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US 2003/0229072 A1Published application
Cyclic and acyclic amidines and pharmaceutical compositions containing them for use as progesterone receptor binning agents
OwnerWilliam H Bullock, Harold C E Kluender +4inventors
InventorsWilliam H Bullock, Harold C E Kluender, William L Collibee, Robert Dally, Martha E Rodriguez, Ming Wang
Life of this patent
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Abstract
Disclosed are cyclic and acyclic amidines, pharmaceutical compositions containing such amidines, and their use in treating or preventing progesterone receptor mediated diseases or conditions, such as osteopenia and osteoporosis.
Claims34
A compound of the formula (I)
- 135
- wherein
- R1
- is selected from the group consisting of aryl of 6-12 carbon atoms and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O;
- T
- is selected from the group consisting of hydrogen, nitro, nitriue, alkyl of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms, and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O or
- T
- may form, together with a carbon atom adjacent to a carbon atom to which it is attached, a fused ring of 6-9 carbon atoms and 4-14 hydrogen atoms;
- t
- is 1-5;
- R2
- is selected from the group consisting of alkyl of 2-10 carbon atoms, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-12 carbon atoms and containing 1-3 rings, and alkynyl of 3-10 carbon atoms;
- G
- is a selected from the group consisting of hydrogen, nitro, nitrile, halogen, OH, OR4, ═O, haloalkyl of 1-4 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-4 carbon atoms, alkenyl of 1-4 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 3-5 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, O, and S, cycloalkenyl of 5-7 carbon atoms, heterocycloalkenyl of 4-6 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, O, and S, CO2R4, C(O)N(R5)(R6), aryl of 6-10 carbon atoms, heteroaryl of 3-9 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, O, and S, S(O)yR7, SO3R7, and SO2N(R5)(R6);
- R4
- is selected from the group consisting of alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms and a number of halogen atoms up to the perhalo level, cycloalkyl of 3-6 carbon atoms, and halocycloalkyl of 3-6 carbon atoms;
- R5 and R6
- are each independently selected from the group consisting of hydrogen and alkyl of 1-5 carbon atoms;
- R7
- is selected from the group consisting of alkyl of 1-5 carbon atoms, SO2F, CHO, OH, nitro, nitrile, halogen, OCF3, N-oxide, O—C(R8)2O, C(O)NHC(O), the carbon atoms being connected to adjacent positions on R, and C(O)C6H4, the carbonyl carbon and the ring carbon ortho to the carbonyl carbon being connected to adjacent positions on R;
- R8
- is selected from the group consisting of hydrogen, halogen and alkyl of 1-4 carbon atoms;
- y
- is 0-2
- g
- is 0-4, with the exception of halogen, which may be employed up to the perhalo level;
- provided that when G is alkyl of 1-4 carbon atoms, alkenyl of 1-4 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 3-5 carbon atoms, cycloalkenyl of 5-7 carbon atoms, or heterocycloalkenyl of 4-6 carbon atoms, then G optionally may bear secondary substituents of halogen up to the perhalo level;
- and when G is aryl or heteroaryl, then G optionally may bear secondary substituents independently selected from the group consisting of alkyl of 1-4 carbon atoms and halogen, the number of said secondary substituents being up to 3 for alkyl moieties, and up to the perhalo level for halogen;
- x
- forms, together with the nitrogen atom and carbon atom to which it is attached, a polycyclic ring structure of containing 3-4 rings, wherein each ring contains 3-8 carbon atoms and may optionally be substituted with one or more of alkyl of 1-6 carbon atoms or alkenyl of 2-6 carbon atoms, or
- X is alkyl of 3-7 carbon atoms or alkenyl of 3-7 carbon atoms;
- R10, R11 and R12
- (i) are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms, or
- (ii) R10 and R11 are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms and R12 forms, together with the carbon atom to which it is attached, a Spiro ring of 3-6 carbon atoms, or
- (iii) R10 and R11 are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms and R12 forms, together with the carbon atom adjacent to the carbon atom to which it is attached, a fused ring of 3-7 carbon atoms and 4-14 hydrogen atoms, or
- (iv) R10 and R11 are each independently-selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms and R12 forms, together with the carbon atom that is 2-4 carbon atoms away from the carbon atom to which it is attached, a fused ring of 3-7 carbon atoms and 4-14 hydrogen atoms;
- with the proviso that when X is alkyl of 3-4 carbon atoms and R10, R11 and R12 are all hydrogen:
- t is 2-5;
