Pyrazinylpiperazinyl steroids

• US 5,382,661 A
• Filed: 12/01/1992
• Issued: 01/17/1995
• Est. Priority Date: 09/12/1985
• Status: Expired due to Term

• Current Assignee: The Upjohn Company (Pharmacia Corp.)
• Original Assignee: The Upjohn Company (Pharmacia Corp.)
• Inventors: McCall, John M.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): SRIPADA, PAVANARAM K
• Application Number:
  US07/984,298
• Time in Patent Office: 777 Days
• Field of Search: 540/108, 540/110, 540/111, 540/107, 540/63, 540/66, 540/5, 544/357, 544/120, 544/58.2, 544/121, 544/296
• US Class Current: 540/111
• CPC Class Codes: C07D 213/65 attached in position 3 or 5
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 239/50 Three nitrogen atoms
• CPC Class Codes: C07D 249/14 Nitrogen atoms
• CPC Class Codes: C07D 251/70 Other substituted melamines
• CPC Class Codes: C07D 295/135 with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 307/68 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 333/66 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07J 21/006 at position 3
• CPC Class Codes: C07J 3/005 the carbon atom being part of a carboxylic function
• CPC Class Codes: C07J 31/006 not covered by C07J31/003
• CPC Class Codes: C07J 41/005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
• CPC Class Codes: C07J 43/003 not condensed
• CPC Class Codes: C07J 5/0076 by an alkyl group
• CPC Class Codes: C07J 7/0085 by an halogen atom

Abstract

Disclosed are amino substituted steroids (XI) which contain a pyrazinylpiperazinyl group attached to the terminal carbon atom of the C₁₇ -side chain which are useful as pharmaceutical agents for treating a number of conditions.

Claims

1. An amino substituted steroid of formula XI ##STR41## where:

(A-I) R₆ is α

-R₆₁ ;

β

-R₆₂, R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂ and R₇ is α

-H;

β

-H, where one of R₆₁ and R₆₂ is --H, and the other is --H, --F, or C₁ -C₃ alkyl, R₁₀₂ is --CH₃, R₁₀₁ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is ═

O or α

-H;

β

-OR₃₄ or α

-OR₃₄ ;

β

-H, where R₃₄ is --H, --CO--CH₃, --CO--C₂ H₅, --CO--C₆ H₅, --CO--O--CH₃ or --CO--O--C₂ H₅ ;

(A-II) R₅ is α

-R₅₃ ;

β

-R₅₄, R₆ is α

-R₆₃ ;

β

-R₆₄, R₁₀ is α

-R₁₀₃ ;

β

-R₁₀₄ and R₇ is α

-H;

β

-H, where one of R₆₃ and R₆₄ is --H, and the other taken together with one of R₅₃ and R₅₄ forms a second bond between C₅ and C₆, R₁₀₄ is --CH₃, R₁₀₃ and the other of R₅₃ and R₅₄ taken together is --(CH₂)₂ --C(H)(OH)--CH₂ --;

(A-III) R₁₀ and R₅ taken together are ═

CH--CH═

C(OR₃)--CH═

where R₃ is --H, C₁ -C₃ alkyl, --CO--H, C₂ -C₄ alkanoyl or benzyl, R₆ is α

-R₆₅ ;

β

-R₆₆ where one of R₆₅ and R₆₆ is --H, and the other is --H, --F, or C₁ -C₃ alkyl and R₇ is α

-H;

β

-H;

(A-IV) R₅ is α

-R₅₇ ;

β

-R₅₈, R₆ is α

-R₆₇ ;

β

-R₆₈, R₇ is α

-H;

β

-H and R₁₀ is α

-R₁₀₇ ;

β

-R₁₀₈, where one of R₅₇ and R₅₈ is --H, R₁₀₇ and the other of R₅₇ and R₅₈ taken together are --(CH₂)₂ --C(═

R₃₃)--CH₂, where R₃₃ is as defined above, R₁₀₈ is --CH₃, where one of R₆₇ and R₆₈ is --H and the other is --H, --F, or C₁ -C₃ alkyl;

