The subject matter described herein is directed to methods of preparing certain antibody-drug conjugates (ADCs) wherein the antibody is linked to the drug through a linker, wherein the drug contains a heteroaryl group having a secondary nitrogen, and the linker is attached to the drug via the secondary nitrogen. The resulting conjugates are useful in treating various diseases and conditions.

The subject matter described herein is directed to methods of preparing certain antibody-drug conjugates (ADCs) wherein the antibody is linked to the drug through a linker, wherein the drug contains a heteroaryl group having a secondary nitrogen, and the linker is attached to the drug via the secondary nitrogen. The resulting conjugates are useful in treating various diseases and conditions.

Fulvestrant formulations suitable for intramuscular injection at concentration in excess of 40 mg/ml in the absence of castor oil and castor oil derivatives are disclosed.

The present invention relates to a compound of the formula (i) wherein Ar represents a phenyl or a 6-membered heteroaryl group, R1 and R2 represent independently a hydrogen atom or a deuterium atom, R3 represents (1) a —COR4 group, (2) a —BOR5OR6 group, (3) a —X—Z group, (4) a (C.sub.1-C.sub.6)alkyl group or a (C.sub.1-C.sub.6)alkenyl group, (5) a —X—S(O).sub.n(R7).sub.p(R8).sub.q group, (6) a halogen atom, a —NH.sub.2 group or a -CN group, (7) a —O—R11 group, (8) a —NH—COR9 group, (9) a —C(═NH)NHOH group, (10) a —NH—C(NH)—R9′ group, or (11) a —NHCOCOOR12 group or a —NHCOCONR12′R12″ group, X represents abond, a —NH— group, a —CONH— group or a —CO— group, Z represents a 4 or 5-membered cycloalkyl, a 4 or 5-membered heterocylcloalkyl group, a 4 or 5-membered heteroaryl group or a phenyl group or a pharmaceutically acceptable salt thereof. The present invention further relates to a medicament comprising said compound of formula (I) and to said compound of formula (I) for use as an inhibitor and degrader of estrogen receptors.

##STR00001##

The present disclosure provides a compound of Formula I:

##STR00001##

or a pharmaceutically acceptable salt wherein X, R.sup.1-R.sup.8, Y.sup.1-Y.sup.5, m, n, p, and q are defined herein. The novel 2H-chromene compounds are useful for the modulation of disorders mediated by estrogen, and other disorders, as described herein. The present invention also relates to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions.

Fulvestrant formulations suitable for intramuscular injection at concentration in excess of 40 mg/ml in the absence of castor oil and castor oil derivatives are disclosed.

The present disclosure provides pharmaceutical compositions that include one or more selective estrogen receptor modulator(s) (SERM(s), e.g., Lasofoxifene) and four or more pharmaceutically acceptable excipients. The pharmaceutical compositions may be able to form nanodroplets (e.g., by self-nanoemulsifying) in vaginal fluid and to deliver the one or more SERM(s) to the vagina of a female subject. The pharmaceutical compositions may be useful in treating or preventing vulvovaginal atrophy, dyspareunia, sexual dysfunction, osteoporosis, or breast cancer in a female subject.

The invention relates to compounds of formula (II), ##STR00001##
and pharmaceutically acceptable salts thereof,
wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

The present invention primarily relates to specific uses of a composition containing a roasted extract and xanthohumol for health-promoting purposes. In particular, the invention relates to a composition, preferably pharmaceutical composition, comprising xanthohumol (XN), preferably in a therapeutically effective amount, for (i) use in the treatment and/or prevention of cancer, and/or (ii) use in the treatment and/or prevention of osteoporosis, and/or (iii) use in the treatment and/or prevention of metabolic syndrome, and/or (iv) use in the treatment and/or prevention of diabetes, and/or (v) use in the treatment and/or prevention of cardiovascular disease(s), and/or (vi) use as anti-oxidant, and/or (vii) use as detoxifying agent, and/or (viii) inhibiting metabolic activation of procarcinogens, and/or (ix) use as anti-mutagenic and/or anti-genotoxic agent, and/or (x) use as anti-estrogenic and/or estrogenic agent, and/or (xi) inducing apoptosis, and/or (xii) use as anti-angiogenetic agent, and/or (xiii) use as anti-inflammatory agent, and/or (xiv) inhibiting NF-κB, and/or (xv) use in the treatment and/or prevention of infection(s), in particular, use as antimicrobial agent, wherein the composition comprises or consists of (a) a roasted extract and (b) XN, preferably a hop extract comprising XN, and/or wherein the composition is obtainable or obtained by mixing (a) a roasted extract and (b) XN or, preferably, a hop extract comprising XN.

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.