- at least one of T is 4-nitro or 4-nitrile and at least one other T is 2-alkyl, 2-halogen or 2-trifluoromethyl;
- and R1 is phenyl;
- and with the further proviso that when X is alkyl of 3-7 carbon atoms or alkenyl of 3-7 carbon atoms and R10, R11 and R12 are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms, then at least one of T is nitro, nitrile, trifluoromethyl or halogen;
- and pharnaceutically acceptable salts thereof
39 more elements
A compound of the formula (II)
- 142
- wherein
- R13
- is selected from the group consisting of aryl of 6-12 carbon atoms and 4-pyridyl;
- R14
- is selected from the group consisting of aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-12 carbon atoms, with the proviso that said cycloalkenyl is mono-cyclic, and R17—R18;
- T′
- is selected from the group consisting of hydrogen, nitro, nitrile, alkyl of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms, and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O with the proviso that when R13 is aryl of 6-12 carbon atoms, at least one of T′ is nitro, nitrile, trifluoromethyl or halogen, or
- T′
- may form, together with a carbon atom adjacent to a carbon atom to which it is attached, a fused ring of 6-9 carbon atoms and 4-14 hydrogen atoms;
- t′
- is 1-5;
- R17
- is selected from the group consisting of alkyl of 1-10 carbon atoms and alkenyl of 2-10 carbon atoms;
- R18
- is selected from the group consisting of aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O, and cycloalkenyl of 5-12 carbon atoms;
- R15 and R16
- (i) are each independently selected from the group consisting of hydrogen, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-12 carbon atoms, and R19—R20, such that the total number of non-hydrogen atoms in R14, R15 and R16 is greater than or equal to 9, or
- (ii) are joined to form, together with the nitrogen atom to which they are attached, a 5-8 membered ring containing 4-7 carbon atoms and 1-2 heteroatoms selected from the group consisting of N, S and O which ring may optionally be substituted with R21 and R22, with the proviso that when R15 and R16 form a morpholine ring together with the nitrogen atom to which they are attached, said morpholine ring is substituted with at least one of R21 and R22;
- R19
- is selected from the group consisting of alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, and cycloalkenyl of 5-12 carbon atoms;
- R20
- is selected from the group consisting of hydrogen, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O cycloalkenyl of 5-12 carbon atoms, and R23—R24, with the proviso that when R20 is phenyl, only one of R15 and R16 can be R19—R20;
- R23
- is selected from the group consisting of aryl of 6-12 carbon atoms and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O;
- R24
- is selected from the group consisting of hydrogen, halogen, nitrile, nitro, alkyl of 1-10 carbon atoms, and haloalkyl of 1-6 carbon atoms and 1-3 halo atoms;
- R21 and R22
- (i) are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O and benzimidazolinone, or
- (ii) each independently forms, together with the carbon atom adjacent to the carbon atom to which it is attached, a fused ring of 3-6 carbon atoms and 4-10 hydrogen atoms, or
- (iii) R21 is selected from the group consisting hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O and benzimidazolinone and R22 forms, together with the carbon atom adjacent to the carbon atom to which it is attached, a fused ring of 3-6 carbon atoms and 4-10 hydrogen atoms;
- and pharmaceutically acceptable salts thereof.
29 more elements
A method of treating a disease or condition in a mammal, comprising administering to a mammal in need thereof an effective amount of a compound according to the general formula (III)
- 148
- wherein
- R25
- is selected from the group consisting of aryl of 6-12 carbon atoms and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O;
- Q
- is selected from the group consisting of hydrogen, nitro, nitrile, alkyl of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms, and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O or
- Q
- may fonn, together with a carbon atom adjacent to a carbon atom to which it is attached, a fused ring of 6-9 carbon atoms and 4-14 hydrogen atoms;
- q
- is 0-5;
- R26
- is selected from the group consisting of hydrogen, alkyl of 1-10 carbon atoms, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-12 carbon atoms and containing 1-3 rings, and alkynyl of 3-10 carbon atoms;
- G′
- is a selected from the group consisting of hydrogen, nitro, nitrile, halogen, OH, OR27, ═O, haloalkyl of 1-4 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-4 carbon atoms, alkenyl of 1-4 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 3-5 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, O, and S, cycloalkenyl of 5-7 carbon atoms, heterocycloalkenyl of 4-6 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, O, and S, CO2R27, C(O)N(R28)(R29), aryl of 6-10 carbon atoms, heteroaryl of 3-9 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, O, and S, S(O)yR30, SO3R30, and SO2N(R28)(R29);