(A-V) R₆ is R₆₉ ;

R₆₁₀, R₇ is R₇₉ ;

R₇₁₀, R₁₀ is α

-R₁₀₉ ;

R₁₀₁₀, where one of R₆₉ and R₆₁₀ is --H and the other taken together with one of R₇₉ and R₇₁₀ forms a second bond between C₆ and C₇, and the other of R₇₉ and R₇₁₀ is --H, R₁₀₁₀ is --CH₃, R₁₀₉ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is as defined above;

(C-I) R₁₁ is α

-R₁₁₁ ;

β

-R₁₁₂, where one of R₁₁₁ and R₁₁₂ is taken together with R₉ to form a second bond between C₉ and C₁₁ and the other of R₁₁₁ and R₁₁₂ is --H;

(C-II) R₉ is --Cl and R₁₁ is ═

O or α

-H;

β

-R₁₁₄ where R₁₁₄ is --Cl or --OH;

(C-III) R₉ is --H or --F and R₁₁ is ═

O or α

-R₁₁₅ ;

β

-R₁₁₆, where one of R₁₁₅ and R₁₁₆ is --H, and the other of R₁₁₅ and R₁₁₆ is --H, --OH or C₁ -C₁₂ alkoxy;

(C-IV) R₉ is --H or --F and R₁₁ is α

-O--CO--R₁₁₇ ;

β

-H, where R₁₁₇ is

(A) C₁ -C₃ alkyl,

(B) C₁ -C₁₂ alkoxy,

(C) furanyl,

(D) --NR₁₂₂ R₁₂₃, where one of R₁₂₂ and R₁₂₃ is --H, methyl or ethyl and the other is --H, C₁ -C₄ alkyl or phenyl,

(E) -X₃ -X₁, where X₃ is --O-- or a valence bond, where X₁ is phenyl optionally substituted with 1 through 2 --Cl, --Br, C₁ -C₃ alkoxy, --COOH, --NH₂, C₁ -C₃ alkylamino, di(C₁ -C₃)alkylamino, where the alkyl groups are the same or different, 1-pyrrolidinyl-, 1-piperidinyl, 1-hexamethylenimino-, 1-heptamethylenimino-, C₂ -C₄ carboxylic acid acylamino and --NH--CHO or with 1 --F or --CF₃ ;

(D-I) R₁₆ is R₁₆₁ ;

R₁₆₂ and R₁₇ is R₁₇₁ ;

R₁₇₂, where one of R₁₆₁ and R₁₆₂ is --H or --CH₃ and the other taken together with one of R₁₇₁ and R₁₇₂ forms a second bond between C₁₆ and C₁₇, and the other of R₁₇₁ and R₁₇₂ is --C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀, where Z is ═

O, ═

CH₂ or R₁₇₉ ;

--H where R₁₇₉ is --H or --CH₃, where n is 1 through 6, where R₂₁ and R₂₁₀ are taken together with the attached nitrogen atom to form (6) 1-piperazinyl substituted in the 4-position with X₂ --(CH₂)_j --[E]

where j is 0 thru 3 and where X₂ is

(1) pyrazin-2-yl optionally substituted with 1 or 2 R₂₁₂ where the R₂₁₂ '"'"'s (7)

are the same or different and are

(i) --F,

(ii) --Cl,

(iii) --Br,

(iv) C₁ -C₅ alkyl,

(v) --CH₂ --CH═

CH₂,

(vi) --X₁, where X₁ is as defined above,

(vii) --NR₂₁₃ R₂₁₃ where the R₂₁₃ '"'"'s are the same or different and are --H, C₁ -C₃ alkyl or --CH₂ --CH═

CH₂,

(viiiα

) *CH₂ --(CH₂)_q --CH₂ --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,

(viiiβ

) *CH₂ --CH₂ --(CH₂)_c --G--(CH₂)_d --CH₂ --CH₂ --N*-- where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, where G is --O--, --S--, --SO--, --SO₂ -- or --NHR₂₁₄, where R₂₁₄ is --H, C₁ -C₃ alkyl, or X₁ 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, [a]

