Claims
- 1. A compound of formula I wherein X is —CH2—CH2—, Y is—CH2—, each of R1 and R2 is a residue of formula (a) wherein R5 is —NH2 or NHY′a wherein Y′a is a protecting group and R6 is —COOH or C2-9alkoxy carbonyl, X1 is H or OH, Z is —CH2—CH2— and R3 is a residue of formula (a) wherein R5 is —NH2 or NHY′a and R6 is CONHRc or —CO—Y2—NHRc wherein Y2 is a spacer and Rc is an antigenic group or wherein R10 is OH or C1-8alkoxy and R11 is C1-6alkyl, or wherein X is —CH2—CH2—, Y is —CH2—, Z is —CH2—CH2—, each of R1 and R3 is a residue of formula (a) wherein R5 is —NH2 or NHY′a and R6 is —COOH or C2-9alkoxycarbonyl, X1 is H or OH, and R2 is a residue of formula (a) wherein R5 is —NH2 or NHY′a, and R6 is —CONHRc or —COY2—NHRc as defined above, R4 being OH; and X2 is an anion which is acetate, chloride, or iodide, provided that the compound of formula I is not hydroxylysyl pyridinoline or lysyl pyridinoline.
- 2. A process for the preparation of a compound of formula in which X is —CH2—CH2—, Y is —CH2—, each of R1 and R2 is a residue of formula (a) wherein R5 is —NH2— or NHYa′, wherein Ya′ is an amine protecting group and R6 is —COOH or C2-9alkoxy carbonyl, X1 is H or OH, Z is —CH2—CH2 and R3 is a residue of formula (a) wherein R5 is —NH2— or NHYa′ and R6 is —CONHRc or —CO—Y2—NHRc wherein Y2 is a spacer and Rc is an antigenic group or wherein R10 is OH or C1-8alkoxy and R11 is C1-4alkyl, or wherein X is —CH2—CH2—, Y is —CH2—, Z is —CH2—CH2—, each of R1 and R3 is a residue of formula (a) wherein R5 is —NH2— or NHYa′, and R6 is —COOH or C2-7alkoxycarbonyl, X1 is H or OH, and R2 is a residue of formula (a) wherein R5 is —NH2— or NHYa′ and R6 is —CONHRc or —CO—Y 2—NHRc as defined above and R4 is OH;which comprisesa) cyclizing a compound of formula in a basic solution to obtain a compound of formula II where X, Y, R1, and R2, are as defined above;Z2 is a leaving group; and R4 is hydroxy; and b) reacting the compound of formula II with a compound of formula III X5—CH2—CHX1—Z—R3 wherein X1, Z and R3, are as defined above, and X5 is a leaving group; and X2 is an anion which is acetate, chloride, or iodide.
- 3. A process according to claim 2 in which the spacer group Za or Y2 is selected from succinyl or a divalent residue derived from 3-aminopropanoic acid, 3-aminoisobutanoic acid, 4-aminobutanoic acid, NH2—C(CH3)2—COOH, 6-aminohexanoic acid, 1,8-diaminooctane, 1,6-diaminohexane and NH2—(CH2)1-4—CO—NH—(CH2)1-6—NH2.
- 4. A process according to claim 2 in which the compound of formula I is 3-hydroxy-1-(5-t-butoxycarbonylamino-5-t-butoxycarbonyl-pentyl)-4-(1 -t-butoxycarbonylamino-1-t-butoxycarbonyl-2-ethyl)-5-(3-t-butoxycarbonylamino-3-t-butoxycarbonyl-propyl)-pyridinium iodide.
- 5. A process according to claim 2 in which the compound of formula I is a 3-hydroxy-1-(5-amino-5-carboxy-pentyl)-4-(2-amino-2-carboxy-ethyl)-5-(3-amino-3-carboxy-propyl)-pyridinium chloride.
- 6. A process according to claim 2 in which the basic solution in step a) is a solution of 1,5-diazabicyclo [4.3.0] non-5-ene or a solution of 1,8-diazabicyclo [5.4.0] undec-7-ene.
- 7. A process according to claim 2 in which the cyclization is carried out in an inert solvent at room temperature.
- 8. A process according to claim 2 in which the compound of formula II is 2-t-butoxycarbonylamino-4-[3-hydroxy-4-(1 -t-butoxycarbonyl-1 -t-butoxycarbonylamino-2-ethyl)-5-pyridinyl] butanoic acid, t-butyl ester.
Priority Claims (2)
Number |
Date |
Country |
Kind |
9202139 |
Jan 1992 |
GB |
|
9315547 |
Jul 1993 |
GB |
|
Parent Case Info
The present application is a continuation-in-part of previously filed application Ser. No. 08/011,445 filed Jan. 29, 1993 abandoned on Aug. 23, 1994.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4973666 |
Eyre |
Nov 1990 |
|
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
08/011445 |
Jan 1993 |
US |
Child |
08/281887 |
|
US |