- R27
- is selected from the group consisting of alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms and a number of halogen atoms up to the perhalo level, cycloalkyl of 3-6 carbon atoms, and halocycloalkyl of 3-6 carbon atoms;
- R28 and R29
- are each independently selected from the group consisting of hydrogen and alkyl of 1-5 carbon atoms;
- R30
- is selected from the group consisting of alyl of 1-5 carbon atoms, SO2F, CHO, OH, nitro, nitrile, halogen, OCF3, N-oxide, O—C(R31)2O, C(O)NHC(O), the carbon atoms being connected to adjacent positions on R, and C(O)C6H4, the carbonyl carbon and the ring carbon ortho to the carbonyl carbon being connected to adjacent positions on R;
- R31
- is selected from the group consisting of hydrogen, halogen and alkyl of 1-4 carbon atoms;
- y
- is 0-2
- g′
- is 0-4, with the exception of halogen, which may be employed up to the perhalo level;
- provided that when G is alkyl of 1-4 carbon atoms, alkenyl of 1-4 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 3-5 carbon atoms, cycloalkenyl of 5-7 carbon atoms, or heterocycloalkenyl of 4-6 carbon atoms, then G optionally may bear secondary substituents of halogen up to the perhalo level;
- and when G is aryl or heteroaryl, then G optionally may bear secondary substituents independently selected from the group consisting of alkyl of 1-4 carbon atoms and halogen, the number of said secondary substituents being up to 3 for alkyl moieties, and up to the perhalo level for halogen;
- X′forms, together with the nitrogen atom and carbon atom to which it is attached, a polycyclic ring structure of containing 3-4 rings, wherein each ring contains 3-8 carbon atoms and may optionally be substituted with one or more of alkyl of 1-6 carbon atoms or alkenyl of 2-6 carbon atoms, or
- X′ is
- 149
- wherein binding is achieved via the terminal carbon atoms;
- n
- is 3-7;
- p
- is 0-7;
- R32, R33 and R34
- (i) are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms, or
- (ii) R32 and R33 are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms and R34 forms, together with the carbon atom to which it is attached, a spiro ring of 3-6 carbon atoms, or
- (iii) R32 and R33 are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms and R34 forms, together with the carbon atom adjacent to the carbon atom to which it is attached, a fused ring of 3-7 carbon atoms and 4-14 hydrogen atoms, or
- (iv) R32 and R33 are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-7 carbon atoms, and alkynyl of 3-10 carbon atoms and R34 forms, together with the carbon atom that is 2-4 carbon atoms away from the carbon atom to which it is attached, a fused ring of 3-7 carbon atoms and 4-14 hydrogen atoms;
- and pharmaceutically acceptable salts thereof for:
- A1) enhancement of bone formation in bone weakening diseases for the treatment or prevention of osteopenia or osteoporosis;
- A2) enhancement of fracture healing;
- B1) use as a female contragestive agent;
- B2) prevention of endometrial implantation;
- B3) induction of labor;
- B4) treatment of luteal deficiency;
- B5) enhanced recognition and maintanence of pregnancy;
- B6) counteracting of preeclampsia, eclampsia of pregnancy, and preterm labor;
- B7) treatment of infertility, including promotion of spermatogenesis, induction of the acrosome reaction, maturation of oocytes, or in vitro fertilization of oocytes;
- C1) treatment of dysmenorrhea;
- C2) treatment of dysfunctional uterine bleeding;
- C3) treatment of ovarian hyperandrogynism;
- C4) treatment of ovarian hyperaldosteronism;
- C5) alleviation of premenstral syndrome and of premenstral tension;
- C6) alleviation of perimenstrual behavior disorders;
- C7) treatment of climeracteric disturbance, including, menopause transition, mood changes, sleep disturbance, and vaginal dryness;
- C8) enhancement of female sexual receptivity and male sexual receptivity;
- C9) treatment of post menopausal urinary incontinence;
- C10) improvement of sensory and motor functions;
- C11) improvement of short term memory;
- C12) alleviation of postpartum depression;
- C13) treatment of genital atrophy;
- C14) prevention of postsurgical adhesion formation;
- C15) regulation of uterine immune function;
- C16) prevention of myocardial infarction;
- D1) hormone replacement;
- E1) treatment of cancers, including hormone mediated cancers, such as breast cancer, uterine cancer, ovarian cancer, and endometrial cancer;
- E2) treatment of endometriosis;
- E3) treatment of uterine fibroids;
- F1) treatment of hirsutism;
- F2) inhibition of hair growth;
- G1) activity as a male contraceptive;
- G2) activity as an abortifacient;
- and
- H1) promotion of mylin repair.
