy-2-methylphenyl)ethyl] - 3α- octahydro -5H- inden- 5 - one , 7a-methyl-l - [2- [4- [3- (ethylamino) -2-pyridinylJ-l-piperazinyl] - acetyl] -4α-[2-(5 -hydroxy- 2 -me thy lphenyl) -ethyl] -2, 3, 3aα, 4, 7, 7a- hexahydr o - Δ^ - 1H - inden , 7a-methyl-4α- [2- (5 -hydroxy -2 -me thy lphenyl) -ethyl] -1 / 9- [2- [4- (2 , 6- bis(l-pyrrolidinyl)-4-pyrimidinyl)-l -piperazinyl] acetyl] -2, 3 , 3aα, 4, 7, 7a-hexahydro-Δ -1H- indene. The amino -9, 10 -secosteroids (I) of the present invention are reacted with acids to form amine salts by methods known to those skilled in the art and the resulting salts are more water soluble and therefore preferable to use when an aqueous formulation is desire such as a solution for IV use. Generally the __nino-9 , 10-secosteroid (I) possess one or more basic nitrogen atoms to be converted to a acid addition pharmaceutically acceptable salt. However, when n is 0 and Z is -0 and the compound does not contain another nitrogen atom, they will not form salts suitable as pharmaceuticals. The pharm¬ aceutically acceptable salt forms of the amino substituted steroids (I) are generally preferred over the free base form since the salts have greater water solubility and form crystals more suitable for pharmaceutical purposes. An acid addition salt of the amino-9,10- secosteroids (I) can be converted to the free base, which can be converted to any desired pharmaceutically acceptable acid addition salt by methods known to those skilled in the art. It is preferred that the acid addition salt be prepared by reacting the free base of the amino -9, 10 -secosteroids (I) with an approximately stoichiometric amount of an acid, such as hydrochloric, hydrobromic, hydroiodic, sulfuric, phosphoric, acetic, lactic, citric, succinic, benzoic, salicylic, pamoic, cyclohexanesulf mic , aethanesulf onic , naph¬ tha lenesulfonic , p-toluenesulfonic, maleic, fu aric, oxalic acid and the like.„ It is preferred that the acid be selected from the group consisting of hydrochloric, maleic, methanesulfonic and fumaric acids. The amino- 9, 10- secosteroids (I) and acid addition salts thereof can be isolated as hydrates or solvates, and such forms are regarded as equivalent to the corresponding amino -9, 10- secosteroids (I) not containing water or solvent. The amino-9,10-secosteroids (I) of the present invention are useful pharmaceutical agents in treating a number of different medical conditions in humans and useful warm blooded animals . In humans, the amino -9, 10 -secosteroids (I) of the present invention are useful in treating spinal trauma, mild and/or moderate to severe head injury, subarachnoid hemorrhage and subsequent cerebral vasospasm, ischemic (thromboembolic) stroke, excess mucous secretion, asthma, muscular dystrophy, adriamycin- induced cardiac toxicity, adriamycin induced cytotoxicity during anti-cancer therapy, Parkinsonism, Alzheimer's disease, other degenerative neurological disorders, multiple sclerosis, organ damage during reperfusion after transplant, skin graft rejection, hemorrhagic, traumatic and septic shock, and conditions such as severe burns, ARDS, inflammatory diseases such as osteo- or rheumatoid arthritis, nephrotic syndrome (immunological) , systemic lupus erythematosis, allergic reactions, atherosclerosis, inflammation (for example dermatological, in- flammatory and psoriasis conditions), emphysema, stress induced ulcers, cluster headaches, complications from brain tumors, radiation damage and damage after MI, infant hypoxia syndrome and such opthai- mic disorders such as uveitis and optic neuritis. In humans, the amino-9,10-secosteroids (I) are useful in preventing damage following cardiopulmonary resuscitation, neurolo¬ gical or cardiovascular surgery and from cardiac infarction. The amino-9,10-secosteroids (I) are useful for reducing the side effects of the tetracycline anti-neoplastic agents such as adriamycin and daunomycin. Generally, the amino-9,10-secosteroids (I) are useful in the same way as glucocorticoid pharmaceuticals for the treatment of the above human conditions as well as the animal conditions listed below. While the amino-9,10-secosteroids (I) are useful in both humans and animals in treating many of the same conditions and preventing damage from the same problems as the glucocorticoids, the amino-9,10-secosteroids (I) are useful- in treating a number of conditions and preventing damage from conditions where the glucocor¬ ticoids are not useful. The amino-9,10-secosteroids (I) have no glucocorticoid activity and therefore, unlike the glucocorticoids, they can be given daily for long periods of time (used chronically) without the side effects associated with the glucocorticoids. This is a distinct advantage. It is to be understood that each of the amino-9,10-secosteroids (I) is useful to a different degree for treating each of the condi- tions above. However, as is known to those skilled in the art, some of the amino-9,10-secosteroids (I) are better for treating some conditions and others are better for treating other conditions. In order to determine which compounds are better than others for a particular condition one can utilize known tests that do not require experimentation but only routine analysis. For example, the fertile egg or chick embryo assay of Folkman, Nature 288, 551 (1980) or Science 221, 719 (1983), discloses an assay to determine antiangiogenie activity which is indicative of irihibi- tion of tumor growth and anti-cancer utility. Because of the abilit of the compounds which are active in the Folkman embryo test t inhibit tumor growth, ' they are useful in the treatment of variou diseases and conditions, especially various forms of cancer Accordingly, they are administered to animals and humans to prolon survival or reduce pain and/or discomfort secondary to tumor growt and the alike. Further, the arachidontic acid LD50 test of Kohler Thrombosis Res., 9, 67 (1976), identifies compounds which ar antioxidants, which inhibit lipid peroxidation, and/or which inhibi the prostaglandin cascade and are useful in treating spinal trauma, mild and/or moderate to severe head injury, degenerative neurologica disorders, etc. Another method useful for determining which par¬ ticular compounds inhibit lipid peroxidation and which are therefor useful in treating spinal trauma, mild and/or moderate to severe hea injury, degenerative neurological disorders, etc is described b Pryor in Methods of Enzymology 105, 293 (1984). Further, the mous head injury assay of Hall, J. Neurosurg. , 62, 882 (1980) discloses a assay from which one skilled in the art can readily determine whic particular amino-9,10-secosterords (I) are useful in the acute treatment of spinal trauma or mild and/or moderate to severe hea injury. Additionally, the cat 48 hr motor nerve degeneration model of Hall et al, Exp. Neurol., 79, 488 (1983) discloses a routine assay from which one skilled in the art can readily determine which particular amino-9,10-secosteroids (I) are useful in treating chronic degenerative neurological disorders such as Parkinsonism, Alzheimer's disease etc. H. Johnson in Int. Arch. Allergy Appl. Immunol., 70, 169 (1983) has described the ascaris sensitized rhesus monkey assay for anti-asthma drugs. The standard conditions for treatment are to give the amino- 9,10-secosteroids (I) orally or parenterally, e.g. IV (that is by injection, infusion or continuous drip) or IM, with a standard dose of about 0.05 to about 100 mg/kg/day, one to four times daily. For treating spinal trauma, mild and moderate to severe head injury, damage following cardiopulmonary resuscitation, cardiac infarction, organ damage during reperfusion after transplant, hemor- rhagic, traumatic and septic shock, severe burns, ARDS, and nephrotic syndrome and preventing skin graft rejection, the standard conditions are used. Typical treatment will involve an initial loading dose, e.g. an IV dose of 0.01 mg to 1 mg/kg followed by maintenance dosing e.g. IV infusion for a day to a week depending on the particular condition of the patient and the particular compound used. This may be supplemented with IM or oral dosing for days, weeks or months to prevent delayed neuronal degeneration in neurological applications (eg spinal trauma, head injury). In treating subarachnoid hemorrhage and subsequent cerebral vasospasm or ischemic (thromboembolic) stroke the standard conditions are used and patients at risk are pre-treated orally. In treating excess mucous secretion and asthma the amino-9,10- secosteroids (I) are administered orally, IV and by inhalation in the standard dose. In treating excess mucous secretions the dose of the amino-9,10-secosteroids (I) used is from about 0.05 to about 100 mg/kg/day. The frequency of administration is one through 4 times daily. The oral administration of the amino-9,10-secosteroids (I) to treat excess mucous secretions may go on for months or even years. The susceptible individuals can be pre-treated a few hours before an expected problem. The IV dose is about 0.05 to about 50 mg/kg/day. The aerosol formulation contains about 0.05 to about 1.0% of the amino-9,10-secosteroids (I) and is administered or used about four times daily as needed. In treating cancer, muscular dystrophy, Parkinsonism, Alz¬ heimer's disease and other degenerative neurological disorders (amyotrophic lateral sclerosis; multiple sclerosis) the amino-9,10- secosteroids (I) are administered orally using a dose of about 0.05 to about 100 mg/kg/day, administered or used one to four times a day. The treatment may go on for years. In addition, utility in cancer as well as other disorders or physiological phenomena dependent on angiogenesis or neovasculariza- tion such as embryo implantation (antifertility), arthritis, and atherosclerosis is exhibited with the amino-9,10-secosteroids (I) with or without co-administered oral heparin or systemic heparin fragments, see Science 221, 719 (1983). In treating adriamycin-induced cardiac toxicity and cytotoxicity during anti-cancer therapy the amino-9,10-secosteroids (I) are administered orally or IV using a dose of about 0.05 to about 100 mg/kg/day, preferably about 0.5 to about 10 mg/kg/day. The amino- 9,10-secosteroids (I) are preferably given concomitantly with IV adriamycin or the individual is pre-treated with the amino-9,10- secosteroids (I) . For prophylaxis prior to and preventing damage after neurologi¬ cal or cardiovascular surgery the amino-9,10-secosteroids (I) are used according to the standard conditions. The patient can be pretreated with a single IV or IM dose just prior to surgery or orally before and after surgery. In treating osteo- or rheumatoid arthritis and other inflam¬ matory diseases the amino-9,10-secosteroids (I) are given orally or IM in doses of about 0.05 to about 100 mg/kg/day, one to four times daily. Orally the drug will be given over a period of months or years alone or with other steroidal agents. The initial dose with some severe rheumatoid patients may be given IV and followed with an IV drip for up to 24 hr or more. In .addition, intra- rterial administration may be employed. In treating drug allergic reactions the amino-9,10-secosteroids (I) are given in a dose of about 0.05 to 100 mg/kg/day, administered one to four times daily orally and IV. Typical treatment would be an initial IV loading dose followed by oral dosing for a few days or more. In treating atherosclerosis and emphysema the amino-9,10- secosteroids (I) are given orally in a dose of about 0.05 to about 100 mg/kg/day, one to four times daily for months or years. In treating dermatological inflammatory conditions including psoriasis the amino-9,10-secosteroids (I) are given orally in a dose of about 0.05 to about 100 mg/kg/day, one to four times daily or applied topically as a cream, ointment or lotion or equivalent dosage form in a concentration of about 0.05 to about 5% as long as needed. In treating these conditions the amino-9,10-secosteroids (I) can be used with steroidal agents. In treating Alzheimer's disease the amino-9,10-secosteroids (I) are given orally in a dose of about 1 to about 100 mg/kg/day, one to four times daily. The amino-9,10-secosteroids (I) are useful in the prevention and treatment of stress ulcers and of