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Patent landscape, scope, and claims: |
US Patent 7,067,522: Scope, Claims, and US Patent Landscape for Pyrimidine Derivatives
US Patent 7,067,522 claims a broad genus of pyrimidine derivatives defined by a tightly controlled core scaffold (Formula (I)) plus extensive enumerations of substituents on (i) the anilino/heteroaryl-linked pyrimidine rings (Q1 and Q2) and (ii) an anilino-like substituent set on the pyrimidine nitrogen- or carbon-linked position (R1, G, and substituent sets on the “anilines”/aryl rings). The claims also cover processes, pharmaceutical compositions, and method-of-use for cell-cycle inhibition, FAK inhibition, and selective CDK2/CDK4/CDK6 inhibition.
What exactly is claimed? (Claim set overview)
US 7,067,522 contains claims 1 to 15, with claims 1 to 9 covering compounds and the remainder covering downstream activities.
Product (compound) claims
- Claim 1: Core genus defined by pyrimidine derivative Formula (I) with variables Q1, Q2, G, R1, plus substituent sets including halo/amino/cyano/nitro/ureido/carbamoyl/sulphamoyl and multiple small substituent classes (alkyl, alkoxy, alkenyl, alkynyl, thioalkylsulfinyl variants, etc.). It also explicitly allows pharmaceutically acceptable salts and in vivo hydrolysable esters.
- Claims 2-3: Narrow Q1 and Q2 to phenyl/phenyl or phenyl/pyridyl.
- Claim 4: Adds a specific list of substituent exemplars on a ring carbon (drawn from substituted dialkylaminoalkyl motifs, aminoalkynyl motifs, cyclic amines, quinuclidinyl analogs, etc.).
- Claims 5-8: Positional and bond-logic limitations:
- Claim 5: Q1 substituted para or meta relative to the “—NH—” position (as defined within the claim’s internal architecture).
- Claim 6: G is —NH— (or salt/ester).
- Claim 7: R1 is hydrogen, chloro, or bromo.
- Claim 8: Q2 is unsubstituted or mono-substituted with fluoro/bromo/methyl/methoxy/cyano.
- Claim 9: Explicit compound examples (anilino/bromo/pyrimidine with specific substituted anilines).
Method and enablement claims
- Claim 10: A process claim, with at least two route classes depending on whether G is —NR2— and reacting substituted pyrimidines (II)/(IV) with (III)/(V), then optional conversion, deprotection, salt/ester formation.
- Claim 11: Pharmaceutical composition (compound + diluent/carrier).
- Claims 12-15: Medical methods in warm-blooded animals:
- Claim 12: “cell cycle inhibitory effect”
- Claim 13: FAK enzyme inhibitory effect
- Claim 14: selective CDK2, CDK4, or CDK6 inhibition
- Claim 15: “anti-cell proliferation effect”
How broad is Claim 1, structurally? (Formula (I) scope and degrees of freedom)
Claim 1 is a genus built from four main “handles”:
1) Pyrimidine core substituted at an anilino position
- Q1 and Q2 are independently selected from aryl or heteroaryl linked via ring carbon.
- The scaffold has a connectivity that makes Q1/Q2 substitution positions meaningful: “linked via ring carbon” ties into the pyrimidine’s ring-carbon substitution pattern.
2) G selects the linker type
- G is —O— or —NR2—.
- This gives two distinct chemical families: aryl ether/anilide-like versus aryl amine-like variants.
- R2: hydrogen, C1-6alkyl, C3-6alkenyl, or C3-6alkynyl, with optional substitution by Rc.
- Rc: a large list of substituents that includes halo, hydroxy, mercapto, nitro, formyl/formamido, carboxy, cyano, amino, ureido, carbamoyl, sulphamoyl, and specific acyl/alkoxycarbonyl/heteroatom-containing sulfoxide-like moieties (e.g., C1-4alkylS(O)a, a=0-2).
3) R1 governs the pyrimidine’s other substituent
- R1 is selected from a long list including:
- hydrogen, halo (as chloro/bromo is later constrained), hydroxy, nitro, amino
- aminoalkyl substituents (including N-(C1-3alkyl)amino and N,N-di-(C1-3alkyl)amino)
- cyano
- CF3 and CCl3 (trifluoromethyl, trichloromethyl)
- alkyl, alkenyl, alkynyl
- alkoxy, mercapto, alkylsulphanyl, carboxy, alkoxycarbonyl
- Many of these also carry optional substitution restrictions.
