This invention relates to compounds that are agonists of the muscarinic M.sub.1 receptor or M.sub.1 and M.sub.4 receptors and which are useful in the treatment of muscarinic M.sub.1 or M.sub.1/M.sub.4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula ##STR00001##
wherein Q.sup.4, Q.sup.5, R.sup.5, p, V, Q.sup.1, Q.sup.2, X.sup.1, X.sup.2 and W are defined herein.

This invention relates to compounds that are agonists of the muscarinic M.sub.1 receptor or M.sub.1 and M.sub.4 receptors and which are useful in the treatment of muscarinic M.sub.1 or M.sub.1/M.sub.4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula ##STR00001##
wherein Q.sup.4, Q.sup.5, R.sup.5, p, V, Q.sup.1, Q.sup.2, X.sup.1, X.sup.2 and W are defined herein.

The present invention discloses a hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d:

##STR00001##

The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.

The present invention discloses a hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d:

##STR00001##

The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.

The present disclosure provides methods of inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The methods are useful for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin. Compositions for use in these methods are also provided.

Capsaicin compositions and methods for enhancing hydrophobicity of a molecule useful for pharmaceutical applications, including: (1) a prodrug using a linker such as a carbamate between capsaicin with other structures in order to optimize kinetic control of capsaicin cleavage; (2) a prodrug using a linker such as an unsaturated carboxylic ester between capsaicin with other structures in order to optimize kinetic control of capsaicin cleavage; (3) esters of long-chain fatty acids and capsaicin where hydroxyl groups provide handles for attachment of additional capsaicin molecules; and (4) the use of carboxylic acid diesters to increase overall hydrophobicity of two or more covalently-linked capsaicin molecules. Formulations of palmitated esters of capsaicin are also described, which are designed to enhance hydrophobicity of a molecule useful for pharmaceutical applications, for example to provide compounded mixtures designed to optimize analgesic efficacy.

Capsaicin compositions and methods for enhancing hydrophobicity of a molecule useful for pharmaceutical applications, including: (1) a prodrug using a linker such as a carbamate between capsaicin with other structures in order to optimize kinetic control of capsaicin cleavage; (2) a prodrug using a linker such as an unsaturated carboxylic ester between capsaicin with other structures in order to optimize kinetic control of capsaicin cleavage; (3) esters of long-chain fatty acids and capsaicin where hydroxyl groups provide handles for attachment of additional capsaicin molecules; and (4) the use of carboxylic acid diesters to increase overall hydrophobicity of two or more covalently-linked capsaicin molecules. Formulations of palmitated esters of capsaicin are also described, which are designed to enhance hydrophobicity of a molecule useful for pharmaceutical applications, for example to provide compounded mixtures designed to optimize analgesic efficacy.

In a preferred embodiment, there is provided a process for separating an amine compound or a conjugate acid thereof and a carbamate compound or a conjugate acid thereof from a mixture having the amine compound, the carbamate compound, carbon dioxide and at least one anionic contaminant salt using an anionic exchange column, the process including passing the mixture through the column to obtain a first effluent and passing through the column an extraction fluid to obtain a second effluent, where the extraction fluid most preferably includes carbonic acid.

In a preferred embodiment, there is provided a process for separating an amine compound or a conjugate acid thereof and a carbamate compound or a conjugate acid thereof from a mixture having the amine compound, the carbamate compound, carbon dioxide and at least one anionic contaminant salt using an anionic exchange column, the process including passing the mixture through the column to obtain a first effluent and passing through the column an extraction fluid to obtain a second effluent, where the extraction fluid most preferably includes carbonic acid.

This compound, which absorbs long-wavelength active energy rays and generates with high-efficiency radicals and strong bases, and which has excellent reaction efficiency in a base generating chain reaction, is represented by formula (1), where, in formula (1), R.sub.1, R.sub.2, R.sub.3, R.sub.5 and R.sub.6 independently represent a hydroxy group, an alkoxy group, or an organic group other than those substituents, the R.sub.4's independently represent an organic group including a thioether bond, and A represents a substituent represented by formula (1-1) or (1-2), where, in formula (1-1), R.sub.7 and R.sub.8 independently represent a hydrogen atom, an alkyl group or a heterocyclic group, and where, in formula (1-2), R.sub.9 and R.sub.10 independently represent an amino group or a substituted amino group. A photopolymerization initiator can include said compound; and a photosensitive resin composition can include said photopolymerization initiator.

##STR00001##