(ix) 3-pyrrolin-1-yl, [b]

(x) pyrrol-1-yl optionally substituted with C₁ -C₃ alkyl,[c]

(xi) piperidin-1-yl optionally substituted with 1 or 2 C₁ -C₃ alkyl, [d]

(xii) 1,2,3,6-tetrahydropyridin-1-yl, [e]

(xiii) 1-hexamethyleneimino containing a 3- or 4- double bond or 3- and 5- double bonds, [f]

(xiv) 1,4-dihydro-1-pyridinyl substituted in the 4 position by two C₁ -C₃ alkyl being the same or different, [g]

(xv) --OH,

(xvi) C₁ -C₃ alkoxy,

(xvii) --NR₂₁₇ --(CH₂)_e --Q where Q is 2-pyridinyl where R₂₁₇ is --H or C₁ -C₃ alkyl and e is 0 through 3,(1)

(xviii) pyridin-2-, 3- or 4-yl,

(D-II) R₁₆ is α

-R₁₆₃ ;

β

-R₁₆₄ where one of R₁₆₃ and R₁₆₄ is --H and the other is --H, --F, --CH₃ or --OH, and R₁₇ is ═

CH--(CH₂)_p --NR₂₁ R₂₁₀, where p is 1 or 2, where R₂₁ and R₂₁₀ are as defined above;

(D-III) R₁₆ is α

-R₁₆₅ ;

β

-R₁₆₆ and R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆, where R₁₆₅ is --H, --OH, --F or --CH₃ and R₁₆₆ is --H, --OH, --F, or --CH₃, with the proviso that at least one of R₁₆₅ and R₁₆₆ is --H, where R₁₇₅ is --H, --OH, --CH₃, --CH₂ CH₃, C₂ -C₇ alkanoyloxy or --O--CO--X₁, where X₁ is as defined above, and where R₁₇₆ is --C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀, where Z, n, R₂₁ and R₂₁₀ are as defined above;

(D-IV) the 16,17-acetonide of a compound where R₁₆₅ is --OH, R₁₆₆ is --H, R₁₇₅ is --OH and R₁₇₆ is --C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀, where Z, n, R₂₁ and R₂₁₀ are as defined above; and

pharmaceutically acceptable salts, hydrates and solvates thereof;

with the following overall provisos that;

(I) one of R₁₆₁ or R₁₆₂ is taken together with one of R₁₇₁ or R₁₇₂ to form a second bond between C₁₆ and C₁₇, only when R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂, α

-R₁₀₃ ;

β

-R₁₀₄, α

-R₁₀₇ ;

β

-R₁₀₈ or α

-R₁₀₉ ;

β

-R₁₀₁₀,

(II) R₁₇ is ═

CH--(CH₂)_p --NR₂₁ R₂₁₀, only when R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂, α

-R₁₀₃ ;

β

-R₁₀₄, α

-R₁₀₇ ;

β

-R₁₀₈ or α

-R₁₀₉ ;

β

-R₁₀₁₀,

(III) R₅ and R₁₀ taken together are ═

CH--CH═

C(OR₃)--CH═

, only when R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆ or the 16,17-acetonide of a compound where R₁₆ is α

-OH;

β

-H and R₁₇ is α

-OH;

β

-C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀, and

(IV) R₅ is α

-R₅₇ ;

β

-R₅₈, only when R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆ or α

-OH;

β

-C--(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀, or the 16,17-acetonide thereof.

2. An amino substituted steroid according to claim 1 where:

(A-I) R₆ is α

-R₆₁ ;

β

-R₆₂, R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂ and R₇ is α

-H;

β

-H, where one of R₆₁ and R₆₂ is --H, and the other is --H, --F, or C₁ -C₃ alkyl, R₁₀₂ is --CH₃, R₁₀₁ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is ═

O or α

-H;

β

-OR₃₄ or α

-OR₃₄ ;

β

-H, where R₃₄ is --H, --CO--CH₃, --CO--C₂ H₅, --CO--C₆ H₅, --CO--O--CH₃ or --CO--O--C₂ H₅ ;