gastric intolerance caused by drugs such as nonsteroidal anti-inflammatory compounds (NOSAIDS). Stress ulcers are ulcers that develop after exposure to severe conditions such as trauma, burns, sepsis, extensive surgery, acute illnesses, and the like. Patients in intensive care units are particularly prone to develop stress ulcers. Stress ulcers also include lesions that can lead to upper gastrointestinal bleeding; such bleeding is likely to be prevented or stopped by these compounds. NOSAC includes drugs such as ibuprofen, aspirin, indomethacin, naproxen, piroxicam and the like that are usually taken for analgesia, and that are often associated with gastrointestinal intolerance characterized by pain and lesions that may lead to bleeding. The amino-9,10-secosteroids (I) will be administered preferentially by the oral route either as tablets, capsules or liquids, in doses ranging from 5 to 500 mg, two to four times a day. The treatment would be either preventive, i.e., starting before ulcers have formed in patients at risk of developing such lesions, or therapeutic, i.e., after the ulcers have formed. In patients whose clinical condition precludes swallowing the oral dosage forms, the amino-9,10-secosteroids (I) would be given either through a nasogastric tube, or parenterally, i.e., IV or IM. The parenteral doses would range from about 1 to about 100 mg and be administered one to four times a day or by IV. In dogs, the amino-9,10-secosteroids (I) are useful in treating head and spinal trauma, intervertebral diseases (slipped disk) , traumatic shock, flea bite and other allergies. In horses, the amino-9,10-secosteroids (I) are useful in treating endotoxic or septic shock which follows colic, pretreatment before surgery for colic and treatment of Founder (la initis) . In cattle, the amino-9,10-secosteroids (I) are useful in treating acute coliform mastitis, bovine mastitis and acute allergic reaction to feed lot vaccination. In pigs, the amlno-9,10-secosteroids (I) are useful in treating porcine stress syndrome and thermal stress syndrome. The term treatment or treating as used in this patent is used broadly and includes both treatment of an existing condition as well as preventing the same condition from occurring where such is possible as Is well known to those skilled in the art. For example, the amino-9,10-secosteroids (I) can be used to treat existing asthma conditions and to prevent future ones from occurring. For example, the amino-9,10-secosteroids (I) treat spinal trauma and prevent rejection of skin grafts. The amino-9,10-secosteroids (I) can be used with other phar- maceutical agents in treatment of the conditions listed above as is known to those skilled in the art. The exact dosage and frequency of administration depends on the particular amino-9,10-secosteroids (I) used, the particular condition being treated, the severity of the condition being treated, the age, weight, general physical condition of the particular patient, other medication the individual may be taking as is well known to those skilled in the art and can be more accurately determined by measuring the blood level or concentration of the amino-9,10-secosteroids (I) in the patient's blood and/or the patients response to the particular condition being treated. DEFINITIONS AND CONVENTIONS The definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims. I. CONVENTIONS FOR FORMULAS AND DEFINITIONS OF VARIABLES The chemical formulas representing various compounds or molecu¬ lar fragments in the specification and claims may contain variable substituents in addition to expressly defined structural features. These variable substituents are identified by a letter or a letter followed by a numerical subscript, for example, "Zχ B or π Rχ B where "i" is an integer. These variable substituents are either monovalent or bivalent, that is, they represent a group attached to the formula by one or two chemical bonds. For example, a group Z_ would repres- ent a bivalent variable if attached to the formula CH3-C(-Zχ)H. Groups Rx and R-; would represent monovalent variable substituents if attached to the formula CH3-CH2"C(Rχ)(R*)H2> When chemical formulas are drawn in a linear fashion, such as those above, variable sub¬ stituents contained in parentheses are bonded to the atom immediately to the left of the variable substituent enclosed in parenthesis. When two or more consecutive variable substituents are enclosed in parentheses, each of the consecutive variable substituents is bonded to the immediately preceding atom to the left which is not enclosed in parentheses. Thus, in the formula above, both Rx and R.s are bonded to the preceding carbon atom. Also, for any molecule with an established system of carbon atom numbering, such as steroids, these carbon atoms are designated as Cx, where "i" is the integer cor¬ responding to the carbon atom number. For example, Cg represents the 65 position or carbon atom number In the compound nucleus as tradi¬ tionally designated by those skilled in the art of that chemistry. Likewise the term "Rg" represents a variable substituent (either monovalent or bivalent) at the Cg position. 5 Chemical formulas or portions thereof drawn in a linear fashion represent atoms In a linear chain. The symbol "-" in general represents a bond between two atoms in the chain. Thus CH3-O-CH2- CH( £)-CH3 represents a 2-substituted-l-methoxypropane compound. In a_ similar fashion, the symbol "-" represents a double bond, e.g., D3 C5_2-C(Rχ)-0-CH3, and the symbol "-" represents a triple bond, e.g., HC«C;-CH(Rχ)-CH2-CH3. Carbonyl groups are represented in either one of" " two ways: -CO- or -C(-O)-, with the former being preferred for simplicity. Chemical formulas of cyclic (ring) compounds or molecular 5 fragments can be represented in a linear fashion. Thus, the compound 4-chloro-2-methylpyridine can be represented in linear fashion by N*-C(CH3)-CH-CC1-CH-C*H with the convention that the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring. Likewise, the cyclic molecular fragment, 4- 0 (ethyl)-1-piperazinyl can be represented by -N*-(CH2)2- (C2H5 -CH2- C*H 2 . A cyclic (ring) structure for any compound herein defines an orientation with respect to the plane of the ring for substituents attached to each carbon atom of the cyclic compound. In formulas 5 depicting such compounds, a substituent attached to a carbon atom bύe-lZαsr the plane of the ring is Identified as being in the alpha (α) cunflgciration and Is indicated by a broken, dashed or dotted line attachment to the carbon atom, i.e., by the symbol n - - -" or m . *. The corresponding substituent attached above the plane of £ the ring is identified as being in the beta ( / 5) configuration. When a variable substituent is bivalent, the valences may be taken together or separately or both in the definition of the variable. For example, a variable R_ attached to a carbon atom as -C(—R^ - might be bivalent and be defined as oxo or keto (thus forming a 5 carbonyl group (-C0-) or as two separately attached monovalent variable substituents t-Rχjj and / 5-Rχ^-. When a bivalent variable, R^, is defined to consist of two monovalent variable substituents, the convention used to define the bivalent variable is of the form "α- or some variant thereof. In such a case both α- R χj and β- Rχi- are attached to the carbon atom to yield -C(α-Rχj) ( -Rχj-)- • For example, when the bivalent variable Rg, -C(-Rg)-, (at Cg) is defined to consist of two monovalent variable substituents, two monovalent variable substituents are α-Rg_χ:j8-Rg_2> •••• α - R 6-9 : "" R 6-10> etc > yielding -C( -Rg.χ)09-Rg. 2 )- -C(α-R _ 9 ) (y3-R .χ 0 )- , etc. Likewise, for the bivalent variable Rχχ > -C(-Rχχ)-, (at __) two monovalent variable substituents are α- R χχ.χ:3-Rχχ_2- or a r i n S substituent for which separate α and β orientations do not exist (e.g. due to the presence of a carbon carbon double bond in the ring) , and for a substituent bonded to a carbon atom which is not part of a ring the above convention is still used, but the and β designations are omitted. Just as a bivalent variable may be defined as two separate monovalent variable substituents, two separate monovalent variable substituents may be defined to be taken together to form a bivalent variable. For example, in the formula -Cχ(Rχ)H-C2(Rj)H- (0χ and C2 define arbitrarily a first and second carbon atom, respectively) Rx and R< may be defined to be taken together to form (1) a second bond between C_ and C2 or (2) a bivalent group such as oxa (-0-) and the formula thereby describes an epoxide. When R_ and Ri are taken together to form a more complex entity, such as the group -X-Y- , then the orientation of the entity is such that C_ in the above formula is bonded to X and C2 is bonded to Y. Thus, by convention the designa- tion "... Rx and Rj are taken together to form -CH 2 -CH 2 -0-CO- ..." means a lactone in which the carbonyl is bonded to C2. However, when designated "... Rj and R are taken together to form -CH2-CH2-O-CO- the convention means a lactone in which the carbonyl is bonded to C_ . The carbon atom content of variable substituents is indicated in one of two ways. The first method uses a prefix to the entire name of the variable such as "Cχ-C4", where both "1" and "4" are integers representing the minimum and maximum number of carbon atoms in the variable. The prefix is separated from the variable by a space. For example, "Cχ-C alkyl" represents alkyl of 1 through 4 carbon atoms, (including isomeric forms thereof unless an express indication to the contrary is given) . Whenever this single prefix is given, the prefix indicates the entire carbon atom content of the variable being defined. Thus C2-C4 alkoxycarbonyl describes a group CH3-(CH 2 ) n -0- CO- where n is zero, one or 2. By the second method the carbon atom content of only each portion of the definition is Indicated separate¬ ly by enclosing the "Ci-Cj" designation in parentheses and placing it Immediately (no Intervening space) before the portion of the defini- tion being defined. By this optional convention (0 -C3)alkox - carbonyl has the same meaning as C2-C4 alkoxycarbonyl because the "Cχ-C3" refers only to the carbon atom content of the alkoxy group. Similarly while both C 2 -Cg alkoxyalkyl and (Cχ-C3)alkoxy(Cχ-C3)alkyl define alkoxyalkyl groups containing from 2 to 6 carbon atoms, the two definitions differ since the former definition allows either the alkoxy or alkyl portion alone to contain 4 or 5 carbon atoms while the latter definition limits either of these groups to 3 carbon atoms. When the claims contain a fairly complex (cyclic) substituent, at the end of the phrase naming/designating that particular sub¬ stituent will be a notation in (parentheses) which will correspond to the same name/designation in one of the CHARTS which will also set forth the chemical structural formula of that particular substituent. II. DEFINITIONS All temperatures are in degrees Centigrade. TLC refers to thin-layer chromatography. HPLC refers to high pressure liquid chromatography. THF refers to tetrahydrofuran. DMF refers to dimethylformamide. DMA refers to dimethylacetamide. p-TSA refers to p-toluenesulfonic acid. Saline refers to an aqueous saturated sodium chloride solution. IR refers to infrared spectroscopy. NMR refers to nuclear (proton) magnetic resonance spectroscopy, chemical shifts are reported in ppm (δ) downfield from tetramethyl- silane. TMS refers to trlmethylsilyl. MS refers to mass spectrometry expressed as m/e or mass/change unit. [MH] + refers to the positive ion of a parent plus a hydrogen atom. El refers to electron impact. Cl refers to chemical ioniza- tion. FAB refers to fast atom bombardment. Ether refers to diethyl ether. Alcohol refers to ethyl alcohol. When solvent pairs are used, the ratios of solvents used are volume/volume (v/v) . Xg is -H or is taken together with one of the monovalent variable substituents at X (Xχχ.χ or Xχχ-2) to orm a second bond between Cg and Cx . x ll is "°> " H: - H > α-H:/3-OH, -0U:β-ti or Xχχ.