4) Q1 and Q2 carry extensive substituent sets
For each of Q1 and Q2, the claim allows up to:
- one to four substituents (for Q1 and Q2 ring carbon positions in the claim text)
- plus independently, or in addition, one to two substituents selected from aryl/cycloalkyl/heterocycle classes.
Both Q1 and Q2 are permitted to contain:
- halo, hydroxy, mercapto, nitro, formyl/formamido, carboxy, cyano, amino, ureido, carbamoyl, sulphamoyl
- C1-4alkyl, C2-4alkenyl, C2-4alkynyl (with optional Rd/Rg substitutions)
- C1-4alkanoyl, C1-4alkoxycarbonyl
- heterocyclic groups
- C1-4alkylS(O)a variants
- multiple N-functionalized urea/carbamoyl/sulphamoyl motifs (including N′- and N,N′-substituted ureido patterns)
- and an extra tier of optional aryl/cycloalkyl/heterocycle substitutions with Re/Rh/Rj/Ri/Rk-like substitution sets.
Salt/ester coverage is explicit:
- “a pharmaceutically acceptable salt or in vivo hydrolysable ester formed from an available carboxy or hydroxy group thereof.”
Business implication: Claim 1 is not limited to a single lead; it is a wide coverage net that captures many medicinal-chemistry permutations around a pyrimidine-anilino-like pharmacophore and preserves a wide substitution allowance on both aromatic appendages.
What is the claim’s “chemical perimeter” (what is tightly constrained vs open)?
Tight constraints
- Core scaffold identity: pyrimidine derivative of Formula (I).
- Q1 and Q2 type: independently aryl/heteroaryl linked via ring carbon.
- G choice: only —O— or —NR2—.
- R1 class: specific chemical families (halo/hydroxy/nitro/amino/cyano/CF3/trichloromethyl/alkyl/alkoxy/mercapto/carboxy/alkoxycarbonyl) with controlled chain lengths and substitution rules.
- Later narrowing claims:
- Claim 6: forces G to —NH—.
- Claim 7: forces R1 to hydrogen/chloro/bromo.
- Claim 8: forces Q2 to mono-substitution pattern limited to fluoro/bromo/methyl/methoxy/cyano.
Open design space
- The claim allows multiple substituents per aromatic ring, including:
- multi-functional nitrogenous groups (ureido/carbamoyl/sulphamoyl and N-alkylated variants)
- thioalkyl and sulfoxide-like patterns (C1-4alkylS(O)a)
- substituted alkynyl/alkenyl substituents
- optional additional aryl/cycloalkyl/heterocycle substituents on Q1/Q2.
Business implication: The patent is strongest where competitors stay within the formula architecture and substitute within these allowed aromatic and linker classes.
How do the dependent claims narrow the genus (and where competitors might attack)?
Claim 2: Q1 = phenyl
Claim 3: Q2 = phenyl or pyridyl
- Narrows Q2 to phenyl/pyridyl.
Claim 4: specific substituent set list
- Provides a curated list of substituents that includes:
- dimethylaminoethoxy, carboxymethoxy
- piperidyl/aminomethyl motifs
- morpholinoethoxy and diethylaminoethoxy
- imidazole-containing substituent
- aminoalkynyl substituent variants (2-aminoethynyl, 2-dimethylaminoethynyl, 3-hydroxyquinuclidin-3-yl ethynyl)
- aminoethylamino motifs and cyclic amines.
Claim 5: Q1 substitution position
- Para or meta relative to the —NH— (internal reference to G-linked nitrogen).
Claim 6: G = —NH—
- Eliminates ether linker and forces an N-linked family.
Claim 7: R1 limited
- R1 = hydrogen/chloro/bromo.
Claim 8: Q2 mono-substitution limited set
- Q2 unsubstituted or one substituent chosen from fluoro/bromo/methyl/methoxy/cyano.
Claim 9: named examples
- Captures specific molecules of the form:
- 4-anilino-5-bromo-2-[anilino substituted pyrimidine]
- with the anilino substituent as one of:
- 2-(dimethylaminoethoxy)anilino
- caroxymethoxy
- 1-methylpiperid-4-yloxy
- 6-methylpyrid-2-yl
- 2-piperid-1-ylethylamino
- 2-isopropylaminoethylamino
- 3-methylamino-1-propynyl
Business implication: Even if you design outside the exemplars, claim 1 still spans broad substitution space. Attacking the patent requires moving outside the claim’s formula boundaries (especially the scaffold identity, Q1/Q2 linking type, and the G class).