(A-II) R₅ is α

-R₅₃ ;

β

-R₅₄, R₆ is α

-R₆₃ ;

β

-R₆₄, R₁₀ is α

-R₁₀₃ ;

β

-R₁₀₄ and R₇ is α

-H;

β

-H, where one of R₆₃ and R₆₄ is --H, and the other taken together with one of R₅₃ and R₅₄ forms a second bond between C₅ and C₆, R₁₀₄ is --CH₃, R₁₀₃ and the other of R₅₃ and R₅₄ taken together is --(CH₂)₂ --C(H)(OH)--CH₂ --;

(A-III) R₁₀ and R₅ taken together are ═

CH--CH═

C(OR₃)--CH═

where R₃ is --H, C₁ -C₃ alkyl, --CO--H, C₂ -C₄ alkanoyl or benzyl, R₆ is α

-R₆₅ ;

β

-R₆₆ where one of R₆₅ and R₆₆ is --H, and the other is --H, --F, or C₁ -C₃ alkyl and R₇ is α

-H;

β

-H;

(A-IV) R₅ is α

-R₅₇ ;

β

-R₅₈, R₆ is α

-R₆₇ ;

β

-R₆₈, R₇ is α

-H;

β

-H and R₁₀ is α

-R₁₀₇ ;

β

-R₁₀₈, where one of R₅₇ and R₅₈ is --H, R₁₀₇ and the other of R₅₇ and R₅₈ taken together are --(CH₂)₂ --C(═

R₃₃)--CH₂, where R₃₃ is as defined above, R₁₀₈ is --CH₃, where one of R₆₇ and R₆₈ is --H and the other is --H, --F, or C₁ -C₃ alkyl;

(A-V) R₆ is R₆₉ ;

R₆₁₀, R₇ is R₇₉ ;

R₇₁₀, R₁₀ is α

-R₁₀₉ ;

R₁₀₁₀, where one of R₆₉ and R₆₁₀ is --H and the other taken together with one of R₇₉ and R₇₁₀ forms a second bond between C₆ and C₇, and the other of R₇₉ and R₇₁₀ is --H, R₁₀₁₀ is --CH₃, R₁₀₉ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is as defined above;

(C-I) R₁₁ is α

-R₁₁₁ ;

β

-R₁₁₂, where one of R₁₁₁ and R₁₁₂ is taken together with R₉ to form a second bond between C₉ and C₁₁ and the other of R₁₁₁ and R₁₁₂ is --H;

(C-II) R₉ is --Cl and R₁₁ is ═

O or α

-H;

β

-R₁₁₄ where R₁₁₄ is --Cl or --OH;

(C-III) R₉ is --H or --F and R₁₁ is ═

O or α

-R₁₁₅ ;

β

-R₁₁₆, where one of R₁₁₅ and R₁₁₆ is --H, and the other of R₁₁₅ and R₁₁₆ is --H, --OH or C₁ -C₁₂ alkoxy;

(C-IV) R₉ is --H or --F and R₁₁ is α

-O--CO--R₁₁₇ ;

β

-H, where R₁₁₇ is

(A) C₁ -C₃ alkyl,

(B) C₁ -C₁₂ alkoxy,

(C) furanyl,

(D) --NR₁₂₂ R₁₂₃, where one of R₁₂₂ and R₁₂₃ is --H, methyl or ethyl and the other is --H, C₁ -C₄ alkyl or phenyl,

(E) --X₃ --X₁, where X₃ is --O-- or a valence bond, where X₁ is phenyl optionally substituted with 1 through 2 --Cl, C₁ -C₃ alkoxy, --NH₂, C₁ -C₃ alkylamino, di(C₁ -C₃)alkylamino, where the alkyl groups are the same or different, 1-pyrrolidinyl-, 1-piperidinyl, C₂ -C₄ acylamino and --NH--CHO;

(D-III) R₁₆ is α

-R₁₆₅ ;

β

-R₁₆₆ and R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆, where R₁₆₅ is --H, --OH, --F or --CH₃ and R₁₆₆ is --H, --OH, --F, or --CH₃, with the proviso that at least one of R₁₆₅ and R₁₆₆ is --H, where R₁₇₅ is --H, --OH, --CH₃, --CH₂ CH₃, C₂ -C₇ alkanoyloxy or --O--CO--X₁, where X₁ is as defined above, and where R₁₇₆ is --C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀, where n is 1.

