Methods for making a dolastatin, auristatin or related compounds comprising the steps of providing a universal dolastatin core of Formula (I) reacting the C-terminal carboxylic acid group with an amine (A) to form an amide bond and reacting the N-terminal amine with a carboxylic acid (CA) to form an amide bond, wherein the steps can be performed in either order. Also provided are an isolated salt of the universal dolastatin core for use in preparation of dolastatins, auristatins and related compounds. Also provided are a number of intermediates and process steps which are useful for the preparation of high purity dolastatin core and high purity dolastatin and auristatin compounds.

[Problem] To provide a nuclear magnetic resonance diagnostic agent that has a lower toxicity to organisms and reduced side effects and yet has a site specificity toward a specific cell, tissue, organ, etc. [Solution] When ALA or an ALA derivative is administered in vivo, a metabolite thereof is accumulated in a specific cell, tissue, organ, etc. Focusing on this phenomenon, a nuclear magnetic resonance analysis was performed on a site wherein the metabolite of ALA that had been administered in vivo would be possibly accumulated. As a result, it was surprisingly found that ALA and an ALA derivative are useful as a diagnostic agent whereby the aforesaid problem can be solved.

[Problem] To provide a nuclear magnetic resonance diagnostic agent that has a lower toxicity to organisms and reduced side effects and yet has a site specificity toward a specific cell, tissue, organ, etc. [Solution] When ALA or an ALA derivative is administered in vivo, a metabolite thereof is accumulated in a specific cell, tissue, organ, etc. Focusing on this phenomenon, a nuclear magnetic resonance analysis was performed on a site wherein the metabolite of ALA that had been administered in vivo would be possibly accumulated. As a result, it was surprisingly found that ALA and an ALA derivative are useful as a diagnostic agent whereby the aforesaid problem can be solved.

Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein:

##STR00001##

wherein m, n, p, R′, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, Z, W, Y, and Z are as defined herein.

Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein:

##STR00001##

wherein m, n, p, R′, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, Z, W, Y, and Z are as defined herein.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II):

##STR00001## including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II):

##STR00001## including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Disclosed in the present invention are a crystal form of aromatic vinyl derivatives, and a preparation method therefor and the use thereof. Specifically disclosed in the present invention are crystal form A, crystal form B and crystal form C of a compound as shown in formula I. The crystal forms of the present invention have a good stability, are less hygroscopic and are easy to prepare, and have an important value in terms of the optimization and development of drugs.

##STR00001##

Disclosed in the present invention are a crystal form of aromatic vinyl derivatives, and a preparation method therefor and the use thereof. Specifically disclosed in the present invention are crystal form A, crystal form B and crystal form C of a compound as shown in formula I. The crystal forms of the present invention have a good stability, are less hygroscopic and are easy to prepare, and have an important value in terms of the optimization and development of drugs.

##STR00001##

The present invention relates to a composition comprising a photosensitizer use in prevention or treatment of dermatological disease in a patient, wherein the composition is used in the following order of steps: (a) topical application or subcutaneous injection of said composition to an area of the skin of said patient, (b) exposure of at least said area of the skin to light with a wavelength spectrum similar or identical to sun light for a duration of 30 min to 5 hours, and (c) exposure of at least said area of the skin to light of a wavelength spectrum comprising only one maximum in the absorbance spectrum of said photosensitizer
as well as to methods of treating dermatological disease using the outlined steps and kits of parts comprising such compositions and light sources suitable to apply the respectively indicated light.