χ:Xχχ-2 where one of Xχχ_χ and Xχχ_2 i taken together with Xg to form a second bond between Cg and Oχχ. X 17 is -C(-Z)-(CH 2 ) n -0H or -CH-(CH 2 ) p -OH and hydroxy protected forms thereof, where n and p are as defined in claim 1. The amino-9,10-secosteroids (I) are also known as octahydro indenones or indenes. EXAMPLES Without further elaboration, it is believed that one skilled in the art can, using the preceding description, practice the present invention to its fullest extent. The following detailed examples describe how to prepare the various compounds and/or perform the various processes of the invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. Those skilled in the art will promptly recognize appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques. PREPARATION A-6 4-(2-Pyridinyl)piperazine [34803-66-2], see French Patent 7253 M. PREPARATION A-14 4-[4,6-Bis(2-propenylamino)-l,3,5-triazin-2-yl] - piperazine A solution of 2-chloro-4,6-bis(2-propenylamino)-l,3,5-triazine (10.44 g) and 15.95 g of N-formyl piperazine in 150 ml of DMF is heated under reflux for about 18 hours. The reaction mixture is cooled and stored at 5° and crystals are deposited. The soluble fraction is concentrated and the residue is extracted with ethyl acetate. The extracts are washed with aqueous potassium carbonate, 50% saline, saline and dried over magnesium sulfate and concentrated to give a gum. Chromatography on silica gel (400 g) and elution (200 ml fractions) with 20% acetone-methylene chloride gives the for- mamide. The formamide (9.2 g) in 200 ml of methanol is heated to reflux, then cooled under nitrogen and mixed with 4 ml of 45% potassium hydroxide solution. The mixture is heated under reflux for about 20 hours, then cooled and concentrated. The residue is partitioned between ethyl acetate and water. The organic extracts are washed with water and saline, dried over magnesium sulfate and concentrated to give a gum. Crystallization from 50 ml of carbon tetrachlbride gives the title compound, πrp 93-94.5". PREPARATION A-22 4- [ 2 , 6-Bis (1-pyrrolidinyl) -4-pyrimidinyl] - piperazine A solution of pyrrolidine (80 g) in THF (500 ml) is chilled in an ice water bath and stirred mechanically under nitrogen. With a syringe pump of 2,4,6-trichloropyrimidine (50 g) is added over 35 minutes. The reaction is stirred in the ice bath for 1 hour and is then warmed to 20-25° over 4 h. Pyridine (100 ml) is added to the reaction and the mixture stirred at 20-25" overnight. The reaction is concentrated. The residue is partitioned between methylene chloride and aqueous sodium bicarbonate. The organic phase is concentrated and the residue chromatographed on silica gel (10% ethyl ace ate/hexane) to yield 51 g of crystalline 2,4-bis[pyrrolidino] - -6-chloropyrimidine. Immediately after the initial addition of reagents, two spots are seen with 25% ethyl acetate on a silica gel plate. These are the 2- and the 4- adducts. The bis product forms over time. It moves between these first two spots. The 51 g of product is reacted with piperazine (40 g) in 100 ml of dry pyridine at 100° for 50 h. The reaction is concentrated. The residue is partitioned between methyle e chloride and sodium bicarbonate solution. The organic phase is dried and concentrated. The residue is chromatographed on silica gel eluting with methylene chloride to 10% methanol/1% ammonia/methylene chloride to give the title com¬ pound, NMR (CDC1 3 ) 1.90, 2:9, 3.35 and 4.80 S . PREPARATION A-23 4- [2,6-Bis(morphollno)-4-pyrimidinyl]piperazine A solution of 160 g of morpholine in 1000 " ml of methylene chloride is treated dropwise with 100 g of 2,4,6-trichloropyrimidine. The reaction is immersed in an ice water bath. After 1 h, 300 ml of pyridine is added. The reaction is stirred for two days and .concen¬ trated. The residue is partitioned between methylene chloride and aqueous sodium bicarbonate. The residue is chromatographed on silica gel (10% ethyl acetate/hexane to 25% to methylene chloride) to give 2,4-[bis(morpholino)] -6-chloropyrimidine. A solution of 40 g of 2,4- [bis-morpholino] -6-chloropyrimidine and 34 g of piperazine In 60 g of pyridine is heated at 100° for 24 h. The mixture is partitione between methylene chloride and aqueous potassium carbonate. The organic phase is filtered through sodium sulfate and concentrated. The residue is chromatographed (methylene chloride to 4% methanol/1% ammonium hydroxide/methylene chloride) to give the title compound, NMR (CDC1 3 ) 2.90, 3.50, 3.75, 3.80 and 5.10 δ . PREPARATION A-24 4- [2,6-Bis(allylamino)-4-pyrimidinyl]piperazine Following the general procedure for PREPARATION A-22, and making non-critical variation but substituting allylamine for pyrrolidine the title compound is obtained. PREPARATION A-25 4-(2-Pyrimidinyl)piperazine [20980-22-7] See US Patent 4,409,223. PREPARATION A-26 4- [4,6-Bis(diethylamino)-2-pyrimidinyl] iperazine Diethylamine (80 g) is reacted with trichloropyrimidine (50 g) in THF. The reaction after chromatography yields a mixture of the mono- and di-addμct. This material is dissolved in pyridine (58- g) and reacted with diethylamine (35 g) at 50° for 3 h. The reaction is concentrated to a residue. The residue is partitioned between methylene chloride and aqueous sodium bicarbonate. The organic phase is separated and concentrated. The residue is chromatographed on silica gel, eluting with ethyl acetate/hexane (10/90). The ap¬ propriate fractions are pooled and concentrated to give 2,4-bis[di¬ ethylamino] -6-chloropyrimidine. This material is dissolved in pyridine (100 g) and reacted with piperazine (40 g) at 100" for 50 h. Following the above workup procedure the title compound is obtained, NMR (CDCI3) 1.15, 2.90, 3.45 and 4.9 S . PREPARATION A-45 4- [4,6-Bis(l-pyrrolidinyl)-l,3,5-triazin-2-yl]-1- piperazine Pyrrolidine (28.5 g) is cooled with an ice bath. 1,3,5-Tri- chlorotriazine (18.4 g) is added with vigorous stirring. After 1-1.5 h the mixture is permitted to warm to 20-25°. The solid is filtered and rinsed several times with water and dried under reduced pressure to give the monochloro-bis(l-pyrrolidinyl)triazine. This material (23.18 g) in piperazine (31.55 g) at DMF (295 ml) is refluxed under nitrogen. When the reaction is complete (TLC) the solvent is removed under reduced pressure. The mixture is trans¬ ferred to a separatory funnel containing ethyl acetate (100 ml) and potassium carbonate (100 ml) . The layers are separated, the organic layer is washed with saline (100 ml) and back-washed with ethyl acetate (2 x 100 ml) . The organic layers are combined, dried over magnesium sulfate at room temperature, filtered and concentrated under reduced pressure. This material is chromatographed on a silica gel column (500 g) eluting with acetone/methylene chloride (5/95) . The appropriate fractions (500 ml) are pooled and concentrated to give a solid. The solid (10.13 g) is refluxed in methanol (200 ml) and cooled under nitrogen. Potassium hydroxide (45% aqueous, 4 al) is added, the mixture degassed with nitrogen and heated to reflux. After 8 h the mixture is cooled to room temperature and concentrated under reduced pressure. The solid is transferred to a separatory funnel containing ethyl acetate (200 ml) and water (100 ml) . The phases are separated, the organic layer is washed with water (2 x 100 ml) and 50% brine (100 ml) followed by brine (2 x 100 ml) . The aqueous washes are back-washed with 200 ml of ethyl acetate, the organic phases are combined, dried over magnesium sulfate, filtered, con¬ centrated under reduced pressure to give the title compound, m.p. 162.5-166° . PREPARATION A-46 4-[3,6-Bis(diethylamino)-2-pyridinyl]piperazine Diethylamine (3.29 ml) is added dropwise over 1 h to a mixture of 2,6-dichloro-3-nitropyridine (6.13 g) , acetonitrile (100 ml) and potassium carbonate (5.2 g) precooled to 0°. The mixture is allowed slowly to warm to 20-25° and stirred for 16 h. The mixture is filtered, the filtrate combined with piperazine (12.2 g) and potas¬ sium carbonate (6 g) . The resulting mixture is heated at reflux for 24 h and then permitted to cool to 20-25°. Aqueous workup (methylene chloride, water washed over organic layers,-potassium carbonate) and purification by flash chromatography (silica gel) eluting with chloroform/methanol (20:1 25:1) gives 6-N,N-dlethylamino-3-nitro-2- (l-piperazinyl)pyridine. This material (21.8 g) , ethanol (275 ml), hydrochloric acid (1.2 N, 27 ml) and 10% palladium on charcoal (5.25 g) is exposed to hydrogen at 50 pounds per square inch In a Parr flask. After 16 h the residue is filtered through celite, concentrated and partitioned between chloroform and sodium hydroxide (5%) . The organic layers are separated, dried using potassium carbonate, concentrated. The concentrate is passed through a plug of silica gel, eluting with chloroform/methanol/ammonium hydroxide (4/1/0.25) to give 3-amino- N,N-diethylamino-2-(l-piperazinyl)pyridine. A solution of di t-butyl dicarbonate (11.8 g) and methyle chloride (25 ml) is added dropwise over 30 min to a mixture of amino-6-N,N-diethylamino-2-(l-piperazinyl)pyridine (13.5 g) , trieth lamine (8.33 ml) and methylene chloride (400 ml) precooled to 0° The resulting mixture is allowed to slowly warm to 20-25° . After 1 h using basic workup (methylene chloride, sodium bicarbonate potassium carbonate) the t-butyl carbonate as a solid is obtained. The protected piperazinyl pyridine (4 g) acetaldehyde (12.8 ml) acetonitrile (80 ml) is mixed. Sodium cyanoborohydride (1.73 g) i added to the pyridine mixture. The resultant solution is stirred fo 48 h at 20-25°. After 24 h additional sodium cyanoborohydride (50 ml) and acetaldehyde (5 ml) is added. Basic workup (chloroform/ potassium carbonate, potassium carbonate) and purification by flas chromatography using silica gel and eluting with hexane ethyl acetat (5/1) gives an oil. The oil (2.36 g) , ethyl acetate (50 ml), an hydrochloric acid (3.0 N, 37.5 ml) are stirred for 16 h at 20-25° Basic workup (chloroform, 10% sodium hydroxide, potassium carbonate gives the title compound, MS (electron impact) 305. PREPARATION A-47 4-[3-(Ethylamino)-2-pyridinyl]piperazine 2-(l-Piperazinyl)-3-nitropyridine (24.50 g) , ethanol (445 ml and hydrochloric acid (1.2 N, 44 ml) are combined and hydrogenate overnight at 40 psi initial pressure in a Parr Bomb, refilling whe necessary. The mixture is filtered through celite, washed wit ethanol, chloroform, ethanol and water. The organic solvents ar removed with heat and reduced pressure. The remaining material i partitioned between methylene chloride (3 x 250 ml) and sodiu bicarbonate. The organic layers are combined, dried over potassiu carbonate, filtered and concentrated under reduced pressure to giv an oil which slowly solidified upon standing to give 3-amino-2-(1- piρerazinyl)pyridine. 3-Amino-2-(l-piperazinyl)pyridine (19.58 g) , methylene chloride 600 ml), triethylamine (17.2 ml) are combined and cooled to 6°. Di- t-butyl-dicarbonate (24.34 g) in methylene chloride (50 ml) is added to the pyridine mixture over 30 min and permitted to stand at 0° for 1 hr, then allowed to warm to 20 - 25°. After 30 min, TLC indicates o starting material remains. The reaction mixture is partitioned between sodium bicarbonate (500 ml) and methylene chloride (3 x 250 ml). The organic phases are combined, dried over potassium car¬ bonate, filtered and concentrated under reduced pressure and heat to give a solid which is recrystallized from ethyl acetate to give 3- amino-2-[(4-t-butoxycarbonyl)-1-piperazinyl]pyridine. 3-Amino-2-[(4- -butoxycarbonyl)-l-piperazinyl]pyridine (2.361 g) , methanol (23.6 ml) and acetaldehyde (2.1 ml) are combined at 20- 25° to form a solution. Sodium cyanoborohydride (586 mg) is added and the mixture stirred overnight. The organic solvent is removed with reduced pressure and heat, the remaining mixture Is partitioned between sodium bicarbonate (50 ml) and chloroform (3 x 50 ml) . The chloroform extracts are combined and dried over potassium carbonate and filtered. The filtrate is concentrated with heat and reduced pressure. The concentrate is column chromatographed on silica gel 60 (40 63 μ) eluting with hexane/ethyl acetate (2/1) containing tri- ethylamine (1%) . The appropriate fractions are pooled and con¬ centrated to give 3-ethylamino-2-[(4-t-butylcarbonyl)-l-piperazin- yl]pyridine. 