3. An amino substituted steroid according to claim 2 where:

(A-I) R₆ is α

-R₆₁ ;

β

-R₆₂, R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂ and R₇ is α

-H;

β

-H, where one of R₆₁ and R₆₂ is --H, and the other is --H, --F, or C₁ -C₃ alkyl, R₁₀₂ is --CH₃, R₁₀₁ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is ═

O;

(C-I) R₁₁ is α

-R₁₁₁ ;

β

-R₁₁₂, where one of R₁₁₁ and R₁₁₂ is taken together with R₉ to form a second bond between C₉ and C₁₁ and the other of R₁₁₁ and R₁₁₂ is --H;

(C-III) R₉ is --H and R₁₁ is α

-R₁₁₅ ;

β

-R₁₁₆, where both R₁₁₅ and R₁₁₆ are --H;

(D-III) R₁₆ is α

-R₁₆₅ ;

β

-R₁₆₆ and R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆, where R₁₆₅ is --H, --OH, --F or --CH₃ and R₁₆₆ is --H, --OH, --F, or --CH₃, with the proviso that at least one of R₁₆₅ and R₁₆₆ is --H, where R₁₇₅ is --H, --OH, --CH₃, --CH₂ CH₃, C₂ -C₇ alkanoyloxy or --O--CO--X₁, where X₁ is phenyl optionally substituted with 1 through 2 --Cl, --Br, C₁ -C₃ alkoxy, --COOH, --NH₂, C₁ -C₃ alkylamino, di(C₁ -C₃)alkylamino, where the alkyl groups are the same or different, 1-pyrrolidinyl-, 1-piperidinyl, 1-hexamethylenimino-, 1-heptamethylenimino-, C₂ -C₄ acylamino and --NH--CHO or with 1 --F or --CF₃, and where R₁₇₆ is --C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀, where n is 1.

4. An amino substituted steroid according to claim 1 where R₆ is α

-R₆₁ ;

β

-R₆₂ and R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂, where one of R₆₁ and R₆₂ is --H, and the other is --H, --F or C₁ -C₃ alkyl, R₁₀₂ is --CH₃, R₁₀₁ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is ═

O or α

-H;

β

-OR₃₄ or α

-OR₃₄ ;

β

-H, where R₃₄ is --H, --CO--CH₃, --CO--C₂ H₅, --CO--C₆ H₅, --CO--O--CH₃ or --CO--O--C₂ H₅ or R₅ is α

-R₅₃ ;

β

-R₅₄, R₆ is α

-₆₃ ;

β

-R₆₄ and R₁₀ is α

-R₁₀₃ ;

β

-R₁₀₄ where one of R₆₃ and R₆₄ is --H, and the other taken together with one of R₅₃ and R₅₄ forms a second bond between C₅ and C₆, R₁₀₄ is --CH₃, R₁₀₃ and the other of R₅₃ and R₅₄ taken together is --(CH₂)₂ --C(H)(OH)--CH₂ --, R₇ is α

-H;

β

-H and R₁₆ is α

-R₁₆₅ ;

β

-R₁₆₆ and R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆, where R₁₆₅ is --H, --OH, --F or --CH₃ and R₁₆₆ is --H, --OH, --F, or --CH₃, with the proviso that at least one of R₁₆₅ and R₁₆₆ must be --H, where R₁₇₅ is --H, --OH, --CH₃, --CH₂ CH₃, C₂ -C₇ alkanoyloxy or --O--CO--X₁, and where R₁₇₆ is --C(═

Z)--(CH₂)_n -- NR₂₁ R₂₁₀ ;

which is the amino steroid of formula Ia or Ib ##STR42## is a single or double bond and _-- indicates that there are 2 possible orientations for the attached group, (1) α

or β

when attached to the steroid ring and (2) cis or trans when attached to a carbon atom of a double bond.

