US 9,409,945 B2Granted

Combinatorial synthesis of libraries of macrocyclic compounds useful in drug discovery

AssigneeOcera Therapeutics, Inc.

InventorsPierre Deslongchamps, Yves Dory, Gilles Berthiaume, Luc Ouellet, Ruoxi Lan

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Abstract

A library of macrocyclic compounds of the formula (I) where part (A) is a bivalent radical, a —(CH2)y— bivalent radical or a covalent bond; where part (B) is a bivalent radical, a —(CH2)z— bivalent radical, or a covalent bond; where part (C) is a bivalent radical, a —(CH2)t— bivalent radical, or a covalent bond; and where part (T) is a —Y-L-Z— radical wherein Y is CH2 or CO, Z is NH or O and L is a bivalent radical. These compounds are useful for carrying out screening assays or as intermediates for the synthesis of other compounds of pharmaceutical interest. A process for the preparation of these compounds in a combinatorial manner, is also disclosed.

Claims3

Dependent claims

A macrocyclic compound of formula I:

and pharmaceutically acceptable salts thereof, wherein A1 is
where the nitrogen is bonded to T and the carbonyl is bonded to A2;
x is 0, 1 or 2;
R1 is selected from the group consisting of:
wherein (P) indicates the point of attachment to CH;
W1 to W16 are each independently hydrogen or a protecting group used for orthogonal protection in peptide synthesis;
and
X is selected from the group consisting of:
A2 is selected from the group consisting of prolinyl, 4-hydroxyprolinyl, 4-tert-butoxyprolinyl;
and
where the nitrogen is bonded to the carbonyl of Al and the carbonyl is bonded to
A3;
wherein
y is 0, 1 or 2;
R2 is selected from the group consisting of:
wherein (P) indicates the point of attachment to CH;
and
W1 to W16 are each independently hydrogen or a protecting group used for orthogonal protection in peptide synthesis;
A3 is selected from the group consisting of prolinyl, 4-hydroxyprolinyl, 4-tert-butoxyprolinyl;
and
where the nitrogen is bonded to the carbonyl of A2 and the carbonyl is bonded to T;
wherein
z is 0, 1 or 2;
R3 is selected from the group consisting of:
wherein (P) indicates the point of attachment to CH;
and
W1 to W16 are each independently hydrogen or a protecting group used for orthogonal protection in peptide synthesis;
and
(T) is selected from the group consisting of:
wherein (A3) indicates the site of a covalent bond to A3 of formula I and (A1) indicates the site of a covalent bond to A1 of formula I.

27 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/696,742Filed 27 Apr 2015 · continuation
Priority: CA 22844594 Oct 1999
Published: US 2015/0315235 A15 Nov 2015
Granted: 9 Aug 2016
Term ends: Not estimatedThe source records don’t support an estimate.

Classification39 codes

C07K 5/0808
And aliphatic: the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
A61P 5/28
Of the sex hormones: antiandrogens
A61P 7/10
Drugs for disorders of the blood or the extracellular fluid: antioedematous agents; Diuretics
A61P 9/00
Drugs for disorders of the cardiovascular system

Family

Application09/679,331Parent of this continuation · filed 4 Oct 2000
Application11/615,332Parent of this continuation · filed 22 Dec 2006
US 7,169,899 B1Parent of this continuation · filed 30 Jan 2007
Application13/218,784Parent of this continuation · filed 26 Aug 2011
US 8,008,440 B2Parent of this continuation · filed 30 Aug 2011
US 2015/0315235 A1Pre-grant publication · published 5 Nov 2015
US 9,018,419 B2Parent of this continuation
US 2007/0117154 A1Published application
US 2012/0046441 A1Published application
US 9,409,945 B2This patent

From the US filing history. Foreign family members aren’t listed.