74 more elements
A method of treating a disease or condition in a mammal, comprising administering to a mammal in need thereof an effective amount of a compound according to the general formula (IV)
- 150
- wherein
- R35
- is selected from the group consisting of aryl of 6-12 carbon atoms and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O;
- R36
- is selected from the group consisting of aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-12 carbon atoms, and R39—R40;
- Q′
- is selected from the group consisting of hydrogen, nitro, nitrile, alkyl of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms, and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O or
- Q′
- may form, together with a carbon atom adjacent to a carbon atom to which it is attached, a fused ring of 6-9 carbon atoms and 4-14 hydrogen atoms;
- q′
- is 0-5;
- R39
- is selected from the group consisting of alkyl of 1-10 carbon atoms and alkenyl of 2-10 carbon atoms;
- R40
- is selected from the group consisting of aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O, and cycloalkenyl of 5-12 carbon atoms;
- R37 and R38
- (i) are each independently selected from the group consisting of hydrogen, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-12 carbon atoms, and R41—R42, such that the total number of atoms in R36, R37 and R38 is greater than or equal to 9, or
- (ii) are joined to form, together with the nitrogen atom to which they are attached, a 5-8 membered ring containing 4-7 carbon atoms and 1-2 heteroatoms selected from the group consisting of N, S and O which ring may optionally be substituted with R43 and R44;
- R41
- is selected from the group consisting of alkyl of 1-10 carbon atoms, cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O alkenyl of 2-10 carbon atoms, cycloalkenyl of 5-12 carbon atoms, and alkynyl of 3-10 carbon atoms;
- R42
- is selected from the group consisting of hydrogen, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O cycloalkyl of 3-12 carbon atoms, heterocycloalkyl of 4-7 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O cycloalkenyl of 5-12 carbon atoms, and R45—R46;
- R45
- is selected from the group consisting of aryl of 6-12 carbon atoms and heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O;
- R46
- is selected from the group consisting of hydrogen, halogen, nitrile, nitro, alkyl of 1-10 carbon atoms, and haloalkyl of 1-6 carbon atoms and 1-3 halo atoms;
- R43 and R44
- (i) are each independently selected from the group consisting of hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O and benzimidazolinone, or
- (ii) each independently forms, together with the carbon atom adjacent to the carbon atom to which it is attached, a fused ring of 3-6 carbon atoms and 4-10 hydrogen atoms, or
- (iii) R43 is selected from the group consisting hydrogen, haloalkyl of 1-10 carbon atoms and a number of halogen atoms up to the perhalo level, alkyl of 1-10 carbon atoms, aryl of 6-12 carbon atoms, heteroaryl of 2-11 carbon atoms and 1-3 heteroatoms selected from the group consisting of N, S and O and benzimidazolinone and Re forms, together with the carbon atom adjacent to the carbon atom to which it is attached, a fused ring of 3-6 carbon atoms and 4-10 hydrogen atoms;
- and pharmaceutically acceptable salts thereof for:
- A1) enhancement of bone formation in bone weakening diseases for the treatment or prevention of osteopenia or osteoporosis;
- A2) enhancement of fracture healing;
- B1) use as a female contragestive agent;
- B2) prevention of endometrial implantation;
- B3) induction of labor;
- B4) treatment of luteal deficiency;
- B5) enhanced recognition and maintanence of pregnancy;
- B6) counteracting of preeclampsia, eclampsia of pregnancy, and preterm labor;
- B7) treatment of infertility, including promotion of spermatogenesis, induction of the acrosome reaction, maturation of oocytes, or in vitro fertilization of oocytes;
- C1) treatment of dysmenorrhea;
- C2) treatment of dysfunctional uterine bleeding;
- C3) treatment of ovarian hyperandrogynism;
- C4) treatment of ovarian hyperaldosteronism;
- C5) alleviation of premenstral syndrome and of premenstral tension;
- C6) alleviation of perimenstrual behavior disorders;
- C7) treatment of climeracteric disturbance, including. menopause transition, mood changes, sleep disturbance, and vaginal dryness;
- C8) enhancement of female sexual receptivity and male sexual receptivity;
- C9) treatment of post menopausal urinary incontinence;
- C10) improvement of sensory and motor functions;
- C b 11) improvement of short term memory;
- C12) alleviation of postpartum depression;
- C13) treatment of genital atrophy;
- C14) prevention of postsurgical adhesion formation;
- C15) regulation of uterine immune fimction;
- C16) prevention of myocardial infarction;
- D1) hormone replacement;
- E1) treatment of cancers, including hormone mediated cancers, such as breast cancer, uterine cancer, ovarian cancer, and endometrial cancer;
- E2) treatment of endometriosis;
- E3) treatment of uterine fibroids;
- F1) treatment of hirsutism;
- F2) inhibition of hair growth;
- G1) activity as a male contraceptive;
- G2) activity as an abortifacient;
- and
- H1) promotion of mylin repair.
64 more elements
Dependencies are inferred from the claim text.