5. An amino substituted steroid according to claim 4 where R₁₀₁ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is ═

O.

6. An amino steroid (Ia and Ib) according to claim 4 which is

17α

-hydroxy-21-[4-(3,6-dimethylpyrazinyl)-1-piperazinyl]pregna-4,9(11)-diene-3,20-dione.

7. An amino substituted steroid according to claim 1 where R₁₀ and R₅ taken together are ═

CH--CH═

C(OR₃)--CH═

where R₃ is --H, C₁ -C₃ alkyl, --CO--H, C₂ -C₄ alkanoyl or benzyl, R₆ is α

-R₆₅ ;

β

-R₆₆ where one of R₆₅ and R₆₆ is --H, and the other is --H, --F or C₁ -C₃ alkyl, R₇ is α

-H;

β

-H and R₁₆ is α

-R₁₆₅ ;

β

-R₁₆₆ and R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆, where R₁₆₅ is --H, --OH, --F or --CH₃ and R₁₆₆ is --H, --OH, --F, --CH₃, with the proviso that at least one of R₁₆₅ and R₁₆₆ must be --H, where R₁₇₅ is --H, --OH, --CH₃, --CH₂ CH₃, C₂ -C.sub. 7 alkanoyloxy or --O--CO--X₁, and where R₁₇₆ is --C(═

Z)--(CH₂)_n --N-- R₂₁ R₂₁₀ ;

which is the aromatic steroid of formula II ##STR43##

8. An amino substituted steroid according to claim 1 where R₆ is α

-R₆₁ ;

β

-R₆₂ and R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂, where one of R₆₁ or R₆₂ is --H, and the other is --H, --OH, --F, C₁ -C₃ alkyl or phenyl, R₁₀₂ is --CH₃, R₁₀₁ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is ═

O or α

-H;

β

-OR₃₄ or α

-OR₃₄ ;

β

-H, where R₃₄ is --H, --CO--CH₃, --CO--C₂ H₅, --CO--C₆ H₅, --CO--O--CH₃ or --CO--O--C₂ H₅ or R₅ is α

-R₅₃ ;

β

-R₅₄, R₆ is α

-R₆₃ ;

β

-R₆₄ and R₁₀ is α

-R₁₀₃ ;

β

-R₁₀₄ where one of R₆₃ and R₆₄ is --H, and the other taken together with one of R₅₃ and R₅₄ forms a second bond between C₅ and C₆, R₁₀₄ is --CH₃, R₁₀₃ and the other of R₅₃ and R₅₄ taken together is --(CH₂)₂ --C(H)(OH)--CH₂ --, R₇ is α

-H;

β

-H and R₁₆ is R₁₆₁ ;

R₁₆₂ and R₁₇ is R₁₇₁ ;

R₁₇₂, where one of R₁₆₁ and R₁₆₂ is --H or --CH₃ and the other taken together with one of R₁₇₁ and R₁₇₂ forms a second bond between C₁₆ and C₁₇, and the other of R₁₇₁ and R₁₇₂ is --C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀ ;

which is the Δ

¹⁶ steroid of formula IIIa or IIIb ##STR44## is a single or double bond and where -- indicates that there are 2 possible orientations for the attached group, (1) α

or β

when attached to the steroid ring and (2) cis or trans when attached to a carbon atom of a double bond.

9. An amino substituted steroid according to claim 1 where R₅ is α

-₅₇ ;

β

-R₅₈, R₆ is α

-R₆₇ ;

β

-R₆₈ and R₁₀ is α

-R₁₀₇ ;

β

-R₁₀₈, where one of R₅₇ and R₅₈ is --H, R₁₀₇ and the other of R₅₇ and R₅₈ taken together are --(CH₂)₂ --C(R₃₃)--CH₂, where R₃₃ is ═

O or α

-H;

β

-OR₃₄ or α

-OR₃₄ ;

