Vitamin D analogues

• US 4,772,433 A
• Filed: 02/10/1986
• Issued: 09/20/1988
• Est. Priority Date: 11/02/1981
• Status: Expired due to Term

• Current Assignee: Research Institute For Medicine and Chemistry Incorporated
• Original Assignee: Research Institute For Medicine and Chemistry Incorporated
• Inventors: Hesse, Robert
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US06/827,553
• Time in Patent Office: 953 Days
• Field of Search: 260/397.2
• US Class Current: 544/233
• CPC Class Codes: C07C 29/40 with compounds containing carbon-to-metal bonds
• CPC Class Codes: C07C 31/36 the halogen not being fluorine
• CPC Class Codes: C07D 303/04 containing only hydrogen and carbon atoms in addition to the ring oxygen atoms
• CPC Class Codes: C07D 309/12 only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
• CPC Class Codes: C07D 333/72 Benzo[c]thiophenes; Hydrogenated benzo[c]thiophenes
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C07F 9/5316 Unsaturated acyclic phosphine oxides or thioxides
• CPC Class Codes: C07F 9/5325 Aromatic phosphine oxides or thioxides (P-C aromatic linkage)
• CPC Class Codes: C07F 9/5428 Acyclic unsaturated phosphonium compounds
• CPC Class Codes: C07F 9/65515 the oxygen atom being part of a five-membered ring
• CPC Class Codes: C08G 18/615 containing carboxylic acid groups
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Compounds of the general formula ##STR1## wherein R represents a hydrogen atom or a hydroxyl protecting group, Y represents a hydrogen atom or an optionally protected hydroxyl group, X represents the residue of a dienophile and either R¹ represents a halogen atom a hydrocarbylsulphonyloxy group or a group of the formula --Z--R³ (in which Z represents --O--, --S--, --SO--, --NR⁴ -- or --CR⁴ R⁵ -- and R³, R⁴ and R⁵, which may be the same or different, each represent a hydrogen atom or a straight or branched aliphatic group having 1-12 carbon atoms and which may optionally carry one or more substituents) and R² represents a hydrogen atom or R¹ and R² together represent an oxo group or an optionally substituted alkylidene group, except that R¹ and R² together with the group --CH(CH₃)CH-- to which they are attached do not represent a group having the branched 17β-hydrocarbyl side chain skeleton of vitamin D₂ or vitamin D₃ or use in the preparation of novel vitamin D analogues.

Claims

1. Compounds of the general formula:

##STR8## wherein R represents a hydrogen atom or a hydroxyl protecting group, Y represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group, X represents the residue of a dienophile and R¹ represents a halogen atom, hydroxyl or tosyloxy group or a group of formula;

Z--R³ where Z represents --O--, --S--, --NR⁴ or --SO--, where R³ represents a straight or branched aliphatic group having 1-12 carbon atoms which may carry one or more substituents selected from halogen atoms, hydroxyl groups and protected hydroxy groups and R⁴ represents hydrogen or a straight or branched aliphatic group having 1-12 carbon atoms which may carry one or more substituents selected from halogen atoms, hydroxyl groups and protected hydroxy groups and R² represents a hydrogen atom or R¹ and R² together represent an oxo group.

2. Compounds as claimed in claim 1 in which the dienophile is SO₂ or a diacylazo compound.

5. Compounds of general formula I as claimed in claim 1 wherein R¹ represents a halogen atom, a hydroxyl or tosyloxy group or a group formula:

##STR11## in which Z'"'"' represents --O--, --S--, --NH-- or --SO-- and R⁶ represents a hydrogen atom or a hydroxyl protecting group and R² represents a hydrogen atom.

3. Compounds of general formula IV or IVa:

##STR9## wherein R represents a hydrogen atom or a hydroxyl protecting group, Y represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group, R¹ represents a halogen atom, hydroxyl or tosyloxy group or a group of formula;

Z-R³ where Z represents --O--,--S--, --NR⁴, or --SO--, where R³ represents a straight or branched aliphatic group having 1-12 carbon atoms which may carry one or more substituents selected from halogen atoms, hydroxyl groups and protected hydroxy groups and R⁴ represents hydrogen or a straight or branched aliphatic group having 1-12 carbon atoms which may carry one or more substituents selected from halogen atoms, hydroxyl groups and protected hydroxy groups and R² represents a hydrogen atom or R¹ and R² together represent an oxo group.

4. Compounds of general formulae IV or IVa as claimed in claim 3 wherein R¹ represents a halogen atom, a hydroxyl or tosyloxy group or a group of formula:

##STR10## in which Z'"'"' represents --O--, --S--, --NH-- or --SO-- and R⁶ represents a hydrogen atom or a hydroxyl protecting group and R² represents a hydrogen atom.