3-Ethylamino-2-[(4- -butylcarbonyl)-1-piperazinyl]pyridine (2.47 g) , ethyl acetate (67 ml) and hydrochloric acid (3 N, 49 ml) are combined and stirred for 2 hr at 20 - 25° . TLC indicates no starting material. Potassium hydroxide (14 g) and water (80 ml) is added. The organic layer Is removed and extracted with chloroform (3 x 60 ml) . The organic layers are combined, dried over potassium car- bonate, filtered and the filtrate concentrated to give the title compound, NMR (CDC1 3 ) 1.25, 1.50, 3.1, 3.5, 6.90 and 7.75 δ . PREPARATION A-48 4-[3-(Diethylamino)-2-pyridinyllpiperazine Following the general procedure of PREPARATION A-47 and making non-critical variations but reacting the protected ethylamine compound with additional acetaldehyde and again reducing the title compound is obtained, NMR (CDCI3) 0.95, 3.25,6.80, 7.20 and 7.90 δ . PREPARATION A-49 4-[4,6-Bis(2-pyridinyl)-l,3,5-triazin-2-yl]- piperazine A mixture of 4-formyl-piperazInecarboximidamide hydroiodide (prepared according to US Patent 4,351,832) In ethanol (4 ml) and ethanolic sodium ethoxide (1.4 N, 6.8 ml) Is stirred for 15 min, then 2-cyanopyridine (2.08 g) is added. The mixture is concentrated at atmospheric pressure and heated at about 200° for 5 hr, then cooled and chromatographed on silica gel eluting with methanol/methylen chloride (30/70). The appropriate fractions are pooled and con¬ centrated to give the 1-formyl 4-[4,6-bis(2-pyridinyl)-l,3,5-triazin- 2-yl]piperazine. Hydrolysis of the formanide in the usual wa (PREPARATION A-14) gives the title compound. PREPARATION A-51 4- [2,6-Bis(2-pyridinyl)-4-pyrimidinyl] -piperazin 4-Chloro-2,6-bis(2-pyridinyl)pyrimidine [prepared by the metho of J.A.C.S. 32, 1591 (1967), 4.2 g] piperazine (13.44 g) and ethanol (70 ml) is heated at reflux for 2 hr. The mixture is allowed to cool and the solvent is removed under reduced pressure. The residue is dissolved in chloroform (250 ml), washed with water (twice), dried over sodium sulfate and concentrated under reduced pressure to give an oil. The oil is crystallized from ether to give the title compound, mp 159 - 161°; MS (m/e) 318 (M+) . PREPARATION A-55 3,6-Bis(2-pyridinyl)-4-pyridazine PREPARATION A-56 6-Methoxy-2-morpholino-4-(l-piperazinyl)- pyrimidine A solution of 2,4,6-trichloropyrimidine (55 g) , methanol (50 ml) and collidine (50 g) is heated in dry tetrahydrofuran (400 ml) for 48 hr. Ether is added and the precipitate is collected. The precipit¬ ate is column chromatographed on silica gel to ■ give 6-methoxy-2,4- dichloropyrimidine. This product is mixed with morpholine in THF and stirred at 20-25° to give 6-methoxy-2-morpholino-4-chloropyrimidine. The 6-methoxy-2-morpholino-4-chloropyrimidine is heated with piperaz- ine in pyridine at 60" for 24 hr to give the title compound. PREPARATION A-57 4-(3-Chlorophenyl)piperazine [65369-76-8], see Aldrich catalog, 1986-7, 12,518-0. PREPARATION A-58 1-[2-(3-Diethylamino)pyridinyl]piperazine Sodium cyanoborohydride (3.06 g) is added to a solution of l-[2- (3-ethylamino)pyridinyl] -4(t-butyoxycarbonyl)piperazine (5.38 g) , acetaldehyde (5.0 ml) and methanol (54 ml). The mixture is stirred for 10 days at 20-25°. Acetaldehyde (5.0 ml) is added at 2, 3, 4 and 7 days. Sodium cyanoborohydride (3.06 g) is added at 3 and 7 days. After 10 days no further change in the reaction occurred as measured by TLC. Basic workup (chloroform/sodium bicarbonate/magnesium sulfate) gives an oil. The crude residue is resubmitted to the above reaction conditions. After 5 days the reaction is worked up as described above. Purification by flash chroaatography (hexane/ethyl acetate; 5/1) provides the carbamate of the title compound, NMR (CDC1 3 ) 0.98, 1.49, 3.21, 3.35-3.65, 6.82, 7.16 and 7.92 δ; IR (neat) 2974, 1699, 1577, 1438, 1234 and 1172 cm -1 ; MS (El) m/e (relative percent) 334 (79), 205 (64), 178 (45), 162 (56), 57 (100). 5 The carbamate (1.17 g) , ethyl acetate (29.0 ml) and hydrochloric acid (3 N, 21.2 ml) are stirred at 20-25° for 1.5 hr. Potassium hydroxide (8 g) and water (30 ml) are added. Aqueous workup (chloro¬ form/potassium carbonate) gives the title compound, IR (nujol) 2957, 2925, 1574, 1450, 1249 and 776 cm" 1 ; NMR (CDCI3) 0.96, 3.16, 3.15- 0 3.3- 3.7-3.85, 6.84, 7.17 and 7.91 δ; MS (El, relative percent) 234 (60')) r 178 (66), 162 (100) and 148 (67). PREPARATION A-59 1-(5-Diethylamino-2-pyridinyl)piperazine 2-Chloro-5-nitropyridine (25 g) is dissolved in acetonitrile ( . 150 ml) and the mixture is added dropwise over 30 min to a stirred 5 suspension of piperazine (61.3 g) and potassium carbonate (26.2g) in acetonitrile (550 ml). The reaction mixture is stirred at 20-25° for 16 hr. The solvent is removed on a rotary evaporator and the residue is diluted with methylene chloride/water. The organic layer Is separated and washed with water (twice) and saline, dried over 0 potassium carbonate and concentrated to give 1-(4-nitro-2-pyridinyl)- piperazine, IR 3338, 3102, 3068, 1603, 1570, 1482, 1347, 1340, 1320, 1306 and 1253 cm "1 . The nitro compound (30.7 g) is dissolved in ethanol (500ml), and palladium/carbon (10%, 10 g) and hydrochloric acid (1.2 N, 55 ml) are -Ξc added and the mixture hydrogenated on a Parr apparatus (50 psi) for 4 hr-- The mixture is then filtered thru celite and the filtrate €szεqiβrated to dryness to give an oil. The residue is partitioned be≥tween saturated sodium bicarbonate and chloroform, the layers are sεeparated, the aqueous layer is reextracted with chloroform (2 x 250 0 ml) and the organic phases are combined, dried over potassium car¬ bonate and concentrated under reduced pressure. The pH of the aqueous phase is raised to 11 by the addition of solid potassium hydroxide, the mixture reextracted with chloroform, dried and con¬ centrated to give the crude 4-amino compound. The aqueous layer is 5 concentrated to half the volume, excess sodium chloride is added and the mixture is reextracted with chloroform. The extract Is dried and concentrated to obtain additional 4-amino compound. The amine (21 g) , triethylamine (17.9 g) and methylene chloride (600 ml) are cooled to 0°. Di- -butyl dicarbonate (25.8 g) in methylene chloride (200 ml) is added over 30 min at 0° . The reaction mixture is stirred at 0° for 1 hr and allowed to warm to 20-25°. The reaction mixture is washed with saturated sodium bicarbonate (3 x 200 ml) , dried over potassium carbonate and the solvent removed under reduced pressure to give a solid. The solid is dissolved in ether, petroleum ether is added until the mixture is cloudy, the mixture is filtered thru celite and the filtrate is concentrated to give the protected piperazine compound. The piperazine protected compound (2.6 g) and acetaldehyde (1.7 g) in methanol (25 ml) is cooled to 0° . Sodium cyanoborohydride (0.62 g) is added in one portion. The cooling bath is removed and the mixture is permitted to warm to 20° . The mixture is stirred at • 20-25° for 2 hr. The methanol is removed under reduced pressure and the residue is partitioned between methylene chloride and a saturated sodium bicarbonate solution. The phases are separated and the organic phase is washed with saturated sodium bicarbonate solution, saline, dried over magnesium sulfate and concentrated under reduced pressure to give an oil. The oil is purified by HPLC on silica gel, MS (M+) 234. The oil (2.1 g) , aqueous hydrochloric acid (3 N, 42 ml) and ethyl acetate (57 ml) are stirred for 1 hr at 20-25°. The mixture is cooled in ice, basified (pH - 11) with potassium hydroxide (20%), the phases separated and the aqueous phase extracted again with ethyl acetate. The combined extracts are washed with saline, dried over magnesium sulfate, and concentrated under reduced pressure to give the title compound. NMR was in agreement. PREPARATION A-60 1- [4-(5-Ethylamino-6-diethylamino)pyrimidinyl]- piperazine A solution of di-t-butyldicarbonate (4.78 g) and methylene chloride (20 ml) is added to a mixture of 1- [4-(5-amino-6-diethyl- amino)pyrimidinyl]piperazine (4.97 g) , methylene chloride (70 ml), triethylamine (3.33 ml) and dimethylaminopyridine (10 mg) . The mixture is stirred overnight. Basic workup (sodium bicarbonate/- methylene chloride/magnesium sulfate) and purification by flash chromatography (hexane/ethyl acetate; 2/1) gives the carbamate of 1- [4-(5-amino-6-diethylamino)pyrimidinyl]piperazine, MS (El, relative percent) 350 (100), 251 (38), 207 (38) and 194 (89). Sodium cyanoborohydride (0.300 g) is added to a solution of the carbamate (0.652 g) , methanol (13 ml) and acetaldehyde (2.1 ml). The mixture is stirred for 1 week at 20-25° . At two day intervals similar amounts of sodium cyanoborohydride and acetaldehyde are added. Concentration and basic workup (chloroform/sodium bicar¬ bonate/magnesium sulfate) and purification by flash chromatography (hexane/ethyl acetate; 2/1) give the t-butyl carbamate of the title compound, MS (El, relative percent) 378 (100), 322 (21), 293 (43), 277 (18) and 249 (44). The carbamate of the title compound (465 mg) , ethyl acetate (9.5 ml) and hydrochloric acid (3 N, 7 ml) are stirred at 20-25° for 2 hr. Basic workup (chloroform/solid potassium hydroxide/magnesium sulfate) provide the title compound, NMR (CDCI3) 1.06, 1.07, 2.98, 2.95-3.1, 3.25 and 3.35-3.45 δ. PREPARATION A-61 4-(5-amino-6-diethylamino)pyrimidinylpiperazine A solution of diethylamine (4.0 ml) and acetonitrile (25 ml) is added dropwise over 40 min to a mixture of 4,6-dichloro-5-nitro- pyrimidine (7.5 g) , acetonitrile (150 ml) and potassium carbonate (6.41 g) at 0°. The mixture is stirred for an additional 50 min at 0° and is then allowed to warm to 20-25°. After 16 hr, the mixture is filtered, and the residue washed with acetonitrile (2 x 25 ml) . The crude filtrate, piperazine (25.8 g) and potassium carbonate (6.41 g) are combined and heated at reflux for 6 hr. After cooling to 20-25° , basic workup (sodium bicarbonate/chloroform/magnesium sulfate) and purification by flash chromatography (chloroform/- methanol/ammonium hydroxide; 200/10/1) an oil is obtained which solidifies upon standing to give 5-nitro-6-diethylamino-4-piperazln- ylpyrimidine, MS (Cl, relative percent) 281 (100), 265 (13), 249 (18) and 234 (71) . 5-Nitro-6-diethylamino-4-piperazinylpyrimidine (0.980 g) , ethanol (25 ml) and palladium/carbon (10%., 0.25 g) are exposed to hydrogen (50 psi) for 24 hr. The mixture is filtered and the residual solids are washed with chloroform/ethanol. The combined filtrates are concentrated under reduced pressure. Basic workup (aqueous potassium hydroxide, chloroform, magnesium sulfate) provided a solid, mp 58-59°; NMR (CDCI3) 1.11, 2.95-3.05, 3.15-3.4 and 3.29 δ. EXAMPLE 1 ll / 5,17a,21-Trihydroxypregna-l,4-diene-3,20-dione 17,21-acetonide A solution of ll ,17α,21-trihydroxypregna-l,4-diene-3,20-dione (13.0 g), dimethoxypropane (166 ml), p-TSA (278 mg) and DMF (83 ml) is heated at reflux for 6 hours. The reaction is quenched with sodium bicarbonate (1.19 g) , cooled to 20-25°, filtered and con- centrated to a solid. The solid is flash chromatographed on silica gel, eluting with ethyl acetate/hexane (1/1). The appropriate fractions are pooled and concentrated to give the title compound, mp 232-235°; IR (nujol) 3385, 1715, 1657 cm "1 ; NMR (CDC1 3 ) 1..39, 1.42, 4.16, 4.49, 6.01, 6.27 and 7.28 δ; MS (El) 342 and 121. EXAMPLE 2 17α,21-Dihydroxypregna-l,4-diene-3,11,20-trione 17,21- acetonide 11 ,17α,21-Trihydroxypregna-l,4-diene-3,20-dione 17,21-acetonide (EXAMPLE 1, 25.6 g) is added to a mixture of pyridinium chlorochrom- ate (20.7 g) , anhydrous sodium acetate (1.56 g) and methylene chloride (130 ml) at 20-25°. After 2 hours, ether (300 ml) is added and the mixture filtered through a pad of florasil. The precipitate is washed with ether (180 ml) and chloroform (300 ml) . The filtrates are combined and concentrated to a solid which is flash chromato¬ graphed on silica gel, eluting with ethyl acetate/hexane (1/1). The appropriate fractions are pooled and concentrated to obtain the title compound, mp 200.5-201.5°; IR (nujol) 1718, 1709 and 1662 cm" 1 ; NMR (CDCI3) 1.44, 4.16, 6.09, 6.22 and 7.68 δ; MS (FAB) 399, (MH+) . EXAMPLE 3 Oc tahydro - 4 ' - [ 2 - ( 5 -hydroxy- 2 -me thylphenyl) ethyl ] - 2 , 2 , 7 ' a- trime hylspiro [l , 3-dioxane-4 , l' [1H] - indene ] - 5 , 6 ' (2 'H) -dione Lithium (20 mg) is added to liquid ammonia (1200 ml) at -78". In a second flask, 17 ,21-dihydroxypregna-l,4-diene-3,11,20-trione 17,21-acetonide, (EXAMPLE 2, 14.0 g) is added to freshly distilled THF (280 ml)- under nitrogen. The anhydrous ammonia is allowed to condense into the second flask. To this mixture is added lithium (716 mg) in chunks periodically over 2 hours at reflux. The lithium uptake is monitored by the loss of blue color to yellow. Ammonium chloride (5.90 g) is added to the mixture and the ammonia allowed to evaporate at 20-25°. The mixture is concentrated to a solid and partitioned between chloroform and water (1/1, 400 ml). Hydrochloric acid (10%) is added to the mixture until the pH is about 8. The layers are separated and the aqueous layer is extracted with chloro¬ form (2 x 200 ml). The organic layers are combined and washed with water (2 x 100 ml) , dried over sodium sulfate and concentrated to a solid. The solid is flash chromatographed on silica gel, eluting with chloroform/methanol (50/1) . The appropriate fractions are pooled and concentrated to give the title compound, mp 226-227.5°; IR (nujol) 3280, 1718, 1683, 1620 and 1586 cm "1 ; NMR (CDCI3) 1.44, 1.49, 2.19, 4.16, 4.82, 6.4-6.6 and 6.9-7.0 δ; MS (FAB) 401 (MH + ) and 121. EXAMPLE 4 0ctahydro-4'-[2- [2-methyl-5-(phenylmethoxy)phenyl] - ethyl] -2, 2 , 7'a-trimethylspiro[1,3-dioxane-4,1' [1H] - indene] -5,6' (2'H)-dione A mixture of octahydro-4' -[2-(5-hydroxy-2-methylphenyl)ethyl]- 2,2,7'a-trimethylspiro[l,3-dioxane-4,l'[lH]-indene]-5,6'(2'H)-dione (EXAMPLE 3, 4.85 g) methylene chloride (55 ml), benzyl bromide (2.28 g) , tetrabutylammonium hydrogen sulfate (535 ml) and sodium hydroxide (50%, 26 ml) are stirred at 20-25° for 3 hours. The mixture is distributed between chloroform and water. The layers are separated, the aqueous layer is extracted with chloroform (2 x 50 ml) . The organic layers are combined and partitioned with water (100 ml) . Hydrochloric acid (10%) is added until the aqueous layer is neutral¬ ized. The organic layer is dried over sodium sulfate and con- centrated to an oil which crystallizes upon standing to give the title compound, mp 121-124; IR (nujol) 1718, 1701, 1617 and 1580 cm" 1 ; NMR (CDCI3) 1.44, 1.49, 2.21, 4.16, 5.20, 6.7-6.8, 7.0-7.1 and 7.3-7.5 δ; MS (FAB) 490, 433, and 91. EXAMPLE 5 3a-Methy1-3o-hydroxy-7-[2-(5-phenylmethoxy-2-methyl- phenyl)-ethyl] -3-(2-hydroxyacetyl)octahydro-5H-Indene- 5-one A mixture of octahydro-4' -[2-[2-methyl-5-phenylmethoxy)phenyl]- ethyl] -2,2,7'a-trimethylspiro[l,3-dioxane-4,l'[lH]-indene]-5,6' (2'H)- dione (EXAMPLE 4, 5.90 g) , THF (50 ml) and hydrochloric acid (I N, 50 ml) is stirred at 20-25° for 22 hours. Additional portions of hydrochloric acid (I N, 10 ml) are added at approximately 24 hour intervals over 4 days. Excess amounts of sodium bicarbonate are added and the mixture is concentrated to a solid. The solid is partitioned between chloroform and water. The phases are separated and the aqueous phase is extracted with chloroform (2 x 100 ml) . The organic layers are combined, washed with water, dried over sodium sulfate and concentrated to an oil. The oil Is flash chromatographed on silica gel, eluting with ethyl acetate/hexane (3/2, 800 ml) and ethyl acetate (1 liter). The appropriate fractions are pooled an concentrated to give the title compound, mp 95-97; IR (nujol) 3416, 1723, 1688 and 1610 cm" 1 ; NMR (CDC1 3 ) 2.21, 4.42, 5.02, 6.6-6.8, 7.0 7.1 δ; MS (FAB) 450, 91. EXAMPLE 6 3a-Methyl-3 -hydroxy-7- [2-(5-phenylmethoxy-2-methyl- phenyl)-ethyl]-3-(2-chloroacetyl)-octahydro-5H-indene 5-one and 3a-methyl-3α-hydroxy-7- [2-(5-phenylmethoxy 2-methylphenyl)-ethyl] -3-(2-tosyloxyacetyl)-octahydro 5H-indene-5-one A mixture of 3a-methyl-3α-hydroxy-7-[2-(5-phenylmethoxy-2- methylphenyl) -ethyl] -3- (2-hydroxyacetyl)octahydro-5H-indene-5-on (EXAMPLE 5, 2.20 g) pyridine (17 ml) .and p-toluenesulfonyl chlorid (1.02 g) is stirred at 0° for 1.5 hours. The mixture is allowed to warm to 20-25° and stirred for 3 hours. The pyridine is remove under reduced pressure and the residue is partitioned betwee chloroform and hydrochloric acid (1 N) . The layers are separated and the aqueous layer is extracted with ethyl acetate/chloroform (1/1, 4 x 150 ml) . The organic layers are combined, washed with water (twice), dried over sodium sulfate and concentrated to an oil. The oil is flash chromatographed on silica gel, eluting with chloroform/- methanol (50/1) . The appropriate fractions are pooled and con¬ centrated to give the title compound as an oil. IR (nujol) 3363, 1734, 1688, 1614 and 1579 cm "1 ; NMR (CDCI3) 2.21, 4.42, 5.02, 6.6- 6.8, 7.0-7.1 and 7.3-7.5 δ; MS (FAB) 468, 470 and 91. EXAMPLE 7 3a-Methyl-3α-hydroxy-7- [2- [2-methyl-5-(phenylmethoxy)- phenyl]ethyl]-3-[2-[4-(2,6-bis(l-pyrrolidinyl)-4- py rimidinyl) -l -piperazinyl] acetyl] octahydro -5H-inden- 5-one (I) A mixture of 3a-methyl-3α-hydroxy-7-[2-(5-phenylmethoxy-2- methylphenyl)-ethyl] -3-(2-chloroacetyl)-octahydro-5H-indene-5-one and 3a-methyl-3αr-hydroxy-7-[2-(5-phenylmethoxy-2-methylphenyl)-ethyl]-3- (2-tosyloxyacetyl)-octahydro-5H-indene-5-one (EXAMPLE 6, 1.16 g) , 4- [ (2,6-bis(l-pyrrolidinyl)-4-pyrimidinyl]piperazine (published PCT patent application Serial No 86/01797, PREPARATION A-22, 0.930 g) , potassium carbonate (748 mg) , and acetonitrile (31 ml) are heated at reflux for 28 hours. The acetonitrile is removed under reduced pressure and the residue is taken up in chloroform and saline. The layers are separated, the aqueous phase is extracted with chloroform (2 x 100 ml). The organic phases are combined, washed with water (100 ml) , dried over sodium sulfate and concentrated to give a solid. The solid is flash chromatographed on silica gel, eluting with ethyl acetate/hexane (4/1) . The appropriate fractions are pooled and concentrated to give the title compound, IR (nujol) 1708 cm "1 ; NMR (CDC1 3 ) 1.7-2.0, 2.21, 2.4-2.7, 3.2-3.7, 4.83, 5.02, 6.6-6.8, 7.0-7.1 and 7.3-7.5 δ; MS (FAB) 735 (MH+) and 246. EXAMPLE 7A 3a-Hethyl-3α-hydroxy-7-[2-[2-methyl-5-(phenylmethoxy)- phenyl]ethyl]-3-[2-[4-(2,6-bis(l-pyrrolidinyl)-4- pyrimidinyl)-1-piperazinyl]acetyl]-octahydro-5H-inden- 5-one hydrochloride (I) The hydrochloride salt of the amino-9,10-secosteroid (I) of EXAMPLE 7 is prepared by methods well known to those skilled in the art, mp 180-187° (dec). EXAMPLE 8 3a-Methyl-3α-hydroxy-7=[2-(5-hydroxy-2-methylphenyl)- ethyl] -3- [2- [4-(2,6-bis(l-pyrrolidinyl)-4-pyrimidin- yl)-1-piperazinyl]acetyl]octahydro-5H-inden-5-one (I) A mixture of 3a-methyl-3ct-hydroxy-7-[2-[2-methyl-5-(phenyl¬ methoxy)phenyl]ethyl]-3-[2-[4-(2,6-bis(l-pyrrolidinyl)-4-pyrimidin- yl)-1-piperazinyl]acetyl] -octahydro-5H-Inden-5-one (EXAMPLE 7, 1.12 g) , cyclohexene (20 ml), 10% palladium on carbon (0.28 g) , ethyl acetate (10 ml) and ethanol (5 ml) is heated at reflux under nitrog¬ en. After 3 hours additional 10% palladium on carbon (0.12 g) is added and the mixture heated at reflux overnight. The mixture is cooled to 20-25° filtered through celite and concentrated to a solid. The solid is flash chromatographed on silica gel, eluting with chloroform/methanol (17/1) . The appropriate fractions are pooled and concentrated to give the title compound, IR 3324 and 1708 cm' 1 ; NMR (CDCI3) 1.7-2.0, 2.21, 2.4-2.7, 3.2-3.7, 4.83, 6.5-6.6, 6.9-7.0 δ; MS (FAB) 645 (MH + ) and 246. EXAMPLE 8A 3a-Methyl-3α-hydroxy-7-[2-(5-hydroxy-2-methylphenyl)- ethyl] -3- [2- [4-(2, 6-bis(l-pyrrolidinyl)-4-pyrimidin- yl) -1-piperazinyl]acetyl]octahydro-5H-inden-5-one fumara e (I) Following the general procedure of EXAMPLE 7A and making non- critical variations but starting with the compound of EXAMPLE 8 and using fumaric acid, the title compound is obtained, mp 120-127° (dec) . EXAMPLE 9 3a-Methyl-3 -hydroxy-7- [ [2-aethyl-5-(phenylmethoxy)- phenyl] ethyl] -3- [2- [4- (2-pyridinyl) -1-piperazin¬ yl]acetyl]octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLE 7 and making non- critical variations but starting with l-(2-pyridinyl)piperazine (34803-66-2, French patent 7253 M, and published PCT patent applica¬ tion Serial No 86/01797, PREPARATION A-6) the title compound is obtained, mp 77-84°; IR (nujol) 3434, 1703, 1673 and 1592 cm" 1 ; NMR (CDC1 3 ) 2.20, 2.4-2.7, 3.4-3.7, 5.02, 6.6-6.8, 7.0-7.1, 7.3-7.6 and 8.1-8.2 δ; MS(FAB) 596 (MH 1 ) , 594, 176 and 91. EXAMPLE 10 3a-Methyl-3α-hydroxy-7- [2-(5-hydroxy-2-methylphenyl)- ethyl] -3- [2- [4- (2-pyridinyl) -1-piperazinyl]acetyl] - octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLE 8 and making non- critical variations but starting with the compound of EXAMPLE 9, the title compound is obtained, IR (nujol) 3448, 1720, 1674 and 1591 cm " i; NMR (CD3OD/CDCI3) 2.18, 3.5-3.7, 6.5-6.7, 6.9-7.0, 7.4-7.6 and 8.1-8.2 δ; MS (FAB) 506 (MH 1 ) , 176 and 121. EXAMPLE 10A 3a-Methyl-3α-hydroxy-7- [2-(5-hydroxy-2-methylphenyl)- ethyl] -3- [2- [4- (2-pyridinyl) -1-piperazinyl]acetyl] - octahydro-5H-inden-5-one hydrochloride (I) Following the general procedure of EXAMPLE 7A and making non- critical variations but starting with the compound of EXAMPLE 10 and using hydrochloric acid, the title compound is obtained, mp 170-177° (dec). EXAMPLE 11 3a-Methyl-3α-hydroxy-7- [ [2-methyl-5-(phenylmethoxy)- phenyl]ethyl]-3- [2- [4- [3-(ethylamino)-2-pyridinyl]-1- piperazinyl]acetyl] -octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLE 7 and making non- critical variations but starting with 4- [3-(ethylamino)-2-pyridinyl] - piperazine (published PCT patent application Serial No 86/01797, PREPARATION A-47) the title compound is obtained, IR (nujol) 3363, 1708, 1608, and 1580 cm "1 ; NMR (CDCI3) 2.21, 2.9-3.4, 3.9-4.2, 5.02, 6.6-7.1, 7.3-7.5 and 7.6-7.7; MS (FAB) 639 (MH 1 ) , 219 and 91. EXAMPLE 12 3a-Methyl-3α-hydroxy-7-[2-(5-hydroxy-2-methylphenyl) - ethyl] -3-[2-[4-[3- (ethylamino)-2-pyridinyl] -1-piper¬ azinyl]acetyl] -octahydro-5H-inden-5«one (I) Following the general procedure of EXAMPLE 8 and making non- critical variations but starting with 3a-methyl-3α-hydroxy-7-[[2- methyl-5-(phenylmethoxy)phenyl]ethyl] -3- [2- [4- [3-(ethylamino)-2- pyridinyl] -1-piperazinyl]acetyl] -octahydro-5H-inden-5-one (EXAMPLE 11), the title compound is obtained, IR (nujol) 3355, 1707, 1610 and 5 1580 cm -1 ; NMR (CDC1 3 ) 2.2, 3.0-3.4, 4.0-4.2, 6.6-7.1 and 7.6-7.7 δ; MS (FAB) 549 (MH 1 ) and 219. EXAMPLE 12A 3a-Methy1-3α-hydroxy-7- [2-(5-hydroxy-2-methylphenyl)- ethyl] -3- [2- [4-[3- (ethylamino)-2-pyridinyl] -1-piper- azinyl]acetyl] -octahydro-5H-inden-5-one dihydro- 10 chloride dihydrate (I) Following the general procedure of EXAMPLE 7A and making non- critical variations but starting with 3a-methyl-3β-hydroxy-7- [2-(5- hydroxy-2-methylphenyl)-ethyl]-3-[2- [4-[3-(ethylamino)-2-pyridinyl] - 1-piperazinyl]acetyl] -octahydro-5H-inden-5-one (EXAMPLE 12) and using 15 ethereal hydrochloric acid and recrystallizing from methanol/ether, the title compound is obtained, mp 167-173° (dec). EXAMPLE 13 3a-Methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl]-3-(2- hydroxyeth lidene)-octahydro-5H-inden-5-one Following the general procedure of EXAMPLE 3 and making non- 20 critical variations but starting with 21-hydroxypregna-l,4,17(20)- trien-3-one [Steroids, 3, 189 (1964), 2.30 g] the title compound is obtained, MS (El) 310 (M-H 2 0) ; NMR (CDCI3) 2.20, 4.1-4.4, 5.1, 5.4- 5.5, 6.5-6.7 and 6.99 δ; IR (nujol) 3373 and 1700 cm" 1 . EXAMPLE 14 3a-Methyl-7-[2-(5-hydroxy-2-π_ethylphenyl)-ethyl] -3-(2- Z5 hydroxyethyl)- 3a-octahydro-5H-inden-5-one 3a-Methyl-7- [2-(5-hydroxy-2-methylphenyl)-ethyl]-3-(2-hydroxy- ethylidene)-octahydro-5H-inden-5-one (EXAMPLE 13, 2.30g) is placed in a Parr bomb with palladium on carbon (10%, 0.46 g). Ethanol (46 ml) is - added. The Parr bomb is then flushed with nitrogen (3 x) and 30 hydrogen (3x) . The pressure is then brought to 50 Ib/in^ and stirred for 1.5 hr. The mixture is filtered using celite and the filtrate removed under reduced pressure. The solid is chromatographed by eluting with ethyl acetate/hexane (70/30) . The appropriate fractions are pooled and concentrated to give the title compound, mp 150-152° . 