β

-H, where R₃₄ is --H, --CO--CH₃, --CO--C₂ H₅, --CO--C₆ H₅, --CO--O--CH₃ or --CO--O--C₂ H₅, R₁₀₈ is --CH₃, where one of R₆₇ and R₆₈ is --H and the other is --H, --F or C₁ -C₃ alkyl, R₇ is α

-H;

β

-H and R₁₆ is α

-R₁₆₅ ;

β

-R₁₆₆ and R₁₇ is α

-R₁₇₅ ;

β

-R₁₇₆, where R₁₆₅ is --H, --OH, --F or --CH₃ and R₁₆₆ is --H, --OH, --F or --CH₃, with the proviso that at least one of R₁₆₅ and R₁₆₆ must be --H, where R₁₇₅ is --H, --OH, --CH₃, --CH₂ CH₃, C₂ -C₇ alkanoyloxy or --O--CO--X₁, and where R₁₇₆ is --C(═

Z)--(CH₂)_n --NR₂₁ R₂₁₀ ;

which is the reduced A/B-ring steroid of formula IV ##STR45## is a single or double bond and where -- indicates that there are 2 possible orientations for the attached group, (1) α

or β

when attached to the steroid ring and (2) cis or trans when attached to a carbon atom of a double bond.

10. An amino substituted steroid according to claim 1 where R₆ is α

-R₆₁ ;

β

-R₆₂ and R₁₀ is α

-R₁₀₁ ;

β

-R₁₀₂, where one of R₆₁ and R₆₂ is --H, and the other is --H, --F or C₁ -C₃ alkyl, R₁₀₂ is --CH₃, R₁₀₁ and R₅ taken together are --(CH₂)₂ --C(═

R₃₃)--CH═

or --CH═

CH--CO--CH═

, where R₃₃ is ═

O or α

-H;

β

-OR₃₄ or α

-OR₃₄ ;

β

-H, where R₃₄ is --H, --CO--CH₃, --CO--C₂ H₅, --CO--C₆ H₅, --CO--O--CH₃ or --CO--O--C₂ H₅ or R₅ is α

-R₅₃ ;

β

-R₅₄, R₆ is α

-R₆₃ ;

β

-R₆₄ and R₁₀ is α

-R₁₀₃ ;

β

-R₁₀₄ where one of R₆₃ and R₆₄ is --H, and the other taken together with one of R₅₃ and R₅₄ forms a second bond between C₅ and C₆, R₁₀₄ is --CH₃, R₁₀₃ and the other of R₅₃ and R₅₄ taken together is --(CH₂)₂ --C(H)(OH)--CH₂ --, R₇ is α

-H;

β

-H and R₁₆ is α

-R₁₆₃ ;

β

-R₁₆₄ where one of R₁₆₃ and R₁₆₄ is --H and the other is --H, --OH, --F or --CH₃, and R₁₇ is ═

CH--(CH₂)_p --NR₂₁ R₂₁₀, where p is 1 or 2 which is the Δ

¹⁷ steroid of formula Va or Vb ##STR46## where is a single or double bond and where -- indicates that there are 2 possible orientations for the attached group, (1) α

or β

when attached to the steroid ring and (2) cis or trans when attached to a carbon atom of a double bond.

11. An amino substituted steroid according to claim 1 where R₁₁ is α

-R₁₁₁ ;

β

-R₁₁₂, where one of R₁₁₁ and R₁₁₂ is taken together with R₉ to form a second bond between C₉ and C₁₁ and the other of R₁₁₁ and R₁₁₂ is --H.

12. An amino substituted steroid according to claim 1 where R₉ is --H.

13. An amino substituted steroid according to claim 1 where Z is═

O.

14. An amino substituted steroid according to claim 1 where n is 1.

15. An amino substituted steroid according to claim 1 where j is 0.

16. An amino substituted steroid according to claim 1 where the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, hydrogen iodide, sulfate, phosphate, acetate, lactate, citrate, succinate, benzoate, salicyclate, pamoate, cyclohexanesulfamate, methanesulfonate, naphthalenesulfonate, p-toluenesulfonate, maleate, fumarate and oxalate.