What are the method-of-use hooks (and how they shape enforcement risk)?
Claims 12-15 connect compounds of Formula (I) to target biology:
- Claim 12: “cell cycle inhibitory effect”
- Claim 13: “FAK enzyme inhibitory effect”
- Claim 14: selective “CDK2, CDK4 or CDK6 enzyme inhibitory effect”
- Claim 15: “anti-cell proliferation effect”
Business implication: This set is designed to support enforcement across:
1) broad anti-proliferation claims (lower threshold),
2) specific target engagement (FAK, CDKs),
3) and a functional readout (cell cycle inhibition).
It also means the same chemical coverage can be argued across multiple therapeutic hypotheses if label statements or study reports align to those endpoints.
What does Claim 10 cover on the chemistry side (process scope)?
Claim 10 is a route claim that depends on whether G is —NR2—, with key elements:
- reacting a pyrimidine of formula (II) where L is a displaceable group with a compound of formula (III) (G = —NR2—)
- or reacting a pyrimidine of formula (IV) with formula (V)
- followed by optional conversions:
- converting compound of Formula (I) into another Formula (I) variant
- removing protecting groups
- forming salts/esters.
Business implication: Process coverage can matter for contract manufacturing and for generic entry routes, even if competitor structures differ but still use the same core substitution strategy inside Formula (I).
How would you map the patent landscape in the US (practical landscape logic for this specific patent)?
This patent’s landscape impact typically falls into four buckets:
1) Freedom-to-operate risk anchored to Formula (I)
- If a candidate drug-like compound stays within Formula (I) and uses Q1/Q2 aryl/heteroaryl linked via ring carbon with G = —O— or —NR2—, it is structurally exposed to Claim 1.
2) Target-label alignment risk
- If a compound’s pharmacology package is positioned around:
- FAK inhibition
- CDK2/CDK4/CDK6 selective inhibition
- cell cycle inhibition
- anti-cell proliferation
it raises the risk that method claims are asserted in parallel with compound claims.
3) Synthesis-route overlap risk
- If internal or third-party synthesis uses substitution at a displaceable leaving group L on a pyrimidine intermediate and couples the corresponding amine/ether substituent to reach Formula (I), it can implicate Claim 10.
4) Stepping-stone claim narrowing
- Claims 6-8 and the exemplars in Claim 9 can be used to strengthen enforcement for specific analog series and for commercial candidates that match those narrower parameters.
Key takeaways
- US 7,067,522 is a broad pyrimidine derivative genus patent with wide aromatic substitution latitude on Q1 and Q2, controlled linker G (—O— or —NR2—), and a defined pyrimidine substituent R1.
- The claim set combines broad compound coverage (Claim 1) with narrowing dependent claims (Claims 6-9) that capture specific structural motifs and positional constraints.
- Enforcement leverage extends beyond composition into method-of-use for cell-cycle, FAK, and CDK2/CDK4/CDK6 endpoints.
- Process coverage in Claim 10 targets a substitution workflow using pyrimidine intermediates with a displaceable leaving group L and optional conversion steps (deprotection, salt/ester formation).
FAQs
1) What is the central structure protected by US 7,067,522?
A pyrimidine derivative of Formula (I) defined by Q1/Q2 aryl or heteroaryl linked via ring carbon, with linker G = —O— or —NR2— and a pyrimidine substituent R1 selected from enumerated classes, plus wide substitution options on Q1 and Q2 and on R2/Rc-related moieties.
2) Does the patent cover both ether and amine linker families?
Yes. Claim 1 allows G = —O— (ether family) or G = —NR2— (amine family). Claim 6 narrows to G = —NH—.
3) Are salts and hydrolysable esters included?
Yes. Claim 1 explicitly covers pharmaceutically acceptable salts and in vivo hydrolysable esters formed from available carboxy or hydroxy groups.
4) What biological targets and endpoints are claimed?
- Cell cycle inhibitory effect (Claim 12)
- FAK enzyme inhibitory effect (Claim 13)
- Selective CDK2, CDK4, or CDK6 inhibition (Claim 14)
- Anti-cell proliferation effect (Claim 15)
5) Are specific chemical examples explicitly listed?
Yes. Claim 9 enumerates multiple named compounds, including 4-anilino-5-bromo-2-[substituted anilino]pyrimidines with specific substituent patterns on the anilino ring.
References
[1] US Patent 7,067,522, “Pyrimidine derivatives,” claims 1-15 (provided claim text).
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