35 EXAMPLE 15 3a-Methyl-7- [2-(5-hydroxy-2-methylphenyl)-ethyl]-3-(2- chloroethyl)-3α-octahydro-5H-inden-5-one Triphenylphosphine (1.77 g) and carbon tetrachloride (7.0 ml) • are mixed in a flask with a condenser. In a second flask 3a-methyl- 7- [2- (5-hydroxy-2-methylphenyl)ethyl] -3- (2-hydroxyethyl)-3α-octa- hydro-5H-inden-5-one (EXAMPLE 14, 1.49g), acetonitrile (9 ml) and chloroform (7.5 ml) are mixed. The contents of the two flasks are combined and stirred at 20-25° for 30 min then heated at 55° for 5 hr. The mixture is then taken up in chloroform/saline (60 ml/60 ml) and extracted with chloroform (2x) . The chloroform extracts are combined and washed with saline (60 ml), dried over sodium sulfate, concentrated, and chromatographed eluting with ethyl acetate/hexane (33/67). The appropriate fractions are pooled, concentrated and recrystallized from ethyl acetate/hexane to give the title compound, mp 166-167°; MS (El) 350, 348, 227, 213 and 122. EXAMPLE 16 • 3a-Methyl-7- [2-(5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4-(2,6-bis(l-pyrrolidinyl)-4-pyrimidinyl)-1-piperazi¬ nyl]ethyl] -3α-octahydro-5H-inden-5-one (I) 3a-Methyl-7- [2- (5-hydroxy-2-methylphenyl)-ethyl]-3-(2-chloro- ethyl)-3α-octahydro-5H-inden-5-one (EXAMPLE 15, 52 mg) , 4-[(2,6- bis(l-pyrrolidinyl)-4-pyrimidinyl]piperazine (PREPARATION A-22, 68 mg) , sodium iodide (67 mg) and potassium carbonate (46 mg) are mixed and flushed with nitrogen. Acetonitrile (1.2 ml) is added by a syringe and the mixture is stirred at 20-25° for 15 min followed by heating at 80° for 27 hr. Additional acetonitrile (0.3 ml) is added and the mixture stirred 4 hr. DMF (0.3 ml) is added. Four hours later additional DMF (0.3 ml) is added and the mixture is heated at 90° overnight. The mixture is taken up in chloroform/saline. Hydrochloric acid (10%) is added dropwise to pH 8. The phases are separated, the aqueous phase is extracted with chloroform, the chloroform extracts are combined, washed with water (2 x) , dried over sodium sulfate and concentrated. The concentrate is flash chromato¬ graphed on silica gel eluting with methanol/chloroform (5/95) containing a trace of ammonium hydroxide. The appropriate fractions are pooled and concentrated to give the title compound, NMR (CDCI3) 1.8-2.0, 2.19, 2.4-2.5, 3.3-3.6, 4.85, 6.5-6.6 and 6.97 δ; MS (El) 614, 246 and 233. EXAMPLE 17 3a-methyl-7- [2-(5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- [3- (ethylamino)-2-pyridinyl]-1-piperazinyl]ethyl]- 3α-octahydro-5H-inden-5-one (I) 4- [3-(Ethylamino)-2-pyridinyl]piperazine (PREPARATION A-47, 361 mg) , 3a-methyl-7- [2-(5-hydroxy-2-methylphenyl)ethyl] -3- (2-chloro- ethyl)-3α-octahydro-5H-inden-5-one (EXAMPLE 15, 349 mg) , sodium iodide (450 mg) and sodium carbonate (304) are mixed and the flask is flushed with nitrogen. DMF (6 ml) is added by a syringe. The mixture is stirred at 20-25° for 15 min, then heated at 90° over- night. The mixture is taken up in chloroform/saline and the phases are separated. The aqueous phase Is extracted with chloroform (2 x 40 ml) , the organic phases are combined, washed with water (3 x 100 ml) and dried over sodium sulfate. The mixture still contains some DMF. The mixture is taken up in chloroform/water (50 ml/50 ml), the phases are separated, the chloroform phase is washed with water (3 x 50 ml) , dried over sodium sulfate and concentrated. The concentrate is flashed chromatographed following the procedure of EXAMPLE 16 to give the title compound, NMR (CDCL 3 ) 1.30, 2.19, 3.0-3.2, 4.1-4.2, 6.5-6.6, 6.80, 6.85-6.95, 6.97 and 7.70 δ; MS (El) 518 and 371. EXAMPLE 17A 3a-Methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl] -3-[2- [4- [3- (ethylamino)-2-pyridinyl]-1-piperazinyl]ethyl]- 3α-octahydro-5H-inden-5-one oxalate (I) Following the general procedure of EXAMPLE 7A and making non- critical variations but starting with the compound of EXAMPLE 7 and using oxalic acid, the title compound is obtained, mp 134-139° . EXAMPLE 18 3a-Methyl-3α-hydroxy-7- [2-(5-hydroxy-2-methylphenyl)- ethyl] -3- [2-[4-[2,6-bis(2-pyridinyl)-4-pyrimidinyl] -1- piperazinyl]acetyl]octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLE 17 and making non- critical variations but starting with 3a-methyl-3α-hydroxy-7-[2-(5- hydroxy-2-meth lphenyl)ethyl] -3- (2-chloroacetyl)-octahydro-5H- indene-5-one and 3a-methyl-3α-hydroxy-7-[2-(5-hydrox -2-methy1- phenyl) -ethyl] -3 - (2-tosyloxyacetyl)-octahydro-5H-Indene-5-one (EXAMPLE 6) and 4-[2,6-bis(2-pyridinyl)-4-pyrimidinyl]piperazine (PREPARATION A-51) , the title compound is obtained. EXAMPLE 19 3a-Methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl] -3-(2- chloroethylidene)-octahydro-5H-inden-5-one Following the general procedure of EXAMPLE 15 and making non- critical variations but starting with 3a-methyl-7-[2-(5-hydroxy-2- methylphenyl)-ethyl] -3-(2-hydroxyethylidene)-octahydro-5H-inden-5-one (EXAMPLE 13) the title compound is obtained. EXAMPLE 20 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)ethyl]-3-[2- [4- [3- (ethylamino) -2-pyridinyl]-1-piperazinyl]ethyl- idene] -3α-octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLE 17 and making non- critical variations but starting with 3a-methyl-7- [2-(5-hydroxy-2- ethylphenyl) ethyl] -3- (2 -chloroethylidene) octahydro- 5H-inden-5- one (EXAMPLE 19) and 4- [3- (ethylamino) -2 -pyridinyl] piperazine (PREPARA¬ TION A-47) , the title compound is obtained. EXAMPLE 21 21-hydroxypregna-l,4-diene-3 , 11,20- trione 17α,21-Dihydroxypregna-l,4-diene-3,ll,20-trione [JACS 77, 4438 (1955), 3.226 g] is placed in a flask and flushed with nitrogen. Freshly distilled acetonitrile (225 ml) are added and the mixture cooled to 0°. Trimethylsilyl iodide (TMS-I, 5.12 ml) is added dropwise. After 30 minutes sodium sulfite (5%, 150 ml) is added followed by chloroform (400 ml) . The phases are separated and the aqueous phase is extracted with chloroform ( 2 x 100 ml). The organic phases are combined, washed with sodium bicarbonate (5%, 150 ml) followed by a saline wash. The organic phase is then dried over sodium sulfate and concentrated. The concentrate is flashed chromat¬ ographed on silica gel, eluting with ethyl acetate. The appropriate fractions are pooled and concentrated to a solid. The solid Is dissolved in ethyl acetate/hexane and an impurity is crystallized and filtered off. The filtrate, containing the title compound, is concentrated and rechromatographed on silica gel eluting with ethyl acetate/hexane (70/30) . The appropriate fractions are pooled and concentrated to give the title compound. EXAMPLE 22 3a-Methyl- 7- [2- (5-hydroxy-2-methylphenyl)ethyl] -3- (2- hy droxy ace tyl)-3α-oc ahydro - 5H - inden - 5 - one Following the general procedure of EXAMPLE 3 and making non- critical variations but starting with 21-hydroxypregna-l,4-diene- 3,11,20-dione (EXAMPLE 21) the title compound is obtained. EXAMPLE 23 3a-Methyl- 7- [2- (5 -hydroxy- 2 -me thy lphenyl) ethyl] -3- (2- chloroacetyl) -3α- octahydro- 5H- inden- 5 -one Following the general procedure of EXAMPLE 15 and making non- critical variations but starting with 3a-methyl-7- [2- (5-hydroxy-2- me thy lphenyl ) e thy 1 ] - 3 - ( 2 -hydroxyacetyl ) - 3α- octahydro - 5H- inden- 5 - one (EXAMPLES 22 or 38) the title compound is obtained. EXAMPLE 24 3a-Methyl- 7- [2- (5 -hydroxy -2 -me thylphenyl) ethyl] -3- [2- [4- [3- (ethylamino) -2 -pyridinyl] -1 -piperazinyl] acetyl] - 3 - octahydro -5H- inden- 5 -oiie (I) Following the general procedure of EXAMPLE 17 and making non- critical variations but starting with 3a-methyl-7- [2-(5-hydroxy-2- methylphenyl)-ethyl] -3-(2-chloroacetyl)-3α-octahydro-5H-inden-5-one (EXAMPLE 23) and 4- [3-(ethylamino)-2-pyridinyl]piperazine (PREPARA- TION A-47) , the title compound is obtained. EXAMPLE 25 3a-Methyl-7- [2-(5-hydroxy-2-methylphenyl)ethyl] -3-(2- bromoethylidene)-octahydro-5H-inden-5-one Following the general procedure of EXAMPLE 15 and making non- critical variations but starting with 3a-methyl-7- [2-(5-hydroxy-2- methylphenyl)-ethyl] -3-(2-hydroxyethylidene)-octahydro-5H-inden-5-one (EXAMPLE 13) and using carbon tetrabromide in place of carbon tetrachloride, the title compound Is obtained, MS (El) 392 and 390; NMR (CDC1 3 ) 0.94, 1.61-2.1, 2.20, 2.3-2.8, 2.94, 4.0-4.2, 4.9, 5.4- 5".5, 6.5-6.7 and 6.99 δ. EXAMPLE 26 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl] -3-[2- [4- [3- (ethylamino)-2-pyridinyl]-1-piperazinyl]ethyl- idene]-3α-octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLE 17 and making non- critical variations but starting with 3a-methyl-7-[2-(5-hydroxy-2- methylphenyl) -ethy1] -3-(2-bromoethylidene)-octahydro-5H-inden-5-one (EXAMPLE 25) and 4-[3-(ethylamino)-2-pyridinyl]piperazine (PREPARA¬ TION A-47), the title compound is obtained, MS (El) 516 and 501; NMR (CDCI3) 0.78, 1.31, 1.4-1.5, 1.7-2.1, 2.57, 2.3-2.7, 2.97, 3.0-3.2, 4.1-4.2, 5.25-5.35, 6.58, 6.63, 6.91, 6.98 and 7.70 δ. EXAMPLE 26A 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- [3- (ethylamino) -2-pyridinyl]-1-piperazinyl]ethyl- idene] -3α-octahydro-5H-inden-5-one hydrochloride (I) Following the general procedure of EXAMPLE 7A and making non- critical variations but starting with the compound of EXAMPLE 26 and using hydrochloric acid, the title compound is obtained, mp 182-188" . EXAMPLE ' 27 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl] -3-[2- [4-(2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl)-1- piperazinyl]ethyl] -3α-octahydro-5H-Inden-5-one (I) Following the general procedure of EXAMPLE 16 and making non- critical variations but starting with 3a-methyl-7- [2-(5-hydroxy-2- methylphenyl)ethyl] -3- (2-bromoethylidene)-octahydro-5H-inden-5-one (EXAMPLE 25) and 4- [(2,6-bis(l-pyrrolidinyl)-4-pyrimidinyl]piperazine - (PREPARATION A-22) , the title compound is obtained, MS (El) 612; NMR (CDCI3) 0.89, 1.35-1.50, 1.5-1.7, 1.8-2.0, 2.3-2.6, 2.6-2.7, 2.91, 3.3-3.5, 3.5-3.6, 4.85, 5.25-5.35, 6.56, 6.60 and 6.98 δ; IR (nujol) 1706 cm "1 . EXAMPLE 28 21-Hydroxypregna-l,4-diene-3,11,20-trione and 17-epi- 21-hydroxypregna-1,4-diene-3,11,20-trione Trimethylsilyl iodide (5.12 ml, 7.20 g, 36.0 mmol) is added dropwise to a solution of 17α,21-dihydroxypregna-l,4-diene-3,11,20- trione (3.23 g) in freshly distilled acetonitrile. After 30 min, sodium sulfite solution (5%, 150 ml) is added to the reaction mixture. The mixture is partitioned with chloroform (400 ml). The phases are separated, and the aqueous phases is extracted twice with chloroform. The organic layers are combined, washed with sodium bicarbonate (5%), saline, dried over sodium sulfate and concentrated. The concentrate is flash chromatographed eluting with ethyl acetate- /hexane (2.3/1). The appropriate fractions are pooled to give 21- hydroxypregna-l,4-diene-3,ll,20-trione as an oil and 17-epi-21- hydroxypregna-l,4-diene-3,ll,20-trione as a solid, mp 203-206". EXAMPLE 29 3a-Methyl-7- [2- (5-hydroxy-2-me hylphenyl)ethyl] -3α- acetyl -3β-octahydro-5H-inden-5-one A solution of 17-epi-21-hydroxypregna-l,4-diene-3,ll,20-trione (EXAMPLE 28, 0.14 g) in freshly distilled THF (5 ml) is added dropwise to a solution of lithium (24 mg) in distilled ammonia (50 ml) at -78° . After 30 min ammonium chloride (300 mg) is added and the ammonia is allowed to evaporate overnight. The mixture is partitioned between chloroform and saline, the layers separated and the aqueous layer is extracted twice with chloroform. The organic phases are combined, washed with saline, dried over sodium sulfate and concentrated to a solid. The solid is flash chromatographed on silica gel eluting with hexane/ethyl acetate (3/2, 300 ml) and hexane/ethyl acetate (2/3, 200 ml). The appropriate fractions are pooled and concentrated to give a solid, mp 159-160°; MS (El) 328, 313 and 285. EXAMPLE 30 3a-Methyl-7- [2- (5-hydroxy- 2-methylphenyl)ethyl] -2a- (2-bromoacetyl) -33-octahydro-5H-inden-5-one 3a-Methyl-7- [2- (5-hydroxy-2-methylphenyl)ethyl] -3α-acetyl-33- octahydro-5H-inden-5-one (EXAMPLE 29) is treated with bromine (1 equivalent) in acetic acid to give the title compound. EXAMPLE 31 3a-Methyl-7- [2- (5-hydroxy-2-methylphenyl)ethyl] -3 - [2- [4- (2,6-bis(l-pyrrolidinyl) -4-pyrimidinyl) -1- piperazinyl]acetyl] - β-octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLES 16 and 17 and making non-critical variations but starting with 3a-methyl-7- [2-(5-hydroxy- 2-methylphenyl)ethyl] -3 -(2-bromoacetyl)-3/3-octahydro-5H-inden-5-one (EXAMPLE 30) and 4- [ (2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl]piperazine (PREPARATION A-22), the title compound is obtained. EXAMPLE 32 3a-Methyl-7- [2-(5-hydroxy-2-methylphenyl)ethyl] -3α-[2- [4-[3-(ethylamino) -2-pyridinyl] -1-piperazinyl]acetyl] - 3/9-octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLES 16 and 17 and making non-critical variations but starting with 3a-methyl-7- [2-(5-hydroxy- 2-methylphenyl)ethyl] - 3a-(2-bromoacetyl) -3/3-octahydro-5H-inden-5-one (EXAMPLE 30) and 4- [3-(ethylamino) -2-pyridinyl]piperazine (PREPARA- TION A-47) , the title compound is obtained. EXAMPLE 33 Pregna-l,4~diene-3,ll,20-trione llα-Hydroxypregna-l,4-dIene-3,20-dIone (120 mol) in acetone (950 ml) is treated with Jones reagent (38.7 ml) at 0°. Following work-up the title compound is obtained. EXAMPLE 34 3a-Methyl-7- [2-(5-hydroxy-2-methylphenyl)ethyl] -3-(2- acetyl)-3α-octahydro-5H-inden-5-one Following the general procedure of EXAMPLE 3 and making non- critical variations but starting with pregna-l,4-diene-3,ll,20-trione (EXAMPLE 33) the title compound- is obtained. EXAMPLE 35 3a-Methyl-7- [2-(5-hydroxy-2-methylphenyl)ethyl]-3-(2- bromoacetyl) -3a-octahydro-5H-inden-5-one Following the general procedure of EXAMPLE 30 and making non- critical variations but with 3a-methyl-7-[2-(5-hydroxy-2-methyl- phenyl)ethyl]-3-(2-acetyl)-3α-octahydro-5H-inden-5-one (EXAMPLE 34) the title compound is obtained. EXAMPLE 36 3a-Methyl-7-[2-(5-hydroxy-2-methylphenyl)ethyl] - 3β- [2- [4- [3-(ethylamino) -2-pyridinyl] -1-piperazinyl]acetyl] - 3 -octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLES 16 and 17 and making non-critical variations but starting with 3a-methyl-7- [2-(5-hydroxy- 2-methylphenyl)ethyl] - 3β-(2-bromoacetyl) - 3a-octahydro-5H-inden-5-one (EXAMPLE 30) and 4- [3-(ethylamino) -2-pyridinyl]piperazine (PREPARA¬ TION A-47), the title compound is obtained. EXAMPLE 37 3a-Methyl-39-acetoxyacetyl-7- [2- (5-hydroxy-2-methyl¬ phenyl)ethyl] -3α-octahydro-5H-inden-5-one Following the general procedure of Cocker, et al. , J. Chem. Soc, 6 (1965) 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)ethyl]-3-(2- acetyl)-3α-octahydro-5H-inden-5-one (EXAMPLE 34) is treated with boron trifluoride/ether and lead tetraacetate in methanol/benzene (5/95) at 20-25°. After 3 hr the reaction mixture is quenched with water and the product extracted with ether and crystallized to give the title compound. EXAMPLE 38 3a-Methyl-30-hydroxyacetyl-7- [2- (5-hydroxy-2-methyl- phenyl)ethyl] -3α-octahydro-5H-inden-5-one 3a-Methyl-39-acetoxyacetyl-7- [2- (5-hydroxy-2-methylphenyl) - ethyl]-3α-octahydro-5H-inden-5-one (EXAMPLE 37) is treated with anhydrous sodium carbonate in methanol and stirred at 20-25° for 5.5 hr. The excess base is neutralized with ammonium chloride and the resulting solution is concentrated under reduced pressure to a solid which is partitioned between chloroform and water (1/1) . The aqueous layer is further extracted with chloroform and combined with the organic layer. The organic phase is dried over sodium sulfate, concentrated under reduced pressure to give the title compound. EXAMPLE 39 3a-Methyl-3/3- [2- [4- [3, 6-bis(diethylamino) -2-pyridin- yl] -1-piperazinyl] acetyl] -7- [2-(5-hydroxy-2-methyl¬ phenyl)ethyl] -3α-octahydro-5H-inden-5-one (I) Following the general procedure of EXAMPLES 16 and 17 and making non-critical variations but starting with 3a-methyl-7- [2-(5-hydroxy- 2-methylphen l)e h l] -3-(2-chloroacetyl) -3α-octahydro-5H-inden-5-one (EXAMPLE 23) and 4- [3,6-bis(diethylamino)-2-pyridinyl]piperazine (PREPARATION A-46) , the title compound is obtained. EXAMPLE 40 7a-Methyl-lS-acetyl-4 - [2-(5-hydroxy-2-methylphenyl) - ethyl] -2, 3, 3a , 4, 7, 7a-hexahydro-Δ^-lH-indene Following the procedure of Ananthamarayan, et al, J. C. S. Chem. Commun., 709 (1982) , llα-hydroxypregna-l,4-diene-3,20-dione 11- xanthate is added to samarium iodide (4 equivalents) prepared from samarium metal and 4 equivalents of freshly prepared 1,2-diodoethane in THF. The mixture is stirred for 5 min at 20-25° then quenched in cold hydrochloric acid (10% aqueous) and extracted with ethyl acetate. The ethyl acetate layer is washed with sodium thiosulfate, dried over sodium sulfate and concentrated under reduced pressure. The concentrate is chromatographed over silica gel by eluting with chloroform/hexane/ethyl acetate (95/4/1) . The appropriate fractions are pooled and concentrated to give the title compound, mp 153-154°. EXAMPLE 41 7a-Methyl- 1/3-(2-bromoacetyl)-4α- [2-(5-hydroxy-2- methylphenyl)-ethyl] -2, 3, 3aα, 4, 7, 7a-hexahydro-Δ 5 - 1H-indene Following the procedure of Elks, et al, J. Chem. Soc, 4001 (1958) the methyl ketone is selectively brominated In the presence of the double bond using bromine in methylene chloride containing ether. The reaction mixture is cautiously added to cold saline and extracted with ether. The combined organic layers are dried over sodium sulfate and concentrated under reduced pressure. Flash chromatog¬ raphy provides the title compound. EXAMPLE 42 7a-Methyl-l/9-[2-[4- [3-(ethylamino)-2-pyrIdinyl]-1- piperazinyl]acetyl] -4α-[2-(5-hydroxy-2-methylphenyl)- ethyl]-2, 3, 3ao, 4, 7, 7a-hexahydro-Δ^-lH-indene (I) Following the general procedure of EXAMPLES 16 and 17 and making non-critical variations but starting with 7a-methyl-lS-(2-bromo- acetyl)-4α-[2-(5-hydroxy-2-methylphenyl)-ethyl]-2, 3, 3a , 4, 7, 7a- hexahydro-Δ 5 -lH-indene (EXAMPLE 41) and 4-[3-(ethylamino)-2-pyridin- yl]piperazine (PREPARATION A-47) , the title coapound is obtained. EXAMPLE 43 7a-Methyl-4α- [2-(5-hydroxy-2-aethylphenyl)-ethyl] -19- [2-[4-(2,6-bis(l-pyrrolidinyl)-4-pyrimidinyl)-1- piperazinyl] cetyl]-2, 3, 3aα, 4, 7, 7a-hexahydro-Δ^- 1H-indene (I) Following the general procedure of EXAMPLES 16 and 17 and making non-critical variations but starting with 7a-methyl-l?-(2-bromo- acetyl)-4α-[2-(5-hydroxy-2-methylphenyl)-ethyl]-2, 3, 3aα, 4, 7, 7a- hexahydro-Δ 5 -lH-indene (EXAMPLE 41) and 4-[(2,6-bis(l-pyrrolidinyl)- 4-pyrimidinyl]piperazine (PREPARATION A-22) , the title compound is obtained. __a____ __ (I) CHART B Formula Name Chemical Structure No. pyridin-2- , (F-1) ( °'o-ι (0) 0-1 or 4-yl optionally substituted (F-3) optionally as the N-oxide -*CH 2 -(CH2) c -G-(CH2 d -CH 2 -N* (F-4) 3-pyrrolin-l-yl -N (F-5) pyrrol-1-yl optionally (C r C 3 alkyl ) fJ _ 1 -N (F-6) substituted CHART B - Continued Formula Name Chemical Structure No . piperidin- 1-yl optionally (F- 7) substituted 1,2,3,6-tetrahydropyridin-l-yl (F-8) 1-hexamethy1eneimino containing a 3- or 4- (F-9) double bond or 3- and 5- double bonds 1,4-dihydro-1-pyridinyl substituted in the (F-10) 4-position different groups l , 3 , 5- triazin-2-yl or the (R 21-2 ) 0-l Nχ~ oxide thereof optionally (F-ll) substituted at the 4- and/or - ' - (0) 0-l 6- position ( R 21-2^0-l pyrimidin-4-yl or the Nχ-oxide thereof optionally substituted (F-12) at the 2- and/or 6- and 5- and/or 6-position CHART B - Continued Formula Name Chemical Structure No. pyrimidin-2-yl optionally (F-13) substituted pyrazin-2-yl optionally (F-14) substituted imidazol-2-yl optionally (F-15) substituted in (C- | -C 3 al kyl or aryl ) Q _ 1 N— N l,3,4-triazol-2-yl optionally (F-16) substituted -ζ*- ( R 21 -2^0-1 c r c 3 al kyl or aryl ) imidazol-4- or 5-yl optionally substituted benzo[b]thien-2-yl (F-18) indol-2-yl (F-19) CHART B - Continued Formula Name Chemical Structure No. benzo[b]thiazol-2-yl (F- 20) benzimidazol-2-yl (F-21) (F-22) (F-23) (1 -piperazinyl) - (C2-C4) optionally substituted (C 2 -C 4 alkyl)-N N-(aryl or heteroaryl) in the 4-position ' (F-24) (1-piperazinyl)acetyl substituted in the ■C0-CH 2 -N N-heteroaryl (F-25) 4-position CHART B - Continued Formula Name Chemical Structure No . (l-piperazlnyl) carbonyl - methyl substituted in -CH 2 -C0-N N-heteroaryl (F-26) the 4-position 2 - (carboxy) - 1 -pyrrolidinyl (F-27) 2-(carboxy)-1-piperidinyl (F-28) 2-(carboxy)-1-hexamethyleneimino (F-29) C00H 2 -(carboxy)-1-heptamethyleneimino _,f) (F-30) COOH 1-piperazinyl substituted in -N N-(CH2)j -C0-R 2 χ.χ2 (F-31) the 4-position 1-piperazinyl substituted in -N N- (CH 2 ) j -heteroaryl (F-32) the 4 -position CHART B - Continued Formula Name Chemical Structure No. 1-piperazinyl substituted in -N N-(CHo) -aryl (F-33) the 4-position 4-hydroxy-l-piperidinyl (F-34) substituted in the 4-position 1-piperazinyl substituted in -N N-(CH2)χ-CO-NR 2 χ.χ3-heteroaryl the 4-position / (F-35) 1-(4-methyl)piperazinyl -N N-CH 3 (F-36) 1-(4-acetyl)piperazinyl (F-37) 1-(4-hydroxy)piperidinyl (F-38) • _> H 1-piperidinyl optionally (F-39) substituted with 2-hydroxyethyl -morpholinyl -N 0 (F-40)

Claims: CLAIMS 1. An amino-9,10-secosteroid of formula I where: R3 is -H or -CO-R3.X where R 3 .χ is C -C4 alkyl or phenyl optionally substituted with 1 or 2 3.2 where R3.2 is -GH3, -OCH3, -F and -Cl; where: ( C-I ) Rg is Rg_χ: 9_2 an( R ll ls R ll-l :R ll-2' w ^ ere one °f R 9-X and Rg_2 is -H and the other taken together with one of Rχχ_χ and Rχχ_2 to form a second bond between Cg and 0χχ and the other of Rχχ_χ and Rχχ_2 - s "**» (C-II) Rg is -H:-H and R L is -0; (C-III) Rg is -H:-H and Rxx is ce-Rχχ_3: - χχ_4 where one of Rχχ_3 and Rχχ.4 is -H or -OH and the other is -H; ( D-I ) Rxg is Rχ6-X ; Rχ6-2 an< R 17 ls R 17-l :R 17-2' wnere one °f Rχg_χ and χβ-2 ls '** or - H3 and the other taken together with one of Rχ7_χ and Rχ7_2 forms a second bond between Oχg and Cχ7, and the other of Rχ7_χ and χ7_2 is -C(-Z ) -(CH 2 ) n -NR2XA R 21B' wnere z Is -0, -CH2 or R2Q-χ:-H where R20-I is -H or -CH3, where n is 0 through 6, where < A > R 21A ls (1) -(CH2) m -NR2χ_χ-heteroaryl, where is 2, 3 or 4, where 21-I is -H or C -C3 alkyl, where heteroaryl is: (a) pyridin-2- (F-1), 3- (F-2) or 4-yl (F-3) or the N-oxide thereof optionally substituted by 1 or 2 R2X-2 > De in tne same or different, where R2I-2 ls (i) -F, ( ϋ) -Cl , (iϋ) -Br , ( iv) Cχ-C 5 alkyl , (v) -CH 2 -CH-CH 2 , (vi) -aryl, where aryl is phenyl optionally substituted with 1 through 2 -F, -Cl, -Br, Cχ-C3 alkoxy, -C00H, -NH2, C 1 -C 3 alkylamino, di(Cχ-C3)alkylamino, where the alkyl groups are the same or different, 1-pyrrolidinyl- , 1-piperidinyl, 1-hexa- methylenimino-, 1-heptamethylenimino- , C2-C4 acylamino and -NH-CHO or with 1 -F or -CF3; (vii) -NR2χ_3 2X-3 where the 2I-3S are the same or different and are -H, Cχ-C3 alkyl or -CH2-CH-CH2, (viiiα) *CH2- CH2)q-CH 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/9) *CH2-CH2-(CH 2 ) c -G-(CH 2 ) d -CH2-CH2-N*- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring (F-4) , where G is -0- , -S-, -SO-, -SO2- or -NHR2 .4, where R2X-4 is -H, Cχ-C3 alkyl, or aryl 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-l-yl, (F-5) (x) pyrrol-1-yl optionally substituted with Cχ-C 3 alkyl, (F-6) (xi) piperidin-1-yl optionally substituted with 1 or 2 Cχ-C 3 alkyl, - ■ (F-7) (xii) 1,2,3,6-tetrahydropyridin-l-yl, (F-8) (xiii) 1-hexamethyleneimino containing a 3- or 4- double bond or 3- and 5- double bonds, (F-9) (xiv) 1,4-dihydro-1-pyridinyl substituted in the 4 position by two C -C3 alkyl being the same or different, (F-10) (xv) -OH, (xvi) Cχ-C 3 alkoxy, (xvii) -NR2χ_7-(CH 2 ) e -Q where Q is 2-pyridi- nyl where 21-7 is -H or C -C3 alkyl and e is 0 through 3, (xviii) pyridin-2-, 3- or 4-yl, (xix) -CF3 (xx) -CCI3 (b) l,3,5-triazin-2-yl or the N-oxide thereof optionally substituted at the 4- and/or 6- position with 2I-2 where R21-2 ls as defined above, (F-ll) (c) pyrimidin-4-yl or the N-oxide thereof optionally substituted at the 2- and/or 6- and 5- and/or 6- position with R2I-2 where 2I-2 ls as defined above, (F-12) (d) pyrimidin-2-yl optionally substituted at 4- and/or 6- position with 1 or 2 2I-2 as ε defined above, (F-13) (e) pyrazin-2-yl optionally substituted with 1 or 2 R2I-2 as ls defined above, (F-14) (f) imidazol-2-yl optionally substituted in the 1 position with Cχ-C3 alkyl or -aryl, where aryl is as defined above, andfurther optionallysubstitutedwith 1 or 2 21-2 as definedabove, (F-15) (g) l,3,4-triazol-2-yl optionally substituted in the 1 position with C -C alkyl or -aryl, where aryl is as defined above, andfurther optionally substitutedwith 21-2 as definedabove, (F-16) (h). imidazol-4- or 5-yl optionally substituted in the 1 position with Cχ-C3 alkyl or -aryl, where aryl is as defined above, and further optionally substituted with 1 or 2 21-2 as defined above, (F-17) (i) benzo[b]thien-2-yl, (F-18) (j) indol-2-yl, (F-19) (k) benzo [b] thiazol-2-yl, (F-20) (1) benzimidazol-2-yl, (F-21) (m) 4- [2- [4- [2 , 6-bis(l-pyrrolidinyl) -4- pyrimidinyl] -l-piperazinyl] ethyl] piperazinyl , (F-22) (n) l , 2 ,4-triazin-3-yl optionally substituted at the 5- and/or 6- position with R2I- as ls defined above, (F-23) (2) (l-piperazinyl) - (C2-C4)alkyl optionally sub¬ stituted in the 4- position with -aryl or -heteroaryl as defined above, (F-24) (3) -heteroaryl, as defined above, (4) - (CH2) m -X4 where m is as defined above and where X is (a) -0-CH 2 CH2-Y, where Y is Cχ-C 3 alkylamino , di(Cχ-C3)alk lamino where the alkyl groups are the same or different, C3-Cg alkyleneimino, optionally substituted with 1 or 2 Cχ-C3 alkyl (b) - R2χ.5CH 2 CH 2 - , where 21-5 is -H or Cχ- alkyl and Y is as defined above, (c) -(CH2 g -N(R2χ.5)-heteroaryl, where g is 2, or 4, and where R21-5 and heteroaryl are as defined above, (5) -(CH 2 ) m -NR 2 I-6R21-8> where R 21-6 ls *H or C -C3 alkyl and 2I-8 ls -aryl or -heteroaryl as defined above, R 21-6 an< * 21-8 are taken together with the attached nitrogen at to form a saturated mono-nitrogen C3-C5 heterocyclic ring and where is as defined above, (6) -(CHCH3) b -(CH 2 )f-R2χ-9, where b is 0 and f is through 3 or b is one and f is 0 through 3, where 21-9 is phen substituted with 1 through 3 -OH, Cχ-C3 alkoxy, -NR2X-X0 R 21-11 wher R 21-10 an R 21-ll are c ^ e same or different and are -H, Cχ-C3 alky or are taken together with the attached nitrogen .atom to form a 0 .0 cyclicamino ring, (7) -(CH2 -heteroaryl, where i is 1 through 4 an heteroaryl is as defined above, (8) (1-piperazinyl)acetyl substituted in the 4 position by heteroaryl where heteroaryl is as defined above, (F-25 (9) (1-piperazinyl)carbonylmethyl substituted in the 4- positionby -heteroarylwhereheteroaryl is as defined above, and(F-26 (B) R 21B is (1) -H, (2) Cχ-C 3 alkyl, (3) C5-C7 cycloalkyl, (4) -(CH2) m -NR2χ.χ-heteroaryl, where m, 2I-1 an heteroaryl are as defined above, (5) (l-piperazinyl)-(C2-C4)alkyl optionally sub stituted in the 4- position with -aryl or -heteroaryl as defined above, (F-24 (6) -(CH2) m -X4, where m and X4 are as defined above, (7) - CH 2 ) m -NR 2 _6R2χ_8. where m, R21-6 and R 21-8 ar as defined above, (8) -(CHCH 3 ) -(CH2)f-R2i-9, where b, f and R21.9 ar as defined above, (C) 2IA an d R 21B are taken together with the attache nitrogen atom to form a heterocyclic ring selected from the grou conslsting of (1) 2-(carboxy)-1-pyrrolidinyl optionally as the Cχ-C3 alkyl ester or as a pharmaceutically acceptable salt, (F-27) (2) 2-(carboxy)-1-piperidinyl optionally as the Cχ-C3 alkyl ester or as a pharmaceutically acceptable salt, (F-28) (3) 2-(carboxy)-1-hexamethyleneimino optionally as the Cχ-C3 alkyl ester or as a pharmaceutically acceptable salt, (F-29) (4) 2-(carboxy)-1-heptamethyleneimino optionally as the Cχ-C3 alkyl ester or as a pharmaceutically acceptable salt, (F-30) (5) 1-piperazinyl substituted in the 4- position with R 21-12~CO-(GH2)- 5 - where 2I-I2 s -heteroaryl, -NR2χ. 3heteroaryl and 2-furanyl, where R21-I3 is -H or Cχ-C3 alkyl, where j is 0 through 3 and aryl is as defined above, (F-31) (6) 1-piperazinyl substituted in the 4- position with heteroaryl-(CH2)j- , where heteroaryl and j are as defined above, (F-32) (7) 1-piperazinyl substituted in the 4- position with aryl-(CH 2 ) -, where aryl and j are as defined above, (F-33) (8) 4-hydroxy-l-piperidinyl substituted in the 4- position with aryl as defined above, (F-34) (9) 1-piperazinyl substituted in the 4- position with he eroaryl-N 2χ.χ3-CO-(CH2) - , where heteroaryl, R2I-I3 an d i are as defined above; (F-35) (D-II) R_β is tt-Rχ6-3 : /3" R 16-4 where one of χβ.3 and χβ_4 is -H and the other is -H, -F, -CH3 or -OH, and Rχ 7 is -CH-(CH 2 ) p -NR2χA- R 21B' where p is 1 or 2, where 21A an d 2XB are as defined above; (D-III) R 16 is c.-R 16 _ 5 :0-Rχ 6 _ 6 and R 7 is α- R χ7-5:/9-Rχ7-6» where R 16-5 is " H > *0H > " F or " CH 3 and R X6-6 is " H » *0H > ~ F » or - H3, with the proviso that at least one of χ _5 and χ -6 s "** > where Rχ7_5 is -H, -OH, -CH 3 , -CH2CH3, C2-C7 alkanoyloxy or -O-CO-aryl, where aryl is as defined above, and χ7_g is -C(-Z -(CH2 n - R2 A 2XB' where Z, n, R2IA an R21B are as defined above; (D-IV) the 16,17-acetonlde of a compound where χ6-5 is -OH, R 16-6 is -H, RX7.5 is -OH and χ7_β is -C(-Z)-(CH 2 ) n -NR2χA 2XB> where Z, n, -R2XA an d R 21B are as defined above; (D-V) R 16 Is α-Rχ 6 _ 7 :/_-Rχ 6 _ 8 and R 17 is α-C(-Z)-(CH 2 ) n -N- 21A 21B : ^" where Z, n, 2XA an R 21B are as defined above, where R 16-7 is -H, -OH, -F or -CH3 and Rχ6-8 is -H, -OH, -F, or -CH 3 , with the proviso that at least one of Rχ β -5 and Rχg_6 is -H and pharmaceutically acceptable salts thereof, and hydrates and solvates thereof. 2. An amino-9,10-secosteroid according to claim 1 where Rχ$ and R are (D-II) Rχ6 is α-R 6 _3:0-Rχ6_4 where one of Rχβ_3 and Rχ6_4 is -H and the other is -H, -F, -CH 3 or -OH, and Rχ 7 is -CH-(CH 2 ) p -NR2χ R 21B! (D-III) R 16 is α-Rχ6-5^- χ6-6 and R 17 is α ' R 17-5 : ^" R 17-6. whe R 16 _5 is -H, -OH, -F or -CH 3 and Rχ 6 . 6 is -H, -OH, -F, or -CH 3 , wi the proviso that at least one of R 6-5 an Rχ6-6 - s "H» where 7 is -H, -OH, -CH3, -CH2CH3, C2-C7 alkanoyloxy or -0-CO-aryl, and whe R 17-6 is -C(-Z -(CH2) n -NR2χ A 2XB; (D-IV) the 16,17-acetonide of a co&pound where χ -5' i -O R 16 _ 6 is -H, Rχ 7 _5 is -OH and Rχ 7 . 6 is -C(-Z)-(CH 2 ) n -NR 2 χ A R2χB; (D-V) R 16 is α-Rχ6-7:ιS- R χ6-8 and R 17 is α-C(-Z)-(CH 2 ) n - R 21A R 21B : " H where Rχ -7 i -H, -OH, -F or -CH3 and -8 is " H » -OH, -F, or -CH3, with the proviso that at least one of Rχς.5 a R 16-6 is - H - 3. An amino-9,10-secosteroid according to claim 1 where R_- is R 17-5 : ^" R 17-6> where RX7.5 is -H, -OH, -CH3, -CH2CH3, C 2 -C 7 alkano loxy or -O-CO-aryl, and where Rχ7_g is -C( « Z)-(CH2) n -NR2XA R 21B- 4. An amino-9,10-secosteroid according to claim 1 where Rχ7 is -C (CH 2 )p-N 2iAR 2 XB- 5. An amino-9,10-secosteroid according to claim 1 where Rxx is -0. 6. An amino-9,10-secosteroid according to claim 1 where Rg is 9-l :R 9-2 and ll ^- s ll-l : ll-2' where one of g_χ and 9.2 s - and the other taken together with one of Rχχ.χ and Rχχ_2 to form second bond between C9 and 0χχ and the other of Rχχ.χ and χχ.2 I s -H. 7. An amino-9,10-secosteroid according to claim 1 where Rg is -H:- and Rx is ct-Rχχ-3 : - R H-4 where one of Rχχ.3 and Rχχ.4 is -OH an the other is -H. 8. An amino-9,10-secosterold according to claim 1 where n is 1. 9. An amino-9,10-secosteroid according to claim 1 where Z is -0. 10. An amino-9,10-secosteroid according to claim 1 where Z is -H:-H. 11. An amIno-9,10-secosteroId according to claim 1 where R21A an 21B are taken together with the attached nitrogen atom form 1- piperazinyl substituted in the 4- position with -(CH 2 )•»-heteroaryl. 12. An amino-9,10-secosteroid according to claim 1 where j Is 0. 13-. An amino-9,10-secosteroid according to claim 1 where R 2 χA ar *d R 21B are taken together with the attached nitrogen atom form 1- piperazinyl substituted in the 4-position with -(CH2)j-heteroaryl where j is 0 and heteroaryl Is selected from the group consisting of (a) l,3,5-triazin-2-yl optionally substituted in the 4- and/or 6- position with 2l-2> (b) pyrimidin-2-yl optionally substituted at 4- and/or 6- position with 1 or 2 R2X-2> (c) pyrimidin-4-yl optionally substituted at the 2- and/or 6- position with R2X-2 and (d) pyridin-2-yl optionally substituted by 1 or 2 2X-2' De i n g the same or different. 14. An amino-9,10-secosteroid according to claim 13 where 21 an R 21B are taken together with the attached nitrogen atom form 1- piperazinyl substituted in the 4-position with -(C^)*-heteroaryl where j is 0 and heteroaryl is selected from the group consisting of (a) l,3,5-triazin-2-yl substituted at the 4- and 6- position with pyrrolidine or diethylamine, (b) pyrimidin-2-yl optionally substituted at the 4- and 6- position with pyrrolidine, (c) pyrimidin-4-yl optionally substituted at the 2- and 6- position with pyrrolidine or diethylamine, (d) pyridin-2-yl and (e) pyridin-2-yl substituted with pyrrolidine, ethylamine or diethylamine. 15. An amino-9,10-secosteroid according to claim 1 where 2IA an 21B are taken together with the attached nitrogen atom form a cycli amine substituent selected from the group consisting of 4- (2-pyridinyl)-l-piperazinyl, 4- [4,6-bis(2-propenylamino) -l,3,5-triazin-2-yl] -1-piperazinyl, 4- [2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl] -1-piperazinyl, 4- [2,6-bis(morpholino)-4-pyrimidinyl] -1-piperazinyl, 4- [4,6-bis(diethylamino)-2-pyrimidinyl] -1-piperazinyl, 4- [4,6-bis(l-pyrrolidinyl)-l,3,5-triazin-2-yl] -1-piperazinyl, 4- [3,6-bis(diethylamino) -2-pyridinyl] -1-piperazinyl, 4- [3- (ethylamino)-2-pyridinyl] -1-piperazinyl, 4- [6- (diethylamino)-2-pyridinyl] -1-piperazinyl, 4- [4,6-bis(2-pyridinyl)-l, 3,5-triazin-2-yl] -1-piperazinyl and 4- [2,6-bis(2-pyridinyl)-4-pyrimidinyl]-l-piperazinyl. 16. An amino-9,10-secosteroid according to claim 1 which is 3a-methyl-3α-hydroxy-7- [2-'(5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- (2 , 6-bis(1-pyrrolidinyl) -4-pyri idinyl)-1-piperazinyl]acetyl] - octahydro-5H-inden-5-one, 3a-methyl-3 -hydroxy-7- [2-(5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- (2-pyridiny1) -1-piperazinyl]acetyl]octahydro-5H-inden-5-one, 3a-methyl-3α-hydroxy-7- [2-(5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- [3- (ethylamino)-2-pyridinyl] -1-piperazinyl]acetyl]-octahydro- 5H-inden-5-one, 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)-ethyl]-3-[2-[4-(2,6- bis(l-pyrrolidinyl)-4-pyrimidinyl)-l-piperazinyl]ethyl] - 3a-octahydro- 5H-inden-5-one, 3a-methyl-7- [2- (5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- [3- (ethylamino) -2-pyridinyl] -1-piperazinyl]ethyl] -3α-octahydro-5H- inden-5-one, 3a-Methyl-3α-hydroxy-7- [2- (5-hydroxy-2-methylphenyl)-ethyl] -3- [2- [4- [2 , 6-bis (2-pyridinyl) -4-pyrimidinyl] -1-piperazinyl]acetyl] - octahydro-5H-inden-5-one, 3a-methyl-7- [2- (5-hydroxy-2-methylphenyl) -ethyl] -3- [2- [4- [3- (ethy1amino)-2-pyridinyl] -1-piperazinyl]ethylidene] - 3a-octahydro-5H- inden-5-one, 3a-methyl-7- [2- (5-hydroxy-2-methylphenyl)-ethyl]-3-[2-[4-[3- (ethylamlno) -2-pyridinyl] -1-piperazlnyl]acetyl] -3α-octahydro-5H- inden-5-one, 3a-methyl- 1 - [2- (5-hydroxy-2-methylphenyl)-ethyl]-3-[2-[4-(2,6- bis(l-pyrrolidinyl)-4-pyrimidinyl)-l-piperazinyl]ethyl] -3a-octahydro- 5H-inden-5-one, 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)ethyl]-3α-[2-[4-(2,6- bis(l-pyrrolidinyl)-4-pyrimidinyl) -l-piperazlnyl]acetyl]-3^-octa- hydro-5H-inden-5-one, 3a-methyl-7-[2-(5-hydroxy-2-methylphenyl)ethyl]-3α-[2-[4-[3- (ethylamino) -2-pyridinyl] -1-piperazinyl]acetyl] -3/3-octahydro-5H- inden-5-one, 3a-methyl-33-[2-[4-[3,6-bis(diethylamino)-2-pyridinyl]-l-piper- azinyl]acetyl] -7-[2-(5-hydroxy-2-methylphenyl)ethyl] -3α-octahydro-5H- inden-5-one, 7a-methyl-13-[2-[4-[3-(ethylamino)-2-pyridinyl]-1-piperazinyl] - acetyl]-4β- [2-(5-hydroxy-2-methylphenyl)-ethyl] -2, 3, 3aα, 4, 7, 7a- hexahydro-Δ^-1H-Indene, 7a-methyl-4α-[2-(5-hydroxy-2-methylphenyl)-ethyl]-19-[2-[4-(2,6- bis(l-pyrrolidinyl)-4-pyrimIdinyl)-l-piperazinyl]acetyl]-2, 3, 3aα, 4, 7, 7a-hexahydro-Δ^-lH-indene. 17. An amino-9,10-secosteroid according to claim 1 where 2I an R 21B are taken together with the attached nitrogen atom form 1- piperazinyl substituted in the 4- position with - CH2)j-aryl. 18. An amino-9,10-secosteroid according to claim 1 where the pharmaceutically acceptable salt is selected from the group consist¬ ing of hydrochloride, hydrobromide, hydrogen iodide, sulfate, phosphate, acetate, lactate, citrate, succinate, benzoate, salicycla- te, pamoate, cyclohexanesulfa ate, methanesulfonate, naphthalenesul- fonate, p-toluenesulfonate, maleate, fumarate and oxalate.

Inventors: GALL MARTIN, HIGUCHI ROBERT I, GALL, MARTIN, HIGUCHI, ROBERT, I.
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1988
Main classification: C07D239
IPC codes: A61K31, A61P3, A61P9, A61P11, A61P25, A61P27, A61P29, A61P35, A61P37, A61P39, A61P43, C07C401, C07D207, C07D209, C07D211, C07D213, C07D223, C07D225, C07D233, C07D235, C07D239, C07D251, C07D277, C07D333, C07D401, C07D409, C07D417, C07D521